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10,400 | 23,996,298 | Abdominal wall lift with or without pneumoperitoneum does not seem to offer an advantage over pneumoperitoneum in any of the patient-oriented outcomes for laparoscopic cholecystectomy in people with low anaesthetic risk . | BACKGROUND Laparoscopic cholecystectomy ( key-hole removal of the gallbladder ) is now the most often used method for treatment of symptomatic gallstones .
Several cardiopulmonary changes ( decreased cardiac output , pulmonary compliance , and increased peak airway pressure ) occur during pneumoperitoneum , which is now introduced to allow laparoscopic cholecystectomy .
These cardiopulmonary changes may not be tolerated in individuals with poor cardiopulmonary reserve .
OBJECTIVES To assess the benefits and harms of abdominal wall lift compared to pneumoperitoneum in patients undergoing laparoscopic cholecystectomy . | Background Because of absorbed carbon dioxide ( CO2 ) and elevated intraabdominal pressure ( IAP ) , CO2 pneumoperitoneum ( CO2PP ) has potentially harmful intraoperative circulatory and ventilatory effects . Although not clinical ly significant for healthy patients , these effects are assumed to be deleterious for patients with a high risk for anesthesia ( American Society of Anesthesiology [ ASA ] 3 and 4 ) and significant cardiopulmonary , renal , or hepatic diseases . The authors assessed CO2PP-related adverse effects by comparing ASA 3 and 4 patients who underwent laparoscopic cholecystectomy ( LC ) with or without CO2PP . Methods A total of 20 successive ASA 3 and 4 patients who underwent LC were r and omized into CO2PP ( n = 10 ) and abdominal wall elevator ( Laparolift ) ( n = 10 ) groups . The parameters for perioperative hemodynamics , ventilation , perfusion of intraabdominal organs , and blood chemistry were recorded periodically from before the induction of the anesthesia until postoperative day 2 and compared between the groups . Results Mean age , height , weight , the proportional number of ASA 3 vs ASA 4 patients , the volume of perioperative fluid loading , and the dose of analgesics did not differ significantly between the groups . The length of the operation was 49.9 ± 10.6 min for the CO2PP group and 50.6 ± 17.2 min for Laparolift group ( nonsignificant difference ) . The mean central venous pressure ( CVP ) 30 min after insufflation was higher ( 12.3 ± 4.8 vs 7.9 ± 3.7 mmHg ) and the ( Gastric Mucosal pH ) pHi at the end of the operation was lower ( 7.29 ± 0.07 vs 7.35 ± 0.04 ) in the CO2PP group than in the Laparolift group ( p < 0.05 ) . Later , CVP and pHi did not differ significantly . Other parameters of hemodynamics including oxygenation , perfusion , and blood chemistry did not differ significantly . Conclusions For LC for patients with an ASA 3 and 4 risk for anesthesia , no significant adverse effects could be attributed to CO2 pneumoperitoneum . For high-risk patients , preoperative preparation and active perioperative monitoring are essential for safe anesthesia for LC with or without CO2PP We have compared , in a r and omized study , conventional carbon dioxide pneumoperitoneum with abdominal wall lift in 25 patients undergoing laparoscopic cholecystectomy . Intra-abdominal pressure ( IAP ) ( 11 ( SD 2 ) mm Hg vs 2.7 ( 9 ) mm Hg ) ( P < 0.01 ) and total amount of carbon dioxide used ( 40 ( 23 ) litre vs 9 ( 7 ) litre ) ( P < 0.001 ) were significantly less with abdominal wall lift . Pulmonary compliance was significantly greater ( P < 0.01 ) in the abdominal wall lift group throughout operation . During the first 15 min of insufflation , arterial pressures were lower with abdominal wall lift ( P < 0.05 ) . In the conventional pneumoperitoneum group , femoral vein pressure increased ( P < 0.01 ) and remained elevated for 3 h in the recovery room . Postoperative drowsiness was of significantly longer duration in the conventional pneumoperitoneum group than in the abdominal wall lift group ( 98 ( 46 ) min vs 13 ( 34 ) min ) ( P < 0.01 ) . Postoperative nausea and vomiting and right shoulder pain occurred more often in patients with conventional pneumoperitoneum ( P < 0.05 ) . We conclude that the benefits of abdominal wall lift may be attributed to avoiding excessive carbon dioxide and high IAP Abstract Background : Laparoscopic cholecystectomy using low-pressure pneumoperitoneum ( 8 mmHg ) minimizes adverse hemodynamic effects , reduces postoperative pain , and accelerates recovery . Similar cl aims are made for gasless laparoscopy using abdominal wall lifting . The aim of this study was to compare gasless laparoscopic cholecystectomy to low-pressure cholecystectomy with respect to postoperative pain and recovery . Methods : Thirty-six patients were r and omized to low-pressure or gasless laparoscopic cholecystectomy using a subcutaneous lifting system ( Laparotenser ) . Results : The characteristics of the patients were similar in the two groups . The procedure was completed in all patients in the low-pressure group , but two patients in the gasless group were converted to pneumoperitoneum . There were no significant differences in postoperative pain and analgesic consumption , but patients in the gasless group developed shoulder pain more frequently ( 50 % vs 11 % , p < 0.05 ) . Gasless operation took longer to perform ( 95 vs 72.5 min , p= 0.01 ) . Conclusions : Gasless and low-pressure laparoscopic cholecystectomy were similar with respect to postoperative pain and recovery . The gasless technique provided inferior exposure and the operation took longer , but the technique may still have value in high-risk patients with cardiorespiratory disease We have compared , in a r and omized study in 26 patients , immediate and late postoperative recovery after elective laparoscopic cholecystectomy using the gasless , mechanical abdominal wall lift method with conventional carbon dioxide pneumoperitoneum . After the gasless method , tracheal extubation was performed significantly earlier than after the conventional method ( P < 0.01 ) . End-tidal carbon dioxide concentrations were significantly higher after pneumoperitoneum for 30 min after operation ( P < 0.01 ) . In the conventional group , deviation in Maddox-Wing recordings from preoperative values remained at a significantly higher level during the 3-h recovery room period ( P < 0.01 ) . There was a positive correlation between the total amount of carbon dioxide used and duration of drowsiness ( r = 0.61 , P < 0.001 ) and the Maddox-Wing deviation ( r = 0.62 , P < 0.001 ) . Postoperative nausea and vomiting , and right shoulder pain occurred less often after the gasless method ( P < 0.05 ) . Late recovery criteria ( ability to drink , void and walk ) in patients in the gasless group were fulfilled approximately 7 h earlier than in those in the pneumoperitoneum group ( P < 0.01 ) . Gasless laparoscopic cholecystectomy result ed in more uneventful and faster immediate and late postoperative recovery than conventional carbon dioxide pneumoperitoneum Although laparoscopic cholecystectomy has rapidly developed in the treatment of gall bladder disease in the absence of controlled clinical trial data its outcome parameters compared with open cholecystectomy remain unclear . A prospect i ve audit of the introduction of laparoscopic cholecystectomy in the west of Scotl and over a two year period was carried out to attempt to assess this new procedure . A total of 45 surgeons in 19 hospitals performing laparoscopic cholecystectomy su bmi tted prospect i ve data from September 1990 - 1992 . A total of 2285 cholecystectomies were audited ( a completed data collection rate of 99 % ) . Laparoscopic cholecystectomy was attempted in 1683 ( 74 % ) patients and completed in 1448 patients ( median conversion rate to the open procedure 17 % ) . The median operation time in the completed laparoscopic cholecystectomy patients was 100 minutes ( range 30 - 330 ) and overall hospital stay three days ( 1 - 33 ) . There were nine deaths ( 0.5 % ) after laparoscopic cholecystectomy although only two were directly attributable to the laparoscopic procedure . In the laparoscopic cholecystectomy group there were 99 complications ( 5.9 % ) , 53 ( 3 % ) of these were major requiring further invasive intervention . Forty patients ( 2.4 % ) required early or delayed laparotomy for major complications such as bleeding or bile duct injuries . There were 11 ( 0.7 % ) bile duct injuries in the laparoscopic cholecystectomy series , five were noted during the initial procedure and six were recognised later result ing from jaundice or bile leaks . Ductal injuries occurred after a median of 20 laparoscopic cholecystectomies . In conclusion laparoscopic cholecystectomy has rapidly replaced open cholecystectomy in the treatment of gall bladder disease . Although the overall death and complication rate associated with laparoscopic cholecystectomy is similar to open cholecystectomy , the bile duct injury rate is higher We have studied the cardiorespiratory changes produced by abdominal wall elevation ( AWE ) or carbon dioxide pneumoperitoneum ( PN ) in 20 women undergoing gynaecological laparoscopy . Arterial pressure , heart rate , lung/chest complicance and blood-gas tensions were measured 10 min after induction of general anaesthesia ( T0 ) , 10 min after abdominal distension in the supine position ( T1 ) and 10 min after the Trendelenburg position was assumed ( T2 ) . Visual analogue scores for pain were recorded 1 and 6 h after the end of surgery . We found that lung/chest compliance was reduced significantly in group PN at T1 and T2 compared with both T0 and group AWE . Diastolic arterial pressure increased significantly in group PN at T1 and T2 compared with both T0 and group AWE , while it remained unchanged in group AWE . Arterial PCO2 increased significantly only in group PN after pneumoperitoneum , while oxygenation was almost unchanged in both groups . AWE patients had greater abdominal pain 1 h after surgery . Six hours after surgery pain was similar in the two groups . These data indicate that abdominal wall elevation reduced pulmonary compliance less than a pneumoperitoneum in patients undergoing gynaecological laparoscopy OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials Objective : Carbon dioxide ( CO2 ) pneumoperitoneum has been implicated as a possible factor in early immune preservation in laparoscopic surgery . Although the current analysis was not adequate to clarify this issue , the aim of this study was to compare CO2 insufflation laparoscopic cholecystectomy to gasless abdominal wall lift laparoscopic cholecystectomy with respect to preservation of the immune system . Method : An analysis of the temporal immune responses was performed in 2 similar groups of patients ( n = 50 ) who were divided r and omly into the categories of gas or abdominal wall lift laparoscopic cholecystectomy . The patients were matched with respect to age , weight , and operation time . The immune parameters ( serum white blood cell count , cortisol , erythrocyte sedimentation rate [ ESR ] , tumor necrosis factor-α[TNF-α ] , interferon-γ[INF-γ ] , interleukin-6 [ IL-6 ] , interleukin-8 [ IL-8 ] ) were assessed at preoperative 24 hours and at postoperative 24 and 72 hours for the 2 groups . During the operation , the levels of cytokines that were cultured in the peritoneal macrophages were also checked . Results : The serum white blood cell count , cortisol , and ESR levels were not statistically different in either of the 2 groups . Further , the serum TNF-α , INF-γ , IL-6 , and IL-8 levels in both groups were not significantly different from each other at preoperative 24 hours , and postoperative 24 and 72 hours . However , an immediate decrease in the cytokine levels at 24 hours after the operation was significant in both groups . The cytokine levels were particularly higher in the cultured peritoneal macrophages than in the serum , but were not statistically different between the 2 groups . Conclusion : Our results showed that the beneficial immune response obtained in the CO2 gas insufflation laparoscopic procedure could also be obtained in the gasless abdominal wall lift laparoscopic procedure . An immediate preservation of the immune functions in the postoperative period was detected similarly in the 2 groups Adequate reporting of r and omized , controlled trials ( RCTs ) is necessary to allow accurate critical appraisal of the validity and applicability of the results . The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement , a 22-item checklist and flow diagram , is intended to address this problem by improving the reporting of RCTs . However , some specific issues that apply to trials of nonpharmacologic treatments ( for example , surgery , technical interventions , devices , rehabilitation , psychotherapy , and behavioral intervention ) are not specifically addressed in the CONSORT Statement . Furthermore , considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement . Therefore , the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments . A consensus meeting of 33 experts was organized in Paris , France , in February 2006 , to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments . The participants extended 11 items from the CONSORT Statement , added 1 item , and developed a modified flow diagram . To allow adequate underst and ing and implementation of the CONSORT extension , the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting . This extension , in conjunction with the main CONSORT Statement and other CONSORT extensions , should help to improve the reporting of RCTs performed in this field A r and om sample of 4,807 men and women , aged 30 , 40 , 50 , and 60 years , who lived in the western part of Copenhagen County , was drawn from the National Central Person Registry . A total of 226 subjects who were not of Danish origin were omitted . The response rate was 78.8 % ( 3,608/4,581 ) . Each person had his or her gallbladder examined by ultrasonography . The examinations took place between November 1982 and February 1984 . The overall prevalence of gallstone disease ( cases with stones and cholecystectomized cases ) in males aged 30 , 40 , 50 , and 60 years was 1.8 % , 1.5 % , 6.7 % , and 12.9 % , respectively . The corresponding prevalence in females was 4.8 % , 6.1 % , 14.4 % , and 22.4 % , respectively . Differences according to sex were significant in all age groups . Differences between the 40- and 50-year and 50- and 60-year age groups were significant in both sexes . Among subjects with gallstone disease , the disease was unknown to the prob and in the majority of males and in the 30-year-old females , but only in half of the women aged 40 , 50 , and 60 years . The prevalence of clinical ly diagnosed gallstones was not significantly different between respondents and nonrespondents BACKGROUND Although abdominal wall retraction is said to be advantageous in laparoscopic cholecystectomy ( LC ) , many surgeons have found that , when this option is chosen , more time is needed to prepare for and carry out the surgical procedure . Our aim was to determine the time required for surgical preparation and operation in patients undergoing LC with carbon dioxide ( CO2 ) pneumoperitoneum ( CO2 PP ) vs abdominal wall retraction ( AWR ) . METHODS We performed a prospect i ve r and omized study of a CO2 PP LC group ( n = 19 ) vs an AWR LC group ( n = 15 ) . Demographic data were collected preoperatively . LC was performed with either CO2 PP ( 12 mmHg ) or AWR ( 6 - 10 kps ) . Two phases were considered : ( a ) time employed to create the surgical field ( phase 1 ) and ( b ) operating time ( phase 2 ) . The chi-square test was used to compare the medians of the two groups . RESULTS The two groups were homogeneous . Phase 1 required 35 min in the CO2 PP group vs 25 min in the AWR group ( p = 0.24 ) . Phase 2 required 60 min in both groups ( p = 0.76 ) . CONCLUSION We found no statistically significant difference between the PP CO2 and AWR groups in either time spent to create the surgical field or actual operating time BACKGROUND Gasless laparoscopy using abdominal wall lifting ( AWL ) has been developed in an attempt to avoid the adverse effects of carbon dioxide pneumoperitoneum that may occur in conventional laparoscopy . However , lifting has been criticized for its poor operative space and surgical invasiveness . This study compared the AWL method with conventional CO2 pneumoperitoneum for laparoscopic cholecystectomy with respect to operation performance , postoperative course , and stress response . PATIENTS AND METHODS During a 6-month period , 95 patients with symptomatic gallstones were r and omly assigned to receive laparoscopic cholecystectomy with conventional CO2 pneumoperitoneum ( CO2 group ; N = 47 ) or the AWL method ( AWL group ; N = 48 ) . Operative results and operative time were recorded . Cardiopulmonary functions were assessed , and arterial blood gases were analyzed during surgery . Urinary cortisol , vanillylm and elic acid , metanephrines , and nitrogen loss ; serum complement 3 , C-reactive protein , and interleukin-6 ; postoperative pain ; and the presence of nausea and vomiting were assessed for 48 hours after surgery . Postoperative time to recovery of flatus , tolerance of a full oral diet , and full activity were also determined . RESULTS Only three significant differences were found . First , intraoperative ventilatory function deteriorated significantly less in the AWL group . Second , arterial blood gas determinations and capnography showed a greater decrease in intraoperative arterial pH and compliance with CO2 retention and an increase in peak airway pressure in the CO2 group ( P < 0.05 ) , reflecting poorer ventilatory performance . Third , preparation time and total operating time were significantly greater with the AWL method ( P < 0.05 ) . CONCLUSIONS Although AWL required a longer operation time , our results suggest that the technique may still have value in high-risk patients with cardiorespiratory diseases Summary Between April and August 1991 , 83 Japanese patients with symptomatic gallstones underwent laparoscopic cholecystectomy in our clinics . A prospect i ve r and omized trial was carried out to examine the safety , efficacy , and complications of the two techniques , pneumoperitoneum vs an elevating method using a U-shaped retractor . Forty-two patients were r and omly allocated to the pneumoperitoneum ( P ) group and 41 to the U-shaped retractor ( U ) group . These two groups were well matched with respect to age , sex , etiology , and the severity of the chronic cholecystitis . Laparoscopic resection was successful for 88.1 % ( 37/42 ) in the P group and 100 % ( 41/41 ) in the U group . In patients with a severe fibrotic gallbladder , the rate of success was significantly higher ( P<0.05 ) in the U group ( 100 % , 6/6 ) than in the P group ( 11.8 % , 1/6 ) . In the moderately inflamed group , the operation time ( mean±SD ) was significantly ( P<0.01 ) less in the U group ( 58.7±22.7 ) than in theP group ( 87.3±18.3 ) . With the U-shaped retractor the usual surgical instruments can be used , and a rapid and safer laparoscopic cholecystectomy can be carried out . We prefer this approach to a pneumoperitoneum for patients with an inflamed gallbladder as hospital stay and pain are minimal Objective : To compare intraoperative cardiac function , postoperative cognitive recovery , and surgical performance of laparoscopic cholecystectomy with abdominal wall lift ( AWL ) versus positive-pressure capnoperitoneum ( PPCpn ) . Summary Background Data : AWL has been proposed as an alternative approach to PPCpn to avoid adverse cardio-respiratory changes . However , the workspace obtained with the AWL is less optimal than PPCpn and previous studies documenting delayed postoperative recovery of consciousness following PPCpn have not assessed mental alertness despite its importance . Methods : Forty operations were r and omized into AWL and PPCpn . A st and ard anesthetic protocol was followed . Cardiac indices were measured with an esophageal Doppler machine . An auditory vigilance test was used to measure alertness level following extubation . All operations were videotaped and human reliability assessment techniques were used to identify surgical errors . Results : There was a significant reduction in cardiac output during the first 20 minutes following CO2 insufflation in the PPCpn group , whereas in the AWL group it did not exhibit any significant change . Patients in AWL arm had better vigilance scores at 90 and 180 minutes following extubation compared with the PPn group ( P < 0.05 ) . Significantly more surgical errors were observed during surgery with AWL than with PPCpn ( 7.1 ± 1.1 ; versus 2.9 ± 0.4 ; P = 0.001 ) . Conclusions : The AWL approach avoids fall in cardiac output associated with PPCpn during laparoscopic surgery and is associated with a more rapid recovery of postoperative cognitive function compared with PPCpn . However , AWL increases the level of difficulty in the execution of the operation Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . The positive CO2 pneumoperitoneum needed to create the working space for laparoscopic surgery induces cardiovascular , neuroendocrine , and renal changes . Concern about these pathophysiologic changes has led to the introduction of a gasless technique . Fifty consecutive patients with symptomatic gallstones were r and omized to conventional ( CLC ) or gasless laparoscopic cholecystectomy ( GLC ) , with special reference to overall patient satisfaction , technical difficulties , duration of surgery , postoperative pain , and recovery . The overall exposure of the operative field was extremely poor in the GLC group , whereas the duration of surgery , steps involved in the cholecystectomy technique , length of hospital stay , and postoperative pain score did not differ significantly . After discharge , the median time to complete relief of pain tended to be shorter in the gasless group ( 5 days [ range 1 to 15 ] ) vs. the conventional group ( 8 days [ range 1 to 15 ] ) . The period to return to normal activity was shorter in the GLC group ( 6 days [ range 1 to 1.5 ] ) compared to the CLC group ( 8.5 days [ range 1 to 15 ] ) ( P = 0.031 ) . No differences were found in terms of fatigue , dizziness and nausea , and overall satisfaction with the outcome . This study demonstrates a significantly shorter convalescence after laparoscopic cholecystectomy by means of the gasless technique compared to the conventional CO2 technique . Exposure of the operative field was less than optimal using the gasless technique Background Carbon dioxide ( CO2 ) pneumoperitoneum ( PP ) increases mean arterial blood pressure ( MAP ) and systemic vascular resistance ( SVR ) but decreases stroke volume ( SV ) and cardiac output ( CO ) . This study evaluated the hemodynamic effects of elevated intraabdominal pressure ( IAP ) occurring during laparoscopic donor nephrectomy ( LDN ) . Methods Twenty-two patients undergoing LDN were investigated and hemodynamic parameters , PvCO2 ( carbon dioxide partial pressure ) , and VCO2 ( carbon dioxide production ) were monitored during the procedure . Before and after PP , IAP was raised from 12 to 20 mmHg and the hemodynamic effects were measured every 30 s. Results During IAP of 12 mmHg and stable serum CO2 , there was no change in SV compared to preinsufflation levels . When IAP was elevated from 12 to 20 mmHg , SV initially decreased ( p < 05 ) , followed by an increase in MAP and SVR ( p < 0.05 ) . Conclusion This study shows that with the fluid and ventilation protocol used , PP has no significant effect on SV at an IAP of 12 mmHg , whereas increasing IAP to 20 mmHg does . In this study , the hemodynamic effects induced by CO2 PP of 12 mmHg are not due to changes in serum CO2 . Compression of the venous system during a PP of 20 mmHg reduces preload , with an subsequent increase in SVR Background : In a previous clinical study , we showed that the duration and level of pneumoperitoneum are responsible for changes in hepatic function during laparoscopic procedures . These findings encouraged us to evaluate hepatic function during laparoscopy with and without carbon dioxide ( CO2 ) pneumoperitoneum in a clinical setting . Methods : We performed 63 laparoscopic cholecystectomies and 30 non-hepatobiliary laparoscopic procedures in 93 consecutive patients with normal preoperative liver function tests . The anesthesiologic protocol was uniform , using drugs at low hepatic metabolism . We performed laparoscopic cholecystectomies in 43 patients with a pneumoperitoneum ; in the remaining 20 , we used a gasless technique . We r and omized the 43 laparoscopic cholecystectomies into 23 performed with pneumoperitoneum at 14 mmHg and 20 performed at 10 mmHg . All non-hepatobiliary laparoscopic procedures were performed with a pneumoperitoneum of 14 mmHg . The postoperative serologic levels of AST , ALT , and bilirubin , and the prothrombin time were measured at 6 , 24 , 48 , and 72 h. The alterations in the serologic hepatic tests were then related to the type of procedure , its duration , and the level of pneumoperitoneum . Results : The study group was comprised of 93 patients , 39 male and 54 female , with a mean age of 50.5 years ( range , 15 - 74 ) . There were no deaths . There was no morbidity in the pneumoperitoneum group , but there was one case of accidental omental injury during the placement of the abdominal , wall retractor in the gasless group . All patients had postoperative changes in serologic hepatic tests . Slow return to normality occurred 48 or 72 h after the operation . The increase in AST and ALT was statistically significant and correlated to the level and duration of pneumoperitoneum . The serologic change in the gasless group were significantly lower than in the laparoscopic cholecystectomy group with pneumoperitoneum at 14 mmHg . There was no statistically significant difference between the gasless group and the laparoscopic cholecystectomy group with pneumoperitoneum at 10 mmHg . There was a statistically the significant increase in the non-hepatobiliary laparoscopy group over the gasless group , despite the absence of hepatobiliary injuries in the first group . No symptoms were related to these serologic hepatic changes . Conclusions : The gasless technique causes smaller alterations in serological hepatic parameters than pneumoperitoneum at 14 mmHg . By contrast , the gasless technique and low-pressure pneumoperitoneum have the same effect on hepatic function . Therefore , the use of a subcutaneous abdominal wall retractor combined with a low-pressure pneumoperitoneum is recommended for patients with severe hepatic failure . In general , laparoscopic cholecystectomy produces a surgical stress response very similar to which occurs after open cholecystectomy . The question is whether the pneumoperitoneum constitutes a significant pathophysiologic trauma , which might be followed by profound changes in the stress response . We conducted a prospect i ve , r and omized trial involving 50 consecutive patients scheduled for laparoscopic cholecystectomy , who had a body mass index equal to or less than 30 kg/m2 with no acute cholecystitis , pancreatitis , or liver or renal disease . These patients were r and omized to undergo either the gasless ( GLC , n= 24 ) or the carbon dioxide pneumoperitoneum ( CLC , n = 26 ) procedure . Perioperative assessment of cortisol , insulin , glucose , and C-reactive protein levels was the main determinant of outcome . During the operative procedure , significantly higher levels of serum cortisol and insulin were found in the CLC group than in the GLC group ( P < 0.05 ) . No difference in glucose levels was observed between the two groups . The inflammatory response was moderate in both groups . However , on postoperative day 1 the median C-reactive protein level was significantly higher in the GLC group than that in the CLC group ( P < 0.05 ) . Carbon dioxide and the positive intra-abdominal pressure during conventional laparoscopy may contribute to the activation of the surgical stress response OBJECTIVE To evaluate the effects of pneumoperitoneum with carbon dioxide , argon , and helium ; different abdominal pressures ( ie , 8 , 12 , and 16 mm Hg ) ; and different positions ( ie , head up , head down , supine ) on hemodynamic and respiratory function in a porcine model . DESIGN Prospect i ve r and omized trial . SETTING Animal research laboratory . ANIMALS Eighteen pigs weighing 25.5 + /- 6.9 kg ( mean + /- SD ) . INTERVENTIONS General anesthesia with endotracheal intubation . Implantation of pulmonal artery catheter and central venous line in jugular vein and catheters in femoral artery and vein . Carbon dioxide , argon , or helium was insufflated through a cannula in the left upper quadrant . The type of gas was r and omly assigned to each animal . After recording baseline values at the beginning and at the end without pneumoperitoneum , each animal was placed in 1 of the 3 positions and under 1 of the 3 pressures kept by the insufflator . After 15 minutes of adaptation to the new circumstances , all factors were recorded . This procedure was repeated until all 9 combinations of pressures and positions were evaluated . MAIN OUTCOME MEASURES Cardiac output ; heart rate ; stroke volume ; right ventricular stroke work ; pressures in the pulmonal artery , vena cava , and femoral artery and vein ; systemic vascular resistance ; respiratory pressure ; tidal volume ; pH ; base excess ; oxygen partial pressure ; and carbon dioxide partial pressure . RESULTS The type of gas did not affect cardiac output . Only carbon dioxide demonstrated negative effects on respiratory function . Argon markedly increased afterload . Carbon dioxide increased central venous and mean arterial pressure , which was only moderate using helium . A head-up position decreased cardiac output and central venous pressure and increased mean arterial and peripheral venous pressures , which were partly compensated in a head-down position . An intraperitoneal pressure of 16 mm Hg increased peripheral and central venous pressures , heart rate , and respiratory pressure , and decreased cardiac output , tidal volume , and pH. CONCLUSIONS Helium may be an alternative gas to establish pneumoperitoneum because it does not have any effect on respiratory function and has only a moderate effect on hemodynamic function . Argon insufflation has some hemodynamic disadvantages . An intraperitoneal pressure greater than 12 mm Hg and a head-up position should be avoided because both have a markedly negative effect on respiratory and hemodynamic factors Carbon dioxide pneumoperitoneum may be an important pathophysiological factor stimulating the coagulation system during conventional laparoscopic cholecystectomy . The aim of this study was to test the hypothesis that gasless laparoscopy produces smaller changes in the coagulation and fibrinolytic system than carbon dioxide pneumoperitoneum in patients undergoing laparoscopic cholecystectomy This study compared the effect of intraperitoneal CO2 insufflation with abdominal wall lift on RR interval , QT interval , the rate-corrected QT ( QTc ) interval , QT dispersion ( QTD ) , and the rate-corrected QTD ( QTcD ) using computerized measurement during laparoscopic cholecystectomy . Thirty patients scheduled for laparoscopic cholecystectomy were r and omly assigned to 2 groups : intraperitoneal CO2 insufflation ( CO2 group ) or abdominal wall lift ( lift group ) . A 12-lead electrocardiogram was monitored to measure parameters . The RR interval , QT interval , and QTc interval did not change significantly during the study in both groups . The QTD and QTcD in the CO2 group increased significantly during CO2 insufflation , and were significantly higher than those of the lift group . Statistically significant increases of QTD and QTcD , which are associated with an increased risk of arrhythmias and cardiac events , occur during CO2 insufflation , and QTD and QTcD in the CO2 group were significantly higher than those of the lift group Abstract Background : After laparoscopy with carbon dioxide ( CO2 ) insufflation early postoperative recovery is often complicated with drowsiness and postoperative nausea and vomiting ( PONV ) . Methods : 25 ASA I − II patients undergoing elective laparoscopic cholecystectomy under st and ardized anaesthesia were studied in a r and omized , prospect i ve study . The conventional CO2 pneumoperitoneum was compared with the mechanical abdominal wall lift ( AWL ) method with minimal CO2 insufflation with special reference to postoperative recovery . Results : Postoperative drowsiness was of a significantly longer duration with the conventional method ( p < 0.001 ) compared with the AWL technique . There was a positive correlation with the total amount of CO2 used and the duration of drowsiness ( r = 0.75 , p < 0.01 ) . PONV was seen significantly more often in patients with CO2 insufflation of more than 121 ( p < 0.05 ) . Conclusions : Avoiding excessive CO2 is beneficial for smoother and more uneventful recovery after laparoscopic cholecystectomy Carbon dioxide ( CO2 ) pneumoperitoneum together with an increased intraabdominal pressure ( IAP ) induces a hemodynamic stress response , diminishes urine output , and may compromise splanchnic perfusion . A new retractor method may be less traumatic . Accordingly , 30 ASA physical status I or II patients undergoing laparoscopic cholecystectomy were r and omly allocated to a CO2 pneumoperitoneum ( IAP 12 - 13 mm Hg ) ( control ) or to a gasless abdominal wall lift method ( retractor ) group . Anesthesia and intravascular fluids were st and ardized . Direct mean arterial pressure ( MAP ) , urine output , urine-N-acetyl-beta-D-glucosaminidase ( U-NAG ) , arterial blood gases , gastric mucosal PCO2 , and intramucosal pH ( pHi ) were measured . Normoventilation was instituted in all patients . MAP increased ( P < 0.001 ) only with CO2 pneumoperitoneum . Minute volume of ventilation had to be increased by 35 % with CO2 insufflation . PaCO2 was significantly higher ( P < 0.05 ) for 3 h postoperatively in the control group . Diuresis was less ( P < 0.01 ) and U-NAG levels ( P < 0.01 ) higher in the control group . The pHi decreased after induction of pneumoperitoneum up to three hours postoperatively and remained intact in the retractor group . We conclude that the retractor method for laparoscopic cholecystectomy ensures stable hemodynamics , prevents respiratory acidosis , and provides protection against biochemical effects , which reveal the renal and splanchic ischemia caused by CO2 insufflation . Implication s : A mechanical retractor method ( gasless ) was compared with conventional CO2 pneumoperitoneum for laparoscopic cholestectomy . The gasless method ensured stable hemodynamics , prevented respiratory acidosis , and provided protection against the renal and splanchnic ischemia seen with CO2 pneumoperitoneum . ( Anesth Analg 1997;85:886 - 91 The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating Background : Two alternative surgical techniques for elective laparoscopic cholecystectomy ( LC ) , low‐pressure insufflation of the peritoneal cavity and abdominal wall lifting ( AWL ) , have been developed over time to minimize the disadvantages associated with CO2‐elicited pneumoperitoneum . To the best of our knowledge , the 2 methods have seldom been compared as regards their relative advantages and disadvantages . Methods : Eighty patients scheduled for elective LC were r and omized into either a low‐pressure ( 8 mmHg ) CO2 insufflation method ( LPLC ) group , or a gasless technique using a subcutaneous abdominal wall lifting device ( GLC group ) . The duration of the surgical procedure , the surgical results including level of postoperative pain , and perioperative cardiopulmonary function changes experienced by the members of both groups were compared . Results : Laparoscopic surgery was completed for all but 1 patient from each group due to an inadequate surgical‐site exposure . There was no mortality for study participants , and no major complications were noted for members of either group . The LPLC group evidence d a shorter surgical duration as compared to the GLC group ( 77 ± 28 minutes vs. 98 ± 27 minutes , respectively ; p < 0.01 ) and a lower incidence of postoperative shoulder pain ( 2/38 vs. 8/39 , respectively ; p < 0.05 ) , although significant differences in intraoperative pulmonary function were noted ( an increased PaCO2 , PetCO2 and peak‐airway pressure and decreased arterial blood pH ; p < 0.01 ) for the LPLC group compared to the GLC group . Conclusion : Both alternative methods for this type of surgery appeared feasible and safe for LC . Low‐pressure CO2 pneumoperitoneum had a shorter surgical duration and less postoperative shoulder pain compared to the GLC technique , but did not feature any other advantage over the AWL technique with regard to impact on cardiopulmonary function Increases in plasma renin activity and noradrenaline concentration occur in response to carbon dioxide insufflation during laparoscopic cholecystectomy . In a r and omized study the conventional carbon dioxide pneumoperitoneum was compared with the abdominal wall lift method for laparoscopic cholecystectomy , with special reference to neuroendocrine changes and renal function . The total mean(s.d . ) volume of carbon dioxide insufflated was 42(23 ) litres with the conventional method and 9(7 ) litres with abdominal wall lift ( P < 0·001 ) . Mean(s.d . ) intra‐abdominal pressure after 15 min of insufflation was 11(2 ) and 3(9 ) mmHg respectively ( P<0·01 ) . In the conventional group mean(s.d . ) plasma renin activity increased slightly from 5·5(2·1 ) to 6·1(2·0 ) ng ml−1 during the first 55 min of laparoscopic cholecystectomy . In the abdominal wall lift group plasma renin activity decreased from 5·3(2·7 ) to 3·8(0·9 ) ng ml−1 ( P<0·01 between the groups ) . Plasma antidiuretic hormone concentration increased similarly in both groups . Diuresis was significantly less with conventional pneumoperitoneum during the first 35 min of the operation compared with the abdominal wall lift method ( P < 0·001 ) . There were significant increases in plasma noradrenaline concentration in both groups ( P < 0·001 ) , but the increase was slightly higher in the conventional group during the first 15 min of insufflation . The abdominal wall lift method with minimal carbon dioxide insufflation was associated with smaller neuroendocrine responses and better preservation of renal function compared with conventional carbon dioxide pneumoperitoneum INTRODUCTION The positive CO2 pneumoperitoneum needed to create the working space for laparoscopic surgery may induce pathophysiological changes . Concern about these changes has led to the introduction of a gasless technique . The aim of the present study was to compare the gasless CLC and GLC with regard to exposure , technical problems , operation time , postoperative pain , clinical course , and convalescence . MATERIAL AND METHODS Fifty consecutive patients with symptomatic gallstones were r and omised to conventional ( CLC ) or gasless laparoscopic cholecystectomy ( GLC ) , with special reference to overall patient satisfaction , technical difficulties , duration of surgery , postoperative pain , and recovery . RESULTS The overall exposure of the operative field was poorer in the GLC group , whereas the duration of surgery , steps involved in the cholecystectomy technique , length of hospital stay , and postoperative pain score did not differ significantly . The period to return to normal activity was significantly shorter in the GLC group , six days compared to 8.5 days in the CLC group ( p < 0.05 ) . No differences were found in terms of fatigue , dizziness and nausea , and overall satisfaction with the outcome . DISCUSSION This study shows that convalescence is significantly shorter after laparoscopic cholecystectomy by the gasless technique than by the conventional CO2 technique . However , exposure of the operative field was less than optimal with the gasless technique Background Carbon dioxide ( CO2 ) pneumoperitoneum effects are still controversial . The aim of this study was to investigate cardiopulmonary changes in patients subjected to different surgical procedures for cholecystectomy . Methods In this study , 15 patients were assigned r and omly to three groups according to the surgical procedure to be used : open cholecystectomy ( OC ) , CO2 pneumoperitoneum cholecystectomy ( PP ) , and laparoscopic gasless cholecystectomy ( abdominal wall lifting [ AWL ] ) , respectively . A pulmonary artery catheter was used for hemodynamic monitoring in all patients . A subcutaneous multiplanar device ( Laparo Tenser ) was used for abdominal wall lifting . To avoid misinterpretation of results , conventional anesthesia was performed with all parameters , and the position of the patients held fixed thoroughout surgery . The following parameters were analyzed : men arterial pressure ( MAP ) , heart rate ( HR ) , cardiac output ( CO ) , cardiac index ( CI ) , stroke volume index ( SVI ) , central venous pressure ( CVP ) , systemic vascular resistances index ( SVRI ) , mean pulmonary arterial pressure ( MPAP ) , pulmonary capillary wedge pressure ( PCWP ) , pulmonary vascular resistances index ( PVRI ) , peak inspiratory pressure ( PIP ) , end-tidal CO2 pressure (ETCO)2 , CO2 arterial pressure ( PaCO2 ) , and arterial pH. Results All the operations were completed successfully . The Laparo Tenser allowed good exposition of the surgical field . A slight impairment of the cardiopulmonary functions , with reduction of SVRI , MAP , and CI and elevation of pulmonary pressures and vascular resistance , followed induction of anesthesia . However , these effects tended to normalize in the OC and AWL groups over time . In contrast , CO2 insufflation produced a complex hemodynamic and pulmonary syndrome result ing in increased right- and left side filling pressures , significant cardiac index reduction , derangement of the respiratory mechanics , and respiratory acidosis . All of these effects normalized after desufflation . Conclusions Cardiopulmonary adverse effects of general anesthesia were significant but transitory and normalized during surgery . Carbon dioxide pneumoperitoneum caused a significant impairment in cardiopulmonary functions . In high-risk patients , gasless laparoscopy may be preferred for reliability and absence of cardiopulmonary alterations Background : It has been shown repeatedly that laparoscopic cholecystectomy using pneumoperitoneum ( CO2 insufflation ) may be associated with increased cardiac filling pressures and an increase in blood pressure and systemic vascular resistance . In the present study , the effects on the central circulation during abdominal wall lift ( a gasless method of laparoscopic cholecystectomy ) were compared with those during pneumoperitoneum . The study was also aim ed at elucidating the relationships between the central filling pressures and the intrathoracic pressure Carbon dioxide ( CO2 ) insufflation with increased intraabdominal pressure ( IAP ) has adverse hemodynamic , pulmonary , and renal effects . To avoid these problems , an abdominal wall lift method with a retractor was used to provide the surgical view without CO2 insufflation . Twenty-six patients undergoing elective laparoscopic cholecystectomy were r and omly allocated to either the gasless , retractor group , or conventional CO2 pneumoperitoneum group ( CPP ) . Hemodynamic data , ventilatory variables , urine output , urine oxygen tension , and blood sample s for determining stress hormones were collected throughout the perioperative period . Patients in the retractor group had lower mean arterial pressure , heart rate , and central venous pressure ( P < 0.001 ) . They also had higher pulmonary dynamic compliance and needed a lower minute volume of ventilation to achieve normocarbia ( P < 0.001 ) . Urine output and oxygen tension in urine were higher ( P < 0.05 ) with the retractor method than with CPP . Increase in plasma renin activity ( P < 0.05 ) and decrease in core temperature ( P < 0.001 ) were smaller with the gasless method than with CPP . The gasless method for laparoscopic cholecystectomy might be beneficial , especially in patients with compromised cardiorespiratory or renal function . Implication s : Totally gasless laparoscopic cholecystectomy was compared with conventional pressure pneumoperitoneum with CO ( 2 ) insufflation . The gasless method result ed in more stable hemodynamics and pulmonary function , as well as higher urine , output than conventional pressure pneumoperitoneum . No changes in renal oxygenation was seen with the gasless method , compared with conventional pressure pneumoperitoneum Conventional laparoscopic cholecystectomy ( CLC ) with carbon dioxide pneumoperitoneum may cause major cardiovascular changes . The aim of this study was to evaluate the effect of carbon dioxide pneumoperitoneum and positional changes on haemodynamics and cardiac function in patients assigned r and omly to CLC or gasless laparoscopic cholecystectomy ( GLC ) To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrollment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results Published evidence suggests that aspects of trial design lead to biased intervention effect estimates , but findings from different studies are inconsistent . This study combined data from 7 meta-epidemiologic studies and removed overlaps to derive a final data set of 234 unique meta-analyses containing 1973 trials . Outcome measures were classified as " mortality , " " other objective , " " or subjective , " and Bayesian hierarchical models were used to estimate associations of trial characteristics with average bias and between-trial heterogeneity . Intervention effect estimates seemed to be exaggerated in trials with inadequate or unclear ( vs. adequate ) r and om-sequence generation ( ratio of odds ratios , 0.89 [ 95 % credible interval { CrI } , 0.82 to 0.96 ] ) and with inadequate or unclear ( vs. adequate ) allocation concealment ( ratio of odds ratios , 0.93 [ CrI , 0.87 to 0.99 ] ) . Lack of or unclear double-blinding ( vs. double-blinding ) was associated with an average of 13 % exaggeration of intervention effects ( ratio of odds ratios , 0.87 [ CrI , 0.79 to 0.96 ] ) , and between-trial heterogeneity was increased for such studies ( SD increase in heterogeneity , 0.14 [ CrI , 0.02 to 0.30 ] ) . For each characteristic , average bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes , with little evidence of bias in trials with objective and mortality outcomes . This study is limited by incomplete trial reporting , and findings may be confounded by other study design characteristics . Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes |
10,401 | 24,432,301 | Major findings include supportive evidence for increased gastroesophageal reflux disease and esophageal motility disorders in obesity , and a rapid gastric emptying time seen in obese individuals .
The proximal small intestinal transit seems to be increased in obesity and this may be secondary to efficient nutrient absorption and subsequent lack of nutrient-induced satiety signals conveyed from the small intestine .
In obesity , there is some evidence for delayed colonic transit as well as a reduction in colonic serotonin availability .
The molecular mechanisms underlying altered motility in obesity could be secondary to reduced cannabinoids or its receptor cannabinoid receptor 1 ( CB1 ) expression as well as due to loss of neuronal nitric oxide synthase ( nNOS ) neurons . | Obesity is highly prevalent worldwide and is associated with significant morbidity and mortality .
The focus of this review is to delineate the changes in gastrointestinal motility observed in obesity .
A systematic review of the published literature on obesity and gastrointestinal motility was performed .
Here , we describe the current underst and ing of the changes in obesity in the esophagus , stomach , small intestine and colon . | There is evidence from studies in animals that the effects of both fat and CCK on gastrointestinal function and energy intake are attenuated by consumption of a high-fat diet . In humans , the effects of exogenous CCK-8 on antropyloroduodenal motility , plasma CCK , peptide YY ( PYY ) , and ghrelin concentrations , appetite , and energy intake are attenuated by a high-fat diet . Ten healthy lean males consumed isocaloric diets ( ~15,400 kJ per day ) , containing either 44 % ( high-fat , HF ) or 9 % ( low-fat , LF ) fat , for 21 days in single-blind , r and omized , cross-over fashion . Immediately following each diet ( i.e. , on day 22 ) , subjects received a 45-min intravenous infusion of CCK-8 ( 2 ng.kg(-1).min(-1 ) ) , and effects on antropyloroduodenal motility , plasma CCK , PYY , ghrelin concentrations , hunger , and fullness were determined . Thirty minutes after commencement of the infusion , subjects were offered a buffet-style meal , from which energy intake ( in kilojoules ) was quantified . Body weight was unaffected by the diets . Fasting CCK ( P < 0.05 ) , but not PYY and ghrelin , concentrations were greater following the HF , compared with the LF , diet . Infusion of CCK-8 stimulated pyloric pressures ( P < 0.01 ) and suppressed antral and duodenal pressures ( P < 0.05 ) , with no difference between the diets . Energy intake also did not differ between the diets . Short-term consumption of a HF diet increases fasting plasma CCK concentrations but does not affect upper gut motility , PYY and ghrelin , or energy intake during CCK-8 infusion , in a dose of 2 ng.kg(-1).min(-1 ) , in healthy males OBJECTIVES : Perception of sensations arising from the gastrointestinal tract may be diminished in obese subjects and thus facilitate overeating . Alternatively , excess food intake may cause gastrointestinal ( GI ) symptoms in obese patients . We evaluated the relationship between body mass index ( BMI ) and specific GI symptoms in the community . METHODS : Residents of Olmsted County , MN were selected at r and om to receive by mail one of two vali date d question naires . The association of reported GI symptoms with BMI ( kg/m2 ) was assessed using a logistic regression analysis adjusting for age , gender , psychosomatic symptom score , and alcohol and tobacco use . RESULTS : Response rate was 74 % ( 1,963 of 2,660 ) . The prevalence of obesity ( BMI ≥ 30 kg/m2 ) was 23 % . There was a positive relationship between BMI and frequent vomiting ( p = 0.02 ) , upper abdominal pain ( p = 0.03 ) , bloating ( p = 0.002 ) , and diarrhea ( p = 0.01 ) . The prevalence of frequent lower abdominal pain , nausea , and constipation was increased among obese ( BMI ≥ 30 kg/m2 ) compared to normal weight participants , however , no significant association was found between BMI and these symptoms . CONCLUSIONS : In the community , increasing BMI is associated with increased upper GI symptoms , bloating , and diarrhea . Clarification of the cause- and -effect relationships and the mechanisms of these associations require further investigation Introduction : Intestinal electric stimulation ( IES ) is proposed as a potential tool for the treatment of morbid obesity . Our earlier study showed that IES with one pair of electrodes accelerated intestinal transit and decreased fat absorption in a segment of the jejunum in anesthetized rats . The aims of this study were to assess the effects of IES on whole gut transit and fat absorption in conscious rats , to examine the effects of multi-pairs IES and to explore the cholinergic mechanism behind the effects of IES . Methods : Thirty-eight male rats implanted with serosal electrodes were r and omized into five groups : control without IES , two- or three-pairs IES with short pulses , atropine and atropine plus IES . The whole gut transit and fat remained and emptied from the gut were analyzed after continuous 2-h IES . Results : Two- and three-pairs IES significantly accelerated phenol red ( PR , marker used for transit ) excretion ( analysis of variance ( ANOVA ) , P<0.001 ) . No significant difference was found between two- and three-pairs IES . Two-pairs IES significantly increased the excretion of fat ( P<0.05 ) . Atropine significantly blocked the accelerated transit induced by IES ( ANOVA , P<0.001 ) . Correlation was found between the percentage of PR and fat retained in the whole gut ( r=0.497 , P<0.01 ) . Conclusions : IES accelerates whole gut transit and promotes fat excrement in conscious rats , and these effects are mediated through the cholinergic nerves . These findings are in support of the concept that IES may be a promising treatment option for obesity AIM To clarify the association between physical activity and gastroesophageal reflux disease ( GERD ) in non-obese and obese people . METHODS A Swedish population -based cross-sectional survey was conducted . Participants aged 40 - 79 years were r and omly selected from the Swedish Registry of the Total Population . Data on physical activity , GERD , body mass index ( BMI ) and the covariates age , gender , comorbidity , education , sleeping problems , and tobacco smoking were obtained using vali date d question naires . GERD was self-reported and defined as heartburn or regurgitation at least once weekly , and having at least moderate problems from such symptoms . Frequency of physical activity was categorized into three groups : ( 1 ) " high " ( several times/week ) ; ( 2 ) " intermediate " ( approximately once weekly ) ; and ( 3 ) " low " ( 1 - 3 times/mo or less ) . Analyses were stratified for participants with " normal weight " ( BMI < 25 kg/m² ) , " overweight " ( BMI 25 to ≤ 30 kg/m² ) and " obese " ( BMI > 30 kg/m² ) . Multivariate logistic regression was used to calculate odds ratios ( ORs ) with 95 % confidence intervals ( CIs ) , adjusted for potential confounding by covariates . RESULTS Of 6969 eligible and r and omly selected individuals , 4910 ( 70.5 % ) participated . High frequency of physical activity was reported by 2463 ( 50 % ) participants , GERD was identified in 472 ( 10 % ) participants , and obesity was found in 680 ( 14 % ) . There were 226 ( 5 % ) individuals with missing information about BMI . Normal weight , overweight and obese participants were similar regarding distribution of gender and tobacco smoking status , while obese participants were on average slightly older , had fewer years of education , more comorbidity , slightly more sleeping problems , lower frequency of physical activity , and higher occurrence of GERD . Among the 2146 normal-weight participants , crude point estimates indicated a decreased risk of GERD among individuals with high frequency of physical activity ( OR : 0.59 , 95 % CI : 0.39 - 0.89 ) , compared to low frequency of physical activity . However , after adjustment for potential confounding factors , neither intermediate ( OR : 1.30 , 95 % CI : 0.75 - 2.26 ) nor high ( OR : 0.99 , 95 % CI : 0.62 - 1.60 ) frequency of physical activity was followed by decreased risk of GERD . Sleeping problems and high comorbidity were identified as potential confounders . Among the 1859 overweight participants , crude point estimates indicated no increased or decreased risk of GERD among individuals with intermediate or high frequency of physical activity , compared to low frequency . After adjustment for confounding , neither intermediate ( OR : 0.75 , 95 % CI : 0.46 - 1.22 ) nor high frequency of physical activity were followed by increased or decreased risk of GERD compared to low frequency among nonobese participants . Sleeping problems and high comorbidity were identified as potential confounders for overweight participants . In obese individuals , crude ORs were similar to the adjusted ORs and no particular confounding factors were identified . Intermediate frequency of physical activity was associated with a decreased occurrence of GERD compared to low frequency of physical activity ( adjusted OR : 0.41 , 95 % CI : 0.22 - 0.77 ) . CONCLUSION Intermediate frequency of physical activity might decrease the risk of GERD among obese individuals , while no influence of physical activity on GERD was found in non-obese people Objectives : The aim of the study was to determine the frequency of functional constipation according to the Rome III criteria in children with morbid obesity and to evaluate by measuring colonic transit times ( CTTs ) whether decreased colonic motility is present in these children . Patients and Methods : Ninety-one children with morbid obesity ages 8 to 18 years , entering a prospect i ve , r and omized controlled study evaluating the effect of an outpatient versus inpatient treatment program of obesity , participated . All of the children filled out a st and ardized question naire regarding their bowel habits , and CTTs were measured using radioopaque markers . Food diaries were also recorded to evaluate their diet . Results : A total of 19 children ( 21 % ) had functional constipation according to the Rome III criteria , whereas 1 child had functional nonretentive fecal incontinence . Total CTT exceeded 62 hours in only 10.5 % of the children with constipation , and among them , 2 had a total CTT of > 100 hours . In the nonconstipated group 8.3 % had a delayed CTT . Furthermore , no difference was found between the diet of children with or without constipation , specifically not with respect to fiber and fat intake . Conclusions : Our study confirms a high frequency of functional constipation in children with obesity , using the Rome III criteria . However , abnormal colonic motility , as measured by CTT , was delayed in only a minority of patients . No relation was found between constipation in these children and fiber or fat intake Accommodation of the stomach consists of a vagally mediated relaxation of the proximal stomach , providing the meal with a reservoir . Our aim was to study whether , similar to other vagally mediated processes , the accommodation reflex is also determined by cephalic , oropharyngeal , gastric , and intestinal phases . Eleven healthy subjects underwent in r and omized order five gastric barostat studies and two satiety drinking tests . In all studies , isobaric tone measurements ( at minimal distending pressure + 2 mmHg ) were performed 20 min before and 20 min after a nutrient stimulus . The stimuli included only visual and olfactory exposure to a meal ( cephalic stimulation ) , taking liquid nutrient in the mouth without swallowing ( sham feeding ) , ingestion of a 200-ml 300-kcal nutrient meal with blocked outflow to the pylorus ( gastric retention ) , and meal infusion through a nasointestinal tube ( duodenal instillation ) , or normal ingestion ( control ) . During satiety testing , subjects ingested liquid nutrient at a fixed rate of 15 ml/min until maximum satiety , with an inflated or deflated intrapyloric balloon assembly . Progressively bigger gastric relaxatory responses were seen with cephalic stimulation ( 18 + /- 19 ml ) , sham feeding ( 54 + /- 21 ml ) , gastric retention ( 95 + /- 47 ) , duodenal instillation ( 144 + /- 33 ) , and control ( 232 + /- 33 ml ) . The amount of nutrient ingested at maximum satiety was significantly lower with an inflated intrapyloric balloon ( 1,223 + /- 103 vs. 1,392 + /- 124 ml , P < 0.05 ) . The accommodation reflex in humans lacks a cephalic phase , but it can be activated from the oropharynx , the stomach , and the duodenum . Blocking passage to the duodenum significantly decreases the amplitude of the accommodation reflex and induces early satiety BACKGROUND AND AIMS Obesity has been associated with gastroesophageal reflux disease ( GERD ) and its complication , but the mechanism is unclear . We evaluated the association between obesity and function of lower esophageal sphincter ( LOS ) in subjects without GERD . METHODS We prospect ively recruited consecutive obese ( BMI > 30 ) patients referred for weight reduction procedure and age- and sex-matched overweight ( BMI 25 - 30 ) and normal weight ( BMI > or = 20 and < 25 ) subjects . Exclusion criteria included esophagitis , reflux symptoms , use of proton pump inhibitor , hiatus hernia > 2 cm , and diabetes mellitus with microvascular complication . All participants underwent combined 2-hour postpr and ial esophageal manometry and pH monitoring after a st and ard test meal followed by 24-hour ambulatory pH monitoring . RESULTS Eighty-four subjects ( obese , 28 ; overweight , 28 ; normal weight , 28 ) were studied . All 3 groups had comparable mean LOS pressure , LOS length , and peristaltic function . During the postpr and ial period , both obese and overweight groups had substantial increase in 2-hour rate of transient lower esophageal sphincter relaxation ( TLOSR ) ( normal weight : 2.1 + /- 1.2 vs overweight : 3.8 + /- 1.6 vs obese : 7.3 + /- 2.0 , P < .001 ) , proportion of TLOSR with acid reflux ( normal weight : 17.6 % + /- 22.0 % vs overweight 51.8 % + /- 22.5 % vs obese : 63.5 % + /- 21.7 % , P < .001 ) , and gastroesophageal pressure gradient ( GOPG ) ( normal weight : 4.5 + /- 1.2 mm Hg vs overweight : 7.1 + /- 1.4 mm Hg vs obese : 10.0 + /- 1.5 mm Hg , P < .001 ) . Using multiple regression model , BMI ( r(2 ) : 0.70 , B : 0.28 , 95 % CI : 0.24 - 0.33 , P < .001 ) and waist circumference ( r(2 ) : 0.65 , unst and ardized regression coefficient [ B ] : 0.10 , 95 % CI : 0.08 - 0.11 , P < .001 ) were significantly correlated with TLOSR . CONCLUSIONS Obesity is associated with increased TLOSR and acid reflux during the postpr and ial period in subjects without GERD . Abnormal postpr and ial LOS function may be an early event in the pathogenesis of obesity-related GERD Previous work has shown that the gastric emptying rate in animals and humans can adapt due to previous dietary intake . The present study investigated whether adaptation in gastric emptying rate due to consumption of a high-fat diet ( HFD ) is nutrient specific in humans . Gastric emptying of high-fat and high-carbohydrate test meals was measured ( using gamma scintigraphy ) before and after consumption of an HFD for 14 days in eight free-living male volunteers . Visual analog ratings of appetite were recorded throughout each test . There was no effect of HFD on any parameters of gastric emptying rate ( lag phase , half-emptying time , and linear emptying rate ) measured for carbohydrate test meals . HFD led to an acceleration of the linear emptying rate of the high-fat test meal ( 0.36 vs. 0.47%/min ; P < 0.05 ) . All meals reduced appetite ratings , but there were no differences between tests . These results support our previous findings of accelerated gastric emptying of high-fat test meals following an HFD and show that these changes appear to be nutrient specific , confirming recent studies in rats There is evidence that gastrointestinal function adapts in response to a high-fat ( HF ) diet . This study investigated the hypothesis that an HF diet modifies the acute effects of duodenal lipid on appetite , antropyloroduodenal pressures , plasma CCK and plasma glucagon-like peptide-1 ( GLP-1 ) levels in humans . Twelve healthy men were studied twice in r and omized , crossover fashion . The effects of a 90-min duodenal lipid infusion ( 6.3 kJ/min ) on the above parameters were assessed immediately following 14-day periods on either an HF or a low-fat ( LF ) diet . After the HF diet , pyloric tonic and phasic pressures were attenuated , and the number of antropyloroduodenal pressure-wave sequences was increased when compared with the LF diet . Plasma CCK and GLP-1 levels did not differ between the two diets . Hunger was greater during the lipid infusion following the HF diet , but there was no difference in food intake . Therefore , exposure to an HF diet for 14 days attenuates the effects of duodenal lipid on antropyloroduodenal pressures and hunger without affecting food intake or plasma hormone levels BACKGROUND Ingestion of a meal stimulates colonic motility . It is unclear whether the nutrient composition of a meal affects colonic motor response . AIMS To investigate and compare the effects of a predominantly fat or carbohydrate meal on colonic motility . METHODS In 18 healthy subjects , ambulatory colonic manometry was performed by placing a six sensor , solid state probe from the mid-transverse colon to the rectum . In a r and omised , crossover design , 10 and 27 hours after probe placement , subjects received 4.18 MJ meals containing 60 % calories from fat or carbohydrate sources . Prepr and ial and postpr and ial pressure activity and motor patterns were evaluated . RESULTS Both meals induced phasic activity with a greater area under the curve ( p<0.03 ) in the first postpr and ial hour , compared with the control period . Fat induced motor activity persisted longer ( p<0.05 ) than that of the carbohydrate meal , but the onset of motor response was slower ( p<0.001 ) . Although both meals induced more ( p<0.001 ) propagating pressure waves , only the fat meal induced more ( p<0.05 ) simultaneous and retro grade waves . After both meals , 50 % of subjects exhibited high amplitude ( more than 103 mm Hg ) , prolonged duration ( more than 13 seconds ) propagating waves . Both meals induced greater activity ( p<0.05 ) in the transverse/descending colon than in the rectosigmoid colon . CONCLUSIONS Carbohydrate meals induce colonic motor response , but the effects are short lived when compared with fat meals . The prolonged , segmental , and retro grade phasic activity induced by the fat meal may delay colon transit . Thus meal composition influences colonic motor response Stomach motility contributes significantly to fullness sensation while eating and cessation of food intake in humans . Genes controlling adrenergic and serotonergic mechanisms ( ADRA2A , GNB3 , and SLC6A4 ) affect gastric emptying ( GE ) , volume ( GV ) , and satiation . Fat mass and obesity-associated gene ( FTO ) is linked with satiety . Our aim was to examine the association of these c and i date genes with stomach functions that signal postpr and ial fullness : GE , GV , and maximum tolerated volume ( MTV ) . These biomarkers constitute a component of the intermediate phenotype of satiation . A total of 62 overweight or obese participants underwent genotyping of the c and i date genes , and vali date d measurements of GE of solids and liquids by scintigraphy , fasting and postpr and ial change in GV by SPECT ( single photon emission computed tomography ) , and MTV by nutrient drink test . These markers of satiation were compared for 38 genetic variants in ADRA2A , ADR2C , ADRB3 , uncoupling protein (UCP)-2 and -3 , GNB3 , FTO , and SLC6A4 using a recessive model of inheritance . ADRA2A , ADR2C , UCP-3 , GNB3 , and FTO loci were significantly associated with the intermediate phenotype markers of satiation : ADR2C ( Ins-Del322_325 ) with accelerated GE ; GNB3 ( rs1047776 ) with delayed GE ; ADRA2A ( rs491589 and rs553668 ) and GNB3 ( rs2269355 , rs10849527 , and rs3759348 ) with decreased postpr and ial GV ; ADRA2A ( rs3750625 ) and GNB3 ( rs4963517 and rs1129649 ) with increased postpr and ial GV ; UCP-3 ( rs1685356 ) with increased MTV , and FTO ( rs9939609 ) decreased MTV . Genetic susceptibility to postpr and ial satiation can be identified through intermediate phenotype markers . With independent validation , these markers may guide patient selection of weight-loss therapies directed at gastric motor functions Objective : Accelerated gastric emptying of solids may play a role in the pathogenesis of obesity . Orlistat , a potent lipase inhibitor , induces fat malabsorption and body weight loss but might accelerate gastric emptying as a result of suppressed CCK release . The aim was to investigate the role of fat restriction and lipase inhibition in CCK release and gastric emptying . Subjects : A total of 28 patients ( three male (M)/25 female ( F ) ; mean ( s.d . ) BMI 37.4(3.9 ) kg/m2 ) entering a r and omized , double-blind , placebo-controlled study . Measurements : CCK release and gastric emptying by scintigraphy at the start ( T0 ) , after 1 month of an energy- and fat-restricted diet and placebo ( T1 ) , and after 1 month ( T2 ) and 1 year ( T3 ) of r and omization to placebo or 120 mg orlistat three times a day . Results : One month of dieting and a weight loss of 2.3 kg ( 2.1 % of initial weight ) did not affect gastric emptying of liquids and solids . Basal and meal-stimulated CCK levels remained unaltered . Placebo-treated subjects who continued the diet for 1 month demonstrated a borderline significant suppressed CCK secretion and a weight loss of 1.2 kg ( 1.0 % ) without an effect on gastric emptying . After 1 year , the CCK secretion recovered to or beyond values at the start . A significantly slower emptying of solids ( 17.6 ( T3 ) versus 25.9 (T1)%/h ) and a weight loss of 10.4 kg ( 9.9 % ) was observed . Subjects on 120 mg orlistat lost 2.5 kg ( 2.5 % ) after 1 month , and 9.8 kg ( 9.9 % ) after 1 year . Basal and postpr and ial CCK release decreased significantly after the first month of orlistat treatment but normalized after 1 year . Diet and lipase inhibition did not have any influence on gastric emptying . Conclusion : Energy and fat restriction of 1 month did not alter gastric emptying in the whole group . Continuation of the diet for 1 year result ed in a delayed gastric emptying of solids . Lipase inhibition did not result in a sustained depressed CCK release and the anticipated acceleration of gastric emptying did not occur BACKGROUND Overweight and obese persons are at increased risk for gastroesophageal reflux disease . An association between body-mass index ( BMI ) --the weight in kilograms divided by the square of the height in meters - and symptoms of gastroesophageal reflux disease in persons of normal weight has not been demonstrated . METHODS In 2000 , we used a supplemental question naire to determine the frequency , severity , and duration of symptoms of gastroesophageal reflux disease among r and omly selected participants in the Nurses ' Health Study . After categorizing women according to BMI as measured in 1998 , we used logistic-regression models to study the association between BMI and symptoms of gastroesophageal reflux disease . RESULTS Of 10,545 women who completed the question naire ( response rate , 86 percent ) , 2310 ( 22 percent ) reported having symptoms at least once a week , and 3419 ( 55 percent of those who had any symptoms ) described their symptoms as moderate in severity . We observed a dose-dependent relationship between increasing BMI and frequent reflux symptoms ( multivariate P for trend < 0.001 ) . As compared with women who had a BMI of 20.0 to 22.4 , the multivariate odds ratios for frequent symptoms were 0.67 ( 95 percent confidence interval , 0.48 to 0.93 ) for a BMI of less than 20.0 , 1.38 ( 95 percent confidence interval , 1.13 to 1.67 ) for a BMI of 22.5 to 24.9 , 2.20 ( 95 percent confidence interval , 1.81 to 2.66 ) for a BMI of 25.0 to 27.4 , 2.43 ( 95 percent confidence interval , 1.96 to 3.01 ) for a BMI of 27.5 to 29.9 , 2.92 ( 95 percent confidence interval , 2.35 to 3.62 ) for a BMI of 30.0 to 34.9 , and 2.93 ( 95 percent confidence interval , 2.24 to 3.85 ) for a BMI of 35.0 or more . Even in women with a normal baseline BMI , an increase in BMI of more than 3.5 , as compared with no weight changes , was associated with an increased risk of frequent symptoms of reflux ( odds ratio , 2.80 ; 95 percent confidence interval , 1.63 to 4.82 ) . CONCLUSIONS BMI is associated with symptoms of gastroesophageal reflux disease in both normal-weight and overweight women . Even moderate weight gain among persons of normal weight may cause or exacerbate symptoms of reflux Orocecal transit time was assessed with lactulose hydrogen breath test in 12 obese patients during intravenous infusion of placebo or naloxone 40 μg/kg/hr given in r and omized order and in double-blind conditions . Transit time was also evaluated in 22 healthy controls . Orocecal transit was significantly ( P<0.01 ) longer in the obese patients during placebo treatment ( median 130 , range 100–200 min ) than in the healthy controls ( median 75 , range 40–170 min ) . Compared with placebo , transit time in the obese subjects was delayed ( P<0.05 ) during naloxone treatment ( median 150 , range 100–230 min ) The gastrointestinal effects of intraluminal fats may be critically dependent on the chain length of fatty acids released during lipolysis . We postulated that intraduodenal administration of lauric acid ( 12 carbon atoms ; C12 ) would suppress appetite , modulate antropyloroduodenal pressure waves ( PWs ) , and stimulate the release of cholecystokinin ( CCK ) and glucagon-like peptide-1 ( GLP-1 ) more than an identical dose of decanoic acid ( 10 carbon atoms ; C10 ) . Eight healthy males ( 19 - 47 yr old ) were studied on three occasions in a double-blind , r and omized fashion . Appetite perceptions , antropyloroduodenal PWs , and plasma CCK and GLP-1 concentrations were measured during a 90-min intraduodenal infusion of 1 ) C12 , 2 ) C10 , or 3 ) control ( rate : 2 ml/min , 0.375 kcal/min for C12/C10 ) . Energy intake at a buffet meal , immediately after completion of the infusion , was also quantified . C12 , but not C10 , suppressed appetite perceptions ( P < 0.001 ) and energy intake ( control : 4,604 + /- 464 kJ , C10 : 4,109 + /- 588 kJ , and C12 : 1,747 + /- 632 kJ ; P < 0.001 , C12 vs. control/C10 ) . C12 , but not C10 , also induced nausea ( P < 0.001 ) . C12 stimulated basal pyloric pressures and isolated pyloric PWs and suppressed antral and duodenal PWs compared with control ( P < 0.05 for all ) . C10 transiently stimulated isolated pyloric PWs ( P = 0.001 ) and had no effect on antral PWs but markedly stimulated duodenal PWs ( P = 0.004 ) . C12 and C10 increased plasma CCK ( P < 0.001 ) , but the effect of C12 was substantially greater ( P = 0.001 ) ; C12 stimulated GLP-1 ( P < 0.05 ) , whereas C10 did not . In conclusion , there are major differences in the effects of intraduodenal C12 and C10 , administered at 0.375 kcal/min , on appetite , energy intake , antropyloroduodenal PWs , and gut hormone release in humans Glucagon-like peptide-1 ( GLP-1 ) relaxes the stomach during fasting but decreases hunger and food consumption and retards gastric emptying . The interrelationships between volume , emptying , and postpr and ial symptoms in response to GLP-1 are unclear . We performed , in healthy human volunteers , a placebo-controlled study of the effects of intravenous GLP-1 on gastric volume using (99m)Tc-single photon emission computed tomography imaging , gastric emptying of a nutrient liquid meal ( Ensure ) using scintigraphy , maximum tolerated volume ( MTV ) of Ensure , and postpr and ial symptoms 30 min after MTV . The role of vagal cholinergic function in the effects of GLP-1 was assessed by human pancreatic polypeptide ( HPP ) response to the Ensure meal . GLP-1 increased fasting and postpr and ial gastric volumes and retarded gastric emptying ; MTV and postpr and ial symptoms were not different compared with controls . Effects on postpr and ial gastric function were associated with reduced postpr and ial HPP levels . GLP-1 does not induce postpr and ial symptoms despite significant inhibition of gastric emptying and vagal function ; this may be partly explained by the increase in postpr and ial gastric volume Background : Glucagon-like peptide-1(7–36)amide ( GLP-1 ) retards gastric emptying , reduces food intake , and inhibits antroduodenal and stimulates pyloric motility . Aims : To assess the effects of synthetic GLP-1 on fundus tone and volume waves , gastric compliance , and perception of gastric distension . Subjects : Eleven healthy male volunteers . Methods : Background infusions were saline , or GLP-1 at 0.3 or 0.9 pmol/ kg/min on separate days in r and om order . Interdigestive fundus motility was recorded by barostat ( maximum capacity of intragastric bag 1200 ml ) during basal and peptide periods of 60 minutes each . Thereafter stepwise isobaric distensions were performed with ongoing peptide infusion , and gastric sensation was scored . Results : Low and high loads of GLP-1 induced physiological and supraphysiological plasma immunoreactivities , respectively . GLP-1 dose dependently diminished fundus tone ( 162.9 ( 15.0 ) and 259.5 ( 17.2 ) v 121.1 ( 6.0 ) ml with saline ; p<0.0001 ) . It greatly reduced volume waves and total volume displaced by these events ( p<0.0001 ) . Gastric compliance derived from isobaric distension rose in a dose related manner ( 42.6 ( 5.5 ) and 63.6 ( 7.7 ) v 27.0 ( 3.5 ) ml/mm Hg ; p=0.0004 ) with a concomitant reduction of the pressure at half maximum bag volume ( 6.4 ( 0.4 ) and 5.5 ( 0.4 ) v 7.2 ( 0.1 ) mm Hg ; p<0.0001 ) . GLP-1 did not change perception of isobaric distension but reduced the perception score related to corresponding bag volume ( p<0.0001 ) . Conclusions : GLP-1 is a c and i date physiological inhibitory regulator of fundus motility . It allows the stomach to afford a larger volume without increase in sensation Constipation frequency was investigated among 1897 subjects ( 874 males and 1023 females ) , ranging in age from 6 to 70 years , chosen at r and om between city inhabitants and farmers . Bowel habit was studied in 966 obese patients ( 390 males and 576 females ) . The authors followed for the diagnosis of constipation either the commonest and restrictive criterion of the weekly bowel actions or the clinical one which implies also others parameters , like hard or small stools , difficulties of expulsion or feeling of incomplete evacuation after defecation . The statistical analysis showed that constipation frequency is 8.3 % in obese patients and 1.5 % in normal-weighting , according to weekly bowel actions criterion : the difference is statistically significative ( p less than 0.001 ) OBJECTIVE To evaluate the effect of hepatic insulin gene therapy on diabetic enteric neuropathy . METHODS Mice were r and omly allocated into 3 groups : a normal control group , a diabetic group , and a diabetic gene therapy group . Diabetes were induced by penial vein injection of streptozocin ( STZ ) . The gene therapy group received hepatic insulin gene therapy while the other 2 groups only received an empty virus expressing green fluorescent protein . R and om blood glucose , body weight growth , gastric emptying , total bowel length , absolute and relative bowel transit , electric field stimulation of colon smooth muscle , colon nuclei staining and counting were measured . RESULTS We successully established a mouse model of diabetic enteric neuropathy which manifests as : 8 weeks of continuous hyperglycemia , increased total bowel length , decreased relative bowel transit , impaired colon smooth muscle relaxation and loss of inhibitory neurons in colon . Through gene therapy , the above indexes were normalized or ameliorated , suggesting hepatic insulin gene therapy is capable of preventing diabetic enteric neuropathy . CONCLUSION Hepatic insulin gene therapy can prevent STZ induced diabetic enteric neuropathy The reasons for the increase in the incidence of esophageal and gastric cardia adenocarcinoma in several industrialized countries ( 1 - 4 ) are largely unknown ( 5 ) . In the United States , the relative increase in the incidence of esophageal adenocarcinoma exceeds that of any other type of cancer ( 1 ) . Obesity , which has been found to be linked with a moderately increased risk for adenocarcinoma in some ( 6 - 9 ) but not all ( 10 , 11 ) previous epidemiologic studies , is one factor that could explain this epidemic because the prevalence of obesity has increased concomitantly ( 12 - 14 ) . No evidence shows a link between obesity and squamous-cell carcinoma ( the other main histologic type of esophageal cancer ) or adenocarcinoma of the distal stomach ( 9 ) . As part of a nationwide casecontrol study of risk factors for esophageal and gastric cardia adenocarcinoma , we analyzed body measures in relation to the risk for developing these tumors . Our primary aim was to precisely estimate the strength of the association while adjusting for potential confounding factors . We also examined the effects of body mass early in life compared with its effects late in life and assessed the relative importance of physical activity and energy intake . Methods Participants Our methods have been described in detail previously ( 15 ) . The study base consisted of all Swedish residents who had been born in Sweden , were younger than 80 years of age , and lived in Sweden from 1995 through 1997 . All persons in the study base who developed new esophageal or cardia adenocarcinomas and persons who developed esophageal squamous-cell carcinoma and were born on even date s were eligible as case- patients . We included 189 patients with esophageal adenocarcinoma , 262 patients with cardia adenocarcinoma , and 167 patients with esophageal squamous-cell carcinoma . These persons constituted 87 % , 83 % , and 73 % , respectively , of all eligible patients in the study base . Physical disorders , mental disorders , or early death prevented participation in 12 % to 22 % of the eligible patients , and 1 % to 5 % of patients declined to participate . The 820 population -based controls represented 73 % of those originally selected ; of these persons , 19 % declined to participate , 6 % had physical or mental disorders , and 2 % could not be contacted . The proportions of men among patients with esophageal adenocarcinoma , cardia adenocarcinoma , and esophageal squamous-cell carcinoma were 87 % , 85 % , and 72 % , respectively ; 83 % of controls were men . The median ages for both sexes in these four groups were 69 years , 66 years , 67 years , and 68 years , respectively . The study was approved by all regional ethics committees in Sweden , and individual informed consent was obtained from each participant before the interview . Exposure Information At face-to-face interviews conducted by trained professional interviewers , participants were asked about height and weight at 20 years of age and at 20 years before the interview . Body mass index ( BMI ) ( 16 ) was calculated as body weight in kilograms divided by the square of body height in meters ( kg/m2 ) . To obtain an independent measure of body fat , we asked each interviewee to choose the picture that best resembled his or her body build 20 years ago from a pictogram that showed nine somatotypes ranging from very lean to grossly obese . The Spearman correlation coefficient with BMI is 0.5 to 0.8 ( 17 ) . Weight change between 20 years of age and 20 years before the interview was calculated in kilograms and in percentage of body weight at 20 years of age . Meal sizeself-reported by each participant by using photographs of seven common disheswas divided into three categories and used as a measure of energy intake . This method gives an acceptably valid representation of energy intake ( 18 , 19 ) . Physical activity was divided into four levels by using a combination of 12 variables , including usual activities , such as st and ing , walking , and climbing stairs ; physical activities during leisure time ; and physical exertion at work . The interviewers could not be blinded to the casecontrol status of the interviewees , but they were completely blinded to the study hypothesis and were urged to treat patients and controls equally . Clinical Information All 195 hospital departments involved in the diagnosis or management of these patients collaborated in the recruitment of patients . The regional tumor registries helped us to identify missed cases . We used a common protocol for uniform documentation and classification of the tumors . At endoscopy , we measured the distances between the gastroesophageal junction ( defined as the point at which the proximal longitudinal mucosal folds begin in the stomach ) and the upper and lower borders of the tumor . The protocol also prescribed that serial biopsy specimens should be taken at points 2 cm apart , from the proximal stomach , through the gastroesophageal junction , and into the esophagus until normal squamous-cell epithelium was reached . Additional specimens were to be obtained proximal , distal , and lateral to the tumor . Surgeons and pathologists were required to provide st and ardized , detailed descriptions of the location of the cancer in the 424 patients in whom surgery was performed . In addition , 97 % of all biopsy and surgical specimens were reexamined by one pathologist . Barrett esophagus was defined as columnar-cell metaplasia of the specialized type , with goblet cells and villiform surface configuration of the mucosa resembling the features of the intestines . Cancer of the gastric cardia had to have its center within 2 cm proximal , or 3 cm distal , to the gastroesophageal junction . If Barrett esophagus was detected adjacent to the tumor , it was classified as esophageal regardless of its location . We classified squamous-cell carcinomas as esophageal even if they were located in the gastric cardia . Population -based controls were r and omly selected from age and sex strata in the complete and continuously up date d population register to obtain an age and sex distribution similar to that of patients with esophageal adenocarcinoma . Statistical Analysis Logistic regression was used in univariate and multivariate analyses of the relation among anthropometric measures , potential confounding variables , and cancer risk . Patients in each category of cancer were compared with all controls . Model variables were estimated by the maximum likelihood method ( 20 ) and converted to odds ratios and 95 % CIs . In the baseline model , adjustments were made for age ( in 5-year classes ) and sex ; in the multivariate analyses , we further adjusted for tobacco smoking ( never-smokers , former smokers , and current smokers 2 years before the interview ) , alcohol use ( grams of pure alcohol in four classes ) , years of formal education ( in four classes ) , reflux symptoms ( heartburn or regurgitation at least once per week occurring at least 5 years before the interview ) , intake of fruit and vegetables ( in four classes ) , meal size , and physical activity . Variables were considered in both categorized and continuous form . Wald tests and likelihood ratio tests were used . The relation of BMI to physical activity and meal sizeadjusted for age , sex , and diagnostic groupwas analyzed by linear regression analysis . Role of the Funding Sources The funding sources had no role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the paper for publication . Results Esophageal Adenocarcinoma We found a positive association between BMI 20 years before the interview and risk for esophageal adenocarcinoma . This association was dose-dependent across the entire range of BMI values ( Table 1 ) . The multivariate-adjusted odds ratio was 7.6 ( 95 % CI , 3.8 to 15.2 ) among persons in the highest BMI quartile compared with those in the lowest BMI quartile . The highest BMI quartile included both overweight and obese persons , as defined according to World Health Organization criteria ( 21 ) . We therefore reanalyzed the association using more commonly applied BMI cutoff points . Obese persons ( persons with BMI > 30 kg/m2 ) had an odds ratio of 16.2 ( CI , 6.3 to 41.4 ) compared with persons whose BMI was less than 22 kg/m2 . Table 1 . Body Measures and Risk for Esophageal Adenocarcinoma The association between esophageal adenocarcinoma and BMI was supported by our finding of a dose-dependent relation between esophageal adenocarcinoma and somatotype ( P for trend<0.001 ) . The adjusted odds ratio among persons who reported that their body build 20 years before the interview corresponded to one of the four obese somatotypes in our pictogram was 4.1 ( CI , 2.6 to 6.7 ) compared with persons reporting one of the three lean somatotypes . Weight gain after 20 years of age , both in absolute values and expressed as percentage of weight at 20 years of age , increased the risk monotonically ( P for trend<0.001 ) ; after adjustments for BMI 20 years before the interview , however , this effect disappeared almost entirely . Height was inversely and significantly ( P=0.03 ) associated with risk . A 50 % risk reduction was found among the tallest persons compared with the shortest persons . Stratified analyses showed a seemingly stronger association between BMI and risk for esophageal adenocarcinoma among persons 60 to 69 years of age compared with those in other age strata and among women compared with men ; however , the CIs were wide and the differences were not statistically significant ( Table 2 ) . No important confounding was caused by any of the seven additional covariates . The presence of reflux symptoms at least 5 years before the interview did not affect the association between BMI and esophageal adenocarcinoma . Therefore , BMI was a risk factor independent of the occurrence of gastroesophageal reflux . The strength of the association with BMI was equally strong among the 118 patients with histologically verified Barrett esophagus and the 71 patients without this metaplasia ( data not shown ) . Table 2 . Stratified Analyses of the Association Background Obesity is now one of the world ’s major chronic diseases . The etiology of the severe comorbid conditions associated with morbid obesity is not fully understood , and in particular the relationship between gastroesophageal reflux and obesity . Methods Sixty-seven patients were enrolled in this prospect i ve study . Patients and control individuals were divided into four subgroups according to their body mass index ( BMI ) . Esophageal motility was assessed using a conventional water-perfused esophageal manometry catheter , and 24-h pH-metry was carried out using multichannel intraluminal impedance equipment . Results In the group with the highest BMI ( > 50 ) , contraction amplitudes in the middle and distal esophagus were significantly higher in comparison both with the control group and groups with a lower BMI ( P < 0.05 ) . Lower esophageal sphincter pressure was reduced in the majority of patients with morbid obesity and differed significantly from the control group ( P < 0.001 ) . Significant differences between the control group and the patient groups were also observed on 24-h pH-metry ( P < 0.05 ) . The 24-h impedance measurements distinguished between acid and nonacid status and between the upright and recumbent positions . The total number of reflux episodes differed significantly between the control and patient groups and between groups III and IV , with lower and higher BMI values ( P < 0.008 and P < 0.05 , respectively ) . Conclusions The impedance data obtained in this study confirm that patients with morbid obesity are at risk of developing gastroesophageal reflux disease . However , there is no evidence of a direct correlation between the severity of reflux and the extent of obesity |
10,402 | 29,695,180 | The administration of Lactobacillus casei strain Shirota in CFS patients , over the course of 8 weeks , reduced anxiety scores .
Likewise , this probiotic changed the faecal composition following 8 weeks of treatment .
Additionally , the treatment with Bifidobacterium infantis 35624 in CFS patients , during the same period , reduced inflammatory biomarkers .
The evidence about the usefulness of probiotics in CFS and FMS patients remains limited .
The studied strains of probiotics have demonstrated a significant effect on modulating the anxiety and inflammatory processes in CFS patients . | Evidence suggests that the gut microbiota might play an important role in fibromyalgia syndrome ( FMS ) and chronic fatigue syndrome ( CFS ) .
Our goal is to systematic ally review the reported effect of probiotic treatments in patients diagnosed with FMS or CFS . | Background Alterations in the intestinal bacterial flora are believed to be contributing factors to many chronic inflammatory and degenerative diseases including rheumatic diseases . While microbiological fecal culture analysis is now increasingly used , little is known about the relationship of changes in intestinal flora , dietary patterns and clinical outcome in specific diseases . To clarify the role of microbiological culture analysis we aim ed to evaluate whether in patients with rheumatoid arthritis ( RA ) or fibromyalgia ( FM ) a Mediterranean diet or an 8-day fasting period are associated with changes in fecal flora and whether changes in fecal flora are associated with clinical outcome . Methods During a two-months-period 51 consecutive patients from an Integrative Medicine hospital department with an established diagnosis of RA ( n = 16 ) or FM ( n = 35 ) were included in the study . According to predefined clinical criteria and the subjects ' choice the patients received a mostly vegetarian Mediterranean diet ( n = 21 ; mean age 50.9 + /-13.3 y ) or participated in an intermittent modified 8-day fasting therapy ( n = 30 ; mean age 53.7 + /- 9.4 y ) . Quantitative aerob and anaerob bacterial flora , stool pH and concentrations of secretory immunoglobulin A ( sIgA ) were analysed from stool sample s at the beginning , at the end of the 2-week hospital stay and at a 3-months follow-up . Clinical outcome was assessed with the DAS 28 for RA patients and with a disease severity rating scale in FM patients . Results We found no significant changes in the fecal bacterial counts following the two dietary interventions within and between groups , nor were significant differences found in the analysis of sIgA and stool ph . Clinical improvement at the end of the hospital stay tended to be greater in fasting vs. non-fasting patients with RA ( p = 0.09 ) . Clinical outcome was not related to alterations in the intestinal flora . Conclusion Neither Mediterranean diet nor fasting treatments affect the microbiologically assessed intestinal flora and sIgA levels in patients with RA and FM . The impact of dietary interventions on the human intestinal flora and the role of the fecal flora in rheumatic diseases have to be clarified with newer molecular analysis techniques . The potential benefit of fasting treatment in RA and FM should be further tested in r and omised trials Background Chronic fatigue syndrome ( CFS ) is characterized by profound fatigue , which substantially interferes with daily activities , and a characteristic symptom complex . Patients use a variety of prescribed and self-administered medications , vitamins , and supplements for relief of their symptoms . The objective of this study was to describe utilization of medications and supplements by persons with CFS and non-fatigued individuals representative of the general population of Wichita , Kansas . Methods We used a r and om-digit dialing telephone survey to identify persons with CFS in the general population of Wichita , Kansas . Subjects who on the basis of telephone interview met the CFS case definition , and r and omly selected non-fatigued controls , were invited for a clinic evaluation that included self-reported use of medications and supplements . Sex-adjusted odds ratios and 95 % confidence interval were estimated to measure the association between CFS and use of various drug categories . Results We clinical ly evaluated and classified 90 subjects as CFS during the study and also collected clinical data on 63 who never described fatigue . Subjects with CFS reported using 316 different drugs compared to 157 reported by non-fatigued controls . CFS subjects were more likely to use any drug category than controls ( p = 0.0009 ) . Pain relievers and vitamins/supplements were the two most common agents listed by both groups . In addition CFS persons were more likely to use pain relievers , hormones , antidepressants , benzodiazepines , gastro-intestinal , and central nervous system medications ( Sex-adjusted odds ratios range = 2.97 – 12.78 ) . Conclusion Although the reasons for increased use of these agents were not eluci date d , the data indicated the CFS patients ' need for symptom relief Objective : The impact on mood and memory of consuming a probiotic containing milk drink , or a placebo , was examined as , previously , a poor mood has been found to correlate with the frequency of constipation . Design : A double-blind placebo-controlled trial with r and om allocation of subjects . Setting : Subjects went about their normal life in the community apart from three visits to the laboratory . Subjects : One hundred and thirty-two healthy members of general population , mean age 61.8 years , volunteered in response to local media coverage . One hundred and twenty-four finished the trial . Intervention : For a 3-week period , either a probiotic containing milk drink , or a placebo , were consumed daily . Mood and cognition were measured at baseline , and after 10 and 20 days of consumption . Results : At baseline those who reported themselves to be less frequently constipated were more clearheaded , confident and elated . Although the taking of the probiotic did not generally change the mood , this appeared to be a reflection of the generally good mood in this sample . When those in the bottom third of the depressed/elated dimension at baseline were considered , they selectively responded by reporting themselves as happy rather than depressed after taking the probiotic . The intervention did not , however , influence the reported frequency of defaecation , probably a reflection of the initially low incidence of constipation . An unexpected and possibly chance finding was that the consumption of probiotics result ed in a slightly-poorer performance on two measures of memory . Conclusions : The consumption of a probiotic-containing yoghurt improved the mood of those whose mood was initially poor . This improvement in mood was not , however , associated with an increased frequency of defaecation . Sponsorship : Funded by Yakult , Japan In a previous clinical study , a probiotic formulation ( PF ) consisting of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 ( PF ) decreased stress-induced gastrointestinal discomfort . Emerging evidence of a role for gut microbiota on central nervous system functions therefore suggests that oral intake of probiotics may have beneficial consequences on mood and psychological distress . The aim of the present study was to investigate the anxiolytic-like activity of PF in rats , and its possible effects on anxiety , depression , stress and coping strategies in healthy human volunteers . In the pre clinical study , rats were daily administered PF for 2 weeks and subsequently tested in the conditioned defensive burying test , a screening model for anti-anxiety agents . In the clinical trial , volunteers participated in a double-blind , placebo-controlled , r and omised parallel group study with PF administered for 30 d and assessed with the Hopkins Symptom Checklist ( HSCL-90 ) , the Hospital Anxiety and Depression Scale ( HADS ) , the Perceived Stress Scale , the Coping Checklist ( CCL ) and 24 h urinary free cortisol ( UFC ) . Daily subchronic administration of PF significantly reduced anxiety-like behaviour in rats ( P < 0·05 ) and alleviated psychological distress in volunteers , as measured particularly by the HSCL-90 scale ( global severity index , P < 0·05 ; somatisation , P < 0·05 ; depression , P < 0·05 ; and anger-hostility , P < 0·05 ) , the HADS ( HADS global score , P < 0·05 ; and HADS-anxiety , P < 0·06 ) , and by the CCL ( problem solving , P < 0·05 ) and the UFC level ( P < 0·05 ) . L. helveticus R0052 and B. longum R0175 taken in combination display anxiolytic-like activity in rats and beneficial psychological effects in healthy human volunteers Background & objectives : Small intestinal bacterial overgrowth ( SIBO ) leads to several gastrointestinal ( GI ) problems and complications leading to malabsorption . The effectiveness of probiotics in the treatment of SIBO syndrome has not been well studied . This pilot study was aim ed to assess the efficacy of a probiotic consisting of lactobacilli in the treatment of SIBO . Methods : In this study , 30 cases suffering from chronic abdominal pain or diarrhoea and with a positive hydrogen breath test were r and omized in a double-blind manner into two groups : probiotic drug user and control group . After an initial 3-week aggressive therapy with broad-spectrum antibiotics , a 15-day maintenance antibiotic therapy with lactol was administered for the study group and the same regimen without lactol for the control group . After six months the HBT result and the GI symptoms were analyzed and compared between the two groups . Results : The result of hydrogen breath test and the clinical symptoms in patients receiving the maintenance regimen with lactol probiotic showed a better response . The hydrogen breath test turned negative in 93.3 per cent of those receiving lactol compared to 66.7 per cent of the controls . In all the cases receiving lactol , the abdominal pain disappeared completely ( P=0.002 ) . In addition , other GI problems including flatulence , belching and diarrhoea significantly improved in the study group ( P<0.05 ) . Interpretation & conclusions : Based on the preliminary data it seems that adding lactol probiotic to the maintenance therapy of small intestinal bacterial overgrowth patients on routine antibiotic therapy will be beneficial in preventing the complications of this syndrome Certain therapeutic microbes , including Bifidobacteria infantis ( B. infantis ) 35624 exert beneficial immunoregulatory effects by mimicking commensal-immune interactions ; however , the value of these effects in patients with non-gastrointestinal inflammatory conditions remains unclear . In this study , we assessed the impact of oral administration of B. infantis 35624 , for 6‒8 weeks on inflammatory biomarker and plasma cytokine levels in patients with ulcerative colitis ( UC ) ( n = 22 ) , chronic fatigue syndrome ( CFS ) ( n = 48 ) and psoriasis ( n = 26 ) in three separate r and omized , double-blind , placebo-controlled interventions . Additionally , the effect of B. infantis 35624 on immunological biomarkers in healthy subjects ( n = 22 ) was assessed . At baseline , both gastrointestinal ( UC ) and non-gastrointestinal ( CFS and psoriasis ) patients had significantly increased plasma levels of C-reactive protein ( CRP ) and the pro-inflammatory cytokines tumor necrosis factor α ( TNF-α ) and interleukin-6 ( IL-6 ) compared with healthy volunteers . B. infantis 35624 feeding result ed in reduced plasma CRP levels in all three inflammatory disorders compared with placebo . Interestingly , plasma TNF-α was reduced in CFS and psoriasis while IL-6 was reduced in UC and CFS . Furthermore , in healthy subjects , LPS-stimulated TNF-α and IL-6 secretion by peripheral blood mononuclear cells ( P BMC s ) was significantly reduced in the B. infantis 35624-treated groups compared with placebo following eight weeks of feeding . These results demonstrate the ability of this microbe to reduce systemic pro-inflammatory biomarkers in both gastrointestinal and non-gastrointestinal conditions . In conclusion , these data show that the immunomodulatory effects of the microbiota in humans are not limited to the mucosal immune system but extend to the systemic immune system Background Lactic acid-producing bacteria ( LAB ) probiotics demonstrate immunomodulating and anti-inflammatory effects and the ability to lessen the symptoms of arthritis in both animals and humans . This r and omized , double-blind , placebo-controlled , parallel- design , clinical pilot trial was conducted to evaluate the effects of the LAB probiotic preparation , Bacillus coagulans GBI-30 , 6086 , on symptoms and measures of functional capacity in patients with rheumatoid arthritis ( RA ) in combination with pharmacological anti-arthritic medications . Methods Forty-five adult men and women with symptoms of RA were r and omly assigned to receive Bacillus coagulans GBI-30 , 6086 or placebo once a day in a double-blind fashion for 60 days in addition to their st and ard anti-arthritic medications . Arthritis activity was evaluated by clinical examination , the American College of Rheumatology ( ACR ) criteria , the Stanford Health Assessment Question naire Disability Index ( HAQ-DI ) , and laboratory tests for erythrocyte sedimentation rate ( ESR ) and C-reactive protein ( CRP ) . Results Subjects who received Bacillus coagulans GBI-30 , 6086 experienced borderline statistically significant improvement in the Patient Pain Assessment score ( P = .052 ) and statistically significant improvement in Pain Scale ( P = .046 ) vs placebo . Compared with placebo , Bacillus coagulans GBI-30 , 6086 treatment result ed in greater improvement in patient global assessment and self-assessed disability ; reduction in CRP ; as well as the ability to walk 2 miles , reach , and participate in daily activities . There were no treatment-related adverse events reported throughout this study . Conclusions Results of this pilot study suggest that adjunctive treatment with Bacillus coagulans GBI-30 , 6086 LAB probiotic appeared to be a safe and effective for patients suffering from RA . Because of the low study population size , larger trials are needed to verify these results .Trial registration Chronic fatigue syndrome ( CFS ) is complex illness of unknown etiology . Among the broad range of symptoms , many patients report disturbances in the emotional realm , the most frequent of which is anxiety . Research shows that patients with CFS and other so-called functional somatic disorders have alterations in the intestinal microbial flora . Emerging studies have suggested that pathogenic and non-pathogenic gut bacteria might influence mood-related symptoms and even behavior in animals and humans . In this pilot study , 39 CFS patients were r and omized to receive either 24 billion colony forming units of Lactobacillus casei strain Shirota ( LcS ) or a placebo daily for two months . Patients provided stool sample s and completed the Beck Depression and Beck Anxiety Inventories before and after the intervention . We found a significant rise in both Lactobacillus and Bifidobacteria in those taking the LcS , and there was also a significant decrease in anxiety symptoms among those taking the probiotic vs controls ( p = 0.01 ) . These results lend further support to the presence of a gut-brain interface , one that may be mediated by microbes that reside or pass through the intestinal tract In a recent clinical study , we demonstrated in the general population that Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 ( PF ) taken in combination for 30 days decreased the global scores of hospital anxiety and depression scale ( HADs ) , and the global severity index of the Hopkins symptoms checklist ( HSCL-90 ) , due to the decrease of the sub-scores of somatization , depression and anger-hostility spheres . Therefore , oral intake of PF showed beneficial effects on anxiety and depression related behaviors in human volunteers . From there , it is interesting to focus on the role of this probiotic formulation in the subjects with the lowest urinary free cortisol levels at baseline . This addendum presents a secondary analyse of the effects of PF in a sub- population of 25 subjects with urinary free cortisol ( UFC ) levels less than 50 ng/ml at baseline , on psychological distress based on the percentage of change of the perceived stress scale ( PSs ) , the HADs and the HSCL-90 scores between baseline and follow-up . The data show that PF improves the same scores as in the general population ( the HADs global score , the global severity index of the HSCL-90 and three of its sub-scores , i.e. somatization , depression and anger-hostility ) , as well as the PSs score and three other sub-scores of the HSCL-90 , i.e. " obsessive compulsive " , " anxiety " , and " paranoid-ideation " . Moreover , in the HSCL-90 , the score of the Factor 1 , related to anxiety and depression , is significantly improved over time in PF-treated subjects compared with controls . Additional pre clinical data showed that PF formulation does not induce side effects such as addiction or learning and memory impairments , and therefore displays a good safety profile . Complementary hypothetical mechanisms of action are proposed to explain the functioning of the brain-gut axis , particularly the relationship between probiotics and stress-related psychopathologies , such as anxiety and depression BACKGROUND Recent insights into the role of the human microbiota in cognitive and affective functioning have led to the hypothesis that probiotic supplementation may act as an adjuvant strategy to ameliorate or prevent depression . OBJECTIVE Heightened cognitive reactivity to normal , transient changes in sad mood is an established marker of vulnerability to depression and is considered an important target for interventions . The present study aim ed to test if a multispecies probiotic containing Bifidobacterium bifidum W23 , Bifidobacterium lactis W52 , Lactobacillus acidophilus W37 , Lactobacillus brevis W63 , Lactobacillus casei W56 , Lactobacillus salivarius W24 , and Lactococcus lactis ( W19 and W58 ) may reduce cognitive reactivity in non-depressed individuals . DESIGN In a triple-blind , placebo-controlled , r and omized , pre- and post-intervention assessment design , 20 healthy participants without current mood disorder received a 4-week probiotic food-supplement intervention with the multispecies probiotics , while 20 control participants received an inert placebo for the same period . In the pre- and post-intervention assessment , cognitive reactivity to sad mood was assessed using the revised Leiden index of depression sensitivity scale . RESULTS Compared to participants who received the placebo intervention , participants who received the 4-week multispecies probiotics intervention showed a significantly reduced overall cognitive reactivity to sad mood , which was largely accounted for by reduced rumination and aggressive thoughts . CONCLUSION These results provide the first evidence that the intake of probiotics may help reduce negative thoughts associated with sad mood . Probiotics supplementation warrants further research as a potential preventive strategy for depression BACKGROUND Chronic fatigue syndrome ( CFS ) , fibromyalgia ( FM ) , and multiple chemical sensitivities ( MCS ) are conditions associated with fatigue and a variety of other symptoms that appear to share many clinical and demographic features . Our objectives were to describe the similarities and differences among patients with CFS , FM , and MCS . Additional objectives were to determine how frequently patients with MCS and FM met the criteria for CFS and if they differed in their health locus of control . METHODS Demographic , clinical , and psychosocial measures were prospect ively collected in 90 patients , 30 each with CFS , FM , and MCS . Patients were recruited from a university-based referral clinic devoted to the evaluation and treatment of chronic fatigue and three private practice s. Variables included demographic features , symptoms characteristic of each condition , psychological complaints , a measure of health locus of control , and information on health care use . RESULTS Overall , the three patient groups were remarkably similar in demographic characteristics and the presence of specific symptoms . Patients with CFS and FM frequently reported symptoms compatible with MCS . Likewise , 70 % of patients with FM and 30 % of those with MCS met the criteria for CFS . Health care use was substantial among patients with CFS , FM , and MCS , with an average of 22.1 , 39.7 , and 23.3 visits , respectively , to a medical provider during the prior year . Health locus of control did not differ among the three population s. CONCLUSIONS In general , demographic and clinical factors and health locus of control do not clearly distinguish patients with CFS , FM , and MCS . Symptoms typical of each disorder are prevalent in the other two conditions BACKGROUND Fibromyalgia syndrome ( FMS ) is a chronic , generalized and diffuse pain disorder accompanied by other symptoms such as emotional and cognitive deficits . The FMS patients show a high prevalence of gastrointestinal symptoms . Recently it has been found that microbes in the gut may regulate brain processes through the gut-microbiota-brain axis , modulating thus affection , motivation and higher cognitive functions . Therefore , the use of probiotics might be a new treatment that could improve the physical , psychological and cognitive state in FMS ; however , no evidence about this issue is available . METHODS This paper describes the design and protocol of a double-blind , placebo-controlled and r and omized pilot study . We use vali date d question naires , cognitive task through E-Prime and biological measures like urine cortisol and stool fecal sample s. The trial aim is to explore the effects of eight weeks of probiotics therapy in physical ( pain , impact of the FMS and quality of life ) , emotional ( depression , and anxiety ) and cognitive symptoms ( attention , memory , and impulsivity ) in FMS patients as compared to placebo . CONCLUSION This pilot study is the first , to our knowledge , to evaluate the effects of probiotics in FMS . The primary hypothesis was that FMS patients will show a better performance on cognitive tasks , and an improvement in emotional and physical symptoms . These results will contribute to a better underst and ing in the gut-brain axis . Here we present the design and protocol of the study AIM To determine the dose-related effects of a novel probiotic combination , I.31 , on irritable bowel syndrome (IBS)-related quality of life ( IBS-QoL ) . METHODS A multicenter , r and omized , double-blind , placebo-controlled intervention clinical trial with three parallel arms was design ed . A total of 84 patients ( 53 female , 31 male ; age range 20 - 70 years ) with IBS and diarrhea according to Rome-III criteria were r and omly allocated to receive one capsule a day for 6 wk containing : ( 1 ) I.31 high dose ( n = 28 ) ; ( 2 ) I.31 low dose ( n = 27 ) ; and ( 3 ) placebo ( n = 29 ) . At baseline , and 3 and 6 wk of treatment , patients filled the IBSQoL , Visceral Sensitivity Index ( VSI ) , and global symptom relief question naires . RESULTS During treatment , IBS-QoL increased in all groups , but this increment was significantly larger in patients treated with I.31 than in those receiving placebo ( P = 0.008 ) . After 6 wk of treatment , IBS-QoL increased by 18 ± 3 and 22 ± 4 points in the high and the low dose groups , respectively ( P = 0.041 and P = 0.023 vs placebo ) , but only 9 ± 3 in the placebo group . Gut-specific anxiety , as measured with VSI , also showed a significantly greater improvement after 6 wk of treatment in patients treated with probiotics ( by 10 ± 2 and 14 ± 2 points , high and low dose respectively , P < 0.05 for both vs 7 ± 1 score increment in placebo ) . Symptom relief showed no significant changes between groups . No adverse drug reactions were reported following the consumption of probiotic or placebo capsules . CONCLUSION A new combination of three different probiotic bacteria was superior to placebo in improving IBS-related quality of life in patients with IBS and diarrhea Objective . To investigate the effect of an orally administered probiotic on disease activity , fatigue , quality of life , and intestinal symptoms in patients with active spondyloarthritis . Methods . Patients with active spondyloarthritis [ defined as Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) ≥ 3 , Bath Ankylosing Spondylitis Functional Index ( BASFI ) ≥ 3 , Maastricht Ankylosing Spondylitis Enthesitis Score ( MASES ) ≥ 2 , or peripheral joint count ≥ 2 ] were r and omized to oral probiotic or placebo for 12 weeks . Patients and assessors were blinded to treatment allocation . The primary outcome measure was 10 % improvement in the BASFI . Additional outcome measures were improvements in the ASsessment s in Ankylosing Spondylitis (ASAS)-endorsed core domains : pain , spinal mobility , patient global , peripheral joint and entheseal scores , stiffness , C-reactive protein , and fatigue . The ASAS20 criteria , a composite measure of response , were also applied . Quality of life and bowel symptoms were quantified using the Ankylosing Spondylitis Quality of Life Question naire ( ASQoL ) and Dudley Inflammatory Bowel Symptom Question naire ( DISQ ) . Results . Sixty-three patients were r and omized to oral probiotic ( n = 32 ) or placebo ( n = 31 ) . All patients completed the trial . No significant difference was noted between groups in any of the core domains . The mean BASFI fell from 3.5 ± 2.0 to 2.9 ± 1.9 in the probiotic group and from 3.6 ± 1.9 to 3.1 ± 2.2 in the placebo group ( p = 0.839 ) . The mean BASDAI fell from 4.2 ± 2.2 to 3.2 ± 2.1 in the probiotic group and 4.5 ± 2.0 to 3.9 ± 2.2 in the placebo group ( p = 0.182 ) . No significant adverse events were recorded in the probiotic-treated group . Conclusion . In this r and omized controlled trial , the probiotic combination administered did not demonstrate significant benefit over placebo , despite a theoretical rationale for this therapy AIM To assess the effects and safety of Lactobacillus casei rhamnosus LCR35 complete freeze-dried culture ( LCR35 ) in patients suffering from irritable bowel syndrome ( IBS ) . METHODS A r and omized , double-blind pilot study was performed in 50 patients complaining of IBS symptoms complying with Rome III criteria . Patients were allocated to receive either LCR35 ( n = 25 ) at a minimum daily dose of 6 × 10(8 ) colony forming units or placebo ( n = 25 ) for 4 wk . At inclusion , after treatment and 2 wk later , patients completed the IBS severity scale . Change from baseline in the IBS severity score at the end of treatment was the primary efficacy criterion . Changes were compared between groups in the whole population and in IBS subtypes ( IBS with predominance of constipation , IBS with predominance of diarrhoea , mixed IBS , unsubtyped IBS ) . The presence of lactobacillus casei rhamnosus in stools was investigated at inclusion and at the end of treatment . The gastrointestinal quality of life question naire and the hospital anxiety and depression ( HAD ) scale were also completed . RESULTS Both groups were balanced for baseline characteristics . In 85 % of patients , stool analyses showed that lactobacillus casei rhamnosus able to survive in the digestive tract . In the whole population , improvements in the IBS severity score did not differ significantly between treatments with a 25 % decrease after 4-wk treatment , and a 15 % decrease from baseline 2 wk later in both groups . In IBS subgroups , statistical analysis could not be performed due to small sample size , but a clinical response in favour of LCR35 was observed in IBS patients with predominance of diarrhoea : no change in the symptom severity score was seen with the placebo after 4 wk treatment , whereas a clinical ly relevant decrease occurred with LCR35 ( -37 % vs -3 % ) . Furthermore , in spite of an increase in symptom intensity , the IBS severity score was maintained below the baseline value 2 wk later with LCR35 ( -19 % from baseline ) , whilst a slight 5 % increase from baseline was observed with placebo . In the IBS subgroup with predominance of diarrhoea only , a clinical ly relevant decrease in abdominal pain severity score ( -36 % ) was observed with LCR35 , whereas no change occurred with placebo . In mixed IBS patients , the 20 % and 30 % decreases in the IBS severity score observed after treatment with LCR35 and placebo , respectively , were maintained 2 wk later in both groups . A clinical response slightly in favour of placebo was observed at the end of the treatment period in IBS patients with predominance of constipation ( -41 % vs -20 % ) and unsubtyped IBS patients ( -47 % vs -17 % ) , with the same value maintained 2 wk later . In both groups , no clinical ly relevant changes were observed either for the gastrointestinal quality of life index or HAD score . Thus , these results suggest that sub-grouping of IBS patients may be important for optimizing treatment responses by the physician . CONCLUSION This pilot study suggests that LCR35 could have some efficacy in IBS patients complaining of diarrhoea . These preliminary results need to be confirmed in larger studies There is now evidence that major depression ( MDD ) is accompanied by an activation of the inflammatory response system ( IRS ) and that pro-inflammatory cytokines and lipopolysacharide ( LPS ) may induce depressive symptoms . The aim of the present study was to examine whether an increased gastrointestinal permeability with an increased translocation of LPS from gram negative bacteria may play a role in the pathophysiology of MDD . Toward this end , the present study examines the serum concentrations of IgM and IgA against LPS of the gram-negative enterobacteria , Hafnia Alvei , Pseudomonas Aeruginosa , Morganella Morganii , Pseudomonas Putida , Citrobacter Koseri , and Klebsielle Pneumoniae in MDD patients and normal controls . We found that the prevalences and median values for serum IgM and IgA against LPS of enterobacteria are significantly greater in patients with MDD than in normal volunteers . These differences are significant to the extent that a significant diagnostic performance is obtained , i.e. the area under the ROC curve is 90.1 % . The symptom profiles of increased IgM and IgA levels are fatigue , autonomic and gastro-intestinal symptoms and a subjective feeling of infection . The results show that intestinal mucosal dysfunction characterized by an increased translocation of gram-negative bacteria ( leaky gut ) plays a role in the inflammatory pathophysiology of depression . It is suggested that the increased LPS translocation may mount an immune response and thus IRS activation in some patients with MDD and may induce specific " sickness behaviour " symptoms . It is suggested that patients with MDD should be checked for leaky gut by means of the IgM and IgA panel used in the present study and accordingly should be treated for leaky gut OBJECTIVE : We have recently found an association between abnormal lactulose breath test ( LBT ) findings and irritable bowel syndrome ( IBS ) . The current study was design ed to test the effect of antibiotic treatment for IBS in a double-blind fashion . METHODS : Consecutive IBS subjects underwent an LBT with the results blinded . All subjects were subsequently r and omized into two treatment groups ( neomycin or placebo ) . The prevalence of abnormal LBT was compared with a gender-matched control group . Seven days after completion of treatment , subjects returned for repeat LBT . A symptom question naire was administered on both days . RESULTS : After exclusion criteria were met , 111 IBS subjects ( 55 neomycin , 56 placebo ) entered the study , with 84 % having an abnormal LBT , compared with 20 % in healthy controls ( p < 0.01 ) . In an intention-to-treat analysis of all 111 subjects , neomycin result ed in a 35.0 % improvement in a composite score , compared with 11.4 % for placebo ( p < 0.05 ) . Additionally , patients reported a percent bowel normalization of 35.3 % after neomycin , compared with 13.9 % for placebo ( p < 0.001 ) . There was a grade d response to treatment , such that the best outcome was observed if neomycin was successful in normalizing the LBT ( 75 % improvement ) ( one-way ANOVA , p < 0.0001 ) . LBT gas production was associated with IBS subgroup , such that methane excretion was 100 % associated with constipation-predominant IBS . Methane excretors had a mean constipation severity of 4.1 , compared with 2.3 in all other subjects ( p < 0.001 ) . CONCLUSIONS : An abnormal LBT is common in subjects with IBS . Normalization of LBT with neomycin leads to a significant reduction in IBS symptoms . The type of gas seen on LBT is also associated with IBS subgroup OBJECTIVE : Our aim was to determine whether Lactobacillus rhamnosus GG ( LGG ) relieves symptoms in children with recurrent abdominal pain . PATIENTS AND METHODS : A total of 141 children with irritable bowel syndrome ( IBS ) or functional pain were enrolled in 9 primary care sites and a referral center . Children entered a r and omized , double-blind , placebo-controlled trial and received LGG or placebo for 8 weeks and entered follow-up for 8 weeks . The primary outcome was overall pain at the end of the intervention period . At entry and at the end of the trial , children underwent a double-sugar intestinal permeability test . RESULTS : Compared with baseline , LGG , but not placebo , caused a significant reduction of both frequency ( P < .01 ) and severity ( P < .01 ) of abdominal pain . These differences still were significant at the end of follow-up ( P < .02 and P < .001 , respectively ) . At week 12 , treatment success was achieved in 48 children in the LGG group compared with 37 children in the placebo group ( P < .03 ) ; this difference still was present at the end of follow-up ( P < .03 ) . At entry , 59 % of the children had abnormal results from the intestinal permeability test ; LGG , but not placebo , determined a significant decrease in the number of patients with abnormal results from the intestinal permeability testing ( P < .03 ) . These effects mainly were in children with IBS . CONCLUSIONS : LGG significantly reduces the frequency and severity of abdominal pain in children with IBS ; this effect is sustained and may be secondary to improvement of the gut barrier |
10,403 | 29,405,627 | CONCLUSIONS Available evidence suggests that oral sprays are an acceptable delivery method for antiseptic agents . | OBJECTIVES To review the effectiveness of antiseptic oral sprays on oral health . | BACKGROUND The aim of this clinical trial was to compare the effects of three oral sprays containing chlorhexidine ( CHX ) , benzydamine hydrochloride ( B-HCl ) , and CHX plus B-HCl ( CHX/B-HCl ) on plaque and gingivitis . METHODS Fifty-one periodontally healthy volunteers , r and omly divided into three spray groups , refrained from all mechanical oral hygiene measures for 7 days and , instead , used one of the r and omly assigned sprays twice daily . The plaque index ( PI ) , gingival index ( GI ) , and gingival bleeding time index ( GBTI ) were assessed at days 0 and 7 . Side effects were also evaluated . RESULTS In all groups , PI , GI , and GBTI showed significant increases from the baseline to day 7 . There were no significant side effects for B-HCl spray and CHX spray at day 7 , but , for CHX/B-HCl , burning sensation significantly increased from the baseline . For all parameters , there were significant differences between B-HCl and CHX/B-HCl and between B-HCl and CHX , but no significant differences were observed between CHX/B-HCl and CHX . In addition , a significant difference was found between CHX/B-HCl and CHX with regard to burning sensation . CONCLUSIONS These results indicate that both CHX and CHX/B-HCl sprays have equal clinical effectiveness , but only B-HCl spray has less anti-plaque and anti-gingivitis effects . Furthermore , CHX/B-HCl spray causes more side effects OBJECTIVE The objective of this independent , double-blind , seven-day clinical study was to assess the efficacy of a commercially available mouthrinse containing 0.05 % CPC for controlling dental plaque relative to that of a control mouthrinse without 0.05 % CPC . METHODS Adult male and female subjects from the San Juan , Puerto Rico area reported to the clinical facility , having refrained from any oral hygiene procedures for 12 hours , and from eating , drinking , and smoking for four hours , for an assessment of the oral soft and hard tissues and a baseline dental plaque evaluation . Qualifying subjects were r and omly assigned into one of the two treatment groups , and were provided with their assigned mouthrinse , an adult soft-bristled toothbrush , and a commercially available fluoride toothpaste for home use . Over the seven-day period of home use , during which there were no restrictions regarding diet or smoking habits , subjects were instructed to brush their teeth for one minute twice daily ( morning and evening ) with the toothbrush and toothpaste supplied , to rinse their mouths with water after brushing , and then to rinse with 15 ml of their assigned mouthrinse for one minute before expectorating . The use of other oral hygiene products or procedures , such as floss or interdental stimulators , was not permitted during the study . After seven days of product use , subjects returned to the clinical facility having followed the same restrictions with respect to oral hygiene procedures , eating , and drinking as prior to the baseline examination , and the oral soft and hard tissue assessment s and dental plaque evaluations were repeated . Comparisons between treatment groups with respect to baseline-adjusted Plaque Index scores at the seven-day examination were performed using Analyses of Covariance , p < or = 0.05 . RESULTS Forty-eight subjects complied with the protocol and completed the study . Results demonstrated that , after seven days of product use and 12 hours after rinsing , both the CPC mouthrinse group and the control mouthrinse group exhibited statistically significant reductions in whole-mouth Plaque Index scores ( 25.3 % and 6.6 % , respectively ) , in Plaque Index scores measured at interproximal sites ( 51.3 % and 32.9 % , respectively ) , and in Plaque Severity Index scores ( 43.5 % and 25.4 % , respectively ) . Relative to the control mouthrinse , the 0.05 % CPC mouthrinse group exhibited statistically significant greater reductions in whole-mouth plaque scores ( 15.9 % ) , in Plaque Index scores measured at interproximal sites ( 23 % ) , and in Plaque Severity Index scores ( 17 % ) . As the measurements were made 12 hours after final product use , the results also demonstrate that the CPC mouthrinse provides 12-hour protection against plaque accumulation in individuals with existing plaque . CONCLUSION The overall results of this double-blind clinical study support the conclusion that after seven days of product use , a mouthrinse containing 0.05 % CPC provides significantly greater efficacy for reducing dental plaque 12 hours after use , than does a control mouthrinse without 0.05 % CPC OBJECTIVE The efficacy of a topical application of hyaluronic acid ( HA ) was tested for treating gingivitis . METHOD AND MATERIAL S Sixty nonsmoking out patients in good general condition , with clinical signs of gingivitis , were included in the study . Forty patients ( HA group , 20 men , 20 women ; age : 32.8 + /- 11.3 years ) used a spray containing HA 5 times daily over a period of 1 week . The control group consisted of 20 patients ( 10 men , 10 women ; age : 31.3 + /- 9.3 years ) . The clinical parameters DMF-T ( decayed , missed , filled teeth ) index , approximal plaque index , sulcus bleeding index , papilla bleeding index , and gingival crevicular fluid were measured at baseline ( T1 ) , after 3 days ( T2 ) , and after 7 days ( T3 ) . RESULTS A reduction in the sulcus bleeding index of the HA group ( T1 : 72.9 + /- 19.5 % ) to 50.3 + /- 21.1 % was noted at T2 , and at T3 the sulcus bleeding index was 40.7 + /- 23.0 % . The papilla bleeding index values of the HA group were 1.6 at T1 , 1.0 at T2 , and 0.7 at T3 . The gingival crevicular fluid showed significant reductions in the HA group . At T1 the recorded mean value was 16.3 , at T2 it was 11.8 , and at T3 it was 7.9 . Only insignificant changes were observed in the respective indices of the control group . There were no significant alterations in the plaque values of either group throughout the study period . CONCLUSION The results obtained by this study demonstrate that the topical application of an HA-containing preparation represents a potentially useful adjunct in the therapy of gingivitis , although its use does not diminish the need for plaque reduction as a primary therapeutic measure The present study contains data from a 4-week clinical study where the effect of an experimental toothpaste containing 0.4 % SnF2 on plaque and gingivitis was tested in a group of teenagers . The study was performed according to a double-blind , cross-over design . It was shown that the SnF2 containing toothpaste reduced both plaque and gingivitis significantly compared to a placebo paste which contained no fluoride or stannous ions A long-term prospect i ve , r and omized dietary intervention to prevent exposure of children to the known atherosclerosis risk factors ( the STRIP baby project ) was started when the age of the children was 7 months . The aim of this sub study was to analyze the oral effects of the dietary intervention in the children and their parents when the children had reached the age of 3 years . Every fifth family of the main study was invited to this sub study ( n = 179 ) . Those studied ( n = 148 ) represented well the intervention and the control groups and both genders in terms of intake of saturated fatty acids , the dietary polyunsaturated fatty acid to saturated fatty acid ( PUFA/SAFA ) ration and serum cholesterol and HDL cholesterol concentrations . Though no difference was found in sucrose consumption between the intervention and the control groups , the intervention children received relatively ( in E% ) more energy from carbohydrates than the control children ( p < 0.005 ) , used absolutely ( in g ) and relatively ( in E% ) less fat ( p < 0.05 ) and had a higher PUFA/SAFA ratio in their diet ( p < 0.001 ) . Of the 3-year-old children 93 % were caries free , and dental decay was a prevalent in the intervention as in the control children . Control children brushed their teeth unassisted more often than the intervention children ( p < 0.05 ) . The intervention fathers also received more energy ( in E% ) from carbohydrates ( p < 0.01 ) , the intervention mothers used less fat ( p < 0.05 ) and had a higher PUFA/SAFA ratio in the diet ( p < 0.05 ) than the control fathers and mothers , respectively . Dental and periodontal health of the intervention and control parents ( n = 250 , 84 % attending , mean + /- SD age : 34.2 + /- 54.5 years also showed no differences even though the control parents had more commonly last visited a dentist over 3 years before this examination ( p < 0.05 ) . We conclude that a 29-month period of a low-saturated-fat , low-cholesterol but high-carbohydrate diet as advocated in the STRIP baby trial does not seem to have harmful effects on the oral health of the children or their parents . Minor untoward differences had occurred in the dental health behavior of the control children and their parents BACKGROUND Due to the side effects of chlorhexidine digluconate ( CHX ) mouthrinsing , a spray has been proposed as an alternative method of CHX delivery to the oral cavity . The aim of this study was to investigate the plaque inhibitory effects of CHX , cetylpyridinium chloride ( CPC ) , and triclosan ( TRN ) delivered by sprays and mouthrinses . METHODS The study was an observer-masked , r and omized cross-over design balanced for carryover effects , involving 15 healthy volunteers in a 4-day plaque regrowth model . Products being tested ( 0.2 % CHX , 0.12 % CHX , 0.05 % CPC , and 0.03 % TRN ) were used both as sprays and mouthrinses . A saline solution served as a negative control . On day 1 , subjects received professional prophylaxis , suspended oral hygiene measures , and commenced using their allocated products . On day 5 , subjects were scored for disclosed plaque . RESULTS CHX sprays ( P<0.01 ) were the most effective sprays in preventing plaque regrowth , without significant differences between the two concentrations tested ( P>0.05 ) . TRN spray showed a significant inhibition of plaque regrowth in comparison to the negative control ( P<0.05 ) . CPC spray did not differ from saline spray ( P>0.05 ) . A similar trend of efficacy was detected for rinses . Although the effect on plaque regrowth observed with CHX rinses was superior to that of CHX sprays ( P<0.0003 ) , the latter did not cause side effects ( P>0.2 ) . CONCLUSIONS These findings , together with those from clinical trials , suggest that the CHX-containing sprays may represent an effective alternative to CHX rinses when mechanical oral hygiene has to be avoided in restricted areas . On the contrary , the TRN and CPC sprays showed little or no plaque inhibitory effects BACKGROUND / AIMS Chlorhexidine ( CHX ) spray has proven to be an easily applicable method for the chemical control of plaque in elderly and h and icapped patients . A r and omized double-blind cross-over placebo-controlled trial was undertaken to compare the effects of 0.2 % CHX spray applied once or twice daily on the plaque and gingival indexes in 13 institutionalized elderly patients . METHOD The study subjects were r and omly assigned to one of two groups . During the first 30-day period , one group received 0.2 % chlorhexidine spray twice daily and the other received 0.2 % CHX spray once daily plus placebo spray once daily . A washout period of 42 days then followed , after which the groups were interchanged and the process was repeated for another 30-day period . Plaque index and gingival index were determined at the beginning and end of each period . The patients continued with their usual oral hygiene practice s throughout the study . RESULTS A significant reduction in plaque and gingival indexes was produced in both the groups . There were no significant differences in index scores between the groups . CONCLUSIONS The results of the present study suggest that a single-daily application of 0.2 % CHX spray is equally as effective in reducing plaque accumulation and gingival inflammation in institutionalized elderly patients as are two-daily applications of the same spray BACKGROUND This study aims to investigate the effect of various oral hygiene strategies on the symptoms of inflammation in neuromuscularly disabled patients and to define the optimum hygiene method . METHODS Fifty-nine neuromuscularly disabled participants , suffering from cerebral palsy , were r and omly divided into five groups as follows : Group M : manual toothbrush ( n=14 ) , Group E : electrically powered toothbrush ( n=9 ) , Group MC : manual toothbrush and chlorhexidine gluconate ( CHX ) spray ( n=13 ) , Group EC : electrically powered toothbrush and CHX spray ( n=9 ) , and Group C : CHX spray ( n=14 ) . The oral hygiene applications were provided by the parents and staff . At baseline and after 21 days the plaque index ( PI ) , the gingival index ( GI ) , and bleeding on probing ( BOP ) were recorded . RESULTS In intra-group comparisons of the pre- and post-application scores , in all groups the PI and GI scores and BOP percentages , except in Group C , were found significantly different ( p<0.05 ) . There were significant differences among the post-application scores , between Group M and Group E and between Group C and Group E in PI scores ; between Group C and Group E the difference in GI scores were found statistically significant ( p<0.05 ) . CONCLUSIONS Although all oral hygiene strategies reduced plaque and gingival inflammation , the results of our study suggested the electrically powered toothbrush could be more recommendable to neuromuscularly disabled people in these strategies , while the combined procedures appeared to be neither beneficial nor favorable BACKGROUND / AIMS This clinical trial aim ed at comparing 2 different means of delivering chlorhexidine digluconate ( CHX ) in the oral hygiene phase during the 2 weeks following periodontal surgery . METHOD 40 patients were r and omly divided into 2 groups : A ( using CHX mouthwash ) and B ( using CHX spray ) . Professional oral hygiene was carried out immediately before surgical operation . For 7 days after surgery , group A used CHX mouthwash and group B CHX spray on the teeth involved in the surgical procedure , while mechanical oral hygiene was maintained only on the teeth not involved surgically . After suture removal , on the 7th day , patients were allowed to perform mechanical oral hygiene also on surgical sites . Plaque index ( PI ) and stain index ( SI ) were evaluated on the 7th and 14th days after the operation . RESULTS In both groups , PI increased similarly with respect to the baseline in surgically involved teeth , being 0.25+/-0.41 ( SD ) and 0.15+/-0.26 , respectively , in A and B , on day 7 , and 0.14+/-0.23 ( A ) and 0.10+/-0.22 ( B ) , on day 14 . There was no significant difference between A and B on either day 7 or 14 . On the contrary , SI increased significantly in respect to the baseline over the 14 days in group A at both involved and not involved sites , while it did not differ from the baseline in group B. CONCLUSIONS The present results indicate that the efficacy of CHX spray in the post-surgical control of dental plaque is not different from that of CHX mouthwash . Tooth staining , on the contrary , was significantly lower in the group using CHX spray . The observed effects might be related to the way of delivering CHX and to the total dose administered , about 80 % lower in group B in respect to A. Further studies are needed to vali date the preliminary findings of the present study AIM To evaluate the clinical efficacy of two gel formulations containing chlorhexidine gluconate and neem extract with a commercially available chlorhexidine gluconate mouthwash . METHOD An open labelled r and omised six-week clinical study with parallel group design in 48 subjects divided into four groups . Plaque accumulation and gingival condition were recorded using plaque index and gingival index . On the basis of mean baseline plaque and gingival scores , subjects were allocated to four different groups , using their assigned products twice a day , before bed and after breakfast . Plaque and gingival scores were recorded after three and six weeks . RESULTS Mean plaque and gingival scores were reduced over the six-week trial period for experimental and control groups . Chlorhexidine gluconate gel reduced the plaque and gingival scores significantly more ( p<0.05 ) than the chlorhexidine gluconate mouthwash . Neem extract gel also showed significant ( p<0,05 ) reduction in plaque and gingival scores when compared with the control group . But there was no significant difference between the groups treated with chlorhexidine gel and neem extract gel . CONCLUSION The results of this clinical study indicate that better therapeutic efficacy can be achieved using gels for treating oral infections than conventional treatments using mouthwash OBJECTIVE To evaluate the effectiveness of oral health promotion interventions on clinical oral health . DESIGN Single-blind r and omized controlled trial conducted over 3 weeks of in-hospital rehabilitation . SETTING Stroke rehabilitation ward in Hong Kong . PARTICIPANTS Patients with stroke ( N=102 ) admitted to the rehabilitation ward . INTERVENTIONS Patients were r and omly assigned either : ( 1 ) oral hygiene instruction , ( 2 ) oral hygiene instruction and chlorhexidine mouthrinse , or ( 3 ) oral hygiene instruction , chlorhexidine mouthrinse , and assisted brushing . MAIN OUTCOME MEASURES Dental plaque , gingival bleeding , and oral functional status were assessed at baseline and review . Development of infectious complications were also monitored during the clinical trial . RESULTS Poor oral hygiene and an overall neglect of oral hygiene practice s were observed at baseline . Reductions in dental plaque were significantly greater in the 2 groups receiving chlorhexidine compared with the group receiving oral hygiene instruction alone ( P<.001 ) . Reductions in gingival bleeding scores were 3- to 4-fold greater in groups receiving chlorhexidine . No cases of pneumonia were observed during the course of the clinical trial . CONCLUSIONS The oral health condition of patients may be safeguarded after acute stroke with the use of chlorhexidine mouthrinse in conjunction with a st and ard mechanical plaque removal tool , such as an electric toothbrush . These interventions are acceptable to the majority of patients , and their administration poses a minimal burden to rehabilitation ward staff Chlorhexidine has been used as an aid to or replacement for oral hygiene measures in special needs groups such as the h and icapped . Previous studies have indicated that spray delivery of chlorhexidine is both effective and acceptable . This study evaluated twice daily use of a 0.2 % chlorhexidine spray as an adjunct to toothbrushing in a group of physically and mentally h and icapped adults attending a day training center . The study was a double-blind , placebo controlled , cross-over design involving two 31 days regimens separated by 30 days . Plaque , bleeding on probing , and pocketing were measured at the beginning and end of each regimen . There were clinical ly and statistically significantly lower plaque and bleeding scores at the end of the chlorhexidine compared to the placebo period . Pocketing was also significantly less after chlorhexidine , although in clinical terms the difference was small . The apparent acceptability and effectiveness of the regimen suggests that small doses of chlorhexidine delivered by sprays may be of considerable value as an aid to oral hygiene in h and icapped individuals There are a large number of mouthrinse products available to the general public for use as adjuncts to oral hygiene . Many have not been evaluated and relatively few comparisons of products have been made . This study compared 4 mouthrinse products containing cetylpyridinium chloride ( CPC ) , chlorhexidine , C31 G , or triclosan with saline rinse included as a placebo control . Twenty dentate volunteers took part in this 4-day plaque regrowth study which had a single blind , r and omized cross-over design balanced for residual effects . On day 1 of each study period , volunteers were rendered plaque free by a professional prophylaxis , suspended normal oral hygiene measures , and rinsed twice daily for 1 minute with 15 mL of the allocated rinse . On day 5 , subjects were scored for disclosed plaque by plaque index and plaque area . By both measures the order of decreasing product efficacy was chlorhexidine , CPC and triclosan , C31 G , and saline . All the differences in favor of the chlorhexidine product were highly significant as were those in favor of the other rinses compared to saline . It is concluded that the findings of this study reflect the actual chemical benefits of the products divorced from the indeterminate variable of toothbrushing The delivery of chlorhexidine by spray systems have been found useful in controlling plaque in h and icapped individuals . This study using a single blind crossover design compared chlorhexidine delivery by mouthwash and spray for plaque inhibitory effects . A group of 14 volunteers participated in two 4 day , no oral hygiene regimens . During one regimen chlorhexidine was professionally sprayed onto the teeth twice a day and during the other chlorhexidine was rinsed twice a day under supervision . Plaque regrowth from a zero baseline was recorded using a plaque index and by area . Little plaque accumulated during the two periods . There was no significant difference in plaque measurements following the use of the spray or mouthwash . This study demonstrated that chlorhexidine when sprayed under optimal conditions was as effective as a mouthwash at controlling plaque despite only requiring one seventh of a dose from a rinse . The results have implication s for the use and delivery of chlorhexidine for plaque control and are relevant to the proposed mode of action of this antiseptic A blind crossover trial was carried out to compare the effects of a 0.2 % chlorhexidine gluconate mouthrinse and a 0.035 % alexidine mouthrinse on plaque accumulation and salivary bacteria in a group of volunteers . The subjects refrained from all forms of oral hygiene during two 10-day periods and rinsed twice a day with the mouthwash r and omly allocated to the respective period . Prerinse , day 4 and day 10 total salivary aerobic and anaerobic bacterial counts were determined during each period . Plaque scores were recorded at the end of each 10-day period . Significantly more plaque accumulated in subjects rinsing with alexidine when compared with chlorhexidine . Significant and comparable reductions in salivary bacterial counts were observed with both chlorhexidine and alexidine on day 4 and day 10 when compared with pre-rinse counts . Although at the concentrations used alexidine was less effective than chlorhexidine , it may be of value as a short-term adjunct to oral hygiene The optimum dose of chlorhexidine delivered by mouthrinse , which balances efficacy against local side-effects , is generally considered to be in the region of 20 mg 2 x daily . Unfortunately , there have been few dose-response studies for chlorhexidine mouthrinses and for these , only limited details are published . The aims of this study were to determine the dose response of chlorhexidine to plaque inhibition and position a 0.1 % triclosan rinse within this model . 28 subjects took part in this 7-treatment , double-blind , r and omised cross-over 4-day plaque regrowth study . The rinses were 0.01 % , 0.05 % , 0.1 % and 0.2 % chlorhexidine , 0.1 % triclosan and minus active controls for chlorhexidine and triclosan . On day 1 from a zero plaque baseline , volunteers suspended tooth-cleaning and commenced supervised 2 x daily rinsing with 10 ml volumes of the allocated rinses . On Day 5 , plaque was scored by index and area . Treatment differences between the 7 rinses were highly significant . A clear dose-response pattern was seen for chlorhexidine with mean plaque scores decreasing with increasing dose . Even at 0.01 % , chlorhexidine showed considerable and significant plaque inhibition compared to control . Triclosan at 0.1 % showed limited plaque inhibition and less than 0.01 % chlorhexidine . The findings of this study suggest that consideration could be given to low concentration chlorhexidine rinses as adjuncts to oral hygiene The aim of the present study was to determine the effects of a 0.2 % hexetidine spray , used as a supplement to regular oral hygiene measures , on dental plaque and gingival condition following periodontal surgery . This study was carried out on 38 patients who required 2 episodes of periodontal surgery . Examinations regarding dental plaque were performed at 0 , 7 , 14 , 21 and 28 days , while the condition of the gingiva were examined at 0 and 28 days . Dental plaque was assessed by the Turesky modification of Quigley-Hein index ; the gingival condition was evaluated using the gingival index of Löe-Silness and the papilla bleeding index . In a double-blind cross-over study of 28 days duration , significant reduction in plaque accumulation and an improvement in wound healing were demonstrated for the test spray compared to the placebo In this study , eight institutionalized males received a 0.12 % chlorhexidine gluconate spray twice daily . A second group of eight males received a placebo spray in the same manner . The results indicated that pump-administered chlorhexidine spray can effectively reduce plaque and gingivitis in patients with mental retardation who are unable to brush their own teeth The objective of this study was to evaluate the effect of twice-daily oral sprays of 2 ml chlorhexidine ( 0.2 % ) and 2 ml stannous fluoride ( 0.2 % ) as the sole oral hygiene measure on plaque and gingivitis in h and icapped children . 52 institutionalized mentally h and icapped individuals ( aged 10 - 26 years ) were divided into 4 groups to participate in a 9-week , double-blind , r and omized clinical ly controlled trial , which included a cross-over . For the first 3 weeks , groups 3 and 2 had their mouths sprayed with chlorhexidine and stannous fluoride , respectively . Following a 3-week wash-out interval , groups 1 and 4 were sprayed with chlorhexidine and stannous fluoride , respectively . The alternate groups received a placebo , water . Plaque ( PI ) and gingival indices ( GI ) were recorded . Subgingival plaque sample s were collected and counts of spirochaetes , motile rods and cocci were taken using darkfield microscopy . By the 9th week of trial , the PI and GI were reduced by 48 % and 52 % for the stannous fluoride group . In the chlorhexidine group , reductions of 75 % ( PI ) and 78 % ( GI ) were achieved . Pair-wise comparisons of placebo , stannous fluoride and chlorhexidine using the U-test of Mann-Whitney revealed significant ( p less than 0.05 ) differences for both PI and GI scores in the placebo/stannous fluoride and placebo/chlorhexidine pair by the 9th week of the trial . In the stannous fluoride/chlorhexidine pair , only the PI was significantly reduced for those on chlorhexidine . Coccoid cells were more dominant at sites with low PI and GI scores ( stannous fluoride and chlorhexidine groups ) , while spirochaetes and motile rods were more frequent at sites with high PI and GI scores ( placebo group ) A 6-month double-blind , controlled clinical study was completed with 124 healthy adult subjects to determine the efficacy of 2 mouthrinses , Listerine ( LA ) and Peridex ( PX ) , used as supplements to regular oral hygiene measures in reducing supragingival dental plaque and gingivitis . Following screening examinations for entry levels of existing gingivitis and plaque , baseline gingival and plaque area indices , extrinsic tooth stain , supragingival calculus , bleeding and soft tissue condition were recorded . All subjects then received a complete dental prophylaxis to remove plaque , calculus and extrinsic stain . Subjects were r and omly assigned to 1 of 3 groups and performed supervised rinses twice daily for 30 s in addition to their normal oral hygiene , for 6 months . All indices were again evaluated at 3 and 6 months . After 6 months , LA and PX significantly ( p less than 0.001 ) inhibited development of plaque by 36.1 % and 50.3 % , respectively , and the development of gingivitis by 35.9 % and 30.5 % , respectively , compared to a hydroalcohol control . PX was more effective in inhibiting plaque and both mouthrinses appeared to be equally effective in inhibiting gingivitis . LA patients did not develop significant levels of stain or supragingival calculus at 6 months , compared to baseline or control . PX patients developed significant levels of extrinsic stain and supragingival calculus compared to baseline and control . Though PX was more effective than LA in the control of plaque , this study indicates that both LA and PX were effective agents in a regimen for the control of plaque and gingivitis OBJECTIVE The aim of this experimental gingivitis study was to assess the efficacy and safety of two new chlorhexidine ( CHX ) mouthrinses . MATERIAL AND METHODS Ninety volunteers participated in this investigator-blind , r and omized , clinical -controlled trial in parallel groups . During the treatment period , no oral hygiene measures except rinsing with non-alcoholic 0.2 % CHX or 0.2 % CHX/0.055 % sodium fluoride mouthrinses , a positive control , or a negative control were permitted . The primary parameter was the gingival index ; the secondary parameters were plaque index , discolouration index , and bleeding on probing . Clinical examinations were conducted 14 days before the start of the study , at baseline , and after 7 , 14 , and 21 days . The two sample t-test , anova , and ancova were used for the statistical analysis . RESULTS No difference in efficacy was found between the two new CHX formulations and the positive control . On day 21 , statistically significantly less gingival inflammation and plaque accumulation compared with placebo were observed . Besides discolouration and taste irritations , no adverse events were recorded . CONCLUSION The two new CHX mouthrinses were able to inhibit plaque re-growth and gingivitis . Neither the omission of alcohol nor the supplementation with sodium fluoride had weakened the clinical efficacy of CHX with respect to the analysed clinical parameters Experimental mouthrinses containing 0.4 % zinc sulphate and 0.15 % triclosan , which differed in base formulations were compared to a commercially available non-active control mouthrinse . Following baseline clinical examinations for plaque , gingival bleeding and calculus , the volunteers were provided with a dental prophylaxis and given oral hygiene instruction , stratified into 3 groups and given 1 of 3 mouthrinses . Further clinical assessment s were performed after 4 , 16 and 28 weeks . Salivary mutans streptococci were also monitored during the study . At 4 weeks , plaque and calculus scores in all groups were low compared to baseline . During the remainder of the study , these improvements were not maintained and both plaque and calculus levels increased in all groups . Plaque was significantly lower ( P < 0.05 ) than in the control at all time points . Calculus was significantly lower ( P < 0.05 ) than in the control at all time points . Calculus was significantly lower at week 28 for experimental mouthrinse group 2 . Gingival bleeding also decreased in the initial 4 weeks but increased thereafter in the control group . In contrast , gingival bleeding was significantly ( P < 0.05 ) lower in the two experimental groups than in the control group . No significant changes in mutans streptococci were observed A relatively small number of agents are used in mouthrinse products , although the possible variability in the final formulations is enormous . The aim of this study was to compare equal concentrations of 3 antimicrobial agents , in simple formulations , for plaque inhibition . This 4-day plaque regrowth study was a 5-cell , r and omised , double blind cross-over design , involving 20 healthy human volunteers . The mouthrinse formulations were aqueous 0.05 % solutions of cetylpyridinium chloride ( CPC ) , chlorhexidine and triclosan , together with a 0.1 % CPC and a minus active control rinse . On Day 1 , from a zero plaque baseline , volunteers ceased normal oral hygiene and rinsed 2x daily for 1 min . with 10-ml volumes of the allocated rinses . On Day 5 , plaque was scored by index and area . All rinses produced lower mean plaque values compared to control , but unlike the CPC and chlorhexidine rinses , the differences with triclosan did not always reach significance . The CPC and chlorhexidine rinses were always significantly more effective than the triclosan rinse . The greatest plaque inhibition was with 0.1 % CPC although rarely significantly greater than the 0.05 % CPC and chlorhexidine rinses which were similar in efficacy . The results indicate that further studies on lower concentration chlorhexidine solutions are warranted INTRODUCTION Chemical management of dental plaque for controlling oral hygiene becomes necessary in high-risk patients such as the mentally retarded . MATERIAL AND METHODS Thirty-seven mentally h and icapped patients aged 10 - 19 years and with severe plaque and gingivitis were divided into two treatment groups : Group I ( daily mouthrinse with triclosan-zinc for 8 weeks ) and Group II ( 0.2 % chlorhexidine spray for 2 weeks ) . Both groups were evaluated at the start of the study and after 2 and 8 weeks . RESULTS Significant reductions in plaque were observed in Group I after two weeks , with very significant improvements in both plaque and gingivitis after 8 weeks . In Group II , highly significant reductions in both indices were recorded after two weeks of treatment - significance persisting after 8 weeks . CONCLUSIONS Triclosan-zinc mouthrinse and chlorhexidine spray can be effective adjuncts to tooth brushing for controlling dental plaque and gingivitis in mentally retarded patients Background : The aim of this study was to evaluate the antiplaque effects of an alcohol‐free essential oil ( alcohol‐free EO ) mouthwash and an amine fluoride/stannous fluoride with zinc lactate ( SnFl‐Zn ) mouthwash compared to a positive control of chlorhexidine ( CHX ) mouthwash , using an in vivo plaque regrowth model of 3 days . Material s and methods : The study was design ed as a double‐masked , r and omized , crossover clinical trial , involving 20 volunteers to compare two different mouthwashes , using a 3‐day plaque accumulation model . After receiving thorough professional prophylaxis at baseline , over the next 3 days , each volunteer refrained from all oral hygiene measures and performed two daily rinses with 20 ml of the test mouthwashes . A 0.20 % CHX rinse served as a positive control . At the end of each experimental period , plaque was assessed , and the panellists completed a question naire . Each subject underwent a 14‐day washout period , and then , there was another allocation . Results : The SnFl‐Zn mouthwash has shown a better inhibitory activity on plaque regrowth compared to the alcohol‐free EO mouthwash in the whole mouth ( plaque index = 1.93 against 2.45 , respectively ) , but there was less of an effect compared to the CHX group , with an overall plaque index of 1.41 . The differences of 0.52 between alcohol‐free EO and SnFl‐Zn and between SnFl‐Zn and CHX and of 0.96 between alcohol‐free EO and CHX were all statistically significant ( P < 0.001 ) . Conclusion : The alcohol‐free EO mouthwash seemed to have less of an inhibiting effect on plaque regrowth than the amine fluoride/SnFl‐Zn mouthwash and the CHX control A staining index has been proposed which is simple to use clinical ly and yet is sensitive enough to detect small changes in staining levels between different groups . Accurate scale drawings from An atlas of tooth form were reproduced . Outlines of the labial and lingual surfaces of all eight incisor teeth were enlarged to scale ( magnification X 4 ) and each tooth face divided into 4-mm squares . All areas of extrinsic stain were drawn by the examiner on the grid system . This method has been tested in three clinical trials and the reproducibility investigated . In 161 duplicate examinations a total of 1,830 stained squares were scored by one examiner , compared with 1,853 squares by the second examiner ; the reproducibility ratio was 0.155 and the coefficient of correlation was 0.956 . The method proved sufficiently sensitive to record differences in staining levels in groups using two dentifrices ; one was a normal commercial product with an abrasivity against dentin approximately two-thirds that of the other paste . The proposed Extrinsic Stain Index provides data which can be analyzed by appling parametric or nonparametric tests OBJECTIVE The objective of this independent , double-blind , parallel , six-week clinical study was to assess the efficacy of a commercially available mouthrinse containing 0.05 % cetylpyridinium chloride ( CPC ) for controlling established dental plaque and gingivitis relative to that of a control mouthrinse without CPC . METHODS Adult male and female subjects from the Maceió , Brazil area reported to the clinical facility , after having refrained from any oral hygiene procedures for 12 hours , and from eating , drinking , and smoking for four hours , for an assessment of the oral soft and hard tissues , and for a baseline gingivitis and dental plaque evaluation . Qualifying subjects were r and omly assigned to one of the two treatment groups , and were provided with their assigned mouthrinse , and an adult soft-bristled toothbrush and toothpaste for home use . Over the six-week period of home use , during which there were no restrictions regarding diet or smoking habits , subjects were instructed to brush their teeth for one minute twice daily with the supplied toothbrush and a commercially available fluoride toothpaste , to rinse their mouths with water after brushing , and then to rinse with their assigned mouthrinse for one minute before expectorating . The use of any other oral hygiene products or procedures , such as floss or interdental stimulators , was not permitted during the study . After six weeks of product use , subjects returned to the clinical facility , having followed the same restrictions with respect to oral-hygiene procedures , eating and drinking , as with the baseline visit , and the oral soft and hard tissue assessment s and gingivitis and dental plaque evaluations were repeated . RESULTS One-hundred and ten subjects complied with the protocol and completed the study . With regard to supragingival plaque , after six weeks of product use , the subjects using the 0.05 % CPC mouthrinse exhibited statistically significant reductions from baseline in whole-mouth Plaque Index scores ( 32.1 % ) , in Plaque Index scores measured at interproximal sites ( 31.3 % ) , and in Plaque Severity Index scores ( 84.8 % ) . Subjects using the control mouthrinse exhibited statistically significant reductions from baseline in whole-mouth Plaque Index scores ( 7.0 % ) , in Plaque Index scores measured at interproximal sites ( 6.4 % ) , and in Plaque Severity Index scores ( 24.5 % ) . When compared to the control mouthrinse group , the 0.05 % CPC mouthrinse group presented statistically significant greater reductions in whole-mouth Plaque Index scores ( 27.9 % ) , in Plaque Index scores measured at interproximal sites ( 27.9 % ) , and in Plaque Severity Index scores ( 81.1 % ) after six weeks of product use . With regard to gingivitis , after six weeks of product use , subjects using the 0.05 % CPC mouthrinse exhibited statistically significant reductions from baseline in whole-mouth Gingival Index scores ( 25.0 % ) , in Gingival Index scores measured at interproximal sites ( 25.3 % ) , and in Gingivitis Severity Index scores ( 42.4 % ) . Subjects using the control mouthrinse exhibited statistically significant reductions from baseline in whole-mouth Gingival Index scores ( 6.5 % ) , in Gingival Index scores measured at interproximal sites ( 5.5 % ) , and in Gingivitis Severity Index scores ( 11.6 % ) . When compared to the control mouthrinse group , the 0.05 % CPC mouthrinse group presented statistically significant greater reductions in whole-mouth Gingival Index scores ( 19.8 % ) , in Gingival Index scores measured at interproximal sites ( 20.7 % ) , and in Gingivitis Severity Index scores ( 35.5 % ) after six weeks of product use . CONCLUSION The results of this double-blind , parallel , six-week clinical study support the conclusion that a mouthrinse containing 0.05 % CPC is efficacious for controlling established dental plaque and gingivitis . As measurements were conducted 12 hours after product use , the results also demonstrate that the 0.5 % CPC mouthrinse provides 12-hour protection against plaque and gingivitis BACKGROUND AND AIM The experimental gingivitis model is a well-established method in comparing the chemical antiplaque activity of agents and products . The aim of the present study was to use time in order to achieve an exit level of bleeding on probing ( BOP ) as the primary outcome variable . METHODS The study was a single blind , r and omised four treatment parallel group design employing 76 healthy volunteers . The cohort was accepted into the study proper if they achieved a level of < /= 25 % BOP after a 5-week pre- study oral hygiene phase . At baseline , 1 , 2 , 3 , 4 , 5 weeks BOP , modified gingival index ( MGI ) and plaque index scores were obtained from each subject . After baseline , oral hygiene was suspended and subjects rinsed twice daily with one of the test rinses , namely : 1 0.05 % cetylpyridinium chloride 2 Control fluoride 3 0.2 % chlorhexidine 4 0.3 % triclosan Subjects were removed from the study when they achieved > /= 50 % BOP . Using the baseline and exit BOP , MGI and plaque , a deterioration rate for each parameter was derived and used as the unit of analysis . RESULTS There were highly significant treatment differences for all three parameters . Paired analyses revealed chlorhexidine was highly significantly more effective than the other rinses for all three parameters . CPC and triclosan were not different from the control for BOP , but CPC was significantly different from the control for MGI and plaque , and triclosan was different from the control for plaque . There were no differences between the CPC and triclosan rinses . CONCLUSIONS The method achieved the expected result of differentiating between the chlorhexidine and the other rinses . Some modification of the method , primarily to group sizes , should improve specificity . The method has the considerable volunteer appeal of early exit , particularly when allocated to control or low activity treatments for plaque PURPOSE Hyaluronan , commonly known as hyaluronic acid , has been shown to have anti-inflammatory action , bacteriostatic effect and antioxidant properties , thus making its use as a long-term anti-plaque and anti-gingivitis agent an appealing proposition . The aim of the present study was to evaluate the efficacy of 0.025 % hyaluronan-containing mouthwash in comparison with 0.2 % chlorhexidine and a water-based mouthwash and also to evaluate its antibacterial efficacy on isolated strains of periodontopathogens . MATERIAL S AND METHODS Forty-five volunteers in a hospital setting were recruited . A single-blinded , parallel design , r and omised controlled trial was carried out and the 4-day plaque re-growth model was used to study the efficacy of the three mouthwashes . Microbiological and clinical evaluation was performed by culturing and using dental indices , respectively . The three mouthwashes used in the present study were commercially available 0.025 % sodium hyaluronate , 0.2 % chlorhexidine and a water-based rinse ( negative control ) . Effects of the three mouthwashes were tested on the growth of isolated strains of Porphyromonas gingivalis ( Pg ) , Aggregatibacter actinomycetemcomitans ( Aa ) and Prevotella intermedia ( Pi ) . RESULTS In vitro , hyaluronan had a distinct effect on the growth of Aa and Pi with no effect on the growth of Pg . In vivo , the differences between the individual rinse solutions and the water-based solution showed significantly less plaque regrowth with respect to both chlorhexidine ( P = 0.033 ) and hyaluronan ( P = 0.045 ) when compared to the negative control . The difference between chlorhexidine and hyaluronan was not statistically significant ( P = 0.69 ) . CONCLUSIONS Hyaluronan (0.025%)-containing mouthwash was comparable to chlorhexidine ( 0.2 % ) in inhibiting plaque growth in vivo , and it significantly reduced the growth of Aa and Pi in OBJECTIVES Hyaluronic acid ( hyaluronan ) is a glycosaminoglycan with anti-inflammatory and antiedematous properties . It was evaluated in a gel formulation for its effect in the treatment of plaque-induced gingivitis . METHOD In a r and omised double-blind study , 50 male subjects with plaque-induced gingivitis were divided into two groups and used a verum or placebo gel twice daily additionally to oral hygiene for a 3-week treatment period . Clinical indices ( API , Turesky index , PBI ) and crevicular fluid variables ( peroxidase , lysozyme ) were determined at baseline and after 4 , 7 , 14 and 21 days , respectively . RESULTS Significant improvements could be found for all clinical variables in both groups . The verum group showed significant improvement in the study area for the plaque indices beginning with day 4 ( P = 0.011 ) and the PBI beginning with day 7 ( P = 0.001 ) in comparison with the placebo group . The crevicular fluid variables were significantly improved in the centre of the studied inflammation area in the verum group . Here all studied sites had significant decreases in peroxidase ( 176.72 - 128.75 and 188.74 - 128.75 U/L ) and lysozyme ( 1.27 - 0.27 and 1.30 - 0.33 mg/L ) activities after 7 , 14 and 21 days ( P between 0.034 and < 0.001 ) , whereas in the placebo group only one site showed a significant decrease for lysozyme ( 1.74 - 0.75 mg/L ) after 7 and 21 days ( P = 0.048 and 0.025 ) . CONCLUSIONS These data suggest that a hyaluronan containing gel has a beneficial effect in the treatment of plaque-induced gingivitis Chlorhexidine gluconate has been studied as an adjunct to st and ard oral hygiene techniques in developmentally disabled patients in reducing plaque accumulation . The purpose of this double blind crossover study was to determine the efficacy of two concentrations of chlorhexidine spray ( 0.12 % and 0.06 % ) on plaque accumulation in developmentally disabled patients . Informed consent was obtained for 8 developmentally disabled patients 12 to 33 years of age . Patients were r and omly assigned to one of two groups of four each . One group received twice daily 0.12 % chlorhexidine spray while the other received the 0.06 % chlorhexidine spray for 30 days , followed by twice daily chlorhexidine spray ( 0.12 % and 0.06 % ) alternating groups , for a period of 30 days . Final plaque indices were determined . Normal oral hygiene practice s continued throughout the study . Significant plaque reduction occurred with the 0.12 % and 0.06 % spray solutions . No significant differences occurred between the two concentrations . The results of this study suggest that twice daily chlorhexidine spray at a concentration of 0.06 % is as effective in reducing plaque accumulation as a 0.12 % chlorhexidine concentration BACKGROUND Chlorhexidine ( CHX ) is widely accepted as the most effective product in the control of supragingival plaque . It is available in different delivery devices . The aim of this study was to test whether 0.12 % CHX spray was as effective as 0.2 % CHX spray and 0.2 % CHX mouthwash in a 3-day " de novo " plaque formation model . METHODS Ninety volunteers were enrolled into a single-blind , r and omized , three-group parallel study . They received a thorough dental prophylaxis prior to the test period . Subjects were divided r and omly into three equal groups . They were requested to refrain from all forms of mechanical oral hygiene and instructed to use only their assigned product during the 3-day experimental period . After 3 days , the plaque growth was assessed using the Quigley and Hein plaque index ( Q&H PI ) at six sites per tooth . RESULTS After 3 days , the CHX mouthwash group had a mean Q&H PI of 1.17 compared to 1.41 for the 0.2 % CHX spray and 1.49 for the 0.12 % CHX spray . The difference between the mouthwash and the two sprays was statistically significant , whereas the two sprays did not differ significantly from each other . CONCLUSIONS Within the limitations of this 3-day " de novo " plaque formation study , the two sprays were not as effective as the mouthwash in plaque inhibition . No significant difference was found between the two sprays . To achieve the same effectiveness as a mouthwash , a higher dose ( number of puffs ) of CHX spray may be necessary Caries and gingivitis prevention may benefit from chemotherapeutic plaque control , therefore we compared in a cross – over study with 5 subjects the anti – acidogenic effects of a single use of AmF – SnF2 mouthrinse solutions ( Meridol ® with and without 5 % alcohol ) with baseline and with the effects of a placebo and a chlorhexidine mouthrinse ( CHX ) . Buccal plaque was collected 0.5 , 3 and 8 h after the subjects used one of the mouthrinses , each time before and after a rinse with 10 % sucrose to induce lactic acid production . Sample s were analysed for acid anions by capillary electrophoresis and for protein . At 0.5 h after the use of AmF – SnF2 or CHX , the concentration of acetate in resting plaque was 70 % lower than at baseline or after using the placebo . Average post – sucrose acetate and lactate concentrations in the placebo group were 30–80 % higher than at baseline ; up to 3 h this difference was significant . 8 h after using AmF – SnF2 or CHX , the post – sucrose acetate and lactate concentrations were still 30–50 % lower than after the placebo , and up to 40 % lower than at baseline . To conclude , AmF – SnF2 in both Meridol formulations and CHX were shown to have a similar potency to inhibit acid production after a single rinse BACKGROUND / PURPOSE This r and omized clinical trial was aim ed at comparing two different means of delivering chlorhexidine digluconate ( CHX ) for plaque control during the 2 weeks following implant surgery . MATERIAL S AND METHODS Twenty patients selected for implant therapy were r and omly divided into two groups : 10 subjects used 15 ml of 0.12 % CHX mouthrinse ( control group ) and 10 used 0.2 % CHX spray ( test group ) . Professional oral hygiene was carried out immediately before surgery . During the 14 days following surgery mechanical oral hygiene was performed only at the teeth not surgically involved . Plaque index ( PI ) , stain index ( SI ) , modified gingival index and taste alteration were assessed on the 7th and 14th day after surgery . The clinical parameters were evaluated at four tooth surfaces by a single examiner . Teeth proximal to surgical site and teeth not involved were statistically compared . RESULTS In both groups , the PI increased similarly , with respect to the baseline , at days 7 and 14 . There was no significant difference between the two groups at either time point . On the contrary , in the control group , the SI increased significantly when compared with baseline over the 14 days both at teeth nearest to surgical sites and at not-involved sites . In the test group pigmentation was consistent only at teeth proximal to the surgical site . When considering not-involved sites , tooth staining was significantly lower in the test with respect to the control group . CONCLUSIONS The present study indicates that the efficacy of CHX spray in the post-surgical control of dental plaque is similar to that of CHX mouthwash . Tooth staining , however , is significantly lower in the spray group at sites not surgically involved . These effects might be related to the route of CHX delivery , as well as the total dose administered that was significantly lower in the spray group with respect to the rinse group OBJECTIVE To evaluate the effect of a mouth-rinse formulation combining benzydamine hydrochloride and cetylpyridinium chloride ( BNZ+CPC ) in preventing de novo plaque formation , in comparison with CPC and placebo mouth rinses . PATIENTS AND METHODS This was a controlled , observer-blind , cross-over study . In this model of plaque re-growth , subjects received a session of oral prophylaxis and were directed to withdraw oral hygiene measures for the next 4 days , using only the mouth rinse assigned . The outcome parameters were the plaque index ( PlI ) and gingival index ( GI ) . In addition , microbiological evaluation of the subgingival microflora , by means of culture , was performed , as well as patient-based variables . Data analysis was carried out using anova for Latin-square design . RESULTS The analysis of variance showed a significant statistical difference between the BNZ+CPC association and placebo ( p<0.0001 ) . No differences between CPC and placebo were detected considering multiple comparisons between treatments . The 90 % confidence interval of the differences between BNZ+CPC and CPC showed no equivalence between treatments , being the PlI lower in the BNZ+CPC group . No significant difference between groups in GI was observed . Mean anaerobic colony-forming units ( CFU ) demonstrated a significant increase between visits in all groups ( p<0.001 ) and differences among groups were not significant . Subjects treated with BNZ+CPC frequently reported " tingling mouth " and " numbness mouth " . CONCLUSION Within the limitations of the study model , the BNZ+CPC combination showed a statistically significant plaque-inhibitory capacity , as compared with the placebo mouth rinse , and an additive effect as compared with CPC . No relevant clinical or microbiological adverse effects were detected OBJECTIVE The objective of this independent , double-blind , seven-day clinical study was to assess the efficacy of a commercially available mouthrinse containing 0.05 % cetylpyridinium chloride ( CPC ) in preventing dental plaque build-up relative to that of a control mouthrinse without 0.05 % CPC . METHODS Adult male and female subjects from the São Paulo , Brazil area reported to the clinical facility , having refrained from any oral hygiene procedures for 12 hours , and from eating , drinking , and smoking for four hours , for an assessment of the oral soft and hard tissues and a baseline dental plaque evaluation . Subjects qualifying for participation received a complete dental prophylaxis . Qualifying subjects were r and omly assigned into one of the two treatment groups and were provided with their assigned mouthrinse , an adult soft-bristled toothbrush , and a commercially available fluoride toothpaste for home use . Over the seven-day period of home use , during which there were no restrictions regarding diet or smoking habits , subjects were instructed to brush their teeth for one minute twice daily ( morning and evening ) with the toothbrush and toothpaste supplied , to rinse their mouths with water after brushing , and then to rinse with 15 ml of their assigned mouthrinse for one minute before expectorating . The use of other oral hygiene products or procedures , such as floss or interdental stimulators , was not permitted during the study . After seven days of product use , subjects returned to the clinical facility having followed the same restrictions with respect to oral hygiene procedures , eating and drinking , as prior to the baseline examination , and the oral soft and hard tissue assessment s and dental plaque evaluations were repeated . RESULTS Forty-three subjects complied with the protocol and completed the study . Results demonstrated that after seven days of product use , mean plaque levels were statistically significantly lower ( p < 0.05 ) than the pre-prophylaxis levels for both treatment groups . The mean plaque level for the CPC mouthrinse group was 46.1 % of the pre-prophylaxis plaque level , whereas the mean plaque level for the control mouthrinse group was 75.5 % of the pre-prophylaxis plaque level . The results demonstrate a statistically significant reduction in plaque build-up for the CPC mouthrinse group ( 29.3 % ) as compared to the control group . CONCLUSION The overall results from this double-blind clinical study support the conclusion that , after seven days of product use , a mouthrinse containing 0.05 % CPC provides significantly greater efficacy in preventing dental plaque build-up than a control mouthrinse without 0.05 % CPC . As measurements were made 12 hours after final product use , the results also demonstrate that the CPC rinse provides 12-hour protection against dental plaque build-up OBJECTIVES Evaluate the efficacy and safety of an experimental toothbrush with a slow-release system of chlorhexidine ( CHX ) and determine its ability to inhibit plaque , bleeding , staining and oral tissue abnormalities during 6 weeks of use . MATERIAL AND METHODS One hundred and fifty healthy volunteers were r and omly assigned to one of three groups : the Test Brush group with a template slow-delivery system of CHX ( Ttb ) , the Control Brush group without CHX ( Ctb ) and the Control Brush group without CHX but rinsing post-brushing with a 0.2 % CHX mouthrinse ( Ctb+R ) . At baseline as well as at 3 and 6 weeks , all clinical parameters were assessed . Following the baseline assessment , a supragingival prophylaxis was provided . RESULTS One hundred and forty subjects completed the study . The Ctb+R group had lower plaque and bleeding scores than the Ttb and the Ctb group and significantly ( p=0.0001 ) higher stain scores . There were no significant differences in plaque , bleeding and stain scores between the Ttb and the Ctb group . No differences were detected in oral tissue changes , except for discoloration of the tongue . CONCLUSIONS In the present study , no beneficial effect could be demonstrated for the experimental CHX-releasing toothbrush . The use of a 0.2 % CHX mouthrinse ( in combination with brushing ) remains the gold st and ard for additional chemical plaque control |
10,404 | 28,717,987 | Rankogram plots revealed sumatriptan and combined continuous and pulsed radiofrequency thermocoagualtion have the highest probability of being the best treatments in the respective group of interventions .
No inconsistency was observed between direct and indirect comparisons .
Conclusion We found that drug-related interventions that include sumatriptan , intranasal lidocaine , intravenous lidocaine , and botulinum toxin and combined continuous and pulsed radiofrequency thermocoagulation had significant effects in reducing pain in patients with refractory TN .
However , the quality of evidence was grade d as very low for all except botulinum toxin | Introduction Patients with trigeminal neuralgia ( TN ) are often refractory to recommended first-line agents .
Due to the absence of a systematic review , we undertook a network meta- analysis to assess various interventions that can be used to manage refractory TN . | BACKGROUND Pharmacotherapy is the main treatment for management of trigeminal neuralgia . However , many patients become refractory to drugs . OBJECTIVES The present study aim ed to evaluate the effect of adding calcitonin to local anesthetic and methylprednisolone using a modified coronoid approach in management of trigeminal neuralgia pain involving the m and ibular and /or maxillary branches . STUDY DESIGN R and omized double blind clinical trial . SETTING Hospital outpatient setting . METHODS Thirty-three patients received maxillary and m and ibular blocks by a modified coronoid approach . Patients were allocated into 2 groups . Group 1 received a block with 3 mL of lidocaine 0.5 % plus 40 mg of methylprednisolone and another syringe contained 1 mL of 0.9 % saline . Group 2 received a block with 3 mL of lidocaine 0.5 % plus 40 mg of methylprednisolone and another syringe contained 50 international units of calcitonin . Pain was evaluated by visual analog scale ( VAS ) before the block ( basal ) , at 2 weeks , one month after the procedure , and monthly for one year . Duration of the effective pain relief of the first block ( VAS = 3 ) was reported . Repeated blockade was allowed for any patient reporting a VAS > 30 mm during one year of follow-up and the number of blocks were reported . Adverse effects were also reported . RESULTS A significantly longer duration of effective pain relief was noticed in group 2 compared with group 1 ( P < 0.0004 ) while the duration of effective pain relief of the second block in group 1 was 28.5 ± 8.9 weeks . Four patients did not need repeated blocks in group 1 versus 15 in group 2 . Six patients received 2 blocks versus 2 patients in each group , respectively . Moreover , 6 patients needed 3 blocks in group1 versus none in group 2 . No serious adverse events were reported during or after the interventional procedure . VAS was comparable in both groups ( P > 0.05 ) . LIMITATIONS Small sample size . CONCLUSION Calcitonin may be a useful additive to local anesthetic and steroid in management of trigeminal neuralgia . Also , a modified coronoid approach for maxillary and m and ibular nerve is simple , free of radiation , safe , and may be an effective percutaneous procedure in trigeminal neuralgia . KEY WORDS Calcitonine , modifed , coronoid approach , trigeminal neuralgia Background In the majority of cases , trigeminal neuralgia ( TN ) is a unilateral condition with ultra-short stabbing pain located along one or more branches of the trigeminal nerve . Although prophylactic pharmacological treatment is first choise , considering of insufficient effect or unacceptable side effects , neurosurgical treatment or lesion treatment should be considered . In addition to all these procedures mentioned above , one approach has been based on local intradermal and /or submucosal injections of Botulinum Toxin Type A ( BTX-A ) . Methods We conducted a r and omized , double-blind , placebo-controlled since November 2012 , and adopted local multi-point injection in 84 cases of classical TN with different doses of BTX-A. Eighty four patients were r and omized into following groups : placebo ( n = 28 ) ; BTX-A 25U ( n = 27 ) ; BTX-A 75U ( n = 29 ) . Follow-up visits were conducted every week after the injection , and the overall duration of the study for each patient were 8 weeks to observe the pain severity , efficacy and adverse reactions at endpoint . Results The visual analogue scale ( VAS ) scores of 25U and 75U groups reduced significantly compared to placebo as early as week 1 , and sustained until week 8 throughout the study . There was no significant difference in VAS between 25U and 75U groups throughout the study . The response rates of 25U group ( 70.4 % ) and 75U group ( 86.2 % ) were significantly higher than placebo group ( 32.1 % ) at week 8 , and there was no significant difference between 25U and 75U groups . Evaluation of the Patient Global Impression of Change ( PGIC ) demonstrated that 66.7 % ( 25U group ) and 75.9 % ( 75U group ) of the patients reported that their pain symptoms were ‘ much improved ’ or ‘ very much improved ’ versus 32.1 % of the placebo group , and there was also no significant difference between 25U and 75U groups . All adverse reactions were grade d as mild or moderate . Conclusions BTX-A injection in TN is safe and efficient . It is a useful treatment for refractory TN . Lower dose ( 25U ) and high dose ( 75U ) were similar in efficacy in short-term Background Carbamazepine ( CBZ ) formed the gold st and ard drug in trigeminal neuralgia ( TN ) treatment but faces high therapeutic failure . This defined the need to explore a second line of drug therapy . The study aim ed at comparing two alternate drugs i.e. Lamotrigine ( LTG ) and Pregabalin ( PGB ) , in the management of TN refractory to therapeutic doses of CBZ . Methods Twenty-two patients with diagnosis of refractory TN were enrolled and r and omly allotted into 2 groups of 11 each . Each group was subjected to a crossover analysis using LTG and PGB together with CBZ , for a period of 6 weeks . Patients maintained a pain diary , the scores of which , along with global evaluation scores , determined the primary outcome . Reevaluation of symptoms after 6 months was done to assess long term efficacy with study drugs . Results Both LTG and PGB were effective over CBZ alone ( p < 0.05 ) ; however , statistically insignificant difference ( p > 0.05 ) was observed between the two groups using Mann – Whitney tests . Unlike LTG , side effects like nausea , insomnia and concentration loss were minimal with PGB thus exhibiting greater patient compliance . Secondary analysis showed complete relief in 4 patients on PGB ( mean dose 240.68 mg/day ) while 6 had partial relief . Three patients on LTG ( mean dose 310.90 mg/day ) reported relapse of acute symptoms and required peripheral alcohol blocks . Conclusion Pregabalin has potential anti-neuralgia properties comparable to LTG . However , the level of patient ’s tolerance seen with PGB exceeds that with LTG . 6 months follow-up records suggest that PGB together with CBZ offers a more reliable pain control than with LTG BACKGROUND Trigeminal nerve block has been widely used for trigeminal neuralgia . This may induce paraesthesia . The second division of the trigeminal nerve passes through the sphenopalatine ganglion , which is located posterior to the middle turbinate and is covered by a mucous membrane . We examined the effectiveness of intranasal lidocaine 8 % spray on paroxysmal pain in second-division trigeminal neuralgia . METHODS Twenty-five patients with second-division trigeminal neuralgia were r and omized to receive two sprays ( 0.2 ml ) of either lidocaine 8 % or saline placebo in the affected nostril using a metered-dose spray . After a 7 day period , patients were crossed over to receive the alternative treatment . The paroxysmal pain triggered by touching or moving face was assessed with a 10 cm visual analogue scale ( VAS ) before and 15 min after treatment . Patients used a descriptive scale to grade pain outcome , and were asked to note whether the pain returned and how long after therapy it recurred . RESULTS Intranasal lidocaine 8 % spray significantly decreased VAS [ baseline : 8.0 ( 2.0 ) cm , 15 min postspray : 1.5 ( 1.9 ) cm , mean ( SD ) ] , whereas the placebo spray did not [ 7.9 ( 2.0 ) cm , 7.6 ( 2.0 ) cm ] . Moreover , pain was described as moderate or better by 23 patients of the lidocaine spray and 1 of the placebo group . The effect of treatment persisted for 4.3 h ( range 0.5 - 24 h ) . CONCLUSIONS Intranasal lidocaine 8 % administered by a metered-dose spray produced prompt but temporary analgesia without serious adverse reactions in patients with second-division trigeminal neuralgia Trigeminal neuralgia is the most common neuralgia . Its therapeutic approach is challenging as the first line treatment often does not help , or even causes intolerable side effects . The aim of our r and omized double blind , placebo controlled , crossover study was to investigate in a prospect i ve way the effect of lidocaine in patients with trigeminal neuralgia . Twenty patients met our inclusion criteria and completed the study . Each patient underwent four weekly sessions , two of which were with lidocaine ( 5 mgs/kg ) and two with placebo infusions administered over 60 minutes . Intravenous lidocaine was superior regarding the reduction of the intensity of pain , the allodynia , and the hyperalgesia compared to placebo . Moreover , contrary to placebo , lidocaine managed to maintain its therapeutic results for the first 24 hours after intravenous infusion . Although , intravenous lidocaine is not a first line treatment , when first line medications fail to help , pain specialists may try it as an add-on treatment . This trial is registered with NCT01955967 We conducted a prospect i ve r and omized controlled study to evaluate whether continuous radiofrequency ( CRF ) combined with pulsed radiofrequency ( PRF ) to the Gasserian ganglion ( GG ) decreases the side effects of CRF while preserving efficacy . Sixty patients diagnosed with classic trigeminal neuralgia ( TN ) were treated with either 75 ° C CRF for 120 s to 180 s ( SCRF group ) , 75 ° C CRF for 240 s to 300 s ( LCRF group ) , or 42 ° C PRF for 10 minutes ( min ) followed by 75 ° C CRF for 120 s to 180 s ( PCRF group ) . Patients were assessed for pain intensity , quality of life ( QOL ) , and intensity of facial dysesthesia before ( baseline ) , and at seven days , three months , six months , and 12 months after the procedure . The efficacy in pain relief was most significant on the seventh day after treatment and there were no significant differences between groups . After 12 months , > 70 % of patients in each group had complete pain relief , and the QOL in all three groups had increased significantly compared to baseline . The intensity of facial dysesthesia was mildest in the SCRF group and most severe in the PCRF group on the seventh day after the procedure , but most persistent in the LCRF group . Patients who receive PRF combined with CRF to the GG can achieve comparable pain relief to those who receive CRF alone , and shorter exposure of CRF could result in less destruction of the target tissue Objective : To estimate the lifetime prevalence of trigeminal neuralgia ( TN ) and persistent idiopathic facial pain ( PIFP ) in a population -based sample in Germany . Methods : A total of 3336 responders of 6000 contacted inhabitants of the city of Essen in Germany were screened using a self- assessment question naire . 327 individuals , who reported recurrent facial pain and r and omly selected 150 ( 5 % of 3009 ) screening negative subjects , received a phone interview by one of six neurologists and if necessary a face-to-face examination . Those with suspected TN or PIFP following the phone interview underwent neurological examination by two neurologists who were unaware of the presumed diagnosis . A r and om group of 25 ( 10 % of 247 ) phone interview negative subjects was examined face-to-face . All suspected cases of PIFP received otorhinolaryngological examination and diagnostic cranial magnetic resonance imaging ( MRI ) . In TN patients the number of vessel-nerve contacts was determined by thin-slice cranial MRI . Results : Lifetime prevalence of TN was estimated to be 0.3 % [ 10 of 3336 ; 95 % CI 0.1–0.5 % ] , of PIFP 0.03 % [ 1 of 3336 ; 95 % CI < 0.08 % ] . Thin-slice cranial MRI detected five vessel-nerve contacts and no symptomatic lesions in the 10 TN patients . Conclusions : This large population -based study revealed that TN and PIFP are rare facial pain disorders Aim : To investigate the efficacy , safety and tolerability of intradermal and /or submucosal administration of botulinum toxin type A ( BTX-A ) for patients with trigeminal neuralgia ( TN ) . Methods : In this r and omized , double-blind , placebo-controlled study , 42 TN patients were r and omly allocated into two groups , namely , intradermal and /or submucosal injection of BTX-A ( 75 U/1.5 mL ; n = 22 ) or saline ( 1.5 mL ; n = 20 ) in the skin and /or mucosa where pain was experienced . The primary endpoints were pain severity ( assessed by the visual analogue scale ) and pain attack frequency per day . The secondary endpoint was the patient ’s overall response to treatment , assessed using the Patient Global Impression of Change scale . Patients with ≥ 50 % reduction in mean pain score at week 12 were defined as responders . Results : A total of 40 patients completed the study . BTX-A significantly reduced pain intensity at week 2 and pain attack frequency at week 1 . The efficacy was maintained throughout the course of the study . More BTX-A treated patients reported that pain had improved by the end of the study . Significantly more responders were present in the BTX-A group ( 68.18 % ) than in the placebo group ( 15.00 % ) . BTX-A was well tolerated , with few treatment-related adverse events . Conclusions : BTX-A may be an efficient , safe and novel strategy for TN treatment To evaluate the reported benefit of ipsilateral single-application ophthalmic anesthetic eyedrops in patients with typical trigeminal neuralgia , a r and omized double-blind placebo-controlled trial was performed . Forty-seven patients were r and omly assigned to receive two drops of either proparacaine ( 25 cases ) or saline placebo ( 22 cases ) . The experimental and placebo groups were equivalent in regard to patient age , distribution of trigeminal neuralgia pain , duration of pain , current medication regimens , and number of prior procedures performed . Pain response was assessed at 3 , 10 , and 30 days after instillation using two pain rating scales and a measure of pain frequency . Treatment failure was defined in advance as any of the following : a lack of clinical response , the need for an increase in medication , or the need for surgery . No significant difference in outcomes was found between the two groups either when using a verbal pain rating scale ( p = 0.24 ) or when comparing overall pain status ( unchanged , improved throughout the study period , or temporarily improved ) ( p = 0.98 ) . No difference in the frequency of trigeminal neuralgia attacks between the two treatment groups ( scaled within five levels of pain frequency ) was detected ( p = 0.09 ) . During follow-up monitoring , 11 patients in the test drug group and 14 in the placebo group required surgery because of persistent pain ( p = 0.24 ) . The results of this study indicate that single-application topical ophthalmic anesthesia reduces neither the severity nor the frequency of pain in comparison to placebo administration . Although a simple and safe treatment , the single application of topical ophthalmic eyedrops provides no short- or long-term benefit to patients with trigeminal neuralgia Abstract A double-blind , r and omized , placebo-controlled study of patients with essential trigeminal neuralgia and treatment with a single injection of onabotulinum toxin A ( BTX ) was carried out . The efficacy , safety , and tolerability of either 1 mL 0.9 % saline plus 50 U of BTX or only 1 mL of 0.9 % saline injected subcutaneously in the affected area were evaluated . Cases with involvement of the third branch of the trigeminal nerve also received intramuscularly either 10 U of BTX or matching placebo in the masseter muscle , ipsilateral to the pain location . Pain was assessed with the visual analog scale ( VAS ) . Twenty subjects were administered BTX , and 16 subjects received placebo . Two months after the intervention , a trend to statistical significance was observed for the VAS mean values in subjects treated with BTX and those who received placebo ( VAS 4.9 vs 6.63 , t test , P = 0.07 ) . Three months after the injection , significant differences were observed in the average VAS score for subjects treated with BTX and those treated with placebo ( VAS 4.75 vs 6.94 , respectively ; t test , P = 0.01 ) . Onabotulinum toxin A was well tolerated and seems to be a safe and useful therapy for patients with essential trigeminal neuralgia Abstract Patients may develop serious eye complications after continuous radiofrequency thermocoagulation ( CRF ) for V1 ( ophthalmic division ) trigeminal neuralgia ( TN ) at a higher temperature . Therefore , the temperature of clinical CRF for V1 TN has long been disputed , but there have few reports been found about how to achieve satisfactory pain relief , reduce the incidence rates of complications , and shorten the recovery time after CRF for V1 TN.To observe whether pulsed radiofrequency ( PRF ) can lead to increased rate in pain relief , reduced rate of complications , or shortened recovery time after CRF is used to treat V1 idiopathic trigeminal neuralgia (ITN).The prospect i ve cohort study enrolled 56 patients with V1 ITN from May 2012 to April 2015 . The patients were r and omized into 2 treatment groups as follows : CRF only ( group A , n = 28 ) and CRF plus PRF ( group B , n = 28 ) . The patients were followed 3 years up for pain relief , complications , and health-related quality of life (HRQoL).All the patients in either group achieved satisfactory pain relief at discharge . After treatment , patients completely pain free in group A and group B accounted for 81.6 % , 92.0 % at 1 year , 68.4 % , 92.0 % at 2 years , and 68.4 % , 83.6 % at 3 years , respectively . The pain relief rate was higher in group B patients than in group A , but the difference was not statistically significant . During the follow-up period , 9 ( 32.1 % ) patients in group A and 2 ( 7.1 % ) patients in group B developed recurrence ( P < 0.05 ) . Eleven patients in group A occurred corneal hypoesthesia and with recovery time was 11.9 ± 7.5 ( 4–18 ) months versus 3 patients in group B with recovery time was 3.4 ± 2.5 ( 2–6 ) months , the differences of incidence rate and recovery times were all significant ( P < 0.05 ) between groups A and B. The mean scores of HRQoL in group B patients were higher than that in group A patients ( P < 0.05).PRF after CRF results in decreased recurrence of V1 TN , reduced numbers of corneal hypoesthesia , shortened recovery time , and increased HRQoL scores . Its clinical use is recommended INTRODUCTION Multiple modalities have been adapted to treat medically refractory trigeminal neuralgia ( TN ) . Until recently , the preferred treatment modality was microvascular decompression (MVD),9 especially if a vessel was thought to be abutting the trigeminal nerve entry zone . Less-invasive techniques have since been developed . Percutaneous ablation is one technique that uses radiofrequency ( RF ) , pressure , or chemolysis to provide instantaneous relief by lesioning the nerve . Even less invasive is radiosurgery ( RS ) , which uses stereotaxy to lesion the nerve . The degree of invasiveness is important , as is the treatment efficacy . MVD was the first treatment to be rigorously tested . The results showed a significant reduction of pain in four of five patients .2,7 Conversely , 20 to 30 % of patients have persistent TN pain and require retreatment.1,2,4 Recurrent symptoms typically surface after 1.9 years,2 thus , the length of follow-up in published studies is very important . Refractory or recurrent TN is also seen with other treatment modalities.3,6,11,13,14 At this time , there have been no prospect i ve r and omized controlled studies comparing the different treatment modalities for TN with respect to effectiveness . In this chapter , we evaluated patients with idiopathic TN who were prospect ively entered into our University of California , San Francisco ( UCSF ) TN Data base and required retreatment after MVD , RS , or RF . We compare the effectiveness of each treatment modality The aim of this prospect i ve , r and omized , double-blinded study was to evaluate the effect of pulsed radiofrequency ( PRF ) in comparison with conventional radiofrequency ( CRF ) in the treatment of idiopathic trigeminal neuralgia . A total of 40 patients with idiopathic trigeminal neuralgia were included . The 20 patients in each group were r and omly assigned to one of the two treatment groups . Each patient in the Group 1 was treated with CRF , whereas each patient in the Group 2 was treated by PRF . Evaluation parameters were : pain intensity using a Visual Analogue Scale ( VAS ) , patient satisfaction using a Patient Satisfaction Scale ( PSS ) , additional pharmacological treatment , side effects , and complications related to the technique . The VAS scores decreased significantly ( p<0.001 ) and PSS improved significantly after the procedure in Group 1 . The VAS score decreased in only 2 of 20 patients from the PRF group ( Group 2 ) and pain recurrence occurred 3 months after the procedure . At the end of 3 months , we decided to perform CRF in Group 2 , because all patients in this group still had intractable pain . After the CRF treatment , the median VAS score decreased ( p<0.001 ) and PSS improved ( p<0.001 ) significantly . In conclusion , the results of our study demonstrate that unlike CRF , PRF is not an effective method of pain treatment for idiopathic trigeminal neuralgia |
10,405 | 10,796,208 | REVIEW ER 'S CONCLUSIONS Antiplatelet agents , in this review largely low dose aspirin , have small-moderate benefits when used for prevention of pre-eclampsia . | BACKGROUND Pre-eclampsia is associated with deficient intravascular production of prostacyclin , a vasodilator , and excessive production of thromboxane , a platelet-derived vasoconstrictor and stimulant of platelet aggregation .
These observations led to the hypotheses that antiplatelet agents , and low dose aspirin in particular , might prevent or delay the development of pre-eclampsia .
OBJECTIVES To assess the effectiveness and safety of antiplatelet agents when given to women at risk of developing pre-eclampsia , and to those with established pre-eclampsia . | Objective To assess the effect of low dose aspirin on severe pre‐eclampsia when given to women identified as high risk by abnormal uterine artery Doppler ultrasound Summary : The purpose of this study was to investigate the hypothesis that maternal administration of lOOmg aspirin each day will improve birth‐weight and other measures of neonatal size when given as a treatment to pregnancies complicated by fetal growth restriction and umbilical‐placental insufficiency . A r and omized , double‐blind , placebo controlled study design was employed ; 51 pregnant women were enrolled . The entry criteria were a fetal abdominal circumference < 10th per centile together with an umbilical artery Doppler systolic/diastolic ratio > 95th per centile between 28 and 36 weeks'gestation . Compliance was assessed by serial measurement of maternal serum thromboxane B2 levels . The mean gestational age at enrolment was 32 weeks and at delivery was 36 weeks . There were no differences between the 2 groups in gestational age at birth ; birth‐weight or birth‐weight ratio ; circumferences of the head , chest or abdomen ; skin fold thicknesses ; or neonatal morbidity . Low dose aspirin therapy did not alter Doppler systolic/diastolic ratios . After 14 days therapy , mean thromboxane B2 levels fell more than 80 % from baseline values ; 10.5 % of women did not demonstrate biochemical confirmation of aspirin ingestion , despite verbal confirmation of compliance . We conclude that low dose aspirin therapy is not of benefit in the treatment of pregnancies complicated by fetal growth restriction and umbilical‐placental insufficiency between 28 and 36 weeks ' gestation In a prospect i ve , r and omized , double-blind study for the prevention of pregnancy-induced hypertension and preeclampsia , 41 primigravidae with positive roll-over test ( 28th-32nd week of pregnancy ) received 80 mg aspirin/day or placebo until the end of the 37th week . In the patients treated with acetylsalicylic acid ( n = 22 ) , 3 cases of proteinuria occurred , but no hypertensive pregnancy complication . In the placebo group ( n = 19 ) , 10 patients developed pregnancy-induced hypertension ( 6 of them preeclampsia ) . Group-specific differences concerning the occurrence of hypertension were statistically highly significant ( p = 0.0004 ) . No relevant differences were observed with regard to pregnancy duration , birth weight and umbilical artery pH value . The placebo group included 1 intrauterine death . No increased tendency to maternal or fetal bleeding was noticed OBJECTIVES The aims of this prospect i ve study were to explore the changes in platelet angiotensin II ( A-II ) binding in pregnancy amongst Chinese women at high risk of developing pregnancy-induced hypertension ( PIH ) and the effects of low-dose aspirin and calcium supplementation on A-II binding . METHODS Platelet A-II binding was assayed in 15 non-pregnant women and in 63 pregnant women determined to be at risk of PIH on the basis of 2nd-trimester mean arterial pressure ( MAP ) . The pregnant patients were r and omized into three groups : control , low-dose aspirin , and calcium supplementation . A-II binding was assayed again during the 3rd trimester in half the women and 8 weeks after delivery . RESULTS A-II binding was negatively correlated with MAP measured in the left lateral position ( p < 0.05 ) but not with MAP measured in the supine position . There were no significant differences between A-II binding in non-pregnant and pregnant women . Neither low-dose aspirin nor calcium supplementation caused significant reductions in A-II binding . CONCLUSION The measurement of platelet A-II binding is unlikely to provide significant information regarding the risk of PIH over and above that obtained from measurement of 2nd-trimester MAP Pre-eclampsia is a common complication of pregnancy , in which platelets may have an early pathogenetic role . In this prospect i ve study a whole blood flow cytometric method has been used to detect circulating activated platelets in pregnant women prior to the development of pre-eclampsia . Activated platelets were identified by bound fibrinogen or by CD63 antigen expression . Of 121 healthy primiparous women studied at 28 weeks of pregnancy , 18 ( 15 % ) developed clinical pre-eclampsia six to thirteen weeks later . The platelets of these women showed increased fibrinogen binding ex vivo ( 5.1 % platelets positive , compared with 3.4 % in those who completed a normal pregnancy , p < 0.02 ) , and increased CD63 antigen expression ( 0.73 % positive compared to 0.45 % , p = 0.01 ) . In contrast , no differences between the women with different outcomes were detected at 28 weeks in platelet counts , or plasma beta-thromboglobulin levels . These findings confirm that whole blood flow cytometry is a sensitive technique for investigating platelet activation in a clinical setting and support the hypothesis that platelets have a critical role in the pathogenesis of pre-eclampsia Objectives Concern has been expressed about possible neonatal side effects after the use of maternal anti‐platelet agents in pregnancy , particularly low dose aspirin treatment . We have studied neonatal platelet behaviour using whole blood techniques , and assessed the neonatal effect of the maternal ingestion of 60 mg aspirin daily Screening of 1226 nulliparous women by means of doppler uteroplacental flow-velocity waveforms in early pregnancy identified 148 ( 12 % ) as being at high risk of pregnancy-induced hypertension . After exclusions and refusals , 100 women were r and omly allocated to groups receiving either low-dose aspirin ( 75 mg daily ; 48 patients ) or identical placebo ( 52 patients ) for the remainder of the pregnancy . The difference between the aspirin and placebo groups in the frequency of pregnancy-induced hypertension ( 13 % vs 25 % ) did not achieve significance , but there were significant differences in the frequencies of proteinuric hypertension ( 2 % vs 19 % ) and hypertension occurring before 37 weeks ' gestation ( 0 % vs 17 % ) . Fewer aspirin-treated than placebo-treated women had low birthweight babies ( 15 % vs 25 % ) , but this difference was not significant . The only perinatal death in the aspirin group followed a cord accident during labour , whereas the 3 perinatal deaths in the placebo group were all due to severe hypertensive disease . No maternal or neonatal side-effects were observed in either group Objectives To examine the fetal effects of a novel controlled‐release , low dose aspirin preparation in normal and hypertensive pregnancies OBJECTIVE We conducted a large clinical trial to evaluate the effect of low-dose aspirin on the frequency of preeclampsia in nulliparous women . A secondary objective of the trial was to identify those clinical characteristics that might be predictive for the development of preeclampsia . STUDY DESIGN A total of 2947 healthy women with a single fetus were prospect ively followed up from r and omization at 13 to 27 weeks ' gestation to the end of pregnancy . Of these , 1465 women were assigned to low-dose aspirin and 1482 to placebo . Baseline maternal blood pressure and demographic characteristics were examined for the prediction of preeclampsia . RESULTS Preeclampsia developed in 156 women ( 5.3 % ) . Four characteristics predicted the development of preeclampsia : in order of importance , systolic blood pressure at entry , prepregnancy obesity ( weight as a percentage of desirable weight ) , number of previous abortions or miscarriages , and smoking history . Contrary to previous reports , black race was not a risk factor for preeclampsia . Systolic blood pressure was a better predictor of preeclampsia than either diastolic or mean arterial blood pressure . The greater the blood pressure or prepregnancy weight , the greater was the risk for preeclampsia . If the woman had never smoked or had never been previously pregnant , her risk was also higher than average . A multivariate logistic regression equation based on these four factors was able to define a tenth of the population at very high risk and another tenth at very low risk ; the ratio of risk between these two groups was 12:1 . The p value for each of the multivariate coefficients of the risk equation was systolic blood pressure ( p < 0.001 ) , prepregnancy weight ( p < 0.01 ) , smoking history ( p < 0.01 ) , and gravidity ( p < 0.05 ) . There were no statistically significant differences in the predictive values of these risk factors between women receiving low-dose aspirin or placebo . CONCLUSIONS These risk factors should be of value to practitioners counseling women regarding preeclampsia . Moreover , such risk factors should be considered in the design of future studies dealing with preeclampsia A prospect i ve study conducted between January , 1985 and September , 1987 involved 60 pregnant women who had previously suffered from hypertension in pregnancy with or without foetal and maternal complications . Thirty women received aspirin 250 mg every other day and dipyridamole 300 mg per day , starting from the 3rd month of pregnancy ( group I ) ; 30 women were examined regularly from the onset of pregnancy and received the conventional symptomatic treatment of complications that occurred ( group II ) . Women in these two groups were similar in age , parity and previous obstetrical complications . Twenty-five women of group I had a perfectly normal pregnancy , as against 5 women of group II ( P less than 0.001 ) . Hypertension and /or proteinuria were observed in 5 women of group I and 15 of group II ( NS ) . The 13 severe complications recorded ( foetal death , eclampsia , retroplacental haematoma ) occurred exclusively in women of group II . The duration of pregnancy and weight of the newborn were significantly greater in group I than in group II . Thus , antiplatelets appear to have an uncertain preventive effect on hypertension of pregnancy and a much more obvious prophylactic effect on major foetal and maternal complications BACKGROUND Although low-dose aspirin has been reported to reduce the incidence of preeclampsia among women at high risk for this complication , its efficacy and safety in healthy , nulliparous pregnant women are not known . METHODS We studied 3135 normotensive nulliparous women who were 13 to 26 weeks pregnant to determine whether treatment with aspirin reduced the incidence of preeclampsia . Of this group , 1570 women received 60 mg of aspirin per day and 1565 received placebo for the remainder of their pregnancies . We also evaluated the effect of aspirin on maternal and neonatal morbidity . RESULTS Of the original group of 3135 women , 2985 ( 95 percent ) were followed throughout pregnancy and the immediate puerperium . The incidence of preeclampsia was lower in the aspirin group ( 69 of 1485 women [ 4.6 percent ] ) than in the placebo group ( 94 of 1500 women [ 6.3 percent ] ) ( relative risk , 0.7 ; 95 percent confidence interval , 0.6 to 1.0 ; P = 0.05 ) , whereas the incidence of gestational hypertension was 6.7 and 5.9 percent , respectively . There were no significant differences in the infants ' birth weight or in the incidence of fetal growth retardation , postpartum hemorrhage , or neonatal bleeding problems between the two groups . Subgroup analysis showed that preeclampsia occurred primarily in women whose initial systolic blood pressure was 120 to 134 mm Hg ( incidence among such women , 5.6 percent in the aspirin group vs. 11.9 percent in the placebo group ; P = 0.01 ) . The incidence of abruptio placentae was greater among the women who received aspirin ( 11 women , vs. 2 in the placebo group ; P = 0.01 ) . CONCLUSIONS Low-dose aspirin decreases the incidence of preeclampsia among nulliparous women , primarily through its effect in those who have elevated systolic blood pressure initially . This treatment does not decrease perinatal morbidity but increases the risk of abruptio placentae This study investigated the effects of low-dose acetylsalicylic acid ( aspirin ) on blood pressure in pregnant women who were at risk of developing gestational hypertension or preeclampsia and who received aspirin at different times of the day according to their rest-activity cycle . A double-blind , r and omized , controlled trial was conducted in 100 pregnant women . Blood pressure for each subject was automatically monitored for 2 days every 4 weeks from the day of recruitment until delivery . Women were r and omly assigned to one of six groups according to treatment ( placebo , 50 subjects or aspirin , 100 mg/d , starting at 12 to 16 weeks of gestation ) and the time of treatment : on awakening ( time 1 ) , 8 hours after awakening ( time 2 ) , or before bedtime ( time 3 ) . Results indicated that there was ( 1 ) no effect on blood pressure from placebo at any time ( P>.212 ) and ( 2 ) a highly statistically significant ( P<.001 ) time-dependent effect on blood pressure from aspirin . There was no effect of aspirin on blood pressure at time 1 ( compared with placebo ) , but the blood pressure reduction was highly statistically significant after time 2 and , to a greater extent , after time 3 ( mean reduction of 12 and 8 mm Hg in 24 hours for systolic and diastolic blood pressure , respectively , at the time of delivery compared with placebo given at the same time ) . These time-dependent effects of aspirin on blood pressure should be taken into account for the optimization of long-term aspirin administration at low doses for prevention of preeclampsia . In any meta- analysis of aspirin effects , inquiries about the time when the subjects took the drug are indicated and may account for discrepancies in the literature BACKGROUND The purpose of this study was to determine which low dose of low dose aspirin ( LDA ) optimized the urinary prostacyclin (PGI2)/thromboxane ( TXA2 ) ratio and minimized evidence of platelet aggregation during normal late pregnancy . METHODS Twelve women with uncomplicated singleton pregnancies between 28 and 34 weeks gestation participated in a r and omized blinded study . Blood sample s for salicylate levels were obtained pretreatment , 4 hours and 7 days after administration of placebo , 20 mg , 40 mg or 80 mg of aspirin . Twenty-four hour urine specimens collected at the same intervals were assayed for PGI2 and TXA2 metabolites . In addition , bleeding time and platelet aggregation studies were performed prior to and after 7 days of LDA or placebo . RESULTS A dose-related increase in bleeding time occurred with 40 mg and 80 mg of LDA , but not with the 20 mg dose or placebo . Platelet aggregation studies changed progressively from a normal baseline to abnormal with an increasing dose of LDA . The PGI2/TXA2 ratio increased with aspirin doses as low as 20 mg , with a decrease in TXA2 metabolites but not in PGI2 metabolites . Serum salicylate was not detectable in any sample from any patient . CONCLUSION There are dose-related changes in platelet aggregation and bleeding times with progressively increasing doses of LDA . A lower dose of LDA , such as 20 - 40 mg per day , may be as efficacious as higher doses in the prophylaxis of pre-eclampsia in high risk population Objective To evaluate color Doppler imaging of the uterine arteries as a screening test in nulliparous women , and to examine the role of low-dose aspirin therapy in pregnancies with abnormal uteroplacental resistance . Methods At the routine 18-week fetal morphology ultrasound scan , 955 nulliparous women underwent color Doppler imaging of the uterine arteries . Abnormal uteroplacental vascular resistance was defined with respect to both the systolic-diastolic ratio of the flow velocity waveform and the presence of an ipsilateral early diastolic notch . Those with abnormal uterine artery waveforms were asked to participate in a r and omized controlled trial of aspirin therapy . Pregnancy outcomes were compared in women with normal or abnormal flow velocity waveforms , as well as in the two arms of the intervention study . Results Of 186 women with abnormal uteroplacental resistance according to criteria defined previously , 102 agreed to r and omization to either low-dose aspirin ( 100 mg/day ) or placebo for the remainder of the pregnancy . Abnormal uterine artery flow velocity waveforms were associated with statistically significant increases in preeclampsia ( 11 versus 4 % ) , birth weith below the tenth percentile ( 28 versus 11 % ) , and adverse pregnancy outcome ( 45 versus 28 % ) . Prophylactic aspirin therapy did not result in a significant reduction in pregnancy complications . Conclusion Abnormal uteroplacental resistance at 18 weeks ' gestation was associated with a significant increase in adverse pregnancy outcome . Low-dose aspirin did not reduce pregnancy complications in women with uteroplacental insufficiency OBJECTIVE To determine the value of low-dose aspirin in high-risk pregnancies , and assess its impact on fetal growth , as well as on perinatal mortality and morbidity . METHODOLOGY One hundred and eight women with singleton pregnancies were enrolled in a r and omized , double-blind , placebo-controlled trial of 100 mg/day aspirin from 17 to 19 week gestation . Enrolment criteria included pre-existing chronic essential hypertension or renal disease , or a history of previous early , severe pre-eclampsia . RESULTS There were four stillbirths ( all aspirin ) and two neonatal deaths ( both placebo ) , to yield respective perinatal mortality rates of 69/1000 and 40/1000 ( P = 0.499 ) . Liveborn infants in the aspirin group were significantly more mature ( P = 0.017 ) and of heavier birthweight ( P = 0.034 ) but had similar length ( P = 0.091 ) and head circumference ( P = 0.257 ) . Fewer infants in the aspirin group were liveborn prematurely ( 5/54 vs 14/50 ; P = 0.016 ) or were of low birthweight ( 3/54 vs 9/50 ; P = 0.052 ) . There were no significant between-group differences for st and ard deviation ( Z ) scores for weight , length or head circumference , or for skinfold thickness measurements . There was no significant difference in occurrence of low Apgar scores or in neonatal intensive care unit use between the groups . CONCLUSIONS Low-dose aspirin does not appear to have a significant effect on perinatal morbidity . The increase in weight at birth associated with low-dose aspirin therapy is due to prolongation of pregnancy rather than prevention of intra-uterine growth retardation In a prospect i ve study , we evaluated the effects of low-dose aspirin on maternal and neonatal plasma 6-keto-prostagl and in ( PG ) F1α concentration , platelet aggregation , platelet thromboxane production , and neonatal transitional circulation . Forty women , at a mean ( ± SD ) of 37 ± 2 weeks ' gestation , were r and omized to receive ( N = 10 each ) placebo or 20 , 60 , or 80 mg of aspirin per day until delivery . Maternal serum 6-keto-PGF1α levels were not affected by these doses of aspirin , whereas thromboxane B2 generated during clotting of maternal blood was decreased significantly by 60 and 80 mg of aspirin by 1 week of therapy . Maternal platelet thromboxane B2 production in response to adenosine diphosphate or collagen was reduced 98 % by the 80-mg dose after 1 week of aspirin therapy . The 60-mg dose reduced maternal platelet thromboxane B2 production in response to adenosine diphosphate ( 50 % decrease ) or collagen ( 60 % decrease ) after 1 week of treatment , a nonsignificant difference . After 2 weeks of treatment with 60 mg of aspirin , platelet thromboxane B2 production induced by both collagen and adenosine diphosphate was inhibited significantly ( P < .01 ) . Neonatal serum levels of 6-keto-PGF1α and thromboxane B2 were not affected by any doses of aspirin . Further , neonatal platelet aggregation in response to platelet stimulation by collagen and adenosine diphosphate was not inhibited . All neonates had echocardiographic evidence of a patent ductus arteriosus , and noninvasive estimates of pulmonary arterial pressure were similar among the groups of infants . We conclude that 60–80 mg of aspirin per day in the third trimester of pregnancy selectively inhibits maternal platelet cyclooxygenase without affecting neonatal platelet aggregation or pulmonary circulation OBJECTIVE Patients given prostagl and in synthetase inhibitors in doses sufficient to inhibit labor are at risk for developing oligohydramnios ( possibly related to a reduction in fetal urine output ) . We sought to ascertain whether the fetuses of women who received 60 mg of aspirin daily had a lower urine output than those whose mothers were given a placebo . STUDY DESIGN Nulliparous women with singleton gestations in a double-blind preeclampsia prevention trial were r and omly selected at 24 weeks ' gestation to receive either 60 mg of aspirin daily or a placebo . Urine output was assessed in 59 fetuses ( aspirin 32 , placebo 27 ) by serial ultrasonographic measurement of their bladder volume ( volume = 4/3 pi r3 ) . Biochemical evidence of aspirin compliance was defined as an 80 % reduction in maternal serum thromboxane B2 levels when comparing values obtained at r and omization with those at 34 to 36 weeks ' gestation . RESULTS Visual assessment of amniotic fluid volume was similar in both groups . Four-quadrant amniotic fluid indexes also were similar ( 13.5 cm in aspirin group vs 12.2 cm in placebo group , p = 0.15 ) . Mean fetal urine outputs were similar in the aspirin ( 57.7 ml/hr ) and placebo ( 55.1 ml/hr ) groups ( p = 0.71 ) . Moreover , the 23 women with a fourfold thromboxane B2 reduction had a higher mean fetal urine output ( 63.5 vs 51.8 ml/hr , p = 0.08 ) than did the remaining 35 patients . This study has a 96 % chance ( 1-beta ) of detecting a 50 % ( 30 ml ) reduction in fetal urine output . CONCLUSIONS Daily maternal ingestion of 60 mg of aspirin did not decrease fetal urine output or amniotic fluid volume OBJECTIVE Our purpose was to assess the efficiency of the angiotensin sensitivity test as a predictive test for preeclampsia and the effectiveness of low-dose aspirin to prevent preeclampsia when commenced at 28 weeks ' gestation in angiotensin II-sensitive women . STUDY DESIGN A total of 495 healthy nulliparous women underwent the angiotensin sensitivity test at 28 weeks ' gestation . The angiotensin II-sensitive women were r and omized to 60 mg of aspirin or placebo as a subset of a large multicenter , r and omized , controlled trial of low-dose aspirin therapy in pregnancy . Assessment of the efficiency of the angiotensin sensitivity test and low-dose aspirin in pregnancy was performed after detailed review of case notes after delivery . The Oxford definition of preeclampsia was used . This includes women without proteinuria but requires blood pressure increments that have been vali date d to bias the selection to primigravid women . RESULTS Five women had proteinuric preeclampsia in the angiotensin II-sensitive group r and omized to aspirin compared with none in the group r and omized to placebo . Overall , 11 ( 25 % ) of the women r and omized to aspirin had preeclampsia compared with four ( 11 % ) r and omized to placebo ( p < 0.05 , not significant ) . The positive and negative predictive values for the angiotensin sensitivity test were 19 % and 87 % , respectively . CONCLUSION The angiotensin sensitivity test is not an effective screening test for preeclampsia , and low-dose aspirin does not prevent preeclampsia when commenced at 28 weeks ' gestation in angiotensin II-sensitive women OBJECTIVE We compared the use of aspirin alone with combined therapy ( prednisone plus aspirin ) in antiphospholipid antibody-positive obstetric patients with prior adverse pregnancy outcome . STUDY DESIGN Thirty-nine patients meeting specific laboratory and clinical inclusion criteria were r and omized to receive either combined therapy ( prednisone plus low-dose aspirin , n = 17 ) or aspirin alone ( n = 22 ) . The daily aspirin dose was 81 mg ; prednisone was begun at 20 mg/day and increased or decreased on the basis of observed changes in serial antibody levels . Perinatal outcomes were compared between groups . Evaluation of treatment-related maternal complications and serial antibody titers was also accomplished . RESULTS Thirty-four r and omized subjects were evaluable ( prednisone plus low-dose aspirin , n = 12 vs aspirin only , n = 22 ) ; no perinatal losses were observed in the study cohort . Preterm delivery was experienced by significantly more patients receiving prednisone plus low-dose aspirin than aspirin only ( 8/12 vs 3/22 , respectively ; p = 0.003 ) , and prednisone exposure appeared to be an independent risk factor for preterm birth . CONCLUSIONS The use of prednisone therapy in conjunction with low-dose aspirin does not appear to improve outcome and may provoke obstetric complications in antiphospholipid antibody-positive patients Objectives : To find out whether the tendency toward poor outcome in lupus pregnancies could be explained by changes in prostacyclin/thromboxane production , to relate these changes to the presence of antiphospholipid antibodies , and to study the potential benefits of low‐dose aspirin . Methods : We followed the urinary output of prostacyclin metabolites ( 6‐keto‐prostagl and in [PG]F1α , 2,3‐dinor‐6‐keto‐PGF1α ) and thromboxane metabolites ( thromboxane B2 , 2,3‐dinor‐thromboxane B2 ) using high‐pressure liquid chromatography followed by radioimmunoassay . We studied 14 pregnant women with systemic lupus erythematosus ( SLE ) , of whom six had detectable antiphospholipid antibodies . The patients were r and omized by a computerized program to receive either 50 mg aspirin daily ( six women ) or placebo ( eight women ) . Nine healthy pregnant women served as controls . Results : The production of prostacyclin was normal in early pregnancy in SLE patients but was reduced during late gestation in those without antiphospholipid antibodies . The production of thromboxane was increased in SLE patients compared with controls , and this increase was highest ( two‐to threefold rise ) when antiphospholipid antibodies were detectable . Aspirin eliminated thromboxane dominance without affecting prostacyclin production . Conclusion : These data suggest that the presence of antiphospholipid antibodies in SLE patients may trigger thromboxane dominance , possibly contributing to the adverse outcome of these pregnancies . This thromboxane dominance can be eliminated with aspirin OBJECTIVE Our purpose was to determine if the maternal administration of low-dose ( 60 mg ) aspirin from 24 weeks ' gestation until delivery is associated with significant changes in longitudinal umbilical artery Doppler index values . STUDY DESIGN Healthy , young nulliparous women with singleton gestations who were enrolled in a double-blind trial of low-dose aspirin for preeclampsia prevention underwent prer and omization and monthly postr and omization continuous-wave umbilical artery Doppler evaluations . The systolic-to-diastolic ratio and the resistance index were determined at each examination . Compliance with the medical regimen was assessed by pill counts and measurement of maternal serum thromboxane B2 levels . RESULTS The prer and omization Doppler index values were similar between the two r and omization groups in the 538 ( aspirin 266 , placebo 272 ) patients studied . We found no significant differences with univariate comparisons and multiple linear regression modeling in the postr and omization Doppler index values ( p = 0.21 to 0.96 ) . No differences were found when patients were assessed by r and omization assignment group ( intent to treat ) or by biochemical evidence for compliance and absence of crossover with maternal serum thromboxane B2 levels . CONCLUSION The use of low-dose aspirin from 24 weeks ' gestation until delivery does not significantly affect umbilical artery Doppler index values OBJECTIVE Our purpose was to determine whether in a low-dose aspirin trial a longitudinal decrease in maternal serum thromboxane B2 is associated with improvement in pregnancy outcomes . STUDY DESIGN A total of 606 healthy nulliparous women with singleton gestations were r and omized at 24 weeks to either 60 mg of aspirin or a placebo . Maternal serum thromboxane B2 was measured at r and omization , at 29 to 31 weeks , at 34 to 36 weeks , and at delivery . After delivery , and without knowledge of patient outcome or group assignment , patients were categorized as having had either a longitudinal twofold or greater ( > or = 50 % ) or less than twofold reduction ( < 50 % ) in thromboxane B2 from baseline levels at r and omization . RESULTS Of 606 entrants , 92 % had sufficient thromboxane B2 determinations to allow categorization . Whether patients were assigned to aspirin or placebo , birth weight was significantly greater in women who had a twofold or greater reduction in maternal serum thromboxane B2 levels . When the aspirin and placebo groups were combined , women with a twofold or greater reduction in thromboxane B2 levels had less preeclampsia , 1.9 % ( 6/314 ) versus 5.7 % ( 14/244 ) ( p = 0.016 ) , less preterm delivery ( 5.7 % vs 10.7 % , p = 0.032 ) , fewer small-for-gestational-age newborns , 9 of 314 ( 2.95 ) versus 17 of 244 ( 7 % ) ( p = 0.023 ) , and a higher mean birth weight , 3314 gm versus 3121 gm ( p = 0.0001 ) . CONCLUSION Women with a twofold or greater longitudinal reduction in maternal serum thromboxane B2 had less preeclampsia and prematurity , fewer small-for-gestational-age newborns , and higher birth weights than women with less than a twofold reduction Objective To determine whether antenatal treatment ( for ≥= 14 days ) with 100 mg aspirin daily , given to mothers with small for gestational age fetuses and abnormal umbilical Doppler , will increase birthweight OBJECTIVE In an attempt to investigate the prophylactic effect of a thromboxane A2 ( TXA2 ) synthetase inhibitor on pregnant women with a high risk of preeclampsia , the following clinical study was undertaken . METHODS Forty pregnant women were r and omly allocated to control or treatment groups . Ozagrel Hydrochloride ( 400 mg/day , orally ) and placebo were started at 20 weeks of gestation and continued until delivery . RESULTS Seventeen of 20 ( 85 % ) women in the control group developed preeclampsia , whereas 9 of 20 ( 45 % ) in the treatment group developed preeclampsia . Ozagrel Hydrochloride significantly ( p < 0.01 ) reduced the occurrence of preeclampsia , and the incidence of both hypertension ( p < 0.05 ) and proteinuria ( p < 0.01 ) was significantly less in the treatment group compared with the control group . One month after administration , the mean plasma concentration of TXB2 , a metabolite of TXA2 , was significantly decreased ( p < 0.01 ) to 62.4 + /- 13.6 % , whereas that of 6-keto prostagl and in F1 alpha , a metabolite of PGI2 , was significantly increased ( p < 0.01 ) to 206.7 + /- 52.8 % . There were no maternal or fetal side effects observed . CONCLUSIONS It seems likely that Ozagrel Hydrochloride could be used for the prevention of preeclampsia in high-risk pregnant women OBJECTIVES To determine whether low-dose aspirin reduces the incidence of pre-eclampsia , reduces perinatal mortality and improves birth weights in pregnant women considered at high risk of developing pre-eclampsia . METHOD Two-hundred fifty subjects were recruited from the antenatal clinics at Harare Central Hospital with either a previous history of pregnancy-induced hypertension or pre-existing chronic hypertension and were r and omized to receive either 75 mg of aspirin ( ASA ) or placebo ( PLA ) . RESULTS Two-hundred thirty subjects ( ASA , n = 113 ; PLA , n = 117 ) completed the trial . The odds of developing pre-eclampsia for those on aspirin was 0.72 times those on placebo ( 95 % CI , 0.34 - 1.52 ) . The mean birth weight was 2774 g for those on aspirin and 2694 g for those on placebo ( P = 0.80 ) . No difference was noted in the perinatal deaths ( OR = 0.38 ; 95 % CI , 0.10 - 1.20 ) . CONCLUSION Prophylactic use of aspirin was not associated with a significant effect on the major pregnancy outcomes assessed in this study Objective To investigate whether low dose aspirin medication given to primiparous women provides benefit in preventing pre‐eclampsia or intrauterine growth retardation The use of low-dose aspirin for the prevention and treatment of pre-eclampsia and intrauterine growth restriction has been studied extensively during the last 10 years . The large clinical trials do not support routine prophylaxis or therapeutic administration of low-dose aspirin in high-risk pregnant patients . We report on 87 Israeli women who were recruited for the CLASP study ( a collaborative trial for the prevention and treatment of pre-eclampsia and intrauterine growth restriction ) . Of these women , 41 were treated with 60 mg aspirin daily , and 46 with placebo . The fetal circulation was evaluated by repeated Doppler flow waveform measurements of the umbilical artery and descending aorta from 20 to 34 weeks of gestation . The peak-systolic/ lowest-diastolic velocity ratio , pulsatility index and resistance index were calculated . No significant differences in Doppler measurements were observed for any of the indices between the aspirin and placebo groups . There were no statistically significant changes in the flow parameters during the course of pregnancy in any of the women studied , nor was there a correlation between waveform analysis and pregnancy outcome . Thus , based on the present results , it appears that low-dose aspirin does not improve fetal circulation parameters OBJECTIVE The objectives of the study were to confirm the validity of using oscillometric measurement of MAP in the left lateral position to identify those at high risk for developing pregnancy-induced hypertension ( PIH ) , and to assess and compare the efficacy of prophylaxis with low-dose aspirin or calcium supplementation in high-risk patients . STUDY DESIGN A prospect i ve study in pregnancy ; 500 normotensive , primigravid Chinese women were recruited in the second trimester of pregnancy on the basis of 80 mm Hg > or = MAP < 106 mm Hg in the antenatal clinic . They were then screened by Dinamap in a research setting , measuring MAP in the left lateral position after rest and using a cutoff value of 60 mm Hg for inclusion in the r and omized study . R and omization was divided into three groups : control , low-dose aspirin , and calcium supplementation . After delivery , patients were classified as either having remained normotensive or having developed PIH , with or without proteinuria . RESULTS The incidence of both proteinuric and nonproteinuric PIH was significantly lower in patients screened out as low risk than in those selected as high risk using a critical value of 60 mm Hg for left lateral MAP ( p < 0.05 ) . The incidence of proteinuric PIH was significantly lower in patients given low-dose aspirin than in the control group ( p < 0.05 ) . However , the confidence intervals for the effect were wide , comparable with aspirin having no effect or leading to a 16-fold reduction in the risk of preeclampsia . For those given calcium supplementation , the reduction was not significant . There was no significant difference in the incidence of nonproteinuric PIH between the control group and the two groups receiving prophylaxis . CONCLUSION Oscillometric measurement of second-trimester left lateral MAP is a valid predictor of proteinuric PIH . Low-dose aspirin may offer a degree of protection from proteinuric PIH in these high-risk women . Calcium supplementation was not shown to significantly reduce the incidence of PIH A prospect i ve r and omised clinical trial comprising 510 pregnant patients was performed to determine whether supplementation with calcium , low-dose aspirin or a combination of calcium and low-dose aspirin can lower the incidence of hypertension in pregnancy . Greatest benefits were obtained with calcium . Perinatal mortality was lowest in the aspirin group Objective To determine the effectiveness of low dose aspirin in women at high risk of adverse outcomes associated with pre‐eclampsia The hypothesis that an enhanced vasopressor response to angiotensin II in pregnancy may be corrected by suppressing production of platelet thromboxane A2 with low-dose aspirin was tested in a r and omized , placebo-controlled , double-blind trial . We studied 36 normotensive primigravid women with an elevated blood pressure response to intravenously infused angiotensin II at 28 weeks ' gestation ; 18 women received 60 mg of aspirin daily and the same number received matched placebo until 34 weeks ' gestation , when angiotensin-sensitivity was again determined . In women taking aspirin , values of thrombin-induced platelet malondialdehyde production were approximately 10 % of those determined in the placebo group , indicating marked suppression of thromboxane A2 synthesis . In the aspirin group vascular refractoriness to angiotensin II was restored in 14 of 17 treated women , by comparison with 5 of 15 women in the placebo group who had remained normotensive . These results support the hypothesis that prostacyclin/thromboxane imbalance is an important pathophysiologic factor in the development of the enhanced angiotensin-sensitivity associated with pregnancy-induced hypertensive disorders Objective To determine whether prophylactic , low dose controlled‐release aspirin improves outcome for pregnant women and their babies in Barbados PROBLEM : Effectiveness of early administered low‐dose aspirin in prevention of pregnancy‐induced hypertension ( PIH ) and fetal growth retardation in twin pregnancies was investigated in a r and omized placebo controlled , double‐blind trial in 47 twin pregnancies Twenty pregnant patients in the third trimester with severe preeclampsia were allocated at r and om into two equal groups . The first group was treated for 10 days with a low dose ( 75 mg/day ) of acetyl salicylic acid ( ASA ) then with conventional therapy for another 10 days . The second group received the same regimen but conventional therapy in the first 10 days and ASA in the second 10 days . Changes in systolic and diastolic blood pressure , albuminuria , lower limb edema and urinary output were closely monitored and recorded . This comparative crossover study indicated that both the low dose ASA and conventional therapy significantly reduced systolic and diastolic blood pressure which was more pronounced with ASA and in group I. Crossover from one treatment to the other maintained the response but was more beneficial when ASA was given first 102 patients at high risk of pre-eclampsia and /or fetal growth retardation were r and omly allocated to treatment with 300 mg dipyridamole and 150 mg aspirin daily from 3 months ' gestation onwards ( group A ) or to the control group ( group B , no treatment ) . Group A was twice as likely as group B to have a normal pregnancy . Pre-eclampsia occurred in 6 patients in group B and none in group A. Major complications ( fetal death or severe growth retardation ) occurred in 9 patients in group B and none in group A. Platelet count and plasma volume were significantly higher in group A than in group B throughout pregnancy . The treatment did not produce serious adverse effects . Antiplatelet therapy given early in pregnancy to high-risk patients may thus protect against pre-eclampsia and fetal growth retardation The efficacy of low-dose aspirin in preventing fetal growth retardation was tested in a r and omised , placebo-controlled , double-blind trial . A secondary aim was to find out whether dipyridamole improves the efficacy of aspirin . 323 women at 15 - 18 weeks ' amenorrhoea were selected at twenty-five participating centres on the basis of fetal growth retardation and /or fetal death or abruptio placentae in at least one previous pregnancy . They were r and omly allocated to groups receiving placebo , 150 mg/day aspirin , or 150 mg/day aspirin plus 225 mg/day dipyridamole , for the remainder of the pregnancy . In the first phase of the trial all actively treated patients ( n = 156 ) were compared with the placebo group ( n = 73 ) . Mean birthweight was significantly higher in the treated than in the placebo group ( 2751 [ SD 670 ] vs 2526 [ 848 ] g ; difference 225 g [ 95 % CI 129 - 321 g ] , p = 0.029 ) and the frequency of fetal growth retardation in the placebo group was twice that in the treated group ( 19 [ 26 % ] vs 20 [ 13 % ] ; p less than 0.02 ) . The frequencies of stillbirth ( 4 [ 5 % ] vs 2 [ 1 % ] ) and abruptio placentae ( 6 [ 8 % ] vs 7 [ 5 % ] ) were also higher in the placebo than in the treated group . The benefits of aspirin treatment were greater in patients with two or more previous poor outcomes than in those with only one . In the second analysis , of aspirin only ( n = 127 ) vs aspirin plus dipyridamole ( n = 119 ) , no significant differences were found . There was no excess of maternal or neonatal side-effects in the aspirin-treated patients Objective To investigate the use of low dose aspirin in the reduction of perinatal morbidity and mortality in women with unexplained raised maternal serum alpha‐fetoprotein and abnormal uteroplacental Doppler waveform patterns A r and omized , placebo-controlled , double-blind trial was carried out to evaluate the fetal benefits of low-dose aspirin ( 150 mg/day ) as a treatment of placental insufficiency during the last trimester of pregnancy . Forty-six women referred for study because there was concern about fetal welfare were found to have an elevated umbilical artery wave form systolic/diastolic ratio . Mothers with severe hypertension were excluded because fetal condition would not necessarily be the dominant determinant of obstetric decision making . A distinction was made between a high systolic/diastolic ratio ( greater than 95th but less than 99.95th percentile ) and an extreme systolic/diastolic ratio ( greater than 99.95th percentile ) . There were 34 patients in the high ratio group and 12 in the extreme group . Aspirin therapy was associated with an increase in birth weight ( mean difference 526 gm [ p less than 0.02 ] ) , head circumference ( 1.7 cm [ p less than 0.025 ] ) , and placental weight ( 136 gm [ p less than 0.02 ] ) in those patients with a high initial umbilical artery systolic/diastolic ratio . For the 12 women with an extreme initial systolic/diastolic ratio , aspirin therapy did not result in a significantly different pregnancy outcome There is evidence that aspirin in low doses favorably influences the course of pregnancy-induced hypertension , but the mechanism , although assumed to involve suppression of the production of thromboxane by platelets , has not been established . We performed a r and omized study of the effect of the long-term daily administration of 60 mg of aspirin ( n = 17 ) or placebo ( n = 16 ) on platelet thromboxane A2 and vascular prostacyclin in women at risk for pregnancy-induced hypertension . Low doses of aspirin were associated with a longer pregnancy and increased weight of newborns . Serum levels of thromboxane B2 , a stable product of thromboxane A2 , were almost completely ( greater than 90 percent ) inhibited by low doses of aspirin . The urinary excretion of immunoreactive thromboxane B2 was significantly reduced without changes in the level of 6-keto-prostagl and in F1 alpha , a product of prostacyclin . Mass spectrometric analysis showed that aspirin reduced the excretion of the 2,3-dinor-thromboxane B2 metabolite -- mainly of platelet origin -- by 81 percent and of thromboxane B2 , probably chiefly of renal origin , by 59 percent . The urinary excretion of 6-keto-prostagl and in F1 alpha and of its metabolite 2,3-dinor-6-keto-prostagl and in F1 alpha was not affected . Low doses of aspirin only partially ( 63 percent ) reduced neonatal serum thromboxane B2 . No hemorrhagic complications were observed in the newborns . Thus , in women at risk for pregnancy-induced hypertension , low doses of aspirin selectively suppressed maternal platelet thromboxane B2 while sparing vascular prostacyclin , but only partially suppressed neonatal platelet thromboxane B2 , allowing hemostatic competence in the fetus and newborn OBJECTIVE The purpose of this study was to determine if acetaminophen decreased prostacyclin production by endothelial cells in culture and by pregnant women . STUDY DESIGN The effect of acetaminophen on endothelial cells in culture was determined by the addition of acetaminophen in concentrations of 10 and 100 micrograms/ml with comparison to control and indomethacin at 10 micrograms/ml . Prostacyclin production was estimated in 24 and thromboxane A2 production in six third-trimester pregnant women by measurement of excretion of urinary metabolites before and after ingestion of either 1000 mg of acetaminophen or placebo . RESULTS Compared with control ( 549 + /- 61 pg/well , mean + /- SD ) , production of prostacyclin in vitro was significantly inhibited by acetaminophen at 10 micrograms/ml ( 321 + /- 25 ) and 100 micrograms/ml ( 257 + /- 14 ) . This inhibition is similar to inhibition by 10 micrograms/ml of indomethacin ( 228 + /- 11 ) . Excretion of prostacyclin metabolite was significantly lower after ingestion of acetaminophen ( 2233 + /- 446 vs 1246 + /- 199 pg/mg creatinine , mean + /- SEM ) but unchanged after ingestion of placebo ( 1745 + /- 304 vs 1712 + /- 211 ) . There was no difference in response between normal and hypertensive women , and there was no effect of acetaminophen on thromboxane metabolite excretion . CONCLUSION Acetaminophen in typical oral doses results in reduced production of prostacyclin by endothelial cells in culture and in a reduction in prostacyclin , but not thromboxane , production in pregnant women OBJECTIVE To evaluate the effects of low-dose aspirin on placental circulation and on the prevention of intrauterine growth retardation ( IUGR ) . MATERIAL AND METHODS We conducted a prospect i ve r and omized , double blind , controlled clinical trial in 84 pregnant women ( mainly nulliparous women ) at high risk of IUGR . From the 28th-30th week of gestation onward , low dose aspirin ( 75 mg daily , study group , n = 40 ) or placebo ( control group , n = 44 ) was given consecutively for 6 to 8 weeks . Pulse-wave umbilical artery Doppler velocimetry was measured before and after drug use . RESULTS The mean value of systolic/diastolic ratio of umbilical artery flow velocity waveforms in the study group was significantly lower than that in the control group after drug use , but there was no difference between the two groups before drug use . The incidences of IRGR and preeclampsia in the study group ( 7.5 % and 10.0 % respectively ) were significantly lower than those in the control group ( 27.3 % of both ) . No adverse effects of low dose aspirin on both mother and fetus were observed . CONCLUSIONS Low dose aspirin administration ( 75 mg daily ) beginning at the early stage of third trimester may improve the fetoplacental circulation , and thus prevent IUGR and /or preeclampsia effectively There is evidence that aspirin in low doses favourably influences the course and outcome of pregnancy in women at risk of developing pregnancy-induced hypertension . We conducted a double blind prospect i ve r and omized study to investigate the effect of low dose aspirin in preventing pregnancy-induced hypertension . Two hundred and one primigravidae from twenty weeks of pregnancy and above were screened using the roll-over test . Of the 127 women with an increase in blood pressure during the roll-over test , 126 women entered the study and were treated with a daily dose of either aspirin ( 80 mg ) or placebo up to 10 days before the expected date of delivery . Sample s of urine were collected for detection of aspirin . The incidence of pregnancy-induced hypertension in the aspirin treated group was significantly lower than in the placebo treated group ; 3.17 % versus 15.9 % with a p value of 0.02 . It is concluded that low daily doses of aspirin taken from twenty weeks of pregnancy significantly reduce the incidence of pregnancy-induced hypertension , possibly through the correction of an imbalance in levels of thromboxane and prostacyclin OBJECTIVE The aim of the study was too determine whether , in a low-dose aspirin trial in high-risk pregnancies , a decrease in maternal serum thromboxane B2 level predicted improved pregnancy outcomes . STUDY DESIGN This multicenter , r and omized , double-blind trial included 2539 women , 1010 of whom had sufficient serum sample s at enrollment and at 24 to 28 weeks ' gestation , 34 to 38 weeks ' gestation , or both to assess longitudinal changes in thromboxane B2 level and their effects on pregnancy outcomes . Women were r and omly assigned between 13 and 26 weeks ' gestation to receive daily aspirin ( 60 mg ) or placebo . RESULTS Overall and in all subgroups women assigned to receive aspirin had markedly lower maternal thromboxane B2 concentration values than did those assigned to receive a placebo ( P = .0001 ) . Changes in thromboxane levels were not , however , correlated with adverse pregnancy outcomes . Women with > /=50 % reduction in maternal serum thromboxane B2 concentrations from baseline had occurrences of preeclampsia ( P = .922 ) , preterm birth ( P = .375 ) , small for gestational age neonates ( P = .938 ) , and grade III or IV intraventricular hemorrhage ( P = 1.000 ) similar to those of women who had < 50 % reduction . Similar results were found for women with thromboxane B2 level decreases of < 15 versus > 15 ng/mL and women with thromboxane B2 level decreases to < 10 versus > /=10 , < 5 versus > /=5 , and < 1 versus > /=1 ng/mL. Maternal thromboxane B2 concentrations at enrollment were also not predictive of adverse outcomes . CONCLUSION Neither maternal serum thromboxane B2 concentrations at enrollment nor their subsequent reduction were predictive of adverse pregnancy outcomes in a low-dose aspirin trial A multicentric r and omized double-blind trial was realized in order to determine whether a treatment with a low-dose aspirin ( 150 mg/day ) with or without dipyridamole ( 225 mg/day ) was able to prevent the perinatal consequences of pre-eclampsia . This study demonstrated a significant difference in birthweight and incidence of fetal growth retardation between treatment and placebo groups . No difference was demonstrated between aspirin and aspirin + dipyridamole patients The possibility of preventing pregnancy-induced hypertension ( PIH ) and pre-eclampsia in primigravidae by suppressing production of thromboxane A2 with low-dose aspirin was investigated in a r and omised , placebo-controlled , double-blind trial . 46 normotensive women at 28 weeks ' gestation , judged to be at risk of PIH or pre-eclampsia because of an increased blood-pressure response to intravenously infused angiotensin II , were studied . 23 women received 60 mg aspirin daily , and the same number received matching placebo until delivery . In the placebo group PIH , pre-eclampsia , and eclampsia developed in 4 , 7 , and 1 cases , respectively , whereas only 2 women in the aspirin group had mild PIH . There were no adverse effects of treatment in mothers or infants . Low-dose aspirin may restore prostacyclin/thromboxane imbalance , previously suggested as an important aetiological factor in PIH and pre-eclampsia |
10,406 | 17,054,269 | MAIN RESULTS Men with prostate cancer have different clinical outcomes based on their risk ( T1-T2 , T3-T4 , PSA levels and Gleason score ) .
Hormone therapy combined with either prostatectomy or radiotherapy is associated with significant clinical benefits in patients with local or locally advanced prostate cancer .
Significant local control may be achieved when given prior to prostatectomy or radiotherapy , which may improve patient 's quality of life .
When given adjuvant to these primary therapies , hormone therapy , not only provides a method for local control , but there is also evidence for a significant survival advantage . | BACKGROUND Hormone therapy for early prostate cancer has demonstrated an improvement in clinical and pathological variables , but not always an improvement in overall survival .
We performed a systematic review of both adjuvant and neo-adjuvant hormone therapy combined with surgery or radiotherapy in localised or locally advanced prostate cancer .
OBJECTIVES The objective of this review was to undertake a systematic review and , if possible , a meta- analysis of neo-adjuvant and adjuvant hormone therapy in localised or locally advanced prostate cancer . | PURPOSE Patients who present with localized and locally advanced prostate cancer may be c and i date s for prostate brachytherapy . We evaluated the treatment outcomes in a diverse group of prostate cancer patients who presented with low , moderate and high risk features . MATERIAL S AND METHODS A total of 301 patients who presented with T1 to T3 prostate cancer were treated with brachytherapy alone or combined with hormonal therapy and /or external beam irradiation . Of these patients 109 at low risk with prostate specific antigen ( PSA ) 10 ng./ml . or less , Gleason score 6 or less and clinical stage T2a or less were treated with 125iodine alone , 152 at moderate risk with PSA greater than 10 ng./ml . , Gleason score greater than 6 or stage T2b or greater were treated with 125iodine or 103palladium or combined implant alone with 5 months of hormonal therapy , and 40 at high risk with PSA greater than 15 ng./ml . , Gleason 8 or greater , clinical stage T2c to T3 or positive seminal vesicle biopsy ( 20 ) were treated with combination brachytherapy , external beam irradiation and 9 months of hormonal therapy . Patients with a positive seminal vesicle biopsy ( T3c disease ) and negative pelvic lymph nodes were included in the high risk group , and the walls of the seminal vesicles were also treated with implantation . Followup was performed every 6 months with digital rectal examination and ultrasound evaluation . Prostate biopsy was routinely recommended 2 years after completion of the radiation . Failure was defined as PSA increase on 2 consecutive determinations above 1 ng./ml . or evidence of local recurrence on digital rectal examination , transrectal ultrasound or biopsy . Kaplan-Meier projections were used to calculate progression-free survival rates . RESULTS Of the 109 patients at low risk followed from 1 to 7 years ( median 18 months ) 91 % were free of PSA failure at 4 years . No patient experienced urinary incontinence following implantation , although grade 1 to 2 radiation proctitis occurred in 5 ( 4.5 % ) . Of the 152 patients at moderate risk 73 received implantation and 79 received implantation combined with hormonal therapy . The 4-year biochemical freedom from failure rate for the hormone group was 85 % versus 58 % for the no hormone group ( p = 0.08 ) . The difference was more significant for those with Gleason score 7 or greater ( 90 versus 43 % , p = 0.01 ) and for those with PSA greater than 10 ng./ml . ( 87 versus 59 % , p = 0.04 ) . Grade 1 to 2 radiation proctitis occurred in 1 of the 79 patients ( 1.3 % ) receiving hormonal therapy and in 3 ( 4 % ) treated with implantation only . There were no cases of urinary incontinence . Of the 40 patients at high risk 71 % were free of biochemical failure at 3 years . Of the 4 patients with failure ( 10 % ) 3 ( 75 % ) originally had positive seminal vesicle biopsies . Five patients experienced gastrointestinal complications , although none was grade 3 or 4 . The actuarial freedom from grade 2 proctitis was 82 % . No patient experienced urinary incontinence . Prostate biopsies were negative in 87 % of the low risk , 96.8 ( hormone group ) versus 68.6 % ( no hormone group ) of the moderate risk ( p = 0.0023 ) and 86 % of the high risk patients . CONCLUSIONS Brachytherapy appears to offer comparable results to external beam irradiation and radical prostatectomy when patients are stratified by disease extent . Adopting a strategy of implant alone , implant with hormonal therapy or implant with hormonal therapy and external beam irradiation in patients who present with low to high risk features can improve the overall results in the more advanced cases OBJECTIVES To evaluate the short- and long-term effects of neoadjuvant hormonal treatment in locally confined prostate cancer . METHODS We report the preliminary results of 354 patients ( 199 with a clinical T2 tumor and 155 with a clinical T3 tumor ) of whom 164 r and omly received neoadjuvant total and rogen deprivation using a luteinizing-hormone-releasing hormone ( LHRH ) analog ( goserelin ) plus flutamide for a period of 3 months . RESULTS Serum prostate-specific antigen ( PSA ) levels and prostatic volume decreased from a mean of 19.9 ng/mL and 37.7 cm3 to a mean of 0.8 ng/mL and 26.5 cm3 after 3 months of neoadjuvant therapy . " Clinical down-staging " was seen in 32 % in the neoadjuvantly treated group . " Pathological downstaging " percentages were 6 % and 16 % in the direct radical prostatectomy group and neoadjuvantly-treated group , respectively ( P < 0.01 ) . In patients with clinical T2 tumors , a significant difference in number of positive margins was shown in favor of the neoadjuvantly treated group ( P < 0.01 ) . In patients with clinical T3 tumors , a significant difference could not be detected ( P = 0.14 ) . In 215 patients with a mean follow-up time of 15 months , the calculated 95 % confidence intervals of mean time of PSA progression-free survival were 26 to 35 months in the neoadjuvantly-treated group and 28 to 37 months in the direct radical prostatectomy group , indicating no significant differences between treatment groups . However , follow-up time is currently too short to draw definite conclusions . CONCLUSIONS These early data confirm high understaging percentages in clinical staging . The clinical relevance of the statistically significant smaller numbers of patients with positive margins in the neoadjuvantly treated group with a clinical T2 tumor will have to be confirmed when further follow-up allows an accurate evaluation of time to PSA progression , local recurrence , and distant metastases . Presently , neoadjuvant therapy is not advisable outside clinical research setting A total of 161 patients diagnosed as having stage B ( 134 patients ) or C ( 27 patients ) prostate cancer were r and omly assigned to radical prostatectomy alone or to 3 months of neoadjuvant combination therapy with the anti- and rogen flutamide and an LHRH agonist before radical prostatectomy . Neoadjuvant combination therapy before radical prostatectomy decreased cancer positive surgical margins from 33.8 % in the control group to only 7.8 % , thus leaving 92.2 % of patients with negative margins at surgery for a 39.2 % increase in specimen confined disease . Although on average the final stage determined at histopathological examination of the surgical specimen was more advanced than predicted at initial diagnosis in 33.8 % of control patients , an opposite observation was made in the group of men who received the 3 month neoadjuvant combination therapy where the final stage , instead of being more advanced , was less advanced than at diagnosis in an average of 21.1 % of men for a net 54.9 % improvement of staging in favour of combination therapy . On the other h and , organ confined disease increased from 49.3 % to 77.8 % of patients after 3 months of combination therapy , for a 57.9 % increase in the incidence of organ confined disease . Although long term follow up of these patients is required to determine the impact on survival , the marked influence of neoadjuvant combination therapy on the stage of the disease suggests the possibility of a major improvement in the morbidity and mortality from prostate cancer BACKGROUND AND PURPOSE The ongoing Early Prostate Cancer ( EPC ) programme is assessing bicalutamide ( ' Casodex ' ) 150 mg , either alone or as adjuvant to treatment of curative intent , in patients with localised or locally advanced prostate cancer ( n=8113 ) . This paper presents an exploratory analysis of the subgroup of the EPC programme who received radiotherapy with curative intent ( n=1370 ) in order to determine the efficacy ( in terms of progression-free survival [ PFS ] ) and tolerability of bicalutamide 150 mg in this setting . PATIENTS AND METHODS 1370 patients with T1 - 4 , MO , any N prostate cancer received bicalutamide 150 mg or placebo adjuvant to radiotherapy of curative intent . This analysis was undertaken at median 5.3 years ' follow-up . RESULTS In patients with locally advanced disease ( n=305 ) , bicalutamide adjuvant to radiotherapy significantly increased PFS by 53 % ( event-time ratio 1.53 ; 95 % confidence intervals [ CI ] 1.16 , 2.02 ) compared with placebo and reduced the risk of disease progression by 42 % ( hazard ration [ HR ] 0.58 ; 95 % CI 0.41 , 0.84 ; P=0.00348 ) . In these patients , objective progression was experienced by 33.5 % of those r and omised to bicalutamide versus 48.6 % for those r and omised to placebo . The between-group difference in patients with localised disease ( n=1065 ) failed to reach statistical significance ( HR 0.80 ; 95 % CI 0.62 , 1.03 ; P=0.088 ) . The most common adverse events were breast pain ( 74.8 % ) and gynaecomastia ( 66.6 % ) , which were mild to moderate in > 90 % of cases . CONCLUSIONS Bicalutamide 150 mg/day given as adjuvant to radiotherapy significantly improved PFS in patients with locally advanced prostate cancer . For patients with localised disease , the results at this stage from the radiotherapy subgroup and the overall EPC programme suggest that adjuvant hormonal therapy is currently not appropriate . There were no unexpected tolerability findings PURPOSE A prospect i ve phase 3 trial was initiated to determine whether 8 compared with 3-month neoadjuvant hormonal therapy reduces prostate specific antigen ( PSA ) recurrence rates after radical prostatectomy . Our interim analysis includes secondary end points of differences in biochemistry , pathology and adverse events between the 2 groups . MATERIAL S AND METHODS Men with clinical ly confined prostate cancer were r and omized to receive 7.5 mg . leuprolide intramuscularly monthly and 250 mg . flutamide orally 3 times daily for 3 or 8 months before radical prostatectomy . Our study was powered to detect a 35 % decrease in PSA recurrence , assuming a 30 % recurrence rate in the 3-month arm after 3 years . RESULTS A total of 547 men were r and omized between August 1995 and April 1998 . Men in the 8 and 3-month groups were equally stratified for T stage ( 29 % T1c , 70 % T2 ) , Gleason grade ( 68 % less than 4 , 32 % 4 or greater ) and pretreatment PSA ( 63 % less than 10 , 27 % 10 to 20 and 10 % greater than 20 microg./l . ) . Mean pretreatment PSA was slightly higher in the 8-month compared with the 3-month group ( 11.64 versus 9.95 microg./l . , respectively , p = 0.0539 ) . A total of 44 men withdrew from study before surgery and , therefore , were nonevaluable . Preoperative PSA nadir was less than 0.1 microg./l . in 43.3 % versus 75.1 % ( p < 0.0001 ) , and 0.3 microg./l . or greater in 21 % versus 9.2 % after 3 versus 8 months , respectively ( p < 0.0006 ) . Mean serum PSA decreased 98 % to 0.12 microg./l . after 3 months , with a further 57 % to 0.052 microg./l . from 3 to 8 months . Transrectal ultrasound determined that prostatic volume decreased 37 % from a mean of 40.6 to 25.4 cc after 3-month neoadjuvant hormonal therapy ( p = 0.0001 ) and a further 13 % to 22.2 cc after 8 months ( p = 0.03 ) . Mean hemoglobin decreased 15 % ( 148.2 to 125.4 gm./dl . ) after 3-month neoadjuvant hormonal therapy but stabilized thereafter . Radical prostatectomy was completed in 500 men , while surgery was aborted intraoperatively in 3 . Positive margin rates were significantly lower in the 8 than 3-month group ( 12 % versus 23 % , respectively , p = 0.0106 ) . There were no fatal adverse events and no differences between the 2 groups in the severity or causality ( p = 0.287 , 0.0564 ) of adverse events , or incidence of increased liver enzymes or diarrhea ( p = 0.691 , 0.288 , respectively ) . However , men in the 8-month group noticed a higher number of newly reported adverse events ( 4.5 versus 2.9 , p < 0.0001 ) and higher incidence of hot flushes than the 3-month group ( 87 % versus 72 % , respectively , p < 0.0001 ) . CONCLUSIONS Ongoing biochemical and pathological regression of prostate tumors occurs between 3 and 8 months of neoadjuvant hormonal therapy , suggesting that the optimal duration of neoadjuvant hormonal therapy is longer than 3 months . Longer followup is needed to determine whether longer therapy alters PSA recurrence rates The likelihood of finding organ-confined untreated prostate cancer ( PCa ) by pathological examination at the time of radical prostatectomy ( RP ) is only 50 % in patients with clinical ly organ-confined disease . In addition , tumour is present at the resection margin in approximately 30 % of clinical T2 ( clinical stage B ) cases . The issue of clinical " understaging " and of resection limit positivity have led to the development of novel management practice s , including " neoadjuvant " hormonal therapy ( NHT ) . The optimal duration of NHT is unknown . We undertook the present analysis to evaluate the effect of NHT on pathologic stage of PCa and resection limit status in patients with prostate cancer and treated with total and rogen ablation either for three or six months before RP . Between January 1996 and February 1998 , 259 men with prostate cancer underwent radical retropubic prostatectomy and bilateral pelvic node dissection in the 26 centres participating in the Italian r and omised prospect i ve PROSIT study . Whole mount sectioning of the complete RP specimens was adopted in each centre for accurately evaluating the pathologic stage and resection limit status . By February 1998 , haematoxylin and eosin stained sections from 155 RP specimens had been received and evaluated by the review ing pathologist ( RM ) . 64 cases had not been treated with total and rogen ablation ( e.g. NHT ) before RP was performed , whereas 58 and 33 had been treated for three and six months , respectively . 114 patients were clinical stage B whereas 41 were clinical stage C. After three months of total and rogen ablation , pathological stage B was more prevalent among patients with clinical B tumours , compared with untreated patients ( 57 % in treated patients vs. 36 % in untreated ) . The percentage of cancers with negative margins was statistically significantly greater in patients treated with neoadjuvant therapy than those treated with immediate surgery alone ( 69 % vs. 42 % , respectively ) . After six months of NHT therapy the proportion of patients with pathological stage B ( 67 % vs. 36 % , respectively ) and negative margins was greater than after 3 months ( 92 % vs. 42 % , respectively ) . For clinical C tumours , the prevalence of pathological stage B and negative margins in the patients treated for either 3 or 6 months was not as high as in the clinical B tumours , when compared with the untreated group ( pathological stage B : 31 % and 33 % vs. 6 % in the clinical C cases , respectively . Negative margins : 56 % and 67 % vs. 31 % , respectively ) . The initial results of this study suggest that total and rogen ablation before RP is beneficial in men with clinical stage B because of the significant pathological downstaging and decrease in the number of positive margins in the RP specimens . These two effects are more pronounced after six months of NHT than after three months of therapy . The same degree of beneficial effects are not observed in clinical C tumours OBJECTIVES To test the hypothesis that neoadjuvant and rogen ablation before radical prostatectomy reduces the likelihood of biochemical progression at 36 months . METHODS Two hundred thirteen patients with localized prostate cancer were r and omized to radical prostatectomy alone ( Sx , n = 101 ) or a 12-week course of 300 mg of cyproterone acetate daily followed by surgery ( CPA , n = 112 ) . Biochemical progression ( two consecutive detectable prostate-specific antigen [ PSA ] values ) was determined for the entire group and by baseline PSA , Gleason score , clinical stage , and pathologic stage . RESULTS The probability of biochemical progression at 36 months was similar in both groups ( CPA 40.2 % , Sx 30.1 % ; P = 0.3233 ) . CPA patients with baseline serum PSA between 25 and 50 ng/mL had a lower probability of biochemical progression ( CPA 63.5 % , Sx 84.6 % ; P = 0.0038 ) . No difference in the probability of biochemical progression was seen between groups when analyzed by clinical stage or Gleason score . When analyzed by pathologic margin status , no difference was observed in the probability of biochemical progression in patients with organ-confined disease ( P = 0.4484 ) . There was a trend for a higher probability of progression in the neoadjuvant arm in patients with positive and negative surgical margins ( P = 0.0105 , P = 0.0459 ; alpha = 0.005 with Bonferroni adjustment ) . CONCLUSIONS Neoadjuvant and rogen ablation with CPA reduces the positive margin rate significantly but does not result in a difference in biochemical progression at 3 years . This may be due to a lack of sufficient follow-up , insufficient power of the trial to demonstrate a small benefit , or a true lack of benefit of neoadjuvant and rogen ablation before radical prostatectomy OBJECTIVE To evaluate the effect of bicalutamide ( ' Casodex ' ) 150 mg ( in addition to st and ard care ) , on the risk of prostate-specific antigen ( PSA ) progression , in patients with early prostate cancer . METHODS The bicalutamide 150 mg Early Prostate Cancer ( EPC ) programme is the largest clinical trial programme in the treatment of prostate cancer to date . This paper reports the PSA progression data from the EPC programme at a median of 3years ' follow-up , for the overall study population , and across the radical prostatectomy and radiotherapy primary therapy strategies . PSA progression was predefined as the earliest occurrence of PSA doubling from baseline , objective progression , or death from any cause . RESULT Overall , bicalutamide 150 mg in addition to st and ard care significantly reduced the risk of PSA progression by 59 % compared with st and ard care alone ( HR 0.41 ; 95 % CI 0.38 , 0.45 ; p<<0.0001 ) . Significant reductions were observed following radical prostatectomy ( 51 % ; HR 0.49 ; 95 % CI 0.43 , 0.56 ; p<<0.0001 ) and radiotherapy ( 58 % ; HR 0.42 ; 95 % CI 0.33 , 0.53 ; p<<0.0001 ) . Further exploration of the data by disease stage , nodal status , Gleason score and pre-treatment PSA level revealed significant reductions in the risk of PSA progression across most prognostic risk factor subgroups . CONCLUSIONS Bicalutamide 150 mg significantly reduces the risk of PSA progression , irrespective of whether patients received radical prostatectomy or radiotherapy as st and ard care . The EPC programme is ongoing and further progression and survival data are awaited OBJECTIVES To report an exploratory subgroup analysis assessing the extent to which the overall benefit found in the Early Prostate Cancer program is dependent on lymph node status at r and omization . The program is ongoing , and the overall survival data are immature . The first combined analysis of the bicalutamide ( Casodex ) Early Prostate Cancer program at 3 years ' median follow-up showed that bicalutamide , 150 mg once daily , plus st and ard care ( radical prostatectomy , radiotherapy , or watchful waiting ) , significantly reduced the risk of objective progression and prostate-specific antigen ( PSA ) doubling in patients with localized/locally advanced prostate cancer . METHODS Men ( n = 8113 ) with localized/locally advanced disease received bicalutamide 150 mg or placebo once daily , plus st and ard care . The time to event data ( objective progression , PSA doubling ) was analyzed by lymph node status at r and omization . RESULTS Compared with st and ard care alone , bicalutamide significantly reduced the risk of objective progression , irrespective of lymph node status , with the most pronounced reduction in patients with N+ ( hazard ratio [ HR ] 0.29 ; 95 % confidence interval [ CI ] 0.15 to 0.56 ) compared with those with N0 ( HR 0.59 ; 95 % CI 0.48 to 0.73 ) and Nx ( HR 0.60 ; 95 % CI 0.50 to 0.72 ) disease . The largest decrease in risk of PSA doubling with bicalutamide was observed in N+ disease ( HR 0.16 ; 95 % CI 0.09 to 0.29 ) , with significantly reduced risks seen in N0 ( HR 0.45 ; 95 % CI 0.40 to 0.51 ) and Nx ( HR 0.38 ; 95 % CI 0.33 to 0.44 ) disease . CONCLUSIONS The greatest reduction in the risk of objective progression and PSA doubling with bicalutamide was seen in patients with N+ disease . However , bicalutamide also provided a statistically significant benefit in those with N0 and Nx disease PURPOSE We evaluated the benefits and sequencing of and rogen suppression ( AS ) administered with external beam radiation therapy ( EBRT ) in T2-T3 prostate cancers . MATERIAL S AND METHODS Between 1990 and 1999 , 481 patients were entered in 2 successive , prospect i ve , r and omized studies , including 161 in the study 1 and 325 in study 2 . Eligible patients had clinical stages T2-T3 prostate cancer . In the first study ( L-101 ) subjects were r and omly allocated among EBRT alone ( group 1 ) , EBRT preceded by 3 months of AS ( group 2 ) , and neoadjuvant , concomitant and adjuvant AS for a total of 10 months ( group 3 ) . In the second study ( L-200 ) we analyzed neoadjuvant and concomitant AS ( total 5 months ) vs neoadjuvant , concomitant and short course adjuvant ( total 10 months ) AS with EBRT . In each study we used a total AS ( a luteinizing hormone-releasing hormone agonist plus an anti and rogen ) and a st and ard dose of radiation therapy at that time . Patient characteristics were well balanced in regard to age , stage , prostate specific antigen and Gleason score . No biochemical evidence of disease ( BNED ) was defined as an end point according to the Vancouver rule . RESULTS In the study 1 at a median followup of 5 years 7-year biochemical-free survival rates were 42 % , 66 % and 69 % in groups 1 to 3 , respectively . BNED was significantly different between groups 1 and 2 ( p = 0.009 ) and between groups 1 and 3 ( p = 0.003 ) but not between groups 2 and 3 ( p = 0.6 ) . Multivariate analysis using a Cox proportional hazards model showed an HR of 6.1 for Gleason score ( p = 0.001 ) , 1.4 for PSA ( p = 0.002 ) , 0.5 for group 1 vs group 2 ( p = 0.01 ) and 0.35 for group 1 vs group 3 ( p = 0.008 ) . In study 2 BNED at 4 years was 65 % . There was no significant difference between arms 1 and 2 ( p = 0.55 ) . CONCLUSIONS The analysis of study 1 shows a benefit of using a short course of neoadjuvant AS with EBRT vs EBRT alone for localized T2-T3 prostate cancers . Moreover , in each study adding a short course of adjuvant AS after neoadjuvant 1 provided no more advantage in these patients BACKGROUND We conducted a r and omized , prospect i ve trial comparing external irradiation with external irradiation plus goserelin ( an agonist analogue of gonadotropin-releasing hormone that reduces testosterone secretion ) in patients with locally advanced prostate cancer . METHODS From 1987 to 1995 , 415 patients with locally advanced prostate cancer were r and omly assigned to receive radiotherapy alone or radiotherapy plus immediate treatment with goserelin . The patients had a median age of 71 years ( range , 51 to 80 ) . Patients in both groups received 50 Gy of radiation to the pelvis over a period of five weeks and an additional 20 Gy over an additional two weeks as a prostatic boost . Patients in the combined-treatment group received 3.6 mg of goserelin ( Zoladex ) subcutaneously every four weeks starting on the first day of irradiation and continuing for three years ; those patients also received cyproterone acetate ( 150 mg orally per day ) during the first month of treatment to inhibit the transient rise in testosterone associated with the administration of goserelin . RESULTS Data were available for analysis on 401 patients . The median follow-up was 45 months . Kaplan-Meier estimates of overall survival at five years were 79 percent ( 95 percent confidence interval , 72 to 86 percent ) in the combined-treatment group and 62 percent ( 95 percent confidence interval , 52 to 72 percent ) in the radiotherapy group ( P=0.001 ) . The proportion of surviving patients who were free of disease at five years was 85 percent ( 95 percent confidence interval , 78 to 92 percent ) in the combined-treatment group and 48 percent ( 95 percent confidence interval , 38 to 58 percent ) in the radiotherapy group ( P<0.001 ) . CONCLUSIONS Adjuvant treatment with goserelin , when started simultaneously with external irradiation , improves local control and survival in patients with locally advanced prostate cancer PURPOSE To determine the potential advantage of and rogen ablation following st and ard external-beam radiation therapy in patients with locally advanced ( clinical or pathologic T3 ; clinical or pathologic node positive ) carcinoma of the prostate . METHODS AND MATERIAL S In 1987 the RTOG initiated a Phase III trial of long-term adjuvant goserelin in definitively irradiated patients with carcinoma of the prostate . A total of 977 patients were accrued to the study of which 945 remain analyzable : 477 on the adjuvant hormone arm ( Arm I ) ; and 468 on the radiation only arm ( Arm II ) with hormones initiated at relapse . The initial results were reported in the Journal of Clinical Oncology in 1997 . RESULTS With a median follow up of 5.6 years for all patients and 6.0 years for living patients local failure at 8 years was 23 % for Arm I and 37 % for Arm II ( p < 0.0001 ) . Distant metastasis was likewise favorably impacted with the immediate use of hormonal manipulation with a distant metastasis rate in Arm I of 27 % and 37 % in Arm II ( p < 0.0001 ) . Disease-free survival ( NED survival ) and NED survival with PSA of 1.5 ng/mL ( bNED ) or less were both statistically significant in favor of the immediate hormone arm ( both p < 0.0001 ) . Cause-specific failure was not statistically different with a cause-specific failure of 16 % for Arm I and 21 % in Arm II ( p = 0.23 ) . Overall survival was likewise not statistically different between two arms , with a 49 % overall survival at 8 years in Arm I and 47 % in Arm II ( p = 0.36 ) . Subset analysis of central ly review ed Gleason 8 - 10 patients who did not undergo prostatectomy showed that for patients receiving radiation therapy plus adjuvant hormones there was a statistically significant improvement in both absolute ( p = 0.036 ) and cause-specific survival ( p = 0.019 ) . CONCLUSIONS Use of long-term adjuvant and rogen deprivation in addition to definitive radiation therapy results in a highly significant improvement in regards to local control , freedom from distant metastasis , and biochemical free survival in unfavorable prognosis patients with carcinoma of the prostate PURPOSE To compare , by a secondary analysis , the therapeutic benefits of and rogen suppression in protocol prostate cancer patients with relapse after radiotherapy ( RT ) for locally advanced disease who , in the Phase III trial beginning in 1987 , were assigned to receive or not receive a short course of neoadjuvant maximal and rogen suppression before definitive RT . METHODS AND MATERIAL S Between 1987 and 1991 , 456 patients were entered in the Radiation Therapy Oncology Group trail 86 - 10 and r and omized to receive ( Arm I ) or not to receive ( Arm II ) neoadjuvant hormonal therapy ( HT ) , which was 4 months of goserelin ( 3.6 mg every 4 weeks ) and flutamide ( 250 mg t.i.d . ) before and during RT for bulky T2-T4 tumors . The overall and disease-specific survival after both r and omization and salvage HT for patients with relapse was evaluated , as well as the duration of response in those patients undergoing salvage HT . The outcomes in patients who had received neoadjuvant HT vs. those who had not were compared . The median follow-up after r and omization for all alive patients was 9.0 years and was 5.5 years for alive patients after beginning salvage HT . RESULTS Fewer patients received salvage HT on Arm I than on Arm II ( 45 % vs. 63 % , p < 0.001 ) . The outcomes by r and omized treatment arm ( I vs. II ) from the time of beginning salvage HT were similar . At 5 years after salvage HT , the overall survival rates were 41 % and 41 % and the disease-specific survival rates were 50 % and 50 % . At 8 years after r and omization , the overall survival rates were 47 % and 44 % and the disease-specific survival rates were 55 % and 56 % . CONCLUSION Although a 4-month course of neoadjuvant and concurrent maximum and rogen suppression and RT ( compared with RT alone ) significantly increases the freedom from relapse rate and freedom from receiving salvage HT , it does not compromise the long-term beneficial effect of subsequent salvage HT , if needed for relapse . These findings with long follow-up in patients treated for locally advanced disease diagnosed 9 - 14 years previously should help allay concerns of the possible development of " resistance " to and rogen suppression when 4-month courses of neoadjuvant HT are used before primary treatment PURPOSE In 1992 we initiated a national r and omized prospect i ve trial of 3 months of cyproterone acetate before radical prostatectomy compared to prostatectomy alone . Initial results indicated a 50 % decrease in the rate of positive surgical margins . This decrease did not translate into a difference in prostate specific antigen ( PSA ) progression at 3 years . This report is on the long-term outcome ( median followup 6 years ) of this cohort . MATERIAL S AND METHODS This prospect i ve , r and omized , open label trial compared 100 mg cyproterone acetate 3 times daily for 3 months before surgery to surgery alone . R and omization occurred between January 1993 and April 1994 . Patients were stratified according to clinical stage , baseline serum PSA and Gleason sum . A total of 213 patients were accrued . Biochemical progression was defined as 2 consecutive detectable PSAs ( greater than 0.2 ng/ml ) at least 4 weeks apart , re-treatment or death from prostate cancer . RESULTS A total of 34 ( 33.6 % ) patients undergoing surgery only and 42 ( 37.5 % ) patients given neoadjuvant hormone therapy ( NHT ) had biochemical recurrence during the median followup of 6 years . Despite the significant pathological down staging in this study , there was no significant difference in number of patients with no evidence of biochemical disease ( bNED ) survival ( p = 0.732 ) . A bNED survival benefit favoring NHT was seen in men with a baseline PSA greater than 20 ( p = 0.015 ) . CONCLUSIONS After 6 years of followup there was no overall benefit with 3 months of NHT . Improved bNED survival was seen in the highest risk PSA group ( PSA greater than 20 ) . The possibility that high risk patients may benefit from NHT warrants further investigation Objectives : To assess the effect of neoadjuvant hormone treatment before radical prostatectomy on : tumor/prostate volume , prostate-specific antigen ( PSA ) and testosterone levels , surgical margin status and tumor stage , and the ease of surgery following treatment . Methods : Patients with clinical ly localized prostatic carcinoma were r and omized to receive leuprolide acetate depot 3.75 mg once a month for 3 months and cyproterone acetate 300 mg once a week for 3 weeks prior to surgery ( group A ) . A control group of patients had surgery without any pretreatment ( group B ) . Results : 167 patients were evaluated for the efficacy parameters . In group A , 31 % of patients had a reduction in tumor/prostate volume following hormone therapy . PSA and testosterone levels were significantly reduced ( p = 0.0001 ) in patients in group A compared to basal values . Central ized histopathological data evaluated in 145 patients ( group A and 75 group B ) showed that more patients in group B had tumors at stages T3A and T3B than in group A ; this difference was close to significance ( p = 0.057 ) . Positive surgical margins were more common in group B ( 60 % of patients ) compared to group A ( 39 % of patients ) . Similarly lymph node involvement was more common in group B compared to group A ( 11 versus 3 % ) . There was little difference between the 2 study groups for the other surgical parameters assessed ( ease of dissection , duration of surgery , blood loss ) . Conclusions : Neoadjuvant hormone therapy before radical prostatectomy has some effects in the treatment of prostate cancer . However , long-term follow-up of patients is needed to assess the impact of this therapy on morbidity and mortality Prostate specific membrane antigen ( PSMA ) is a transmembrane glycoprotein highly expressed in benign prostate secretory‐acinar epithelium and prostate carcinoma . The results of several studies suggest that PSMA expression is increased in prostate carcinoma cell lines subjected to and rogen deprivation and in and rogen‐independent tumors . The authors studied the effects of short term ( 3‐month ) and rogen deprivation on PSMA expression in prostate carcinoma specimens using two anti‐PSMA monoclonal antibodies ( mAbs ) , 7E11 and PM2J004.5 OBJECTIVES To evaluate bicalutamide ( Casodex ) 80 mg as a component of maximum and rogen blockade ( MAB ) in Japanese patients with previously untreated advanced prostate cancer . METHODS 205 patients with previously untreated stage C/D prostate cancer were r and omized ( 1:1 ) to receive once-daily bicalutamide 80 mg or placebo , each combined with a luteinizing hormone-releasing hormone ( LHRH ) agonist . Primary study variables were the 12 week prostate-specific antigen ( PSA ) normalization ( i.e. PSA level < or=4 ng/ml ) rate , the 12 week overall tumor response rate ( proportion with a partial response or better ) and the proportion of withdrawals due to adverse drug reactions ( ADRs ) at follow-up . This interim analysis was undertaken after a minimum of 6 months ' follow-up ( median 15 months ) . RESULTS The 12 week PSA normalization rate was 79.4 % for MAB and 38.6 % for LHRH agonist monotherapy ( P < 0.001 ) . The 12 week overall tumor response rate was 77.5 and 65.3 % , respectively ( P = 0.063 ) . The withdrawal rate due to ADRs was 8.8 % and 10.9 % , respectively . There were differences in favor of MAB over monotherapy with respect to time to treatment failure ( TTTF ) ( P = 0.038 ) and time to progression ( TTP ) ( P = 0.016 ) . There have been too few deaths ( n = 10 ) to analyze survival . The profiles of adverse events and ADRs were broadly similar in the two treatment groups . CONCLUSION In Japanese patients with advanced prostate cancer , first-line treatment with bicalutamide 80 mg in combination with an LHRH agonist is superior to LHRH agonist monotherapy in terms of the antitumor response at 12 weeks , and also time to treatment failure and progression , and does not compromise treatment safety . The study is ongoing PURPOSE Radiation Therapy Oncology Group ( RTOG ) Protocol 92 - 02 was a r and omized trial testing long-term ( LT ) adjuvant and rogen deprivation ( AD ) after initial AD with external-beam radiotherapy ( RT ) in patients with locally advanced prostate cancer ( PC ; T2c-4 ) and with prostate-specific antigen level less than 150 ng/mL. PATIENTS AND METHODS Patients received a total of 4 months of goserelin and flutamide , 2 months before and 2 months during RT . A radiation dose of 65 to 70 Gy was given to the prostate and a dose of 44 to 50 Gy to the pelvic lymph nodes . Patients were r and omly assigned to receive no additional therapy ( short-term [ST]AD-RT ) or 24 months of goserelin ( LTAD-RT ) ; 1,554 patients were entered onto the study . RESULTS The LTAD-RT arm showed significant improvement in all efficacy end points except overall survival ( OS ; 80.0 % v 78.5 % at 5 years , P = .73 ) , compared with the STAD-RT arm . In a subset of patients not part of the original study design , with tumors assigned Gleason scores of 8 to 10 by the contributing institutions , the LTAD-RT arm had significantly better OS ( 81.0 % v 70.7 % , P = .044 ) . There was a small but significant increase in the frequency of late radiation grade s 3 , 4 , and 5 gastrointestinal toxicity ascribed to the LTAD-RT arm ( 2.6 % v 1.2 % at 5 years , P = .037 ) , the cause of which is not clear . CONCLUSION The RTOG 92 - 02 trial supports the addition of LT adjuvant AD to STAD with RT for T2c-4 PC . In the exploratory subset analysis of patients with Gleason scores 8 to 10 , LT adjuvant AD result ed in a survival advantage BACKGROUND The objective of this study was to document previously unreported anemia in prostate cancer patients treated with neoadjuvant combined and rogen blockade ( CAB ) and pelvic radiotherapy ( XRT ) . METHODS Four institutions treated 141 patients ( mean age + /- SD , 70.9 + /- 6.5 years ) with zoladex 3.6 mg injection subcutaneous depot monthly and flutamide 250 mg orally three times per day for 2 months ( CAB ) , followed by zoladex and flutamide with concurrent XRT ( 65 - 70 Gy ) for 7 - 8 weeks . RESULTS After the XRT , the patients were r and omized to receive no further treatment ( Z- group , 71 patients ) or zoladex alone ( Z+ group , 70 patients ) for 2 years . Hemoglobin ( Hb ) levels decreased > or = 1 g/dl ( mean + /- SE , 2.1 + /- 0.1 g/dl ) in 98/131 patients ( 75 % ) after 2 months of CAB , and > or = 2 g/dl ( 3.1 + /- 0.1 g/dl ; range , 0.1 - 6.8 g/dl ) in 106/131 patients ( 81 % ) after an additional 2 months of CAB with concurrent XRT . The decrease in Hb levels paralleled the decreased in testosterone levels . No evidence of blood loss or hemolysis was found . CONCLUSIONS There was no association between incidence or rate of Hb decrease and race , age , or pretreatment prostate-specific antigen ( PSA ) levels . However , the recovery from anemia after completion of CAB in African-Americans was slower than in Whites in the Z+ group ( P < 0.04 ) . Whereas grade 1 hematologic toxicity may occur in < 5 % of the patients with zoladex alone , and approximately 6 % with flutamide alone , in our study 81 % showed mild to pronounced anemia . Since anemia has not been observed after treatment with XRT alone or XRT followed by zoladex , we conclude that the anemia was due to CAB . Recognition of this side effect should avoid unnecessary diagnostic evaluations OBJECTIVES We analysed the acute toxicity observed in the European Organisation for Research and Treatment of Cancer ( EORTC ) r and omised trial 22863 comparing conventional external irradiation with or without an agonist analogue of gonadotropin-releasing hormone in high-risk prostate cancer patients . METHODS Four hundred five patients that received a dose of at least 30 Gy were considered evaluable for acute toxicity assessment . Toxicity was grouped in a few categories : general , genito-urinary , and lower gastro-intestinal . Univariate and multivariate analyses were performed using the World Health Organisation ( WHO ) toxicity score and grouping together toxicity scores in different bimodal and trimodal groups . RESULTS Overall , our data show that age , previous surgery and irradiation dose are important predictive factors for acute toxicity , but not the use of combined hormone therapy . Fifteen percent of patients suffered of moderate to severe acute toxicity ( WHO G3-G4 ) . Life threatening toxicity was observed in six cases ( 1.5 % ) . CONCLUSIONS The assessment of toxicity combining in different groups the original five scores scale produced conflicting results similar to those commonly reported in literature . Interpretation of the role of pre-treatment factors with uneven distribution in the study requires careful evaluation . These data obtained with conventional curative irradiation of high-risk prostate cancer patients are proposed for comparison with results achieved using modern state-of-the-art irradiation techniques Background . In 1978 , the National Prostatic Cancer Project launched two protocol s evaluating adjuvant therapy after surgery ( Protocol 900 ) or irradiation ( Protocol 1000 ) for clinical ly localized prostate cancer . All patients underwent staging pelvic lymphadenectomy A r and omized clinical trial of neoadjuvant endocrine therapy followed by either surgery or irradiation and a resumption of endocrine therapy for stages B2 and C prostate cancer has been in progress since 1989 . A hundred patients entered the trial between 1989 and 1993 , and 95 cases were evaluated . Forty-six patients received surgery and 49 were treated with irradiation . Neoadjuvant endocrine therapy for two months result ed in prostate shrinkage and prostate specific antigen lowering . Except for two patients , one dying of a progression of disease and the other of another concurrent cancer , all are alive with an average follow-up term of 25 ( range 3 - 53 ) months . The good prognostic results obtained from both treatment groups at present seem to be due in part to the neoadjuvant endocrine therapy ; but in order to reach a final conclusion further comparisons need to be made OBJECTIVES To study neuroendocrine ( NE ) tumor cell differentiation in prostate cancer in relation to failure after radical prostatectomy . METHODS Radical prostatectomy specimens from 103 of 111 patients r and omized to 3-month neoadjuvant luteinizing hormone-releasing hormone-analogue treatment ( neoadjuvant group ) or to surgery alone ( control group ) were available for analysis . Immunohistochemistry using antibodies to chromogranin A ( CGA ) enabled detection of tumor cells with NE differentiation . NE differentiation was scored as NE-negative ( 0 to 1 + ) or NE-positive ( 2 to 3 + ) . The number of CGA-positive cells/cm(2 ) tumor area on the slides was assessed in a separate analysis . The patients were followed up for 39 months after surgery , and a prostate-specific antigen value of 0.5 ng/mL or greater in two consecutive blood sample s was considered biochemical failure . RESULTS Kaplan-Meier analysis stratified for neoadjuvant hormonal treatment showed the failure rate to be significantly greater among those with NE-positive tumors than among those with NE-negative tumors . However , the number of CGA-positive cells/cm(2 ) was not a variable of prognostic significance . Instead , both NE differentiation and the CGA-positive cell count correlated with the tumor area on the slides ( P = 0.0001 ) . Multivariate analysis revealed the tumor area on the slide ( P < 0.0001 ) and positive surgical margins ( P = 0.03 ) to be the only significant predictors of biochemical failure . CONCLUSIONS The extension of NE differentiation in prostate cancer correlates with tumor volume and is not an independent prognostic factor of failure after radical prostatectomy PURPOSE This prospect i ve r and omized trial was used to compare predictive factors for organ confined margin negative status after radical prostatectomy with and without a 3-month course of neoadjuvant and rogen withdrawal therapy . MATERIAL S AND METHODS A total of 213 patients with localized adenocarcinoma of the prostate were r and omized to radical prostatectomy with or without a 3-month course of 300 mg . neoadjuvant cyproterone acetate daily . Multivariate logistic regression analysis was used to determine significant predictors of organ confined margin negative status after radical prostatectomy in both groups . Parameters evaluated included baseline prostate specific antigen ( PSA 4 or less , 4.1 to 10 , greater than 10 ng./ml . ) , clinical stage ( T2c versus T2b or less ) , biopsy Gleason score and percentage of surface area of biopsies involved with cancer . The multivariate analysis was repeated with PSA density and the natural logarithm of PSA to optimize the model . RESULTS In the radical prostatectomy alone arm a model incorporating only PSA density was the best predictor of organ confined margin negative status . In the neoadjuvant and rogen withdrawal therapy arm a model incorporating biopsy Gleason score , PSA density and clinical stage was the best predictor . CONCLUSIONS The conventional predictors of pathology at radical prostatectomy , biopsy Gleason score , PSA density and clinical stage retain significance as predictors in patients treated with a 3-month course of neoadjuvant and rogen withdrawal therapy before radical prostatectomy PURPOSE Radiation Therapy Oncology Group protocol 85 - 31 was design ed to evaluate the effectiveness of adjuvant and rogen suppression , using goserelin , in unfavorable prognosis carcinoma of the prostate treated with definitive radiotherapy ( RT ) . METHODS AND MATERIAL S Eligible patients were those with palpable primary tumor extending beyond the prostate ( clinical Stage T3 ) or those with regional lymphatic involvement . Patients who had undergone prostatectomy were eligible if penetration through the prostatic capsule to the margin of resection and /or seminal vesicle involvement was documented histologically . Stratification was based on histologic differentiation , nodal status , acid phosphatase status , and prior prostatectomy . The patients were r and omized to either RT and adjuvant goserelin ( Arm I ) or RT alone followed by observation and application of goserelin at relapse ( Arm II ) . In Arm I , the drug was to be started during the last week of RT and was to be continued indefinitely or until signs of progression . RESULTS Between 1987 and 1992 , when the study was closed , 977 patients were entered : 488 to Arm I and 489 to Arm II . As of July 2003 , the median follow-up for all patients was 7.6 years and for living patients was 11 years . At 10 years , the absolute survival rate was significantly greater for the adjuvant arm than for the control arm : 49 % vs. 39 % , respectively ( p = 0.002 ) . The 10-year local failure rate for the adjuvant arm was 23 % vs. 38 % for the control arm ( p < 0.0001 ) . The corresponding 10-year rates for the incidence of distant metastases and disease-specific mortality was 24 % vs. 39 % ( p < 0.001 ) and 16 % vs. 22 % ( p = 0.0052 ) , respectively , both in favor of the adjuvant arm . CONCLUSION In a population of patients with unfavorable prognosis carcinoma of the prostate , and rogen suppression applied as an adjuvant after definitive RT was associated not only with a reduction in disease progression but in a statistically significant improvement in absolute survival . The improvement in survival appeared preferentially in patients with a Gleason score of 7 - 10 PURPOSE RTOG 83 - 07 is a Phase II r and omized protocol design ed to compare the efficacy and toxicity of Megestrol vs. Diethylstilbestrol ( DES ) used as cytoreductive agents prior to and during radiotherapy . The end points of this study include tumor clearance rate , effect on serum testosterone , loco-regional control , disease-free interval , and survival . METHODS AND MATERIAL S Eligible patients were those with histologically confirmed locally advanced adenocarcinoma , clinical Stage B2 ( T2B ) and C ( T3 ) without regional lymph node involvement , or with lymph node involvement limited to the pelvis . Patients were stratified by clinical stage , histological grade , and nodal status , and were r and omized to receive either Megestrol 40 mg three times per day by mouth , or Diethylstilbestrol 1 mg three times per day by mouth . The drugs were started 2 months prior to initiation of radiotherapy and were continued throughout the radiotherapy course . Radiotherapy consisted of 44 - 46 Gy , 1.8 - 2 Gy per day to the regional lymphatics , followed by a boost to the prostate consisting of 20 - 25 Gy , 1.8 - 2 Gy per day , to a total of 65 - 70 Gy . Serum testosterone levels were recorded throughout the treatment course . Tumor response was assessed clinical ly and radiographically ( CT scan ) . From March 1983 through June 1986 a total of 203 patients were accessioned to the study ; 198 were analyzable . RESULTS Correlation of the incidence of drug-related toxicity and treatment arm assignment revealed a significantly higher incidence of complications in the Diethylstilbestrol ( DES ) arm . The most prominent were the differences in the incidence of gynecomastia ( 55 % vs. 7 % ) and fluid retention ( 21 % vs. 6 % ) . The incidence of thromboembolic phenomena was comparable ( 8 % vs. 5 % in the Megestrol arm ) . Patients on the DES arm demonstrated a significantly greater median decrease in testosterone level . Correlation of the treatment arm assignment and the rate of tumor regression and the incidence of complete response revealed no significant difference between the arms . At 7 years , 16 % of patients on the Megace arm and 21 % of patients on the DES arm manifested evidence of local failure . CONCLUSIONS The results of the study indicate comparable efficacy ( using tumor clearance as an end point ) of DES and Megestrol . Although DES appears more effective in suppressing testosterone , it is also associated with a higher incidence of drug-related toxicity CONTEXT Survival benefit in the management of high- grade clinical ly localized prostate cancer has been shown for 70 Gy radiation therapy combined with 3 years of and rogen suppression therapy ( AST ) , but long-term AST is associated with many adverse events . OBJECTIVE To assess the survival benefit of 3-dimensional conformal radiation therapy ( 3D-CRT ) alone or in combination with 6 months of AST in patients with clinical ly localized prostate cancer . DESIGN , SETTING , AND PATIENTS A prospect i ve r and omized controlled trial of 206 patients with clinical ly localized prostate cancer who were r and omized to receive 70 Gy 3D-CRT alone ( n = 104 ) or in combination with 6 months of AST ( n = 102 ) from December 1 , 1995 , to April 15 , 2001 . Eligible patients included those with a prostate-specific antigen ( PSA ) of at least 10 ng/mL , a Gleason score of at least 7 , or radiographic evidence of extraprostatic disease . MAIN OUTCOME MEASURES Time to PSA failure ( PSA > 1.0 ng/mL and increasing > 0.2 ng/mL on 2 consecutive visits ) and overall survival . RESULTS After a median follow-up of 4.52 years , patients r and omized to receive 3D-CRT plus AST had a significantly higher survival ( P = .04 ) , lower prostate cancer-specific mortality ( P = .02 ) , and higher survival free of salvage AST ( P = .002 ) . Kaplan-Meier estimates of 5-year survival rates were 88 % ( 95 % confidence interval [ CI ] , 80%-95 % ) in the 3D-CRT plus AST group vs 78 % ( 95 % CI , 68%-88 % ) in the 3D-CRT group . Rates of survival free of salvage AST at 5 years were 82 % ( 95 % CI , 73%-90 % ) in the 3D-CRT plus AST group vs 57 % ( 95 % CI , 46%-69 % ) in the 3D-CRT group . CONCLUSION The addition of 6 months of AST to 70 Gy 3D-CRT confers an overall survival benefit for patients with clinical ly localized prostate cancer Objectives : Long-term results of radiotherapy in locally advanced prostate cancer are poor due to local and distant failures . Since prostate cancer is hormone dependent , tumor and rogen deprivation may enhance tumor eradication . Methods : Three r and omized phase III trials , RTOG and EORTC are reported : they assess and rogen suppression by using a luteinizing hormone-releasing hormone analogue ( LH-RHa ) with or without and rogen blockade before and during , or during and after external irradiation . Results : A gain in disease-free , local relapse-free and metastasis-free survival has been obtained ( p < 0.001 ) . Only the EORTC 22863 trial has reported a significant improvement in overall survival ( p = 0.001 ) with an LH-RHa started the first day of radiotherapy and administered every 4 weeks over 3 years . In the RTOG 85 - 10 trial , and LH-RHa , initiated in the last week of radiation therapy and continued until relapse , increased overall survival only in patients with poorly differentiated tumor with a Gleason score of 8–10 ( p = 0.03 ) . Conclusion : And rogen suppression prior to and during radiation improves disease-free survival ; adjuvant hormonal therapy with an LH-RHa during and after radiation improves overall survival OBJECTIVE To assess the efficacy and the tolerability of flutamide as adjuvant treatment after radical prostatectomy for locally advanced , lymph node-negative prostate cancer . METHODS Men with locally advanced , lymph node-negative prostate cancer were r and omized after radical prostatectomy to receive either flutamide 750 mg daily or no adjuvant treatment . Recurrence-free and overall survival were the study end points . Recurrence was defined as a PSA value greater than 5ng/ml or two values greater than 2ng/ml more than three months apart with increasing tendency or three values greater than 1ng/ml more than three months apart with increasing tendency or any clinical recurrence . RESULTS 309 patients ( 157 in the control arm and 152 in the flutamide arm ) were eligible for efficacy analysis . The median follow-up was 6.1 years . Recurrence-free survival was better in the flutamide group ( P=0.0041 ) , there was , however , no detectable difference in overall survival ( p=0.92 ) . Moreover , there was a considerable toxicity reported in the flutamide group . CONCLUSION Although having some effect on disease recurrence , adjuvant flutamide treatment does not improve median-term overall survival after radical prostatectomy for locally advanced , lymph node-negative prostate cancer PURPOSE We determined whether 12 weeks of neoadjuvant testicular and rogen ablation therapy using a luteinizing hormone-releasing hormone agonist could improve pathological outcomes in men undergoing radical retropubic prostatectomy for clinical ly localized ( stages T1C , T2A and T2B ) prostatic carcinoma . MATERIAL S AND METHODS A total of 56 participants was r and omized to receive either monthly injections of a luteinizing hormone-releasing hormone agonist at 4-week intervals followed by radical retropubic prostatectomy ( 28 ) or to undergo immediate radical retropubic prostatectomy alone ( 28 ) . Operations were performed via similar technique and all prostatic specimens were processed histologically in their entirety . RESULTS There was no improvement in pathological outcome using luteinizing hormone-releasing hormone agonist preoperatively compared to surgery alone . Of 28 men undergoing immediate radical retropubic prostatectomy 23 had organ-confined ( 17 ) or specimen-confined ( 6 ) disease versus 22 of 28 who received luteinizing hormone-releasing hormone neoadjuvant therapy for 12 weeks preoperatively ( 16 with organ-confined and 6 with specimen-confined disease , p = 1.00 ) . In addition , when the study population was analyzed by pretreatment prostate specific antigen ( PSA ) levels ( 10 ng./ml . or less , or greater than 10 ng./ml/ ) there was also no difference in pathological outcome ( p = 0.65 for PSA greater than 10 and p = 0.32 for PSA less than 10 ) . CONCLUSIONS Neoadjuvant and rogen ablation therapy for 12 weeks before radical prostatectomy in patients with clinical ly localized adenocarcinoma of the prostate does not result in improved pathological outcomes In Radiation Therapy Oncology Group ( RTOG ) trial 92‐02 , after men received neoadjuvant hormone cytoreduction and radiotherapy for locally advanced prostate carcinoma , they were r and omized to receive either 2 years of long‐term and rogen‐deprivation ( LTAD ) or no further treatment ( short‐term and rogen‐deprivation [ STAD ] ) . The specific objective of the current study was to determine whether LTAD was a cost‐effective treatment for patients with locally advanced prostate carcinoma PURPOSE To test the hypothesis that and rogen ablation before and during radiotherapy for locally advanced carcinoma of the prostate may , by reducing tumor bulk and enhancing tumor cell kill , improve locoregional control and ultimately survival . METHODS AND MATERIAL S The study was conducted from 1987 to 1991 . Eligible patients were those with bulky tumors ( T2 - -T4 ) with or without pelvic lymph node involvement and without evidence of distant metastases . They were r and omized to receive goserelin , 3.6 mg every 4 weeks ; and flutamide , 250 mg t.i.d . for 2 months before radiation therapy and during radiation therapy ( Arm I ) , or radiation therapy alone ( Arm II ) . Of 471 r and omized patients , 456 were evaluable : 226 on Arm I and 230 on Arm II . RESULTS As of November 1999 , the median follow-up has reached 6.7 years for all patients and 8.6 years for alive patients . At 8 years , and rogen ablation has been associated with an improvement in local control ( 42 % vs. 30 % , p = 0.016 ) , reduction in the incidence of distant metastases ( 34 % vs. 45 % , p = 0.04 ) , disease-free survival ( 33 % vs. 21 % , p = 0.004 ) , biochemical disease-free survival = PSA < 1.5 ( 24 % vs. 10 % , p < 0.0001 ) , and cause-specific mortality ( 23 % vs. 31 % , p = 0.05 ) . However , subset analysis indicates that the beneficial effect of short-term and rogen ablation appears preferentially in patients with Gleason score 2 - -6 . In that population , there is a highly significant improvement in all endpoints , including survival ( 70 % vs. 52 % , p = 0.015 ) . In patients with Gleason 7 - -10 tumors , the regimen has not result ed in a significant enhancement in either locoregional control or survival . CONCLUSION In patients with Gleason score 2 - -6 carcinoma of the prostate , a short course of and rogen ablation administered before and during radiotherapy has been associated with a highly significant improvement in local control , reduction in disease progression , and overall survival OBJECTIVES To evaluate prostate cancer detection and prostate-specific antigen ( PSA ) among men with benign prostatic hyperplasia treated with finasteride . METHODS Three thous and forty men 45 to 78 years of age with PSA less than 10 ng/mL and no history of prostate cancer were r and omized in a double-blind , placebo-controlled trial to finasteride ( n = 1524 ) or placebo ( n = 1516 ) for up to 4 years . A prer and omization biopsy negative for prostate cancer was obtained in 98 % of patients with a screening PSA of 4.0 ng/mL or more , and an end-of- study biopsy was requested of all such patients without a recent second negative biopsy or a prostate cancer diagnosis . RESULTS Overall , 644 patients ( 21 % ) underwent biopsy and 201 ( 6.6 % ) underwent transurethral resection of the prostate . Prostate cancer was diagnosed in 4.7 % of men on finasteride and 5.1 % on placebo ( P = 0.7 ) . Elevated PSA prompted diagnosis in 35 % of cases on finasteride and 34 % on placebo . The area under the receiver operating characteristic curve for last PSA was 0.84 on finasteride and 0.79 on placebo ( P = 0.07 ) . Use of an upper limit of normal for last PSA of 2.0 ng/mL for finasteride and 4.0 ng/mL for placebo yielded similar sensitivity ( 66 % versus 70 % , P = 0.6 ) , higher specificity ( 82 % versus 74 % , P < 0.0001 ) , and a higher likelihood ratio ( 3.6 versus 2.7 , P < 0.05 ) for finasteride than for placebo . CONCLUSIONS In men treated with finasteride , multiplying PSA by 2 and using normal ranges for untreated men preserves the usefulness of PSA for prostate cancer detection To quantify the incremental costs and outcomes of using long-term adjuvant goserelin in addition to radiotherapy for locally advanced prostate cancer . The cost of radiotherapy for prostate cancer has been calculated using an activity-costing model . The total cost of administering adjuvant hormonal therapy for 3 years is based on local pharmacy charges plus typical physician billing fees and additional laboratory costs . Outcome data were obtained from the published EORTC 22,863 r and omized trial comparing treatment of locally advanced prostate cancer with radiotherapy alone or in combination with 3 years of adjuvant goserelin . Using this information , the cost-effectiveness of adjuvant goserelin was calculated and expressed in terms of dollars per life-years ( LY ) gained . The total institutional costs of radiotherapy are $ 9000 Cdn . and the additional costs of providing adjuvant goserelin for 3 years are approximately $ 19,800 CDN . The improvement in outcome with the use of adjuvant goserelin was estimated to be 1.2 LY per patient treated , giving a cost-effectiveness ratio of $ 16,500 Cdn ( $ 11,000 US ) per LY from an institutional perspective . Our sensitivity analysis confirms the robustness of our findings since even in our " worst case " scenario the cost-effectiveness ratio was estimated to be $ 21,600 Can ( $ 14,400 US ) per LY gained . This figure is still below $ 50,000 US per LY gained which is the quoted current st and ard for cost-effectiveness . This analysis demonstrates that the use of long-term adjuvant goserelin for locally advanced prostate cancer provides substantial benefit at an acceptable cost Objective : This prospect i ve , r and omized , multicenter comparative trial studied the effect of neoadjuvant hormonal treatment ( NHT ) prior to radical prostatectomy . Methods : Histopathologic tissue specimens were obtained from 91 consecutive patients ( aged 60–70 years ) who underwent a radical prostatectomy for stage B prostate adenocarcinoma . The patients had received NHT for three months . Specimens were compared with those from 48 age-matched control patients who underwent similar surgery for stage B disease without receiving preoperative therapy . Results : Treated tumors with an acinar pattern were distinguishable from the untreated tumors by neoplastic acini that appeared shrunken and areas of individual infiltrating tumor cells separated by an abundant intergl and ular connective tissue . The epithelial tumor cells had inconspicuous nucleoli , nuclear shrinkage , chromatin condensation and pyknosis , cytoplasmic clearing , and enlargement by coalescence of vacuoles and rupture of cell membranes . No mitotic figures were seen in any treated tumors . Conclusions : Preliminary results show a benefit for patients receiving NHT in regard to the histologic indicators that we evaluated PURPOSE The aim of this study is to analyze , during the prostate-specific antigen ( PSA ) era , the long-term outcome of patients treated with conformal high-dose-rate ( HDR ) brachytherapy boost to the prostate with or without and rogen deprivation therapy ( ADT ) when patients are stratified by risk factors for failure . METHODS AND MATERIAL S Between 1986 and 2000 , 611 patients were treated for clinical ly localized prostate cancer in three prospect i ve trials of external beam radiation therapy ( EBRT ) and dose-escalating HDR brachytherapy ( BT ) boost . There were 104 patients treated at Seattle , 198 at Kiel University , and 309 at William Beaumont Hospital . Of the 611 patients , 177 received a short course of neoadjuvant/concurrent ADT . The patients were divided into three risk groups . Group I , comprised of 46 patients , had stage < or = T2a , Gleason score ( GS ) < or = 6 , and initial PSA ( iPSA ) < or = 10 ng/mL. Group II comprised 188 patients with stage > or = T2b , GS > or = 7 , and iPSA > or = 10 , with any one factor higher . Group III included 359 patients with any two risk factors higher . The American Society for Therapeutic Radiology and Oncology definition for biochemical failure was used . RESULTS The mean follow-up was 5 years ( range , 0.2 - 15.3 ) . For the 611 patients , the 5-year and 10-year biochemical control ( BC ) rates were 77 % and 73 % , disease-free survival ( DFS ) was 67 % and 49 % , and cause-specific survival ( CSS ) was 96 % and 92 % , respectively . BC at 5 years for Group I patients was 96 % , for Group II 88 % , and for Group III patients 69 % . CSS at 5 years was 100 % in Group I , 99 % in Group II , and 95 % in Group III patients . In univariate and multiple regression analyses for BC , risk group , stage , iPSA , and GS were significant in predicting failure . However , age , follow-up interval , and ADT did not . CONCLUSIONS EBRT with HDR-BT produced excellent long-term outcomes in terms of BC , DFS , and CSS in patients with prostate cancer even for those at highest risk . Conformal HDR-BT is both a precise dose delivery system and an effective treatment for both favorable and unfavorable prostate cancer . The addition of a short course of neoadjuvant/concurrent ADT failed to improve outcome . The results were similar at all three institutions , giving credence to the reproducibility of the brachytherapy treatment PURPOSE A prospect i ve , multicenter , r and omized study was done to test the hypothesis that neoadjuvant and rogen withdrawal decreases the incidence of positive margins following radical prostatectomy for localized prostate cancer . MATERIAL S AND METHODS Observations were made of 213 patients r and omized to undergo radical prostatectomy alone ( 101 ) or to receive a 12-week course of 300 mg . cyproterone acetate daily followed by surgery ( 112 ) . Groups were similar at baseline in terms of clinical stage , serum prostate specific antigen and Gleason score . Of 192 patients available for efficacy analysis 9 had stage T1b , 8 stage T1c , 63 stage T2a , 36 stage T2b and 76 stage T2c disease . RESULTS One or more positive surgical margins were found in 59 of 91 patients ( 64.8 % ) in the surgery only group compared to 28 of 101 ( 27.7 % ) in the cyproterone acetate group ( p = 0.001 ) . Patients who received preoperative therapy had a statistically significantly lower rate of apical margin involvement than those who did not ( 17.8 versus 47.8 % , respectively , p < 0.0001 ) . There was no statistically significant difference in surgical ( p = 0.8645 ) or postoperative ( p = 0.173 ) complications between the 2 groups . CONCLUSIONS Neoadjuvant and rogen withdrawal with a 12-week course of 300 mg . cyproterone acetate daily results in a lower rate of positive margins without adversely affecting postoperative recovery . The impact on patient survival will be determined by long-term followup PURPOSE Since most patients do not undergo repeat sextant prostate biopsies after a biopsy is positive for prostate cancer , the true incidence of false-negative biopsies is not well defined . We assess the incidence and clinical significance of false-negative sextant prostate biopsies in patients undergoing radical prostatectomy . MATERIAL S AND METHODS A total of 118 patients with biopsy proved prostate cancer underwent repeat sextant prostate biopsy before enrollment in a prospect i ve r and omized trial of radical prostatectomy with or without neoadjuvant hormonal therapy . Clinical parameters were assessed to determine potential sources of bias . Pathological parameters and prostate specific antigen relapse-free survival rates were compared to determine the clinical significance of false-negative biopsies . RESULTS Of the 118 patients 27 ( 23 % ) had a negative repeat sextant biopsy . Except for initial clinical stage , no differences were noted in the clinical or pathological parameters , or prostate specific antigen relapse rates in patients with negative versus positive repeat biopsies . CONCLUSIONS Our findings suggest that this 23 % incidence of false-negative biopsies represents significant cancer . This relatively high incidence is important to consider in treatment modalities in which prostate biopsy may be performed to determine response to therapy PURPOSE We determine the efficacy and tolerability of bicalutamide as immediate therapy , either alone or as adjuvant to treatment of curative intent , in patients with clinical ly localized or locally advanced prostate cancer . MATERIAL S AND METHODS This international program consists of 3 ongoing , r and omized , double-blind , placebo controlled clinical trials ( trials 23 , 24 , and 25 ) . Men with localized or locally advanced ( T1-T4 , Nx/N0 , M0 ) prostate cancer were r and omized to receive 150 mg . bicalutamide daily or placebo , in addition to st and ard care with radical prostatectomy , radiotherapy or watchful waiting . Primary end points are time to objective progression and overall survival . In this first analysis data from the trials were combined in a single overview analysis according to protocol . RESULTS Data are available for 8,113 patients ( 4,052 r and omized to bicalutamide , 4,061 to st and ard care alone ) at a median followup of 3.0 years . Treatment with bicalutamide provided a highly significant reduction of 42 % in the risk of objective progression compared with st and ard care alone ( 9.0 % versus 13.8 % , hazards ratio 0.58 ; 95 % confidence interval 0.51 , 0.66 ; p < < 0.0001 ) . The overall result was reflected in 2 of the 3 trials ( trials 24 and 25 ) with trial 3 ( trial 23 ) showing a nonsignificant difference at this time . Reductions in the risk of disease progression were seen across the entire patient population , irrespective of primary treatment or disease stage . Overall survival data are currently immature and longer followup will determine if there is also a survival benefit with bicalutamide . The most frequently reported side effects of bicalutamide were gynecomastia and breast pain . CONCLUSIONS Immediate treatment with 150 mg . bicalutamide daily , either alone or as adjuvant to treatment of curative intent , significantly reduces the risk of disease progression in patients with localized or locally advanced prostate cancer . This benefit must be balanced with the morbidity associated with long-term hormonal therapy . Followup is ongoing to determine potential survival benefits of this treatment approach Two hundred consecutive patients with presumed localized prostate cancer had radical prostatectomy alone ( n = 119 ) or were treated for an average period of 3 months with combination therapy using the anti and rogen flutamide and one luteinizing hormone-releasing hormone ( LHRH ) agonist ( Lupron or Zoladex ) . The positive margins decreased from 35.3 % in the group undergoing prostatectomy alone to 11.5 % in the group of men who received combination therapy before radical prostatectomy . In 41 apical tumors , the incidence of positive margins decreased from 50 % in the control group to 18.6 % in the combination therapy group . In stage C disease , the incidence of positive tumor showed a tendency to decrease with the extended duration of endocrine treatment with a rate of 37.5 % after 3 months and 16.7 % after 6 months . Whether the decreased incidence of positive surgical margins will all translate into prolonged survival remains to be verified by long-term follow-up of these patients . However , the initial results obtained in the present study are very encouraging The morphologic changes induced by neoadjuvant combination endocrine therapy were evaluated in prostatectomy specimens from patients diagnosed with localized prostate cancer . These patients participated in a prospect i ve , r and omized clinical trial investigating the effect of 3 months of combination therapy with flutamide and an LHRH agonist prior to radical prostatectomy versus radical prostatectomy alone . Ninety-six radical prostatectomy specimens processed according to the same protocol were evaluated without knowledge of prior treatment . Forty-seven patients were r and omly assigned to the neoadjuvant combination therapy group and 49 to the control arm . Compared with the control group , several changes were strongly and significantly associated with exposure to neoadjuvant combination therapy . The nonmalignant prostatic tissue showed strong prominence and hyperplasia of the basal cell layer , accompanied by epithelial cell vacuolization and markedly reduced occurrence of prostatic intraepithelial neoplasia ( p < 0.001 ) after combination therapy . Prostate cancer tissue , on the other h and , showed smaller nucleoli ( p < 0.001 ) , cell vacuolization ( p < 0.001 ) , rare intraluminal crystalloids ( p < 0.001 ) , higher Gleason grade ( p < 0.001 ) , lower prevalence of capsular penetration ( p < 0.001 ) , and less frequent invasion of the perineural spaces ( p < 0.001 ) and surgical margins ( p = 0.002 ) . Tumor volume , was also reduced by more than 40 % in the treated group ( p = 0.007 ) . The present findings show that preoperative endocrine combination therapy induces highly characteristic changes in both nonmalignant and cancerous prostatic tissue . Furthermore , following endocrine treatment , the surgical margins are less likely to be involved by cancer and capsular penetration is reduced PURPOSE We investigated the effect of neoadjuvant treatment before radical prostatectomy for clinical ly localized prostate cancer . MATERIAL S AND METHODS A total of 130 patients with stages T2b and T3 prostate cancer was r and omized in a multicenter study : 62 underwent immediate radical prostatectomy and 65 received 560 mg . estramustine phosphate daily for 6 weeks preoperatively . RESULTS For clinical stage T2b tumors the neoadjuvant treatment result ed in a significant decrease in positive surgical margins compared to the nonpretreated group . This difference was not found for clinical stage T3 tumors . The impact on progression and survival still must be analyzed . CONCLUSIONS Neoadjuvant treatment can be beneficial for clinical stage T2 prostate cancer . Optimal treatment for stage T3 tumors remains controversial In 1978 the National Prostate Cancer Project launched two protocol s evaluating adjuvant therapy following surgery ( Protocol 900 ) or irradiation ( Protocol 1,000 ) for clinical ly localized prostate cancer . All patients underwent staging pelvic lymphadenectomy . Following definitive treatment , patients were r and omized to either cyclophosphamide 1 gram/m2-IV every 3 weeks for 2 years , estramustine phosphate 600 mg/m2-po daily for up to 2 years , or to observation only . Patient accession closed in 1985 and includes 184 to Protocol 900 ( 170 evaluable ) and 253 to Protocol 1,000 ( 233 evaluable ) . Lymph node involvement was identified in 198 patients ( 49 % of total ) , 29 % in Protocol 900 , 63 % in Protocol 1,000 . Median progression-free survival ( PFS ) for patients with nodal involvement in Protocol 1,000 receiving estramustine phosphate adjuvant was longer ( 37.3 mo ) compared to cyclophosphamide ( 30.9 mo ) and to no treatment ( 20.9 mo ) . Median PFS for patients with limited nodal disease in Protocol 1,000 was longer ( 39.9 mo ) , regardless of adjuvant , compared to extensive nodal disease ( 20.7 mo ) . However for patients with extensive nodal involvement , those receiving adjuvant estramustine phosphate experienced a significantly longer median PFS ( 32.8 mo ) compared to adjuvant cyclophosphamide ( 22.7 mo ) and no adjuvant ( 12.9 mo ) . We conclude that adjuvant estramustine phosphate is of benefit in prostate cancer patients with extensive pelvic node involvement receiving irradiation as definitive treatment OBJECTIVES To assess the pathological staging and biochemical progression-free survival ( assessed using serum prostate-specific antigen level ) of patients with clinical ly localized prostate cancer using neoadjuvant and rogen deprivation therapy ( ADT ) in combination with radical retropubic prostatectomy ( RRP ) . PATIENTS AND METHODS A prospect i ve study was carried out on 69 patients with localized prostate cancer who were enrolled in a trial of 3 months of ADT followed by RRP ( group 1 ) . These patients were compared with 72 patients matched for age and clinical stage who declined ADT therapy and had RRP concurrently ( group 2 ) . Assignment to the individual treatment groups was thus determined by the patient 's preference and not the physician 's selection . Pathological staging and biochemical progression-free recurrence were compared between the groups . RESULTS The rate of organ-confined ( pT2 ) tumours was 74 % in group 1 and 49 % in group 2 ( P < 0.01 ) , and the rate of margin-negative tumours was 87 % in group 1 and 64 % in group 2 ( P < 0.01 ) . Within a median follow-up of 35 months , there was no significant difference in biochemical failure between the groups ( P = 0.37 ) . Patients with pT2 disease , regardless of treatment , had similar biochemical failure rates . In the patients with margin-positive disease , there was a significantly higher biochemical failure rate in group 1 ( P = 0.02 ) . CONCLUSIONS The rates of organ- and specimen-confined disease were higher among the patients treated with ADT . The preliminary follow-up suggested that patients with pT2 disease after ADT have a biochemical progression-free recurrence rate similar to pT2 patients treated with RRP alone . Additionally , high biochemical failure rates in patients with margin-positive disease after ADT may identify a subset of more biologically aggressive tumours in need of early adjuvant treatment AIMS To compare the pathological stage and surgical margin status in patients undergoing either immediate radical prostatectomy or 12 and 24 weeks of neoadjuvant hormonal treatment ( NHT ) in a prospect i ve , r and omised study . METHODS Whole mount sections of 393 radical prostatectomy specimens were evaluated : 128 patients had immediate surgery , 143 were treated for 12 weeks and 122 for 24 weeks with complete and rogen blockade . RESULTS Histopathology revealed organ confined tumours in 40.4 % of patients with clinical stage B disease in the immediate surgery group , whereas 12 and 24 weeks of NHT increased the number of organ confined tumours to 54.6 % and 64.8 % , respectively . Among patients with clinical stage C tumours , pathological staging found organ confined disease in 10.4 % , 31.4 % , and 61.2 % in the immediate surgery , 12 weeks of NHT , and 24 weeks of NHT groups , respectively . Preoperative NHT caused a significant decrease in positive margins both in patients with clinical stage B and C disease . The extent of margin involvement was not influenced by preoperative treatment . CONCLUSIONS Neoadjuvant and rogenic suppression is effective in reducing both the pathological stage and the positive margin rate in patients with stage B and C prostatic cancer undergoing radical surgery . Some beneficial effects are evident in those patients treated for 24 weeks , and it is reasonable to assume that the optimal duration of NHT is longer than three months BACKGROUND Because the optimal timing of the institution of anti and rogen therapy for prostate cancer is controversial , we compared immediate and delayed treatment in patients who had minimal residual disease after radical prostatectomy . METHODS Ninety-eight men who underwent radical prostatectomy and pelvic lymphadenectomy and who were found to have nodal metastases were r and omly assigned to receive immediate anti and rogen therapy , with either goserelin , a synthetic agonist of gonadotropin-releasing hormone , or bilateral orchiectomy , or to be followed until disease progression . The patients were assessed quarterly during the first year and then semiannually . RESULTS After a median of 7.1 years of follow-up , 7 of 47 men who received immediate anti and rogen treatment had died , as compared with 18 of 51 men in the observation group ( P=0.02 ) . The cause of death was prostate cancer in 3 men in the immediate-treatment group and in 16 men in the observation group ( P<0.01 ) . At the time of the last follow-up , 36 men in the immediate-treatment group ( 77 percent ) and 9 men in the observation group ( 18 percent ) were alive and had no evidence of recurrent disease , including undetectable serum prostate-specific antigen levels ( P<0.001 ) . In the observation group , the disease recurred in 42 men ; 13 of the 36 who were treated had a complete response to local treatment or hormonal therapy ( or both ) , 16 died of prostate cancer , and 1 died of another disease . The remaining men in this group were alive with progressive disease at the time of the last follow-up or had had a recent relapse . Except for the treatment group ( immediate therapy or observation ) , no clinical or histologic characteristic significantly influenced the outcome . CONCLUSIONS Immediate anti and rogen therapy after radical prostatectomy and pelvic lymphadenectomy improves survival and reduces the risk of recurrence in patients with node-positive prostate cancer Neoadjuvant hormonal therapy ( NHT ; and rogen ablation ) is used prior to radical prostatectomy ( RP ) in an attempt to pathologically “ downstage ” prostatic adenocarcinoma and ultimately to improve disease-free survival . This study describes the pathologic effects of NHT with the anti and rogen cyproterone acetate , 300 mg/day for 12 weeks , on the RP specimens from men with clinical ly localized ( stage T1 or T2 ) prostatic adenocarcinoma . There were 101 men in the pretreatment group ( CPA ) and 91 men in a control group who were treated with surgery alone . The prevalence and extent of morphologic effects were recorded for the nonneoplastic prostate , high- grade prostatic intraepithelial neoplasia , and invasive adenocarcinoma . The commonest effects on the nonneoplastic prostate were atrophy and basal cell hyperplasia and prominence . High- grade prostatic intraepithelial neoplasia was more commonly identified in the surgery alone group than the CPA group ( p < 0.01 ) . In the CPA group , flat and low tufted patterns of high- grade prostatic intraepithelial neoplasia predominated . Following NHT , the adenocarcinoma showed characteristic morphologic alterations , including reduction in cytoplasmic quantity , cytoplasmic vacuolation , nuclear pyknosis , reduced gl and diameter , and mucinous breakdown . In many cases there was prominence of collagenous stroma , obscuring malignant gl and s. Compared with the surgery alone group , the CPA group RP specimens had a significantly lower mean specimen weight ( 40.3 g vs 46.5 g , p = 0.025 ) and less tumor extent by several measures . Organ-confined tumor ( stage pT2 , margin negative ) was found in 41.6 % of the CPA group compared with 19.8 % of the surgery alone group ( p = 0.0017 ) . The overall rate of margin positivity was lower in the CPA group ( 27.7 % vs 64.8 % , p = 0.001 ) . We consider that the difference in margin positivity is the result of tumor shrinkage with a decreased likelihood of sampling in routine sections . There was no significant difference in the rate of extraprostatic extension between the two groups . There was elevation of the Gleason score in the RP specimens versus baseline biopsy in 60 % of the CPA group compared with 33 % of the surgery alone group ( p = 0.02 ) . The higher rate of elevation in the CPA group largely result ed from an increase in primary or secondary Gleason score 5 tumor , a morphologic artifact introduced by NHT . Because of this , we recommend not giving a Gleason grade to RP specimens following NHT . Monotherapy with CPA has similar pathologic effects on benign and malignant prostate tissue as does dual agent and rogen blockade . Prolonged follow-up of these patients is required to determine if NHT with CPA leads to improved disease-free survival OBJECTIVES To investigate the outcome of neo-adjuvant hormone treatment before radical prostatectomy regarding local tumour extension , peri-operative blood loss and operation time . PATIENTS Of 111 surgically treated patients with prostate cancer ( T1b-T3a , N0 , M0 , G1 - 3 ) , 55 were r and omised to immediate radical prostatectomy and 56 to 3 months of neo-adjuvant treatment with triptorelin ( 3.75 mg i.m . every 28 days ) and cyproterone acetate ( 50 mg b.i.d . for 3 weeks to prevent flare ) . RESULTS No differences were found in blood loss or operation time but patients who had neo-adjuvant treatment had a significantly lower frequency of positive margins ( 41 vs. 23 % , p = 0.013 ) . CONCLUSION Neo-adjuvant treatment does not facilitate radical prostatectomy but may improve the chance of local cure . This must , however , be documented with long-term follow-up in r and omised patients PURPOSE To evaluate the effect of 3 months vs. 8 months of neoadjuvant hormonal therapy before conventional dose radiotherapy ( RT ) on disease-free survival using prostate-specific antigen PSA and biopsies as end points for clinical ly localized prostate cancer . METHODS AND MATERIAL S Between February 1995 and June 2001 , 378 men were r and omized to either 3 or 8 months of flutamide and goserelin before conventional-dose RT ( 66 Gy ) at four participating centers . The median patient age was 72 years ( range , 50 - 84 years ) . The stage distribution was 17 % T1c , 35 % T2a , 34 % T2b-T2c , 13 % T3-T4 . The Gleason score ( GS ) was < or = 6 in 51 % , 7 in 38 % , and 8 - 10 in 11 % . The median baseline PSA level was 9.7 ng/mL ( range , 1.3 - 189 ng/mL ) . Of the 378 men , 26 % were low risk ( Stage T1c-T2a , GS < or = 6 , PSA < 10 ng/mL ) , 43 % were intermediate risk ( Stage T2b or GS 7 or PSA 10 - 20 ng/mL ) , and 31 % were high risk ( Stage T3 or GS 8 - 10 or PSA > 20 ng/mL ) . The two arms were balanced in terms of age , GS , T stage , risk group , and presenting PSA level . The median follow-up was 44 months ( range , 10 - 84 months ) , and 361 patients were available for evaluation . RESULTS The 8-month arm achieved a lower PSA level before starting RT ( 0.37 vs. 0.74 ng/mL , p < or = 0.001 ) and had a greater downsizing of the prostate ( mean volume 26.6 cm(3 ) vs. 30.5 cm(3 ) , p < or = 0.001 ) . However , the actuarial freedom from failure rate ( biochemical by American Society for Therapeutic Radiology and Oncology definition , local or distant ) for the 3-month vs. 8-month arms at 3 years was 66 % vs. 68 % and by 5 years was 61 % vs. 62 % , respectively ( p = 0.36 ) . No statistically significant difference was noted in the types of failure between the two arms ( crude final status ) : biochemical , 22.2 % vs. 22.3 % ; local , 10.2 % vs. 6.5 % ; and distant , 3.4 % vs. 4.4 % ( p = 0.61 ) . Two-year post-RT biopsies were done in 57 % ( n = 205 ) . Negative biopsies were obtained in 68 % of the 3-month and 77 % of the 8-month patients ; 18 % and 14 % had indeterminate biopsies and 14 % and 9 % were positive for residual cancer ( p = 0.34 ) in the two arms , respectively . The median PSA level for nonfailing patients was 0.50 ng/mL in both the 3-months and 8-month arms . A suggestion of improvement was found in the 8-month arm for disease-free survival at 5 years for high-risk patients ( 39 % vs. 52 % ) but did not achieve statistical significance . CONCLUSION A longer period of neoadjuvant hormonal therapy before st and ard-dose RT does not appear to confer a benefit in terms of disease-free survival or to alter failure patterns . Failure was delayed in the 8-month arm , but this advantage was lost by 5 years of follow-up . A suggestion of benefit was noted with a longer period of hormonal therapy for high-risk patients PURPOSE In the initial report of the Lupron Depot Neoadjuvant Prostate Cancer Study Group patients who received 3 months of and rogen deprivation had a significant decrease in the positive margin rate . We monitored these patients for 5 years and to our knowledge present the longest followup of any neoadjuvant trial . MATERIAL S AND METHODS A multi-institutional prospect i ve r and omized trial was performed between February 1992 and April 1994 involving patients with stage cT2b prostate cancer , including 138 who received 3 months of leuprolide plus flutamide before radical prostatectomy and 144 who underwent radical prostatectomy only . Patients were followed every 6 months with serum prostate specific antigen ( PSA ) testing for 5 years . Biochemical recurrence was defined as PSA greater than 0.4 ng./ml . RESULTS At 5 years there was no difference in the biochemical recurrence rate . PSA was less than 0.4 ng./ml . in 64.8 % of the patients in the neoadjuvant and rogen ablation plus prostatectomy and 67.6 % in the prostatectomy only group ( p = 0.663 ) . CONCLUSIONS Although 3 months of and rogen deprivation before radical prostatectomy result ed in an apparently significant decrease in positive surgical margins , a 5-year followup does not indicate any difference in the recurrence rate . Until studies document improvement in biochemical or clinical recurrence with longer periods of treatment , induction and rogen deprivation before radical prostatectomy is not indicated OBJECTIVE To assess the effect of neoadjuvant combination therapy with the anti and rogen flutamide and a luteinizing-hormone-releasing hormone ( LHRH ) agonist administered for 3 months before radical prostatectomy , compared with surgery alone in early stage prostate cancer on histopathologic findings at surgery and serum prostate-specific antigen ( PSA ) . METHODS A sample of 161 r and omly screened patients diagnosed as having stage B ( 134 patients ) or C ( 27 patients ) prostate cancer were r and omly assigned to radical prostatectomy alone or to 3 months of neoadjuvant combination therapy with the anti and rogen flutamide and an LHRH agonist before radical prostatectomy . RESULTS Neoadjuvant combination therapy before radical prostatectomy decreased cancer-positive surgical margins from 33.8 % in the control group to only 7.8 % , thus leaving 92.2 % of patients with negative margins at surgery . A net 54 % improvement of staging was observed in favor of combination therapy . Organ-confined disease , on the other h and , increased from 49.3 % to 77.8 % of patients after 3 months of combination therapy , for a 57.8 % increase in the incidence of organ-confined disease . No cancer was found in 6 ( 6.7 % ) prostatectomy specimens from the treated group . A close correlation was found between serum PSA at diagnosis and the stage of the disease at surgery . Upstaging increased from 30 % at serum PSA values of 0 to 3.0 ng/mL up to 100 % at serum PSA values above 15 ng/mL. CONCLUSIONS Although long-term follow-up of these patients is required to determine the impact on survival , the marked influence of neoadjuvant combination therapy on the stage of the disease suggests the possibility of a major improvement in the morbidity and mortality from prostate cancer OBJECTIVE Because of efficacy demonstrated with chemotherapy in patients with metastatic disease , the National Prostate Cancer Project in 1978 initiated two protocol s evaluating adjuvant therapy following surgery ( Protocol 900 ) and irradiation ( Protocol 1000 ) for patients with localized disease at high risk for relapse . METHODS All patients underwent staging pelvic lymph node dissection . Following definitive treatment , patients were r and omized to either cyclophosphamide 1 g/m2 intravenously every 3 weeks for 2 years , estramustine phosphate 600 mg/m2 orally daily for 2 years or to observation only . Accession closed in 1985 and included 184 patients in Protocol 900 ( 170 evaluable ) and 253 in Protocol 1000 ( 233 evaluable ) . RESULTS Nodal involvement was identified in 198 patients ( 49 % of total ) : 29 % in Protocol 900 and 63 % in protocol 1000 . Median progression-free survival ( PFS ) and survival have been greater for patients in Protocol 900 regardless of adjuvant , reflecting their lower pathologic stage . Median PFS is significantly greater for patients in Protocol 1000 receiving estramustine ( 52.2 months ) compared to cyclophosphamide ( 35.0 months ) . Median PFS for patients with nodal involvement in Protocol 1000 receiving estramustine is increased ( 43.5 months ) compared to no treatment ( 21.5 months ) . Patients with limited nodal involvement in Protocol 1000 have a longer median PFS ( 45.6 months ) compared to patients with extensive disease ( 23.6 months ) . But in the latter group patients receiving estramustine experienced a significantly longer median PFS ( 43.5 months ) compared to cyclophosphamide ( 29.1 months ) or no adjuvant ( 13.5 months ) . Increased PFS with estramustine adjuvant was also noted in stage C patients ( only Protocol 900 ) and in those with high- grade ( grade 3 ) tumors ( both protocol s ) . CONCLUSIONS With now over 10 years mean follow-up for this series of patients , we conclude that adjuvant estramustine is beneficial for prostate cancer patients receiving definitive irradiation . This benefit is particularly noted in those patients with extensive nodal involvement ( N+ , D-1 ) BACKGROUND We retrospectively compared the 5-year survival rates of T1b-T3N0M0 prostate cancer patients treated either by endocrine therapy plus radical prostatectomy or endocrine therapy alone . METHODS Clinical T1b-T3N0M0 prostate cancer patients were enrolled at 104 institutions in Japan . They were assigned to study 1 ( n = 176 ) , if they were indicated to prostatectomy , if not indicated , they were assigned to study 2 ( n = 151 ) . The indication of prostatectomy was based on the clinical judgement of physicians and /or patients . Those assigned to study 1 underwent prostatectomy and adjuvant endocrine therapy with or without preoperative and rogen deprivation . Those assigned to study 2 were treated with leuprorelin acetate with or without chlormadinone acetate . They were followed-up every 3 months until death or for 5 years and over . RESULTS Those assigned to study 1 were younger ( mean age 67.2 vs 75.7 years ) , less advanced in clinical stage , and had lower prostate specific antigen levels ( mean 43.8 vs 103.6 ng/mL ) . Death for any reason was observed less frequently in study 1 ( n = 29 , 16 % ) than study 2 ( n = 50 , 33 % ) , and the 5-year overall survival rate was higher in study 1 ( 87 vs. 68 % ) . However , prostate cancer deaths were comparatively seldom ( 9 % in study 1 and 7 % in study 2 ) , result ing in the identical 5-year cause specific survival rate in both study groups ( 91 % ) . In both study groups the overall survival was almost equal to the natural survival of age-matched men . CONCLUSIONS Endocrine therapy offers a reasonable survival rate in T1b-T3 prostate cancer patients within a 5-year follow-up . Observation will be extended to determine 10-year outcomes Although the only opportunity to cure prostate cancer is treatment at an early stage , radical prostatectomy has remained relatively unpopular because 40 - 50 % of prostate cancers estimated at diagnosis as confined to the prostate are found to be at a more advanced stage following histopathological analysis of the surgical specimen . This first prospect i ve , r and omized trial investigated the potential advantages of 3-month neoadjuvant combination therapy with flutamide and lupron before radical prostatectomy vs. prostatectomy alone in early stage prostate cancer . Cancer-positive margins were reduced from 38.5 % ( 25 of 65 ) in control patients to only 13.0 % ( 10 of 77 ) in men who received neoadjuvant combination therapy with the anti and rogen flutamide and the luteinizing hormone-releasing hormone ( LHRH ) super-agonist Lupron before radical prostatectomy ( p = 0.006 ) . Moreover , comparison of the final stage determined by histopathological examination of the surgical specimen with that estimated at diagnosis showed that a more advanced stage ( upstaging ) was found in 53.8 % of controls , but patients who received combination therapy had an opposite effect : a more favorable stage than expected at diagnosis was found in 23.4 % of cases ( downstaging ) , a 77.2 % advantage of neoadjuvant combination therapy . The concern about radical prostatectomy , underestimation of stage , is thus markedly improved by 3-month neoadjuvant therapy with flutamide and a LHRH superagonist . Cancer-negative margins are expected to be accompanied by a life expectancy not different from that of men of similar age with no prostate cancer ; therefore , the present data , combined with efficient detection of early stage prostate cancer , offer the basis for dramatic improvement in the morbidity and mortality of prostate cancer BACKGROUND We studied the extent of neuroendocrine ( NE ) tumor cell differentiation and its relation to regressive changes in prostate cancer after 3-month hormonal treatment . METHODS Radical prostatectomy specimens from 103 patients , r and omized to 3-month neoadjuvant LH-RH-analogue treatment ( neoadjuvant group ) or to surgery alone ( control group ) , were available for analysis . The effects of hormonal treatment in terms of positive surgical margins , the degree of histopathological changes , and tumor cell proliferation were evaluated in relation to NE-differentiation assessed with antibodies against chromogranin A ( CGA ) . RESULTS Both the number of CGA-positive cells/cm(2 ) ( P < 0.003 ) and the proportion of NE-positive tumors ( P = 0.07 ) were greater in the neoadjuvant group than in the control group . No correlation existed between NE-differentiation and the effects of the neoadjuvant hormonal treatment ; nor did NE-differentiation correlate to the decrease in serum PSA . CONCLUSIONS Neuroendocrine differentiation in prostate cancer increases after 3 months of neoadjuvant hormonal treatment but does not correlate to the effects of hormonal treatment To evaluate the effect of primary hormonal therapy for patients with localized and locally advanced prostate cancer OBJECTIVES To compare the pathologic stage and surgical margin status in patients undergoing either immediate radical prostatectomy or surgery preceded by 3 or 6 months of neoadjuvant hormonal treatment ( NHT ) in a prospect i ve , r and omized study . METHODS Four hundred thirty-one men with prostate cancer were enrolled in the Italian r and omized prospect i ve PROSIT study . The whole-mount sectioning technique was used . By May 1999 , the review ing pathologist had evaluated 303 specimens . One hundred seven patients were untreated before radical prostatectomy was performed , and 114 and 82 patients had been treated for 3 and 6 months , respectively , with complete and rogen blockade . RESULTS Pathologic organ-confined disease was found in 63.1 % of patients with clinical Stage B disease treated with 6 months of NHT versus 61.0 % after 3 months of NHT and 37.5 % after immediate surgery . Among patients with clinical Stage C tumors , pathologic staging found organ-confined disease in 62.5 % , 32.1 % , and 11.1 % of patients after 6 months of NHT , 3 months of NHT , and immediate surgery , respectively . Three months of NHT produced a significant increase in negative margins both in patients with clinical Stage B and C disease , but the addition of another 3 months of treatment did not significantly improve this result . A lower degree of benefit was observed in patients with clinical Stage C tumors . CONCLUSIONS This study shows that complete and rogen blockade before surgery is beneficial in men with clinical Stage B disease . The effects are more pronounced after 6 months of NHT than after 3 months PURPOSE To clarify the optimal duration and methods for adjuvant endocrine therapy after external beam radiation therapy ( EBRT ) in patients with locally advanced prostate cancer . MATERIAL S AND METHODS Between 2001 and 2003 , 215 patients with locally advanced prostate cancer were enrolled in the study . Patients were registered as primary c and i date s of the study and were treated with 6 months of LHRH agonist , with short-term of anti and rogen treatment for flare-up prevention . Patients with PSA levels below 10 ng/ml after the 6-month endocrine treatment were r and omly divided into two arms . Then , a total dose of 72 Gy was given to the prostate . After 14 months of the protocol treatment , patients were treated with continuous and rogen ablation ( arm 1 ) or intermittent and rogen ablation ( arm 2 ) . RESULTS A total of 188 cases ( 87 % ) remained in the protocol . The median PSA level at entry was 25.3 ng/ml . The Gleason score was 2 - 6 in 32 cases ( 16 % ) , 7 in 94 cases ( 48 % ) , and 8 - 10 in 68 cases ( 35 % ) . The median PSA level showed a remarkable decrease to 1.1 , 0.2 , and 0.1 ng/ml , after 6 , 8 , and 14 months of the protocol treatment , respectively . Of the 157 cases treated with EBRT , 153 cases ( 97.5 % ) had no biochemical failure in the mean follow-up of 17.3 months . CONCLUSIONS The present study may reveal the possibilities of intermittent endocrine therapy after EBRT . However , the follow-up interval is short and little can be said about the results observed so far , exception of acute tolerance and patient acceptance of the protocol A total of 277 patients with apparently localised prostatic cancer ( T2-T4 NXMO ) were allocated at r and om to receive radiotherapy alone ( 88 ) , orchiectomy alone ( 90 ) and combined therapy ( 99 ) between 1980 and 1985 . The main outcome measures were survival , time to appearance of metastases and treatment of local disease progression by further transurethral resection . Orchiectomy , whether alone or with radiotherapy , produced a significant delay in detection of metastases when compared with radiotherapy alone . There were no statistically significant differences between the 3 treatment groups in local disease control or in overall survival OBJECTIVES And rogen deprivation therapy before and during radiation therapy could , by reducing tumor volume , increase local tumor control , disease-free survival , and overall survival in patients with locally advanced adenocarcinomas of the prostate . METHODS In a r and omized controlled clinical trial , patients with large T2 , T3 , and T4 prostate tumors , but no evidence of osseous metastasis , were r and omized to receive goserelin 3.6 mg subcutaneously every 4 weeks and flutamide 250 mg orally three times daily 2 months before and during the radiation therapy course ( Arm I ) compared with radiation therapy alone ( Arm II ) . Pelvic irradiation was administered with 1.8 to 2.0 Gy per day to a total dose of 45 + /- 1 Gy followed by a boost to the prostate target volume to a total dose of 65 to 70 Gy . RESULTS Of 471 r and omized patients , 456 were evaluable , 226 on Arm I and 230 on Arm II . With a median potential follow-up of 4.5 years , the cumulative incidence of local progression at 5 years was 46 % in Arm I and 71 % in Arm II ( P < 0.001 ) . The 5-year incidence of distant metastasis on Arms I and II was 34 % and 41 % , respectively ( P = 0.09 ) . Progression-free survival rates including normal prostate-specific antigen ( PSA ) levels for 396 patients with at least one PSA recorded were 36 % in Arm I and 15 % in Arm II at 5 years ( P < 0.001 ) . At this time , no significant difference in overall survival could be detected ( P = 0.7 ) . CONCLUSIONS Short-term and rogen deprivation with radiation therapy results in a marked increase in local control and disease-free survival compared with pelvic irradiation alone in patients with locally advanced carcinoma of the prostate . Long-term surveillance is required to assess effects on overall survival PURPOSE To evaluate the cost-effectiveness of adding hormone therapy to radiation for patients with locally advanced prostate cancer , using a Monte Carlo simulation of a Markov Model . METHODS AND MATERIAL S Radiation Therapy Oncology Group ( RTOG ) protocol 86 - 10 r and omized patients to receive radiation therapy ( RT ) alone or RT plus total and rogen suppression ( RTHormones ) 2 months before and during RT for the treatment of locally advanced prostate cancer . A Markov model was design ed with Data Pro ( TreeAge Software , Williamstown , MA ) . The analysis took a payer 's perspective . Transition probabilities from one state of health ( i.e. , with no disease progression or with hormone-responsive metastatic disease ) to another were calculated from published rates pertaining to RTOG 86 - 10 . Patients remained in one state of health for 1 year . Utility values for each health state and treatment were obtained from the literature . Distributions were sample d at r and om from the treatment utilities according to a second-order Monte Carlo simulation technique . RESULTS The mean expected cost for the RT-only treatments was 29,240 dollars ( range , 29,138 - 29,403 dollars ) . The mean effectiveness for the RT-only treatment was 5.48 quality -adjusted life years ( QALYs ) ( range , 5.47 - 5.50 ) . The mean expected cost for RTHormones was 31,286 dollars ( range , 31,058 - 31,555 dollars ) . The mean effectiveness was 6.43 QALYs ( range , 6.42 - 6.44 ) . Incremental cost-effectiveness analysis showed RTHormones to be within the range of cost-effectiveness at 2,153 dollars/QALY . Cost-effectiveness acceptability curve analysis result ed in a > 80 % probability that RTHormones is cost-effective . CONCLUSIONS Our analysis shows that adding hormonal treatment to RT improves health outcomes at a cost that is within the acceptable cost-effectiveness range PURPOSE To determine the acceptability of short term neo-adjuvant maximal and rogen deprivation ( MAD ) to patients treated with external beam radiation for locally advanced prostate cancer . METHODS Between 1996 and 2000 , 818 patients with locally advanced , but non-metastatic , prostate cancer were entered into a r and omised clinical trial ( TROG 96.01 ) , which compared radiation treatment alone with the same radiation treatment and 3 or 6 months neo-adjuvant MAD with goserelin and flutamide . Relevant symptoms , and how troublesome they were to the patient , were scored using a self- assessment question naire . This was completed by the patient at registration , and at specified times during and after treatment . Patients taking flutamide had liver function tests checked at regular intervals . RESULTS All patients have completed at least 12 months follow-up after treatment . Nearly all patients completed planned treatment with goserelin , but 27 % of patients in the 6-month MAD treatment arm , and 20 % in the 3-month arm , had to stop flutamide early . This was mainly due to altered liver function ( up to 17 % patients ) and bowel side effects ( up to 8 % patients ) . However , although flutamide result ed in more bowel symptoms for patients on MAD , there was significant reduction in some urinary symptoms on this treatment . Acute bowel and urinary side effects at the end of radiation treatment were similar in all treatment arms . Side effect severity was unrelated to radiation target volume size , which was reduced by MAD , but symptomatology prior to any treatment was a powerful predictor . Of the 36 % of patients who were sexually active before any treatment , the majority became inactive whilst on MAD . However , sexual activity at 12 months after radiation treatment was similar in all treatment arms , indicating that the effects of short term MAD on sexual function are reversible . CONCLUSION Despite temporary effects on sexual activity , and compliance difficulties with flutamide , short-term neo-adjuvant MAD was not perceived by patients to be a major inconvenience . If neo-adjuvant MAD in the way tested can be demonstrated to lead to improved biochemical control and /or survival , then patients would view these therapeutic gains as worthwhile . Compliance with short-term goserelin was excellent , confirming that LH-RH analogues have a potential role in more long-term adjuvant treatment . However , for more protracted and rogen deprivation , survival advantages and deleterious effects need to be assessed in parallel , in order to determine the optimal duration of treatment PURPOSE Cooperative groups have investigated the outcome of and rogen deprivation therapy combined with radiation therapy in prostate cancer patients with variable pretreatment prognostic indicators . This report describes an objective means of selecting patients for adjuvant hormonal therapy by a retrospective matched case/control comparison of outcome between patients with specific pretreatment characteristics who receive adjuvant hormones ( RT+H ) vs. patients with identical pretreatment characteristics treated with radiation therapy alone ( RT ) . In addition , this report shows the 5-year bNED control for patients selected by this method for RT+H vs. RT alone . METHODS AND MATERIAL S From 10/88 to 12/93 , 517 T1-T3 NXM0 patients with known pretreatment PSA level were treated at Fox Chase Cancer Center . Four hundred fifty-nine of those patients were treated with RT alone while 58 were treated with RT+H. The patients were categorized according to putative prognostic factors indicative of bNED control , which include the palpation stage , Gleason score , and pretreatment PSA . We compared actuarial bNED control rates according to treatment group within each of the prognostic groups . In addition , we devised a retrospective matched case/control selection of RT patients for comparison with the RT+H group . Five-year bNED control was compared for the two treatment groups , excluding the best prognosis group , using 56 RT+H patients and 56 matched ( by stage , grade , and pretreatment PSA level ) controls r and omly selected from the RT alone group . bNED control for the entire group of 517 patients was then analyzed multivariately using step-wise Cox regression to determine independent predictors of outcome . Covariates considered for entry into the model included stage ( T1/T2AB vs. T2C/T3 ) , grade ( 2 - 6 vs. 7 - 10 ) , pretreatment PSA ( 0 - 15 vs. > 15 ) , treatment ( RT vs. RT+H ) , and center of prostate dose . bNED failure is defined as PSA > or = 1.5 ngm/ml and rising on two consecutive determinations . The median follow-up for the 112 matched case/control patients was 41 months . The median follow-up was 46 months for the RT ( range 11 - 102 months ) and 37 months for the RT+H group ( range 6 - 82 months ) . RESULTS Univariate analysis according to treatment for the prognostic factors of palpation stage , Gleason score , and pretreatment PSA demonstrates a significant improvement in 3-year bNED control with the addition of hormones for patients with T2C/T3 , Gleason score 7 - 10 , or pretreatment PSA > 15 ngm/ml . A comparison of bNED control according to treatment demonstrates improvement in 5-year bNED control of 55 % for patients treated with RT+H vs. 31 % for those patients treated with RT alone ( p = 0.0088 ) , although there is not a survival advantage . Multivariate analysis demonstrates that hormonal treatment is a highly significant independent predictor of bNED control ( p = 0.0006 ) along with pretreatment PSA ( p = 0.0001 ) , palpation stage ( p = 0.0001 ) , grade ( p = 0.0030 ) , and dose ( p = 0.0001 ) . CONCLUSIONS ( 1 ) Patients with specific adverse pretreatment prognostic factors ( i.e. , T2C/T3 , Gleason score 7 - 10 , pretreatment PSA > 15 ) benefit from adjuvant hormonal therapy . ( 2 ) Upon multivariate analysis , hormonal therapy is determined to be a highly significant predictor of bNED control , after adjusting for all other covariates . ( 3 ) The 5-year bNED control rates of 55 % for RT+H vs. 31 % for RT alone represents the magnitude of benefit from adjuvant hormone therapy . ( 4 ) The bNED control curves are separated by about 20 months , representing a delay in disease progression with adjuvant hormonal therapy , as there is no overall survival difference PURPOSE Although and rogen suppression results in a tumor response/remission in the majority of patients with carcinoma of the prostate , its potential value as an adjuvant has not been substantiated . MATERIAL S AND METHODS In 1987 , the Radiation Therapy Oncology Group ( RTOG ) initiated a r and omized phase III trial of adjuvant goserelin in definitively irradiated patients with carcinoma of the prostate . A total of 977 patients had been accessioned to the study . Of these , 945 remained analyzable : 477 on the adjuvant arm and 468 on the observation arm . RESULTS Actuarial projections show that at 5 years , 84 % of patients on the adjuvant goserelin arm and 71 % on the observation arm remain without evidence of local recurrence ( P < .0001 ) . The corresponding figures for freedom from distant metastases and disease-free survival are 83 % versus 70 % ( P < .001 ) and 60 % and 44 % ( P < .0001 ) . If prostate-specific antigen ( PSA ) level greater than 1.5 ng is included as a failure ( after > or = 1 year ) , the 5-year disease-free survival rate on the adjuvant goserelin arm is 53 % versus 20 % on the observation arm ( P < .0001 ) . The 5-year survival rate ( for the entire population ) is 75 % on the adjuvant arm versus 71 % on the observation arm ( P = .52 ) . However , in patients with central ly review ed tumors with a Gleason score of 8 to 10 , the difference in actuarial 5-year survival ( 66 % on the adjuvant goserelin arm v 55 % on the observation arm ) reaches statistical significance ( P = .03 ) . CONCLUSION Application of and rogen suppression as an adjuvant to definitive radiotherapy has been associated with a highly significant improvement in local control and freedom from disease progression . At this point , with a median follow-up time of 4.5 years , a significant improvement in survival has been observed only in patients with central ly review ed tumors with a Gleason score of 8 to 10 PURPOSE We evaluated the efficacy and tolerability of 150 mg bicalutamide daily given in addition to st and ard care , in patients with localized or locally advanced prostate cancer . MATERIAL S AND METHODS The bicalutamide Early Prostate Cancer program consists of 3 r and omized , double blind , placebo controlled trials prospect ively design ed for combined analysis . A total of 8,113 men with T1b-T4 , M0 , any N ( N0 in 1 trial ) prostate cancer were r and omized to bicalutamide 150 mg/day ( 4,052 ) or placebo ( 4,061 ) in addition to st and ard care ( radical prostatectomy , radiotherapy or watchful waiting ) . Primary end points were objective progression-free survival ( PFS ) and overall survival . RESULTS At median 5.4 years of followup ( 21.6 % progression events ) bicalutamide significantly improved PFS in the overall population . This result was driven by positive results in trials 24 and 25 , with the North American trial ( trial 23 ) showing no difference . Patients with locally advanced disease gained most benefit from bicalutamide in terms of PFS , irrespective of underlying therapy . Overall survival was similar in the bicalutamide and placebo groups , across the program and in each trial . Among watchful waiting patients survival appeared to be improved with bicalutamide in those with locally advanced disease , whereas survival appeared to be reduced with bicalutamide in those with localized disease . The most common adverse events with bicalutamide were gynecomastia and breast pain . Other adverse events occurred with a similarly low incidence in the 2 treatment groups . CONCLUSIONS This analysis confirms that bicalutamide provides benefit in patients with locally advanced disease . The current data suggest that early or adjuvant hormonal therapy for patients at low risk of disease progression , such as those with localized disease , is not appropriate OBJECTIVES To evaluate tumor cell proliferation in relation to histopathologic regressive changes and failure after radical prostatectomy after a 3-month course of neoadjuvant luteinizing hormone-releasing hormone ( LHRH ) analogue treatment . METHODS We evaluated slides from 103 radical prostatectomy specimens of the 111 patients participating in a r and omized trial of a 3-month course of neoadjuvant LHRH analogue treatment before radical retropubic prostatectomy ( n = 50 ) versus surgery alone ( n = 53 ) . The histopathologic regressive changes in the specimens were scored by two pathologists . Sections were stained with the anti-Ki-67 monoclonal antibody MIB-1 . The proliferation index ( PI ) was defined as the proportion of Ki-67-positive cells in a r and om cell count . The patients were followed up until treatment failure or for a mean of 39 months among those without failure . RESULTS In the neoadjuvant group , increasing histopathologic regressive changes correlated with a decrease in capsular penetration , positive surgical margins , and tumor cell proliferation but did not correlate with Gleason score in biopsies . Treatment failure was not related to the histopathologic regressive changes . In the neoadjuvant treatment group , progression-free survival was longer in the subgroup of patients with tumors with a PI less than 1.2 % compared with those with tumors with a PI greater than 1.2 % ( P = 0.02 ) . Multivariate analysis of PI and histopathologic and clinical features showed the PI ( P = 0.002 ) and the pretreatment serum prostate-specific antigen level ( P = 0.003 ) to be significant prognostic markers of failure in the neoadjuvant group . CONCLUSIONS Tumor cell proliferation after 3 months of neoadjuvant hormonal treatment is a prognostic marker of failure after radical prostatectomy without correlation to Gleason score or the histopathologic regressive changes result ing from hormonal treatment The aim of this study was to compare the efficacy of total intermittent and rogen deprivation ( IAD ) versus total continuous and rogen deprivation ( CAD ) for treating patients with advanced prostate cancer in a phase III r and omized trial . A total of 68 evaluable patients with hormone-naive advanced or relapsing prostate cancer were r and omized to receive combined and rogen blockade according to a continuous ( n = 33 ) or intermittent ( n = 35 ) regimen . Therapeutic monitoring was assessed by use of serum prostate-specific antigen ( PSA ) measurements . Patients in the CAD and IAD groups were equally stratified for age , biopsy Gleason score , and baseline serum PSA levels . The outcome variable was time to and rogen-independence of the tumor , which was defined as increasing serum PSA levels despite and rogen blockade . Mean follow-up was 30.8 months . The 35 IAD-treated patients completed 91 cycles , and 19 of them ( 54.3 % ) completed > or = 3 cycles . Median cycle length and percentage of time off therapy were 9.0 months and 59.5 , respectively . The estimated 3-year progression rate was significantly lower in the IAD group ( 7.0 % + /- 4.8 % ) than in the CAD group ( 38.9 % + /- 11.2 % , P = 0.0052 ) . Our data suggest that IAD treatment may maintain the and rogen-dependent state of advanced human prostate cancer , as assessed by PSA measurements , at least as long as CAD treatment . Further studies with longer follow-up times and larger patient cohorts are needed to determine the comparative impacts of CAD and IAD on survival BACKGROUND We did a r and omised phase III trial comparing external irradiation alone and external irradiation combined with an analogue of luteinising-hormone releasing hormone ( LHRH ) to investigate the added value of long-term and rogen suppression in locally advanced prostate cancer . METHODS Between 1987 and 1995 , 415 patients were r and omly assigned radiotherapy alone or radiotherapy plus immediate and rogen suppression . Eligible patients had T1 - 2 tumours of WHO grade 3 or T3 - 4 N0 - 1 M0 tumours ; the median age of participants was 71 years ( range 51 - 80 ) . In both treatment groups , 50 Gy radiation was delivered to the pelvis over 5 weeks , and 20 Gy over 2 weeks as a prostatic boost . Goserelin ( 3.6 mg subcutaneously every 4 weeks ) was started on the first day of irradiation and continued for 3 years ; cyproterone acetate ( 150 mg orally ) was given for 1 month starting 1 week before the first goserelin injection . The primary endpoint was clinical disease-free survival . Analyses were by intention to treat . FINDINGS 412 patients had evaluable data , with median follow-up of 66 months ( range 1 - 126 ) . 5-year clinical disease-free survival was 40 % ( 95 % CI 32 - 48 ) in the radiotherapy-alone group and 74 % ( 67 - 81 ) in the combined-treatment group ( p=0.0001 ) . 5-year overall survival was 62 % ( 52 - 72 ) and 78 % ( 72 - 84 ) , respectively ( p=0.0002 ) and 5-year specific survival 79 % ( 72 - 86 ) and 94 % ( 90 - 98 ) . INTERPRETATION Immediate and rogen suppression with an LHRH analogue given during and for 3 years after external irradiation improves disease-free and overall survival of patients with locally advanced prostate cancer OBJECTIVES To improve the treatment of locally advanced prostate cancer ( Stages B2 and C ) , a prospect i ve r and omized trial was conducted to compare radical prostatectomy versus external beam radiotherapy with the combination of endocrine therapy in both modalities . METHODS One hundred patients were enrolled and 95 were evaluated . Forty-six patients underwent radical prostatectomy with pelvic lymph node dissection , and 49 were treated with radiation by linear accelerator with 40 to 50 Gy to the whole pelvis and a 20-Gy boost to the prostatic area . For all patients , endocrine therapy was initiated 8 weeks before surgery or radiation , and continued thereafter . The living patients were asked to respond to a quality -of-life question naire . RESULTS The follow-up period ranged from 6.0 to 94.4 months ( median 58.5 ) . The progression-free and cause-specific survival rates at 5 years were 90.5 % and 96.6 % in the surgery group and 81.2 % and 84.6 % in the radiation group , respectively . The surgery group had better progression-free and cause-specific survival rates ( P = 0.044 and 0.024 , respectively ) . More patients in the surgery group complained of urinary incontinence . The question naire revealed that quality of life was less disturbed in the radiation group . CONCLUSIONS Radical prostatectomy combined with endocrine therapy may contribute to the survival benefit of patients with locally advanced prostate cancer . External beam radiotherapy in combination with endocrine therapy can be used in selected patients because of its low morbidity OBJECTIVES In most clinical trials that have investigated the potential beneficial effects of neoadjuvant combined and rogen blockade ( CAB ) in clinical ly localized prostate cancer , CAB has been given for 3 months , but no data are available on the influence of a longer duration of neoadjuvant CAB on the pathologic features of prostate cancer . METHODS Prostatectomy specimens of 40 patients , r and omized to 3 ( n = 18 ) or 6 ( n = 22 ) months of neoadjuvant CAB , were blindly evaluated with regard to tumor volume , pathologic stage , and surgical margins . The morphologically most vital tumor areas were investigated for nucleolar size and MIB-1 defined proliferative activity . RESULTS The patients treated for 6 months had a median tumor volume 60 % lower than the 3-month treatment group ( P = 0.005 ) . In the 6-month treatment group , no residual tumor could be found in 2 cases , but the proportion of prostatectomy specimens with seminal vesical invasion and positive surgical margins was not statistically different from that after 3 months . Compared with untreated controls , tumor proliferative activity assessed by MIB-1 immunoreactivity was significantly lower at 3 and 6 months of neoadjuvant CAB ( P = 0.01 ) . However , in 2 of 1 7 examined tumors that had been treated for 6 months , high MIB-1 scores suggested a development toward therapy-resistant cancer . CONCLUSIONS Prolonged neoadjuvant CAB for 6 months leads to a further decrease in prostatic tumor volume compared with the findings after 3 months . In a few instances , residual tumor areas with substantial MIB-1 defined proliferative activity persist at 6 months , thus indicating that in at least some cases , despite the overall decrease in tumor size , cancer cells can continue the cell cycle under CAB BACKGROUND The effects of preoperative and rogen deprivation were explored in the patients who received radical prostatectomy and subsequent adjuvant endocrine therapy for prostate cancer . METHODS Stage A2 , B or C prostate cancers were r and omized to one of two groups : ( i ) group I ( n=90 ) , who received and rogen deprivation ( leuploride and chlormadinone acetate ) for 3 months preoperatively followed by radical prostatectomy and adjuvant endocrine therapy ( leuploride only ) ; and ( ii ) group II ( n=86 ) , who underwent the surgery followed by 3 month and rogen deprivation and subsequent adjuvant endocrine therapy . The effects of preoperative and rogen deprivation on clinical relapse ( serum prostate specific antigen ( PSA ) > 1.98 ng/mL , local recurrence or distant metastasis ) and PSA relapse ( PSA > 0.2ng/mL ) were evaluated at 2 years after r and omization . RESULTS There was no significant difference in clinical or PSA relapse-free survival and quality of life measures between the two groups , although relapses occurred significantly more frequently in patients who had more advanced stages , higher pretreatment PSA values or lower histologic differentiation in either group . Subgroup analysis indicated that clinical relapse-free survival in stage C cancer tended to be better in patients with preoperative and rogen deprivation than in those patients without it ( P < 0.1 ) . CONCLUSIONS Preoperative and rogen deprivation may be beneficial for stage C prostate cancer patients receiving radical prostatectomy and adjuvant endocrine therapy over the 2 year observation period . A longer follow up is needed to clarify the exact extent of benefit in terms of survival and quality of life In this retrospective study the relationship between serum prostate-specific antigen ( PSA ) and tumour volume ( assessed by the planimetric method on whole mount section ) was analysed in 56 patients subjected to radical prostatectomy , of whom 28 received 3 months of neoadjuvant GnRH analogue ( triptorelin ) treatment . Serum PSA in the control group was strongly correlated to the tumour volume while no such correlation was found after hormonal pretreatment ( r = 0.84 vs. 0.18 ) , indicating that serum PSA is unreliable as a tumour marker after hormonal deprivation . When the pretreatment PSA ( before hormonal deprivation ) per tumour volume ratio was calculated , a group of 10 patients ( 36 % ) showed considerably higher values , suggesting true tumour volume reduction in those patients as a result of the neoadjuvant hormonal treatment PURPOSE The aim of the present study is to investigate whether combined and rogen blockade associated with radiation therapy for localized prostate cancer decreases at 12 and 24 months the rate of positive follow-up biopsies and serum PSA compared to radiation therapy alone . This is the report of an interim analysis . METHODS AND MATERIAL S One hundred and twenty patients with clinical Stage B1-T2a , B2-T2b/T2c , and C-T3/T4 , adenocarcinoma of the prostate were entered in a prospect i ve r and omized study . After written informed consent , the subjects were r and omly allocated between external beam radiation therapy ( EBRT ) alone ( group 1 ) , 3 months of neoadjuvant combination therapy ( LHRH-agonist + Flutamide ) prior to EBRT ( group 2 ) , and a third group receiving combination therapy 3 months before , during , and 6 months after EBRT . There is no significant difference between the three groups concerning age , stage of disease , grade of tumor , and pretreatment PSA levels . Control transrectal ultrasound (TRUS)-guided needle biopsies ( one core was taken from the initial cancer site regardless of the presence or absence of TRUS abnormalities ) were done 12 and 24 months after the end of EBRT . Serum PSA measurements were done on schedule visits . RESULTS Ninety-two and 68 patients underwent biopsies at 12 and 24 months , respectively , after the end of radiation therapy . While 62 % of control patients at 12 months in Group 1 disclosed residual neoplasm , only 30 % and 4 % showed residual disease in groups 2 and 3 , respectively ( p = 0.00005 ) . When looking at 24 months , 65 , 28 , and 5 % showed residual cancer for groups 1 , 2 , and 3 , respectively ( p = 0.00001 ) . The PSA measurements indicate also at 12 months a difference between the three groups ( p < 0.0001 ) , except at 24 months , the difference between the group 2 and 3 is no longer significant . CONCLUSION The preliminary analysis of this clinical trial indicates that patients treated with radiation therapy alone show a significantly higher rate of positive biopsies at 12 and 24 months after the end of radiation therapy as compared with those treated with total anti and rogen blockade ( TAB ) and radiation therapy . When analyzing the median PSA serum levels , we found the same advantage at 12 months , but , at the time of the analysis at 24 months , the PSA levels are not different between groups 2 and 3 Seventy-eight patients with clinical Stage C adenocarcinoma of the prostate were prospect ively r and omized to receive either radiation alone or radiation and adjuvant estrogen ( diethylstilbestrol ) . No patient had received any prior definitive treatment for cancer . Forty patients were r and omized to receive radiotherapy only and 38 patients to receive radiotherapy and estrogen . The median follow-up for all surviving patients was 14.5 years . Whether analyzed according to the original r and omization or according to the treatment actually received , disease-free survival in the adjuvant estrogen group was strikingly and significantly higher than in the radiation-only group . At 5 , 10 , and 15 years patients receiving adjuvant estrogen had respective disease-free survival rates of 71 % , 63 % , and 63 % compared with 49 % , 43 % , and 35 % in patients having radiation only ( p = 0.008 ) . However , because of greater intercurrent disease-related mortality in patients receiving estrogen , there was no improvement in survival . This study suggests that a prospect i ve r and omized evaluation of early and rogen deprivation with orchiectomy or with one of the nonestrogenic agents should be undertaken and that patients receiving early and rogen deprivation should not be included in series reporting on the curative potential of radiation as a single modality BACKGROUND And rogen deprivation is an established treatment regimen for disseminated prostate cancer ; however , its role in patients with localised cancer is less clear . We did a large r and omised controlled trial to determine whether 3 months or 6 months of and rogen deprivation given before and during radiotherapy improves outcomes for patients with locally advanced prostate cancer . METHODS 818 men with locally advanced prostate cancer were r and omly assigned to : no and rogen deprivation ( ie , radiotherapy alone : 66 Gy in 33 fractions of 2 Gy per day over 6.5 - 7.0 weeks to the prostate and seminal vesicles ) ; 3 months ' and rogen deprivation with 3.6 mg goserelin given subcutaneously every month and 250 mg flutamide given orally three times a day starting 2 months before radiotherapy ( same regimen as control group ) ; or 6 months ' and rogen deprivation , with the same regimen , starting 5 months before radiotherapy ( same regimen as control group ) . Primary endpoints were time to local failure and prostate-cancer-specific survival ; secondary endpoints were distant failure , disease-free survival , and freedom from salvage treatment . Analyses were done by intention to treat . FINDINGS 802 ( 98 % ) patients were eligible for analysis . Median follow-up was 5.9 years ( range 0.1 - 8.5 ) . Compared with patients assigned no and rogen deprivation , those assigned 3 months ' treatment had significantly improved local failure ( hazard ratio [ HR ] 0.56 [ 95 % CI 0.39 - 0.79 ] , p=0.001 ) , biochemical failure-free survival ( 0.70 [ 0.56 - 0.88 ] , p=0.002 ) , disease-free survival ( 0.65 [ 0.52 - 0.80 ] , p=0.0001 ) , and freedom from salvage treatment ( 0.73 [ 0.56 - 0.96 ] , p=0.025 ) . 6 months ' and rogen deprivation significantly improved local failure ( 0.42 [ 0.28 - 0.62 ] , p<0.0001 ) , biochemical failure-free survival ( 0.58 [ 0.46 - 0.74 ] , p<0.0001 ) , disease-free survival ( 0.56 [ 0.45 - 0.69 ] , p<0.0001 ) , freedom from salvage treatment ( 0.53 [ 0.40 - 0.71 ] , p<0.0001 ) , distant failure ( 0.67 [ 0.45 - 0.99 ] , p=0.046 ) and prostate-cancer-specific survival ( 0.56 [ 0.32 - 0.98 ] , p=0.04 ) compared with no and rogen deprivation . INTERPRETATION 6 months ' and rogen deprivation given before and during radiotherapy improves the outlook of patients with locally advanced prostate cancer . Further follow-up is needed to estimate precisely the size of survival benefits . Increased radiation doses and additional periods of and rogen deprivation might lead to further benefit PURPOSE To up date the effect of immediate and rogen suppression in conjunction with st and ard external-beam irradiation versus radiation alone on a group of histologically lymph node-positive patients with adenocarcinoma of the prostate . MATERIAL S AND METHODS A national prospect i ve r and omized trial ( Radiation Therapy Oncology Group 85 - 31 ) of st and ard external-beam irradiation plus immediate and rogen suppression versus external-beam irradiation alone was initiated in 1985 for patients with locally advanced adenocarcinoma of the prostate . One hundred seventy-three patients in this trial had histologically involved lymph nodes . Ninety-eight patients received radiation plus immediate and rogen suppression ( luteinizing hormone-releasing hormone [ LHRH ] agonist ) , whereas 75 patients received radiation alone with hormonal manipulation instituted at the time of relapse . RESULTS With a median follow-up of 6.5 years for all patients and 9.5 years for living patients , estimated progression-free survival with prostate-specific antigen ( PSA ) level less than 1.5 ng/mL at 5 and 9 years was 54 % and 33 % , respectively , for patients who received immediate LHRH agonist versus 10 % [ corrected ] and 4 % for patients who received radiation alone with hormonal manipulation instituted at time of relapse ( P < .0001 ) . Multivariate analysis revealed radiation therapy and immediate hormonal manipulation as having a statistically significant impact on all end points analyzed : absolute survival , disease-specific failure , metastatic failure , and biochemical control with PSA less than 4 ng/mL and less than 1.5 ng/mL. CONCLUSION Pending the results of r and omized trials , patients with adenocarcinoma of the prostate who have pathologically involved pelvic lymph nodes ( pathologic node-positive or clinical stage D1 ) should be considered for external-beam irradiation plus immediate hormonal manipulation rather than radiation alone with hormone manipulation at the time of relapse Between January 1996 and June 2000 , 192 men with prostate cancer underwent radical retropubic prostatectomy ( RP ) and bilateral pelvic node dissection in 26 centers participating in the Italian r and omized prospect i ve TAP study . The review ing pathologist evaluated 145 RP specimens . Seventy-five cases had not been treated with total and rogen ablation before RP was performed , whereas 70 had been treated for three months . Whole-mount sectioning of the complete radical prostatectomy specimens was adopted in each center for accurately evaluating the pathological stage of prostate cancer and resection limit status . The results of this study suggest that total and rogen ablation before RP is beneficial in men with clinical stage T2 because of the significant pathological down-staging and decrease in the number of positive margins in the RP specimens . On the basis of the experience acquired through the Italian TAP study and recent publications on prognostic factors in prostate cancer , the original practice protocol for examination of RP specimens removed from patients with carcinoma of the prostate gl and s was up date Objectives : To evaluate the long – term effects of 3–month neoadjuvant hormonal treatment in patients treated by radical prostatectomy for locally confined prostate cancer . Methods : We report the results of 402 patients ( 220 with a clinical T2 tumor and 182 with a clinical T3 tumor ) of whom 192 r and omly received neoadjuvant total and rogen deprivation using a LHRH analogue ( goserelin ) plus flutamide for a period of 3 months and 210 underwent radical prostatectomy only . Results : ‘ Clinical downstaging ’ was seen in 30 % of cases in the neoadjuvantly treated group ( NEO ) . ‘ Pathological downstaging ’ occurred in 7 and 15 % of cases in the direct radical prostatectomy ( DP ) group and the NEO group , respectively ( p<0.01 ) . In patients with clinical T2 as well as in patients with clinical T3 tumors , a significant difference in the number of positive margins was shown in favor of the NEO group ( cT2 , p<0.01 ; cT3 , p = 0.01 ) . This advantage , although there was a trend in favor of the NEO group , specifically in cT2 tumors , did not translate in a significantly better PSA progression rate ( p = 0.18 ) . However , when evaluating the local control rate in cT2 tumors , we observed local recurrence in 3 of 102 ( 3 % ) patients in the NEO group versus 12 of 114 ( 11 % ) patients in the DP group . The difference is statistically significant ( p = 0.03 ) . In the cT3 group , this difference was not statistically significant ( NEO group : 15 of 87 ( 17 % ) , and DP group : 21 of 95 ( 22 % ) patients ; p = 0.41 ) . Conclusions : In this study , the clinical revelance of pathological downstaging and the lower percentage of patients with positive margins in the neoadjuvantly treated group with a clinical T2 tumor is not confirmed by a lower PSA progression rate . However , this study indicates that there may be a trend that this advantage in favor of the NEO group directly translates into a better local control rate in clinical T2 tumors . Better local control in cT2 tumors is only going to be of relevance if subsequently you can show that there is a better survival for these patients . Unfortunately , this article reports a study which is not yet mature enough to show relevant information . Presently , neoadjuvant therapy should not be given outside clinical research setting |
10,407 | 25,879,091 | This meta- analysis currently offers no clear evidence that perioperative beta-adrenergic blockade reduces postoperative cardiac morbidity and mortality in people undergoing major non-cardiac vascular surgery . | BACKGROUND People undergoing major vascular surgery have an increased risk of postoperative cardiac complications .
Beta-adrenergic blockers represent an important and established pharmacological intervention in the prevention of cardiac complications in people with coronary artery disease .
It has been proposed that this class of drugs may reduce the risk of perioperative cardiac complications in people undergoing major non-cardiac vascular surgery .
OBJECTIVES To review the efficacy and safety of perioperative beta-adrenergic blockade in reducing cardiac or all-cause mortality , myocardial infa rct ion , and other cardiovascular safety outcomes in people undergoing major non-cardiac vascular surgery . | BACKGROUND Trials of beta blockers in patients undergoing non-cardiac surgery have reported conflicting results . This r and omised controlled trial , done in 190 hospitals in 23 countries , was design ed to investigate the effects of perioperative beta blockers . METHODS We r and omly assigned 8351 patients with , or at risk of , atherosclerotic disease who were undergoing non-cardiac surgery to receive extended-release metoprolol succinate ( n=4174 ) or placebo ( n=4177 ) , by a computerised r and omisation phone service . Study treatment was started 2 - 4 h before surgery and continued for 30 days . Patients , health-care providers , data collectors , and outcome adjudicators were masked to treatment allocation . The primary endpoint was a composite of cardiovascular death , non-fatal myocardial infa rct ion , and non-fatal cardiac arrest . Analyses were by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00182039 . FINDINGS All 8351 patients were included in analyses ; 8331 ( 99.8 % ) patients completed the 30-day follow-up . Fewer patients in the metoprolol group than in the placebo group reached the primary endpoint ( 244 [ 5.8 % ] patients in the metoprolol group vs 290 [ 6.9 % ] in the placebo group ; hazard ratio 0.84 , 95 % CI 0.70 - 0.99 ; p=0.0399 ) . Fewer patients in the metoprolol group than in the placebo group had a myocardial infa rct ion ( 176 [ 4.2 % ] vs 239 [ 5.7 % ] patients ; 0.73 , 0.60 - 0.89 ; p=0.0017 ) . However , there were more deaths in the metoprolol group than in the placebo group ( 129 [ 3.1 % ] vs 97 [ 2.3 % ] patients ; 1.33 , 1.03 - 1.74 ; p=0.0317 ) . More patients in the metoprolol group than in the placebo group had a stroke ( 41 [ 1.0 % ] vs 19 [ 0.5 % ] patients ; 2.17 , 1.26 - 3.74 ; p=0.0053 ) . INTERPRETATION Our results highlight the risk in assuming a perioperative beta-blocker regimen has benefit without substantial harm , and the importance and need for large r and omised trials in the perioperative setting . Patients are unlikely to accept the risks associated with perioperative extended-release metoprolol BACKGROUND This post hoc analysis aim ed to determine whether neuraxial block was associated with a composite of cardiovascular death , non-fatal myocardial infa rct ion ( MI ) and non-fatal cardiac arrest within 30 days of r and omization in POISE trial patients . METHODS A total of 8351 non-cardiac surgical patients at high risk of cardiovascular complications were r and omized to β-blocker or placebo . Neuraxial block was defined as spinal , lumbar or thoracic epidural anaesthesia . Logistic regression , with weighting using estimated propensity scores , was used to determine the association between neuraxial block and primary and secondary outcomes . RESULTS Neuraxial block was associated with an increased risk of the primary outcome [ 287 ( 7.3 % ) vs 229 ( 5.7 % ) ; odds ratio ( OR ) , 1.24 ; 95 % confidence interval ( CI ) , 1.02 - 1.49 ; P=0.03 ] and MI [ 230 ( 5.9 % ) vs 177 ( 4.4 % ) ; OR , 1.32 ; 95 % CI , 1.07 - 1.64 ; P=0.009 ] but not stroke [ 23 ( 0.6 % ) vs 32 ( 0.8 % ) ; OR , 0.76 ; 95 % CI , 0.44 - 1.33 ; P=0.34 ] , death [ 96 ( 2.5 % ) vs 111 ( 2.8 % ) ; OR , 0.87 ; 95 % CI , 0.65 - 1.17 ; P=0.37 ] or clinical ly significant hypotension [ 522 ( 13.4 % ) vs 484 ( 12.1 % ) ; OR , 1.13 ; 95 % CI , 0.99 - 1.30 ; P=0.08 ] . Thoracic epidural with general anaesthesia was associated with a worse primary outcome than general anaesthesia alone [ 86 ( 12.1 % ) vs 119 ( 5.4 % ) ; OR , 2.95 ; 95 % CI , 2.00 - 4.35 ; P<0.001 ] . CONCLUSIONS In patients at high risk of cardiovascular morbidity , neuraxial block was associated with an increased risk of adverse cardiovascular outcomes , which could be causal or because of residual confounding AIM To assess the long-term cardioprotective effect of bisoprolol in a r and omized high-risk population after successful major vascular surgery . High-risk patients were defined by the presence of one or more cardiac risk factor(s ) and a dobutamine echocardiography test positive for ischaemia . METHODS 1351 patients were screened prior to surgery , 846 patients had one or more risk factor(s ) , and 173 of these patients also had ischaemia during dobutamine echocardiography . One hundred and twelve patients could be r and omized for additional bisoprolol therapy or st and ard care . Eleven patients died in the peri-operative period ( up to 1 month after surgery ) . R and omized patients continued bisoprolol or st and ard care after surgery . During follow-up of 101 survivors ( median 22 months , range 11 - 30 ) cardiac death or myocardial infa rct ion was noted . No patient was lost during follow-up . Results The incidence of cardiac events during follow-up in the bisoprolol group was 12 % vs 32 % in the st and ard care group ( P=0.025 ) . Cardiac death occurred in 15 patients , nine patients in the st and ard care and in six in the bisoprolol group ; myocardial infa rct ion occurred in six patients , five in the st and ard care and one in the bisoprolol group . The odds ratio for cardiac death or myocardial infa rct ion after surgery in high-risk patients with additional bisoprolol therapy was 0.30 ( 0.11 - 0.83 ) . CONCLUSIONS Bisoprolol significantly reduced long-term cardiac death and myocardial infa rct ion in high-risk patients after successful major cardiac vascular surgery BACKGROUND We sought to assess the intra- and postoperative haemodynamic effects of continuous perioperative beta-adrenergic blockade combined with phosphodiesterase ( PDE ) III inhibition and its potential benefits in limiting perioperative myocardial ischaemia in high-risk vascular surgery patients . METHODS Seventy-five patients were r and omly assigned to receive tight heart rate ( HR ) control by a continuous infusion of : esmolol in combination with the PDE III inhibitor enoximone ( esmolol+enoximone group ) , esmolol infusion alone ( esmolol group ) , or st and ard therapy ( control group ) for a period of 48 h. Myocardial ischaemia and dysfunction were detected by serial plasma Troponin T ( TnT ) and B-type natriuretic peptide ( BNP ) measurements . RESULTS Cardiac index ( CI ) increased significantly only in esmolol+enoximone-treated patients [ CI : from 2.4 ( 0.2 ) litre min(-1 ) m(-2 ) at baseline to 3.2 ( 0.2 ) litre min(-1 ) m(-2 ) at 24 h after surgery ; P=0.001 ] and was significantly higher than in the esmolol [ CI : from 2.5 ( 0.2 ) litre min(-1 ) m(-2 ) at baseline to 2.6 ( 0.2 ) litre min(-1 ) m(-2 ) at 24 h ; P=0.18 ] and the control groups [ CI : from 2.4 ( 0.2 ) litre min(-1 ) m(-2 ) at baseline to 2.7 ( 0.2 ) litre min(-1 ) m(-2 ) at 24 h ; P=0.13 ] . A significant postoperative release of TnT was detected only in control patients . Plasma BNP levels increased towards the end of surgery in all patients . Peak plasma BNP concentrations were significantly higher in control patients [ 293 ( 98 ) pg ml(-1 ) ] than in esmolol [ 118 ( 71 ) pg ml(-1 ) ] and in esmolol+enoximone-treated patients [ 78 ( 21 ) pg ml(-1 ) ] . CONCLUSIONS Inotropic therapy with the PDE III inhibitor enoximone combined with tight HR control by a continuous infusion of esmolol improved cardiac function and reduced myocardial ischaemia in high-risk vascular surgery patients . CLINICAL TRIAL REGISTRATION INFORMATION-URL : http://www . clinical trials.gov . Unique identifier : NCT00348101 OBJECTIVES The aim of this study was to determine the long-term prognosis with postoperative markers of myocardial ischemia and infa rct ion . BACKGROUND Cardiac troponins ( cTn ) are superior to creatine kinase-MB fraction ( CK-MB ) in detecting perioperative myocardial infa rct ion ( PMI ) . However , their threshold levels signifying PMI and their long-term prognostic value are not yet determined . METHODS A cohort of 447 consecutive patients who underwent 501 major vascular procedures was prospect ively studied . Perioperative continuous 12-lead electrocardiogram monitoring , cardiac troponin-I ( cTn-I ) and /or cardiac troponin-T ( cTn-T ) , and CK-MB levels on the first three postoperative days , and long-term survival were determined . The association of different cutoff levels of CK-MB , troponin , and ischemia duration with long-term survival was investigated . RESULTS Between 14 ( 2.9 % ) and 107 ( 23.9 % ) of the patients sustained PMI , depending on the biochemical criteria used . Elevated postoperative CK-MB , cTn , and prolonged ( > 30 min ) ischemia , at all cutoff levels examined , predicted long-term mortality independent of the preoperative predictors : patient 's age , type of vascular surgery , previous myocardial infa rct ion , and renal failure ( Cox multivariate analysis ) . Both CK-MB > 10 % and cTn-I > 1.5 ng/ml and /or cTn-T > 0.1 ng/ml independently predicted a 3.75-fold and 2.06-fold increase in long-term mortality ( p = 0.006 and 0.012 , respectively ) . Similarly , both CK-MB > 5 % and cTn-I > 0.6 ng/ml and /or cTn-T > 0.03 ng/ml independently predicted a 2.15-fold and 1.89-fold increase in mortality ( p = 0.018 and 0.01 , respectively ) . Patients with both these markers elevated had a 4.19-fold increase in mortality ( p < 0.001 ) . CONCLUSIONS Postoperative CK-MB and troponin , even at low cutoff levels , are independent and complementary predictors of long-term mortality after major vascular surgery OBJECTIVES This article describes the rationale and design of the DECREASE-XIII trial , which aims to evaluate the potential of esmolol infusion , an ultra-short-acting beta-blocker , during surgery as an add-on to chronic low-dose beta-blocker therapy to maintain perioperative haemodynamic stability during major vascular surgery . DESIGN A double-blind , placebo-controlled , r and omised trial . MATERIAL S & METHODS A total of 260 vascular surgery patients will be r and omised to esmolol or placebo as an add-on to st and ard medical care , including chronic low-dose beta-blockers . Esmolol is titrated to maintain a heart rate within a target window of 60 - 80 beats per minute for 24 h from the induction of anaesthesia . Heart rate and ischaemia are assessed by continuous 12-lead electrocardiographic monitoring for 72 h , starting 1 day prior to surgery . The primary outcome measure is duration of heart rate outside the target window during infusion of the study drug . Secondary outcome measures will be the efficacy parameters of occurrence of cardiac ischaemia , troponin T release , myocardial infa rct ion and cardiac death within 30 days after surgery and safety parameters such as the occurrence of stroke and hypotension . CONCLUSIONS This study will provide data on the efficacy of esmolol titration in chronic beta-blocker users for tight heart-rate control and reduction of ischaemia in patients undergoing vascular surgery as well as data on safety parameters Abstract Objectives To evaluate the long term effects of perioperative β blockade on mortality and cardiac morbidity in patients with diabetes undergoing major non-cardiac surgery . Design R and omised placebo controlled and blinded multicentre trial . Analyses were by intention to treat . Setting University anaesthesia and surgical centres and one coordinating centre . Participants 921 patients aged > 39 scheduled for major non-cardiac surgery . Interventions 100 mg metoprolol controlled and extended release or placebo administered from the day before surgery to a maximum of eight perioperative days . Main outcome measures The composite primary outcome measure was time to all cause mortality , acute myocardial infa rct ion , unstable angina , or congestive heart failure . Secondary outcome measures were time to all cause mortality , cardiac mortality , and non-fatal cardiac morbidity . Results Mean duration of intervention was 4.6 days in the metoprolol group and 4.9 days in the placebo group . Metoprolol significantly reduced the mean heart rate by 11 % ( 95 % confidence interval 9 % to 13 % ) and mean blood pressure by 3 % ( 1 % to 5 % ) . The primary outcome occurred in 99 of 462 patients in the metoprolol group ( 21 % ) and 93 of 459 patients in the placebo group ( 20 % ) ( hazard ratio 1.06 , 0.80 to 1.41 ) during a median follow-up of 18 months ( range 6 - 30 ) . All cause mortality was 16 % ( 74/462 ) in the metoprolol group and 16 % ( 72/459 ) in the placebo group ( 1.03 , 0.74 to 1.42 ) . The difference in risk for the proportion of patients with serious adverse events was 2.4 % ( − 0.8 % to 5.6 % ) . Conclusions Perioperative metoprolol did not significantly affect mortality and cardiac morbidity in these patients with diabetes . Confidence intervals , however , were wide , and the issue needs re assessment . Trial registration Current Controlled Trials IS RCT N58485613 [ controlled-trials.com BACKGROUND Patients undergoing vascular surgery comprise the highest risk group for perioperative cardiac mortality and morbidity after noncardiac procedures . Many current guidelines recommend the use of beta-blockers in all patients undergoing vascular surgery . We report a trial of the perioperative administration of metoprolol and its effects on the incidence of cardiac complications at 30 days and 6 months after vascular surgery . METHODS Patients undergoing abdominal aortic surgery and infrainguinal or axillofemoral revascularizations were recruited to a double-blind r and omized controlled trial of perioperative metoprolol versus placebo . Patients were r and omized to receive study medication , starting 2 hours preoperatively until hospital discharge or maximum of 5 days postoperatively . Primary outcome were postoperative 30-day composite incidence of nonfatal myocardial infa rct ion , unstable angina , new congestive heart failure , new atrial or ventricular dysrhythmia requiring treatment , or cardiac death . RESULTS Patients were r and omized to receive either metoprolol ( n = 246 ) or placebo ( n = 250 ) . Primary outcome events at 30 days postoperative occurred in 25 ( 10.2 % ) versus 30 ( 12.0 % ) ( P = .57 ) in metoprolol and placebo groups , respectively ( relative risk reduction 15.3 % , 95 % CI -38.3 % to 48.2 % ) . Observed effects at 6 months were not significantly different ( P = .81 ) ( relative risk reduction 6.2 % , 95 % CI% -58.4 % to 43.8 % ) . Intraoperative bradycardia requiring treatment was more frequent in the metoprolol group ( 53/246 vs 19/250 , P = .00001 ) , as was intraoperative hypotension requiring treatment ( 114/246 vs 84/250 , P = .0045 ) . CONCLUSION Our results showed metoprolol was not effective in reducing the 30-day and 6-month postoperative cardiac event rates . Prophylactic use of perioperative beta-blockers in all vascular patients is not indicated BACKGROUND Noncardiac surgery is associated with significant cardiovascular mortality , morbidity , and cost . Small trials of beta-blockers suggest that they may prevent cardiovascular events in patients undergoing noncardiac surgery , but trial results are inconclusive . We have initiated the POISE trial to definitively establish the effects of beta-blocker therapy in patients undergoing noncardiac surgery . METHODS The POISE trial is a blinded , r and omized , and controlled trial of controlled-release metoprolol versus placebo in 10000 patients at risk for a perioperative cardiovascular event who are undergoing noncardiac surgery . Patients will receive the study drug 2 to 4 hours before surgery and subsequently for 30 days . The primary outcome is a composite of cardiovascular death , nonfatal myocardial infa rct ion , and nonfatal cardiac arrest at 30 days . Patients will also be followed for events at 1 year . RESULTS To date , the POISE trial has recruited > 6300 patients in 182 centers in 21 countries . Currently , the patients ' mean age is 69 years ; 63 % are males , 43 % have a history of coronary artery disease , 43 % have a history of peripheral arterial disease , and 30 % have diabetes . Most participants have undergone vascular ( 42 % ) , intraabdominal ( 23 % ) , or orthopedic ( 19 % ) surgery . CONCLUSIONS The POISE trial is a large international trial that will provide a reliable assessment of the effects of beta-blocker therapy in patients undergoing noncardiac surgery In a non-double-blind , prospect i ve , r and omized study , the intraoperative electrocardiograms of 128 mildly hypertensive surgical patients were examined in order to determine the incidence of myocardial ischemia during anesthesia . No patient had been receiving chronic antihypertensive therapy prior to the study , but a single small oral dose of a beat-adrenergic blocking agent ( labetalol , atenolol , or oxprenolol ) was given to 89 of them along with premedication-Forty-four per cent of the untreated control patients and 61 % of the patients pretreated with a beat-adrenergic blocking agent had normal preoperative electroca rdiograms and no risk factors for coronary artery disease other than hypertension ( this difference between groups was not statistically significant ) . During tracheal intubation and /or emergence from anesthesia , a brief , self-limited episode of myocardial ischemia was detected in 11 of 39 untreated control patients , and in two of 89 patients pretreated with a betaadrenergic blocking agent ( P < 0.001 ) . Tachycardia always accompanied the ischemic events , but a conspicuous increase in blood pressure did not . The authors conclude that mild hypertension , when untereated prior to the induction of anesthesia , is associated with a high incidence of myocardial ischemia ; and that a single small oral dose of a beat-adrenergic blocking agent , given with premedication , can significantly reduce that risk Renal artery stenosis ( RAS ) is a progressive disease and may lead to chronic kidney disease by deterioration of renal functions . Endothelial dysfunction is an important causative factor for kidney damage after RAS revascularization . Nebivolol , a new generation beta blocker induces endothelium-related arterial relaxation by nitric oxide ( NO ) and may improve endothelial dysfunction . This pilot study tested the effect of nebivolol on the glomerular filtration rate ( GFR ) in a series of 33 patients with severe RAS ( > 70 % ) who underwent revascularization . After revascularization , nebivolol was added to antihypertensive treatment in 17 r and omly selected patients while 16 patients ( control group ) continued their st and ard treatment . Estimated glomerular filtration rate ( eGFR ) , proteinuria as well as nitrite and nitrate levels were measured at baseline and 6 months after the revascularization procedure . Six months after revascularization , eGFR increased from 44.8 to 50.6 ml/min in the nebivolol group . In contrast , eGFR did not change in the control group . Nitrite/nitrate levels decreased to a significant extent both in the nebivolol and in the control group . Proteinuria decreased more in the nebivolol group compared to the control group . These pilot data support a full-fledged clinical trial , testing whether nebivolol may be beneficial in the post-revascularization phase in patients with RAS BACKGROUND Perioperative myocardial ischemia is the single most important potentially reversible risk factor for mortality and cardiovascular complications after noncardiac surgery . Although more than 1 million patients have such complications annually , there is no effective preventive therapy . METHODS We performed a r and omized , double-blind , placebo-controlled trial to compare the effect of atenolol with that of a placebo on overall survival and cardiovascular morbidity in patients with or at risk for coronary artery disease who were undergoing noncardiac surgery . Atenolol was given intravenously before and immediately after surgery and orally thereafter for the duration of hospitalization . Patients were followed over the subsequent two years . RESULTS A total of 200 patients were enrolled . Ninety-nine were assigned to the atenolol group , and 101 to the placebo group . One hundred ninety-four patients survived to be discharged from the hospital , and 192 of these were followed for two years . Overall mortality after discharge from the hospital was significantly lower among the atenolol-treated patients than among those who were given placebo over the six months following hospital discharge ( 0 vs. 8 percent , P<0.001 ) , over the first year ( 3 percent vs. 14 percent , P=0.005 ) , and over two years ( 10 percent vs. 21 percent , P=0.019 ) . The principal effect was a reduction in deaths from cardiac causes during the first six to eight months . Combined cardiovascular outcomes were similarly reduced among the atenolol-treated patients ; event-free survival throughout the two-year study period was 68 percent in the placebo group and 83 percent in the atenolol group ( P=0.008 ) . CONCLUSIONS In patients who have or are at risk for coronary artery disease who must undergo noncardiac surgery , treatment with atenolol during hospitalization can reduce mortality and the incidence of cardiovascular complications for as long as two years after surgery beta Blockers are widely used to improve the postoperative cardiac outcome in patients with coronary artery disease scheduled for noncardiac surgery . However , recently serious concerns regarding the safety of perioperative beta blockers have emerged . To assess the incidence , risk factors , and beta-blocker use associated with postoperative stroke in the Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography ( DECREASE ) trials , we evaluated all 3,884 patients of the DECREASE trials for postoperative stroke . All cardiac risk factors and medication use were assessed . The incidence of stroke within 30 days after surgery was recorded . The incidence of postoperative stroke in the DECREASE trials was 0.46 % ( 18 of 3,884 ) . For the beta-blocker users , the incidence was 0.5 % . All the strokes had an ischemic origin . A history of stroke was associated with a greater incidence of postoperative stroke ( odds ratio [ OR ] 3.79 , 95 % confidence interval [ CI ] 1.2 to 11.6 ) . Statins and anticoagulants were not associated with postoperative stroke ( OR 0.85 , 95 % CI 0.3 to 2.4 ; and OR 1.27 , 95 % CI 0.4 to 4.6 , respectively ) . No association with bisoprolol therapy was found ( OR 1.16 , 95 % CI 0.4 to 3.4 ) . In conclusion , with a low-dose bisoprolol regimen started > or = 30 days before surgery , no association was observed between beta-blocker use and postoperative stroke BACKGROUND Recent trials suggest that perioperative beta-blockade reduces the risk of cardiac events in patients with a risk of myocardial ischemia who are undergoing noncardiac surgery . Patients with diabetes mellitus are at a high-risk for postoperative cardiac morbidity and mortality . They may , therefore , benefit from perioperative beta-blockade . METHODS The Diabetic Postoperative Mortality and Morbidity ( DIPOM ) trial is an investigator-initiated and -controlled , central ly r and omized , double-blind , placebo-controlled , multicenter trial . We compared the effect of metoprolol with placebo on mortality and cardiovascular morbidity rates in patients with diabetes mellitus who were beta-blocker naive , > or=40 years old , and undergoing noncardiac surgery . The study drug was given during hospitalization for a maximum of 7 days beginning the evening before surgery . The primary outcome measure is the composite of all-cause mortality , acute myocardial infa rct ion , unstable angina , or congestive heart failure leading to hospitalization or discovered or aggravated during hospitalization . Follow-up involves re-examination of patients at 6 months and collection of mortality and morbidity data via linkage to public data bases . The study was powered on the basis of an estimated 30 % 1-year event rate in the placebo arm and a 33 % relative risk reduction in the metoprolol arm . The median follow-up period was 18 months . RESULTS Enrollment started in July 2000 and ended in June 2002 . A total of 921 patients were r and omized , and 54 % of these patients had known cardiac disease , hypertension , or both . CONCLUSION The results of this study may have implication s for reduction of perioperative and postoperative risk in patients with diabetes mellitus who are undergoing major noncardiac surgery BACKGROUND Cardiovascular complications are the most important causes of perioperative morbidity and mortality among patients undergoing major vascular surgery . METHODS We performed a r and omized , multicenter trial to assess the effect of perioperative blockade of beta-adrenergic receptors on the incidence of death from cardiac causes and nonfatal myocardial infa rct ion within 30 days after major vascular surgery in patients at high risk for these events . High-risk patients were identified by the presence of both clinical risk factors and positive results on dobutamine echocardiography . Eligible patients were r and omly assigned to receive st and ard perioperative care or st and ard care plus perioperative beta-blockade with bisoprolol . RESULTS A total of 1351 patients were screened , and 846 were found to have one or more cardiac risk factors . Of these 846 patients , 173 had positive results on dobutamine echocardiography . Fifty-nine patients were r and omly assigned to receive bisoprolol , and 53 to receive st and ard care . Fifty-three patients were excluded from r and omization because they were already taking a beta-blocker , and eight were excluded because they had extensive wall-motion abnormalities either at rest or during stress testing . Two patients in the bisoprolol group died of cardiac causes ( 3.4 percent ) , as compared with nine patients in the st and ard-care group ( 17 percent , P=0.02 ) . Nonfatal myocardial infa rct ion occurred in nine patients given st and ard care only ( 17 percent ) and in none of those given st and ard care plus bisoprolol ( P<0.001 ) . Thus , the primary study end point of death from cardiac causes or nonfatal myocardial infa rct ion occurred in 2 patients in the bisoprolol group ( 3.4 percent ) and 18 patients in the st and ard-care group ( 34 percent , P<0.001 ) . CONCLUSIONS Bisoprolol reduces the perioperative incidence of death from cardiac causes and nonfatal myocardial infa rct ion in high-risk patients who are undergoing major vascular surgery BACKGROUND : In this post hoc sub analysis of the Perioperative Ischemic Evaluation ( POISE ) trial , we sought to determine whether nitrous oxide was associated with the primary composite outcome of cardiovascular death , nonfatal myocardial infa rct ion ( MI ) , and nonfatal cardiac arrest within 30 days of r and omization . METHODS : The POISE trial of perioperative & bgr;-blockade was undertaken in 8351 patients . Nitrous oxide anesthesia was defined as the coadministration of nitrous oxide in patients receiving general anesthesia , with or without additional neuraxial blockade or peripheral nerve blockade . Logistic regression , with inverse probability weighting using estimated propensity scores , was used to determine the association of nitrous oxide with the primary outcome , MI , stroke , death , and clinical ly significant hypotension . RESULTS : Nitrous oxide was administered to 1489 ( 29 % ) of the 5133 patients included in this analysis . Nitrous oxide had no significant effect on the risk of the primary outcome ( 112 [ 7.5 % ] vs 248 [ 6.9 % ] ; odds ratio [ OR ] , 1.08 ; 95 % confidence interval [ CI ] , 0.82–1.44 ; 99 % CI , 0.75–1.57 ; P = 0.58 ) , MI ( 89 [ 6.0 ] vs 204 [ 5.6 ] ; OR , 0.99 ; 95 % CI , 0.75–1.31 ; 99 % CI , 0.69–1.42 ; P = 0.94 ) , stroke ( 6 [ 0.4 % ] vs 28 [ 0.8 % ] ; OR , 0.85 ; 95 % CI , 0.26–2.82 ; 99 % CI , 0.17–4.11 ; P = 0.79 ) , death ( 40 [ 2.7 % ] vs 100 [ 2.8 % ] ; OR , 1.04 ; 95 % CI , 0.6–1.81 ; 99 % CI , 0.51–2.15 ; P = 0.88 ) or clinical ly significant hypotension ( 219 [ 14.7 % ] vs 544 [ 15.0 % ] ; OR , 0.92 ; 95 % CI , 0.74–1.15 ; 99 % CI , 0.70–1.23 ; P = 0.48 ) . CONCLUSIONS : In this post hoc sub analysis , nitrous oxide was not associated with an increased risk of adverse outcomes in the POISE trial patients . This analysis was limited by the observational nature of the data and the lack of information on the concentration and duration of nitrous oxide administration . Further r and omized controlled trial evidence is required BACKGROUND Each year , millions of patients worldwide have a perioperative myocardial infa rct ion ( MI ) after noncardiac surgery . OBJECTIVE To examine the characteristics and short-term outcome of perioperative MI . DESIGN Cohort study . ( Clinical Trials.gov registration number : NCT00182039 ) SETTING 190 centers in 23 countries . PATIENTS 8351 patients included in the POISE ( PeriOperative ISchemic Evaluation ) trial . MEASUREMENTS Four cardiac biomarker or enzyme assays were measured within 3 days of surgery . The definition of perioperative MI included either autopsy findings of acute MI or an elevated level of a cardiac biomarker or enzyme and at least 1 of the following defining features : ischemic symptoms , development of pathologic Q waves , ischemic changes on electrocardiography , coronary artery intervention , or cardiac imaging evidence of MI . RESULTS Within 30 days of r and om assignment , 415 patients ( 5.0 % ) had a perioperative MI . Most MIs ( 74.1 % ) occurred within 48 hours of surgery ; 65.3 % of patients did not experience ischemic symptoms . The 30-day mortality rate was 11.6 % ( 48 of 415 patients ) among patients who had a perioperative MI and 2.2 % ( 178 of 7936 patients ) among those who did not ( P < 0.001 ) . Among patients with a perioperative MI , mortality rates were elevated and similar between those with ( 9.7 % ; adjusted odds ratio , 4.76 [ 95 % CI , 2.68 to 8.43 ] ) and without ( 12.5 % ; adjusted odds ratio , 4.00 [ CI , 2.65 to 6.06 ] ) ischemic symptoms . LIMITATION Cardiac markers were measured only until day 3 after surgery , and additional asymptomatic MIs may have been missed . CONCLUSION Most patients with a perioperative MI will not experience ischemic symptoms . Data suggest that routine monitoring of troponin levels in at-risk patients is needed after surgery to detect most MIs , which have an equally poor prognosis regardless of whether they are symptomatic or asymptomatic |
10,408 | 17,687,245 | The results of this review provide strong evidence that universal school-based programs decrease rates of violence and aggressive behavior among school-aged children .
Program effects were demonstrated at all grade levels . | Universal school-based programs to reduce or prevent violent behavior are delivered to all children in classrooms in a grade or in a school .
Similarly , programs targeted to schools in high-risk areas ( defined by low socioeconomic status or high crime rates ) are delivered to all children in a grade or school in those high-risk areas . | A population -based r and omized intervention trial for the prevention of conduct problems ( i.e. , oppositional defiant disorder and conduct disorder ) is described . The LIFT ( Linking the Interests of Families and Teachers ) intervention was design ed for all first- and fifth- grade elementary school boys and girls and their families living in at-risk neighborhoods characterized by high rates of juvenile delinquency . The 10-week intervention strategy was carefully targeted at proximal and malleable antecedents in three social domains that were identified by a developmental model of conduct problems . From 12 elementary schools , 671 first and fifth grade rs and their families participated either in the theory-based universal preventive intervention or in a control condition . The intervention consisted of parent training , a classroom-based social skills program , a playground behavioral program , and systematic communication between teachers and parents . A multiple measure assessment strategy was used to evaluate participant satisfaction and participation , fidelity of implementation , and the immediate impacts of the program on targeted antecedents PURPOSE To examine whether participation in a school-sponsored community youth service program reduces self-reported violent behaviors among young urban adolescents . METHODS A total of 972 seventh- and eighth- grade students at two large , urban , public middle schools were surveyed at baseline and at 6-month follow-up . One school was assigned to interventions and the other served as a control . All students at the intervention school received the Reach for Health classroom curriculum that included a 10-lesson unit focusing on violence prevention . In addition , approximately half the students were r and omly assigned by classroom to participate in the Reach for Health Community Youth Service program ( CYS ) . Under the guidance of teachers and community nurses , these students spent several hours each week providing service in local health care agencies . Regression analyses were used to assess the influence of treatment condition on violent behavior outcomes . RESULTS Comparing students in the curriculum-only and curriculum-plus-CYS interventions to the control group , there is a statistically significant interaction ( p < .03 ) among grade , CYS participation , and violence at follow-up . Eighth- grade CYS students reported significantly less violence at follow-up than students in the control school , taking into account baseline level of risk behavior , gender , ethnicity , and social desirability ( p < .04 ) . There was no significant difference between controls and students in the curriculum-only condition . Comparing students in the CYS intervention to the curriculum-only condition within the intervention school , the grade by intervention interaction again is significant ( p < .05 ) . Eighth- grade CYS students-who received the broadest CYS experience-reported less violence at follow-up than their curriculum-only counterparts . CONCLUSION When delivered with sufficient intensity , school programs which couple community service with classroom health instruction can have a measurable impact on violent behaviors of a population of young adolescents at high risk for being both the perpetrators and victims of peer violence . Community service programs may be an effective supplement to curricular interventions and a valuable part of multicomponent violence prevention programs PURPOSE To evaluate the effect of a violence prevention curriculum and of trained peer leaders on self-reported aggressive behaviors , knowledge about violence and conflict-resolution skills , self-efficacy , and attitudes among 223 6th grade rs . METHODS The effect of two intervention groups ( violence prevention curriculum taught by the teacher with or without the assistance of trained peer leaders ) and one control group were compared . Ten 6th grade classes ( four control and six intervention classes ) of four middle schools participated in the study . Students were evaluated before and shortly after the implementation of the curriculum , as well as 3 months later . RESULTS The intervention reduced self-reported aggressive behaviors among boys , but this reduction was significant only in two of the six intervention classes . Both interventions had an overall significant effect on increasing knowledge about violence and skills to reduce violence . After the intervention , students also developed a more negative attitude toward responding violently when provoked . Attitude change was stronger among students from the teacher plus peer leader group . No intervention effect was observed on self-efficacy nor on attitudes toward skills to reduce violence . Changes were not maintained over time . CONCLUSIONS Results emphasize the need for continuous and comprehensive interventions , follow-up evaluations , and careful selection of peer leaders . Aggressive behaviors , not knowledge alone , should be used as the main dependent variable OBJECTIVE To examine the long-term effects of an intervention combining teacher training , parent education , and social competence training for children during the elementary grade s on adolescent health-risk behaviors at age 18 years . DESIGN Nonr and omized controlled trial with follow-up 6 years after intervention . SETTING Public elementary schools serving high-crime areas in Seattle , Wash. PARTICIPANTS Of the fifth- grade students enrolled in participating schools , 643 ( 76 % ) were given written parental consent for the longitudinal study and 598 ( 93 % ) were followed up and interviewed at age 18 years . INTERVENTIONS A full intervention provided in grade s 1 through 6 of 5 days of in-service training for teachers each intervention year , developmentally appropriate parenting classes offered to parents when children were in grade s 1 through 3 and 5 through 6 , and developmentally adjusted social competence training for children in grade s 1 and 6 . A late intervention , provided in grade s 5 and 6 only , paralleled the full intervention at these grade s. MAIN OUTCOME MEASURES Self-reported violent and nonviolent crime , substance use , sexual activity , pregnancy , bonding to school , school achievement , grade repetition and school dropout , suspension and /or expulsion , and school misbehavior ; delinquency charges from court records ; grade point average ; California Achievement Test scores : and disciplinary action reports from school records . RESULTS Fewer students receiving full intervention than control students reported violent delinquent acts ( 48.3 % vs 59.7 % ; P=.04 ) , heavy drinking ( 15.4 % vs 25.6 % ; P=.04 ) , sexual intercourse ( 72.1 % vs 83.0 % ; P=.02 ) , having multiple sex partners ( 49.7 % vs 61.5 % ; P=.04 ) , and pregnancy or causing pregnancy ( 17.1 % vs 26.4 % ; P=.06 ) by age 18 years . The full intervention student group reported more commitment ( P=.03 ) and attachment ( P=.006 ) to school , better academic achievement ( P=.01 ) , and less school misbehavior ( P=.02 ) than control students . Late intervention in grade s 5 and 6 only did not significantly affect health-risk behaviors in adolescence . CONCLUSIONS A package of interventions with teachers , parents , and children provided throughout the elementary grade s can have enduring effects in reducing violent behavior , heavy drinking , and sexual intercourse by age 18 years among multiethnic urban children . Results are consistent with the theoretical model guiding the intervention and support efforts to reduce health-risk behaviors through universal interventions in selected communities or schools serving high-crime neighborhoods OBJECTIVE To test the efficacy of 2 programs design ed to reduce high-risk behaviors among inner-city African American youth . DESIGN Cluster r and omized trial . SETTING Twelve metropolitan Chicago , Ill , schools and the communities they serve , 1994 through 1998 . PARTICIPANTS Students in grade s 5 through 8 and their parents and teachers . INTERVENTIONS The social development curriculum ( SDC ) consisted of 16 to 21 lessons per year focusing on social competence skills necessary to manage situations in which high-risk behaviors occur . The school/community intervention ( SCI ) consisted of SDC and school-wide climate and parent and community components . The control group received an attention-placebo health enhancement curriculum ( HEC ) of equal intensity to the SDC focusing on nutrition , physical activity , and general health care . MAIN OUTCOME MEASURES Student self-reports of violence , provocative behavior , school delinquency , substance use , and sexual behaviors ( intercourse and condom use ) . RESULTS For boys , the SDC and SCI significantly reduced the rate of increase in violent behavior ( by 35 % and 47 % compared with HEC , respectively ) , provoking behavior ( 41 % and 59 % ) , school delinquency ( 31 % and 66 % ) , drug use ( 32 % and 34 % ) , and recent sexual intercourse ( 44 % and 65 % ) , and improved the rate of increase in condom use ( 95 % and 165 % ) . The SCI was significantly more effective than the SDC for a combined behavioral measure ( 79 % improvement vs 51 % ) . There were no significant effects for girls . CONCLUSIONS Theoretically derived social-emotional programs that are culturally sensitive , developmentally appropriate , and offered in multiple grade s can reduce multiple risk behaviors for inner-city African American boys in grade s 5 through 8 . The lack of effects for girls deserves further research This study evaluated the effect of Students for Peace , a multi-component violence-prevention intervention , on reducing aggressive behaviors among students of eight middle schools r and omly assigned into intervention or control conditions . The intervention , based on Social Cognitive Theory , included the formation of a School Health Promotion Council , training of peer mediators and peer helpers , training of teachers in conflict resolution , a violence-prevention curriculum , and newsletters for parents . All students were evaluated in the spring of 1994 , 1995 and 1996 ( approximately 9000 students per evaluation ) . Sixth grade rs in 1994 were followed through seventh grade in 1995 or eighth grade in 1996 or both ( n = 2246 ) . Cohort and cross-sectional evaluations indicated little to no intervention effect in reducing aggressive behaviors , fights at school , injuries due to fighting , missing classes because of feeling unsafe at school or being threatened to be hurt . For all variables , the strongest predictors of violence in eighth grade were violence in sixth grade and low academic performance . Although ideal and frequently recommended , the holistic approach to prevention in schools in which teachers , administrators and staff model peaceful conflict resolution is difficult to implement , and , in this case , proved ineffective . The Students for Peace experience suggests that interventions begin prior to middle school , explore social environmental intervention strategies , and involve parents and community members OBJECTIVE To compare the effectiveness of the Violence Prevention Curriculum for Adolescents to the Conflict Resolution : A Curriculum for Youth Providers among middle school students . METHODS A sample ( N = 225 ) of adolescents ( males = 48 % ) representing 20 % of the student population in two middle schools were administered a pretest question naire . Of these students , 89 % were African-American , 10 % were white , and 1 % were Native-American and lived in public housing ( 40 % ) or in neighborhoods adjacent to public housing ( 60 % ) . Each school was r and omly assigned to one of the curricula . Each curriculum was administered during 10 50-min sessions held twice a week over 5 weeks . One week later , 209 students who completed the 10 sessions were tested with the same question naire . The data were analyzed with a repeated- measures analysis of variance . RESULTS Students who received either curriculum reported significant decreases in their self-reported use of violence in hypothetical conflict situations , frequency of use of violence in the previous 30 days , and frequency of physical fights in the previous 30 days . The conflict resolution curriculum was more effective in reducing the frequency of fights result ing in an injury requiring medical treatment in the previous 30 days . CONCLUSIONS Both curricula were successful in reducing three indicators of violence . However , the conflict resolution approach was more successful in reducing the frequency of more severe physical fights requiring medical treatment . The latter finding is of particular importance , because that physical fighting is the form of violence behavior in which young adolescents most often engage Students for Peace is a three-year project ( October 1993- September 1996 ) design ed to evaluate a comprehensive , school-based intervention that seeks to prevent violence among sixth- , seventh- , and eighth- grade students in a large urban school district in Texas . This study examines the hypothesis that students exposed to a two-year multiple-component intervention will reduce aggressive behavior compared to students who receive the district 's " usual care " of violence prevention activities . Students for Peace is based largely on Social Learning . Theory ( SLT ) , which addresses both the psychosocial dynamics underlying health behavior and the methods of promoting behavior change , while emphasizing cognitive processes and their effect on behavior . SLT explains human behavior in terms of a model in which three factors-behavior , social-environmental influences , and personal factors ( such as personality , perceptions and expectations , and affect)-all interact . Theoretically , an individual 's behavior is uniquely determined by a combination of these factors ; thus , these factors become the elements for intervention strategies . The intervention program includes four main components : ( 1 ) modification of the school environment , ( 2 ) a violence-prevention curriculum , ( 3 ) peer leadership , and ( 4 ) parent education . Students for Peace is using a nested cross-sectional and cohort design in which school is the unit of design , allocation , and analysis . Eight schools , four intervention and four control , are participating . In May 1994 , a question naire was administered to all students in school the day of the survey . A posttest evaluation was taken in the spring of 1995 and will be followed by a final posttest in spring 1996 . A total of 8,865 students responded to the baseline survey . Nearly all variables indicated comparability between treatment and control conditions . As a population , Students for Peace participants are largely Hispanic ( 65 % ) or African American ( 19 % ) . Violence-related variables indicated 30-day fighting prevalence , 23 % ; 12-month prevalence of injuries due to fighting , 14 % ; 30-day h and -gun carrying prevalence , 11 % ; 30-day prevalence of taunts and threats at school , 27 % , and threats going to and from school , 26 % . Overall , the data from Year 1 activities indicate a population in need of violence-prevention intervention . The challenge is to mold existing district re sources into a theoretically sound program of interventions . If that program is found effective , the district will already have the necessary documentation , personnel , and skills for broader dissemination We assessed the immediate effects of two universal , first- grade preventive interventions on the proximal targets of poor achievement , concentration problems , aggression , and shy behaviors , known early risk behaviors for later substance use/abuse , affective disorder , and conduct disorder . The classroom-centered ( CC ) intervention was design ed to reduce these early risk behaviors by enhancing teachers ' behavior management and instructional skills , whereas the family-school partnership ( FSP ) intervention was aim ed at improving parent-teacher communication and parental teaching and child behavior management strategies . Over the course of first and second grade s , the CC intervention yielded the greatest degree of impact on its proximal targets , whereas the FSP 's impact was somewhat less . The effects were influenced by gender and by preintervention levels of risk . Analyses of implementation measures demonstrated that greater fidelity to the intervention protocol s was associated with greater impact on behavior ratings and on achievement scores , thus providing some evidence of specificity in the effect of the interventions PeaceBuilders is a universal , elementary-school-based violence prevention program that attempts to alter the climate of a school by teaching students and staff simple rules and activities aim ed at improving child social competence and reducing aggressive behavior . Eight matched schools ( N > 4,000 students in Grade s K-5 ) were r and omly assigned to either immediate postbaseline intervention ( PBI ) or to a delayed intervention 1 year later ( PBD ) . Hierarchical linear modeling was used to analyze results from assessment s in the fall and spring of 2 consecutive school years . In Year 1 , significant gains in teacher-rated social competence for students in Grade s K-2 , in childself-reported peace-building behavior in Grade s K-5 , and reductions in aggressive behavior in Grade s 3 - 5 were found for PBI but not PBD schools . Differential effects in Year 1 were also observed for aggression and prosocial behavior . Most effects were maintained in Year 2 for PBI schools , including increases in child prosocial behavior in Grade s K-2 . Implication s for early universal school-based prevention and challenges related toevaluating large-scale prevention trials are discussed When the GUIDE TO COMMUNITY PREVENTIVE SERVICES : Systematic Review s and Evidence -Based Recommendations ( the Guide ) is published in 2001 , it will represent a significant national effort in encouraging evidence -based public health practice in defined population s ( e.g. , communities or members of specific managed care plans ) . The Guide will make recommendations regarding public health interventions to reduce illness , disability , premature death , and environmental hazards that impair community health and quality of life . The Guide is being developed under the guidance of the Task Force on Community Preventive Services ( the Task Force)-a 15-member , nonfederal , independent panel of experts . Subject matter experts , method ologists , and scientific staff are supporting the Task Force in using explicit rules to conduct systematic literature review s of evidence of effectiveness , economic efficiency , and feasibility on which to base recommendations for community action . Contributors to the Guide are building on the experience of others to confront method ologic challenges unique to the assessment of complex multicomponent intervention studies with nonexperimental or nonr and omized design s and diverse measures of outcome and effectiveness . Persons who plan , fund , and implement population -based services and policies to improve health at the state and local levels are invited to scrutinize the work in progress and to communicate with contributors . When the Guide is complete , readers are encouraged to consider critically the value and relevance of its contents , the implementation of interventions the Task Force recommends , the ab and onment of interventions the Task Force does not recommend , and the need for rigorous evaluation of the benefits and harms of promising interventions of unknown effectiveness PeaceBuilders is a schoolwide violence-prevention program for elementary schools ( K-5 ) . A coalition of the Pima County Community Services Department , University of Arizona , and Heartsprings , Inc. , ( a Tucson-based company ) are conducting a formal evaluation . Children who grow up to commit acts of violence show cognitive , social , and imitative differences from their peers . These characteristics can be ameliorated , most successfully through interventions that begin at an early age and involve multiple segments of the child 's social experiences and interactions . PeaceBuilders activities are built into the school environment and the daily interactions among students , teachers , and administrative staff , all of whom are taught a common language and provided models of positive behavior , environmental cues to signal such behavior , opportunities to rehearse positive behavior , and rewards for practicing it . Four schools , one from each of four matched pairs , were r and omly assigned to begin PeaceBuilders in Year 1 . The remaining four schools begin in Year 2 . Outcome assessment s include student self-reports , st and ardized teacher reports , playground observations , and school and law enforcement records . Process assessment s include school observations and surveys of teacher practice s and satisfaction . Surveys were completed by 2,736 children . The sample is about 55 % Hispanic , 26 % Anglo , 14 % Native American , and 4 % African American . Among children in grade s 3 - 5 , during the past week 15 % had been sent to the office for disciplinary problems , 13 % tried to start a fight 27 % hit someone , and 12 % reported being threatened with a gun or knife . Violent behaviors and experiences are common among the studied children . A valid evaluation is underway of PeaceBuilders BACKGROUND The positive of the Norwegian anti-bullying programme ( Olweus , 1992 ) stimulated other countries to tackle bully/victim problems . However , outcome studies found rather low levels of effect or even inconsistent results . AIMS The purpose of the present study was to evaluate behavioural effectiveness of a school-based anti-bullying approach within Flemish schools . In addition , specific attention was given to the relationship between outcome findings and external support . SAMPLE A total of 18 schools , comprising 1104 primary and secondary school children were recruited for this study . Students ranged in age from 10 to 16 years . METHOD For this study , an experimental pre-test/post-test design was used which included a control group . Three groups were established . The first group , Treatment with Support , involved students from schools that implemented a school-based anti-bullying intervention with additional support from the research group . The second group , Treatment without Support , also involved students from schools that implemented a school-based anti-bullying programme . However , in contrast with those falling under the first condition , this group of schools could not appeal to the research group for additional help . The last group involved students from schools that did not implement the anti-bullying programme and served as a Control condition . Repeated measures analyses of variance were carried out . RESULTS The findings regarding the effects of the school-based anti-bullying intervention programme on the extent of bullying and victimisation showed a mixed pattern of positive changes in primary schools and zero outcomes in secondary schools . The findings regarding the effects of external support revealed limited outcomes . CONCLUSIONS The outcomes of the evaluation study confirm that a school-based anti-bullying intervention strategy can be effective in reducing problems with bullying , especially within primary schools . It was argued that the developmental characteristics of secondary school students interfered with the programme outcomes . In addition , the findings revealed no extra effects of specific training sessions Evaluated Responding in Peaceful and Positive Ways (RIPP)-a 6th- grade universal violence prevention program . Classes of 6th grade rs at 3 urban middle schools serving predominantly African American youth were r and omized to intervention ( N = 321 ) and control groups ( N = 305 ) . Intervention effects were found on a knowledge test but not on other mediating variables . RIPP participants had fewer disciplinary violations for violent offenses and in-school suspensions at posttest compared with the control group . The reduction in suspensions was maintained at 12-month follow-up for boys but not for girls . RIPP participants also reported more frequent use of peer mediation and reductions in fight-related injuries at posttest . Intervention effects on several measures approached significance at 6-month and 12-month follow-up . The program 's impact on violent behavior was more evident among those with high pretest levels of problem behavior OBJECTIVE To determine if a commonly used violence prevention curriculum , Second Step : A Violence Prevention Curriculum , leads to a reduction in aggressive behavior and an increase in prosocial behavior among elementary school students . DESIGN R and omized controlled trial . SETTING Urban and suburban elementary schools in the state of Washington . PARTICIPANTS Six matched pairs of schools with 790 second- grade and third- grade students . The students were 53 % male and 79 % white . INTERVENTION The curriculum uses 30 specific lessons to teach social skills related to anger management , impulse control , and empathy . MAIN OUTCOME MEASURES Aggressive and prosocial behavior changes were measured 2 weeks and 6 months after participation in the curriculum by parent and teacher reports ( Achenbach Child Behavior Checklist and Teacher Report Form , the School Social Behavior Scale , and the Parent-Child Rating Scale ) and by observation of a r and om sub sample of 588 students in the classroom and playground/cafeteria setting s. RESULTS After adjusting for sex , age , socioeconomic status , race , academic performance , household size , and class size , change scores did not differ significantly between the intervention and control schools for any of the parent-reported or teacher-reported behavior scales . However , the behavior observations did reveal an overall decrease 2 weeks after the curriculum in physical aggression ( P=.03 ) and an increase in neutral/prosocial behavior ( P=.04 ) in the intervention group compared with the control group . Most effects persisted 6 months later . CONCLUSIONS The Second Step violence prevention curriculum appears to lead to a moderate observed decrease in physically aggressive behavior and an increase in neutral and prosocial behavior in school OBJECTIVES An earlier report described desirable 1-month follow-up effects of the Safe Date s program on psychological , physical , and sexual dating violence . Mediators of the program-behavior relationship also were identified . The present report describes the 1-year follow-up effects of the Safe Date s program . METHODS Fourteen schools were in the r and omized experiment . Data were gathered by question naires in schools before program activities and 1 year after the program ended . RESULTS The short-term behavioral effects had disappeared at 1 year , but effects on mediating variables such as dating violence norms , conflict management skills , and awareness of community services for dating violence were maintained . CONCLUSIONS The findings are considered in the context of why program effects might have decayed and the possible role of boosters for effect maintenance OBJECTIVE To evaluate the effectiveness of the Rochester Social Problem Solving Program to reduce emotional and behavioural problems amongst primary school children . METHODOLOGY Children in years 3 and 4 at primary school were assessed prior to receiving the program , immediately after the program and 1 year after the program . At each assessment , the functioning of the children who received the program was compared to the functioning of children enrolled in years 3 and 4 at a comparable school who did not receive the program . RESULTS The program improved the ability of children to cope with potentially difficult social situations . However , the program did not reduce the prevalence of teacher-reported or mother-reported childhood emotional and behavioural problems . CONCLUSIONS School-based social skills programs may be more effective in reducing childhood emotional and behavioural problems if they include components which focus specifically on childhood behaviour problems as well as components focusing on social skills and peer relationships |
10,409 | 29,868,815 | You 'd think taking the Fosamax would be easy because you only take it once a week .
I would usually take it on Sundays but then I could n't lie down or eat or anything for 45 minutes , so I 'm thinking , Oh gee , I could go back to bed , but I did n't .
So , it was easy enough to take , and it did n't bother me .
I did n't have any reactions or side effects .
I stopped taking it in 2014 , but I continued with the vitamin D and the calcium .
What I understood about this most recent bone density in 2017 was that it was a little more serious than I thought .
I do n't knowprobably because I 'm getting older and I 'm starting to think about these things .
I 'd have to hear my options before I could make any decisions about how to treat itI mean , if I had to take medication again I certainly would .
I do n't know what other options there are , probably exercise more .
Moderate- quality evidence showed that women treated with antiresportive agents and the anabolic agent teriparatide had reduced fractures , even if BMD did not increase or if it decreased .
This suggests that large changes in BMD are often due to r and om error rather than true change .
Thus , it is unclear that monitoring BMD while taking an osteoporosis medication improves outcomes .
Consequently , yearly monitoring of BMD may not improve adherence . | Current medications include doxycycline , lisinopril , calcium , and vitamin D. She has never received prednisone .
Another question I have is how severe is my osteoporosis ?
I do n't want to fall and break my hip , and I do n't know how much more my bones are going to deteriorate .
Context , Evidence , and Guidelines Osteoporosis is a skeletal disorder characterized by compromised bone strength that increases risk for fracture ( 2 ) .
Approximately 10 million men and women in the United States have osteoporosis ( 3 ) , whereas more than 2 million osteoporosis-related fractures occur annually ( 4 ) .
Historically , osteoporosis has been diagnosed when a dual-energy x-ray absorptiometry ( DXA ) T-score is less than 2.5 .
This score is defined as the SD of an individual 's bone mineral density ( BMD ) from the mean value for healthy young white women ( 5 ) .
In 2016 , the American Association of Clinical Endocrinologists ( AACE ) issued Clinical Practice Guideline for the Diagnosis and Treatment of Postmenopausal Osteoporosis ( 6 ) .
Treatment Options for Osteoporosis * The guidelines disagree on how long patients with osteoporosis should be treated and what monitoring should be done , if any , during and after the treatment period .
Clinical Questions To structure a debate between our discussants , we agreed on the following key questions to consider when applying these guidelines to clinical practice and to Ms. L in particular : 1.Would you monitor a patient with osteoporosis who is receiving a 5-year course of alendronate ?
If so , how ?
2.Would you monitor a patient who has completed a 5-year course of alendronate ?
If so , how ?
3.When and how would you treat a patient whose bone density decreases during or after a 5-year course of alendronate ?
Discussion Sarah Berry , MD Question 1 : Would you monitor a patient with osteoporosis who is receiving a 5-year course of alendronate ?
If so , how ?
First , even though DXA BMD measurement is the gold st and ard for diagnosing osteoporosis , it tends to be imprecise .
Operator skill largely determines precision at the spine , whereas the patient 's anatomy determines precision at the hip ( 9 ) .
Further , interviews suggest that the most common reasons for nonadherence are related to the false perception that fractures can not be prevented or to concerns about side effects ( 15 ) . | IMPORTANCE Discontinuation of bisphosphonate therapy after 3 to 5 years is increasingly considered , but methods to monitor fracture risk after discontinuation have not been established . OBJECTIVE To test methods of predicting fracture risk among women who have discontinued alendronate therapy after 4 to 5 years . DESIGN , SETTING , AND PARTICIPANTS The prospect i ve Fracture Intervention Trial Long-term Extension ( FLEX ) study r and omized postmenopausal women aged 61 to 86 years previously treated with 4 to 5 years of alendronate therapy to 5 more years of alendronate or placebo from 1998 through 2003 ; the present analysis includes only the placebo group . Hip and spine dual-energy x-ray absorptiometry ( DXA ) were measured when placebo was begun ( FLEX baseline ) and after 1 to 3 years of follow-up . Two biochemical markers of bone turnover , urinary type 1 collagen cross-linked N-telopeptide ( NTX ) and serum bone-specific alkaline phosphatase ( BAP ) , were measured at FLEX baseline and after 1 and 3 years . MAIN OUTCOMES AND MEASURES Symptomatic spine and nonspine fractures occurring after the follow-up measurement of DXA or bone turnover . RESULTS During 5 years of placebo , 94 of 437 women ( 22 % ) experienced 1 or more symptomatic fractures ; 82 had fractures after 1 year . One-year changes in hip DXA , NTX , and BAP were not related to subsequent fracture risk , but older age and lower hip DXA at time of discontinuation were significantly related to increased fracture risk ( lowest tertile of baseline femoral neck DXA vs other 2 tertiles relative hazard ratio , 2.17 [ 95 % CI , 1.38 - 3.41 ] ; total hip DXA relative hazard ratio , 1.87 [ 95 % CI , 1.20 - 2.92 ] ) . CONCLUSIONS AND RELEVANCE Among postmenopausal women who discontinue alendronate therapy after 4 to 5 years , age and hip BMD at discontinuation predict clinical fractures during the subsequent 5 years . Follow-up measurements of DXA 1 year after discontinuation and of BAP or NTX 1 to 2 years after discontinuation are not associated with fracture risk and can not be recommended . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00398931 ABBREVIATIONS AACE = American Association of Clinical Endocrinologists AFF = atypical femur fracture ASBMR = American Society for Bone and Mineral Research BEL = best evidence level BMD = bone mineral density BTM = bone turnover marker CBC = complete blood count CI = confidence interval DXA = dual-energy X-ray absorptiometry EL = evidence level FDA = U.S. Food and Drug Administration FLEX = Fracture Intervention Trial ( FIT ) Long-term Extension FRAX ® = Fracture Risk Assessment Tool GFR = glomerular filtration rate GI = gastrointestinal HORIZON = Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly IOF = International Osteoporosis Foundation ISCD = International Society for Clinical Densitometry IU = international units IV = intravenous LSC = least significant change NBHA = National Bone Health Alliance NOF = National Osteoporosis Foundation 25(OH)D = 25-hydroxy vitamin D ONJ = osteonecrosis of the jaw PINP = serum carboxy-terminal propeptide of type I collagen PTH = parathyroid hormone R = recommendation RANK = receptor activator of nuclear factor kappa-B RANKL = receptor activator of nuclear factor kappa-B lig and RCT = r and omized controlled trial RR = relative risk S-CTX = serum C-terminal telopeptide SQ = subcutaneous VFA = vertebral fracture assessment WHO = World Health Organization Osteoporosis-related fractures are common and impose a large societal burden in terms of human and economic costs ( 1 ) . In the absence of a typical low-trauma fracture ( for example , vertebral compression fracture ) ( 2 ) , the diagnosis of osteoporosis is usually based on finding low bone mineral density ( BMD ) from dual-energy x-ray absorptiometry ( DXA ) ( 3 , 4 ) . Screening with DXA is recommended for women aged 65 years or older and in younger women with elevated fracture risk ( 5 ) . In appropriately selected women , approved treatments can reduce fracture risk in primary and secondary prevention setting s ( 6 , 7 ) . The role for repeated BMD testing after initial evaluation is uncertain because prospect i ve studies have not shown that repeated BMD measurements or changes in BMD were more predictive of subsequent fractures than the baseline measurement ( 5 , 8) . The practice of repeated BMD testing during pharmacotherapy also remains controversial ( 9 , 10 ) . Group-level clinical trial data suggest that greater increases in BMD are associated with greater fracture risk reduction ( 11 , 12 ) , but this may be more difficult to show in individuals as measurement error is typically 3 % to 5 % ( 1315 ) . In clinical trials in which good patients are selected for participation and their adherence is closely monitored , treatment failuredefined as detectable BMD lossis uncommon , particularly when the patients are receiving bisphosphonates , which is the most widely used class of drugs for osteoporosis ( 16 ) . Results from clinical trials are not always applicable to clinical practice in which patients are lost to follow-up , adherence and persistence with medications are difficult to monitor , and patients often have underlying conditions that would exclude many from trial participation . We used population -based registries from Manitoba , Canada , to assess the effectiveness of repeated BMD testing in routine clinical practice as a predictor of treatment-related fracture risk reduction in women initiating treatment . Methods Patient Population In Manitoba , Canada ( population , 1.2 million persons ) , health services are provided to virtually all residents through a public health care system . Since 1997 , DXA testing has been managed as an integrated program ( the Manitoba Bone Density Program ) ; criteria for baseline testing include screening women at age 65 years and younger women with additional risk factors ( 17 ) . Consistent with national guidelines , the program 's recommended interval for initial follow-up is 3 years for most patients , 1 year for those receiving systemic glucocorticoid therapy or aromatase inhibitors , and at least 5 years for those previously reported as low-risk ( 18 ) . The program maintains a data base of all DXA results that can be linked with other population -based computerized health data bases through an anonymous personal identifier . The DXA data base has completeness and accuracy in excess of 99 % ( 19 ) . From this data base , we identified all women aged 40 years or older with baseline DXA measurements of the hip or lumbar spine obtained from 1 of the program 's cross-calibrated primary DXA instruments ( Prodigy ; GE Healthcare Lunar ) after 1 April 1998 . We then identified those with a follow-up DXA examination before 31 March 2013 ( minimum interval of 1 year ) for assessment of change in BMD in at least 1 measurement site ( total hip , femoral neck , or lumbar spine ) . Using linkage to the province-wide retail pharmacy network ( 20 ) , we identified women not receiving osteoporosis treatment during the year before baseline DXA testing ( defined as no pharmacy-dispensed bisphosphonate , calcitonin , systemic estrogen product , raloxifene , or teriparatide ) who initiated 1 of these same osteoporosis treatments between the first and second DXA scans ( defined as 1 or more prescription dispensations ) . Analyses did not consider subsequent medication switching . The study was approved by the Health Research Ethics Board of the University of Manitoba . BMD Measurements Lumbar spine and hip DXA scans were performed and analyzed in accordance with manufacturer recommendations . Femoral neck and total hip T-scores ( number of SDs above or below the mean BMD for young adults ) were calculated from NHANES III ( Third National Health and Nutrition Examination Survey ) reference values for white women ( 21 ) ; lumbar spine ( L1 to L4 ) T-scores were based on the manufacturer 's reference values for white women ( 22 ) . The program 's quality assurance is under strict supervision by a medical physicist ( 17 ) . The instruments used for this study exhibited stable long-term performance ( coefficient of variation , < 0.5 % ) . All reporting physicians and supervising technologists are required to maintain DXA certification with the International Society for Clinical Densitometry . The absolute BMD difference ( measured in g/cm2 ) between the 2 DXA tests was compared with 95 % least-significant change ( LSC ) values for assessment of change using accepted methods , where LSC is the least amount of change in BMD that can be considered statistically significant ( 2325 ) . The BMD measurement error of the Manitoba Bone Density Program used for computing the LSC is derived from more than 400 DXA scan pairs ( most performed on different days but within 28 days by different technologists ) . We have previously reported that this approach ( rather than same-day repositioning with the same technologist ) is more representative of measurement error encountered during clinical monitoring ( 26 ) . From these scan pairs , we obtained the following 95 % LSC values , which are within acceptable ranges ( 25 ) : total hip , 0.030 g/cm2 ; lumbar spine , 0.050 g/cm2 ; and femoral neck , 0.055 g/cm2 . An observed absolute difference less than these values would be considered to be within the range of measurement error ( stable ) , whereas an increase or decrease exceeding these values would be outside the range of measurement error ( detectable increase or decrease in BMD , respectively ) . The use of the absolute difference for BMD monitoring follows International Society for Clinical Densitometry recommendations and avoids errors that can arise when change is expressed as a percentage ( 27 , 28 ) . Baseline Fracture Probability Calculations The 10-year probability of the risk for major osteoporotic fracture was calculated by using the Canadian version of the World Health Organization Fracture Risk Assessment Tool ( FRAX ) , version 3.7 ( FRAX Desktop Multi-Patient Entry ) ( 29 , 30 ) . Age , body mass index , femoral neck BMD , and other data required for calculating fracture probability with FRAX were assessed through a combination of hospital discharge abstract s ( diagnoses and procedures coded using the International Classification of Diseases , Ninth Revision , Clinical Modification , before 2004 and International Statistical Classification of Diseases and Related Health Problems , 10th Revision , Canada thereafter ) , physician billing cl aims ( coded using International Classification of Diseases , Ninth Revision , Clinical Modification ) , and information collected directly from patients at the time of DXA scanning as previously described ( Appendix Table ) ( 31 ) . The Canadian FRAX was calibrated by using nationwide hip fracture data ( 30 ) . Predictions agreed closely with observed fracture risk in our population ( 31 , 32 ) . Appendix Table . Study Population Baseline Characteristics , by Variables Used in Fracture Probability Assessment and Incident Fracture Outcomes * Fractures Outcomes Records from Manitoba Health were assessed for the presence of incident nontraumatic hip , clinical vertebral , forearm , and humerus fracture diagnostic codes ( collectively design ated as major osteoporotic fractures ) using previously vali date d algorithms ( 33 , 34 ) . Fractures that were not associated with trauma codes were assessed through a combination of hospital discharge abstract s and physician billing cl aims . We required that hip and forearm fracture codes be associated with site-specific fracture reduction , fixation , or casting codes to enhance specificity for an acute fracture event . To minimize potential misclassification of prior incident fractures , we conservatively required that there be no hospitalization or physician visit for the same fracture type in the 6 months preceding an incident fracture diagnosis . Statistical Analysis Cumulative fracture incidence after the first DXA scan ( index date ) was studied using survival analysis . Observations were censored for death , migration out of province , or end of follow-up ( 31 March 2013 ) . Our primary analysis examined change in total hip BMD between DXA scans , which was the site with the smallest measurement error ; these scans were categorized as stable ( referent ) , detectable decrease , or detectable increase . Cumulative incidence curves , along with point estimates and 95 % CIs at 5 and 10 years , were directly adjusted for baseline fracture probability ( 35 ) . Average absolute differences in cumulative fracture risk were compared based on change in BMD ( detectable decrease or increase vs. stable BMD ) , and 95 % CIs were estimated . Analyses were conducted using SAS , version 9.3 ( SAS Institute ) . We did a series of secondary sensitivity analyses to test the robustness of our findings and explore potential interactions . First , we examined hip fractures as the outcome of interest given their large implication s on morbidity , mortality , and cost compared with other fractures . Second , we constructed separate models for change in femoral neck and lumbar spine BMD . Finally , we explored potential interactions in multiplicative Cox proportional hazards models stratified according to age ( 40 to 64 , 65 to 74 , and 75 years ) ; baseline BMD ( osteoporotic vs. nonosteoporotic T-scores ) ; BMD testing interval ( 1 to 2.9 , 3 to 5 , and > 5 years ) ; and medication possession ratio ( < 0.5 , 0.50 to 0.79 , and 0.80 ) , which is an adherence measure calculated as the total days of medication supplied between the BMD tests divided by the testing interval . In the Cox regression models , we Dual-energy X-ray absorptiometric bone mineral density ( DXA BMD ) is a strong predictor of fracture risk in untreated patients . However , previous patient-level studies suggest that BMD changes explain little of the fracture risk reduction observed with osteoporosis treatment . We investigated the relevance of DXA BMD changes as a predictor for fracture risk reduction using data from the FREEDOM trial , which r and omly assigned placebo or denosumab 60 mg every 6 months to 7808 women aged 60 to 90 years with a spine or total hip BMD T-score < −2.5 and not < −4.0 . We took a st and ard approach to estimate the percent of treatment effect explained using percent changes in BMD at a single visit ( months 12 , 24 , or 36 ) . We also applied a novel approach using estimated percent changes in BMD from baseline at the time of fracture occurrence ( time-dependent models ) . Denosumab significantly increased total hip BMD by 3.2 % , 4.4 % , and 5.0 % at 12 , 24 , and 36 months , respectively . Denosumab decreased the risk of new vertebral fractures by 68 % ( p < 0.0001 ) and nonvertebral fracture by 20 % ( p = 0.01 ) over 36 months . Regardless of the method used , the change in total hip BMD explained a considerable proportion of the effect of denosumab in reducing new or worsening vertebral fracture risk ( 35 % [ 95 % confidence interval ( CI ) : 20%–61 % ] and 51 % [ 95 % CI : 39%–66 % ] accounted for by percent change at month 36 and change in time-dependent BMD , respectively ) and explained a considerable amount of the reduction in nonvertebral fracture risk ( 87 % [ 95 % CI : 35 % – > 100 % ] and 72 % [ 95 % CI : 24 % – > 100 % ] , respectively ) . Previous patient-level studies may have underestimated the strength of the relationship between BMD change and the effect of treatment on fracture risk or this relationship may be unique to denosumab . © 2012 American Society for Bone and Mineral It is commonly believed that the response to treatment in patients on alendronate is proportional to the increase in bone mineral density ( BMD ) , and that those who lose BMD during treatment might not respond to treatment . In the Fracture Intervention Trial 6,459 women were r and omly assigned to treatment with alendronate or placebo ; BMD was measured annually , and new spine fractures were assessed by lateral spine films , taken at baseline and end of follow-up . Among subjects who took at least 70 % of the study drug ( 5,220 women ) , we compared reductions in risk of spine fractures at end of follow-up ( 3 or 4 years ) within various levels of change in total hip and spine BMD after 1 and 2 years of treatment , after adjustment for differences in characteristics between the treatment and control groups . Women “ losing ” BMD at the lumbar spine ( 0 % to 4 % ) while on alendronate had a reduction of 60 % in vertebral fracture risk [ OR=0.40 ( 0.16 , 0.99 ) ] compared to their counterparts in the placebo group . The few women that lost more than 4 % did not have a significant benefit [ OR=0.15 ( 0.02 , 1.29 ) ] . Those who “ gained ” BMD ( 0 % to 4 % ) during treatment had a reduction in risk of 51 % [ OR=0.49 ( 0.30 , 0.78 ) ] . Similarly , women who “ lost ” total hip BMD ( 0 % to 4 % ) during the first year on alendronate had a 53 % decreased risk of vertebral fracture compared to their controls taking placebo [ OR=0.47 ( 0.27 , 0.81 ) ] , whereas those “ gaining ” BMD ( 0 % to 4 % ) had a comparable risk reduction [ OR=0.49 ( 0.34 , 0.71 ) ] . This was not observed for the few women who lost more than 4 % [ OR=0.61 ( 0.11 , 3.45 ) ] . Patients who lost BMD at both the hip and spine were not protected by alendronate . Among patients who adhere to treatment with alendronate , even those who lose BMD benefit from a substantial reduction in risk of vertebral fracture . So , the reduction in bone turnover induced by alendronate might be more important than BMD changes . The few women who lose the most BMD ( more than 4 % per year ) might not benefit from the treatment Objective : To assess the value of monitoring response to bisphosphonate treatment by means of measuring bone mineral density . Design Secondary analysis of trial data using mixed models . Data source The Fracture Intervention Trial , a r and omised controlled trial that compared the effects of alendronate and placebo in 6459 postmenopausal women with low bone mineral density recruited between May 1992 and May 1993 . Bone density measurements of hip and spine were obtained at baseline and at one , two , and three years after r and omisation . Main outcome measures Between-person ( treatment related ) variation and within-person ( measurement related ) variation in hip and spine bone mineral density . Results The mean effect of three years ’ treatment with alendronate was to increase hip bone mineral density by 0.030 g/cm2 . There was some between-person variation in the effects of alendronate , but this was small in size compared with within-person variation . Alendronate treatment is estimated to result in increases in hip bone density ≥0.019 g/cm2 in 97.5 % of patients . Conclusions : Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent bisphosphonate is unnecessary and may be misleading . Routine monitoring should be avoided in this early period after bisphosphonate treatment is commenced Both raloxifene ( RLX ) and alendronate ( ALN ) can treat and prevent new vertebral fractures , increase bone mineral density ( BMD ) , and decrease biochemical markers of bone turnover in postmenopausal women with osteoporosis . This phase 3 , r and omized , double-blind 1-yr study assessed the effects of combined RLX and ALN in 331 postmenopausal women with osteoporosis ( femoral neck BMD T-score , less than -2 ) . Women ( aged < or = 75 yr ; > or = 2 yr since their last menstrual period ) received placebo , RLX 60 mg/d , ALN 10 mg/d , or RLX 60 mg/d and ALN 10 mg/d combined . At baseline , 6 and 12 months , BMD was measured by dual x-ray absorptiometry . The bone turnover markers serum osteocalcin , bone-specific alkaline phosphatase , and urinary N- and C-telopeptide corrected for creatinine were measured . The effects of RLX and ALN were considered to be independent and additive if the interaction effect was not statistically significant ( P > 0.10 ) in a two-way ANOVA model . All changes in BMD and bone markers at 12 months were different between placebo and each of the active treatment groups , and between the RLX and RLX+ALN groups ( P < 0.05 ) . On average , lumbar spine BMD increased by 2.1 , 4.3 , and 5.3 % from baseline with RLX , ALN , and RLX+ALN , respectively . The increase in femoral neck BMD in the RLX+ALN group ( 3.7 % ) was greater than the 2.7 and 1.7 % increases in the ALN ( P = 0.02 ) and RLX ( P < 0.001 ) groups , respectively . The changes from baseline to 12 months in bone markers ranged from 7.1 to -16.0 % with placebo , -23.8 to -46.5 % with RLX , -42.3 to -74.2 % with ALN , and -54.1 to -81.0 % in the RLX+ALN group . RLX and ALN increased lumbar spine and femoral neck BMD , and decreased osteocalcin and C-telopeptide corrected for creatinine in an additive and independent manner , because the interaction effects were not significant . Although the ALN group had changes in BMD and bone markers that were approximately twice the magnitude as in the RLX group , it is not known how well these changes correlate to the clinical outcome of fracture . RLX+ALN reduced bone turnover more than either drug alone , result ing in greater BMD increment , but whether this difference reflects better fracture risk reduction was not assessed in this study BACKGROUND Receptor activator of nuclear factor-kappaB lig and ( RANKL ) is essential for osteoclast differentiation , activation , and survival . The fully human monoclonal antibody denosumab ( formerly known as AMG 162 ) binds RANKL with high affinity and specificity and inhibits RANKL action . METHODS The efficacy and safety of subcutaneously administered denosumab were evaluated over a period of 12 months in 412 postmenopausal women with low bone mineral density ( T score of -1.8 to -4.0 at the lumbar spine or -1.8 to -3.5 at the proximal femur ) . Subjects were r and omly assigned to receive denosumab either every three months ( at a dose of 6 , 14 , or 30 mg ) or every six months ( at a dose of 14 , 60 , 100 , or 210 mg ) , open-label oral alendronate once weekly ( at a dose of 70 mg ) , or placebo . The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months . Changes in bone turnover were assessed by measurement of serum and urine telopeptides and bone-specific alkaline phosphatase . RESULTS Denosumab treatment for 12 months result ed in an increase in bone mineral density at the lumbar spine of 3.0 to 6.7 percent ( as compared with an increase of 4.6 percent with alendronate and a loss of 0.8 percent with placebo ) , at the total hip of 1.9 to 3.6 percent ( as compared with an increase of 2.1 percent with alendronate and a loss of 0.6 percent with placebo ) , and at the distal third of the radius of 0.4 to 1.3 percent ( as compared with decreases of 0.5 percent with alendronate and 2.0 percent with placebo ) . Near-maximal reductions in mean levels of serum C-telopeptide from baseline were evident three days after the administration of denosumab . The duration of the suppression of bone turnover appeared to be dose-dependent . CONCLUSIONS In postmenopausal women with low bone mass , denosumab increased bone mineral density and decreased bone resorption . These preliminary data suggest that denosumab might be an effective treatment for osteoporosis . ( Clinical Trials.gov number , NCT00043186 . ) CONTEXT Risedronate , a potent bisphosphonate , has been shown to be effective in the treatment of Paget disease of bone and other metabolic bone diseases but , to our knowledge , it has not been evaluated in the treatment of established postmenopausal osteoporosis . OBJECTIVE To test the efficacy and safety of daily treatment with risedronate to reduce the risk of vertebral and other fractures in postmenopausal women with established osteoporosis . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial of 2458 ambulatory postmenopausal women younger than 85 years with at least 1 vertebral fracture at baseline who were enrolled at 1 of 110 centers in North America conducted between December 1993 and January 1998 . INTERVENTIONS Subjects were r and omly assigned to receive oral treatment for 3 years with risedronate ( 2.5 or 5 mg/d ) or placebo . All subjects received calcium , 1000 mg/d . Vitamin D ( cholecalciferol , up to 500 IU/d ) was provided if baseline levels of 25-hydroxyvitamin D were low . MAIN OUTCOME MEASURES Incidence of new vertebral fractures as detected by quantitative and semiquantitative assessment s of radiographs ; incidence of radiographically confirmed nonvertebral fractures and change from baseline in bone mineral density as determined by dual x-ray absorptiometry . RESULTS The 2.5 mg/d of risedronate arm was discontinued after 1 year ; in the placebo and 5 mg/d of risedronate arms , 450 and 489 subjects , respectively , completed all 3 years of the trial . Treatment with 5 mg/d of risedronate , compared with placebo , decreased the cumulative incidence of new vertebral fractures by 41 % ( 95 % confidence interval [ CI ] , 18%-58 % ) over 3 years ( 11.3 % vs 16.3 % ; P= .003 ) . A fracture reduction of 65 % ( 95 % CI , 38%-81 % ) was observed after the first year ( 2.4 % vs 6.4 % ; P<.001 ) . The cumulative incidence of nonvertebral fractures over 3 years was reduced by 39 % ( 95 % CI , 6%-61 % ) ( 5.2 % vs 8.4 % ; P = .02 ) . Bone mineral density increased significantly compared with placebo at the lumbar spine ( 5.4 % vs 1.1 % ) , femoral neck ( 1.6 % vs -1.2 % ) , femoral trochanter ( 3.3 % vs -0.7 % ) , and midshaft of the radius ( 0.2 % vs -1.4 % ) . Bone formed during risedronate treatment was histologically normal . The overall safety profile of risedronate , including gastrointestinal safety , was similar to that of placebo . CONCLUSIONS These data suggest that risedronate therapy is effective and well tolerated in the treatment of women with established postmenopausal osteoporosis CONTEXT The principle of " regression to the mean " predicts that patients with unusual responses to treatment might represent outliers who are likely to have more typical responses if treatment is continued without change . OBJECTIVE To test whether women who lose bone mineral density ( BMD ) during the first year of treatment for osteoporosis continue to lose BMD if the same treatment is continued beyond 1 year . DESIGN AND SETTING Two r and omized , double-blind , placebo-controlled trials in 11 US clinical research centers for the Fracture Intervention Trial and 180 centers in the United States and other countries for the Multiple Outcomes of Raloxifene Evaluation Trial . PARTICIPANTS AND INTERVENTIONS Postmenopausal women with low BMD assigned to treatment with 5 mg/d of alendronate sodium in the Fracture intervention Trial who completed 2 years of BMD monitoring and adhered to study medication ( n = 2634 ) , and postmenopausal women with osteoporosis assigned to treatment with 60 or 120 mg/d of raloxifene hydrochloride in the Multiple Outcomes of Raloxifene Evaluation trial who similarly completed 2 years of monitoring while adhering to study medication ( n = 3954 ) . MAIN OUTCOME MEASURES Baseline , 12- , and 24-month hip and spine BMD . RESULTS Women with the greatest loss of BMD during the first year of treatment were the most likely to gain BMD during continued treatment . Specifically , among women taking alendronate whose hip BMD decreased by more than 4 % during the first year , 83 % ( 95 % confidence interval [ CI ] , 82%-84%)had increases in hip BMD during the second year , with an overall mean increase of 4.7 % . In contrast , those who seemed to gain at least 8 % during the first year lost an average of 1 % ( 95 % CI , 0.1%-1.9 % ) during the next year . Similar results were observed among women taking raloxifene for 2 years . CONCLUSIONS Our data suggest that most women who lose BMD during the first year of treatment with alendronate or raloxifene will gain BMD if the same treatment is continued for a second year . These results illustrate the principle of regression to the mean and suggest that effective treatments for osteoporosis should not be changed because of loss of BMD during the first year of use OBJECTIVE A 1-yr extension of the Fosamax Actonel Comparison Trial was completed to compare changes in bone mineral density ( BMD ) , bone turnover , and upper gastrointestinal tolerability over 2 yr of treatment . DESIGN This was a r and omized , double-blind extension conducted at 72 U.S. sites . PATIENTS AND METHODS Of the 1053 women who completed yr 1 , 833 postmenopausal women with low BMD entered the extension , continuing their same treatment allocation [ once-weekly ( OW ) alendronate 70 mg or OW risedronate 35 mg ] . Changes in BMD at the hip trochanter , total hip , femoral neck , and lumbar spine and in markers of bone turnover were compared at 24 months . Tolerability was assessed by adverse experience reporting . RESULTS Alendronate produced greater increases from baseline in BMD at 24 months than did risedronate at the trochanter ( alendronate , 4.6 % ; risedronate , 2.5 % , P < 0.001 ) as well as at all other BMD sites . Significantly more alendronate than risedronate patients had measured BMD increases of 0 % or more and 3 % or more at all BMD sites ( P < 0.001 ) , and fewer alendronate patients had measured decreases of 3 % or more at all BMD sites . Significantly greater reductions in all biochemical markers of bone turnover occurred with alendronate , compared with risedronate . No differences were seen in occurrence or discontinuations due to upper gastrointestinal adverse experiences . CONCLUSIONS Patients receiving 70 mg OW alendronate had greater gains in BMD , were more likely to maintain or gain BMD , and had greater reductions in bone turnover markers than patients receiving 35 mg OW risedronate after 24 months , with no differences in upper gastrointestinal tolerability Long-term adherence and persistence with any therapy are very poor ( approximately 50 % ) . Adherence to therapy is defined as the percentage of prescribed medication taken , and persistence is defined as continuing to take prescribed medication . We examined whether monitoring by nursing staff could enhance adherence and persistence with antiresorptive therapy and whether presenting information on response to therapy provided additional benefit . In addition we evaluated the impact of monitoring on treatment efficacy . Seventy-five postmenopausal women with osteopenia were r and omized to 1 ) no monitoring , 2 ) nurse-monitoring , or 3 ) marker-monitoring . All subjects were prescribed raloxifene . At 12 , 24 , and 36 wk , the nursing staff review ed subjects in the monitored ( nurse-monitoring or marker-monitoring ) groups using a predefined protocol . The marker-monitored group were also presented a graph of response to therapy using percentage change in urinary N-telopeptide of type I collagen ( uNTX ) , a bone resorption marker , at each visit . Biological response to therapy at 1 yr was determined using the percent change in bone mineral density ( BMD ) and uNTX . Treatment adherence and persistence were assessed using electronic monitoring devices . Survival analysis showed that the monitored group increased cumulative adherence to therapy by 57 % compared with no monitoring ( P = 0.04 ) . There was a trend for the monitored group to persist with therapy for 25 % longer compared with no monitoring ( P = 0.07 ) . Marker measurements did not improve adherence or persistence to therapy compared with nurse-monitoring alone . Adherence at 1 yr was correlated with percent change in hip ( BMD ) ( r = 0.28 ; P = 0.01 ) and percent change in uNTX ( r = -0.36 ; P = 0.002 ) . In conclusion , monitoring of patients increased adherence to therapy by 57 % at 1 yr . Increased adherence to therapy increased the effectiveness of raloxifene therapy determined using surrogate end points Surrogate markers of fracture risk -- bone turnover markers ( BTMs ) and bone mineral density (BMD)--can be used to monitor treatment response . We assessed whether changes in these markers greater than the least significant change ( LSC ) were associated with fracture risk reduction and greater adherence . This secondary analysis of the Improving Measurements of Persistence on ACtonel Treatment ( IMPACT ) study --a multinational prospect i ve , open-label , cluster-r and omized study of postmenopausal women on oral risedronate 5 mg/d for 52 weeks-assessed adherence by electronic monitors . Urinary N-terminal cross-linked telopeptide of type 1 collagen ( uNTX ) and serum C-terminal cross-linked telopeptide of type 1 collagen ( sCTX ) levels were assessed at baseline and weeks 10 and 22 , and BMD at baseline and week 52 . Fractures were recorded as adverse events . In 2302 women , responses beyond LSC in BTMs ( uNTX and sCTX ) and BMD ( spine only ) were associated with a reduced risk of nonvertebral fractures ( NVFs ) and all fractures . NVF incidence was about 50 % lower in patients with 30 % or more of uNTX reduction at week 22 ( 1.6 % ) than in those with less than 30 % reduction ( 3.2 % , p = .015 ) . NVFs also were reduced in patients with more than 3 % spine BMD increase at 52 weeks than those with 3 % or less . Responses greater than LSC in BTMs and BMD were associated with greater adherence , but there was no association between adherence and fracture outcomes at 52 weeks . Changes greater than the LSC in BTMs and BMD reflect better treatment adherence , were associated with fracture risk reduction , and identify differences in individual responsiveness to risedronate BACKGROUND A single infusion of intravenous zoledronic acid decreases bone turnover and improves bone density at 12 months in postmenopausal women with osteoporosis . We assessed the effects of annual infusions of zoledronic acid on fracture risk during a 3-year period . METHODS In this double-blind , placebo-controlled trial , 3889 patients ( mean age , 73 years ) were r and omly assigned to receive a single 15-minute infusion of zoledronic acid ( 5 mg ) and 3876 were assigned to receive placebo at baseline , at 12 months , and at 24 months ; the patients were followed until 36 months . Primary end points were new vertebral fracture ( in patients not taking concomitant osteoporosis medications ) and hip fracture ( in all patients ) . Secondary end points included bone mineral density , bone turnover markers , and safety outcomes . RESULTS Treatment with zoledronic acid reduced the risk of morphometric vertebral fracture by 70 % during a 3-year period , as compared with placebo ( 3.3 % in the zoledronic-acid group vs. 10.9 % in the placebo group ; relative risk , 0.30 ; 95 % confidence interval [ CI ] , 0.24 to 0.38 ) and reduced the risk of hip fracture by 41 % ( 1.4 % in the zoledronic-acid group vs. 2.5 % in the placebo group ; hazard ratio , 0.59 ; 95 % CI , 0.42 to 0.83 ) . Nonvertebral fractures , clinical fractures , and clinical vertebral fractures were reduced by 25 % , 33 % , and 77 % , respectively ( P<0.001 for all comparisons ) . Zoledronic acid was also associated with a significant improvement in bone mineral density and bone metabolism markers . Adverse events , including change in renal function , were similar in the two study groups . However , serious atrial fibrillation occurred more frequently in the zoledronic acid group ( in 50 vs. 20 patients , P<0.001 ) . CONCLUSIONS A once-yearly infusion of zoledronic acid during a 3-year period significantly reduced the risk of vertebral , hip , and other fractures . ( Clinical Trials.gov number , NCT00049829 . CONTEXT The optimal duration of treatment of women with postmenopausal osteoporosis is uncertain . OBJECTIVE To compare the effects of discontinuing alendronate treatment after 5 years vs continuing for 10 years . DESIGN AND SETTING R and omized , double-blind trial conducted at 10 US clinical centers that participated in the Fracture Intervention Trial ( FIT ) . PARTICIPANTS One thous and ninety-nine postmenopausal women who had been r and omized to alendronate in FIT , with a mean of 5 years of prior alendronate treatment . INTERVENTION R and omization to alendronate , 5 mg/d ( n = 329 ) or 10 mg/d ( n = 333 ) , or placebo ( n = 437 ) for 5 years ( 1998 - 2003 ) . MAIN OUTCOME MEASURES The primary outcome measure was total hip bone mineral density ( BMD ) ; secondary measures were BMD at other sites and biochemical markers of bone remodeling . An exploratory outcome measure was fracture incidence . RESULTS Compared with continuing alendronate , switching to placebo for 5 years result ed in declines in BMD at the total hip ( -2.4 % ; 95 % confidence interval [ CI ] , -2.9 % to -1.8 % ; P<.001 ) and spine ( -3.7 % ; 95 % CI , -4.5 % to -3.0 % ; P<.001 ) , but mean levels remained at or above pretreatment levels 10 years earlier . Similarly , those discontinuing alendronate had increased serum markers of bone turnover compared with continuing alendronate : 55.6 % ( P<.001 ) for C-telopeptide of type 1 collagen , 59.5 % ( P < .001 ) for serum n = propeptide of type 1 collagen , and 28.1 % ( P<.001 ) for bone-specific alkaline phosphatase , but after 5 years without therapy , bone marker levels remained somewhat below pretreatment levels 10 years earlier . After 5 years , the cumulative risk of nonvertebral fractures ( RR , 1.00 ; 95 % CI , 0.76 - 1.32 ) was not significantly different between those continuing ( 19 % ) and discontinuing ( 18.9 % ) alendronate . Among those who continued , there was a significantly lower risk of clinical ly recognized vertebral fractures ( 5.3 % for placebo and 2.4 % for alendronate ; RR , 0.45 ; 95 % CI , 0.24 - 0.85 ) but no significant reduction in morphometric vertebral fractures ( 11.3 % for placebo and 9.8 % for alendronate ; RR , 0.86 ; 95 % CI , 0.60 - 1.22 ) . A small sample of 18 transilial bone biopsies did not show any qualitative abnormalities , with bone turnover ( double labeling ) seen in all specimens . CONCLUSIONS Women who discontinued alendronate after 5 years showed a moderate decline in BMD and a gradual rise in biochemical markers but no higher fracture risk other than for clinical vertebral fractures compared with those who continued alendronate . These results suggest that for many women , discontinuation of alendronate for up to 5 years does not appear to significantly increase fracture risk . However , women at very high risk of clinical vertebral fractures may benefit by continuing beyond 5 years . TRIAL REGISTRATION clinical trials.gov Identifier : NCT 00398931 |
10,410 | 30,828,897 | Positive effects of mild to moderate magnitude were found in the posttests for some outcome measures .
Behavioral interventions seem to be the most promising .
Interventions achieved the best results when they were long in duration and low in intensity and when they were applied to family members with young children who were undergoing medical treatment .
At follow-up , the intervention benefits were diminished . | OBJECTIVE This meta-analytical study examined the effects of psychological treatments applied to family members of children and adolescents with cancer , as well as the characteristics of the studies that can be associated with their effects . | Uncertainty is a central feature of long-term childhood cancer survivorship during which time it principally has to do with late effects . Therefore , the purpose s of this article are ( a ) to assess feasibility of a r and omized clinical trial of a telephone-delivered coping skills training ( CST ) intervention in terms of recruitment , retention , and timeline , as well as the performance of the study measures ; and ( b ) to demonstrate trends in change on outcomes within the context of a small pilot study . The results of this pilot study suggest that HEROS PLUS CST has clinical relevance and that in-person long-term follow-up plus telephone-delivered psychosocial care is a practical way to deliver integrated care to adolescent — young adult childhood cancer survivors and their parents Background Since siblings of pediatric cancer patients are at risk for emotional , behavioral , and social problems , there is considerable interest in development of early psychological interventions . This paper aim ed at evaluating the effectiveness of a two-session psychological intervention for siblings of newly diagnosed pediatric cancer patients . Methods Thirty siblings age 6 - 17 years were r and omly assigned to an intervention group or an active control group with st and ard psychosocial care . The manualized intervention provided to siblings in the first 2 months after the cancer diagnosis of the ill child included medical information , promotion of coping skills , and a psychoeducational booklet for parents . At 4 to 6 weeks , 4 months , and 7 months after the diagnosis , all siblings and their parents completed measures ( from st and ardized instruments ) of social support , quality of life , medical knowledge , posttraumatic stress symptoms , and anxiety . Results At follow-up siblings in the intervention group showed better psychological well-being , had better medical knowledge , and reported receiving social support from more people . However , the intervention had no effects on posttraumatic stress symptoms and anxiety . Conclusions The results of this pilot trial suggest that a two-session sibling intervention can improve siblings ' adjustment , particularly psychological well-being , in the early stage after a cancer diagnosis . Trial Registration Clinical Trials.gov Abstract Objective The aim of the study was to investigate the feasibility and preliminary efficacy of an Internet‐based guided self‐help intervention for posttraumatic stress symptoms ( PTSS ) and related symptoms in parents of children on cancer treatment . Methods Parents of children on cancer treatment , who fulfilled the modified symptom criteria on the PTSD Checklist , were r and omly allocated to the intervention or to a wait‐list control condition . The intervention group accessed a 10‐week guided self‐help program via the Internet based on principles from cognitve behavior therapy . The primary outcome PTSS and the secondary outcomes depression and anxiety were assessed by self‐report preintervention and postintervention . Results Seven hundred forty‐seven parents were approached and informed about the study , 92 were assessed for eligibility , and 58 were included and r and omized to the intervention ( n = 31 ) or wait list ( n = 27 ) . Eightteen participants completed the intervention . Intention‐to‐treat analyses indicated a significant effect of the intervention on PTSS with a large between‐group effect size at post assessment ( Cohen 's d = 0.88 ) . The intervention group reported reductions in PTSS with a large within‐group effect size ( d = 1.62 ) compared with a minimal reduction in the wait‐list group ( d = 0.09 ) . There was a significant intervention effect on depression and anxiety and reductions in the intervention group with large within‐group effect sizes ( d = 0.85–1.09 ) . Conclusions Findings indicate a low enrollment rate and considerable attrition but also that Internet‐based guided self‐help shows promise for parents of children on cancer treatment who report a high level of PTSS and would like to take part in an Internet‐based intervention . © 2015 The Authors . Psycho‐Oncology published by John Wiley & Sons , BACKGROUND We conducted a prospect i ve two-group evaluation of pediatric cancer patients and their siblings regarding experiences and affective changes result ing from a 1-week summer camp experience . METHODS The patients and siblings were assessed prior to camp ( Baseline ) , at the end of camp ( Follow-up 1 ) , and again 4 - 6 months later ( Follow-up 2 ) . Assessment s included st and ardized tests for depressive affects , social competency , and a measure of pleasure and participation in camp activities . RESULTS Sixty-six children were assessed , including 31 ( 47 % ) patients and 35 ( 53 % ) siblings . Ages ranged from 7 to 17 years . Of the patient campers 19 ( 61 % ) had leukemia or lymphoma and 12 ( 39 % ) had solid tumors . Results showed marked changes in affective symptoms for patient campers over time ( improvements ) , not shown by sibling campers . For patient campers these affective changes were not present immediately after camp , but were quite significant when measured 4 - 6 months later . Both patient and sibling campers reflected the same positive memories and pleasure in camp activities over time . For neither group did memories or pleasure fade over time . The camping experience did not have differential impacts on first time versus returning campers . Twelve campers ( 18 % of sample ) indicated suicidal ideation on the measure of depressive affects . They did well at camp and presented no special management issues . CONCLUSION Expectations appear substantially different for patient versus sibling campers . The camping experience appeared to impact these groups differently , with patient campers impacted in ways not experienced by sibling campers OBJECTIVES ( 1 ) To examine the acceptability and feasibility of a stress management intervention for caregivers of children recently diagnosed with cancer . ( 2 ) To explore whether caregivers with lower baseline perceived social support derive greater benefit from the intervention than those with higher perceived support . METHODS 45 primary caregivers were r and omly assigned to intervention or st and ard care . Of these , 37 completed measures of social support , depression , anxiety , and perceived stress at both pre-intervention ( T1 ; mean = 24 days post-diagnosis ) and post-intervention time points ( T2 ; mean = 165 days post-diagnosis ) . RESULTS Enrollment , retention , and satisfaction data support feasibility and acceptability of the intervention . There was no overall significant impact of participation in the intervention on levels of distress at T2 . However , T1 social support moderated intervention response , with caregivers who perceived lower T1 support showing greater psychological benefit from the intervention . CONCLUSIONS Primary caregivers with lower levels of perceived social support may benefit from preemptive stress management intervention This study investigated a behavioral intervention incorporating parent coaching , attentional distraction , and positive reinforcement to control child distress during invasive cancer treatment . Children ( N = 23 ) requiring physical restraint to complete venipuncture were alternately assigned to either a behavioral intervention or an attention control condition . Child distress behaviors were recorded , and self-reports of parent , child , and nurse distress were obtained . Parent and nurse also rated child distress . Results of planned comparisons indicate that observed child distress , parent-rated child distress , and parent ratings of his/her own distress were significantly reduced by behavioral intervention and were maintained across the course of three intervention trials . The use of physical restraint to manage child behavior was also significantly reduced . Child self-reported pain and nurse ratings of child distress were not significantly affected Posttraumatic stress symptoms ( PTSS ) , particularly intrusive thoughts , avoidance , and arousal , are among the most common psychological aftereffects of childhood cancer for survivors and their mothers and fathers . We conducted a r and omized wait-list control trial of a newly developed 4-session , 1-day intervention aim ed at reducing PTSS that integrates cognitive-behavioral and family therapy approaches -- the Surviving Cancer Competently Intervention Program ( SCCIP ) . Participants were 150 adolescent survivors and their mothers , fathers , and adolescent siblings . Significant reductions in intrusive thoughts among fathers and in arousal among survivors were found in the treatment group . A multiple imputations approach was used to address nonr and om missing data and indicated that treatment effects would likely have been stronger had more distressed families been retained . The data are supportive of brief interventions to reduce PTSS in this population and provide additional support for the importance of intervention for multiple members of the family OBJECTIVE To report acceptability , feasibility , and outcome data from a r and omized clinical trial ( RCT ) of a brief intervention for caregivers of children newly diagnosed with cancer . METHOD Eighty-one families were r and omly assigned following collection of baseline data to Intervention or Treatment as Usual ( TAU ) . Recruitment and retention rates and progression through the protocol were tracked . Measures of state anxiety and posttraumatic stress symptoms served as outcomes . RESULTS Difficulties enrolling participants included a high percentage of newly diagnosed families failing to meet inclusion criteria ( 40 % ) and an unexpectedly low participation rate ( 23 % ) . However , movement through the protocol was generally completed in a timely manner and those completing the intervention provided positive feedback . Outcome data showed no significant differences between the arms of the RCT . CONCLUSIONS There are many challenges inherent in conducting a RCT shortly after cancer diagnosis . Consideration of alternative research design s and optimal timing for interventions are essential next steps OBJECTIVE To document levels of stress in parents of children undergoing bone marrow transplantation ( BMT ) over the course of hospitalization and to pilot a psychological intervention program design ed to teach parents techniques for managing stress associated with their child 's illness and hospitalization . METHODS Twenty-two mothers of children ( ages 2 - 16 ) undergoing BMT were followed prospect ively from preadmission to three weeks posttransplant . Eleven mothers , r and omly assigned to participate in a pilot intervention program , were compared with 11 control mothers receiving st and ard care preparation of their child 's BMT . RESULTS Repeated measures ANOVAs detected significant changes in stress over time , with most stress reported preadmission . Mothers in the intervention condition reported using more stress management techniques than mothers in the st and ard care condition , though the majority of analyses revealed no significant differences in stress between groups . CONCLUSIONS Increased levels of parenting distress may occur pretransplant , suggesting the need for additional psychological intervention at that time IMPORTANCE Parent psychological distress can impact the well-being of childhood cancer patients and other children in the home . Recognizing and alleviating factors of parent distress may improve overall family survivorship experiences following childhood cancer . OBJECTIVES To describe the prevalence and factors of psychological distress ( PD ) among parents of children with advanced cancer . DESIGN Cohort study embedded within a r and omized clinical trial ( Pediatric Quality of Life and Evaluation of Symptoms Technology [ PediQUEST ] study ) . SETTING Multicenter study conducted at 3 children 's hospitals ( Boston Children 's Hospital , Children 's Hospital of Philadelphia , and Seattle Children 's Hospital ) . PARTICIPANTS Parents of children with advanced ( progressive , recurrent , or refractory ) cancer . MAIN OUTCOME MEASURE Parental PD , as measured by the Kessler-6 Psychological Distress Scale . RESULTS Eighty-six of 104 parents completed the Survey About Caring for Children With Cancer ( 83 % participation ) ; 81 parents had complete Kessler-6 Psychological Distress Scale data . More than 50 % of parents reported high PD and 16 % met criteria for serious PD ( compared with US prevalence of 2%-3 % ) . Parent perceptions of prognosis , goals of therapy , child symptoms/suffering , and financial hardship were associated with PD . In multivariate analyses , average parent Kessler-6 Psychological Distress Scale scores were higher among parents who believed their child was suffering highly and who reported great economic hardship . Conversely , PD was significantly lower among parents whose prognostic underst and ing was aligned with concrete goals of care . CONCLUSIONS AND RELEVANCE Parenting a child with advanced cancer is strongly associated with high to severe levels of PD . Interventions aim ed at aligning prognostic underst and ing with concrete care goals and easing child suffering and financial hardship may mitigate parental PD OBJECTIVE To investigate whether adolescent siblings of childhood cancer survivors experience posttraumatic stress ( PTS ) . METHODS Participants included 78 adolescent siblings of adolescent cancer survivors who completed self-report measures of anxiety , PTS , and perceptions of the cancer experience . RESULTS Nearly half ( 49 % ) of our sample reported mild PTS and 32 % indicated moderate to severe levels . One fourth of siblings thought their brother/sister would die during treatment ; over half found the cancer experience scary and difficult . These perceptions were related to PTS . Siblings reported more PTS symptoms than a reference group of nonaffected teens but had similar levels of general anxiety . CONCLUSIONS Levels of PTS are elevated for siblings of childhood cancer survivors . Thus , PTS may be a useful model for underst and ing siblings ' long-term reactions to cancer . Future research and clinical efforts should consider the needs of siblings of childhood cancer survivors in a family context OBJECTIVE To report initial feasibility and outcome from a pilot study of a new three-session intervention for caregivers of children newly diagnosed with cancer , Surviving Cancer Competently Intervention Program-Newly Diagnosed ( SCCIP-ND ) . METHOD Nineteen families ( 38 caregivers ) were r and omly assigned to SCCIP-ND or treatment as usual subsequent to learning of their child 's illness . The study design included pre- and 2-month postintervention assessment s , with state anxiety and posttraumatic stress symptoms as outcomes . Feasibility was based on therapist feedback and supervision , program evaluations , and data from study -tracking procedures . RESULTS SCCIP-ND appears to be an acceptable intervention that can be used successfully with caregivers over the first few months after diagnosis . Recruitment and retention data document feasibility but also highlight challenges . Preliminary outcome data show changes in the desired direction [ e.g. , reduced anxiety and parental posttraumatic stress symptoms ( PTSS ) ] . CONCLUSIONS The pilot data are supportive of the value and challenges of developing evidence -based family interventions in pediatric psychology OBJECTIVE : To evaluate feasibility and preliminary efficacy of an intervention directed at parents of childhood cancer survivors ( CCSs ) with neurobehavioral late effects to improve targeted parenting skills , and thus to indirectly benefit the child 's educational functioning . METHODS : 44 CCSs and their parents were r and omized . Intervention-arm parents participated in eight individual training sessions augmented by a 3-month telephone support period . Pre- and postparent measures and child performance on Wechsler Individual Achievement Test-II and School Motivation and Learning Strategies Inventory assessed intervention effects . RESULTS : 90 % of intervention parents completed the program with high adherence/perceived benefit . Between-group effect sizes ranged from d = 0.77 to d = 1.45 for parent knowledge , efficacy , frequency of pro-learning behaviors , and d = 0.21 to d = 0.76 for child academic scores . Parental time spent in intervention activities was associated with academic change . CONCLUSIONS : A parent-directed intervention to indirectly promote academic functioning in CCSs appears feasible and effective in improving targeted parenting outcomes and for selected child academic outcomes OBJECTIVES To evaluate the feasibility and efficacy of a h and held personal digital assistant (PDA)-based supplement for maternal Problem-Solving Skills Training ( PSST ) and to explore Spanish-speaking mothers ' experiences with it . METHODS Mothers ( n = 197 ) of children with newly diagnosed cancer were r and omized to traditional PSST or PSST + PDA 8-week programs . Participants completed the Social Problem-Solving Inventory-Revised , Beck Depression Inventory-II , Profile of Mood States , and Impact of Event Scale-Revised pre- , post-treatment , and 3 months after completion of the intervention . Mothers also rated optimism , logic , and confidence in the intervention and technology . RESULTS Both groups demonstrated significant positive change over time on all psychosocial measures . No between-group differences emerged . Despite technological " glitches , " mothers expressed moderately high optimism , appreciation for logic , and confidence in both interventions and rated the PDA-based program favorably . Technology appealed to all Spanish-speaking mothers , with younger mothers showing greater proficiency . CONCLUSIONS Well- design ed , supported technology holds promise for enhancing psychological interventions OBJECTIVE To evaluate a psychoeducational intervention program for parents of pediatric cancer patients , using cognitive and behavioral techniques . METHODS Parents were r and omly assigned to an intervention ( n = 39 ) and a control condition ( n = 42 ) . Baseline assessment took place at diagnosis . Short-term effects were measured immediately after the intervention , long-term effects six months later . Control parents received st and ard care . Intervention parents received , in addition , a manual-guided program during the first six months following the diagnosis . RESULTS With time all parents became significantly less psychologically distressed . However , no between-group differences were noted in psychological functioning , satisfaction with support , and intensity of emotions immediately postintervention and six months later . CONCLUSIONS Although the clinical evaluation of the intervention was positive , it appeared that a structured intervention program as described in this study was not any more effective than st and ard care ABSTRACT . Mothers of children with serious illnesses have lower levels of well-being than mothers in the general population . Problem-solving therapy ( PST ) , a cognitive-behavioral intervention , has been shown to be effective in treating negative affectivity ( depression , anxiety ) and other manifestations of reduced well-being . This report describes a problem-solving skills training ( PSST ) intervention , based on problem-solving therapy , for mothers of newly diagnosed pediatric cancer patients . Ninety-two mothers were r and omly assigned to receive PSST or to receive st and ard psychosocial care ( Control Group ) . After the 8-week intervention , mothers in the PSST Group had significantly enhanced problem-solving skills and significantly decreased negative affectivity compared with controls . Analysis revealed that changes in self-reports of problem-solving behaviors accounted for 40 % of the difference in mood scores between the two groups . Interestingly , PSST had the greatest impact on improving constructive problem solving , whereas improvement in mood was most influenced by decreases in dysfunctional problem solving . The implication s of these findings for refinement of the PSST intervention and for extension to other groups of children with serious illnesses are discussed This study assesses the effects of Guided Written Disclosure Protocol on psychological distress in mothers and fathers of off-therapy acute lymphoblastic leukemia children . An experimental group participated in the writing intervention with a control group subject only to test-taking st and ards . The Symptom Question naire and Profile of Mood States were administered at baseline , post-intervention , and follow-up . Guided Written Disclosure Protocol had significant effects on the progressive reduction of anxiety , depression , somatic symptoms , hostility , tension – anxiety , and fatigue – inertia within the experimental group . However , the control group distress levels tended to worsen over time . The mediating role of emotional processing was highlighted IMPORTANCE Advance care planning ( ACP ) prepares patients and their families for future health care decisions ; however , the needs of adolescent oncology patients for participation in ACP have not been well studied . OBJECTIVE To examine the efficacy of family-centered ACP . DESIGN AND SETTING Two-group r and omized controlled trial in a pediatric oncology program . PARTICIPANTS Sixty adolescents aged 14 to 21 years with cancer and their surrogates or families were enrolled in the study between January 17 , 2011 , and March 29 , 2012 . INTERVENTION Thirty dyads received 3- to 60-minute sessions 1 week apart . Intervention dyads completed ( 1 ) the Lyon Family-Centered ACP Survey , ( 2 ) the Respecting Choices interview , and ( 3 ) Five Wishes . Control subjects received st and ard care plus information . MAIN OUTCOME MEASURES Statement of treatment preferences and Decisional Conflict Scale score . RESULTS The mean age of the adolescents was 16 years ; 36 ( 60 % ) were male , 30 ( 50 % ) white , 26 ( 43 % ) black , and 4 ( 7 % ) Asian . Diagnoses were as follows : leukemia ( 14 patients [ 47 % ] ) , brain tumor ( 8 [ 27 % ] ) , solid tumor ( 6 [ 20 % ] ) , and lymphoma ( 2 [ 7 % ] ) . Significantly increased congruence was observed for intervention dyads compared with controls for 4 of the 6 disease-specific scenarios ; for example , for situation 2 ( " treatment would extend my life by not more than 2 to 3 months " ) , intervention dyads demonstrated higher congruence ( κ = 0.660 ; P < .001 ) vs control dyads ( κ = -0.0636 ; P = .70 ) . Intervention adolescents ( 100 % ) wanted their families to do what is best at the time , whereas fewer control adolescents ( 62 % ) gave families this leeway . Intervention adolescents were significantly better informed about end-of-life decisions ( t = 2.93 ; effect size , 0.961 ; 95 % CI , 0.742 - 1.180 ; P = .007 ) . Intervention families were more likely to concur on limiting treatments than controls . An ethnic difference was found in only one situation . CONCLUSIONS Advance care planning enabled families to underst and and honor their adolescents ' wishes . Intervention dyads were more likely than controls to limit treatments . Underserved African American families were willing to participate Mothers of children with cancer experience significant distress associated with their children 's diagnosis and treatment . The efficacy of problem-solving skills training ( PSST ) , a cognitive-behavioral intervention based on problem-solving therapy , was assessed among 430 English- and Spanish-speaking mothers of recently diagnosed patients . Participants were r and omized to usual psychosocial care ( UPC ; n=213 ) or UPC plus 8 sessions of PSST ( PSST ; n=217 ) . Compared with UPC mothers , PSST mothers reported significantly enhanced problem-solving skills and significantly decreased negative affectivity . Although effects were largest immediately after PSST , several differences in problem-solving skills and distress levels persisted to the 3-month follow-up . In general , efficacy for Spanish-speaking mothers exceeded that for English-speaking mothers . Findings also suggest young , single mothers profit most from PSST PURPOSE The purpose of this study was to evaluate the feasibility of a computer-mediated support group ( CMSG ) intervention for parents whose children had been diagnosed with cancer . DESIGN AND METHODS An evaluative one-group , before- and -after research design . A CMSG , an unstructured listserve group where participants used their E-mail for communication , was conducted over a 4-month period . Participation in the CMSG was offered to parents in Icel and whose children had completed cancer treatment in the past 5 years . Outcome measures were done : before the intervention ( Time 1 ) , after 2 months of intervention ( Time 2 ) and after 4 months of intervention ( Time 3 ) when the project ended . Measures included : demographic and background variables ; health related vulnerability factors of parents : anxiety , depression , somatization , and stress ; perceived mutual support ; and use of the CMSG . Data were collected from November 2002 to June 2003 . Twenty-one of 58 eligible parents participated in the study , with 71 % retention rate for both post-tests . FINDINGS Mothers ' depression decreased significantly from Time 2 to Time 3 ( p<.03 ) . Fathers ' anxiety decreased significantly from Time 1 to Time 3 ( p<.01 ) . Fathers ' stress decreased significantly from Time 2 to Time 3 ( p<.02 ) . To some extent , mothers and fathers perceived mutual support from participating in the CMSG . Both mothers and fathers used the CMSG by reading messages . Messages were primarily written by mothers . CONCLUSIONS Study findings support further development of CMSGs for parents whose children have been diagnosed with cancer . CLINICAL RELEVANCE Using computer technology for support is particularly useful for dispersed population s and groups that have restrictions on their time . Computer-mediated support groups have been shown to be a valuable addition to , or substitute for , a traditional face-to-face mutual support group and might suit both genders equally PURPOSE Diagnosis of cancer in a child can be extremely stressful for parents . Bright IDEAS , a problem-solving skills training ( PSST ) intervention , has been shown to decrease negative affectivity ( anxiety , depression , post-traumatic stress symptoms ) in mothers of newly diagnosed patients . This study was design ed to determine the specificity of PSST by examining its direct and indirect ( eg , social support ) effects compared with a nondirective support ( NDS ) intervention . PATIENTS AND METHODS This r and omized clinical trial included 309 English- or Spanish-speaking mothers of children diagnosed 2 to 16 weeks before recruitment . Participants completed assessment s prer and omization ( T1 ) , immediately postintervention ( T2 ) , and at 3-month follow-up ( T3 ) . Both PSST and NDS consisted of eight weekly 1-hour individual sessions . Outcomes included measures of problem-solving skill and negative affectivity . RESULTS There were no significant between-group differences at baseline ( T1 ) . Except for level of problem-solving skill , which was directly taught in the PSST arm , outcome measures improved equally in both groups immediately postintervention ( T2 ) . However , at the 3-month follow-up ( T3 ) , mothers in the PSST group continued to show significant improvements in mood , anxiety , and post-traumatic stress ; mothers in the NDS group showed no further significant gains . CONCLUSION PSST is an effective and specific intervention whose beneficial effects continue to grow after the intervention ends . In contrast , NDS is an effective intervention while it is being administered , but its benefits plateau when active support is removed . Therefore , teaching coping skills at diagnosis has the potential to facilitate family resilience over the entire course of treatment |
10,411 | 26,189,925 | High- quality evidence supports the effect of vitamin E , TZDs , and obeticholic acid over placebo in improving ballooning degeneration .
All four interventions seemed to have at least moderate- quality evidence over placebo to improve steatosis .
Moderate- quality evidence supports that TZDs , pentoxifylline , and obeticholic acid decrease lobular inflammation .
All the head-to-head comparisons were supported by very-low- quality evidence except for superiority of TZDs over vitamin E on improving steatosis and lobular inflammation , which had moderate- quality evidence .
Based on direct and network meta- analysis , pentoxifylline and obeticholic acid improve fibrosis , and vitamin E , TZDs , and obeticholic acid improve ballooning degeneration in patients with NASH . | UNLABELLED We performed a Bayesian network meta- analysis combining direct and indirect treatment comparisons to assess the comparative effectiveness of pharmacological agents for the treatment of nonalcoholic steatohepatitis ( NASH ) . | BACKGROUND / AIMS Non-Alcoholic Steatohepatitis ( NASH ) is a chronic liver disease frequently associated with insulin resistance and type 2 diabetes mellitus ( T2DM ) . Pioglitazone reverses the metabolic and histological abnormalities of patients with impaired glucose tolerance or T2DM and NASH , but also leads to weight gain . To underst and the nature of weight gain associated with pioglitazone treatment in NASH we analyzed 35 patients who completed tests for determination of whole body fat ( WBF ) and total body water ( TBW ) . METHODS Twenty-one patients received pioglitazone and 14 placebo in a double-blind , r and omized fashion for a period of 6 months . WBF and TBW were measured before and after treatment using DXA , a water dilution technique and bioimpedance . RESULTS Pioglitazone increased body weight ( from 93.6+/-4.2 to 96.1+/-4.5 kg , p<0.003 ) and WBF measured with DXA ( from 32.9+/-2.1 to 35.4+/-2.5 kg , p<0.002 ) while no changes were seen with placebo . Total body water was not altered significantly either after pioglitazone ( from 45.4+/-2.3 to 45.6+/-2.7 l , p = NS ) or placebo . Muscle hydration and extracellular water were unchanged both by pioglitazone and placebo treatments . CONCLUSIONS Six months of pioglitazone treatment in patients with NASH is associated with weight gain that is attributable to an increase in adipose tissue mass and not to water retention BACKGROUND / AIMS Despite a proposed role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis , antioxidant approaches have not been investigated sufficiently in the therapy of nonalcoholic steatohepatitis . Our aim was to determine whether vitamin E plus C therapy is effective in normalization of liver enzymes compared to ursodeoxycholic acid treatment in patients with fatty liver disease . METHODS This was an open-labeled , prospect i ve , r and omized study enrolling patients with histologically proven fatty liver disease who had chronically elevated alanine aminotransferase , despite a three-month reducing diet . Patients consuming alcohol ( more than 20 g/day ) were excluded . The patients were r and omly prescribed either oral vitamin E ( 600 IU/day ) plus vitamin C ( 500 mg/day ) or ursodeoxycholic acid ( 10 mg/kg/day ) . Patients were r and omized as two groups to receive vitamin E plus vitamin C combination ( 28 patients , 10 F ) or ursodeoxycholic acid treatment ( 29 patients , 13 F ) . RESULTS There was no significant change in body mass index before and after the treatment in both groups . At the end of six months of therapy , serum aspartate aminotransferase and aminotransferase levels significantly decreased in both treatment options . Vitamin E and C combination was more efficacious on serum aminotransferase levels than ursodeoxycholic acid , but the difference was not significant . Alanine aminotransferase decreased to normal levels in 17 of 27 ( 63 % ) and in 16 of 29 patients ( 55 % ) , respectively , in the two groups . Gamma-glutamyl transpeptidase decreased in patients receiving ursodeoxycholic acid , but no change was obtained in the vitamin-treated patients . CONCLUSIONS Vitamin E plus C combination treatment is a safe , inexpensive and effective treatment option in patients with fatty liver disease , with results comparable to those obtained with ursodeoxycholic acid . Since more effective new therapeutic options are lacking , patients with fatty liver disease should be encouraged to take vitamin E and C supplements , which are safe and affordable BACKGROUND No pharmacologic therapy has conclusively proved to be effective for the treatment of nonalcoholic steatohepatitis , which is characterized by insulin resistance , steatosis , and necroinflammation with or without centrilobular fibrosis . Pioglitazone is a thiazolidinedione that ameliorates insulin resistance and improves glucose and lipid metabolism in type 2 diabetes mellitus . METHODS We r and omly assigned 55 patients with impaired glucose tolerance or type 2 diabetes and liver biopsy-confirmed nonalcoholic steatohepatitis to 6 months of treatment with a hypocaloric diet ( a reduction of 500 kcal per day in relation to the calculated daily intake required to maintain body weight ) plus pioglitazone ( 45 mg daily ) or a hypocaloric diet plus placebo . Before and after treatment , we assessed hepatic histologic features , hepatic fat content by means of magnetic resonance spectroscopy , and glucose turnover during an oral glucose tolerance test ( [14C]glucose given with the oral glucose load and [3H]glucose given by intravenous infusion ) . RESULTS Diet plus pioglitazone , as compared with diet plus placebo , improved glycemic control and glucose tolerance ( P<0.001 ) , normalized liver aminotransferase levels as it decreased plasma aspartate aminotransferase levels ( by 40 % vs. 21 % , P=0.04 ) , decreased alanine aminotransferase levels ( by 58 % vs. 34 % , P<0.001 ) , decreased hepatic fat content ( by 54 % vs. 0 % , P<0.001 ) , and increased hepatic insulin sensitivity ( by 48 % vs. 14 % , P=0.008 ) . Administration of pioglitazone , as compared with placebo , was associated with improvement in histologic findings with regard to steatosis ( P=0.003 ) , ballooning necrosis ( P=0.02 ) , and inflammation ( P=0.008 ) . Subjects in the pioglitazone group had a greater reduction in necroinflammation ( 85 % vs. 38 % , P=0.001 ) , but the reduction in fibrosis did not differ significantly from that in the placebo group ( P=0.08 ) . Fatigue and mild lower-extremity edema developed in one subject who received pioglitazone ; no other adverse events were observed . CONCLUSIONS In this proof-of-concept study , the administration of pioglitazone led to metabolic and histologic improvement in subjects with nonalcoholic steatohepatitis . Larger controlled trials of longer duration are warranted to assess the long-term clinical benefit of pioglitazone . ( Clinical Trials.gov number , NCT00227110 [ Clinical Trials.gov ] . ) OBJECTIVE Hepatic steatosis is a common complication in patients with lipodystrophies and can lead to cirrhosis . There is no proven effective therapy for hepatic steatosis , but cholic acid ( CA ) , a farnesoid X receptor agonist , has previously been shown to reduce hepatic triglyceride ( TG ) content in mice and serum TG in humans . Our objective was to assess clinical efficacy and tolerability of CA therapy in patients with lipodystrophy and hepatic steatosis . DESIGN A r and omized , double-blind , placebo-controlled , crossover study . METHODS Eighteen patients with genetic or autoimmune lipodystrophies and elevated hepatic TG content participated in the study . The intervention was CA ( 15 mg/kg per day ) compared with placebo for a period of 6 months each . Hepatic TG content , the primary outcome variable , was measured with (1)H magnetic resonance spectroscopy at baseline and at 3 and 6 months during each study period . Levels of serum alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) , gamma-glutamyl transpeptidase ( GGT ) , and TG were secondary end points of the study . RESULTS Compared with placebo , CA did not reduce ( median ( interquartile range ) hepatic TG content ( 14.8 % ( 9.4 - 19.0 % ) vs 15.9 % ( 10.5 - 26.5 % ) respectively ; P=0.42 ) or serum TG ( ( 340 mg/dl ( 233 - 433 mg/dl ) vs 390 mg/dl ( 233 - 595 mg/dl ) respectively ; P=0.45 ) ) . CA therapy also did not change AST , ALT , or GGT levels . Two patients developed diarrhea and excessive flatus while taking CA and these symptoms resolved after reducing the dose of CA . CONCLUSION CA was well tolerated but did not reduce hepatic TG content in patients with lipodystrophy Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed BACKGROUND & AIMS Nonalcoholic steatohepatitis ( NASH ) is a leading cause of chronic liver disease for which there is limited therapy available . Insulin sensitizing , anti-inflammatory , and antifibrotic properties of thiazolidinediones support their use in treating NASH . We have evaluated pioglitazone in the treatment of nondiabetic patients with NASH . METHODS We r and omized 74 nondiabetic patients ( 45 men ; median age , 54 y ) with histologically proven NASH to 12 months of st and ard diet , exercise , and either placebo or pioglitazone ( 30 mg/day ) . Sixty-one patients ( 30 placebo , 31 pioglitazone ) had liver biopsies both at the beginning and the end of the study . RESULTS Compared with placebo , pioglitazone therapy was associated with an increase in weight ( mean change , -0.55 vs + 2.77 kg ; P = .04 ) and a reduction in glucose ( + 0.4 vs -0.1 mmol/L ; P = .02 ) , HbA1c ( + 0.16 % vs -0.18 % ; P = .006 ) , insulin C peptide level ( + 42 vs -78 pmol/L ; P = .02 ) , alanine aminotransferase level ( -10.9 vs -36.2 u/L ; P = .009 ) , gamma-glutamyltransferase level ( -9.4 vs -41.2 u/L ; P = .002 ) , and ferritin ( -11.3 vs -90.5 microg/L ; P = .01 ) . Histologic features including hepatocellular injury ( P = .005 ) , Mallory-Denk bodies ( P = .004 ) , and fibrosis ( P = .05 ) were reduced in patients treated with pioglitazone compared with those in the placebo group . CONCLUSIONS Pioglitazone therapy over a 12-month period in nondiabetic subjects with NASH result ed in improvements in metabolic and histologic parameters , most notably liver injury and fibrosis . Larger extended trials are justified to assess the long-term efficacy of pioglitazone in this patient group INTRODUCTION The burden of non-alcoholic steatohepatitis ( NASH ) is growing and current pharmacologic treatments are limited by side effects and inconsistent efficacy . Pilot studies suggest that pentoxifylline ( PTX ) can reduce liver injury in patients with NASH . OBJECTIVE We sought to determine the tolerability of PTX and its effect on aminotransferases and liver histology in patients with NASH . MATERIAL AND METHODS Thirty patients with biopsy proven NASH were r and omized in a 2:1 fashion to receive 1,200 mg PTX or placebo for 12 months . Metabolic parameters , aminotransferases , liver histology and hepatic gene expression changes were compared . RESULTS At baseline the groups were similar . Adverse events were mild , most frequently headache and abdominal cramps , and did not differ between groups ( p = NS ) . After 12 months , ALT and AST decreased from 92 ± 12 IU/L to 67 ± 13 IU/L and 67 ± 6 IU/L to 47 ± 6 IU/L ( p < 0.05 ) , respectively in patients treated with PTX . No significant effect was seen with placebo . Steatosis and cellular ballooning improved in the PTX group ( p < 0.05 ) , whereas no histological feature of steatohepatitis improved with placebo . However , between groups comparison of both biochemical and histological features were nonsignificant . CONCLUSION Pentoxifylline is safe , well tolerated and improves transaminases and histology in patients with NASH when compared to baseline and may be a reasonable therapeutic modality for the treatment of NASH . However PTX failed to reduce transaminases compared to placebo and did not positively affect any of the metabolic markers postulated to contribute to NASH . Although animal data and small pilot studies in humans have suggested that PTX may be effective as a treatment for NASH , translating this therapy to clinical practice may prove challenging BACKGROUND & AIMS Nonalcoholic steatohepatitis ( NASH ) is a liver disease that complicates insulin-resistant states . This trial tested the efficacy and safety of rosiglitazone , an insulin-sensitizing agent , in patients with NASH . METHODS Sixty-three patients with histologically proven NASH were r and omly assigned to receive rosiglitazone ( 4 mg/day for the first month and 8 mg/day thereafter ; n = 32 ) or placebo ( n = 31 ) for 1 year . Liver biopsy was performed at the end of treatment . End points were improvement in the histologic score of steatosis , normalization of serum transaminase levels , and improvement in necroinflammation and fibrosis . RESULTS More patients treated with rosiglitazone than receiving placebo had improved steatosis ( 47 % vs 16 % ; P = .014 ) and normalized transaminase levels ( 38 % vs 7 % ; P = .005 ) , although only half of patients responded . There was no improvement in other histologic lesions , including fibrosis , and a composite score of activity , the nonalcoholic fatty liver disease activity score . Improvement of steatosis correlated with reduction of transaminase levels ( r = 0.36 ; P < .005 ) , improvement in insulin sensitivity ( r = 0.34 ; P = .008 ) , and increase in adiponectin levels ( r = -0.54 ; P < .01 ) but not with weight variations . Independent predictors of response were rosiglitazone treatment , the absence of diabetes , and massive steatosis . Weight gain was the main adverse effect ( mean gain of 1.5 kg in the rosiglitazone group vs -1 kg in the placebo group ; P < .01 ) , and painful swollen legs was the main reason for dose reduction/discontinuation . Serum hemoglobin level was slightly but significantly reduced . There was no hepatic toxicity . CONCLUSIONS In patients with NASH , rosiglitazone improves steatosis and transaminase levels despite weight gain , an effect related to an improvement in insulin sensitivity . However , there is no improvement in other parameters of liver injury BACKGROUND & AIMS Insulin resistance and oxidative stress contribute to the pathogenesis of nonalcoholic steatohepatitis ( NASH ) . We conducted a pilot study for the following reasons : ( 1 ) to test the hypothesis that a combination of an antioxidant ( vitamin E ) and an insulin sensitizer ( pioglitazone ) would be superior to vitamin E alone for the treatment of NASH , and ( 2 ) to define the effects of these interventions on insulin-sensitive metabolic functions and correlate the effects with changes in liver histology . METHODS A r and omized prospect i ve trial was performed to compare the efficacy and safety of vitamin E alone ( 400 IU/day ) vs. vitamin E ( 400 IU/day ) and pioglitazone ( 30 mg/day ) in nondiabetic , noncirrhotic subjects with NASH . Metabolic functions were assessed by a 2-step , hyperinsulinemic ( 10 and 40 mU/m2/min ) euglycemic clamp . RESULTS A total of 10 patients were r and omized to each arm . Two patients on combination therapy discontinued treatment ; one because of pregnancy and the other because of hepatotoxicity . Treatment with vitamin E only produced a significant decrease in steatosis ( mean grade , 2.2 vs. 1.4 ; P < .02 ) . Compared with baseline , combination therapy produced a significant decrease in steatosis ( mean , 2.3 vs. 1 ; P < .002 ) , cytologic ballooning ( 1.3 vs. 0.2 ; P < .01 ) , Mallory 's hyaline ( 0.7 vs. 0.2 ; P < .04 ) , and pericellular fibrosis ( 1.2 vs. 0.6 ; P < .03 ) . Although vitamin E had no significant effects , combination therapy produced a significant increase in metabolic clearance of glucose and a decrease in fasting free fatty acid ( FFA ) and insulin . The decrease in fasting FFA and insulin independently predicted improvement in hepatic steatosis and cytologic ballooning . CONCLUSIONS A combination of vitamin E and pioglitazone produces a greater improvement in NASH histology . The improvement in steatosis and cytologic ballooning are related to treatment-associated decreases in fasting FFA and insulin levels The only currently recommended treatment for nonalcoholic fatty liver disease ( NAFLD ) is lifestyle modification . Preliminary studies of silybin showed beneficial effects on liver function . Realsil ( RA ) comprises the silybin phytosome complex ( silybin plus phosphatidylcholine ) coformulated with vitamin E. We report on a multicenter , phase III , double-blind clinical trial to assess RA in patients with histologically documented NAFLD . Patients were r and omized 1:1 to RA or placebo ( P ) orally twice daily for 12 months . Prespecified primary outcomes were improvement over time in clinical condition , normalization of liver enzyme plasma levels , and improvement of ultrasonographic liver steatosis , homeostatic model assessment ( HOMA ) , and quality of life . Secondary outcomes were improvement in liver histologic score and /or decrease in NAFLD score without worsening of fibrosis and plasma changes in cytokines , ferritin , and liver fibrosis markers . We treated 179 patients with NAFLD ; 36 were also HCV positive . Forty-one patients were prematurely withdrawn and 138 patients analyzed per protocol ( 69 per group ) . Baseline patient characteristics were generally well balanced between groups , except for steatosis , portal infiltration , and fibrosis . Adverse events ( AEs ) were generally transient and included diarrhea , dysgeusia , and pruritus ; no serious AEs were recorded . Patients receiving RA but not P showed significant improvements in liver enzyme plasma levels , HOMA , and liver histology . Body mass index normalized in 15 % of RA patients ( 2.1 % with P ) . HCV-positive patients in the RA but not the P group showed improvements in fibrogenesis markers . This is the first study to systematic ally assess silybin in NAFLD patients . Treatment with RA but not P for 12 months was associated with improvement in liver enzymes , insulin resistance , and liver histology , without increases in body weight . These findings warrant further investigation OBJECTIVE : Nonalcoholic steatohepatitis ( NASH ) is a common cause of liver disease . Although usually indolent , this disease can progress to cirrhosis in some patients . There is currently no proven medical therapy for the treatment of NASH . The aim of our study was to evaluate the efficacy of combination α-tocopherol ( vitamin E ) and vitamin C in reducing histologic inflammation and fibrosis . METHODS : This was a prospect i ve , double-blind , r and omized , placebo-controlled trial with a total enrollment of 49 patients ; 45 patients completed the study . All patients were r and omized to receive either vitamins E and C ( 1000 IU and 1000 mg , respectively ) or placebo daily for 6 months , based on their initial histologic diagnosis of NASH . Additionally , all patients were given st and ard weight-loss counseling and encouraged to follow a low fat diet ( < 30 fat g/day ) . The pre- and posttreatment liver biopsies were review ed by a single pathologist , who was blinded to the patient 's medication . Biopsies were scored based on a modification of the scoring system published by Brunt et al. ( Am J Gastroenterol 1999;94:2467–74 ) . A score of 0–4 was possible for fibrosis , and a score of 0–6 was possible for inflammation and hepatocyte degeneration and necrosis . In addition , body mass index , glycohemoglobin , lipids , and liver enzymes were followed throughout the study . RESULTS : Forty-five patients completed 6 months of therapy without significant side effects . Vitamin treatment result ed in a statistically significant improvement in fibrosis score ( p = 0.002 ) . No changes were noted in inflammation with treatment . CONCLUSIONS : Vitamin E and vitamin C , in the doses used in this study , were well tolerated and were effective in improving fibrosis scores in NASH patients . No improvement in necroinflammatory activity or ALT was seen with this combination of drug therapy . A larger , multicenter , longer-term trial with vitamin E and vitamin C seems to be warranted UNLABELLED The primary aim of this study was to compare the effects of pentoxifylline ( PTX ) versus placebo on the histological features of nonalcoholic steatohepatitis ( NASH ) . In all , 55 adults with biopsy-confirmed NASH were r and omized to receive PTX at a dose of 400 mg three times a day ( n = 26 ) or placebo ( n = 29 ) over 1 year . The primary efficacy endpoint was defined as improvement in histological features of NASH through reduction in steatosis , lobular inflammation , and /or hepatocellular ballooning as reflected by a decrease of ≥ 2 points in the nonalcoholic fatty liver disease ( NAFLD ) activity score ( NAS ) . After 1 year , intention-to-treat analysis showed a decrease of ≥ 2 points in the NAS in 38.5 % of patients on PTX versus 13.8 % of those on placebo ( P = 0.036 ) . Per protocol analysis , a decrease of ≥ 2 points in the NAS from baseline was observed in 50 % of the patients on PTX versus 15.4 % of those on placebo ( P = 0.01 ) . The mean change in NAS score from baseline was -1.6 in the PTX group , versus -0.1 in the placebo group ( P < 0.001 ) . PTX significantly improved steatosis ( mean change in score -0.9 versus -0.04 with placebo , P < 0.001 ) and lobular inflammation ( median change -1 versus 0 with placebo , P = 0.02 ) . No significant effects in hepatocellular ballooning were observed . PTX also improved liver fibrosis ( mean change in fibrosis score was -0.2 among those on PTX versus + 0.4 among those on placebo , P = 0.038 ) . Although not statistically significant ( P = 0.17 ) , improvement in fibrosis was observed in a greater proportion ( 35 % ) of patients in the PTX group compared to placebo ( 15 % ) . Adverse effects were similar in both groups . CONCLUSION PTX improved histological features of NASH compared to placebo . PTX was well tolerated in patients with NASH OBJECTIVES : Metformin proved useful in the treatment of nonalcoholic fatty liver disease ( NAFLD ) , but its superiority over nutritional treatment and antioxidants has never been demonstrated . We aim ed to compare the usefulness of metformin versus prescriptive diet or vitamin E. METHODS : In an open label , r and omized trial , nondiabetic NAFLD patients were given metformin ( 2 g/day ; n = 55 ) for 12 months . The control cases were given either vitamin E ( 800 IU/day ; n = 28 ) or were treated by a prescriptive , weight-reducing diet ( n = 27 ) . Outcome measures were liver enzymes , insulin resistance ( homeostasis model assessment ) , parameters of the metabolic syndrome , and histology . RESULTS : Aminotransferase levels improved in all groups , in association with weight loss . The effects in the metformin arm were larger ( p < 0.0001 ) , and alanine aminotransferase normalized in 56 % of cases ( odds ratio ( OR ) versus . controls , 3.11 ; 95 % confidence interval ( CI ) , 1.56–6.20 ; p = 0.0013 ) . In multivariate analysis , metformin treatment was associated with higher rates of aminotransferase normalization , after correction for age , gender , basal aminotransferases , and change in body mass index ( OR , 5.98 ; 95 % CI , 2.05–17.45 ) . Differences were maintained when the two control groups were separately analyzed . The distribution of positive criteria for the metabolic syndrome was reduced only in the metformin arm ( p = 0.001 , signed rank test ) . A control biopsy in 17 metformin-treated cases ( 14 nonresponders ) showed a significant decrease in liver fat ( p = 0.0004 ) , necroinflammation , and fibrosis ( p = 0.012 for both ) . No side effects were observed during metformin treatment . CONCLUSIONS : Metformin treatment is better than a prescriptive diet or vitamin E in the therapy of NAFLD patients receiving nutritional counseling . Limited histological data support an association between improved aminotransferases and biopsy findings , which require confirmation in a double-blind trial with appropriate statistical power based on liver histology UNLABELLED Medication combinations that improve the efficacy of thiazolidinediones or ameliorate weight-gain side effects of therapy represent an attractive potential treatment for ( NASH ) . The aim of this r and omized , open-label trial was to assess the efficacy of rosiglitazone and metformin in combination versus rosiglitazone and losartan , compared to rosiglitazone alone , after 48 weeks of therapy . A total of 137 subjects with biopsy-proven NASH were enrolled and r and omly assigned to receive either 4 mg twice-daily of rosiglitazone , 4 mg of rosiglitazone and 500 mg of metformin twice-daily , or 4 mg of rosiglitazone twice-daily and 50 mg of losartan once-daily for 48 weeks . Patients were screened for other etiologies of chronic liver disease , including daily alcohol intake in excess of 20 g. Repeat liver biopsy was performed after 48 weeks of therapy and review ed in a blinded fashion by a single expert hepatopathologist . The primary aim of the study was to assess for differences between treatment groups in the improvement of steatosis , hepatocellular inflammation , and fibrosis . In total , 108 subjects completed the trial . Primary outcome revealed no significant difference between treatment groups in all histologic parameters ( steatosis , P = 0.137 ; hepatocellular inflammation , P = 0.320 ; fibrosis , P = 0.229 ) . Overall improvement in steatosis , hepatocellular inflammation , ballooning degeneration , and fibrosis was observed ( P ≤ 0.001 ) . Serum aminotransferases were reduced in all three groups ( P < 0.001 within treatment , P > 0.05 between groups ) . Metformin did not significantly mitigate weight gain ( P = 0.051 ) . CONCLUSIONS Forty-eight weeks of combination therapy with rosiglitazone and metformin or rosiglitazone and losartan confers no greater benefit than rosiglitazone alone with respect to histopathology PURPOSE To conduct a r and omized clinical trial to determine whether the combination of pentoxifylline ( PTX ) and vitamin E given for 6 months after breast/chest wall irradiation effectively prevents radiation-induced fibrosis ( RIF ) . METHODS AND MATERIAL S Fifty-three breast cancer patients with localized disease were enrolled and r and omized to treatment with oral PTX 400 mg 3 times daily and oral vitamin E 400 IU daily for 6 months after radiation ( n=26 ) , or st and ard follow up ( n=27 ) . Tissue compliance meter ( TCM ) measurements were obtained at 18 months to compare tissue compliance in the irradiated and untreated breast/chest wall in treated subjects and controls . Measurements were obtained at 2 mirror image sites on each breast/chest wall , and the average difference in tissue compliance was scored . Differences in TCM measurements were compared using a t test . Subjects were followed a minimum of 2 years for local recurrence , disease-free survival , and overall survival . RESULTS The mean difference in TCM measurements in the 2 groups was 0.88 mm , median of 1.00 mm ( treated ) and 2.10 mm , median of 2.4 mm ( untreated ) . The difference between the 2 groups was significant ( P=.0478 ) . Overall survival ( 100 % treated , 90.6 % controls at 5 years ) and disease-free survival ( 96.2 % treated , 86.8 % controls at 5 years ) were not significantly different in the 2 groups . CONCLUSIONS This study of postirradiation breast cancer patients treated with PTX/vitamin E or st and ard follow-up indicated a significant difference in radiation-induced fibrosis as measured by TCM . There was no observed impact on local control or survival within the first 2 years of follow-up . The treatment was safe and well tolerated . Pentoxifylline/vitamin E may be clinical ly useful in preventing fibrosis after radiation in high-risk patients BACKGROUND The bile acid derivative 6-ethylchenodeoxycholic acid ( obeticholic acid ) is a potent activator of the farnesoid X nuclear receptor that reduces liver fat and fibrosis in animal models of fatty liver disease . We assessed the efficacy of obeticholic acid in adult patients with non-alcoholic steatohepatitis . METHODS We did a multicentre , double-blind , placebo-controlled , parallel group , r and omised clinical trial at medical centres in the USA in patients with non-cirrhotic , non-alcoholic steatohepatitis to assess treatment with obeticholic acid given orally ( 25 mg daily ) or placebo for 72 weeks . Patients were r and omly assigned 1:1 using a computer-generated , central ly administered procedure , stratified by clinical centre and diabetes status . The primary outcome measure was improvement in central ly scored liver histology defined as a decrease in non-alcoholic fatty liver disease activity score by at least 2 points without worsening of fibrosis from baseline to the end of treatment . A planned interim analysis of change in alanine aminotransferase at 24 weeks undertaken before end-of-treatment ( 72 weeks ) biopsies supported the decision to continue the trial ( relative change in alanine aminotransferase -24 % , 95 % CI -45 to -3 ) . A planned interim analysis of the primary outcome showed improved efficacy of obeticholic acid ( p=0·0024 ) and supported a decision not to do end-of-treatment biopsies and end treatment early in 64 patients , but to continue the trial to obtain the 24-week post-treatment measures . Analyses were done by intention-to-treat . This trial was registered with Clinical Trials.gov , number NCT01265498 . FINDINGS Between March 16 , 2011 , and Dec 3 , 2012 , 141 patients were r and omly assigned to receive obeticholic acid and 142 to placebo . 50 ( 45 % ) of 110 patients in the obeticholic acid group who were meant to have biopsies at baseline and 72 weeks had improved liver histology compared with 23 ( 21 % ) of 109 such patients in the placebo group ( relative risk 1·9 , 95 % CI 1·3 to 2·8 ; p=0·0002 ) . 33 ( 23 % ) of 141 patients in the obeticholic acid developed pruritus compared with nine ( 6 % ) of 142 in the placebo group . INTERPRETATION Obeticholic acid improved the histological features of non-alcoholic steatohepatitis , but its long-term benefits and safety need further clarification . FUNDING National Institute of Diabetes and Digestive and Kidney Diseases , Intercept Pharmaceuticals BACKGROUND & AIMS Nonalcoholic steatohepatitis ( NASH ) is a frequent liver disease that can progress to cirrhosis and for which there is no recognized therapy . UDCA and vitamin E have been considered separately as therapeutic options and have not been shown to be effective . This study tested their combination . METHODS Patients with elevated aminotransferase levels and drinking less than 40 g alcohol/week with biopsy-proven NASH were r and omly assigned to receive UDCA 12 - 15 mg.kg-1.day-1 with vitamin E 400 IU twice a day ( UDCA/Vit E ) , UDCA with placebo ( UDCA/P ) , or placebo/placebo ( P/P ) . After 2 years , they underwent a second liver biopsy . Biopsy specimens were collected , blinded , and scored by a single liver pathologist . RESULTS Forty eight patients were included , 15 in the UDCA/Vit E group , 18 in the UDCA/P group , and 15 in the P/P group ; 8 patients dropped out , none because of side effects . Baseline parameters were not significantly different between the 3 groups . Body mass index remained unchanged during the study . Serum aspartate aminotransferase ( AST ) and alanine aminotransferase ( ALT ) levels diminished significantly in the UDCA/Vit E group . Neither the AST nor the ALT levels improved in the P/P group and only the ALT levels in the UDCA/P group . Histologically , the activity index was unchanged at the end of the study in the P/P and UDCA/P groups , but it was significantly better in the UDCA/Vit E group , mostly as a result of regression of steatosis . CONCLUSIONS Two years of treatment with UDCA in combination with vitamin E improved laboratory values and hepatic steatosis of patients with NASH . Larger trials are warranted UNLABELLED Pentoxifylline ( PTX ) improved the histological features of nonalcoholic steatohepatitis ( NASH ) in a recent r and omized placebo-controlled trial . However , the underlying mechanism responsible for the beneficial effects of PTX in NASH remains unidentified . A key role of lipid oxidation in the pathogenesis and progression of NASH has been established . PTX is known to decrease free-radical-mediated oxidative stress and inhibit lipid oxidation . The primary aim of this study was to evaluate the effects of PTX on levels of lipid oxidation products in patients with NASH . Levels of multiple structurally specific oxidized fatty acids including hydroxy-octadecadienoic acids ( HODEs ) , oxo-octadecadienoic acids ( oxoODEs ) , and hydroxy-eicosatetraenoic acids ( HETEs ) were quantified by mass spectrometry in plasma obtained at baseline and at study completion in patients who completed 1 year of therapy with PTX or placebo in a r and omized controlled trial . Therapy with PTX result ed in significant decreases in 9-HODE and 13-oxoODE , oxidized lipid products of linoleic acid ( LA ) linked to histological severity in nonalcoholic fatty liver disease . Similarly , PTX therapy was associated with significant decreases in 8-HETE , 9-HETE , and 11-HETE compared to placebo . Statistically significant correlations were demonstrated between the decrease in HODEs and oxoODEs and improved histological scores of fibrosis and between the decrease in HETEs and improved lobular inflammation . CONCLUSION Therapy with PTX compared to placebo was associated with a significant reduction of oxidized fatty acids . This novel evidence supports that the beneficial effects of PTX in patients with NASH are likely partly mediated through decreasing lipid oxidation , largely free-radical-mediated lipid oxidation . Additionally , this is the first report on the link between decreased oxidized lipid products and improved histological disease in the setting of a therapeutic trial in NASH BACKGROUND Pioglitazone ( Pio ) treatment induces weight gain in Type 2 diabetes mellitus ( T2DM ) , which could worsen hepatic lipid accumulation , and alter adiponectin and high-sensitivity C-reactive protein ( hs-CRP ) . OBJECTIVE To compare changes in hepatic lipid , serum adiponectin and hs-CRP in diabetics treated with Pio ( with and without weight gain ) against metformin ( Met ) treatment , which produces weight loss . DESIGN Fifty-one men and women with T2DM , naive to thiazolidinediones , entered a 16-week , open-label , parallel arm study , where participants were r and omized to one of three groups : ( 1 ) Pio plus the American Diabetes Association diet ( Pio+ADA ) ; ( 2 ) Pio plus a portion control weight loss diet ( Pio+PC ) , or ( 3 ) metformin plus ADA diet ( Met+ADA ) . METHODS Hepatic lipid was assessed with abdominal computed tomography ( CT ) and the serum adiponectin and hs-CRP by enzyme-linked immunosorbent assay at baseline and study end . RESULTS Forty-eight subjects completed the study . The Pio+ADA group gained ( mean+/-S.E.M. ) 2.15+/-1.09 kg , while Pio+PC and Met+ADA group lost -2.59+/-1.25 and -3.21+/-0.7 kg , respectively . Pio-treated groups ( Pio+ADA and Pio+PC ) significantly decreased hepatic fat as indicated by increased liver density on CT scan [ 10.1+/-2.4 : 11.4+/-1.0 Hounsfield units ( HU ) ] , compared with Met+ADA group ( -2.4+/-3.1 HU ) . The Pio groups demonstrated significantly increased serum adiponectin , ( 8.6+/-1.5 ; 7.4+/-1.6 microg/ml ) independent of weight change , compared to Met+ADA ( -0.14+/-0.6 microgm/ml ) group which lost weight . Serum hs-CRP decreased in groups showing weight loss ( Pio+PC , -3.1+/-1.7 mg/l ; Met+ADA , -1.5+/-1.2 mg/l ) compared to Pio+ADA ( 1.8+/-3.0 mg/l ) group that gained weight . CONCLUSIONS Pio treatment in T2DM significantly reduced hepatic lipid and increased adiponectin independent of weight change , while decreasing hs-CRP with weight loss |
10,412 | 28,149,476 | Major and Brauchli showed no significant differences in torque expression of active and passive SL brackets .
Conventionally ligated brackets presented with highest torque expression compared to SL brackets .
Minor difference was recorded in a torque expression of active and passive SL brackets . | BACKGROUND To evaluate the torque expression of self ligating ( SL ) orthodontic brackets and conventionally ligated brackets and the torque expression in active and passive SL brackets . | INTRODUCTION In this prospect i ve clinical study , we assessed the relative speed of archwire changes , comparing self-ligating brackets with conventional elastomeric ligation methods , and further assessed this in relation to the stage of orthodontic treatment represented by different wire sizes and types . METHODS The time taken to remove and ligate archwires for 131 consecutive patients treated with either self-ligating or conventional brackets was prospect ively assessed . The study was carried out in the orthodontic department of a district general hospital in the United Kingdom . The main outcome measure was the time to remove or place elastomeric ligatures or open/close self-ligating brackets for 2 matched groups of fixed appliance patients : Damon2 self-ligating bracket ( SDS Ormco , Orange , Calif ) and a conventional mini-twin bracket ( Orthos , SDS Ormco ) . The relative effects of various wire sizes and material s on ligation times were investigated . The study was carried out by 1 operator experienced in the use of self-ligating and conventional brackets . RESULTS The Damon2 self-ligating system had a significantly shorter mean archwire ligation time for both placing ( P < .001 ) and removing ( P < .01 ) wires compared with the conventional elastomeric system . Ligation of an archwire was approximately twice as quick with the self-ligating system . Opening a Damon slide was on average 1 second quicker per bracket than removing an elastic from the mini-twin brackets , and closing a slide was 2 seconds faster per bracket . This difference in ligation time between the Damon2 and the conventional mini-twin brackets became more marked for larger wire sizes used in later treatment stages . CONCLUSIONS The type of bracket and the size of wire used are statistically significant predictors for speed of ligation and chairside time . The self-ligating system offered quicker and arguably more efficient wire removal and placement for most orthodontic treatment stages |
10,413 | 26,154,169 | METHODS We performed a systematic review of empirical research via PubMed and Google Scholar with keywords including ' addiction ' , ' exteroception ' , ' precuneus ' , and ' self-awareness ' , to identify human behavioral and neuroimaging studies that report mechanisms of self-awareness in healthy population s , and altered self-awareness processes , specifically exteroception , in addicted population s. RESULTS Results demonstrate that exteroceptive processes play a critical role in conditioned cue response in addiction and serve as targets for interventions such as mindfulness training .
Further , a hub of the default mode network , namely , the precuneus , is ( i ) consistently implicated in exteroceptive processes , and ( ii ) widely demonstrated to have increased activation and connectivity in addicted population s. CONCLUSION Heightened exteroceptive processes may underlie cue-elicited craving , which in turn may lead to the maintenance and worsening of substance use disorders . | BACKGROUND Exteroception involves processes related to the perception of environmental stimuli important for an organism 's ability to adapt to its environment .
As such , exteroception plays a critical role in conditioned response .
In addiction , behavioral and neuroimaging studies show that the conditioned response to drug-related cues is often associated with alterations in brain regions including the precuneus/posterior cingulate cortex , an important node within the default mode network dedicated to processes such as self-monitoring .
OBJECTIVE This review aim ed to summarize the growing , but largely fragmented , literature that supports a central role of exteroceptive processes in addiction . | Using fMRI , our group previously found that after a sip of alcohol and exposure to alcohol beverage pictures , alcoholics compared to social drinkers had increased differential brain activity in the prefrontal cortex and anterior thalamus . This study extends this earlier work with several improvements including imaging the entire brain ( rather than the anterior half previously ) and recording craving , while the subjects viewed images within the scanner . In a Philips 1.5 T MRI scanner , 10 nontreatment-seeking alcoholics and 10 age-matched healthy social drinkers were given a sip of alcohol before viewing a 12 min r and omized presentation of pictures of alcoholic beverages , nonalcoholic beverages , and two different visual control tasks . During picture presentation , changes in regional brain activity were measured in 15 transverse T2 * -weighted blood oxygen level dependent slices . Subjects rated their urge to drink after each picture sequence . After a sip of alcohol , while viewing alcohol cues compared to viewing other beverage cues , the alcoholics , but not social drinkers , reported higher craving ratings and had increased activity in the prefrontal cortex and anterior limbic regions . Brain activity in the left nucleus accumbens , anterior cingulate , and left orbitofrontal cortex significantly correlated with subjective craving ratings in alcohol subjects but not in control subjects . This study suggests , as did our earlier study , that alcoholics and not social drinkers , when exposed to alcohol cues , have increased brain activity in areas that reportedly subserve craving for other addictive substances This pilot study tested the efficacy of a brief intervention using motivational interviewing ( MI ) plus mindfulness meditation ( MM ) to reduce marijuana use among young adult females . Thirty-four female marijuana users between the ages of 18 and 29 were r and omized to either the intervention group ( n = 22 ) , consisting of two sessions of MI-MM , or an assessment -only control group ( n = 12 ) . The participants ' marijuana use was assessed at baseline and at 1 , 2 , and 3 months posttreatment . Fixed-effects regression modeling was used to analyze treatment effects . Participants r and omized to the intervention group were found to use marijuana on 6.15 ( z = -2.42 , p = .015 ) , 7.81 ( z = -2.78 , p = .005 ) , and 6.83 ( z = -2.23 , p = .026 ) fewer days at Months 1 , 2 , and 3 , respectively , than controls . Findings from this pilot study provide preliminary evidence for the feasibility and effectiveness of a brief MI-MM for young adult female marijuana users BACKGROUND In alcohol-dependent patients , alcohol-associated cues elicit brain activation in mesocorticolimbic networks involved in relapse mechanisms . Cue-exposure based extinction training ( CET ) has been shown to be efficacious in the treatment of alcoholism ; however , it has remained unexplored whether CET mediates its therapeutic effects via changes of activity in mesolimbic networks in response to alcohol cues . In this study , we assessed CET treatment effects on cue-induced responses using functional magnetic resonance imaging ( fMRI ) . METHODS In a r and omized controlled trial , abstinent alcohol-dependent patients were r and omly assigned to a CET group ( n = 15 ) or a control group ( n = 15 ) . All patients underwent an extended detoxification treatment comprising medically supervised detoxification , health education , and supportive therapy . The CET patients additionally received nine CET sessions over 3 weeks , exposing the patient to his/her preferred alcoholic beverage . Cue-induced fMRI activation to alcohol cues was measured at pretreatment and posttreatment . RESULTS Compared with pretreatment , fMRI cue-reactivity reduction was greater in the CET relative to the control group , especially in the anterior cingulate gyrus and the insula , as well as limbic and frontal regions . Before treatment , increased cue-induced fMRI activation was found in limbic and reward-related brain regions and in visual areas . After treatment , the CET group showed less activation than the control group in the left ventral striatum . CONCLUSIONS The study provides first evidence that an exposure-based psychotherapeutic intervention in the treatment of alcoholism impacts on brain areas relevant for addiction memory and attentional focus to alcohol-associated cues and affects mesocorticolimbic reward pathways suggested to be pathophysiologically involved in addiction |
10,414 | 24,901,271 | The effect size was similar for the following subgroups : pain scores reported as means or medians and use of McGill compared with VAS pain scales .
A stratified analysis of trials including ring tubal ligation compared with clip tubal ligation showed the use of local anesthetic decreased pain substantially for both .
: Use of local anesthetic during laparoscopic tubal ligation substantially reduces postoperative pain up to 8 hours after surgery | OBJECTIVE : To assess the effectiveness of using local anesthesia during interval laparoscopic tubal ligation to control postoperative pain . | Outpatient surgery benefits patients only if postoperative sequelae are effectively treated . After laparoscopic tubal ligation ( TL ) intense pain and consequent postoperative nausea and vomiting ( PONV ) has been a problem delaying recovery and result ing in hospital admission The use of local anaesthetic has been shown to reduce the incidence of pain after laparoscopic sterilisation and the need for opioid analgesia from day surgery . We investigated a technique in which a catheter is placed in the pouch of Douglas allowing repeated administration of local anaesthetic in the postoperative period . Forty patients were r and omly allocated pre‐operatively into one of two groups to receive in a double‐blind manner either lignocaine 1 % or normal saline . Pain was assessed using visual analogue and subjective scoring systems . Postoperative pain scores were significantly reduced ( p < 0.05 ) after injection of lignocaine through the catheter . There were no complications related to the technique and no evidence of local anaesthetic toxicity . Lignocaine instilled into the Pouch of Douglas is an effective method for postoperative pain relief after laparoscopic sterilisation OBJECTIVE The intraperitoneal route of analgesia has been studied over the years for effective perioperative pain relief during minimally invasive surgery , but there were conflicting reports of the use of intraperitoneal analgesic administration and moreover there was no consensus regarding the dose and type of drugs used . We report a r and omized trial to assess the safety and effectiveness of intraperitoneal lignocaine as an intraoperative and postoperative analgesic in laparoscopic tubal ligation . STUDY DESIGN This is a double masked , r and omized parallel group placebo-controlled trial of women seeking laparoscopic sterilization under local anaesthesia at a university hospital . The intervention group and placebo group received 20 ml of 0.5 % lignocaine and 20 ml of isotonic saline intraperitoneally respectively . Allocation concealment was done by fixed block r and omization . The participating women , the surgeon , anaesthetist , technician and the doctor who assessed the pain score were masked to the type of intervention . Intraoperative and postoperative pain was assessed by visual analogue pain scale and the scores are expressed as mean difference ( 95 % confidence interval ) between groups . Our trial is registered with the Clinical Trials Registry , India ( http://www.ctri.nic.in/ , CTRI/2009/091/000072 ) . RESULTS Out of 200 women recruited , 196 were available for final analysis with 98 women in each arm . The mean difference in the intraoperative pain score at the time of tubal ligation was 3.5 cm ( 95 % CI 2.91 - 4.09 ) . The mean difference in the postoperative pain scores at half an hour was 2.9 ( 95 % CI 2.50 - 3.44 ) , 1h was 2.5 ( 95 % CI 2.08 - 3.00 ) and 3h was 1.2 ( 95 % CI 0.75 - 1.76 ) . There was no case of adverse reaction to lignocaine . CONCLUSION Our findings show that intraperitoneal instillation of lignocaine is a safe and effective method for perioperative pain relief during laparoscopic tubal occlusion performed under conscious sedation Narcotic requirements in 51 day-surgery patients following laparoscopic tubal occlusion were significantly reduced ( P less than .01 ) by the use of 1 % etidocaine 5 mL , dropped on each fallopian tube from uterus to fimbrias before tubal b and ing when compared with a control group of 51 day-surgery patients who had no topical anesthetic agent . All patients received general anesthesia . Although there was no significant difference in nausea rate , the incidence of vomiting was decreased . Eight of 51 patients ( 16 % ) having topical etidocaine and 19 of 51 ( 37 % ) who had no etidocaine vomited during the postoperative period . The frequency of overnight stay was significantly reduced in the topical etidocaine group of patients ( P less than or equal to .01 ) Objective To investigate the efficacy of applying 10 ml bupivacaine 0.5%versus normal saline to the fallopian tubes under direct vision during day case laparoscopic sterilisation under general anaesthesia OBJECTIVES To determine the minimum clinical ly significant difference in visual analog scale ( VAS ) pain scores for acute pain in the ED setting and to determine whether this difference varies with gender , age , or cause of pain . METHODS A prospect i ve , descriptive study of 152 adult patients presenting to the ED with acute pain . At presentation and at 20-minute intervals to a maximum of three measurements , patients marked the level of their pain on a 100-mm , nonhatched VAS . At each follow-up they also gave a verbal rating of their pain as " a lot better , " " much the same , " " a little worse , " or " much worse . " The minimum clinical ly significant difference in VAS pain scores was defined as the mean difference between current and preceding scores when pain was reported as a little worse or a little better . Data were compared based on gender , age more than or less than 50 years , and traumatic vs nontraumatic causes of pain . RESULTS The minimum clinical ly significant difference in VAS pain scores is 9 mm ( 95 % CI , 6 to 13 mm ) . There is no statistically significant difference between the minimum clinical ly significant differences in VAS pain scores based on gender ( p=0.172 ) , age ( p=0.782 ) , or cause of pain ( p=0.84 ) . CONCLUSIONS The minimum clinical ly significant difference in VAS pain scores was found to be 9 mm . Differences of less than this amount , even if statistically significant , are unlikely to be of clinical significance . No significant difference in minimum significant VAS scores was found between gender , age , and cause-of-pain groups Bupivacaine infiltration of the mesosalpinx was compared to lidocaine , normal saline or no injection for pain relief in women having elective laparoscopic tubal sterilization by Yoon fallopian ring application , One hundred women were assigned r and omly to four groups . In a double-blind study , the mesosalpinx was infiltrated in three groups : Group I - lidocaine one per cent ; Group II - bupivacaine 0.5 per cent ; Group III - normal saline . Group IV ( control ) received no injection . Pain intensity was reported at four study times by the patients on a self- assessment pain intensity scale . Responses were compared using the Kruskall-Wallis H-Test and Wilcoxen ’s Rank-Sum Test . Both tests indicated significant differences in pain intensity levels at various study times . The amount of supplemental fentany I given was used as a secondary measure of effectiveness . One-way analysis of variance ( ANOVA ) and Duncan ’s Multiple-Range Test showed the bupivcaine group to receive significantly less fentanyl ( p < 0.05 ) in the postanesthesia care unit . RésuméOn a comparé ľinfiltration de bupivacaine dans le mésosalpinx , è celle de la lidocaïne , du salin normal ou è aucune injection pour le soulagement de la douleur chez des femmes subissant une laparoscopie élective pour stérilisation tuhaire par anneaux de trompes de Yoon . On a réparti de façon aléatoire , 100 femmes en quatre groupes . Dans une étude è double insu , on a infiltré le mésosalpinx dans trois groupes : Groupe 1 - 1.0 pour cent de lidocaïne ; Group II-0.5 pour cent de bupivacaine ; Groupe III-salin normal . Le groupe IV ( groupe-témoin ) n’a pas reçu ď injection . Les patients ont rapporté ľintensité de leur douleur è quatre moments dans ľétude , en faisant une évaluation personnelle sur une échelle ďintensité de la douleur . On a comparé les réponses en utilisant le test H Kruskall-Wallis et le test de somme des rangs de Wilcoxen . Les deux tests démontraient des différences significatives dans les niveaux ďintensité de la douleur , è différents moments de ľétude . La quantité de fentanyl supplémentaire donnée a été utilisée comme mesure secondaire de ľefficacité . Une analyse de variance unidirectionnelle ( ANOVA ) et le , test è écarts multiples de Duncan ont démontré que le groupe bupivacaine recevait significativement moins de fentanyl ( p < 0.05 ) dans ľunité des soins postanesthésiques Objective To evaluate the efficacy of injecting 1 % lignocaine into the subserosal aspect of the cornual end of the fallopian tubes to control post‐operative pain after laparoscopic Filshie clip application Purpose To determine the incidence , the reasons , and the predictive factors for unanticipated admission after ambulatory surgery . Methods Preoperative , intraoperative , and postoperative data were collected prospect ively on 15,172 consecutive ambulatory surgical patients during a 32-month period . The data were built into a statistical model , and predictive factors were identified and classified . Results The overall incidence of unanticipated admission was 1.42 % . Admitted patients were more likely to be older , male , and ASA status II or III . Duration of anaesthesia was longer , and surgery was more likely to be completed after 3 pm . Length of stay in the Postanaesthesia Care Unit and the Ambulatory Surgery Unit was longer . Surgical reasons were cited in 38.1 % of admitted patients ; anaesthesia-related reasons were cited in 25 % ; social reasons accounted for 19.5 % , and medical reasons for 17.2 % . Ear , nose and throat ( ENT ) patients had the highest unanticipated admission rate ( 18.2 % ) , followed by urology ( 4.8 % ) and chronic pain block ( 3.9 % ) . Gynaecological patients had the lowest rate ( 0.4 % ) . Among the predictive factors found were male , ASA status II and III , long duration of surgery , surgery finishing after 3 pm , postoperative bleeding , excessive pain , nausea and vomiting , and excessive drowsiness or dizziness . Conclusion Earlier operating time for certain surgical procedures , screening for proper support at home , and implementation of clinical pathways to deal aggressively with problems such as pain , nausea and vomiting should decrease the incidence of unanticipated admission . RésuméObjectifDéterminer l’incidence , les raisons et les facteurs prédictifs d’une admission non prévue à la suite d’une chirurgie ambulatoire . MéthodeLes données préopératoires , intraopératoires et postopératoires ont été recueillies pendant 32 mois de façon prospect i ve auprès de 15 172 patients consécutifs , à la suite d’une chirurgie ambulatoire . Ces données ont été intégrées à un modèle statistique et les facteurs prédictifs ont été identifiés et classifies . RésultatsL’incidence totale d’admission imprévue était de 1,42 % . Les patients admis étaient plus susceptibles d’être âgés , de sexe mâle et d’état ASA II ou III . La durée de l’anesthésie était longue et plus susceptible de se prolonger après 15 h. Les séjours à l’unité des soins postanesthésiques et à l’unité de chirurgie ambulatoire étaient prolongés . Les raisons chirurgicales ont été invoquées pour 38,1 % des patients admis ; les raisons reliées à l’anesthésie pour 25 % ; les raisons sociales pour 19,5 % et les raisons médicales pour 17,2 % . Les patients d’oto-rhino-laryngologie ( ORL ) ont présenté le plus haut taux d’admission non planifiée ( 18,2 % ) suivis des patients d’urologie ( 4,8 % ) et de ceux qui avaient reçu un bloc thérapeutique pour douleurs chroniques ( 3,9 % ) . Les patientes de gynécologie avaient le taux le plus bas ( 0,4 % ) . Parmi les facteurs prédictifs identifiés , on a trouvé le sexe mâle , l’état ASA II et III , une chirurgie de durée prolongée , une chirurgie qui se termine après 15 h , les saignements postopératoires , la douleur excessive , les nausées et les vomissements , une gr and e somnolence et des étourdissements importants . Conclusion Le fait de procéder plus tôt dans la journée à certaines interventions chirurgicales , le dépistage préalable d’un soutien approprié pour le patient à domicile et la mise en application des moyens cliniques permettant de s’occuper énergiquement des effets secondaires comme la douleur et , les nausées et vomissements devraient diminuer l’incidence de l’admission non prévue OBJECTIVE The purpose of this study was to evaluate postoperative pain after the administration of topical bupivacaine during laparoscopic sterilization with Filshie clips . STUDY DESIGN Sixty-three women who underwent laparoscopic tubal sterilization with Filshie clips were assigned r and omly to receive topical bupivacaine or placebo . Presence of pain , pain intensity , nausea , vomiting , timing of request for pain medication , and pain medication requirements were assessed postoperatively . RESULTS Patient demographics were similar between the 2 groups . Topical bupivacaine decreased the incidence ( P=.005 ) and intensity ( P=.028 ) of postoperative pain at 30 minutes . No differences in incidence or severity of pain were seen at hospital discharge or on postoperative day 1 . CONCLUSION Topical bupivacaine that is applied to the fallopian tubes at the time of laparoscopic tubal sterilization with the Filshie clip decreases immediate postoperative pain Self-reported postoperative pain was reduced significantly ( P less than .05 ) for up to six hours in a group of ambulatory surgical patients with the application of 5 mL of 1 % etidocaine to the b and ed portion of each fallopian tube after laparoscopic tubal ligation with Falope Rings in comparison to a control group receiving normal saline . The etidocaine group had less nausea and vomiting and smaller antiemetic and analgesic requirements than did the control group , though those results were not statistically significant The visual analog scale ( VAS ) is one of the most commonly used measures of pain intensity in pain research . However , there remain important unanswered questions concerning interpretation of specific VAS ratings and change scores . To address these questions , we performed a re analysis of data from 2 r and omized controlled trials of postoperative pain ( N = 123 and N = 125 ) to determine the meaning of VAS pain intensity ratings and change scores . The findings suggested that 100-mm VAS ratings of 0 to 4 mm can be considered no pain ; 5 to 44 mm , mild pain ; 45 to 74 mm , moderate pain ; and 75 to 100 mm , severe pain . As predicted , in assessment of the amount of change corresponding to differing levels of pain relief , percentage change in a patient 's VAS score was less biased by pretreatment pain than was absolute change score . The findings also suggested that a 33 % decrease in pain represents a reasonable st and ard for determining that a change in pain is meaningful from the patient 's perspective Objective To evaluate postoperative pain relief of intramuscular ketorolac , topical bupivacaine , and placebo in patients undergoing laparoscopic tubal sterilization with silastic b and s. Methods One hundred five women undergoing laparoscopic tubal sterilization with silastic b and s were r and omized to one of three groups : one received intramuscular ketorolac and topical placebo applied to the fallopian tubes , the second received intramuscular placebo and topical bupivacaine , and the third received intramuscular placebo and topical placebo . Surgical procedures , anesthesia , and recovery were conducted with st and ardized protocol s. Postoperative pain perception was grade d using the modified McGill pain intensity scale at 30 minutes postoperatively , at discharge from the recovery room , and the next morning by telephone interview . Other measured variables included postoperative vomiting , additional analgesia requirement , and length of time spent in the recovery room . Results Only topical bupivacaine was found to decrease postoperative pain scores significantly over those with placebo , at 30 minutes postoperatively ( median score 2 compared with 4 , P = .002 ) and at discharge from the recovery room ( median score 2 compared with 3 , P = .03 ) . There was no significant decrease in pain scores with intramuscular ketorolac compared with placebo . No differences in pain scores were found between the three groups at the next morning phone call . There were no significant differences between the three groups with respect to requirements for supplemental pain medications in the recovery room , incidence of postoperative vomiting , or length of time spent in the recovery room . Conclusion Topical bupivacaine decreases postoperative pain scores significantly compared with placebo in women undergoing laparoscopic tubal sterilization with silastic b and We performed a r and omised controlled study in patients undergoing day case laparoscopic sterilisation to assess whether coating Filshie clips with 2 % lignocaine gel prior to application to the Fallopian tubes would reduce postoperative pain . Sixty‐two patients were studied , in 33 of whom the Filshie clips were coated in sterile 2 % lignocaine gel . Pain scores in the lignocaine gel group were significantly lower than in the control group at 1 h after return to the ward , but no differences were found immediately on return to the ward , or at discharge or at 24 h. There were no significant differences between the two groups in postoperative analgesic requirements or in side effects Acta Obstet Gynecol Sc and 2003 ; 82 : 57–60 . © Acta Obstet Gynecol Sc and 2003 Pain complicates the recovery process after ambulatory surgery . We surveyed 175 ambulatory surgery patients to determine pain severity , analgesic use , relationship of pain to duration of recovery , and the relative importance of various factors to predicting these outcomes . Multivariate regression analysis was used to determine unique contributions of predictor variables to outcome . Surgical procedures included knee arthroscopy ( n = 50 ) , hernia surgery ( n = 25 ) , pelvic laparoscopy ( n = 25 ) , transvaginal uterine surgery ( n = 25 ) , surgery for breast disease ( n = 25 ) , and plastic surgery ( n = 25 ) . Maximum pain ( on a scale of 0–10 ) varied from 2.3 ± 0.5 to 5.1 ± 0.5 ( mean ± se ) , depending on surgical procedure ; 24 % of patients had pain scores of ≥7 , and 24 % were delayed in Phase 1 recovery by pain . Pain scores were lower if local anesthetic or ketorolac was administered intraoperatively ( 22 % and 26 % respectively ) . Fentanyl dose during recovery correlated with maximum pain scores ; fentanyl dose was 42 % less if ketorolac was administered intraoperatively . In females , the recovery fentanyl dose increased in proportion to the intraoperative fentanyl dose . The maximum pain score was predictive of total recovery time ( 135 , 172 , and 212 min of recovery for maximum pain scores of 0–3 , 4–6 , and 7–10 , respectively;P < 0.001 ) . We conclude that improvements in pain therapy are warranted to improve patient comfort and to expedite recovery We have studied the effect of ropivacaine for combined port site and mesosalpinx infiltration , and peritoneal instillation on pain , nausea and vomiting after laparoscopic sterilization , in a double-blind , placebo-controlled study in 80 patients . The total dose of ropivacaine was 285 mg . All patients received intra- and postoperative NSAID in fixed doses . Abdominal and shoulder pain , nausea and vomiting were recorded during the first 8 h after operation and in a diary for 3 days . In the ropivacaine group , abdominal pain scores were lower during the first 4 h ( P < 0.00001 ) , additional use of morphine was less ( P < 0.001 ) and fewer patients had nausea or vomiting during the first 72 h ( five vs 14 ; P < 0.05 ) . There were no signs of local anaesthetic toxicity Summary . In an attempt to reduce pain after laparoscopy , presumed to be due to persistence of CO2 in the peritoneal cavity especially under the diaphragm , women were kept 30 ° head down for 30 min immediately after operation . By r and om selection 67 treated patients were compared with 64 kept flat , postoperative symptoms being recorded at fixed times for 3 days . Although tilting was found to be of no significant benefit there were two useful findings . In both groups there was a significant fall in the frequency of upper abdominal pain during the first postoperative night from about 53 % to about 25 % , followed by a rise after returning home on the first postoperative day to about 60 % and only a slow fall in the next 2 days . The severity of pain followed the same pattern . Patients should be warned to expect increased pain on ambulation after leaving hospital . Also , there was doubling in lower abdominal pain during the first 6 h associated with the use of Falope rings for sterilization , compared with either Hulka clip sterilization or only diagnostic laparoscopy Central to high quality day-case care is the provision of good analgesia with minimal side effects . The success of laparoscopic sterilisation as a day case procedure may be hampered by severe post-operative pain1 . Opioid drugs have a poor side effect profile ; a reduction in their use should contribute significantly to patient care . Local anaesthetic blocks used to improve post-operative pain relief after laparoscopic sterilisation include combined rectus sheath and mesosalpinx block2 , but an extra surgical procedure is involved . Small volumes of concentrated bupivacaine applied directly to the fallopian tubes are safe and effective3 . Since pain after laparoscopic sterilisation may arise from manipulation of pelvic organs during visualisation of the fallopian tubes , as well as from the direct application of Filshie clips , this study was design ed to assess the analgesic effect , as measured by visual analogue scores for pain and post-operative analgesic requirements , of a large volume of dilute bupivacaine instilled into the pelvic peritoneal cavity Sixty women having laparoscopic sterilisation performed under general anaesthesia were r and omly allocated to one of two groups . Intraoperatively , one group had bupivacaine applied topically to the fallopian tubes and injected into the skin wounds , while the other group received no local anaesthetic . A double-blind investigation utilising a visual analogue scale failed to demonstrate a statistically significant difference in postoperative pain between the two groups . In both groups there was a significant reduction in mean pain scores between 1/2 and 7 hours , but there was no further reduction between 7 hours and 17 hours . At 7 hours , only 10 % of patients scored their pain as 3 or greater ( out of a possible 10 ) . It is concluded that the use of bupivacaine as described is not a useful adjuvant to general anaesthesia and that the low incidence of even moderate pain at 7 hours confirms the view that these patients are suitable for management in the day-stay unit OBJECTIVE Increasing attention has been given to the assessment of patient satisfaction as a way to monitor quality of care in hospital setting s. Postoperative patient satisfaction has been thought to be related to level of pain intensity , expectations of outcome , perceived concern by the staff , and helpfulness of treatments . The aim of this study is to develop a simple , reliable measure to assess pain and satisfaction in postsurgical patients and to examine factors related to patient satisfaction . DESIGN A satisfaction question naire was developed for this study and administered to 119 patients who had undergone a major orthopedic surgical procedure . The majority of the patients were diagnosed with osteoarthritis and reported moderate to severe preoperative pain . The 13-item measure was found to be reliable ( test-retest r = .86 ; interexaminer r = .98 ) , valid ( exploratory factor analyses ; intercorrelations ) , and easy to administer . RESULTS Results showed that the majority of the patients were satisfied with their care ( 91 % ) , postoperative pain intensity ( 94 % ) , and the way they were treated by the physicians and nurses ( 98 % ) . Patients with low postoperative pain ratings who perceived that the physicians and nurses showed concern with how much pain they were feeling reported greatest satisfaction with their care ( p < .001 ) . In general , lower postoperative pain ratings were the best predictors of satisfaction and helpfulness of treatment . Preoperative pain status , expected level of postoperative pain , and time waiting for pain medication after a request was made were not significantly correlated with ratings of postoperative pain or satisfaction . CONCLUSIONS These results highlight the important influence of adequate treatment of postoperative pain and perceived concern by the hospital staff on patient satisfaction Pain during tubal sterilisation is thought to be due to either ischaemia or pressure at the site of impact of sterilising devices on the fallopian tubes . We have evaluated the effectiveness of an application of 2 % lignocaine gel to Filshie clips to relieve postoperative pain . In a r and omised double-blind placebo-controlled study , 80 healthy women undergoing tubal sterilisation under general anaesthesia at the County Hospital , Lincoln , UK , were allocated to be sterilised by Flishie clips covered with 2 % lignocaine gel or K-Y gel as placebo . Pelvic pain was assessed , with a 100 mm visual analogue scale , at 1 hour , at hospital discharge , and time of first analgesia or any other time analgesia was dem and ed . The lignocaine-treated group had significantly longer time to first analgesia , less pain at 1 hour , less nausea and vomiting , and shorter recovery time . Fewer lignocaine-treated patients needed additional analgesia and they required fewer opioids . There was no case of failed sterilisation or adverse reaction to lignocaine . The application of local anaesthetic gel to Filshie clips is a safe , non-invasive , and effective method of relieving postoperative pain during laparoscopic tubal sterilisation procedures and a reduced incidence of complications . It may also increase the confidence of gynaecologists training in hysteroscopic surgery if the difficulties of introducing the hysteroscope are minimised . The method used for reducing resistance prior to hysteroscopic surgery must however be effective , easy to use , convenient for hospital staff , inexpensive and free from side effects . Our second study revealed that , while misoprostol fulfilled all the other aforementioned criteria , it was not effective at reducing cervical resistance in the dose , route and timing of administration investigated . As a rule , interim analysis of a r and omised trial should not be undertaken , but in this study it was felt appropriate , in that to be of any clinical value misoprostol should confer an obvious worthwhile reduction in cervical resistance to the vast majority of recipients . On analysis after 64 cases there was no demonstrable benefit ( Table 2 ; all the betweengroup confidence intervals include 0 ) . It was therefore decided to discontinue the study at this number . It could be argued that , given operating times averaging less than 20 min , it is not necessary to reduce the cervical resistance . However , these operations were carried out by experienced hysteroscopists and one case of cervical trauma did occur in this series . These figures may well be less favourable for trainees . We feel that the search for an acceptable cervical relaxant which is effective on the hypo-oestrogenised cervix is worth pursuing . Agents suitable for investigation include pre-operative vaginal oestrogen tablets , hydroscopic tents or prostagl and in E analogues by a different dose , time or route of delivery Summary : The aim of this study was to examine the effectiveness of ropivacaine administered by a simple intraperitoneal technique in relieving pain following laparoscopic application of Filshie clips Objective To determine whether preoperative ketoprofen and mesosalpinx infiltration , either alone or in combination , favorably influence postoperative recovery after outpatient laparoscopic sterilization . Methods In a double-blind , r and omized , placebo-controlled study , 20 women received 100 mg of oral ketoprofen preoperatively , and each mesosalpinx was infiltrated with 5 mL of saline plus epinephrine 1:200,000 ; 20 women were given oral ketoprofen , and each mesosalpinx was infiltrated with 5 mL of bupivacaine 0.5 % with epinephrine 1:200,000 ; and 20 women received a placebo capsule with mesosalpinx infiltration . Pain was assessed by a visual analogue scale and a self- assessment 11-point scale ; outcome was assessed by discharge time , consumption of analgesics , incidence of nausea and vomiting , and the number of postoperative days to full recovery . Results Pain ratings in the ketoprofen-only group were significantly higher than in the two other groups ( P < .001 ) . Preoperative ketoprofen alone provided insufficient postoperative pain relief , necessitating the use of opiates and peripheral analgesics . Nausea and vomiting were highest in these subjects , as was intake of peripheral analgesics at home . Times to discharge were also the longest in this group ( median 385 minutes , range 260 - 510 ) and differed significantly from both other groups ( P < .001 ) . It took 4 - 13 days to recover . In contrast , women with only a mesosalpinx block ambulated and recovered sooner , but times to discharge were still prolonged ( median 240 minutes , range 105 - 375 ) . Recovery usually occurred by the fourth postoperative day . The combination of preoperative ketoprofen and mesosalpinx block result ed in the shortest times to discharge ( median 190 minutes , range 80 - 330 ) , the least consumption of peripheral analgesics , and the lowest incidence of nausea and vomiting . Recovery occurred by the fourth postoperative day . Conclusion Mesosalpinx infiltration has a favorable effect on postoperative recovery after day-surgery laparoscopic sterilization . Still better results can be obtained with a multimodal analgesic approach , combining mesosalpinx infiltration with preoperative ketoprofen Conflicting reports exist in the literature on the effectiveness of topical local anesthetic applied to the serosal surface of the fallopian tubes for the control of immediate postoperative pain after mechanical ( b and or clip ) tubal ligation . Sixty-four patients were studied prospect ively during outpatient laparoscopic Falope ring tubal ligation using the modified McGill Present Pain Intensity Scale . Patients r and omly assigned to four groups received topical bupivacaine hydrochloride on both fallopian tubes , the right tube only , or the left tube only , or received none ( controls ) . A unique study design was incorporated which allowed the untreated fallopian tube to serve as a within-subject control for each patient receiving unilateral treatment . Statistical analysis confirmed significant benefit when both fallopian tubes were treated as compared with no treatment ( P less than .05 ) . There was also consistent evidence of decreased immediate postoperative pain perception on the treated side for patients receiving unilateral treatment . The value of topical bupivacaine was demonstrated by both subjective patient response ( McGill Pain Scale ) and reduced need for pain medication before outpatient discharge . Our data support the value of topical bupivacaine applied to the serosal surface of the fallopian tubes for the reduction of postoperative pain after outpatient laparoscopic mechanical ( b and or clip ) tubal ligation Objective : To test the effectiveness of intraperitoneal local anesthesia in relieving postoperative pain after laparoscopic sterilization . Methods : In a double-blind , placebo-controlled r and omized study of two groups of 25 subjects each , women scheduled for tubal sterilization under general anesthesia received 80 mL of 0.5 % lidocaine with 1/320,000 epinephrine intraperitoneally in the right subdiaphragmatic quadrant at the beginning of the procedure . At the end of the procedure , they received 10 mL of 2 % lidocaine with 1/80,000 epinephrine injected into each mesosalpinx . Controls received saline instead of lidocaine . Shoulder and pelvic pain assessed by visual analogue pain scale , postoperative analgesic requirements , nausea or vomiting , and time to return to normal daily activities were evaluated in the ambulatory unit and after discharge during the first 48 postoperative hours . Blood sample s were taken in ten subjects receiving lidocaine to evaluate peak plasma concentrations and time to peak plasma concentrations . Results : Pain was significantly less in patients who received lidocaine , and the difference lasted for the duration of the study ( P<.05 ) . Analgesic requirements and time to return to normal daily activities were significantly reduced in patients who received lidocaine ( P<.05 ) . Blood sample s revealed no toxic concentrations . The peak plasma concentration was 3.22 ± 1.21 µg/mL , and the time to peak plasma concentration was 42 ± 15 minutes . Conclusion : Intraperitoneal instillation of lidocaine-epinephrine combined with mesosalpinx infiltration of lidocaine during tubal sterilization produces effective , longlasting analgesia and improves the postoperative course Thirty patients scheduled to undergo laparoscopic sterilisation were allocated at r and om to receive either a st and ardised general anaesthetic and rectus sheath block ( group A ) , or st and ardised general anaesthetic combined with both rectus sheath and mesosalpinx blocks ( group B ) . Group B patients had significantly less postoperative pain , as assessed by linear analogue scores ( p < 0.025 ) , and analgesic requirement ( p < 0.05 ) . By the 8th postoperative hour all 15 group B patients had been discharged from hospital , whilst only seven of 15 patients in group A were considered suitable for discharge at this time , ( p < 0.05 ) STUDY OBJECTIVE To determine the amount of change in pain severity , as measured by a visual analog scale , that constitutes a minimum clinical ly significant difference . METHODS Patients 18 years of age or older who presented with acute pain result ing from trauma were enrolled in this prospect i ve , descriptive study . The setting was an urban county hospital emergency department with a Level 1 trauma center . In the course of a brief interview , patients were asked to indicate their current pain severity with a single mark through a st and ard 100-mm visual analog scale . At intervals of 20 minutes for the next 2 hours , patients were asked to repeat this measurement and , in addition , to contrast their present pain severity with that at the time of the previous measurement . They were to indicate whether they had " much less , " " a little less , " " about the same , " " a little more , " or " much more " pain . All contrasts were made without reference to prior visual analog scale measurements . A maximum of six measurements of pain change were recorded per patient . Measurements ended when the patient left the ED or when the patient reported a pain score of zero . The minimum clinical ly significant change in visual analog scale pain score was defined as the mean difference between current and preceding visual analog scale scores when the subject noted a little less or a little more pain . RESULTS Forty-eight subjects were enrolled , and 248 pain contrasts were recorded . Of these contrasts , 41 were rated as a little less and 39 as a little more pain . The mean difference between current and preceding visual analog scale scores in these 80 contrasts was 13 mm ( 95 % confidence interval , 10 to 17 mm ) . CONCLUSION The minimum clinical ly significant change in patient pain severity measured with a 100-mm visual analog scale was 13 mm . Studies of pain experience that report less than a 13-mm change in pain severity , although statistically significant , may have no clinical importance |
10,415 | 28,440,323 | Conclusions : Our data demonstrate that higher dietary and circulating lycopene concentrations are inversely associated with PCa risk .
This was accompanied by dose-response relationships for dietary and circulating lycopene .
However , lycopene was not associated with a reduced risk of advanced PCa . | Background : Prostate cancer ( PCa ) is the fifth leading cause of cancer-related deaths worldwide .
Many epidemiological studies have investigated the association between prostate cancer and lycopene , however , results have been inconsistent .
This study aims to determine the impact of dietary and circulating concentrations of lycopene on PCa risk and to investigate potential dose-response associations . | Oxidative stress may enhance prostatic carcinogenesis . A polymorphism [ valine ( V ) -- > alanine ( A ) ] of manganese superoxide dismutase ( MnSOD ) , the primary antioxidant enzyme in mitochondria , has been recently associated with prostate cancer . We examined the relationship between prostate cancer and the MnSOD polymorphism and its interactions with baseline plasma antioxidant levels ( selenium , lycopene , and alpha-tocopherol ) and beta-carotene treatment among 567 cases and 764 controls nested in the prospect i ve Physicians ' Health Study . We found little overall association between MnSOD polymorphism and prostate cancer risk ; however , this polymorphism significantly modified risk of prostate cancer associated with prediagnostic plasma antioxidants ( P(interaction ) > or = 0.05 ) . Among men with the AA genotype , high selenium level ( 4th versus 1st quartile ) was associated with a relative risk ( RR ) of 0.3 [ 95 % confidence interval ( CI ) , 0.2 - 0.7 ] for total prostate cancer ; for clinical ly aggressive prostate cancer , the RR was 0.2 ( 95 % CI , 0.1 - 0.5 ) . In contrast , among men with the VV/VA genotype , the RRs were 0.6 ( 0.4 - 1.0 ) and 0.7 ( 0.4 - 1.2 ) for total and clinical ly aggressive prostate cancer . These patterns were similar for lycopene and alpha-tocopherol and were particularly strong when these antioxidants and selenium were combined ; men with the AA genotype had a 10-fold gradient in risk for aggressive prostate cancer across quartiles of antioxidant status . Men with AA genotype who were r and omly assigned to beta-carotene treatment ( versus placebo ) had a RR of 0.6 ( 95 % CI , 0.2 - 0.9 ; P(interaction ) = 0.03 ) for fatal prostate cancer , but no significant association was observed in men with the VV/VA genotype . Both endogenous and exogenous antioxidants play an important and interdependent role in preventing clinical ly significant prostate cancer The association between plasma carotenoids and prostate cancer risk was investigated in a case-control study nested within the prospect i ve Health Professionals Follow-up Study . We matched 450 incident prostate cancer cases diagnosed from 1993–1998 to 450 controls by age , time , month , and year of blood donation . Modest inverse , but not statistically significant , associations were observed among plasma α-carotene , β-carotene , and lycopene concentrations , and overall risk of prostate cancer diagnosis { odds ratio ( highest versus lowest quintile ; OR ) , α-carotene : OR , 0.67 [ 95 % confidence interval ( CI ) , −0.40–1.09 ] ; β-carotene : OR , 0.78 ( 95 % CI , 0.48–1.25 ) ; lycopene : OR , 0.66 ( 95 % CI , 0.38–1.13)}. The inverse association between plasma lycopene concentrations and prostate cancer risk was limited to participants who were 65 years or older ( OR , 0.47 ; 95 % CI , 0.23–0.98 ) and without a family history of prostate cancer ( OR , 0.48 ; 95 % CI , 0.26–0.89 ) . Combining , older age and a negative family history provided similar results ( OR , 0.43 ; 95 % CI , 0.18–1.02 ) . Inverse associations between β-carotene and prostate cancer risk were also found among younger participants ( < 65 years of age ; OR , 0.36 ; 95 % CI , 0.14–0.91 ; Ptrend = 0.03 ) . Combining dietary intake and plasma data confirmed our results . We found a statistically significant inverse association between higher plasma lycopene concentrations and lower risk of prostate cancer , which was restricted to older participants and those without a family history of prostate cancer . This observation suggests that tomato products may exhibit more potent protection against sporadic prostate cancer rather than those with a stronger familial or hereditary component . In addition , our findings also suggest that among younger men , diets rich in β-carotene may also play a protective role in prostate carcinogenesis BACKGROUND Several human studies have observed a direct association between retinol ( vitamin A ) intake and risk of prostate cancer ; other studies have found either an inverse association or no association of intake of beta-carotene ( the major provitamin A ) with risk of prostate cancer . Data regarding carotenoids other than beta-carotene in relation to prostate cancer risk are sparse . PURPOSE We concluded a prospect i ve cohort study to examine the relationship between the intake of various carotenoids , retinol , fruits , and vegetables and the risk of prostate cancer . METHODS Using responses to a vali date d , semiquantitative food-frequency question naire mailed to participants in the Health Professionals Follow-up Study in 1986 , we assessed dietary intake for a 1-year period for a cohort of 47,894 eligible subjects initially free of diagnosed cancer . Follow-up question naires were sent to the entire cohort in 1988 , 1990 , and 1992 . We calculated the relative risk ( RR ) for each of the upper categories of intake of a specific food or nutrient by dividing the incidence rate of prostate cancer among men in each of these categories by the rate among men in the lowest intake level . All P values result ed from two-sided tests . RESULTS Between 1986 and 1992 , 812 new cases of prostate cancer , including 773 non-stage A1 cases , were documented . Intakes of the carotenoids beta-carotene , alpha-carotene , lutein , and beta-cryptoxanthin were not associated with risk of non-stage A1 prostate cancer ; only lycopene intake was related to lower risk ( age- and energy-adjusted RR = 0.79 ; 95 % confidence interval [ CI ] = 0.64 - 0.99 for high versus low quintile of intake ; P for trend = .04 ) . Of 46 vegetables and fruits or related products , four were significantly associated with lower prostate cancer risk ; of the four -- tomato sauce ( P for trend = .001 ) , tomatoes ( P for trend = .03 ) , and pizza ( P for trend = .05 ) , but not strawberries -- were primary sources of lycopene . Combined intake of tomatoes , tomato sauce , tomato juice , and pizza ( which accounted for 82 % of lycopene intake ) was inversely associated with risk of prostate cancer ( multivariate RR = 0.65 ; 95 % CI = 0.44 - 0.95 , for consumption frequency greater than 10 versus less than 1.5 servings per week ; P for trend = .01 ) and advanced ( stages C and D ) prostate cancers ( multivariate RR = 0.47 ; 95 % CI = 0.22 - 1.00 ; P for trend = .03 ) . No consistent association was observed for dietary retinol and risk of prostate cancer . CONCLUSIONS These findings suggest that intake of lycopene or other compounds in tomatoes may reduce prostate cancer risk , but other measured carotenoids are unrelated to risk . IMPLICATION S Our findings support recommendations to increase vegetable and fruit consumption to reduce cancer incidence but suggest that tomato-based foods may be especially beneficial regarding prostate cancer risk Dietary consumption of the carotenoid lycopene ( mostly from tomato products ) has been associated with a lower risk of prostate cancer . Evidence relating other carotenoids , tocopherols , and retinol to prostate cancer risk has been equivocal . This prospect i ve study was design ed to examine the relationship between plasma concentrations of several major antioxidants and risk of prostate cancer . We conducted a nested case-control study using plasma sample s obtained in 1982 from healthy men enrolled in the Physicians ' Health Study , a r and omized , placebo-controlled trial of aspirin and beta-carotene . Subjects included 578 men who developed prostate cancer within 13 years of follow-up and 1294 age- and smoking status-matched controls . We quantified the five major plasma carotenoid peaks ( alpha- and beta-carotene , beta-cryptoxanthin , lutein , and lycopene ) plus alpha- and gamma-tocopherol and retinol using high-performance liquid chromatography . Results for plasma beta-carotene are reported separately . Odds ratios ( ORs ) , 95 % confidence intervals ( Cls ) , and Ps for trend were calculated for each quintile of plasma antioxidant using logistic regression models that allowed for adjustment of potential confounders and estimation of effect modification by assignment to either active beta-carotene or placebo in the trial . Lycopene was the only antioxidant found at significantly lower mean levels in cases than in matched controls ( P = 0.04 for all cases ) . The ORs for all prostate cancers declined slightly with increasing quintile of plasma lycopene ( 5th quintile OR = 0.75 , 95 % CI = 0.54 - 1.06 ; P , trend = 0.12 ) ; there was a stronger inverse association for aggressive prostate cancers ( 5th quintile OR = 0.56 , 95 % CI = 0.34 - 0.91 ; P , trend = 0.05 ) . In the placebo group , plasma lycopene was very strongly related to lower prostate cancer risk ( 5th quintile OR = 0.40 ; P , trend = 0.006 for aggressive cancer ) , whereas there was no evidence for a trend among those assigned to beta-carotene supplements . However , in the beta-carotene group , prostate cancer risk was reduced in each lycopene quintile relative to men with low lycopene and placebo . The only other notable association was a reduced risk of aggressive cancer with higher alpha-tocopherol levels that was not statistically significant . None of the associations for lycopene were confounded by age , smoking , body mass index , exercise , alcohol , multivitamin use , or plasma total cholesterol level . These results concur with a recent prospect i ve dietary analysis , which identified lycopene as the carotenoid with the clearest inverse relation to the development of prostate cancer . The inverse association was particularly apparent for aggressive cancer and for men not consuming beta-carotene supplements . For men with low lycopene , beta-carotene supplements were associated with risk reductions comparable to those observed with high lycopene . These data provide further evidence that increased consumption of tomato products and other lycopene-containing foods might reduce the occurrence or progression of prostate cancer BACKGROUND Evidence has accumulated from observational studies that people eating more fruits and vegetables , which are rich in beta-carotene ( a violet to yellow plant pigment that acts as an antioxidant and can be converted to vitamin A by enzymes in the intestinal wall and liver ) and retinol ( an alcohol chemical form of vitamin A ) , and people having higher serum beta-carotene concentrations had lower rates of lung cancer . The Beta-Carotene and Retinol Efficacy Trial ( CARET ) tested the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate ( vitamin A ) taken daily against placebo in 18314 men and women at high risk of developing lung cancer . The CARET intervention was stopped 21 months early because of clear evidence of no benefit and substantial evidence of possible harm ; there were 28 % more lung cancers and 17 % more deaths in the active intervention group ( active = the daily combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate ) . Promptly after the January 18 , 1996 , announcement that the CARET active intervention had been stopped , we published preliminary findings from CARET regarding cancer , heart disease , and total mortality . PURPOSE We present for the first time results based on the pre-specified analytic method , details about risk factors for lung cancer , and analyses of subgroups and of factors that possibly influence response to the intervention . METHODS CARET was a r and omized , double-blinded , placebo-controlled chemoprevention trial , initiated with a pilot phase and then exp and ed 10-fold at six study centers . Cigarette smoking history and status and alcohol intake were assessed through participant self-report . Serum was collected from the participants at base line and periodically after r and omization and was analyzed for beta-carotene concentration . An Endpoints Review Committee evaluated endpoint reports , including pathologic review of tissue specimens . The primary analysis is a stratified logrank test for intervention arm differences in lung cancer incidence , with weighting linearly to hypothesized full effect at 24 months after r and omization . Relative risks ( RRs ) were estimated by use of Cox regression models ; tests were performed for quantitative and qualitative interactions between the intervention and smoking status or alcohol intake . O'Brien-Fleming boundaries were used for stopping criteria at interim analyses . Statistical significance was set at the .05 alpha value , and all P values were derived from two-sided statistical tests . RESULTS According to CARET 's pre-specified analysis , there was an RR of 1.36 ( 95 % confidence interval [ CI ] = 1.07 - 1.73 ; P = .01 ) for weighted lung cancer incidence for the active intervention group compared with the placebo group , and RR = 1.59 ( 95 % CI = 1.13 - 2.23 ; P = .01 ) for weighted lung cancer mortality . All subgroups , except former smokers , had a point estimate of RR of 1.10 or greater for lung cancer . There are suggestions of associations of the excess lung cancer incidence with the highest quartile of alcohol intake ( RR = 1.99 ; 95 % CI = 1.28 - 3.09 ; test for heterogeneity of RR among quartiles of alcohol intake has P = .01 , unadjusted for multiple comparisons ) and with large-cell histology ( RR = 1.89 ; 95 % CI = 1.09 - 3.26 ; test for heterogeneity among histologic categories has P = .35 ) , but not with base-line serum beta-carotene concentrations . CONCLUSIONS CARET participants receiving the combination of beta-carotene and vitamin A had no chemopreventive benefit and had excess lung cancer incidence and mortality . The results are highly consistent with those found for beta-carotene in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study in 29133 male smokers in Finl and Variations in lycopene blood levels and tomato consumption across European countries based on the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) study Lycopene is a promising nutritional component for chemoprevention of prostate cancer ( PCa ) . A possibly beneficial role of lycopene in patients diagnosed with benign prostate hyperplasia ( BPH ) , who are at increased risk of developing PCa , has been suggested , although clinical data are lacking . Therefore , this pilot study aim ed to investigate the effects of lycopene supplementation in elderly men diagnosed with BPH . A total of 40 patients with histologically proven BPH free of PCa were r and omized to receive either lycopene at a dose of 15 mg/d or placebo for 6 mo . The effects of the intervention on carotenoid status , clinical diagnostic markers of prostate proliferation , and symptoms of the disease were assessed . The primary endpoint of the study was the inhibition or reduction of increased serum prostate-specific antigen ( PSA ) levels . The 6-mo lycopene supplementation decreased PSA levels in men ( P < 0.05 ) , whereas there was no change in the placebo group . The plasma lycopene concentration increased in the group taking lycopene ( P < 0.0001 ) but other plasma carotenoids were not affected . Whereas progression of prostate enlargement occurred in the placebo group as assessed by trans-rectal ultrasonography ( P < 0.05 ) and digital rectal examination ( P < 0.01 ) , the prostate did not enlarge in the lycopene group . Symptoms of the disease , as assessed via the International Prostate Symptom Score question naire , were improved in both groups with a significantly greater effect in men taking lycopene supplements . In conclusion , lycopene inhibited progression of BPH BACKGROUND There is limited evidence that supports etiologically distinct molecular subtypes of prostate cancer , the identification of which may improve prevention . Given their antioxidant properties , we hypothesized that lycopene and tomato sauce may be especially protective against diseases harboring the common gene fusion transmembrane protease , serine 2 (TMPRSS2):v-ets avian erythroblastosis virus E26 oncogene homolog ( ERG ) . OBJECTIVE We aim ed to examine associations between estimated lycopene and tomato sauce intake and the risk of prostate cancer defined by ERG protein expression subtype . DESIGN Our study population consisted of a prospect i ve cohort of 46,719 men from the Health Professionals Follow-Up Study . TMPRSS2:ERG was assessed by ERG immunohistochemistry on tumor tissue microarrays constructed from radical prostatectomy specimens . We used multivariable competing risk models to calculate HRs and 95 % CIs for the risk of ERG-positive and , separately , ERG-negative disease . We implemented inverse probability weighting to account for evaluating ERG status only in surgically treated cases . RESULTS During 23 y of follow-up , 5543 men were diagnosed with prostate cancer , among whom 884 were assayed for ERG ( 426 ERG-positive ) . With inclusion of only the latter cases , increasing cumulative average tomato sauce intake was associated with a decreased risk of prostate cancer overall ( ≥2 servings/wk compared with < 1 serving/mo ; multivariable HR : 0.70 ; 95 % CI : 0.52 , 0.95 ; P-trend = 0.002 ) . With respect to molecular subtypes , cumulative average tomato sauce intake was associated with a decreased risk of ERG-positive disease ( HR : 0.54 ; 95 % CI : 0.37 , 0.81 ; P-trend = 0.004 ) but not with ERG-negative disease ( HR : 0.96 ; 95 % CI : 0.62 , 1.50 ; P-trend = 0.10 ) ( P-heterogeneity = 0.04 ) . Increasing quintiles of lycopene intake were associated with a decreased risk of both subtypes ( P-heterogeneity = 0.79 ) . Inverse probability weighting did not material ly change the results . CONCLUSIONS Our results lend some support to the hypothesis that prostate cancers that harbor TMPRSS2:ERG may be etiologically distinct from fusion-negative cancers . In particular , tomato sauce consumption may play a role in reducing TMPRSS2:ERG-positive disease The aim of this study was to determine whether serum concentrations of micronutrients , antioxidants and vitamins predict rate of disease progression in untreated , localised prostate cancer . Patients with localised prostatic adenocarcinoma on a prospect i ve study of active surveillance underwent monitoring with serial PSA levels and repeat prostate biopsies . Disease progression was defined as either adverse histology on repeat biopsy ( primary Gleason grade ≥4 or > 50 % positive cores of total ) or radical treatment for PSA velocity > 1 ng ml−1 year−1 . Time to disease progression was analysed with respect to baseline levels of alpha-tocopherol , gamma-tocopherol , alpha-carotene and beta-carotene , lycopene , retinol and selenium . One hundred four patients were evaluable , with a median follow-up of 2.5 years . Thirty-eight patients experienced disease progression , 13 biochemical and 25 histologic progression . Median time to disease progression was 2.62 years . No significant association was seen between time to disease progression and baseline serum levels of alpha-tocopherol ( p = 0.86 ) , gamma-tocopherol ( p = 0.84 ) , alpha-carotenoid ( p = 0.66 ) , beta-carotene ( p = 0.65 ) , lycopene ( p = 0.0.15 ) , retinol ( p = 0.76 ) or selenium ( p = 0.76 ) . No significant association was seen between serum levels of the micronutrients , antioxidants or vitamins and either adverse histology on repeat biopsy or PSA velocity . Our data do not support the hypothesis that high serum concentrations of micronutrients , antioxidants and vitamins prevent disease progression in men with localised prostate cancer Consumption of tomato products is associated with a decreased risk of developing prostate cancer , and lycopene , the red carotenoid in the tomato , is a potent antioxidant that might contribute to this chemoprevention activity . A double-blind , r and omized , placebo-controlled trial of 105 African American men veterans , recommended for prostate biopsy to detect cancer , was carried out to investigate whether oral administration of lycopene increases lycopene levels in blood and prostate tissue and lowers markers of oxidative stress . Urology patients were r and omly assigned to receive 30 mg/d of lycopene as a tomato oleoresin or placebo for 21 days prior to prostate biopsy for possible diagnosis of prostate cancer . A total of 47 men had a diagnosis of prostate cancer , and 58 men had a diagnosis of benign prostate hyperplasia . Diet , smoking , and drinking habits were assessed . For the men receiving lycopene , the mean lycopene concentration increased from 0.74 ± 0.39 to 1.43 ± 0.61 μmol/L in plasma ( P < 0.0001 ) and from 0.45 ± 0.53 to 0.59 ± 0.47 pmol/mg in prostate tissue ( P = 0.005 ) . No significant changes in the DNA oxidation product 8-oxo-deoxyguanosine and the lipid peroxidation product malondialdehyde were observed in prostate tissue and plasma , respectively , as a result of lycopene administration . Cancer Prev Res ; 4(5 ) ; 711–8 . © 2011 AACR PURPOSE We investigated the influence of lycopene on the clinical and laboratory course in men with hormone refractory prostate cancer . To our knowledge this study represents the first time that subjective assessment s of the course of therapy have been recorded . MATERIAL AND METHODS We performed a prospect i ve , open phase II pilot study , in which patients with progressive hormone refractory prostate cancer were included . Lycopene supplementation ( 15 mg ) was given daily for 6 months . Followup laboratory tests and clinical examinations were done monthly . Changes to analgesic use and quality of life ( European Organisation for Research and Treatment of Cancer QLQ-C30 ) were measured . The study end point was a significant change in serum prostate specific antigen , clinical progression or the end of the 6-month observation period . RESULTS A total of 18 patients 64 to 85 years old ( median age 73 ) were enrolled in the study during a 20-month period , of whom 17 could be analyzed . Five of the 17 patients ( 29 % ) withdrew from the study prematurely , including 4 of 5 because of prostate specific antigen progression and /or tumor associated complications , and 1 due to an allergic reaction to lycopene . Median prostate specific antigen doubled in 6 months from 42.7 ng/ml ( range 13.8 to 521.6 ) in 17 patients to 96.4 ng/ml ( range 13.5 to 1,240 ) in 12 . Stable prostate specific antigen was observed in 5 of 17 patients ( 29 % ) . None of the patients had a greater than 50 % decrease in prostate specific antigen . Patients experienced a slight deterioration in mean health status at the end of the study compared to the outset . However , two-thirds of the patients experienced an improved or unchanged situation regardless of the clinical and biochemical course . CONCLUSIONS No clinical ly relevant benefits were shown for patients with advanced stages of the disease Background : Reports from several studies have suggested that carotenoids , and in particular lycopene , could be prostate cancer – preventive agents . This has stimulated extensive laboratory and clinical research , as well as much commercial and public enthusiasm . However , the epidemiologic evidence remains inconclusive . Material s and Methods : We investigated the association between prediagnostic serum carotenoids ( lycopene , α-carotene , β-carotene , β-cryptoxanthin , lutein , and zeaxanthin ) and risk of prostate cancer in the Prostate , Lung , Colorectal , and Ovarian Cancer Screening Trial , a multicenter study design ed to examine methods of early detection and risk factors for cancer . The study included 692 incident prostate cancer cases , diagnosed 1 to 8 years after study entry , including 270 aggressive cases , with regional or distant stage ( n = 90 ) or Gleason score ≥7 ( n = 235 ) , and 844 r and omly selected , matched controls . As study participants were selected from those who were assigned to annual st and ardized screening for prostate cancer , results are unlikely to be biased by differential screening , a circumstance that is difficult to attain under non – trial conditions . Results : No association was observed between serum lycopene and total prostate cancer [ odds ratios ( OR ) , 1.14 ; 95 % confidence intervals ( 95 % CI ) , 0.82 - 1.58 for highest versus lowest quintile ; P for trend , 0.28 ] or aggressive prostate cancer ( OR , 0.99 ; 95 % CI , 0.62 - 1.57 for highest versus lowest quintile ; P for trend , 0.433 ) . β-Carotene was associated with an increased risk of aggressive prostate cancer ( OR , 1.67 ; 95 % CI , 1.03 - 2.72 for highest versus lowest quintile ; P for trend , 0.13 ) ; in particular , regional or distant stage disease ( OR , 3.16 ; 95 % CI , 1.37 - 7.31 for highest versus lowest quintile ; P for trend , 0.02 ) ; other carotenoids were not associated with risk . Conclusion : In this large prospect i ve study , high serum β-carotene concentrations were associated with increased risk for aggressive , clinical ly relevant prostate cancer . Lycopene and other carotenoids were unrelated to prostate cancer . Consistent with other recent publications , these results suggest that lycopene or tomato-based regimens will not be effective for prostate cancer prevention . ( Cancer Epidemiol Biomarkers Prev 2007;16(5):962–8 OBJECTIVES To report a prospect i ve trial of lycopene supplementation in biochemically relapsed prostate cancer . METHODS A total of 36 men with biochemically relapsed prostate cancer were enrolled in a dose-escalating , Phase I-II trial of lycopene supplementation . Six consecutive cohorts of 6 patients each received daily supplementation with 15 , 30 , 45 , 60 , 90 , and 120 mg/day for 1 year . The serum levels of prostate-specific antigen ( PSA ) and plasma levels of lycopene were measured at baseline and every 3 months . The primary endpoints were PSA response ( defined as a 50 % decrease in serum PSA from baseline ) , pharmacokinetics , and the toxicity/tolerability of this regimen . RESULTS A total of 36 patients were enrolled . The median age was 74 years ( range 56 to 83 ) , with a median serum PSA at entry of 4.4 ng/mL ( range 0.8 to 24.9 ) . No serum PSA responses were observed , and 37 % of patients had PSA progression . The median time to progression was not reached . Toxicity was mild , with 1 patient discontinuing therapy because of diarrhea . Significant elevations of plasma lycopene were noted at 3 months and then appeared to plateau for all six dose levels . The plasma levels for doses between 15 and 90 mg/day were similar , with additional elevation only at 120 mg/day . CONCLUSIONS Lycopene supplementation in men with biochemically relapsed prostate cancer is safe and well tolerated . The plasma levels of lycopene were similar for a wide dose range ( 15 to 90 mg/day ) and plateaued by 3 months . Lycopene supplementation at the doses used in this study did not result in any discernible response in serum PSA OBJECTIVE Because of its long latency , slow growing nature , and high prevalence , prostate cancer is the best model for chemoprevention . High- grade prostate intraepithelial neoplasia ( HGPIN ) is a precursor of prostate cancer . Chemoprevention with lycopene has shown definite results in prostate cancer . We undertook a study to use lycopene as a chemopreventive agent in the treatment of HGPIN for preventing prostate cancer from developing in this vulnerable group of patients . MATERIAL S AND METHODS A total of 40 patients with HGPIN were r and omized into 2 groups : one received 4 mg lycopene twice a day for one year , and the other was periodically followed up . Total follow-up was one year . RESULTS Our results show that lycopene can delay or prevent HGPIN from developing into occult prostate cancer , and there exists an inverse relationship between lycopene and prostate-specific antigen . Being a vegetable carotenoid , lycopene is a safe drug to be used for a longer period without any adverse reaction . CONCLUSION Lycopene is an effective chemopreventive agent in the treatment of HGPIN , with no toxicity and good patient tolerance BACKGROUND In addition to their possible direct biological effects , plasma carotenoids can be used as biochemical markers of fruit and vegetable consumption for identifying diet-disease associations in epidemiological studies . Few studies have compared levels of these carotenoids between countries in Europe . OBJECTIVE Our aim was to assess the variability of plasma carotenoid levels within the cohort of the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) . METHODS Plasma levels of six carotenoids -- alpha-carotene , beta-carotene , beta-cryptoxanthin , lycopene , lutein and zeaxanthin -- were measured cross-sectionally in 3043 study subjects from 16 regions in nine European countries . We investigated the relative influence of gender , season , age , body mass index ( BMI ) , alcohol intake and smoking status on plasma levels of the carotenoids . RESULTS Mean plasma level of the sum of the six carotenoids varied twofold between regions ( 1.35 micromol l(-1 ) for men in Malmö , Sweden vs. 2.79 micromol l(-1 ) for men in Ragusa/Naples , Italy ; 1.61 micromol l(-1 ) for women in The Netherl and s vs. 3.52 micromol l(-1 ) in Ragusa/Naples , Italy ) . Mean levels of individual carotenoids varied up to fourfold ( alpha-carotene : 0.06 micromol l(-1 ) for men in Murcia , Spain vs. 0.25 micromol l(-1 ) for vegetarian men living in the UK ) . In multivariate regression analyses , region was the most important predictor of total plasma carotenoid level ( partial R(2)=27.3 % ) , followed by BMI ( partial R(2)=5.2 % ) , gender ( partial R(2)=2.7 % ) and smoking status ( partial R(2)=2.8 % ) . Females had higher total carotenoid levels than males across Europe . CONCLUSIONS Plasma levels of carotenoids vary substantially between 16 different regions in Italy , Greece , Spain , France , Germany , the UK , Sweden , Denmark and The Netherl and s. Compared with region of residence , the other demographic and lifestyle factors and laboratory measurements have limited predictive value for plasma carotenoid levels in Europe Prostate cancer ( PC ) is a frequent male malignancy and represents the second most diagnosed cancer in men . Since pre-cancerous lesions , i.e. , the high- grade prostatic intraepithelial neoplasia ( HGPIN ) , can be detected years before progression to PC , early diagnosis and chemoprevention are targeted strategies to reduce PC rates . Animal studies have shown that lycopene , a carotenoid contained in tomatoes , is a promising c and i date for the chemoprevention of PC . However , its efficacy in humans remains controversial . The present study aim ed to investigate the relevance of plasma and prostate concentration of lycopene after a lycopene-enriched diet in patients diagnosed with HGPIN . Thirty-two patients diagnosed with HGPIN were administered a lycopene-enriched diet ( 20–25 mg/day of lycopene ; through 30 g/day of triple concentrated tomato paste ) for 6 months . A 6-month follow-up prostate biopsy assessed progression to PC . Patients were classified into three groups according to the histopathological features of the 6-month follow-up biopsy results : prostatitis ; HGPIN and PC . PSA and plasma lycopene levels were measured before and after the dietary lycopene supplementation . Prostatic lycopene concentration was only assessed after the supplementation diet . Only prostatic lycopene concentration showed significant differences between the three groups ( p = 0.03 ) . Prostatic lycopene concentration below a 1 ng/mg threshold was associated with PC at 6-month follow-up biopsy ( p = 0.003 ) . We observed no overall benefits from a 6-month lycopene supplementation , as the rate of HGPIN progression to PC in our population ( 9/32 , 28 % ) was similar to rates reported in the literature . Baseline PSA levels also showed no significant changes after a lycopene-enriched diet . Our findings point to prostatic lycopene concentration as a promising biomarker of PC . Further prospect i ve longitudinal studies are needed to assess the prognostic role of prostatic lycopene in PC BACKGROUND Prostate cancer is a disease with a complex etiology . Oxidative stress has been implicated in its pathogenesis ; however , few prospect i ve studies have investigated the association between an oxidative stress/balance score and risk of prostate cancer . METHODS We investigated associations between an oxidative balance score , calculated as the summation of individual scores obtained from five pro-oxidative and eight anti-oxidative exposures , as well as each individual constituent of the score and risks of prostate cancer overall , and by clinical characteristics , in a case-cohort study ( 661 cases and 1864 subcohort ) nested within the Canadian Study of Diet , Lifestyle , and Health cohort . Men in the lowest quintiles of each pro-oxidant exposure received a score of four ( the highest score ) , while those in the highest quintile received a score of zero ( the lowest score ) . In contrast , scoring for all anti-oxidants was performed in the opposite way . Total oxidative balance score was calculated by summating all individual scores of pro- and anti-oxidative variables , with higher values indicating a higher antioxidant status . RESULTS The average oxidative balance score was similar between prostate cancer cases and men in the subcohort : 25.2 and 25.3 , respectively . There was no association between oxidative balance score and overall risk of prostate cancer with hazard ratios ( HRs ) of 1.00 , 1.02 , 1.03 , 0.97 and 1.01 for increasing quintiles of the score ( p-trend=0.71 ) . There were also no associations for non-advanced or advanced disease , or when analysis was restricted to incident cases that arose after two years of follow-up ( n=508 ) . In general constituents of the score were not associated with prostate cancer , except for red meat intake ( HR=1.44 ; 95%CI 1.06 - 1.95 comparing Q5 vs. Q1 ) and lycopene ( HRs of 0.7 - 0.8 for increasing quintiles ) . CONCLUSION Our findings do not support an association between oxidative balance score and risks of overall prostate cancer or advanced disease Objective : To examine the risk of prostate cancer associated with foods and nutrients , including individual fatty acids and carotenoids . Methods : Population -based case – control study of 858 men aged < 70 years at diagnosis with histologically confirmed prostate cancer of Gleason Grade 5 or greater , and 905 age-frequency-matched men , selected at r and om from the electoral rolls . Dietary intakes were assessed with a 121-item food frequency question naire . Results : Inverse associations with prostate cancer were observed for ( Odds ratio , OR , 95 % confidence intervals , 95 % CI for tertile III compared with tertile I ) allium vegetables 0.7 , 0.5–0.9 ; p trend 0.01 , tomato-based foods 0.8 , 0.6–1.0 ; p trend 0.03 and total vegetables 0.7 , 0.5–1.0 ; p trend 0.04 . Margarine intake was positively associated with prostate cancer 1.3 , 1.0–1.7 ; p trend 0.04 . The only statistically significant associations observed with nutrients were weak inverse associations for palmitoleic acid ( p trend 0.04 ) , fatty acid 17:1 ( p trend 0.04 ) , and 20:5 n-6 ( p trend 0.05 ) ; and a non-significant trend for oleic acid ( p trend 0.09 ) . Neither total , nor beverage-specific , intake of alcohol was associated with risk . Conclusions : Based on these findings , diets rich in olive oil ( a source of oleic acid ) , tomatoes and allium vegetables might reduce the risk of prostate cancer Epidemiological data on most cancer sites suggest that consumption of plant foods , which contain high levels of antioxidants , might slow or prevent the appearance of cancer . We used data from three case-control studies to test this hypothesis . The total study population consisted of 617 incident cases of prostate cancer and 636 population controls from Ontario , Quebec , and British Columbia . Dietary information was collected by an in-person interview with a detailed quantitative dietary history . Unconditional logistic regression analyses were performed to estimate odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) . A decreasing , statistically significant association was found with increasing intakes of green vegetables ( OR = 0.54 , 95 % CI = 0.40 - 0.71 for 4th quartile ) , tomatoes ( OR = 0.64 , 95 % CI = 0.45 - 0.91 ) , beans/lentils/nuts ( OR = 0.69 , 95 % CI = 0.53 - 0.91 ) , and cruciferous vegetables ( OR = 0.69 , 95 % CI = 0.52 - 0.91 for 3rd quartile ) . Higher intakes of fruit were associated with higher ORs ( OR = 1.51 , 95 % CI = 1.14 - 2.01 for 4th quartile ) , an effect that was seen for total fruit and citrus fruit , as well as for all other noncitrus fruits . Among the grains , refined-grain bread intake was associated with a decrease in risk ( OR = 0.65 for 4th quartile ) , whereas whole-grain breakfast cereals were associated with a higher risk for prostate cancer . Of all the antioxidant nutrients studied , the ORs were higher with higher intakes of cryptoxanthin ( OR = 1.44 , 95 % CI = 1.09 - 1.89 for 4th quartile ) . Exposure to certain dietary components of plant origin , which are potentially modifiable , indicates the theoretical scope for reducing the risk from prostate cancer . Future experimental studies or trials are warranted for further underst and ing The association between diet and prostate cancer ( PC ) risk , although suggestive , still remains largely elusive particularly in the Asian population . This study sought to further evaluate the possible effects of different dietary factors on risk of PC in Iran . Using data from a prospect i ve hospital-based multicenter case-control study , dietary intakes of red meat , fat , garlic , and tomato/tomato products , as well as thorough demographic and medical characteristics , were determined in 194 cases with the newly diagnosed , clinicopathologically confirmed PC and 317 controls , without any malignant disease , admitted to the same network of hospitals . Odds ratios ( ORs ) and corresponding 95 % confidence intervals ( CIs ) were obtained after adjustment for major potential confounders , including age , body mass index , smoking , alcohol , education , occupation , family history of PC , and total dietary calories . Comparing the highest with the lowest tertile , a significant trend of increasing risk with more frequent consumption was found for dietary fat ( OR : 1.79 , 95 % CI : 1.71–4.51 ) , whereas inverse association was observed for tomato/tomato products ( OR : 0.33 , 95 % CI : 0.16–0.65 ) . A nonsignificant increase in PC risk was revealed for dietary red meat ( OR : 1.69 , 95 % CI : 0.93–3.06 ) . For garlic consumption , a borderline reduction in risk was observed ( OR : 0.58 , 95 % CI : 0.32–1.01 ; P = 0.05 ) . In conclusion , our study supports the hypothesis that total fat may increase PC risk and tomatoes/tomato products and garlic may protect patients against PC The role of diet in the etiology of prostate cancer remains unclear , because results from several case‐control and cohort studies on fat intake and risk of prostate cancer have been inconsistent ; few of the studies have adjusted the results for caloric intake . To examine the relationship between energy , intake of several nutrients and risk of prostate cancer ( all stages combined and advanced stages separately ) , we conducted a population ‐based case‐control study in Örebro County , Sweden , from 1989 through 1994 . A total of 526 patients with newly diagnosed prostate cancer and 536 controls , r and omly selected from the population register and frequency‐matched by age , were included in the analyses . Information about dietary intake was obtained from a self‐administered semi‐quantitative food frequency question naire . Odds ratios with 95 % confidence intervals were estimated by unconditional logistic regression . In age‐adjusted analyses , there were positive associations of prostate cancer ( all stages combined ) risk with total energy intake as well as intake of total fat ( saturated and monounsaturated ) , protein , retinol and zinc . The positive association with energy intake was stronger for advanced cancer , with an excess risk of 70 % for the highest quartile vs. the lowest . After adjustment for energy intake , there was no apparent association of prostate cancers ( all stages combined ) with any of the investigated nutrients . However , a weak positive association between intake of retinol and advanced cancer was observed . We conclude that our results provide some evidence that total energy intake is a risk factor for prostate cancer . © 1996 Wiley‐Liss , OBJECTIVE To compare the efficacy of lycopene plus orchidectomy with orchidectomy alone in the management of advanced prostate cancer . PATIENTS AND METHODS Fifty-four patients with histologically confirmed metastatic prostatic cancer ( M1b or D2 ) and a performance status of 0 - 2 ( World Health Organization ) were entered into the trial between March 2000 and June 2002 . The trial comprised two treatment arms , i.e. patients were r and omized to orchidectomy alone or orchidectomy plus lycopene ( OL ) , each of 27 patients . Lycopene was started on the day of orchidectomy at 2 mg twice daily . Patients were evaluated clinical ly before and every 3 months after the intervention , with measurements of prostate-specific antigen ( PSA ) , a bone scan and uroflowmetry , with the clinical response assessed as the change in these variables . RESULTS At 6 months there was a significant reduction in PSA level in both treatments , but more marked in the OL group ( mean 9.1 and 26.4 ng/mL , P = 0.9 ) . After 2 years these changes were more consistent in the OL group ( mean 3.01 and 9.02 ng/mL ; P < 0.001 ) . Eleven ( 40 % ) patients in orchidectomy and 21 ( 78 % ) in the OL group had a complete PSA response ( P < 0.05 ) , with a partial response in nine ( 33 % ) and four ( 15 % ) , and progression in seven ( 25 % ) and two ( 7 % ) , respectively ( P < 0.05 ) . Bone scans showed that in the orchidectomy arm only four ( 15 % ) patients had a complete response , vs eight ( 30 % ) in the OL group ( P < 0.02 ) , with a partial response in 19 ( 70 % ) and 17 ( 63 % ) , and progression in four ( 15 % ) and two ( 7 % ) , respectively ( P < 0.02 ) . There was a significant improvement in peak flow rate in the OL group , with a mean difference of + 1.17 mL/s ( P < 0.04 ) . Of the 54 patients who entered the trial , 19 ( 35 % ) died , 12 ( 22 % ) in orchidectomy and seven ( 13 % ) in OL group ( P < 0.001 ) . CONCLUSION Adding lycopene to orchidectomy produced a more reliable and consistent decrease in serum PSA level ; it not only shrinks the primary tumour but also diminishes the secondary tumours , providing better relief from bone pain and lower urinary tract symptoms , and improving survival compared with orchidectomy alone Carotenoids are thought to diminish the incidence of certain degenerative diseases , but the mechanisms involved in their intestinal absorption are poorly understood . Our aim was to obtain basic data on the fate of carotenoids in the human stomach and duodenum . Ten healthy men were intragastrically fed three liquid test meals differing only in the vegetable added 3 wk apart and in a r and om order . They contained 40 g sunflower oil and mashed vegetables as the sole source of carotenoids . Tomato purée provided 10 mg lycopene as the main carotenoid , chopped spinach ( 10 mg lutein ) , and carrot purée ( 10 mg beta-carotene ) . Sample s of stomach and duodenal contents and blood sample s were collected at regular time intervals after meal intake . all-trans and cis carotenoids were assayed in stomach and duodenal contents , in the fat and aqueous phases of those contents , and in chylomicrons . The cis-trans beta-carotene and lycopene ratios did not significantly vary in the stomach during digestion . Carotenoids were recovered in the fat phase present in the stomach during digestion . The proportion of all-trans carotenoids found in the micellar phase of the duodenum was as follows ( means + /- SE ) : lutein ( 5.6 + /- 0.4 % ) , beta-carotene ( 4.7 + /- 0.3 % ) , lycopene ( 2.0 + /- 0.2 % ) . The proportion of 13-cis beta-carotene in the micellar phase was significantly higher ( 14.8 + /- 1.6 % ) than that of the all-trans isomer ( 4.7 + /- 0.3 % ) . There was no significant variation in chylomicron lycopene after the tomato meal , whereas there was significant increase in chylomicron beta-carotene and lutein after the carrot and the spinach meals , respectively . There is no significant cis-trans isomerization of beta-carotene and lycopene in the human stomach . The stomach initiates the transfer of carotenoids from the vegetable matrix to the fat phase of the meal . Lycopene is less efficiently transferred to micelles than beta-carotene and lutein . The very small transfer of carotenoids from their vegetable matrices to micelles explains the poor bioavailability of these phytomicroconstituents OBJECTIVES Tomatoes are rich in lycopene . This study explored the efficacy of a lycopene-rich tomato product in and rogen-independent prostate cancer and the reasons patients participated in an " alternative medicine " study . METHODS This Phase II study evaluated 46 patients with and rogen-independent prostate cancer . All were asymptomatic and had serum prostate-specific antigen elevation despite hormonal manipulation . All patients completed a question naire on their motivations for enrolling in an " alternative medicine " study . Patients were prescribed a lycopene-rich tomato supplement at a lycopene dose of 15 mg twice daily . RESULTS One patient manifested a tumor response with a 50 % or greater confirmed decline in serum prostate-specific antigen level , yielding a response rate of 2 % . Lycopene was well tolerated , but 1 patient died of a cancer-related hemorrhage , and 1 had grade 4 diarrhea . Grade 1 or 2 events included diarrhea in 18 , nausea in 12 , abdominal distension in 8 , flatulence in 2 , vomiting in 2 , anorexia in 1 , and dyspepsia in 1 . The reasons for entering the trial are discussed and were overall positive . CONCLUSIONS Lycopene , as prescribed in our study , did not appear effective for and rogen-independent prostate cancer . The patients ' reasons for enrolling in this trial were positive and realistic beta-Carotene and Retinol Efficacy Trial is a nationwide chemoprevention trial that recruited 18,314 high-risk individuals to test the effect of supplemental beta-carotene and retinol on lung cancer incidence . In this report , we conducted a prospect i ve nested case-control study of the association between serum carotenoids , retinoids , and tocopherols on both lung and prostate cancer incidence . Prer and omization serum sample s were selected from 278 lung cancer cases and 205 prostate cancer cases , and 483 controls matched by high-risk population , study center location , age , sex ( lung cancer only ) , smoking status , and year of r and omization . Carotenoids , retinoids , and tocopherols were analyzed by high-performance liquid chromatography . Endpoints were confirmed by pathology review ( lung cancer ) or review of the pathology report ( prostate cancer ) . In the control-only population , there was a significant association between tobacco use and serum micronutrient concentration . Current smokers compared with former smokers had lower mean levels of all of the micronutrients tested with zeaxanthin , beta-cryptoxanthin , alpha-carotene , alpha-tocopherol , retinol , and retinyl palmitate reaching statistical significance at P = 0.05 . In the overall population , the mean serum concentrations of all of the micronutrients except gamma-tocopherol were lower for lung cancer cases than controls . Statistically significant trends across quartiles were observed in lutein ( P = 0.02 ) , zeaxanthin ( P = 0.02 ) , and alpha-tocopherol ( P = 0.03 ) . The carotenoid findings in the overall population were because of the strong inverse association between serum micronutrients and lung cancer in females . Statistically significant odds ratios ( ORs ) comparing 4(th ) to 1st quartiles in the female population were seen in lutein [ OR , 0.31 ; confidence interval ( CI ) , 0.13 - 0.75 ] , zeaxanthin ( OR , 0.31 ; CI , 0.12 - 0.77 ) , and beta-cryptoxanthin ( OR , 0.34 ; CI , 0.14 - 0.81 ) . For prostate cancer , mean serum concentrations were lower in cases for all of the nutrients except alpha-carotene . Only for alpha-tocopherol ( P(trend ) = 0.04 ) were the findings statistically significant . There was no statistically significant association between serum carotenoids and prostate cancer . Our findings provide additional support for the association between physiological levels of dietary micronutrients and cancer incidence A diverse body of evidence suggests that lycopene might inhibit prostate cancer development . We conducted a 6-mo repeat biopsy r and omized trial among men with high- grade prostatic intraepithelial neoplasia ( HGPIN ) . Here we report results for serum lycopene , prostate specific antigen ( PSA ) and insulin-like growth factor ( IGF ) proteins , histopathological review , and tissue markers for proliferation [ minichromosome maintenance protein 2 ( MCM-2 ) ] and cell cycle inhibition ( p27 ) . Participants consumed placebo or tomato extract capsules containing 30 mg/day lycopene . Pre- and posttreatment biopsies were immunostained and digitally scored . Serum lycopene was determined by LC-MS-MS . In secondary analyses , pathologists blindly review ed each biopsy to score histological features . Fifty-eight men completed the trial . Serum lycopene increased 0.55 μmol/L with treatment and declined 0.29 μmol/L with placebo . We observed no meaningful differences in PSA , IGF-1 , or IGF binding protein 3 concentrations between groups , nor any differences in expression of MCM-2 or p27 in epithelial nuclei . Prevalences of cancer , HGPIN , atrophy , or inflammation posttreatment were similar ; however , more extensive atrophy and less extensive HGPIN was more common in the lycopene group . Despite large differences in serum lycopene following intervention , no treatment effects were apparent on either the serum or benign tissue endpoints . Larger studies are warranted to determine whether changes observed in extent of HGPIN and focal atrophy can be replicated . Trial registration : Clinical Trials.gov identifier : NCT00416325 OBJECTIVES To evaluate the feasibility of implementing a diet-based intervention in men with prostate cancer . METHODS Seventy-four men aged 50 to 80 years with biopsy-proven adenocarcinoma of the prostate were r and omized to receive either telephone-based dietary counseling or st and ardized , written nutritional information . Telephone dietary counseling targets included increased intakes of vegetables ( particularly cruciferous vegetables and tomato products ) , whole grains , and beans/legumes . Dietary intakes and plasma carotenoid levels were assessed at baseline and at 6 months ' follow-up . RESULTS In the intervention arm , mean daily intakes of total vegetables , crucifers , tomato products , and beans/legumes increased by 76 % , 143 % , 292 % , and 95 % , respectively , whereas fat intake decreased by 12 % ( P = 0.02 ) . In the control arm , there were no significant changes in mean intakes of total vegetables , tomato products , crucifers , beans/legumes , or fat . Similarly , in the intervention arm , mean plasma levels of alpha-carotene , beta-carotene , lutein , lycopene , and total carotenoids increased by 33 % , 36 % , 19 % , 30 % , and 26 % , respectively ( P < 0.05 ) . In the control arm , there were no significant changes in plasma levels of alpha- or beta-carotene , lutein , lycopene , or total carotenoids . CONCLUSIONS Telephone-based dietary counseling increases vegetable intake , decreases fat intake , and significantly increases plasma levels of potentially anticarcinogenic carotenoids in men with prostate cancer . These data support the feasibility of implementing clinical trials of dietary intervention in men with prostate cancer Previous studies relating increased serum levels of folate and fat-soluble vitamins to prostate cancer risk have variously shown null associations or to either decrease or increase the risk of developing prostate cancer . Prospect i ve studies of serum folate levels have been reported to show a null association and increased serum levels to either decrease or increase the risk of subsequently developing prostate cancer . Similarly , serum β-carotene and lycopene levels have either been reported to be inversely correlated or not associated with prostate cancer risk . Using a prospect i ve nested case-control study design , which minimized the possibility of disease effects on serum-vitamin concentrations , we report null associations for serum concentrations of folate , lycopene , β-carotene , vitamin A and vitamin E , and subsequent development of prostate cancer BACKGROUND The rate of decrease in advanced cancers is an estimate for determining prostate cancer ( PCa ) screening program effectiveness . OBJECTIVE Assess the effectiveness of PCa screening programs using a 2- or 4-yr screening interval . DESIGN , SETTING , AND PARTICIPANTS Men aged 55 - 64 yr were participants at two centers of the European R and omized Study of Screening for Prostate Cancer : Gothenburg , Sweden ( 2-yr screening interval , n=4202 ) , and Rotterdam , the Netherl and s ( 4-yr screening interval , n=13 301 ) . We followed participants until the date of PCa , the date of death , or the last follow-up at December 31 , 2008 , or up to a maximum of 12 yr after initial screening . Potentially life-threatening ( advanced ) cancer was defined as cancer with at least one of following characteristics : clinical stage ≥T3a , M1 , or N1 ; serum prostate-specific antigen ( PSA ) > 20.0 ng/ml ; or Gleason score ≥8 at biopsy . INTERVENTION We compared the proportional total ( advanced ) cancer incidence ( screen-detected and interval cases ) , defined as the ratio of the observed number of ( advanced ) cancers to the expected numbers of ( advanced ) cancers based on the control arm of the study . MEASUREMENTS The proportional cancer incidence from the second screening round until the end of observation was compared using a 2- or 4-yr screening interval . RESULTS AND LIMITATIONS From screening round 2 until the end of observation , the proportional cancer incidence was 3.64 in Gothenburg and 3.08 in Rotterdam ( relative risk [ RR ] : 1.18 ; 95 % confidence interval [ CI ] , 1.04 - 1.33 ; p=0.009 ) . The proportional advanced cancer incidence was 0.40 in Gothenburg and 0.69 in Rotterdam ( RR : 0.57 ; 95 % CI , 0.33 - 0.99 ; p=0.048 ) ; the RR for detection of low-risk PCa was 1.46 ( 95 % CI , 1.25 - 1.71 ; p<0.001 ) . This study was limited by the assumption that PSA testing in the control arm was similar in both centers . CONCLUSIONS A 2-yr screening interval significantly reduced the incidence of advanced PCa ; however , the 2-yr interval increased the overall risk of being diagnosed with ( low-risk ) PCa compared with a 4-yr interval in men aged 55 - 64 yr . Individualized screening algorithms must be improved to provide the strategy for this issue BACKGROUND Diet may substantially alter prostate cancer initiation and progression . However , large-scale clinical trials of diet modification have yet to be performed for prostate cancer . The Men 's Eating and Living ( MEAL ) Study ( CALGB 70807 [ Alliance ] ) is investigating the effect of increased vegetable consumption on clinical progression in men with localized prostate cancer . STUDY DESIGN MEAL is a r and omized , phase III clinical trial design ed to test whether an intervention that increases vegetable intake will decrease the incidence of clinical progression in men with clinical ly localized prostate cancer on active surveillance . We are r and omizing 464 patients to either a vali date d telephone-based diet counseling intervention or a control condition in which patients receive a published diet guideline . The intervention will continue for two years . The primary outcome variable is clinical progression defined by serum prostate-specific antigen ( PSA ) and pathological findings on follow-up prostate biopsy . Secondary outcome variables include incidence of surgical and non-surgical treatments for prostate cancer , prostate-cancer related patient anxiety and health-related quality of life . CONCLUSION The MEAL Study is assessing the effectiveness of a high-vegetable diet intervention for preventing clinical progression in men with localized prostate cancer on active surveillance |
10,416 | 16,894,798 | For acute low back pain , segmental stabilizing exercises are equally effective in reducing short-term disability and pain and more effective in reducing long-term recurrence of low back pain than treatment by GP .
For chronic low back pain , segmental stabilizing exercises are , in the short and long term , more effective than GP treatment and may be as effective as other physiotherapy treatments in reducing disability and pain .
There is limited evidence that segmental stabilizing exercises additional to other physiotherapy treatment are equally effective for pain and more effective concerning disability than other physiotherapy treatments alone .
There is no evidence concerning subacute low back pain . | Objectives : To evaluate the effectiveness of segmental stabilizing exercises for acute , subacute and chronic low back pain with regard to pain , recurrence of pain , disability and return to work . | Study Design . A prospect i ve r and omized controlled trial . Objectives . To examine the effectiveness of combined manipulative treatment , stabilizing exercises , and physician consultation compared with physician consultation alone for chronic low back pain . Summary of Background Data . Strong evidence exists that manual therapy provides more effective short-term pain relief than does placebo treatment in the management of chronic low back pain . The evidence for long-term effect is lacking . Methods . Two hundred four chronic low back pain patients , whose Oswestry disability index was at least 16 % , were r and omly assigned to either a manipulative-treatment group or a consultation group . All were clinical ly examined , informed about their back pain , provided with an educational booklet , and were given specific instructions based on the clinical evaluation . The treatment included four sessions of manipulation and stabilizing exercises aim ing to correct the lumbopelvic rhythm . Question naires inquired about pain intensity , self-rated disability , mental depression , health-related quality of life , health care costs , and production costs . Results . At the baseline , the groups were comparable , except for the percentage of employees ( P = 0.01 ) . At the 5- and 12-month follow-ups , the manipulative-treatment group showed more significant reductions in pain intensity ( P < 0.001 ) and in self-rated disability ( P = 0.002 ) than the consultation group . However , we detected no significant difference between the groups in health-related quality of life or in costs . Conclusions . The manipulative treatment with stabilizing exercises was more effective in reducing pain intensity and disability than the physician consultation alone . The present study showed that short , specific treatment programs with proper patient information may alter the course of chronic low back pain AIM The aim of the study was to evaluate the outcome of outpatient rehabilitation in patients with low back pain and lumbar disk disease with a specific stabilizing exercise of the M. multifidus and M. transversus abdominis . METHOD 99 out patients admitted to a rehabilitation unit were included in a prospect i ve r and omized controlled interventional trial . The interventional group consisted of 50 patients ( 34 male , 16 female ; mean age 41.1 + /- 9.1 , range ; 21 - 54 years ) , 49 patients ( 31 male , 18 female ; mean age 37.9 + /- 9.5 , range ; 19 - 55 years ) were in the control group . Outcomes were assessed at the beginning and the end of the treatment and at a three month follow-up with the Oswestry Low Back Pain Disability Question naire , the Hannover Functional Ability Question naire FFbH-R , the pain scale SES and a numeric rating scale . RESULTS In both groups there was a significant functional improvement as measured with the Oswestry Score and the FFbH-R. The interventional group showed better values at the end of the treatment . Pain as well could be reduced significantly by the treatment , but no differences were noted between the two groups . CONCLUSION Outpatient rehabilitation improved functional capacity and pain in both groups . Advantages could be seen in the interventional group concerning functional status . The specific stabilizing exercise approach appears to be effective in conservative treatment programs of low back pain and lumbar disk disease Many studies have identified changes in trunk muscle recruitment in clinical low back pain ( LBP ) . However , due to the heterogeneity of the LBP population these changes have been variable and it has been impossible to identify a cause-effect relationship . Several studies have identified a consistent change in the feedforward postural response of transversus abdominis ( TrA ) , the deepest abdominal muscle , in association with arm movements in chronic LBP . This study aim ed to determine whether the feedforward recruitment of the trunk muscles in a postural task could be altered by acute experimentally induced LBP . Electromyographic ( EMG ) recordings of the abdominal and paraspinal muscles were made during arm movements in a control trial , following the injection of isotonic ( non-painful ) and hypertonic ( painful ) saline into the longissimus muscle at L4 , and during a 1-h follow-up . Movements included rapid arm flexion in response to a light and repetitive arm flexion-extension . Temporal and spatial EMG parameters were measured . The onset and amplitude of EMG of most muscles was changed in a variable manner during the period of experimentally induced pain . However , across movement trials and subjects the activation of TrA was consistently reduced in amplitude or delayed . Analyses in the time and frequency domain were used to confirm these findings . The results suggest that acute experimentally induced pain may affect feedforward postural activity of the trunk muscles . Although the response was variable , pain produced differential changes in the motor control of the trunk muscles , with consistent impairment of TrA activity Study Design . A r and omized clinical trial with 1-year and 3-year telephone question naire follow-ups . Objective . To report a specific exercise intervention ’s long-term effects on recurrence rates in acute , first-episode low back pain patients . Summary of Background Data . The pain and disability associated with an initial episode of acute low back pain ( LBP ) is known to resolve spontaneously in the short-term in the majority of cases . However , the recurrence rate is high , and recurrent disabling episodes remain one of the most costly problems in LBP . A deficit in the multifidus muscle has been identified in acute LBP patients , and does not resolve spontaneously on resolution of painful symptoms and resumption of normal activity . Any relation between this deficit and recurrence rate was investigated in the long-term . Methods . Thirty-nine patients with acute , first-episode LBP were medically managed and r and omly allocated to either a control group or specific exercise group . Medical management included advice and use of medications . Intervention consisted of exercises aim ed at rehabilitating the multifidus in cocontraction with the transversus abdominis muscle . One year and three years after treatment , telephone question naires were conducted with patients . Results . Question naire results revealed that patients from the specific exercise group experienced fewer recurrences of LBP than patients from the control group . One year after treatment , specific exercise group recurrence was 30 % , and control group recurrence was 84 % ( P < 0.001 ) . Two to three years after treatment , specific exercise group recurrence was 35 % , and control group recurrence was 75 % ( P < 0.01 ) . Conclusion . Long-term results suggest that specific exercise therapy in addition to medical management and resumption of normal activity may be more effective in reducing low back pain recurrences than medical management and normal activity alone & NA ; Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy , postherpetic neuralgia , chronic low back pain , fibromyalgia , and osteoarthritis were used . The studies had similar design s and measurement instruments , including the PI‐NRS , collected in a daily diary , and the st and ard seven‐point patient global impression of change ( PGIC ) , collected at the endpoint . The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject . Categories of ‘ much improved ’ and ‘ very much improved ’ were used as determinants of a clinical ly important difference and the relationship to the PI‐NRS was explored using graphs , box plots , and sensitivity/specificity analyses . A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study , disease type , age , sex , study result , or treatment group . On average , a reduction of approximately two points or a reduction of approximately 30 % in the PI‐NRS represented a clinical ly important difference . The relationship between percent change and the PGIC was also consistent regardless of baseline pain , while higher baseline scores required larger raw changes to represent a clinical ly important difference . The application of these results to future studies may provide a st and ard definition of clinical ly important improvement in clinical trials of chronic pain therapies . Use of a st and ard outcome across chronic pain studies would greatly enhance the comparability , validity , and clinical applicability of these studies The efficacy of specific exercise interventions that advocate training the co-contraction of the deep abdominal muscles with lumbar multifidus for treating chronic back pain conditions has not been tested . A r and omized controlled trial involving 42 subjects with a specific chronic back pain condition investigated whether this form of intervention results in changes to the ratio of activation of the internal oblique relative to the rectus abdominis . Data were collected before and after the intervention , using surface electromyography , while subjects performed different abdominal maneuvers . Subjects were r and omly allocated to either a specific exercise group or control group . Following intervention , the specific exercise group showed a significant ( p < 0.05 ) increase in the ratio of activation of the internal oblique relative to the rectus abdominis . The control group showed no significant change . The study findings provide evidence that the conscious and automatic patterns of abdominal muscle activation can be altered by specific exercise interventions BACKGROUND The prescription of exercise as a conservative treatment for lumbar pain is frequent and seems effective for the chronic cases of nonspecific low back pain . However , there is no evidence favoring one type of exercise over another . Often , exercise programs are prescribed without adequate evaluation of the individual characteristics like posture , muscular force , and extensibility . Patients with totally different causes of low back pain will often be given the same type of exercises . OBJECTIVE Our objective was to compare the effectiveness of 2 home exercise programs in decreasing disability and pain related to subacute and chronic nonspecific low back pain . To do so we compared a specific ( individualized ) exercise program with a program of commonly prescribed exercises for low back pain . METHOD In a control group study , 20 patients with chronic or subacute nonspecific low back pain participated after giving their informed consent . All subjects were evaluated ( physical evaluation of lumbar and pelvic muscles [ 1 ] force and [ 2 ] extensibility , [ 3 ] trunk range of motion ) and then divided in 2 groups : 10 patients received specific exercises ( experimental group ) based on their evaluation , and 10 patients received a commonly prescribed exercise program for low back pain ( control group ) . Six weeks later a second physical evaluation was conducted . Pain ( visual analog pain scale ) and disability ( modified Oswestry ) question naires were also completed by each subject at both evaluations . DESIGN This was a r and omized experimental study . RESULTS Both groups had similar age , weight , and sex characteristics . The experimental group showed significant improvements for some components targeted by the program . The control group significantly had improvement of some physical characteristics not related to their initial deficits . Even if both groups showed some improvements in muscular force and extensibility , only the members of the group who received specific exercises significantly reduced their level of pain and disability . Both groups showed a similar rate of participation in the program . CONCLUSION The results of this study suggest that applying a specific physical evaluation and exercise prescription is an appropriate treatment for people having subacute or chronic nonspecific pain . Thus clinicians should prescribe exercise programs based on individual muscular deficits rather than most commonly prescribed exercise programs Study Design . A r and omized , controlled trial , test‐retest design , with a 3‐ , 6‐ , and 30‐month postal question naire follow‐up . Objective . To determine the efficacy of a specific exercise intervention in the treatment of patients with chronic low back pain and a radiologic diagnosis of spondylolysis or spondylolisthesis . Summary of Background Data . A recent focus in the physiotherapy management of patients with back pain has been the specific training of muscles surrounding the spine ( deep abdominal muscles and lumbar multifidus ) , considered to provide dynamic stability and fine control to the lumbar spine . In no study have research ers evaluated the efficacy of this intervention in a population with chronic low back pain where the anatomic stability of the spine was compromised . Methods . Forty‐four patients with this condition were assigned r and omly to two treatment groups . The first group underwent a 10‐week specific exercise treatment program involving the specific training of the deep abdominal muscles , with co‐activation of the lumbar multifidus proximal to the pars defects . The activation of these muscles was incorporated into previously aggravating static postures and functional tasks . The control group underwent treatment as directed by their treating practitioner . Results . After intervention , the specific exercise group showed a statistically significant reduction in pain intensity and functional disability levels , which was maintained at a 30‐month follow‐up . The control group showed no significant change in these parameters after intervention or at follow‐up . Summary . A " specific exercise " treatment approach appears more effective than other commonly prescribed conservative treatment programs in patients with chronically symptomatic spondylolysis or spondylolisthesis Degenerative disc disease may affect younger and middle-aged people with a kind of premature disc degeneration . The majority of these low back pain patients are not c and i date s for a spinal fusion and are in need of a structured conservative treatment . In a controlled clinical trial , 27 low back pain patients ( mean age 40 years , range 25 - 48 ) with a mean duration of symptoms of 7.4 years , were r and omized to mobilizing ( n = 12 ) or stabilizing ( n = 15 ) daily half hour exercise for an eight weeks period . A clinical overall score ( COS ) based on pain intensity ( VAS ) , physical signs , functional status ( Oswestry ) and analgetics was used as outcome criterion . The treatment results were best for the group undergoing stabilizing treatment . They achieved a 17 % reduction in COS , compared to a 10 % increase in the group undergoing mobilizing treatment ( p = 0.02 ) . These types of exercises are discussed in relation to the instability theory in disc degeneration & NA ; The purpose of this study was to determine the levels of change on st and ard pain scales that represent clinical ly important differences to patients . Data from analgesic studies are often difficult to interpret because the clinical importance of the results is not obvious . Differences between groups , as summarized by a change in mean values over time , can be difficult to apply to clinical care . Baseline scores vary widely and group mean differences could reflect large changes in a few patients , small changes in many patients , or any combination of these outcomes . Determination of the proportion of patients who have a clinical ly important improvement in their pain would provide a more interpretable result with direct clinical implication s. However , determining a clinical ly important outcome requires information about the degree of change over time that is clinical ly important . Data from the titration phase of a multiple cross‐over r and omized clinical trial of oral transmucosal fentanyl citrate ( OTFC ) for the treatment of cancer‐related breakthrough pain were re‐analyzed to examine the differences in pain scores between treatment episodes that did and did not yield adequate pain relief . The scales evaluated were absolute pain intensity difference ( PID , 0–10 scale ) , percentage pain intensity difference ( PID% , 0–100 % scale ) , pain relief ( PR , 0 ( none ) , 1 ( slight ) , 2 ( moderate ) , 3 ( lots ) , 4 ( complete ) ) , sum of the pain intensity difference ( SPID over 60 min ) , percentage of maximum total pain relief ( % Max TOTPAR over 60 min ) , and global medication performance ( 0 ( poor ) , 1 ( fair ) , 2 ( good ) , 3 ( very good ) , 4 ( excellent ) ) . Adequate relief was defined by the patient 's decision not to use another dose of opioid medication as a rescue , in addition to the study medication , to treat each painful episode . One hundred thirty OTFC naive patients contributed data on 1268 episodes of breakthrough pain . The scales that were converted to a percentage change yielded the best accuracy in predicting adequate relief , with balanced sensitivity and specificity . The best cut‐off point for both the % Max TOTPAR and the PID% was 33 % . The best cut‐off points for the absolute scales were absolute pain intensity difference of 2 , pain relief of 2 ( moderate ) , and SPID of 2 . The global medication performance of 2 ( good ) had excellent values as well . This study presents data ‐derived cut‐off points for the changes in several pain scales , each reflecting the clinical ly important improvement for patients treating breakthrough cancer pain episodes with OTFC . Confirmation in other patient population s and different pain syndromes will be needed . The use of consistent clinical ly important cut‐off points as the primary outcome in future pain therapy clinical trials will enhance their validity , comparability , and clinical applicability Objectives —To determine the effect of different training schedules on the cross sectional area ( CSA ) of the lumbar multifidus muscle in patients with chronic low back pain . Methods —Each of 59 nine patients was r and omly assigned to one of three programmes : 10 weeks of stabilisation training ( group 1 ; n = 19 ) ; 10 weeks of stabilisation training combined with dynamic resistance training ( group 2 ; n = 20 ) ; 10 weeks of stabilisation training combined with dynamic-static resistance training ( group 3 ; n = 20 ) . Before and after 10 weeks of training , multifidus CSAs were measured from st and ard computed tomography images at three different levels ( upper end plate of L3 and L4 , and lower end plate of L4 ) . Results —The CSA of the multifidus muscle was significantly increased at all levels after training in group 3 . In contrast , no significant differences were found in groups 1 and 2 . Conclusions —General stabilisation exercises and dynamic intensive lumbar resistance training have no significant effect on the CSA of the lumbar multifidus muscle in patients with chronic low back pain . The static holding component between the concentric and eccentric phase was found to be critical in inducing muscle hypertrophy during the first 10 weeks . Treatment consisting of stabilisation training combined with an intensive lumbar dynamic-static strengthening programme seems to be the most appropriate method of restoring the size of the multifidus muscle Background : A pathological cause can not be identified for most new episodes of low back pain ( LBP ) presenting to the general practitioner . One important potential influence on susceptibility is previous pain experience . To accurately investigate the contribution of this phenomenon to the onset of new episodes of LBP a prospect i ve population study is required . Aims : To determine the relationship of prior pain in the back and other musculoskeletal sites to risk of subsequent new episodes of LBP . Methods : The population studied included all 2715 adults from the South Manchester Back Pain Study who were free of LBP during the month prior to the baseline survey . At baseline a detailed musculoskeletal pain history was obtained . New episodes of LBP over the subsequent 12 months were ascertained by : ( i ) prospect ively monitoring all primary care consultations in the study cohort ( consulting episodes ) and ( ii ) a follow‐up survey after 1 year to determine new episodes during that 12‐month period not leading to consultation ( non‐consulting episodes ) . Results : The 12‐month cumulative incidence of new consulting episodes was 3 % in males and 5 % in females , and for new non‐consulting episodes 31 % in males and 32 % in females . Those with a history of previous LBP had twice the rate of new episodes , both consulting and non‐consulting , compared to those with no LBP in the past . Neck pain or pain in other musculoskeletal sites at baseline also doubled the risk of a subsequent new episode of LBP . Adjusting for psychological distress and the other pain variables had little influence on the findings . Conclusion : In those currently free of LBP a previous history of the symptom substantially increases the risk of a further episode , with pain in other sites an equally strong independent predictor of subsequent LBP Study Design A clinical study was conducted on 39 patients with acute , first‐episode , unilateral low back pain and unilateral , segmental inhibition of the multifidus muscle . Patients were allocated r and omly to a control or treatment group . Objectives To document the natural course of lumbar multifidus recovery and to evaluate the effectiveness of specific , localized , exercise therapy on muscle recovery . Summary of Background Data Acute low back pain usually resolves spontaneously , but the recurrence rate is high . Inhibition of multifidus occurs with acute , first‐episode , low back pain , and pathologic changes in this muscle have been linked with poor outcome and recurrence of symptoms . Methods Patients in group 1 received medical treatment only . Patients in group 2 received medical treatment and specific , localized , exercise therapy . Outcome measures for both groups included 4 weekly assessment s of pain , disability , range of motion , and size of the multifidus cross‐sectional area . Independent examiners were blinded to group allocation . Patients were reassessed at a 10‐week follow‐up examination . Results Multifidus muscle recovery was not spontaneous on remission of painful symptoms in patients in group 1 . Muscle recovery was more rapid and more complete in patients in group 2 who received exercise therapy ( P = 0.0001 ) . Other outcome measurements were similar for the two groups at the 4‐week examination . Although they resumed normal levels of activity , patients in group 1 still had decreased multifidus muscle size at the 10‐week follow‐up examination . Conclusions Multifidus muscle recovery is not spontaneous on remission of painful symptoms . Lack of localized , muscle support may be one reason for the high recurrence rate of low back pain following the initial episode The purpose of this study was to determine the effect of different training schedules on the cross-sectional area ( CSA ) of the paravertebral muscles ( PA ) in chronic low back pain ( CLBP ) patients . To achieve this goal 59 patients were r and omly assigned to three different 10-week rehabilitation programs : stabilization training ( group 1 , n=19 ) , stabilization training combined with dynamic resistance training ( group 2 , n=20 ) and stabilization training combined with dynamic-static resistance training ( group 3 , n=20 ) . The CSA of the PA was derived from st and ard computerized tomography ( CT ) images at three different levels . The CSA of the PA was found to increase statistically in group 2 ( upper end-plate of L4 ) and group 3 ( upper end-plate of L3 and lower end-plate of L4 ) . In contrast , no statistical differences over time were found in group 1 . Since stabilization exercises have no effect on the CSA of the PA , intensive lumbar resistance training seems to be necessary to restore the size of the PA in CLBP patients with atrophied back muscles . No systematic difference in hypertrophy between dynamic and dynamic-static strengthening training modes was found The present aim was to compare the effects of stabilizing training with those of manual treatment in patients with sub-acute or chronic low-back pain ( LBP ) . Forty-seven patients were r and omized to a stabilizing training group ( ST group ) or a manual treatment group ( MT group ) . The patients underwent a 6-week treatment programme on a weekly basis . Pain , health and functional disability level at the start of treatment , after treatment , and at 3- and 12-month follow-ups were assessed . In the ST group all assessed variables improved significantly ( P<0.05 ) after the treatment period and were maintained long term . After the treatment period there was a significant difference between the groups in assessed function ( P<0.05 ) . More individuals in the ST group had improved than in the MT group . At the 3-month follow-up significantly more improved individuals were evident in the ST group regarding pain , general health and functional disability levels . In the long term , significantly more ( P<0.05 ) patients in the MT group reported recurrent treatment periods . The study did not indicate any clear short-term differences between the groups in the accessed outcome measures . In the long term , however , stabilizing training seemed to be more effective than manual treatment in terms of improvement of individuals and the reduced need for recurrent treatment periods Abstract Objectives : To investigate the cl aim that 90 % of episodes of low back pain that present to general practice have resolved within one month . Design : Prospect i ve study of all adults consulting in general practice because of low back pain over 12 months with follow up at 1 week , 3 months , and 12 months after consultation . Setting : Two general practice s in south Manchester . Subjects : 490 subjects ( 203 men , 287 women ) aged 18 - 75 years . Main outcome measures : Proportion of patients who have ceased to consult with low back pain after 3 months ; proportion of patients who are free of pain and back related disability at 3 and 12 months . Results : Annual cumulative consultation rate among adults in the practice s was 6.4 % . Of the 463 patients who consulted with a new episode of low back pain , 275 ( 59 % ) had only a single consultation , and 150 ( 32 % ) had repeat consultations confined to the 3 months after initial consultation . However , of those interviewed at 3 and 12 months follow up , only 39/188 ( 21 % ) and 42/170 ( 25 % ) respectively had completely recovered in terms of pain and disability . Conclusions : The results are consistent with the interpretation that 90 % of patients with low back pain in primary care will have stopped consulting with symptoms within three months . However most will still be experiencing low back pain and related disability one year after consultation . Key messages It is widely believed that 90 % of episodes of low back pain seen in general practice resolve within one month In a large population based study we examined the outcome of episodes of low back pain in general practice with respect to both consultation behaviour and self reported pain and disability While 90 % of subjects consulting general practice with low back pain ceased to consult about the symptoms within three months , most still had substantial low back pain and related disability Only 25 % of the patients who consulted about low back pain had fully recovered 12 months later Since most consulters continue to have long term low back pain and disability , effective early treatment could reduce the burden of these symptoms and their social , economic , and medical |
10,417 | 25,749,077 | After flapless extraction of teeth , and using a minimum healing period of 12 weeks as a temporal measure , xenografts and allografts result ed in the least loss of socket dimensions compared to alloplasts or sockets with no grafting .
Histologic outcomes after a minimum of 12 weeks of healing showed that sockets grafted with alloplasts had the maximum amount of vital bone and the least amount of remnant graft material and remnant connective tissue .
There is a limited but emerging body of evidence for the predictable regeneration of deficient buccal bone with socket grafting material s , need for barrier membranes , use of tissue engineering , and use of autogenous soft tissue grafts from the palate to cover the socket | STATEMENT OF PROBLEM Several bio material s and techniques have been reported for socket grafting and alveolar ridge preservation .
However , the evidence for clinical and histologic outcomes for socket grafting with different types of material s in flapless extraction is not clear .
PURPOSE The purpose of this systematic review was to analyze the outcomes of a socket grafting procedure performed with flapless extraction of teeth in order to determine which graft material results in the least loss of socket dimensions , the maximum amount of vital bone , the least remnant graft material , and the least amount of connective tissue after a minimum of 12 weeks of healing .
Secondary outcomes , including the predictability of regenerating deficient buccal bone , necessity of barrier membranes , and coverage with autogenous soft tissue graft , were also evaluated . | Healing of the extraction socket after tooth removal involves retention of the blood clot followed by a sequence of events that lead to changes in the alveolar process in a three dimensional fashion . This normal healing event results in a minimal loss of vertical height ( around 1 mm ) , but a substantial loss of width in the buccal-lingual plane ( 4 - 6 mm ) . During the first three months following extraction that loss has been shown to be significant and may result in both a hard tissue and soft tissue deformity affecting the ability to restore the site with acceptable esthetics . Procedures that reduce the resorptive process have been shown to be predictable and potentially capable of eliminating secondary surgery for site preparation when implant therapy is planned . The key element is prior planning by the dental therapist to act at the time of extraction to prevent the collapse of the ridge due to the loss of the alveolus . Several techniques have been employed as ridge preservation procedures involving the use of bone grafts , barrier membranes and biologics to provide a better restorative outcome . This review will explore the evidence behind each technique and their efficacy in accomplishing site preparation . The literature does not identify a single technique as superior to others ; however , all accepted therapeutic procedures for ridge preservation have been shown to be more effective than blood clot alone in r and omized controlled studies OBJECTIVE To volumetrically evaluate soft tissue changes of different ridge preservation techniques compared to spontaneous healing 6 months after tooth extraction . MATERIAL S AND METHODS In each of 40 patients , one single-rooted tooth was extracted and four treatment modalities were r and omly assigned to the following groups ( n = 10 each ) : A ) ß-tricalcium-phosphate-particles with a polylactid coating ( ß-TCP ) , B ) demineralized bovine bone mineral with 10 % collagen covered with a collagen matrix ( DBBM-C/CM ) , C ) DBBM with 10 % collagen covered with an autogenous soft tissue punch graft ( DBBM-C/PG ) , D ) spontaneous healing ( control ) . Impressions were obtained before extraction and 6 months later , casts were digitized and volumetric changes at the buccal soft tissues were determined . One-way anova was performed and pair-wise Wilcoxon rank sum test with Bonferroni-Holm method was applied for comparison of differences between two groups . RESULTS After 6 months , horizontal contour changes accounted for -1.7 ± 0.7 mm ( A ) , -1.2 ± 0.5 mm ( B ) , -1.2 ± 0.7 mm ( C ) and -1.8 ± 0.8 mm ( D ) . None of the group comparisons reached statistical significance . CONCLUSIONS Six months after tooth extraction all groups revealed a horizontal volume change in the buccal soft tissue contour . Application of DBBM-C/CM or DBBM-C/PG reduced the amount of volume resorption compared to ß-TCP or spontaneous healing without reaching statistically significant difference PURPOSE This r and omized clinical trial was conducted to assess the safety and effectiveness of the ErhBMP-2 in alveolar bone regeneration as well as preservation of the β-TCP bone graft material that contains ErhBMP-2 . MATERIAL S AND METHODS This study involved 72 patients at the 3 study centers . The patients , who were divided into 2 groups : the experiment group who had ErhBMP-2 coated TCP/HA and the control group who had TCP/HA graft material alone transplanted immediately after tooth extraction . CT was taken before and 3 months after the transplantation and healing status was compared between the two groups . The efficacy endpoints that were used to measure the degree of bone induction included alveolar bone height and 3 measurements of bone width . The paired t test was used to determine the significance of the changes ( P<.05 ) . RESULTS Changes in alveolar bone height were -1.087 ± 1.413 mm in the control group and -.059 ± 0.960 mm in the experimental group ( P<.01 ) . At 25 % extraction socket length [ ESL ] , the changes were 0.006 ± 1.149 mm in the control group and 1.279 ± 1.387 mm in the experimental group . At 50 % ESL , the changes were 0.542 ± 1.157 mm and 1.239 ± 1.249 mm , respectively ( P<.01 for 25 % ESL , and P<.05 for 50 % ESL ) . During the experiment , no adverse reactions to the graft material were observed . CONCLUSION ErhBMP-2 coated β-TCP/HA were found to be more effective in preserving alveolar bone than conventional β-TCP/HA alloplastic bone graft material The aim of the study was to determine the fate of demineralized freeze-dried bone allograft ( DFDBA ) used in conjunction with a barrier membrane in the management of extraction sockets and deficient alveolar ridges , and to compare the amount of bone formed with that found in untreated sites . Ten biopsies were obtained from 8 grafted patients . Five biopsies were harvested from untreated sites during routine implant placement and analyzed for comparison . In the socket management procedure , DFDBA was packed tightly into the socket and covered with an exp and ed polytetrafluoroethylene ( e-PTFE ) membrane . Primary closure was achieved in all cases . In the ridge regeneration procedure , cortical columns were placed in the ridge projecting outward approximately 3 mm to create and maintain space for DFDBA particles packed between them ; the columns were then covered by an e-PTFE membrane . Healing time ranged from 8 to 23 months . At the time of implant placement , bone cores ( 7 mm x 2 mm ) were harvested , fixed in 10 % formalin solution , and prepared for histologic examination . At the light microscopic level , no inflammation or fibrous encapsulation was observed . New bone formation on and around DFDBA particles was widespread . Histomorphometric analysis of the grafted specimens and untreated sites was carried out using the trabecular bone volume ( TBV ) index . The TBV in the maxillary test specimens was 55.03 % , as compared to 57.33 % of control cores . Unaltered DFDBA made up 8.7 % of the test specimens . In the m and ibular biopsies , the TBV was 56.6 % , while for the controls it was 40.9 % . The volume of DFDBA still present was 2.45 % . The results tended to indicate that treatment with DFDBA in conjunction with cell occlusive membranes will result in new bone formation , predominantly by the process of conduction , which appears to be similar in amount and nature to that found in cores harvested from healed nonfunctional edentulous areas OBJECTIVES The aim of the following study was to assess contour changes after socket preservation techniques . MATERIAL AND METHODS In five beagle dogs , the distal root of the third and fourth m and ibular premolars was extracted . The following treatments ( Tx ) were r and omly assigned for the extraction socket . Tx 1 : BioOss Collagen . Tx 2 : BioOss Collagen and a free soft tissue graft . Tx 3 : No treatment . Tx 4 : The internal buccal aspect was covered with an experimental collagen membrane , the extraction socket was filled with BioOss Collagen and the membrane folded on top of the graft . Impressions were obtained at baseline , 2 and 4 months after surgery . Bucco-lingual measurements were performed using digital imaging analysis . RESULTS All groups displayed contour shrinkage at the buccal aspect . Only the differences between the two test groups ( Tx 1 , Tx 2 ) and the control group ( Tx 3 ) were significant at the buccal aspect ( p < or = 0.001 ) . No measurements of the Tx 4 group could be performed . CONCLUSION Socket preservation techniques , used in the present experiment , were not able to entirely compensate for the alterations after tooth extraction . Yet , incorporation of BioOss Collagen seems to have the potential to limit but not avoid the post-operative contour shrinkage BACKGROUND Reduction of alveolar height and width after tooth extraction may present problems for implant placement , especially in the anterior maxilla where bone volume is important for biologic and esthetic reasons . Different graft material s have been proposed to minimize the reduction in ridge volume . The aim of this study was to compare radiographic and histomorphometric results of magnesium-enriched hydroxyapatite ( MHA ) and calcium sulfate ( CS ) grafts in fresh sockets after tooth extraction s. METHODS Forty-five fresh extraction sockets with three bone walls were selected in 15 patients . A split-mouth design was used : 15 sockets on the right side of the jaw received MHA , 15 sockets on the left side received CS , and 15 r and om unfilled sockets were considered the control ( C ) group . Intraoral digital radiographs were taken at baseline and at 3 months after graft material placement . At 3 months , cylinder bone sample s were obtained for histology and histomorphometry analysis . RESULTS The difference in mean radiographic vertical bone level from baseline to 3 months was -2.48 + /- 0.65 mm in the CS group , -0.48 + /- 0.21 mm in the MHA group , and -3.75 + /- 0.63 mm in the unfilled C group . Statistically significant differences ( P < 0.05 ) were found between CS and MHA groups and between MHA and C groups . Histologic examination revealed bone formation in all treated sites ; trabecular bone assessment did not differ among apical , mesial , and coronal portions of the specimens . Mean vital bone measurements for CS , MHA , and C groups were 45.0 % + /- 6.5 % , 40.0 % + /- 2.7 % , and 32.8 % + /- 5.8 % , respectively . Statistically significant differences ( P < 0.05 ) were found among all groups . Connective tissue percentages averaged 41.5 % + /- 6.7 % for the CS group , 41.3 % + /- 1.3 % for the MHA group , and 64.6 % + /- 6.8 % for the C group . Statistically significant differences ( P < 0.05 ) were found between CS and C groups and between MHA and C groups . The CS-grafted sockets showed 13.9 % + /- 3.4 % residual implant material , whereas the MHA-treated sockets showed 20.2 % + /- 3.2 % residual material . The difference between the groups was statistically significant ( P < 0.05 ) . CONCLUSIONS Radiographs revealed a greater reduction of alveolar ridge in the CS group than in the MHA group . Histologic examination showed more bone formation and faster resorption in the CS group and more residual implant material in the MHA group Background and Purpose : The resorption of alveolar bone following tooth extraction results in a narrowing and shortening of the residual ridge , which leads to esthetic and restorative problems , and reduces the bone volume available for implant therapy . The aim of this study was to evaluate the prevention of alveolar collapse after tooth extraction , using titanium membrane ( Frios Boneshield ; DENTSPLY Friadent , Mannheim , Germany ) , associated ( or not ) with autologous bone graft . Material s and Methods : A total of 10 nonsmoking healthy subjects , ranging from 35 to 60 years old , were selected for this study . Each patient had a minimum of 2 uni-radicular periodontally hopeless teeth , which were scheduled for extraction . After the procedure , 2 titanium pins were fixed on the vestibular bone surfaces that were used as references for the initial measures ( depth , width , and height ) of the socket . Of the sockets,1 was r and omly chosen to be filled with autologous bone graft ( test ) removed from superior maxillary tuber , and the other one did not receive the graft ( control ) . A titanium membrane was adapted and fixed , covering the sockets , which remained for at least 10 weeks . After a 6-month healing , the final measures were performed . Results : There was exposure of the membrane in 5 of the 10 treated subjects . Average bone filling ( ±st and ard deviation ) among the 10 subjects was 8.80 ± 2.93 mm ( range 4 - 13 ) in the control group and 8.40 ± 3.35 mm ( range 4 - 13 ) in the test group . Average bone loss in width in both group was 1.40 ± 1.97 mm ( range −4 - 1 ) in the control group and 1.40 ± 0.98 mm ( range −4 - 0 ) in the test group . There was no significant statistical difference between groups considering the evaluated st and ards . Conclusion : The use of titanium membrane , alone or in association with autogenous bone , favored the prevention of alveolar ridge after tooth extraction . This membrane seems to be a possible and safe alternative to other nonresorbable membranes when the prevention of alveolar ridge resorption is the objective The aim of this study was to compare the effectiveness of two bone substitute material s for socket preservation after tooth extraction . Extraction sockets in 10 patients were filled with either inorganic bovine bone material ( Bio-Oss ) or with synthetic material consisting of hydroxyapatite and silicon dioxide ( NanoBone ) . Extraction sockets without filling served as the control . The results demonstrate the effectiveness of the presented protocol for socket preservation and that the choice of a suitable bone substitute material is crucial . The dimensions of the alveolar ridge were significantly better preserved with Bio-Oss than with NanoBone or without treatment . Bio-Oss treatment result ed in better bone quality and quantity for successful implant placement BACKGROUND Different approaches were advocated to preserve or improve the dimension and contour of the ridge following tooth extraction . In some of studies , socket ' flapless extraction ' apparently had a successful outcome . AIM The objective of the present experiment was to compare hard tissue healing following tooth extraction with or without the prior elevation of mucosal full-thickness flaps . MATERIAL AND METHODS Five mongrel dogs were used . The two second m and ibular premolars ( (2)P(2 ) ) were hemi-sected . The mesial roots were retained . By r and om selection the distal root in one side was removed after the elevation of full-thickness flaps while on the contralateral side , root extraction was performed in a flapless procedure . The soft tissue wound was closed with interrupted sutures . After 6 months of healing , the dogs were euthanized and biopsies were sample d. From each experimental site , four ground sections - two from the mesial root and two from the healed socket - were prepared , stained and examined in the microscope . RESULTS The data showed that the removal of a single tooth ( root ) during healing caused a marked change in the edentulous ridge . In the apical and middle portions of the socket site minor dimensional alterations occurred while in the coronal portion of the ridge the reduction of the hard tissue volume was substantial . Similar amounts of hard tissue loss occurred during healing irrespective of the procedure used to remove the tooth was , i.e. flapless or following flap elevation . CONCLUSION Tooth loss ( extraction ) result ed in marked alterations of the ridge . The size of the alveolar process was reduced . The procedure used for tooth extraction - flapless or following flap elevation - apparently did not influence the more long-term outcome of healing The purpose of this study was to evaluate the clinical effectiveness of a bioabsorbable membrane made of glycolide and lactide polymers in preserving alveolar ridges following tooth extraction using a surgical technique based on the principles of guided bone regeneration . Sixteen patients requiring extraction s of 2 anterior teeth or bicuspids participated in the study ( split-mouth design ) . Following elevation of buccal and lingual full-thickness flaps and extraction of teeth , experimental sites were covered with bioabsorbable membranes ; control sites did not receive any membrane . Titanium pins served as fixed reference points for measurements . Flaps were advanced in order to achieve primary closure of the surgical wound . No membrane became exposed in the course of healing . Reentry surgeries were performed at 6 months . Results showed that experimental sites presented with significantly less loss of alveolar bone height , more internal socket bone fill , and less horizontal resorption of the alveolar bone ridge . This study suggests that treatment of extraction sockets with membranes made of glycolide and lactide polymers is valuable in preserving alveolar bone in extraction sockets and preventing alveolar ridge defects TEN PATIENTS WHO REQUIRED two or more anterior teeth extraction s were utilized in this study . Extraction procedures were carried out with a full thickness surgical flap approach . After flap reflection , teeth were removed with a minimum of trauma to the surrounding bone . Following extraction silicone-based impression techniques were used to produce a model of the alveolar process and small metal pins were placed in the alveolus to be used as fixed points to make measurements of ridge dimensions . One socket was covered with an exp and ed polytetrafluoroethylene ( ePTFE ) barrier membrane ( experimental site ) ; the other socket was a conventional control . The soft tissue flaps were then mobilized using periosteal releasing incision and the wound closed with ePTFE mattress sutures . Six months following extraction , patients were treated with flap surgery to expose both extraction s sites to remove the ePTFE membranes and to measure ridge dimensions using the pins as fixed points . Clinical and model measurements have shown statistically significant better ridge dimensions at experimental sites than at control ( P < or = 0.05 ) . Three patients with exposed membranes had similar dimensional changes as controls . Results from this study suggested that this improved technique offers a predictable alveolar ridge maintenance enhancing the bone quality for dental implant procedures and esthetic restorative dentistry BACKGROUND Flapless extraction of teeth allows for undisturbed preservation of the nearby periosteum and a source of osteoprogenitor cells . Recombinant human bone morphogenetic protein 2 ( rhBMP-2 ) has been used for different bone augmentation purpose s with great osteoinductive capacity . The aim of this study is to compare the bone regenerative ability of rhBMP-2 on an absorbable collagen sponge ( ACS ) carrier to a collagen sponge ( CS ) alone in extraction sites with ≥50 % buccal dehiscence . METHODS Thirty-nine patients requiring extraction of a hopeless tooth with ≥50 % buccal dehiscence were enrolled . After flapless extraction and r and omization , either rhBMP-2/ACS carrier or CS alone was placed in the extraction site . After extraction , a baseline cone beam computed tomography ( CBCT ) scan was obtained of the site , and a similar scan was obtained 5 months postoperatively . Medical imaging and viewing software were used to compare the baseline and 5-month postoperative images of the study site and assess ridge width measurements , vertical height changes , and buccal plate regeneration . RESULTS Radiographically , CBCT analysis showed that with ≥50 % of buccal bone destruction , rhBMP-2/ACS was able to regenerate a portion of the lost buccal plate , maintain theoretical ridge dimensions , and allow for implant placement 5 months after extraction . The test group performed significantly ( P < 0.05 ) better in regard to clinical buccal plate regeneration ( 4.75 versus 1.85 mm ) , clinical ridge width at 5 months ( 6.0 versus 4.62 mm ) , and radiographic ridge width at 3 mm from the alveolar crest ( 6.17 versus 4.48 mm ) after molar exclusion . There was also significantly ( P < 0.05 ) less remaining buccal dehiscence , both clinical ly ( 6.81 versus 10.0 mm ) and radiographically ( 3.42 versus 5.16 mm ) , at 5 months in the test group . Significantly ( P < 0.05 ) more implants were placed in the test group without the need for additional augmentation . The mean loss in vertical ridge height ( lingual/palatal ) was less in the test sites but was not significantly ( P = 0.514 ) different between the test and control groups ( 0.39 versus 0.64 mm ) . CONCLUSIONS rhBMP-2/ACS compared to CS alone used in flapless extraction sites with a buccal dehiscence is able to regenerate lost buccal plate , maintain theoretical ridge dimensions , and allow for implant placement 5 months later Dimensional alterations of the facial bone wall following tooth extraction s in the esthetic zone have a profound effect on treatment outcomes . This prospect i ve study in 39 patients is the first to investigate three-dimensional ( 3D ) alterations of facial bone in the esthetic zone during the initial 8 wks following flapless tooth extraction . A novel 3D analysis was carried out , based on 2 consecutive cone beam computed tomographies ( CBCTs ) . A risk zone for significant bone resorption was identified in central areas , whereas proximal areas yielded only minor changes . Correlation analysis identified a facial bone wall thickness of ≤ 1 mm as a critical factor associated with the extent of bone resorption . Thin-wall phenotypes displayed pronounced vertical bone resorption , with a median bone loss of 7.5 mm , as compared with thick-wall phenotypes , which decreased by only 1.1 mm . For the first time , 3D analysis has allowed for documentation of dimensional alterations of the facial bone wall in the esthetic zone of humans following extraction . It also characterized a risk zone prone to pronounced bone resorption in thin-wall phenotypes . Vertical bone loss was 3.5 times more severe than findings reported in the existing literature BACKGROUND Preventing ridge collapse with the extraction of maxillary anterior teeth is vital to an esthetic restorative result . Several regenerative techniques are available and are used for socket preservation . The aim of this study is to analyze by clinical parameters the use of acellular dermal matrix ( ADM ) and anorganic bovine bone matrix ( ABM ) with synthetic cell-binding peptide P-15 to preserve alveolar bone after tooth extraction . METHODS Eighteen patients in need of extraction of maxillary anterior teeth were selected and r and omly assigned to the test group ( ADM plus ABM/P-15 ) or the control group ( ADM only ) . Clinical measurements were recorded initially and at 6 months after ridge-preservation procedures . RESULTS In the clinical measurements ( external vertical palatal measurement [ EVPM ] , external vertical buccal measurement [ EVBM ] , and alveolar horizontal measurement [ AHM ] ) the statistical analysis showed no difference between test and control groups initially and at 6 months . The intragroup analysis , after 6 months , showed a statistically significant reduction in the measurements for both groups . In the comparison between the two groups , the differences in the test group were as follows : EVPM = 0.83 ± 1.53 mm ; EVBM = 1.20 ± 2.02 mm ; and AHM = 2.53 ± 1.81 mm . The differences in the control group were as follows : EVPM = 0.87 ± 1.13 mm ; EVBM = 1.50 ± 1.15 mm ; and AHM = 3.40 ± 1.39 mm . The differences in EVPM and EVBM were not statistically significant ; however , in horizontal measurement ( AHM ) , there was a statistically significant difference ( P<0.05 ) . CONCLUSION The results of this study show that ADM used as membrane associated with ABM/P-15 can be used to reduce buccal-palatal dimensions compared to ADM alone for preservation of the alveolar ridge after extraction of anterior maxillary teeth The aims of this article were to perform a detailed evaluation of the healing of extraction sockets covered with a resorbable collagen membrane 12 weeks following exodontia and to determine if this device had ossifying properties . Ten consecutive subjects in need of extraction of maxillary premolars were recruited . Each subject had a hopeless maxillary premolar extracted with minimal trauma . Sockets were then covered with a collagen barrier membrane alone . At 12 weeks , reentry surgery was performed , clinical measurements were repeated , and bone core biopsies were obtained prior to dental implant placement for histologic and microcomputed tomography ( micro-CT ) analysis . Study sites showed mean bone regeneration horizontally of 7.7 mm ( buccopalatally ) and 4.6 mm ( mesiodistally ) . Vertical bone repair showed a mean gain of 10.9 mm . Subtraction radiography showed a mean apical shift of the crestal bone at the center of the socket of 2.1 mm ( range , 0.7 to 4.3 mm ) . Micro-CT and histology revealed formation of well-mineralized tissue at 12 weeks , with a mean percentage of vital bone of 45.87 % ± 12.35 % . No signs of membrane ossification were observed . A detailed analysis of tissue neogenesis in extraction sites protected by this barrier membrane has demonstrated that adequate bone formation for implant placement occurs as early as 12 weeks following exodontia , with minimal changes in alveolar ridge dimensions . No evidence of membrane ossification was observed OBJECTIVE To radiographically analyze extraction sites left untreated or treated using a socket preservation technique . MATERIAL S AND METHODS A total of 20 patients scheduled for single extraction in the maxilla from second to second premolar were enrolled in this study . All sites showed a bone defect > 5 mm at the buccal wall and no soft tissue recession . At baseline ( T0 ) , tooth extraction was performed ; subsequently , sites were r and omly allocated to the control ( CG : left to heal without grafting ) or test group ( TG : grafted using hydroxyapatite ) . Two months later ( T1 ) , implants were inserted and eventual GBR procedure was performed . Three months later , the definitive crown was placed . Follow up was 24 months ( T2 ) . A cone-beam computed tomographic examination ( CT ) was performed at each time point . At each radiographic analysis , horizontal and vertical widths of the sockets were measured . Comparisons between CG and TG were performed by a Wilcoxon non-parametric test . RESULTS At the end of the study , no patient dropped out and all implants inserted ( 10 in each group ) result ed integrated . GBR procedures were performed at T1 only in the CG . In the CG , the mean value of the horizontal width in the coronal CT slices was 0.98 mm ( ± 0.37 ) , 7.70 mm ( ± 0.92 ) , 7.45 mm ( ± 0.69 ) at T0 , T1 ( after bone regeneration ) and T2 , respectively . In the TG , the mean value of the horizontal width in the coronal CT slices was 0.96 mm ( ± 0.41 ) , 8.97 mm ( ± 1.91 ) , 9.48 mm ( ± 1.56 ) ; at T2 , it was 9.52 mm ( ± 1.87 ) at T0 ( pre- and post-socket preservation ) T1 and T2 , respectively . At each follow up , the mean horizontal bone width in TG was statistically significantly greater than in the control group ( P < 0.05 ) . At T0 , mean value of the vertical bone defect length ( BDL ) was 6.93 mm for TG , 6.5 mm for CG . At T1 and T2 , mean BDL value was 0 for both groups . Statistically significant difference was not found between TC and CG at any time point ( P > 0.05 ) . CONCLUSIONS This r and omized controlled trial suggested that in sites with buccal bone defects > 5 mm , the application of HA can minimize alveolar crest resorption following tooth extraction . Furthermore , compared with traditional regenerative procedure carried out following socket healing , this preservation technique seems to result in better horizontal regeneration of the buccal bone wall After tooth extraction , varying amounts of bone resorption occur because of qualitative and quantitative changes at the edentulous site of the alveolar process . The aims of this r and omized controlled clinical trial were ( 1 ) to compare the post extraction changes in residual ridge dimensions during spontaneous healing with those during socket preservation , ( 2 ) to analyze the histologic and histomorphometric aspects of the grafted sockets , and ( 3 ) to compare probing procket depth ( PPD ) and clinical attachment level ( CAL ) changes at teeth adjacent to extraction sites . Forty-eight teeth were extracted from 41 patients referred for extraction of 1 or more maxillary or m and ibular premolars or molars . The edentulous sites were r and omly assigned to the control ( EXT , extraction alone ) or experimental groups ( SP , extraction and socket preservation ) . In the SP group , the sockets were filled with bovine bone mineral and covered with porcine collagen membrane . At baseline and after 4 months , PPD , gingival recession ( REC ) , and CAL were measured at teeth adjacent to the edentulous sites . The changes in ridge dimensions from baseline to 4 months were assessed on dental casts . At 4 months , bone was harvested from the grafted areas in the SP group and the edentulous areas in the EXT group . PPD , REC , and CAL were comparable between groups . However , from baseline to 4 months , the SP group showed significantly less reduction in ridge width ( 1.04 ± 1.08 mm vs 4.48 ± 0.65 mm , P < .001 ) and height ( 0.46 ± 0.46 mm vs 1.54 ± 0.33 mm , P < .001 ) . Histologically , the grafted sockets exhibited various stages of bone maturation and formation without inflammatory responses . No significant difference in the mineralized and nonmineralized fractions was noted between the groups . Socket preservation using bovine bone mineral and porcine collagen membrane considerably limits the amount of horizontal and vertical bone resorption when compared with extraction alone OBJECTIVE This systematic review aims to evaluate the scientific evidence on the efficacy in the surgical protocol s design ed for preserving the alveolar ridge after tooth extraction and to evaluate how these techniques affect the placement of dental implants and the final implant supported restoration . MATERIAL AND METHODS A thorough search in MEDLINE - PubMed , Embase and the Cochrane Central Register of controlled trials ( CENTRAL ) was conducted up to February 2011 . R and omized clinical trials and prospect i ve cohort studies with a follow-up of at least 3 months reporting changes on both the hard and soft tissues ( height and /or width ) of the alveolar process ( mm or % ) after tooth extraction were considered for inclusion . RESULTS The screening of titles and abstract s result ed in 14 publications meeting the eligibility criteria . Data from nine of these 14 studies could be grouped in the meta-analyses . Results from the meta-analyses showed a statistically significant greater ridge reduction in bone height for control groups as compared to test groups ( weighted mean differences , WMD = -1.47 mm ; 95 % CI [ -1.982 , -0.953 ] ; P < 0.001 ; heterogeneity : I(2 ) = 13.1 % ; χ(2 ) P-value = 0.314 ) and a significant greater reduction in bone width for control groups compared to the test groups ( WMD = -1.830 mm ; 95 % CI [ -2.947 , -0.732 ] ; P = 0.001 ; heterogeneity : I(2 ) = 0 % ; χ(2 ) P-value = 0.837 ) . Subgroup analysis was based on the surgical protocol used for the socket preservation ( flapless/flapped , barrier membrane/no membrane , primary intention healing/no primary healing ) and on the measurement method utilized to evaluate morphological changes . Meta-regression analyses demonstrated a statistically significant difference favoring the flapped subgroup in terms of bone width ( meta-regression ; slope = 2.26 ; 95 % IC [ 1.01 ; 3.51 ] ; P = 0.003 ) . CONCLUSIONS The potential benefit of socket preservation therapies was demonstrated result ing in significantly less vertical and horizontal contraction of the alveolar bone crest . The scientific evidence does not provide clear guidelines in regards to the type of bio material , or surgical procedure , although a significant positive effect of the flapped surgery was observed . There are no data available to draw conclusions on the consequences of such benefits on the long-term outcomes of implant therapy Aim The aim of this study was to investigate the influence of platelet-rich fibrin ( PRF ) on early wound healing and preservation of the alveolar ridge shape following tooth extraction . Methods In this clinical trial , 20 symmetrical , premolar extraction sockets using split-mouth design were r and omly selected with PRF or blood clot . The evaluations of wound healing , alveolar ridge contour changes , and crestal bone resorption were performed in dental casts and periapical radiographs ( T0 , initial ; T1 , 1 week ; T2 , 2 weeks ; T4 , 4 weeks ; T6 , 6 weeks ; T8 , 8 weeks ) . Results Platelet-rich fibrin clinical ly showed early healing of soft tissue covering socket orifices in the first 4 weeks . At the first week , the horizontal resorption on buccal aspect of PRF ( 1.07 ± 0.31 mm ) was significantly less than that of the control ( 1.81 ± 0.88 mm ) . Platelet-rich fibrin demonstrated the tendency to enter the steady stage after the fourth week following tooth extraction , whereas in the control group the progression of buccal contour contraction was still detected through the eighth week . Radiographically , the overall resorption of marginal bone levels at mesial and distal to the extraction site in PRF ( 0.70 , 1.23 mm ) was comparable to that of the control ( 1.33 , 1.14 mm ) . Although the PRF group demonstrated faster bone healing compared with the control , no statistically significant difference was detected . Conclusions This preliminary result demonstrated neither better alveolar ridge preservation nor enhanced bone formation of PRF in the extraction socket . The use of PRF revealed limited effectiveness by accelerated soft-tissue healing on the first 4 weeks INTRODUCTION As a consequence of extraction , the height of the buccal wall tends to decrease and results in the disappearance of bundle bone . To modify bone remodelling after extraction , various ridge preservation techniques have been proposed . The present research was drawn up with the following considerations in mind : to evaluate and to compare changes of hard and soft tissues in post- extraction sockets which received a ridge preservation procedure , with post- extraction sockets which had healed naturally . MATERIAL S AND METHODS Each patient was r and omly allocated to a test or control group using a specific software package . After extraction , the sockets were carefully inspected and any granulation tissue was removed . The control sites received silk sutures to stabilize the clot without any grafting material . The test sites were grafted with corticocancellous porcine bone and a collagen membrane . All experimental sites had the membranes left exposed to the oral cavity with a secondary wound healing . The thickness of the buccal alveolar bone , if present , was carefully measured at the time of tooth extraction using a calliper at 1 mm from the edge of the wall . The following clinical parameters were evaluated at baseline and after 4 months at implant placement : vertical bone changes , horizontal bone changes and width of keratinized gingiva . The length , diameter and need for additional bone augmentation were assessed for both groups at the time of implant insertion . RESULTS The control group showed vertical bone resorption of 1 ± 0.7 mm , 2.1 ± 0.6 mm , 1 ± 0.8 mm and 2 ± 0.73 mm at the mesial , vestibular , distal and lingual sites respectively . Moreover , changes in horizontal dimension showed an average resorption of 3.6 ± 0.72 mm . The test sites showed a horizontal bone remodelling of 0.3 ± 0.76 mm , 1.1 ± 0.96 mm , 0.3 ± 0.85 mm , 0.9 ± 0.98 mm at the mesial , vestibular , distal and lingual sites respectively . The horizontal bone resorption at the test sites was 1.6 ± 0.55 mm . The keratinized gingiva showed a coronal shift of 0.7 mm in the control group when compared to 1.1 mm in the test group . In addition , 42 % of sites in the control group required an additional bone augmentation at implant placement , when compared to 7 % in the test sites . CONCLUSIONS This study clearly points out that an alveolar ridge preservation technique performed with collagenated porcine bone and a resorbable membrane -- according to the procedure reported in this study --was able to limit the contour changes after tooth extraction . Finally , the test sites showed a better preservation of facial keratinized tissue when compared to control sites ; grafted sites allowed the placement of longer and wider implants when compared to implants inserted in non-grafted sites BACKGROUND The aim of this single-masked , r and omized controlled clinical trial is to compare hard and soft tissue changes after ridge preservation performed with ( control , RPc ) and without ( test , RPe ) primary soft tissue closure in a split-mouth design . METHODS Eleven patients completed this 6-month trial . Extraction and ridge preservation were performed using a composite bone graft of inorganic bovine-derived hydroxyapatite matrix and cell binding peptide P-15 ( ABM/P-15 ) , demineralized freeze-dried bone allograft , and a copolymer bioabsorbable membrane . Primary wound closure was achieved on the control sites ( RPc ) , whereas test sites ( RPe ) left the membrane exposed . Pocket probing depth on adjacent teeth , repositioning of the mucogingival junction , bone width , bone fill , and postoperative discomfort were assessed . Bone cores were obtained for histological examination . RESULTS Intragroup analyses for both groups demonstrated statistically significant mean reductions in probing depth ( RPc : 0.42 mm , P = 0.012 ; RPe : 0.25 mm , P = 0.012 ) and bone width ( RPc : 3 mm , P = 0.002 ; RPe : 3.42 mm , P < 0.001 ) . However , intergroup analysis did not find these parameters to be statistically different at 6 months . The test group showed statistically significant mean change in bone fill ( 7.21 mm ; P < 0.001 ) . Compared to the control group , the test group showed statistically significant lower mean postoperative discomfort ( RPc 4 versus RPe 2 ; P = 0.002 ) . Histomorphometric analysis showed presence of 0 % to 40 % of ABM/P-15 and 5 % to 20 % of new bone formation in both groups . Comparison of clinical variables between the two groups at 6 months revealed that the mucogingival junction was statistically significantly more coronally displaced in the control group than in the test group , with a mean of 3.83 mm versus 1.21 mm ( P = 0.002 ) . CONCLUSIONS Ridge preservation without flap advancement preserves more keratinized tissue and has less postoperative discomfort and swelling . Although ridge preservation is performed with either method , ≈27 % to 30 % of bone width is lost PURPOSE In this prospect i ve study , bone formation in human extraction sockets augmented with Bio-Oss Collagen after a 12-week healing period was quantified and compared to bone formation in unaugmented extraction sockets . MATERIAL S AND METHODS Selected patients with four-walled extraction sockets were included in this prospect i ve study . After extraction , the sockets were r and omly augmented using Bio-Oss Collagen or left to heal unfilled without raising a mucoperiosteal flap . At the time of implant placement , histologic specimens were obtained from the socket and analyzed . Statistical analysis was performed using the Wilcoxon signed-rank test . RESULTS Twenty-five patients with a total of 39 sockets ( 20 augmented , 19 unaugmented ) were included in the study and the histologic specimens analyzed . All specimens were free of inflammatory cells . The mean overall new bone formation in the augmented sites was 25 % ( range , 8%-41 % ) and in the unaugmented sockets it was 44 % ( range , 3%-79 % ) . There was a significant difference in the rate of new bone formation between the grafted and ungrafted sockets and a significant difference in the bone formation rate in the apical compared to the coronal regions of all sockets , independent of the healing mode . CONCLUSION This descriptive study demonstrated that bone formation in Bio-Oss Collagen-grafted human extraction sockets was lower than bone formation in ungrafted sockets . Bone formation occurred in all specimens with varying degrees of maturation independent of the grafting material and was initiated from the apical region OBJECTIVE To evaluate the radiographic changes of the alveolar ridge following application of different ridge preservation techniques 6 months after tooth extraction . MATERIAL S AND METHODS Four treatment modalities were r and omly assigned in 40 patients : β-tricalcium-phosphate-particles with polylactid coating ( β-TCP ) , demineralized bovine bone mineral with 10 % collagen covered with a collagen matrix ( DBBM-C/CM ) , DBBM-C covered with an autogenous soft-tissue graft ( DBBM-C/PG ) and spontaneous healing ( control ) . Cone-beam computed tomography scans were performed after treatment and 6 months later . RESULTS After 6 months , the vertical changes ranged between -0.6 mm ( -10.2 % ) for control and a gain of 0.3 mm ( 5.6 % ) for DBBM-C/PG on the lingual side , and between -2.0 mm ( -20.9 % ) for β-TCP and a gain of 1.2 mm ( 8.1 % ) for DBBM-C/PG on the buccal side . The most accentuated ridge width changes were recorded 1 mm below the crest : -3.3 mm ( -43.3 % , C ) , -6.1 mm ( -77.5 % , β-TCP ) , -1.2 mm ( -17.4 % , DBBM-C/CM ) and -1.4 mm ( -18.1 % , DBBM-C/PG ) . At all three levels , DBBM-C with either CM or PG was not significantly differing ( p > 0.05 ) , while most other differences between the groups reached statistical significance ( p < 0.05 ) . CONCLUSIONS Application of DBBM-C , covered with CM or PG , result ed in less vertical and horizontal changes of the alveolar ridge as compared with controls 6 months after extraction PURPOSE Different graft material s have been proposed to minimize the reduction in ridge volume after tooth extraction . The aim of the present study was to compare the use of synthetic magnesium-enriched hydroxyapatite ( MHA ) with porcine bone ( PB ) grafts in fresh sockets by histologic and histomorphometric analyses . MATERIAL S AND METHODS Forty-five fresh extraction sockets were selected in 15 patients . A split-mouth design was used : 15 sockets received MHA in one side of the jaw ( MHA group ) , 15 sockets on the other side received PB ( PB group ) , and 15 r and om unfilled sockets were considered the control group . Four months after surgery , cylindric bone specimens were harvested for histologic and histomorphometric analyses . RESULTS Histologic examinations revealed an absence of inflammatory cells , bone formation in all treated sites , and the presence of bio material particles and connective tissue . Mean vital bone measurements for the MHA , PB , and control groups were 36.5 % ± 2.6 % , 38.0 % ± 16.2 % , and 30.3 % ± 4.8 % , respectively . Statistically significant differences were found between the MHA and control groups and between the PB and control groups ; differences between the MHA and PB groups were not significant . Connective tissue percentages averaged 33.3 % ± 1.5 % for the MHA group , 25.3 % ± 9.4 % for the PB group , and 58.3 % ± 7.1 % for the control group . Statistically significant differences were found between all groups . Residual graft material occupied 32.2 % ± 3.2 % of the MHA-grafted sites and 36.6 % ± 4.8 % of the PB sites . This difference was not statistically significant . CONCLUSIONS Within the limits of this study , histologic examination showed the same biologic behavior in bone formation and resorption processes for the two examined bio material PURPOSE The aim of this clinical study was to assess horizontal width changes in grafted and ungrafted sites after bone expansion and implant placement . MATERIAL S AND METHODS Twenty-three patients were included in this prospect i ve study . Each patient required extraction of two teeth and replacement with implants . After dental extraction in 23 alveoli ( group 1 ) , a collagen sponge was used to cover fresh sockets , and the remaining 23 alveoli ( group 2 ) were grafted with corticocancellous porcine bone . Three months after extraction , bone expansion was performed in each site , and 46 dental implants were placed . To evaluate tissue volume changes , the variations in width of the buccal ridge were recorded with a periodontal probe immediately after tooth extraction , 3 months later ( before implant placement ) , and 3 months after implant placement . RESULTS In group 1 , at 3 months after implant placement , mean volume changes of + 1.6 ± 0.8 mm for incisors and canines , + 1.4 ± 0.5 mm for premolars , and + 0.8 ± 0.5 mm for molars were seen . In group 2 , mean changes of + 1.5 ± 0.8 mm for incisors and canines , + 1.3 ± 0.3 mm for premolars , and + 2.8 ± 0.6 mm for molars were observed . Statistically significant differences were found only for molars . CONCLUSIONS In both groups , incisor , canine , and premolar sites showed no differences in volume changes , but statistically significant differences were found between molars in the two groups ; the bio material graft prevented collapse of the large defects and significant volume loss BACKGROUND The preservation of hard and soft tissue volume , partially lost after tooth removal , can potentially reduce the need for the more dem and ing augmentation procedures used in implant-supported rehabilitation . The objective of this research study is to investigate the effect of filling with xenogeneic material the postextractive sockets of two surgical procedures ( flapless versus flapped ) . METHODS In this prospect i ve r and omized clinical survey , two types of socket preservation were performed on two groups of patients : the control , treated via full-thickness mucoperiosteal flap , and the test , via a flapless procedure . Anatomic measurements and related outcome variables at the third month were analyzed using multiway analysis of variance . Multiple comparison tests , using Tukey honestly significant difference test , and appropriate pairwise comparison tests for independent sample s were carried out . RESULTS Sixty-four patients were treated , 32 for each of the two socket preservation procedures . Statistically significant differences were registered for the output variables -- changes in width of keratinized gingiva , changes in bucco-lingual width , and vertical bone changes at four sites -- between the two socket preservation techniques , with P values of < 0.001 , < 0.001 , and 0.0105 , respectively . CONCLUSIONS A full-thickness mucoperiosteal flap gave significantly more negative results than that of the less-dem and ing flapless procedure , with an increased width resorption of the post extraction site . Moreover , the increased value of the keratinized gingival width attested to the positive outcome of a flapless procedure in terms of soft tissue preservation and improvement . On the other h and , the flapped technique seemed to show less vertical bone resorption on the buccal aspect than the flapless technique BACKGROUND The aim of this r and omized , controlled clinical trial is to determine whether ridge preservation using an osteoinductive allograft ( test ) would prevent ridge resorption and promote bone maturation compared to extraction alone ( control ) . METHODS Seventeen patients ( 20 total sites ) , in need of a non-molar extraction and delayed implant placement were r and omly selected to receive either ridge preservation or extraction alone . A cone-beam computed tomography was completed with a radiographic stent in place before extraction and 10 to 12 weeks postoperatively for dimensional and buccal plate analyses . Bone cores were taken for micro-computed tomography ( microCT ) and histologic analyses . RESULTS Resorption of the alveolar ridge occurred at all sites with no statistically significant differences found between test and control sites . A significant correlation was found between the initial buccal plate thickness and the loss of vertical ridge height . microCT and histologic analyses found a mean new bone volume of 44.9 % with microCT and 37.4 % with histology in test sites and 39 % and 35.5 % , respectively , in control sites . The residual graft volume was 2.4 % with microCT and 4.5 % with histology . CONCLUSIONS Test and control sites lost similar amounts of alveolar ridge , with the loss of buccolingual width occurring predominantly at the expense of the buccal bone . A thicker buccal plate was associated with less ridge loss in the vertical dimension . The percentage of new bone was not statistically significant between either the test or control sites , using either microCT or histologic analyses Material and methods : Following tooth extraction , 30 patients were r and omly assigned to the following treatments ( Tx ) : Tx 1 : xenogenic bone substitute ( mp3 OsteoBiol , Tecnoss , Torino , Italy ) and free gingival graft ; Tx 2 : free gingival graft alone ; Tx 3 : xenogenic bone substitute ( mp3 OsteoBiol , Tecnoss , Torino , Italy ) , and Gore-Tex-Membran ( Gore-Tex CV5 , W.L. Gore & Associates , Putzbrunn , Germany ) ; Tx 4 : no further treatment ( control ) . Impressions were obtained before tooth extraction ( baseline ) and 4 months after surgery . Cast models were optically scanned , digitally superimposed and horizontal measurements of the contour alterations between time points taken via digital imaging analysis BACKGROUND An adequate alveolar crest is essential for implant placement in terms of esthetics and function . The objective of this r and omized clinical trial was to compare the preservation of the alveolar ridge dimensions following tooth extraction using porcine-derived xenograft combined with a membrane versus extraction -alone ( EXT ) sites . METHODS Fifteen patients who required double extraction of contralateral premolars and delayed implant placement were r and omly selected to receive both ridge-preservation procedure and EXT . The test sites ( alveolar ridge preservation [ ARP ] ) included 15 sockets treated using a corticocancellous porcine bone xenograft ( OsteoBiol ® Gen-Os ; Tecnoss srl , Giaveno , Italy ) associated with a soft cortical membrane ( OsteoBiol ® Lamina ; Tecnoss srl ) , while the corresponding control sites ( EXT ) were left without grafting for EXT . Horizontal and vertical ridge dimensions were recorded at baseline and 6 months after extraction s. RESULTS After 6 months , the EXT sites showed a significantly greater reabsorption of the buccolingual/palatal dimension of the alveolar ridge ( 3.7 ± 1.2 mm ) compared with the ARP sites ( 1.8 ± 1.3 mm ) . The mean vertical ridge height reduction in the control sockets was 3.1 ± 1.3 mm at the buccal sites and 2.4 ± 1.6 mm at the lingual sites compared with 0.6 ± 1.4 and 0.5 ± 1.3 mm , respectively , in the test sockets . The differences between test and control sockets were not significant for the mesial and distal measurements . CONCLUSIONS The placement of a porcine xenograft with a membrane in an extraction socket can be used to reduce the hard tissue reabsorption after tooth extraction compared with EXT BACKGROUND The objective of this study is to compare histologic and clinical healing following tooth extraction and ridge preservation with either cortical or cancellous freeze-dried bone allograft ( FDBA ) in non-molar extraction sockets . METHODS Forty patients requiring implant placement were enrolled , with 20 patients r and omly assigned to each group ( cortical versus cancellous FDBA ) . All of the allograft material s were obtained from the same donor to control for variability between donors and processing . Patients returned after 17 to 21 weeks ( average : 18.2 weeks ) , and a 2-mm-diameter core biopsy was obtained before implant placement . Histomorphometric analysis was performed to determine percentage of new bone formation , residual graft material , and non-mineralized connective tissue (CT)/other material . Clinical measurements of ridge dimensions were taken at the time of tooth extraction and again at implant placement . RESULTS There was no significant difference in new bone formation between the cortical and cancellous FDBA groups ( P = 0.857 ) . A significantly greater percentage of residual graft material was detected in the cortical FDBA group compared with the cancellous FDBA group ( P = 0.019 ) . A significantly greater percentage of non-mineralized CT/other material was found in the cancellous FDBA group compared with the cortical FDBA group ( P = 0.040 ) . The only significant clinical difference between groups was a greater loss of lingual ridge height in the cancellous group . CONCLUSIONS This is the first reported study to compare the histologic changes following tooth extraction with ridge preservation in humans using cortical versus cancellous FDBA . There were no differences in the percentage of new bone formation between the groups The goal of the present clinical study was to evaluate new bone formation in human extraction sockets augmented with enamel matrix derivatives ( EMD ) and Bio-Oss Collagen . Patients with symmetrical single-rooted teeth in the bilateral quadrants of the upper jaw condemned for extraction participated in this study . Following extraction , the sockets ( 20 sockets ) were r and omly augmented using either EMD or Bio-Oss Collagen . After 3 months of healing , bone biopsies were obtained and prepared for histological analyses . Dental implants were then placed . Implant stability quotient ( ISQ ) readings were obtained for each implant at the time of surgery and at 1 and 3 months postoperatively . The mean new bone formation was 34.57 ± 25.67 % in the EMD sites and 28.80 ± 16.14 % in the Bio-Oss Collagen sites . There was no significant difference between the groups . The ISQ values were significantly higher for the implants placed in the EMD sites at the first and third months , but no significant differences were observed in the ISQ values for the implants placed in the Bio-Oss Collagen sites . The augmentation of the extraction sockets with EMD or Bio-Oss Collagen leads to similar behaviour in bone regeneration OBJECTIVE The aim of this clinical trial was to compare the effect of Bio-Oss ( ® ) and a new bovine xenograft ( Osseus ( ® ) ) in alveolar sockets after a 24-week healing period . MATERIAL S AND METHODS A total of 20 adult volunteers ages 30 - 60 were subjected to single tooth extraction . A tooth extraction was performed at the baseline . All sites were r and omly allocated to two test groups ( TG1 : grafted using a new bovine xenograft , Osseus ( ® ) , and TG2 : grafted using commercially available bovine xenograft-Bio-Oss ( ® ) ) . Six months later , a sample of the grafted area was obtained and implants were inserted in the same site . Histological sections were examined focusing on the presence of fibrous connective tissue ( CT ) , and newly formed bone in direct contact with the graft . The HE-stained sections were subjected to histomorphometrical evaluation using Image Pro-Plus ( ® ) software ( Release 7.0 ) . The definitive crown was placed 3 months later . RESULTS Upon completion of the study , no patients were removed from the study and all inserted implants ( 10 in each group ) were eventually integrated . After 6 months , in the TG1 , the mean value of new bone formation was 33.7 ( ± 7.1 ) , for CT was 32.3 ( ± 8.9 ) and for the remaining bio material was 10.7 ( ± 16.2 ) . In the TG2 , the mean value of new bone formation was 19.3 ( ± 22.6 ) , of the CT was 49.9 ( ± 14.1 ) and of the remaining bio material was 22.6 ( ± 7.9 ) . CONCLUSIONS No statistically significant difference was observed between TG1 and TG2 after 6 months ( P > 0.05 ) , and both bio material s afforded a more favorable implant position OBJECTIVE To evaluate dimensional alterations of the alveolar ridge that occurred following tooth extraction at sites grafted with Bio-Oss ( ® ) Collagen . MATERIAL AND METHODS Twenty-eight subjects with maxillary incisors , canines , and premolars scheduled for extraction were included . The tooth was carefully removed . The patients were r and omly assigned to a test or a control group . In the test group patients , Bio-Oss ( ® ) Collagen was placed in the fresh extraction socket while in the controls no grafting was performed . Radiographic examination ( cone beam computed tomograms , CBCT ) was performed immediately after tooth extraction and socket treatment . Four months later , a new CBCT was obtained . In the radiographs , ( i ) the distance ( mm ) between base of the alveolar process ( apex ) and the buccal and palatal crests was determined , ( ii ) the outer profile of alveolar process of the experimental sites was outlined , and the cross section of the area ( mm(2 ) ) determined . RESULTS After 4 months of healing , the buccal and to a less extent also the palatal bone plate had become markedly reduced in height . The placement of a bio material in the socket failed to prevent resorption of the buccal and palatal bone walls . The cross-sectional area of the control ridge was reduced about 25 % and of the test ridge with 3 % . CONCLUSION The placement of a xenograft in fresh extraction sockets markedly counteracted the reduction in the hard tissue component of the edentulous sites PURPOSE The aim of this study was to evaluate the potential of an autologous bone marrow graft in preserving the alveolar ridges following tooth extraction . MATERIAL S Thirteen patients requiring extraction s of 30 upper anterior teeth were enrolled in this study . They were r and omized into two groups : seven patients with 15 teeth to be extracted in the test group and six patients with 15 teeth to be extracted in the control group . Hematologists collected 5 ml of bone marrow from the iliac crest of the patients in the test group immediately before the extraction s. Following tooth extraction and elevation of a buccal full-thickness flap , titanium screws were positioned throughout the buccal to the lingual plate and were used as reference points for measurement purpose s. The sockets were grafted with an autologous bone marrow in the test sites and nothing was grafted in the control sites . After 6 months , the sites were re-opened and bone loss measurements for thickness and height were taken . Additionally , before implant placement , bone cores were harvested and prepared for histologic and histomorphometric evaluation . RESULTS The test group showed better results ( P<0.05 ) in preserving alveolar ridges for thickness , with 1.14+/-0.87 mm ( median 1 ) of bone loss , compared with the control group , which had 2.46+/-0.4 mm ( median 2.5 ) of bone loss . The height of bone loss on the buccal plate was also greater in the control group than in the test group ( P<0.05 ) , 1.17+/-0.26 mm ( median 1 ) and 0.62 + 0.51 ( median 0.5 ) , respectively . In five locations in the control group , expansion or bone grafting complementary procedures were required to install implants while these procedures were not required for any of the locations in the test group . The histomorphometric analysis showed similar amounts of mineralized bone in both the control and the test groups , 42.87+/-11.33 % ( median 43.75 % ) and 45.47+/-7.21 % ( median 45 % ) , respectively . CONCLUSION These findings suggest that the autologous bone marrow graft can contribute to alveolar bone repair after tooth extraction Objective : The purpose of this study was to evaluate the efficacy of the alveolar ridge preservation technique using collagen sponge and xenograft after extraction . Study Design : Twenty patients were divided into the control group and the experimental group , which contained about 10 patients each . The control group patients were planned 3-unit bridge without performing implant and without special treatments for the extraction socket , and prosthetic treatments were performed after 3 months . In the experimental group , using collagen sponge and xenogeneic bone graft , alveolar ridge preservation was performed simultaneously with tooth extraction ; implants were placed after 3 months . Clinical and histological evaluations and statistical analysis were performed . Results : The resorption rate of the width of alveolar bone 3 mm below the alveolar ridge of the control group was shown to be 20.74 % and of the experimental group was an average of 14.26 % , approximately a difference of 6 % was observed , and it was statistically significant . New bone formation in the vicinity of bone graft material s was achieved well , and inflammation findings were not observed . Conclusion : The results indicated that in the ridge preservation using collagen sponge and xenograft , xenograft prevents the horizontal resorption of the alveolar ridge , and the upper collagen sponge blocks the infiltration of soft tissues to the lower area , and thus it has the advantage of the enhancement of bone fill BACKGROUND The aim of this investigation is to evaluate clinical and histologic outcome of using medical- grade calcium sulfate hemihydrate ( MGCSH ) mixed with platelet-rich plasma ( PRP ) for extraction socket preservation graft before implant placement . METHODS This study is a single-site , r and omized and controlled investigation . Sixteen patients with a non-restorable tooth requiring extraction followed by implant placement were enrolled in this study . After extraction of a tooth , eight selected patients r and omly received MGCSH mixed with PRP in the extraction sockets ( test group ) , and eight selected patients r and omly received collagen resorbable plug dressing material ( control group ) . At the time of extraction and 3 months later ( at implant placement surgery ) , vertical and horizontal socket dimensions were measured . Bone core sample s were retrieved from the center of the healed socket before implant placement for histomorphometric analysis . RESULTS There was a statistically significant difference between the two groups based on histomorphometric analysis ( P < 0.05 ) . New vital bone percentage regenerated after 3 months of healing was 66.5 % ± 10.4 % in sockets grafted with MGCSH mixed with PRP compared to 38.3 % ± 9.3 % collagen resorbable plug . There was no statistically significant difference in the amount of vertical and horizontal bone resorption ( P > 0.05 ) between groups . In all cases but two in the control group , implants were placed with primary stability . CONCLUSION MGCSH mixed with PRP showed greater vital bone volume at 3 months with rapid enhancement of bone healing compared to PRP-free collagen resorbable graft BACKGROUND Allografts , such as demineralized freeze-dried bone allograft ( DFDBA ) and mineralized freeze-dried bone allograft ( FDBA ) are commonly used by clinicians for ridge preservation procedures . The primary objective of this study is to histologically evaluate and compare the healing of non-molar extraction sockets grafted with DFDBA versus FDBA for ridge preservation . The secondary aim of this study is to compare dimensional changes in ridge height and width after grafting with these two material s. MATERIAL S Forty patients were r and omly divided into two groups of 20 . Extraction sockets were filled with either FDBA or DFDBA . To minimize variables associated with the organ donor and with tissue processing , all of the graft material was procured from a single donor ; the only difference in the two material s was the percentage mineralization of the final bone graft . A 2-mm-diameter core biopsy was taken from each grafted site ≈19 weeks after grafting . Histomorphometric analysis was performed to determine percentage of vital bone , residual graft particles , and connective tissue (CT)/other non-bone components . RESULTS There were no significant differences when comparing changes in alveolar ridge dimensions of the two groups . There was no significant difference in percentage CT/other between groups . DFDBA had a significantly greater percentage of vital bone at 38.42 % versus FDBA at 24.63 % . The DFDBA group also had a significantly lower mean percentage of residual graft particles at 8.88 % compared to FDBA at 25.42 % . CONCLUSION This study provides the first histologic and clinical evidence directly comparing ridge preservation with DFDBA versus FDBA in humans and demonstrates significantly greater new bone formation with DFDBA BACKGROUND Many material s have been found to be effective in ridge preservation . The purpose of this study is to determine whether calcium sulfate ( CS ) is as effective as freeze-dried bone allograft ( FDBA ) in preserving post extraction ridge dimensions and to evaluate the amount of new bone formation and graft clearance through histologic analysis . METHODS Thirty-one extraction sites were selected . Post extraction clinical measurements were made , and sites were divided r and omly into the test group ( CS ) or the control group ( FDBA ) . After graft placement , all individuals received the same postoperative treatment and instructions . Participants were recalled after 3 months , measurements were made , and sites were re-entered . Bone sample s were harvested and analyzed with histologic methodology for new bone formation and remaining residual graft . RESULTS Thirteen test and 15 control sites were evaluated . There was no significant change in vertical ridge height before or after surgery within the test and control groups ( P = 0.57 , P = 0.68 , respectively ) . There was a significant decrease in bucco-lingual ridge width for both groups ( P = 0.0003 , P = 0.0075 , respectively ) , but the difference between groups was not significant ( P = 0.11 ) . Histologic analysis revealed an average of 32 % new bone formation with 2.5 % graft remaining for the test group and 16.7 % new bone formation with 21 % graft remaining for the control . CONCLUSIONS Results indicate that CS is as effective as FDBA in preserving post extraction ridge dimensions in non-molar extraction sites . There is greater clearance of CS with more new bone formation after ≈3 months compared with FDBA in these sites . This paper received the Maynard K. Hine Award for Excellence in Dental Research presented by the Indiana Section of the American Association for Dental Research and supported by Procter & Gamble PURPOSE Ridge preservation protocol s reduce crestal remodeling after tooth extraction . There is insufficient evidence on bone grafting in combination with platelet-rich plasma ( PRP ) or recombinant human platelet-derived growth factor ( rhPDGF-BB ) . The aim of this study is to evaluate healing of grafted and nongrafted sockets and the effect of PRP and rhPDGF-BB on early remodeling . MATERIAL S AND METHODS Forty-one patients whose treatment plan included extraction of anterior or premolar teeth were r and omized into four groups . Group 1 : collagen plug ( control ) . Group 2 : mineralized freeze-dried bone allograft (FDBA)/β-tricalcium phosphate (β-TCP)/collagen plug . Group 3 : FDBA/β-TCP/PRP/collagen plug . Group 4 : FDBA/β-TCP/rhPDGF-BB/collagen plug . At 8 weeks , a core was harvested from the center of 41 sockets . Histomorphometric analysis took place . Differences were analyzed using one-way analysis of variance ( ANOVA ) or chi-square tests for continuous and categorical data . Pairwise comparisons were tested using least squares means . Spearman correlation coefficients were used to evaluate the relationship of bone growth with potential confounders . A P value < .05 was considered statistically significant . RESULTS ANOVA did not indicate statistical significance in age , gender , smoking , ethnicity , or race distribution . Significant differences in tissue distribution were identified between groups and between different thirds of harvested core . More new bone and amorphous organic matrix was noted in the control group . In sites where bone graft was combined with growth factors , the amount of residual particles was less than in sites where bone graft was used alone . CONCLUSIONS Inclusion of bone replacement graft suppressed new bone formation during early healing . Inclusion of PRP and rhPDGF-BB produced less residual bone graft material , indicating more rapid turnover of bone graft . All treatment modalities achieved a significant amount of new vital bone at 8 weeks post extraction |
10,418 | 20,721,676 | Patients with NSLBP exhibit greater postural instability than healthy controls , signified by greater COP excursions and a higher mean velocity .
While the decreased postural stability in NSLBP sufferers further appears to be associated with the presence of pain , it seems unrelated to the exact location and pain duration .
No correlation between the pain intensity and the magnitude of COP excursions could be identified | Over the past 20 years , the center of pressure ( COP ) has been commonly used as an index of postural stability in st and ing .
While many studies investigated COP excursions in low back pain patients and healthy individuals , no comprehensive analysis of the reported differences in postural sway pattern exists . | Study Design . Three factors mixed- design with 1 between-subject and 2 within-subject factors . Objective . To compare the main effects and interactions of postural and cognitive difficulty on quiet stance between subjects with and without nonspecific low back pain ( LBP ) . Summary of Background Data . The interference between postural control and cognitive tasks depends on factors such as sensorimotor/cognitive integrity . Changes in peripheral sensory and muscular systems as well as cognitive processes have been observed in LBP patients . It was hypothesized that the effect of cognitive task on postural performance might be different in subjects with nonspecific LBP as compared with healthy individuals . To the authors ’ knowledge this has not been investigated before . Methods . Postural stability was measured by center of pressure parameters while nonspecific LBP ( n = 22 ) and healthy ( n = 22 ) subjects r and omly performed quiet st and ing task with 3 levels of difficulty ( rigid-surface eyes open , rigid-surface eyes-closed , and foam-surface eyes-closed ) in isolation or concurrently with an easy or difficult digits backward cognitive task . Results . Subjects with nonspecific LBP had less postural sway than healthy subjects , while postural sway decreased with increase in the level of cognitive difficulty . Nonspecific LBP and healthy subjects had larger postural sway at more difficult sensory conditions such as rigid-surface eyes-closed and foam-surface eyes-closed . The response to dual-tasking was not significantly different between the 2 groups . Conclusion . The dual-tasking did not change the postural performance of nonspecific LBP subjects with low level of pain and disability differently compared to healthy subjects This study evaluated the degree to which the disturbance to posture from respiration is compensated for in healthy normals and whether this is different in people with recurrent low back pain ( LBP ) , and to compare the changes when respiratory dem and is increased . Angular displacement of the lumbar spine and hips , and motion of the centre of pressure ( COP ) , were recorded with high resolution and respiratory phase was recorded from ribcage motion . With subjects st and ing in a relaxed posture , recordings were made during quiet breathing , while breathing with increased dead-space to induce hypercapnoea , and while subjects voluntarily increased their respiration to match ribcage expansion that was induced in the hypercapnoea condition . The relationship between respiration and the movement parameters was measured from the coherence between breathing and COP and angular motion at the frequency of respiration , and from averages triggered from the respiratory data . Small angular changes in the lumbopelvic and hip angles were evident at the frequency of respiration in both groups . However , in quiet st and ing , the LBP subjects had a greater displacement of their COP that was associated with respiration than the control subjects . The LBP group had a trend for less hip motion . There were no changes in the movement parameters when respiratory dem and increased involuntarily via hypercapnoea , but when respiration increased voluntarily , the amplitude of motion and the displacement of the COP increased in both groups . The present data suggest that the postural compensation to respiration counteracts at least part of the disturbance to posture caused by respiration and that this compensation may be less effective in people with LBP Tonic muscle nociceptive discharge evoked chemically from the foot extensor digitorum brevis muscle in man produces a depression of Ia excitation and Ib inhibition of the soleus ( Sol ) motoneurones ( Mns ) . The possibility that both these changes partly result from presynaptic inhibition of Ia fibres projecting to Sol Mns and to interneurones mediating group I non-reciprocal inhibition is tested . Convergence of Ia fibres on these interneurones was deduced from evidence that reducing the excitatory effect of the extensor Ia fibres ( by potentiation of their presynaptic inhibition ) result ed in Ib disinhibition . Nociceptive-induced potentiation of Ia presynaptic inhibition was deduced from the following congruent results obtained by two independent methods : ( 1 ) depression of heteronymous Ia monosynaptic facilitation of the quadriceps muscle to Sol Mns ; ( 2 ) potentiation of presynaptic inhibition of Sol Ia fibres evoked by mechanical activation of the tibialis anterior primary spindle afferents . It is concluded that nociceptive volleys arising from dorsal foot muscles facilitate the activity of interneurones intercalated in pathways responsible for presynaptic inhibition of Sol Ia fibres . It is also proposed that the same Ia presynaptic inhibition depresses the excitability of interneurones mediating group I non-reciprocal inhibition , thus result ing in Ib disinhibition of Sol Mns Objectives : To describe postural sway and its associations to background factors , low back pain and functional capacity . To evaluate the changes in postural sway after three months of therapeutic exercise in the gym or at home . Design : A one-year r and omized experimental trial evaluated postural sway in three study groups : intensive training , home exercise and control group . Setting : Subjects were recruited from seven local occupational health care centres in Central Finl and and were examined at Central Finl and Hospital by medical doctors . Measurements and therapeutic exercise programmes were carried out in the Research Laboratory of Sport and Health Sciences at Jyväskylä University . Subjects : Initially , 49 male and 41 female subjects ( aged 20–55 years ) with nonspecific and subacute low back pain were examined . Main outcome measures : Postural sway using a force platform , the Oswestry Index , as well as a measure of low back pain intensity were measured at the initial stage of the study , directly after interventions , as well as at three and nine months after the interventions . Results : The background variables were not strongly correlated with postural sway . No changes occurred in the amplitude of sway during the study , but the sway velocity of the home exercise group increased . Conclusions : Postural sway measurements with a force platform may be suitable for detecting impairments of balance performance among subjects with pronounced functional or activity limitations and severe low back pain problems . In order to enhance balance performance , specific and customized exercise programmes are required 1 . We studied quiet stance investigating strategies for maintaining balance . Normal subjects stood with natural stance and with feet together , with eyes open or closed . Kinematic , kinetic and EMG data were evaluated and cross-correlated . 2 . Cross-correlation analysis revealed a high , positive , zero-phased correlation between anteroposterior motions of the centre of gravity ( COG ) and centre of pressure ( COP ) , head and COG , and between linear motions of the shoulder and knee in both sagittal and frontal planes . There was a moderate , negative , zero-phased correlation between the anteroposterior motion of COP and ankle angular motion . 3 . Narrow stance width increased ankle angular motion , hip angular motion , mediolateral sway of the COG , and the correlation between linear motions of the shoulder and knee in the frontal plane . Correlations between COG and COP and linear motions of the shoulder and knee in the sagittal plane were decreased . The correlation between the hip angular sway in the sagittal and frontal planes was dependent on interaction between support and vision . 4 . Low , significant positive correlations with time lags of the maximum of cross-correlation of 250 - 300 ms were found between the EMG activity of the lateral gastrocnemius muscle and anteroposterior motions of the COG and COP during normal stance . Narrow stance width decreased both correlations whereas absence of vision increased the correlation with COP . 5 . Ankle mechanisms dominate during normal stance especially in the sagittal plane . Narrow stance width decreased the role of the ankle and increased the role of hip mechanisms in the sagittal plane , while in the frontal plane both increased . 6 . The modulation pattern of the lateral gastrocnemius muscle suggests a central program of control of the ankle joint stiffness working to predict the loading pattern OBJECTIVE To determine whether body balance is perturbed more in low back pain patients than in healthy subjects , under the concept of posturo-kinetic capacity . DESIGN Comparison of posturographic and respiratory parameters between low back pain and healthy subjects . BACKGROUND It has been demonstrated that respiratory movements constitute a perturbation to posture , compensated by movements of the spine and of the hips , and that low back pain is frequently associated with a loss of back mobility . METHOD Ten low back pain patients and ten healthy subjects performed five posturographic tests under three different respiratory rate conditions : quiet breathing ( spontaneous ) , slow breathing ( 0.1 Hz ) and fast breathing ( 0.5 Hz ) . RESULTS Intergroup comparison showed that the mean displacements of the center of pressure were greater for the low back pain group , especially along the antero-posterior axis , where respiratory perturbation is primarily exerted . Inter-condition comparison showed that in slow and fast breathing relatively to quiet breathing , the mean displacement of the center of pressure along the antero-posterior axis was significantly increased only for the low back pain group . CONCLUSION According to the results , respiration presented a greater disturbing effect on body balance in low back pain subjects . RELEVANCE This study provides information on the causes of the impaired body balance associated with chronic low back pain , which could be used to improve treatment strategy In this study , we describe a device for the direct measurement of intrinsic ankle stiffness in quiet st and ing . It consists of a motorised footplate mounted on a force platform . By generating r and om sequences of step-like disturbances ( 1 degrees amplitude , 150 ms duration ) and measuring the corresponding displacements of the center of pressure in the antero-posterior direction , we obtained torque-rotation patterns after aligning , averaging , and scaling the postural responses . Such patterns were used for estimating the value of the ankle stiffness , which was normalized as a fraction of the critical value . In order to be confident that the measurements addressed the intrinsic ankle stiffness and were not affected in a significant way by the reflex activation of the muscles in response to the test disturbances , we performed the estimates in different ways : least squares estimates with time windows of different widths and an instantaneous estimate at the time in which the angular acceleration vanishes . The statistical analysis showed that there is no significant difference among the different methods of estimate and the inspection of the electromyographic activity in response to the perturbations showed that at least two of the estimates were certainly outside the possible influence of reflex patterns . The intrinsic ankle stiffness was evaluated to be 64+/-8 % of the critical stiffness for test disturbances of the order of 1 degrees . We argue that this figure identifies the lower bound of the range of values which characterise normal sway in quiet st and ing , whereas the upper bound is given by the estimates performed with much smaller test disturbances [ 1 ] which yield a higher value : 91+/-23 % . The two estimation paradigms ( with very small and very large test disturbances , respectively ) are complementary also because they behave in a different way as regards the sensitivity to a bias torque : it is close to zero in the Loram & Lakie 's paradigm , whereas it is significant in our paradigm . Thus , as the bias grows , it appears that the range of stiffness values is narrowed and is pushed towards the upper bound . There is a clear potential for the clinical application of these methods , in the sense that the identification of the range of stiffness values used by a patient is a measurable index of motor organisation/reorganisation Insight into the mechanisms of altered postural control in persons with low back pain ( LBP ) could lead to better interventions for patients with LBP . This study investigated ( 1 ) whether persons with recurrent LBP have an altered body inclination , and ( 2 ) whether anticipation of postural instability further alters body inclination . Thirty-three young healthy individuals and 56 young persons with recurrent LBP participated in this study . The upright st and ing posture was evaluated by means of two piezo-resistive electrogoniometers and a force platform for the conditions as follows : ( 1 ) quiet stance with and without vision , and ( 2 ) in anticipation of postural instability due to a ballistic arm movement or ankle muscle vibration . No differences in body inclination were observed when visual information was available between the two groups ( P>0.05 ) . However , significant more forward inclination was seen in the persons with recurrent LBP when vision was occluded ( + 7.4 % ) and in anticipation of postural instability ( + 19 % ) ( P<0.05 ) compared to the healthy individuals . The results suggest that young persons with recurrent LBP have an altered body inclination that might be caused by anticipation of postural instability . The adopted forward inclined posture may potentially be a factor in the recurrence of LBP Abstract : To determine whether the presence of back pain and its related disabilities are determinants of balance and functional mobility in a group of women with osteoporosis , we carried out a cross-sectional analysis of 93 community-dwelling women with osteoporosis between the ages of 65 and 75 years old . We assessed health history , anthropometrics , self-report of current physical activity level and self-report of back pain ( intensity and pain-related disabilities ) . Balance was measured by computerized dynamic posturography and functional mobility was assessed by timed figure-of-eight test . The prevalence of back pain was high ( 75 % ) in this cohort of older women with osteoporosis . Age was the major determinant of both balance and functional mobility and accounted for 9 % and 14 % of the variance , respectively . After accounting for age , back pain explained an additional 9 % of the variance in balance and 13 % of the variance in functional mobility . The high prevalence of back pain demonstrates the importance of pain management in the treatment of osteoporosis . Furthermore , the finding of self-reported back pain as a determinant of both balance and functional mobility suggests that this measure may deserve attention when screening women with osteoporosis for fracture risk . Prospect i ve studies are needed to determine whether pain management will improve balance and functional mobility Study Design . A follow-up study evaluating postural control , lumbar movement perception , and paraspinal muscle reflexes in disc herniation-related chronic low back pain ( LBP ) before and after discectomy . Objectives . To assess the effect of discectomy on postural control , lumbar perception , and reflex activation of paraspinal muscles during sudden upper limb loading . Summary of Background Data . Impaired muscle function , postural control , and lumbar proprioception have been observed in LBP . However , they have not been studied in sciatica patients after surgery . Methods . The study included 20 patients selected for an operation for chronic LBP caused by disc herniation and 15 controls without chronic LBP . The paraspinal muscle responses for upper limb loading during unexpected and expected conditions were measured by surface electromyography . The ability to sense lumbar rotation was assessed in a previously vali date d motorized trunk rotation unit in the seated position . The postural control was measured with a vertical force platform . Pain , disability , and depression scores were recorded . Results . Patients had poorer lumbar perception ( P = 0.012 ) and postural control ( P < 0.05 ) than did healthy controls . The postural control remained unchanged , but lumbar perception ( P = 0.054 ) and the lumbar feed-forward control ( P = 0.043 ) improved after the surgery . Conclusions . The results demonstrate impaired lumbar proprioception and postural control in sciatica patients . During short-term follow-up after operative treatment , postural control does not seem to change , but impaired lumbar proprioception and feed-forward control of paraspinal muscles seem to recover |
10,419 | 29,984,498 | RESULTS The review of the findings suggest that individuals with AN may experience reduced taste sensitivity that may improve following recovery .
DISCUSSION This review suggests that altered taste sensitivity could represent a component in the wider altered taste processing observed in anorexia nervosa . | OBJECTIVE There is evidence for altered processing of taste in anorexia nervosa , particularly in the areas of reward processing and hedonic sensitivity .
However , research on whether people with anorexia nervosa identify taste stimuli accurately , known as taste sensitivity , has yielded mixed findings .
The objective of this study was to synthesize the literature on taste sensitivity in this disorder to provide a basis for future discussion on whether altered taste sensitivity may be also implicated in wider atypical taste processing in anorexia . | The possible differences in processing gustatory stimuli in anorexic patients compared to healthy control subjects was investigated by electrophysiological methods . The electroencephalogram ( EEG ) was recorded in out patients treated with anorexia nervosa ( AN ) and age-matched controls after exposure to sweet ( milk chocolate ) and bitter ( black tea ) taste stimuli . Power spectrum analysis was performed on EEG epochs recorded in the above conditions . Compared to controls a significantly higher percent of theta , and lower percent of alpha1 b and power was found in anorexic patients , irrespective of the kind of taste effects and hemispheric side . The pattern of activation caused by sweet and bitter stimuli was found to be different in these two groups , possibly indicating altered gustatory processing mechanisms in AN We evaluated the changes in taste responsiveness of anorexia nervosa ( AN ) patients during behavior therapy . Taste responsiveness of AN patients was lower at admission when compared to controls but it improved significantly over the course of treatment ( p < 0.01 ) . Taste responsiveness improved prior to increase in body weight . No significant correlation was noted between weight gain and improvement in taste responsiveness . The period required to reach a food intake of 1600 Kcal/day and the duration of hospitalization were highly correlated ( r = 0.72 , p < 0.05 ) . Those who reached 1600 Kcal/day earlier showed more rapid improvements in taste responsiveness . These results suggest that decreased taste responsiveness in AN patients can rapidly improve and such early improvement may result in better progression of treatment Taste responses to sucrose and fat-containing stimuli were examined in a population of young women with eating disorders . Anorectic-restrictor and anorectic-bulimic patients were compared with normal-weight bulimic patients and with normal-weight control subjects . Sensory estimates of sweetness and fat content of 20 different mixtures of milk , cream , and sugar did not differ among subject groups . In contrast , relative preferences for sugar vs fat as determined by the Response Surface Method differed between patients with eating disorders and control subjects . Normal-weight bulimic patients preferred sweeter stimuli than did control subjects . Anorectic-restrictor and anorectic-bulimic patients liked sweet but disliked high-fat stimuli and showed elevated optimal sugar : fat ( S : F ) ratios . This pattern of response did not change following weight regain . The stability of preference profiles suggests that taste responsiveness may be independent of diagnostic categories , bulimic behaviors , or acute changes in body weight Assessment of gustatory sensitivity in a clinical setting is the prerequisite for correct diagnosis and adequate treatment of taste dysfunction . Despite of this , no taste test has been established for the routine clinical testing . The aim of the present study was to create a protocol which is easy to administer . The presently used technique is based on strips made from filter paper which were impregnated with different taste solutions ( four concentrations each for sweet , sour , salty and bitter ) . These strips are placed on the tongue and subjects are asked to identify the taste quality . After establishing the concentration range of the taste solutions , the test was tried in 69 subjects . Each subject received eighteen taste strips ( four concentrations of each taste quality plus two blanks ) in a pseudo-r and omized sequence . Results from this new procedure correlated significantly with the results of the well established extensive three-drop-technique ( r69 = 0.67 ) . Repeated measures indicated good reproducibility of the results for the taste strips ( r69 = 0.68 ) . These data suggest the usefulness of this new technique in routine clinical practice . Major advantages are long shelf-life , convenience of administration , short time needed for testing ( approximately 8 min ) , and the possibility to test each side of the tongue separately OBJECTIVE Impaired interoceptive awareness ( IA ) , the subjective perception of internal body sensations , has been proposed as a vulnerability or maintaining factor in anorexia nervosa ( AN ) . We examined whether IA of heartbeat and breathing sensations was impaired in AN across a range of arousal levels , and whether it was influenced by meal anticipation and consumption . METHOD IA was assessed using r and omized , double-blinded , bolus intravenous infusions of isoproterenol , a peripheral beta-adrenergic sympathetic agonist , and saline . Fifteen women with AN and 15 age- , and sex- matched healthy comparisons ( HC ) were evaluated before and after consumption of a 1,000 Calorie meal . During each infusion participants rated their moment-to-moment intensity of heartbeat and breathing sensations with a dial . To measure IA we evaluated interoceptive detection thresholds , retrospective ratings of palpitation and dyspnea intensity , and interoceptive accuracy via correlations between subjective dial ratings and observed heart rate responses . RESULTS Contrary to prediction the AN group was more likely to report detection of interoceptive sensations across all conditions , an effect driven by false discriminations at low arousal levels . Concordant with prediction , meal anticipation was associated with intensified interoceptive sensations , particularly dyspnea . There were no differences in interoceptive accuracy . DISCUSSION This represents the first demonstration of interoceptive prediction errors in AN . Although IA is unimpaired at high arousal levels in AN , prediction signals are abnormal at low arousal levels , especially during meal anticipation . Altered interoceptive prediction signaling during meal anticipation could contribute to phenotypes of high anxiety in AN or alternatively , might be explained by enhanced meal associated anxiety Background : Taste abnormalities are common among cancer patients after starting radiotherapy or chemotherapy . Considering the role of zinc and reports on its beneficial effects in taste perception , we evaluated the preventive effects of zinc sulfate on radiation-induced taste alterations . Material s and Methods : In a r and omized , placebo-controlled trial , adult patients with head and neck cancers who were on schedule for radiotherapy , with or without chemotherapy , were allocated to receive zinc sulfate ( 50 mg , three times a day ) or placebo ; started with beginning of radiotherapy and continued for one month later . Taste acuity was determined by measuring detection and recognition thresholds for four taste qualities at baseline , at the end of radiotherapy , and a month later using the Henkin method . Results : Thirty-five patients ( mean age = 59.2 ± 16.5 , 60 % male ) completed the trial . The two groups were similar at baseline . After radiotherapy , and one month later , there was a significant increase in taste perception threshold for bitter , salty , sweet , and sour tastes in the placebo group ( P = 0.001 ) . In those who received zinc , there was only slight increase in threshold for perception of the salty taste ( P = 0.046 ) . No relevant side effects due to zinc sulfate were reported . Conclusion : Zinc supplementation in head/neck cancer patients under radiotherapy can prevent radiation-induced taste alterations . Further studies with longer follow-ups and with different doses of zinc supplementation are warranted in this regard The influence of sweet taste sensitivity on food intake is not well understood . We investigated the involvement of salivary leptin and SNP of the sweet taste receptor genes ( TAS1R2/TAS1R3 ) on sweet taste sensitivity , sensory-specific satiety ( SSS ) and macronutrient intake in healthy human adults . In all , nineteen high sweet sensitivity ( HS ) and eleven low sweet sensitivity ( LS ) subjects were classified based on the sweetness perception of one solution ( 9 mm sucrose ) forced-choice triangle test . All participants completed a r and omised crossover design experiment where they consumed one of three iso-energetic soup preloads differing in primary taste quality ( sweet , non-sweet taste-control or no-taste energy-control ) . A period of 1 h after the preload , participants were offered a buffet meal consisting of foods varying in taste ( sweet or non-sweet ) and fat content . Subjective measures included hunger/fullness and SSS for sweetness . Saliva and buccal cells were collected to measure leptin level and to study the TAS1R2/TAS1R3 specific SNP , respectively . Salivary leptin concentrations were significantly higher in LS than HS participants ( P<0·05 ) . In addition , HS showed stronger sweet SSS compared with LH participants ( P<0·05 ) , and consumed less carbohydrate ( % energy ) and more non-sweet foods than LS ( P<0·01 and P<0·05 , respectively ) . Alleles from each TAS1R2 locus ( GG compared with AA alleles of rs12033832 , and CT/CC compared with TT alleles of rs35874116 ) were related to higher consumption of carbohydrates ( % energy ) and higher amount of sweet foods , respectively ( P<0·05 ) . In contrast , no associations were found for the TAS1R3 alleles . These results contribute to underst and the links between taste sensitivity , macronutrient appetite and food consumption Previous research has shown that patients with bulimia nervosa ( B ) , anorexia nervosa , restricting type , or restrictive-anorectic ( RA ) , and anorexia nervosa , binge eating , purging type , or anorectic-bulimic ( AB ) exhibit a reduced hedonic response to sucrose compared with control subjects . We hypothesized that this response could be linked to an excessive fear of weight gain rather than a decreased ability to experience pleasure . We therefore compared the hedonic responses to sucrose solutions in B , RA and AB women ( n=20/group ) in two different conditions : sucrose solution swallowed vs. sucrose solution spit . Under double-blind conditions and according to a Latin square design , patients received sucrose in solution ( 0 , 5 , 10 , 20 , and 40 % ) and rated each concentration for pleasantness on a nine-point scale . The two test conditions were r and omly administered . The threshold concentration of sweet taste perception was also assessed , and the subjects filled out Chapman 's Social and Physical Anhedonia Scale . The hedonic response to sucrose adjusted for the sweet taste perception threshold was significantly lower in the ' swallow ' than in the ' spit ' condition . There was a significant effect of sucrose concentrations as well as a significant condition by concentration interaction . When ' fear to swallow ' sucrose solution responses were included as a covariate , the significant difference between the conditions of ' swallow ' or ' spit ' disappeared , but there was a significant concentration by condition by fear to swallow interaction and an almost significant covariate effect . When ' Drive for Thinness ' on the Eating Disorder Inventory was included as a covariate , similar results were obtained . Social Anhedonia but not Physical Anhedonia correlated positively with ' Drive for Thinness ' and ' fear of swallowing sucrose solutions ' , and correlated inversely with maximal hedonic response to the ' swallow ' condition . ' We conclude that the hedonic responses to sucrose in patients with eating disorders are decreased when solutions are swallowed . This may reflect excessive fear of gaining weight rather than decreased ability to experience pleasure ' Anorexia Nervosa ( AN ) is a disorder of self-starvation characterized by decreased meal size and food intake . While it is possible that reduced food intake in AN reflects an excess of inhibitory factors , e.g. , cognitive inhibition related to fear of weight gain or abnormal postingestive negative feedback , it is also possible that decreased intake reflects diminished orosensory stimulation of food intake . This has been difficult to test directly because the amount of food ingested during a test meal by patients with AN reflects an integration of orosensory excitatory , and cognitive , learned , and postingestive inhibitory controls of eating . To begin to dissociate these controls , we adapted the modified sham feeding technique ( MSF ) to measure the intake of a series of sweetened solutions in the absence of postingestive stimulation . Subjects with AN ( n=24 ) and normal controls ( NC , n=10 ) were r and omly presented with cherry Kool Aid solutions sweetened with five concentrations of aspartame ( 0 , 0.01 , 0.03 , 0.08 and 0.28 % ) in a closed opaque container fitted with a straw . They were instructed to sip as much as they wanted of the solution during 15 1-minute trials and to spit the fluid out into another opaque container . Subjects with AN sipped less unsweetened solution than NC ( p<0.05 ) . Because this difference appeared to account completely for the smaller intakes of sweetened solutions by AN , responsiveness of intake to sweet taste per se was not different in AN and NC . Since MSF eliminated postingestive and presumably cognitive inhibitory controls , and the orosensory response to sweet taste was not different in AN than NC , we conclude that decreased intake by AN subjects under these conditions reflects the increased inhibition characteristic of this disorder that is presumably learned , with a possible contribution of decreased potency of orosensory stimulation by the sipped solutions BACKGROUND The majority of studies on taste and smell in eating disorders have revealed several alterations of olfactory or gustatory functions . Aim of this prospect i ve study was to employ detailed olfactory and gustatory testing in female subjects of three homogenous groups - anorexia nervosa , bulimia nervosa and healthy controls - and to look at the effects of treatment on these measures . METHODS Sixteen hospitalized female patients with anorexia ( restricting type , mean age [M]=24.5 years ) , 24 female patients with bulimia ( purging type , M=24.3 years ) as well as 23 healthy controls ( M=24.5 years ) received olfactory ( " Sniffin ' Sticks " ) and gustatory testing ( " Taste Strips " ) . Group differences in olfactory and gustatory sensitivity , body mass index ( BMI ) , the Beck depression inventory , the eating attitudes test ( EAT ) , and the influence of therapy on gustatory and olfactory function were investigated . RESULTS ( 1 ) Group differences were present for odor discrimination and overall olfactory function with anorexic patients having the lowest scores . ( 2 ) Regarding taste function , controls scored higher than patients with anorexia . ( 3 ) At admission small but significant correlations were found between overall olfactory function and body weight ( r(63)=0.35 ) , BMI ( r(63 ) = 0.37 ) , and EAT score ( r(63 ) = -0.27 ) . Similarly , ( 4 ) the taste test score correlated significantly with body weight ( r(63)= 0.48 ) , and BMI ( r(63 ) = 0.45 ) . Finally , ( 5 ) at discharge overall olfactory and gustatory function were significantly higher compared to admission in anorexic patients . CONCLUSIONS As compared to healthy controls and bulimic patients our results show lowered olfactory and gustatory sensitivities in anorexic patients that improved with increasing BMI and decreasing eating pathology in the course of treatment BACKGROUND In anorexia nervosa ( AN ) , taste and smell are believed to be anhedonic , hunger and pain are muted , and body-image distortion obscures wasting , which together facilitate self-starvation . However , the emphasis on these deficits may be biased because other sensory systems have been sparsely investigated . OBJECTIVES Objectives of the study were to clarify whether these dysfunctions are specific or part of a pattern of sensory-perceptual deficits in AN patients and to test the gustatory senses dissociated from ingestion to clarify whether any deficit is sensory or affective . DESIGN In 15 adolescent , first-episode , hospitalized , restrictive AN patients and 15 matched healthy controls who responded to gustatory stimuli ( intensity and hedonics of 5 basic tastes and tastes and odors of foods and nonfoods ) , size estimation ( manual and oral judgment of size and shape , kinesthesia , and body size and esthetics ) , cold pain , and auditory and visual processing were compared . RESULTS AN patients did not differ on most tests , were better at odor recognition , were less successful in central auditory processing and oral assessment of size and shape , and may have been more sensitive to cold . Body-image dissatisfaction in AN patients was not related to dysfunctional size estimation . CONCLUSIONS There is no systematic sensory-perceptual deficit in AN patients , and specifically , not in gustatory function . The few differences shown might be due to fear of food-related stimuli or comorbidity |
10,420 | 30,178,872 | AUTHORS ' CONCLUSIONS The results demonstrate that pharmacist services have varying effects on patient outcomes compared with usual care . | BACKGROUND This review focuses on non-dispensing services from pharmacists , i.e. pharmacists in community , primary or ambulatory-care setting s , to non-hospitalised patients , and is an up date of a previously-published Cochrane Review .
OBJECTIVES To examine the effect of pharmacists ' non-dispensing services on non-hospitalised patient outcomes . | Objectives : The aim of the study was twofold ; 1 ) to develop a clinical pharmacist-led 12 month lasting follow-up program for patients with established coronary heart disease ( CHD ) discharged from the University Hospital of North Norway , and 2 ) to explore the impact of the program with regards to adherence to a medication assessment tool for secondary prevention of CHD and change in biomedical risk factors . Methods : A total of 102 patients aged 18 - 82 years were enrolled in a non-blinded r and omized controlled trial with an intervention group and a control group . The intervention comprised medication reconciliation , medication review and patient education during three meetings ; at discharge , after three months and after twelve months . The control group received st and ard care from their general practitioner . Primary outcomes were adherence to clinical guideline recommendations concerning prescription , therapy goal achievement and lifestyle education defined in the medication assessment tool for secondary prevention of CHD ( MAT-CHDSP ) . Secondary outcomes included changes in the biomedical risk factors cholesterol , blood pressure and blood glucose . Results : Ninety-four patients completed the trial , 48 intervention group patients and 46 controls . Appropriate prescribing was high , but therapy goal achievement was low in both groups . Overall adherence to MAT-CHDSP criteria increased in both groups and was significantly higher in the intervention group at study end , 78.4 % vs. 62.0 % , p<0.001 . The difference was statistically significant for the documented lifestyle advices in intervention group patients . No significant improvements in biomedical risk factors were observed in favor of the intervention group . Conclusions : The study showed an increased guideline adherence in both study groups . This indicates that attention to clinical practice guideline recommendations in itself increases adherence – which may be a clinical pharmacist task . A larger adequately powered study is needed to show a significant difference in biomedical risk factor improvements in favor of the intervention . Amendments to the follow-up program are suggested before implementation in st and ard patient care can be recommended Background : No r and omised studies have addressed whether self-management for asthma can be successfully delivered by community pharmacists . Most r and omised trials of asthma self-management have recruited participants from secondary care ; there is uncertainty regarding its effectiveness in primary care . A r and omised controlled study was undertaken to determine whether a community pharmacist could improve asthma control using self-management advice for individuals recruited during attendance at a community pharmacy . Methods : Twenty four adults attending a community pharmacy in Tower Hamlets , east London for routine asthma medication were r and omised into two groups : the intervention group received self-management advice from the pharmacist with weekly telephone follow up for 3 months and the control group received no input from the pharmacist . Participants self-completed the North of Engl and asthma symptom scale at baseline and 3 months later . Results : The groups were well matched at baseline for demographic characteristics and mean ( SD ) symptom scores ( 26.3 ( 4.8 ) and 27.8 ( 3.7 ) in the intervention and control groups , respectively ) . Symptom scores improved in the intervention group and marginally worsened in the control group to 20.3 ( 4.2 ) and 28.1 ( 3.5 ) , respectively ( p<0.001 ; difference adjusted for baseline scores = 7.0 ( 95 % CI 4.4 to 9.5 ) . Conclusions : A self-management programme delivered by a community pharmacist can improve asthma control in individuals recruited at a community pharmacy . Further studies should attempt to confirm these findings using larger sample s and a wider range of outcome measures BACKGROUND Falls are the leading cause of both fatal and nonfatal injuries among older adults in the United States . Medications that affect the central nervous system are known to increase the risk of falling . OBJECTIVE The purpose of this study was to assess the effects of a community pharmacy-based falls-prevention program targeting high-risk older adults on the rates of recurrent falls , injurious falls , and filling prescriptions for medications that have been associated with an increased risk of falling . METHODS This was a r and omized controlled trial of participants recruited through a community pharmacy chain in North Carolina . The 2-year study consisted of a 1-year " look-back " period before r and omization and a 1-year follow-up period after r and omization . Patients were eligible to participate if they were ≥65 years of age , had fallen at least once during the 1-year period preceding enrollment , and were taking medications associated with an increased risk of falling . Medications classified as high risk included benzodiazepines , antidepressants , anticonvulsants , sedative hypnotics , opioid analgesics , antipsychotics , and skeletal muscle relaxants . Participants were assigned to either the intervention arm or the control arm ; participants in the intervention arm were invited to attend a face-to-face medication consultation conducted by a community pharmacy resident , whereas those in the control arm received no medication consultation . The primary end point was the rate of recurrent falls during the 1-year followup period . Secondary end points were the total number of prescriptions for high-risk medications filled during the follow-up period and either discontinued use or a reduction in the dosage of a high-risk medication during the follow-up period . RESULTS One hundred eighty-six patients ( 132 women , 54 men ; 88.7 % white ) were enrolled . Intention-to-treat ( ITT ) analyses revealed no significant differences in the rates of recurrent falls , injurious falls , or filling prescriptions for high-risk medications . However , 13 patients in the intervention group either discontinued use of a high-risk medication or had the dosage reduced during the follow-up period , compared with 5 patients in the control group ( χ(2 ) = 3.94 ; P < 0.05 ) . As-treated analyses revealed numeric reductions in the rates of falls ( rate ratio [ RR ] = 0.76 ; 95 % CI , 0.53 - 1.09 ) , injurious falls ( RR= 0.67 ; 95 % CI , 0.43 - 1.05 ) , and filling prescriptions for high-risk medications ( RR= 0.85 ; 95 % CI , 0.72 - 1.03 ) after receipt of the intervention , but the differences were not statistically significant . CONCLUSIONS Results of this study support the feasibility of using community pharmacies to deliver a falls-prevention program targeting high-risk older adults . Although the ITT analyses revealed no significant reduction in the rate of recurrent falls , injurious falls , or overall use of high-risk medications , individuals in the intervention group were more likely than those in the control group to discontinue use of a high-risk medication or have the dosage reduced during the 1-year follow-up period . More work is needed to evaluate the intervention using a larger sample size that provides greater power to detect clinical ly meaningful effects of reduction in the use of high-risk medications on preventing or reducing falls in the high-risk population The effect of pharmaceutical care on the prevention , detection , and resolution of medication-related problems in high-risk patients in a rural community was studied . Adult patients who received care at clinics in a medically underserved area of Alabama and who were identified as being at high risk of medication-related adverse events were r and omly assigned to a control group or an intervention group . The control group received st and ard medical care , and the intervention group received pharmaceutical care , including a medical record review , a medication history review , pharmacotherapeutic evaluation , and patient medication education and monitoring over a one-year period . A total of 69 patients completed the study ( 33 in the intervention group and 36 in the control group ) . The percentage of patients responding to hypertension , diabetes , dyslipidemia , and anticoagulation therapy increased significantly in the intervention group and declined in the control group . Ratings for inappropriate prescribing improved in all 10 domains evaluated in the intervention group but worsened in 5 domains in the control group . There were no significant differences between the groups at 12 months in health-related quality of life or medication misadventures . Medication compliance scores improved in the intervention group but not in the control group . Medication knowledge increased in the intervention group and decreased in the control group . Pharmaceutical care in a rural , community-based setting appeared to reduce inappropriate prescribing , enhance disease management , and improve medication compliance and knowledge without adversely affecting health-related quality of life OBJECTIVE To compare the effectiveness of an evidence -based , systematic approach to hypertension care involving comanagement of patients by primary care physicians and clinical pharmacists versus usual care in reducing blood pressure in patients with uncontrolled hypertension . METHODS Patients in a staff model medical group with uncontrolled hypertension were r and omized to either a usual care ( UC ) or a physician-pharmacist comanagement ( PPCM ) group . All physicians in the study received both group and individual education and participated in the development of an evidence -based hypertension treatment algorithm . Physicians were then given the names of their patients whose medical records documented elevated blood pressures ( defined as systolic > or = 140 mm Hg and /or diastolic > or = 90 mm Hg for patients aged < 65 yrs , and systolic > or = 160 mm Hg and /or diastolic > or = 90 mm Hg for those aged > or = 65 yrs ) . Patients r and omized to the UC group were managed by primary care physicians alone . Those r and omized to the PPCM group were comanaged by their primary care physician and a clinical pharmacist , who provided patient education , made treatment recommendations , and provided follow-up . Blood pressure measurements , antihypertensive drugs , and visit costs/patient were obtained from medical records . RESULTS One hundred ninety-seven patients with uncontrolled hypertension participated in the study . Both PPCM and UC groups experienced significant reductions in blood pressure ( systolic -22 and -11 mm Hg , respectively , p < 0.01 ; diastolic -7 and -8 mm Hg , respectively , p < 0.01 ) . The reduction in systolic blood pressure was greater in the PPCM group after adjusting for differences in baseline blood pressure between the groups ( p < 0.01 ) . More patients achieved blood pressure control in the PPCM than in the UC group ( 60 % vs 43 % , p = 0.02 ) . Average provider visit costs/patient were higher in the UC than the PPCM group ( $ 195 vs $ 160 , p = 0.02 ) . CONCLUSIONS An evidence -based , systematic approach using physician-pharmacist comanagement for patients with uncontrolled hypertension result ed in improved blood pressure control and reduced average visit costs/patient Background Older people are at increased risk of drug-related problems ( DRPs ) caused by inappropriate use or underuse of medications which may be increased during care transitions . Objective To examine the effects of applying a vali date d prescribing appropriateness criteria -set during medication review in a cohort of older ( ≥65 years ) Australians at the time of discharge from hospital . Setting Private hospital and homes of older patients in Sydney , Australia . Methods Cognitively well English speaking patients aged 65 years or over taking five or more medications were recruited . A prescribing appropriateness criteria -set and SF-36 health-related quality of life health ( HRQoL ) survey were applied to all patients at discharge . Patients were then r and omly assigned to receive either usual care ( control , n = 91 ) or discharge medication counselling and a medication review by a clinical pharmacist ( intervention , n = 92 ) . Medication review recommendations were sent to the general practitioners of intervention group patients . All patients were followed up at 3 months post discharge , where the prescribing appropriateness criteria -set was reapplied and HRQoL survey repeated . Main outcome measures change in the number of prescribing appropriateness criteria met ; change in HRQoL ; number and causes of DRPS identified by medication review ; intervention patient medication recommendation implementation rates . Results There was no significant difference in the number of criteria applicable and met in intervention patients , compared to control patients , between follow-up and discharge ( 0.09 ≤ p ≤ 0.97 ) . While the difference between groups was positive at follow-up for SF-36 scores , the only domain that reached statistical significance was that for vitality ( p = 0.04 ) . Eighty-eight intervention patient medication review s identified 750 causes of DRPs ( 8.5 ± 2.7 per patient ) . No causes of DRPs were identified in four patients . Of these causes , 76.4 % ( 573/750 ) were identified by application of the prescribing appropriateness criteria -set . GPs implemented a relatively low number ( 42.4 % , 318/750 ) of recommendations . Conclusion Application of a prescribing appropriateness criteria -set during medication review in intervention patients did not increase the number of criteria met , nor result in a significant improvement in HRQoL. Higher recommendation implementation rates may require additional facilitators , including a higher quality of collaboration RATIONALE , AIMS AND OBJECTIVES This study aim ed to evaluate the effect of a pharmacist-physician collaborative care model on clinical outcomes in patients with uncontrolled type 2 diabetes and determine characteristics that influence this effect . METHODS A r and omized controlled trial was conducted in a secondary care clinic for 80 patients with type 2 diabetes , aged 40 - 79 years and glycosylated haemoglobin ( A1C ) level ≥ 7.0 % . The intervention group received individual , face-to-face pharmaceutical consultations and remote telephone support after a routine visit . The main measures were clinical outcomes ( A1C , blood pressure , LDL cholesterol ) and process indicators ( medication adherence , medication regimen complexity , use of medicines ) . Multiple regression models were used to determine the variables that could explain the reduction and individualized control of A1C . RESULTS From the initial sample of 80 patients , 73 completed this study . Compared with usual care , patients in the intervention group showed greater reduction in A1C ( -0.79 vs. -0.16 ; P = 0.010 ) ; and an increase in the percentage of patients achieving the individualized goal of A1C ( 25.0 % vs. 5.4 % ; P = 0.020 ) . In addition , there was an increase in the percentage of adherent patients and in the average scores of medication adherence . Participation in the intervention group , higher baseline A1C levels and greater change in medication adherence were all significant predictors of improvement in A1C levels . CONCLUSIONS The results suggest that the collaborative care model proposed is feasible and more effective than the usual care in the reduction and individualized control of A1C levels in patients with uncontrolled type 2 diabetes BACKGROUND AND OBJECTIVES CKD is characterized by remarkably high hospitalization and readmission rates . Our study aim was to test a medication therapy management intervention to reduce subsequent acute care utilization . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS The CKD Medication Intervention Trial was a single-blind ( investigators ) , r and omized clinical trial conducted at Providence Health Care in Spokane , Washington . Patients with CKD stages 3 - 5 not treated by dialysis who were hospitalized for acute illness were recruited . The intervention was design ed to improve posthospitalization care by medication therapy management . A pharmacist delivered the intervention as a single home visit within 7 days of discharge . The intervention included these fundamental elements : comprehensive medication review , medication action plan , and a personal medication list . The primary outcome was a composite of acute care utilization ( hospital readmissions and emergency department and urgent care visits ) for 90 days after hospitalization . RESULTS Baseline characteristics of participants ( n=141 ) included the following : age , 69±11 ( mean±SD ) years old ; women , 48 % ( 67 of 141 ) ; diabetes , 56 % ( 79 of 141 ) ; hypertension , 83 % ( 117 of 141 ) ; eGFR , 41±14 ml/min per 1.73 m2 ( serum creatinine-based Chronic Kidney Disease Epidemiology Collaboration equation ) ; and urine albumin-to-creatinine ratio median , 43 mg/g ( interquartile range , 8 - 528 ) creatinine . The most common primary diagnoses for hospitalization were the following : cardiovascular events , 36 % ( 51 of 141 ) ; infections , 18 % ( 26 of 141 ) ; and kidney diseases , 12 % ( 17 of 141 ) . The primary outcome occurred in 32 of 72 ( 44 % ) of the medication intervention group and 28 of 69 ( 41 % ) of those in usual care ( log rank P=0.72 ) . For only hospital readmission , the rate was 19 of 72 ( 26 % ) in the medication intervention group and 18 of 69 ( 26 % ) in the usual care group ( log rank P=0.95 ) . There was no between-group difference in achievement of guideline -based goals for use of renin-angiotensin system inhibition or for BP , hemoglobin , phosphorus , or parathyroid hormone . CONCLUSIONS Acute care utilization after hospitalization was not reduced by a pharmacist-led medication therapy management intervention at the transition from hospital to home OBJECTIVE To evaluate the effectiveness of clinical pharmacist 's intervention on achieving better asthma control , quality of life and other clinical parameters . METHODS A prospect i ve r and omized controlled study in north Jordan was conducted . Pediatric patients with asthma ( aged 7 - 18 years old ) were included and r and omly allocated into two groups , intervention and control . Both groups were interviewed at the first visit and followed up twice by phone ( at 3 and 6 months ) . Education was provided to patients and their caregivers in the intervention group only . RESULTS Of 206 eligible patients recruited and r and omized to our study , 178 patients completed the study ( 48.3 % intervention versus 51.7 % control ) . There were no significant differences in all baseline data between both groups . We identified significant differences in the improvement of asthma control ( p<0.001 ) and consequently pediatric and caregiver quality of life ( p<0.001 ) between both groups at the end of study . Significant differences were also detected in other clinical parameters ( p<0.05 ) . CONCLUSION Implementation of clinical pharmacy service can positively influence asthma control , pediatric and caregiver 's quality of life , and other clinical parameters . PRACTICE IMPLICATION S To maintain a good asthma status , education of pediatric patients and their caregivers should be part of routine assessment during clinic visit Background and objective Hyperglycemia in pregnancy is a risk factor for cardiovascular disease and postpartum ( PP ) diabetes . This study aim ed to assess the impact of the clinical pharmacist-assisted program ( CPAP ) of optimizing drug therapy and intensive education on main management outcome measures of patient knowledge about diabetes , Quality of life ( QoL ) as measured by SF-36 including maternal complications , fasting plasma glucose ( FPG ) control , and HbA1c . Method This is a r and omized controlled study . Pregnant ( 20–28 weeks ) patients with hyperglycemia received CPAP ( n = 51 ) as compared with conventional management ( n = 34 ) . Patients were then followed up for 6 weeks pp . Results A significant change was shown in the intervention group for diabetes knowledge ( 3.47 % vs. control 2.03 % , P < 0.05 ) and three aspects of health-related QoL. The need for caesarian delivery ( 58.8 % vs. control 35.3 % ) and severe episodes of hypoglycemia ( 0 % vs. control 8.8 % ) were significantly ( P < 0.05 ) reduced in the intervention group . Six weeks PP reduction in HbA1c values was greater in the intervention group ( − 0.54 % vs. control − 0.08 % , P = 0.04 ) with more FPG-controlled patients during pregnancy ( 94 % vs. control 64.7 % ) . Conclusion Clinical pharmacist assisted services in the management of pregnancy hyperglycemia fundamentally and significantly improve knowledge and disease control BACKGROUND Poor adherence to antidiabetic medications leads to a higher rate of hospital admissions and adverse health outcomes in type 2 diabetes mellitus patients . OBJECTIVE This study aims to evaluate whether a pharmacist-led medication therapy management , compared to the usual care , could enhance medication adherence and reduce hospital admission in patients with type 2 diabetes mellitus . METHODS A prospect i ve r and omized controlled study was conducted in patients with type 2 diabetes mellitus from February 1 to July 30 , 2016 . Patients in the control group ( n=65 ) received the usual care while patients in the intervention group ( n=62 ) received a personalized pharmacotherapeutic care plan and diabetes education . The two groups were compared by repeated measure ANOVA at 3 and 6-months with medication adherence ( using Morisky medication adherence scale ) and number of hospital admissions as the main outcome variables . RESULTS A total of 127 patients were included in the study . A marked and statistically significant increase in medication adherence from baseline to 3 and 6 months were noted in the intervention group ( increased from 9.2 % at baseline to 61 % at 6 month ) compared with the control group ( increased from 13.2 % at baseline ( to 30.2 % at 6 month ; p-value<0.01 ) . Furthermore , at the 6-month follow-up , only 23 patients in MTM group with poorly controlled blood glucose levels result ed in hospital admissions compared to 48 patients in non-MTM group , result ing in a 52.1 % fewer hospital admissions ( p < 0.001 ) . CONCLUSIONS The findings of this study implied that pharmacist-led medication therapy management might improve medication adherence and reduce number of hospitalizations in patients with type 2 diabetes mellitus . Hence , policies and guidelines should be in place in order for clinical pharmacists to fully engage in patient care and improve the medication therapy outcomes Aim To test the effectiveness of a tailored , pharmacist-led central ised advice service to improve adherence to patients on established medications . Methods A parallel group r and omised controlled trial was conducted . Patients prescribed at least one oral medication for type 2 diabetes and /or lipid regulation were eligible to participate . 677 patients of a mail-order pharmacy were recruited and r and omised ( 340 intervention , 337 control ) . The intervention comprised two tailored telephone consultations with a pharmacist , 4–6 weeks apart , plus a written summary of the discussion and a medicines reminder chart . The primary outcome was self-reported adherence to medication at 6-month follow-up , collected via a postal question naire , analysed using generalised estimating equations . Secondary outcomes included prescription refill adherence , lipid and glycaemic control and patient satisfaction . Results In intention-to-treat analysis 36/340 ( 10.6 % ) of the intervention group were non-adherent ( < 90 % of medication taken in the past 7 days ) at 6 months compared with 66/337 ( 19.6 % ) in the control group , yielding an unadjusted OR of 1.54 ( 95 % CI 1.11 to 2.15 , p=0.01 ) . Analyses of dispensing data also showed that the odds of being classified as adherent ( ≥90 % ) were 60 % greater for the intervention group compared with the control group ( OR 1.60 , 95 % CI 1.14 to 2.24 , p<0.01 ) . In a sub sample of patients who provided blood sample s , glycaemic and lipid control did not differ significantly between groups ( p=0.06 and p=0.24 , respectively ) but positive trends were observed . Ninety-two per cent of intervention group patients reported that they were satisfied with the service overall . Conclusions A telephone intervention , led by a pharmacist and tailored to the individuals ’ needs , can significantly improve medication adherence in patients with long-term conditions , using a mail-order pharmacy . Further work is needed to confirm a trend towards improved clinical outcome . Trial registration number NCT01864239 OBJECTIVES The aim was to determine the impact of a telephone counseling service , provided bi-monthly by pharmacist , on patients ' beliefs about antihypertensive medicines and blood pressure ( BP ) control . METHODS Either hypertensive patients were r and omly assigned to a control group ( CG , usual care ) or an intervention group ( IG ) . All patients had BP values registered and filled in the Italian version of the Belief Medicine Question naire ( BMQ ) . After 12 months , patients filled in the BMQ again and had their self-reported BP registered . The intervention consisted of an educational/counseling session based on patients ' needs assessment provided bi-monthly by a pharmacist for one year via telephone . RESULTS 80 CG and 84 IG patients were recruited . After 12 months , there were significant differences between IG and CG for both BMQ 's Necessity and Concern score ( p < 0.001 ; p < 0.001 respectively ) and a significant reduction in BP values in IG ( p < 0.001 ) . CONCLUSIONS The intervention improves BP control by modifying patients ' perception about treatments and involving patients as participants in the management of their health . PRACTICE IMPLICATION S This paper could serve as a guideline for other studies to confirm the effectiveness of this intervention in modifying health behavior , and the role of hospital pharmacist Background In the People ’s Republic of China , out patients have limited time with their physicians . Thus , compared to in patients , out patients have lower medication adherence and are less knowledgeable about their disease . Objective The objective of this study was to evaluate the effect of pharmaceutical care on clinical outcomes of out patients with type 2 diabetes mellitus ( T2DM ) . Patients and methods A r and omized , controlled , prospect i ve clinical trial was conducted recruiting a total of 240 T2DM out patients from Zhongda Hospital , Southeast University . The control group ( CG ) received only common care from medical staff , whereas the inter vention group ( IG ) received extra pharmaceutical care from clinical pharmacists . Biochemical data such as blood pressure ( BP ) , fasting blood glucose ( FBG ) , glycosylated hemoglobin A1 ( HbA1c ) , and blood lipid were collected before and after 6-month intervention . The primary end points in this study were FBG and HbA1c . Results After the intervention , most of the baseline clinical outcomes of the patients in IG significantly improved , while only body mass index , diastolic BP , low-density lipoprotein cholesterol , and total cholesterol ( TC ) improved significantly in patients in the CG . Compared to CG , in IG , there were significant improvements in FBG , HbA1c , TC , the target attainment rates of HbA1c , and BP . Conclusion Pharmaceutical care provided by clinical pharmacists could improve the control of diabetes of out patients , and clinical pharmacists could play an important role in diabetes management BACKGROUND Pharmaceutical care programs may be an option to improve blood pressure ( BP ) control in patients with uncontrolled hypertension . The aim of this study was to evaluate the efficacy of pharmaceutical care programs in treating patients with resistant hypertension . METHODS In a double-blind r and omized clinical trial , 71 patients with uncontrolled BP were enrolled in a pharmaceutical care program or in a control group and underwent a series of cognitive tests . The primary outcome was change in ambulatory BP ( ABP ) between the baseline evaluation and the final visit 6 months later . The secondary outcomes were the frequency of drug-related problems and adherence as determined by plasma levels of hydrochlorothiazide . RESULTS The delta-values between the intervention and control groups for ABP in the different daily periods , with the corresponding 95 % confidence limits , adjusted for age and baseline BP were : 3 ( -1 to 5 ) , 2 ( -2 to 4 ) , and 5 ( -1 to 6 ) mm Hg for 24 h , daily and nightly systolic BP , respectively . The corresponding values for diastolic BP were 1 ( -1 to 3 ) , 0 ( -2 to 2 ) , and 3 ( -1 to 4 ) mm Hg , respectively . Hydrochlorothiazide was detected in the plasma in 21 of 27 patients in the intervention group that attended to all appointments and 24 of 30 patients in the control group ( P = .904 ) . CONCLUSIONS The pharmaceutical care program tested in this trial was feasible and showed a trend for better BP control in patients with uncontrolled hypertension Background Selection bias and non-participation bias are major method ological concerns which impact external validity . Cluster-r and omized controlled trials are especially prone to selection bias as it is impractical to blind clusters to their allocation into intervention or control . This study assessed the impact of selection bias in a large cluster-r and omized controlled trial . Methods The Improved Cardiovascular Risk Reduction to Enhance Rural Primary Care ( ICARE ) study examined the impact of a remote pharmacist-led intervention in twelve medical offices . To assess eligibility , a st and ardized form containing patient demographics and medical information was completed for each screened patient . Eligible patients were approached by the study coordinator for recruitment . Both the study coordinator and the patient were aware of the site ’s allocation prior to consent . Patients who consented or declined to participate were compared across control and intervention arms for differing characteristics . Statistical significance was determined using a two-tailed , equal variance t-test and a chi-square test with adjusted Bonferroni p-values . Results were adjusted for r and om cluster variation . Results There were 2749 completed screening forms returned to research staff with 461 subjects who had either consented or declined participation . Patients with poorly controlled diabetes were found to be significantly more likely to decline participation in intervention sites compared to those in control sites . A higher mean diastolic blood pressure was seen in patients with uncontrolled hypertension who declined in the control sites compared to those who declined in the intervention sites . However , these findings were no longer significant after adjustment for r and om variation among the sites . After this adjustment , females were now found to be significantly more likely to consent than males ( odds ratio = 1.41 ; 95 % confidence interval = 1.03 , 1.92 ) . Conclusions Though there appeared to be a higher consent rate for females than for males , the overall impact of potential selection bias and refusal to participate was minimal . Without rigorous methodology , selection bias may be a threat to external validity in cluster-r and omized trials . Trial registration NCT01983813 . Date of registration : Oct. 28 , 2013 Abstract Objective To investigate the effects of compliance and periodic telephone counselling by a pharmacist on mortality in patients receiving polypharmacy . Design Two year r and omised controlled trial . Setting Hospital medical clinic . Participants 502 of 1011 patients receiving five or more drugs for chronic disease found to be non-compliant at the screening visit were invited for r and omisation to either the telephone counselling group ( n = 219 ) or control group ( n = 223 ) at enrolment 12 - 16 weeks later . Main outcome measures Primary outcome was all cause mortality in r and omised patients . Associations between compliance and mortality in the entire cohort of 1011 patients were also examined . Patients were defined as compliant with a drug if they took 80 - 120 % of the prescribed daily dose . To calculate a compliance score for the whole treatment regimen , the number of drugs that the patient was fully compliant with was divided by the total number of prescribed drugs and expressed as a percentage . Only patients who complied with all recommended drugs were considered compliant ( 100 % score ) . Results 60 of the 502 eligible patients defaulted and only 442 patients were r and omised . After two years , 31 ( 52 % ) of the defaulters had died , 38 ( 17 % ) of the control group had died , and 25 ( 11 % ) of the intervention group had died . After adjustment for confounders , telephone counselling was associated with a 41 % reduction in the risk of death ( relative risk 0.59 , 95 % confidence interval 0.35 to 0.97 ; P = 0.039 ) . The number needed to treat to prevent one death at two years was 16 . Other predictors included old age , living alone , rate of admission to hospital , compliance score , number of drugs for chronic disease , and non-treatment with lipid lowering drugs at screening visit . In the cohort of 1011 patients , the adjusted relative risk for death was 1.61 ( 1.05 to 2.48 ; P = 0.029 ) and 2.87 ( 1.80 to 2.57 ; P < 0.001 ) in patients with compliance scores of 34 - 66 % and 0 - 33 % , respectively , compared with those who had a compliance score of 67 % or more . Conclusion In patients receiving polypharmacy , poor compliance was associated with increased mortality . Periodic telephone counselling by a pharmacist improved compliance and reduced mortality . Trial registration International St and ard R and omised Controlled Trial Number Register : S RCT N48076318 Abstract Objective To determine whether home based medication review by pharmacists affects hospital readmission rates among older people . Design R and omised controlled trial . Setting Home based medication review after discharge from acute or community hospitals in Norfolk and Suffolk . Participants 872 patients aged over 80 recruited during an emergency admission ( any cause ) if returning to own home or warden controlled accommodation and taking two or more drugs daily on discharge . Intervention Two home visits by a pharmacist within two weeks and eight weeks of discharge to educate patients and carers about their drugs , remove out of date drugs , inform general practitioners of drug reactions or interactions , and inform the local pharmacist if a compliance aid is needed . Control arm received usual care . Main outcome measure Total emergency readmissions to hospital at six months . Secondary outcomes included death and quality of life measured with the EQ-5D . Results By six months 178 readmissions had occurred in the control group and 234 in the intervention group ( rate ratio = 1.30 , 95 % confidence interval 1.07 to 1.58 ; P = 0.009 , Poisson model ) . 49 deaths occurred in the intervention group compared with 63 in the control group ( hazard ratio = 0.75 , 0.52 to 1.10 ; P = 0.14 ) . EQ-5D scores decreased ( worsened ) by a mean of 0.14 in the control group and 0.13 in the intervention group ( difference = 0.01 , -0.05 to 0.06 ; P = 0.84 , t test ) . Conclusions The intervention was associated with a significantly higher rate of hospital admissions and did not significantly improve quality of life or reduce deaths . Further research is needed to explain this counterintuitive finding and to identify more effective methods of medication review CONTEXT Poor medication adherence diminishes the health benefits of pharmacotherapies . Elderly patients with coronary risk factors frequently require treatment with multiple medications , placing them at increased risk for nonadherence . OBJECTIVE To test the efficacy of a comprehensive pharmacy care program to improve medication adherence and its associated effects on blood pressure ( BP ) and low-density lipoprotein cholesterol ( LDL-C ) . DESIGN , SETTING , AND PATIENTS A multiphase , prospect i ve study with an observational phase and a r and omized controlled trial conducted at the Walter Reed Army Medical Center of 200 community-based patients aged 65 years or older taking at least 4 chronic medications . The study was conducted from June 2004 to August 2006 . INTERVENTION After a 2-month run-in phase ( measurement of baseline adherence , BP , and LDL-C ) , patients entered a 6-month intervention phase ( st and ardized medication education , regular follow-up by pharmacists , and medications dispensed in time-specific packs ) . Following the intervention phase , patients were r and omized to continued pharmacy care vs usual care for an additional 6 months . MAIN OUTCOME MEASURES Primary end point of the observation phase was change in the proportion of pills taken vs baseline ; secondary end points were the associated changes in BP and LDL-C. Primary end point of the r and omization phase was the between-group comparison of medication persistence . RESULTS A total of 200 elderly patients ( 77.1 % men ; mean [ SD ] age , 78 [ 8.3 ] years ) , taking a mean ( SD ) of 9 ( 3 ) chronic medications were enrolled . Coronary risk factors included drug-treated hypertension in 184 patients ( 91.5 % ) and drug-treated hyperlipidemia in 162 ( 80.6 % ) . Mean ( SD ) baseline medication adherence was 61.2 % ( 13.5 % ) . After 6 months of intervention , medication adherence increased to 96.9 % ( 5.2 % ; P<.001 ) and was associated with significant improvements in systolic BP ( 133.2 [ 14.9 ] to 129.9 [ 16.0 ] mm Hg ; P = .02 ) and LDL-C ( 91.7 [ 26.1 ] to 86.8 [ 23.4 ] mg/dL ; P = .001 ) . Six months after r and omization , the persistence of medication adherence decreased to 69.1 % ( 16.4 % ) among those patients assigned to usual care , whereas it was sustained at 95.5 % ( 7.7 % ) in pharmacy care ( P<.001 ) . This was associated with significant reductions in systolic BP in the pharmacy care group ( -6.9 mm Hg ; 95 % CI , -10.7 to -3.1 mm Hg ) vs the usual care group ( -1.0 mm Hg ; 95 % CI , -5.9 to 3.9 mm Hg ; P = .04 ) , but no significant between-group differences in LDL-C levels or reductions . CONCLUSIONS A pharmacy care program led to increases in medication adherence , medication persistence , and clinical ly meaningful reductions in BP , whereas discontinuation of the program was associated with decreased medication adherence and persistence . TRIAL REGISTRATION clinical trials.gov Identifier : OBJECTIVE The aim of this study was to assess the efficacy of a 12-month prevention program conducted in 42 community pharmacies in reducing the risk for diabetes . RESEARCH DESIGN AND METHODS In a cluster-r and omized controlled trial in 1,092 participants , mean change in the risk for diabetes ( indicated by the Finnish Diabetes Risk Score [ FINDRISC ] ) between intervention and control groups was calculated . In the intervention program GLICEMIA , three appointments with individual counseling and five educational group sessions were combined , whereas in the control group , only information about the participants ’ health was obtained in three assessment s. RESULTS After adjusting for cluster structure and differences in baseline characteristics , improvement in FINDRISC in the intervention group was 0.74 points ( 95 % CI 0.42–1.04 ) above the control group . CONCLUSIONS The GLICEMIA program shows the feasibility of a pharmacy-based intervention and leads to a significant modest reduction in diabetes risk score but does not reduce the rate of diabetes progression over 1 year RATIONALE , AIMS , AND OBJECTIVES Long-term exposure to glucocorticoids can cause adverse drug reactions of long latency ( ADRLLs ) , including glucocorticoid-induced diabetes mellitus ( GID ) . Providers can monitor for GID using the glycosylated haemoglobin blood ( HbA1C ) test . This study examined the utility of decisional support to improve HbA1C-based screening for GID . US veterans were identified as chronic users of oral glucocorticoids ( > 120 days of oral glucocorticoids in the last 2 years ) . The primary care providers caring for these patients were the target of the intervention . Providers were r and omized to receive automatic HbA1C orders for their patients receiving chronic glucocorticoid or usual care . METHODS This study was a pilot two-arm , group-r and omized , controlled trial ( n = 12 providers , n = 38 patients ) . Data collection occurred from 5 May 2013 until 10 January 2014 . A pharmacist generated the order for an HbA1C through the electronic medical record . The time between the intervention start date and the date on which an HbA1C order was signed were compared using Cox proportional and hierarchical linear regression . RESULTS The time to sign HbA1C orders ( mean 12.0 days for the intervention arm ; 104.0 days for control arm ) was associated with significant differences favouring the intervention [ HR ( Hazard Ratio ) 50.2 , P < 0.001 , confidence interval ( CI ) 6.3 to 398.7 ] . For the intervention group , 95 % of orders were signed , whereas only 12 % of control providers signed orders ( odds ratio 150 , P < 0.001 , CI 12.4 to 1812.9 ) . CONCLUSIONS The results of this study strongly suggest that the clinical pharmacist-triggered order intervention is effective . This method of computerized decisional support may be useful in improving screening for GID and ADRLLs The object of the study was to evaluate outcomes of a r and omized clinical trial ( RCT ) of a pharmacist intervention for depressed patients in primary care ( PC ) . We report antidepressant ( AD ) use and depression severity outcomes at 6-months . The RCT was conducted between 1998 and 2000 in 9 eastern Massachusetts PC practice s. We studied 533 patients with major depression and /or dysthymia as determined by a screening test done at the time of a routine PC office visit . The majority of participants had recurrent depressive episodes ( 63.5 % with > /=4 lifetime episodes ) , and 49.5 % were taking AD medications at enrollment . Consultation in person and by telephone was performed by a clinical pharmacist who assisted the primary care practitioner ( PCP ) and patient in medication choice , dose , and regimen , in accordance with AHCPR depression guidelines . Six-month AD use rates for intervention patients exceeded controls ( 57.5 % vs. 46.2 % , P = .03 ) . Furthermore , the intervention was effective in improving AD use rates for patients not on ADs at enrollment ( 32.3 % vs. 10.9 % , P = .001 ) . The pharmacist intervention proved equally effective in subgroups traditionally considered difficult to treat : those with chronic depression and dysthymia . Patients taking ADs had better modified Beck Depression Inventory ( mBDI ) outcomes than patients not taking ADs , ( -6.3 points change , vs. -2.8 , P = .01 ) but the outcome differences between intervention and control patients were not statistically significant ( 17.7 BDI points vs. 19.4 BDI points , P = .16 ) . Pharmacists significantly improved rates of AD use in PC patients , especially for those not on ADs at enrollment , but outcome differences were too small to be statistically significant . Difficult-to-treat subgroups may benefit from pharmacists ' care Background : Despite national disease management plans , optimal asthma management remains a challenge in Australia . Community pharmacists are ideally placed to implement new strategies that aim to ensure asthma care meets current st and ards of best practice . The impact of the Pharmacy Asthma Care Program ( PACP ) on asthma control was assessed using a multi-site r and omised intervention versus control repeated measures study design . Methods : Fifty Australian pharmacies were r and omised into two groups : intervention pharmacies implemented the PACP ( an ongoing cycle of assessment , goal setting , monitoring and review ) to 191 patients over 6 months , while control pharmacies gave their usual care to 205 control patients . Both groups administered question naires and conducted spirometric testing at baseline and 6 months later . The main outcome measure was asthma severity/control status . Results : 186 of 205 control patients ( 91 % ) and 165 of 191 intervention patients ( 86 % ) completed the study . The intervention result ed in improved asthma control : patients receiving the intervention were 2.7 times more likely to improve from “ severe ” to “ not severe ” than control patients ( OR 2.68 , 95 % CI 1.64 to 4.37 ; p<0.001 ) . The intervention also result ed in improved adherence to preventer medication ( OR 1.89 , 95 % CI 1.08 to 3.30 ; p = 0.03 ) , decreased mean daily dose of reliever medication ( difference −149.11 μg , 95 % CI −283.87 to −14.36 ; p = 0.03 ) , a shift in medication profile from reliever only to a combination of preventer , reliever with or without long-acting β agonist ( OR 3.80 , 95 % CI 1.40 to 10.32 ; p = 0.01 ) and improved scores on risk of non-adherence ( difference −0.44 , 95 % CI −0.69 to −0.18 ; p = 0.04 ) , quality of life ( difference −0.23 , 95 % CI −0.46 to 0.00 ; p = 0.05 ) , asthma knowledge ( difference 1.18 , 95 % CI 0.73 to 1.63 ; p<0.01 ) and perceived control of asthma question naires ( difference −1.39 , 95 % CI −2.44 to −0.35 ; p<0.01 ) . No significant change in spirometric measures occurred in either group . Conclusions : A pharmacist-delivered asthma care programme based on national guidelines improves asthma control . The sustainability and implementation of the programme within the healthcare system remains to be investigated IMPORTANCE Only about half of patients with high blood pressure ( BP ) in the United States have their BP controlled . Practical , robust , and sustainable models are needed to improve BP control in patients with uncontrolled hypertension . OBJECTIVES To determine whether an intervention combining home BP telemonitoring with pharmacist case management improves BP control compared with usual care and to determine whether BP control is maintained after the intervention is stopped . DESIGN , SETTING , AND PATIENTS A cluster r and omized clinical trial of 450 adults with uncontrolled BP recruited from 14,692 patients with electronic medical records across 16 primary care clinics in an integrated health system in Minneapolis-St Paul , Minnesota , with 12 months of intervention and 6 months of postintervention follow-up . INTERVENTIONS Eight clinics were r and omized to provide usual care to patients ( n = 222 ) and 8 clinics were r and omized to provide a telemonitoring intervention ( n = 228 ) . Intervention patients received home BP telemonitors and transmitted BP data to pharmacists who adjusted antihypertensive therapy accordingly . MAIN OUTCOMES AND MEASURES Control of systolic BP to less than 140 mm Hg and diastolic BP to less than 90 mm Hg ( < 130/80 mm Hg in patients with diabetes or chronic kidney disease ) at 6 and 12 months . Secondary outcomes were change in BP , patient satisfaction , and BP control at 18 months ( 6 months after intervention stopped ) . RESULTS At baseline , enrollees were 45 % women , 82 % white , mean ( SD ) age was 61.1 ( 12.0 ) years , and mean systolic BP was 148 mm Hg and diastolic BP was 85 mm Hg . Blood pressure was controlled at both 6 and 12 months in 57.2 % ( 95 % CI , 44.8 % to 68.7 % ) of patients in the telemonitoring intervention group vs 30.0 % ( 95 % CI , 23.2 % to 37.8 % ) of patients in the usual care group ( P = .001 ) . At 18 months ( 6 months of postintervention follow-up ) , BP was controlled in 71.8 % ( 95 % CI , 65.0 % to 77.8 % ) of patients in the telemonitoring intervention group vs 57.1 % ( 95 % CI , 51.5 % to 62.6 % ) of patients in the usual care group ( P = .003 ) . Compared with the usual care group , systolic BP decreased more from baseline among patients in the telemonitoring intervention group at 6 months ( -10.7 mm Hg [ 95 % CI , -14.3 to -7.3 mm Hg ] ; P<.001 ) , at 12 months ( -9.7 mm Hg [ 95 % CI , -13.4 to -6.0 mm Hg ] ; P<.001 ) , and at 18 months ( -6.6 mm Hg [ 95 % CI , -10.7 to -2.5 mm Hg ] ; P = .004 ) . Compared with the usual care group , diastolic BP decreased more from baseline among patients in the telemonitoring intervention group at 6 months ( -6.0 mm Hg [ 95 % CI , -8.6 to -3.4 mm Hg ] ; P<.001 ) , at 12 months ( -5.1 mm Hg [ 95 % CI , -7.4 to -2.8 mm Hg ] ; P<.001 ) , and at 18 months ( -3.0 mm Hg [ 95 % CI , -6.3 to 0.3 mm Hg ] ; P = .07 ) . CONCLUSIONS AND RELEVANCE Home BP telemonitoring and pharmacist case management achieved better BP control compared with usual care during 12 months of intervention that persisted during 6 months of postintervention follow-up . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00781365 Background Medications are an effective intervention for managing and preventing health problems but their benefit can be undermined by non-adherence or adverse drug events ( ADEs ) . Since these issues may be interconnected , efforts to improve non-adherence should also include reduction of ADEs . We have developed the ISTOP-ADE system ( Information Systems-enabled Outreach for Preventing Adverse Drug Events ) , which enables timely monitoring and managing of ADEs . The objectives of this study are to determine whether the ISTOP-ADE system , compared to routine care , will reduce : a ) the probability of discontinuing the use of prognosis-altering medications ; b ) the probability of a patient experiencing a severe ADE ; c ) the proportion of patients experiencing ADEs , preventable ADEs and ameliorable ADEs ; and d ) health services utilization . Methods / design We will r and omly assign 2,200 adult ambulatory patients in the province of Québec who have been prescribed an incident medication for the management or prevention of a chronic health condition , to routine care or the ISTOP-ADE system . The ISTOP-ADE system consists of an interactive voice response system ( IVRS ) paired with pharmacist support . The IVRS will call patients at 3 and 17 days post-prescription to determine if they are experiencing any problems and connect them with a pharmacist when required or desired by the patient . We will evaluate medication persistence at 180 days and health-care utilization using provincial administrative data . Two blinded physicians will ascertain ADE status through a case review . Discussion We expect the ISTOP-ADE intervention to be feasible and to improve the quality of patient care through improved medication adherence , reduced ADE duration and reduced number of ADEs result ing in an emergency department or inpatient encounter . This in turn could lower health-care utilization , saving costs and lowering the burden on emergency departments and family practice s. The success of ISTOP-ADE would present opportunities to implement this intervention through health systems , health insurance agents and commercial pharmacies . Trial registration Clinical Trials.gov Identifier : NCT02059044 . Date registered : 10 January 2014 OBJECTIVE To evaluate the effect of adding pharmacists to primary care teams on the management of hypertension and other cardiovascular risk factors in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS We conducted a r and omized controlled trial with blinded ascertainment of outcomes within primary care clinics in Edmonton , Canada . Pharmacists performed medication assessment s and limited history and physical examinations and provided guideline -concordant recommendations to optimize medication management . Follow-up contact was completed as necessary . Control patients received usual care . The primary outcome was a ≥10 % decrease in systolic blood pressure at 1 year . RESULTS A total of 260 patients were enrolled , 57 % were women , the mean age was 59 years , diabetes duration was 6 years , and blood pressure was 129/74 mmHg . Forty-eight of 131 ( 37 % ) intervention patients and 30 of 129 ( 23 % ) control patients achieved the primary outcome ( odds ratio 1.9 [ 95 % CI 1.1–3.3 ] ; P = 0.02 ) . Among 153 patients with inadequately controlled hypertension at baseline , intervention patients ( n = 82 ) were significantly more likely than control patients ( n = 71 ) to achieve the primary outcome ( 41 [ 50 % ] vs. 20 [ 28 % ] ; 2.6 [ 1.3–5.0 ] ; P = 0.007 ) and recommended blood pressure targets ( 44 [ 54 % ] vs. 21 [ 30 % ] ; 2.8 [ 1.4–5.4 ] ; P = 0.003 ) . The 10-year risk of cardiovascular disease , based on changes to the UK Prospect i ve Diabetes Study Risk Engine , were predicted to decrease by 3 % for intervention patients and 1 % for control patients ( P = 0.005 ) . CONCLUSIONS Significantly more patients with type 2 diabetes achieved better blood pressure control when pharmacists were added to primary care teams , which suggests that pharmacists can make important contributions to the primary care of these patients Background Medication regimens for asthma are particularly vulnerable to adherence problems because of the requirement for long-term use and periods of symptom remission experienced by patients . Pharmacists are suited to impact medication adherence given their training , skills , and frequent contact with patients . The Empowering pharmacists in asthma management through interactive SMS ( EmPhAsIS ) trial involves an intervention leveraging mobile health ( mHealth ) technology to support community pharmacy practice with the hypothesis of improved medication adherence in asthma . Methods / Design This study is a pragmatic pharmacy-based , cluster , r and omized controlled trial with 12 months of intervention delivery and follow-up . Pharmacies ( the clusters ) will be r and omized at a 1:1 ratio to provide intervention or usual care . The EmPhAsIS intervention consists of patient asthma education , short message service (SMS)-based monthly assessment of adherence , and follow-up of non-adherent individuals by community pharmacists . There are no inclusion or exclusion criteria for pharmacies . Patients are eligible if they : are 14 years of age or older , fill a prescription for inhaled corticosteroid ( either monotherapy or in a combination inhaler with long-acting beta-agonists ) , have been diagnosed with asthma , possess a mobile phone with SMS capabilities , and have no communication difficulties such as inability to communicate in English , or significant impairment in vision , hearing , or speech . The primary outcome is adherence to inhaled corticosteroids ascertained by the medication possession ratio , the ratio of the days of medication supplied to days in a given time interval . This study will also evaluate secondary outcomes including : asthma control , asthma-related quality of life , asthma-related hospital admissions , and use of reliever medications during the follow-up period . A nested economic evaluation using a probabilistic decision-analytic model will be used to perform a cost-effectiveness analysis from the societal perspective of the intervention compared with usual care over a 10-year time horizon . Discussion Considering the prevalence of asthma , the extent of the non-adherence problem in this disease , and the availability of effective treatments , there is a tremendous potential to reduce the burden of asthma through improving adherence . This is the first study of an intervention based on mobile communication technology involving community pharmacists in asthma management . Trial registration Clinical Trials.gov identifier : NCT02170883 ; date of registration : 19 June 2014 Education on optimal medication use is an essential strategy to improve asthma control . The current authors investigated whether pharmacist interventions , focused on appropriate use of asthma medication and tailor-made to the patient 's current asthma control , would improve asthma control in adult patients . A 6-month r and omised , controlled , parallel-group trial was conducted in 66 community pharmacies in Belgium . Patients were r and omly assigned to receive usual pharmacist care ( n = 94 ) or a pre-defined pharmacist intervention ( n = 107 ) . This intervention mainly focused on improving inhalation technique and medication adherence . Primary outcome was the level of asthma control , as assessed by the Asthma Control Test ® ( ACT ) . Mean ACT scores did not change from baseline for both study groups . However , a pre-defined subgroup analysis of patients having insufficiently controlled asthma at baseline showed that the intervention had significantly increased the ACT score after 6 months compared with usual care . The intervention also reduced , for the complete study group , reliever medication use and the frequency of night-time awakenings due to asthma . Inhalation technique and adherence to controller medication were significantly better in the intervention group . In conclusion , pragmatic community pharmacy-based programmes can significantly improve therapeutic outcomes in adult asthma patients BACKGROUND The practice of pharmaceutical care in primary care setting s in Thail and is currently not generally accepted . OBJECTIVE To evaluate the effect of pharmacist involvement in treatment with hypertensive patients in primary care setting s. METHODS The treatment objective was to stabilize the blood pressure ( BP ) of hypertensive patients in accordance with the Joint National Committee on Prevention , Detection , Evaluation and Treatment of High Blood Pressure guidelines . Patients were r and omly assigned to a pharmacist-involved group ( treatment ) or a group with no pharmacist involvement ( control ) . Pre- and post-test BPs , tablet counts , lifestyle modifications , and pharmacists ’ recommendations were recorded . The 6-month study was carried out in Mahasarakham University pharmacy and 2 primary care units . Patients were monitored monthly by review ing their medications and supported by providing pharmaceutical care and counseling . RESULTS From a total of 235 patients , the treatment group ( n = 118 ) had a significant reduction in both systolic ( S ) and diastolic ( D ) BP compared with the 117 patients of the control group ( p = 0.037 , 0.027 , respectively ) . The 158 patients ( 76 treatment , 82 control ) with BPs 140/90 mm Hg at the beginning of the study showed significant BP reductions ( p = 0.002 SBP , 0.008 DBP ) . The proportion of 158 patients whose BP became stabilized was higher in the treatment group ( p = 0.017 ) . The treatment group showed significantly better adherence ( p = 0.014 ) and exercise control ( p = 0.012 ) at the end of the study . Physicians accepted 42.72 % of medication modifications and 5.34 % of the suggestions for additional investigations . CONCLUSIONS Hypertensive patients who received pharmacist input achieved a significantly greater benefit in BP reduction , BP control , and improvement in adherence rate and lifestyle modification Accessibility , availability and frequent public contact place community pharmacists in an ideal position to provide medically necessary , intensive health education and preventive health services to diabetes patients , thus reducing physician burden . We assessed the cost-effectiveness of reducing glycaemic episodes in patients with type 2 diabetes mellitus through a pharmacist-led Diabetes Management Education Program ( DMEP ) compared to st and ard care . We recruited eight metropolitan community pharmacies in Perth , Western Australia for the study . We paired them based on geographical location and the socioeconomic status of the population served , and then r and omly selected one pharmacy in each pair to be in the intervention group , with the other assigned to the control group . We conducted an incremental cost-effectiveness analysis to compare the costs and effectiveness of DMEP with st and ard pharmacy care . Cost per patient of implementing DMEP was AU$394 ( US$ 356 ) for the 6-month intervention period . Significantly greater reductions in number of hyperglycaemic and hypoglycaemic episodes occurred in the intervention relative to the control group [ OR 0.34 ( 95 % CI 0.22 , 0.52 ) , p = 0.001 ; OR 0.54 ( 95 % CI 0.34 , 0.86 ) , p = 0.009 ] , respectively , with a net reduction of 1.86 days with glycaemic episodes per patient per month . The cost-effectiveness of DMEP relative to st and ard pharmacy care was AU$43 ( US$ 39 ) per day of glycaemic symptoms avoided . Patients with type 2 diabetes in three surveys were willing to pay an average of 1.9 times that amount to avoid a hypoglycaemic day . We conclude that DMEP decreased days with glycaemic symptoms at a reasonable cost . If a larger-scale replication study confirms these findings , widespread adoption of this approach would improve diabetes health without burdening general practitioners OBJECTIVE To examine the effect of a 12-month pharmaceutical care ( PC ) program on vascular risk in type 2 diabetes . RESEARCH DESIGN AND METHODS We recruited 198 community-based patients r and omized to PC or usual care . PC patients had face-to-face goal -directed medication and lifestyle counseling at baseline and at 6 and 12 months plus 6-weekly telephone assessment s and provision of other educational material . Clinical , biochemical , and medication-related data were sent regularly to each patient 's physician(s ) . The main outcome measure was change in HbA(1c ) . A diabetes-specific risk engine was used to estimate changes in 10-year coronary heart disease ( CHD ) and stroke risk in patients without a history of cardiovascular disease . RESULTS At total of 180 patients ( 91 % ) completed the study . Mean ( 95 % CI ) reductions were greater in PC case subjects ( n = 92 ) than control subjects ( n = 88 ) for HbA(1c ) ( -0.5 % [ 95 % CI -0.7 to -0.3 ] vs. 0 [ -0.2 to 0.2 ] ) and systolic ( -14 mmHg [ -19 to -9 ] vs. -7 [ -11 to -2 ] ) and diastolic ( -5 mmHg [ -8 to -3 ] vs. -2 [ -4 to 1 ] ) blood pressure ( P < or = 0.043 ) . The improvement in HbA(1c ) persisted after adjustment for baseline value and demographic and treatment-specific variables . The median ( interquartile range ) 10-year estimated risk of a first CHD event decreased in the PC case subjects ( 25.1 % [ 15.6 - 36.2 ] to 20.3 [ 14.6 - 30.2 ] ; n = 42 , P = 0.002 ) but not in the control subjects ( 26.1 % [ 17.2 - 39.4 ] vs. 26.4 [ 16.7 - 38.0 ] ; n = 52 , P = 0.17 ) . CONCLUSIONS A 12-month PC program in type 2 diabetes reduced glycemia and blood pressure . Pharmacist involvement contributed to improvement in HbA(1c ) independently of pharmacotherapeutic changes . PC could prove a valuable component of community-based multidisciplinary diabetes care Abstract Objective : To determine whether a pharmacist can effectively review repeat prescriptions through consultations with elderly patients in general practice . Design : R and omised controlled trial of clinical medication review by a pharmacist against normal general practice review . Setting : Four general practice s. Participants : 1188 patients aged 65 or over who were receiving at least one repeat prescription and living in the community . Intervention : Patients were invited to a consultation at which the pharmacist review ed their medical conditions and current treatment . Main outcome measures : Number of changes to repeat prescriptions over one year , drug costs , and use of healthcare services . Results : 590 ( 97 % ) patients in the intervention group were review ed compared with 233 ( 44 % ) in the control group . Patients seen by the pharmacist were more likely to have changes made to their repeat prescriptions ( mean number of changes per patient 2.2 v 1.9 ; difference=0.31 , 95 % confidence interval 0.06 to 0.57 ; P=0.02 ) . Monthly drug costs rose in both groups over the year , but the rise was less in the intervention group ( mean difference £ 4.72 per 28 days , −£7.04 to -£2.41 ) ; equivalent to £ 61 per patient a year . Intervention patients had a smaller rise in the number of drugs prescribed ( 0.2 v 0.4 ; mean difference −0.2 , −0.4 to −0.1 ) . There was no evidence that review of treatment by the pharmacist affected practice consultation rates , outpatient consultations , hospital admissions , or death rate . Conclusions : A clinical pharmacist can conduct effective consultations with elderly patients in general practice to review their drugs . Such review results in significant changes in patients ' drugs and saves more than the cost of the intervention without affecting the workload of general practitioners . What is already known on this topic Review of patients on long term drug treatment is important but is done inadequately Evidence from the United States shows that pharmacists can improve patient care by review ing drug treatment What this study adds Consultations with a clinical pharmacist are an effective method of review ing the drug treatment of older patients Review by a pharmacist results in more drug changes and lower prescribing costs than normal care plus a much higher review rate Use of healthcare services by patients is not Summary Background Medication errors are common in primary care and are associated with considerable risk of patient harm . We tested whether a pharmacist-led , information technology-based intervention was more effective than simple feedback in reducing the number of patients at risk of measures related to hazardous prescribing and inadequate blood-test monitoring of medicines 6 months after the intervention . Methods In this pragmatic , cluster r and omised trial general practice s in the UK were stratified by research site and list size , and r and omly assigned by a web-based r and omisation service in block sizes of two or four to one of two groups . The practice s were allocated to either computer-generated simple feedback for at-risk patients ( control ) or a pharmacist-led information technology intervention ( PINCER ) , composed of feedback , educational outreach , and dedicated support . The allocation was masked to general practice s , patients , pharmacists , research ers , and statisticians . Primary outcomes were the proportions of patients at 6 months after the intervention who had had any of three clinical ly important errors : non-selective non-steroidal anti-inflammatory drugs ( NSAIDs ) prescribed to those with a history of peptic ulcer without co-prescription of a proton-pump inhibitor ; β blockers prescribed to those with a history of asthma ; long-term prescription of angiotensin converting enzyme ( ACE ) inhibitor or loop diuretics to those 75 years or older without assessment of urea and electrolytes in the preceding 15 months . The cost per error avoided was estimated by incremental cost-effectiveness analysis . This study is registered with Controlled-Trials.com , number IS RCT N21785299 . Findings 72 general practice s with a combined list size of 480 942 patients were r and omised . At 6 months ' follow-up , patients in the PINCER group were significantly less likely to have been prescribed a non-selective NSAID if they had a history of peptic ulcer without gastroprotection ( OR 0·58 , 95 % CI 0·38–0·89 ) ; a β blocker if they had asthma ( 0·73 , 0·58–0·91 ) ; or an ACE inhibitor or loop diuretic without appropriate monitoring ( 0·51 , 0·34–0·78 ) . PINCER has a 95 % probability of being cost effective if the decision-maker 's ceiling willingness to pay reaches £ 75 per error avoided at 6 months . Interpretation The PINCER intervention is an effective method for reducing a range of medication errors in general practice s with computerised clinical records . Funding Patient Safety Research Portfolio , Department of Health , Engl and STUDY OBJECTIVE To assess the impact of a medication management review ( MMR ) service on treatment-related problems ( TRPs ) and certain clinical outcomes in out patients . DESIGN Prospect i ve r and omized controlled study . SETTING Two community pharmacies in Amman , Jordan . PATIENTS A total of 160 people who visited the two community pharmacies between September 2009 and June 2010 . INTERVENTION Patients were r and omized into two groups : intervention ( 82 patients ) and control ( 78 patients ) groups . The clinical pharmacist conducted a baseline assessment MMR for patients in both groups to determine the prevalence and type of TRPs ; however , recommendations regarding the identified TRPs were only su bmi tted to the physicians of patients in the intervention group . MEASUREMENTS AND MAIN RESULTS All patients were followed for an average of 3.39 months after their baseline visit to the pharmacy . The impact of the MMR service for the intervention group was assessed by evaluating the outcomes of the recommendations su bmi tted by the clinical pharmacist to resolve the identified TRPs , physicians ' acceptance of the recommended interventions , and the effect of the intervention on certain clinical outcomes : blood glucose levels , blood pressure , and triglyceride levels . Follow-up assessment of the control group included evaluating the outcomes of the identified TRPs ( identified and corrected by physicians without any input from the clinical pharmacist ) and comparing glucose level , blood pressure , and triglyceride-level results with baseline values . No significant differences in mean number of medical conditions ( 3.7 vs 3.42 , p=0.134 ) , mean number of medications ( 4.51 vs 4.96 , p=0.135 ) , or mean number of TRPs per patient ( 5.55 vs 5.17 , p=0.42 ) were observed at baseline in the intervention group versus the control group . Follow-up results revealed a high acceptance rate of recommendations by the physicians ( 94 % ) . Regarding outcomes of TRPs , almost 70 % of the identified TRPs in the intervention group were resolved or improved compared with 2 % in the control group ( p<0.001 ) . Significant differences were found between the intervention group versus control group with regard to mean ± SD glucose levels ( 99.08 ± 9.66 vs 115.48 ± 17.34 , p<0.001 ) , blood pressure ( 110.36/81.55 ± 9.45/3.91 vs 125.0/88.73 ± 10.34/4.12 , p<0.001 ) , and triglyceride levels ( 148.53 ± 15.98 vs 170.74 ± 6.26 , p=0.001 ) . CONCLUSION The MMR service result ed in a significantly lower number of TRPs and significantly improved clinical outcomes , and it was highly accepted by the physicians ABSTRACT OBJECTIVE Evaluate the effectiveness of collaborative management of hypertension by primary care-pharmacist teams in community-based clinics . STUDY DESIGN A 12-month prospect i ve , single-blind , r and omized , controlled trial in the Providence Primary Care Research Network of patients with hypertension and uncontrolled blood pressure . METHODS As compared to usual primary care , intervention consisted of pharmacy practitioners participating in the active management of hypertension in the primary care office according to established collaborative treatment protocol s. At baseline , there was no significant difference in blood pressure between groups . Primary outcome measures were the differences in mean systolic and diastolic blood pressures between arms at study end . Secondary measures included blood pressure goal attainment ( < 140/90 mmHg ) , hypertension-related knowledge , medication adherence , home blood pressure monitoring , re source utilization , quality of life , and satisfaction . RESULTS A total of 463 subjects were enrolled ( n = 233 control , n = 230 intervention ) . Subjects receiving the intervention achieved significantly lower systolic ( p = 0.007 ) and diastolic ( p = 0.002 ) blood pressures compared to control ( 137/75 mmHg vs. 143/78 mmHg ) . In addition , 62 % of intervention subjects achieved target blood pressure compared to 44 % of control subjects ( p = 0.003 ) . The intervention group received more total office visits ( 7.2 vs. 4.9 , p < 0.0001 ) , however had fewer physician visits ( 3.2 vs. 4.7 , p < 0.0001 ) compared to control . Intervention subjects were prescribed more antihypertensive medications ( 2.7 vs. 2.4 , p = 0.02 ) , but did not take more antihypertensive pills per day ( 2.4 vs. 2.5 , p = 0.87 ) . There were minimal differences between groups in hypertension-related knowledge , medication adherence , quality of life , or satisfaction . CONCLUSIONS Patients r and omized to collaborative primary care-pharmacist hypertension management achieved significantly better blood pressure control compared to usual care with no difference in quality of life or satisfaction BACKGROUND Affecting a substantial proportion of adults , chronic kidney disease ( CKD ) is considered a major risk factor for cardiovascular ( CV ) events . It has been reported that patients with CKD are underserved when it comes to CV risk reduction efforts . STUDY DESIGN Prespecified subgroup analysis of a r and omized controlled trial . SETTING & PARTICIPANTS Adults with CKD and at least 1 uncontrolled CV risk factor were enrolled from 56 pharmacies across Alberta , Canada . INTERVENTION Patient , laboratory , and individualized CV risk assessment s ; treatment recommendations ; prescription adaptation(s ) and /or initiation as necessary ; and regular monthly follow-up for 3 months . OUTCOMES The primary outcome was change in estimated CV risk from baseline to 3 months after r and omization . Secondary outcomes were change between baseline and 3 months after r and omization in individual CV risk factors ( ie , low-density lipoprotein cholesterol , blood pressure , and hemoglobin A1c ) , risk for developing end-stage renal disease , and medication use and dosage ; tobacco cessation 3 months after r and omization for those who used tobacco at baseline ; and the impact of rural versus urban residence on the difference in change in estimated CV risk . MEASUREMENTS CV risk was estimated using the Framingham , UK Prospect i ve Diabetes Study , and international risk assessment equations depending on the patients ' comorbid conditions . RESULTS 290 of the 723 participants enrolled in RxEACH had CKD . After adjusting for baseline values , the difference in change in CV risk was 20 % ( P<0.001 ) . Changes of 0.2mmol/L in low-density lipoprotein cholesterol concentration ( P=0.004 ) , 10.5mmHg in systolic blood pressure ( P<0.001 ) , 0.7 % in hemoglobin A1c concentration ( P<0.001 ) , and 19.6 % in smoking cessation ( P=0.04 ) were observed when comparing the intervention and control groups . There was a larger reduction in CV risk in patients living in rural locations versus those living in urban areas . LIMITATIONS The 3-month follow-up period can be considered relatively short . It is possible that larger reduction in CV risk could have been observed with a longer follow up period . CONCLUSIONS This subgroup analysis demonstrated that a community pharmacy-based intervention program reduced CV risk and improved control of individual CV risk factors . This represents a promising approach to identifying and managing patients with CKD that could have important public health implication The impacts of two models of pharmacist consultation on patient function and health-related quality of life ( HRQOL ) relative to a control model were studied . Patients in the r and om-assignment study and the areawide study of the Kaiser Permanente/USC Patient Consultation Study were surveyed three times over a two-year period . The patients were receiving pharmaceutical services under the Kaiser Permanente model of consultation ( KP model ) , a state model of consultation , or a control model and were stratified according to prescription drug use . A global visual-analogue scale and Short Form-36 were used to assess HRQOL . In the areawide study , only 2 of 42 comparisons of the effects of the KP or state model on HRQOL were significant ; both were associated with the state model and involved only small increases . In the r and om-assignment study , 3 of 21 estimated effects of the KP model on HRQOL were positive and significant ; 2 of these were significantly different between the KP model and the state model . Although the KP and state models of consultation were associated with some changes in HRQOL , the overall influence was not consistent and not clinical ly important Objectives To evaluate the effectiveness of two primary care strategies for delivering evidence based care to people aged 55 or over with knee pain : enhanced pharmacy review and community physiotherapy . Design Pragmatic multicentre r and omised clinical trial . Setting 15 general practice s in North Staffordshire . Participants 325 adults aged 55 years or over ( mean 68 years ) consulting with knee pain ; 297 ( 91 % ) reached six month follow-up . Interventions Enhanced pharmacy review ( pharmacological management in accordance with an algorithm ) ; community physiotherapy ( advice about activity and pacing and an individualised exercise programme ) ; control ( advice leaflet reinforced by telephone call ) . Main outcome measure Change in Western Ontario and McMaster Universities osteoarthritis index ( WOMAC ) at 3 , 6 , and 12 months . Results Mean baseline WOMAC pain score was 9.1 ( SD 3.7 ) , and mean baseline function score was 29.9 ( SD 12.8 ) . At three months , the mean reductions in pain scores were 0.41 ( SD 2.8 ) for control , 1.59 ( 3.2 ) for pharmacy , and 1.56 ( 3.4 ) for physiotherapy ; reductions in function scores were 0.80 ( 8.5 ) , 2.61 ( 9.8 ) , and 4.79 ( 10.8 ) . Compared with control , mean differences in change scores for physiotherapy were 1.15 ( 95 % confidence interval 0.2 to 2.1 ) for pain and 3.99 ( 1.2 to 6.8 ) for function ; those for pharmacy were 1.18 ( 0.3 to 2.1 ) for pain and 1.80 ( −0.8 to 4.5 ) for function . These differences were not sustained to six or 12 months . Significantly fewer participants in the physiotherapy group reported consulting their general practitioner for knee pain in the follow-up period , and use of non-steroidal anti-inflammatory drugs was lower in the physiotherapy and pharmacy groups than in the control group . Conclusions Evidence based care for older adults with knee pain , delivered by primary care physiotherapists and pharmacists , result ed in short term improvements in health outcomes , reduced use of non-steroidal anti-inflammatory drugs , and high patient satisfaction . Physiotherapy seemed to produce a shift in consultation behaviour away from the traditional general practitioner led model of care . Trial registration UK National Research Register N0286046917 ; Current Controlled Trials IS RCT N55376150 Background —The purpose of this study was to evaluate if a physician/pharmacist collaborative model would be implemented as determined by improved blood pressure ( BP ) control in primary care medical offices with diverse geographic and patient characteristics and whether long-term BP control could be sustained . Methods and Results — Prospect i ve , cluster-r and omized trial of 32 primary care offices stratified and r and omized to control , 9-month intervention ( brief ) , and 24-month intervention ( sustained ) . We enrolled 625 subjects with uncontrolled hypertension ; 54 % from racial/ethnic minority groups and 50 % with diabetes mellitus or chronic kidney disease . The primary outcome of BP control at 9 months was 43 % in intervention offices ( n=401 ) compared with 34 % in the control group ( n=224 ; adjusted odds ratio , 1.57 [ 95 % confidence interval , 0.99–2.50 ] ; P=0.059 ) . The adjusted difference in mean systolic/diastolic BP between the intervention and control groups for all subjects at 9 months was −6.1/−2.9 mm Hg ( P=0.002 and P=0.005 , respectively ) , and it was −6.4/−2.9 mm Hg ( P=0.009 and P=0.044 , respectively ) in subjects from racial or ethnic minorities . BP control and mean BP were significantly improved in subjects from racial minorities in intervention offices at 18 and 24 months ( P=0.048 to P<0.001 ) compared with the control group . Conclusions —Although the results of the primary outcome ( BP control ) were negative , the key secondary end point ( mean BP ) was significantly improved in the intervention group . Thus , the findings for secondary end points suggest that team-based care using clinical pharmacists was implemented in diverse primary care offices and BP was reduced in subjects from racial minority groups . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT00935077 Background Polypharmacy in the Swedish elderly population is currently a prioritised area of research with a focus on reducing the use of potentially inappropriate medications ( PIMs ) . Multi-professional interventions have previously been tested for their ability to improve drug therapy in frail elderly patients . Objective This study aim ed to assess a structured model for pharmacist-led medication review s in primary health care in southern Sweden and to measure its effects on numbers of patients with PIMs ( using the definition of the Swedish National Board of Health and Welfare ) using ≥10 drugs and using ≥3 psychotropics . Methods This study was a r and omised controlled clinical trial performed in a group of patients aged ≥75 years and living in nursing homes or the community and receiving municipal health care . Medication review s were performed by trained clinical pharmacists based on nurse-initiated symptom assessment s with team-based or distance feedback to the physician . Data were collected from the patients ’ electronic medication lists and medical records at baseline and 2 months after the medication review . Results A total of 369 patients were included : 182 in the intervention group and 187 in the control group . One-third of the patients in both groups had at least one PIM at baseline . Two months after the medication review s , the number of intervention group patients with at least one PIM and the number of intervention group patients using ten or more drugs had decreased ( p = 0.007 and p = 0.001 , respectively ) , while there were no statistically significant changes in the control patients . No changes were seen in the number of patients using three or more psychotropic drugs , although the dosages of these drugs tended to decrease . Drug-related problems ( DRPs ) were identified in 93 % of the 182 patients in the intervention group . In total , there were 431 DRPs in the intervention group ( a mean of 2.5 DRPs per patient , range 0–9 , SD 1.5 at 95 % CI ) and 16 % of the DRPs were related to PIMs . Conclusions Medication review s involving pharmacists in primary health care appear to be a feasible method to reduce the number of patients with PIMs , thus improving the quality of pharmacotherapy in elderly patients BACKGROUND Despite clear evidence for the efficacy of lowering cholesterol levels , there is a deficiency in its real-world application . There is a need to explore alternative strategies to address this important public health problem . This study aim ed to determine the effect of a program of community pharmacist intervention on the process of cholesterol risk management in patients at high risk for cardiovascular events . METHODS A r and omized controlled trial conducted in 54 community pharmacies ( 1998 - 2000 ) included patients at high risk for cardiovascular events ( with atherosclerotic disease or diabetes mellitus with another risk factor ) . Patients r and omized to pharmacist intervention received education and a brochure on risk factors , point-of-care cholesterol measurement , referral to their physician , and regular follow-up for 16 weeks . Pharmacists faxed a simple form to the primary care physician identifying risk factors and any suggestions . Usual care patients received the same brochure and general advice only , with minimal follow-up . The primary end point was a composite of performance of a fasting cholesterol panel by the physician or addition or increase in dose of cholesterol-lowering medication . RESULTS The external monitoring committee recommended early study termination owing to benefit . Of the 675 patients enrolled , approximately 40 % were women , and the average age was 64 years . The primary end point was reached in 57 % of intervention patients vs 31 % in usual care ( odds ratio , 3.0 ; 95 % confidence interval , 2.2 - 4.1 ; P<.001 ) . CONCLUSIONS A community-based intervention program improved the process of cholesterol management in high-risk patients . This program demonstrates the value of community pharmacists working in collaboration with patients and physicians BACKGROUND AND PURPOSE In patients with hypertension , medication adherence is often suboptimal , thereby increasing the risk of ischemic heart disease and stroke . In a r and omized trial , we investigated the effectiveness of a multifaceted pharmacist intervention in a hospital setting to improve medication adherence in hypertensive patients . Motivational interviewing was a key element of the intervention . METHODS Patients ( n = 532 ) were recruited from 3 hospital outpatient clinics and r and omized to usual care or a 6-month pharmacist intervention comprising collaborative care , medication review , and tailored adherence counseling including motivational interviewing and telephone follow-ups . The primary outcome was composite medication possession ratio ( MPR ) to antihypertensive and lipid-lowering agents , at 1-year follow-up , assessed by analyzing pharmacy records . Secondary outcomes at 12 months included persistence to medications , blood pressure , hospital admission , and a combined clinical endpoint of cardiovascular death , stroke , or acute myocardial infa rct ion . RESULTS At 12 months , 20.3 % of the patients in the intervention group ( n = 231 ) were nonadherent ( MPR < 0.80 ) , compared with 30.2 % in the control group ( n = 285 ) ( risk difference -9.8 ; 95 % confidence interval [ CI ] , -17.3 , -2.4 ) and median MPR ( interquartile range ) was 0.93 ( 0.82 - 0.99 ) and 0.91 ( 0.76 - 0.98 ) , respectively , P = .02 . The combined clinical endpoint was reached by 1.3 % in the intervention group and 3.1 % in the control group ( relative risk 0.41 ; 95 % CI , 0.11 - 1.50 ) . No significant differences were found for persistence , blood pressure , or hospital admission . CONCLUSIONS A multifaceted pharmacist intervention in a hospital setting led to a sustained improvement in medication adherence for patients with hypertension . The intervention had no significant impact on blood pressure and secondary clinical outcomes Objectives : To determine if pharmacists providing advice on self-monitoring of blood glucose ( SMBG ) to new meter users , based on the Canadian Diabetes Association ( CDA ) Clinical Practice Guidelines ( CPGs ) , result ed in improvements in A1C . SMBG testing patterns and pharmacist interactions were also observed . Methods : A cluster r and omized , pilot study was performed , with pharmacies r and omized to an intervention or control group . The intervention group provided SMBG education according to the CDA CPGs at baseline , 2 weeks , 1 month and 3 months ; the control group provided usual care . The primary endpoint was the mean change in A1C measured at 6 months . Secondary endpoints included a description of SMBG patterns and lifestyle changes and were determined via a self-administered question naire . Results : Thirty-six participants ( 26 intervention , 10 control ) were recruited from 9 pharmacies across Saskatchewan , Canada . Mean A1C decreased by −1.69 and −0.70 in the intervention and control groups , respectively ( p = 0.376 ) . A total of 12 of 26 ( 46.2 % ) participants in the intervention group indicated they performed SMBG ≥7 times per week ; 75 % ( 9/12 ) of these were controlled by lifestyle or metformin alone . When applicable , most participants in the intervention group indicated they perform SMBG with exercise ( 62.5 % ) , during illness ( 62.5 % ) and with hypoglycemic symptoms ( 81.3 % ) compared with 33.3 % , 42.9 % and 42.9 % in the control group , respectively . Most participants in the intervention group ( 20/26 ; 76.9 % ) reported making lifestyle changes as a result of speaking with the pharmacist , with all indicating that they maintained these changes at 6 months . Conclusions : The results of this pilot study indicate that a larger study examining pharmacist interventions related to SMBG is feasible . Future studies are required to determine patient motivations and further evaluate the role of pharmacists in ensuring best practice s to positively influence guideline -based blood glucose monitoring Background Pharmaceutical care is the direct interaction between pharmacist and patient , in order to improve therapeutic compliance , promote adequate pharmacotherapeutic follow-up , and improve quality of life . Pharmaceutical care may be effective in reducing complications and in improving the quality of life of patients with chronic diseases , like Chagas heart disease , while bringing a positive impact on health system costs . The morbidity and mortality indexes for patients with Chagas heart disease are high , especially if this heart disease is complicated by heart failure . In this setting , we hypothesize that pharmaceutical care might be an important tool for the clinical management of these patients by improving their quality of life , as a better compliance to their treatment and the avoidance and prompt correction of drug-related problems will minimize their symptoms , improve their functional class , and decrease the number of hospital admissions . Therefore , the aim of this trial is to evaluate the contribution of pharmaceutical care to clinical treatment of patients with Chagas heart disease complicated by heart failure . Methods / design A prospect i ve , single-center r and omized clinical trial will be conducted in patients with Chagas heart disease complicated by heart failure . A total of 88 patients will be r and omly assigned into two parallel groups : an intervention group will receive st and ard care and pharmaceutical care , and a control group will receive only st and ard care . Both groups will be subjected to a follow-up period of 12 months . The primary outcome of this trial is the evaluation of quality of life , measured by the 36-item short-form and the Minnesota Living with Heart Failure Question naire . Secondary outcomes include drug-related problems , exercise tolerance as measured by the st and ard six-minute-walk test , and compliance . Discussion Patients with Chagas heart disease complicated by heart failure under pharmaceutical care are expected to improve their quality of life , present with a lower incidence of drug-related problems , improve their functional capacity , and improve in their compliance to treatment . Trial registration Clinical Trials.gov Identifier : BACKGROUND regular medication review has been recommended for those over 75 and those on multiple drug therapy . Pharmacists are a potential source of assistance in review ing medication . Evidence of the benefits of this process is needed . OBJECTIVE to study the effect of medication review led by a pharmacist on resolution of pharmaceutical care issues , medicine costs , use of health and social services and health-related quality of life . DESIGN r and omized , controlled trial . SETTING general medical practice s in the Grampian region of Scotl and . SUBJECTS patients aged at least 65 years , with at least two chronic disease states who were taking at least four prescribed medicines regularly . METHODS pharmacists review ed the drug therapy of 332 patients , using information obtained from the practice computer , medical records and patient interviews . In 168 patients , a pharmaceutical care plan was then drawn up and implemented . The 164 control patients continued to receive normal care . All outcome measures were assessed at baseline and after 3 months . RESULTS all patients had at least two pharmaceutical care issues at baseline . Half of these were identified from the prescription record , the rest from notes and patient interview . Of all the issues , 21 % were resolved by information found in notes and 8.5 % by patient interview . General practitioners agreed with 96 % of all care issues documented on the care plans in the intervention group . At the time of follow-up , 70 % of the remaining care issues had been resolved in the intervention group , while only 14 % had been resolved in the control group . There were no changes in medicine costs or health-related quality of life in either group . There were small increases in contacts with health-care professionals and slightly fewer hospital admissions among the intervention group than the control group . CONCLUSIONS pharmacist-led medication review has the capacity to identify and resolve pharmaceutical care issues and may have some impact on the use of other health services BACKGROUND Traditional systems of managing repeat prescribing have been criticised for their lack of clinical and administrative controls . AIM To compare a community pharmacist-managed repeat prescribing system with established methods of managing repeat prescribing . METHOD A r and omised controlled intervention study ( 19 general medical practice s , 3074 patients , 62 community pharmacists ) . Patients on repeat medication were given sufficient three-monthly scripts , endorsed for monthly dispensing , to last until their next clinical review consultation with their general practitioner ( GP ) . The scripts were stored by a pharmacist of the patient 's choice . Each monthly dispensing was authorised by the pharmacist , using a st and ard protocol . The cost of the drugs prescribed and dispensed was calculated . Data on patient outcomes were obtained from pharmacist-generated patient records and GP notes . RESULTS A total of 12.4 % of patients had compliance problems , side-effects , adverse drug reactions , or drug interactions identified by the pharmacist . There were significantly more problems identified in total in the intervention group . The total number of consultations , deaths , and non-elective hospital admissions was the same in both groups . Sixty-six per cent of the study patients did not require their full quota of prescribed drugs , representing 18 % of the total prescribed costs ( estimated annual drug cost avoidance of 43 Pounds per patient ) . CONCLUSION This system of managing repeat prescribing has been demonstrated to be logistically feasible , to identify clinical problems , and to make savings in the drugs bill Objectives To compare the effectiveness of pharmacist medication review , with or without pharmacist prescribing , with st and ard care , for patients with chronic pain . Design An exploratory r and omised controlled trial . Setting Six general practice s with prescribing pharmacists in Grampian ( 3 ) and East Anglia ( 3 ) . Participants Patients on repeat prescribed pain medication ( 4815 ) were screened by general practitioners ( GPs ) , and mailed invitations ( 1397 ) . 196 were r and omised and 180 ( 92 % ) completed . Exclusion criteria included : severe mental illness , terminally ill , cancer related pain , history of addiction . R and omisation and intervention Patients were r and omised using a remote telephone service to : ( 1 ) pharmacist medication review with face-to-face pharmacist prescribing ; ( 2 ) pharmacist medication review with feedback to GP and no planned patient contact or ( 3 ) treatment as usual ( TAU ) . Blinding was not possible . Outcome measures Outcomes were the SF-12v2 , the Chronic Pain Grade ( CPG ) , the Health Utilities Index 3 and the Hospital Anxiety and Depression Scale ( HADS ) . Outcomes were collected at 0 , 3 and 6 months . Results In the prescribing arm ( n=70 ) two patients were excluded/nine withdrew . In the review arm ( n=63 ) one was excluded/three withdrew . In the TAU arm ( n=63 ) four withdrew . Compared with baseline , patients had an improved CPG in the prescribing arm , 47.7 % ( 21/44 ; p=0.003 ) and in the review arm , 38.6 % ( 17/44 ; p=0.001 ) , but not the TAU group , 31.3 % ( 15/48 ; ns ) . The SF-12 Physical Component Score showed no effect in the prescribing or review arms but improvement in TAU ( p=0.02 ) . The SF-12 Mental Component Score showed no effect for the prescribing or review arms and deterioration in the TAU arm ( p=0.002 ) . HADS scores improved within the prescribing arm for depression ( p=0.022 ) and anxiety ( p=0.007 ) , between groups ( p=0.022 and p=0.045 , respectively ) . Conclusions This is the first r and omised controlled trial of pharmacist prescribing in the UK , and suggests that there may be a benefit for patients with chronic pain . A larger trial is required . Trial registration : www.is rct n.org/IS RCT N06131530 . Medical Research Council funding BACKGROUND Most diabetic and hypertensive patients , principally the elderly , do not achieve adequate disease control and consume 5%-15 % of annual health care budgets . Previous studies verified that pharmaceutical care is useful for achieving adequate disease control in diabetes and hypertension . OBJECTIVE To evaluate the economic cost and the incremental cost-effectiveness ratio ( ICER ) per quality -adjusted life-year ( QALY ) of pharmaceutical care in the management of diabetes and hypertension in elderly patients in a primary public health care system in a developing country . METHODS A 36-month r and omized controlled clinical trial was performed with 200 patients who were divided into a control group ( n = 100 ) and an intervention group ( n = 100 ) . The control group received the usual care offered by the Primary Health Care Unit ( medical and nurse consultations ) . The intervention group received the usual care plus a pharmaceutical care intervention . The intervention and control groups were compared with regard to the direct costs of health services ( i.e. , general practitioner , specialist , nurse , and pharmacist appointments ; emergency room visits ; and drug therapy costs ) and the ICER per QALY . These evaluations used the health system perspective . RESULTS No statistically significant difference was found between the intervention and control groups in total direct health care costs ( $ 281.97 ± $ 49.73 per patient vs. $ 212.28 ± $ 43.49 per patient , respectively ; P = 0.089 ) ; pharmaceutical care added incremental costs of $ 69.60 ( ± $ 7.90 ) per patient . The ICER per QALY was $ 53.50 ( 95 % CI = $ 51.60-$54.00 ; monetary amounts are given in U.S. dollars ) . Every clinical parameter evaluated improved for the pharmaceutical care group , whereas these clinical parameters remained unchanged in the usual care group . The difference in differences ( DID ) tests indicated that for each clinical parameter , the patients in the intervention group improved more from pre to post than the control group ( P < 0.001 ) . CONCLUSIONS While pharmaceutical care did not significantly increase total direct health care costs , significantly improved health outcomes were seen . The mean ICER per QALY gained suggests a favorable cost-effectiveness OBJECTIVE : To assess the effect of a physician and pharmacist teamwork approach to uncontrolled hypertension in a medical resident teaching clinic , for patients who failed to meet the recommended goals of the fifth Joint National Commission on Detection , Evaluation and Treatment of High Blood Pressure . HYPOTHESIS : Physician and pharmacist teamwork can improve the rate of meeting national blood pressure goals in patients with previously uncontrolled hypertension . DESIGN : A single-blinded r and omized controlled trial lasting 6 months . SETTING : A primary care outpatient teaching clinic . PATIENTS : A sample of 95 adult hypertensive patients who failed to meet national blood pressure goals based on three consecutive visits over a 6-month period . INTERVENTION : Patients were r and omly assigned to a control arm of st and ard medical care or to an intervention arm in which a physician and pharmacist worked together as a team . MAIN RESULTS : At study completion , the percentage of patients achieving national goals due to intervention was more than double the percentage in the control arm ( 55 % vs 20 % , p < .001 ) . Systolic blood pressure declined 23 mm Hg in the intervention arm versus 11 mm Hg in the control arm ( p < .01 ) . Diastolic blood pressure declined 14 and 3 mm Hg in the intervention and control arms , respectively ( p < .001 ) . The intervention worked equally as well in men and women and demonstrated noticeable promise in a minority of mixed-ancestry Hawaiians in whom hypertension is of special concern . CONCLUSIONS : Patients who fail to achieve national blood pressure goals under st and ard outpatient medical care may benefit from a program that includes a physician and pharmacist teamwork approach Background —To determine whether a pharmacist-led , Heart360-enabled , home blood pressure monitoring ( HBPM ) intervention improves blood pressure ( BP ) control compared with usual care ( UC ) . Methods and Results —This r and omized , controlled trial was conducted in 10 Kaiser Permanente Colorado clinics . Overall , 348 patients with BP above recommended levels were r and omized to the HBPM ( n=175 ) or UC ( n=173 ) groups . There were no statistically significant differences in baseline characteristics between the groups ; however , there was a trend toward a higher baseline BP for the HBPM group compared with the UC group ( 148.8 versus 145.5 mm Hg for systolic BP ; 89.6 versus 88.0 mm Hg for diastolic BP ) . At 6 months , the proportion of patients achieving BP goal was significantly higher in the HBPM group ( 54.1 % ) than in the UC group ( 35.4 % ; P<0.001 ) . Compared with the UC group , the HBPM group experienced a −12.4-mm Hg larger ( 95 % confidence interval , −16.3 to −8.6 ) reduction in systolic BP and a −5.7-mm Hg larger ( 95 % confidence interval , −7.8 to −3.6 ) reduction in diastolic BP . The impact of the intervention on BP reduction was even larger for the subgroup of patients with diabetes mellitus or chronic kidney disease . The HBPM group had more e-mail and telephone contacts and greater medication regimen intensification . The proportion of patients reporting high satisfaction with hypertension care was significantly greater in the HBPM group ( 58 % ) than in the UC group ( 42 % ) , P<0.001 . Conclusions —A pharmacist-led , Heart360-supported , home BP monitoring intervention led to greater BP reductions , superior BP control , and higher patient satisfaction than UC . Clinical Trial Registration —URL : http://www . clinical trials.gov/ct2/show/NCT01162759 . Unique identifier : NCT01162759 Type 2 diabetes disproportionately affects Latinos increasing their risk of diabetes-related complications . This study used a r and omized controlled design with a community-based approach to evaluate the impact of a culturally tailored pharmacist intervention on clinical outcomes in Latino diabetics . The intervention included a focused discussion and two individual pharmacist counseling sessions on medication , nutrition , exercise , and self-care to promote behavior changes . Sessions were culturally adapted for language , diet , family participation , and cultural beliefs . Clinical outcomes were measured at baseline and three months . Nineteen intervention and 24 control participants completed the study . Mean BMI reduction was greater for intervention than for control group participants ( –0.73± 0.07 kg/m2 versus + 0.37±0.02 kg/m2 p<.009 respectively ) . Hemoglobin A1c was significantly reduced by 0.93±0.45 % in the intervention group only . There was no significant difference in blood glucose , blood pressure , or lipid levels . An innovative culturally-sensitive pharmacist intervention improved selected clinical outcomes among Latino diabetics Aims / Introduction The purpose of the present study was to examine glycemic control in suboptimally controlled type 2 diabetes provided by a structured education group using the Diabetes Conversation Map ™ ( CM ™ ) vs usual care in a university-based hospital primary care clinic . Material s and Methods This was a r and omized , pragmatic clinical trial . Patients with type 2 diabetes were r and omly assigned to structured education or usual care groups . The primary outcome was the difference in the mean change of glycated hemoglobin ( HbA1c ) from baseline to 12 months . Secondary outcomes included the percentage achieving therapeutic HbA1c goal and self-behavioral changes . Results A total of 245 patients were r and omly assigned to two groups ( CM ™ group n = 121 ; usual care group , n = 116 ) . The absolute reduction of HbA1c was significantly greater in the CM ™ group at 3 and 6 months ( Δ = −0.59 % and Δ = −1.13 % , P < 0.01 ) , but the difference was no longer statistically significant at 9 and 12 months ( Δ = −0.43 % and Δ = −0.49 % ) , based on an intention-to-treat analysis . A per- protocol analysis showed the significant change was maintained at 12 months ( Δ = −0.67 % ) . In the intervention group , greater percentages of patients achieved their American Association of Diabetes Educators Self-Care Behaviours ™ framework ( AADE7 ) behavioral goals at 3 months , in particular being active , problem-solving , reducing risk and health coping . Conclusions In type 2 diabetic patients with suboptimally controlled glucose , there were greater improvements in glucose control and self-care behavioral goals in those who underwent the CM ™ education program compared with outcomes achieved in patients receiving usual care Abstract Objective . To determine whether a pharmacist-led medications review in primary care reduces the number of drugs and the number of drug-related problems . Design . Prospect i ve r and omized controlled trial . Setting . Liljeholmen Primary Care Centre , Stockholm , Sweden . Subjects . 209 patients aged ≥ 65 years with five or more different medications . Intervention . Patients answered a question naire regarding medications . The pharmacist review ed all medications ( prescription , non-prescription , and herbal ) regarding recommendations and renal impairment , giving advice to patients and GPs . Each patient met the pharmacist before seeing their GP . Control patients received their usual care . Main outcome measures . Drug-related problems and number of drugs . Secondary outcomes included health care utilization and self-rated health during 12 months of follow-up . Results . No significant difference was seen when comparing change in drug-related problems between the groups . However , a significant decrease in drug-related problems was observed in the intervention group ( from 1.73 per patient at baseline to 1.31 at follow-up , p < 0.05 ) . The change in number of drugs was more pronounced in the intervention group ( p < 0.046 ) . Intervention group patients were not admitted to hospital on fewer occasions or for fewer days , and there was no significant difference between the two groups regarding utilization of primary care during follow-up . Self-rated health remained unchanged in the intervention group , whereas a drop ( p < 0.02 ) was reported in the control group . This result ed in a significant difference in change in self-rated health between the groups ( p < 0.047 ) . Conclusions . The addition of a skilled pharmacist to the primary care team may contribute to reductions in numbers of drugs and maintenance of self-rated health in elderly patients with polypharmacy INTRODUCTION Chemotherapy is the most common form of treatment among cancer patients . It is also known to cause many physical and psychological side-effects . OBJECTIVE This study developed , implemented and evaluated the outcome of a chemotherapy counseling module among oncology patients by pharmacists based on their psychological effects ( depression , anxiety ) and selfesteem . METHODS A r and omized , single blind , placebo controlled study was conducted among 162 patients undergoing chemotherapy in a government hospital in Malaysia . INTERVENTION Counseling sessions were conducted using the ' Managing Patients on Chemotherapy ' module for oncology patients undergoing chemotherapy at each treatment cycle . OUTCOME The outcome of repetitive chemotherapy counseling using the module was determined at baseline , first follow-up , second follow-up and third follow-up . RESULTS The findings revealed that there was significant improvement in the intervention group as compared to the control group with large effect size on depression ( p = 0.001 , partial η(2 ) = 0.394 ) , anxiety ( p = 0.001 , partial η(2 ) = 0.232 ) and self-esteem ( p = 0.001 , partial η(2 ) = 0.541 ) . CONCLUSION Repetitive counseling using the ' Managing Patients on Chemotherapy ' module was found to be effective in improving psychological effects and self-esteem among patients undergoing chemotherapy Abstract Background Medication non-adherence is considered an important cause of morbidity and mortality in primary care . This study aims to determine the effectiveness , cost effectiveness and acceptability of a complex intervention delivered by community pharmacists , the New Medicine Service ( NMS ) , compared with current practice in reducing non-adherence to , and problems with , newly prescribed medicines for chronic conditions . Methods / design Research subject group : patients aged 14 years and above presenting in a community pharmacy for a newly prescribed medicine for asthma/chronic obstructive pulmonary disease ( COPD ) ; hypertension ; type 2 diabetes or anticoagulant/antiplatelet agents in two geographical regions in Engl and . Design : parallel group patient-level pragmatic r and omized controlled trial . Interventions : patients r and omized to either : ( i ) current practice ; or ( ii ) NMS intervention comprising pharmacist-delivered support for a newly prescribed medicine . Primary outcomes : proportion of adherent patients at six , ten and 26 weeks from the date of presenting their prescriptions at the pharmacy ; cost effectiveness of the intervention versus current practice at 10 weeks and 26 weeks ; in-depth qualitative underst and ing of the operationalization of NMS in pharmacies . Secondary outcomes : impact of NMS on : patients ’ underst and ing of their medicines , pharmacovigilance , interprofessional and patient-professional relationships and experiences of service users and stakeholders . Economic analysis : Trial-based economic analysis ( cost per extra adherent patient ) and long-term modeling of costs and health effects ( cost per quality -adjusted-life-year ) will be conducted from the perspective of National Health Service ( NHS ) Engl and , comparing NMS with current practice .Qualitative analysis : a qualitative study of NMS implementation in different community setting s , how organizational influences affect NMS delivery , patterns of NMS consultations and experiences of professionals and patients participating in NMS , and patients receiving current practice . Sample size : 250 patients in each treatment arm would provide at least 80 % power ( two-tailed alpha of 0.05 ) to demonstrate a reduction in patient-reported non-adherence from 20 % to 10 % in the NMS arm compared with current practice , assuming a 20 % drop-out rate . Discussion At the time of su bmi ssion of this article , 58 community pharmacies have been recruited and the interventions are being delivered . Analysis has not yet been undertaken . Trial registration Current controlled trials : IS RCT N23560818 Clinical Trials US ( clinical trials.gov ) : BACKGROUND The management of type 2 diabetes mellitus is complex , requiring continuous medical care by health care professionals and considerable self-care efforts by patients . Pharmacist-led care programs have been shown to help patients with diabetes succeed in achieving treatment goals and improving outcomes . Pharmacist-led care is a new health care concept in Northern Cyprus . OBJECTIVE To evaluate the effect of a pharmacist-led care program on glycemic control , determined by hemoglobin A1c ( A1c ) , and secondarily on blood pressure , lipid profile , body mass index ( BMI ) , waist circumference , medication adherence , and self-care activities , for patients with type 2 diabetes over a 12-month period . METHODS This was a prospect i ve , r and omized controlled study conducted in a public hospital 's outpatient diabetes clinic , with 152 patients who had been diagnosed with type 2 diabetes . Of these , 75 patients were in the intervention group , and 77 patients were in the usual care group . The intervention group participated in a pharmacist-led care program with a clinical pharmacist who provided 5 face-to-face educational sessions over a period of 12 months . The main outcome measure was change in A1c , and secondary outcome measures were changes in fasting blood glucose , systolic and diastolic blood pressure , lipid values ( total cholesterol , low-density lipoprotein cholesterol [ LDL-C ] , high-density lipoprotein cholesterol [ HDL-C ] , and serum levels of triglycerides [ TGs ] ) , BMI , waist circumference , self-reported medication adherence ( Morisky-Green test ) , and self-care activities . Changes in outcome measures from baseline to the end of the study were assessed using the Mann-Whitney U-test and Wilcoxon test . RESULTS At the end of the 12-month study period , the intervention patients showed a greater reduction in A1c values than the usual care patients ( -0.74 % vs. -0.04 % ; P < 0.001 ) . Both groups showed significant reductions in fasting blood glucose levels between baseline and the end of 12 months ; the difference between the groups was statistically nonsignificant ( P = 0.410 ) . When comparing the intervention and usual care groups , there was a significant decrease in systolic ( P = 0.01 ) and diastolic blood pressure ( P = 0.04 ) at the end of the trial . No significant differences were found between the groups in LDL-C , HDL-C , or TG values ; however , total cholesterol levels did decrease significantly ( P = 0.063 , 0.331 , 0.896 , and 0.04 , respectively ) . Significant reductions occurred in BMI ( P < 0.001 ) and waist circumference ( P < 0.001 ) , and improvements were observed in self-reported medication adherence and self-care activities in the intervention group . CONCLUSIONS A clinical pharmacist-led care program in a public hospital 's outpatient diabetes clinic was associated with significant improvements in reducing A1c and other secondary outcomes in a 12-month r and omized controlled study . DISCLOSURES This study was conducted as a PhD thesis by Korcegez under the supervision of Sancar for the clinical pharmacy program at Near East University , Health Sciences Institute , Northern Cyprus , and received no external funding . The authors have no potential conflicts of interest to report . Study concept and design were contributed by Korcegez , with assistance from Sancar and Demirkan . Korcegez took the lead in data collection , and data interpretation was performed by Korcegez , along with Sancar and Korcegez . The manuscript was written and revised by Korcegez , along with Sancar , and with assistance from Demirkan BACKGROUND Pharmacists can improve patient outcomes in institutional and pharmacy setting s , but little is known about their effectiveness as consultants to primary care physicians . We examined whether an intervention by a specially trained pharmacist could reduce the number of daily medication units taken by elderly patients , as well as costs and health care use . METHODS We conducted a r and omized controlled trial in family practice s in 24 sites in Ontario . We r and omly allocated 48 r and omly selected family physicians ( 69.6 % participation rate ) to the intervention or the control arm , along with 889 ( 69.5 % participation rate ) of their r and omly selected community-dwelling , elderly patients who were taking 5 or more medications daily . In the intervention group , pharmacists conducted face-to-face medication review s with the patients and then gave written recommendations to the physicians to resolve any drug-related problems . Process outcomes included the number of drug-related problems identified among the senior citizens in the intervention arm and the proportion of recommendations implemented by the physicians . RESULTS After 5 months , seniors in the intervention and control groups were taking a mean of 12.4 and 12.2 medication units per day respectively ( p = 0.50 ) . There were no statistically significant differences in health care use or costs between groups . A mean of 2.5 drug-related problems per senior was identified in the intervention arm . Physicians implemented or attempted to implement 72.3 % ( 790/1093 ) of the recommendations . INTERPRETATION The intervention did not have a significant effect on patient outcomes . However , physicians were receptive to the recommendations to resolve drug-related problems , suggesting that collaboration between physicians and pharmacists is feasible AIMS The primary aim of this study was to evaluate the impact of pharmaceutical care interventions on glycemic control and other health-related clinical outcomes in patients with type 2 diabetes patients in Jordan . METHODS A r and omized controlled clinical trial was conducted on 106 patients with uncontrolled type 2 diabetes seeking care in the diabetes clinics at Jordan University Hospital . Patients were r and omly allocated into control and intervention group . The intervention group patients received pharmaceutical care interventions developed by the clinical pharmacist in collaboration with the physician while the control group patients received usual care without clinical pharmacist 's input . Fasting blood glucose and HbA1c were measured at the baseline , at three months , and six months intervals for both intervention and control groups . RESULTS After the six months follow-up , mean of HbA1c and FBS of the patients in the intervention group decreased significantly compared to the control group patients ( P<0.05 ) . Also , the results indicated that mean scores of patients ' knowledge about medications , knowledge about diabetes and adherence to medications and diabetes self-care activities of the patients in the intervention group increased significantly compared to the control group ( P<0.05 ) . CONCLUSIONS This study demonstrated an improvement in HbA1c , FBS , and lipid profile , in addition to self-reported medication adherence , diabetes knowledge , and diabetes self-care activities in patients with type 2 diabetes who received pharmaceutical care interventions . The results suggest the benefits of integrating clinical pharmacist services in multidisciplinary healthcare team and diabetes management in Jordan OBJECTIVE : To evaluate the impact of a clinical pharmacy program on health outcomes in patients with type 2 diabetes undergoing insulin therapy at a teaching hospital in Brazil . METHOD : A r and omized controlled trial with a 6-month follow-up period was performed in 70 adults , aged 45 years or older , with type 2 diabetes who were taking insulin and who had an HbA1c level ≥8 % . Patients in the control group ( CG ) ( n = 36 ) received st and ard care , patients in the intervention group ( IG ) ( n = 34 ) received an individualized pharmacotherapeutic care plan and diabetes education . The primary outcome measure was change in HbA1c . Secondary outcomes included diabetes and medication knowledge , adherence to medication , insulin injection and home blood glucose monitoring techniques and diabetes-related quality of life . Outcomes were evaluated at baseline and 6 months using question naires . RESULTS : Diabetes knowledge , medication knowledge , adherence to medication and correct insulin injection and home blood glucose monitoring techniques significantly improved in the intervention group but remained unchanged in the control group . At the end of the study , mean HbA1c values in the control group remained unchanged but were significantly reduced in the intervention group . Diabetes-related quality of life significantly improved in the intervention group but worsened significantly in the control group . CONCLUSION : The program improved health outcomes and result ed in better glycemic control in patients with type 2 diabetes undergoing insulin therapy Background Admission medication history ( AMH ) errors frequently cause medication order errors and patient harm . Objective To quantify AMH error reduction achieved when pharmacy staff obtain AMHs before admission medication orders ( AMO ) are placed . Methods This was a three-arm r and omised controlled trial of 306 in patients . In one intervention arm , pharmacists , and in the second intervention arm , pharmacy technicians , obtained initial AMHs prior to admission . They obtained and reconciled medication information from multiple sources . All arms , including the control arm , received usual AMH care , which included variation in several common processes . The primary outcome was severity-weighted mean AMH error score . To detect AMH errors , all patients received reference st and ard AMHs , which were compared with intervention and control group AMHs . AMH errors and result ant AMO errors were independently identified and rated by ≥2 investigators as significant , serious or life threatening . Each error was assigned 1 , 4 or 9 points , respectively , to calculate severity-weighted AMH and AMO error scores for each patient . Results Patient characteristics were similar across arms ( mean±SD age 72±16 years , number of medications 15±7 ) . Analysis was limited to 278 patients ( 91 % ) with reference st and ard AMHs . Mean±SD AMH errors per patient in the usual care , pharmacist and technician arms were 8.0±5.6 , 1.4±1.9 and 1.5±2.1 , respectively ( p<0.0001 ) . Mean±SD severity-weighted AMH error scores were 23.0±16.1 , 4.1±6.8 and 4.1±7.0 per patient , respectively ( p<0.0001 ) . These AMH errors led to a mean±SD of 3.2±2.9 , 0.6±1.1 and 0.6±1.1 AMO errors per patient , and mean severity-weighted AMO error scores of 6.9±7.2 , 1.5±2.9 and 1.2±2.5 per patient , respectively ( both p<0.0001 ) . Conclusions Pharmacists and technicians reduced AMH errors and result ant AMO errors by over 80 % . Future research should examine other sites and patient-centred outcomes . Trial registration number NCT02026453 PURPOSE Potentially inappropriate prescribing ( PIP ) is common in older people and can result in increased morbidity , adverse drug events , and hospitalizations . The OPTI-SCRIPT study ( Optimizing Prescribing for Older People in Primary Care , a cluster-r and omized controlled trial ) tested the effectiveness of a multifaceted intervention for reducing PIP in primary care . METHODS We conducted a cluster-r and omized controlled trial among 21 general practitioner practice s and 196 patients with PIP . Intervention participants received a complex , multifaceted intervention incorporating academic detailing ; review of medicines with web-based pharmaceutical treatment algorithms that provide recommended alternative-treatment options ; and tailored patient information leaflets . Control practice s delivered usual care and received simple , patient-level PIP feedback . Primary outcomes were the proportion of patients with PIP and the mean number of potentially inappropriate prescriptions . We performed intention-to-treat analysis using r and om-effects regression . RESULTS All 21 practice s and 190 patients were followed . At intervention completion , patients in the intervention group had significantly lower odds of having PIP than patients in the control group ( adjusted odds ratio = 0.32 ; 95 % CI , 0.15–0.70 ; P = .02 ) . The mean number of PIP drugs in the intervention group was 0.70 , compared with 1.18 in the control group ( P = .02 ) . The intervention group was almost one-third less likely than the control group to have PIP drugs at intervention completion , but this difference was not significant ( incidence rate ratio = 0.71 ; 95 % CI , 0.50–1.02 ; P = .49 ) . The intervention was effective in reducing proton pump inhibitor prescribing ( adjusted odds ratio = 0.30 ; 95 % CI , 0.14–0.68 ; P = .04 ) . CONCLUSIONS The OPTI-SCRIPT intervention incorporating academic detailing with a pharmacist , and a review of medicines with web-based pharmaceutical treatment algorithms , was effective in reducing PIP , particularly in modifying prescribing of proton pump inhibitors , the most commonly occurring PIP drugs nationally Background The economic burden of asthma , which relates to the degree of control , is € 5 billion annually in Italy . Pharmacists could help improve asthma control , reducing this burden . This study aim ed to evaluate the effectiveness and cost-effectiveness of Medicines Use Review s provided by community pharmacists in asthma . Methods This cluster r and omised , multi-centre , controlled trial in adult patients with asthma was conducted in 15 of the 20 regions of Italy between September 2014 and July 2015 . After stratification by region , community pharmacists were r and omly allocated to group A ( trained in and delivered the intervention at baseline ) or B ( training and delivery 3 months later ) , using computerised r and om number generation in blocks of 10 . Each recruited up to five patients , with both groups followed for 9 months . The intervention consisted of a systematic , structured face-to-face consultation with a pharmacist , covering asthma symptoms , medicines used , attitude towards medicines and adherence , recording pharmacist-identified pharmaceutical care issues ( PCIs ) . The primary outcome was asthma control , assessed using the Asthma-Control-Test ( ACT ) score ( ACT ≥ 20 represents good control ) . Secondary outcomes were : number of active ingredients , adherence , cost-effectiveness compared with usual care . Although blinding was not possible for either pharmacists or patients , assessment of outcomes was conducted by research ers blind to group allocation . Results Numbers of pharmacists and patients enrolled were 283 ( A = 136 ; B = 147 ) and 1263 ( A = 600 ; B = 663 ) , numbers completing were 201 ( A = 97 ; B = 104 ) and 816 ( A = 400 ; B = 416 ) , respectively . Patients were similar in age and gender and 56.13 % ( 458/816 ) had poor/partial asthma control . Pharmacists identified 1256 PCIs ( mean 1.54/patient ) , mostly need for education , monitoring and potentially ineffective therapy . Median ACT score at baseline differed between groups ( A = 19 , B = 18 ; p < 0.01 ) . Odds ratio for improved asthma control was 1.76 ( 95 % CI 1.33–2.33 ) and number needed to treat 10 ( 95 % CI 6–28 ) . Number of active ingredients reduced by 7.9 % post-intervention ( p < 0.01 ) . Adherence improved by 35.4 % 3 months post-intervention and 40.0 % at 6 months ( p < 0.01 ) . The probability of the intervention being more cost-effective than usual care was 100 % at 9 months . Conclusions This community pharmacist-based intervention demonstrated both effectiveness and cost-effectiveness . It has since been implemented as the first community pharmacy cognitive service in Italy . Trial registration TRN : IS RCT N72438848 ( registered 5th January 2015 , retrospectively ) Background and Purpose : Adherence to medication is often suboptimal after stroke and transient ischemic attack ( TIA ) , which increases the risk of recurrent stroke and death . Complex interventions and motivational interviewing ( MI ) have been proven effective in other areas of medicine . The objective of this study was to investigate the effectiveness of a multifaceted intervention including MI in improving medication adherence for secondary stroke prevention . Methods : In this r and omized controlled trial , TIA and stroke patients receiving a pharmacist intervention in a hospital setting were compared with patients receiving usual care . The intervention consisted of a focused medication review , an MI-approached consultation and 3 follow-up telephone calls and lasted for 6 months . The primary outcome was a composite medication possession ratio ( MPR ) for antiplatelets , anticoagulants and statins in the year after hospitalization , assessed by analyzing pharmacy records and reported as both a continuous rate and a binary outcome . Secondary outcomes included composite MPRs at 3 , 6 and 9 months as well as adherence and persistence to specific thrombopreventive medications at 12 months . Clinical outcomes included a combined end point of cardiovascular death , stroke or acute myocardial infa rct ion . Patient satisfaction with the service was assessed for the intervention patients . Results : The analyses included 102 intervention patients and 101 controls . At 12 months , the median MPRs ( IQR ) were 0.95 ( 0.77 - 1 ) in the intervention group and 0.91 ( 0.83 - 0.99 ) in the control group , and 28 and 21 % of the patients , respectively , were nonadherent ( MPR < 0.80 ; risk difference : 7 % ; 95 % CI : -5 to 19 % ) . In both groups , the median MPR decreased over time . From 3 to 12 months , the MPR fell by 5 % ( p < 0.05 ) in the intervention group and by 9 % ( p < 0.05 ) in the control group , but between the groups , comparisons showed no statistically significant difference . No significant differences were found for adherence and persistence to specific thrombopreventive agents or for the clinical outcome . The intervention patients were satisfied with the service ; about half of them reported increased knowledge about medication , and one third reported increased confidence with medication use . Pharmacists identified drug-related problems in one third of the patients . Conclusions : A multifaceted pharmacist intervention including MI did not improve adherence or persistence to secondary stroke prevention therapy and had no impact on clinical outcomes . However , due to the high adherence rates , only little room for improvement existed . Future studies should focus on patients at high risk of nonadherence and include outcomes more sensitive to the impact of behavioral interventions Background Epilepsy is a complex chronic disorder which affects health-related quality of life ( HRQOL ) , especially in women . Pharmaceutical care ( PC ) allows direct intervention between the pharmacist , the patient and the other healthcare team members to optimise treatments in order to reduce negative outcomes related to medication and contribute to improving HRQOL.The aim of the study was to establish the impact of the application of a pharmaceutical care programme on the HRQOL of women with epilepsy . Methods This study is a pragmatic r and omised controlled trial involving women with epilepsy ( WWE ) over 18 years of age . The intervention group ( IG ) received a pharmaceutical care programme consisting of medication review follow-up according to Dáder 's method , health education and therapeutic drug monitoring of anticonvulsants . The impact was assessed by changes in seizure frequency , in the self-administered question naires ( the QOLIE-31 , Liverpool AEP , CES-D , Haynes-Sackett test and Moriski-Green test ) and between the first interview and the one at the end of six months of follow-up . A Student 's t-test was performed to compare the final QOLIE-31 score between groups and a paired Student 's t-test was used to determine the change in each group between the start and the end of follow-up . Results One hundred eighty-two WWE entered the study and 144 ( 79.1 % ) completed it . The t-test for comparing the final QOLIE-31 scores between groups yielded a t = −2.166 and confidence interval ( CI ) ( 95 % ) : −10.125 ; −0.4625 , p-value = 0.0319 . The change ( Δ ) in the QOLIE-31 score for the IG was 12.45 points ( p-value < 0.001 ) and for the control group it was 2.61 ( p-value = 0.072 ) . With 10.7 as the minimally important change we found a relative risk of 2.17 ( CI : 1.37 ; 3.43 ) and a number needed to treat ( NNT ) of 3.5 . Conclusions The study demonstrated that the application of a pharmaceutical care programme significantly improves HRQOL in WWE . The NNT we found allows a recommendation to implement the PC programme for the additional benefit that would be obtained in patients ' HRQOL.Trial registration Current Controlled Trials IS RCT N46864306 IPHIWWE study .ResumenAntecedentesLa epilepsia es un desorden crónico complejo que afecta la calidad de vida relacionada con la salud ( CVRS ) , especialmente en las mujeres . La atención farmacéutica ( AF ) permite la interacción directa del farmacéutico con el paciente y con los demás integrantes del equipo de salud para optimizar los tratamientos con el fin de disminuir los result ados negativos asociados con la medicación y contribuir a mejorar la CVRS.El objetivo del estudio fue establecer el impacto de la aplicación de un programa de AF en la CVRS de mujeres con epilepsia (MCE).MétodosEnsayo clínico controlado aleatorizado pragmático en MCE mayores de 18 años . Al grupo intervención se le aplicó un programa de AF consistente en seguimiento farmacoterapéutico según el método Dáder , educación para la salud y monitoreo de anticonvulsivantes . El impacto se evaluó con el cambio en la frecuencia de crisis y de los cuestionarios auto-administrados ( QOLIE-31 , Liverpool AEP , CES-D , test de Haynes-Sackett , y test de Moriski-Green ) entre la primera entrevista y al finalizar los seis meses de seguimiento . Se realizó una t de student para comparar el puntaje final entre los grupos y una t de student pareada para comparar el cambio en el QOLIE-31 entre el inicio y el final en cada grupo . Result adosSe incluyeron 182 pacientes y finalizaron 144 ( 79,1 % ) . La prueba t para QOLIE-31 final entre grupos arrojó un t = −2,166 ( IC [ 95 % ] : −10,125 -0,4625 ; p = 0,0319 ) . Para el GI el cambio ( Δ ) en el QOLIE-31 fue de 12,45 puntos ( p < 0,001 ) y para el GC de 2,61 ( p = 0,072 ) . Tom and o 10,7 como cambio mínimo importante se encontró un Riesgo Relativo de 2,17 ( IC : 1,37 - 3,43 ) y un Número Necesario a Tratar ( NNT ) de 3,5 . Conclusion esEl estudio demostró que la aplicación del programa de AF mejora significativamente la CVRS en MCE . El NNT encontrado nos permite recomendar la implementación del programa de AF por el beneficio adicional que se obtendría en la CVRS de los pacientes Background : Optimization of systolic blood pressure and lipid levels are essential for secondary prevention after ischemic stroke , but there are substantial gaps in care , which could be addressed by nurse- or pharmacist-led care . We compared 2 types of case management ( active prescribing by pharmacists or nurse-led screening and feedback to primary care physicians ) in addition to usual care . Methods : We performed a prospect i ve r and omized controlled trial involving adults with recent minor ischemic stroke or transient ischemic attack whose systolic blood pressure or lipid levels were above guideline targets . Participants in both groups had a monthly visit for 6 months with either a nurse or pharmacist . Nurses measured cardiovascular risk factors , counselled patients and faxed results to primary care physicians ( active control ) . Pharmacists did all of the above as well as prescribed according to treatment algorithms ( intervention ) . Results : Most of the 279 study participants ( mean age 67.6 yr , mean systolic blood pressure 134 mm Hg , mean low-density lipoprotein [ LDL ] cholesterol 3.23 mmol/L ) were already receiving treatment at baseline ( antihypertensives : 78.1 % ; statins : 84.6 % ) , but none met guideline targets ( systolic blood pressure ≤ 140 mm Hg , fasting LDL cholesterol ≤ 2.0 mmol/L ) . Substantial improvements were observed in both groups after 6 months : 43.4 % of participants in the pharmacist case manager group met both systolic blood pressure and LDL guideline targets compared with 30.9 % in the nurse-led group ( 12.5 % absolute difference ; number needed to treat = 8 , p = 0.03 ) . Interpretation : Compared with nurse-led case management ( risk factor evaluation , counselling and feedback to primary care providers ) , active case management by pharmacists substantially improved risk factor control at 6 months among patients who had experienced a stroke . Trial registration : Clinical Trials.gov , no. Background Primary care providers do not routinely follow guidelines for the care of patients with chronic kidney disease ( CKD ) . Multidisciplinary efforts may improve care for patients with chronic disease . Pharmacist based interventions have effectively improved management of hypertension . We performed a pragmatic , r and omized , controlled trial to evaluate the effect of a pharmacist based quality improvement program on 1 ) outcomes for patients with CKD and 2 ) adherence to CKD guidelines in the primary care setting . Methods Patients with moderate to severe CKD receiving primary care services at one of thirteen community-based Veterans Affairs outpatient clinics were r and omized to a multifactorial intervention that included a phone-based pharmacist intervention , pharmacist-physician collaboration , patient education , and a CKD registry ( n = 1070 ) or usual care ( n = 1129 ) . The primary process outcome was measurement of parathyroid hormone ( PTH ) during the one year study period . The primary clinical outcome was blood pressure ( BP ) control in subjects with poorly controlled hypertension at baseline . Results Among those with poorly controlled baseline BP , there was no difference in the last recorded BP or the percent at goal BP during the study period ( 42.0 % vs. 41.2 % in the control arm ) . Subjects in the intervention arm were more likely to have a PTH measured during the study period ( 46.9 % vs. 16.1 % in the control arm , P < 0.001 ) and were on more classes of antihypertensive medications at the end of the study ( P = 0.02 ) . Conclusions A one-time pharmacist based intervention proved feasible in patients with CKD . While the intervention did not improve BP control , it did improve guideline adherence and increased the number of antihypertensive medications prescribed to subjects with poorly controlled BP . These findings can inform the design of quality improvement programs and future studies which are needed to improve care of patients with CKD.Trial registration Clinical Trials.gov : NCT01290614 Background Despite the availability of evidence -based guidelines for managing allergic rhinitis in primary care , management of the condition in the United Kingdom ( UK ) remains sub-optimal . Its high prevalence and negative effects on quality of life , school performance , productivity and co-morbid respiratory conditions ( in particular , asthma ) , and high health and societal costs , make this a priority for developing novel models of care . Recent Australian research demonstrated the potential of a community pharmacy-based ‘ goal -focused ’ intervention to help people with intermittent allergic rhinitis to self-manage their condition better , reduce symptom severity and improve quality of life . In this pilot study we will assess the transferability of the goal -focused intervention to a UK context , the suitability of the intervention material s , procedures and outcome measures and collect data to inform a future definitive UK r and omized controlled trial ( RCT ) . Methods / Design A pilot cluster RCT with associated preliminary economic analysis and embedded qualitative evaluation . The pilot trial will take place in two Scottish Health Board areas : Grampian and Greater Glasgow & Clyde . Twelve community pharmacies will be r and omly assigned to intervention or usual care group . Each will recruit 12 customers seeking advice or treatment for intermittent allergic rhinitis . Pharmacy staff in intervention pharmacies will support recruited customers in developing strategies for setting and achieving goals that aim to avoid/minimize triggers for , and eliminate/minimize symptoms of allergic rhinitis . Customers recruited in non-intervention pharmacies will receive usual care . The co- primary outcome measures , selected to inform a sample size calculation for a future RCT , are : community pharmacy and customer recruitment and completion rates ; and effect size of change in the vali date d mini-Rhinoconjunctivitis Quality of Life Question naire between baseline , one-week and six-weeks post-intervention . Secondary outcome measures relate to changes in symptom severity , productivity , medication adherence and self-efficacy . Quantitative data about accrual , retention and economic measures , and qualitative data about participants ’ experiences during the trial will be collected to inform the future RCT . Discussion This work will lay the foundations for a definitive RCT of a community pharmacy-based ‘ goal -focused ’ self-management intervention for people with intermittent allergic rhinitis . Results of the pilot trial are expected to be available in April 2013.Trial registration Current Controlled TrialsIS RCT BACKGROUND Meta- analysis of small trials suggests that pharmacist-led collaborative review and revision of medical treatment may improve outcomes in heart failure . METHODS AND RESULTS We studied patients with left ventricular systolic dysfunction in a cluster-r and omized controlled , event driven , trial in primary care . We allocated 87 practice s ( 1090 patients ) to pharmacist intervention and 87 practice s ( 1074 patients ) to usual care . The intervention was delivered by non-specialist pharmacists working with family doctors to optimize medical treatment . The primary outcome was a composite of death or hospital admission for worsening heart failure . This trial is registered , number IS RCT N70118765 . The median follow-up was 4.7 years . At baseline , 86 % of patients in both groups were treated with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker . In patients not receiving one or other of these medications , or receiving less than the recommended dose , treatment was started , or the dose increased , in 33.1 % of patients in the intervention group and in 18.5 % of the usual care group [ odds ratio ( OR ) 2.26 , 95 % CI 1.64 - 3.10 ; P < 0.001 ] . At baseline , 62 % of each group were treated with a β-blocker and the proportions starting or having an increase in the dose were 17.9 % in the intervention group and 11.1 % in the usual care group ( OR 1.76 , 95 % CI 1.31 - 2.35 ; P < 0.001 ) . The primary outcome occurred in 35.8 % of patients in the intervention group and 35.4 % in the usual care group ( hazard ratio 0.97 , 95 % CI 0.83 - 1.14 ; P = 0.72 ) . There was no difference in any secondary outcome . CONCLUSION A low-intensity , pharmacist-led collaborative intervention in primary care result ed in modest improvements in prescribing of disease-modifying medications but did not improve clinical outcomes in a population that was relatively well treated at baseline AIMS Few well- design ed r and omized controlled trials have been conducted regarding the impact of community pharmacist interventions on pharmacotherapeutic monitoring of patients with chronic obstructive pulmonary disease ( COPD ) . We assessed the effectiveness of a pharmaceutical care programme for patients with COPD . METHODS The pharmaceutical care for patients with COPD ( PHARMACOP ) trial is a single-blind 3 month r and omized controlled trial , conducted in 170 community pharmacies in Belgium , enrolling patients prescribed daily COPD medication , aged ≥ 50 years and with a smoking history of ≥ 10 pack-years . A computer-generated r and omization sequence allocated patients to an intervention group ( n = 371 ) , receiving protocol -defined pharmacist care , or a control group ( n = 363 ) , receiving usual pharmacist care ( 1:1 ratio , stratified by centre ) . Interventions focusing on inhalation technique and adherence to maintenance therapy were carried out at start of the trial and at 1 month follow-up . Primary outcomes were inhalation technique and medication adherence . Secondary outcomes were exacerbation rate , dyspnoea , COPD -specific and generic health status and smoking behaviour . RESULTS From December 2010 to April 2011 , 734 patients were enrolled . Forty-two patients ( 5.7 % ) were lost to follow-up . At the end of the trial , inhalation score [ mean estimated difference (Δ),13.5 % ; 95 % confidence interval ( CI ) , 10.8 - 16.1 ; P < 0.0001 ] and medication adherence ( Δ , 8.51 % ; 95 % CI , 4.63 - 12.4 ; P < 0.0001 ) were significantly higher in the intervention group compared with the control group . In the intervention group , a significantly lower hospitalization rate was observed ( 9 vs. 35 ; rate ratio , 0.28 ; 95 % CI , 0.12 - 0.64 ; P = 0.003 ) . No other significant between-group differences were observed . CONCLUSIONS Pragmatic pharmacist care programmes improve the pharmacotherapeutic regimen in patients with COPD and could reduce hospitalization rates Background : To be sustainable , pharmacists providing direct patient care must receive appropriate payment for these services . This prespecified sub study of the RxACTION trial ( a r and omized trial of pharmacist prescribing vs usual care in patients with above-target blood pressure [ BP ] ) aim ed to determine if BP reduction achieved differed between patients whose pharmacist was paid by pay-for-performance ( P4P ) vs fee-for-service ( FFS ) . Methods : Within RxACTION , patients with elevated BP assigned to the pharmacist prescribing group were further r and omized to P4P or FFS payment for the pharmacist . In FFS , pharmacists received $ 150 for the initial visit and $ 75 for follow-up visits . P4P included FFS payments plus incentives of $ 125 and $ 250 for each patient who reached 50 % and 100 % of the BP target , respectively . The primary outcome was difference in change in systolic BP between P4P and FFS groups . Results : A total of 89 patients were r and omized to P4P and 92 to the FFS group . Patients ’ average ( SD ) age was 63.0 ( 13.2 ) years , 49 % were male and 76 % were on antihypertensive drug therapy at baseline , taking a median of 2 ( interquartile range = 1 ) medications . Mean systolic BP reductions in the P4P and FFS groups were 19.7 ( SD = 18.4 ) vs 17.0 ( SD = 16.4 ) mmHg , respectively ( p = 0.47 for the comparison of deltas and p = 0.29 after multivariate adjustment ) . Conclusions : This trial of pharmacist prescribing found substantial reductions in systolic BP among poorly controlled hypertensive individuals but with no appreciable difference when pharmacists were paid by P4P vs FFS Background This study describes the analysis of secondary outcomes from a previously published r and omised controlled trial , which assessed the effects of pharmaceutical care on medication adherence , persistence and bone turnover markers . The main focus of this manuscript is the effect of the provision of pharmaceutical care on these secondary outcomes , and details on the design of the intervention provided , the osteoporosis care plan and material s used to deliver the intervention . Objectives To evaluate the effects of pharmaceutical care on knowledge , quality of life ( QOL ) and satisfaction of postmenopausal osteoporotic women prescribed bisphosphonates , and their associating factors . Setting R and omised controlled trial , performed at an osteoporosis clinic of a tertiary hospital in Malaysia . Methods Postmenopausal women diagnosed with osteoporosis ( T-score ≤−2.5/lowtrauma fracture ) , just been prescribed weekly alendronate/risedronate were r and omly allocated to receive intervention or st and ard care ( controls ) . Intervention participants received a medication review , education on osteoporosis , risk factors , lifestyle modifications , goals of therapy , side effects and the importance of medication adherence at months 0 , 3 , 6 and 12 . Main outcomes measure Knowledge , QOL and satisfaction . Results A total of 198 postmenopausal osteoporotic women were recruited : intervention = 100 and control = 98 . Intervention participants reported significantly higher knowledge scores at months 3 ( 72.50 vs. 62.50 % ) , 6 ( 75.00 vs. 65.00 % ) and 12 ( 78.75 vs. 68.75 % ) compared to control participants . QOL scores were also lower ( which indicates better QOL ) at months 3 ( 29.33 vs. 38.41 ) , 6 ( 27.50 vs. 36.56 ) and 12 ( 27.53 vs. 37.56 ) compared to control participants . Similarly , satisfaction score was higher in intervention participants ( 93.67 vs. 84.83 % ) . More educated women , with back pain , who were provided pharmaceutical care had better knowledge levels . Similarly , older , more educated women , with previous falls and back pain tend to have poorer QOL , whilst women who exercised more frequently and were provided pharmaceutical care had better QOL . Satisfaction also increased as QOL increases and when provided pharmaceutical care . Conclusion The provision of pharmaceutical care improved knowledge , QOL and satisfaction in Malaysian postmenopausal osteoporotic women , showing that pharmacists have the potential to improve patients ’ overall bone health . Policymakers should consider placing a clinical pharmacist in the osteoporosis clinic to provide counselling to improve these outcomes WHAT IS KNOWN AND OBJECTIVES About half of all patients taking antihypertensives discontinue treatment by 12 months . There is potential for substantial health gains at both individual and population levels through improved treatment adherence . The objective was to evaluate a community pharmacist intervention to improve adherence with antihypertensive medicines with a view to improving blood pressure ( BP ) control . METHODS DESIGN prospect i ve , non-blinded , cluster-r and omized , controlled trial . PARTICIPANTS adults with primary hypertension who obtained antihypertensives in the previous 6 months . Patients with poor refill adherence were preferentially identified with the help of a purpose -built software application . INTERVENTION package comprising BP monitor ; training on BP self-monitoring ; motivational interviewing ; medication use review ; prescription refill reminders . FOLLOW-UP six months . PRIMARY OUTCOME change in proportion self-reporting medication adherence . Secondary outcome : BP changes . RESULTS Participants ( n = 395 ; intervention - 207 ; control - 188 ) had a mean age of 66.7 years ; 51.1 % were males . The proportion of adherent participants increased in both groups but was not significantly different between groups [ 57·2 % to 63·6 % ( control ) vs. 60·0 % to 73·5 % ( intervention ) , P = 0·23 ] . The mean reduction in systolic BP was significantly greater in the intervention group ( 10·0 mmHg vs. 4·6 mmHg ; P = 0·05 ) . The proportion of patients who were non-adherent at baseline and adherent at 6 months was 22·6 % ( 95%CI 5·1 - 40·0 % ) higher in the intervention group ( 61·8 % vs. 39·2 % , P = 0·007 ) . Among participants with baseline BP above target , reduction of systolic BP was significantly greater in the intervention group [ by 7·2 mmHg ( 95%CI 1·6 - 12·8 mmHg ) ; ( P = 0·01 ) ] . Among participants non-adherent at baseline and above target BP , the proportion reporting adherence at 6 months was significantly greater in the intervention group [ 56·8 % vs. 35·9 % , P = 0·039 ) . WHAT IS NEW AND CONCLUSION This community pharmacist intervention result ed in improved adherence to antihypertensive medication and reduced systolic BP Major depression is associated with high burden , disability and costs . Non-adherence limits the effectiveness of antidepressants . Community pharmacists ( CP ) are in a privileged position to help patients cope with antidepressant treatment . The aim of the study was to evaluate the impact of a CP intervention on primary care patients who had initiated antidepressant treatment . Newly diagnosed primary care patients were r and omised to usual care ( UC ) ( 92 ) or pharmacist intervention ( 87 ) . Patients were followed up at 6 months and evaluated three times ( Baseline , and at 3 and 6 months ) . Outcome measurements included clinical severity of depression ( PHQ-9 ) , health-related quality of life ( HRQOL ) ( Euroqol-5D ) and satisfaction with pharmacy care . Adherence was continuously registered from the computerised pharmacy records . Non-adherence was defined as refilling less than 80 % of doses or having a medication-free gap of more than 1 month . Patients in the intervention group were more likely to remain adherent at 3 and 6 months follow-up but the difference was not statistically significant . Patients in the intervention group showed greater statistically significant improvement in HRQOL compared with UC patients both in the main analysis and PP analyses . No statistically significant differences were observed in clinical symptoms or satisfaction with the pharmacy service . The results of our study indicate that a brief intervention in community pharmacies does not improve depressed patients ' adherence or clinical symptoms . This intervention helped patients to improve their HRQOL , which is an overall measure of patient status OBJECTIVE To evaluate the effect of case management by a clinical pharmacist on glycemic control and preventive measures in patients with type 2 diabetes mellitus . STUDY DESIGN R and omized controlled trial in a university-affiliated primary care internal medicine clinic . METHODS We recruited 80 patients with poorly controlled type 2 diabetes mellitus . A clinical pharmacist provided evaluation and modification of pharmacotherapy , self-management diabetes education , and reinforcement of diabetes complications screening processes through clinic visits and telephone follow-up . The main clinical outcome was hemoglobin A1C ( HbA1C ) level ; process measures included HbA1C and low-density lipoprotein measurement , retinal examination , urine microalbumin testing ( or use of angiotensin-converting enzyme inhibitors ) , and monofilament screening for diabetic neuropathy . RESULTS Patients in the intervention and control groups were similar in age , sex , mean HbA1C levels ( 10.1 % and 10.2 % , respectively ; P = .65 ) , and current treatment regimens at baseline . Patients who received case management by the clinical pharmacist achieved greater reduction in HbA1C levels than those in the control group ( 2.1 % vs 0.9 % , P = .03 ) . Three of the 5 process measures were conducted more frequently in the intervention group than the control group , including low-density lipoprotein measurement ( 100.0 % vs 85.7 % , P = .02 ) , retinal examination ( 97.3 % vs 74.3 % ) , and monofilament foot screening ( 92.3 % vs 62.9 % ) . CONCLUSIONS Proactive diabetes case management by a pharmacist substantially improved glycemic control and diabetes process-of-care measures . This approach , integrated with and based in the primary care setting , was an effective and efficient approach to improving care , especially for those with poor glycemic control at baseline STUDY OBJECTIVE To implement and assess a community-based pharmaceutical care program for patients with asthma . DESIGN Prospect i ve , r and omized , controlled trial . SETTING Community pharmacies ( 11 control , 11 intervention ) in Malta . PATIENTS Community-dwelling patients with asthma . INTERVENTIONS A comprehensive asthma education and monitoring program was implemented . Intervention patients received verbal counseling , an educational video , an information leaflet , and subsequent monitoring with reinforcement ; control patients received routine dispensing services . MEASUREMENTS AND MAIN RESULTS Parameters assessed at baseline and at 4 , 8 , and 12 months were health-related quality of life , peak expiratory flow ( PEF ) , inhaler technique , compliance with therapy , hospitalization rates , days lost from work , asthma symptoms , and patient satisfaction . Health-related quality of life of the intervention patients improved at 12 months ( p=0.044 ) . In the same time period , PEF significantly decreased in control patients compared with intervention patients ( p=0.009 ) whereas inhaler technique improved in the intervention group ( p=0.021 ) . There were significantly fewer self-reported hospitalizations in intervention patients . CONCLUSIONS A community-based pharmaceutical care program was appreciated by the participants and had a positive impact on the vitality of patients with asthma , inhaler technique , and PEE BACKGROUND : Inappropriate use of medications is a significant problem in health care today . A possible solution to this problem may be achieved through better control of patients ' drug therapy . OBJECTIVE : To design a pharmaceutical care program for dyslipidemic patients within a community pharmacy setting that provides education in the areas of medication compliance and lifestyle modifications , while emphasizing the importance of achieving cholesterol goals to ensure improvement in quality of life . METHODS : Patients at an outpatient pharmacy volunteered to be surveyed for 16 weeks . Although both the intervention and control groups were surveyed , the r and omly selected intervention group was interviewed more frequently and more comprehensively . Cholesterol , triglycerides , glucose , weight , risk factors , drug-related problems ( DRPs ) , and quality of life were measured via a survey at the onset of the study and continually measured until the study 's conclusion . RESULTS : In the intervention group , 26 DRPs were detected , of which 24 were resolved ; in the control group , 26 DRPs were detected , of which 5 were resolved . When comparing initial and final blood cholesterol levels in the intervention group , the mean decrease was 27.0 ± 41.1 mg/dL ( p = 0.0266 ) ; in the control group , the average blood cholesterol level decreased by a mean of 1.4 ± 37.2 mg/dL ( p = 0.6624 ) . In the intervention group , the triglyceride level decreased an average of 50.5 ± 80.3 mg/dL ( p = 0.0169 ) , while the control group experienced a mean triglyceride level increase of 29.6 ± 118.5 mg/dL ( p = 0.1435 ) . As a result of the intervention , the quality of life in the intervention group was improved . CONCLUSIONS : Short-term pharmaceutical care plans developed in a retail pharmacy within the proper setting may contribute to improved blood lipid values , cardiovascular disease risk factors , and patients ' quality of life This prospect i ve , r and omized , controlled study evaluated the impact of pharmacist-initiated home blood pressure monitoring and intervention on blood pressure control , therapy compliance , and quality of life ( QOL ) . Subjects were 36 patients with uncontrolled stage 1 or 2 hypertension . Eighteen subjects received home blood pressure monitors , a diary , and instructions to measure blood pressure twice every morning . Home measurements were evaluated by a clinical pharmacist by telephone , and the patient 's family physician was contacted with recommendations if mean monthly values were 140/90 mm Hg or higher . Eighteen control patients did not receive home monitors or pharmacist intervention . Office blood pressure measurements and QOL surveys ( SF-36 ) were obtained at baseline and after 6 months . Mean absolute reductions in systolic and diastolic pressures were significantly reduced from baseline in intervention subjects ( 17.0 and 10.5 mm Hg , both p < 0.0001 ) but not in controls ( 7.0 and 3.8 mm Hg , p = 0.12 and p = 0.09 ) . More intervention subjects ( 8) had blood pressure values below 140/90 at 6 months compared with controls ( 4 ) . During the study 83.3 % ( 15 ) of intervention subjects had drug therapy changes versus 33 % ( 6 ) of controls ( p < 0.01 ) . Compliance and QOL were not significantly affected . Our data suggest that the combination of pharmacist intervention with home monitoring can improve blood pressure control in patients with uncontrolled hypertension . This may be related to increased modifications of drug regimens Abstract Background Physiological and psychological changes during puberty and a low adherence to complex treatment regimens often result in poor glycemic control in adolescents with type 1 diabetes mellitus ( T1DM ) . The benefit of pharmaceutical care in adults with diabetes mellitus type 2 has been explored ; however , evidence in adolescents with T1DM is scarce . Objective To evaluate the impact of pharmaceutical care in adolescents with T1DM provided by pharmacists , in collaboration with physicians and diabetes educators on important clinical outcomes ( e.g. , HbA1c and severe hypoglycemia ) Setting : At the outpatient Helios Paediatric Clinic and at the 12 regular community pharmacies of the study patients with 14 pharmacists in the Krefeld area , Germany , and at the University Pediatric Clinic with one clinical pharmacist on-site in Sarajevo , Bosnia-Herzegovina . Methods A r and omized , controlled , prospect i ve , multicenter study in 68 adolescents with T1DM . The intervention group received monthly structured pharmaceutical care visits delivered by pharmacists plus supplementary visits and phone calls on an as needed basis , for 6 months . The control group received usual diabetic care . Data were collected at baseline and after 3 and 6 months . Main outcome measures : The between-group difference in the change from baseline in glycosylated hemoglobin ( HbA1c ) and the number of severe hypoglycemic events in both groups . Results The improvement from baseline in HbA1c was significantly greater in the intervention group than in the control group after 6 months ( change from baseline −0.54 vs. + 0.32 % , p = 0.0075 ) , even after adjustment for country-specific variables ( p = 0.0078 ) . However , the effect was more pronounced after only 3 months ( −1.09 vs. + 0.23 % , p = 0.00002 ) . There was no significant between-group difference in the number of severe hypoglycemia events . ( p = 0.1276 ) . Conclusion This study suggests that multidisciplinary PhC may add value in the management of T1DM in adolescents with inadequate glycemic control . However , the optimal methods on how to achieve sustained , long-term improvements in this challenging population require further study STUDY OBJECTIVE To measure clinical , economic , and humanistic outcomes associated with a pharmacist-managed hypertension clinic compared with physician-managed clinics . DESIGN Prospect i ve , r and omized , comparative study . SETTING Managed care organization . PATIENTS A total of 330 patients with mild-to-moderate essential hypertension . INTERVENTION Hypertension care provided by either the pharmacist-managed hypertension clinic or physician-managed general medical clinics . MEASUREMENTS AND MAIN RESULTS Baseline and 6-month evaluations consisted of systolic and diastolic blood pressure measurements , a short-form health survey , and collection of health care utilization information . After treatment , blood pressure measurements were significantly lower ( p<0.001 ) in the pharmacist-managed hypertension clinic group than in the physician-managed clinic group . Patient satisfaction was significantly higher in the hypertension clinic group . Total costs for the hypertension clinic group were not different from those of the physician-managed clinic group ( $ 242.46 vs $ 233.20 , p=0.71 ) , but cost : effectiveness ratios were lower in the hypertension clinic group ( $ 27 vs $ 193/mm Hg for systolic blood pressure readings , and $ 48 vs $ 151/mm Hg for diastolic blood pressure readings ) . CONCLUSION In a hypertension clinic , pharmacists can be a cost-effective alternative to physicians in management of patients , and they can improve clinical outcomes and patient satisfaction This was a prospect i ve , cluster r and omized controlled trial in patients with uncontrolled hypertension aged 21 to 85 years ( mean , 61 years ) . Pharmacists made recommendations to physicians for patients in the intervention clinics ( n=101 ) but not patients in the control clinics ( n=78 ) . The mean adjusted difference in systolic blood pressure ( BP ) between the control and intervention groups was 8.7 mm Hg ( 95 % confidence interval [ CI ] , 4.4 - 12.9 ) , while the difference in diastolic BP was 5.4 mm Hg ( CI , 2.8 - 8.0 ) at 9 months . The 24-hour BP levels showed similar effects , with a mean systolic BP level that was 8.8 mm Hg lower ( CI , 5.0 - 12.6 ) and a mean diastolic BP level that was 4.6 mm Hg ( CI , 2.4 - 6.8 ) lower in the intervention group . BP was controlled in 89.1 % of patients in the intervention group and 52.9 % in the control group ( adjusted odds ratio , 8.9 ; CI , 3.8 - 20.7 ; P<.001 ) . Physician/pharmacist collaboration achieved significantly better mean BP values and overall BP control rates , primarily by intensification of medication therapy and improving patient adherence The impacts of three alternative models of pharmacist consultation on the use and cost of health care services were studied . Two studies were conducted concurrently in an HMO over two years . In one , 6000 patients were r and omly assigned to one of three consultation models ; in the other , the three models were implemented in six geographic regions of California ( 4600 patients ) . The models were ( 1 ) consultation about new or changed prescriptions as m and ated by state law ( state model ) , ( 2 ) consultation focused on selected high-risk ambulatory care patients ( Kaiser Permanente [ KP ] model ) , and ( 3 ) a control model . The patients were surveyed three times about their health status and satisfaction , and computerized data on health care use and cost were collected . The effect of the consultation models on the use and cost of health care services was examined across five risk groups that were based on drug-use profiles . An additional 37,750 patients ( 10 % of the patients residing in the areawide study sites ) were included in a supplemental analysis of the use and cost of health care services . There was no indication in the r and om-assignment study that pharmacist consultations affected either drug costs or the cost of office visits . Similar results were found in the areawide study , with the exception that the KP model was associated with lower drug costs than the control model . In the 10 % sample , the KP model appeared to be associated with lower office visit costs but higher drug costs . Both models were associated with a lower likelihood of a hospital admission and with lower total health care costs for some high-risk patients compared with the control model . Counseling patients about their medications may be unlikely to reduce medication costs or the cost of office visits but may reduce the likelihood of hospital admissions and the overall costs of health care services ; a combination of counseling patients at high risk for drug-related problems and counseling all patients about any new or changed prescription should be considered BACKGROUND Drug related problem ( DRPs ) is a key factor which will affect the outcome of therapy and safety . OBJECTIVE To assess the DRPs in type 2 diabetes mellitus ( T2DM ) patients and psychological aspects of patients by community pharmacists to observe the rate of DRP . METHODS Prospect i ve r and omized controlled intervention study involved T2DM patients and conducted in two community pharmacies at Kanpur from January 2012 to December 2012 . The assessment of DRPs was based on the PCNE . Changes in glycosylated hemoglobin ( HBA1c ) , low density lipoproteins ( LDL ) , blood pressure(BP ) , foot examinations , changes medical and medication utilization were studied . Using as control group , received usual care , and interventional group provided , intervened with use of the st and ard treatment guidelines ( STG ) . Research er provided the knowledge to community pharmacists and patients . Baseline and interventional data were collected at 0,3,6,9 and 12 months . RESULTS Over the 12 month study , participants ' average HBA1C reduced from 8.9 % at initial visit to 7.5 % . During this time , the eye examination rate was raised from 31 % to 48 % , and the foot examination rate was raised from 35 % to 50 % . CONCLUSION The intervention of pharmacists showed little influence on any of the intermediate health outcomes in T2DM AIM The aim of this study was to investigate the impact of a pharmacist-led pharmaceutical care programme , involving optimization of drug treatment and intensive education and self-monitoring of patients with heart failure ( HF ) within the United Arab Emirates ( UAE ) , on a range of clinical and humanistic outcome measures . METHODS The study was a r and omized , controlled , longitudinal , prospect i ve clinical trial at Al-Ain Hospital , Al-Ain , UAE . Patients were recruited from the general medical wards and from cardiology and medical outpatient clinics . HF patients who fulfilled the entrance criteria , and had no exclusion criteria present , were identified for inclusion in the study . After recruitment , patients were r and omly assigned to one of two groups : intervention group or control group . Intervention patients received a structured pharmaceutical care service while control patients received traditional services . Patient follow-up took place when patients attended scheduled outpatient clinics ( every 3 months ) . A total of 104 patients in each group completed the trial ( 12 months ) . The patients were generally suffering from mild to moderate HF ( NYHA Class 1 , 29.5 % ; Class 2 , 50.5 % ; Class 3 , 16 % ; and Class 4 , 4 % ) . RESULTS Over the study period , intervention patients showed significant ( P < 0.05 ) improvements in a range of summary outcome measures [ AUC ( 95 % confidence limits ) ] including exercise tolerance [ 2-min walk test : 1607.2 ( 1474.9 , 1739.5 ) m.month in intervention patients vs. 1403.3 ( 1256.5 , 1549.8 ) in control patients ] , forced vital capacity [ 31.6 ( 30.8 , 32.4 ) l.month in the intervention patients vs. 27.8 ( 26.8 , 28.9 ) in control patients ] , health-related quality of life , as measured by the Minnesota living with heart failure question naire [ 463.5 ( 433.2 , 493.9 ) unit.month in intervention patients vs. 637.5 ( 597.2 , 677.7 ) in control patients ; a lower score in this measure indicates better health-related quality of life ] . The number of individual patients who reported adherence to prescribed medications was higher ( P < 0.05 ) in the intervention group ( 85 vs. 35 ) , as was adherence to lifestyle advice ( 75 vs. 29 ) at the final assessment ( 12 months ) . There was a tendency to have a higher incidence of casualty department visits by intervention patients , but a lower rate of hospitalization . CONCLUSIONS The research provides clear evidence that the delivery of pharmaceutical care to patients with HF can lead to significant clinical and humanistic benefits Lack of information about medications coupled with high rates of utilization complicates compliance with medication regimens and increases the risk of adverse effects among older adults . We undertook a study of the efficacy of community-based interventions by pharmacists in a r and omly-allocated one-half of a sample of 284 older adults considered to be at high risk for medication-related problems . Information and attitudes towards prescription and over-the-counter medications did not differ significantly between the intervention and comparison groups , either before or after the pharmacist interventions . However , visits to physicians were significantly less in the intervention group , suggesting an important if unexpected impact on health-related behavior Background .An objective of pharmaceutical care is for pharmacists to improve patients ’ health-related quality of life ( HRQOL ) by optimizing medication therapy . Objectives .The objective of this study was to determine whether ambulatory care clinical pharmacists could affect HRQOL in veterans who were likely to experience a drug-related problem . Research Design . This was a 9-site , r and omized , controlled trial involving Veterans Affairs Medical Centers ( VAMCs ) . Patients were eligible if they met ≥3 criteria for being at high risk for drug-related problems . Enrolled patients were r and omized to either usual medical care or usual medical care plus clinical pharmacist interventions . HRQOL was measured with the SF-36 question naire administered at baseline and at 6 and 12 months . Results .In total , 1,054 patients were enrolled ; 523 were r and omized to intervention , and 531 to control . After patient age , site , and chronic disease score were controlled for , the only domain that was significantly different between groups over time was the bodily pain scale , which converged to similar values at the end of the study . Patients ’ rating of the change in health status in the past 12 months was statistically different between groups , intervention patients declining less ( −2.4 units ) than control subjects ( −6.3 units ) ( P < 0.004 ) . This difference was not considered clinical ly meaningful . However , a dose-response relationship was observed for general health perceptions ( P = 0.004 ) , vitality ( P = 0.006 ) , and change in health over the past year ( P = 0.007 ) . Conclusions .These results suggest that clinical pharmacists had no significant impact on HRQOL as measured by the SF-36 for veterans at high risk for medication-related problems To measure the effects of a collaborative care model that emphasized the role of clinical pharmacists in providing drug therapy management and treatment follow-up to patients with depression , we conducted a r and omized controlled trial at a staff model health maintenance organization . We compared the outcomes of subjects treated in this collaborative care model ( 75 patients , intervention group ) with subjects receiving usual care ( 50 patients , control group ) . After 6 months , the intervention group demonstrated a significantly higher drug adherence rate than that of the control group ( 67 % vs 48 % , odds ratio 2.17 , 95 % confidence interval 1.04 - 4.51 , p=0.038 ) . Patient satisfaction was significantly greater among members r and omly assigned to pharmacists ' services than among controls , and provider satisfaction surveys revealed high approval rates as well . Changes in re source utilization were favorable for the intervention group , but differences from the control group did not achieve statistical significance . Clinical improvement was noted in both groups , but the difference was not significant . Clinical pharmacists had a favorable effect on multiple aspects of patient care . Future studies of this model in other health care setting s appear warranted We evaluated a structured pharmaceutical care program for elderly patients ( > 65 yrs ) with congestive heart failure ( CHF ) based on objective measures of disease control , quality of life , and use of health care facilities in a r and omized , controlled , longitudinal , prospect i ve clinical trial . The 42 patients in group A received education from a pharmacist on the disease and its treatment , and lifestyle changes that could help control symptoms . Patients also were encouraged to monitor their symptoms and comply with prescribed drug therapy . If necessary , dosage regimens were simplified in liaison with hospital physicians . The 41 control patients ( group B ) received st and ard care . The following outcome measures were assessed in all patients at baseline ( before the start of the trial ) and at 3 , 6 , 9 , and 12 months : 2-minute walk test , blood pressure , body weight , pulse , forced vital capacity , quality of life [ disease-specific ( Minnesota Living with Heart Failure question naire ) and generic ( SF-36 ) ] , knowledge of symptoms and drugs , compliance with therapy , and use of health care facilities ( hospital admissions , visits to emergency room , emergency calls ) . Patients in group A showed improved compliance with drug therapy , which in turn improved their exercise capacity compared with those in group B ; education on management of symptoms , lifestyle changes , and dietary recommendations were also of benefit . Group A patients significantly improved knowledge of their drug therapy over the 12-month study and had fewer hospital admissions compared with group B patients . They also had improved outcomes compared with group B , despite the small sample s. An extension of this trial to other sites with pooling of results would provide additional evidence of the value of this structured program in elderly patients with CHF OBJECTIVE To investigate the role of clinical pharmacists in managing iron deficiency anaemia patients . METHODS A prospect i ve parallel r and omised controlled trial conducted in an outpatient clinic enrolled adult iron deficiency anaemia patients . Patients were r and omised into either an intervention or a control group . Patients in the intervention group were followed closely by a clinical pharmacist who offered pharmaceutical care services and worked closely with physicians to manage iron deficiency anaemia . Patients in the control group received the usual medical care . KEY FINDINGS One hundred and four patients were enrolled in the study . Eighty-two patients completed the 4 - 6 week study , with 43 patients in the intervention group and 39 patients in the control group . By the end of the study , 86 % of intervention group patients and 59 % of control group patients reached their haemoglobin goal values , with statistically significant improvement in intervention group patients versus control group patients ( P value = 0.006 ) . Most of the clinical pharmacist 's recommendations were adopted by physicians ( 83.9 % ) . CONCLUSION Clinical pharmacist interventions improved iron deficiency anaemia patients ' outcomes BACKGROUND The optimization of medication use during care transitions represents an opportunity to improve overall health-related outcomes . The utilization of clinical pharmacists during care transitions has demonstrated benefit , although the optimal method of integration during the care transition process remains unclear . OBJECTIVE To evaluate the impact of pharmacist-provided telephonic medication therapy management ( MTM ) on care quality in a care transitions program ( CTP ) for high-risk older adults . METHODS This prospect i ve , r and omized , controlled study was conducted from December 8 , 2011 , through October 25 , 2012 , in a primary care work group at a tertiary care academic medical center in the midwestern United States . High-risk elderly ( aged ≥60 years ) patients were r and omized to a pharmacist-provided MTM program via telephone or to usual care within an existing outpatient CTP . The primary outcome was the quality of medication prescribing and utilization based on the Screening Tool to Alert Doctors to the Right Treatment ( START ) and the Screening Tool of Older Persons ' Prescriptions ( STOPP ) scores . The secondary outcomes were medication utilization using a modified version of the Medication Appropriateness Index , hospital re source utilization within 30 days of discharge , and drug therapy problems . RESULTS Of 222 eligible high-risk patients , 25 were included in the study and were r and omized to the pharmacist MTM intervention ( N = 13 ) or to usual care ( N = 12 ) . No significant differences were found between the 2 groups in medications meeting the STOPP or START criteria . At 30-day follow-up , no significant differences were found between the 2 cohorts in medication utilization quality indicators or in hospital utilization . At 30-day follow-up , 3 ( 13.6 % ) patients had an emergency department visit or a hospital readmission since discharge . In all , 22 patients completed the study . Medication underuse was common , with 20 START criteria absent medications evident for all 25 patients at baseline , representing 15 ( 60 % ) patients with ≥1 missing medications . Overall , 55 drug therapy problems were identified at baseline , 24 ( 43.6 % ) of which remained unresolved at 30-day follow-up . CONCLUSION The use of a pharmacist-provided MTM program did not achieve a significant difference compared with usual care in an existing CTP ; however , the findings demonstrated frequent utilization of inappropriate medications as well as medication underuse , and many drug therapy problems remained unresolved . The small size of the study may have limited the ability to detect a difference between the intervention and usual care groups BACKGROUND The multidisciplinary approach to managing heart failure has been shown to improve outcomes . The role of a clinical pharmacist in treating heart failure has not been evaluated . METHODS One hundred eighty-one patients with heart failure and left ventricular dysfunction ( ejection fraction < 45 ) undergoing evaluation in clinic were r and omized to an intervention or a control group . Patients in the intervention group received clinical pharmacist evaluation , which included medication evaluation , therapeutic recommendations to the attending physician , patient education , and follow-up telemonitoring . The control group received usual care . The primary end point was combined all-cause mortality and heart failure clinical events . All clinical events were adjudicated by a blinded end point committee . RESULTS Baseline characteristics were similar except for slightly higher age in the intervention group . Median follow-up was 6 months . All-cause mortality and heart failure events were significantly lower in the intervention group compared with the control group ( 4 vs 16 ; P= .005 ) . In addition , patients in the intervention group received higher angiotensin-converting enzyme inhibitor doses as reflected by the median fraction of target reached ( 25th and 75th percentiles ) , 1.0 ( 0.5 and 1 ) and 0.5 ( 0.1875 and 1 ) in the intervention and control groups , respectively ( P<.001 ) . The use of other vasodilators in angiotensin-converting enzyme inhibitor-intolerant patients was higher in the intervention group ( 75 % vs 26 % ; P= .02 ) . CONCLUSIONS Outcomes in heart failure can be improved with a clinical pharmacist as a member of the multidisciplinary heart failure team . This observation may be due to higher doses of angiotensin-converting enzyme inhibitors and /or closer follow-up INTRODUCTION Achievement and maintenance of good asthma control is a major objective in asthma management . However , asthma control in many patients is suboptimal , due to improper use of asthma medications and non-adherence . The aim of this study was to evaluate the effect of a pharmacist intervention on asthma control in adult patients . METHODS A 6-month cluster r and omized controlled trial was undertaken with allocation of community pharmacies to intervention or control group . Adult asthma patients in the intervention group received a protocol -based intervention addressing individual needs related to asthma control , inhaler technique and medication adherence . Patients in the control group received usual care . Main variables were measured at baseline , 3 and 6 months . RESULTS 336 patients completed the study , 150 in the control group and 186 in the intervention group . The intervention result ed in enhanced asthma control : Patients receiving the intervention had an Odds ratio of 3.06 ( 95 % CI:1.63 - 5.73 ; p < 0.001 ) of having controlled asthma six months later . In the intervention group mean ACQ scores significantly improved [ 0.66 points ( SD : 0.78 ) ; p < 0.001 ] and the number of controlled asthma patients increased by 30.1 % ( p < 0.001 ) after 6 months . The intervention also result ed in improved medication adherence ( by 40.3 % , p < 0.001 ) and inhaler technique ( by 56.2 % , p < 0.001 ) . No significant changes for any of these variables were observed in the control group . CONCLUSION The AFasma study focused on the important outcomes of asthma management , and showed that through the design ed intervention , community pharmacists can increase controlled asthma patients compared to usual care . Trial registration NCT01085474 Instruction is critical in order to ensure correct technique with pressurized metered-dose inhalers ( pMDIs ) by patients . The aim of this study was to compare the effects over time of two educational interventions delivered in community pharmacy to pMDI users . In this r and omized controlled parallel-group study , pMDI technique was assessed before and after written and verbal instruction , alone or with physical demonstration , at baseline and 4 , 8 , and 16 weeks . The study recruited 52 subjects with asthma or chronic obstructive pulmonary disease ( COPD ) . Initially only 1/52 ( 6 % ) subject had correct pMDI technique (= checklist score 8/8 ) , with mean baseline score 5 ( SD 1 ) for both groups . Written and verbal information improved pMDI technique at 16 weeks ( 7 ± 1 , p < .05 ) . Addition of physical demonstration result ed in significant improvement at weeks 4 , 8 , and 16 ( 7 ± 1 , 7 ± 1 , 7 ± 1 respectively ; p < .05 for each ) . Subjects receiving written and verbal information alone were less likely to return for follow-up than those receiving physical demonstration ( 8 weeks : 6/25 versus 19/27 ; p < .001 ) . By the 8-week visit , 80 % subjects in the physical demonstration group had correct technique prior to education , compared with 10 % of subjects receiving written and verbal information alone ( p < .05 ) . There was some decline in inhaler technique by 16 weeks . The results demonstrate that adding a physical demonstration is more effective in improving pMDI technique than written and verbal instructions alone OBJECTIVES The objectives of this study were to evaluate the effects of medication education and behavioral intervention on Chinese patients with epilepsy and to compare the difference between them . METHODS A total of 109 patients with epilepsy who did not to take their antiepileptic drugs ( AEDs ) more than once were r and omly assigned to two intervention groups : the medication education group ( group I ) and the medication education with behavioral intervention group ( group II ) . Group I was initially provided with medication education in the form of oral education and written material s , and this education was reinforced by monthly calls from the pharmacist over the next six months . The behavioral intervention provided to group II consisted of a modified medication schedule which was based on cue-dose training therapy . The outcomes that were evaluated both in the beginning and in the end of the study included adherence , which was measured using the four-item Morisky Medication Adherence Scale ( MMAS-4 ) , the number of seizures , knowledge of AEDs , and the number of patients who missed a dose of their AEDs . Differences within and between the groups were analyzed . RESULTS After intervention , the adherence and knowledge of AEDs increased greatly in all patients , and the number of patients who had seizures or missed AEDs decreased . However , no significant differences were observed between groups I and II . The observed changes were ( group I vs group II , p value ) increased adherence : 62.3 % vs 64.3 % , 0.827 ; increased knowledge of AEDs : 88.7 % vs 80.4 % , 0.231 ; and improved seizure control : 64.2 % vs 64.3 % , 0.988 . In addition , the percentage of patients who forgot to take their AEDs decreased to 45.0 % from more than 70 % , and 44.9 % of these patients took the missed AEDs as soon as they remembered . DISCUSSION These findings clearly demonstrate that medication education and reinforced telephone calls from pharmacists can help to increase adherence to AEDs , the knowledge of patients regarding AEDs , and seizure control . However , the inclusion of a behavioral strategy that was easy to administer and use in this program did not lead to any significant effects on improving adherence . The results indicate that pharmacists can play an important role in improving the effects of medication regimens , but further research is required to identify strategies for improving adherence to behavioral theory Background : Dyslipidemia is an important risk factor for cardiovascular disease but is suboptimally managed . Pharmacists are accessible primary care professionals and with exp and ed scopes of practice ( including prescribing ) , could identify and manage patients with dyslipidemia . We sought to evaluate the effect of pharmacist prescribing of dyslipidemia medications on the proportion of participants achieving target LDL-cholesterol ( LDL-c ) levels . Methods : We conducted a r and omized controlled trial in 14 community pharmacies in Alberta , Canada . We enrolled adults with uncontrolled dyslipidemia as defined by the 2009 Canadian Dyslipidemia Guidelines . Intervention was pharmacist-directed dyslipidemia care , including assessment of cardiovascular risk , review of LDL-c , prescribing of medications , health behaviour interventions and follow-up every 6 weeks for 6 months . Usual care patients received their lipid results and a pamphlet on cardiovascular disease and usual care from their physician and pharmacist . Primary outcome was the proportion of participants achieving their target LDL-c ( < 2 mmol/L or ≥50 % reduction ) at 6 months between groups . Results : We enrolled 99 patients with a mean ( SD ) age of 63 ( 13 ) years , 49 % male and baseline LDL-c of 3.37 mmol/L ( 0.98 ) . Proportion of patients achieving LDL-c target was 43 % intervention versus 18 % control ( p = 0.007 ) . Adjusted odds of achieving target LDL-c were 3.3 times higher for the intervention group ( p = 0.031 ) , who also achieved greater reduction in LDL-c ( 1.12 mmol/L , SE = 0.112 ) versus control ( 0.42 mmol/L , SE = 0.109 ) , for an adjusted mean difference of 0.546 mmol/L ( SE = 0.157 ) , p < 0.001 . Conclusion : Pharmacist prescribing result ed in > 3-fold more patients achieving target LDL-c levels . This could have major public health implication PURPOSE The impact of pharmacist interventions on the care and outcomes of patients with depression in a primary care setting was evaluated . METHODS Patients diagnosed with a new episode of depression and started on anti-depressant medications were r and omized to enhanced care ( EC ) or usual care ( UC ) for one year . EC consisted of a pharmacist collaborating with primary care providers to facilitate patient education , the initiation and adjustment of antidepressant dosages , the monitoring of patient adherence to the regimen , the management of adverse reactions , and the prevention of relapse . The patients in the UC group served as controls . Outcomes were measured by the Hopkins Symptom Checklist , Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , criteria for major depression , health-related quality of life , medication adherence , patient satisfaction , and use of depression-related health care services . An intent-to-treat analysis was used . RESULTS Seventy-four patients were r and omized to EC or UC . At baseline , the EC group included more patients diagnosed with major depression than did the UC group ( p = 0.04 ) . All analyses were adjusted for this difference . In both groups , mean scores significantly improved from baseline for symptoms of depression and quality of life at three months and were maintained for one year . There were no statistically significant differences between treatment groups in depression symptoms , quality of life , medication adherence , provider visits , or patient satisfaction . CONCLUSION Frequent telephone contacts and interventions by pharmacists and UC in a primary care setting result ed in similar rates of adherence to antidepressant regimens and improvements in the outcomes of depression at one year OBJECTIVE : To develop a pharmacist intervention to improve depression care and outcomes within a primary care setting . METHODS : Pragmatic , r and omized trial of a clinical pharmacist collaborative care intervention versus usual care in a busy , academic family practice clinic . RESULTS : Seventy-four patients diagnosed with a new episode of major depression and started on antidepressant medications were r and omized to enhanced care ( EC ) or usual care ( UC ) groups . EC consists of a clinical pharmacist collaborating with primary care providers ( PCPs ) to facilitate education , initiation , and titration of acute-phase antidepressant treatment to monitor treatment adherence and to prevent relapse . Control patients receive UC by their PCP . The main end point is reduction of depression symptoms over time as measured by the Hopkins Symptom Checklist ( SCL-20 ) . Other outcomes include the Diagnostic and Statistical Manual of Mental Disorders , ( DSM-IV ) criteria for major depression , health-related quality of life measured by the Medical Outcomes Study Short Form 12 ( SF-12 ) , medication adherence , patient satisfaction , and healthcare utilization . The main end point and the cost of treating major depression will be used to estimate the cost-effectiveness of the collaborative care model . CONCLUSIONS : The study is a unique , ongoing trial that may have important implication s for the treatment of depression in primary care setting s as well as new roles for clinical pharmacists Involvement of pharmacists in improving medication adherence among diabetic patients is recognized globally . In Malaysian healthcare system , pharmacists are also operating health services i.e. Diabetes Medication Therapy Adherence Clinic ( DMTAC ) . This study aim ed to assess the clinical outcomes of patients managed by pharmacists ( DMTAC ) , in a Malaysian hospital setting . This was an open labelled r and omised study . Type 2 diabetes patients with HbA1c ≥8 % were recruited and arbitrarily divided into the intervention group ( usual care plus DMTAC ) and the non-intervention group ( usual care only ) . Those enrolled in the intervention group were scheduled for follow-up for eight consecutive visits . Improvements in lab results were compared longitudinally ( pre and post analysis ) between the groups . Data analysis was done using PASW 18 ® version . A total of 76 patients were enrolled , with 39 patients in the intervention group and 37 patients in the non-intervention group . Mean HbA1c ( -0.90 % vs. -0.08 % , p=0.011 ) and fasting blood glucose levels ( -3.45 mmol.l vs. + 0.79 mmol/l , p=0.002 ) reduced significantly between the intervention group vs. non-intervention group . Total cholesterol and low-density lipoprotein cholesterol ( LDL-C ) were also significantly reduced in the intervention group ( TC -0.34 mmol/l , p=0.018 ) ( LDL -0.45 mmol/l , p=0.001 ) . In conclusion , pharmacists managed DMTAC significantly improved glycaemic control and lipid profile of diabetic patients AIMS To examine the influence of a pharmaceutical care programme on disease control and health-related quality of life in Type 2 diabetes patients in the United Arab Emirates . METHODS A total of 240 Type 2 diabetes patients were recruited into a r and omized , controlled , prospect i ve clinical trial with a 12-month follow-up . A range of clinical measures , medication adherence and health-related quality of life ( Short Form 36 ) were evaluated at baseline and up to 12 months . Intervention group patients received pharmaceutical care from a clinical pharmacist , whereas control group patients received their usual care from medical and nursing staff . The primary outcome measure was change in HbA(1c ) . British National Formulary and Framingham scoring methods were used to estimate changes in 10-year coronary heart disease risk scores in all patients . RESULTS A total of 234 patients completed the study . Significant reductions ( P < 0.001 ) in mean values ( baseline vs. 12 months ; 95 % confidence interval ) of HbA(1c)[8.5 % ( 8.3 , 8.7 ) vs. 6.9 % ( 6.7 , 7.1 ) ] , systolic [ 131.4 mmHg ( 128.1 , 134.7 ) vs. 127.2 mmHg ( 124.4 , 130.1 ) ] and diastolic blood pressure [ 85.2 mmHg ( 83.5 , 86.8 ) vs. 76.3 mmHg ( 74.9 , 77.7 ) ] were observed in the intervention group ; no significant changes were noted in the control group . The mean Framingham risk prediction score in the intervention group was 10.56 % ( 9.7 , 11.4 ) at baseline ; this decreased to 7.7 % ( 6.9 , 8.5 ) ( P < 0.001 ) at 12 months but remained unchanged in the control group . CONCLUSIONS The pharmaceutical care programme result ed in better glycaemic control and reduced cardiovascular risk scores in Type 2 diabetes patients over a 12-month period ABSTRACT Background It is important to underst and which components of successful multifaceted interventions are responsible for study outcomes , since some components may be more important contributors to the intervention effect than others . Objective We conducted a mediation analysis to determine which of seven factors had the greatest effect on change in systolic blood pressure ( BP ) after 6 months in a trial to improve hypertension control . Design The study was a preplanned secondary analysis of a cluster-r and omized clinical trial . Eight clinics in an integrated health system were r and omized to provide usual care to their patients ( n = 222 ) , and eight were r and omized to provide a telemonitoring intervention ( n = 228 ) . Participants Four hundred three of 450 trial participants completing the 6-month follow-up visit were included . Interventions Intervention group participants received home BP telemonitors and transmitted measurements to pharmacists , who adjusted medications and provided advice to improve adherence to medications and lifestyle modification via telephone visits . Main measures Path analytic models estimated indirect effects of the seven potential mediators of intervention effect ( defined as the difference between the intervention and usual care groups in change in systolic BP from baseline to 6 months ) . The potential mediators were change in home BP monitor use , number of BP medication classes , adherence to BP medications , physical activity , salt intake , alcohol use , and weight . Key Results The difference in change in systolic BP was 11.3 mmHg . The multivariable mediation model explained 47 % ( 5.3 mmHg ) of the intervention effect . Nearly all of this was mediated by two factors : an increase in medication treatment intensity ( 24 % ) and increased home BP monitor use ( 19 % ) . The other five factors were not significant mediators , although medication adherence and salt intake improved more in the intervention group than in the usual care group . Conclusions Most of the explained intervention effect was attributable to the combination of self-monitoring and medication intensification . High adherence at baseline and the relatively low intensity of re sources directed toward lifestyle change may explain why these factors did not contribute to the improvement in BP Few studies have demonstrated an effect of educational interventions on glycaemic control in persons with Type 2 diabetes longer than 3 - 6 months after baseline . We aim ed to investigate the effectiveness of an experience-based group educational programme 24 months after baseline and to pinpoint mediators that might play a role in achieving desired metabolic outcomes . We conducted a r and omised controlled trial inviting self-referred persons with Type 2 diabetes ( N=77 r and omised ) . The pharmacist-led , year-long intervention was based on participants ' experiences of glucose regulation during the monthly group discussion s. We measured HbA1c at 0 , 6 , 12 , and 24 months and a question naire was administered at baseline and final follow-up . Our findings indicated that participating in the intervention programme significantly decreased HbA1c by 0.4 % at 24 months after baseline . Initial HbA1c , satisfaction with own diabetes-related knowledge , and treatment were found directly related to glycaemic outcomes . The intervention group exercised more in order to lower blood-glucose levels and was also more able to predict current blood-glucose levels before measuring it . Experience-based group education was effective in decreasing participants ' HbA1c 1-year after completed intervention . Early effect of the intervention was followed by relapse after 12 months and a new , significant decrease at 24 months ; this dual course implies that follow-up of educational interventions should involve several consecutive measurements to capture possible late effects . Both biomedical and subjective factors played a role in accounting for the variance of HbA1c at 2-year follow-up after baseline Purpose The purpose of the study was to investigate the efficacy of a community pharmacist – delivered diabetes support program for patients receiving specialty medical care in a middle-income country ( Iran ) . Methods A r and omized controlled trial was conducted on 101 patients who received diabetes care from an endocrinologist . A qualified community pharmacist educated patients about medications , clinical goals , self-care activities , and self-monitoring of blood glucose . The pharmacist trained patients in the intervention group for 5 months ( 5 follow-up visits and 5 phone calls ) and recommended physician visits when necessary . The primary outcome was A1C , and the secondary outcomes included self-care activities , medication adherence , blood pressure , and body mass index . Satisfaction and willingness to pay was assessed in the intervention group . Results Eighty-five patients completed the study , and baseline A1C was similar between groups ( intervention : 7.6 ± 1.6 [ 59 mmol/mol ] vs control : 7.5 ± 1.9 [ 58 mmol/mol ] ) . No significant difference was observed between study groups at the end of the trial period ; however , the amount of A1C reduction was higher in the intervention group ( 1.0 % ± 1.5 % vs 0.5 % ± 1.5 % ) . Self-care activity was improved in general diet , blood glucose monitoring , and foot care subcategories in the intervention group . Medication adherence and body mass index were significantly improved in the intervention group at the end of study . Conclusions A community pharmacist intervention improved self-care activity , medication adherence , and body mass index in patients receiving specialty medical care . Baseline A1C values and the presence of specialty medical care should be considered in the interpretation of clinical findings Purpose : Medication errors related to hospital discharge result in rehospitalization and emergency department ( ED ) visits , yet no systematic approach has been implemented nationally to decrease these medication errors . Pharmacist involvement during postdischarge transitions of care may be an important strategy to prevent and correct medication discrepancies and reduce costly rehospitalization and ED visits . Methods : This prospect i ve , r and omized , open-label , pilot study evaluated the effect of a pharmacy clinic visit focused on medication reconciliation and patient education after hospital discharge on the incidence of rehospitalization and ED visits and the resolution of medication discrepancies . Results : Of the 61 subjects included in the study , 33 ( 54 % ) had medication discrepancies identified at discharge . Fifty percent of medication discrepancies were resolved in subjects r and omized to the pharmacist intervention arm compared with 9.5 % in the usual care arm ( P = .015 ) . Patients r and omized to the intervention arm had significantly lower rates of the primary composite outcome of 30-day rehospitalization and ED visits compared with the usual care arm ( 0 % vs 40.5 % , P < .001 ) . Conclusion : A pharmacist-driven intervention focused on patient education and medication reconciliation after discharge improved medication use and reduced health care re source utilization in this pilot study OBJECTIVES A number of studies have reported that the risk of bleeding associated with warfarin is highest early in the course of therapy . This study examined the effect of a programme focused on the transition of newly anticoagulated patients from hospital to the community . DESIGN Open-label r and omized controlled trial . SETTING Home-based follow-up of patients discharged from acute care hospital in southern Tasmania , Australia . SUBJECTS A total of 128 patients initiated on warfarin in hospital and subsequently discharged to general practitioner ( GP ) care were enrolled in the study . Sixty were r and omized to home monitoring ( HM ) and 68 received usual care ( UC ) . INTERVENTIONS HM patients received a home-visit by the project pharmacist and point-of-care international normalized ratio ( INR ) testing on alternate days on 4 occasions , with the initial visit two days after discharge . The UC group was solely managed by the GP and only received a visit 8 days after discharge to determine anticoagulant control . RESULTS At discharge , 42 % of the HM group and 45 % of the UC group had a therapeutic INR . At day 8 , 67 % of the HM patients had a therapeutic INR , compared with 42 % of UC patients ( P < 0.002 ) . In addition , 26 % of UC patients had a high INR , compared with only 4 % of HM patients . Bleeding events were assessed 3 months after discharge and occurred in 15 % of HM patients , compared with 36 % of the UC group ( P < 0.01 ) . CONCLUSIONS This programme improved the initiation of warfarin therapy and result ed in a significant decrease in haemorrhagic complications in the first 3 months of therapy OBJECTIVE To assess whether home-based medication review by a pharmacist for at-risk older patients in a primary care setting can reduce hospital admissions . DESIGN R and omised controlled trial comparing home-based medication review with st and ard care . SETTING Home-based medication review of 136 patients registered with one general practice . METHOD Study participants were over 80 years of age , living at home , taking four or more medicines , and had at least one additional medicines-related risk factor . The intervention comprised two home visits by a community pharmacist who educated the patient/carer about their medicines , noted any pharmaceutical care issues , assessed need for an adherence aid , and subsequently met with the lead GP to agree on actions . MAIN OUTCOME MEASURE Total non-elective hospital admissions within 6 months . Secondary outcomes included number of deaths , care home admissions and quality of life ( EQ-5d ) . Impact on number of medicines prescribed was also assessed . RESULTS At 6 months , no difference in hospital admissions ( 21 intervention versus 20 control P = 0.80 ) , and no difference in care home admissions or deaths were detected between groups . There was a small ( non-significant ) decrease in quality of life in the intervention group . There was a statistically significant reduction in the mean number of medicines prescribed ( -0.87 items in favour of the intervention group , 95 % confidence interval -1.66 to -0.08 , P = 0.03 ) . CONCLUSIONS No positive impact on clinical outcomes or quality of life was demonstrated , however , this intervention did appear to reduce prescribing . This is in line with other evidence and suggests that this form of intervention may not have a clear health gain , but may lead to modest savings in terms of reduced prescribing . Future research should focus on whether such a prescribing effect would make this type of intervention cost effective The study determined pharmacist support on patients receiving multi-drug therapy for coronary heart disease by evaluating patient self-care ability , quality of life , and drug therapy compliance . In this study , ninety patients were r and omly assigned to an experimental group ( n=45 ) and a control group ( n=45 ) . The control group received conventional clinical care . The experimental group received clinical care plus pharmacist support that included medication review , patient education , lifestyle management , discharge guidance , and telephone follow-up . Eighty-five patients completed the study . Self-care ability and quality of life were evaluated before hospital discharge . The experimental group understood their condition better than the control group ( P<0.05 ) , the differences between the groups in underst and ing treatment goals , drug regimens , lifestyle modifications , psychogenic disorders , and satisfaction evaluations were more pronounced ( P<0.01 ) . At six-month follow-up , the difference between the groups in drug therapy compliance was P<0.01 , as was success rate by intention-to-treat ( 77.8 % vs. 48.9 % ) and per- protocol ( 81.4 % vs. 52.4 % ) . Two adverse drug reactions occurred in the experimental group and three in the control group . Pharmacist support improved self-care ability , quality of life , drug therapy compliance , and treatment success rate in coronary heart disease patients Background Chronic obstructive pulmonary disease ( COPD ) treatment goals are often not achieved despite the availability of many effective treatments . Furthermore , clinical pharmacist interventions to improve clinical and humanistic outcomes in COPD patients have not yet been explored and few r and omized controlled trials have been reported to evaluate the impact of pharmaceutical care on health outcomes in patients with COPD . Objective The aim of the present study was to evaluate the impact of pharmaceutical care intervention , with a strong focus on self-management , on a range of clinical and humanistic outcomes in patients with COPD . Setting Outpatient COPD Clinic at the Royal Medical Services Hospital . Method In a r and omised , controlled , prospect i ve clinical trial , a total of 133 COPD patients were r and omly assigned to intervention or control group . A structured education about COPD and management of its symptoms was delivered by the clinical pharmacist for patients in the intervention group . Patients were followed up at 6 months during a scheduled visit . Effectiveness of the intervention was assessed in terms of improvement in health-related quality of life , medication adherence , disease knowledge and healthcare utilization . Data collected at baseline and at the 6 month assessment was coded and entered into SPSS ® software version 17 for statistical analysis . A P value of < 0.05 was considered statistically significant . Main outcome measure The primary outcome measure was health-related quality of life improvement . All other data collected including healthcare utilization , COPD knowledge and medication adherence formed secondary outcome measures . Results A total of 66 patients were r and omized to the intervention group and 67 patients were r and omized to the control group . Although the current study failed to illustrate significant improvement in health-related quality of life parameters , the results indicated significant improvements in COPD knowledge ( P < 0.001 ) , medication adherence ( P < 0.05 ) , medication beliefs ( P < 0.01 ) and significant reduction in hospital admission rates ( P < 0.05 ) in intervention patients when compared with control group patients at the end of the study . Conclusion The enhanced patient outcomes as a result of the pharmaceutical care programme in the present study demonstrate the value of an enhanced clinical pharmacy service in achieving the desired health outcomes for patients with COPD OBJECTIVE To evaluate the effect of teamwork ( physician and pharmacist ) on the management of uncontrolled hypertensive patients . METHODS This is a r and omized controlled clinical trial conducted from March to November 2009 . Patients attending the Family Medicine Clinic at Jordan University Hospital , Amman , Jordan with uncontrolled hypertension were invited to participate in the study . A total of 253 patients were r and omly allocated to an intervention ( n=130 ) or control group . In the intervention group , patients were managed by a physician-pharmacist team . In the control group , patients were managed by physician(s ) only . RESULTS In the intervention group , 79.4 % of patients achieved blood pressure ( BP ) goals specified by the Joint National Committee on Prevention and Management , Detection , Evaluation , and Treatment of High Blood Pressure ( JNC VII ) compared to 65.6 % in the control group ( p=0.01 ) . Decline in systolic BP was 16.1 + /- 14.6 mm Hg in the intervention group , and 10.6 + /- 13.5 mm Hg in the control group ( p=0.002 ) . Reduction in diastolic BP was 10.5 + /- 12.9 mm Hg in the intervention group , and 7.17 + /- 13.11 mm Hg in the control group , ( p=0.04 ) . Data were presented as mean + /- st and ard deviation . CONCLUSION This study found that the physician-pharmacist collaborative approach to uncontrolled hypertension in Jordan improved the rate of BP control in hypertensive patients , and result ed in more profound decline in both systolic and diastolic BP , and this will probably reflect on better outcomes in cardiovascular diseases . Establishing pharmaceutical care managed clinic in the setting of outpatient-clinics is possible , and provides better management of patients Background Elderly polypharmacy patients may be more at risk of not adhering to medication . If so , the underlying reasons may be more readily disclosed during private discussion s with patients . Hence pharmaceutical care discussion s at home might improve treatment adherence . Objective The aim of this study was to investigate the impact of pharmaceutical care on medication adherence , hospitalisation and mortality in elderly patients prescribed polypharmacy . Setting Pharmaceutical care discussed at home . Methods A r and omised controlled trial with two arms ; pharmaceutical care ( n = 315 ) and controls ( n = 315 ) was design ed . It involved patients aged 65 + years living in Aarhus , Denmark who used five drugs or more without assistance . Pharmacists visited the pharmaceuticalcare patients at home , once only , and followed them during the subsequent year with three telephone calls . Non-adherence was measured by a pill-count . Patients were categorised as non-adherent if their mean adherence rate for all drugs consumed was < 80 % . The impact of pharmaceutical care on non-adherence and hospitalisation was analysed by 2 × 2 tables , and mortality by Cox regression . Main outcome measure Medication adherence , hospitalisation and mortality . Results The final analyses included 517 patients ( median age 74 years ; females 52 % ) . Dropouts were more frequent for the pharmaceutical-care group than for controls . Pharmacists encountered drug-related problems amongst 72 % of pharmaceutical-care patients . Pharmaceutical-care patients ( 11 % ) and control patients ( 10 % ) were similarly nonadherent ( Odds ratio 1.14 ; 95 % confidence interval 0.65–2.00 ) , and similar with respect to hospitalisation frequency ( 30 vs. 28 % ; Odds ratio 1.14 ; 95 % confidence interval 0.78–1.67 ) and mortality ( 7.5 vs. 5 % ; Hazard ratio 1.41 ; 95 % confidence interval 0.71–2.82 ) . Conclusions Pharmaceutical care given to our elderly polypharmacy patients made no significant impact on medication adherence , hospitalisation or mortality , when compared to comparable control patients OBJECTIVES To evaluate the impact of pharmaceutical care ( PC ) intervention on health-related quality of life ( HRQOL ) of patients with type 2 diabetes . METHODS This study was a r and omized , controlled study with a 12-month patient follow-up . The study protocol was approved by the Research Ethical Committees of the institutions in which this study was conducted . A total of 110 patients were r and omly assigned to each of the " intervention " ( PC ) and " control " ( usual care [ UC ] ) groups . Patients in the UC group received the usual/conventional care offered by the hospitals . Patients in the PC group received UC and additional PC for 12 months . The HUI23S4EN.40Q ( developed by HUInc - Mark index 2&3 ) question naire was used to assess the HRQOL of the patients at baseline , 6 months , and 12 months . Two- sample comparisons were made by using Student 's t tests for normally distributed variables or Mann-Whitney U tests for nonnormally distributed data at baseline , 6 months , and 12 months . Comparisons of proportions were done by using the chi-square test . RESULTS The overall HRQOL ( 0.86 ± 0.12 vs. 0.64 ± 0.10 ; P < 0.0001 ) and single attributes except " hearing " functioning of the patients were significantly improved at 12 months in the PC intervention arm when compared with the UC arm . The HRQOL utility score was highly negatively ( deficit ≥10 % ) associated with increasing age ( ≥52 years ) , diabetes duration ( > 4 years ) , emergency room visits , comorbidity of hypertension , and stroke in both PC and UC groups . CONCLUSION Addition of PC to UC improved the quality of life in patients with type 2 diabetes Objective : To measure length of hospital stay ( LHS ) in patients receiving medication reconciliation . Secondary characteristics included analysis of number of preadmission medications , medications prescribed at admission , number of discrepancies , and pharmacists interventions done and accepted by the attending physician . Methods : A 6 month , r and omized , controlled trial conducted at a public teaching hospital in southern Brazil . Patients admitted to general wards were r and omized to receive usual care or medication reconciliation , performed within the first 72 hours of hospital admission . Results : The r and omization process assigned 68 patients to UC and 65 to MR . LHS was 10±15 days in usual care and 9±16 days in medication reconciliation ( p=0.620 ) . The total number of discrepancies was 327 in the medication reconciliation group , comprising 52.6 % of unintentional discrepancies . Physicians accepted approximately 75.0 % of the interventions . Conclusion : These results highlight weakness at patient transition care levels in a public teaching hospital . LHS , the primary outcome , should be further investigated in larger studies . Medication reconciliation was well accepted by physicians and it is a useful tool to find and correct discrepancies , minimizing the risk of adverse drug events and improving patient safety Context Patients sometimes have difficulty following complicated treatment regimens . Contribution In this trial , 314 low-income patients with congestive heart failure were r and omly assigned to a pharmacist intervention or usual care . The pharmacist assessed patient knowledge and provided instructions about medication use . During the 9-month intervention , patients in the intervention group had greater medication adherence than patients in the usual care group ( 79 % vs. 68 % ) . These differences dissipated within 3 months of stopping the intervention . Patients in the intervention group also had fewer exacerbations result ing in emergency department visits or hospitalizations than patients in the usual care group . Implication Ongoing educational intervention by a pharmacist can improve medication adherence and outcomes in patients with heart failure . The Editors In the United States , 5 million people have heart failure , with total health care costs exceeding $ 29 billion ( 1 ) . These costs are largely derived from expensive exacerbations that require emergency visits and hospitalizations ( 1 , 2 ) . Regularly administered cardiovascular medications may preserve cardiac function , improve quality of life , and reduce risk for costly exacerbations . However , patients sometimes do not adhere to prescribed instructions and have poor outcomes ( 35 ) . Research ers have estimated that approximately 50 % of patients with chronic illnesses do not take their medications as prescribed ( 6 ) . Reasons for nonadherence include lack of patient knowledge , skills , and support to appropriately self-manage complicated medication regimens ( 7 , 8) . Although chronic disease management programs abound , few studies have rigorously tested interventions aim ed at improving patient adherence to prescribed medications and their effect on health outcomes ( 9 , 10 ) . We conducted a r and omized clinical trial to assess the effect of a pharmacist intervention on patients who are socioeconomically disadvantaged and medically vulnerable . We hypothesized that the intervention would improve adherence to heart failure medications , reduce exacerbations requiring emergency department visits or hospitalization , improve disease-specific quality of life , increase patient satisfaction , and reduce health care costs . Methods Design Overview The methods for our r and omized trial are described elsewhere ( 1113 ) . We recruited patients from the general medicine and cardiology practice s of Wishard Health Services , Indianapolis , Indiana , which serves socioeconomically disadvantaged and medically vulnerable patients . The study was conducted from February 2001 to June 2004 . Patients took part in the study for 12 months and received 9 months of active intervention by the pharmacist or usual care followed by 3 months of postintervention assessment . Patients in the usual care and intervention groups visited the same pharmacy location , but the intervention pharmacist was instructed to have no contact with patients in the usual care group . The institutional review boards of Indiana UniversityPurdue University and the University of North Carolina at Chapel Hill approved this study . Setting and Patients Indiana University Medical Group , Indianapolis , is an academic primary care group practice composed of primary and specialty care clinics affiliated with Wishard Health Services . Faculty physicians , residents , and nurse practitioners provide care to 13000 adults ( mean age , 57 years [ SD , 15 ] ; 60 % women ; 50 % African American ) . Annually , these patients make approximately 50000 visits to practice s , 72000 visits to emergency departments , and 135000 visits to pharmacies and have 16000 hospitalizations . We recruited patients from 4 identical general medicine practice s , 1 cardiology practice , and Wishard Memorial Hospital . Practice s met in half-day sessions per week that were attended by 2 or 3 faculty members and 3 to 5 residents or fellows from each practice . Faculty physicians practice d 1 to 5 half-days per week , whereas fellows practice d 1 to 2 half-days per week and residents attended the practice 1 half-day per week . Out patients of Wishard Health Services fill their prescriptions at central or de central ized outpatient pharmacies located at the ambulatory care center or at 1 of several satellite pharmacies stationed at neighborhood clinics . Fully stocked de central ized pharmacies serviced all study patients . From February 2001 to January 2003 , the study pharmacy was located in a building adjacent to the ambulatory care center . From February 2003 to June 2004 , the study pharmacy was moved to a space adjacent to the general medicine practice s in the ambulatory care center . Two pharmacists and 1 technician were stationed at the pharmacy . The study pharmacist was instructed to service patients in the intervention group only , and a second pharmacist serviced patients in the usual care group and filled prescriptions to be delivered to patients at outlying clinics . The technician filled prescriptions and read electronic adherence monitors . Weekly lists of eligible patients were created by using the Regenstrief Medical Record System ( Regenstrief Institute , Indianapolis , Indiana ) ( 14 , 15 ) . We invited clinical ly stable patients from general internal medicine practice s , a cardiology clinic , and Wishard Memorial Hospital ( at discharge ) to participate in the study . Of 3034 patients with a diagnosis of heart failure , 1512 met criteria for enrollment . Patients were eligible if they were 50 years of age or older ; planned to receive all of their care , including prescribed medications , at Wishard Health Services ; had a diagnosis of heart failure confirmed by their primary care physician ; regularly used at least 1 cardiovascular medication for heart failure ( angiotensin-converting enzyme [ ACE ] inhibitor or angiotensin-receptor blocker , -adrenergic antagonist , diuretic , digoxin , or aldosterone antagonist ) ; were not using or were not planning to use a medication container adherence aid ( for example , a pill box ) ; had access to a working telephone ; and could hear within the range of normal conversation . We excluded patients with dementia . Patients received their prescription medications through state and local assistance plans at no cost . Thus , cost of medicines was not a deterrent to adherence . R and omization A trained interviewer conducted a baseline interview at enrollment . Interviewers were blinded to patients ' study status and played no role in the delivery of the intervention . Interviewers contacted a central ized data manager at the end of each interview to determine the patient 's study assignment , which was otherwise concealed . We r and omly assigned patients , without blocking or stratification , to receive the pharmacy intervention or usual care by using a univariate discrete distribution from the IMSL Fortran Library 's subroutine RNGDA pseudor and om number generator ( Absoft Corp. , Rochester Hills , Michigan ) ( 16 ) . We r and omly assigned more patients to the usual care group so that this group could also be a prospect i ve cohort for study ing risk factors associated with the clinical deterioration of heart failure . Of the 314 patients included in the study , 229 were recruited from the general internal medicine practice s , 15 from the cardiology clinic , and 70 on discharge from the Wishard Memorial Hospital . The numbers of patients assigned to the intervention and usual care groups did not differ by recruitment site ( P= 0.83 ) . Intervention A pharmacist delivered the intervention by using a protocol ( Appendix Table 1 ) that included a baseline medication history of all prescription and over-the-counter drugs and dietary supplements taken by patients , which patients brought with them to the baseline interview , and the results of an assessment of patient medication knowledge and skills ( 7 , 8) . The pharmacist dispensed enough of the patient 's medications to last approximately 2 months . Appendix Table 1 . Pharmacist 's Intervention Protocol * When medications were dispensed , the pharmacist provided patient-centered verbal instructions and written material s about the medications ( 11 , 13 , 17 ) by using a schema for instruction that has been tested ( 18 , 19 ) . We assigned each medication category an icon ( for example , the icon for ACE inhibitors was a red ace of hearts ) . The same icon appeared on the container label and lid and on the written patient instructions . Written instructions were aim ed at patients with low health literacy and contained an easy-to-follow timeline to remind patients when to take their medications ( 13 ) . The pharmacist monitored patients ' medication use , health care encounters , body weight , and other relevant data by using a study data base ( 20 , 21 ) . Information about patients was communicated as needed to clinic nurses and primary care physicians by face-to-face visits , telephone , paging ( physician only ) , and e-mail ( physician only ) . Technicians supported the pharmacist 's dispensing efforts within the pharmacy throughout the study . We incorporated costs therein into the economic analysis . Pharmacists serviced patients in the usual care group who were not associated with the intervention or the study . An interdisciplinary team of investigators that included pharmacists with advanced training in patient education and cardiovascular pharmacotherapy , a geriatrician , a cardiologist with expertise in heart failure , a behavioral scientist , and a cognitive psychologist trained the intervention pharmacist . The intervention pharmacist also studied guidelines for treating heart failure ( 22 ) , key concepts in the pharmaceutical care of older adults , communication techniques , and the pharmacotherapy of the cardiovascular drugs for heart failure . All pharmacists at Wishard Health Services were aware of the study and were instructed on how to h and le and redirect intervention patients who inadvertently arrived at their pharmacy . Usual Care Patients in the usual care group were aware of the purpose of the study , and their primary care Background — Hypertension control rates remain suboptimal . Pharmacists ’ scope of practice is evolving , and their position in the community may be ideal for improving hypertension care . We aim ed to study the impact of pharmacist prescribing on blood pressure ( BP ) control in community-dwelling patients . Methods and Results — We design ed a patient-level , r and omized , controlled trial , enrolling adults with above-target BP ( as defined by Canadian guidelines ) through community pharmacies , hospitals , or primary care teams in 23 communities in Alberta . Intervention group patients received an assessment of BP and cardiovascular risk , education on hypertension , prescribing of antihypertensive medications , laboratory monitoring , and monthly follow-up visits for 6 months ( all by their pharmacist ) . Control group patients received a wallet card for BP recording , written hypertension information , and usual care from their pharmacist and physician . Primary outcome was the change in systolic BP at 6 months . A total of 248 patients ( mean age , 64 years ; 49 % male ) were enrolled . Baseline mean±SD systolic/diastolic BP was 150±14/84±11 mm Hg . The intervention group had a mean±SE reduction in systolic BP at 6 months of 18.3±1.2 compared with 11.8±1.9 mm Hg in the control group , an adjusted difference of 6.6±1.9 mm Hg ( P=0.0006 ) . The adjusted odds of patients achieving BP targets was 2.32 ( 95 % confidence interval , 1.17–4.15 in favor of the intervention ) . Conclusions — Pharmacist prescribing for patients with hypertension result ed in a clinical ly important and statistically significant reduction in BP . Policy makers should consider an exp and ed role for pharmacists , including prescribing , to address the burden of hypertension . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00878566 The COMmunity Pharamcists ASSist for Blood Pressure ( COMPASS-BP ) study aim ed to assess the effectiveness of lifestyle support programs administered in community pharmacies on hypertension control . This open-label , two-armed parallel group , cluster-r and omized controlled trial included 73 pharmacies ( clusters ) in Japan r and omized to a control or intervention group . Eligible hypertensive patients ( n = 125 ) , aged 20 - 75 years , received the intervention ( n = 64 ) or the control treatment ( n = 61 ) , as dictated by their pharmacy r and omization . Patients in the intervention group received brochures and healthy lifestyle advice from pharmacists using motivational interviewing methods during pharmacy visits over a 12-week period , with their usual pharmacy care . Conversely , the control group just received usual care . The main outcome measure was a change in morning systolic blood pressure ( SBP ) from baseline to week 12 . The intervention group exhibited a decrease in morning SBP that was 6.0 mmHg greater than that of the control group ( 95 % confidence interval [ CI ] : -11.0 to -0.9 , p = 0.021 ) . In a mixed-effect model for repeated measures analysis , the intergroup difference in morning SBP decrease was -4.5 mmHg ( 95 % CI : -8.5 to -0.6 , p = 0.024 ) . Our findings indicate that implementation of a lifestyle advice program in pharmacies is feasible and may lead to reduced blood pressure The primary goal of seamless care is improved patient outcomes and improved st and ards of care for patients with cancer . The pharmacy service of the Newfoundl and Cancer Treatment and Research Foundation conducted a r and omized control study that measured clinical and humanistic outcomes of a pharmacist-directed seamless care program in an ambulatory oncology clinic . This article focuses on the intervention group , particularly the identification of drug-related problems ( DRPs ) and utilization of health care services as well the satisfaction of 3 types of health professionals with the services provided by the pharmacist-directed seamless care program . Overall , the seamless care pharmacist ( SCP ) identified an average of 3.7 DRPs per intervention patient ; the most common DRP reported was a patient not receiving or taking a drug therapy for which there is an indication . The SCP identified more DRPs in patients receiving adjuvant treatment compared to those receiving palliative treatment . On average , family physicians , oncology nurses , and hospital pharmacists were satisfied with the SCP intervention indicating that they agreed the information collected and distributed by the SCP was useful to them . Pharmacist-directed seamless care services in an ambulatory oncology clinic have a significant impact on clinical outcomes and processes of patient care . The presence of a SCP can help identify and resolve DRPs experienced by patients in an outpatient oncology clinic , ensuring that patients are receiving the highest st and ard of care OBJECTIVE : To assess the effectiveness of a pharmaceutical care model on the management of non-insulin-dependent diabetes mellitus ( NIDDM ) in urban African-American patients . DESIGN : Eligible patients were r and omized to either a pharmacist intervention or control group and followed over a 4-month period . Patients in the intervention group received diabetes education , medication counseling , instructions on dietary regulation , exercise , and home blood glucose monitoring , and evaluation and adjustment of their hypoglycemic regimen . Patients in the control group continued to receive st and ard medical care provided by their physicians . SETTING : A university-affiliated internal medicine outpatient clinic . PARTICIPANTS : The study population consisted of urban African-American patients with NIDDM currently attending the clinic . MAIN OUTCOME MEASURES : Primary outcome measures included fasting plasma glucose and glycated hemoglobin concentrations . Secondary outcome endpoints included blood pressure , serum creatinine , creatinine clearance , microalbumin to creatinine ratio , total cholesterol , triglycerides , high-density lipoprotein , and low-density lipoprotein concentrations . Quality -of-life assessment s were performed in both groups at baseline and at the end of the study . RESULTS : Thirty-nine patients ( 17 intervention , 22 control ) completed the study . The intervention group consisted of 12 women and 5 men with a mean ± SD age of 59 ± 12 years , total body weight ( TBW ) of 93 ± 22 kg , body mass index ( BMI ) of 34 ± 7 kg/m2 , and duration of NIDDM 6.8 ± 6.5 years . The control group consisted of 15 women and 7 men with a mean age of 65 ± 12 years , TBW of 88 ± 19 kg , BMI of 33 ± 7 kg/m2 , and a duration of NIDDM of 6.2 ± 4.8 y. Significant improvement in glycated hemoglobin ( p = 0.003 ) and fasting plasma glucose ( p = 0.015 ) was achieved in the intervention group . No change in glycemia was observed in the control subjects . Statistically significant differences in the final glycated hemoglobin ( p = 0.003 ) and fasting plasma glucose ( p = 0.022 ) concentrations were noted between groups . No significant changes in blood pressure control , lipid profile , renal function parameters , weight , or quality -of-life measures were noted within or between groups . CONCLUSIONS : Our data demonstrate the effectiveness of pharmaceutical care in the reduction of hyperglycemia associated with NIDDM in a group of urban African-American patients Background : : Depression is associated with poor glycemic control , increased number of microvascular and macrovascular complications , functional impairment , mortality , and 4.5 times higher total health care costs in patients with diabetes . Shared medical appointments ( SMAs ) may be an effective method to attain national guideline recommendations for glycemic control in diabetes for patients with depression through peer support , counseling , problem solving , and improved access to care . Objective : To test the efficacy as assessed by attainment of a hemoglobin A1c ( A1C ) < 7 % of pharmacistted group SMA visits , Veterans Affairs Multidisciplinary Education in Diabetes and Intervention for Cardiac Risk Reduction in Depression ( VA-MEDIC-D ) , in patients with type 2 diabetes mellitus . Methods : This was a r and omized controlled trial of VA-MEDIC-D added to st and ard care versus st and ard care alone in depressed patients with diabetes with A1C > 6.5 % . VA-MEDIC-D consisted of 4 once-weekly , 2-hour sessions followed by 5 monthly 90-minute group sessions . Each SMA session consisted of multidisciplinary education and pharmacist-led behavioral and pharmacologic interventions for diabetes , lipids , smoking , and blood pressure . No pharmacologic interventions for depression were provided . The change in the proportion of participants who achieved an A1C < 7 % at 6 months was compared . Results : Compared to st and ard care ( n = 44 ) , a lower proportion of patients in VA-MEDIC-D ( n = 44 ) had systolic blood pressure ( SBP ) < 130 mm Hg at baseline , but were similar in other cardiovascular risk factors and psychiatric comorbidity . The change in the proportion of participants achieving an A1C < 7 % was greater in the VA-MEDIC-D arm than in the st and ard care arm ( 29.6 % vs 11.9 % ) , with odds ratio 3.6 ( 95 % CI 1.1 to 12.3 ) . VA-MEDIC-D participants also achieved significant reductions in SBP , low-density lipoprotein cholesterol , and non – high-density lipoprotein ( HDL ) cholesterol from baseline , whereas significant reductions were attained only in non – HDL cholesterol with st and ard care . There was no significant change in depressive symptoms for either arm . Conclusions : Pharmacist-led group SMA visits are efficacious in attainment of glycemic control in patients with diabetes and depression without change in depression symptoms IMPORTANCE Adherence to cardioprotective medication regimens in the year after hospitalization for acute coronary syndrome ( ACS ) is poor . OBJECTIVE To test a multifaceted intervention to improve adherence to cardiac medications . DESIGN , SETTING , AND PARTICIPANTS In this r and omized clinical trial , 253 patients from 4 Department of Veterans Affairs medical centers located in Denver ( Colorado ) , Seattle ( Washington ) ; Durham ( North Carolina ) , and Little Rock ( Arkansas ) admitted with ACS were r and omized to the multifaceted intervention ( INT ) or usual care ( UC ) prior to discharge . INTERVENTIONS The INT lasted for 1 year following discharge and comprised ( 1 ) pharmacist-led medication reconciliation and tailoring ; ( 2 ) patient education ; ( 3 ) collaborative care between pharmacist and a patient 's primary care clinician and /or cardiologist ; and ( 4 ) 2 types of voice messaging ( educational and medication refill reminder calls ) . MAIN OUTCOMES AND MEASURES The primary outcome of interest was proportion of patients adherent to medication regimens based on a mean proportion of days covered ( PDC ) greater than 0.80 in the year after hospital discharge using pharmacy refill data for 4 cardioprotective medications ( clopidogrel , β-blockers , 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors [ statins ] , and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers [ ACEI/ARB ] ) . Secondary outcomes included achievement of blood pressure ( BP ) and low-density lipoprotein cholesterol ( LDL-C ) level targets . RESULTS Of 253 patients , 241 ( 95.3 % ) completed the study ( 122 in INT and 119 in UC ) . In the INT group , 89.3 % of patients were adherent compared with 73.9 % in the UC group ( P = .003 ) . Mean PDC was higher in the INT group ( 0.94 vs 0.87 ; P < .001 ) . A greater proportion of intervention patients were adherent to clopidogrel ( 86.8 % vs 70.7 % ; P = .03 ) , statins ( 93.2 % vs 71.3 % ; P < .001 ) , and ACEI/ARB ( 93.1 % vs 81.7 % ; P = .03 ) but not β-blockers ( 88.1 % vs 84.8 % ; P = .59 ) . There were no statistically significant differences in the proportion of patients who achieved BP and LDL-C level goals . CONCLUSIONS AND RELEVANCE A multifaceted intervention comprising pharmacist-led medication reconciliation and tailoring , patient education , collaborative care between pharmacist and patients ' primary care clinician and /or cardiologist , and voice messaging increased adherence to medication regimens in the year after ACS hospital discharge without improving BP and LDL-C levels . Underst and ing the impact of such improvement in adherence on clinical outcomes is needed prior to broader dissemination of the program . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00903032 Background Cancer is now becoming a leading cause of death . Chemotherapy is an important treatment for cancer patients . These patients also need consultation during their treatment to improve quality of life and decrease psychological disorders . The objectives of the study were to develop , implement and evaluate the effectiveness of a chemotherapy counseling module by pharmacists among oncology patients on their quality of life and psychological outcomes in Malaysia . Method A single-blind r and omized controlled trial was carried out among 162 oncology patients undergoing chemotherapy from July 2013 to February 2014 in a government hospital with oncology facilities in Malaysia . Participants were r and omized to either the intervention group or the control group . Chemotherapy counseling using the module on ‘ Managing Patients on Chemotherapy ’ by Pharmacists was delivered to the intervention group . The outcome measures were assessed at baseline , first follow-up and second follow-up and third follow-up post-intervention . Chi-square , independent sample s t-test and two-way repeated measures ANOVA were conducted in the course of the data analyses . Results In assessing the impact of the chemotherapy counseling module , the study revealed that the module along with repetitive counseling showed significant improvement of quality of life in the intervention group as compared to the control group with a large effect size in physical health ( p = 0.001 , partial Ƞ2 = 0.66 ) , psychological ( p = 0.001 , partial Ƞ2 = 0.65 ) , social relationships ( p = 0.001 , partial Ƞ2 = 0.30 ) , and environment ( p = 0.001 , partial Ƞ2 = 0.67 ) and decrease in the anxiety ( p = 0.000 ; partial Ƞ2 = 0.23 ) , depression ( p = 0.000 ; partial Ƞ2 = 0.40 ) . Conclusion The module on ‘ Managing Patients on Chemotherapy ’ along with repetitive counseling by pharmacists has been shown to be effective in improving quality of life and decreasing anxiety and depression among oncology patients undergoing chemotherapy . Trial registration numberNational Medical Research Register ( NMRR ) of Malaysia and given a registration number NMRR-12 - 1057 - 12,363 on 21 December 2012 IMPORTANCE The American Board of Internal Medicine Foundation Choosing Wisely Campaign recommends against the use of benzodiazepine drugs for adults 65 years and older . The effect of direct patient education to catalyze collaborative care for reducing inappropriate prescriptions remains unknown . OBJECTIVE To compare the effect of a direct-to-consumer educational intervention against usual care on benzodiazepine therapy discontinuation in community-dwelling older adults . DESIGN , SETTING , AND PARTICIPANTS Cluster r and omized trial ( EMPOWER [ Eliminating Medications Through Patient Ownership of End Results ] study [ 2010 - 2012 , 6-month follow-up ] ) . Community pharmacies were r and omly allocated to the intervention or control arm in nonstratified , blocked groups of 4 . Participants ( 303 long-term users of benzodiazepine medication aged 65 - 95 years , recruited from 30 community pharmacies ) were screened and enrolled prior to r and omization : 15 pharmacies r and omized to the educational intervention included 148 participants and 15 pharmacies r and omized to the " wait list " control included 155 participants . Participants , physicians , pharmacists , and evaluators were blinded to outcome assessment . INTERVENTIONS The active arm received a deprescribing patient empowerment intervention describing the risks of benzodiazepine use and a stepwise tapering protocol . The control arm received usual care . MAIN OUTCOMES AND MEASURES Benzodiazepine therapy discontinuation at 6 months after r and omization , ascertained by pharmacy medication renewal profiles . RESULTS A total of 261 participants ( 86 % ) completed the 6-month follow-up . Of the recipients in the intervention group , 62 % initiated conversation about benzodiazepine therapy cessation with a physician and /or pharmacist . At 6 months , 27 % of the intervention group had discontinued benzodiazepine use compared with 5 % of the control group ( risk difference , 23 % [ 95 % CI , 14%-32 % ] ; intracluster correlation , 0.008 ; number needed to treat , 4 ) . Dose reduction occurred in an additional 11 % ( 95 % CI , 6%-16 % ) . In multivariate subanalyses , age greater than 80 years , sex , duration of use , indication for use , dose , previous attempt to taper , and concomitant polypharmacy ( 10 drugs or more per day ) did not have a significant interaction effect with benzodiazepine therapy discontinuation . CONCLUSIONS AND RELEVANCE Direct-to-consumer education effectively elicits shared decision making around the overuse of medications that increase the risk of harm in older adults . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01148186 This r and omized , controlled trial evaluated the impact of personalized follow-up on compliance rates in high-risk patients receiving combination lipid-lowering therapy over 2 years . A r and om sample of 30 patients 7 - 30 days after cardiac surgery had baseline fasting low-density lipoprotein levels higher than 130 mg/dl . All patients received lovastatin 20 mg/day and colestipol 5 g twice/day . Weekly telephone contact was made with each patient for 12 weeks . Short- and long-term compliance was assessed by pill and packet counts and refill records . Compliance and lipid profile results were significantly better in the intervention group ( p<0.05 ) up to 2 years after the start of therapy than in the control group for all parameters except high-density lipoprotein . However , this effect was not apparent during the first 12 weeks of therapy . Short-term telephone follow-up favorably affected compliance and lipid profile results up to 2 years after start of therapy WHAT IS KNOWN AND OBJECTIVE With the increasing prevalence of diabetes , the physician-centred model is challenged to deliver holistic care in Asia . Diabetes may be managed effectively within a multidisciplinary collaborative care model ; however , evidence on its effectiveness in Asian patients is lacking . Therefore , the primary objective was to evaluate the clinical outcomes of multidisciplinary collaborative care vs physician-centred care in diabetes . The secondary objectives were to evaluate humanistic and economic outcomes among the two types of care . METHODS This 6-month prospect i ve , open-label , parallel-arm , r and omized , controlled study was conducted at four outpatient healthcare institutions . High-risk patients aged ≥21 years with uncontrolled type 2 diabetes , polypharmacy and comorbidities were included . Patients with type 1 diabetes or those who were unable to communicate independently were excluded . The control arm received usual care with referrals to nurses and dietitians as needed . The intervention arm ( multidisciplinary collaborative care ) was followed up with pharmacists regularly , in addition to receiving the usual care . The primary outcomes included HbA1c , systolic blood pressure , low-density lipoprotein and triglycerides . The secondary outcomes included scores from the Problem Areas in Diabetes ( PAID ) and the Diabetes Treatment Satisfaction Question naires ( DTSQ ) , and diabetes-related health service utilization rates and costs . RESULTS AND DISCUSSION Of 411 eligible patients , 214 and 197 patients were r and omized into the intervention and control arms , respectively . At 6 months , 141 patients in the intervention arm ( 65.9 % ) and 189 patients in the control arm ( 95.9 % ) completed the study . Mean HbA1c reduced from 8.6%±1.5 % at baseline to 8.1%±1.3 % at 6 months in the intervention arm ( P=.04 ) , with up to mean HbA1c improvement of 0.8 % in patients with greater levels of uncontrolled glycemia . Whereas the mean HbA1c in the control arm remained unchanged ( 8.5%±1.4 % ) throughout the 6-month period . Improvements in PAID and DTSQ scores , reduction in physician workload and an average cost savings of US$ 91.01 per patient were observed in the intervention arm over 6 months . WHAT IS NEW AND CONCLUSIONS The positive clinical , humanistic and economic outcomes highlighted the value of multidisciplinary collaborative care for Asian diabetic patients , thereby supporting the effectiveness of this approach in managing chronic diseases BACKGROUND Several studies have established the effectiveness of pharmaceutical care ( PC ) in patients with heart failure , diabetes , hypertension , and dyslipidemia . However , there are few studies using st and ardized methods , e.g. , r and omized controlled trials , to assess the effectiveness of pharmacotherapy follow-up ( PF ) in patients with depression . OBJECTIVE To assess the effectiveness of PC via PF according to the Dáder Method in female patients diagnosed with depression . METHODS Sixty-eight patients were selected and r and omly allocated to groups , stratified by age , type of medication , severity of depression , and presence of recurrence and /or relapse . Patients in the intervention group ( IG ) received clinical pharmacy intervention at monthly visits over a 3-month follow-up period . The control group ( CG ) also received monthly visits from the pharmacist , but PF intervention was not performed . RESULTS A comparison of the effects of usual treatment ( CG ) and PC ( IG ) on depressive symptoms showed a statistically significant difference between groups , with a median reduction in Beck Depression Inventory score ( Δ ) of 2.5 points in the CG and 13.5 points in the IG . Similarly , statistically significant results were observed for anxiety symptoms , with a median reduction in Beck Anxiety Inventory score ( Δ ) of 3.5 points in the CG and 13.0 points in the IG . The patients who underwent PF showed a high level of satisfaction with the service . CONCLUSION The PF is well accepted and effective in treating depressed patients , as indicated by the reduction of the depressive and anxious symptoms STUDY OBJECTIVE To evaluate the impact of a pharmacist-led warfarin patient self-management program on quality of life and anticoagulation control compared with management in a physician-led specialized anticoagulation clinic . DESIGN Prospect i ve , r and omized , controlled , open-label trial . SETTING Tertiary care academic medical center . PATIENTS A total of 114 patients aged 18 - 75 years who were followed at a specialized anticoagulation clinic , had received warfarin for at least 6 months , and were expected to continue warfarin for a minimum of 4 months . INTERVENTION All patients attended an educational session on anticoagulation provided by a pharmacist . Patients r and omized to the self-management group ( 58 patients ) also received practical training to use the CoaguChek XS device and a self-management dosing algorithm . Patients in the control group ( 56 patients ) continued to undergo st and ard management at the anticoagulation clinic . MEASUREMENTS AND MAIN RESULTS Patients completed a vali date d quality -of-life question naire and the vali date d Oral Anticoagulation Knowledge test at the beginning and end of the study . The quality of anticoagulation control was evaluated by using the time spent in therapeutic range . After 4 months of follow-up , a significant improvement in the self-management group was observed compared with the control group in four of the five quality -of-life topics ( p<0.05 ) . Improvements in knowledge were observed in both groups after the training session and persisted after 4 months ( p<0.05 for all ) . The time spent in the therapeutic range ( 80.0 % in the self-management group vs 75 % in the control group , p=0.79 ) and in the extended therapeutic range ( [ target international normalized ratio ± 0.3 ] 93.2 % in the self-management group vs 91.1 % in the control group , p=0.30 ) were similar between groups . CONCLUSION A self-management warfarin program led by pharmacists result ed in significant improvement in the quality of life of patients receiving warfarin therapy as well as a reduction in the time required for anticoagulation monitoring , while maintaining a level of anticoagulation control similar to a high- quality specialized anticoagulation clinic A non-blinded r and omized controlled trial evaluated efficacy of pharmaceutical care ( PC ) ( Dáder method ) on self-reported antiretroviral adherence and undetectable plasma viral load ( UPVL ) , compared with usual care ( UC ) in HIV-positive patients in Brazil . Most were male ( 63 % ) , mean age 40.3 years ( SD = 10 ) . After 12 months , 79.8 % of those receiving PC versus 73.8 % in UC were adherent ( RR 1.05 , 95 % CI 0.95–1.15 , P = 0.35 ) , and 50.3 versus 49.8 % ( PC vs. UC , respectively ) had UPVL ( RR 1.08 , 95 % CI 0.97–1.20 , P = 0.15 ) . Factors associated with self-reported adherence were regular employment , UPVL , no depressive symptoms , and lower pill load in the treatment regimen . Older age , education , CD4 count < 200 cells/mm3 , and shorter treatment duration were associated with UPVL . Of 94 reported drug-related problems , 43 % resolved . In subgroup analyses of patients who experienced therapeutic failure and who were non-adherent at the beginning of the trial ( N = 50 ) , no differences were found in UPVL ( HR 1.35 , 95 % CI 0.57–3.19 ) . Only education level ( > 12 years ) was independently predictive of viral suppression ( HR 7.47 , 95 % CI 1.69–32.91 ) . In conclusion , PC was not associated with increased self-reported adherence to ART or UPVL in patients treated at a health care facility in southern Brazil . The study suggests , however , that PC could be effective for the subgroup of patients with poor adherence . ResumenSe evalúo , a través de ensayo clínico abierto , la eficacia de la Atención Farmacéutica ( AF ) ( Método Dáder ) sobre la adherencia auto-reportada a la terapia antirretroviral y obtención de carga viral indetectable ( CVi ) , comparada con cuidado habitual ( CH ) , en pacientes HIV-positivos en Brazil . La mayoría fue hombres ( 63 % ) , edad media de 40.3 ( DP = 10 ) años . Después de 12 meses , 79.8 % del grupo AF frente 73.8 % en CH estaban adherentes ( RR = 1.05 , 95 % CI 0.95–1.15 , P = 0.35 ) , y 50.3 frente 49.8 % ( AF vs. CH , respectivamente ) tenían CVi ( RR = 1.08 , 95 % CI 0.97–1.20 , P = 0.15 ) . Los factores asociados con adherencia auto-reportada fueron empleo regular , CVi , sin síntomas depresivos y menor número de comprimidos . Ser mayor , educación , CD4 < 200 cel/mm3 y menor duración de tratamiento , se asociaron con CVi . De los 94 problemas relacionados a los medicamentos encontrados , 43 % fueron resueltos . En la análisis de subgrupo con pacientes que habían experimentado fracaso terapéutico y no adhesión al principio del ensayo ( N = 50 ) , tampoco se encontró diferencia ( HR 1.35 , 95 % CI 0.57–3.19 ) . Apenas educación > 12 años fue preditor independiente de CVi ( HR 7.47 , 95 % CI 1.69–32.91 ) . En conclusión , AF no se mostro asociada con aumento de la adherencia auto-reportada o CVi entre los pacientes de este estudio . Entretanto , los result ados sugieren que AF puede ser efectiva para un subgrupo de pacientes con poca adherencia OBJECTIVE Translation of evidence -based guidelines into clinical practice has been inconsistent . We performed a r and omized , controlled trial of guideline -based care suggestions delivered to physicians when writing orders on computer workstations . STUDY SETTING Inner-city academic general internal medicine practice . STUDY DESIGN R and omized , controlled trial of 246 physicians ( 25 percent faculty general internists , 75 percent internal medicine residents ) and 20 outpatient pharmacists . We enrolled 706 of their primary care patients with asthma or chronic obstructive pulmonary disease . Care suggestions concerning drugs and monitoring were delivered to a r and om half of the physicians and pharmacists when writing orders or filling prescriptions using computer workstations . A 2 x 2 factorial r and omization of practice sessions and pharmacists result ed in four groups of patients : physician intervention , pharmacist intervention , both interventions , and controls . DATA EXTRACTION / COLLECTION METHODS : Adherence to the guidelines and clinical activity was assessed using patients ' electronic medical records . Health-related quality of life , medication adherence , and satisfaction with care were assessed using telephone question naires . PRINCIPAL FINDINGS During their year in the study , patients made an average of five scheduled primary care visits . There were no differences between groups in adherence to the care suggestions , generic or condition-specific quality of life , satisfaction with physicians or pharmacists , medication compliance , emergency department visits , or hospitalizations . Physicians receiving the intervention had significantly higher total health care costs . Physician attitudes toward guidelines were mixed . CONCLUSIONS Care suggestions shown to physicians and pharmacists on computer workstations had no effect on the delivery or outcomes of care for patients with reactive airways disease BACKGROUND Appropriate training for community pharmacists may improve the quality of medication use . Few studies have reported the impact of such programs on medication management for patients with chronic kidney disease ( CKD ) . STUDY DESIGN Multicenter , cluster-r and omized , controlled trial . SETTING & PARTICIPANTS Patients with CKD stage 3a , 3b , or 4 from 6 CKD clinics ( Quebec , Canada ) and their community pharmacies . INTERVENTION Each cluster ( a pharmacy and its patients ) was r and omly assigned to either ProFiL , a training- and -communication network program , or the control group . ProFiL pharmacists completed a 90-minute interactive web-based training program on use of medications in CKD and received a clinical guide , patients ' clinical summaries , and facilitated access to the CKD clinic . OUTCOMES Drug-related problems ( primary outcome ) , pharmacists ' knowledge and clinical skills , and patients ' clinical attributes ( eg , blood pressure and glycated hemoglobin concentration ) . MEASUREMENTS Drug-related problems were evaluated the year before and after the recruitment of patients using a vali date d set of significant drug-related problems , the Pharmacotherapy Assessment in Chronic Renal Disease ( PAIR ) criteria . Pharmacists ' question naires were completed at baseline and after 1 year . Clinical attributes were documented at baseline and after 1 year using available information in medical charts . RESULTS 207 community pharmacies , 494 pharmacists , and 442 patients with CKD participated . After 1 year , the mean number of drug-related problems per patient decreased from 2.16 to 1.60 and from 1.70 to 1.62 in the ProFiL and control groups , respectively . The difference in reduction of drug-related problems per patient between the ProFiL and control groups was -0.32 ( 95 % CI , -0.63 to -0.01 ) . Improvements in knowledge ( difference , 4.5 % ; 95 % CI , 1.6%-7.4 % ) and clinical competencies ( difference , 7.4 % ; 95 % CI , 3.5%-11.3 % ) were observed among ProFiL pharmacists . No significant differences in clinical attributes were observed across the groups . LIMITATIONS High proportion of missing data on knowledge and clinical skills question naire ( 34.6 % ) and clinical attributes ( 11.1 % ) . CONCLUSIONS Providing community pharmacists with essential clinical data , appropriate training , and support from hospital pharmacists with expertise in nephrology increases pharmacists ' knowledge and reduces drug-related problems in patients with CKD who are followed up in clinics incorporating a multidisciplinary health care team Integration of clinical pharmacists in patient care may offer increased access to health care and improved patient outcomes . Recently introduced legislation would establish pharmacists as health care providers and enable coverage of pharmacists ' services through Medicare Part B in medically underserved communities ( 1 , 2 ) . Pharmaceutical care involves pharmacist collaboration with health team members to optimize therapeutic outcomes ( 3 ) . Since 1995 , the Department of Veterans Affairs has allowed clinical pharmacy specialists an exp and ed scope of practice , with independent prescribing privileges ( 4 ) . The scope of practice for clinical pharmacy specialists includes pharmaceutical care or comprehensive medication management for patients with chronic diseases in addition to less complex services , such as counseling patients on medications or responding to questions about drug information . A 2014 systematic review evaluated outpatient medication therapy management interventions ( 5 ) . Study inclusion criteria required that interventions have , at minimum , 3 elements : comprehensive medication review ; patient-directed education and counseling ; and coordination of care , including prescriber-directed interventions . The research ers concluded that evidence was insufficient for health outcomes , although interventions may reduce the frequency of some medication-related problems and decrease some health care use and costs . We determined the effectiveness and harms of pharmacist-led chronic disease management compared with usual care for community-dwelling adults . Chronic disease management is typically a multicomponent intervention ( Figure 1 ) , and we required that the pharmacist take a lead role in at least 1 component . Studies where the pharmacist was a collaborator on a Patient Aligned Care Team or similar care strategy were not included . This report summarizes findings of a Department of Veterans Affairs Evidence -based Synthesis Program review ( available at www.hsrd . research .va.gov/publications/esp ) . Figure 1 . Components of pharmacist-led chronic disease management . * Follow-up after prescription for medication effectiveness and safety and drug-related problems . Includes medication reconciliation . The pharmacist provides immunization , which was not an outcome of interest . Facilitate access to other health care professionals and provide education about disease , lifestyle changes , aspirin therapy , and tobacco cessation . Supplement . Study Protocol Methods We developed a protocol for the review with input from content experts and method ologists . The protocol was not registered but was available for comment during review development . Data Sources and Search es We search ed MEDLINE ( Ovid ) , CINAHL , the Cochrane Library , and International Pharmaceutical Abstract s from 1995 through February 2016 for English- language literature ( Appendix Table 1 ) . We obtained additional articles by h and - search ing reference lists of systematic review s and other articles and from peer- review ers . Appendix Table 1 . Search Strategy for MEDLINE ( Ovid ) Study Selection We focused on chronic disease management for out patients in health care facilities , excluding retail pharmacies . We emphasized patient- or health system-centered outcomes but also addressed intermediate measures . MEDLINE abstract s were review ed for eligibility by 2 research ers ; abstract s from other data bases were review ed by a single research er . Full-text articles of studies identified as potentially eligible on the basis of abstract review were obtained for further review . Each article was independently review ed by 2 investigators or research associates . We included studies of any design that had a control group , evaluated outpatient adults with or at risk for a chronic disease , tested an intervention where the pharmacist was responsible for a distinct component of patient care , and were set in U.S. health care facilities . We excluded studies that did not involve interventions intended to manage or prevent 1 or more chronic diseases and studies of anticoagulation clinics because pharmacist management is considered st and ard care in those setting s. The Appendix Figure shows the reasons for study exclusion at full-text review . Appendix Figure . Summary of evidence search and selection . CCT = controlled clinical trial ; IPA = International Pharmaceutical Abstract s ; RCT = r and omized , controlled trial . Data Extraction and Quality Assessment Study data were extracted by one investigator and independently verified by a second . Our main outcomes of interest were clinical events , mortality , patient satisfaction , health care utilization ( including urgent care or emergency department visits and hospitalizations ) , medication adherence , and goal attainment ( Appendix Table 2 ) We also assessed access to care , quality of life , drug-related problems , and costs . We assessed risk of bias ( low , medium , or high ) for individual studies on the basis of sequence generation , allocation concealment , confounding ( for nonr and omized studies ) , blinding , and incomplete or selective outcome reportinga modification of the Cochrane approach ( 6 ) ( Appendix Table 2 ) . Appendix Table 2 . Evidence From Included Studies Appendix Table 2Continued Appendix Table 2Continued Appendix Table 2Continued Data Synthesis and Analysis We grouped studies by disease state and described and qualitatively compared the characteristics and findings of included studies . We rated the overall strength of the body of evidence across disease states for clinical events , patient satisfaction , target goal attainment , urgent care or emergency department visits and hospitalizations , and medication adherence by using the method of Owens and colleagues ( 7 ) . Two trained review ers grade d the strength of evidence regarding the outcomes as high , moderate , low , or insufficient on the basis of risk of bias , consistency , precision , and directness . We resolved discrepancies in risk of bias and strength of evidence ratings by discussion with final determination arrived through consensus that included the principal investigator . Most findings are summarized in narrative form , but we pooled results if studies were r and omized ( noncluster ) trials and enrolled participants and outcome measures were similar within each disease condition . DerSimonianLaird r and om-effects models were used to calculate pooled risk ratios ( RRs ) and 95 % CIs . We assessed statistical heterogeneity by using the I 2 statistic ( 75 % indicates substantial heterogeneity ) ( 8) . Role of the Funding Source The Department of Veterans Affairs , Veterans Health Administration , Office of Research and Development , Quality Enhancement Research Initiative assigned the topic and review ed the key questions but was not involved in data collection , analysis , or manuscript preparation or su bmi ssion . Results Search results are shown in the Appendix Figure . We included 72 articles representing 63 studies ( 40 r and omized , controlled trials [ RCTs ] ) with 65 unique study population s ( 940 - 4172 - 7381 ) . We grouped studies by disease state of the population and study characteristics ( Table 1 ) . Most studies were conducted in primary care setting s ( community-based or university-affiliated ) , but a few were in specialty clinics ( cardiology , nephrology , endocrinology ) . Interventions were typically delivered by pharmacists in person or with a mix of in-person and remote visits ( in 89 % of studies ) over multiple sessions ( 89 % ) . However , interventions varied in composition , delivery mode , and intensity , making it difficult to identify important intervention characteristics . Fifty-two studies were judged as low or medium risk of bias . Table 1 . Summary of Included Studies , by Disease State and Study Characteristics * Studies were generally short term ( 12 months ) and had small sample s. They mainly assessed intermediate outcomes , such as blood pressure , cholesterol , or glucose goal attainment , in patients with hypertension , cardiovascular disease , or diabetes ( 45 of 65 unique studies ) . Goal attainment was listed as the primary study outcome in 23 unique studies . Clinical events were described in 15 unique studies and were the primary outcome in 2 of those studies . Office visits , medication adherence or nonadherence , hospitalizations , patient satisfaction , and health-related quality of life were noted in 26 , 27 , 20 , 19 , and 19 studies , respectively , but they rarely were the primary outcome . Additional study details are presented in Appendix Table 2 . Findings Across All Disease Conditions In 15 trials ( 12 RCTs ) reporting clinical events ( for example , hypotension or hypoglycemia requiring additional intervention ) , pharmacist-led care and usual care ( typically continuing a pre study visit schedule ) were generally similar ( Appendix Table 3 ) ( 12 , 14 , 1922 , 3437 , 59 , 62 , 64 , 71 , 75 , 77 ) Eight studies reported all-cause mortality , of which 6 found similar mortality in the pharmacist-led care and control groups and 2 did not report significance ( 12 , 13 , 16 , 18 , 28 , 30 , 37 , 71 ) . One of these studies in patients with diabetes also reported no disease-related deaths ( 28 ) . However , of studies reporting clinical events or mortality , only 2 were design ed to assess clinical events ( 13 , 14 ) , outcomes were sporadically and inconsistently reported , and there were few events ( low strength of evidence ) ( Table 2 ) . Evidence was insufficient to evaluate the effect of pharmacist-led care on patient satisfaction ( overall and for each disease condition ) and limited reporting of quality -of-life outcomes . Compared with usual care , pharmacist-led care improved study -selected goal attainment ( typically for blood pressure , lipid , and glycemic goals ) . Strength of evidence was moderate , with consistent findings across disease conditions . Table 2 . Strength of Evidence , by Outcome Evaluated * Appendix Table 3 . Summary of Direction of Evidence For re source use outcomes , pharmacist-led care was similar to usual care for incidences or rates of office visits ( 26 studies ) , urgent care or BACKGROUND Bipolar I disorder ( BD-I ) is a chronic illness characterized by relapses alternating with periods of remission . Pharmacists can contribute to improved health outcomes in these patients through pharmaceutical care in association with a multidisciplinary health team ; however , more evidence derived from r and omized controlled trials ( RCTs ) is needed to demonstrate the effect of pharmaceutical care on patients with BD-I. OBJECTIVE To assess the effectiveness of a pharmaceutical intervention using the Dader Method on patients with BD-I , measured by the decrease in the number of hospitalizations , emergency service consultations , and unscheduled outpatient visits from baseline through 1 year of follow-up . METHODS This study is based on the EMDADER-TAB trial , which was an RCT design ed to compare pharmaceutical care with the usual care given to out patients with BD-I in a psychiatric clinic . The main outcome was the use of health care services , using Kaplan-Meier methods and Cox regression . The trial protocol was registered in Clinical Trials.gov ( Identifier NCT01750255 ) . RESULTS 92 patients were included in the EMDADER-TAB study : 43 pharmaceutical care patients ( intervention group ) and 49 usual care patients ( control group ) . At baseline , no significant differences in demographic and clinical characteristics were found across the 2 groups . After 1 year of follow-up , the risk of hospitalizations and emergencies was higher for the control group than for the intervention group ( HR = 9.03 , P = 0.042 ; HR = 3.38 , P = 0.034 , respectively ) ; however , the risk of unscheduled outpatient visits was higher for the intervention group ( HR = 4.18 , P = 0.028 ) . There was no " placebo " treatment , and patients in the control group might have produced positive outcomes and reduced the magnitude of differences compared with the intervention group . CONCLUSIONS Compared with usual care , pharmaceutical care significantly reduced hospitalizations and emergency service consultations by out patients with BD-I. DISCLOSURES This study received funding from the Universidad de Antioquia , Committee for Development Research and Sustainability Program , CODI , ( 2013 - 2014 and 2014 - 2015 ) . Humax Pharmaceutical provided support for the initial development of the EMDADER-TAB trial without commercial interest in the outcomes derived from the trial . Salazar-Ospina reports grants from Credito Beca Francisco José de Caldas Scholarship for Doctoral Programs ( 528 ) , which also contributed to the support of this study . González-Avendaño is an employee of Humax Pharmaceutical . The other authors have nothing to disclose . Study concept and design were contributed by Benjumea , Faus , and Rodriguez , along with Salazar-Ospina and Amariles . Salazar-Ospina took the lead in data collection , assisted by González-Avendaño , and data interpretation was performed by Salazar-Ospina , Hincapié-García , and González-Avendaño . The manuscript was written primarily by Salazar-Ospina , with assistance from Amariles and González-Avendaño , and revised by all the authors BACKGROUND Poor adherence leads to a high rate of exacerbation and poor health-related quality of life ( HRQoL ) in patients with chronic obstructive pulmonary disease ( COPD ) . However , few strategies are acceptable and effective in improving medication adherence . We investigated whether pharmaceutical care by clinical pharmacists could reinforce medication adherence to reduce exacerbation and improve HRQoL. METHODS A r and omized controlled study was carried out at The First Affiliated Hospital of Guangzhou Medical University from February 2012 to January 2014 . Non-adherence patients were r and omly assigned to receive pharmaceutical care or to usual care . The pharmaceutical care consisted of individualized education and a series of telephone counseling for 6 months provided by clinical pharmacists . Medication adherence was measured by pill counts plus direct interview at 1- and 6-month pharmaceutical care and one-year follow-up . Severe exacerbations were defined as events that led to hospitalization for acute COPD attack . An interview was conducted to investigate hospital admissions and evaluate severe exacerbations at one-year follow-up . HRQoL was measured by St George 's Respiratory Question naire at 6 months . RESULTS At 6-month pharmaceutical care and one-year follow-up , the pharmaceutical care group exhibited higher medication adherence than the usual care group ( 73.4±11.1 vs. 55.7±11.9 , P=0.016 and 54.4±12.5 vs. 66.5±8.6 , P=0.039 , respectively ) . There are 60 acute exacerbations result ed in a hospital admission in the usual group while 37 ones in the pharmaceutical care group during one-year follow-up ( P=0.01 ) . Hospital admissions due to acute exacerbation in the pharmaceutical care group were 56.3 % less than the usual care group ( P=0.01 ) . There was a significant difference in the symptoms and impact subscales respectively at 6-month pharmaceutical care between two groups ( P=0.032 , P=0.018 ) . CONCLUSIONS Individualized pharmaceutical care improved medication adherence , reduced hospitalization and elevated HRQoL in patients with COPD The aim of this study was to determine whether improved compliance by intensive medication counselling , given by a pharmacist , to elderly patients with chronic stable heart failure can influence both objective and subjective measures of heart failure . Elderly patients were r and omly allocated to receive a 3-month counselling programme , or no counselling . Measures recorded at the beginning and end of the study included ; submaximal 6-minute exercise tests , visual analogue scores of breathlessness , the Nottingham Health Profile , and clinical signs of heart failure . Compliance was measured by a tablet count and medication knowledge assessed by means of a question naire . There was no significant difference between the groups in their initial level of compliance , medication knowledge or other assessment s. Compliance improved for the counselled group by 32 % ( P < 0.001 ) but remained unchanged for controls . Medication knowledge improved for the counselled group only . The 6-minute exercise test improved by 20 metres from a baseline of 137 m for the counselled group ( P < 0.005 ) but worsened by 22 m for the control group ( P < 0.01 ) . Distance to breathlessness improved for the counselled patients and worsened for controls . In contrast bodyweight , jugular venous pressure and Nottingham Health Profile scores did not change significantly for either group . Peripheral and pulmonary oedema scores improved for the counselled group ( P < 0.01 ) but remained unchanged for controls . A small improvement was seen in the visual analogue scores ( P < 0.05 ) for the counselled group only . Improved compliance due to intensive medication counselling had a small but measurable beneficial effect on objective measures of heart failure . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVES To evaluate the community pharmacist 's capacity to positively influence the results of antihypertensive drug therapy through a pharmaceutical care program and to determine what factors limit the program . DESIGN R and omized , controlled study . SETTING Private pharmacy caring for a semiliterate , rural Portuguese population . PATIENTS R and om sample of 100 patients with a diagnosis of essential hypertension who had been on drug treatment for less than 6 months . Patients were r and omly assigned to an intervention ( n = 50 ) or a control ( n = 50 ) group . INTERVENTION Individualized health promotion by a research pharmacist involving monthly appointments for 6 months to monitor blood pressure ; assess adherence to treatment ; prevent , detect , and resolve drug-related problems ( DRPs ) ; and encourage nonpharmacologic measures for blood pressure control . Control patients received traditional care . MAIN OUTCOME MEASURES Control of blood pressure ; decreases in systolic/diastolic blood pressure ; number of detected , resolved , and prevented DRPs . RESULTS From the initial sample of 100 patients , 41 patients in the intervention group and 41 patients in the control group completed the longitudinal study . After 6 months , prevalence of uncontrolled blood pressure decreased by 77.4 % in the intervention group ( P < .0001 ) and by 10.3 % in the control group ( P = .48 ) . Systolic blood pressure fell from a mean + /- st and ard deviation of 152 mm Hg + /- 23 mm Hg to 129 + /- 15 mm Hg in intervention patients and 148 + /- 16 mm Hg to 143 + /- 20 mm Hg in control patients ( P < .001 ) . Twenty-four of 29 ( 83 % ) detected actual DRPs were resolved . About 40 % of potential DRPs were prevented . CONCLUSION In this rural community , a pharmaceutical care program was associated with significant improvements in blood pressure control in hypertensive patients WHAT IS KNOWN AND OBJECTIVES Psychopharmacologic therapy has so far focused on ameliorating disruptive behaviours to improve patient 's function and quality of life . Due to the complicated neurobiological aetiology of autism spectrum disorder ( ASD ) , a traditional pharmacist intervention may be insufficient to initiate the optimal care for this vulnerable population . We evaluate the impact of providing specialty psychiatry ( PS ) pharmacist intervention in identifying and resolving drug-related problems ( DRPs ) among children with ASD associated with disruptive behaviours . METHODS An eight-week-long , prospect i ve , r and omized open-label study was conducted . Children between 2.5 and 12 years of age with ASD and showing disruptive behaviours were included . They were r and omly assigned to an intervention or a control group . Patients in the intervention group received pharmacist interventions delivered by a PS pharmacist , while those in control group were cared by a hospital pharmacist . The primary outcome was the number of patients who resolved of at least one DRP by the end of the study . The secondary outcome was to compare the mean Aberrant Behavior Checklist-Irritability ( ABC-I ) scores between the two groups . RESULTS Twenty-five patients were r and omly assigned to either an intervention or control group . At week 8 , the total number of patients who resolved of at least one DRP was 13 ( 52 % ) in the intervention group and 4 ( 16 % ) in the control group , respectively ( P=.016 ) . Improper drug selection , medication non-adherence and subtherapeutic dosage were the most common DRPs . Mean ABC-I scores improved in the intervention group more than in the control group ( 9.8±5.6 vs 17.7±7.9 ; P<.001 ) . WHAT IS NEW AND CONCLUSION To the best of our knowledge , this is the first study which demonstrated that PS pharmacist intervention is an effective strategy to resolve DRPs in patient with ASD . The reduction in common DRPs mostly result ed from the PS pharmacist interventions , including selection of antipsychotic agent , adjustment of dosage based on ABC-I scores and provision of individualized drug counselling . Reducing DRPs led to the improvement of any disruptive behaviour . In addition , multidisciplinary team should develop drug therapy protocol s to promote the role of pharmacists in this setting BACKGROUND Although some studies have demonstrated that pharmacist intervention can improve drug therapy among patients with cardiovascular disease ( CVD ) , more evidence derived from r and omized controlled trials ( RCTs ) is needed , including assessment of the effect of community pharmacist interventions in patients with CVD . OBJECTIVE To assess the effectiveness of the Dader Method for pharmaceutical care on achieving therapeutic goals for blood pressure ( BP ) , total cholesterol ( TC ) , and both BP and TC ( BP/TC ) in patients with CVD and /or high or intermediate cardiovascular ( CV ) risk attending community pharmacies in Spain . METHODS Patients aged 25 to 74 years attending community pharmacies with a prescription for at least 1 drug indicated for CVD or CV risk factors were r and omized to 2 groups : an intervention group that received pharmaceutical care , which was provided by specially trained pharmacists working in collaboration with physicians , and a control group that received usual care ( routine dispensing counseling ) and verbal and written counseling regarding CVD prevention . Patients were recruited from December 2005 to September 2006 , and both groups were followed for 8 months . Study outcomes were assessed at baseline and at 16 and 32 weeks after r and omization . The primary outcome measures were the proportions of patients achieving BP , TC , and BP/TC therapeutic goals ( BP lower than 140/90 mm Hg for patients with uncomplicated hypertension and lower than 130/80 mm Hg for patients with diabetes , chronic kidney disease , or history of myocardial infa rct ion or stroke ; TC lower than 200 mg per dL for patients without CVD and lower than 175 mg per dL for patients with CVD ) . Secondary outcomes were mean BP and TC values . BP was assessed manually by the pharmacist after a 10-minute rest in the supine position . This measurement was performed twice for every participant , and the average of the 2 measurements was calculated . TC was measured by the pharmacist during the study visit using the enzymatic dry method . Statistical analyses were performed using 2-tailed McNemar tests , Pearson chi-square tests , and Student 's t-tests ; P < 0.05 was considered statistically significant . RESULTS 714 patients were included in the study ( 356 intervention , 358 control ) , and the mean [ SD ] age was 62.8 [ 8.1 ] years . The 2 groups were similar at baseline in clinical and demographic characteristics , including the proportion of patients at therapeutic goals for BP , TC , and BP/TC . After 8 months of follow-up , there were statistically significant differences in favor of pharmaceutical care in the proportions of patients who achieved therapeutic goals for BP ( 52.5 % vs. 43.0 % , P=0.017 ) , TC ( 56.5 % vs. 44.1 % , P=0.001 ) , and BP/TC ( 37.1 % vs. 21.8 % , P < 0.001 ) . CONCLUSION Compared with usual care plus written education , pharmaceutical care focused on patient evaluation and follow-up in collaboration with physicians improved the achievement of BP , TC , and BP/TC treatment goals in patients with CVD and /or high or intermediate CV risk attending community pharmacies in Spain OBJECTIVE To identify which activities produced a significant improvement in blood pressure control in patients with type 2 diabetes when pharmacists were added to primary care teams . METHODS This prespecified , secondary analysis evaluated medication management data from a r and omized controlled trial . The primary outcome was a change in treatment , defined as addition , dosage increase , or switching of an antihypertensive medication during the 1-year study period . The secondary outcome was a change in antihypertensive medication adherence using the medication possession ratio ( MPR ) . RESULTS The 200 evaluable trial patients had a mean age of 59 ( SD , 11 ) years , 44 % were men , and mean blood pressure was 130 ( SD , 16)/74 ( SD , 10 ) mm Hg at baseline . Treatment changes occurred in 45 ( 42 % ) of 107 patients in the intervention group and 24 ( 26 % ) of 93 patients in the control group ( RR , 1.63 ; 95 % CI , 1.08 - 2.46 ) . Addition of a new medication was the most common type of change , occurring in 34 ( 32 % ) patients in the intervention group and 17 ( 18 % ) patients in the control group ( P = 0.029 ) . Adherence to antihypertensive medication was high at baseline ( MPR , 93 % ) . Although medication adherence improved in the intervention group ( MPR , 97 % ) and declined in the control group ( MPR , 91 % ) , the difference between groups was not significant ( P = 0.21 ) . CONCLUSION The observed improvement in blood pressure control when pharmacists were added to primary care teams was likely achieved through antihypertensive treatment changes and not through improvements in antihypertensive medication adherence OBJECTIVE To evaluate a pharmacist-conducted educational and monitoring programme , design ed to promote dietary and lifestyle modification and compliance with lipid-lowering drug therapy , for patients with dyslipidaemia . METHODS This was a prospect i ve , r and omized , controlled study . The participants were 94 adults , with 81 completing the study ( intervention group : 39 ; control group : 42 ) , with a cardiovascular-related diagnosis and discharged from hospital , between April and October 2001 , on lipid-lowering drug therapy . Patients in the intervention group were visited at home monthly by a pharmacist , who educated the patients on the goals of lipid-lowering treatment and the importance of lifestyle issues in dyslipidaemia and compliance with therapy , assessed patients for drug-related problems , and measured total blood cholesterol levels using point-of-care testing . Patients in the control group received st and ard medical care . The main outcome measure was total blood cholesterol levels after 6 months , and an evaluation of patient and general practitioner satisfaction with the programme . RESULTS There was no significant difference in baseline total blood cholesterol levels between the two groups . The reduction over the course of the study in cholesterol levels within the intervention group was statistically significant ( 4.9 + /- 0.7 to 4.4 + /- 0.6 , P<0.005 ) , whereas there was no change within the control group ( P=0.26 ) . At follow-up , 44 % of the intervention group patients and 24 % of the control group patients had cholesterol levels below 4.0 mmol/L ( P=0.06 ) . The reduction in total cholesterol in the intervention group should translate to an expected 21 % reduction in cardiovascular mortality risk and a 16 % reduction in total mortality risk -- more than twice the risk reduction achieved in the control group . In addition , the programme was very well received by the patients and their general practitioners , by satisfaction question naire . CONCLUSION A pharmacist-conducted educational and monitoring intervention improved the outcomes of lipid-lowering drug therapy BACKGROUND Community pharmacists strive to deliver pharmaceutical care to patients . At the moment , coaching of depressive primary care patients on taking their antidepressants ( ADs ) is not yet part of their st and ard care package . AIMS To investigate the effects of coaching by community pharmacists on psychological symptoms . METHOD A r and omised controlled trial with a 6-month follow-up . OUTCOMES psychological symptoms with the Hopkins Symptom Checklist ( SCL ) . Intention-to-treat ( ITT ) was performed with ( 1 ) last observation carried forward and ( 2 ) with group mean imputation ( GMI ) . RESULTS Analyses with LOCF and GMI result ed in different findings . The LOCF method revealed that at the 6-month follow-up , the intervention patients were less depressed and less anxious than the controls . The intervention was particularly effective in patients with lower levels of education who received pharmacist 's coaching . However , ITT with the GMI method showed no differences in psychological symptoms . Differences between LOCF and GMI were explained by the selective attrition in the intervention arm ( attrition intervention patients had lower initial SCL-item scores on depression and anxiety than the completers ) and by the higher attrition rate in controls . CONCLUSIONS Our study indicates that the interpretation of the effects of an intervention on psychological symptoms can differ substantially by the way missing values are imputed . If both LOCF and GMI produce significant differences , efficacy can be concluded . If not , the effects based on ITT analyses with LOCF are based on artefacts . We recommend that positive intervention effects should only be reported when findings with LOCF and GMI are in accordance CONTEXT It is not known whether patient outcomes are enhanced by effective pharmacist-patient interactions . OBJECTIVE To assess the effectiveness of a pharmaceutical care program for patients with asthma or chronic obstructive pulmonary disease ( COPD ) . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial conducted at 36 community drugstores in Indianapolis , Ind. We enrolled 1113 participants with active COPD or asthma from July 1998 to December 1999 . Outcomes were assessed in 947 ( 85.1 % ) participants at 6 months and 898 ( 80.7 % ) at 12 months . INTERVENTIONS The pharmaceutical care program ( n = 447 ) provided pharmacists with recent patient-specific clinical data ( peak expiratory flow rates [ PEFRs ] , emergency department [ ED ] visits , hospitalizations , and medication compliance ) , training , customized patient educational material s , and re sources to facilitate program implementation . The PEFR monitoring control group ( n = 363 ) received a peak flow meter , instructions about its use , and monthly calls to elicit PEFRs . However , PEFR data were not provided to the pharmacist . Patients in the usual care group ( n = 303 ) received neither peak flow meters nor instructions in their use ; during monthly telephone interviews , PEFR rates were not elicited . Pharmacists in both control groups had a training session but received no components of the pharmaceutical care intervention . MAIN OUTCOME MEASURES Peak expiratory flow rates , breathing-related ED or hospital visits , health-related quality of life ( HRQOL ) , medication compliance , and patient satisfaction . RESULTS At 12 months , patients receiving pharmaceutical care had significantly higher peak flow rates than the usual care group ( P = .02 ) but not than PEFR monitoring controls ( P = .28 ) . There were no significant between-group differences in medication compliance or HRQOL . Asthma patients receiving pharmaceutical care had significantly more breathing-related ED or hospital visits than the usual care group ( odds ratio , 2.16 ; 95 % confidence interval , 1.76 - 2.63 ; P<.001 ) . Patients receiving pharmaceutical care were more satisfied with their pharmacist than the usual care group ( P = .03 ) and the PEFR monitoring group ( P = .001 ) and were more satisfied with their health care than the usual care group at 6 months only ( P = .01 ) . Despite ample opportunities to implement the program , pharmacists accessed patient-specific data only about half of the time and documented actions about half of the time that records were accessed . CONCLUSIONS This pharmaceutical care program increased patients ' PEFRs compared with usual care but provided little benefit compared with peak flow monitoring alone . Pharmaceutical care increased patient satisfaction but also increased the amount of breathing-related medical care sought Results 115 patients and 68 healthcare professionals completed question naires ( 98 and 85 r and omised to V1 and V2 respectively ) . The percentage of PRO items rated as essential in V1 was 31.6 % and in V2 63.2 % ( difference=31.6 % , 95 % CI 14.2 - 49.0 , P<0.001 ) . Looking at stakeholder groups separately , patients rated 36.8 % essential in V1 and 78.9 % in V2 ( 42.1 % , 95 % CI 23.8 - 60.4 , P<0.0001 ) and professionals 31.6 % in V1 and 18.4 % in V2 ( 13.2 % , 95 % CI -30.7 - 4.4 , P=0.096 ) Background Pharmacists in various setting s have been effective in initiating diabetes treatment . Patients with diabetes require ongoing disease management , and community pharmacists are in a strategic position to provide such extended care . Little is known , however , about the effects of community pharmacist – provided interventions beyond the initial treatment period . Objective To evaluate the effect of community pharmacist – provided extended diabetes care service on primary clinical outcomes , including hemoglobin A1c ( A1C ) , low-density lipoprotein cholesterol ( LDL-C ) , and blood pressure , and on patients ' reported self-care activities . Methods A r and omized controlled trial was conducted in patients with diabetes . Participants had already completed at least 2 diabetes education sessions at a local diabetes education center . Nine specially trained pharmacists administered interventions during up to 4 quarterly visits per patient . Interventions included discussing medications , clinical goals , and self-care activities with patients and recommending medication changes to physicians when appropriate . The main outcome measures were 12-month changes in A1C , LDL-C , blood pressure , and self-report of self-care activities . Results Seventy-eight patients participated in the study ( 36 intervention , 42 control ) ; 66 were included in the final analysis ( 31 intervention , 35 control ) . Compared with changes in the control group , patients who received interventions significantly increased the number of days per week that they engaged in a set of diet and diabetes self-care activities ( 1.25 and 0.73 more days/wk , respectively ) . The mean 12-month changes for A1C , LDL-C , and blood pressure were not significantly different between the 2 study groups . Conclusions Although pharmacist-provided interventions did not demonstrate statistically significant improvements in clinical outcomes over the study period , study results did show that pharmacists were effective at increasing the number of days that patients spent engaging in healthy diet and diabetes self-care activities . Addressing lifestyle and self-care behaviors can be a beneficial component of a pharmacist-provided extended diabetes care service STUDY OBJECTIVE Physician-pharmacist collaborative models have been shown to improve the care of patients with numerous chronic medical conditions . Team-based health care using integrated clinical pharmacists provides one opportunity to improve quality in health care systems that use population -based financing . In November 2015 , the Centers for Medicare and Medicaid Services ( CMS ) requested that the relative value of pharmacists ' work in team-based care needs to be established . Thus the objective of this study was to describe the components of pharmacists ' work in the management of hypertension with a physician-pharmacist collaborative model . DESIGN Descriptive analysis of the components of pharmacists ' work in the Collaboration Among Pharmacists and Physicians to Improve Outcomes Now ( CAPTION ) study , a prospect i ve , cluster r and omized trial . MEASUREMENTS AND MAIN RESULTS This analysis was intended to provide policymakers with data and information , using the CAPTION study model , on the time and intensity of pharmacists ' work to underst and pharmacists ' relative value contributions in the context of CMS financing and population management aims . The CAPTION trial was conducted in 32 community-based medical offices in 15 U.S. states and included 390 patients with multiple cardiovascular risk factors . Blood pressure was measured by trained study coordinators in each office , and patients were included in the study if they had uncontrolled blood pressure . Included patients were r and omized to a 9-month intervention , a 24-month intervention , or usual care . The goal of the pharmacist intervention was to improve blood pressure control and resolve drug therapy problems impeding progress toward blood pressure goals . This intervention included medical record review , a structured assessment with the patient , collaboration to achieve goals of therapy , and patient follow-up . The two intervention arms ( 9 and 24 mo ) were identical the first 9 months , and that time frame is the focus of this workload evaluation . Pharmacists completed study encounter forms for every patient encounter and estimated time spent in pre-visit , face-to-face care , and post-visit activities . Among the 390 patients , there were 2811 encounters with pharmacists that involved 3.44 hours/patient for face-to-face care visits plus 1.55 hours/patient for pre-visit and post-visit work . Intensity of work was reflected in interventions to resolve drug therapy problems with patients ( 43 % of encounters ) and with physicians ( 1169 recommendations , of which physicians accepted 1153 [ 98.6 % ] ) , result ing in improvement of patients ' blood pressure goals achieved ( from 0 % at baseline to 43 % at 9 months based on the primary study end point ) . CONCLUSION Pharmacists provided extensive interventions to patients with hypertension . This analysis provides a framework for health systems , provider groups , and payers to measure pharmacists ' work in value-based financing and population management AIMS To evaluate the efficacy of two maintenance strategies compared to usual care after discharge from a pharmacist-led cardiovascular risk reduction clinic ( CRRC ) . METHODS Open-label , r and omized-controlled trial of 200 consecutive CRRC patients that met clinic discharge criteria ( HbA1c ≤7 % ( 53 mmol/mol ) ; blood pressure ≤140/80 mmHg for those with diabetes and ≤140/90 mmHg for those without diabetes ; and an LDL-cholesterol ≤2.59 mmol/l ) . Participants were r and omized to either quarterly group medical visits or quarterly CRRC individual clinic visits , or a usual care control arm with the st and ard primary care alone first in a 1:1:1 ratio , followed by a 2:2:1 ratio after first 100 patients . Primary outcome measures were time to failure for guideline recommended goals of HbA1c and blood pressure over 12-months . RESULTS Of the 200 participants r and omized , 89 % had diabetes and were similar in other cardiovascular risk factors . After 1-year , the HbA1c failure rate was 0.36 [ 95 % CI , 0.28 - 0.47 ] per quarter for the group medical visit arm , 0.24 [ 95 % CI , 0.18 - 0.33 ] per quarter for the quarterly CRRC individual arm and , 0.82 [ 95 % CI , 0.69 - 0.96 ] per quarter for the usual care control arm , p<0.001 . The rate of failure for blood pressure was 0.31 [ 95 % CI , 0.23 - 0.41 ] per quarter for the group medical visit arm , 0.22 [ 95 % CI , 0.16 - 0.30 ] per quarter for the CRRC individual arm and , 0.53 [ 95 % CI , 0.40 - 0.71 ] per quarter the control arm , p<0.001 . CONCLUSION After discharge from a CRRC program , both individual and group interventions are more effective in maintaining glycemia and blood pressure control for patients with diabetes than usual care after 1-year of follow-up OBJECTIVE To determine whether pharmaceutical care provided by a pharmacist-managed hypertension clinic results in better treatment outcomes when compared with traditional health care from a primary care physician . DESIGN Prospect i ve , controlled study SETTING Veterans Affairs Medical Center , Philadelphia , Pennsylvania . PATIENTS Fifty six patients with essential hypertension ; 27 were r and omly assigned to the intervention group and 29 to the control group . INTERVENTION Patients in the intervention group were scheduled monthly to meet with a clinical pharmacist who made appropriate changes in prescribed drugs , adjusted dosages , and provided drug counseling in accordance with the hypertension guidelines in the sixth report of the Joint National Committee on the Detection , Evaluation , and Treatment of High Blood Pressure ( JNC VI ) . Patients in the control group received st and ard care from their physicians . The study period was 6 months . MEASUREMENTS AND MAIN RESULTS Treatment outcomes were measured by changes in compliance , blood pressure , and patient satisfaction . The Short Form-36 health survey and a patient satisfaction survey were used to measure changes in patient satisfaction , and a compliance evaluation survey measured compliance . Twenty-one ( 81 % ) patients in the intervention group attained their blood pressure goal of below 140/90 mm Hg at the completion of the study versus only eight ( 30 % ) in the control group ( p < 0.0001 ) . Of 11 patients with diabetes in the intervention group , 10 ( 91 % ) attained their blood pressure goal ( < 130/80 mm Hg ) versus only two ( 12 % ) of 16 patients with diabetes in the control group ( p < 0.0001 ) . No significant differences in patient satisfaction or compliance were reported between the intervention and control groups . CONCLUSIONS Pharmaceutical care improves blood pressure control and results in more patients with hypertension reaching their blood pressure goal Objective This study aim ed to measure the outcomes of a harmonised , structured pharmaceutical care programme provided to elderly patients ( ≥65 years of age ) by community pharmacists in a multicentre international study performed in 7 European countries . Design and setting The study was a r and omised , controlled , longitudinal , clinical trial with repeated measures performed over an 18-month period . A total of 104 intervention and 86 control pharmacy sites participated in the research and 1290 intervention patients and 1164 control patients were recruited into the study .Main outcome measures and results A general decline in health-related quality of life over time was observed in the pooled data ; however , significant improvements were achieved in patients involved in the pharmaceutical care programme in some countries . Intervention patients reported better control of their medical conditions as a result of the study and cost savings associated with pharmaceutical care provision were observed in most countries . The new structured service was well accepted by intervention patients and patient satisfaction with the services improved during the study . The pharmacists involved in providing pharmaceutical care had a positive opinion on the new approach , as did the majority of general practitioners surveyed . The positive effects appear to have been achieved via social and psychosocial aspects of the intervention , such as the increased support provided by community pharmacists , rather than via biomedical mechanisms . Conclusions This study is the first large-scale , multicentre study to investigate the effects of pharmaceutical care provision by community pharmacists to elderly patients . Future research methodology and implementation will be informed by the experience gained from this challenging trial BACKGROUND Despite the cardiovascular disease ( CVD ) risk associated with hypertension , diabetes , dyslipidemia , and smoking , these risk factors remain poorly identified and controlled . OBJECTIVES The study sought to evaluate the effectiveness of a community pharmacy-based case finding and intervention on cardiovascular risk . METHODS The RxEACH ( Alberta Vascular Risk Reduction Community Pharmacy Project ) study was a r and omized trial conducted in 56 community pharmacies . Participants were recruited by their pharmacist , who enrolled adults at high risk for CVD . Patients were r and omized to usual care ( usual pharmacist care with no specific intervention ) or intervention , comprising a Medication Therapy Management review from their pharmacist and CVD risk assessment and education . Pharmacists prescribed medications and ordered laboratory tests as per their scope of practice to achieve treatment targets . Subjects received monthly follow-up visits for 3 months . The primary outcome was difference in change in estimated CVD risk between groups at 3 months . CVD risk was estimated using the greater of the Framingham , International , or United Kingdom Prospect i ve Diabetes Study risk scores . RESULTS We enrolled 723 patients ( mean 62 years of age ; 58 % male , and 27 % smokers ) . After adjusting for baseline values and center effect , there was a 21 % difference in change in risk for CVD events ( p < 0.001 ) between the intervention and usual care groups . The intervention group had greater improvements in low-density lipoprotein cholesterol ( -0.2 mmol/l ; p < 0.001 ) , systolic blood pressure ( -9.37 mm Hg ; p < 0.001 ) , glycosylated hemoglobin ( -0.92 % ; p < 0.001 ) , and smoking cessation ( 20.2 % ; p = 0.002 ) . CONCLUSIONS The RxEACH study was the first large r and omized trial of CVD risk reduction by community pharmacists , demonstrating a significant reduction in risk for CVD events . Engagement of community pharmacists with an exp and ed scope of practice could have significant public health implication s. ( The Alberta Vascular Risk Reduction Community Pharmacy Project : RxEACH [ RxEACH ] ; NCT01979471 ) PURPOSE To assess the efficacy of a pharmacist-led , primary care-based , disease management program to improve cardiovascular risk factors and glycated hemoglobin ( A(1C ) ) levels in vulnerable patients with poorly controlled diabetes . METHODS A r and omized controlled trial of 217 patients with type 2 diabetes and poor glycemic control ( A(1C ) level > or=8.0 % ) was conducted at an academic general medicine practice from February 2001 to April 2003 . Intervention patients received intensive management from clinical pharmacists , as well as from a diabetes care coordinator who provided diabetes education , applied algorithms for managing glucose control and decreasing cardiovascular risk factors , and addressed barriers to care . Control patients received a one-time management session from a pharmacist followed by usual care from their primary care provider . Outcomes were recorded at baseline and at 6 and 12 months . Primary outcomes included blood pressure , A(1C ) level , cholesterol level , and aspirin use . Secondary outcomes included diabetes knowledge , satisfaction , use of clinical services , and adverse events . RESULTS For the 194 patients ( 89 % ) with 12-month data , the intervention group had significantly greater improvement than did the control group for systolic blood pressure ( -9 mm Hg ; 95 % confidence interval [ CI ] : -16 to -3 mm Hg ) and A(1C ) level ( -0.8 % ; 95 % CI : -1.7 % to 0 % ) . Change in total cholesterol level was not significant . At 12 months , aspirin use was 91 % in the intervention group versus 58 % among controls ( P < 0.0001 ) . Intervention patients had greater improvements in diabetes knowledge and satisfaction than did control patients . There were no significant differences in use of clinical services or adverse events . CONCLUSION Our comprehensive disease management program reduced cardiovascular risk factors and A(1C ) levels among vulnerable patients with type 2 diabetes and poor glycemic control PURPOSE A collaborative pharmacist- primary care provider ( PharmD-PCP ) team approach to medication-therapy management ( MTM ) , with pharmacists initiating and changing medications at separate office visits , holds promise for the cost-effective management of hypertension , but has not been evaluated in many systematic trials . The primary objective of this study was to examine blood pressure ( BP ) control in hypertensive patients managed by a newly formed PharmD-PCP MTM team versus usual care in a university-based primary care clinic . METHODS This r and omized , pragmatic clinical trial was conducted in hypertensive patients r and omly selected for PharmD-PCP MTM or usual care . In the PharmD-PCP MTM group , pharmacists managed drug-therapy initiation and monitoring , medication adjustments , biometric assessment s , laboratory tests , and patient education . In the usual-care group , patients continued to see their PCPs . Participants were aged ≥ 18 years , were diagnosed with hypertension , had a most recent BP measurement of ≥ 140/≥ 90 mm Hg ( ≥ 130/≥ 80 mm Hg if codiagnosed with diabetes mellitus ) , were on at least 1 antihypertensive medication , and were English speaking . The primary outcome was the difference in the mean change from baseline in systolic BP at 6 months . Secondary outcomes included the percentage achieving therapeutic BP goal and the mean changes from baseline in diastolic BP and low- and high-density lipoprotein cholesterol . FINDINGS A total of 166 patients were enrolled ( 69 men ; mean age , 67.7 years ; PharmD-PCP MTM group , n = 75 ; usual-care group , n = 91 ) . Mean reduction in SBP was significantly greater in the PharmD-PCP MTM group at 6 months ( -7.1 [ 19.4 ] vs + 1.6 [ 21.0 ] mm Hg ; P = 0.008 ) , but the difference was no longer statistically significant at 9 months ( -5.2 [ 16.9 ] vs -1.7 [ 17.7 ] mm Hg ; P = 0.22 ) , based on an intent-to-treat analysis . In the intervention group , greater percentages of patients who continued to see the MTM pharmacist versus those who returned to their PCP were at goal at 6 months ( 81 % vs 44 % ) and at 9 months ( 70 % vs 52 % ) . No significant between-group differences in changes in cholesterol were detected at 6 and 9 months ; however , the mean baseline values were near recommended levels . The PharmD-PCP MTM group had significantly fewer PCP visits compared with the usual-care group ( 1.8 [ 1.5 ] vs 4.2 [ 1.0 ] ; P < 0.001 ) . IMPLICATION S A PharmD-PCP collaborative MTM service was more effective in lowering BP than was usual care at 6 months in all patients and at 9 months in patients who continued to see the pharmacist . Incorporating pharmacists into the primary care team may be a successful strategy for managing medication therapy , improving patient outcomes and possibly extending the capacity of primary care . Clinical Trials.gov identifier : NCT01973556 OBJECTIVE To explore the impact of telephone-based education and monitoring by community pharmacists on multiple outcomes of pharmacist-patient collaboration . DESIGN A r and omized , controlled , unblinded , mixed experimental design . SETTING Eight Wisconsin community pharmacies within a large managed care organization . PATIENTS A total of 63 patients presenting new antidepressant prescriptions to their community pharmacies . INTERVENTIONS Patients were r and omized to receive either three monthly telephone calls from pharmacists providing pharmacist-guided education and monitoring ( PGEM ) or usual pharmacist 's care . Usual care is defined as that education and monitoring which pharmacists may typically provide patients at the study pharmacies . MAIN OUTCOME MEASURES Patient 's frequency of feedback with the pharmacist , antidepressant knowledge , antidepressant beliefs , antidepressant adherence at 3 and 6 months , improvement in depression symptoms , and orientation toward treatment progress . RESULTS Of the 60 patients who completed the study , 28 received PGEM and 32 received usual pharmacist 's care . Results showed that PGEM had a significant and positive effect on patient feedback , knowledge , medication beliefs , and perceptions of progress . There were no significant group differences in patient adherence or symptoms at 3 months ; however , PGEM patients who completed the protocol missed fewer doses than did the usual care group at 6 months ( P < or = .05 ) . CONCLUSION Antidepressant telemonitoring by community pharmacists can significantly and positively affect patient feedback and collaboration with pharmacists . Longer-term studies with larger sample s are needed to assess the generalizability of findings . Future research also needs to explore additional ways to improve clinical outcomes OBJECTIVE The objective of this study was to determine if African-American renal transplant patients who received direct patient care from a clinical pharmacist had better blood pressure control compared to African-American renal transplant patients who did not have clinical pharmacy services . METHODS Renal transplant patients were prospect ively r and omized into an intervention group or a control group . Patients in the intervention group received clinical pharmacy services that included a clinical pharmacist performing patient medication review s , with emphasis on preventing or resolving medication-related problems and providing medication recommendations . Patients in the control group received routine clinic services , but had no clinical pharmacist interaction . Analysis was performed to detect differences between the intervention and control groups in baseline and quarterly systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) for one year post- study enrollment . RESULTS There were no differences between the intervention ( N = 13 ) and control ( N = 10 ) groups in baseline blood pressures or in the percentage of hypertensive patients . Significant differences in the change in SBP and DBP from baseline between the intervention and control groups were observed at the second , third , and fourth quarters of the study , favoring the intervention group ( P < .01 ) . Mean SBP was significantly lower in the intervention group at the second ( 137.8 + /- 15.0 vs 168.9 + /- 15.3 ) , third ( 135.9 + /- 11.7 vs 164.6 + /- 20.1 ) , and fourth ( 145.3 + /- 16.8 vs 175.8 + /- 33.9 ) quarters of the study ( P < .05 ) . Mean DBP was significantly lower in the intervention group at the second ( 76.0 + /- 11.8 vs 84.9 + /- 6.1 ) and fourth ( 77.0 + /- 10.2 vs 91.8 + /- 12.0 ) quarters ( P < .05 ) . CONCLUSION Direct patient care services provided by a clinical pharmacist , in addition to routine clinical services , have a positive effect on the blood pressure of African-American renal transplant patients . A multidisciplinary team that includes a clinical pharmacist is beneficial to patient care Background . This study aim ed to compare the effects of two small-group asthma education interventions ( one delivered by specially trained pharmacists ( group A ) and one delivered by a pharmacist research er trained as an asthma educator ( group B ) ) with usual care provided by community pharmacists ( group C ) on clinical and humanistic outcomes for people with asthma . Methods . Pharmacies were r and omly selected to provide either group A , B , or C interventions . Data were collected at baseline , post intervention ( groups A and B ) and at 6 and 12 weeks ( final visit ) . Results . Forty-eight people with asthma were recruited into groups A ( n = 16 ) , B ( n = 16 ) , and C ( n = 16 ) and there were no significant differences between the groups at baseline . At 12 weeks there was a significant decrease in the proportion of patients with severe asthma/poor control in groups A and B compared with group C ( 56 % , 44 % and 50 % to 25 % , 13 % and 50 % [ n = 48 , p < 0.05 ] , respectively ) . In Groups A and B , the proportion of patients with optimal metered dose inhaler ( MDI ) technique improved from 9 % and 14 % , respectively , at baseline to 82 % and 93 % ( n = 11 , p = 0.02 , n = 14 , p < 0.001 ) , respectively , at 12 weeks . The proportion of patients with optimal dry powder inhaler ( DPI ) technique improved in Groups A and B from 0 % and 8 % , respectively , at baseline to 86 % and 92 % ( n = 7 , p < 0.001 ; n = 13 , p = 0.002 ) , respectively , at 12 weeks . No change in inhaler technique was observed for Group C. There were significant improvements in asthma knowledge scores in Groups A and B compared to Group C over time . Conclusions . Small-group asthma education delivered by pharmacists appears to be more effective than usual care in improving clinical and humanistic asthma outcomes Background Treatment of depression , the most prevalent and costly mental disorder , needs to be improved . Non-concordance with clinical guidelines and non-adherence can limit the efficacy of pharmacological treatment of depression . Through pharmaceutical care , pharmacists can improve patients ' compliance and wellbeing . The aim of this study is to evaluate the effectiveness and cost-effectiveness of a community pharmacist intervention developed to improve adherence and outcomes of primary care patients with depression . Methods / design A r and omized controlled trial , with 6-month follow-up , comparing patients receiving a pharmaceutical care support programme in primary care with patients receiving usual care . The total sample comprises 194 patients ( aged between 18 and 75 ) diagnosed with depressive disorder in a primary care health centre in the province of Barcelona ( Spain ) . Subjects will be asked for written informed consent in order to participate in the study . Diagnosis will be confirmed using the SCID-I. The intervention consists of an educational programme focused on improving knowledge about medication , making patients aware of the importance of compliance , reducing stigma , reassuring patients about side-effects and stressing the importance of carrying out general practitioners ' advice . Measurements will take place at baseline , and after 3 and 6 months . Main outcome measure is compliance with antidepressants . Secondary outcomes include ; clinical severity of depression ( PHQ-9 ) , anxiety ( STAI-S ) , health-related quality of life ( EuroQol-5D ) , satisfaction with the treatment received , side-effects , chronic physical conditions and socio-demographics . The use of healthcare and social care services will be assessed with an adapted version of the Client Service Receipt Inventory ( CSRI ) . Discussion This trial will provide valuable information for health professionals and policy makers on the effectiveness and cost-effectiveness of a pharmaceutical intervention programme in the context of primary care . Trial registration Objective To test the practicality , acceptability and feasibility of recruitment , data collection , blood pressure ( BP ) monitoring and pharmaceutical care processes , in order to inform the design of a definitive r and omised controlled trial of a pharmacist complex intervention on patients with stroke in their own homes . Methods Patients with new stroke from acute , rehabilitation wards and a neurovascular clinic ( NVC ) were r and omised to usual care or to an intervention group who received a home visit at 1 , 3 and 6 months from a clinical pharmacist . Pharmaceutical care comprised medication review , medicines and lifestyle advice , pharmaceutical care issue ( PCI ) resolution and supply of individualised patient information . A pharmaceutical care plan was sent to the General Practitioner and Community Pharmacy . BP and lipids were measured for both groups at baseline and at 6 months . Question naires covering satisfaction , quality of life and medicine adherence were administered at 6 months . Results Of the 430 potentially eligible patients , 30 in patients and 10 NVC out patients were recruited . Only 33/364 NVC out patients ( 9.1 % ) had new stroke . 35 patients completed the study ( intervention=18 , usual care=17 ) . Question naire completion rates were 91.4 % and 84.4 % , respectively . BP and lipid measurement processes were unreliable . From 104 identified PCIs , 19/23 recommendations ( 83 % ) made to general practitioners were accepted . Conclusion Modifications to recruitment is required to include patients with transient ischaemic attack . Question naire response rates met criteria but completion rates did not , which merits further analysis . Lipid measurements are not necessary as an outcome measure . A reliable BP-monitoring process is required Information for patients provided by the pharmacist is reflected in adhesion to treatment , clinical results and patient quality of life . The objective of this study was to assess an asthma self-management model for rational medicine use . This was a r and omized controlled trial with 60 asthmatic patients assigned to attend five modules presented by a pharmacist ( intervention group ) and 59 patients in the control group . Data collection was performed before and after this 4-month intervention and included an evaluation of asthma knowledge , lifestyle , inhaler techniques , adhesion to treatment , pulmonary function and quality of life . An economic viability analysis was also performed . The intervention group obtained an increase in asthma knowledge scores of 58.3 - 79.5 % ( P < 0.001 ) . In this group , there was also an increase in the number of individuals who practice d physical exercise ( 36 - 43 % ) , in the number of correct replies regarding the use of inhalers , in the percentage of adherent patients , and in quality of life scores for all domains . We concluded that this asthma self-management model was effective in improving the quality of life of asthma patients CONTEXT Treating hypertension decreases mortality and disability from cardiovascular disease , but most hypertension remains inadequately controlled . OBJECTIVE To determine if a new model of care that uses patient Web services , home blood pressure ( BP ) monitoring , and pharmacist-assisted care improves BP control . DESIGN , SETTING , AND PARTICIPANTS A 3-group r and omized controlled trial , the Electronic Communications and Home Blood Pressure Monitoring study was based on the Chronic Care Model . The trial was conducted at an integrated group practice in Washington state , enrolling 778 participants aged 25 to 75 years with uncontrolled essential hypertension and Internet access . Care was delivered over a secure patient Web site from June 2005 to December 2007 . INTERVENTIONS Participants were r and omly assigned to usual care , home BP monitoring and secure patient Web site training only , or home BP monitoring and secure patient Web site training plus pharmacist care management delivered through Web communications . MAIN OUTCOME MEASURES Percentage of patients with controlled BP ( < 140/90 mm Hg ) and changes in systolic and diastolic BP at 12 months . RESULTS Of 778 patients , 730 ( 94 % ) completed the 1-year follow-up visit . Patients assigned to the home BP monitoring and Web training only group had a nonsignificant increase in the percentage of patients with controlled BP ( < 140/90 mm Hg ) compared with usual care ( 36 % [ 95 % confidence interval { CI } , 30%-42 % ] vs 31 % [ 95 % CI , 25%-37 % ] ; P = .21 ) . Adding Web-based pharmacist care to home BP monitoring and Web training significantly increased the percentage of patients with controlled BP ( 56 % ; 95 % CI , 49%-62 % ) compared with usual care ( P < .001 ) and home BP monitoring and Web training only ( P < .001 ) . Systolic BP was decreased stepwise from usual care to home BP monitoring and Web training only to home BP monitoring and Web training plus pharmacist care . Diastolic BP was decreased only in the pharmacist care group compared with both the usual care and home BP monitoring and Web training only groups . Compared with usual care , the patients who had baseline systolic BP of 160 mm Hg or higher and received home BP monitoring and Web training plus pharmacist care had a greater net reduction in systolic BP ( -13.2 mm Hg [ 95 % CI , -19.2 to -7.1 ] ; P < .001 ) and diastolic BP ( -4.6 mm Hg [ 95 % CI , -8.0 to -1.2 ] ; P < .001 ) , and improved BP control ( relative risk , 3.32 [ 95 % CI , 1.86 to 5.94 ] ; P<.001 ) . CONCLUSION Pharmacist care management delivered through secure patient Web communications improved BP control in patients with hypertension . Trial Registration clinical trials.gov Identifier : NCT00158639 AIM The aim was to investigate the impact of a disease and medicine management programme , focusing on self-management in patients with chronic obstructive pulmonary disease ( COPD ) . METHODS One hundred and seventy-three patients ( mean age 67 years ; 54 % female ) were recruited ; 86 patients were r and omly assigned to an intervention group and 87 to a usual care ( control ) group . Intervention patients received education on disease state , medications and breathing techniques . Patients were given booklets and a customized action plan ( antibiotic and oral steroid to be initiated promptly by patients for exacerbations ) . Patients were followed up at 6 and 12 months during a scheduled visit . The St George 's Respiratory Question naire ( SGRQ ) , COPD Knowledge and Morisky adherence question naires were administered to all patients at baseline , 6 and 12 months . Outcome measures included hospital admissions , emergency department ( ED ) visits , health-related quality of life ( HRQoL ) and medication adherence . RESULTS Over the 12-month period in the intervention group , ED visits decreased by 50 % ( P= 0.02 ) and hospitalization by approximately 60 % ( P= 0.01 ) . On the SGRQ , differences reached statistical significance on the symptom ( -7.5 ; P= 0.04 ) and impact ( -7.4 ; P= 0.03 ) subscales but not on the physical activity subscale . There was a significant difference between the intervention and usual care groups regarding knowledge scores ( 75.0 vs. 59.3 ; P= 0.001 ) and good adherence to medication ( 77.8 % vs. 60.0 % , P= 0.019 ) . There was no significant difference regarding smoking between study groups . CONCLUSIONS The clinical pharmacy-led management programme can improve adherence , reduce the need for hospital care in patients with COPD and improve aspects of their Malaysia is situated in Western Pacific region which bears 36.17 % of total diabetes mellitus population . Pharmacist led diabetes interventions have been shown to improve the clinical outcomes amongst diabetes patients in various parts of the world . Despite high prevalence of disease in this region there is a lack of reported intervention outcomes from this region . The aim of this study was to evaluate the impact of a pharmacist led intervention on HbA1c , medication adherence , quality of life and other secondary outcomes amongst type 2 diabetes patients . Method : Type 2 diabetes mellitus patients ( n = 73 ) attending endocrine clinic at Universiti Kebangsaan Malaysia Medical Centre ( UKMMC ) were r and omised to either control ( n = 36 ) or intervention group ( n = 37 ) after screening . Patients in the intervention group received an intervention from a pharmacist during the enrolment , after three and six months of the enrolment . Outcome measures such as HbA1c , BMI , lipid profile , Morisky scores and quality of life ( QoL ) scores were assessed at the enrolment and after 6 months of the study in both groups . Patients in the control group did not undergo intervention or educational module other than the st and ard care at UKMMC . Results : HbA1c values reduced significantly from 9.66 % to 8.47 % ( P = 0.001 ) in the intervention group . However , no significant changes were noted in the control group ( 9.64–9.26 % , P = 0.14 ) . BMI values showed significant reduction in the intervention group ( 29.34–28.92 kg/m2 ; P = 0.03 ) and lipid profiles were unchanged in both groups . Morisky adherence scores significantly increased from 5.83 to 6.77 ( P = 0.02 ) in the intervention group ; however , no significant change was observed in the control group ( 5.95–5.98 , P = 0.85 ) . QoL profiles produced mixed results . Conclusion : This r and omised controlled study provides evidence about favourable impact of a pharmacist led diabetes intervention programme on HbA1c , medication adherence and QoL scores amongst type 2 diabetes patients at UKMMC , Malaysia Background : Drug therapy problems , adverse drug events ( ADEs ) , and symptom burden are high among adults with disabilities . Objective : To compare the effects of a modified medication therapy management ( MTM ) program within a self-efficacy workshop versus the workshop alone or usual care on symptom burden among adults with activity limitations . Methods : Three-group r and omized controlled trial among adults ( age 40 and older ) with self-reported activity limitations in community practice . Interventions : 8 weekly Living Well With a Disability ( LWD ) 2-hour workshop sessions with and without a collaborative medication management ( CMM ) module . Primary outcome : mean number of moderate to very severe symptoms from a list of 11 physical and mental symptoms . Process measures : changes in medication regimens and self-reported ADEs . Analysis : general linear mixed models ( continuous outcomes ) and generalized estimating equations ( categorical outcomes ) . Results : Participants had high symptom burden , low physical health , and took many medications . There was a significant increase in ADE reporting in the LWD + CMM group relative to the other 2 groups ( Study group × Time P = .014 ) , and there were significantly more changes in medication regimens in the LWD + CMM group ( P = .013 LWD only vs LWD + CMM ) . The oldest third of participants had significantly fewer mean symptoms but received more intense CMM . There was no difference between the LWD-only , LWD + CMM , and usual care groups in symptom burden over time . Conclusion : Pharmacist MTM practice s and MTM guidelines may need to be modified to affect symptom burden in a population with physical activity limitations |
10,421 | 30,291,745 | All interventions seemed to improve inhaler performance and clinical ly relevant outcomes , but a placebo device could be the most effective .
There is evidence that interventions reduce exacerbation risk in older adults , although to an overall moderate degree . | OBJECTIVES To evaluate the effect of inhaler education programs on clinical outcomes and exacerbation rates in older adults with asthma or chronic obstructive pulmonary disease ( COPD ) . | BACKGROUND patients with dementia are almost invariably unable to use any form of inhaler . Some elderly patients are unable to learn to use a metered dose inhaler or Turbohaler despite a normal abbreviated mental test score . Studies have shown that in many people this is due to unrecognised cognitive impairment and /or dyspraxia . The executive domains of cognition are particularly important in planning and sequencing ; it might be expected therefore that disordered frontal ( executive ) function could be a predictor of poor inhaler technique in subjects with no overt features of dementia . OBJECTIVE to explore the relationship between cognitive , and executive , function and the ability to acquire metered dose inhaler and Turbohaler technique in old age . DESIGN a prospect i ve r and omised observational study with blinded evaluation . SUBJECTS 30 inhaler-naive in patients ( 21 female ) with a mean age of 85 ( range 75 - 94 ) and having a normal ( 8 - 10 ) abbreviated mental test score . METHODS subjects received st and ardised metered dose inhaler and Turbohaler training and were scored on an analogue scale ( for metered dose inhaler ) or for competence ( Turbohaler ) the following day . The Mini-Mental State Examination and EXIT25 ( for executive function ) were performed by separate observers . RESULTS significant correlation was found between the metered dose inhaler score and Mini-Mental State Examination ( r 0.540 , P<0.002 ) and EXIT25 ( r -0.702 , P<0.0001 ) . Threshold effects emerged for the metered dose inhaler in that 18/19 with a competent score compared to 2/11 scored as incompetent had a Mini-Mental State Examination of > 23 ( P<0.01 ) and 19/19 compared to 0/11 had an EXIT25 of < 15 ( P<0.01 ) . Similarly , for the Turbohaler 21/21 of the competent subjects had a Mini-Mental State Examination of > 23 compared with 3/9 incompetent subjects ( P<0.01 ) , with 21/21 competent compared with 0/9 incompetent having an EXIT25 < 15 ( P<0.01 ) . CONCLUSION acquisition and short-term retention of metered dose inhaler and Turbohaler techniques is unlikely to be successful in frail elderly people who have an abnormal Mini-Mental State Examination and /or EXIT25 test . The latter test , when abnormal , is probably the superior predictor of inability to learn inhaler techniques Background : Little is known about adherence to inhaled medication in chronic obstructive pulmonary disease ( COPD ) and the impact on mortality and morbidity . Methods : Data on drug adherence from a r and omised double-blind trial comparing inhaled salmeterol 50 μg + fluticasone propionate 500 μg twice daily with placebo and each drug individually in 6112 patients with moderate to severe COPD over 3 years in the TORCH study were used . All-cause mortality and exacerbations leading to hospital admission were primary and secondary end points . The study of adherence was not specified a priori as an ancillary study . Results : Of the 4880 patients ( 79.8 % ) with good adherence defined as > 80 % use of study medication , 11.3 % died compared with 26.4 % of the 1232 patients ( 20.2 % ) with poor adherence . The annual rates of hospital admission for exacerbations were 0.15 and 0.27 , respectively . The association between adherence and mortality remained unchanged and statistically significant after adjusting for other factors related to prognosis ( hazard ratio 0.40 ( 95 % CI 0.35 to 0.46 ) , p<0.001 ) . The association was even stronger when analysing on-treatment deaths only . Similarly , the association between adherence and hospital admission remained unchanged and significant in a multivariate analysis ( rate ratio 0.58 ( 95 % CI 0.44 to 0.73 , p<0.001 ) . The association between increased adherence and improved mortality and reduction in hospital admission was independent of study treatment . The effect of treatment was more pronounced in patients with good adherence than in those with poor adherence . Conclusion : Adherence to inhaled medication is significantly associated with reduced risk of death and admission to hospital due to exacerbations in COPD . Further research is needed to underst and these strong associations Aim : To investigate the effects of inhaler device technique education on improving inhaler technique in older people with asthma . Methods : In a r and omised controlled trial , device technique education was provided to a sample of 123 adults aged > 55 years who had a doctor diagnosis of asthma . The active education group received one-on-one technique coaching , including observation , verbal instruction and physical demonstration at baseline . The passive group received a device-specific instruction pamphlet only . Inhaler technique , including the critical steps for each device type , was assessed and scored according to Australian National Asthma Council ( NAC ) guidelines . Device technique was scored objective ly at baseline and again at 3 and 12 months post education . Results : The majority of participants demonstrated poor technique at baseline . Only 11 ( 21 % ) of the active intervention group and 7 ( 16 % ) of the passive group demonstrated 100 % correct technique . By 3 months 26 ( 48 % ) of the active group achieved adequate technique . Improvement in technique was observed in the active group at 3 months ( P<0.001 ) and remained significant at 12 months ( P<0.001 ) . No statistically significant improvement was observed in the passive group . Conclusion : The provision of active device technique education improves device technique in older adults . Passive education alone fails to achieve any improvement in device technique AIMS Few well- design ed r and omized controlled trials have been conducted regarding the impact of community pharmacist interventions on pharmacotherapeutic monitoring of patients with chronic obstructive pulmonary disease ( COPD ) . We assessed the effectiveness of a pharmaceutical care programme for patients with COPD . METHODS The pharmaceutical care for patients with COPD ( PHARMACOP ) trial is a single-blind 3 month r and omized controlled trial , conducted in 170 community pharmacies in Belgium , enrolling patients prescribed daily COPD medication , aged ≥ 50 years and with a smoking history of ≥ 10 pack-years . A computer-generated r and omization sequence allocated patients to an intervention group ( n = 371 ) , receiving protocol -defined pharmacist care , or a control group ( n = 363 ) , receiving usual pharmacist care ( 1:1 ratio , stratified by centre ) . Interventions focusing on inhalation technique and adherence to maintenance therapy were carried out at start of the trial and at 1 month follow-up . Primary outcomes were inhalation technique and medication adherence . Secondary outcomes were exacerbation rate , dyspnoea , COPD -specific and generic health status and smoking behaviour . RESULTS From December 2010 to April 2011 , 734 patients were enrolled . Forty-two patients ( 5.7 % ) were lost to follow-up . At the end of the trial , inhalation score [ mean estimated difference (Δ),13.5 % ; 95 % confidence interval ( CI ) , 10.8 - 16.1 ; P < 0.0001 ] and medication adherence ( Δ , 8.51 % ; 95 % CI , 4.63 - 12.4 ; P < 0.0001 ) were significantly higher in the intervention group compared with the control group . In the intervention group , a significantly lower hospitalization rate was observed ( 9 vs. 35 ; rate ratio , 0.28 ; 95 % CI , 0.12 - 0.64 ; P = 0.003 ) . No other significant between-group differences were observed . CONCLUSIONS Pragmatic pharmacist care programmes improve the pharmacotherapeutic regimen in patients with COPD and could reduce hospitalization rates UNLABELLED Twenty-five COPD patients , aged 65years or above , were recruited to test their ability to use dry powder inhaler H and ihaler ( Boeringher-Ingelheim ) and Aerolizer ( Novartis ) . The results of a score created to evaluate the inhalation technique were compared with age , MMSE , Barthel Index , FEV(1 ) , maximum inspiratory and expiratory pressures , and peak inspiratory flow ( PIF ) . RESULTS Dry powder inhalers were correctly used by 60 % of the patients ( 15 out of 25 ) . Among the capable ones , 13 out of 15 were aged less than 80 years ( p < or = 0.02 ) , 13 out of 15 had a maximum inspiratory pressure greater or equal to 53 cm H(2)O ( p < or = 0.001 ) and a PIF greater or equal to 120l/min ( p < or = 0.05 ) . All skilled patients had a minimum MMSE of 25 ( p < or = 0.001 ) . CONCLUSION In a geriatric population , age , the decrease of maximum inspiratory pressure and PIF as well as cognitive functions , limit the use of dry powder inhalers Non-compliance is a major problem in the treatment of any chronic disease . Asthma is one such chronic disease where non-compliance is a major problem . Several factors for non-compliance like cost of the drugs and relief of symptoms on taking medications for a short time are common to all chronic diseases but in asthma , inhalational therapy especially in elderly because of senile changes , economic factors and comorbidities is an added factor . Health education can improve the compliance . So a study was undertaken to observe the causes of non-compliance in asthmatics , to compare these causes in elderly and young asthmatics and to see the effect of health education on non-compliance in asthmatics . One hundred patients of bronchial asthma , group A consisting 50 patients > or = 65 years old and group B 50 patients < 40 years attending tuberculosis and chest diseases hospital , Patiala were studied . Initial compliance and reasons for non-compliance , initial usage of inhalational devices and their techniques of inhalation were studied . Patients were educated on asthma and inhalational techniques . These patients were followed up at 15th day , 1st , 2nd and 3rd months for changes in compliance and lung functions . At the initial stage , non-compliance was observed in 30 patients ( 60 % ) amongst elderly and only 15 patients ( 30 % ) amongst the young . Cause for non-compliance was cost in 6 , memory in 11 , both cost and memory in 7 and relief of symptoms in 6 in elderly and 4 , 0 , 0 and 11 in young respectively . Only 23 patients ( 40 % ) amongst the elderly and 33 patients ( 66 % ) amongst the young were put on inhalational therapy . There were statistically significant differences between elderly and young with respect to all the above factors . Out of these 23 elderly , only 7 ( 30.4 % ) were confident of the technique of inhalation and demonstrated it correctly . The health education result ed in significant improvement in compliance in both the groups , but more so in the young . The compliance for medications improved from a baseline of 40 % to 88 % amongst elderly and from 70 % to 96 % amongst young . There was an improvement in the confidence and technique of inhalation from 44 % to 86 % amongst elderly and from 64 % to 98 % amongst young at follow-ups . Mean PEFR improved statistically significantly from 75.25 % to 81.13 % in elderly and 84.38 % to 89.74 % in young asthmatics . However , during the follow-up at 2nd month , it was realised that 7 patients amongst elderly and 1 amongst young could not be sustained on inhalational medications because of the cost factor , therefore they were put on only oral medications which were supplied free of cost to them and thus at followup at 3rd month , these patients were not on inhalational medications any more Turbuhaler and Salbutamol-Diskus produce therapeutic doses at peak inspiratory flow ( PIF ) of > 30 L/min . However , the optimum flow for Fluticasone-Diskus and Turbuhaler , in terms of total emitted dose and fine particle mass , is > 60 L/min . The Turbuhaler achieved a higher output at this flow , as compared to Diskus . For pMDI 25 < PIF < 90 L/min , an actuation time of 0.0 - 0.2 sec is optimal . The aim of this study was to examine the incidence of optimum inhalation profiles , the effect of instruction , reproducibility , and the relationship between inhalation profiles and patient characteristics in stable asthmatics and mild/moderate/severe COPD patients . For each device , triplicate inhalation profiles were recorded during 6 sessions in a 10-week period . All patients achieved PIF > 30 L/min using Diskus . After instruction , all Diskus inhalations were performed with > 60 L/min , except 7 % of the inhalations of the severe COPD patients . At least 95 % of the Turbuhaler inhalations was also performed with the minimum flow ; however , 19 % of the inhalations of the severe COPD patients were not optimally performed . The h and -lung coordination was inadequate in 40 % of pMDI inhalation profiles , and 80 % was performed with a too high flow . The reproducibility of PIF of both dry powder inhalers ( DPIs ) was very high ( coefficient of variation = 4 - 10 % ) . The reproducibility of the pMDI variables was lower ( coefficient of variation = 9 - 18 % ) . The major lung function variables predictive for PIF(diskus ) and PIF(turbuhaler ) were maximal inspiratory mouth pressure ( MIP ) , PIF , and inspiratory capacity . No significant predictive lung function variables for PIF(pMDI ) were found . Most patients performed reproducible optimum inhalation profiles through Diskus and Turbuhaler . However , in the severe COPD group , 7 - 19 % of the patients were not able to generate the optimum flows through the DPIs . For these patients , a flow-independent aerosol delivery system might be more suitable . The majority of patients were using the pMDI incorrectly . Instruction had no effect . So , we concluded that the pMDI should not be used in these patient groups because of the coordination problems OBJECTIVE To assess the effects of additional information based nursing care program in the treatment of asthma and COPD patients at a pulmonary outpatient clinic . METHODS In a double blind , r and omized clinical trial , 191 patients were allocated to an additional care group or control group . Patients in the intervention group received a protocol -based education program on individual basis by a pulmonary nurse on individual basis ( average duration 60 min per patient ) . All patients were masked for the trial objectives . Effectiveness was expressed in terms of knowledge , inhalation technique , self-management , exacerbation rate ( primary outcomes ) , and health-related quality of life and satisfaction with care received ( secondary outcomes ) . The time interval between the initial and final assessment s was 6 months . RESULTS Ninety-seven patients were r and omized into the additional care group and 94 into the control group , of which 157 had a complete data set . (Un)adjusted analyses did not show differences between treatment groups in terms of knowledge , inhalation technique , self-management , health-related quality of life , and satisfaction with care . Multivariate logistic regression adjusting for baseline covariates showed a significant treatment effect with regard to exacerbation rate ( odds ratio=0.35 ; 95 % confidence limits : 0.13/0.94 , p=0.04 ) . CONCLUSION With the exception of exacerbation rate , we could not demonstrate efficacy of additional nursing care in a broad range of outcome parameters . PRACTICE IMPLICATION S At present we do not recommend to implement our patient-tailored education program in daily practice Instruction is critical in order to ensure correct technique with pressurized metered-dose inhalers ( pMDIs ) by patients . The aim of this study was to compare the effects over time of two educational interventions delivered in community pharmacy to pMDI users . In this r and omized controlled parallel-group study , pMDI technique was assessed before and after written and verbal instruction , alone or with physical demonstration , at baseline and 4 , 8 , and 16 weeks . The study recruited 52 subjects with asthma or chronic obstructive pulmonary disease ( COPD ) . Initially only 1/52 ( 6 % ) subject had correct pMDI technique (= checklist score 8/8 ) , with mean baseline score 5 ( SD 1 ) for both groups . Written and verbal information improved pMDI technique at 16 weeks ( 7 ± 1 , p < .05 ) . Addition of physical demonstration result ed in significant improvement at weeks 4 , 8 , and 16 ( 7 ± 1 , 7 ± 1 , 7 ± 1 respectively ; p < .05 for each ) . Subjects receiving written and verbal information alone were less likely to return for follow-up than those receiving physical demonstration ( 8 weeks : 6/25 versus 19/27 ; p < .001 ) . By the 8-week visit , 80 % subjects in the physical demonstration group had correct technique prior to education , compared with 10 % of subjects receiving written and verbal information alone ( p < .05 ) . There was some decline in inhaler technique by 16 weeks . The results demonstrate that adding a physical demonstration is more effective in improving pMDI technique than written and verbal instructions alone OBJECTIVE To determine whether peak flow monitoring has value above and beyond symptom monitoring when used as part of an asthma management plan . METHODS From a large managed-care organization , 296 adults , aged 50 - 92 yr , were recruited and r and omly assigned in equal numbers to either use of symptoms or peak flow rate ( twice daily or " as needed " ) for asthma monitoring , and monitored every 6 mo for 2 yr . Interventions were delivered in four 90-min small-group classes and included a personalized action plan and coaching in proper use of asthma inhalers . RESULTS We found no significant differences between peak flow rate and symptom monitoring , or between twice-daily and as-needed peak flow monitoring in the primary or secondary study outcomes : health care utilization ( acute , nonacute , or total asthma visits ) , Asthma Quality -of-Life Question naire ( AQLQ ) scores , and lung function . AQLQ scores and prebronchodilator FEV1 increased significantly for both groups between baseline and 6 mo ( AQLQ : mean , 0.4 units ; 95 % confidence interval , 0.3 , 0.5 ; p < 0.0001 ; FEV1 % predicted : mean , 4 % ) . Inhaler technique improved substantially in both groups . CONCLUSIONS Peak flow monitoring has no advantage over symptom monitoring as an asthma management strategy for older adults with moderate-severe asthma when used in a comprehensive asthma management program . Improved outcomes in both groups suggest that underst and ing proper medication use , regular monitoring of asthma status , and underst and ing how to respond to changes are of primary importance This Cochrane review contains 29 r and omised controlled trials ( RCT ) involving 2210 participants ( range 21–201 ) ( Normansell et al. , 2017 ) . Included studies targeted adults and adolescents ( aged 12 years and over ) and children ( aged under 12 years ) with asthma . Follow-up ranged from 2 to 26 weeks . Participants with other respiratory comorbidities , including chronic obstructive pulmonary disease and bronchiectasis , were excluded . Studies examined interventions conducted in hospital , primary care , community or outpatient care setting s. These included interventions aim ed at improving inhaler technique compared with usual care with no additional intervention , or with alternative interventions such as asthma education only or a different type/intensity of inhaler technique intervention . Twelve studies evaluated enhanced face-to-face training , nine used multimedia-delivered training and the rest used technique feedback devices . Studies were conducted in Europe ( n= 11 , of which 6 were in UK and 1 each in Belgium , Denmark , France , Irel and and Italy ) , USA ( n= 7 ) , Australia ( n= 4 ) , Asia ( n= 3 ) , Africa ( n= 1 ) and 3 were of unknown origin . Interventions were delivered by trained health care professionals including nurses , respiratory or physiotherapists , pharmacists and physicians AIM The aim was to investigate the impact of a disease and medicine management programme , focusing on self-management in patients with chronic obstructive pulmonary disease ( COPD ) . METHODS One hundred and seventy-three patients ( mean age 67 years ; 54 % female ) were recruited ; 86 patients were r and omly assigned to an intervention group and 87 to a usual care ( control ) group . Intervention patients received education on disease state , medications and breathing techniques . Patients were given booklets and a customized action plan ( antibiotic and oral steroid to be initiated promptly by patients for exacerbations ) . Patients were followed up at 6 and 12 months during a scheduled visit . The St George 's Respiratory Question naire ( SGRQ ) , COPD Knowledge and Morisky adherence question naires were administered to all patients at baseline , 6 and 12 months . Outcome measures included hospital admissions , emergency department ( ED ) visits , health-related quality of life ( HRQoL ) and medication adherence . RESULTS Over the 12-month period in the intervention group , ED visits decreased by 50 % ( P= 0.02 ) and hospitalization by approximately 60 % ( P= 0.01 ) . On the SGRQ , differences reached statistical significance on the symptom ( -7.5 ; P= 0.04 ) and impact ( -7.4 ; P= 0.03 ) subscales but not on the physical activity subscale . There was a significant difference between the intervention and usual care groups regarding knowledge scores ( 75.0 vs. 59.3 ; P= 0.001 ) and good adherence to medication ( 77.8 % vs. 60.0 % , P= 0.019 ) . There was no significant difference regarding smoking between study groups . CONCLUSIONS The clinical pharmacy-led management programme can improve adherence , reduce the need for hospital care in patients with COPD and improve aspects of their |
10,422 | 30,687,937 | There were no significant differences between topiramate and valproate in participants responding with a 50 % or more reduction in myoclonic seizures or in PGTCS , or becoming seizure-free .
This review does not provide sufficient evidence to support topiramate for the treatment of people with JME .
Based on the current limited available data , topiramate seems to be better tolerated than valproate , but has no clear benefits over valproate in terms of efficacy . | BACKGROUND Topiramate is a newer broad-spectrum antiepileptic drug ( AED ) .
Some studies have shown the benefits of topiramate in the treatment of juvenile myoclonic epilepsy ( JME ) .
However , there are no current systematic review s to determine the efficacy and tolerability of topiramate in people with JME .
This is an up date of a Cochrane Review first published in 2015 , and last up date d in 2017 .
OBJECTIVES To evaluate the efficacy and tolerability of topiramate in the treatment of JME . | Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the treatment effect estimate was reduced by 20 % or more in 19 ( 23 % ) . Of the 42 meta-analyses with a statistically significant result only , eight ( 19 % ) became non-significant after adjustment for outcome reporting bias and 11 ( 26 % ) would have overestimated the treatment effect by 20 % or more . Conclusions Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane review s. Individuals conducting systematic review s need to address explicitly the issue of missing outcome data for their review to be considered a reliable source of evidence . Extra care is required during data extraction , review ers should identify when a trial reports that an outcome was measured but no results were reported or events observed , and contact with trialists should be encouraged PURPOSE To describe our experience with levetiracetam ( LEV ) as initial or conversion monotherapy treatment for juvenile myoclonic epilepsy ( JME ) . Valproate , the usual first line agent for JME , has chronic adverse effects , particularly for women of childbearing potential . Since JME requires lifetime treatment , chronic adverse effects of therapy are important consideration . METHODS We review ed the medical records of patients with JME treated with LEV in the first 4 years after marketing . We recorded demographic data , results of EEG and imaging studies , antiepileptic drug ( AED ) history , LEV initial dose and final dose , side effects related to LEV , and therapeutic response to treatment . We classified JME into definite and probable based on clinical and EEG criteria . The minimum duration of follow up was 1 year . RESULTS LEV was the first therapy in 12 patients and the initial appropriate agent in 16 . Fourteen patients had been treated with another appropriate AED . Eighty percent ( 24/30 ) of patients became seizure free with LEV monotherapy and two additional patients showed improved seizure control . Final therapeutic doses of LEV ranged from 12 to 50mg/(kgday ) . Complete seizure control using LEV was not predicted by previous AED use . Treatment failure with valproate also did not predict failure of LEV . Patients with definite JME responded best within the study group ( 11 of 11 seizure free , p<0.05 ) . CONCLUSIONS This study supports consideration of LEV for first line treatment of JME and suggests the need for a large prospect i ve trial OBJECTIVE The aim of this study was to evaluate the efficacy and tolerability of topiramate ( TPM ) in juvenile myoclonic epilepsy ( JME ) . METHOD We assessed seizure control and adverse effects of TPM in 22 patients ( 18 females ) aged 13 to 53 years . Target TPM dosage was up to 200 mg/day . The patients were subdivided into 3 groups : those treated with seizure control plus side effects ( n=4 ) ; treated with non-controlled seizures ( n=15 ) and with JME newly diagnosed ( n=3 ) . RESULTS Sixteen patients completed the first year of the follow-up . Generalized tonic-clonic seizures were completely controlled in 10 ( 62.5 % ) ; more than 50 % of reduction in 4 ( 25.0 % ) and less than 50 % in 2 ( 12.5 % ) . Myoclonia were controlled in 11 ( 68.8 % ) and persisted in 5 ( 31.2 % ) patients . Absence seizures were present in 5 ( 22.7 % ) of whom 2 ( 9.0 % ) showed more than 50 % of seizure reduction while 3 ( 13.6 % ) presented worsening . Discontinuations were due to inadequate seizure control and adverse events ( N=4 ) , low compliance and loss of follow-up ( N=2 ) and subject choice ( N=1 ) . CONCLUSION TPM showed to be an effective and well-tolerated drug in the treatment of JME . Although frequently observed , TPM side effects were tolerable and the drug could be maintained in the majority of patients BACKGROUND Topiramate is a broad-spectrum agent effective against primarily generalized tonic-clonic seizures ( PGTCS ) as well as partial-onset seizures . Juvenile myoclonic epilepsy is one of the most common idiopathic generalized epilepsies , with most patients experiencing PGTCS . OBJECTIVE To evaluate topiramate as add-on therapy in patients with juvenile myoclonic epilepsy . DESIGN Post-hoc analysis of a patient subset from 2 multicenter , double-blind , r and omized , placebo-controlled , parallel-group trials . SETTING Eighteen centers in the United States ; 10 centers in Europe ; 1 center in Costa Rica ( primary trials ) . PATIENTS A total of 22 patients with juvenile myoclonic epilepsy participating in placebo-controlled trials assessing topiramate ( target dose , 400 mg/d in adults ) in inadequately controlled PGTCS . MAIN OUTCOME MEASURE Reduction of PGTCS . RESULTS A 50 % or more reduction of PGTCS in 8 of 11 topiramate-treated patients ( 73 % ) and 2 of 11 placebo-treated patients ( 18 % ) ( P = .03 ) . Reductions in myoclonic , absence , and total generalized seizures were also observed , although topiramate vs placebo differences did not achieve statistical significance . CONCLUSION As a broad-spectrum agent , topiramate is an effective option for patients with juvenile myoclonic epilepsy Juvenile myoclonic epilepsy ( JME ) is managed with valproate in most patients ; however , valproate is an antiepileptic drug that has relatively severe adverse effects , especially in women . We performed a prospect i ve , open-label , r and omized observational study for comparison of efficacy and tolerability between topiramate and valproate in patients with JME . The inclusion criteria were patients with newly diagnosed JME or previously diagnosed JME with a history of a poor response or adverse effects to other antiepileptic drugs . The primary endpoint of this study was percentage of patients who were free of myoclonic seizures for 24 weeks in the two groups . The frequency and severity of adverse effects were also assessed . Sixteen patients were r and omized to topiramate and 17 to valproate . In the topiramate arm , 11 of 16 patients ( 68.9 % ) completed 24-week maintenance therapy and seven of the 11 ( 64 % ) were seizure-free . In the valproate arm , 16 of 17 patients ( 94.1 % ) completed 24-week follow-up and nine of 16 ( 56 % ) were seizure-free . The difference ( 64 % topiramate versus 56 % valproate ) did not reach statistical significance in this study group ( p = 0.08 , Fisher 's exact test ) . However , the severity of adverse effects was significantly different . Only 1 of 10 adverse effects from topiramate was ranked moderate-to-severe ( 10 % ) , in comparison with severe rankings for 10 of 17 adverse effects from valproate ( 59 % ) ( p = 0.018 , Fisher 's exact test ) . In summary , the efficacy of topiramate and valproate was not different , but the severity of adverse effects was favourable for topiramate . Our findings suggest that valproate may be replaced with topiramate , especially for the patients with JME who do not tolerate valproate Objectives – Based on dose predictions from animal and human volunteer studies , most patients enrolled in initial r and omized controlled trials of topiramate as adjunctive therapy in adults with partial‐onset seizures were r and omized to ≥ 600 mg/day topiramate . Subsequent experience suggests that dosage needs were overestimated . This double‐blind , placebo‐controlled study evaluated 200 mg/day topiramate in adults with treatment‐resistant partial‐onset seizures receiving a concurrent enzyme‐inducing antiepileptic agent ( carbamazepine ) . Material and methods – After a 4‐week baseline , 263 adults receiving carbamazepine who had at least three partial‐onset seizures during the baseline period were r and omized to placebo or one of two topiramate 200 mg/day treatment arms : topiramate escalated weekly 25 mg/day(8‐week escalation ) or 50 mg/day(4‐week escalation ) . Therapy was then maintained for the remainder of the 12‐week double‐blind study . Results – Median percent reduction in seizure frequency from baseline to study end was 44 % with topiramate and 20 % with placebo ( P ≤ 0.001 ) . A significant therapeutic effect was present at 2 weeks with a dose of 100 mg/day . The most common adverse events ( ≥10 % incidence in topiramate‐treated patients ) were somnolence , fatigue , paresthesia , nervousness and anorexia ; 8 % of topiramate‐treated patients and 2 % of placebo‐treated patients discontinued because of adverse events . As a result of the low incidence of adverse events , differences between titration rates in terms of tolerability were not detected . Conclusion – Topiramate 200 mg/day is an appropriate target dose as adjunctive therapy in adults with treatment‐resistant partial‐onset seizures , even when receiving an enzyme‐inducing agent ; 100 mg/day also appears to be effective . A significant therapeutic effect may be seen in the second week of treatment with a dose of 100 mg/day Few r and omized , controlled trials evaluating antiepileptic drug ( AED ) efficacy and tolerability have focused solely on patients with juvenile myoclonic epilepsy ( JME ) . We conducted a pilot , r and omized controlled trial comparing topiramate ( N=19 ) and valproate ( N=9 ) in adolescents/adults with JME to evaluate clinical response when these broad-spectrum agents are titrated to optimal effect . Rating scales were used to systematic ally assess tolerability . Among patients completing 26 weeks of treatment , 8 of 12 ( 67 % ) in the topiramate group and 4 of 7 ( 57 % ) in the valproate group were seizure-free during the 12-week maintenance period . Median daily dose was 250 mg topiramate or 750 mg valproate . Two ( 11 % ) topiramate-treated patients and one ( 11 % ) valproate-treated patient discontinued due to adverse events . Systemic toxicity scores , but not neurotoxicity scores , differed substantially between the two groups ; greater systemic toxicity was associated with valproate . Our preliminary findings that topiramate may be an effective , well-tolerated alternative to valproate warrant validation in a double-blind trial |
10,423 | 28,173,609 | With respect to plaque removal , evidence that supports the recommendation for usage of a TFTB over an ERTB is lacking .
Regarding GI , there is minimal evidence favouring a TFTB over an ERTB and the clinical relevance of this difference is probably negligible .
Therefore , based on the collective evidence emerging from this systematic review , the strength and direction of the recommendation , there appears to be no firm evidence for a dental healthcare professional to advise the use of a TFTB over the use of an ERTB | AIM This systematic review was performed to establish the effect of a manual toothbrush with tapered toothbrush filaments ( TFTBs ) compared to a manual toothbrush with end-rounded toothbrush filaments ( ERTB ) on clinical parameters of dental plaque , gingivitis and gingival abrasion . | OBJECTIVES The aim of this study was to evaluate the proportions of end-rounded bristles via observations of the end patterns of various children 's toothbrushes with scanning electron microscopy ( SEM ) and stereomicroscopy . METHODS Ten different br and s of children 's toothbrushes were chosen , and tufts from each toothbrush were used . The prepared bristle specimens were observed on SEM and stereomicroscopic images and classified as acceptable ( A1-A3 ) and non-acceptable ( N1-N5 ) according to the modified classification . Then , the proportions of end-rounded bristles were calculated . RESULTS Analyses of the 10 toothbrushes revealed that the proportions of acceptable end-rounded bristles ranged from 1.4 % to 20.2 % on SEM and from 0.0 % to 18.0 % on stereomicroscopic examinations . Additionally , some toothbrushes had labels that indicated bristle end-rounding , but the proportions of end-rounded bristles were low . CONCLUSIONS The types and percentages of bristle ends of children 's toothbrushes marketed in Korea were various , but the amount of acceptable end-rounded bristles was low . The result , that even toothbrushes labelled as end-rounded had potential to harm oral tissue , demonstrates that quality control for rounding bristle ends as well as the labelling for end-rounded bristles is needed OBJECTIVES To compare a tapered filament toothbrush ( TFTB ) to a control toothbrush ( ADA ) in their potential to cause gingival abrasion and improve the gingival condition following a period of experimental gingivitis . METHODS Thirty-two subjects refrained from brushing m and ibular teeth for 21 days . During a subsequent 4-week treatment phase , the left or right side of the mouth was brushed with either the TFTB or ADA as r and omly allocated . Gingival abrasion , plaque and gingival bleeding were assessed . RESULTS During the treatment phase gingival abrasion showed a trend to be lower with the TFTB than the ADA , which was significant at the 2-week assessment . The mean plaque scores changed from 2.98 ( day 21 ) to 1.59 for the TFTB and from 3.00 ( day 21 ) to 1.31 for the ADA . The mean bleeding scores changed from 1.86 ( day 21 ) to 1.35 for the TFTB and from 1.85 ( day 21 ) to 1.20 for the ADA . Plaque and bleeding scores were significantly lower with the ADA . CONCLUSIONS Both toothbrushes improved gingival health and effectively removed plaque . Although there was a tendency towards fewer sites with gingival abrasion with the TFTB brush , it was less effective than the ADA in the removal of plaque biofilm and reduction of bleeding . Subjects considered the TFTB to be more pleasant to use OBJECTIVE The purpose of this study was to test the efficacy and safety of a newly design ed multi-level manual toothbrush ( Profit-Haije-Brush ) compared with a control flat-trimmed manual reference toothbrush from the American Dental Association ( ADA ) . MATERIAL AND METHODS For this study , 36 healthy subjects without previous experience in the use of the Profit-Haije-Brush ( PHB ) were selected . Subjects were given a period of 2 weeks to become familiar with both types of brushes and were instructed to use them on alternate days for 2 min twice daily . Prior to their visit , subjects refrained from all oral hygiene procedures for 48 h. Prebrushing plaque and gingival abrasion scores were assessed . Subsequently , two r and omly chosen contra-lateral quadrants were brushed with one of both brushes and the other two quadrants with the alternate brush . Subjects were supervised during their 2-min brushing exercise . After brushing , plaque and gingival abrasion were re-assessed . A question naire was filled out to investigate the subjects ' attitudes towards both brushes . RESULTS The overall mean prebrushing PI was 2.47 for the PHB and 2.44 for the ADA . The reduction in PI was 1.32 and 1.23 respectively ( P < 0.05 ) . With regard to gingival abrasion the overall mean prebrushing scores were 4.57 ( PHB ) and 5.34 ( ADA ) . Post-brushing scores were 13.49 and 13.77 for the PHB and ADA respectively . CONCLUSION Statistically , the multi-level PHB was significantly more efficacious than the flat-trimmed ADA . However , the difference is clinical ly considered small and the amount of remaining plaque was not significantly different between brushes . No greater potential to cause gingival abrasion to the oral tissues was observed PURPOSE To compare the cleaning efficacy of ( A ) : a newly developed manual toothbrush with tapered filaments ( meridol , GABA International , CH-Münchenstein ) with ( B ) : a st and ard flat trim manual toothbrush ( ADA reference toothbrush ) in vivo . MATERIAL S AND METHODS 87 healthy participants took part in this study . Subjects were asked to abstain from all oral hygiene procedures for 48 hours . After plaque was scored ( Turesky modification of the Quigley Hein Index ) , the subjects brushed their teeth under supervision with the two manual toothbrushes according to a split-mouth design . In total , a cleaning time of two minutes was given for the whole procedure with an alert after every 30 seconds . Immediately after brushing , plaque was scored again by the same investigator , who was blind with respect to the toothbrush used . RESULTS Using the non-parametric Wilcoxon test for paired sample s ( p<0.05 ) the overall plaque scores were reduced for ( A ) from 1.95+/-0.48 to 1.02+/-0.41 ( p<0.001 ) , and ( B ) from 1.93+/-0.52 to 1.09+/-0.44 ( p<0.001 ) . At proximal surfaces the plaque scores were reduced ( A ) from 2.02+/-0.49 to 1.11+/-0.43 ( p<0.001 ) and ( B ) from 2.01+/-0.52 to 1.20+/-0.45 ( p<0.001 ) . The relative plaque reductions overall were ( A ) 47.4+/-18.0 % and ( B ) 44.1+/-15.6 % ( p=0.039 ) , at proximal surfaces ( A ) 44.2+/-18.8 % and ( B ) 40.5+/-15.9 % ( p=0.015 ) , and at lingual surfaces ( A ) 30.6+/-28.1 % and ( B ) 24.0+/-27.1 % ( p=0.016 ) . CONCLUSION Both brushes removed a significant amount of plaque . Overall and in areas difficult to reach , the meridol toothbrush was superior to the ADA reference brush OBJECTIVE The present study was design ed to evaluate the health promotion effectiveness , especially at the gingival margin , and the subjective satisfaction of a new toothbrush with soft conical filaments . METHODOLOGY Sixty-eight healthy adult subjects participated in the clinical trial and were r and omly divided into a test group ( meridol toothbrush ) or control group ( st and ard ADA reference toothbrush ) . Subjects were given oral hygiene instructions and a pre- study cleaning by a dental hygienist . Clinical examinations included the Gingival Index ( GI ) , Bleeding Index ( BLI ) , and Patient Hygiene Performance Index ( PHP ) for plaque levels ( before and after brushing ) , and were conducted at baseline , 30 , and 60 days . A self-administered satisfaction question naire was applied at 30 and 60 days . The statistical test employed for change within each test group was repeated measures ANOVA , and ANCOVA was employed for between-group analysis . For measures of satisfaction , Fisher 's Exact test was applied when comparing the percentages of answers . RESULTS For the GI , the test group demonstrated a highly significant statistical decrease ( from GI = 0.22 to GI = 0.13 , p = 0.0004 ) . The control group showed less of a decrease with statistical significance ( GI = 0.21 to GI = 0.16 , p = 0.05 ) . For the BLI , the test group also demonstrated a highly significant statistical decrease ( from BLI = 0.29 to BLI = 0.11 , p = 0.0013 ) , while the control group showed a very small decrease with no statistical significance ( BLI = 0.24 to BLI = 0.17 ) . The analyses of the PHP plaque levels after brushing showed significant and similar decreases for both groups over the study period ( test group : p = 0.04 , controls : p = 0.01 ) . In an analysis of PHP before brushing , both brushes showed increases from baseline to day 30 . This increase continued from day 30 to day 60 for the control group . For the test group , there was a significant decrease from day 30 to day 60 ( PHP = 0.84 to PHP = 0.75 , p = 0.037 ) . For satisfaction , a significantly higher percentage of test subjects expressed that the brush was " pleasant to use " as compared to controls , both at 30 and 60 days ( 77 % vs. 48 % , p = 0.02 , 80 % vs. 54 % , p = 0.04 , respectively ) . CONCLUSION The initial increase in plaque levels ( before brushing ) in the test group , is explained as a possible " learning curve " effect of using this new and unconventional brush . It is suggested that the conical filaments clean the subgingival pockets and that this is of important gingival health potential . This subgingival cleansing might not be adequately detected by the PHP index . These results might indicate a gingival health promotion potential for this toothbrush with conical filaments The aim of this RCT was to evaluate plaque control and gingival health promotion effectiveness of a new toothbrush with extra-soft filaments in postsurgical sets . Ten consecutive patients with at least two scheduled symmetrical periodontal surgeries were selected . Following the first periodontal surgery , a test ( TB1 ) or control ( TB2 ) toothbrush was r and omly assigned . After the second surgery , the remaining toothbrush was given . Patients were asked to gently wipe the surgical area from days 3 to 7 postoperatively and to gently brush using a roll technique from day 7 till the end of the study . Baseline evaluation took place on the day of surgery and follow-ups were performed at days 7 , 14 , and 30 postoperatively . A more evident PI reduction was recorded for test toothbrush where a regular decrease was observed till day 14 ; then , this parameter tended to stabilize , remaining however lower than that recorded for the control toothbrush . There were no statistical differences in the GI between test and control toothbrushes . All patients introduced the test toothbrush at surgical site at third day ; the control toothbrush was introduced within a mean of 9 days . The introduction of the test toothbrush 3 days after periodontal surgery may be recommended OBJECTIVE The elmex SENSITIVE extra soft toothbrush , with soft conical filaments design ed for plaque removal specifically in the cervical area and interdental spaces , and gentleness for hypersensitive teeth with exposed dentine , was evaluated for plaque removal effectiveness , safety , and subjective satisfaction . METHODS One-hundred and seven healthy adults participated in the clinical trial design ed according to American Dental Association ( ADA ) guidelines , and were r and omly divided into a test group ( N = 54 ) using the elmex brush , and a control group ( N = 53 ) using the ADA reference brush . Subjects were chosen with gingival recession result ing in exposed dental necks and reported sensitivity , and were given a pre- study cleaning by a hygienist . Clinical examinations included the Rustogi plaque index ( before and after brushing ) , and an examination for any soft lesion adverse effects , at baseline , 30 , and 60 days . A subjective question naire , measuring satisfaction , sensitivity , and painless brushing , was administered at 30 and 60 days . An ANCOVA model , with baseline level as the covariate , was employed for testing clinical differences between groups at one and two months . The Mann-Whitney test measured differences in the satisfaction question naires . RESULTS The total plaque index , after brushing and at one and two months , demonstrated a significantly higher mean level for the control compared to the test group ( 3.05 vs. 2.16 ; p = 0.001 and 3.47 vs. 2.56 ; p = 0.0003 , respectively ) . Similar significant differences were detected for plaque levels at the gingival margin and the proximal dental surfaces , after brushing at one and two months . No significant differences were found pre-brushing at any of the measurement points . Most subjective assessment s of the two brushes at one and two months revealed significant differences in favor of the test brush . CONCLUSION These results indicate an effective toothbrush for promoting oral health , and patient acceptance of a toothbrush with soft conical filaments intended specifically for sensitive teeth OBJECTIVE The objective of this study was to evaluate the effect of different levels of filament end rounding on gingival abrasions ( GAs ) . METHODS The study was a crossover , split-mouth , contra-lateral , double-blinded , r and omized design using professional brushing . Three manual toothbrushes , with 0 % , 40 - 50 % and > 90 % end-rounded filaments , were investigated . Participants refrained from all oral hygiene procedures for 48 h prior to each of the three visits . Prior to brushing , oral soft tissue ( OST ) and GAs were assessed . Based on the r and omization , during every visit contra-lateral quadrants were brushed with one of the three test brushes . After brushing , GAs were re-assessed . The means of the GAs prebrushing and post-brushing and differences per brush were calculated . Subanalyses were performed based on the size of the abrasion and its location . RESULTS A total of 46 generally healthy participants without periodontitis completed the study and provided a full data set . All brushes had statistically significant increases of abrasions following their use ( P < 0.001 ) . Non-end-rounded brushes provided significantly more GAs than did the 40 - 50 % and the > 90 % brushes ( P ≥ 0.001 ) . A sub analysis showed that significantly more small-sized ( P ≥ 0.002 ) abrasions located at the gingival margin ( P < 0.001 ) occurred when a non-end-rounded brush was used . No significant differences were found between the 40 - 50 % and > 90 % end-rounded brushes in any of the analyses . OST deviations were not observed . CONCLUSIONS Based on the results of this experiment involving professional brushing , it can be concluded that 40 - 50 % or greater end-rounded filaments can provide a significant reduction in gingival abrasions compared to non-end-rounded filaments Two previous clinical studies evaluated the effect of end-rounded versus tapered bristles of soft manual brushes on the removal of plaque and gingival abrasion . However , the combined effect of an abrasive dentifrice on these outcomes has yet to be understood . The purpose of the present study was to compare the incidence of gingival abrasion and the degree of plaque removal obtained after the use of toothbrushes with tapered or end-rounded bristles in the presence or absence of an abrasive dentifrice . The study involved a r and omized , single-blind , crossover model ( n = 39 ) with a split-mouth design . Subjects were instructed to refrain from performing oral hygiene procedures for 72 hours . Quadrants were r and omized and subjects brushed with both types of toothbrushes using a dentifrice ( relative dentin abrasion = ± 160 ) . Plaque and gingival abrasion were assessed before and after brushing . After 7 days , the experiment was repeated without the dentifrice . The average reduction in plaque scores and the average increase in the number of abrasion sites were assessed by repeated- measures ANOVA and Bonferroni 's post-hoc tests . End-rounded bristles removed significantly more plaque than tapered bristles , regardless of the use of a dentifrice . The dentifrice did not improve plaque removal . In the marginal area ( cervical free gingiva ) , no difference in the incidence of gingival abrasion was detected between toothbrush types when used with a dentifrice ( p ≥ 0.05 ) . However , the dentifrice increased the incidence of abrasion ( p < 0.001 ) , irrespective of the toothbrush type tested . End-rounded bristles therefore removed plaque more effectively without causing a higher incidence of gingival abrasion when compared with tapered bristles . An abrasive dentifrice can increase the incidence of abrasion , and should be used with caution by individuals who are at risk of developing gingival recession The aims of the present study were : ( 1 ) to establish the incidence of gingival abrasion as a result of toothbrushing , using a manual and electric toothbrush ; ( 2 ) to establish the influence of filament end-rounding on the incidence of gingival abrasion and the efficacy of toothbrushing ; ( 3 ) to assess whether the speed of the electric brush has a feedback-effect on the brushing force used and to correlate the incidence of gingival abrasion with force . 2 experiments were carried out . In the first experiment , 50 subjects brushed for 3 weeks every other day with either a manual ( Butler 411 ) or an electric toothbrush ( Braun/Oral-B Ultra Plaque Remover-D9 ) . All received brief instructions and were asked to abstain from oral hygiene 24 hrs before their appointment . After disclosing the teeth and gums with Mira-2-Tone solution , plaque and gingival abrasion were assessed . Next , the panelists brushed in a r and om split-mouth order . After brushing and a second disclosing , plaque and abrasion were re-assessed . The results showed that the incidence of gingival abrasion was comparable for the manual and the D9 . Using a similar design as in experiment no. 1 , in experiment no. 2 a new group of 47 subjects brushed for 3 weeks alternating between the Braun/Oral-B Plaque Remover-D7 and D9 . At the appointment , the subjects first brushed in a split-mouth order with the D9 with 2 different types of endrounding . Plaque and abrasion were assessed . Immediately following this brushing exercise , the subjects re-brushed with the D7 ( 2800 rot/min ) and the D9 ( 3600 rot/min ) during which brushing force was measured . The results of this experiment showed that endrounding has no effect on plaque removal but does effect the incidence of gingival abrasion . Brushing force is not influenced by the speed of the brushhead and no correlation with the incidence of gingival abrasion was observed . In conclusion , the results of this study show that gingival abrasion is not influenced by brushing force , but is affected by filament endrounding OBJECTIVE The purpose of this single-blind clinical study was to evaluate the efficacy of an innovative manual toothbrush versus a traditional one . METHODS The toothbrushes were r and omly assigned to 30 volunteers in a student population of the Dental School of the University of Bologna , Italy , divided into 15 test and 15 control subjects . A clinical examination assessing Plaque Index ( PI ) , Gingival Index ( GI ) and buccal Gingival Recessions was performed at baseline , 3 and 6 months . During the baseline examination , each subject received dental debridement , oral hygiene instructions and a st and ard kit containing : three st and ard tubes of toothpaste , 1 hourglass ( 2 min ) and one plaque disclosing solution ; each subject of the test group received three innovative toothbrushes , while each subject of the control group received three traditional toothbrushes . RESULTS During the 6 months of observation both groups presented a PI and GI decrease . A more evident improvement of both indices was observed in the test group ( PI P = 0.0001 , GI P = 0.0001 ) . The greatest part of recessions remained stable ( 0 - 3 months : 70 % test group , 60 % control group and 3 - 6 months : 86 % test group , 94 % control group ) . Some amplitude modifications ( 0.5 mm ) were mainly detected in the first 3 months ( control group chi(2 ) = 17.55 , P = 0.0001 and test group chi(2 ) = 3.31 , P = 0.07 ) . They always increased in the control group and decreased in the study group . CONCLUSIONS The innovative manual toothbrush is more likely to be effective in reducing PI and GI compared to the traditional one and widely safe on periodontal tissues during the period of observation |
10,424 | 31,710,832 | Our findings showed that HL was instrumental in improving diabetes knowledge , physical activity , self-efficacy and quality of life ; however , its associations with glycaemic control , self-monitoring of blood glucose , foot care and medication adherence was inconclusive .
Customized and community-based HL interventions were more efficient compared to patient-focused HL interventions .
This review concludes that HL is key for T2DM self-management , but customised , structured and community-based interventions are more likely to yield better outcomes | The purpose of this review is to summarise the existing evidence about the association of health literacy ( HL ) with type 2 diabetes mellitus self-management . | The current r and omized controlled study evaluated the effects of a health literacy-considered diabetes self-management program on diabetes-related parameters : diabetes self-management knowledge ( DSK ) , diabetes health beliefs ( DHB ) , diabetes self-efficacy ( DSE ) , diabetes self-management behavior ( DSMB ) , and diabetes biomarkers . Fifty-one Korean older adults with diabetes completed 12 weekly sessions that were developed based on their health literacy and health-related characteristics . The results indicate significant posttest differences between groups in DSK ( p = 0.046 ) , DSE ( p = 0.046 ) , DSMB ( p = 0.012 ) , and the DSMB self-monitored blood glucose subscale ( p = 0.002 ) . Significant pre-post changes between groups were observed in the DHB benefit subscale ( p = 0.043 ) , DSE ( p = 0.006 ) , DSMB ( p = 0.008 ) , DSMB diet ( p = 0.029 ) , and the self-monitored blood glucose subscale ( p < 0.001 ) . A significant pre-post difference was observed in the intervention group 's HbA1c levels ( p = 0.008 ) . The program effectively improved participants ' DSK , DHB , DSE , and DSMB values , which may be helpful for improving HbA1c levels . [ Res Gerontol Nurs . 2017 ; 10(5):215 - 225 . ] Background Developing accessible Web-based material s to support diabetes self-management in people with lower levels of health literacy is a continuing challenge . Objective The objective of this international study was to develop a Web-based intervention promoting physical activity among people with type 2 diabetes to determine whether audiovisual presentation and interactivity ( quizzes , planners , tailoring ) could help to overcome the digital divide by making digital interventions accessible and effective for people with all levels of health literacy . This study also aim ed to determine whether these material s can improve health literacy outcomes for people with lower levels of health literacy and also be effective for people with higher levels of health literacy . Methods To assess the impact of interactivity and audiovisual features on usage , engagement , and health literacy outcomes , we design ed two versions of a Web-based intervention ( one interactive and one plain-text version of the same content ) to promote physical activity in people with type 2 diabetes . We r and omly assigned participants from the United Kingdom , Austria , Germany , Irel and , and Taiwan to either an interactive or plain-text version of the intervention in English , German , or M and arin . Intervention usage was objective ly recorded by the intervention software . Self-report measures were taken at baseline and follow-up ( immediately after participants viewed the intervention ) and included measures of health literacy , engagement ( website satisfaction and willingness to recommend the intervention to others ) , and health literacy outcomes ( diabetes knowledge , enablement , attitude , perceived behavioral control , and intention to undertake physical activity ) . Results In total , 1041 people took part in this study . Of the 1005 who completed health literacy information , 268 ( 26.67 % ) had intermediate or low levels of health literacy . The interactive intervention overall did not produce better outcomes than did the plain-text version . Participants in the plain-text intervention group looked at significantly more sections of the intervention ( mean difference –0.47 , 95 % CI –0.64 to –0.30 , P<.001 ) , but this did not lead to better outcomes . Health literacy outcomes , including attitudes and intentions to engage in physical activity , significantly improved following the intervention for participants in both intervention groups . These improvements were similar across higher and lower health literacy levels and in all countries . Participants in the interactive intervention group had acquired more diabetes knowledge ( mean difference 0.80 , 95 % CI 0.65 - 0.94 , P<.001 ) . Participants from both groups reported high levels of website satisfaction and would recommend the website to others . Conclusions Following established practice for simple , clear design and presentation and using a person-based approach to intervention development , with in-depth iterative feedback from users , may be more important than interactivity and audiovisual presentations when developing accessible digital health interventions to improve health literacy outcomes . Clinical Trial International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 43587048 ; http://www.is rct n.com/IS RCT N43587048 . ( Archived by WebCite at http://www.webcitation.org/6nGhaP9bv OBJECTIVE To compare the effectiveness of different approaches to nutrition education in diabetes self-management education and support ( DSME/S ) . METHODS We r and omized 150 adults with type 2 diabetes to either certified diabetes educator (CDE)-delivered DSME/S with carbohydrate gram counting or the modified plate method versus general health education . The primary outcome was change in HbA1C over 6 months . RESULTS At 6 months , HbA1C improved within the plate method [ -0.83 % ( -1.29 , -0.33 ) , P<0.001 ] and carbohydrate counting [ -0.63 % ( -1.03 , -0.18 ) , P=0.04 ] groups but not the control group [ P=0.34 ] . Change in HbA1C from baseline between the control and intervention groups was not significant at 6 months ( carbohydrate counting , P=0.36 ; modified plate method , P=0.08 ) . In a pre-specified subgroup analysis of patients with a baseline HbA1C 7 - 10 % , change in HbA1C from baseline improved in the carbohydrate counting [ -0.86 % ( -1.47 , -0.26 ) , P=0.006 ] and plate method groups [ -0.76 % ( -1.33 , -0.19 ) , P=0.01 ] compared to controls . CONCLUSION CDE-delivered DSME/S focused on carbohydrate counting or the modified plate method improved glycemic control in patients with an initial HbA1C between 7 and 10 % . PRACTICE IMPLICATION S Both carbohydrate counting and the modified plate method improve glycemic control as part of Background The prevalence of type 2 diabetes mellitus is increasing substantially worldwide , leading to serious economic effects , complications and deaths . This study evaluated the effectiveness of an empowerment program providing support for psychosocial , behavioral , and clinical aspects of diabetes to help Brazilian users of public health services obtain metabolic control of this condition . Methods In this cluster r and omized trial , participants aged 30–80 diagnosed with type 2 diabetes were recruited from ten Brazilian public health units in 2014 and 2015 . Five units were r and omly assigned to receive the empowerment program based on a behavior change protocol , and five continued to receive only conventional treatment . The primary outcome was the biochemical and anthropometric parameters , and the secondary outcomes were self-care , attitude , knowledge and empowerment related to diabetes . The effect of the experiment was defined as the percentage variation between the values at the initial and final periods . To evaluate this effect and to compare it in the two groups , tests were used for paired and independent sample s , respectively . Results There were 238 participants : 127 and 111 in the intervention and control group , respectively . For glycated hemoglobin , the mean effect in the control and intervention groups was 3.93 and −5.13 , respectively ( p < 0.001 ) . Levels of glycated hemoglobin and other metabolic indicators , as well as the most part of the secondary outcomes showed a significant difference in the experimental group compared to the control group . Conclusions The empowerment program improved metabolic control of type 2 diabetes in Brazilian users . Trial registration NCT02132338 - April 22 , 2014 BACKGROUND Despite extensive efforts and advances in evidence -based diabetes management , poor glycaemic control still remains a challenge in many countries . There is a paucity of research addressing the needs of patients with poorly controlled type 2 diabetes , or exploring the effectiveness of empowerment-based interventions in this vulnerable population . OBJECTIVES To evaluate the effectiveness of a patient-centred , empowerment-based programme on glycaemic control and self-management behaviours among patients with poorly controlled type 2 diabetes . DESIGN A prospect i ve multi-centre , single-blind , r and omised controlled trial . SETTING S AND PARTICIPANTS Adult patients with poorly controlled type 2 diabetes [ Haemoglobin A1c ( HbA1c ) ≥7.5 % in the recent six months ] were recruited from two tertiary hospitals in Xi'an city , China . METHODS A total of 242 eligible patients were recruited and r and omly assigned to the intervention or attentional control groups after baseline measurement . Participants in the intervention group received a 6-week patient-centred , empowerment-based self-management programme , which is theoretically grounded on the principles of the Empowerment Process Model- setting personally meaningful goals , taking action towards goals and reflecting on the impact of action plans . Those in the attentional control group received health education classes and post-discharge follow-up . Outcome measures included glycaemic control ( measured by HbA1c ) and self-management behaviours . Data were collected at baseline , and at 8th and 20th week after enrolment . Intervention effect were analysed using the generalised estimating equation model on the basis of the intention-to-treat principle . RESULTS Compared with the attention control group , the intervention group showed a non-significant HbA1c reduction of 0 . 476 % ( Cohen 's d effect size=0.31 , p=0.162 ) . The intervention group exhibited significant improvements in general diet management at the 8th-week ( β=0.740 ; p=0.013 ) , specific diet management at 8th-week ( β=0.646 ; p=0.022 ) and 20th-week ( β=0.517 ; p=0.043 ) , and blood glucose self-monitoring at both the 8th- ( β=0.793 ; p=0.009 ) and 20th-week ( β=0.739 ; p=0.017 ) follow-ups . No intervention-related adverse events were observed . CONCLUSIONS Findings indicate that the patient-centred , empowerment-based self-management intervention program did not induce a significant HbA1c reduction . Whereas this intervention yields improvements in diet management and blood glucose self-monitoring among patients with poorly controlled type 2 diabetes AIMS AND OBJECTIVES To examine the effect of a hospital-based clinic intervention on glycaemic control self-efficacy and glycaemic control behaviour of Chinese patients with type 2 diabetes mellitus ( DM ) . BACKGROUND Self-efficacy expectations are related to self-management of diabetes and , in conjunction with environmental support , are better predictors of behaviour than are knowledge and skills . Enhancing self-efficacy in patients with DM has been shown to have a positive effect on behavioural change and positively influence long-term glycaemic control . DESIGN A r and omised controlled trial study consisting of two-group pretest-post-test . METHODS One hundred and fifty-seven patients with type 2 DM were r and omly divided into two groups : ( 1 ) the experimental group ( 77 patients ) receiving one-month hospital-based clinic intervention and ( 2 ) the control group ( 80 patients ) receiving usual care . Data collection instruments used in this study were Diabetes Management Self-Efficacy Scale and Summary of Diabetes Self-Care Activities Measure . Outcomes were determined by changes in glycaemic control self-efficacy and glycaemic control behaviour of patients with type 2 DM . RESULTS The findings revealed that the experimental group showed statistically significant improvement in glycaemic control self-efficacy and glycaemic control behaviour immediately and four months after the intervention ( F = 26.888 , df = 1 , 155 , p < 0.05 and F = 18.619 , df = 1 , 155 , p < 0.05 , respectively ) . CONCLUSIONS One-month hospital-based clinic intervention could be useful in improving glycaemic control self-efficacy and glycaemic control behaviour . RELEVANCE TO CLINICAL PRACTICE Nurses can learn and use the sources of self-efficacy to enhance patients ' self-efficacy on their glycaemic control in clinical care . The health education is most important in nursing care and should be considered while organising the hospital-based clinic intervention Background Lower socioeconomic status is associated with excess disease burden from diabetes . Diabetes self-management support interventions are needed that are effective in engaging lower income patients , addressing competing life priorities and barriers to self-care , and facilitating behavior change . Objective To pilot test feasibility , acceptability , and effect on disease control of a problem-based diabetes self-management training adapted for low literacy and accessibility . Design Two-arm r and omized controlled trial powered to detect a 0.50 % change in A1C at follow-up with a 2-sided alpha of 0.05 in a pooled analysis . Participants Fifty-six urban African-American patients with type 2 diabetes and suboptimal blood sugar , blood pressure , or cholesterol control recruited from a diabetes registry within a university-affiliated managed care organization . Interventions A group , problem-based diabetes self-management training design ed for delivery in an intensive and a condensed program format . Three intensive and three condensed program groups were conducted during the trial . Main Measures Clinical ( A1C , systolic blood pressure [ SBP ] , diastolic blood pressure [ DBP ] , LDL and HDL cholesterol ) and behavioral ( knowledge , problem solving , self-management behavior ) data were measured at baseline , post-intervention , and 3 months post-intervention ( corresponding with 6–9 months following baseline ) . Results Adoption of both programs was high ( > 85 % attendance rates , 95 % retention ) . At 3 months post-intervention , the between-group difference in A1C change was −0.72 % ( p = 0.02 ) , in favor of the intensive program . A1C reduction was partially mediated by problem-solving skill at follow-up ( ß = −0.13 , p = 0.04 ) . Intensive program patients demonstrated within-group improvements in knowledge ( p < 0.001 ) , problem-solving ( p = 0.01 ) , and self-management behaviors ( p = 0.04 ) . Among the subsets of patients with suboptimal blood pressure or lipids at baseline , the intensive program yielded clinical ly significant individual improvements in SBP , DBP , and LDL cholesterol . Patient satisfaction and usability ratings were high for both programs . Conclusions A literacy-adapted , intensive , problem-solving-based diabetes self-management training was effective for key clinical and behavioral outcomes in a lower income patient sample AIMS We evaluated a theoretically-derived family-oriented intervention aim ed to improve self-efficacy , self-management , glycemic control and quality of life in individuals living with Type 2 diabetes in Thail and . METHODS In a single-blinded r and omized controlled trial , 140 volunteer individuals with Type 2 diabetes , recruited from a diabetes clinic in rural Thail and , were r and omly allocated to intervention and control arms . Those in the intervention arm received routine care plus a family-oriented program that included education classes , group discussion s , a home visit , and a telephone follow-up while the control arm only received routine care . Improvement in outcomes over time ( baseline , Week 3 , and Week 13 following intervention ) was evaluated using Generalized Estimating Equations multivariable analyses . RESULTS Except for age , no between-group significant differences were observed in all other baseline characteristics . Diabetes self-efficacy , self-management , and quality of life improved in the intervention arm but no improvement was observed in the controls . In the risk-adjusted multivariable models , compared to the controls , the intervention arm had significantly better self-efficacy , self-management , outcome expectations , and diabetes knowledge ( p<0.001 , in each ) . Participation in the intervention increased the diabetes self-management score by 14.3 points ( β=14.3 , ( 95 % CI 10.7 - 17.9 ) , p<0.001 ) . Self-management was better in leaner patients and in females . No between-group differences were seen in quality of life or glycemic control , however , in the risk-adjusted multivariable models , higher self-management scores were associated with significantly decreased HbA1c levels ( p<0.001 ) and improved patient quality of life ( p<0.05 ) ( irrespective of group membership ) . CONCLUSIONS Our family-oriented program improved patients ' self-efficacy and self-management , which in turn could decrease HbA1c levels INTRODUCTION Korean Americans are one of the most underserved ethnic/linguistic minority groups owing to cultural and institutional barriers ; there is an urgent need for culturally competent diabetes management programs in the Korean American community for those with type 2 diabetes . The purpose of this study was to test the effectiveness of a community-based , culturally tailored , multimodal behavioral intervention program in an ethnic/linguistic minority group with type 2 diabetes . DESIGN An RCT with waitlist comparison based on the Predisposing , Reinforcing , and Enabling Constructs in Education/environmental Diagnosis and Evaluation (PRECEDE)-Policy , Regulatory , and Organizational Constructs in Educational and Environmental Development ( PROCEED ) and self-help models . Data were collected between September 2010 and June 2013 and were analyzed in August-December 2014 . Statistical significance was set at p<0.05 . SETTING / PARTICIPANTS In a naturally occurring community setting , a total of 250 Korean Americans with type 2 diabetes were r and omized into an intervention group ( n=120 ) or a control group ( n=130 ) . INTERVENTION The intervention consisted of key self-management skill-building activities through 12 hours of group education sessions , followed by integrated counseling and behavioral coaching by a team of RNs and community health workers . MAIN OUTCOME MEASURES Primary ( clinical ) outcomes were hemoglobin A1c , glucose , total cholesterol , and low-density lipoprotein at baseline and at 3 , 6 , 9 , and 12 months . Secondary ( psychosocial and behavioral ) outcomes included diabetes-related quality of life , self-efficacy , adherence to diabetes management regimen , and health literacy . RESULTS During the 12-month project , the intervention group demonstrated 1.0%-1.3 % ( 10.9 - 14.2 mmol/mol ) reductions in hemoglobin A1c , whereas the control group achieved reductions of 0.5%-0.7 % ( 5.5 - 7.7 mmol/mol ) . The differences between the two groups were statistically significant . The intervention group showed statistically significant improvement in diabetes-related self-efficacy and quality of life when compared with the control group . CONCLUSIONS RN/community health worker teams equipped with culturally tailored training can be effective in helping an ethnic/linguistic minority group manage diabetes in the community Among patients with various levels of health literacy , the effects of collaborative , patient-provider , medication-planning tools on outcomes relevant to self-management are uncertain . Objective . Among adult patients with type II diabetes mellitus , we tested the effectiveness of a medication-planning tool ( Medtable ™ ) implemented via an electronic medical record to improve patients ' medication knowledge , adherence , and glycemic control compared to usual care . Design . A multicenter , r and omized controlled trial in outpatient primary care clinics . 674 patients received either the Medtable tool or usual care and were followed up for up to 12 months . Results . Patients who received Medtable had greater knowledge about indications for medications in their regimens and were more satisfied with the information about their medications . Patients ' knowledge of drug indication improved with Medtable regardless of their literacy status . However , Medtable did not improve patients ' demonstrated medication use , regimen adherence , or glycemic control ( HbA1c ) . Conclusion . The Medtable tool supported provider/patient collaboration related to medication use , as reflected in patient satisfaction with communication , but had limited impact on patient medication knowledge , adherence , and HbA1c outcomes . This trial is registered with Clinical Trials.gov NCT01296633 The aim of the study was to evaluate the effect of a structured group education program administered by a primary care nurse in patients with type 2 diabetes mellitus . The sample included 137 patients with type 2 diabetes mellitus , r and omized into two groups : intervention ( 5-week educational course and reinforcements every 4 months for one year ) and control ( with no structured diabetes mellitus education ) with an evaluation of metabolic control , weight , blood pressure , distress scores , and knowledge on diabetes . There were no differences between the two groups in HbA1c at 4 , 8 , or 12 months when compared to baseline values . An increase in HbA1c was observed in the control group after adjusting for baseline HbA1c and insulin dose ( p = 0.044 between groups ) . Knowledge scores and diabetes-related distress improved after the intervention . A structured educational program administered to type 2 diabetes mellitus patients seen at a primary care unit improved the knowledge and distress associated with the disease . The results also suggest the prevention of an increase in HbA1c Mindful eating may be an effective intervention for increasing awareness of hunger and satiety cues , improving eating regulation and dietary patterns , reducing symptoms of depression and anxiety , and promoting weight loss . Diabetes self-management education ( DSME ) , which addresses knowledge , self-efficacy , and outcome expectations for improving food choices , also may be an effective intervention for diabetes self-care . Yet few studies have compared the impact of mindful eating to a DSME-based treatment approach on patient outcomes . Adults 35 to 65 years old with type 2 diabetes for ≥1 year not requiring insulin therapy were recruited from the community and r and omly assigned to treatment group . The impact of a group-based 3-month mindful eating intervention ( MB-EAT-D ; n = 27 ) to a group-based 3-month DSME “ Smart Choices ” ( SC ) intervention ( n = 25 ) postintervention and at 3-month follow-up was evaluated . Repeated- measures ANOVA with contrast analysis compared change in outcomes across time . There was no significant difference between groups in weight change . Significant improvement in depressive symptoms , outcome expectations , nutrition and eating-related self-efficacy , and cognitive control and disinhibition of control regarding eating behaviors occurred for both groups ( all p < .0125 ) at 3-month follow-up . The SC group had greater increase in nutrition knowledge and self-efficacy than the MB-EAT-D group ( all p < .05 ) at 3-month follow-up . MB-EAT-D had significant increase in mindfulness , whereas the SC group had significant increase in fruit and vegetable consumption at study end ( all p < .0125 ) . Both SC and MB-EAT-D were effective treatments for diabetes self-management . The availability of mindful eating and DSME-based approaches offers patients greater choices in meeting their self-care needs Purpose The purpose of the study was to assess the value of reinforcing diabetes self-management for improving glycemia and self-care among adults with type 2 diabetes who had at least 3 hours of prior diabetes education . Methods In this r and omized controlled trial , 134 participants ( 75 % white , 51 % female , 59 ± 9 years old , 13 ± 8 years with diabetes , A1C = 8.4 % ± 1.2 % ) were r and omized to either a group map-based program ( intervention ) or group education on cholesterol and blood pressure ( control ) . Participants were assessed for A1C levels , diabetes self-care behaviors ( 3-day pedometer readings , 6-minute walk test , blood glucose checks , frequency of self-care ) , and psychosocial factors ( distress , frustration , quality of life ) at baseline , 3 , 6 , and 12 months post intervention and health literacy at baseline . Results Groups did not differ on baseline characteristics including A1C levels , health literacy , or self-care ; however , the intervention group had more years of education than controls . Intervention arm participants modestly improved A1C levels at 3 months post intervention but did not maintain that improvement at 6 and 12 months while control patients did not improve A1C levels at any time during follow-up . Importantly , frequency of self-reported self-care , diabetes quality of life , diabetes-related distress , and frustration with diabetes self-care improved in both groups over time . Conclusions Reinforcing self-care with diabetes education for patients who have not met glycemic targets helps improve A1C and could be considered a necessary component of ongoing diabetes care . The best method to accomplish reinforcement needs to be established Chronic obstructive pulmonary disease ( COPD ) is one of the more disabling diseases and the third cause of mortality worldwide . Self-management is considered an effective strategy for controlling and managing COPD . This review aims to summarise the available evidence on the effectiveness of COPD self-management in primary care setting s. Social Sciences , Citation Index , MEDLINE , CINAHL , Academic Search Complete and Scopus were search ed for r and omised controlled trials of COPD self-management in general practice between 2001 and 2018 . Ten r and omised controlled trials of COPD self-management trials conducted in primary care setting s were included in this review . The identified trials have recruited stable patients ; a majority having mild to moderate COPD . The trials implemented different types of interventions and measured improvements in knowledge , skills and behaviours of self-management , mental health , self-efficacy and endpoint outcomes such as hospitalisation and quality of life . The findings showed that COPD self-management trials had positive effects on COPD knowledge and improved self-management behaviours such as adherence to medication , physical activities and smoking cessation in some cases ; however , the effect of trials on hospitalisation rate , quality of life and healthcare utilisation were not conclusive . There was also not enough evidence to suggest that the trials were efficient in improving self-efficacy , a major driver of self-management behaviours . Primary care COPD self-management trials are efficient in improving surrogate outcomes such as knowledge of and adherence to self-management behaviours ; however , such improvements are less likely to be sustainable in the absence of self-efficacy . Future studies should also focus on improving endpoint self-management outcomes like hospitalisation rate and quality of life to benefit both patient and healthcare system |
10,425 | 31,950,450 | PPN – DBS is a potential therapeutic target that could improve gait and fall disorders in patients with PD .
Our findings will help improve the clinical application of DBS in PD patients with gait disorder | Deep brain stimulation ( DBS ) of the pedunculopontine nucleus ( PPN ) has been proposed as a treatment strategy for gait disorder in patients with Parkinson ’s disease ( PD ) .
We thus performed a systematic review and meta- analysis of r and omized and nonr and omized controlled trials to assess the effect of this treatment on gait disorder in patients with PD . | BACKGROUND Gait-related symptoms are often refractory to current available treatment options with a significant reduction in quality of life in Parkinson 's disease . OBJECTIVES The objective of this study was to determine the long-term efficacy and safety of unilateral pedunculopontine area stimulation for refractory gait and balance impairment in Parkinson 's disease . METHODS This study used periodic r and omized double-blinded assessment s until 4 years postoperatively . The primary outcomes were gait-related items of the UPDRS part II and the MDS-UPDRS part III . RESULTS At baseline , the median age and disease duration was 63 years ( interquartile range : 62 , 65 ) and 15 years ( interquartile range : 11 , 20 ) . At 2 years , patient-reported freezing ( UPDRS part II , off-time ) was significantly better when compared with baseline ( P = .028 ) , with 62.5 % of responders . At 4 years , there was no significant change in the used outcomes , but 66.7 % ( n = 4 of 6 ) were responders for off-time patient-reported freezing and falling . CONCLUSIONS Pedunculopontine area stimulation has an initial but not sustained benefit for gait-related symptoms . © 2016 International Parkinson and Movement Disorder Society Gait freezing and postural instability are disabling features of Parkinsonian disorders , treatable with pedunculopontine nucleus stimulation . Both features are considered deficits of proximal and axial musculature , innervated predominantly by reticulospinal pathways and tend to manifest when gait and posture require adjustment . Adjustments to gait and posture are amenable to pre-preparation and rapid triggered release . Experimentally , such accelerated release can be elicited by loud auditory stimuli — a phenomenon known as ‘ StartReact ’ . We observed StartReact in healthy and Parkinsonian controls . However , StartReact was absent in Parkinsonian patients with severe gait freezing and postural instability . Pedunculopontine nucleus stimulation restored StartReact proximally and proximal reaction times to loud stimuli correlated with gait and postural disturbance . These findings suggest a relative block to triggered , pre-prepared movement in gait freezing and postural instability , relieved by pedunculopontine nucleus stimulation Objectives Attentional augmentation and enhanced motor function are potential mechanisms by which stimulation of the region of the pedunculopontine nucleus ( PPN ) may improve gait in parkinsonism . Here , the authors assess the impact of stimulation of this region on attentional and motor aspects of reaction task performance in patients with parkinsonism . Methods Eleven patients implanted with PPN stimulators underwent computerised assessment of simple , choice and digit vigilance reaction tasks . Patients were assessed ‘ off medication ’ during stimulation at different frequencies ( 0 Hz , 5 Hz , 10 Hz and ‘ therapeutic ’ 20–35 Hz ) . There were two primary endpoints : ‘ Speed of Reaction ’ ( sum of the mean task reaction times ) and ‘ Accuracy of Reaction ’ ( reflecting omissions and percentage of correct responses ) . Baseline performance was compared with age- and sex-matched healthy controls . Clinical effects of stimulation were assessed using the Unified Parkinson 's Disease Rating Scale and a falls frequency scale . Results Compared with healthy controls , subjects had significant deficits in ‘ Speed of Reaction ’ and in all mean task reaction times . ‘ Accuracy of Reaction ’ was not different from healthy controls and did not improve with stimulation . ‘ Speed of Reaction ’ significantly improved with stimulation at therapeutic frequencies ( 20–35 Hz ) . Of the individual tasks , only simple reaction time improved significantly . Simple reaction time distribution analysis revealed a general speeding of responses rather than a selective reduction in outliers . Acute PPN stimulation improved gait and balance but not akinesia scores . Chronic PPN stimulation significantly improved falls frequency . Falls score improvement significantly correlated with changes to simple reaction time with therapeutic stimulation . Conclusion The pattern of reaction time improvement with stimulation of the PPN area suggests a benefit on motor performance , rather than augmentation of attention Gait freezing is an episodic arrest of locomotion due to an inability to take normal steps . Pedunculopontine nucleus stimulation is an emerging therapy proposed to improve gait freezing , even where refractory to medication . However , the efficacy and precise effects of pedunculopontine nucleus stimulation on Parkinsonian gait disturbance are not established . The clinical application of this new therapy is controversial and it is unknown if bilateral stimulation is more effective than unilateral . Here , in a double-blinded study using objective spatiotemporal gait analysis , we assessed the impact of unilateral and bilateral pedunculopontine nucleus stimulation on triggered episodes of gait freezing and on background deficits of unconstrained gait in Parkinson ’s disease . Under experimental conditions , while OFF medication , Parkinsonian patients with severe gait freezing implanted with pedunculopontine nucleus stimulators below the pontomesencephalic junction were assessed during three conditions ; off stimulation , unilateral stimulation and bilateral stimulation . Results were compared to Parkinsonian patients without gait freezing matched for disease severity and healthy controls . Pedunculopontine nucleus stimulation improved objective measures of gait freezing , with bilateral stimulation more effective than unilateral . During unconstrained walking , Parkinsonian patients who experience gait freezing had reduced step length and increased step length variability compared to patients without gait freezing ; however , these deficits were unchanged by pedunculopontine nucleus stimulation . Chronic pedunculopontine nucleus stimulation improved Freezing of Gait Question naire scores , reflecting a reduction of the freezing encountered in patients ’ usual environments and medication states . This study provides objective , double-blinded evidence that in a specific subgroup of Parkinsonian patients , stimulation of a caudal pedunculopontine nucleus region selectively improves gait freezing but not background deficits in step length . Bilateral stimulation was more effective than unilateral BACKGROUND Pedunculopontine nucleus ( PPN ) stimulation is a novel therapy for Parkinson disease . However , controversies remain regarding the clinical application of this new therapy , including patient selection , electrode positioning , and how best to assess outcomes . OBJECTIVE To clarify the clinical application of PPN stimulation in Parkinson disease . METHODS Five consecutive patients with Parkinson disease complicated by severe gait freezing , postural instability , and frequent falls ( all persisting even while the patient was on medication ) received bilateral stimulation of the mid-lower PPN without costimulation of other brain targets . Outcomes were assessed prospect ively over 2 years with gait-specific question naires and the Unified Parkinson Disease Rating Scale ( part III ) . RESULTS The primary outcome , the Gait and Falls Question naire score , improved significantly with stimulation . Benefits were maintained over 2 years . Unified Parkinson Disease Rating Scale ( part III ) items assessing gait and posture were relatively insensitive to these treatment effects . Beneficial effects often appeared to outlast stimulation for hours or longer . Thus , single-session on- vs off-stimulation assessment s may be susceptible to “ delayed washout effects . ” Stimulation of the PPN did not change akinesia scores or dopaminergic medication requirements . CONCLUSION Bilateral stimulation of the mid-lower PPN ( more caudal than previous reports ) without costimulation of other brain targets may be beneficial for the subgroup of patients with Parkinson disease who experience severe gait freezing and postural instability with frequent falls , which persist even while on medication . Choosing appropriate outcome measures and accounting for the possibility of prolonged stimulation washout effects appear to be important for detecting the clinical benefits Gait and balance disorders are the major source of motor disabilities in advanced forms of Parkinson ’s disease ( PD ) . Low-frequency stimulation of the pedunculopontine nucleus area ( PPNa-DBS ) has been recently proposed to treat these symptoms with variable clinical results . To further underst and the effects of PPNa-DBS on resistant gait and balance disorders , we performed a r and omised double-blind cross-over study in six PD patients . Evaluation included clinical assessment of parkinsonian disability , quality of life and neurophysiological recordings of gait . Evaluations were done 1 month before , 4 and 6 months after surgery with four double-blinded conditions assessed : with and without PPNa-DBS , with and without levodopa treatment . Four patients completed the study and two patients were excluded from the final analysis because of peri-operative adverse events ( haematoma , infection ) . Clinical ly , the combination of PPNa-DBS and levodopa treatment produced a significant decrease of the freezing episodes . The frequency of falls also decreased in three out of four patients . From a neurophysiological point of view , PPNa-DBS significantly improved the anticipatory postural adjustments and double-stance duration , but not the length and speed of the first step . Interestingly , step length and speed improved after surgery without PPNa-DBS , suggesting that the lesioning effect of PPNa-DBS surgery alleviates parkinsonian akinesia . Quality of life was also significantly improved with PPNa-DBS . These results suggest that PPNa-DBS could improve gait and balance disorders in well-selected PD patients . However , this treatment may be riskier than others DBS surgeries in these patients with an advanced form of PD In Parkinson ’s disease ( PD ) , the effects of deep brain stimulation of the pedunculopontine nucleus ( PPTg-DBS ) on gait has been object of international debate . Some evidence demonstrated that , in the late swing-early stance phase of gait cycle , a reduced surface electromyographic activation ( sEMG ) of tibialis anterior ( TA ) is linked to the striatal dopamine deficiency in PD patients . In the present study we report preliminary results on the effect of PPTg-DBS on electromyographic patterns during gait in individual PD patients . To evaluate the sEMG amplitude of TA , the root mean square ( RMS ) of the TA burst in late swing-early stance phase ( RMS-A ) was normalized as a percent of the RMS of the TA burst in late stance-early swing ( RMS-B ) . We studied three male patients in the following conditions : on PPTg-DBS/on l-dopa , on PPTg-DBS/off l-dopa , off PPTg-DBS/on l-dopa , off PPTg-DBS/off l-dopa . For each assessment the UPDRS III was filled in . We observed no difference between on PPTg-DBS/off l-dopa and off PPTg-DBS/off l-dopa in UPDRS III scores . In off PPTg-DBS/off l-dopa , patient A ( right implant ) showed absence of the right and left RMSA , respectively , in 80 % and 83 % of gait cycles . Patient B ( right implant ) showed absence of the right RMS-A in 86 % of cycles . RMS-A of the patient C ( left implant ) was bilaterally normal . In on PPTg- DBS/off l-dopa , no patient showed reduced RMS-A. Although the very low number of subjects we evaluated , our observations suggest that PPTg plays a role in modulating TA activation pattern during the steady state of gait Objective To compare the influence of low-frequency ( 10–25 Hz ) versus higher ( 60–80 Hz ) frequency stimulation of the pedunculopontine nucleus area ( PPNa ) on akinaesia , freezing of gait and daytime sleepiness . Method We included nine patients with Parkinson 's disease ( PD ) and severe gait disorders . In this double-blind r and omised cross-over study , patients were assessed after 24 h of PPNa stimulation . Assessment s included the motor part of the Unified Parkinson 's Disease Rating Scale , the Epworth Sleepiness Scale and a behavioural gait assessment . Results Compared with 60–80 Hz , 10–25 Hz PPNa stimulation led to decreased akinaesia , gait difficulties and daytime sleepiness in 7/9 patients . In one patient , these symptoms were aggravated under 10–25 Hz stimulation compared with 60–80 Hz . Conclusion These results are in keeping with the benefits of chronic PPNa stimulation for gait and postural difficulties in patients with PD , and with regard to the influence of patients ' clinical characteristics , differential neuronal loss in the PPNa and electrode location . We conclude that in patients with PPNa stimulation , low frequency provides a better outcome than high-frequency stimulation |
10,426 | 32,141,074 | This treatment effect was seen when OFS was added to observation , to tamoxifen , or to chemotherapy and tamoxifen .
This review found evidence that supports adding OFS for premenopausal women with early , hormone receptor-positive breast cancers .
The benefit of OFS persisted when compared to observation , and when added to endocrine therapy ( tamoxifen ) or chemotherapy and endocrine therapy ( tamoxifen ) . | BACKGROUND Approximately 80 % of breast cancers amongst premenopausal women are hormone receptor-positive .
Adjuvant endocrine therapy is an integral component of care for hormone receptor-positive breast cancer and in premenopausal women includes oestrogen receptor blockade with tamoxifen , temporary suppression of ovarian oestrogen synthesis by luteinising hormone releasing hormone ( LHRH ) agonists , and permanent interruption of ovarian oestrogen synthesis with oophorectomy or radiotherapy .
Recent international consensus statements recommend single-agent tamoxifen or aromatase inhibitors with ovarian function suppression ( OFS ) as the current st and ard adjuvant endocrine therapy for premenopausal women ( often preceded by chemotherapy ) .
This review examined the role of adding OFS to another treatment ( i.e. chemotherapy , endocrine therapy , or both ) or comparing OFS to no further adjuvant treatment .
OBJECTIVES To assess effects of OFS for treatment of premenopausal women with hormone receptor-positive early breast cancer . | Gonadotrophin-releasing hormone analogues were investigated as adjuvant treatment for patients with node-negative , hormone-sensitive , premenopausal breast cancer . Patients were r and omised to either three cycles of cyclophosphamide , methotrexate , and 5-fluorouracil ( CMF ) chemotherapy ( n=378 ) or goserelin every 28 d for 2 years ( n=393 ) . During a median follow-up of 4.9 years , 123 events were observed . The first-failure event of CMF versus goserelin , respectively , was ipsilateral locoregional recurrence ( 18 versus 20 ) , contralateral breast cancer ( 7 versus 6 ) , distant failure ( 35 versus 24 ) and death without recurrence ( 2 versus 2 ) . Forty-two ( 23 versus 19 ) deaths of any cause occurred . The estimated adjusted hazard ratio for goserelin versus CMF ( intention-to-treat analysis ) was 0.79 ( 95 % CI=0.54 - 1.14 ; P=0.19 ) . It is concluded that medical ovarian ablation with goserelin represents a valid option for premenopausal patients with node-negative breast cancer Background Single nucleotide polymorphisms ( SNPs ) in the estrogen receptor 1 ( ESR1 ) and cytochrome P450 19A1 ( CYP19A1 ) genes have been associated with breast cancer risk , endocrine therapy response and side effects , mainly in postmenopausal women with early breast cancer . This analysis aim ed to assess the association of selected germline CYP19A1 and ESR1 SNPs with early-onset hot flashes , sweating and musculoskeletal symptoms in premenopausal patients enrolled in the Tamoxifen and Exemestane Trial ( TEXT ) . Methods Blood was collected from consenting premenopausal women with hormone-responsive early breast cancer , r and omly assigned to 5-years of tamoxifen plus ovarian suppression ( OFS ) or exemestane plus OFS . DNA was extracted with QIAamp kits and genotyped for two CYP19A1 ( rs4646 and rs10046 ) and three ESR1 ( rs2077647 , rs2234693 and rs9340799 ) SNPs by a real-time pyrosequencing technique . Adverse events ( AEs ) were recorded at baseline and 3-monthly during the first year . Associations of the genotype variants with grade ≥2 early-onset targeted AEs of hot flashes/sweating or musculoskeletal events were assessed using logistic regression models . Results There were 2660 premenopausal patients with breast cancer in the intention-to-treat population of TEXT , and 1967 ( 74 % ) are included in this translational study . The CYP19A1 rs10046 variant T/T , represented in 23 % of women , was associated with a reduced incidence of grade ≥2 hot flashes/sweating ( univariate odds ratio ( OR ) = 0.78 ; 95 % CI 0.63–0.97 ; P = 0.03 ) , more strongly in patients assigned exemestane + OFS ( TT vs CT/CC : OR = 0.65 , 95 % CI = 0.48–0.89 ) than assigned tamoxifen + OFS ( OR = 0.94 , 95 % CI = 0.69–1.27 , interaction P = 0.03 ) . No association with any of the CYP19A1/ESR1 genotypes and musculoskeletal AEs was found . Conclusion The CYP19A1 rs10046 variant T/T favors lower incidence of hot flashes/sweating under exemestane + OFS treatment , suggesting endocrine-mediated effects . Based on findings from others , this SNP may potentially enhance treatment adherence and treatment efficacy . We plan to evaluate the clinical impact of this polymorphism during time , pending sufficient median follow up . Trial registration Clinical Trials.gov NCT00066703 , registered August 6 , 2003 Optimal adjuvant endocrine therapy for premenopausal women with hormone-receptor positive breast cancer has long been debated . In particular , the role of ovarian function suppression in addition to st and ard tamoxifen divided oncologists worldwide , and more recently , the role of aromatase inhibitors as an alternative to tamoxifen in the setting of ovarian suppression became a key question . In 2014 , the long awaited results of the International Breast Cancer Study Group ( IBCSG ) led r and omized , phase 3 trials , Suppression of Ovarian Function Trial ( SOFT ) and Tamoxifen and Exemestane Trial ( TEXT ) , provided additional evidence to inform the discussion . The interpretation of the SOFT and TEXT trial data can facilitate better selection of appropriate endocrine therapy according to individual disease characteristics , recognizing the complexity of the puzzle , which is still not complete The sequential doxorubicin → CMF ( CMF = cyclophosphamide , methotrexate , fluorouracil ) regimen has never been compared to CMF in a r and omised trial . The role of adding goserelin and tamoxifen after chemotherapy is unclear . In all , 466 premenopausal node-positive patients were r and omised to : ( a ) CMF × 6 cycles ( CMF ) ; ( b ) doxorubicin × 4 cycles followed by CMF × 6 cycles ( A → CMF ) ; ( c ) CMF × 6 cycles followed by goserelin plus tamoxifen × 2 years ( CMF → GT ) ; and ( d ) doxorubicin × 4 cycles followed by CMF × 6 cycles followed by goserelin plus tamoxifen × 2 years ( A → CMF → GT ) . The study used a 2 × 2 factorial experimental design to assess : ( 1 ) the effect of the chemotherapy regimens ( CMF vs A → CMF or arms a+c vs b+d ) and ( 2 ) the effect of adding GT after chemotherapy ( arms a+b vs c+d ) . At a median follow-up of 72 months , A → CMF as compared to CMF significantly improved disease-free survival ( DFS ) with a multivariate hazard ratio (HR)=0.740 ( 95 % confidence interval ( CI ) : 0.556–0.986 ; P=0.040 ) and produced a nonsignificant improvement of overall survival ( OS ) ( HR=0.764 ; 95 % CI : 0.489–1.193 ) . The addition of GT after chemotherapy significantly improved DFS ( HR=0.74 ; 95 % CI : 0.555–0.987 ; P=0.040 ) , with a nonsignificant improvement of OS ( HR=0.84 ; 95 % CI : 0.54–1.32 ) . A → CMF is superior to CMF . Adding GT after chemotherapy is beneficial for premenopausal node-positive patients Background Recent breast cancer treatment guidelines recommend that higher-risk premenopausal patients should receive ovarian function suppression ( OFS ) as part of adjuvant endocrine therapy . If chemotherapy is also given , it is uncertain whether to select concurrent or sequential OFS initiation . Design and methods We analyzed 1872 patients enrolled in the r and omized phase III TEXT and SOFT trials who received adjuvant chemotherapy for hormone receptor-positive , HER2-negative breast cancer and upon r and omization to an OFS-containing adjuvant endocrine therapy , initiated gonadotropin-releasing-hormone-agonist triptorelin . Breast cancer-free interval ( BCFI ) was compared between patients who received OFS concurrently with chemotherapy in TEXT ( n = 1242 ) versus sequentially post-chemotherapy in SOFT ( n = 630 ) . Because timing of trial enrollment relative to adjuvant chemotherapy differed , we implemented l and mark analysis re-defining BCFI beginning 1 year after final dose of chemotherapy ( median , 15.5 and 8.1 months from enrollment to l and mark in TEXT and SOFT , respectively ) . As a non-r and omized treatment comparison , we implemented comparative-effectiveness propensity score methodology with weighted Cox modeling . Results Distributions of several clinico-pathologic characteristics differed between groups . Patients who were premenopausal post-chemotherapy in SOFT were younger on average . The median duration of adjuvant chemotherapy was 18 weeks in both groups . There were 231 ( 12 % ) BC events after post-l and mark median follow-up of about 5 years . Concurrent use of triptorelin with chemotherapy was not associated with a significant difference in post-l and mark BCFI compared with sequential triptorelin post-chemotherapy , either in the overall population ( HR = 1.11 , 95 % CI 0.72 - 1.72 ; P = 0.72 ; 4-year BCFI 89 % in both groups ) , or in the subgroup of 692 women < 40 years at diagnosis ( HR = 1.13 , 95 % CI 0.69 - 1.84 ) who are less likely to develop chemotherapy-induced amenorrhea . Conclusion Based on comparative-effectiveness modeling of TEXT and SOFT after about 5 years median follow-up , with limited statistical power especially for the subgroup < 40 years , neither detrimental nor beneficial effect of concurrent administration of OFS with chemotherapy on the efficacy of adjuvant therapy that includes chemotherapy was detected . Clinical trials.gov NCT00066690 and NCT00066703 PURPOSE The combination of taxanes and anthracyclines has proven efficacy in node-positive ( N+ ) premenopausal primary breast cancer patients . Ovarian ablation is also associated with better survival outcomes in premenopausal hormone-receptor positive ( HR+ ) patients . Therefore , this trial aims to determine the superiority of combined hormonal treatment of ovarian ablation with tamoxifen ( TMX ) versus TMX alone , in premenopausal N+ , HR + patients receiving adjuvant chemotherapy ( AC ) with taxane and anthracycline . MATERIAL S AND METHODS Premenopausal women who had surgically removed breast cancer with histologically confirmed N + and HR+ were included in the trial . The AC consisted of six cycles of taxotere , adriamycin , cytoxan or taxotere , epirubicin and cytoxan with the completion of radiation therapy . Patients were r and omly assigned to receive TMX 20 mg/day for 5 years or up to menopause or TMX 20 mg/day for 5 years plus goserelin ( GOS ) 3.6 mg injection per month for 2 years . The primary end point was disease-free survival ( DFS ) . RESULTS Between 2003 and 2011 , 101 consecutive patients were allocated to TMX ( 51 patients ) and TMX/GOS ( 50 patients ) groups . The mean follow-up period was 52.4 ± 2.8 months . DFS was 43.0 ± 3.6 months versus 49.9 ± 4.22 months ( P = 0.13 ) and overall survival was 51.1 ± 3.8 months versus 53.1 ± 4.2 months ( P = 0.50 ) in the TMX and TMX/GOS groups , respectively . The results showed 9 % absolute risk reduction with respect to DFS in favor of the TMX/GOS group . CONCLUSION This study group was comprised of stage II and III disease patients with high nodal status . The TMX/GOS combination reduced absolute risk of developing first locoregional or distant relapse by almost 9 % . Longer follow-up is required to justify this protocol for routine use PURPOSE To determine whether the addition of surgical ovariectomy to st and ard chemotherapy prolongs disease-free survival ( DFS ) and overall survival in premenopausal patients with estrogen receptor (ER)-positive operable breast cancer with positive axillary nodes . PATIENTS AND METHODS Three hundred fourteen premenopausal patients with ER-positive , node-positive breast cancer were enrolled between July 1979 and July 1989 . Patients were stratified according to number of involved nodes and type of primary surgery and r and omized to receive either of the following : ( 1 ) cyclophosphamide 60 mg/m2/d by mouth for 1 year , methotrexate 15 mg/m2 intravenously ( i.v . ) weekly for 1 year , fluorouracil ( 5-FU ) 400 mg/m2 i.v . weekly for 1 year , vincristine .625 mg/m2 i.v . weekly for the first 10 weeks , and prednisone weeks 1 to 10 with doses decreasing from 30 mg/m2 to 2.5 mg/m2 ( CMFVP ) ; or ( 2 ) bilateral ovariectomy followed by CMFVP . RESULTS The median follow-up time is 7.7 years and the maximum 13.2 years . Treatment arms are not significantly different with respect to either survival or DFS ( one-sided log-rank , P = .55 and .70 , respectively ) . The 7-year survival rate is 71 % on the CMFVP arm and 73 % on CMFVP plus ovariectomy . No significant differences were observed in node or receptor level subsets . CONCLUSION We conclude that , in this study , the addition of ovariectomy did not improve results over chemotherapy alone in the treatment of premenopausal women with node-positive , ER-positive , operable breast cancer . Our sample size was too small to detect a small improvement . The death hazards ratio of CMFVP/CMFVP plus ovariectomy was 1.22 ( 95 % confidence interval [ CI ] , .79 to 1.89 ) Background : To examine the effect on cognitive function of adjuvant ovarian function suppression ( OFS ) for breast cancer . Methods : The Suppression of Ovarian Function ( SOFT ) trial r and omised premenopausal women with hormone receptor-positive breast cancer to 5 years adjuvant endocrine therapy with tamoxifen+OFS , exemestane+OFS or tamoxifen alone . The Co-SOFT sub study assessed objective cognitive function and patient reported outcomes at r and omisation ( T0 ) , and 1 year later ( T1 ) ; the primary endpoint was change in global cognitive function , measured by the composite objective cognitive function score . Data were compared for the pooled tamoxifen+OFS and exemestane+OFS groups vs the tamoxifen alone group using the Wilcoxon rank-sum test . Results : Of 86 participants , 74 underwent both T0 and T1 cognitive testing ; 54 r and omised to OFS+ either tamoxifen ( 28 ) or exemestane ( 26 ) and 20 r and omised to tamoxifen alone . There was no significant difference in the changes in the composite cognitive function scores between the OFS+ tamoxifen or exemestane groups and the tamoxifen group ( mean±s.d . , −0.21±0.92 vs −0.04±0.49 , respectively , P=0.71 , effect size=−0.20 ) , regardless of prior chemotherapy status , and adjusting for baseline characteristics . Conclusions : The Co-SOFT study , although limited by small sample s size , provides no evidence that adding OFS to adjuvant oral endocrine therapy substantially affects global cognitive function Objective Tamoxifen is an estrogen receptor antagonist used to prevent recurrence of breast cancer , which may provoke depression and anxiety and increase follicle-stimulating hormone ( FSH ) to patients . We compared anxiety and depression symptoms and FSH levels who received conventional tamoxifen alone and combination treatment of goserelin , a gonadotropin-releasing hormone ( GnRH ) analogue , with tamoxifen . Methods Sixty-four premenopausal women with hormone receptor-positive early-stage breast cancer were included and were assigned r and omly to receive either tamoxifen and goserelin combination or tamoxifen alone for 12 months . The participants were evaluated blindly using the Hamilton Depression and Anxiety Rating Scale , the Beck Depression Rating Scale , and the Albany Panic and Phobia Question naire ( APPQ ) . Blood FSH levels were assessed at baseline , 6 and 12 months . Results A significant time × group difference was detected in the agoraphobia trends subscale of the APPQ and in FSH levels . The combination group showed significantly less increases in agoraphobia subscale of APPQ and greater decreases in FSH level than those in the tamoxifen-alone group from baseline to 12 months of treatment . No significant differences for age , tumor grade , body mass index , or family history were found at baseline between the two groups . Conclusion Our results suggest that the combination treatment of tamoxifen and goserelin result ed in less agoraphobia than tamoxifen alone in premenopausal women with breast cancer , which may associated with FSH suppression of goserelin BACKGROUND The purpose of this study was to determine optimal adjuvant therapy between complete hormonal blockade in premenopausal patients with hormone receptor positive breast cancer and one to three positive nodes . PATIENTS AND METHODS We r and omised 333 patients to receive either LHRH agonist ( triptorelin 3.75 mg i.m . , monthly ) plus tamoxifen 30 mg/day for 3 years ( TAM-LHRHa , n=164 ) , or fluorouracil 500 mg/m2 , epirubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 every 21 days for six cycles , without any hormonal treatment ( FEC50 , n=169 ) . RESULTS The 7-year disease-free survival ( DFS ) was 76 % with TAM-LHRHa , and 72 % with FEC50 ( P=0.13 ) . The 7-year overall survival ( OS ) was 91 % and 88 % , respectively ( P=0.20 ) . The multivariate analysis confirmed that both treatments were not different for DFS and OS ( P=0.83 and P=0.41 , respectively ) . Amenorrhoea occurred in 64 % of patients treated with FEC50 ; it was temporary in 58 % of cases after hormonotherapy and in 31 % after chemotherapy . CONCLUSION In intermediate-risk breast cancer , complete hormonal blockade and chemotherapy provided similar outcomes . Hormonal treatment is an alternative to chemotherapy in hormone-sensitive patients , considering the preference of patients in terms of quality of life Background Systematic review s have found that luteinizing hormone – releasing hormone ( LHRH ) agonists are effective in treating premenopausal women with early breast cancer . Methods We conducted long-term follow-up ( median 12 years ) of 2706 women in the Zoladex In Premenopausal Patients ( ZIPP ) , which evaluated the LHRH agonist goserelin ( 3.6 mg injection every 4 weeks ) and tamoxifen ( 20 or 40 mg daily ) , given for 2 years . Women were r and omly assigned to receive each therapy alone , both , or neither , after primary therapy ( surgery with or without radiotherapy/chemotherapy ) . Hazard ratios and absolute risk differences were used to assess the effect of goserelin treatment on event-free survival ( breast cancer recurrence , new tumor or death ) , overall survival , risk of recurrence of breast cancer , and risk of dying from breast cancer , in the presence or absence of tamoxifen . Results Fifteen years after the initiation of treatment , for every 100 women not given tamoxifen , there were 13.9 ( 95 % confidence interval [ CI ] = 17.5 to 19.4 ) fewer events among those who were treated with goserelin compared with those who were not treated with goserelin . However , among women who did take tamoxifen , there were 2.8 fewer events ( 95 % CI = 7.7 fewer to 2.0 more ) per 100 women treated with goserelin compared with those not treated with goserelin . The risk of dying from breast cancer was also reduced at 15 years : For every 100 women given goserelin , the number of breast cancer deaths was lower by 2.6 ( 95 % CI = 6.6 fewer to 2.1 more ) and 8.5 ( 95 % CI = 2.2 to 13.7 ) in those who did and did not take tamoxifen , respectively , although in the former group the difference was not statistically significant . Conclusions Two years of goserelin treatment was as effective as 2 years of tamoxifen treatment 15 years after starting therapy . In women who did not take tamoxifen , there was a large benefit of goserelin treatment on survival and recurrence , and in women who did take tamoxifen , there was a marginal potential benefit on these outcomes when goserelin was added GABG-IV B-93 is a prospect i ve , r and omised study comparing goserelin ( n=384 ) with no further treatment ( n=392 ) in hormone receptor (HR)-negative breast cancer patients ( n=465 ) after 3 cycles cyclophosphamide , methotrexate , 5-fluorouracil ( CMF ) for patients with 0 - 3 positive lymph nodes ( LN ) or 4 cycles epirubicin , cyclophosphamide ( EC ) followed by 3 cycles CMF for patients with 4 - 9 positive LN . After completion of the ZEBRA trial the study was amended to enrol also HR-positive patients with 1 - 9+LN ( n=311 ) . After a median follow-up of 4.7 years neither HR-negative nor HR-positive patients showed a benefit for goserelin . The adjusted estimated hazard ratio for event-free survival in HR-negative patients was 1.01 ( goserelin versus control , 95 % confidence interval [ CI ] 0.72 - 1.42 , P=0.97 ) and 0.77 in HR-positive patients ( 95 % CI 0.47 - 1.24 , P=0.27 ) . These results do not support the general use of goserelin after adjuvant chemotherapy in this group of premenopausal patients BACKGROUND The combined efficacy analysis of the TEXT and SOFT trials showed a significant disease-free survival benefit with exemestane plus ovarian function suppression ( OFS ) compared with tamoxifen plus OFS . We present patient-reported outcomes from these trials . METHODS Between Nov 7 , 2003 , and April 7 , 2011 , 4717 premenopausal women with hormone-receptor positive breast cancer were enrolled in TEXT or SOFT to receive unmasked adjuvant treatment with 5 years of exemestane plus OFS or tamoxifen plus OFS . Gonadotropin-releasing hormone analogue triptorelin , bilateral oophorectomy , or bilateral ovarian irradiation were used to achieve OFS . Chemotherapy use was optional . R and omisation with permuted blocks was done with the International Breast Cancer Study Group 's internet-based system and was stratified by chemotherapy use and status of lymph nodes . Patients completed a quality of life ( QoL ) form comprising several global and symptom indicators at baseline , every 6 months for 24 months , and then every year during years 3 to 6 . Differences in the change of QoL from baseline between the two treatments were tested at 6 months , 24 months , and 60 months with mixed-models for repeated measures for each trial with and without chemotherapy and overall . The analysis was by intention to treat . At the time of analysis , the median follow-up was 5·7 years ( IQR 3·7 - 6·9 ) ; treatment and follow-up of patients continue . The trials are registered with Clinical Trials.gov , as NCT00066703 ( TEXT ) and NCT00066690 ( SOFT ) . FINDINGS Patients on tamoxifen plus OFS were more affected by hot flushes and sweats over 5 years than were those on exemestane plus OFS , although these symptoms improved . Patients on exemestane plus OFS reported more vaginal dryness , greater loss of sexual interest , and difficulties becoming aroused than did patients on tamoxifen plus OFS ; these differences persisted over time . An increase in bone or joint pain was more pronounced , particularly in the short term , in patients on exemestane plus OFS than patients on tamoxifen plus OFS . Changes in global QoL indicators from baseline were small and similar between treatments over the 5 years . INTERPRETATION Overall , from a QoL perspective , there is no strong indication to favour either exemestane plus OFS or tamoxifen plus OFS . The distinct effects of the two treatments on the burden of endocrine symptoms need to be addressed with patients individually . FUNDING Pfizer , International Breast Cancer Study Group , and US National Cancer Institute Background : This study is to investigate the effects of geserelin+tamoxifen ( TAM ) on estradiol level , breast density ( BD ) , endometrial thickness ( ET ) , and blood lipids in premenopausal and perimenopausal women with hormone receptor-positive early-stage breast cancer . Methods : This study recruited 110 premenopausal and perimenopausal patients with hormone receptor-positive early-stage breast cancer between 22 June 2008 and 31 December 2009 and r and omly assigned them to receive either goserelin plus TAM or TAM alone for 1.5 years . Blood levels of sex hormones and lipids and ET were determined at 0 , 3 , 6 , 12 , and 18 months . Contralateral BD was also measured at 0 , 12 , and 18 months . Results : Five participants dropped out of the goserelin plus TAM group , and two participants dropped out of the TAM-alone group before initiation of endocrine therapy . The rest of patients received scheduled treatment and 3 years of median follow-up . No serious adverse effects were observed , and only two local recurrences have been observed in these patients . Estradiol level and BD were lower in the goserelin plus TAM group than in the TAM-alone group ( P<0.05 ) . The endometrium in the goserelin plus TAM group was significantly thinner than that in the TAM-alone group ( P<0.05 ) , and women in the TAM-alone group exhibited endometrial thickening over the course of the study . Furthermore , no significant differences in blood lipid levels were reported between the two groups . Conclusion : The data from the current study demonstrated that the addition of goserelin to TAM results in downregulation of estradiol level , followed by significant reduction in BD and ET in premenopausal and perimenopausal women with hormone receptor-positive breast cancer , which may eventually lead to better outcome in these patients BACKGROUND Adjuvant therapy with an aromatase inhibitor improves outcomes , as compared with tamoxifen , in postmenopausal women with hormone-receptor-positive breast cancer . METHODS In two phase 3 trials , we r and omly assigned premenopausal women with hormone-receptor-positive early breast cancer to the aromatase inhibitor exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 years . Suppression of ovarian estrogen production was achieved with the use of the gonadotropin-releasing-hormone agonist triptorelin , oophorectomy , or ovarian irradiation . The primary analysis combined data from 4690 patients in the two trials . RESULTS After a median follow-up of 68 months , disease-free survival at 5 years was 91.1 % in the exemestane-ovarian suppression group and 87.3 % in the tamoxifen-ovarian suppression group ( hazard ratio for disease recurrence , second invasive cancer , or death , 0.72 ; 95 % confidence interval [ CI ] , 0.60 to 0.85 ; P<0.001 ) . The rate of freedom from breast cancer at 5 years was 92.8 % in the exemestane-ovarian suppression group , as compared with 88.8 % in the tamoxifen-ovarian suppression group ( hazard ratio for recurrence , 0.66 ; 95 % CI , 0.55 to 0.80 ; P<0.001 ) . With 194 deaths ( 4.1 % of the patients ) , overall survival did not differ significantly between the two groups ( hazard ratio for death in the exemestane-ovarian suppression group , 1.14 ; 95 % CI , 0.86 to 1.51 ; P=0.37 ) . Selected adverse events of grade 3 or 4 were reported for 30.6 % of the patients in the exemestane-ovarian suppression group and 29.4 % of those in the tamoxifen-ovarian suppression group , with profiles similar to those for postmenopausal women . CONCLUSIONS In premenopausal women with hormone-receptor-positive early breast cancer , adjuvant treatment with exemestane plus ovarian suppression , as compared with tamoxifen plus ovarian suppression , significantly reduced recurrence . ( Funded by Pfizer and others ; TEXT and SOFT Clinical Trials.gov numbers , NCT00066703 and NCT00066690 , respectively . ) PURPOSE Ovarian suppression with luteinizing hormone-releasing hormone ( LHRH ) agonists is an effective adjuvant treatment for premenopausal women with estrogen receptor ( ER ) -positive breast cancer . Whereas monthly LHRH agonist therapy has been well established , the value of every-3-months ( 3-monthly ) formulations is unclear . PATIENTS AND METHODS This r and omized phase III trial was performed to compare the 3-monthly depot LHRH agonist leuprorelin acetate ( LAD-3 M ; n = 299 ) and chemotherapy with cyclophosphamide , methotrexate , and fluorouracil ( CMF ; n = 300 ) in pre- or perimenopausal patients with ER-positive , node-positive breast cancer . RESULTS With a median follow-up of 5.8 years , recurrence-free survival was similar for patients treated with LAD-3 M or CMF ( hazard ratio [ HR ] , 1.19 ; 95 % CI , 0.94 to 1.51 ; P = .15 ) . There was no substantial heterogeneity in the relative treatment effect among subgroups defined by age , progesterone receptor ( PR ) status , nodal status , hormone levels , or menstrual recovery after treatment . Exploratory overall survival analysis favored LAD-3 M ( HR , 1.50 ; 95 % CI , 1.13 to 1.99 ; P = .005 ) . Chemotherapy-related adverse effects such as nausea , vomiting , and alopecia were more common with CMF , whereas symptoms of estrogen suppression such as hot flushes and sweating were initially more pronounced with LAD-3 M . CONCLUSION The 3-monthly depot LHRH-agonist leuprorelin acetate is an effective adjuvant treatment in premenopausal patients with hormone receptor-positive , node-positive breast cancer that is not inferior to CMF PURPOSE To compare quality of life ( QoL ) in premenopausal and perimenopausal patients with node-positive , early breast cancer treated with the endocrine agent goserelin ( Zoladex ; AstraZeneca Pharmaceuticals LP , Wilmington , DE ) or cyclophosphamide + methotrexate + fluorouracil ( CMF ) . PATIENTS AND METHODS Patients from 86 centers worldwide were r and omly assigned to receive either goserelin ( 3.6 mg every 28 days for 2 years ; n = 514 ) or CMF ( six 28-day cycles ; n = 496 ) , and were included in the QoL study . QoL was assessed using a self-administered patient question naire that consisted of 39 items from the Rotterdam Symptom Checklist , including dimensions evaluating physical and psychological symptom distress , activities of daily living , hormonal effects , and an assessment of overall QoL. RESULTS Early benefits were noted during months 3 to 6 of treatment , for goserelin compared with CMF . Significant differences were found for changes in overall QoL ( eg , 6.96 + /- 0.88 v 0.69 + /- 0.92 at 6 months ; P < .0001 ) and for physical symptom distress , activity levels , and " effort to cope with illness " dimensions . At 1 , 2 , and 3 years , there were no significant differences in overall QoL or specific QoL dimensions . Scores for hormonal symptoms were worse with goserelin during the 2-year goserelin treatment period ; however , this trend was reversed at 3 years . CONCLUSION Goserelin offers improved overall QoL during the first 6 months of therapy compared with CMF chemotherapy in premenopausal and perimenopausal patients with early breast cancer . Coupled with equivalent efficacy in estrogen receptor-positive patients , these data support the use of goserelin as an alternative to CMF in premenopausal and perimenopausal patients with estrogen receptor-positive , node-positive early breast cancer AIMS To evaluate possible differences in effect on time to recurrence and overall survival in node positive pre-menopausal breast cancer patients ( age < or = 50 years ) receiving LHRH analogue or tamoxifen as adjuvant endocrine treatment . METHODS Between January 1989 and July 1994 , 320 patients with node positive ( pN(+ ) ) and hormone receptor positive or receptor status unknown tumors were included and r and omized in a national multicenter study to receive either tamoxifen or goserelin as adjuvant treatment for two years . Primary surgical treatment was employed according to current st and ards . Final follow-up was completed as of December 2000 . Time to events were estimated by the Kaplan-Meier method , and compared by the log rank test . Relative risks were estimated by the Cox 's proportional hazards model . RESULTS No differences in time to first recurrence or overall survival were observed between treatment groups . Proportions of patients in each group having a second breast cancer were also similar . CONCLUSIONS St and ard adjuvant treatment with tamoxifen as compared to adjuvant LHRH analogue therapy employed in this group of breast cancer patients gave similar outcomes , but the number of patients was too small to formally exclude a potentially clinical ly relevant difference in survival The purpose of this r and omized study was to examine if goserelin concomitant to CMF-chemotherapy as adjuvant treatment for premenopausal breast cancer , protects the ovaries from premature failure . A total of 285 premenopausal breast cancer patients , in a r and omized adjuvant trial ( Zoladex in premenopausal patients ( ZIPP ) ) , were assigned to a study on ovarian function . Node positive patients were assigned to CMF-(cyclophosphamide , methotrexate and 5-fluorouracil ) chemotherapy in addition to endocrine therapy . All patients were r and omly assigned to receive 2 years of goserelin , goserelin plus tamoxifen , tamoxifen alone or no endocrine treatment . We studied , if menses were affected in the treatment groups , up to 36 months after r and omization . One year after completed CMF- and endocrine therapy , 36 % of the women in the goserelin group reported menses , compared to 7 % in the goserelin plus tamoxifen group , 13 % in the tamoxifen group and 10 % of the controls . Among women treated with goserelin , there was a statistically significant increase in the proportion of menstruating women , 1 year after completed treatment compared to at 24 months of treatment ( P = 0.006 ) , in contrast to all other treatment groups , who were unchanged or more often amenorrheic . In our study , there is some evidence of protective effect of goserelin on ovarian function in CMF treated women . This effect was not observed in the combined tamoxifen and goserelin treatment PURPOSE The purpose of this article is to compare quality of life ( QOL ) and menopausal symptoms among premenopausal patients with lymph node-negative breast cancer receiving chemotherapy , goserelin , or their sequential combination , and to investigate differential effects by age . PATIENTS AND METHODS We evaluated QOL data from 874 pre- and perimenopausal women with lymph node-negative breast cancer who were r and omly assigned to receive six courses of classical cyclophosphamide , methotrexate , and fluorouracil ( CMF ) chemotherapy , ovarian suppression with goserelin for 24 months , or six courses of classical CMF followed by 18 months of goserelin . We report QOL data collected during 3 years after r and om assignment in patients without disease recurrence . RESULTS Overall , patients receiving goserelin alone showed a marked improvement or less deterioration in QOL measures over the first 6 months than those patients treated with CMF . There were no differences at 3 years after r and om assignment according to treatment except for hot flashes . As reflected in the hot flashes scores , patients in all three treatment groups experienced induced amenorrhea , but the onset of ovarian function suppression was slightly delayed for patients receiving chemotherapy . Younger patients ( < 40 years ) who received goserelin alone returned to their premenopausal status at 6 months after the cessation of therapy , while those who received CMF showed marginal changes from their baseline hot flashes scores . CONCLUSION Age-adjusted risk profiles that consider patient-reported outcomes enable patients to adapt to their disease and treatment , such as considering the trade-offs between delayed endocrine symptoms , but higher risk of permanent menopause with chemotherapy , and immediate but reversible endocrine symptoms with goserelin , in younger premenopausal patients BACKGROUND Although chemotherapy and ovarian function suppression are both effective adjuvant therapies for patients with early-stage breast cancer , little is known of the efficacy of their sequential combination . In an International Breast Cancer Study Group ( IBCSG ) r and omized clinical trial ( Trial VIII ) for pre- and perimenopausal women with lymph node-negative breast cancer , we compared sequential chemotherapy followed by the gonadotropin-releasing hormone agonist goserelin with each modality alone . METHODS From March 1990 through October 1999 , 1063 patients stratified by estrogen receptor ( ER ) status and radiotherapy plan were r and omly assigned to receive goserelin for 24 months ( n = 346 ) , six courses of " classical " CMF ( cyclophosphamide , methotrexate , 5-fluorouracil ) chemotherapy ( n = 360 ) , or six courses of classical CMF followed by 18 months of goserelin ( CMF -- > goserelin ; n = 357 ) . A fourth arm ( no adjuvant treatment ) with 46 patients was discontinued in 1992 . Tumors were classified as ER-negative ( 30 % ) , ER-positive ( 68 % ) , or ER status unknown ( 3 % ) . Twenty percent of patients were aged 39 years or younger . The median follow-up was 7 years . The primary outcome was disease-free survival ( DFS ) . RESULTS Patients with ER-negative tumors achieved better disease-free survival if they received CMF ( 5-year DFS for CMF = 84 % , 95 % confidence interval [ CI ] = 77 % to 91 % ; 5-year DFS for CMF -- > goserelin = 88 % , 95 % CI = 82 % to 94 % ) than if they received goserelin alone ( 5-year DFS = 73 % , 95 % CI = 64 % to 81 % ) . By contrast , for patients with ER-positive disease , chemotherapy alone and goserelin alone provided similar outcomes ( 5-year DFS for both treatment groups = 81 % , 95 % CI = 76 % to 87 % ) , whereas sequential therapy ( 5-year DFS = 86 % , 95 % CI = 82 % to 91 % ) provided a statistically nonsignificant improvement compared with either modality alone , primarily because of the results among younger women . CONCLUSIONS Premenopausal women with ER-negative ( i.e. , endocrine nonresponsive ) , lymph node-negative breast cancer should receive adjuvant chemotherapy . For patients with ER-positive ( i.e. , endocrine responsive ) disease , the combination of chemotherapy with ovarian function suppression or other endocrine agents , and the use of endocrine therapy alone should be studied PURPOSE Risk of recurrence is the primary consideration in breast cancer adjuvant therapy recommendations . The TEXT ( Tamoxifen and Exemestane Trial ) and SOFT ( Suppression of Ovarian Function Trial ) trials investigated adjuvant endocrine therapies for premenopausal women with hormone receptor-positive breast cancer , testing exemestane plus ovarian function suppression ( OFS ) , tamoxifen plus OFS , and tamoxifen alone . We examined absolute treatment effect across a continuum of recurrence risk to individualize endocrine therapy decision making for premenopausal women with human epidermal growth factor receptor 2 ( HER2 ) -negative disease . PATIENTS AND METHODS The TEXT and SOFT hormone receptor-positive , HER2-negative analysis population included 4,891 women . The end point was breast cancer-free interval ( BCFI ) , defined as time from r and om assignment to first occurrence of invasive locoregional , distant , or contralateral breast cancer . A continuous , composite measure of recurrence risk for each patient was determined from a Cox model incorporating age , nodal status , tumor size and grade , and estrogen receptor , progesterone receptor , and Ki-67 expression levels . Sub population treatment effect pattern plot methodology revealed differential treatment effects on 5-year BCFI according to composite risk . RESULTS SOFT patients who remained premenopausal after chemotherapy experienced absolute improvement of 5 % or more in 5-year BCFI with exemestane plus OFS versus tamoxifen plus OFS or tamoxifen alone , reaching 10 % to 15 % at intermediate to high composite risk ; the benefit of tamoxifen plus OFS versus tamoxifen alone was apparent at the highest composite risk . The SOFT no-chemotherapy cohort-for whom composite risk was lowest on average-did well with all endocrine therapies . For TEXT patients , the benefit of exemestane plus OFS versus tamoxifen plus OFS in 5-year BCFI ranged from 5 % to 15 % ; patients not receiving chemotherapy and with lowest composite risk did well with both treatments . CONCLUSION Premenopausal women with hormone receptor-positive , HER2-negative disease and high recurrence risk , as defined by clinicopathologic characteristics , may experience improvement of 10 % to 15 % in 5-year BCFI with exemestane plus OFS versus tamoxifen alone . An improvement of at least 5 % may be achieved for women at intermediate risk , and improvement is minimal for those at lowest risk The Zoladex Early Breast Cancer Research Association ( ZEBRA ) trial compared the efficacy and tolerability of goserelin ( Zoladex ) with cyclophosphamide , methotrexate and 5-fluorouracil ( CMF ) chemotherapy in pre-/perimenopausal women with node-positive early breast cancer . The results of disease-free survival ( DFS ) analyses have already been published . Here we present an up date including data on overall survival ( OS ) from the ZEBRA trial at a median follow-up of 7.3 years . In patients with oestrogen receptor (ER)-positive tumours , non-inferiority of goserelin versus CMF for OS was shown ; goserelin was again shown to be equivalent to CMF for DFS . This up date d analysis has demonstrated that the two treatments are also equivalent for distant disease-free survival ( DDFS ) . In patients with ER-negative disease , goserelin was inferior to CMF for DFS , DDFS and OS . This follow-up analysis confirms the previously reported outcomes from the ZEBRA trial and demonstrates that goserelin offers an effective alternative to CMF chemotherapy for adjuvant therapy of premenopausal patients with ER-positive , node-positive early breast cancer 534 Background : Increasing evidence supports the use of GnRH analogues as adjuvant treatment in hormone sensitive , premenopausal breast cancer . However , only limited information is available in patients with node-negative disease . METHODS We r and omised 771 patients to either goserelin ( 3.6 mg every 28 days for 2 years ; n=393 ) or 3 cycles of cyclophosphamide , methotrexate , and fluorouracil ( CMF ) chemotherapy ( 500 mg/m2 , 40 mg/m2 and 600 mg/m2 , days 1,8 q 29 ; n=378 ) . Patients ' characteristics were well balanced with 26 % of the patients being 40 years or younger , 64 % having a tumor size below 21 mm , 79 % having grade 1 or 2 tumors , and 72 % receiving breast conserving surgery . 123 events were observed during a median follow up of 4.9 years . RESULTS The first event of failure ( goserelin vs CMF ) was an isolated locoregional recurrence ( 20 vs 18 ) , a distant failure ( 35 vs 46 ) , and death without recurrence ( 2 vs 2 ) . Five-year event-free survival rates were 84.4 % ( 95 % confidence interval ( CI ) : 80.4 % to 88.5 % ) and 81.0 % ( 95 % CI : 76.3 % to 85.7 % ) in the goserelin and in the CMF group , respectively . The estimated hazard ratio ( intention-to-treat analysis ) of goserelin vs CMF was 0.81 ( 95 % CI : 0.56 to 1.17 , P=0.24 ) . CONCLUSIONS Although the results of the trial are still based on relatively few observed events , they add important information to the current attempts of defining the role of medical ovarian ablation with goserelin in premenopausal patients with node-negative , hormonsensitive breast cancer . [ Table : see text ] OBJECTIVES In 2003 the International Breast Cancer Study Group ( IBCSG ) initiated the TEXT and SOFT r and omized phase III trials to answer two questions concerning adjuvant treatment for premenopausal women with endocrine-responsive early breast cancer : 1-What is the role of aromatase inhibitors ( AI ) for women treated with ovarian function suppression ( OFS ) ? 2-What is the role of OFS for women who remain premenopausal and are treated with tamoxifen ? METHODS TEXT r and omized patients to receive exemestane or tamoxifen with OFS . SOFT r and omized patients to receive exemestane with OFS , tamoxifen with OFS , or tamoxifen alone . Treatment was for 5 years from r and omization . RESULTS TEXT and SOFT successfully met their enrollment goals in 2011 . The 5738 enrolled women had lower-risk disease and lower observed disease-free survival ( DFS ) event rates than anticipated . Consequently , 7 and 13 additional years of follow-up for TEXT and SOFT , respectively , were required to reach the targeted DFS events ( median follow-up about 10.5 and 15 years ) . To provide timely answers , protocol amendments in 2011 specified analyses based on chronological time and median follow-up . To assess the AI question , exemestane + OFS versus tamoxifen + OFS , a combined analysis of TEXT and SOFT became the primary analysis ( n = 4717 ) . The OFS question became the primary analysis from SOFT , assessing the unique comparison of tamoxifen + OFS versus tamoxifen alone ( n = 2045 ) . The first reports are anticipated in mid- and late-2014 . CONCLUSIONS We present the original design s of TEXT and SOFT and adaptations to ensure timely answers to two questions concerning optimal adjuvant endocrine treatment for premenopausal women with endocrine-responsive breast cancer . Trial Registration TEXT : Clinical trials.govNCT00066703 SOFT : Clinical trials.govNCT00066690 PURPOSE Chemotherapy , tamoxifen , and ovarian ablation/suppression ( OA/OS ) are effective adjuvant approaches for premenopausal , steroid hormone receptor-positive breast cancer . The value of combined therapy has not been clearly established . PATIENTS AND METHODS Premenopausal women with axillary lymph node-positive , steroid hormone receptor-positive breast cancer ( 1,503 eligible patients ) were r and omly assigned to six cycles of cyclophosphamide , doxorubicin , and fluorouracil ( CAF ) , CAF followed by 5 years of monthly goserelin ( CAF-Z ) , or CAF followed by 5 years of monthly goserelin and daily tamoxifen ( CAF-ZT ) . The primary end points were time to recurrence ( TTR ) , disease-free survival ( DFS ) , and overall survival ( OS ) for CAF-Z versus CAF , and CAF-ZT versus CAF-Z. RESULTS With a median follow-up of 9.6 years , the addition of tamoxifen to CAF-Z improved TTR and DFS but not OS . There was no overall advantage for addition of goserelin to CAF . CONCLUSION Addition of tamoxifen to CAF-Z improves outcome for premenopausal node-positive , receptor-positive breast cancer . The role of OA/OS alone or with other endocrine agents should be studied more intensely BACKGROUND The International Breast Cancer Study Group Trial VIII compared long-term efficacy of endocrine therapy ( goserelin ) , chemotherapy [ cyclophosphamide , methotrexate and fluorouracil ( CMF ) ] , and chemoendocrine therapy ( CMF followed by goserelin ) for pre/perimenopausal women with lymph-node-negative breast cancer . PATIENTS AND METHODS From 1990 to 1999 , 1063 patients were r and omized to receive ( i ) goserelin for 24 months ( n = 346 ) , ( ii ) six courses of ' classical ' CMF ( cyclophosphamide , methotrexate , 5-fluorouracil ) chemotherapy ( n = 360 ) , or ( iii ) six courses of CMF plus 18 months goserelin ( CMF→ goserelin ; n = 357 ) . Tumors were classified as estrogen receptor ( ER ) negative ( 19 % ) , ER positive ( 80 % ) , or ER unknown ( 1 % ) ; 19 % of patients were younger than 40 . Median follow-up was 12.1 years . RESULTS For the ER-positive cohort , sequential therapy provided a statistically significant benefit in disease-free survival ( DFS ) ( 12-year DFS = 77 % ) compared with CMF alone ( 69 % ) and goserelin alone ( 68 % ) ( P = 0.04 for each comparison ) , due largely to the effect in younger patients . Patients with ER-negative tumors whose treatment included CMF had similar DFS ( 12-year DFS CMF = 67 % ; 12-year DFS CMF→ goserelin = 69 % ) compared with goserelin alone ( 12-year DFS = 61 % , P= NS ) . CONCLUSIONS For pre/perimenopausal women with lymph-node-negative ER-positive breast cancer , CMF followed by goserelin improved DFS in comparison with either modality alone . The improvement was the most pronounced in those aged below 40 , suggesting an endocrine effect of prolonged CMF-induced amenorrhea BACKGROUND Suppression of ovarian estrogen production reduces the recurrence of hormone-receptor-positive early breast cancer in premenopausal women , but its value when added to tamoxifen is uncertain . METHODS We r and omly assigned 3066 premenopausal women , stratified according to prior receipt or nonreceipt of chemotherapy , to receive 5 years of tamoxifen , tamoxifen plus ovarian suppression , or exemestane plus ovarian suppression . The primary analysis tested the hypothesis that tamoxifen plus ovarian suppression would improve disease-free survival , as compared with tamoxifen alone . In the primary analysis , 46.7 % of the patients had not received chemotherapy previously , and 53.3 % had received chemotherapy and remained premenopausal . RESULTS After a median follow-up of 67 months , the estimated disease-free survival rate at 5 years was 86.6 % in the tamoxifen-ovarian suppression group and 84.7 % in the tamoxifen group ( hazard ratio for disease recurrence , second invasive cancer , or death , 0.83 ; 95 % confidence interval [ CI ] , 0.66 to 1.04 ; P=0.10 ) . Multivariable allowance for prognostic factors suggested a greater treatment effect with tamoxifen plus ovarian suppression than with tamoxifen alone ( hazard ratio , 0.78 ; 95 % CI , 0.62 to 0.98 ) . Most recurrences occurred in patients who had received prior chemotherapy , among whom the rate of freedom from breast cancer at 5 years was 82.5 % in the tamoxifen-ovarian suppression group and 78.0 % in the tamoxifen group ( hazard ratio for recurrence , 0.78 ; 95 % CI , 0.60 to 1.02 ) . At 5 years , the rate of freedom from breast cancer was 85.7 % in the exemestane-ovarian suppression group ( hazard ratio for recurrence vs. tamoxifen , 0.65 ; 95 % CI , 0.49 to 0.87 ) . CONCLUSIONS Adding ovarian suppression to tamoxifen did not provide a significant benefit in the overall study population . However , for women who were at sufficient risk for recurrence to warrant adjuvant chemotherapy and who remained premenopausal , the addition of ovarian suppression improved disease outcomes . Further improvement was seen with the use of exemestane plus ovarian suppression . ( Funded by Pfizer and others ; SOFT Clinical Trials.gov number , NCT00066690 . ) Purpose To describe benefits and toxicities of adjuvant endocrine therapies in women younger than 35 years with breast cancer ( n = 582 ) enrolled in the Suppression of Ovarian Function Trial ( SOFT ) and Tamoxifen and Exemestane Trial ( TEXT ) . Methods In SOFT , women still premenopausal after surgery with or without chemotherapy were r and omly assigned to tamoxifen alone , tamoxifen plus ovarian function suppression ( OFS ) , or exemestane plus OFS . In TEXT , all received OFS with or without concomitant chemotherapy and were r and omly assigned to exemestane plus OFS or tamoxifen plus OFS . We summarize treatment efficacy , quality of life , and adherence of the cohort of women younger than 35 years in SOFT and TEXT , alongside data from the cohort of older premenopausal women . Results For 240 human epidermal growth factor receptor 2-negative patients younger than 35 years enrolled in SOFT after receiving chemotherapy , the 5-year breast cancer-free interval ( BCFI ) was 67.1 % ( 95 % CI , 54.6 % to 76.9 % ) with tamoxifen alone , 75.9 % with tamoxifen plus OFS ( 95 % CI , 64.0 % to 84.4 % ) , and 83.2 % with exemestane plus OFS ( 95 % CI , 72.7 % to 90.0 % ) . For 145 human epidermal growth factor receptor 2-negative patients younger than 35 years in TEXT , 5-year BCFI was 79.2 % ( 95 % CI , 66.2 % to 87.7 % ) with tamoxifen plus OFS and 81.6 % ( 95 % CI , 69.8 % to 89.2 % ) with exemestane plus OFS . The most prominent quality of life symptom for patients younger than 35 years receiving OFS was vasomotor symptoms , with the greatest worsening from baseline at 6 months ( on the order of 30 to 40 points ) , but loss of sexual interest and difficulties in becoming aroused were also clinical ly meaningful ( ≥ 8-point change ) . The level of symptom burden was similar in older premenopausal women . A total of 19.8 % of women younger than 35 years stopped all protocol -assigned endocrine therapy early . Conclusion In women younger than 35 years with hormone receptor-positive breast cancer , adjuvant OFS combined with tamoxifen or exemestane produces large improvements in BCFI compared with tamoxifen alone . Menopausal symptoms are significant but are not worse than those seen in older premenopausal women PURPOSE The objective of this study was to evaluate the efficacy and tolerability of leuprorelin acetate in adjuvant treatment in comparison to st and ard chemotherapy with CMF in premenopausal , estrogen-receptor-positive or unknown , node-positive patients with early breast cancer . PATIENTS AND METHODS The patients were r and omly assigned to receive either 2 years of hormone ablation with leuprorelin acetate 11.25 mg as a subcutaneous injection every three months or six courses of CMF ( cyclophosphamide 500 mg/m2 , methotrexate 40 mg/m2 , fluorouracil 600 mg/m2 , days 1 and 8 , q 4 weeks ) . The primary study end-point was recurrence-free survival ( RFS ) after 2 years . Secondary end-points included overall survival , adverse events and hormonal suppression . RESULTS Between 1995 and 1999 , a total of 589 patients with breast cancer were r and omized to treatment with leuprorelin acetate or CMF . The data of 227 patients were available for this first interim analysis . One hundred and ten and 117 patients were assigned to leuprorelin acetate and chemotherapy , respectively . Both treatment arms were well balanced for baseline characteristics . So far , no difference between the groups has emerged with respect to recurrence-free or overall survivaL Suppression of serum estradiol levels and menstruation was less marked in the CMF-group compared to the leuprorelin arm . The most common adverse events were low- grade hot flushes , weight gain and increased sweating in the leuprorelin-treated patients and alopecia , nausea and vomiting in the CMF-group . CONCLUSION According to these preliminary results , ovarian suppression with leuprorelin acetate was as effective as st and ard chemotherapy for premenopausal women with hormone-sensitive , node-positive early breast cancer Ovarian ablation improves survival in premenopausal early breast cancer , but the potential added value by luteinizing hormone-releasing hormone ( LHRH ) agonists to tamoxifen is still not clear . The purpose of our study is to examine the efficacy of the LHRH agonist goserelin for adjuvant therapy of premenopausal breast cancer , the role of interaction between goserelin and tamoxifen and the impact of estrogen receptor ( ER ) content . A total of 927 patients were included in the Stockholm part of the Zoladex in Premenopausal Patients ( ZIPP ) trial . They were r and omly allocated in a 2 × 2 factorial study design to goserelin , tamoxifen , the combination of goserelin and tamoxifen or no endocrine therapy for 2 years , with or without chemotherapy . This is formally not a preplanned subset analysis presenting the end point first event . In this Stockholm sub- study , at a median follow-up of 12.3 years , goserelin reduced the risk of first event by 32 % ( P = 0.005 ) in the absence of tamoxifen , and tamoxifen reduced the risk by 27 % ( P = 0.018 ) in the absence of goserelin . The combined goserelin and tamoxifen treatment reduced the risk by 24 % ( P = 0.021 ) compared with no endocrine treatment . In highly ER-positive tumours , there were 29 % fewer events among goserelin treated ( P = 0.044 ) and a trend towards greater risk reduction depending on the level of ER content . The greatest risk reduction from goserelin treatment was observed among those not receiving tamoxifen ( HR : 0.52 , P = 0.007 ) . In conclusion , goserelin as well as tamoxifen reduces the risk of recurrence in endocrine responsive premenopausal breast cancer . Women with strongly ER-positive tumours may benefit more from goserelin treatment . The combination of goserelin and tamoxifen is not superior to either modality alone . With the limitations of a subset trial , these data have to be interpreted cautiously BACKGROUND Substantial survival benefits exist for patients with early-stage breast cancer who undergo treatment with single-modality tamoxifen , ovarian ablation or suppression , or chemotherapy . To determine whether additional benefits exist with combined treatment , the Adjuvant Breast Cancer ( ABC ) Trials were undertaken . METHODS The ABC Ovarian Ablation or Suppression Trial r and omly assigned pre- and perimenopausal patients with early-stage breast cancer who were receiving prolonged ( 5 years ) tamoxifen treatment with or without chemotherapy to ovarian ablation or suppression ( by oophorectomy , ovarian irradiation , or treatment with luteinizing hormone-releasing hormone agonist ) versus no ovarian ablation or suppression . Trial endpoints included relapse-free and overall survival . Hazard ratios ( HRs ) were derived from Cox models , and all statistical tests were two-sided . RESULTS Between 1993 and 2000 , 2144 ( 1063 ovarian ablation or suppression , 1081 no ovarian ablation or suppression ) patients were r and omly assigned . A total of 942 ( 89 % ) received ovarian ablation or suppression as allocated . Overall , no evidence of a benefit for ovarian ablation or suppression was observed for relapse-free survival ( relapse in the ovarian ablation/suppression versus no ovarian ablation/suppression group , 290 events versus 306 events , HR = 0.95 , 95 % confidence interval [ CI ] = 0.81 to 1.12 ; P = .56 ) or overall survival ( death from any cause in the ovarian ablation or suppression versus no ovarian ablation/suppression group , 215 events versus 230 events , HR = 0.94 , 95 % CI = 0.78 to 1.13 ; P = .44 ) , nor were differences seen after adjustment for age , nodal status , or estrogen receptor ( ER ) status . CONCLUSION Overall , no added effect of ovarian ablation or suppression was seen on relapse-free survival or overall survival of premenopausal women who were treated for early-stage breast cancer . However , the role of ovarian ablation or suppression in young ( < 40 years ) women with ER-positive tumors , especially those not receiving chemotherapy , requires further study Abstract The SOFT and TEXT r and omized phase III trials investigated adjuvant endocrine therapies for premenopausal women with hormone receptor-positive ( HR+ ) early breast cancer . We investigated the prognostic and predictive value of central ly assessed levels of estrogen receptor ( ER ) , progesterone receptor ( PgR ) , and Ki-67 expression in women with HER2-negative disease . Of 5707 women enrolled , 4115 with HER2-negative ( HR+/HER2− ) disease had ER , PgR , and Ki-67 central ly assessed by immunohistochemistry . Breast cancer-free interval ( BCFI ) was defined from r and omization to first invasive local , regional , or distant recurrence or contralateral breast cancer . The prognostic and predictive values of ER , PgR and Ki-67 expression levels were assessed using Cox modeling and STEPP methodology . In this HR+/HER2- population , the median ER , PgR , and Ki-67 expressions were 95 , 90 , and 18 % immunostained cells . As most patients had strongly ER-positive tumors , the predictive value of ER levels could not be investigated . Lower PgR and higher Ki-67 expression were associated with reduced BCFI . There was no consistent evidence of heterogeneity of the relative treatment effects according to PgR or Ki-67 expression levels , though there was a greater 5-year absolute benefit of exemestane + ovarian function suppression ( OFS ) versus tamoxifen with or without OFS at lower levels of PgR and higher levels of Ki-67 . Women with poor prognostic features of low PgR and /or high Ki-67 have greater absolute benefit from exemestane + OFS versus tamoxifen + OFS or tamoxifen alone , but individually PgR and Ki-67 are of limited predictive value for selecting adjuvant endocrine therapy for premenopausal women with HR+/HER2− early breast cancer One of the earliest r and omised trials of a treatment for cancer was of ovarian ablation for breast cancer . Apart from surgical removal of the tumour , this is the oldest treatment still used in breast cancer . Its use was first reported in the Lancet in 1896,1 but not until the 1940s was it first assessed in r and omised trials and it was nearly a century before the Early Breast Cancer Trialists ' Collaborative Group provided a reliable estimate of its effect on resectable breast cancer.2 Now , 50 years after its completion , the first r and omised trial of ovarian ablation has been included in the first of the collaborative group 's overviews to be prepared as a Cochrane review .3 Here I describe this journey along a hierarchy of evidence and show why the research is still relevant . # # # Summary points The hierarchy of evidence needed to determine treatment efficacy ranges from case reports , through case series and comparison with historical groups , to r and omised trials and systematic review s Over the past 100 years the investigation of ovarian ablation for women with breast cancer has progressed along this hierarchy The first case report was published in 1896 and the first r and omised trial began in 1948 Not until 1992 did a systematic review show this treatment to be clearly effective David Byar described an eight point hierarchy for the quality of evidence needed to determine a treatment 's efficacy . This leads from anecdotal case reports , through case series and comparison with historical groups , to r and omised trials and systematic review s.4 Olkin added a ninth point : a meta- analysis in which individual patient data from each relevant trial are collected and analysed.5 He described this as being in the “ realms of luxury , ” but several examples now exist.6 Occasionally , the evidence that a treatment is effective becomes apparent without needing to Adjuvant chemotherapy-induced amenorrhoea has been shown to be associated with reduced relapses and improved survival for premenopausal breast cancer patients . Amenorrhoea was , therefore , studied to define features of chemotherapy ( i.e. duration and timing ) and disease-related factors which are associated with its treatment effects . We review ed data from IBCSG Trial VI , in which accrual was between July 1986 and April 1993 . 1196 of the 1475 eligible patients ( 81 % ) were evaluable for this analysis . The median follow-up was 60 months . Women who experienced amenorrhoea had a significantly better disease-free survival ( DFS ) than those who did not ( P = 0.0004 ) , although the magnitude of the effect was reduced when adjusted for other prognostic factors ( P = 0.09 ) . The largest treatment effect associated with amenorrhoea was seen in patients assigned to receive only three initial CMF courses ( 5-yr DFS : 67 % versus 49 % , no amenorrhoea ; hazard ratio , 0.55 ; 95 % confidence interval , 0.38 to 0.81 ; P = 0.002 ) . DFS differences between amenorrhoea categories were larger for patients with ER/PR positive tumours ( hazard ratio , 0.65 ; 95 % confidence interval , 0.53 to 0.80 ; P = 0.0001 ) . Furthermore , patients whose menses returned after brief amenorrhoea had a DFS similar to those whose menses ceased and did not recover ( hazard ratio , 1.10 ; 95 % confidence interval , 0.75 to 1.62 ; P = 0.63 ) . The effects associated with a permanent or temporary chemotherapy-induced amenorrhoea are especially significant for node-positive breast cancer patients who receive a suboptimal duration of CMF chemotherapy . Cessation of menses , even for a limited time period after diagnosis of breast cancer , might be beneficial and should be prospect ively investigated , especially in patients with oestrogen receptor-positive primaries BACKGROUND Adjuvant systemic therapy prolongs disease-free and overall survival in both pre- and postmenopausal patients . Available data shown benefit from multi-agent chemotherapy , prolonged tamoxifen treatment , and ovarian ablation , and that the combination of chemo- and endocrine therapy might be advantageous . In 1978 the International ( Ludwig ) Breast Cancer Study Group ( IBCSG ) initiated four complementary r and omized controlled clinical trials to evaluate the roles of chemo-endocrine combinations or endocrine therapy alone in specific population s defined by risk ( for pre- and perimenopausal patients ) or by age ( for postmenopausal patients ) . The results at 10 and 13 years ' median follow-up for these trials are summarized in this report and are compared to those of the Overview meta- analysis with regard to chemo-endocrine or endocrine therapy combinations . Furthermore , types of first relapses by sites and second malignant diseases are reported . PATIENTS AND METHODS 1601 evaluable patients with node positive disease were included into the studies I-IV . In Trial I ( 491 premenopausal patients with 1 - 3 positive axillary nodes ) we studied the addition of low-dose continuous prednisone ( p ) to a cyclophosphamide-methotrexate-fluorouracil ( CMF ) combination . In Trial II 327 premenopausal patients with four or more positive axillary nodes were r and omized to one year CMFp or to a surgical oophorectomy followed by CMFp . In Trial III ( 463 postmenopausal patients 65 years old or younger ) , combined chemoendocrine therapy ( one year of CMFp plus tamoxifen ( T ) ) was compared to endocrine therapy ( 1 year of p + T ) or to surgery alone . In Trial IV 320 postmenopausal patients 66 to 80 years old were treated either by surgery alone or by surgery followed by 1 year prednisone and tamoxifen . RESULTS In Trial I the addition of prednisone allowed a higher dose of cytotoxics to be administered compared with CMF alone . Despite this increased dose intensity , 13-year disease-free survival ( DFS ) and overall survival ( OS ) were similar for the two treatment groups ( 49 % vs. 52 % DFS , 59 % vs. 65 % OS for CMFp vs. CMF ) . In Trial II the addition of surgical oophorectomy to CMFp yielded an improved outcome which approached statistical significance for the subset of 107 patients known to have estrogen receptor-positive tumors ( DFS , 23 % vs. 15 % , p = 0.13 ; OS , 41 % vs. 30 % , p = 0.12 ) . In Trial III combined chemoendocrine therapy improved DFS and OS compared with endocrine therapy alone ( p + T ) given for the same duration , or no adjuvant treatment ( DFS , 35 % vs. 25 % vs. 14 % , p < 0.0001 ; OS , 48 % vs. 36 % vs. 32 % , p = 0.01 ) . In Trial IV p + T improved DFS compared with no adjuvant therapy ( 27 % vs. 15 % , p = 0.004 ) . Despite competing risks for this elderly population , OS was also improved but the result was not statistically significant ( 34 % vs. 22 % , p = 0.08 ) . CONCLUSIONS The overall results of these four trials indicate that the continuation of investigations on combined chemo-endocrine therapies is warranted . The prognosis of the patients , all node-positive , treated with the most effective adjuvant treatment is such that there is a large potential for improvement PURPOSE To compare the effect of adjuvant endocrine therapies with and without chemotherapy on physical symptoms , anxiety , and depressive symptoms in premenopausal women with breast cancer in a r and omized clinical trial ( the Zoladex in Premenopausal Patients trial ) . PATIENTS AND METHODS The patients were r and omly assigned to goserelin , goserelin plus tamoxifen , tamoxifen alone , or no endocrine therapy . The duration of the endocrine treatment was 2 years . The groups were observed for 3 years after primary treatment ( ie , during 2 years of active treatment as well as 1 year after cessation of the adjuvant endocrine therapy ) . All patients with node-positive disease received adjuvant chemotherapy with cyclophosphamide , methotrexate , and fluorouracil ( CMF ) , which was given concurrently with the endocrine treatment . RESULTS Patients treated with CMF typically reported higher levels of physical symptoms than did patients who did not receive CMF . It was only among patients who did not receive chemotherapy that the endocrine treatment had differential effects . Goserelin was most burdensome and result ed in similar symptom levels as those of CMF , whereas the side effects of tamoxifen alone were milder . After cessation of the endocrine treatment , the side effects diminished in patients who had not received CMF , whereas patients treated with CMF reported ongoing problems at the 3-year follow-up . In contrast , anxiety and depressive symptoms were not significantly affected by endocrine treatment or chemotherapy during the 3 years of assessment . CONCLUSION Goserelin and tamoxifen result ed in menopausal symptoms , but these symptoms were reversible . However , women treated with CMF experienced physical symptoms throughout the whole study period BACKGROUND The hormonal manipulation 5-Fluoro-uracil Epirubicin Cyclophosphamide ( HMFEC ) trial was developed at a time of uncertainty around the dose intensity of chemotherapy given to premenopausal patients with node positive breast cancer and to the benefits of tailored endocrine therapy in such patients . PATIENTS AND METHODS HMFEC was a multi-centre , phase III , open label , r and omised controlled trial with a 2 × 2 factorial design . Eligible patients were premenopausal with node positive early breast cancer ; significant cardiac disease or uncontrolled hypertension was exclusion criterion . Patients were allocated to receive either eight cycles of FE50C or FE75C ( given 3 weekly ) with or without hormone manipulation ( HM ; tamoxifen or luteinising hormone releasing hormone ( LHRH ) agonists according to residual hormone levels at the end of chemotherapy ) irrespective of ER status . The primary end-point was disease free survival ( DFS ) . Principal analyses were by intention to treat ( ITT ) ; however , to reflect contemporary practice , subgroup analyses according to ER status were also conducted . The mature follow-up now available from this modest sized trial enables presentation of definitive results . RESULTS Between 1992 and 2000 a total of 785 patients were r and omised into the HMFEC trial ( 203 FE50C-HM , 191 FE50C+HM , 198 FE75C-HM , 193 FE75C+HM ) . At a median follow-up of 7.4 years , 245 DFS events have been reported ( 92 ER- , 153 ER+/unknown ) . The effects on DFS were not statistically significantly different according to epirubicin dose ( hazard ratio [ HR ] = 0.82 , 95 % confidence interval [ CI ] 0.63 - 1.06 ; p = 0.13 FE75C versus FE50C ) ; however , FE75C appeared to induce more alopecia and neutropenia . No statistically significant evidence was observed to support an improvement in DFS in patients allocated HM either overall ( HR = 0.88 , 95 % CI 0.68 - 1.13 ; p = 0.32 ) or in patients with ER+/unknown disease ( HR = 0.85 , 95 % CI 0.62 - 1.17 ; p = 0.32 ) although effect sizes are consistent with worthwhile clinical effects . Overall , there was no evidence of a difference in survival between any of the four treatment groups of the trial . CONCLUSION Higher doses of epirubicin cause more adverse events in the absence of clear improvement in overall survival . Endocrine therapy with either tamoxifen or goserelin provided no significant added benefit to cytotoxic chemotherapy in this group of patients . TRIAL REGISTRATION NUMBER IS RCT N98335268 PURPOSE The aim of this multicenter trial was to evaluate the role of ovarian suppression in patients with early breast cancer previously treated with local surgery and adjuvant chemotherapy . PATIENTS AND METHODS Nine hundred and twenty-six premenopausal patients with completely resected breast cancer and either axillary node involvement or histological grade 2 or 3 tumors were r and omized after surgery to adjuvant chemotherapy alone ( control arm ) or adjuvant chemotherapy plus ovarian suppression ( ovarian suppression arm ) . Ovarian suppression was obtained by either radiation-induced ovarian ablation or triptorelin for 3 years . The analyses were performed with Cox models stratified by center . RESULTS Median follow-up was 9.5 years . Mean age was 43 years . Ninety per cent of patients had histologically proven positive axillary nodes , 63 % positive hormonal receptors and 77 % had received an anthracycline-based chemotherapy regimen . Ovarian suppression was by radiation-induced ovarian ablation ( 45 % of patients ) or with triptorelin ( 48 % ) . At the time of r and omization , all patients had regular menses or their follicle-stimulating hormone and estradiol levels indicated a premenopausal status . The 10-year disease-free survival rates were 49 % [ 95 % confidence interval ( CI ) 44 % to 54 % ] in both arms ( P = 0.51 ) . The 10-year overall survival rates were 66 % ( 95 % CI 61 % to 70 % ) for the ovarian suppression arm and 68 % ( 95 % CI 63 % to 73 % ) for the control arm ( P = 0.19 ) . There were no variations in the treatment effect according to age , hormonal receptor status or ovarian suppression modality . However , in patients < 40 years of age and with estrogen receptor-positive tumors , ovarian suppression significantly decreased the risk of recurrence ( P = 0.01 ) . CONCLUSIONS The results of this trial , after at least 10 years of follow-up , do not favor the use of ovarian suppression after adjuvant chemotherapy . The potential beneficial effect in younger women with hormono-dependent tumors should be further assessed PURPOSE Effective adjuvant treatment modalities in premenopausal breast cancer patients today include chemotherapy , ovariectomy , and tamoxifen administration . The purpose of Austrian Breast and Colorectal Cancer Study Group Trial 5 was to compare the efficacy of a combination endocrine treatment with st and ard chemotherapy . PATIENTS AND METHODS Assessable trial subjects ( N = 1,034 ) presenting with hormone-responsive disease were r and omized to receive either 3 years of goserelin plus 5 years of tamoxifen or six cycles of cyclophosphamide , methotrexate , and fluorouracil ( CMF ) . Stratification criteria included tumor stage and grade , number of involved nodes , type of surgery , and steroid hormone receptor content . Relapse-free survival ( RFS ) was defined as time from r and omization to first relapse , local recurrence , or contralateral incidence , and overall survival ( OS ) as time to date of death . RESULTS With a 60-month median follow-up , 17.2 % of patients in the endocrine group and 20.8 % undergoing chemotherapy developed relapses . Local recurrences emerged in 4.7 % and 8.0 % , respectively . RFS and local recurrence-free survival differed significantly in favor of endocrine therapy ( P = .037 and P = .015 ) , with a similar trend observed in OS ( P = .195 ) . CONCLUSION Overall , our data suggest that the goserelin-tamoxifen combination is significantly more effective than CMF in the adjuvant treatment of premenopausal patients with stage I and II breast cancer BACKGROUND Ovarian suppression plus tamoxifen is a st and ard adjuvant treatment in premenopausal women with endocrine-responsive breast cancer . Aromatase inhibitors are superior to tamoxifen in postmenopausal patients , and pre clinical data suggest that zoledronic acid has antitumor properties . METHODS We examined the effect of adding zoledronic acid to a combination of either goserelin and tamoxifen or goserelin and anastrozole in premenopausal women with endocrine-responsive early breast cancer . We r and omly assigned 1803 patients to receive goserelin ( 3.6 mg given subcutaneously every 28 days ) plus tamoxifen ( 20 mg per day given orally ) or anastrozole ( 1 mg per day given orally ) with or without zoledronic acid ( 4 mg given intravenously every 6 months ) for 3 years . The primary end point was disease-free survival ; recurrence-free survival and overall survival were secondary end points . RESULTS After a median follow-up of 47.8 months , 137 events had occurred , with disease-free survival rates of 92.8 % in the tamoxifen group , 92.0 % in the anastrozole group , 90.8 % in the group that received endocrine therapy alone , and 94.0 % in the group that received endocrine therapy with zoledronic acid . There was no significant difference in disease-free survival between the anastrozole and tamoxifen groups ( hazard ratio for disease progression in the anastrozole group , 1.10 ; 95 % confidence interval [ CI ] , 0.78 to 1.53 ; P=0.59 ) . The addition of zoledronic acid to endocrine therapy , as compared with endocrine therapy without zoledronic acid , result ed in an absolute reduction of 3.2 percentage points and a relative reduction of 36 % in the risk of disease progression ( hazard ratio , 0.64 ; 95 % CI , 0.46 to 0.91 ; P=0.01 ) ; the addition of zoledronic acid did not significantly reduce the risk of death ( hazard ratio , 0.60 ; 95 % CI , 0.32 to 1.11 ; P=0.11 ) . Adverse events were consistent with known drug-safety profiles . CONCLUSIONS The addition of zoledronic acid to adjuvant endocrine therapy improves disease-free survival in premenopausal patients with estrogen-responsive early breast cancer . ( Clinical Trials.gov number , NCT00295646 . PURPOSE To compare the efficacy of chemotherapy versus that of tamoxifen plus ovarian suppression in pre-/perimenopausal estrogen receptor-positive patients with early breast cancer . PATIENTS AND METHODS Patients were r and omly assigned to receive either six cycles of a st and ard regimen of cyclophosphamide 100 mg/m(2 ) orally days 1 to 14 , methotrexate 40 mg/m(2 ) intravenously ( IV ) days 1 and 8 , and fluorouracil 600 mg/m(2 ) IV days 1 and 8 ( CMF ) , with all drugs restarted on day 29 , or 5 years of tamoxifen , 30 mg/d , plus ovarian suppression with surgical oophorectomy , ovarian irradiation , or monthly goserelin 3.6-mg injections . Disease-free survival was the main study end point . Overall survival and toxicity were additional end points . RESULTS Between 1989 and 1997 , 120 patients were assigned to CMF and 124 to tamoxifen and ovarian suppression ( oophorectomy , n = 6 ; ovarian irradiation , n = 31 ; and goserelin injections , n = 87 ) . At the time of analysis ( median follow-up time , 76 months ; range , 9 to 121 months ) , 82 patients had relapsed and 39 had died . No difference between groups had emerged with respect to either disease-free or overall survival . Treatments were comparable even in respect to age , tumor size , and nodal status , although a nonsignificant trend favored patients with poorly differentiated tumors treated with CMF . Leukopenia , nausea , vomiting , stomatitis , and alopecia were significantly more common in patients treated with CMF . There were few patients who developed benign gynecologic changes in either group , and numbers were comparable . CONCLUSION The combination of tamoxifen with ovarian suppression seems to be safe and to yield comparable results relative to st and ard CMF Purpose To assess the efficacy , safety , and quality -of-life impact of switching adjuvant treatment in hormone receptor-positive primary breast cancer patients who are still premenopausal after 2–3 years of tamoxifen therapy to anastrozole plus goserelin as compared with continuing tamoxifen over a total period of 5 years . Patients and methods Hormone receptor-positive , premenopausal , lymph node-positive , or tumor size ≥4 cm breast cancer patients who had received tamoxifen for 2–3 years were r and omly assigned to continue tamoxifen treatment ( TAM group ) or switch to adjuvant anastrozole plus goserelin ( ADD group ) and continue treatment for another 2–3 years ( total treatment duration 5 years ) . Endpoints evaluated were adverse events ( AEs ) , changes in bone mineral density , quality of life , and disease-free survival-related events . Results A total of 62 patients ( 33 in the ADD group and 29 in the TAM group ) were evaluated . Grade 3–4 drug-related AEs occurred in five patients ( 15.2 % ) in the ADD group vs none in the TAM group . In the ADD group , arthralgias were the most common AEs ( 5/33 patients ; 15.2 % ) , and three patients in this group were discontinued because of AEs . Treatment was temporarily suspended due to AEs in three patients ( 9.1 % ) in the ADD group and one patient ( 3.4 % ) in the TAM group . Compared with continuing TAM therapy , switching to anastrozole plus goserelin did not result in any worsening of bone mineral density or quality of life . During a median follow-up of 34 months , five patients ( 15.2 % ) in the ADD group had disease-free survival events vs four patients ( 13.8 % ) in the TAM group . Conclusion For early-stage breast cancer patients who remain premenopausal following 2–3 years of adjuvant tamoxifen therapy , switching to anastrozole plus goserelin therapy was safe with tolerable adverse effects . However , it did not show superior efficacy compared to remaining on tamoxifen treatment . Trial Registration Clinical Trials.gov ( identifier NCT01352091 ) The current r and omized , controlled , multicenter clinical trial was conducted to investigate the efficacy of concurrent neoadjuvant chemotherapy ( NCT ) and estrogen deprivation in patients with estrogen receptor (ER)–positive , human epidermal growth factor receptor 2 (HER2)–negative breast cancer Supplement . Supplementary Material . Each year an estimated 425000 U.S. women have a hysterectomy for benign gynecologic conditions ( 1 , 2 ) , and one third ( 3 ) to one half ( 4 ) of them undergo concurrent oophorectomy to minimize ovarian cancer risk . Several observational studies have found that , although it does reduce subsequent risk for ovarian ( 57 ) and breast ( 5 , 8) cancer , bilateral salpingo-oophorectomy ( BSO ) also confers long-term health risks beyond those result ing from hysterectomy itself , especially when ovary removal occurs early ( before age 45 to 50 years ) . Observational studies also suggest that BSO-associated elevations in all-cause mortality ( 5 , 912 ) , coronary heart disease ( CHD ) ( 10 , 1315 ) , and other adverse outcomes are attenuated among women treated with menopausal estrogen therapy ( 4 ) . Given the acute declines ( 16 , 17 ) and sustained reductions ( 18 , 19 ) in endogenous sex hormones that occur after BSO , it is biologically plausible that estrogen therapy might confer long-term benefits , including reduction in all-cause mortality , in women who have undergone this procedure , and such benefits may be greater than in women with conserved ovaries . The Women 's Health Initiative ( WHI ) Estrogen-Alone Trial , a large-scale , r and omized trial of estrogen therapy in 10739 women aged 50 to 79 years with prior hysterectomy with or without BSO , provides a unique opportunity to investigate these issues , which have not been examined in a r and omized trial setting . Because prior analyses of the benefits and risks of estrogen therapy for the WHI study population indicate variation by age at r and om assignment ( 20 , 21 ) , assessing the effects of such therapy not only according to BSO status but also jointly by BSO status and age is of interest . Results of such analyses may inform clinical decision making about estrogen therapy . Methods Study Design The WHI Estrogen-Alone Trial , including the design , compliance , and outcome adjudication procedures , is described elsewhere ( 2023 ) . A total of 10739 postmenopausal women aged 50 to 79 years with prior hysterectomy were recruited from 1993 to 1998 at 40 U.S. clinical centers and r and omly assigned to oral conjugated equine estrogens ( CEE [ Premarin ; Pfizer ] ) ( 0.625 mg/d ) or placebo . Primary outcomes were incident CHD and invasive breast cancer . Each center obtained institutional review board approval , and all participants provided written informed consent . The intervention was stopped on 29 February 2004 ( after a median of 7.2 years [ interquartile range , 6.4 to 8.1 years ] ) , earlier than planned , because of an increased risk for stroke not offset by a lower risk for CHD in the CEE group ( 23 ) . Postintervention follow-up was available through 31 December 2014 ( median , 18 years of cumulative follow-up ) for mortality end points and 30 September 2014 for other incident events . Mortality end points were ascertained by regular surveillance of the cohort through the National Death Index and by next-of-kin or postal service reports ( 20 , 22 ) . Summary statistics may differ slightly from those in previous publications because of more thorough end point ascertainment in this report . After the trial ended , participants were told their r and om assignment ; fewer than 4 % reported personal posttrial use of systemic estrogen . Statistical Analysis Intervention-phase analyses included all r and omly assigned participants with known oophorectomy status ( n = 9939 ) , stratified by whether they reported having undergone surgical removal of both ovaries ( BSO ) before r and om assignment . Women reporting no BSO , and those reporting single or partial oophorectomy , were classified as not having undergone BSO . Of these , nearly three quarters had both ovaries intact , one quarter had 1 ovary removed , and 3 % had part of an ovary removed . Participants were analyzed according to their r and om assignment until the last intervention contact , using time-to-event methods based on the intention-to-treat principle . A composite global index of monitored clinical events was calculated as the time to first event for CHD , invasive breast cancer , stroke , pulmonary embolism , colorectal cancer , hip fracture , and death . Results are presented for the trial 's primary outcomes ( CHD and invasive breast cancer ) , all-cause mortality , and the global index . Analyses of other end points in the global index and other major end points ( total myocardial infa rct ion , coronary revascularization , total cancer , total cardiovascular mortality , and total cancer mortality ) , as in previous reports ( 20 , 21 , 24 , 25 ) , are presented in Appendix Figures 1 and 2 and should be interpreted cautiously because of multiple comparisons . Appendix Figure 1 . Results for various health outcomes in women with BSO in the WHI Estrogen-Alone Trial , by 10-year age group , during cumulative follow-up ( intervention phase plus postintervention phase ) . History of disease was missing for CABG or PCI ( n = 53 ) and total cancer ( n = 37 ) . For the corresponding analyses , baseline hazard functions were stratified according to their missing disease history coded as no. BSO = bilateral salpingo-oophorectomy ; CABG = coronary artery bypass grafting ; CEE = conjugated equine estrogens ; CVD = cardiovascular disease ; HR = hazard ratio ; MI = myocardial infa rct ion ; PCI = percutaneous coronary intervention ; WHI = Women 's Health Initiative . * Percentages are annualized . Difference in estimated absolute risks ( CEE alone minus placebo ) per 10000 PY . P value is 1degree-of-freedom test of trend for the interaction ( product term ) between the indicator variable for r and omization group and age group ( assigned integer values of 0 , 1 , or 2 ) based on a stratified score ( log-rank ) test . Appendix Figure 2 . Results for various health outcomes in women without BSO in the WHI Estrogen-Alone Trial , by 10-year age group , during cumulative follow-up ( intervention phase plus postintervention phase ) . History of disease was missing for CABG or PCI ( n = 77 ) and total cancer ( n = 55 ) . For the corresponding analyses , baseline hazard functions were stratified according to their missing disease history coded as no. BSO = bilateral salpingo-oophorectomy ; CABG = coronary artery bypass grafting ; CEE = conjugated equine estrogens ; CVD = cardiovascular disease ; HR = hazard ratio ; MI = myocardial infa rct ion ; PCI = percutaneous coronary intervention ; WHI = Women 's Health Initiative . * Percentages are annualized . Difference in estimated absolute risks ( CEE alone minus placebo ) per 10000 PY . P value is 1degree-of-freedom test of trend for the interaction ( product term ) between the indicator variable for r and omization group and age group ( assigned integer values of 0 , 1 , or 2 ) based on a stratified score ( log-rank ) test . Hazard ratios ( HRs ) were estimated using Cox proportional hazards models stratified by BSO status ( yes or no ) at enrollment , age , r and omization status in the WHI-DM ( Women 's Health Initiative Dietary Modification Trial ) , prior cardiovascular or other disease ( if appropriate ) , and study phase ( time-dependent strata ) . Preplanned analyses included presentation of intervention-phase and cumulative follow-up HRs and forest plots for women with and without BSO separately , then additionally stratified by 10-year age group . Hazard ratios may exhibit within- or between-phase time dependencies ( 20 , 21 ) . Hazard ratios for varying cumulative follow-ups have been previously reported ( 20 , 21 , 24 , 25 ) , with additional follow-up and extended cumulative incidence curves ( 26 ) included in the current analyses . Cumulative incidence curves were st and ardized using inverse probability weighting ( 26 ) and computed for the full cohort so that BSO and r and omization groups were balanced with respect to age and other variables described earlier ( as used to stratify the baseline hazard functions for the primary analysis ) . Incidence curves by 10-year age group were then computed using these weights . Within each BSO stratum , interactions between r and omization group and age group were assessed with a 1degree-of-freedom test for linear trend , with each age group assigned an integer value of 0 , 1 , or 2 . Exploratory analyses were also stratified by age at BSO . In addition , we examined whether the overall influence of CEE depended on time elapsed ( < 10 , 10 to < 20 , or 20 years ) from age at BSO to age when r and omly assigned to CEE ( defined as gap time ) by including gap-time interaction variables . Statistical tests were based on a 2-sided stratified score ( log-rank ) test , with nominal ( unadjusted ) P values of 0.05 or less considered statistically significant . P values should be interpreted cautiously because of multiple comparisons . Sensitivity analyses censored participants who took fewer than 80 % of study pills during the preceding follow-up period , excluded women who reported unilateral or partial oophorectomy , stratified by prer and omization use of hormone therapy , and adjusted for characteristics that differed by BSO status or age group . The latter analysis included the baseline variables of age , clinic-measured baseline body mass index ( BMI ) , systolic and diastolic blood pressure as linear covariates , and indicator variables for medications recorded at baseline ( aspirin and medications for diabetes , hypertension , and hyperlipidemia ) to account for differences in cardiovascular and mortality risk factors associated with BSO status ( 27 ) , with additional stratification of the baseline hazard functions by race or ethnicity . This select list of covariates maintained the integrity of the r and omization by excluding fewer than 0.5 % of r and omly assigned participants because of missing covariates . Statistical analyses were conducted using SAS , version 9.4 ( SAS Institute ) , and R , version 3.4 , packages survival ( 28 ) and rmeta ( 29 ) ( R Foundation for Statistical Computing ) . Role of the Funding Source The WHI is funded by the National Heart , Lung , and Blood Institute ( NHLBI ) ; National Institutes of Health ; and U.S. Department of Health and Human Services . Wyeth Ayerst BACKGROUND In the Suppression of Ovarian Function Trial ( SOFT ) and the Tamoxifen and Exemestane Trial ( TEXT ) , the 5‐year rates of recurrence of breast cancer were significantly lower among premenopausal women who received the aromatase inhibitor exemestane plus ovarian suppression than among those who received tamoxifen plus ovarian suppression . The addition of ovarian suppression to tamoxifen did not result in significantly lower recurrence rates than those with tamoxifen alone . Here , we report the up date d results from the two trials . METHODS Premenopausal women were r and omly assigned to receive 5 years of tamoxifen , tamoxifen plus ovarian suppression , or exemestane plus ovarian suppression in SOFT and to receive tamoxifen plus ovarian suppression or exemestane plus ovarian suppression in TEXT . R and omization was stratified according to the receipt of chemotherapy . RESULTS In SOFT , the 8‐year disease‐free survival rate was 78.9 % with tamoxifen alone , 83.2 % with tamoxifen plus ovarian suppression , and 85.9 % with exemestane plus ovarian suppression ( P=0.009 for tamoxifen alone vs. tamoxifen plus ovarian suppression ) . The 8‐year rate of overall survival was 91.5 % with tamoxifen alone , 93.3 % with tamoxifen plus ovarian suppression , and 92.1 % with exemestane plus ovarian suppression ( P=0.01 for tamoxifen alone vs. tamoxifen plus ovarian suppression ) ; among the women who remained premenopausal after chemotherapy , the rates were 85.1 % , 89.4 % , and 87.2 % , respectively . Among the women with cancers that were negative for HER2 who received chemotherapy , the 8‐year rate of distant recurrence with exemestane plus ovarian suppression was lower than the rate with tamoxifen plus ovarian suppression ( by 7.0 percentage points in SOFT and by 5.0 percentage points in TEXT ) . Grade 3 or higher adverse events were reported in 24.6 % of the tamoxifen‐alone group , 31.0 % of the tamoxifen – ovarian suppression group , and 32.3 % of the exemestane – ovarian suppression group . CONCLUSIONS Among premenopausal women with breast cancer , the addition of ovarian suppression to tamoxifen result ed in significantly higher 8‐year rates of both disease‐free and overall survival than tamoxifen alone . The use of exemestane plus ovarian suppression result ed in even higher rates of freedom from recurrence . The frequency of adverse events was higher in the two groups that received ovarian suppression than in the tamoxifen‐alone group . ( Funded by Pfizer and others ; SOFT and TEXT Clinical Trials.gov numbers , NCT00066690 and NCT00066703 , respectively . PURPOSE The effects of ovarian function suppression ( OFS ) on survival and patient-reported outcomes were evaluated in a phase III trial in which premenopausal women were r and omly assigned to tamoxifen with or without OFS . PATIENTS AND METHODS Premenopausal women with axillary node-negative , hormone receptor-positive breast cancer tumors measuring ≤ 3 cm were r and omly assigned to tamoxifen alone versus tamoxifen plus OFS ; adjuvant chemotherapy was not permitted . Primary end points were disease-free survival ( DFS ) and overall survival ( OS ) . Secondary end points included toxicity and patient-reported outcomes . Patient-reported outcome data included health-related quality of life , menopausal symptoms , and sexual function . These were evaluated at baseline , 6 months , 12 months , and then annually for up to 5 years after registration . RESULTS In all , 345 premenopausal women were enrolled : 171 on tamoxifen alone and 174 on tamoxifen plus OFS . With a median follow-up of 9.9 years , there was no significant difference between arms for DFS ( 5-year rate : 87.9 % v 89.7 % ; log-rank P = .62 ) or OS ( 5-year rate : 95.2 % v 97.6 % ; log-rank P = .67 ) . Grade 3 or higher toxicity was more common in the tamoxifen plus OFS arm ( 22.4 % v 12.3 % ; P = .004 ) . Patients treated with tamoxifen plus OFS had more menopausal symptoms , lower sexual activity , and inferior health-related quality of life at 3-year follow-up ( P < .01 for all ) . Differences diminished with further follow-up . CONCLUSION When added to tamoxifen , OFS results in more menopausal symptoms and sexual dysfunction , which contributes to inferior self-reported health-related quality of life . Because of early closure , this study is underpowered for drawing conclusions about the impact on survival when adding OFS to tamoxifen PURPOSE To describe estradiol ( E2 ) , estrone ( E1 ) , and estrone sulfate ( E1S ) levels during the first year of monthly triptorelin plus exemestane or tamoxifen and to assess possible suboptimal suppression while receiving exemestane plus triptorelin . PATIENTS AND METHODS Premenopausal patients with early breast cancer on the Suppression of Ovarian Function Trial who selected triptorelin as the ovarian suppression method and were r and omly assigned to exemestane plus triptorelin or tamoxifen plus triptorelin were enrolled until the target population of 120 patients was reached . Blood sampling time points were 0 , 3 , 6 , 12 , 18 , 24 , 36 , and 48 months . Serum estrogens were measured with a highly sensitive and specific assay . This preplanned 12-month analysis evaluated E2 , E1 , E1S , follicle-stimulating hormone , and luteinizing hormone levels in all patients and the proportion of patients with E2 levels greater than 2.72 pg/mL at any time point during treatment with exemestane plus triptorelin . RESULTS One hundred sixteen patients ( exemestane , n = 86 ; tamoxifen , n = 30 ; median age , 44 years ; median E2 , 51 pg/mL ; 55 % prior chemotherapy ) started triptorelin and had one or more sample s drawn . With exemestane plus triptorelin , median reductions from baseline E2 , E1 , and E1S levels were consistently ≥ 95 % , result ing in significantly lower levels than with tamoxifen plus triptorelin at all time points . Among patients on exemestane plus triptorelin , 25 % , 24 % , and 17 % had an E2 level greater than 2.72 pg/mL at 3 , 6 , and 12 months , respectively . Baseline factors related to on-treatment E2 level greater than 2.72 pg/mL were no prior chemotherapy ( P = .06 ) , higher body mass index ( P = .05 ) , and lower follicle-stimulating hormone and luteinizing hormone ( each P < .01 ) . CONCLUSION During the first year , most patients on exemestane plus triptorelin had E2 levels below the defined threshold of 2.72 pg/mL , consistent with levels reported in postmenopausal patients on aromatase inhibitors , but at each time point , at least 17 % of patients had levels greater than the threshold PURPOSE The Suppression of Ovarian Function trial showed improved disease control for tamoxifen plus ovarian function suppression ( OFS ) compared with tamoxifen alone for the cohort of premenopausal patients who received prior chemotherapy . We present the patient-reported outcomes . PATIENTS AND METHODS The quality -of-life ( QoL ) analysis includes 1,722 of 2,045 premenopausal patients with hormone receptor-positive breast cancer r and omly assigned to receive adjuvant treatment with 5 years of tamoxifen plus OFS or tamoxifen alone . Chemotherapy use before enrollment was optional . Patients completed a QoL form consisting of global and symptom indicators at baseline , every 6 months for 24 months , and annually during years 3 to 6 . Differences in the change of QoL from baseline between the two treatments were tested at 6 , 24 , and 60 months with mixed models for repeated measures with and without chemotherapy and overall . RESULTS Patients on tamoxifen plus OFS were more affected than patients on tamoxifen alone by hot flushes at 6 and 24 months , by loss of sexual interest and sleep disturbance at 6 months , and by vaginal dryness up to 60 months . Without prior chemotherapy , patients on tamoxifen alone reported more vaginal discharge over the 5 years than patients on tamoxifen plus OFS . Symptom-specific treatment differences at 6 months were less pronounced in patients with prior chemotherapy . Changes in global QoL indicators from baseline were small and similar between treatments over the whole treatment period . CONCLUSION Overall , OFS added to tamoxifen result ed in worse endocrine symptoms and sexual functioning during the first 2 years of treatment , with variable magnitudes of treatment differences . Short-term differences in symptom-specific QoL , treatment burden , and coping effort between treatment groups were less pronounced for patients with prior chemotherapy , the cohort that benefited most from OFS in terms of disease control |
10,427 | 29,258,056 | This review supports the use of PCC for VKA reversal , specifically for 4F-PCC over FFP for laboratory reversal . | INTRODUCTION Approximately 4 - 6 % of patients treated with oral anticoagulants ( OAC ) will suffer from major hemorrhage or be in need of urgent surgery necessitating anticoagulant reversal therapy .
Several new oral anticoagulants and reversal agents have been introduced that make it difficult for physicians to stay up date d on the current evidence of reversal management .
This study aims to review the recent literature on oral anticoagulation reversal therapy and to present the current evidence in an easily approachable manner .
To date , reversal of laboratory parameters has been demonstrated for two reversal agents specific to DOACs : idarucizumab for dabigatran reversal and and exanet-alfa for factor Xa-inhibitor reversal . | Background — Rivaroxaban and dabigatran are new oral anticoagulants that specifically inhibit factor Xa and thrombin , respectively . Clinical studies on the prevention and treatment of venous and arterial thromboembolism show promising results . A major disadvantage of these anticoagulants is the absence of an antidote in case of serious bleeding or when an emergency intervention needs immediate correction of coagulation . This study evaluated the potential of prothrombin complex concentrate ( PCC ) to reverse the anticoagulant effect of these drugs . Methods and Results — In a r and omized , double-blind , placebo-controlled study , 12 healthy male volunteers received rivaroxaban 20 mg twice daily ( n=6 ) or dabigatran 150 mg twice daily ( n=6 ) for 2½ days , followed by either a single bolus of 50 IU/kg PCC ( Cofact ) or a similar volume of saline . After a washout period , this procedure was repeated with the other anticoagulant treatment . Rivaroxaban induced a significant prolongation of the prothrombin time ( 15.8±1.3 versus 12.3±0.7 seconds at baseline ; P<0.001 ) that was immediately and completely reversed by PCC ( 12.8±1.0 ; P<0.001 ) . The endogenous thrombin potential was inhibited by rivaroxaban ( 51±22 % ; baseline , 92±22 % ; P=0.002 ) and normalized with PCC ( 114±26 % ; P<0.001 ) , whereas saline had no effect . Dabigatran increased the activated partial thromboplastin time , ecarin clotting time ( ECT ) , and thrombin time . Administration of PCC did not restore these coagulation tests . Conclusion — Prothrombin complex concentrate immediately and completely reverses the anticoagulant effect of rivaroxaban in healthy subjects but has no influence on the anticoagulant action of dabigatran at the PCC dose used in this study . Clinical Trial Registration — URL : http://www.trialregister.nl . Unique identifier : NTR2272 BACKGROUND Fresh frozen plasma ( FFP ) and prothrombin complex concentrates ( PCC ) reverse oral anticoagulants . We compared PCC and FFP intraoperative administration in patients undergoing heart surgery with cardiopulmonary bypass ( CPB ) . METHODS Forty patients [ with international normalized ratio (INR)≥ 2·1 ] assigned semi-urgent cardiac surgery were r and omized to receive either FFP ( n = 20 ) or PCC ( n = 20 ) . Prior to CPB , they received either 2 units of FFP or half of the PCC dose calculated according to body weight , initial INR and target INR ( ≤ 1·5 ) . After CPB and protamine administration , patients received either another 2 units of FFP or the other half PCC dose . Additional doses were administered if INR was still too high ( ≥ 1·5 ) . RESULTS Fifteen minutes after CPB , more patients reached INR target with PCC ( P = 0·007 ) : 7/16 patients vs. 0/15 patients with FFP ; there was no difference 1 h after CPB ( 6/15 patients with PCC vs. 4/15 patients with FFP reached target ) . Fifteen minutes after CPB , median INR ( range ) decreased to 1·6 ( 1·2 - 2·2 ) with PCC vs. 2·3 ( 1·5 - 3·5 ) with FFP ; 1 h after CPB both groups reached similar values [ 1·6 ( 1·3 - 2·2 ) with PCC and 1·7 ( 1·3 - 2·7 ) with FFP ] . With PCC , less patients needed additional dose ( 6/20 ) than with FFP ( 20/20 ) ( P < 0·001 ) . Both groups differed significantly on the course of factor II ( P = 0·0023 ) and factor X ( P = 0·008 ) over time . Dilution of coagulation factors was maximal at CPB onset . Safety was good for both groups , with only two related oozing cases with FFP . CONCLUSION PCC reverses anticoagulation safely , faster and with less bleeding than FFP BACKGROUND Rapid reversal of vitamin K antagonist (VKA)-induced anticoagulation is often necessary for patients needing urgent surgical or invasive procedures . The optimum means of VKA reversal has not been established in comparative clinical trials . We compared the efficacy and safety of four-factor prothrombin complex concentrate ( 4F-PCC ) with that of plasma in VKA-treated patients needing urgent surgical or invasive procedures . METHODS In a multicentre , open-label , phase 3b r and omised trial we enrolled patients aged 18 years or older needing rapid VKA reversal before an urgent surgical or invasive procedure . We r and omly assigned patients in a 1:1 ratio to receive vitamin K concomitant with a single dose of either 4F-PCC ( Beriplex/Kcentra/Confidex ; CSL Behring , Marburg , Germany ) or plasma , with dosing based on international normalised ratio ( INR ) and weight . The primary endpoint was effective haemostasis , and the co- primary endpoint was rapid INR reduction ( ≤1·3 at 0·5 h after infusion end ) . The analyses were intended to evaluate , in a hierarchical fashion , first non-inferiority ( lower limit 95 % CI greater than -10 % for group difference ) for both endpoints , then superiority ( lower limit 95 % CI > 0 % ) if non-inferiority was achieved . Adverse events and serious adverse events were reported to days 10 and 45 , respectively . This trial is registered at Clinical Trials.gov , number NCT00803101 . FINDINGS 181 patients were r and omised ( 4F-PCC n=90 ; plasma n=91 ) . The intention-to-treat efficacy population comprised 168 patients ( 4F-PCC , n=87 ; plasma , n=81 ) . Effective haemostasis was achieved in 78 ( 90 % ) patients in the 4F-PCC group compared with 61 ( 75 % ) patients in the plasma group , demonstrating both non-inferiority and superiority of 4F-PCC over plasma ( difference 14·3 % , 95 % CI 2·8 - 25·8 ) . Rapid INR reduction was achieved in 48 ( 55 % ) patients in the 4F-PCC group compared with eight ( 10 % ) patients in the plasma group , demonstrating both non-inferiority and superiority of 4F-PCC over plasma ( difference 45·3 % , 95 % CI 31·9 - 56·4 ) . The safety profile of 4F-PCC was generally similar to that of plasma ; 49 ( 56 % ) patients receiving 4F-PCC had adverse events compared with 53 ( 60 % ) patients receiving plasma . Adverse events of interest were thromboembolic adverse events ( six [ 7 % ] patients receiving 4F-PCC vs seven [ 8 % ] patients receiving plasma ) , fluid overload or similar cardiac events ( three [ 3 % ] patients vs 11 [ 13 % ] patients ) , and late bleeding events ( three [ 3 % ] patients vs four [ 5 % ] patients ) . INTERPRETATION 4F-PCC is non-inferior and superior to plasma for rapid INR reversal and effective haemostasis in patients needing VKA reversal for urgent surgical or invasive procedures . FUNDING CSL Behring Background and Purpose — Intracranial hemorrhage is the most devastating complication of anticoagulation . Outcomes associated with different sites of intracranial bleeding occurring with warfarin versus dabigatran have not been defined . Methods — Analysis of 18 113 participants with atrial fibrillation in the R and omized Evaluation of Long-term anticoagulant therapY ( RE-LY ) trial assigned to adjusted-dose warfarin ( target international normalized ratio , 2–3 ) or dabigatran ( 150 mg or 110 mg , both twice daily ) . Results — During a mean of 2.0 years of follow-up , 154 intracranial hemorrhages occurred in 153 participants : 46 % intracerebral ( 49 % mortality ) , 45 % subdural ( 24 % mortality ) , and 8 % subarachnoid ( 31 % mortality ) . The rates of intracranial hemorrhage were 0.76 % , 0.31 % , and 0.23 % per year among those assigned to warfarin , dabigatran 150 mg , and dabigatran 110 mg , respectively ( P<0.001 for either dabigatran dose versus warfarin ) . Fewer fatal intracranial hemorrhages occurred among those assigned dabigatran 150 mg and 110 mg ( n=13 and n=11 , respectively ) versus warfarin ( n=32 ; P<0.01 for both ) . Fewer traumatic intracranial hemorrhages occurred among those assigned to dabigatran ( 11 patients with each dose ) compared with warfarin ( 24 patients ; P<0.05 for both dabigatran doses versus warfarin ) . Independent predictors of intracranial hemorrhage were assignment to warfarin ( relative risk , 2.9 ; P<0.001 ) , aspirin use ( relative risk , 1.6 ; P=0.01 ) , age ( relative risk , 1.1 per year ; P<0.001 ) , and previous stroke/transient ischemic attack ( relative risk , 1.8 ; P=0.001 ) . Conclusions — The clinical spectrum of intracranial hemorrhage was similar for patients given warfarin and dabigatran . Absolute rates at all sites and both fatal and traumatic intracranial hemorrhages were lower with dabigatran than with warfarin . Concomitant aspirin use was the most important modifiable independent risk factor for intracranial hemorrhage Introduction Prothrombin complex concentrates ( PCC ) are haemostatic blood preparations indicated for urgent anticoagulation reversal , though the optimal dose for effective reversal is still under debate . The latest generation of PCCs include four coagulation factors , the so-called 4-factor PCC . The aim of this study was to compare the efficacy and safety of two doses , 25 and 40 IU/kg , of 4-factor PCC in vitamin K antagonist ( VKA ) associated intracranial haemorrhage . Methods We performed a phase III , prospect i ve , r and omised , open-label study including patients with objective ly diagnosed VKA-associated intracranial haemorrhage between November 2008 and April 2011 in 22 centres in France . Patients were r and omised to receive 25 or 40 IU/kg of 4-factor PCC . The primary endpoint was the international normalised ratio ( INR ) 10 minutes after the end of 4-factor PCC infusion . Secondary endpoints were changes in coagulation factors , global clinical outcomes and incidence of adverse events ( AEs ) . Results A total of 59 patients were r and omised : 29 in the 25 IU/kg and 30 in the 40 IU/kg group . Baseline demographics and clinical characteristics were comparable between the groups . The mean INR was significantly reduced to 1.2 - and ≤1.5 in all patients of both groups - 10 minutes after 4-factor PCC infusion . The INR in the 40 IU/kg group was significantly lower than in the 25 IU/kg group 10 minutes ( P = 0.001 ) , 1 hour ( P = 0.001 ) and 3 hours ( P = 0.02 ) after infusion . The 40 IU/kg dose was also effective in replacing coagulation factors such as PT ( P = 0.038 ) , FII ( P = 0.001 ) , FX ( P < 0.001 ) , protein C ( P = 0.002 ) and protein S ( 0.043 ) , 10 minutes after infusion . However , no differences were found in haematoma volume or global clinical outcomes between the groups . Incidence of death and thrombotic events was similar between the groups . Conclusions Rapid infusion of both doses of 4-factor PCC achieved an INR of 1.5 or less in all patients with a lower INR observed in the 40 IU/kg group . No safety concerns were raised by the 40 IU/kg dose . Further trials are needed to evaluate the impact of the high dose of 4-factor PCC on functional outcomes and mortality . Trial registration Eudra CT number 2007 - 000602 - 73 BACKGROUND Four-factor prothrombin complex concentrates ( PCCs ) , which contain factor II , FVII , FIX , and FX , have shown the potential to reverse the anticoagulant effect of rivaroxaban in healthy volunteers . The purpose of this study was to determine whether a three-factor PCC , which contains little FVII , has a similar effect . METHODS AND RESULTS We performed an open-label , single-center , parallel-group study comparing the effect of a three-factor PCC ( Profilnine SD ) with that of a four-factor PCC ( Beriplex P/N ) on the pharmacodynamics of rivaroxaban in 35 healthy volunteers . After receiving 4 days of rivaroxaban 20 mg twice daily to obtain supratherapeutic steady-state concentrations , volunteers were r and omized to receive a single 50 IU kg(-1 ) bolus dose of four-factor PCC , three-factor PCC or saline 4 h after the morning dose of rivaroxaban on day 5 , and the effects of these interventions on prothrombin time and thrombin generation were determined . Within 30 min , four-factor PCC reduced mean prothrombin time by 2.5 - 3.5 s , whereas three-factor PCC produced only a 0.6 - 1.0-s reduction . In contrast , three-factor PCC reversed rivaroxaban-induced changes in thrombin generation more than four-factor PCC . CONCLUSIONS This study demonstrates the potential of both three-factor and four-factor PCCs to at least partially reverse the anticoagulant effects of rivaroxaban in healthy adults . The discrepant effects of the PCC preparations may reflect differences in the procoagulant components present in each Introduction In vitamin K antagonist (VKA)-treated patients with severe hemorrhage , guidelines recommend prompt VKA reversal with prothrombin complex concentrate ( PCC ) and vitamin K. The aim of this observational cohort study was to evaluate the impact of guideline concordant administration of PCC and vitamin K on seven-day mortality . Methods Data from consecutive patients treated with PCC were prospect ively collected in 44 emergency departments . Type of hemorrhage , coagulation parameters , type of treatment and seven-day mortality mortality were recorded . Guideline -concordant administration of PCC and vitamin K ( GC-PCC-K ) were defined by at least 20 IU/kg factor IX equivalent PCC and at least 5 mg of vitamin K performed within a predefined time frame of eight hours after admission . Multivariate analysis was used to assess the effect of appropriate reversal on seven-day mortality in all patients and in those with intracranial hemorrhage ( ICH ) . Results Data from 822 VKA-treated patients with severe hemorrhage were collected over 14 months . Bleeding was gastrointestinal ( 32 % ) , intracranial ( 32 % ) , muscular ( 13 % ) , and “ other ” ( 23 % ) . In the whole cohort , seven-day mortality was 13 % and 33 % in patients with ICH . GC-PCC-K was performed in 38 % of all patients and 44 % of ICH patients . Multivariate analysis showed a two-fold decrease in seven-day mortality in patients with GC-PCC-K ( odds ratio ( OR ) = 2.15 ( 1.20 to 3.88 ) ; P = 0.011 ) ; this mortality reduction was also observed when only ICH was considered ( OR = 3.23 ( 1.53 to 6.79 ) ; P = 0.002 ) . Conclusions Guideline -concordant VKA reversal with PCC and vitamin K within eight hours after admission was associated with a significant decrease in seven-day mortality Introduction Prothrombin Complex Concentrate ( PCC ) is a key treatment in the management of bleeding related to Vitamin K antagonists ( VKA ) . This study aim ed to evaluate prospect ively PCC use in patients with VKA-related bleeding in view of the French guidelines published in 2008 . Methods All consecutive patients with VKA-related bleeding treated with a 4-factor PCC ( Octaplex ® ) were selected in 33 French hospitals . Collected data included demographics , site and severity of bleeding , modalities of PCC administration , International Normalized Ratio ( INR ) values before and after PCC administration , outcomes and survival rate 15 days after infusion . Results Of 825 patients who received PCC between August 2008 and December 2010 , 646 had severe bleeding . The main haemorrhage sites were intracranial ( 43.7 % ) and abdominal ( 24.3 % ) . Mean INR before PCC was 4.4 ± 1.9 ; INR was unavailable in 12.5 % of patients . The proportions of patients who received a PCC dose according to guidelines were 15.8 % in patients with initial INR 2 - 2.5 , 41.5 % in patients with INR 2.5 - 3 , 40.8 % in patients with INR 3 - 3.5 , 26.9 % in patients with INR > 3.5 , and 63.5 % of patients with unknown INR . Vitamin K was administered in 84.7 % of patients . The infused dose of PCC did not vary with initial INR ; the mean dose was 25.3 ± 9.8 IU/Kg . Rates of controlled bleeding and target INR achievement were similar , regardless of whether or not patients were receiving PCC doses as per the guidelines . No differences in INR after PCC treatment were observed , regardless of whether or not vitamin K was administered . INR was first monitored after a mean time frame of 4.5 ± 5.6 hours post PCC . The overall survival rate at 15 days after PCC infusion was 75.4 % ( 65.1 % in patients with intracranial haemorrhage ) . A better prognosis was observed in patients reaching the target INR . Conclusions Severe bleeding related to VKA needs to be better managed , particularly regarding the PCC infused dose , INR monitoring and administration of vitamin K. A dose of 25 IU/kg PCC appears to be efficacious in achieving a target INR of 1.5 . Further studies are required to assess whether adjusting PCC dose and /or better management of INR would improve outcomes BACKGROUND Edoxaban , a direct factor Xa inhibitor , is a once-daily , non-vitamin K antagonist oral anticoagulant . There is no established method to reverse the activity of non-vitamin K oral anticoagulants in cases of hemorrhage or urgent surgery . This study evaluated the ability of a 3-factor prothrombin complex concentrate ( 3F-PCC ) to reverse the anticoagulatory effects of edoxaban . METHODS In this phase 1 study , 24 healthy subjects were r and omly assigned to receive a single dose of 60 or 180 mg edoxaban , followed by placebo , 25IU/kg 3F-PCC , or 50IU/kg 3F-PCC . Edoxaban pharmacokinetics and pharmacodynamics , including the primary endpoint of prothrombin time ( PT ) and endogenous thrombin potential ( ETP ) , were assessed . D-dimer and prothrombin fragment 1 and 2 ( F1 + 2 ) were also measured . RESULTS Overall , there were no apparent consistent effects of 3F-PCC on edoxaban pharmacokinetics . Administration of 3F-PCC 25 or 50IU/kg with edoxaban 60 or 180 mg did not substantially accelerate the return of PT to baseline levels . However , infusion of 3F-PCC 25 and 50IU/kg did substantially accelerate return to baseline of ETP compared with placebo . D-dimer and F1 + 2 data did not indicate any lasting procoagulant effects of 3F-PCC infusion , although a transient increase in F1 + 2 was noted during and after 3F-PCC infusion . Edoxaban and 3F-PCC co-administration was well tolerated in normal healthy subjects . CONCLUSIONS There was no apparent reversal of PT prolongation with 3F-PCC following edoxaban infusion , but ETP was completely reversed . Co-administration of 3F-PCC was well tolerated , but a dose-dependent increase in F1 + 2 may reflect a procoagulant risk We evaluated the hemostatic alterations in blood from healthy individuals treated for 5 days with direct oral anticoagulants ( DOACs ) rivaroxaban ( 20 mg/d ) or dabigatran ( 150 mg/12 h ) in a single-blind clinical trial with crossover assignment ( NCT01478282 ) . We assessed the potential of prothrombin complex concentrates , activated prothrombin complex concentrates , or recombinant activated factor VII , when added ex vivo , to reverse the alterations caused by these DOACs . Blood was drawn at maximum plasma concentration after the last dose of each DOAC , and modifications in coagulation biomarkers were evaluated using a series of tests performed under steady conditions including routine coagulation , thrombin generation , and thromboelastometry assays . Additional studies in st and ardized flow devices were applied to evaluate alterations on platelet deposition and fibrin formation on damaged vascular surfaces exposed to flowing blood . Both DOACs caused important modifications of all coagulation biomarkers and significantly reduced fibrin formation in flow studies . Alterations in biomarkers observed in steady laboratory tests were normalized and occasionally overcompensated by procoagulant strategies . In contrast , reductions in fibrin formation observed in studies with flowing blood were improved , although never completely restored to baseline levels . Effects of dabigatran in flow studies appeared more resistant to reversal strategies than those of rivaroxaban . Inconsistencies between results of coagulation studies in steady or flowing assays not only raise concerns about the adequacy of the earlier tests to predict the restoration of the coagulopathy induced by DOACs but also suggest limitations of nonspecific procoagulant strategies to control severe coagulopathy in patients inadvertently overexposed these agents INTRODUCTION Prothrombin complex concentrate ( PCC ) for reversal of vitamin K antagonist ( VKA ) is the main therapeutic option in cases of life-threatening bleeding . Clinical use of PCC is poorly documented . METHODS We prospect ively assessed PCC use in four French emergency departments during a two year period 2006 - 2008 before publication of French Guidelines . An appropriate treatment was defined when PCC was recommended , with a dose of PCC above or equal to 20 UI/kg , with vitamin K and with an assessment of international normalized ratio ( INR ) after PCC . Time of diagnosis and PCC administration were collected , as INR values , thromboembolic events within seven days , hospital mortality . RESULTS 256 patients received PCC for reversal of OAT . PCC was mainly prescribed for major intracerebral ( ICH ) or gastrointestinal hemorrhage . An appropriate treatment was observed in 26 % of patients . Intra-hospital mortality for major bleeding was 33 % for ICH and 26 % for non-ICH major bleeding . A PCC dose>20 UI/kg was able to reach an INR<1.5 in 65 % of patients . For major hemorrhages ( 70 % ) , time between patient arrival and treatment delivery exceeded three hours in half of cases . Control of INR was omitted in 20 % of patients . No patients presented a thromboembolic event . CONCLUSION A suitable treatment was administered in 26 % of patients . A PCC dose of 20 - 30 IU/kg seems adequate in most cases to reverse VKA activity , but both higher and lower doses achieve similar effects . Considerable progress is required to improve PCC administration and control of treatment efficacy , and to shorten time to diagnosis Major bleeding is a serious and potentially fatal complication of treatment with vitamin K antagonists ( VKAs ) . Prothrombin complex concentrates ( PCCs ) can substantially shorten the time needed to reverse VKA effects . To determine the efficacy and safety of 3-factor PCCs for the rapid reversal of VKAs in patients with major bleeding . Patients receiving VKAs and suffering from acute major bleeding were eligible for this prospect i ve cohort study if their international normalized ratio ( INR ) was higher than or equal to 2.0 . Stratified 35–50 IU kg−1 PCC doses were infused based on initial INR . A total of 126 patients ( 62 males ; mean age : 74 years , range 37–96 years ) were enrolled . The mean INR at presentation was 3.3 ( range 2–11 ) . At 30 min after PCC administration the mean INR was 1.4 ( range : 0.9–3.1 ) , declining to less than or equal to 1.5 in 75 % of patients . The benefit of PCC was maintained for a long time , since in 97 % of all post-infusion time points through 96 h the mean INR remained lower than or equal to 1.5 ( mean : 1.19 ; range : 0.9–2.3 ) . During hospitalization neither thrombotic complications nor significant adverse events were observed and 12 patients died ( 10 % ) ; none of the deaths was judged to be related to PCC administration . 3-factor PCC administration is an effective , rapid ad safe treatment for the urgent reversal of VKAs in patients with acute major bleeding . Broader use of PCC in this clinical setting appears to be appropriate OBJECTIVES High International Normalized Ratio ( INR ) level result ing from warfarin use increases the risk of gastrointestinal hemorrhages . We aim ed to compare the efficacy of prothrombin complex concentrates ( PCC ) and fresh frozen plasma ( FFP ) at lowering the INR level , decreasing active hemorrhages visible by endoscopy , and shortening the length of stay at the emergency department ( ED ) . METHOD This study is a prospect i ve cohort study of consecutive patents with gastrointestinal hemorrhages that received either PCC or FFP . With strict exclusion criteria , only patients over 18 years of age with a high INR level ( > 2.1 ) due to warfarin usage were included . RESULTS A total of 40 patients ( 18 female ) were included in the study , 20 each in the PCC and FFP groups . For the PCC group , the mean INR levels at the second and sixth hours were lower than those for the FFP group ( second hour INR : 1.53 vs 4.50 , P<.01 , sixth hour INR : 1.52 vs 2.41 , P<.01 ) . Seven patients experienced active bleeding ( Forrest 1 ) in the FFP group , whereas no patient experienced active bleeding in the PCC group based on the Forrest classification ( 35 % vs 0 % , P<.01 ) , and only 3 patients in the FFP group underwent invasive/surgical treatment ( 15 % vs 0 % , P<.01 ) . The ED length of stay was lower for the PCC group ( 1.62 days vs 3.46 days , P<.01 ) . CONCLUSION For patients experiencing a gastrointestinal hemorrhage , INR levels were reversed more quickly , there was less active bleeding on endoscopy , and the ED length of stay was lower in the PCC group than in the FFP group The new anticoagulants dabigatran and rivaroxaban can be responsible for haemorrhagic complications . As for any anticoagulant , bleeding management is challenging . We aim ed to test the effect of all putative haemostatic agents on the anticoagulant activity of these new drugs using thrombin generation tests . In an ex vivo study , 10 healthy white male subjects were r and omised to receive rivaroxaban ( 20 mg ) or dabigatran ( 150 mg ) in one oral administration . After a two weeks washout period , they received the other anticoagulant . Venous blood sample s were collected just before drug administration ( H0 ) and 2 hours thereafter . Reversal of anticoagulation was tested in vitro using prothrombin complex concentrate ( PCC ) , rFVIIa or FEIBA ® at various concentrations . Rivaroxaban affects quantitative and kinetic parameters , including the endogenous thrombin potential ( ETP-AUC and more pronouncedly the thrombin peak ) , the lag-time and time to peak . PCC strongly corrected ETP-AUC , whereas rFVIIa only modified the kinetic parameters . FEIBA corrected all parameters . Dabigatran specially affects the kinetics of thrombin generation with prolonged lag-time and time to peak . Although PCC increased ETP-AUC , only rFVIIa and FEIBA corrected the altered lag-time . For both anticoagulants , lower doses of FEIBA , corresponding to a quarter to half the dose usually used , have potential reversal profile of interest . In conclusion , some non-specific reversal agents appear to be able to reverse the anticoagulant activity of rivaroxaban or dabigatran . However , clinical evaluation is needed regarding haemorrhagic situations , and a meticulous risk-benefit evaluation regarding their use in this context is required INTRODUCTION Rapid reversal of anticoagulant effect from the use of vitamin K antagonists ( VKA ) is essential when acute bleeding or emergency surgery occurs . Prothrombin complex concentrates ( PCCs ) produce a more rapid effect with a better clinical outcome , and do not cause volume overload as compared with fresh-frozen plasma ( FFP ) . Octaplex is a modern , double virus safeguarded PCC with balanced content of vitamin K-dependent coagulation factors , which ensures fast onset of action and efficacious treatment , i.e. rapid correction of international normalized ratio ( INR ) . MATERIAL S AND METHODS The main purpose of this study was to demonstrate that Octaplex , when individually dosed , efficiently corrects INR to pre-determined levels in patients under oral anticoagulation who have bleeding complications or are undergoing invasive procedures . To measure the efficacy response , the INR achieved after PCC application per patient was calculated as geometric mean of three measurements within 1 h post-infusion . RESULTS Sixty patients received a median total Octaplex dose of 41.1 ( 15.3 - 83.3 ) IU/kg body weight ( bw ) . Of 56 patients evaluable in terms of efficacy , 51 ( 91 % ) showed a response as pre-defined in the protocol and in 52 ( 93 % ) the INR decreased to a value below 1.4 within one hour after dosing . The median INR declined from 2.8 ( 1.5 - 9.5 ) to 1.1 ( 1.0 - 1.9 ) within 10 min . All prothrombin complex coagulation factors recovered in parallel . Three patients had minor adverse drug reactions . One patient showed a non-symptomatic parvovirus B19 seroconversion . No thrombotic side effects were observed . CONCLUSIONS Octaplex is efficacious and safe in immediate correction of dosage-dependent INR in patients with VKA-related deficiency of prothrombin complex coagulation factors BACKGROUND There is uncertainty regarding the efficacy and incidence of thromboembolic events in patients treated with prothrombin complex concentrates ( PCC ) for the emergency reversal of warfarin effect . METHODS During 2002 to 2010 we prospect ively included 160 patients treated with PCC for emergency reversal of warfarin either for bleeding or because of the need of emergency surgery . A possible relationship to PCC was considered if objective ly verified thromboembolism occurred within 7days of PCC administration . Efficacy was adjudicated as good if the bleeding was controlled promptly or if the surgeon did not report excessive perioperative bleeding . RESULTS We included 160 patients ; 72 % received PCC for bleeding . The median international normalized ratio ( INR ) before and after treatment with PCC was 3.5 ( interquartile range [ IQR ] 2.6 - 5.4 ) and 1.4 ( IQR 1.2 - 1.6 ) . The mean dose of PCC was 1800IU ( IQR 1200 - 2000 ) . In addition to PCC , 74 % of the patients received vitamin K and 34 % received plasma . Six patients ( 3.8 % ; 95 % confidence interval [ CI ] , 1.4 - 8.0 % ) developed thromboembolic events ( 3 strokes , 1 myocardial infa rct ion , 1 deep vein thrombosis , 1 splenic infa rct ion ) , possibly related to PCC . The clinical efficacy was good in 146 ( 91 % ) , moderate in 6 ( 4 % ) , poor in 4 ( 2.5 % ) and non-evaluable in 4 patients . CONCLUSION The administration of PCC for the emergency reversal of warfarin may be associated with a low risk of thromboembolism . The contribution of an unmasked thrombotic process by cessation of anticoagulation or of activation of coagulation by the hemorrhagic event should also be considered Warfarin-associated intracranial hemorrhage is associated with a high mortality rate . Ongoing coagulopathy increases the likelihood of hematoma expansion and can result in catastrophic hemorrhage if surgery is performed without reversal . The current st and ard of care for emergency reversal of warfarin is with fresh frozen plasma ( FFP ) . In April 2013 , the USA Food and Drug Administration approved a new reversal agent , 4-factor prothrombin complex concentrate ( PCC ) , which has the potential to more rapidly correct coagulopathy . We sought to determine the feasibility and outcomes of using PCC for neurosurgical patients . A prospect i ve , observational study of all patients undergoing coagulopathy reversal for intracranial hemorrhage from April 2013 to December 2013 at a single , tertiary care center was undertaken . Thirty three patients underwent emergent reversal of coagulopathy using either FFP or PCC at the discretion of the treating physician . Intracranial hemorrhage included subdural hematoma , intraparenchymal hematoma , and subarachnoid hemorrhage . FFP was used in 28 patients and PCC was used in five patients . International normalized ratio at presentation was similar between groups ( FFP 2.9 , PCC 3.1 , p=0.89 ) . The time to reversal was significantly shorter in the PCC group ( FFP 256 minutes , PCC 65 minutes , p<0.05 ) . When operations were performed , the time delay to perform operations was also significantly shorter in the PCC group ( FFP 307 minutes , PCC 159 minutes , p<0.05 ) . In this preliminary experience , PCC appears to provide a rapid reversal of coagulopathy . Normalization of coagulation parameters may prevent further intracranial hematoma expansion and facilitate rapid surgical evacuation , thereby improving neurological outcomes We assess the in-vivo relationship between international normalized ratio ( INR ) and global coagulation tests in patients with life-threatening bleeding who received prothrombin complex concentrate ( PCC ) for warfarin reversal . This was a prospect i ve pilot study in adult patients with intracranial bleeding related to anticoagulation with warfarin . Thromboelastography ( TEG ) , thrombin generation parameters and INR were assessed at baseline , 30 min , 2 and 24 h after PCC . Changes in laboratory parameters and relationship between INR and global coagulation tests were assessed over time . Eight patients mean [ st and ard deviation ( SD ) ] age 72 ( 16 ) were included and received mean ( SD ) dose of PCC 24 ( 5 ) units/kg . Four patients died during the study , all with INR values more than 1.5 thirty minutes after PCC . Mean ( SD ) INR was 3.0 ( 1.3 ) and decreased significantly to 1.8 ( 0.48 ) thirty minutes after PCC ( P < 0.01 ) . Baseline endogenous thrombin potential and thrombin peak were 890 nmol/min and 123 nmol and increased significantly to 1943 nmol/min ( P < 0.01 ) and 301 nmol ( P < 0.01 ) 30 min after PCC administration . Reaction (R)-time decreased significantly ( P = 0.02 ) , and maximum amplitude and overall coagulation index ( CI ) significantly increased during treatment ( P < 0.01 , respectively ) . Thrombin generation and TEG values corrected after PCC administration ; however , INR did not fully correct . Patients that died tended to be older with prolonged INR values across the study period . INR and TEG values correlated well with thrombin generation before administration of PCC , but this relationship was lost afterward BACKGROUND Idarucizumab is a monoclonal antibody fragment that binds dabigatran with high affinity in a 1:1 molar ratio . We investigated the safety , tolerability , and efficacy of increasing doses of idarucizumab for the reversal of anticoagulant effects of dabigatran in a two-part phase 1 study ( rising-dose assessment and dose-finding , proof-of-concept investigation ) . Here we present the results of the proof-of-concept part of the study . METHODS In this r and omised , placebo-controlled , double-blind , proof-of-concept phase 1 study , we enrolled healthy volunteers ( aged 18 - 45 years ) with a body-mass index of 18·5 - 29·9 kg/m(2 ) into one of four dose groups at SGS Life Sciences Clinical Research Services , Belgium . Participants were r and omly assigned within groups in a 3:1 ratio to idarucizumab or placebo using a pseudor and om number generator and a supplied seed number . Participants and care providers were masked to treatment assignment . All participants received oral dabigatran etexilate 220 mg twice daily for 3 days and a final dose on day 4 . Idarucizumab ( 1 g , 2 g , or 4 g 5-min infusion , or 5 g plus 2·5 g in two 5-min infusions given 1 h apart ) was administered about 2 h after the final dabigatran etexilate dose . The primary endpoint was incidence of drug-related adverse events , analysed in all r and omly assigned participants who received at least one dose of dabigatran etexilate . Reversal of diluted thrombin time ( dTT ) , ecarin clotting time ( ECT ) , activated partial thromboplastin time ( aPTT ) , and thrombin time ( TT ) were secondary endpoints assessed by measuring the area under the effect curve from 2 h to 12 h ( AUEC2 - 12 ) after dabigatran etexilate ingestion on days 3 and 4 . This trial is registered with Clinical Trials.gov , number NCT01688830 . FINDINGS Between Feb 23 , and Nov 29 , 2013 , 47 men completed this part of the study . 12 were enrolled into each of the 1 g , 2 g , or 5 g plus 2·5 g idarucizumab groups ( nine to idarucizumab and three to placebo in each group ) , and 11 were enrolled into the 4 g idarucizumab group ( eight to idarucizumab and three to placebo ) . Drug-related adverse events were all of mild intensity and reported in seven participants : one in the 1 g idarucizumab group ( infusion site erythema and hot flushes ) , one in the 5 g plus 2·5 g idarucizumab group ( epistaxis ) ; one receiving placebo ( infusion site haematoma ) , and four during dabigatran etexilate pretreatment ( three haematuria and one epistaxis ) . Idarucizumab immediately and completely reversed dabigatran-induced anticoagulation in a dose-dependent manner ; the mean ratio of day 4 AUEC2 - 12 to day 3 AUEC2 - 12 for dTT was 1·01 with placebo , 0·26 with 1 g idarucizumab ( 74 % reduction ) , 0·06 with 2 g idarucizumab ( 94 % reduction ) , 0·02 with 4 g idarucizumab ( 98 % reduction ) , and 0·01 with 5 g plus 2·5 g idarucizumab ( 99 % reduction ) . No serious or severe adverse events were reported , no adverse event led to discontinuation of treatment , and no clinical ly relevant difference in incidence of adverse events was noted between treatment groups . INTERPRETATION These phase 1 results show that idarucizumab was associated with immediate , complete , and sustained reversal of dabigatran-induced anticoagulation in healthy men , and was well tolerated with no unexpected or clinical ly relevant safety concerns , supporting further testing . Further clinical studies are in progress . FUNDING Boehringer Ingelheim Pharma GmbH & Co KG BACKGROUND Four-factor prothrombin complex concentrate ( PCC ) ( Cofact ; Sanquin Blood Supply ) 50 IU kg(-1 ) increased thrombin generation beyond baseline values in healthy , rivaroxaban-treated subjects . OBJECTIVE To assess whether infusion with doses of 37.5 IU kg(-1 ) and 25 IU kg(-1 ) PCC reverses the anticoagulant effect of high-dose apixaban , another oral direct factor Xa inhibitor . METHODS In a r and omized , double-blind , placebo-controlled , crossover study , six healthy subjects received twice-daily apixaban 10 mg for 3.5 days followed by a single bolus of 37.5 IU kg(-1 ) PCC , 25 IU kg(-1 ) PCC , or placebo . The primary outcome was the effect of PCC 15 min after infusion on thrombin generation ( endogenous thrombin potential [ ETP ] ) ; secondary outcomes were the immediate effect of PCC on prothrombin time ( PT ) and the effect of PCC as compared with placebo over a period of 24 h on ETP and PT . RESULTS Fifteen minutes after infusion of 37.5 IU kg(-1 ) and 25 IU kg(-1 ) PCC , ETP increased from 41 % ± 11 % to 56 % ± 23 % ( P = 0.06 ) and from 44 % ± 12 % to 51 % ± 15 % ( P = 0.03 ) , respectively . ETP significantly differed over time between 37.5 IU kg(-1 ) PCC and placebo during 24 h after infusion ( P < 0.01 ) . Both PCC doses restored apixaban-induced PT prolongation after 15 min ( P < 0.01 ) , and this was sustained over a period of 24 h. CONCLUSION Both 37.5 IU kg(-1 ) PCC and 25 IU/kg PCC improved coagulation parameters in healthy subjects , suggesting partial reversal of the anticoagulant effect of apixaban . This implies that PCC might be considered in patients with apixaban-associated bleeding . However , ETP was not immediately restored to pre-apixaban levels , suggesting that these doses are too low to instantly and fully restore hemostasis at peak apixaban levels Background Despite years of experience with vitamin K antagonist-associated bleeding events , there is still no evidence to help identify the optimal treatment with prothrombin complex concentrates . Variable dosing and fixed dose strategies are being used . In this observational prospect i ve two-cohort study , we aim ed to assess the non-inferiority of a low fixed PCC dose ( 1,040 IU Factor IX ) compared to the registered variable dosing regimen based on baseline International Normalized Rate , bodyweight , and target International Normalized Rate , to counteract vitamin K antagonists in a bleeding emergency in a daily clinical practice setting . Design and Methods Non-inferiority of the fixed prothrombin complex concentrate dose was hypothesized with a margin of 4 % . Main end points were proportion of patients reaching the target International Normalized Rate ( < 2.0 ) after prothrombin complex concentrate treatment , and successful clinical outcome . Results Target International Normalized Rate was reached in 92 % of the fixed dose patients ( n=101 ) versus 95 % of variable dose patients ( n=139 ) result ing in a risk difference of -2.99 % ( 90 % CI : - 8.6 to 2.7 ) ( non-inferiority not confirmed ) . Clinical outcome was successful in 96 % and 88 % of fixed versus variable dose , respectively , with a risk difference of 8.3 % ( 90 % CI : 2.7 - 13.9 ; non-inferiority confirmed ) . Conclusions Although a lower fixed prothrombin complex concentrate dose was associated with successful clinical outcome , fewer patients reached the target International Normalized Rate BACKGROUND Specific reversal agents for non-vitamin K antagonist oral anticoagulants are lacking . Idarucizumab , an antibody fragment , was developed to reverse the anticoagulant effects of dabigatran . METHODS We undertook this prospect i ve cohort study to determine the safety of 5 g of intravenous idarucizumab and its capacity to reverse the anticoagulant effects of dabigatran in patients who had serious bleeding ( group A ) or required an urgent procedure ( group B ) . The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab , on the basis of the determination at a central laboratory of the dilute thrombin time or ecarin clotting time . A key secondary end point was the restoration of hemostasis . RESULTS This interim analysis included 90 patients who received idarucizumab ( 51 patients in group A and 39 in group B ) . Among 68 patients with an elevated dilute thrombin time and 81 with an elevated ecarin clotting time at baseline , the median maximum percentage reversal was 100 % ( 95 % confidence interval , 100 to 100 ) . Idarucizumab normalized the test results in 88 to 98 % of the patients , an effect that was evident within minutes . Concentrations of unbound dabigatran remained below 20 ng per milliliter at 24 hours in 79 % of the patients . Among 35 patients in group A who could be assessed , hemostasis , as determined by local investigators , was restored at a median of 11.4 hours . Among 36 patients in group B who underwent a procedure , normal intraoperative hemostasis was reported in 33 , and mildly or moderately abnormal hemostasis was reported in 2 patients and 1 patient , respectively . One thrombotic event occurred within 72 hours after idarucizumab administration in a patient in whom anticoagulants had not been reinitiated . CONCLUSIONS Idarucizumab completely reversed the anticoagulant effect of dabigatran within minutes . ( Funded by Boehringer Ingelheim ; RE-VERSE AD Clinical Trials.gov number , NCT02104947 . ) BACKGROUND Bleeding is a complication of treatment with factor Xa inhibitors , but there are no specific agents for the reversal of the effects of these drugs . And exanet is design ed to reverse the anticoagulant effects of factor Xa inhibitors . METHODS Healthy older volunteers were given 5 mg of apixaban twice daily or 20 mg of rivaroxaban daily . For each factor Xa inhibitor , a two-part r and omized placebo-controlled study was conducted to evaluate and exanet administered as a bolus or as a bolus plus a 2-hour infusion . The primary outcome was the mean percent change in anti-factor Xa activity , which is a measure of factor Xa inhibition by the anticoagulant . RESULTS Among the apixaban-treated participants , anti-factor Xa activity was reduced by 94 % among those who received an and exanet bolus ( 24 participants ) , as compared with 21 % among those who received placebo ( 9 participants ) ( P<0.001 ) , and unbound apixaban concentration was reduced by 9.3 ng per milliliter versus 1.9 ng per milliliter ( P<0.001 ) ; thrombin generation was fully restored in 100 % versus 11 % of the participants ( P<0.001 ) within 2 to 5 minutes . Among the rivaroxaban-treated participants , anti-factor Xa activity was reduced by 92 % among those who received an and exanet bolus ( 27 participants ) , as compared with 18 % among those who received placebo ( 14 participants ) ( P<0.001 ) , and unbound rivaroxaban concentration was reduced by 23.4 ng per milliliter versus 4.2 ng per milliliter ( P<0.001 ) ; thrombin generation was fully restored in 96 % versus 7 % of the participants ( P<0.001 ) . These effects were sustained when and exanet was administered as a bolus plus an infusion . In a subgroup of participants , transient increases in levels of d-dimer and prothrombin fragments 1 and 2 were observed , which resolved within 24 to 72 hours . No serious adverse or thrombotic events were reported . CONCLUSIONS And exanet reversed the anticoagulant activity of apixaban and rivaroxaban in older healthy participants within minutes after administration and for the duration of infusion , without evidence of clinical toxic effects . ( Funded by Portola Pharmaceuticals and others ; ANNEXA-A and ANNEXA-R Clinical Trials.gov numbers , NCT02207725 and NCT02220725 . ) INTRODUCTION Prothrombin complex concentrates ( PCCs ) are a common treatment option for the reversal of oral anticoagulation with vitamin K antagonists ( VKAs ) . This study assessed efficacy and safety of Prothromplex Total ® . MATERIAL S AND METHODS Patients ( ≥18 years ) with acquired prothrombin complex coagulation factor deficiency ( international normalized ratio [ INR ] ≥ 2 at screening ) due to oral VKAs , requiring reversal of anticoagulation , were treated with 25 , 35 , or 50 IU/kg BW PCC . After infusion , efficacy was assessed for 72 ± 4 hours . Adverse events ( AEs ) were captured for 15 days . RESULTS Sixty-one subjects , 48 requiring interventional procedures and 13 with acute bleeds , received a single infusion of PCC . Of 59 subjects analyzed , all achieved normalization of INR ( ≤ 1.3 ) within 30 ± 5 minutes of infusion , demonstrating effective anticoagulant reversal . IVRs of factors II , VII , IX , and X ranged from 1.12 - 2.03 IU/dL : IU/kg . Median INRs remained between 1.00 and 1.18 for up to 6 hours . Overall efficacy of treatment was rated " excellent " for 60 subjects . Three AEs were deemed possibly related to treatment : 1 serious AE ( SAE ) of acute myocardial infa rct ion ( rated severe ) , 1 SAE of deep vein thrombosis ( rated mild ) , and 1 AE of pyrexia ( rated mild ) . Thrombotic adverse events ( 2/61 , 3.3 % ) reported here are comparable to rates observed in other PCC studies . CONCLUSIONS While there is a risk of thromboembolic events following treatment with PCC products , the number of events reported here was low and could have occurred without PCC treatment . The individualized , INR-based dosing of PCC used here for VKA anticoagulant reversal produces rapid normalization of INR to ≤ 1.3 within 30 minutes Background There are no studies demonstrating that prothrombin complex concentrates ( PCC ) improves outcome compared FFP in patients with warfarin-associated intracranial hemorrhage . Methods A prospect i ve , observational study was conducted of patients who received PCC ( Bebulin VH ) , FFP , or PCC + FFP . All groups received vitamin K 10 mg IV . INR reversal ( < 1.4 ) , adverse events ( venous thromboembolism , myocardial infraction , pulmonary edema ) , major hemorrhage ( new or worsened intracranial hemorrhage , anemia requiring transfusion or GI bleed ) , and 3-month functional outcome were compared between the groups using Chi squared and logistic regression analysis . Results Of 64 patients , PCC alone was used in 16 ( mean dose 48 IU/kg ) , FFP alone in 25 ( mean dose 12.5 ml/kg ) , and PCC + FFP in 23 ( median doses 47.4 IU/kg and 11.4 ml/kg , respectively ) . INR correction occurred in 88 , 84 , and 70 % , respectively . There were no differences in time to INR correction or adverse events between the groups , but FFP alone was associated with more major hemorrhage after administration ( 52 % , OR 5.0 , 95 % CI 1.6–15.4 , P = 0.006 ) and PCC with less ( 6 % , OR 0.1 , 95 % CI 0.01–0.8 , P = 0.033 ) . After adjusting for age , admission GCS , initial INR , and bleed type , the use of PCC was associated with a lower risk of death or severe disability at 3-months ( adjusted OR 0.02 , 95 % CI 0.001–0.8 , P = 0.039 ) , while FFP alone was associated with a higher risk ( adjusted OR 51.6 , 95 % CI 1.2–2163.1 , P = 0.039 ) . Conclusions PCC adequately corrected INR without any increase in adverse events compared to FFP and was associated with less major hemorrhage and improved 3-month outcomes in patients with warfarin-associated intracranial hemorrhage Background — Patients experiencing major bleeding while taking vitamin K antagonists require rapid vitamin K antagonist reversal . We performed a prospect i ve clinical trial to compare nonactivated 4-factor prothrombin complex concentrate ( 4F-PCC ) with plasma for urgent vitamin K antagonist reversal . Methods and Results — In this phase IIIb , multicenter , open-label , noninferiority trial , nonsurgical patients were r and omized to 4F-PCC ( containing coagulation factors II , VII , IX , and X and proteins C and S ) or plasma . Primary analyses examined whether 4F-PCC was noninferior to plasma for the co primary end points of 24-hour hemostatic efficacy from start of infusion and international normalized ratio correction ( ⩽1.3 ) at 0.5 hour after end of infusion . The intention-to-treat efficacy population comprised 202 patients ( 4F-PCC , n=98 ; plasma , n=104 ) . Median ( range ) baseline international normalized ratio was 3.90 ( 1.8–20.0 ) for the 4F-PCC group and 3.60 ( 1.9–38.9 ) for the plasma group . Effective hemostasis was achieved in 72.4 % of patients receiving 4F-PCC versus 65.4 % receiving plasma , demonstrating noninferiority ( difference , 7.1 % [ 95 % confidence interval , –5.8 to 19.9 ] ) . Rapid international normalized ratio reduction was achieved in 62.2 % of patients receiving 4F-PCC versus 9.6 % receiving plasma , demonstrating 4F-PCC superiority ( difference , 52.6 % [ 95 % confidence interval , 39.4 to 65.9 ] ) . Assessed coagulation factors were higher in the 4F-PCC group than in the plasma group from 0.5 to 3 hours after infusion start ( P<0.02 ) . The safety profile ( adverse events , serious adverse events , thromboembolic events , and deaths ) was similar between groups ; 66 of 103 ( 4F-PCC group ) and 71 of 109 ( plasma group ) patients experienced ≥1 adverse event . Conclusions — 4F-PCC is an effective alternative to plasma for urgent reversal of vitamin K antagonist therapy in major bleeding events , as demonstrated by clinical assessment s of bleeding and laboratory measurements of international normalized ratio and factor levels . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00708435 |
10,428 | 23,355,159 | IPI saline result ed in a significant reduction in SP severity compared with nothing .
IPI LA was associated with an overall significant reduction of SP severity compared with nothing .
Results regarding the effect IPI LA versus saline showed contradictory results in regards to both SP incidence and severity .
Conclusions Both IPI of saline and LA can be used to reduce SP severity after laparoscopic cholecystectomy .
It is not possible to conclude whether the incidence of SP can be reduced with saline or LA , due to contradictive results | Background The laparoscopic technique has many advantages compared with open surgery for symptomatic cholecystolithiasis .
Despite these advantages , many patients complain about shoulder pain ( SP ) after laparoscopic cholecystectomy .
The purpose of this review was to evaluate intraperitoneal instillation ( IPI ) of saline and local anesthesia ( LA ) to minimize SP . | Abstract . After laparoscopic surgery carbon dioxide remains within the peritoneal cavity for a few days , commonly causing pain . This prospect i ve r and omized study was performed to determine the efficacy of intraperitoneal infusion of normal saline on postoperative pain after laparoscopic cholecystectomy . Altogether 300 patients were r and omly assigned to one of five groups of 60 patients each . Group A : control group , no peritoneal infusion , no subhepatic drain . Group B : no peritoneal infusion but a subhepatic closed drain was left for 24 hours . Group C : normal saline 25 to 30 ml/kg body weight at a temperature of 37 ° C was infused under the right hemidiaphragm and left in the peritoneal cavity . Group D : normal saline in a room temperature was infused under the right hemidiaphragm and suctioned after the pneumoperitoneum was deflated . Group E : normal saline was infused and suctioned as in group D , but a subhepatic closed drain was left for 24 hours . Postoperatively , analgesic medication usage , nausea , vomiting , and pain scores were determined at 2 , 6 , 12 , 24 , 48 , and 72 hours ( during hospitalization and at home ) . Postoperative pain was reduced significantly ( p < 0.001 ) in the patients of groups C , D , and E versus controls , whereas no difference was observed between groups A and B. Among groups C , D , and E , group E ( p < 0.01 ) had the best results followed by group D and then group C. Intraperitoneal normal saline offered a detectable benefit to patients undergoing laparoscopic cholecystectomy . The beneficial effect was better when the fluid was suctioned after deflation of the pneumoperitoneum and even better when a subhepatic closed drain continued fluid suction during the first postoperative hours Background : A controversy exists over the effectiveness and clinical value of intraperitoneal local anaesthetics for treating pain after laparoscopic cholecystectomy . The use of intraperitoneal lidocaine was evaluated in this study Background Some scientific studies , with controversial results , have evaluated the efficacy in reducing pain of some different local anesthetic molecules , which were administered at different dosages and in different ways . The primary goal of this r and omized , controlled , prospect i ve study ( Clinical Trials.gov ID NCT00599144 ) was to assess the effectiveness of 0.5 % bupivacaine for pain control after video-laparoscopic cholecystectomy at its optimal dosage of 2 mg/kg infiltrated in the muscular fasciae of the trocars , or positioned in the gallbladder soaking a sheet of regenerated oxidized cellulose ( Tabotamp ® ) . Methods A total of 45 patients underwent elective video-laparoscopic cholecystectomy . They were r and omized in three groups each made of 15 patients : group A ( bupivacaine-soaked Tabotamp ® positioned in the gallbladder bed ) , group B ( bupivacaine infiltrated in the muscular fasciae of the trocars ’ seat ) , group C ( control group , not using local anesthetic ) . Six and twenty-four hours after the intervention , the nature of the pain and its intensity were recorded with the use of a Visual Analogue Scale ( VAS ) . Results Six hours after the intervention , VAS average was 29.6 ± 10.92 for group A , 25.86 ± 16.06 for group B , and 36.13 ± 16.62 for group C. At 24 h , we recorded 19.26 ± 15.81 , 18.53 ± 12.3 , and 20.46 ± 20.08 for groups A , B , and C , respectively ( p > 0.05 ) . Comparing groups A and B between them and with the control group at 6 and 24 h , we deduced how only the first group showed a statistically significant advantage ( p < 0.05 ) in reducing visceral and shoulder pain compared with the two other groups . Wound infiltration result ed in being statistically favorable in reducing parietal pain only when compared with Group A. For groups A and B , bupivacaine significantly reduced the use of postoperative pain killers . Conclusion Bupivacaine , either infiltrated in trocars ’ wounds or kept soaked in a regenerated oxidized cellulose sheet positioned in the gallbladder bed , although safe and not economically dem and ing , can increase postoperative comfort Background The aim of this study was to test the use of preincisional and intraperitoneal levobupivacaine ( L-B ) 0.25 % in laparoscopic cholecystectomies for postoperative analgesia . Methods A total of 108 patients under general anesthesia were r and omly assigned to receive preincisional local infiltration of 20 ml solution and intraperitoneal instillation of another 20 ml solution . Group A received for local infiltration and intraperitoneal instillation normal saline ( NS ) . Group B received for local infiltration L-B 0.25 % and for intraperitoneal instillation NS . Group C received for local infiltration NS and for intraperitoneal instillation L-B 0.25 % . Group D received both for local infiltration and intraperitoneal instillation L-B 0.25 % . Abdominal and right shoulder pain were recorded for 24 h postoperatively . Results The pain scores were lower in group D than in the other groups during rest , cough , and movement ( p < 0.05 ) . Rescue analgesic treatment was significantly lower in patients of group D ( 35 % ) as compared with that of group A ( 84 % ) ( p < 0.05 ) . The incidence of right shoulder pain was significantly lower in groups C ( 22 % ) and D ( 18 % ) than in any of the other groups ( p < 0.05 ) . Conclusions The combination of preincisional local infiltration and intraperitoneal instillation of L-B 0.25 % shows an advantage for postoperative analgesia after laparoscopic cholecystectomy BACKGROUND Shoulder pain is common after laparoscopic cholecystectomy ( 60.5 % ) and can delay return to normal activities . The cause is unclear but may involve referral of pain from the traumatized area . PATIENTS AND METHODS A total of 75 patients with chronic cholecystitis who underwent laparoscopic cholecystectomy were r and omized into two groups . Group I ( 37 patients ) had 10 mL of 0.25 % bupivacaine instilled into the gallbladder bed and Calot 's triangle area at the end of cholecystectomy . Group II ( 38 patients ) served as controls and had no bupivacaine instillation . Postoperative shoulder pain was evaluated . RESULTS Six patients in Group I developed shoulder pain ( 16 % ) compared with 23 patients in Group II ( 60.5 % ) . The difference was statistically significant ( P = 0.0002 ) . CONCLUSION The raw area of the removed organ is at least partially responsible for shoulder pain after laparoscopic cholecystectomy . Local bupivacaine is effective in reducing such pain BACKGROUND Laparoscopic cholecystectomy ( LC ) has become the st and ard treatment for gall bladder disease . However , despite its low degree of invasiveness , many patients complain of postoperative pain and postoperative nausea/vomiting . This study was planned to evaluate different factors affecting the incidence and severity of postoperative shoulder-tip pain after LC . PATIENTS AND METHODS One hundred consecutive patients who were treated for gall bladder stone by LC at the Gastroenterology Surgical Center , Mansoura University , Mansoura , Egypt , during the period from October 2008 to January 2010 , were r and omized according to different pnemoperitonum pressures ( 8 , 10 , 12 , and 14 mm Hg ) . Each group comprises 25 patients . RESULTS There were 62 patients reported to have postoperative shoulder-tip pain during the first 12 hours after operation , which decreased to 9 patients on the 10th postoperative day . A significant difference was observed in the prevalence of pain at different pressures , 11 % with low pressure and increased to 20 % with high pressure . The incidence of shoulder-tip pain was significantly more in patients with a longer duration of the operation of > 45 minutes at 12 hours ( 23 [ 76.7 % ] versus 39 [ 55.7 % ] ; P = 0.04 ) , at 24 hours ( 23 [ 76.7 % ] versus 29 [ 41.4 % ] ; P = 0.009 ) , and at 3 days postoperatively ( 19 [ 63.3 % ] versus 20 [ 28.6 % ] ; P = 0.01 ) . The volume of used gases during the operation had no effect on the incidence or severity of shoulder-tip pain after LC . Also , the use of intraoperative analgesics had no effect on the incidence or severity of shoulder-tip pain after LC . CONCLUSIONS The origin of pain after LC is multifactorial . We recommend the use of the lower pressure technique during LC , and as patients with and without drains have similar incidence of postoperative shoulder pain , drains should not be used with the intention of preventing shoulder pain Laparoscopy approach to cholecystectomy has shortened the recovery period , reducing discharge times from 1 to 3 days to same-day discharge . We hypothesize that the use of more than one modality to prevent postoperative pain may be more efficacious than single modality . Patients were r and omized to a treatment ( n = 24 ) or control ( n = 25 ) group and studied using a prospect i ve , double-blind design . Preoperatively , at 45 min before induction of anesthesia , the treatment group received an intramuscular ( IM ) bolus injection of meperidine 0.6 mg/kg and ketorolac 0.5 mg/kg . The control group received two bolus IM injections of placebo ( normal saline ) . Ten minutes before incision , local anesthesia ( treatment group ) or saline ( control group ) was infiltrated into the skin of each patient . Anesthetic management , postoperative pain , and nausea treatment were st and ardized . Pain and nausea assessment were done 1 h preoperatively , 0 , 0.5 , 1 , 2 , 3 , and 4 h postoperatively , at discharge , and 10 , 24 , and 48 h postoperatively . Patients were discharged by scoring criteria . Postoperatively , significantly more patients in the treatment group were without pain on arrival in the postanesthesia care unit ( PACU ) , 12/21 ( 57.1 % ) vs 1/24 ( 4.2 % ) in the control group ( P < 0.001 ) . Similarly , the severity of pain was sixfold less in the treatment group than in the control group . The incidence of nausea in the PACU was significantly less in the treatment group ; 4.7 % vs 29.5 % in the control group ( P < 0.05 ) . Patients from the treatment group satisfied Postanesthesia Discharge Score significantly earlier than those in the control group ( 281 + /- 12 min vs 375 + /- 19 min ; P < 005 ) . The concomitant use of local anesthetic and nonsteroidal antiinflammatory and opioid drugs proved to be highly effective in our patients , result ing in faster recovery and discharge . ( Anesth Analg 1996;82:44 - 51 BACKGROUND : The study was design ed to compare the effect of intraincisional vs intraperitoneal infiltration of levobupivacaine 0.25 % on post-operative pain in laparoscopic cholecystectomy . MATERIAL S AND METHODS : This r and omised controlled study was carried out on 189 patients who underwent laparoscopic cholecystectomy . Group 1 was the control group and did not receive either intraperitoneal or intraincisional levobupivacaine . Group 2 was assigned to receive local infiltration ( intraincisional ) of 20 ml solution of levobupivacaine 0.25 % , while Group 3 received 20 ml solution of levobupivacaine 0.25 % intraperitoneally . Post-operative pain was recorded for 24 hours post-operatively . RESULTS : Post-operative abdominal pain was significantly lower with intraincisional infiltration of levobupivacaine 0.25 % in group 2 . This difference was reported from 30 minutes till 24 hours post-operatively . Right shoulder pain showed significantly lower incidence in group 2 and group 3 compared to control group . Although statistically insignificant , shoulder pain was less in group 3 than group 2 . CONCLUSION : Intraincisional infiltration of levobupivacaine is more effective than intraperitoneal route in controlling post-operative abdominal pain . It decreases the need for rescue analgesia Background : We design ed a prospect i ve r and omized clinical trial to investigate whether intraperitoneal saline washout combined with a low-pressure pneumoperitoneum ( LPSW ) was superior to low-pressure pneumoperitoneum ( LP ) alone as a means of reducing postoperative pain and analgesic consumption in the early recovery period after laparoscopic cholecystectomy ( LC ) . Methods : A total of 124 consecutive patients undergoing LC due to uncomplicated symptomatic gallstones were r and omized to the LP or LPSW group . In the LPSW group , normal saline at body temperature ( 25 ml/kg of body weight ) was irrigated under the diaphragm . The fluid was evacuated via the passive-flow method through a 16-F closed drain left under the liver for 24 h. We then assessed the intensity of total abdominal postoperative pain using the Visual Analogue Scale ( VAS ) , including the incidence of shoulder-tip pain ( STP ) , total daily analgesia dem and rate , analgesic consumption . Quality of life ( QOL ) within 7 days after the operation was assessed using the Medical Outcomes Study Short Form 36 Health Survey ( SF-36 ) . A p value of < 0.05 was considered significant . Results : The mean postoperative pain score was lower by 2.64 ± 0.86 in the LPSW ; the difference equaled 9.64 % ( p < 0.05 ) . The incidence of STP was lower in the LPSW group ( LP 11.29 % vs LPSW 1.6 % ; p = 0.028 ) . The analgesia dem and rate was remarkably lower in LPSW vs LP within 24 and 48 h postoperatively ( 70.96 % vs 90.32 % ; p = 0.006 and 64.51 % vs. 83.87 % ; p = 0.013 , respectively ) . After LPSW vs LP , QOL was better in terms of physical functioning , role limitations due to physical problems , and bodily pain ( 90.32 % vs 77.42 % ; p = 0.05 , 90.32 % vs 75.8 % ; p = 0.03 , 91.93 % vs 74.19 % ; p = 0.008 , respectively ) . Conclusion : In terms of lower postoperative pain and a better QOL within the early recovery period , LPSW is superior to LP alone . The saline washout procedure should be recommended during LC because it is a simple way to reduce pain intensity , even after LP operations Introduction Intraabdominal CO2 gas after laparoscopic cholecystectomy causes postoperative shoulder-tip pain . Many methods of analgesia have been used to reduce this pain , including analgesic drugs , intraperitoneal local anesthetic , intraperitoneal saline , a gas drain , heated gas , low-pressure gas , and nitrous oxide pneumoperitoneum . The aim of this study was to evaluate the efficacy of combined low-pressure CO2 pneumoperitoneum and intraperitoneal infusion of normal saline in reducing the incidence of postoperative shoulder-tip pain . Methods Altogether , 109 patients undergoing elective laparoscopic cholecystectomy were r and omized prospect ively into three groups . Patients in group A ( n = 34 ) underwent laparoscopic cholecystectomy with 14 mmHg CO2 pneumoperitoneum ; patients in group B ( n = 37 ) underwent laparoscopic cholecystectomy with 10 mmHg CO2 pneumoperitoneum ; and those in group C ( n = 38 ) underwent laparoscopic cholecystectomy with 10 mmHg CO2 pneumoperitoneum in addition to intraperitoneal normal saline infusion in the right hemidiaphragmatic area . Shoulder-tip pain was recorded on a verbal rating scale 2 , 6 , 12 , 24 , and 48 hours after operation . Results Twelve patients in group A ( 35.2 percent ) , six in group B ( 16.2 percent ) , and seven in group C ( 18.4 percent ) complained of shoulder-tip pain . Hence , there was a significant decrease in the frequency of shoulder-tip pain in groups B and C in relation to group A , but there was no significant difference between groups B and C. The postoperative shoulder-tip pain scores were significantly reduced in group C at 6 , 12 , and 24 hours . The number of patients who required additional analgesics was also reduced in group C. Conclusions Low-pressure CO2 pneumoperitoneum reduces the number of patients complaining of shoulder-tip pain and the intensity of the pain after laparoscopic cholecystectomy . The addition of intraperitoneal normal saline infusion to low-pressure CO2 pneumoperitoneum seems to reduce the intensity but not the frequency of shoulder-tip pain after laparoscopic cholecystectomy Background This study aim ed to evaluate the optimal timing of preemptive analgesia with bupivacaine peritoneal instillation in a prospect i ve , r and omized , double-blind , placebo-controlled trial . Methods In this study , 120 patients qualified for laparoscopic cholecystectomy were r and omized to four groups . Group A received 2 mg/kg of bupivacaine in 200 ml of normal saline before creation of pneumoperitoneum . Group B received 2 mg/kg of bupivacaine in 200 ml of normal saline after creation of pneumoperitoneum . Group C received 200 ml of normal saline before creation of pneumoperitoneum . Group D received 200 ml of normal saline after creation of pneumoperitoneum . Local wound infiltration with bupivacaine was used before skin incisions . The primary end points of the study were postoperative pain intensity on a visual analog scale and incidence of shoulder tip pain . The secondary end points included the latency of nurse-controlled analgesia activation , the analgesia request rate , and analgesic consumption . Results Significantly lower visual analog scores were observed in group A versus groups C and B versus group D during the initial 48 and 24 h , respectively . The patients in group A versus group B reported significantly lower pain at 4 h ( p < 0.001 ) and 8 h ( p = 0.003 ) postoperatively , but the difference was not significant after 12 , 24 , and 48 h. None of the group A patients reported shoulder tip pain , whereas it was reported by 3 patients in group B , 6 patients in group C , and 7 patients in group D ( p < 0.01 ) . The latency of nurse-controlled analgesia activation was 426.8 ±57.2 min in group A , as compared with 307 ± 39.8 min in group B , 109.3 ± 51 min in group C , and 109 ± 46.5 min in group D ( p < 0.001 ) . A significantly lower analgesia request rate was observed in group A versus C , as compared with group B versus D , throughout the entire study period ( p < 0.05 ) . Conclusions Preemptive analgesia with bupivacaine peritoneal instillation is much more effective for pain relief if used before creation of pneumoperitoneum . Although the effect of bupivacaine peritoneal instillation is also noticeable when used after creation of pneumoperitoneum , it confers significantly lower benefits After laparoscopic cholecystectomy , CO2 remains within the peritoneal cavity , commonly causing pain . This prospect i ve r and omized study was performed to determine the efficacy of intraperitoneal normal saline and bupivacaine infusion on postoperative pain after laparoscopic cholecystectomy . Three hundred patients were r and omly assigned to one of six groups of 50 patients each . Group A patients served as controls . In group B patients , normal saline was infused under the right hemidiaphragm and suctioned after the pneumoperitoneum was deflated . After suction , a subhepatic closed drain was left for 24 h. In group C patients , bupivacaine 1.5 mg/kg in solution 2.5 mg/ml , minus 15 ml of this solution , which was infiltrated in the trocar wounds , was infused under the right hemidiaphragm at the end of the cholecystectomy . In group D patients , bupivacaine was given as in group C , but a subhepatic drain was left for 24 h. In group E patients , normal saline was used as in group B plus bupivacaine as in group C. Group F patients were treated as in group E , but a subhepatic drain was left for 24 h. In all groups , 15 ml of a 2.5 mg/ml bupivacaine solution was infiltrated in the trocar wounds . Postoperatively , analgesic medication usage , nausea , vomiting , and pain scores were recorded at 2 , 6 , 12 , 24 , 36 , 48 , and 72 h. Postoperative pain was reduced significantly in the patients of the treatment groups vs. the controls . Between treatment groups , patients in groups B , E , and F had the best results , while those in groups C and D had significantly greater pain than those in groups B , E , and F. It is concluded that postoperative pain after laparoscopic cholecystectomy can be significantly reduced by intraperitoneal normal saline infusion subdiaphragmatically and after its postdeflation suction , bupivacaine infusion in the same area , or without bupivacaine in case a subhepatic drainage has been needed Background Intraperitoneal local anesthesia has been reported to reduce postoperative pain after laparoscopy for gynecologic procedures that do not require a great deal of dissection or manipulation of viscera . This study was performed to determine the efficacy of intraperitoneal bupivacaine in laparoscopic cholecystectomy ( LC ) . Methods Fifty-five patients were evaluable in this r and omized , double-blind , placebo-controlled study . Twenty-six patients received bupivacaine ( 0.1 % ) and 29 patients received placebo ( saline ) . Prior to any dissection of the gallbladder , the surgeon irrigated 100 ml of experimental solution under the right hemidiaphragm , over Glisson ’s capsule , over the gallbladder serosa , and into the subhepatic space . The operation was then performed as usual . Postoperatively , analgesic medication usage , nausea , vomiting , and pain scores were determined during hospitalization . A question naire was given to each patient upon discharge from the hospital in order to continue monitoring medications and pain for the first 48 h at home . Results Postoperative pain was reduced significantly ( P < 0.05 ) in the patients who received bupivacaine , but the effect was modest and observable only during the first 6 h after surgery . Despite this difference , there was no significant reduction in the amount of analgesic medication used by the patients who received bupivacaine , nor was there any reduction in nausea , vomiting , or shoulder pain when queried specifically . Conclusions Intraperitoneal bupivacaine offered a detectable , albeit subtle benefit to patients undergoing LC . However , the effect was transient and had little impact upon the patient ’s convalescence We investigated , in a double-blind study , the effects of intraperitoneal local anesthetics during laparoscopic cholecystectomy . In Part A of the study 30 patients received 50 mL saline 0.9 % ( A 0 ) , bupivacaine 0.125 % ( A 125 ) , or bupivacaine 0.25 % ( A 25 ) intraperitoneally at the end of surgery . Mean maximum plasma concentrations of bupivacaine reached 0.48 mg/L ( range 0.15 - 0.90 mg/L ) in Group A 125 and 1.0 mg/L ( 0.35 - 2.10 mg/L ) in Group A 25 within 15 min ( range , 5 - 30 min ) . There was no significant difference in pain scores or opioid consumption ( patient-controlled analgesia with piritramid ) : 24 , 28 , and 13 mg/24 h among the study groups , respectively ( not significant ) . Postoperative respiratory function deteriorated in comparison to preoperative values in all study groups , but the forced vital capacity was significantly more impaired in Group A.25 . In Part B , 24 patients received placebo ( B 0 ) or bupivacaine 0.25 % ( B 25 ) . Postoperative hypoxemic periods ( oxygen saturation < 92 % ) were significantly more frequent in Group B 25 . Considering the question able benefits and the potential risks , we would not recommend the application of intraperitoneal bupivacaine during laparoscopic cholecystectomy . ( Anesth Analg 1995;81:967 - 72 Background : Postoperative abdominal and shoulder pain are the most common complaints after elective laparoscopic cholecystectomy . Postoperative pain is multifactorial in origin , and therefore multimodal therapy may be needed to optimize pain relief . Methods : We conducted a double-blind study where patients were r and omly allocated to 1 of 5 groups of 20 patients each . Statistical significance was considered P<0.05 . Group 1 received 40mL bupivacaine 0.25 % intraperitoneal spray . Group 2 received 40 mL bupivacaine 0.25 % intraperitoneal spray mixed with 200 mg ketoprofen . Group 3 received 40 mL bupivacaine 0.25 % intraperitoneal spray and intravenous 200 mg ketoprofen . Group 4 received 200 mg ketoprofen intravenously . Group 5 was the control group . Results : Demographic data were similar in the 5 groups . As compared with the control group , group 1 had significantly lower abdominal pain scores at 6 hours ; group 2 at 0 , 1 , 2 , and 6 hours ; group 3 at 0 , 1 , 2 , 6 , 12 , and 24 hours ; and group 4 at 2 hours . Group 1 had significantly lower shoulder pain scores at 1 and 6 hours ; group 2 at 0 and 6 hours ; and groups 3 and 4 at 0 , 1 , and 6 hours . The number of patients requiring postoperative rescue analgesics and the incidence of postoperative vomiting were significantly lower in group 3 only . Conclusions : A multimodal approach to pain management following elective laparoscopic cholecystectomy is best achieved with a combination of 40 mL bupivacaine 0.25 % intraperitoneal spray and 200 mg intravenous ketoprofen , achieving the least incidence of postoperative vomiting This prospect i ve , double-blind , r and omized , and placebo-controlled study evaluates the effectiveness of intraperitoneal bupivacaine in decreasing the length of stay for elective laparoscopic cholecystectomy patients . Seventy-seven patients undergoing elective laparoscopic cholecystectomy before noon at a single institution and by a single group of surgeons were entered into the study . The pharmacy r and omly assigned each patient to one of four study groups ( control , predissection , postdissection , and both ) . Two syringes ( A and B ) containing 15 cm3 of either normal saline or 0.5 per cent bupivacaine were sent with the patient to surgery . Syringe A was sprayed over the perihepatic area before any dissection , and B was sprayed over the perihepatic area just before port removal . Preoperative , intraoperative , and postoperative data were collected . Sixty-six patients completed the study : control , 14 ; predissection , 18 ; postdissection , 15 ; and both , 19 . There was no statistical difference between the predissection , postdissection , and both groups regarding same-day discharge . Therefore , these groups were combined for comparison against the control group . The study found that patients receiving bupivacaine at any time during the surgery were more likely to go home the same day as their procedure ( 79 % vs 43 % , respectively : P < 0.02 ) BACKGROUND The aim of this prospect i ve , double-blind , r and omized , placebo-controlled clinical trial was to investigate the opioid-sparing effects of rectal diclofenac following total abdominal hysterectomy . METHODS Forty ASA I-II patients , aged 20 - 60 yr , were r and omized to receive identical-looking suppositories of either diclofenac 75 mg or placebo , twice daily . All patients were given a st and ardized anaesthetic , with intravenous morphine via a patient-controlled analgesia device and either diclofenac or placebo for postoperative analgesia . RESULTS The median 24 h morphine consumption ( interquartile range ) was significantly higher ( P=0.02 ) in the placebo group [ 59 ( 45 - 85 ) mg ] than in the diclofenac group [ 31 ( 14 - 65 ) mg ] . In comparison with the placebo group , there were significant reductions in total pain score in the diclofenac group at rest ( P=0.04 ) and on movement ( P<0.01 ) . Total ( SD ) sedation score was significantly lower ( P=0.04 ) in the diclofenac group [ 90 ( 73 ) mm ] than in the placebo group [ 148 ( 89 ) mm ] . Total ( interquartile range ) nausea score was significantly lower ( P<0.01 ) in the diclofenac group [ 14 ( 0 - 53 ) mm ] than in the placebo group [ 64 ( 30 - 109 ) mm ] . There was no significant difference between the two groups of patients in episodes of vomiting or number of rescue antiemetics . CONCLUSIONS Rectal diclofenac reduces morphine consumption , improves postoperative analgesia , and reduces the incidence of adverse effects such as sedation and nausea BACKGROUND Postoperative shoulder-tip pain ( STP ) frequently occurs following laparoscopic surgery . In an attempt to abrogate this complication we prospect ively evaluated the efficacy of intraoperative irrigation of the diaphragm with bupivacaine . METHODS One hundred and five consecutive patients undergoing laparoscopic surgery were prospect ively r and omized to treatment or control groups . Treatment group ( B , n = 55 ) received irrigation with 10 mL 0.5 % bupivacaine in 500 mL saline and control group ( A , n = 50 ) received an equal volume of normal saline . Each dome of the diaphragm was irrigated with 250 mL of either solution at the end of surgery . Laparoscopic procedures performed included cholecystectomy ( n = 63 ) , Nissen fundoplication ( n = 21 ) , appendicectomy ( n = 7 ) , hernia repair ( n = 4 ) , and diagnostic laparoscopy ( n = 10 ) . Patients ' anesthesia and perioperative analgesia were st and ardized . STP was recorded on a visual analogue pain scale ( VAPS ) in the recovery room immediately following surgery and at 4 , 10 , and 24 hours thereafter . RESULTS The overall incidence of STP in patients undergoing laparoscopic procedures was approximately 24 % . Twenty-one patients ( 42 % ) in the control group and 4 patients ( 7 % ) in the treatment group complained of shoulder pain during the recording period ( P = 0.003 ) . Mean STP scores as recorded on VAPS were significantly lower in the bupivacaine group than in the control group from 4 to 24 hours after surgery ( P < 0.01 ) . Postoperative analgesia requirements were also significantly reduced in those patients receiving bupivacaine irrigation ( P < 0.04 ) . CONCLUSION Intraperitoneal irrigation with bupivacaine to both hemidiaphragms at the end of surgery significantly reduces both frequency and intensity of STP following laparoscopic procedures thus reducing patient morbidity Summary The present study is a comparison of the pharmacokinetics of four local anaesthetics injected double blind in the right subdiaphragmatic area during outpatient laparoscopy performed under st and ard general anaesthesia in 28 young women . 80 ml of one of the following solutions was injected : Group A 0.5 % plain lidocaine ( n=7 ) , Group B 0.5 % lidocaine with 1/320.000 adrenaline ( n=8 ) , Group C 0.5 % lidocaine with 1/800.000 adrenaline ( n=7 ) , and Group D 0.125 % bupivacaine with 1/800.000 adrenaline ( n=6 ) . Blood sample s were collected over 360 min from an iv catheter and serum concentrations were measured by gas chromatography . No adverse effects occurred in the study period . In Group A ( plain lidocaine ) , Cmax was significantly higher and tmax significantly earlier than in Groups B and C ( lidocaine with adrenaline ) . A toxic level was not found after either solution in any patient . The intraperitoneal use of doses of 400 mg lidocaine or 100 mg bupivacaine for perioperative analgesia was safe and solutions of lidocaine containing adrenaline appeared to pose even less risk than plain solutions Abstract Purpose Afferent stimulus arising from gallbladder and its bed may elicit reflex inhibition of the diaphragm . Pulmonary function would be improved by blocking this stimulus after laparoscopic cholecystectomy . This r and omized prospect i ve study evaluated this hypothesis in patients who underwent laparoscopic cholecystectomy . Material s and methods During the study period , 30 patients who underwent laparoscopic cholecystectomy were r and omly divided into three groups . Group I : Laparoscopic cholecystectomy;Group II : Laparoscopic cholecystectomy + irrigation of gallbladder bed with 20 mL 0.5 % bupivacaine solution;Group III : Laparoscopic cholecystectomy + irrigation of gallbladder bed with bupivacaine + 10 mL 0.5 % bupivacaine solution was given via a catheter every 6 h . Pulmonary function tests were performed on the day before the operation and in the morning of the first postoperative day . Forced vital capacity ( FVC ) , forced expiratory volume at 1 s ( FEV-1 ) , and forced expiratory flow at 25 % to75 % ( FEF 25–75 % ) were obtained . Results Postoperative FVC measured 53.3 ± 4.5 % of preoperative function for group I , 70.8 ± 5.7 % for group II , and 68.8 ± 4.7 % for group III ( p < 0.05 ) . Postoperative FEV-1 measured 52.8 ± 5.3 % of preoperative function for group I , 69.7 ± 4.9 % for group II , and 70.5 ± 5 % for group III ( p < 0.05 ) . Postoperative FEF 25–75 % measured 61.1 ± 4.6 % of the preoperative function for group I , 73.6 ± 3 % for group II , and 72.1 ± 6 % for group III ( p < 0.05 ) . Conclusion The results from this study indicated that considerable improvement of pulmonary function was acquired by gallbladder bed irrigation with bupivacaine after laparoscopic cholecystectomy Purpose In this study , the effects of intravenous paracetamol treatment on early postoperative period analgesia and recovery characteristics after laparoscopic cholecystectomy have been evaluated . Methods Forty patients whose American Society of Anesthesiologists physical status I or II underwent laparoscopic cholecystectomy and r and omly divided into 2 equal groups . In the first group , 1 g paracetamol was given to the patients intravenously after intubation before start of the surgery in 15 minutes . The 100 mL 0.9 % NaCl was infused intravenously for the control group in 15 minutes . Postoperative pain was evaluated and recovery characteristics were evaluated . Results Verbal and visual pain scores of the paracetamol group were significantly lower than control group ( P<0.05 ) . First morphine requirement and total administered morphine dose and duration of staying in recovery room were significantly decreased in the paracetamol group ( P<0.05 ) . Conclusions Beside its effective analgesic properties , paracetamol administration during per operative period supports effective and faster recovery Intraabdominal pain , shoulder pain and tachycardia are observed after pelviscopic interventions . Recent publications blame this on hypothermia caused by the CO2 gas used . The authors discuss in detail the physics of the problems connected with the heating of CO2 gas . The heating of carbon dioxide gas to 37 degrees C in the heating tube of the WISAP-Flow-Therme will not only reduce intra-operative hypothermia ( down to 28 degrees C intra-abdominally and 34 degrees C in the rectum ) but also the occurrence of tachycardia ( reduced by 40 % to 11 % ) . Heating will also result in reduced CO2 consumption , which is also of ecological significance . As a result of the overall improvement of the female patients ' perception of pain there is a significant reduction in postoperative palliative medication required by 31 % . The physical laws and data permit fitting the WISAP Universal Flow Therme to all commercially available CO2 gas insufflators . The rinse water , as an additional factor causing hypothermia , should be preheated to 40 degrees C ( WISAP water bath ) AIM To investigate the safety and efficacy of implanting fibrin sealant with sustained-release ropivacaine in the gallbladder bed for pain after laparoscopic cholecystectomy ( LC ) . METHODS Sixty patients ( American Society of Anesthesiologists physical status was I or II and underwent LC ) were r and omly divided into three equal groups : group A ( implantation of fibrin sealant in the gallbladder bed ) , group B ( implantation of fibrin sealant carrying ropivacaine in the gallbladder bed ) , and group C ( normal saline in the gallbladder bed ) . Postoperative pain was evaluated , and pain relief was assessed by visual analog scale ( VAS ) scoring . RESULTS The findings showed that 81.7 % of patients had visceral pain , 50 % experienced parietal , and 26.7 % reported shoulder pain after LC . Visceral pain was significantly less in group B patients than in the other groups ( P < 0.05 ) , and only one patient in this group experienced shoulder pain . The mean VAS score in group B patients was lower than that in the other groups . CONCLUSION Visceral pain is prominent after LC and can be effectively controlled by implanting fibrin sealant combined with ropivacaine in the gallbladder bed Postoperative pain after laparoscopic cholecystectomy ( LC ) is generally less than open cholecystectomy ; however , the postoperative shoulder and abdominal pain experienced by patients still causes preventable distress . Intraperitoneal irrigation of the diaphragmatic surface and gallbladder fossa using normal saline , bupivacaine , or lignocaine may effectively control visceral abdominal pain after an LC . Two hundred patients with similar demographics undergoing elective LC were r and omized to one of four groups of 50 patients each , including Group A placebo control , Group B with isotonic saline irrigation , Group C with bupivacaine irrigation , and Group D with lignocaine irrigation . All patients received preperitoneal abdominal wall infiltration with 0.25 per cent bupivacaine to control parietal ( somatic ) abdominal pain . The visual analogue and verbal rating pain scores at 0 , 4 , 8 , 12 and 24 hours for both shoulder and abdominal pain were recorded in a prospect i ve double-blind fashion at four points during the first 24 postoperative hours . Analgesia requirements , vital signs , blood glucose , and incidence of nausea and vomiting were also recorded . Patients in each group demonstrated a significant difference in visual analogue and verbal rating pain scores and analgesic consumption when compared with controls . Lignocaine controlled pain significantly better than saline or bupivacaine . Bowel function recovery was similar in all patients , and there were no significant complications . We conclude that intraperitoneal irrigation with either saline , bupivacaine , or lignocaine can significantly reduce visceral abdominal pain after LC . Lignocaine was the most efficacious local anesthetic in this trial and has a high safety profile when used at recommended doses Background The preemptive intravenous and intraperitoneal application of local anesthetics is known to improve the postoperative outcome in abdominal surgery . The aim of this study was to compare the analgesic effect of intravenous lidocaine injection to that of intraperitoneal lidocaine instillation in patients who were undergoing laparoscopic appendectomy ( LA ) . MethodS ixty-eight patients who were undergoing LA for unperforated appendicitis were r and omly divided into three groups . Group IP ( the intraperitoneal instillation group ) received intraperitoneal instillation of lidocaine and intravenous normal saline injection . Group IV ( the intravenous injection group ) received intravenous lidocaine injection and intraperitoneal instillation of normal saline . In group C ( the placebo control group ) , normal saline was given both intravenously and intraperitoneally . The visual analog scale ( VAS ) of pain scores was measured after surgery . The needs for additional intravenous fentanyl were evaluated and the integrated fentanyl consumption ( PCA delivered + additional fentanyl ) was assessed . The incidence of shoulder tip pain and postoperative nausea and vomiting ( PONV ) were noted . Results Reduction of the VAS score and of fentanyl consumption was noted in the IV and IP groups and compared to that of group C ( P < 0.05 ) . The shoulder tip pain and PONV were reduced in groups IP and IV compared to that in group C ( P < 0.05 ) . However , no significant differences were found between the IP and IV groups for all the studied variables . There was no adverse effect from intravenous lidocaine throughout the study . Conclusion Intravenous lidocaine injection is as effective as intraperitoneal instillation for reducing pain and fentanyl consumption . The major benefit of intravenous injection is that this is an easily and universally applicable procedure compared to that of intraperitoneal instillation . Lidocaine intravenous administration is a better alternative for reducing the pain of patients who are undergoing laparoscopic surgery Although pain after laparoscopic cholecystectomy is less intense than after open cholecystectomy , some patients still experience considerable discomfort . Furthermore , the characteristics of post-laparoscopy pain differ considerably from those seen after laparotomy . Therefore , we investigated the time course of different pain components after laparoscopic cholecystectomy and the effects of intraperitoneal bupivacaine on these different components . Forty ASA physical status grade I-II patients were r and omly assigned to receive either 80 mL of bupivacaine 0.125 % with epinephrine 1/200,000 ( n = 20 ) or the same volume of saline ( n = 20 ) instilled under the right hemidiaphragm at the end of surgery . Intensity of total pain , visceral pain , parietal pain , and shoulder pain was assessed 1 , 2 , 4 , 6 , 8 , 24 , and 48 h after surgery . Analgesic consumption was also recorded . Patient data were similar in the two groups . In the saline group , visceral pain was significantly more intense than parietal pain at each time point ; visceral and parietal pain were greater than shoulder pain during the first 8 h postoperatively . Intraperitoneal bupivacaine did not significantly affect any of the different components of postoperative pain . Analgesic consumption was similar in the two groups . This study demonstrates that visceral pain accounts for most of the pain experienced after laparoscopic cholecystectomy . Intraperitoneal bupivacaine is not effective for treating any type of pain after laparoscopic cholecystectomy . ( Anesth Analg 1995;81:379 - 84 Background : Lidocaine has been shown to inhibit neural conduction and to have anti-inflammatory properties . The purpose of this study was to determine whether intraoperative lidocaine infusion reduces opioid consumption in the postanesthesia care unit ( PACU ) . Methods : Fifty patients were enrolled in this prospect i ve , r and omized and observer-blinded study . At induction of anesthesia the control group ( n=25 ) received fentanyl 3 µg·kg−1 while the lidocaine group received fentanyl 1.5 µg·kg−1 and a bolus of lidocaine 1.5 mg·kg−1 followed by a continuous infusion of lidocaine 2 mg·kg−1·hr−1 . General anesthesia included propofol , rocuronium , and desflurane titrated to maintain blood pressure and heart rate within set parameters , and the bispectral index between 35 and 50 . No supplemental opioids were given during surgery . All patients received acetaminophen , ketorolac , dexamethasone , droperidol and local anesthetics in the skin incision . Patients received fentanyl and ondansetron in the PACU . The primary outcome variable was the amount of fentanyl required in the PACU to establish and to maintain visual analogue scale pain scores<3 . Results : Most patients received fentanyl for pain relief in the PACU , but the cumulative mean dose was lower in the lidocaine group compared to the control group ( 98±54 µg , vs154±3 99 µg , respectively , P=0.018 ) . Lidocaine infusion reduced by 10 % the amount of desflurane required ( P=0.012 ) . White-Song scoresτ;12 were attained by all patients in both groups within 30 min of their arrival in the PACU . Median time from arrival to the PACU to discharge home was similar in both groups , 167.5 min in the control groupvs 180 min in the lidocaine group ( P=0.649 ) . Conclusion : Intraoperative lidocaine infusion reduces opioid consumption in the PACU and intraoperative requirements of desflurane . Résumé Context e : Il a été démontré que la lidocaïne inhibe la conduction nerveuse et possède des propriétés anti-inflammatoires . L’objectif de cette étude était de déterminer si une perfusion peropératoire de lidocaïne réduisait la consommation d’opioïdes dans la salle de réveil . Méthode : Cinquante patients ont été recrutés dans le cadre de cette étude prospect i ve , r and omisée et à double insu . Lors de l’induction de l’anesthésie , le groupe témoin ( n=25 ) a reçu 3 µg·kg−1 de fentanyl , et le groupe lidocaïne a reçu 1,5 µg·kg−1 de fentanyl ainsi qu’un bolus de 1,5 mg·kg−1 de lidocaïne suivi d’une perfusion continue de 2 mgsdkg−1·hr−1 de lidocaïne . L’anesthésie générale était composée de propofol , de rocuronium et de desflurane titré afin de maintenir la pression artérielle et la fréquence cardiaque dans la limite de paramètres préétablis , et l’index bispectral entre 35 et 50 . Aucun opioïde supplémentaire n’a été administré pendant la chirurgie . Tous les patients ont reçu de l’acétaminophène , du kétorolac , de la dexaméthasone , du dropéridol et des agents anesthésiques locaux au niveau de l’incision cutanée . Les patients ont reçu du fentanyl et de l’ondansétron en salle de réveil . Le critère d’efficacité principal était la quantité de fentanyl nécessaire en salle de réveil pour établir et maintenir des scores de douleur<3 sur une échelle visuelle analogique . Résultats : La plupart des patients ont reçu du fentanyl en salle de réveil pour soulager la douleur , mais la dose moyenne cumulative était plus basse dans le groupe lidocaïne que dans le groupe témoin ( 98±54 µg , vs 154±99 µg , respectivement , P=0,018 ) . La perfusion de lidocaïne a réduit la quantité de desflurane requise de 10 % ( P=0.012 ) . Des scores de White-Song τ ; 12 ont été obtenus chez tous les patients dans les deux groupes au cours des 30 premières minutes après leur transfer t à la salle de réveil . Le temps médian entre l’arrivée en salle de réveil et le congé de l’hôpital était semblable dans les deux groupes , soit 167,5 min dans le groupe témoin vs 180 min dans le groupe lidocaïne ( P=0,649 ) . Conclusion : Une perfusion peropératoire de lidocaïne réduit la consommation d’opiacés en salle de réveil et les besoins peropératoires de desflurane Purpose The aim of this study was to determine the effect of local anesthetic instillation , to compare bupivacaine and ropivacaine in patients undergoing a laparoscopic cholecystectomy . Methods A total of 80 patients were r and omly assigned to four groups to receive the intraperitoneal instillation of 21 ml of either 100 mg bupivacaine ( Group B ) , 100 mg ropivacaine ( Group R1 ) , 150 mg ropivacaine ( Group R2 ) or saline with epinephrine 1/200 000 at the end of the surgery . The postoperative pain was evaluated and the analgesic requirement was also assessed . Results The intraperitoneal instillation of 100 mg bupivacaine , 100 mg ropivacaine , or 150 mg ropivacaine at the end of a laparoscopic cholecystectomy significantly reduced the morphine consumption during the first 24 h. For preventing postoperative pain 150 mg ropivacaine proved to be significantly more effective than either 100 mg bupivacaine or 100 mg ropivacaine . Conclusion We herein showed that the intraperitoneal instillation of local anesthetic during laparoscopic cholecystectomy is a noninvasive , rapid , safe and simple analgesic technique that reduces the total morphine consumption during first 24 The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials BACKGROUND The goal of this study was to evaluate the effect of peritrocal , intraperitoneal , or combined peritrocal-intraperitoneal ropivacaine on the parietal , visceral , and shoulder tip pain after laparoscopic cholecystectomy . METHODS Eighty patients were r and omly assigned to four groups . Group A received peritrocal and intraperitoneal saline . Group B received peritrocal saline and intraperitoneal ropivacaine . Group C received peritrocal ropivacaine and intraperitoneal saline . Group D received peritrocal and intraperitoneal ropivacaine . The parietal , visceral , and shoulder tip pain were assessed at 2 , 4 , 8 , 12 , 24 , and 48 h postoperatively using a visual analog scale ( VAS ) . The frequency of the patient pushing the button of the PCA and fentanyl use were also recorded . RESULTS In visceral pain , significantly lower VAS scores were observed in Group B from 2 to 4 h and in Group D from 2 to 8 h. In parietal pain , significantly lower VAS scores were observed in Group C from 4 to 24 h and in Group D from 2 to 12 h. In shoulder tip pain , significantly lower VAS scores were observed in Group B from 4 to 48 h and in Group D from 2 to 12 h. The fentanyl use and the frequency to push the button of the PCA were the highest in Group A and the lowest in Group D at every time point . CONCLUSIONS We conclude that peritrocal infiltration of ropivacaine significantly decreases parietal pain and intraperitoneal instillation of ropivacaine significantly decreases the visceral and shoulder tip pain . Their effects are additive with respect to the total pain Purpose To examine the combined preemptive effects of somatovisceral blockade during laparoscopic cholecystectomy ( LC ) . Methods One hundred fifty-seven patients under general anesthesia receiving local infiltration and /or topical peritoneal local anesthesia were studied . Patients were r and omized to receive a total of 150 mg ( 0.25 % 60 mL ) bupivacaine via periportal ( 20 mL ) and intraperitoneal ( 40 mL with 1:200,000 epinephrine ) administration of each . Group A received preoperative periportal bupivacaine before incision and intraperitoneal bupivacaine immediately after the pneumoperitoneum . Group B received periportal and intraperitoneal bupivacaine at the end of the operation . Group C ( preoperative ) and Group D ( postoperative ) received only periportal bupivacaine and Group E ( preoperative ) and Group F ( postoperative ) received only intraperitoneal bupivacaine . The control group received no treatment . Pain and nausea were recorded at one , two , three , six , nine , 12 , 24 , 36 , and 48 hr postoperatively . Results Throughout the postoperative 48 hr , incisional somatic pain dominated over other pain localizations in the control group ( P < 0.05 ) . The incisional pain of groups A , B , C and D was significantly lower than that of the control group in the first and second hours . The incisional pain of groups A and C was significantly lower than that of the control group in the first three hours . Conclusion Incisional pain dominated during the first two postoperative days after LC . Preoperative somato-visceral or somatic local anesthesia reduced incisional pain during the first three postoperative hours . A combination of somato-visceral local anesthetic treatment did not reduce intraabdominal pain , shoulder pain or nausea more than somatic treatment alone . Preoperative incisional infiltration of local anesthetics is recommended . RésuméObjectifVérifier les effets préventifs d’un blocage somato-viscéral combiné , réalisé pendant la cholécystectomie laparoscopique (CL).MéthodeCent cinquante-sept patients sous anesthésie générale ont reçu une infiltration locale et/ou une anesthésie locale péritonéale topique . Les patients , répartis de façon aléatoire , ont reçu au total 150 mg ( 0,25 % 60 mL ) de bupivacaïne administrée par la voie périportale ( 20 mL ) et intrapéritonéale ( 40 mL avec I : 200 000 d’épinéphrine ) . Les modalités intergroupes sont les suivantes : dans le groupe A , une dose préopératoire périportale avant l’incision et une dose intrapéritonéale immédiatement après le pneumopéritoine ; dans le groupe B , une dose périportale et une intrapéritonéale à la fin de l’opération ; dans les groupes C ( préopératoire ) et D ( postopératoire ) , seulement une périportale et dans les groupes E ( préopératoire ) et F ( postopératoire ) , seulement intrapéritonéale . Le groupe témoin n’a reçu aucun médicament . La douleur et les nausées ont été notées à une , deux , trois , six , neuf , 12 , 24 , 36 et 48 h après l’intervention . RésultatsPendant les 48 h d’observation postopératoire , la douleur somatique de l’incision a dominé toute autre douleur chez les patients témoins ( P < 0,05 ) . La douleur incisionnelle a été significativement plus faible dans les groupes A , B , C et D que dans le groupe témoin pendant les deux premières heures . Elle a aussi été significativement plus faible dans les groupes AetC que dans le groupe témoin pendant les trois premières heures . Conclusion La douleur incisionnelle a dominé pendant les deux premiers jours qui ont suivi la CL . L’anesthésie préopératoire somatoviscérale ou somatique locale ont réduit la douleur incisionnelle pendant les trois premières heures postopératoires . Une combinaison d’anesthésiques locaux somatoviscéraux n’a pas réduit la douleur intra-abdominale , la douleur à l’épaule ou les nausées davantage que l’anesthésie somatique employée seule . L’Infiltration préopératoire d’anesthéslque local au site d’Incision est recomm and ée BACKGROUND AND AIMS The clinical value of infiltration of wounds with local anaesthetics ( LA ) and their intraperitoneal application for treating pain after laparoscopic cholecystectomy ( LC ) still remain controversial . In this study the use of intraincisional and intraperitoneal LA was evaluated . MATERIAL AND METHODS Eighty patients were prospect ively r and omised into four groups . In the control group ( G1 ) LA was not used . In G2 all wounds were infiltrated with 80 ml of 0.125 % Bupivacaine containing 5 mg of Phenylephrine . In G3 the wounds were infiltrated with 80 ml of 0.9 % NaCl . In G4 , in addition to wound infiltration with Bupivacaine/Phenylephrine , 200 ml of normal saline , containing 0.15 % of Lidocaine , was left intraperitoneally under the right diaphragm . Postoperative abdominal and shoulder pain scores were recorded on a visual analogue scale ( VAS ) during 24 hours after LC . Narcotic analgesic consumption was also recorded . RESULTS The mean abdominal pain scores were significantly lower in G2 , compared with G3 , 3 to 24 hours after operation , compared with G4 , 3 to 6 hours and compared with G1 , 3 to 24 hours ( except at hour 12 ) after surgery . The incidence of shoulder pain was 30 % . There were no significant differences in the mean shoulder pain scores between the groups . The mean dosage and the total amount of Pethidine at 24 hours were significantly lower in G2 compared with G1 . CONCLUSIONS Intraincisional infiltration with a Bupivacaine/Phenylephrine mixture reduces significantly abdominal postoperative pain ( for up to 24 h ) and narcotic analgesic consumption after LC . An intraperitoneal subdiaphragmatic dilute solution of Lidocaine was not effective in reducing overall pain and shoulder pain after LC OBJECTIVES We aim ed to determine the effects of intraperitoneal administration of levobupivacaine on pain after laparoscopic cholecystectomy in a prospect i ve , r and omized , double-blinded , placebo-controlled trial . METHODS In all patients , infiltration of levobupivacaine 0.25 % ( 15 mL ) was used prior to skin incisions for trocar insertion . After pneumoperitoneum was achieved , patients were allocated r and omly to receive intraperitoneally either 40 mL of 0.25 % levobupivacaine ( LB group , n=20 ) or normal saline ( NS group , n=20 ) under direct vision into the hepatodiaphragmatic lodge and above the gallbladder . Data of intraoperative variables , postoperative pain relief , rescue analgesic consumption , side effects , and patient satisfaction were followed in both groups . RESULTS The postoperative pain scores were significantly lower in the first half-hour period in the LB group than in the NS group ( p<0.05 ) . However , the incidence of right shoulder pain was not significantly different between the LB group ( 10 % ) and NS group ( 15 % ) . The mean dose of meperidine consumption and the number of patients needing rescue meperidine were significantly lower in the LB group than in the NS group ( p<0.05 ) . Significantly lower vomiting incidence and increased patient satisfaction were determined in the LB group compared to the NS group ( p<0.05 ) . CONCLUSION Intraperitoneal administration of 40 mL levobupivacaine 0.25 % given immediately after pneumoperitoneum into the hepatodiaphragmatic lodge and above the gallbladder demonstrated useful effects on postoperative pain relief after laparoscopic cholecystectomy , especially in the early postoperative period , and reduced postoperative rescue analgesic requirement , with excellent patient satisfaction . There were no LB-related complications or side effects Abstract Background A clinical trial was design ed to assess the use of preincisional and intraperitoneal ropivacaine , combined or not with normal saline , to reduce pain after laparoscopic cholecystectomy ( LC ) . Methods For this trial , 120 patients were r and omly assigned to six groups . For all the patients , preincisional local infiltration of ropivacaine around the trocar wounds was performed . Group A had infusion of ropivacaine at the beginning of the LC . Group B had infusion of ropivacaine at the beginning of the LC plus normal saline infusion at the end . Group C had normal saline infusion and ropivacaine at the end of the LC . Group D had infusion of ropivacaine at the beginning of the LC plus normal saline infusion at the end and a subhepatic closed drain . Group E had ropivacaine at the end of the LC . Group F ( control group ) had neither ropivacaine nor normal saline infusion . Shoulder tip and abdominal pain were registered at 2 , 4 , 6 , 12 , 24 , 48 , and 72 h postoperatively using a visual analog score ( VAS ) . Results Significantly lower pain scores were observed in group B than in group A at 2 , 4 , 6 , 12 , and 24 h or in groups C , D , E , and F at 2 , 4 , 6 , 12 , 24 , and 48 h. Group A also had significantly lower pain scores than groups C , D , E , and F at 2 , 4 , 6 , 12 , 24 , and 48 h. Requests for analgesics also were significantly less in group B than in group A at 2 , 4 , 6 , 12 , and 24 h or in groups C , D , and E at 2 , 4 , 6 , 12 , 24 , and 48 h. Dem and for additional analgesia was less in group B than in groups A , C , D , E , and F at 2 , 4 , 6 , 12 , and 24 h and in group A than in groups C , D , E , and F at 2 , 4 , 6 , and 12 h. Conclusion Preincisional local infiltration plus intraperitoneal infusion of ropivacaine at the beginning of LC combined with normal saline infusion at the end of the procedure is a safe and valid method for reducing pain after LC Postoperative pain after laparoscopic surgery is less than after laparotomy , and patients may benefit from an intraperitoneal injection of local anesthetic . Thirty-seven ASA physical status I or II patients received in double-blinded fashion 20 mL of 0.9 % saline solution ( placebo ) , ropivacaine 0.25 % ( Rop 0.25 % ) , or ropivacaine 0.75 % ( Rop 0.75 % ) immediately after trocar placement and at the end of surgery . We measured pain and morphine consumption until 20 h after surgery . Plasma ropivacaine concentrations were measured . The three groups were comparable for shoulder pain , parietal pain , and incidence of side effects . Visceral pain at rest , during cough , and on movement and total consumption of morphine were significantly smaller in Groups Rop 0.25 % and Rop 0.75 % when compared with Placebo . Although no adverse effect occurred in any patient , the largest dose led to large plasma concentrations of ropivacaine ( 2.93 ± 2.46 & mgr;g/mL and 3.76 ± 3.01 & mgr;g/mL after the first and second injection , respectively ) . We conclude that intraperitoneal administration of ropivacaine before and after surgery significantly decreases postoperative pain . Because the smaller dosage ( 2 × 50 mg ) provided similar analgesia and was associated with significantly smaller plasma concentrations than the larger dosage ( 2 × 150 mg ) , this smaller dosage seems more appropriate Laparoscopic cholecystectomy is now widely practised . There are various methods of pain relief used but none has been assessed or compared following this procedure . We have assessed the analgesic effect of intraperitoneal bupivacaine in laparoscopic cholecystectomy . Sixty consecutive patients were r and omly assigned to one of two groups . Patients in group 1 were given 20 ml of saline injected under vision into the region of the gallbladder bed . Patients in group 2 were given 20 ml of 0.25 % bupivacaine in a similar fashion . Postoperative pain was assessed with a visual analogue pain scale and the site of pain was recorded . Patients in the bupivacaine group had less pain in the early postoperative period and a lower incidence of pain in the right hypochondrium . Intraperitoneal bupivacaine is a simple and effective treatment for postoperative pain after laparoscopic cholecystectomy Background The factors affecting cardiorespiratory changes and postoperative pain after laparoscopic cholecystectomy are poorly understood . The aim of this study was to assess these changes in patients undergoing laparoscopic cholecystectomy at an insufflation pressure of 7.5 or 15 mmHg The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials |
10,429 | 24,472,187 | Conclusions The evidence shows that family- and school-based interventions have a considerable effect on treating childhood obesity . | Background The prevalence of childhood obesity , which has seen a rapid increase over the last decade , is now considered a major public health problem .
Current treatment options are based on the two important frameworks of school- and family-based interventions ; however , most research has yet to compare the two frameworks in the treatment of childhood obesity .
The objective of this review is to compare the effectiveness of school-based intervention with family-based intervention in the treatment of childhood obesity .
The review included a r and omised controlled trial and quasi-r and omised controlled trials based on family- and school-based intervention frameworks on the treatment of childhood obesity . | Abstract Objective : To assess if a school based intervention was effective in reducing risk factors for obesity . Design : Group r and omised controlled trial . Setting : 10 primary schools in Leeds . Participants : 634 children aged 7 - 11 years . Intervention : Teacher training , modification of school meals , and the development of school action plans targeting the curriculum , physical education , tuck shops , and playground activities . Main outcome measures : Body mass index , diet , physical activity , and psychological state . Results : Vegetable consumption by 24 hour recall was higher in children in the intervention group than the control group ( weighted mean difference 0.3 portions/day , 95 % confidence interval 0.2 to 0.4 ) , representing a difference equivalent to 50 % of baseline consumption . Fruit consumption was lower in obese children in the intervention group ( −1.0 , −1.8 to −0.2 ) than those in the control group . The three day diary showed higher consumption of high sugar foods ( 0.8 , 0.1 to 1.6 ) ) among overweight children in the intervention group than the control group . Sedentary behaviour was higher in overweight children in the intervention group ( 0.3 , 0.0 to 0.7 ) . Global self worth was higher in obese children in the intervention group ( 0.3 , 0.3 to 0.6 ) . There was no difference in body mass index , other psychological measures , or dieting behaviour between the groups . Focus groups indicated higher levels of self reported behaviour change , underst and ing , and knowledge among children who had received the intervention . Conclusion : Although it was successful in producing changes at school level , the programme had little effect on children 's behaviour other than a modest increase in consumption of vegetables . What is already known on this topic Obesity is increasing among school children and dem and s preventive strategies R and omised controlled trials of school based primary prevention programmes have all used a prescriptive approach What this study adds Behavioural changes were disappointing with this programme based on the health promoting schools philosophy , despite changes at school level The only positive outcome was a modest increase in vegetable consumption The discrepancy between changes achieved at the individual and school level raises issues regarding the problems inherent in such Background : One of the basic principles of behavioral economics interventions is identification of alternative behaviors to compete with the reinforcing value of a highly rewarding commodity . Purpose : Two experiments that attempt to increase alternatives to eating in obese youth are presented . Methods : A r and omized , controlled trial was used in Study 1 to compare a comprehensive family-based behavioral treatment program or an experimental treatment that incorporated reinforcing children for engaging in alternative behaviors to eating for 41 overweight 8-to 12-year-old children . Study 2 used a within-subject design with baseline , enriched environment and a second baseline phase to determine the influence of providing activities that compete with eating for 13 overweight 8-to 12-year-old children . Measurements included body mass index ( BMI ) change , alternatives to eating , eating , and physical activity . Results : In Study I both treatments were associated with significant ( p < .05 ) and maintained reductions in z- BMI over the 24 months of observation . The experimental group showed a significantly ( p < .05 ) greater increase in alternatives to eating , and both groups showed significant ( p < .05 ) increases in physical activity . In Study 2 alternative behaviors to eating were increased by almost I hr/day ( p < .001 ) but were not associated with significant changes in energy intake or physical activity . Conclusion : These results suggest that using the methods studied , increasing behaviors that could compete with eating did not influence relative weight in a clinical outcome study or energy intake in a controlled field study There is a consensus that interventions to prevent and treat childhood obesity should involve the family ; however , the extent of the child 's involvement has received little attention . The goal of the present study was to evaluate the relative efficacy of treating childhood obesity via a family-based health-centred intervention , targeting parents alone v. parents and obese children together . Thirty-two families with obese children of 6 - 11 years of age were r and omised into groups , in which participants were provided for 6 months a comprehensive educational and behavioural programme for a healthy lifestyle . These groups differed in their main agent of change : parents-only v. the parents and the obese child . In both groups , parents were encouraged to foster authoritative parenting styles ( parents are both firm and supportive ; assume a leadership role in the environmental change with appropriate granting of child 's autonomy ) . Only the intervention aim ed at parents-only result ed in a significant reduction in the percentage overweight at the end of the programme ( P=0.02 ) as well as at the 1-year follow-up meeting . The differences between groups at both times were significant ( P<0.05 ) . A greater reduction in food stimuli in the home ( P<0.05 ) was noted in the parents-only group . In both groups , the parents ' weight status did not change . Regression analysis shows that the level of attendance in sessions explained 28 % of the variability in the children 's weight status change , the treatment group explained another 10 % , and the improvement in the obesogenic load explained 11 % of the variability . These results suggest that omitting the obese child from active participation in the health-centred programme may be beneficial for weight loss and for the promotion of a healthy lifestyle among obese children Background Effective interventions to prevent overweight and obesity in children are urgently needed especially in inner-city neighbourhoods where prevalence of overweight and inactivity among primary school children is high . A school based intervention was developed aim ing at the reduction of overweight and inactivity in these children by addressing both behavioural and environmental determinants . Methods / design The main components of the intervention ( Lekker Fit ! ) are the re-establishment of a professional physical education teacher ; three ( instead of two ) PE classes per week ; additional sport and play activities outside school hours ; fitness testing ; classroom education on healthy nutrition , active living and healthy lifestyle choices ; and the involvement of parents . The effectiveness of the intervention is evaluated through a cluster r and omized controlled trial in 20 primary schools among grade s 3 through 8 ( 6–12 year olds ) . Primary outcome measures are BMI , waist circumference and fitness . Secondary outcome measures are assessed in a subgroup of grade 6–8 pupils ( 9–12 year olds ) through classroom question naires and constitute of nutrition and physical activity behaviours and behavioural determinants . Multilevel regression analyses are used to study differences in outcomes between children in the intervention schools and in control schools , taking clustering of children within schools into account . Discussion Hypotheses are that the intervention results in a lower prevalence of children being overweight and an improved mean fitness score , in comparison with a control group where the intervention is not implemented . The results of our study will contribute to the discussion on the role of physical education and physical activity in the school curriculum . Trial registration [ IS RCT N84383524 OBJECTIVE : Family-based , behavioral treatment has been shown to be an effective intervention for the management of pediatric obesity . The goal of this study was to compare the cost-effectiveness of two protocol s for the delivery of family-based behavioral treatment . REA SEARCH METHODS AND PROCEDURES : Thirty-one families with obese children were r and omized to groups in which families were provided mixed treatment incorporating both group and individualized treatment vs group treatment only . Cost-effectiveness of treatment was defined as the magnitude of reduction in st and ardized BMI and percentage overweight per dollar spent for recruitment and treatment . Anthropometric data were assessed at baseline , 6 months and 12 months post-r and omization . RESULTS : Results for the 24 families with complete data showed the group intervention was significantly more cost-effective than the mixed treatment . This was due to the similarity between the two groups in Z- BMI or percentage overweight change for children and their parents , while the mixed treatment was significantly more expensive to deliver than the group treatment . DISCUSSION : These findings suggest that a family-based , behavioral intervention employing group treatment alone is a more cost-effective approach to treating pediatric obesity than a mixed group plus individual format OBJECTIVE : We evaluated the efficacy of family-based , behavioral weight control in the management of severe pediatric obesity . METHODS : Participants were 192 children 8.0 to 12.0 years of age ( mean ± SD : 10.2 ± 1.2 years ) . The average BMI percentile for age and gender was 99.18 ( SD : 0.72 ) . Families were assigned r and omly to the intervention or usual care . Assessment s were conducted at baseline , 6 months , 12 months , and 18 months . The primary outcome was percent overweight ( percent over the median BMI for age and gender ) . Changes in blood pressure , body composition , waist circumference , and health-related quality of life also were evaluated . Finally , we examined factors associated with changes in child percent overweight , particularly session attendance . RESULTS : Intervention was associated with significant decreases in child percent overweight , relative to usual care , at 6 months . Intent-to-treat analyses documented that intervention was associated with a 7.58 % decrease in child percent overweight at 6 months , compared with a 0.66 % decrease with usual care , but differences were not significant at 12 or 18 months . Small significant improvements in medical outcomes were observed at 6 and 12 months . Children who attended ≥75 % of intervention sessions maintained decreases in percent overweight through 18 months . Lower baseline percent overweight , better attendance , higher income , and greater parent BMI reduction were associated with significantly greater reductions in child percent overweight at 6 months among intervention participants . CONCLUSIONS : Intervention was associated with significant short-term reductions in obesity and improvements in medical parameters and conferred longer-term weight change benefits for children who attended ≥75 % of sessions Introduction This study assessed the short- and long-term effects of a 3-month family-based group treatment in the management of childhood obesity versus individual treatment . Material s and methods Eighty obese children , aged between 6 and 14 years , and their parents were included in this prospect i ve controlled clinical study . Forty participants were r and omly assigned for group treatment and the other 40 for individual treatment . A 3-month intervention program was focused on implementing healthy eating behaviors . The weight and height of the children were measured initially and at each treatment session and at follow-up visits . Body mass index was calculated and expressed as st and ard deviation score . Results and discussion At the end of 3-month treatment program , there was a significant decline in BMI SDS in both groups ( p < 0.001 ) . After 1 year of follow-up period , there was still a significant decrease in BMI SDS in the study group ( p < 0.001 ) , whereas the decrease in BMI SDS was not maintained over the follow-up period in the st and ard group . There was a significantly increased consumption of vegetable and fruit and reduced consumption of carbonated drinks and fruit juice in both groups ( p < 0.001 ) . Conclusion These findings demonstrate that the group treatment is more successful than the individual treatment in the management of childhood obesity Background : Childhood obesity has become a nutritional problem in China since the 1990s . Aims : A family based behavioural treatment was developed and tested , to see if its use was feasible in China and to evaluate its impact on obese schoolchildren . Methods : In a single school in Beijing , 33 obese children were r and omly assigned to a treatment group and 35 to a control group . The treatment group participated in a family based behavioural treatment programme for two years . Height and weight were measured every six months for all participants . Blood pressure , cholesterol , and triglyceride levels were measured at baseline and after two years of programme implementation . Results : Body mass index ( BMI , kg/m2 ) was significantly reduced in the treatment group ( from 26.6 ( 1.7 ) to 24.0 ( 0.9 ) , 95 % CI 2.06 to 3.18 ) but not in the control group ( from 26.1 ( 1.5 ) to 26.0 ( 1.6 ) ) . Total cholesterol decreased 5.5 % and triglycerides 9.7 % in the treatment group . There was a significant correlation between change in BMI and change in triglycerides . There were no significant changes in plasma lipids in the controls . Blood pressure values also decreased significantly in the treatment , but not the control group . Conclusions : A family based behavioural intervention was feasible to use in treating obesity in schoolchildren in Beijing , China . After two years of implementation , it successfully decreased the degree of obesity , reduced levels of blood pressure , and decreased serum lipids in treatment ; there were no significant changes among control children BACKGROUND Obesity and poor physical fitness constitute a health problem affecting an increasing number of children . Causes include a pervasive " toxic " environment that facilitates increased caloric intake and reduced physical activity . An effective strategy for prevention and treatment of childhood obesity likely includes a collaborative effort in the school setting . OBJECTIVE To determine whether a school-based fitness program can improve body composition , cardiovascular fitness level , and insulin sensitivity in overweight children . DESIGN Fifty overweight middle school children with a body mass index ( BMI ) above the 95th percentile for age were r and omized to lifestyle-focused , fitness-oriented gym classes ( treatment group ) or st and ard gym classes ( control group ) for 9 months . Children underwent evaluation of fasting insulin and glucose levels , body composition by means of dual energy absorptiometry , and maximum oxygen consumption ( V0(2)max ) treadmill testing at baseline ( before the school year ) and at end of the school year . SETTING S Rural middle school and an academic children 's hospital . MAIN OUTCOME MEASURES Baseline test results for cardiovascular fitness , body composition , and fasting insulin and glucose levels . RESULTS At baseline , there were no differences between groups before intervention ( values for age , 12 + /- 0.5 years [ all results , mean + /- SD ] ; BMI [ calculated as weight in kilograms divided by the square of height in meters ] , 31.0 + /- 3.7 ; percentage of body fat , 36.5 % + /- 4.6 % ; lean body mass , 41.4 + /- 8.6 kg ; and V0(2)max , 31.5 + /- 5.1 mL/kg per minute ) . Compared with the control group , the treatment group demonstrated a significantly greater loss of body fat ( loss , -4.1 % + /- 3.4 % vs -1.9 % + /- 2.3 % ; P = .04 ) , greater increase in cardiovascular fitness ( V0(2)max , 2.7 + /- 2.6 vs 0.4 + /- 3.3 mL/kg per minute ; P<.001 ) , and greater improvement in fasting insulin level ( insulin level , -5.1 + /- 5.2 vs 3.0 + /- 14.3 microIU/mL [ -35.4 + /- 36.1 vs 20.8 + /- 99.3 pmol/L ] ; P = .02 ) . CONCLUSIONS Children enrolled in fitness-oriented gym classes showed greater loss of body fat , increase in cardiovascular fitness , and improvement in fasting insulin levels than control subjects . The modification to the school physical education curriculum demonstrates that small but consistent changes in the amount of physical activity has beneficial effects on body composition , fitness , and insulin levels in children . Partnering with school districts should be a part of a public health approach to improving the health of overweight children Childhood overweight has increased significantly in the past 20 years , with the highest rates noted among Mexican Americans . Schools are an optimal setting for intervention efforts ; however , few programs have demonstrated actual decreases in weight . This study evaluated an intensive school-based program design ed to result in weight reduction for overweight Mexican American children . A total of 71 children ( 32 males , 48 % ) between the ages of 10 and 14 at or above the 85th percentile for body mass index ( BMI ) were r and omized into a six-month intensive intervention ( II ) or self-help ( SH ) condition . Results revealed that children in the II condition significantly reduced their st and ardized BMI ( z BMI ) when compared with the children in the self-help condition ( F(2,62)=6.58 , p=0.003 ) . The change in z BMI was significantly different at both 3 and 6 months ( F(1,63)=5.74 , p=0.019 , F(1,63)=12.61 , p=0.001 , respectively ) with II participants showing greater decreases in weight . The 3-month change in z BMI for the II participants was a decrease of 0.07 compared with a decrease of 0.01 for SH participants . The 6-month change in z BMI was a decrease of 0.11 for II and an increase of 0.03 for SH . Overall , the results are promising , suggesting that an intensive school-based intervention may be an effective means for promoting weight loss in overweight Mexican American children Childhood obesity may be lessened by parent-focused interventions . A pilot parent-directed trial with 46 parents of overweight and obese elementary school students was conducted at two ethnically diverse public schools in Framingham , Massachusetts . Parents were r and omly assigned to either the Material s Group , which received mailed educational material s , or the Material s plus Personal Encounters Group , which received educational material s through interactions with community health workers ( CHWs ) . Parents completed baseline and post-intervention surveys ; children ’s body mass index ( BMI ) percentiles were measured at baseline and post-intervention . There were no differences in the reduction of children ’s BMI between groups . However , the mean BMI percentile for all children dropped from 94.1 to 90.6 ( p = .005 ) , while there was no change in BMI among a nonr and omized contemporaneous control group . Findings are limited by the lack of a true control group and small sample size . Results from this school nurse and CHW outreach program to parents are encouraging The aim of this study was to evaluate the effectiveness of the Mind , Exercise , Nutrition , Do it ( MEND ) Program , a multicomponent community-based childhood obesity intervention ( www.mend central .org ) . One hundred and sixteen obese children ( BMI > or= 98 th percentile , UK 1990 reference data ) were r and omly assigned to intervention or waiting list control ( 6-month delayed intervention ) . Parents and children attended eighteen 2-h group educational and physical activity sessions held twice weekly in sports centers and schools , followed by a 12-week free family swimming pass . Waist circumference , BMI , body composition , physical activity level , sedentary activities , cardiovascular fitness , and self-esteem were assessed at baseline and at 6 months . Children were followed up 12 months from baseline ( 0 and 6 months postintervention for the control and intervention group , respectively ) . Participants in the intervention group had a reduced waist circumference z-score ( -0.37 ; P < 0.0001 ) and BMI z-score ( -0.24 ; P < 0.0001 ) at 6 months when compared to the controls . Significant between-group differences were also observed in cardiovascular fitness , physical activity , sedentary behaviors , and self-esteem . Mean attendance for the MEND Program was 86 % . At 12 months , children in the intervention group had reduced their waist and BMI z-scores by 0.47 ( P < 0.0001 ) and 0.23 ( P < 0.0001 ) , respectively , and benefits in cardiovascular fitness , physical activity levels , and self-esteem were sustained . High-attendance rates suggest that families found this intensive community-based intervention acceptable . Further larger controlled trials are currently underway to confirm the promising findings of this initial trial BACKGROUND Childhood obesity has become a health problem in urban areas in China . Intervention to reduce childhood obesity should be of high priority . School-based intervention programmes are needed to deal with the growing prevalence of childhood obesity in China . METHODS Five primary schools were selected r and omly for this study in the Beijing urban area in China ; two were allocated to the intervention group and three to the control group . A total of 2425 children ( 1029 children in intervention schools and 1396 children in control schools ) took part in the study for 3 years . In the intervention group , children and their parents were involved in a programme of nutrition education and physical activity . Control school students followed their usual health and physical education curriculum with no extra intervention . RESULTS After the 3-year intervention , the prevalence of overweight and obesity were significantly lower in the intervention schools than in the control schools ( overweight : 9.8 % vs. 14.4 % , P < 0.01 ; obesity : 7.9 % vs. 13.3 % , P < 0.01 ) . The prevalence of overweight and obesity decreased by 26.3 % and 32.5 % in intervention schools respectively after intervention . The prevalence of overweight and obesity increased in control schools . There was also significant difference in body mass index between intervention and control schools ( 18.2 + /- 2.6 vs. 20.3 + /- 3.4 , P < 0.01 ) after intervention . More non-obese children became obese in the control schools ( 7.0 % ) than in the intervention schools ( 2.4 % ) at end line ( P < 0.01 ) . Among the children who were obese at baseline , 49.2 % remained obese at end line in intervention schools while 61.9 % remained obese in control schools ( P < 0.01 ) . CONCLUSIONS Our study showed that an intervention programme could be feasible in schools in Beijing , China . The prevalence of overweight and obesity was reduced in schoolchildren in Beijing through an intervention focused on nutrition education and physical activity . Overweight and obesity children as well as normal weight children and their parents should be involved in such an intervention programme OBJECTIVE The authors performed a group-based program for obese children and adolescents in Bavaria , Germany to enable them to establish a health-oriented lifestyle and to reduce overweight . The authors compared this program with a control approach based on the patients ' own initiative . DESIGN This is a controlled clinical trial . SETTING A nutrition program for out patients in a German university hospital . PARTICIPANTS Seventy-three obese patients aged 7 to 15 years ( mean 11.2 years ) were recruited by pediatricians and local newspaper reports and r and omized into intervention and control groups . Children and adolescents in each group were divided into 3 groups according to age--7 - 8 years , 9 - 10 years , and 11 - 13 years . Children were classified overweight ( defined as body mass index ( BMI ) > 90th percentile for age and gender ) , obese ( BMI > 97th percentile ) , and extremely obese ( BMI > 99.5th percentile ) , according to the European Childhood Obesity Group and the German Working Group on Pediatric Obesity , congruent with adult st and ards used to assess overweight and obesity . INTERVENTION Thirty-seven patients ( age 7 - 13 years , mean 10.9 years ) for the 1-year intervention . This intervention consisted of modules for physical activity , nutritional education , and coping strategies . The program was performed twice each week and incorporated parental participation and medical supervision , including laboratory tests . The obese controls ( n = 36 , age 8 - 15 years , mean 11.6 years ) received written therapeutic advice during a visit at 0 and 6 months in the outpatient clinic . MAIN OUTCOME MEASURE The primary outcome variable was the body mass index ( BMI ) z score . ANALYSIS Analysis of variance and t test were used , and a P value < .05 was considered significant . RESULTS There was a reduction of BMI z score in the active treatment group ( P < .05 ) , but not for controls . Moreover , the active group showed beneficial effects for body mass index ( BMI ) , fat mass , and systolic blood pressure 12 months after beginning the intervention . CONCLUSIONS AND IMPLICATION S Group-based programs for young , obese patients can be effective tools for establishing a health-oriented lifestyle and reducing the burden of obesity CONTEXT Metformin therapy for adults and children with type 2 diabetes is well established . However , its role in the treatment of insulin resistance and obesity in children and adolescents is less clearly defined . OBJECTIVE We assessed the effect of metformin on body composition and insulin sensitivity in pediatric subjects with exogenous obesity . DESIGN AND SETTING Patients referred to a pediatric endocrine clinic were enrolled in a r and omized , double-blind , crossover trial . PATIENTS Twenty-eight patients ( 13 males ) aged 9 - 18 yr participated in the study . INTERVENTION Patients received metformin ( 1 g twice daily ) and placebo for 6 months , each with a 2-wk washout period . MAIN OUTCOME MEASURES Body composition ( anthropometry , dual-energy x-ray absorptiometry , and abdominal magnetic resonance imaging ) , and insulin sensitivity ( Si ; minimal model , fasting insulin and glucose ) were measured at baseline and 6 and 12 months . RESULTS Mean age of subjects at baseline was 12.5 + /- 2.2 yr , median body mass index z-score 2.54 ( range , 1.93 - 2.85 ) . Metformin had a greater treatment effect over placebo for weight ( -4.35 kg , P = 0.02 ) , body mass index ( -1.26 kg/m(2 ) , P = 0.002 ) , waist circumference ( -2.8 cm , P = 0.003 ) , sc abdominal adipose tissue ( -52.5 cm(2 ) , P = 0.002 ) , and fasting insulin ( -2.2 mU/liter , P = 0.011 ) . Si improved in 45 % of subjects while on metformin and 27 % of subjects while on placebo ( P = 0.21 ) . CONCLUSIONS Metformin therapy for obese insulin-resistant pediatric patients results in significant improvement in body composition and fasting insulin . Although improvement in Si was noted in many individuals , Si was a less useful parameter for analysis of group data , possibly because of effects of variable compliance and changing Si during puberty OBJECTIVE To evaluate the 4-year outcome of a school-based health promotion on weight status as part of the Kiel Obesity Prevention Study ( KOPS ) . RESEARCH METHODS AND PROCEDURES Within a cluster- sample d quasi-r and omized controlled trial , 1764 children at 6 and 10 years of age were assessed between 1996 and 2005 in 32 primary schools in Kiel , North Germany . Six nutrition units followed by 20-minute running games were performed within the first year at school . Prevalence , incidence , and remission of overweight were main outcome measures . RESULTS The 4-year change in BMI was + 11.6 % , with increases in prevalence of overweight and obesity from 5.2 % to 11.1 % and 3.9 % to 5.1 % , respectively . Cumulative 4-year incidence of overweight and obesity was 9.2 % and 3.1 % , respectively . Intervention had no effect on mean BMI . The effect on prevalence was significant in children from families with high socioeconomic status [ odds ratio ( OR ) , 0.35 ; 95 % confidence interval ( CI ) , 0.14 to 0.91 ] and marginally significant in children of normal-weight mothers ( OR , 0.57 ; 95 % CI , 0.33 to 1.00 ) . Cumulative 4-year incidence of overweight was lower only in intervention children from families with high socioeconomic status ( OR , 0.26 ; 95 % CI , 0.07 to 0.87 ) . Remission of overweight was most pronounced in children of normal-weight mothers ( OR , 5.43 ; 95 % CI , 1.28 to 23.01 ) . Prevalence of underweight was unchanged . The intervention had minor but favorable effects on lifestyle . DISCUSSION A school-based health promotion has sustainable effects on remission and incidence of overweight ; it was most pronounced in children of normal-weight mothers and children from families with high socioeconomic status . There was no effect on obesity . The data argue in favor of additional measures of prevention Objective : To develop and evaluate “ Families for Health ” , a new community based family intervention for childhood obesity . Design : Programme development , pilot study and evaluation using intention-to-treat analysis . Setting : Coventry , Engl and . Participants : 27 overweight or obese children aged 7–13 years ( 18 girls , 9 boys ) and their parents , from 21 families . Intervention : Families for Health is a 12-week programme with parallel groups for parents and children , addressing parenting , lifestyle change and social and emotional development . Main outcome measures : Change in baseline BMI z score at the end of the programme ( 3 months ) and 9-month follow-up . Attendance , drop-out , parents ’ perception of the programme , child ’s quality of life and self-esteem , parental mental health , parent – child relationships and lifestyle changes were also measured . Results : Attendance rate was 62 % , with 18 of the 27 ( 67 % ) children completing the programme . For the 22 children with follow-up data ( including four who dropped out ) , BMI z score was reduced by −0.18 ( 95 % CI −0.30 to −0.05 ) at 3 months and −0.21 ( −0.35 to −0.07 ) at 9 months . Statistically significant improvements were observed in children ’s quality of life and lifestyle ( reduced sedentary behaviour , increased steps and reduced exposure to unhealthy foods ) , child – parent relationships and parents ’ mental health . Fruit and vegetable consumption , participation in moderate/vigorous exercise and children ’s self-esteem did not change significantly . Topics on parenting skills , activity and food were rated as helpful and used with confidence by most parents . Conclusions : Families for Health is a promising new childhood obesity intervention . Definitive evaluation of its clinical effectiveness by r and omised controlled trial is now required |
10,430 | 16,775,498 | Fecal calprotectin correlates well with histological inflammation as detected by colonoscopy with biopsies and has been shown successfully to predict relapses and detect pouchitis in patients with IBD .
Fecal calprotectin has been shown to consistently differentiate IBD from irritable bowel syndrome because it has excellent negative predictive value in ruling out IBD in undiagnosed , symptomatic patients .
Fecal calprotectin also may be useful in determining whether clinical symptoms in patients with known IBD are caused by disease flares or noninflammatory complications/underlying irritable bowel syndrome and in providing objective evidence of response to treatment . | Calprotectin is an abundant neutrophil protein found in both plasma and stool that is markedly elevated in infectious and inflammatory conditions , including inflammatory bowel disease ( IBD ) .
We conducted a systematic review of the published literature regarding fecal calprotectin to evaluate its potential as a noninvasive marker of neutrophilic intestinal inflammation .
Reference ranges for fecal calprotectin have been established in healthy adults and children , and elevated concentrations of fecal calprotectin have been demonstrated in numerous studies of patients with IBD . | OBJECTIVE : Fecal calprotectin concentration in stool has recently been proposed as a marker of colonic neoplasm and inflammation , but the intraindividual day-to-day variability has so far received little attention . The present study was undertaken to determine the biological variability of fecal calprotectin in patients referred for colonoscopy . METHODS : A prospect i ve design was applied . In each of 14 consecutive patients su bmi tted for colonoscopy , eight stool sample s were collected before the endoscopy . A detailed question naire was used . Calprotectin was measured by quantitative enzyme-linked immunoassay , and st and ard deviation for the within-patient variability was estimated from one-way analysis of variance . RESULTS : In absence of colonic neoplasm and inflammation , two population s of patients emerged : one ( 36 % ) with remarkably low and stable fecal calprotectin values all within the recommended cut-off of 50 μg/g , and one ( 64 % ) with labile values also beyond this limit . In this latter group , fecal calprotectin was 70 μg/g ( mean ) ( single tests ranged from 9 to 461 ) , and SD within patients was 52 μg/g , showing considerable day-to-day variation . History , concurrent diseases , or findings at colonoscopy could not explain labile values . A similar pattern was observed for spot variation in one stool sample from healthy volunteers , suggesting that factors other than disease contribute to the significant intraindividual biological variation of fecal calprotectin . CONCLUSIONS : Day-to-day variation of fecal calprotectin is considerable in patients without colonic inflammation or neoplasm , for whom the pattern of stabile low fecal calprotectin may seem to be a valid negative predictor . The origin and pattern of fecal calprotectin excretion deserve further attention BACKGROUND The diagnosis of non-steroidal anti-inflammatory drug ( NSAID ) induced enteropathy is difficult , requiring enteroscopy or the use of four day faecal excretion of 111In labelled white cells . AIMS To assess faecal calprotectin ( a non-de grade d neutrophil cytosolic protein ) as a method for diagnosing NSAID enteropathy . METHODS Single stool faecal calprotectin concentrations were compared with the four day faecal excretion of 111In labelled white cells in 47 patients taking NSAIDs . The prevalence and severity of NSAID enteropathy was assessed using this method in 312 patients ( 192 with rheumatoid arthritis , 65 with osteoarthritis , 55 with other conditions ) taking 18 different NSAIDs . RESULTS The four day faecal excretion of 111In white cells correlated significantly with faecal calprotectin concentrations . In the group of 312 patients on NSAIDs faecal calprotectin concentrations were significantly higher than in controls , the prevalence of NSAID enteropathy being 44 % . The prevalence and severity of NSAID enteropathy was independent of the particular type or dose of NSAID being taken or other patient variables . CONCLUSIONS Assay of faecal calprotectin provides a simple practical method for diagnosing NSAID enteropathy in man . Forty four per cent of patients receiving these drugs had NSAID induced enteropathy when assessed by this technique ; 20 % of these had comparable levels of inflammation to that previously reported in patients with inflammatory bowel disease Background : Calprotectin , a major component of soluble cytosolic proteins in human neutrophil granulocytes , is excreted in excess in stools during inflammatory bowel disease in adults and children . Faecal calprotectin concentrations are also higher during the first year of life than in adults . Objectives : To measure faecal calprotectin concentrations in the neonatal period and define reference values according to the mode of feeding : st and ard infant formula , prebiotic infant formula ( Calisma , Blédina SA , France ) , or breast feeding . Patients and methods : A prospect i ve study was carried out over three months in 69 full term , healthy newborns with a median gestational age of 39.8 weeks ( range 37–41.5 ) and a birth weight of 3300 g ( range 2600–4460 ) . Three groups were formed depending on the mode of feeding : group 1 ( n = 18 ) received a st and ard infant formula , group 2 ( n = 19 ) the prebiotic infant formula , and group 3 ( n = 32 ) was breast fed . One stool sample was taken from each newborn on day 4 ( 3–7 ) , and faecal calprotectin analysed using a commercial enzyme linked immunoassay ( Calprest , Eurospital , Italy ) . Results : Faecal calprotectin concentrations ( median 167 µg/g ) were higher than reference values in healthy adults . The concentration was below the upper reference limit for adults ( 50 µg/g ) for three infants only , one fed the st and ard formula and two fed the prebiotic formula . Concentrations did not differ significantly according to method of feeding . Conclusions : Compared with healthy adults , newborns have high calprotectin concentrations in the first days of life . There is no obvious influence of the mode of feeding The mucosa of the pelvic ileal reservoir undergoes adaptive changes -- inflammatory , architectural , and metaplastic -- on exposure to the faecal stream . Twenty three quadruple loop ileal pouches constructed for ulcerative colitis ( 20 patients ) and familial adenomatous polyposis ( FAP ) ( three patients ) were studied . No patient fulfilled clinical , endoscopic , or histopathological criteria for pouchitis . St and ard duplicate biopsy specimens were taken from the proximal limb , the anterior wall , the posterior wall , and the body of the reservoir . An established scoring system was used and showed a highly significant increase in inflammatory scores in posterior wall biopsy specimens compared with those from the anterior wall . These results suggest that the adaptive changes are the direct result of contact with static faecal contents . One patient only showed significant inflammation in the proximal limb . There was no evidence of mucosal prolapse in any anterior wall biopsy specimen . Patients with colitis showed substantially more inflammatory and architectural changes than those with FAP . Ninety six per cent of pouches showed some colonic phenotypic expression as defined by mucin histochemical and PR 3A5 immunohistochemical studies . Our results suggest , however , that there may not be complete colonic metaplasia and that the mucin changes and other phenotypic alterations may represent a non-specific response to pouch inflammation and not a prerequisite for the development of pouchitis . The focal nature of the inflammatory and architectural changes , which may be the result of direct contact with static faecal residue , are clearly shown . A single r and om biopsy specimen of pouch mucosa is of limited value in assessing pathological changes and screening for potential neoplastic change within the reservoir Backgound : Patients being investigated for symptoms of abdominal pain , diarrhoea and or weight loss often undergo small bowel radiology as part of their diagnostic workup mainly to exclude inflammatory bowel disease OBJECTIVES : Stool testing is a well established method of screening for colorectal neoplasia . Emerging data suggest that novel biomarkers may offer performance advantages over fecal occult blood . In this large , prospect i ve study , we assessed fecal calprotectin ( a leukocyte-derived protein ) as a screening biomarker for colorectal neoplasia . Fecal calprotectin was directly compared to fecal hemoglobin ( Hb ) and colonoscopy as the existing criterion st and ards for stool screening and structural evaluation , respectively . METHODS : Subjects included colonoscopy patients with a personal history of colorectal neoplasia , family history of colorectal cancer , or iron deficiency anemia . Stool specimens were collected before purgation , processed appropriately , and quantitatively analyzed for calprotectin ( Nycomed Pharma , Oslo , Norway ) and for Hb ( Mayo Medical Laboratories , Rochester , MN ) by masked technicians . Colonoscopies were performed by experienced endoscopists without prior knowledge of the fecal assay results . RESULTS : Among 412 subjects , 97 ( 24 % ) subjects had one or more colorectal neoplasms ( including three with adenocarcinomas ) . Fecal calprotectin levels did not differ significantly between subjects with versus subjects without colorectal neoplasms ( p= 0.33 ) . Neither tumor number ( p= 0.85 ) nor tumor size ( p= 0.86 ) significantly influenced the observed fecal calprotectin concentrations . Estimates of the sensitivity , specificity , and positive and negative predictive values of fecal calprotectin for any colorectal neoplasms were 37 % , 63 % , 23 % , and 76 % , respectively . Comparable performance estimates for fecal Hb were 3 % , 97 % , 27 % , and 77 % , respectively . CONCLUSIONS : In this cohort of colonoscopy patients at above average risk , fecal calprotectin was a poor screening biomarker for colorectal neoplasia . Further investigation of tumor-derived , rather than blood-based , biomarkers may be a more rewarding approach to stool screening for colorectal neoplasia Background : Screening for colorectal cancer ( CRC ) using guaiac based faecal occult blood tests ( FOBT ) has an estimated programme sensitivity of > 60 % but < 30 % for strictly asymptomatic CRC in a single screening round . In search for improved non-invasive tests for screening , we compared a test for faecal calprotectin ( PhiCal ) with a human haemoglobin immunochemical FOBT ( FlexSure OBT ) . Methods : In the Norwegian Colorectal Cancer Prevention ( NORCCAP ) trial , screenees in one screening arm were offered screening with combined flexible sigmoidoscopy ( FS ) and FlexSure OBT . They were also requested to bring a fresh frozen sample of stool for the PhiCal test which was performed on sample s from screenees with CRC ( n = 16 ) , high risk adenoma ( n = 195 ) , low risk adenoma ( n = 592 ) , and no adenoma ( n = 1518 ) ( 2321 screenees in total ) . A positive PhiCal test was defined by a calprotectin level ⩾50 μg/g . Results : The PhiCal test was positive in 24–27 % of screenees whether they had no adenoma , low risk adenoma , or high risk adenoma . Ten ( 63 % ) of 16 CRCs gave a positive PhiCal test . The total positivity rate in this population was 25 % for the PhiCal test compared with 12 % for FlexSure OBT , with a sensitivity for advanced neoplasia of 27 % and 35 % , respectively . Specificity for “ any neoplasia ” was 76 % for the PhiCal test and 90 % for FlexSure OBT . Conclusions : In colorectal screening , the performance of the PhiCal test on a single spot from one stool sample was poorer than a single screening round with FlexSure OBT and can not be recommended for population screening purpose s. The findings indicate a place for FlexSure OBT in FOBT screening The Pediatric Crohn 's Disease Activity Index ( PCDAI ) has been proposed as a simple instrument to aid in the classification of patients by disease severity . The PCDAI includes subjective patient reporting of symptoms , physical examination , nutritional parameters , and several common laboratory tests ( hematocrit , erythrocyte sedimentation rate , albumin ) . In this report we examine the relationship of each of the laboratory parameters to the PCDAI , as well as to a modified Harvey-Bradshaw Index score and physician global assessment of disease activity . Data were gathered from the clinical and laboratory observations from 133 children and adolescents at 12 pediatric gastroenterology centers in North America . A statistically significant relationship ( p < 0.05 ) was noted between each of the laboratory tests and the PCDAI for patients with either disease limited to the small bowel or in those with colonic in volvement . For patients with disease limited to the small bowel , a statistically significant ( p < 0.05 ) relationship was also noted between the three laboratory parameters and the modified Harvey-Bradshaw Index and global assessment . For patients with large-bowel involvement , the erythrocyte sedimentation rate was statistically related to the modified Harvey-Bradshaw Index and global assessment ( p < 0.01 ) , as was hematocrit to global assessment ( p < 0.01 ) . Although the laboratory parameters used in the PCDAI appear to generally reflect disease activity in most patients , no single laboratory test is adequate to reflect disease activity in all patients . Future work will need to identify additional laboratory measures to reflect the inflammatory process and serve as important adjuncts in the assessment of disease activity BACKGROUND AND AIMS Assessing the presence and degree of intestinal inflammation objective ly , simply , and reliably is a significant problem in gastroenterology . We assessed faecal excretion of calprotectin , a stable neutrophil specific marker , as an index of intestinal inflammation and its potential use as a screening test to discriminate between patients with Crohn 's disease and those with irritable bowel syndrome . METHODS The validity of faecal calprotectin as a marker of intestinal inflammation was assessed in 22 patients with Crohn 's disease ( 35 studies ) by comparing faecal excretions and concentrations using four day faecal excretion of111indium white cells . A cross sectional study assessed the sensitivity of faecal calprotectin concentration for the detection of established Crohn 's disease ( n=116 ) . A prospect i ve study assessed the value of faecal calprotectin in discriminating between patients with Crohn 's disease and irritable bowel syndrome in 220 patients referred to a gastroenterology clinic . RESULTS Four day faecal excretion of 111indium ( median 8.7 % ; 95 % confidence interval ( CI ) 7–17 % ; normal < 1.0 % ) correlated significantly ( p<0.0001 ) with daily ( median ranged from 39 to 47 mg ; normal <3 mg ; r=0.76–0.82 ) and four day faecal calprotectin excretion ( median 101 mg ; 95 % CI 45–168 mg ; normal < 11 mg ; r=0.80 ) and single stool calprotectin concentrations ( median 118 mg/l ; 95 % CI 36–175 mg/l ; normal < 10 mg/l ; r=0.70 ) in patients with Crohn 's disease . The cross sectional study showed a sensitivity of 96 % for calprotectin in discriminating between normal subjects ( 2 mg/l ; 95 % CI 2–3 mg/l ) and those with Crohn 's disease ( 91 mg/l ; 95 % CI 59–105 mg/l ) . With a cut off point of 30 mg/l faecal calprotectin has 100 % sensitivity and 97 % specificity in discriminating between active Crohn 's disease and irritable bowel syndrome . CONCLUSION The calprotectin method may be a useful adjuvant for discriminating between patients with Crohn 's disease and irritable bowel syndrome UNLABELLED The aim of this prospect i ve study was to compare five different leukocyte proteins in feces of patients with chronic inflammatory bowel disease ( IBD ) , irritable bowel syndrome ( IBS ) and healthy persons who underwent prophylactic colonoscopy . METHODS The leukocyte proteins calprotectin , lactoferrin , lysozyme , myeloperoxidase , and PMN-elastase were determined with immunoassays in fecal sample s of three consecutive feces ( e.g. three days ) in 40 healthy persons , 39 patients with chronic IBD ( of these 21 with Crohn 's disease and 18 with ulcerative colitis ) , and 40 patients with IBS . RESULTS ROC curves calculated for healthy persons and patients with IBD yielded the following areas under the curves ( AUCs ) : PMN-elastase 0.916 , calprotectin 0.872 , myeloperoxidase 0.750 , lysozyme 0.726 , and lactoferrin 0.693 . The AUCs of PMN-elastase and calprotectin were not significantly different ( p = 0.327 ) , whereas PMN-elastase or calprotectin vs. the other proteins were significantly different ( p < 0.001 ) . PMN-elastase and calprotectin correlated with the endoscopically classified severity of inflammation . All fecal leukocyte markers in IBS were found in the range of the healthy persons . Data on storage stability of leukocyte proteins in fecal supernatants are given . CONCLUSION Fecal PMN-elastase and calprotectin support the differentiation of chronic IBD from IBS and correlate with the severity of inflammation BACKGROUND & AIMS Increased stool frequency , urgency , and abdominal pain in patients with ileal pouch-anal anastomosis ( IPAA ) may be due to inflammatory conditions , including pouchitis , cuffitis , or Crohn 's disease or noninflammatory conditions such as irritable pouch syndrome . Distinction among these entities requires pouch endoscopy and biopsy . Noninvasive means of diagnosis are preferable . METHODS Sixty consecutive subjects with IPAA for inflammatory bowel disease had measurements of fecal lactoferrin and alpha1-antitrypsin and underwent pouch endoscopy with biopsy , with calculation of the pouchitis disease activity index in a prospect i ve cross-sectional study . RESULTS Symptomatic patients with an inflammatory condition had significantly higher fecal lactoferrin concentrations ( median , 176.0 microg/mL , interquartile range [ IQR ] 79.0 - 450.8 ) compared with those with a noninflammatory condition ( median , 4.8 microg/mL ; IQR , 1.2 - 11.0 ) or those who were asymptomatic ( median , 7.8 microg/mL ; IQR , 1.4 - 12.9 ) , P < 0.001 . At a cutoff level of 7 microg/mL , fecal lactoferrin could distinguish patients with irritable pouch syndrome from those with pouchitis , cuffitis , or Crohn 's disease with a sensitivity of 100 % and specificity of 85 % . Fecal alpha1-antitrypsin was not able to distinguish symptomatic patients with and without an inflammatory condition . CONCLUSIONS Fecal lactoferrin can serve as a sensitive and noninvasive initial screening test in an algorithm for evaluation of symptomatic patients with IPAA . If fecal lactoferrin levels are low ( < 7 microg/mL ) , IPS can be diagnosed . If fecal lactoferrin levels are high , pouch endoscopy with biopsy is warranted to distinguish among different causes of inflammation . Longitudinal studies are needed to define better the role of this test in the management of patients with IPAA Needing a single index of degree of illness in Crohn 's disease , the National Cooperative Crohn 's Disease Study group collected data prospect ively from 187 visits of 112 patients with Crohn 's disease of the small bowel , colon , or both . Information on 18 predictor variables was gathered at each visit . In addition , the attending physician rated his over-all evaluation of how well the patient was doing and compared the patient 's status with that at the previous visit . A multiple regression computer program was utilized to derive an equation for prediction of the physician 's over-all ratings from a subset of the predictor variables fulfilling a combination of constraints . This equation , numerically simplified and utilizing eight selected variables , is the Crohn 's Disease Activity Index . Index values of 150 and below are associated with quiescent disease ; values above that indicate active disease , and values above 450 are seen with extremely severe disease OBJECTIVE : Chronic diarrhea is a relatively common condition with multiple diverse etiologies . Stool testing may serve as a diagnostic aid to discriminate the presence or absence of organic pathology , such as colorectal inflammation . Calprotectin ( a leukocyte-derived protein ) and hemoglobin can be measured quantitatively from stool and represent c and i date inflammation biomarkers . The aim of this study was to assess and compare the screening performance of fecal calprotectin and fecal hemoglobin among colonoscopy referral patients with chronic diarrhea of unknown origin or chronic colitis of unknown activity . METHODS : All subjects were identified prospect ively and each su bmi tted a single stool sample before purgation . Fecal calprotectin ( PhiCal ; Nycomed Pharma , Oslo , Norway ) and fecal hemoglobin ( HemoQuant ; Mayo Medical Laboratories , Rochester , MN ) assays were performed in separate laboratories by masked technicians . Colonoscopic and histological findings served as criterion st and ards for establishing the presence or absence of colorectal inflammation . RESULTS : Among 110 subjects who provided complete fecal assay data , 29 ( 26 % ) had and 81 ( 74 % ) did not have colorectal inflammation . Increased fecal calprotectin levels were significantly ( p = 0.0001 ) associated with the presence of colorectal inflammation , whereas fecal hemoglobin levels were not ( p = 0.61 ) . Direct comparison of the fecal assays revealed that calprotectin was a more sensitive biomarker for colorectal inflammation at all specificity levels ( p = 0.0001 ) . CONCLUSIONS : In this study of colonoscopy referral patients , colorectal inflammation was reflected by fecal calprotectin but not by fecal hemoglobin levels . Assay of fecal calprotectin holds promise as a triage tool to identify inflammatory causes of chronic diarrhea |
10,431 | 23,247,004 | The qualitative data analysis revealed no clear trend for or against TLA . | OBJECTIVES Therapeutic injections with local anesthetics ( TLA ) are widespread and are used for various symptoms of the musculoskeletal system .
The aim of the present project was to evaluate the efficacy and safety of TLA in the treatment of musculoskeletal disorders . | OBJECTIVE This study was carried out to evaluate the therapeutic effect of epidural steroid injection on pseudoclaudication in patients with lumbar degenerative spinal canal stenosis . DESIGN Fifty-three patients who complained of pseudoclaudication of less than 20 m in walking distance were r and omly divided into three groups . Group 1 ( n = 16 ) underwent epidural injection with 8 ml of saline . Group 2 ( n = 18 ) underwent epidural block with 8 ml of 1 % mepivacaine . Group 3 ( n = 19 ) underwent epidural block with a combination of 8 ml of 1 % mepivacaine and 40 mg of methylprednisolone . The criteria of evaluation were as follows : excellent effect , > 100 m in walking distance ; good effect , 20 - 100 m in walking distance ; poor effect , < 20 m in walking distance . RESULTS In group 1 , the numbers of patients who showed a good effect were two ( 12.5 % ) after 1 week , one ( 6.5 % ) after 1 month , and one ( 6.5 % ) after 3 months . In group 2 , the numbers of patients who showed a good or excellent result were 10 ( 55.5 % ) after 1 week , three ( 16.7 % ) after 1 month , and one ( 5.6 % ) after 3 months . In group 3 , the numbers of patients who showed a good or excellent result were 12 ( 63.2 % ) after 1 week , three ( 15.8 % ) after 1 month , and one ( 5.3 % ) after 3 months . There was no significant difference in the effectiveness of treatment between group 2 and group 3 throughout the time course . CONCLUSION The results suggest that epidural steroid injection has no beneficial effect on the pseudoclaudication associated with spinal canal stenosis as compared with epidural block with a local anesthetic alone BACKGROUND Chronic pain in the cervical zygapophyseal joints is a common problem after a whiplash injury . Treatment with intraarticular injections of corticosteroid preparations has been advocated , but the value of this approach has not been established . We compared the efficacy of a depot injection of a corticosteroid preparation with the efficacy of an injection of a local anesthetic agent in patients with painful cervical zygapophyseal joints . METHODS Sixteen men and 25 women with pain in one or more cervical zygapophyseal joints after automobile accidents ( mean age , 43 years ; median duration of pain , 39 months ) were r and omly assigned to receive an intraarticular injection of either bupivacaine ( 0.5 percent ) or betamethasone ( 5.7 mg ) under double-blind conditions . The patients were followed by means of regular telephone contact and clinic visits until they reported a return to a level of pain equivalent to 50 percent of the preinjection level . The time from treatment to a 50 percent return of pain was compared in the two groups with the use of a survival analysis . RESULTS Less than half the patients reported relief of pain for more than one week , and less than one in five patients reported relief for more than one month , irrespective of the treatment received . The median time to a return of 50 percent of the preinjection level of pain was 3 days in the 21 patients in the corticosteroid group and 3.5 days in the 20 patients in the local-anesthetic group ( P = 0.42 ) . CONCLUSIONS Intraarticular injection of betamethasone is not effective therapy for pain in the cervical zygapophyseal joints after a whiplash injury OBJECTIVE To address the question whether general practitioners ( GPs ) should receive practical training in shoulder problems and to test whether cortisone injections are better than anaesthetic injections for rotator cuff problems . METHODS A pragmatic split-plot , r and omized trial with a cluster factorial design , conducted in general practice s across five centres across the United Kingdom . Ninety-one practice s were r and omized to receive additional training in diagnosing and injecting rotator cuff problems or no additional training . Two hundred patients consulting their general practice s with shoulder pain were then r and omized to receive either a corticosteroid or lignocaine injection . The main outcome was score on the British Shoulder Disability Question naire ( BSDQ ) . The Short-Form 36-item Health Survey and EuroQol at 12 months from entry to the trial were also scored . RESULTS Over the course of the trial there was a mean difference of 0.94 ( s.e . = 1.01 ) on the BSDQ score between the groups , with patients treated by the untrained group having a mean of 9.46 ( s.e . = 0.82 ) and those by the trained group having a mean of 8.51 ( s.e . = 0.60 ) . There were no statistically significant differences between the groups . Analysing by substance injected , there was a mean difference of 0.15 ( s.e . = 0.48 ) throughout the trial between the groups , with patients given the cortisone having a mean BSDQ of 9.67 ( s.e . = 0.39 ) and those given lignocaine , 9.82 ( s.e . = 0.39 ) . This was not statistically significantly different . CONCLUSIONS Training GPs in the diagnosis and treatment of shoulder disorders does not make any difference to the outcome , in terms of pain and disability , 1 yr later . Further , there is no advantage to injecting steroid in a group with predominant rotator cuff disorder . Trial registration . International St and ard R and omized Controlled Trial Number 58537244 . Trial steering committee comprised Prof. Paul Dieppe , Prof. Elaine Hay , Dr Brian Hazleman and Dr Kerenza Hood BACKGROUND Local anesthetics ( LA ) are frequently used in dentistry . Although these drugs are usually well-tolerated , they can sometimes provoke adverse reactions of various types and severity . The true incidence of LA allergic reactions is unknown . The objectives of this study were ( i ) to evaluate the incidence of immediate adverse events in subjects requiring local anesthetic injection in order to receive dental treatment ; ( ii ) to assess the incidence of anaphylactic allergic reactions among those recorded as adverse events and ( iii ) to analyze the relationship between the atopic antecedents of these patients and documented allergic reactions . MATERIAL S AND METHODS A prospect i ve , open-label , non-comparative study including 5,018 subjects who received LA during dental treatment , despite their age , was carried out in 7 private or public odontological centers . All the possible reactions that could appear during the first hour of anesthetic administration were assessed . RESULTS Twenty-five adverse reactions were diagnosed , representing 0.5 % of the study population . None of these reactions was due to an allergic cause . Most ( 22/25 ) were mild , quickly reversible psychogenic or vasovagal reactions . One case was related to defects in the anesthetic technique . In two further cases , allergic etiology was ruled out after skin and dose provocative challenge tests with the anesthetic . In conclusion , allergic reactions to LA are very rare . Most adverse reactions are psychogenic or vasovagal . Physicians and dentists should be aware of these facts in order to minimize the frequent fears and myths concerning the use of LA in the dentist 's office In a double-blind study 28 patients with acute , localised muscle pain received four local injections of mepivacaine 0.5 % , and 25 patients with the same type of pain received local injections of an equivalent volume of physiological saline . The group receiving saline tended to have more relief of pain , especially after the first injection . The results thus show that pain relief is not due merely to the local anaesthetic . The study therefore raises questions about the mechanism by which local injections into muscle relieves pain , since there is the possibility that a similar effect might also be achieved by merely inserting a needle into the trigger point . Physiological saline is considered to be a more appropriate fluid for injection therapy than local anaesthetics since it is less likely to produce side-effects More than two-thirds of patients in Germany use complementary and alternative medicine ( CAM ) provided either by physicians or non-medical practitioners ( “ Heilpraktiker ” ) . There is little information about the number of family physicians ( FPs ) providing CAM . Given the widespread public interest in the use of CAM , this study aim ed to ascertain the use of and attitude toward CAM among FPs in Germany . A postal question naire developed based on qualitatively derived data was sent to 3000 r and omly selected FPs in Germany . A reminder letter including a postcard ( containing a single question about CAM use in practice and reasons for non-particpation in the survey ) was sent to all FPs who had not returned the question naire . Of the 3000 FPs , 1027 ( 34 % ) returned the question naire and 444 ( 15 % ) returned the postcard . Altogether , 886 of the 1471 responding FPs ( 60 % ) reported using CAM in their practice . A positive attitude toward CAM was indicated by 503 FPs ( 55 % ) , a rather negative attitude by 127 FPs ( 14 % ) . Chirotherapy , relaxation and neural therapy were rated as most beneficial CAM therapies by FPs , whereas neural therapy , phytotherapy and acupuncture were the most commonly used therapies in German family practice s. This survey clearly demonstrates that CAM is highly valued by many FPs and is already making a substantial contribution to first-contact primary care in Germany . Therefore , education and research about CAM should be increased . Furthermore , with the provision of CAM by FPs , the role of non-medical CAM practitioners within the German healthcare system is to be question ed Abstract Trigger point injections with different solutions have been studied mainly with regard to the management of myofascial pain ( MFP ) patient management . However , few studies have analyzed their effect in a chronic headache population with associated MFP . The purpose of this study was to assess if trigger point injections using botulinum toxin , lidocaine , and dry-needling injections for the management of local pain and associated headache management . Forty-five ( 45 ) myofascial pain patients with headaches that could be reproduced by activating at least one trigger point , were r and omly assigned into one of the three groups : G1 , dry-needling , G2 , 0.25 % lidocaine , at 0.25 % and G3 botulinum toxin and were assessed during a 12 week period . Levels of pain intensity , frequency and duration , local post-injection sensitivity , obtainment time and duration of relief , and the use of rescue medication were evaluated . Statistically , all the groups showed favorable results for the evaluated requisites ( p≤0.05 ) , except for the use of rescue medication and local post injection sensitivity ( G3 showed better results ) . Considering its reduced cost , lidocaine could be adopted as a substance of choice , and botulinum toxin should be reserved for refractory cases , in which the expected effects could not be achieved , and the use of a more expensive therapy would be m and atory Study Design . Clinical practice guideline . Objective . To develop evidence -based recommendations on use of interventional diagnostic tests and therapies , surgeries , and interdisciplinary rehabilitation for low back pain of any duration , with or without leg pain . Summary of Background Data . Management of patients with persistent and disabling low back pain remains a clinical challenge . A number of interventional diagnostic tests and therapies and surgery are available and their use is increasing , but in some cases their utility remains uncertain or controversial . Interdisciplinary rehabilitation has also been proposed as a potentially effective noninvasive intervention for persistent and disabling low back pain . Methods . A multidisciplinary panel was convened by the American Pain Society . Its recommendations were based on a systematic review that focused on evidence from r and omized controlled trials . Recommendations were grade d using methods adapted from the US Preventive Services Task Force and the Grading of Recommendations , Assessment , Development , and Evaluation Working Group . Results . Investigators review ed 3348 abstract s. A total of 161 r and omized trials were deemed relevant to the recommendations in this guideline . The panel developed a total of 8 recommendations . Conclusion . Recommendations on use of interventional diagnostic tests and therapies , surgery , and interdisciplinary rehabilitation are presented . Due to important trade-offs between potential benefits , harms , costs , and burdens of alternative therapies , shared decision-making is an important component of a number of the recommendations Objectives We report a r and omized , double-blinded comparative study assessing the efficacy of local anesthetic with N-saline intradermal blocks around the knee to reduce pain and improve patient satisfaction while waiting for a total knee joint replacement . Methods Patients were offered involvement in this study while on the hospital waiting list for a knee replacement . Eligible patients , after completing a pre study assessment , received an average of 6.3 ( range : 1 to 10 ) intradermal injections of 0.5 mL either saline or 1 % lignocaine injections into tender points around the knee . Patients were assessed at 2 hours and 1 week after the injections . Pain was assessed using 0 to 100 visual analog pain scale . Global perceived effect ( satisfaction ) was measured on a 7-point Likert scale . Results Thirty-two of 34 patients attended at 1-week assessment , 24 ( 75 % ) felt that they were improved , and 8 ( 25 % ) considered they were unchanged or worse . In both the saline and lignocaine groups , 12 of 16 patients felt that they had improved . N-saline proved as effective as lignocaine in reducing knee pain when injected intradermally . Seventy-five percent of patients were improved at 1 week OBJECTIVES Local anaesthesia is increasingly used by dental hygienists . As little is known about the incidence of adverse effects during and after the administration of local anaesthetics , we evaluated side-effects associated with local anaesthesia . METHODS A prospect i ve observational study was conducted using st and ard criteria among a group of 103 patients receiving m and ibular block anaesthesia . RESULTS Physical reactions like clenching fists ( 14.5 % ) , moaning ( 12.6 % ) and turning pale ( 7.8 % ) were frequently observed . Patients ( 3.8 % ) showed a painful reaction because of needle contact with a nerve or the periosteum . Systemic complications were not observed . After the injection , 41.7 % said they felt tense during the administration ; 4.9 % of the patients reported swallowing problems and 3.9 % a tachycardia . CONCLUSIONS These results suggest that administration of local anaesthesia has a small risk of adverse events . Complications , if they occur , seem minor and transient in nature OBJECTIVES We compared in this study the efficiency of non-invasive techniques including transcutaneous electrical nerve stimulation ( TENS ) and laser treatments with invasive techniques including lidocaine and botulinum toxin-A injection in patients with myofascial pain syndrome ( MPS ) . METHODS One hundred patients who admitted to Firat University Hospital Pain Department and who were diagnosed as MPS were included in the study . Patients were r and omized into four groups of 25 patients each . Sixty sessions of TENS and 20 sessions of laser treatments were performed in the first and second groups , respectively . Lidocaine and botulinum toxin-A were injected in the third and fourth groups , respectively . 2 ml ( 20 mg ) 1 % lidocaine was injected in each patient twice a week for one month in Group III . 25 U ( 0.5 ml ) of botulinum toxin-A was injected in each patient only once in Group IV . Pain was evaluated with visual analogue scale ( VAS ) , palpable muscle spasm scoring ( PMSS ) and anesthesiometer at baseline , 15 , 30 and 45 days . RESULTS There were no statistically significant differences between the groups with respect to age , sex and education level . Pain control was statistically better in Group IV compared with the other groups with respect to VAS , PMSS and anesthesiometer scores . CONCLUSION Botulinum toxin-A injection provided better pain control when compared to trigger point injection with lidocaine and non-invasive techniques including TENS and laser treatments The efficacy of trigger-point injection therapy In treatment of low-back strain was evaluated in a prospect i ve , r and omized , double-blind study . The patient population consisted of 63 individuals with low-back strain . Patients with this diagnosis had nonradiating low-back pain , normal neurologic examination , absence of tension signs , and lumbosacral roentgenograms interpreted as being within normal limits . They were treated conservatively for 4 weeks before entering the study . Injection therapy was of four different types : lldocaine , lldocaine combined with a steroid , acupuncture , and vapocoolant spray with acupressure . Results indicated that therapy without injected medication ( 63 % improvement rate ) was at least as effective as therapy with drug injection ( 42 % improvement rate ) , at a P value of 0.09 . Trigger-point therapy seems to be a useful adjunct In treatment of low-back strain . The injected substance apparently is not the critical factor , since direct mechanical stimulus to the trigger-point seems to give symptomatic relief equal to that of treatment with various types of injected Background : Myofascial pain syndrome ( MPS ) is one of the most common causes of chronic musculoskeletal pain . Several methods have been recommended for the inactivation of trigger points ( TrP ) . Objectives : This prospect i ve , single-blind study was proposed to compare TrP injection with botulinum toxin type A ( BTX-A ) to dry needling and lidocaine injection in MPS . Methods : Eighty-seven trigger points ( cervical and /or periscapular regions ) in 23 female and six male patients with MPS were treated and r and omly assigned to three groups : lidocaine injection ( n=10 , 32 TrP ) , dry needling ( n=10 , 33 TrP ) , and BTX-A injection ( n=9 , 22 TrP ) . Outcome measures : Clinical assessment including cervical range of motion , TrP pain pressure threshold ( PPT ) , pain scores ( PS ) , and visual analog scales for pain , fatigue , and work disability were evaluated at entry and the end of the 4th week . Additionally , depression and anxiety were evaluated with the Hamilton depression and anxiety rating scales , and quality of life was assessed using the Nottingham health profile ( NHP ) . The subjects were also asked to describe side effects . Injection procedure : One milliliter of 0.5 % lidocaine was administered to each TrP in the lidocaine injection group , 10–20 IU of BTX-A to each TrP in the BTX-A group , and dry needling to each TrP in the last group , followed by stretching of the muscle groups involved . The patients were instructed to continue their home exercise programs . Results : Pain pressure thresholds and PS significantly improved in all three groups . In the lidocaine group , PPT values were significantly higher than in the dry needle group , and PS were significantly lower than in both the BTX-A and dry needle groups . In all , visual analog scores significantly decreased in the lidocaine injection and BTX-A groups and did not significantly change in the dry needle group . Disturbance during the injection procedure was lowest in the lidocaine injection group . Quality of life scores assessed by NHP significantly improved in the lidocaine and BTX-A groups but not in the dry needle group . Depression and anxiety scores significantly improved only in the BTX-A-injected group . Conclusions : Injection is more practical and rapid , since it causes less disturbance than dry needling and is more cost effective than BTX-A injection , and seems the treatment of choice in MPS . On the other h and , BTX-A could be selectively used in MPS patients resistant to conventional treatments CONTEXT AND OBJECTIVE Osteoarthritis causes pain and disability in a high percentage of elderly people . The aim of the present study was to assess the efficacy of intra-articular morphine and bupivacaine on the joint flexion and extension angles of patients with knee osteoarthritis . DESIGN AND SETTING A r and omized double-blind study was performed at a pain clinic of Universidade Federal de São Paulo . METHODS Thirty-nine patients with pain for more than three months , of intensity greater than three on a numerical scale ( zero to 10 ) , were included . G1 patients received 1 mg ( 1 ml ) of morphine diluted in 9 ml of saline , intra-articularly , and G2 patients received 25 mg ( 10 ml ) of 0.25 % bupivacaine without epinephrine . Pain was assessed on a numerical scale and knee flexion and extension angles were measured after administration of the drugs at rest and during movement . The total amount of analgesic supplementation using 500 mg doses of paracetamol was also determined . RESULTS No significant difference in pain intensity was observed between G1 and G2 . Significant decreases in pain at rest and during movement and significant increases in mean flexion and extension angles were observed in both groups , with no significant difference between the two groups . The mean total amount of paracetamol used over a seven-day period was 3578 mg in G1 and 5333 mg in G2 ( P = 0.2355 ; Mann-Whitney test ) . CONCLUSION The analgesic effects of 1 mg of morphine and 25 mg of 0.25 % bupivacaine were similar among patients with osteoarthritis of the knee Myofascial pain syndrome of the head and neck is a frequent cause of facial pain and is characterized by tender trigger points . In a double-blind study of 107 patients , local injection therapy using one of three solutions was applied at the trigger points by intracutaneous injection of 0.3 ml solution followed by deep infiltration of the site . Results using bupivacaine 0.25 % , lignocaine 1 % and saline 0.9 % were compared . There was no significant difference among groups with respect to reduction of pain and overall rating by patients of the therapeutic benefits . Fifty-three patients ( 49 % ) were free of symptoms after treatment , 40 patients ( 38 % ) reported substantial relief and in 14 patients ( 13 % ) symptoms remained unchanged . The findings suggest that relief of pain is mainly due to reflex mechanisms rather than to the pharmacological effects of the injected solutions . Physiological saline solution is recommended for use in local injection therapy Summary A total of 15 patients suffering from chronic low back pain were treated with an intradiscal injection of either 1 ml of 50 % glycerol or 2 ml of 0.5 % bupivacaine . Most ( 60 % ) of the patients had previously undergone spinal surgery for lumbar disc herniation or spinal stenosis and 73 % showed clinical signs and symptoms of segmental instability of the lumbar spine . According to self-evaluation question naires , immediate response to both treatments was mainly good . Of the 9 patients who received glycerol , 56 % showed subjective improvement on the first day after the injection and after two weeks , 45 % of the patients still felt improvement . After one month , however , the pain had reappeared in all except one ( 11 % ) patient . The corresponding numbers for the 6 with bupivacaine treated patients were 83 % , 67 % , and 17 % . Based on the very short duration of response to the treatment , we did not find intradiscal injections with these agents to be cost-effective . In our department , this therapeutic approach is no longer employed in patients with chronic discogenic pain This study was design ed to investigate the effects of injection with a local anesthetic agent or dry needling into a myofascial trigger point ( TrP ) of the upper trapezius muscle in 58 patients . Trigger point injections with 0.5 % lidocaine were given to 26 patients ( Group I ) , and dry needling was performed on TrPs in 15 patients ( Group II ) . Local twitch responses ( LTRs ) were elicited during multiple needle insertions in both Groups I and II . In another 17 patients , no LTR was elicited during TrP injection with lidocaine ( 9 patients , group Ia ) or dry needling ( 8 patients , group IIa ) . Improvement was assessed by measuring the subjective pain intensity , the pain threshold of the TrP and the range of motion of the cervical spine . Significant improvement occurred immediately after injection into the patients in both group I and group II . In Groups la and Ib , there was little change in pain , tenderness or tightness after injection . Within 2 - 8 h after injection or dry needling , soreness ( different from patients ' original myofascial pain ) developed in 42 % of the patients in group I and in 100 % of the patients in group II . Patients treated with dry needling had postinjection soreness of significantly greater intensity and longer duration than those treated with lidocaine injection . The author concludes that it is essential to elicit LTRs during injection to obtain an immediately desirable effect . TrP injection with 0.5 % lidocaine is recommended , because it reduces the intensity and duration of postinjection soreness compared with that produced by dry OBJECTIVE The causes of pain in osteoarthritis ( OA ) remain unclear . We examined the effect of intraarticular ( IA ) local anesthetic ( LA ) on pain perception in OA knee to test the hypothesis that pain arises from structures in contact with the intraarticular surface . The effect of intervention on one knee on perception of pain in the other was also studied . METHODS Using a single blind , blind observer design , 20 subjects with bilateral symptomatic OA knee were r and omized to receive either IA LA ( bupivacaine 0.25 % , 5 ml ) or placebo into the most painful knee . Pain from both knees was assessed at 1 h , 24 h , and 7 days using a 100 mm visual analog scale ( VAS ) . Pain descriptors using a st and ardized question naire ( McGill ) were recorded . RESULTS At 1 h there was a significant fall in pain in LA knees ( median VAS 61.5 to 0.0 ; p = 0.007 ) . The change at VAS was significantly different between knees receiving LA and placebo ( median change -45.5 vs + 3.5 ; p = 0.03 ) . 6/10 LA knees scored 0 on VAS at 1 h. Noninjected knees also showed a fall in pain scores . For knees contralateral to those receiving LA , the fall was from median 28.0 to 1.0 ( p = 0.08 ) . The reduction in pain was much less in knees contralateral to those receiving placebo ( median 43.5 to 38.0 ) , though the difference between the changes did not reach statistical significance . VAS scores remained below baseline for 7 days , though this difference was not significant . McGill pain scores fell in the LA group ( for all categories of pain ) , but did not change in the placebo group . CONCLUSION Pain in some cases of OA knee can be abolished by IA LA , suggesting that the structures responsible for pain are in contact with the intraarticular environment . As well , interventions in one knee have significant effects on pain perception in the contralateral knee A double blind r and omised trial was carried out to ascertain whether intra-articular injections of saline , bupivacaine or bupivacaine plus triamcinolone would be of value in the relief of hip pain suffered by patients awaiting total hip replacement for osteoarthritis . The majority of patients had good pain relief for 1 month but in general this was not maintained and some patients were much worse after the injection In a 2-week , double blind , r and omized study we compared the efficacy of a single local injection of 5 ml lignocaine , 0.5 % ( L ) with 5 ml isotonic saline ( S ) in 41 patients with the iliac crest pain syndrome ( ICPS ) , recruited from a rheumatology clinic and from a general practice . For the purpose of comparing both treatment , 2 major outcome variables at the end of the study were defined at the outset : ( 1 ) Pain score . In the L group the mean pain score at Day 14 was 30.5 , in the S group 43.8 ; the difference between both treatment groups was significant ( p less than 0.05 ) . On subgroup analysis similar results were found in the rheumatology setting ( p less than 0.05 ) but not in the general practice setting ( NS ) . ( 2 ) Pain severity compared with baseline . In the L group 52 % of patients improved and in the S group 30 % ( NS ) . In the general practice clinic there was no significant difference ( 44 vs 62 % ) ; however , in the rheumatology setting 58 % of those treated with L were improved compared with 8 % in the S group ( p less than 0.01 ) . Our data demonstrate an effect of a local injection with lignocaine that is somewhat larger than an injection with saline which also has some beneficial effect . The difference is evident in the rheumatology setting but not in the general practice setting To support that myofascial pain syndrome ( MPS ) of gastrocnemius muscle is one cause of nocturnal calf cramps , quantitative assessment of the efficacy of trigger point ( TrP ) injection compared with oral quinine in the treatment of nocturnal calf cramps ( NCC ) associated with MPS of gastrocnemius muscle was design ed . Twenty four subjects with NCC and gastrocnemius TrPs were r and omly divided into two groups of twelve for each treatment . Patients in group 1 were treated with xylocaine injection at the gastrocnemius TrP , and 300 mg of quinine sulfate p.o . was prescribed for patients of group 2 . The treatment period was four weeks with a follow-up 4 weeks later . Cramps were assessed quantitatively ( in terms of frequency , duration , pain intensity , cramp index , and pain threshold of the gastrocnemius TrPs ) before treatment , after treatment and at the end of the follow-up respectively . The outcome of treatment in both groups showed a statistically significant reduction in all quantitative aspects of cramps ( 95 % confidence interval ) . Also the pain threshold of the gastrocnemius TrP was significantly increased in group 1 only when comparing the pre-treatment and at the end of follow-up . In comparing the two groups we found no statistical difference during the period of treatment . The benefit of both strategies lasted up to four weeks following cessation of the treatment but the outcome of all measures ( except pain threshold ) were found to be significantly better in the group treated with TrP injection . The results of this study support that gastrocnemius trigger point is one cause of NCC and show that the TrP injection strategy for NCC associated with myofascial pain is not only as effective as oral quinine during the treatment period but also better in the prolonged effect at follow-up Twenty-four patients with localized myofascial pain were treated with injections , 11 with 2 ml lidocaine 1 % and 13 with 2 ml diclofenac ( Voltaren ) ( 50 mg ) given in the trigger-point . The effect of therapy was measured by visual analogue scale ( VAS ) during 5 h corresponding to the expected pharmacological period of effect . Despite the small number of patients a clear trend was seen towards better treatment results with diclofenac , and after 4 h the difference between the two treatments was significant ( p less than 0.05 ) . Compared with the pain score value at the start the treatment with diclofenac gave a significant alleviation ( p less than 0.05 ) after 3 h , whereas treatment with lidocaine did not give any significant change in pain level . The demonstrated effect of a prostagl and in synthesis inhibitor illustrates how inflammation is involved as an etiological factor in myofascial pain Eighteen patients with unilateral osteoarthrosis of the hip were investigated in a trial which involved the injection of nine with bupivacaine and nine with normal saline . All the patients completed daily pain analogue charts . Their pain , mobility and functional activity were assessed and gait characteristics analysed , once before the injection and then at three monthly intervals . All the patients recorded a decrease in pain level within two weeks of injection , but it subsequently rose to pre‐injection levels . There were no other significant general improvements after the injection . A significant increase in the maximum force at toe‐off for the good leg was recorded one month after the injection . However , no further significant differences were found in the gait performance of either group of patients throughout the study . It is concluded that the hip nerve regional blockade offers no useful relief to the pain of osteoarthrosis of the hip joint In this paper , we describe a stepped-care approach to the activation of patients with back pain who are seen in primary care setting s. This approach is intended to complement medical management . Waddell ( 1 ) states , Advice to stay active and to continue ordinary activities as normally as possible is likely to result in faster recovery , faster return to work and less chronic disability . Simply having a physician advise them to resume activities may be sufficient for most patients , but an important minority of patients may need more substantial support to achieve a favorable functional outcome . A smaller group may require intensive intervention to restore function in major social roles related to work and family . A stepped approach allows care to be guided by functional outcome , with intensity being increased until a favorable outcome is achieved whenever possible . Evidence -based guidelines advocate stepped-care approaches for a wide range of chronic conditions ( 2 ) . Large numbers of patients with back pain seek treatment in primary care setting s. Stepped care provides a framework for integrating behavioral interventions aim ed at restoring function in work and family life into routine medical care ( 3 ) . It provides a way to target the limited professional re sources for helping patients achieve favorable functional outcomes to the patients who have the greatest needs ( 4 , 5 ) . Stepped care is not an intervention in itself . Rather , it is a way to sequence interventions so that the intensity , complexity , and costs of care are guided by each patient 's observed outcome . The objective of stepped care is to give each patient the level and kind of care needed for a favorable outcome no more and no less . Back pain is a chronicrecurrent condition . Although most patients who seek care for a severe flare-up of back pain improve and return to work quickly , the long-term outcomes of patients with back pain are not as favorable as previously believed . Outcome studies show that in the long run , recurrence is typical . About 30 % of patients seen in primary care for back pain have persistent back pain , and 15 % to 20 % continue to have moderate to severe activity limitations 1 or more years after seeking care ( 6 ) . One implication is that back pain management should be appropriate for a chronicrecurrent pain condition with highly variable outcomes . Recent systematic review s of r and omized , controlled trials have concluded that activating interventions improve functional outcomes for patients with chronic or recurrent back pain ( 7 - 10 ) . In a systematic review , Waddell and colleagues ( 7 ) concluded that when physicians avoid prescribing bed rest and advise patients to stay active and to continue normal activities , patients return to work faster and have reduced disability . Turner ( 8) , review ing cognitivebehavioral interventions for back pain , concluded that cognitive-behavioral treatments were superior to control conditions after treatment on measures of chronic low back pain , pain behavior and disability . However , she did not find evidence showing that cognitivebehavioral therapies were superior to other active treatments on specific outcome measures . Koes and coworkers ( 9 ) , review ing r and omized trials of back schools , found that schools that emphasized resumption of normal activities were more likely to report positive results than were schools that offered traditional patient education about back anatomy , biomechanics , and posture . Abenh aim and associates ( 10 ) concluded that patients with back pain benefit from participation in structured exercise programs . Fear avoidance , which is characterized by the belief that activity and movement can cause back pain and increase risk for re-injury , is believed to be an important determinant of disability in patients with back pain ( 11 - 13 ) . Fear-avoidance beliefs are associated with reduced activity and increased disability . Recent r and omized , controlled trials of brief interventions have found that addressing fear-avoidance beliefs and encouraging resumption of normal activities have substantial benefits . For example , Malmivaara and colleagues ( 14 ) showed that advising patients to avoid bed rest and to continue routine activity as normally as possible result ed in better functional outcomes than either advising them to rest in bed for 2 days or implementing back-mobilizing exercises during acute care . Indahl and coworkers ( 15 ) found that reassurance intended to reduce fear of movement , advice to resume normal walking , and the setting of personal goals result ed in reduced work disability . Moffett and associates ( 16 ) found that a program of brief education , strengthening and flexibility exercises , and relaxation reduced the number of work days missed over the following year . Linton and And ersson ( 17 ) found that a brief cognitivebehavioral program result ed in fewer lost work days . Two r and omized , controlled trials conducted by our research group ( 18 , 19 ) showed that brief activating interventions delivered in a group format reduced worry about back pain and reduced activity limitations among primary care patients with back pain over a 1-year period . Burton and coworkers ( 20 ) found that an educational booklet addressing fear-avoidance beliefs reduced fear and yielded a short-term reduction in disability . Overall , these studies suggest that credible activating interventions addressing fear-avoidance beliefs can improve patient outcomes . A Stepped-Care Model Stepped care is based on the principle of starting with low-intensity , low-cost interventions and stepping up to more intense , costly , or complex interventions in patients who show inadequate response ( 2 - 5 ) . A possible stepped-care approach for back pain is summarized in Table 1 . In the case of back pain , simple and brief educational interventions may be sufficient to address fear-avoidance beliefs and ensure resumption of normal activities for many patients ( step 1 ) . However , some patients with back pain continue to have residual activity limitations . These patients may benefit from brief , structured interventions that increase physical exercise and support resumption of normal activities ( step 2 ) . A more intense rehabilitative intervention that targets return to work and work-role performance may be appropriate for patients at risk for chronic work-role disability ( step 3 ) . At step 3 , identification and treatment of comorbid psychological illness ( such as major depression ) , if present , may help improve functional outcomes . Although the intensity of a stepped-care intervention is guided primarily by observed outcome , individualization based on initial evaluation is possible . For example , a patient who can not work and has no definite plans to resume work at the time of the initial visit might receive a more intensive intervention immediately ( 3 ) . Table 1 . A Stepped-Care Approach for Managing Back Pain in Primary Care Patient Needs at Each Level of Care Drawing on data from studies conducted by our research group ( 18 , 19 , 21 ) , we identified patient needs defined in terms of the proposed stepped-care model . Patient Worries and Concerns Addressed at Step 1 As Table 2 shows , 2 months after seeking care for back pain in a primary care setting , a large proportion of patients reported being worried that a wrong movement might injure their back . Patients also frequently reported concern about being unable to do things because of risk for injury and concern that back pain indicates that something is dangerously wrong . Almost one third of patients reported fear of injury with exercise , and one in five reported concern that their back pain might be due to a serious disease . Apparently , fear-avoidance beliefs and related worries are common among primary care patients with back pain , and these concerns are often not laid to rest in the initial medical encounter . Table 2 . Percentage of Patients Reporting Specific Worries about Back Pain and Activity Limitations 2 Months after a Primary Care Visit for Back Pain Activity Limitations Addressed at Step 2 It was also common for patients with back pain to report continuing activity limitations 2 months after they had sought care . As Table 2 shows , the proportions of patients who reported that they were doing no housework , were doing less housework , had decreased sexual activity , had difficulty walking short distances , or had difficulty st and ing for short periods were 23 % to 45 % . These activity limitations , while not indicative of total disability , suggest that many patients have sustained decrements in quality of life because of back pain . Two months after they had sought care , 44 % of participants gave a positive response to 10 or more of the 23 items on the Rol and Disability Question naire . At 1 year , 26 % gave a positive response to 10 or more of the same 23 items . This indicates that substantial activity limitations are often sustained long after the initial primary care visit . Work Disability Addressed at Step 3 The proportion of primary care patients with back pain who reported significant work-role disability was considerably smaller . Using data from a long-term follow-up study of primary care patients with back pain ( 21 ) , we examined three indicators of work disability . At 1 month to 5 years , 2.0 % to 3.8 % of primary care patients with back pain reported being unable to work and 1.5 % to 3.5 % reported receiving worker 's compensation for back pain . However , the percentage reporting that they were being kept from usual activities ( such as work , school , or housework ) for 30 or more days in the previous 6 months because of back pain was considerably greater . At 1 month , 21 % reported more than 30 activity limitation days in the previous 6 months ; at 1 to 5 years , the percentage was 8 % to 10 % . These results support the need for educational interventions that address fear-avoidance beliefs and encourage resumption of normal activities for all patients who seek care for back pain ( step 1 ) . They also show that large numbers of & NA ; Twenty‐eight patients with primary fibromyalgia participated in the study . Eight patients received a stellate ganglion blockade with bupivacaine , and 14 days later an intravenous regional sympathetic blockade with guanethidine . The remaining patients served as controls and were r and omly allocated to receive either a sham ( placebo ) injection with physiologic saline superficial to the stellate ganglion ( n = 10 ) or bupivacaine intramuscularly ( n = 10 ) . The efficiency of the stellate ganglion blockade was evaluated by measuring skin blood flow ( using a laser Doppler flowmeter ) , skin temperature , and skin conductance responses ( ‘ sympathogalvanic reflex ’ ) . Trigger and tender points ( TePs ) were counted , and rest pain in the arm , shoulder and neck evaluated at intervals up to 4 h after the injection . The guanethidine blockade was evaluated 24 h after the injection by counting TePs and by assessment of rest pain in the h and and forearm . The results indicate that a complete sympathetic blockade , produced by a stellate ganglion blockade , markedly reduced the number of TePs and produced a marked decrease in rest pain . The guanethidine blockade reduced the number of TePs , but had no effect on rest pain . The reduction in pain and TePs produced by a sympathetic blockade may be due to an improvement in microcirculation . Sympathetic activity may , in some patients , contribute to the pathogenesis of primary fibromyalgia Thirty women with a history of daily pain in the masseter muscles were injected with either lidocaine or saline . The participants were told that they were being given an anesthetic injection to reduce their muscular discomfort . The dentist performing the injections did not know which fluid was used . The discomfort in the masseter muscle was assessed by using Borg 's new rating scale before and 10 minutes after injection . The evaluation was followed up on day 1 , day 3 , and day 7 . Bite force was registered between the first molars on the injection side . When scale values were compared individually within groups before and after injection , a significant decrease in discomfort was found in both groups , with the exception of day 1 for the lidocaine group and days 1 and 3 in the saline group . The total lidocaine and saline groups assessed the discomfort similarly except on day 3 when the lidocaine group showed significantly less discomfort . The intraindividual force values increased significantly after injection in the saline group . This effect was not found in the lidocaine group . Despite the minor tendencies for lidocaine to have a better effect , the placebo effect was considered to be high and important |
10,432 | 12,011,872 | Despite this variation , there is sufficient evidence to conclude that epidural is associated with a lower rate of spontaneous vaginal delivery , a higher rate of instrumental vaginal delivery and longer labors , particularly in nulliparous women .
Women receiving epidural are also more likely to have intrapartum fever and their infants are more likely to be evaluated and treated for suspected sepsis .
There is insufficient evidence to determine whether epidural does or does not tend to increase the risk of cesarean delivery or fetal malposition .
Adverse effects on the fetus may occur in the subset of women who are febrile . | Epidural analgesia is used by more than half of laboring women , yet there is no consensus about what unintended effects it causes .
To evaluate the state of our knowledge , we performed a systematic review of the literature examining the unintended maternal , fetal , and neonatal effects of epidural analgesia used for pain relief in labor by low-risk women . | OBJECTIVE To evaluate the effect of second-stage epidural bupivacaine on the outcome of labor . METHODS Two groups of 35 patients each were r and omly allocated to receive continuous epidural bupivacaine throughout labor ( group 1 ) or until an 8-cm dilatation of the cervix ( group 2 ) . RESULTS There was no significant difference between the 2 groups in the rates of instrument deliveries and in their Apgar scores . CONCLUSIONS The administration of continuous epidural bupivacaine ( 0.25 % ) throughout labor and delivery does not seem to affect the outcome of labor To compare the use of r and omized controls ( RCTs ) and historical controls ( HCTs ) for clinical trials , we search ed the literature for therapies studied by both methods . We found six therapies for which 50 RCTs and 56 HCTs were reported . Forty-four of 56 HCTs ( 79 percent ) found the therapy better than the control regimen , but only 10 of 50 RCTs ( 20 percent ) agreed . For each therapy , the treated patients in RCTs and HCTs of the same therapy was largely due to differences in outcome for the control groups , with HCT control patients generally doing worse than the RCT control groups . Adjustment of the outcomes of the HCTs for prognostic factors , when possible , did not appreciably change the results . The data suggest that biases in patient selection may irretrievably weight the outcome of HCts in favor of new therapies . RCTs may miss clinical ly important benefits because of inadequate attention to sample size . The predictive value of each might be improved by reconsidering the use of p less than 0.05 as the significance level for all types of clinical trials , and by the use of confidence intervals around estimates of treatment effects BACKGROUND In laboratory animals , cerebral ischaemia is worsened by hyperthermia and improved by hypothermia . Whether these observations apply to human beings with stroke is unknown . We therefore examined the relation between body temperature on admission with acute stroke and various indices of stroke severity and outcome . METHODS In a prospect i ve and consecutive study 390 stroke patients were admitted to hospital within 6 h after stroke ( median 2.4 h ) . We determined body temperature on admission , initial stroke severity , infa rct size , mortality , and outcome in survivors . Stroke severity was measured on admission , weekly , and at discharge on the Sc and inavian Stroke Scale ( SSS ) . Infa rct size was determined by computed tomography . Multiple logistic and linear regression outcome analyses included relevant confounders and potential predictors such as age , gender , stroke severity on admission , body temperature , infections , leucocytosis , diabetes , hypertension , atrial fibrillation , ischaemic heart disease , smoking previous stroke , and comorbidity . FINDINGS Mortality was lower and outcome better in patients with mild hypothermia on admission ; both were worse in patients with hyperthermia . Body temperature was independently related to initial stroke severity ( p < 0.009 ) , infa rct size ( p < 0.0001 ) , mortality ( p < 0.02 ) , and outcome in survivors ( SSS at discharge ) ( p < 0.003 ) . For each 1 degrees C increase in body temperature the relative risk of poor outcome ( death or SSS score on discharge < 30 points ) rose by 2.2 ( 95 % CI 1.4 - 3.5 ) ( p < 0.002 ) . INTERPRETATION We have shown that , in acute human stroke , an association exists between body temperature and initial stroke severity , infa rct size , mortality , and outcome . Only intervention trials of hypothermic treatment can prove whether this relation is causal OBJECTIVE To compare two methods of epidural labor analgesia regarding the incidence of post-partum urinary retention . STUDY DESIGN One thous and parturients who requested epidural analgesia for the relief of labor pain received , at r and om , either bupivacaine 0.25 % with adrenaline 1:200 000 ( n = 500 ) or bupivacaine 0.125 % with 10 micrograms sufentanil ( n = 500 ) . During the same observation period all women with clinical ly significant urinary retention ( > 500 ml , requiring indwelling catheter ) were registered . RESULT Altogether 30/3.364 parturients had clinical ly significant urinary retention . Twenty-seven of these had received epidural analgesia ( EDA ) ( 17 with bupivacaine/adrenaline and ten with bupivacaine/sufentanil , a non-significant differences ) . The number of parturients with urinary retention was highly increased following EDA ( 27/1000 ) as compared to those not receiving EDA ( 3/2364 ) , P < 0.001 ( Fisher 's exact test ) . In patients with EDA and urinary retention there were no difference between the groups in the incidence of instrumental deliveries or vaginal/perirectal tears . All parturients regained normal bladder function . CONCLUSION EDA significantly increased the risk of post-partum urinary retention but no difference was found between the two epidural techniques CONTEXT Exposure to maternal or placental infection is related to risk of preterm birth and , in premature infants , of brain lesions predictive of cerebral palsy ( CP ) . Few studies have investigated whether maternal infection is associated with risk of CP in children of normal birth weight . OBJECTIVE To investigate maternal infection during the admission for delivery as a possible risk factor for CP in infants born weighing 2500 g or more . DESIGN Population -based case-control study . SETTING All hospitals in 4 northern California counties , 1983 through 1985 . PARTICIPANTS A total of 46 children with disabling spastic CP who had no recognized prenatal brain lesions and 378 r and omly selected control children weighing 2500 g or more at birth and surviving to age 3 years . MAIN OUTCOME MEASURES Disabling spastic CP and signs of neonatal morbidity . RESULTS Maternal fever exceeding 38 degrees C in labor was associated with increased risk of unexplained CP ( odds ratio [ OR ] , 9.3 ; 95 % confidence interval [ CI ] , 2.7 - 31.0 ) , as was a clinical diagnosis of chorioamnionitis . One or more indicators of maternal infection were present in 2.9 % of control children , 22 % of children with CP ( OR , 9.3 ; 95 % CI , 3.7 - 23.0 ) , and 37 % of those with the spastic quadriplegic subtype of CP ( OR , 19.0 ; 95 % CI , 6.5 - 56.0 ) . Newborns exposed to maternal infection , both cases and controls , had 5-minute Apgar scores below 6 more often than those unexposed . Among children with CP , those born to infected women were more often hypotensive , needed intubation , had neonatal seizures , and received a clinical diagnosis of hypoxic-ischemic encephalopathy . CONCLUSION Intrauterine exposure to maternal infection was associated with a marked increase in risk of CP in infants of normal birth weight . Maternal infection was also linked with low Apgar scores , other evidence of hypotension [ corrected ] and need for resuscitation , and neonatal seizures-signs commonly attributed to birth asphyxia OBJECTIVE To determine whether cervical dilatation at the time of placement of patient-requested epidural affects cesarean rates or lengths of labors in actively managed parturients . METHODS The charts of 255 women r and omized to active management of labor ( n = 125 ) or control protocol s ( n = 130 ) were review ed and stratified to early epidural placement ( up to 4 cm cervical dilatation ) versus late placement ( more than 4 cm ) . RESULTS Women with early epidural placement had shorter labors than those with late placement ( 11.6 + /- 4.6 versus 13.2 + /- 5.6 hours ; P = .02 ) . Active management reduced the length of labor compared with controls regardless of epidural timing , with a reduction of 1.4 hours in early epidural placement ( 10.9 + /- 4.7 versus 12.3 + /- 4.3 hours ; P = .04 ) and 3.6 hours in those with later placement ( 11.0 + /- 3.6 versus 14.6 + /- 6.2 hours ; P = .004 ) . Cesarean rates did not vary significantly ( early 14.5 % versus late 7.9 % ; P = .21 ) . Early epidural placement did not lengthen the second stage of labor or increase operative vaginal delivery rates . CONCLUSION Early epidural placement did not affect lengths of labor or cesarean rates and was actually associated with shorter labor compared with late epidural placement . Women managed actively in labor , regardless of timing of epidural placement , had shorter labors than controls Objective To use intrapartum sonography as a tool to investigate the development of the persistent occiput posterior position during labor , as well as to identify parameters correlating with the outcome of labor . Methods A prospect i ve study of 408 women in labor after 37 weeks ' gestation with a singleton fetus in a vertex position using sonography at the onset of labor was performed . Fetal position , placental location , and maternal BMI ( body mass index ) were recorded . Outcome of labor was monitored for all relevant parameters . Results Most ( 68 % ) of persistent occiput posterior positions develop through a malrotation during labor from an initially occipitoanterior position . Only 32 % of persistent cases were occipitoposterior ( dorsoposterior ) at the onset of labor ; operative interventions were required in 87.5 % of these . Of the 61 ( 15 % ) occipitoposterior positions at the onset of labor , 53 ( 87 % ) rotated into an occiput anterior position . Persistent occiput posterior position was more common in the initially occipitoposterior group ( P < 0.01 , Fisher exact test ) , and posterior placental locations were fewer ( z test , P = 0.05 ) . Also , operative deliveries were more common in the group remaining occipitoposterior throughout labor ( P < .01 , Fisher exact test ) . A higher maternal BMI correlated with neonatal weight ( P < .01 , Pearson correlation ) , an increase in operative deliveries ( P = .032 , Pearson correlation ) , lower Apgar scores at 1 minute ( P = .02 , Spearman correlation ) , and increase in posterior placental locations ( P = .037 , two-tailed t test ) . Conclusion In most cases , persistent occiput posterior position develops through a malrotation and only in a little more than one-third of cases through absence of rotation from an initially occipitoposterior position . Higher maternal BMI correlates with higher fetal weight , increased operative deliveries , lower Apgar scores at 1 minute , and posterior placental locations . Intrapartum sonography proved to be useful in investigating the development of the persistent occipitoposterior position A r and omized , double-blind , placebo-controlled study was performed to evaluate the analgesic efficacy and influence of continuing an epidural infusion of 0.0625 % bupivacaine-0.0002 % fentanyl during the second stage of labor in nulliparous women . When the cervix was fully dilated , coded study solution was substituted for the known bupivacaine-fentanyl solution . The study solution for 29 patients was 0.0625 % bupivacaine-0.0002 % fentanyl ; 34 patients received saline placebo . The two groups had similar pain scores during the first stage of labor . During the second stage , pain scores were significantly higher in the saline-placebo group at each 30-min interval between 60 and 150 min after the diagnosis of full cervical dilation . Similarly , there was a significant difference between the two groups in global assessment of analgesia quality during the second stage , but the difference occurred in those patients with a second-stage duration of greater than or equal to 60 min . Among the women who delivered vaginally , eleven of 28 ( 39 % ) women in the bupivacaine-fentanyl group , versus five of 34 ( 15 % ) in the saline-placebo group , had surgical perineal anesthesia for vaginal delivery ( P less than .05 ) . Six of 28 ( 21 % ) women in the bupivacaine-fentanyl group , and five of 34 ( 15 % ) in the saline-placebo group , underwent instrumental vaginal delivery ( P = NS ) . The median duration of the second stage of labor was 53 min ( range = 5 - 283 ) in the bupivacaine-fentanyl group , and 63 min ( range = 16 - 181 ) in the saline-placebo group ( P = NS ) . ( ABSTRACT TRUNCATED AT 250 WORDS Abstract Objectives : To assess in a prospect i ve r and omised study the association between motor block result ing from high and low dose epidural infusions of bupivacaine in labour and the incidence of long term backache after childbirth , and to compare the incidence of backache in women not receiving epidural analgesia . Design : Women requesting epidural analgesia in labour between October 1991 and March 1994 were r and omised to receive infusions of either bupivacaine alone or low dose bupivacaine with opioid . Data were collected during labour and the immediate postpartum period from these women and from women recruited at r and om over the same time from those who had laboured without epidural analgesia . A postal question naire about symptoms was sent three months after childbirth to all women . Further data were collected one year after childbirth from those who had reported new backache at three months . Setting : St Thomas 's Hospital , London . Subjects : 599 women were recruited , of whom 450 ( 75 % ) replied to a follow up question naire . Results : 152 women ( 33.8 % of responders ) reported backache lasting three months after delivery and , of these , 33 ( 7.3 % ) had not previously suffered with backache . There were no significant differences between the treatment groups in the incidence of postnatal backache overall or of new backache or any symptoms after childbirth . Among all demographic , obstetric , and epidural variables examined the only factors significantly associated with backache after childbirth were backache before and during pregnancy . Conclusions : The incidence of new long term backache was not significantly increased in women who received epidural analgesia in labour . Motor block result ing from epidural local anaesthetic administration was not a significant factor in the development of backache . Key messages About half of all women suffer backache during pregnancy , but many forget this when question ed retrospectively A prospect i ve study showed that the incidence of new postpartum backache is 7.3 The use of epidural analgesia in labour had no effect on the incidence of postpartum backache In a r and omised trial motor block in labour was not associated with an increase the incidence of Of 10,122 singleton babies born from January 1 , 1984 to March 31 , 1988 , we compared 1,154 term infants with high serum bilirubin levels ( > 12.9 mg/dl ) to 1,154 infants with low serum bilirubin levels ( < 12.9 mg/dl ) r and omly selected from the remaining 8,968 subjects . We found that a high bilirubin level was significantly associated with male sex ; maternal diabetes ( chronic and gestational ) ; pregnancy-induced hypertension ; previous sibling with neonatal jaundice ; delivery by cesarean section , vacuum , or forceps ; epidural anesthesia ; mother with blood type O ; first delivery ; cephalohematoma ; short gestation ; lower birth weight ; and lower birth order ( p < 0.01 ) ; and older maternal age , low percentile for birth weight , and the percentage of weight loss during hospitalization ( p < 0.05 ) . Variables with significantly different frequencies in control and study groups were used in a multivariate analysis , thus further refining the data by the use of logistic regression . Teenage mothers ( < 19 years old ) had the lowest risk , whereas older mothers ( > 35 years old ) had the highest risk of all age groups for having an infant with neonatal jaundice . First delivery and previous sibling with neonatal jaundice were also risk factors . Male sex , short gestation , and delivery by vacuum extraction were other notable risk factors . Our results suggest that , even among industrialized Western societies , risk factors may interact differently to produce higher neonatal serum bilirubin levels . The importance of a risk factor may also be dependent upon its relative prevalence in a parturient population We compared the incidence of Caesarean delivery in nulliparous women r and omized to receive epidural analgesia with those r and omized to intramuscular ( i.m . ) pethidine . On admission to the delivery suite in established labour , 802 nulliparae had already agreed to be r and omized with respect to their first analgesia . One hundred and eighty-eight women required either no analgesia or 50 % nitrous oxide in oxygen ( Entonox ) only . Of the remaining 614 women , 310 were r and omly allocated to receive i.m . pethidine up to 300 mg and 304 to receive epidural bupivacaine . Labour management was st and ardized according to the criteria for active management of labour . The intention-to-treat analysis showed similar Caesarean section rates in those r and omized to epidural ( 12 % ) or pethidine analgesia ( 13 % ) . The difference in Caesarean rate was -1.1 % with 95 % confidence intervals from -6.3 % to + 4.1 % . The normal vaginal delivery rates were similar ( epidural , 59 % ; pethidine , 61 % ) The frequency of " significant " jaundice of the newborn at this hospital increased from 8 - 1 % of all live births in 1971 to 12 - 1 % in 1972 and 15 - 4 % in 1973 . This coincided with an increased use of oxytocic agents and epidural anaesthetics in labour , and a change in the artificial feed given to normal infants . A retrospective study of jaundiced infants born in 1972 failed to explain the increase in jaundice . Though the use of oxytocic agents was not the direct cause , since their use results in the delivery of more infants before 40 weeks of gestation it may be a contributory factor . The use of epidural anaesthetics was sastically related to the development of jaundice but the nature of the association was not clear . Mothers of infants who became jaundiced has a significantly higher frequency of poor past obstetric histories , but once again the association was not clear . The change in artificial feeds was excluded as a possible cause We have performed a r and omized comparison of two low-dose epidural regimens for analgesia in labour , differing only in the manner in which initial analgesia was established . In the epidural ( EPI ) group , 484 women received a loading dose of 20 ml of 0.1 % bupivacaine with fentanyl 2 micrograms ml-1 . In the combined spinal-epidural ( CSE ) group , 524 women received a spinal injection of plain bupivacaine 2.5 mg with fentanyl 25 micrograms . In both groups , these initial doses were followed by 0.1 % bupivacaine with fentanyl 2 micrograms ml-1 infused at a rate of 12 ml h-1 , with 20-ml top-ups for breakthrough pain . The groups were compared for midwife assessment of analgesic efficacy , delivery mode , patient assessment s of first stage analgesia , second stage analgesia , overall analgesia , motor block and complications . Midwives , who were not blinded to the treatment groups , assessed 61.6 % of CSE as providing ' excellent ' analgesia compared with 56.4 % of epidurals ( P = 0.02 ) . Patients assessed overall analgesia as ' excellent ' in 74.8 % of CSE compared with 71.7 % of epidurals ( P = 0.14 ) . Other comparisons between groups revealed no differences . These findings may have been affected by an uneven distribution of multiparous women between the groups ( 25 % in the EPI group and 34.2 % in the CSE group ; P = 0.002 ) . However , subgroup analysis of primiparous and multiparous women did not alter the results The analgesic efficacy and incidence of maternal , fetal and neonatal side-effects of combined spinal epidural ( CSE ) and epidural ( EPI ) analgesia , using a mixture of bupivacaine 0.125 % , epinephrine ( 1.25 micrograms.ml-1 ) and sufentanil ( 0.75 microgram.ml-1 ) for the relief of labor pain , were r and omly and prospect ively compared in 110 parturients . A 29 gauge Whitacre tip spinal needle was used to perforate the dura in CSE patients . Compared to EPI , CSE result ed in rapid ( 326 + /- 22 vs 766 + /- 79 sec , p < 0.05 ) , excellent analgesia , using less bupivacaine ( 23.5 + /- 2.3 vs 33.9 + /- 2.9 mg , p < 0.05 ) and sufentanil ( 12.5 + /- 1.0 vs 16.5 + /- .7 micrograms , p < 0.05 ) . A tendency to improved patient satisfaction in the CSE group was observed . The incidence of maternal or neonatal side effects was similar in both groups . No PDPH was observed . We conclude that CSE analgesia results in excellent pain relief during labor with immediate gratification as compared to epidural analgesia We have studied the efficacy of two extradural infusions ( 10 ml h-1 ) in 50 patients in active labour . Patients in the diamorphine group ( n = 25 ) received 0.0625 % plain bupivacaine 6.25 mg h-1 mixed with 0.005 % diamorphine 0.5 mg h-1 and those in the control group ( n = 25 ) received 0.125 % plain bupivacaine 12.5 mg h-1 . Both groups received intermittent " top-ups " of 0.25 % bupivacaine 10 ml when indicated . Although median pain scores during the infusion were similar in both groups , patients in the diamorphine group indicated greater satisfaction with the infusion ( 88 % very satisfied , compared with 52 % in the control group ( P < 0.02 ) ) . There were no differences in the incidence of hypotension , instrumental vaginal delivery , number of " top-ups " , duration of the second stage or extent of motor block . However , patients in the diamorphine group had a high incidence of pruritus ( 44 % , compared with 0 % in the control group ( P < 0.01 ) ) The aim of this study was to determine the effect on the instrumental delivery rate of two different concentrations of bupivacaine combined with fentanyl in epidural infusions during labour . Only primiparous women in whom a spontaneous vaginal delivery was anticipated , were included in the study . Those women receiving a higher concentration of bupivacaine and therefore a greater amount of local anaesthetic agent during labour were significantly more likely to have an instrumental delivery with Kiell and 's rotational forceps ( p < 0.01 ) . Those women receiving a lower concentration and smaller amount of bupivacaine were significantly more likely to have an instrumental delivery with Neville‐Barnes forceps ( p < 0.05 ) . This provides evidence to support the theory that epidural analgesia may contribute to inadequate rotation of the presenting fetal part due to weakened pelvic floor muscles and that this is more likely to occur when higher concentrations of bupivacaine are used and a greater degree of motor block occurs Background Some studies suggest that epidural analgesia prolongs labor and increases the incidence of cesarean section , especially if it is administered before 5 cm cervical dilation . The purpose of the current study was to determine whether early administration of epidural analgesia affects obstetric outcome in nulliparous women who are receiving intravenous oxytocin . Methods Informed consent was obtained from healthy nulliparous women with a singleton fetus in a vertex presentation , who requested epidural analgesia while receiving intravenous oxytocin at at least 36 weeks ' gestation . Each patient was r and omized to receive either early or late epidural analgesia . R and omization occurred only after the following conditions were met : ( 1 ) the patient requested pain relief at that moment , ( 2 ) a lumbar epidural catheter had been placed , and ( 3 ) the cervix was at least 3 but less than 5 cm dilated . Patients in the early group immediately received epidural bupivacaine analgesia . Patients in the late group received 10 mg nalbuphlne intravenously . Late-group patients did not receive epidural analgesia until they achieved a cervical dilation of at least 5 cm or until at least 1 h had elapsed after a second dose of nalbuphine . Results Early administration of epidural analgesia did not prolong the interval between r and omization and the diagnosis of complete cervical dilation , and it did not increase the incidence of malposition of the vertex at delivery . Also , early administration of epidural analgesia did not result in an increased incidence of cesarean section or instrumental vaginal delivery . Thirteen ( 18 % ) of 74 women In the early group and 14 ( 19 % ) of 75 women in the late group underwent cesarean section ( relative risk for the early group 0.94 ; 95 % confidence interval 0.48–1.84 ) . Patients in the early group had lower pain scores between 30 and 120 min after r and omization , and were more likely to experience transient hypotension . Infants in the late group had lower umbilical arterial and venous blood pH and higher umbilical arterial and venous blood carbon dioxide tension measurements at delivery . Conclusions Early administration of epidural analgesia did not prolong labor or increase the incidence of operative delivery , when compared with intravenous nalbuphine followed by late administration of epidural analgesia , in nulliparous women who were receiving intravenous oxytocin A r and omized , double blind , placebo-controlled study was performed to evaluate the analgesic efficacy and influence of continuing an epidural infusion of 0.125 % bupivacaine beyond a cervical dilatation of 8 cm in nulliparous women . When the cervix was ≥ 8 cm dilated , coded study solution was substituted for the known 0.125 % bupivacaine solution . The study solution for 46 patients was 0.125 % bupivacaine ; 46 patients received saline . During the first stage of labor , 44 ( 96 % ) women in the bupivacaine group , and 45 ( 98 % ) in the saline group , had analgesia of excellent or good quality . During the second stage , 36 ( 82 % ) women in the bupivacaine group , versus 18 ( 41 % ) women in the saline group , had analgesia of excellent or good quality ( P < .0001 ) . Six ( 13 % ) women in each group underwent cesarean delivery after the start of the study solution . Among the women who delivered vaginally , the mean ( ±S.D. ) duration of the second stage of labor was 124 ( ±70 ) min in the bupivacaine group , versus 94 ( ±54 ) min in the saline group ( P < .05 ) . Twenty-one of 40 ( 53 % ) women in the bupivacaine group , versus 11 of 40 ( 28 % ) in the saline group , underwent instrumental vaginal delivery ( P < .05 ) . Twenty-eight of 40 ( 70 % ) women in the bupivacaine group , versus six of 40 ( 15 % ) in the saline group , had surgical perineal anesthesia for vaginal delivery ( P < .0001 ) . There were no significant differences between groups in Apgar scores or umbilical cord blood acid-base values . We conclude that , under the conditions of the present study , epidural bupivacaine infusion beyond a cervical dilatation of 8 cm provided satisfactory analgesia , but prolonged the second stage of labor and increased the frequency of instrumental delivery in nulliparous women . However , maintenance of epidural bupivacaine analgesia did not result in an increased incidence of abnormal position of the vertex or a more frequent performance of cesarean section Our objective was to investigate by ultrasonography whether the risk for postpartum urinary retention is increased following administration of epidural analgesia during labor and delivery . In a prospect i ve study , 106 healthy women who had undergone vaginal delivery were evaluated . Sixty-eight of the women had received epidural analgesia during labor and delivery . All subjects had an ultrasound examination at a mean of 42 h after delivery , and residual urine volume was estimated immediately after voiding . Correlations among obstetric parameters , epidural analgesia and residual urine volumes were evaluated . The mean accuracy rate of ultrasonography for estimation of bladder volumes was + /- 10.2 % . No cases of clinical ly evident urinary retention were diagnosed in the total puerperal population . There were no significant differences between the groups in the average amounts of residual urine as measured by ultrasonography . With modern obstetric practice , epidural analgesia for labor is not associated with an increased risk for postpartum urinary retention . The non-invasive nature of ultrasound renders it especially attractive and useful for measuring residual urine volume in postpartum patients . The safety , simplicity and relative comfort of this method over-ride the slightly imperfect calculations that it currently yields , and makes it preferable to catheterization or cystometry for evaluation of residual urine volume Intrathecal sufentanil provides approximately 2 h of excellent labor analgesia with minimal motor blockade . Epidural sufentanil has received less scrutiny but may provide the same benefits as intrathecal sufentanil . In this study , we compared epidural sufentanil 40 [ micro sign]g after a lidocaine with an epinephrine test dose with intrathecal ( IT ) sufentanil 10 [ micro sign]g with respect to onset and duration of analgesia , degree of motor block , side effect profile , and mode of delivery . Seventy ASA physical status I or II parturients in early labor ( < or = to4 cm cervical dilation ) were r and omized to receive either IT sufentanil 10 [ micro sign]g with a combined spinal-epidural technique ( CSE ) or epidural sufentanil 40 [ micro sign]g ( EP ) after epidural catheter placement and testing with 3 mL of 1.5 % lidocaine with epinephrine ( 15 [ micro sign]g ) . After the administration of analgesia , pain scores and side effects were recorded for each patient at 5 , 10 , 15 , 20 , and 30 min , and every 30 min thereafter , by an observer blinded to the technique used . The study period was completed when the patients requested additional analgesia . All patients , except one , achieved adequate analgesia with the initial study dose and satisfactorily completed the study . There were no demographic differences between the two groups . Pain relief was rapid for all patients ; pain scores were significantly lower at 5 and 10 min in the IT group versus the EP group . The mean duration of analgesia was similar between the EP group ( 127 + /- 40 min ) and the IT group ( 110 + /- 48 min ) . No patient experienced any motor block . Side effects were similar between the two groups , except for pruritus-both the incidence and severity were significantly more profound at 5 , 10 , 15 , 20 , and 30 min in the IT group . There was no difference in time from analgesic to delivery , incidence of operative or assisted delivery , or cervical dilation at the time of redose . For early laboring patients , epidural sufentanil 40 [ micro sign]g after a lidocaine test dose provides analgesia comparable to that of IT sufentanil 10 [ micro sign]g with less pruritus . Implication s : We compared the efficacy and side effects of intrathecal sufentanil with epidural sufentanil with a local anesthetic test dose for analgesia during labor . Analgesia was equally good , although the intrathecal group experienced more itching . ( Anesth Analg 1998;87:331 - 5 Abstract Objective : To determine whether epidural anaesthesia during labour and delivery is a risk factor for postpartum back pain . Design : Prospect i ve cohort study with follow up at one day , seven days , and six weeks after delivery . Setting : Teaching hospital in Montreal . Subjects : 329 women who delivered a live infant(s ) during the study period . Exclusion criteria were back pain before pregnancy and delivery by elective caesarean section . Intervention : Epidural anaesthesia during labour and delivery . Main outcome measures and results : The primary outcome variable was development of postpartum low back pain . Back pain was quantified with self reports ( yes/no ) , a pain score ( numeric rating scale ) , and degree of interference with daily activities . Of the 329 women , 164 received epidural anaesthesia during labour and 165 did not . The incidence of low back pain in epidural v non-epidural group was 53 % v 43 % on day one ; 21 % v 23 % on day seven ; and 14 % v 7 % at six weeks . The relative risk for low back pain ( epidural v non-epidural ) adjusted for parity , delivery , ethnicity , and weight was 1.76 ( 95 % confidence interval 1.06 to 2.92 ) on day one ; 1.00 ( 0.54 to 1.86 ) on day seven ; and 2.22 ( 0.89 to 5.53 ) at six weeks . There were no differences between the two groups in pain scores or the frequency of interference with daily activities . Similar results were obtained in the subgroup of women with low back pain of new onset -- that is , those women with no back pain during their pregnancy . Conclusions : Postpartum low back pain was common but decreased considerably over the short term . The association between epidural anaesthesia and postpartum low back pain was inconsistent over time with a significantly increased risk of low back pain ( epidural v non-epidural ) noted only on the first day after delivery Background Combined spinal‐epidural ( CSE ) analgesia produces rapid‐onset pain relief and allows ambulation in early labor . Epidural local anesthetics may contribute to an increase in operative deliveries by decreasing perineal sensation and causing motor weakness . Operative delivery rates might be reduced with CSE , by avoiding or delaying administration of local anesthetics . This study compares the operative delivery rates associated with a CSE technique and those associated with intravenous meperidine for labor analgesia . Methods Healthy parturients at full term were assigned r and omly to receive CSE or intravenous meperidine analgesia . The CSE group received 10 [ micro sign]g intrathecal sufentanil , followed by epidural bupivacaine and fentanyl at their next request for analgesia . Parturients receiving intravenous meperidine had 50 mg on dem and ( maximum , 200 mg in 4 h ) . Labor and delivery outcomes in both groups were recorded and compared . Results An intent‐to‐treat analysis of 1,223 women indicated that CSE does not increase the rate of cesarean delivery for dystocia in nulliparous and parous women ( CSE , 3.5 % vs. intravenous meperidine , 4 ; P = not significant ) or in nulliparous women alone ( CSE , 7 % vs. intravenous meperidine , 8 % ; P = not significant ) . Profound fetal bradycardia that necessitated emergency cesarean delivery within 1 h of the time the mother received sufentanil occurred in 8 of 400 parturients ( compared with 0 of 352 who received meperidine ; P < 0.01 ) . However , the method of fetal monitoring differed between the two groups . Despite this , neonatal outcomes were similar overall . Conclusions Combined spinal‐epidural analgesia during labor does not increase the cesarean delivery rate for dystocia in healthy parturient patients at full term , regardless of parity . However , an unexpected increase in the number of cesarean deliveries for profound fetal bradycardia after intrathecal sufentanil was observed . Further investigation is warranted The relationship between epidural analgesia and a number of labour and delivery factors , relevant to fetal and neonatal condition , was considered in a prospect i ve study of 200 labours reaching the second stage of labour . The group was representative of the hospital population with regard to the proportion of nulliparous women , the incidence of instrumental vaginal deliveries and the incidence of epidural analgesia ( 37 % ) . The 8 % of labours requiring fetal blood sampling during the first stage , and the labours with fetal heart rate ( FHR ) decelerations in the hour prior to second stage ( 25 % ) and during pushing ( 50 % ) were significantly more likely to have been given an epidural . Nulliparity ( 55 % ) , induced labour ( 34 % ) , a first stage longer than eight hours ( 37 % ) , a second stage longer than 60 min ( 43 % ) , maternal pushing for longer than 36 min ( 50 % ) , forceps delivery ( 28 % ) and a 1 min Apgar score less than 7 ( 12 % ) were also factors associated with significantly higher rates of epidural analgesia whereas meconium ( 15 % ) , a small baby ( 16 % ) and umbilical arterial metabolic acidaemia ( 13 % ) were not . FHR decelerations in labours reaching the second stage with an epidural reflect adjustments to fetal cardiovascular control and not acidaemia OBJECTIVE --To examine the association between obstetric epidural anaesthesia and subsequent long term problems . DESIGN --Postal question naire on health problems after childbirth linked to maternity case note data . SETTING --Maternity hospital in Birmingham . SUBJECTS--11701 women who delivered their most recent child during 1978 - 85 and who returned completed question naires . MAIN OUTCOME MEASURES --Frequencies of long term symptoms after childbirth . RESULTS --Compared with the 6935 women who did not have epidural anaesthesia the 4766 women who did more commonly experienced backache ( 903 ( 18.9 % ) with epidural v 731 ( 10.5 % ) without epidural ) , frequent headaches 220 ( 4.6 % ) v 199 ( 2.9 % ) ) , migraine ( 92 ( 1.9 % ) v 73 ( 1.1 % ) ) , neckache ( 116 ( 2.4 % ) v 112 ( 1.6 % ) ) , and tingling in h and s or fingers ( 143 ( 3.0 % ) v 150 ( 2.2 % ) ) . The results could not be explained by correlated social or obstetric factors . The associations with head , neck , and h and symptoms were found only in women who reported backache . An excess of visual disturbances among women who had epidural anaesthesia ( 83 ( 1.7 % ) v 91 ( 1.3 % ) ) was present only in association with migraine , but excess of dizziness or fainting ( 102 ( 2.1 % ) v 109 ( 1.6 % ) ) was independent of other symptoms . 26 women had numbness or tingling in the lower back , buttocks , and leg , of whom 23 had had epidural anaesthesia . Of 34 women with spinal headache , nine ( five after accidental dural puncture ; four after spinal block ) reported long term headaches . CONCLUSIONS --These associations may indicate a causal sequence , although this can not be proved from this type of study . R and omised trials of epidural anaesthesia are required to determine whether causal relations exist A retrospective review of 202 r and omly selected records of parturient labors examined the relationship between cervical dilation at epidural analgesia administration and length of the second stage of labor . The epidural group received bupivacaine 0.11 % or 0.125 % with sufentanil 1 to 2 micrograms/mL using a Bard Patient Controlled Anesthesia II pump . Labor management and outcomes were compared with a nonepidural group who chose unmedicated childbirth , intravenous narcotics , or pudendal block . A significant inverse correlation was found between cervical dilation at epidural administration and second-stage length in labors that did not use oxytocin . However , linear regression explained only 13.5 % of the variance , leaving 86.5 % unexplained . In labors in the epidural group that used oxytocin , cervical dilation at epidural administration was not correlated with second-stage length . The epidural group experienced a significantly longer mean length of the second stage . Labors in the epidural group were 3.5 times more likely to have oxytocin induction or augmentation and 4.5 times more likely to experience instrument-assisted delivery . There were no significant differences in Apgar scores between the two infant groups Purpose To evaluate the usefulness of intravenous patient-controlled analgesia ( PCA ) fentanyl for labour analgesia , its effectiveness for maternal pain and safety for the fetus and newborn . Methods Twenty primigravidas were r and omised to receive intravenous PCA fentanyl or epidural analgesia for labour pain . Maternal pain , heart rate and arterial oxyhaemoglobin saturation ( SpO2 ) were monitored . Fetal and neonatal monitoring included cardiotocogram ( CTG ) , APGAR , neurological scoring and static-charge-sensitive bed ( SCSB ) recording for 12 hr postnatally with ECG and SpO2 . Fentanyl concentrations and pH of umbilical artery and vein were analysed . Results Initially , epidural analgesia was more effective ( P = 0.01 ) , and three patients in the fentanyl group were given epidural due to unsatisfactory pain relief . Overall satisfaction for analgesia did not differ between the groups . Maternal side-effects were more frequent in the fentanyl group ( dizziness and tiredness most often , P = 0.0001 ) . Severe side-effects were not reported . In CTG there were no differences between groups . All the newborns were healthy , APGAR and pH were normal . Naloxone was not used . Neurological scoring was similar in both groups . In 12 hr monitoring heart rate , breathing frequency and movement time were similar in both groups , but SpO2 was lower in the fentanyl group ( P < 0.001 ) . Umbilical cord fentanyl concentrations were low or beyond the detection limit . Conclusion Intravenous fentanyl can be used for labour analgesia with the doses reported here as an alternative to epidural analgesia . However , the fetus and neonate must be appropriately monitored . Naloxone and oxygen should be available if neonatal distress occurs . RésuméObjectifÉvaluer l ’ importance de l’analgésie intraveineuse auto-contrôlée ( PCA ) au fentanyl en analgésie obstétncale en tenant compte de son efficacité et de la sécurité foeto-maternelle . MéthodesVingt pnmipares ont été assignées aléatoirement à recevoir soit du fentanyl intraveineux en PCA soit une analgésie épidurale dans le but de soulager la douleur de l’accouchement . La douleur maternelle , la fréquence cardiaque et la saturation arténelle ( SpO2 ) ont été notées . Le monitorage foetal et néonatal incluait la cardiotocographie ( CTG ) , le score d’APGAR , l’évaluation neurologique et l’enregistrement au lit sensible à la statique ( SCSB ) pendant 12 h après la naissance avec l’ÉCG ET la SpO2 . La concentration de fentanyl et le pH de l’artère et de la veine ombilicales étaient mesurés . RésultatsInitialement , l’analgésie épidurale s’est avérée plus efficace ( P = 0,01 ) et trois patientes du groupe fentanyl ont dû accepter une analgésie épidurale à cause du manque de soulagement . La satisfaction globale en rapport avec l’analgésie n’a pas différé entre les groupes . Des effets maternels secondaires sans gravité sont survenus plus souvent dans le groupe fentanyl ( surtout des étourdissements et de la fatigue , P = 0,0001 ) . Le CTG n’a pas révélé de différences intergroupes . Tous les enfants sont nés en bon état avec des scores d’APGAR et des pH normaux . On n’a pas administré de naloxone . Lévaluation neurologique était identique dans les deux groupes . Après 12 h de monitorage de la fréquence cardiaque , la fréquence respiratoire et le temps de mouvement étaient identiques dans les deux groupes mais la SpO2 était plus basse dans le groupe fentanyl ( P < 0,001 ) . Les concentrations ombilicales de fentanyl étaient faibles ou impossible à déceler . Conclusion Pour l’analgésie de l’accouchement , on peut substituer le fentanyl intraveineux selon les doses utilisées à l’analgésie épidurale . Cependant , le foetus et le nouveau-né doivent être surveillés de près . Il faut avoir du naloxone ou de l’oxygène à portée de main pour traiter la détresse néonatale potentielle To identify the risk factors associated with subgaleal haemorrhage and to assess the long-term neurological and developmental morbidity in survivors , data were prospect ively collected over 5 years on 69 newborns with subgaleal haemorrhage from a cohort of 23,353 live and term deliveries , giving an incidence of subgaleal haemorrhage of 3.0 per 1000 live and term births . Multivariate analysis of risk factors associated with subgaleal haemorrhage on univariate analysis showed that prolonged second stage of labour ( OR = 9.02 ; 95 % CI 6.15 - 17.51 ) , fetal distress ( OR = 5.05 ; 95 % CI 2.67 - 11.12 ) , vacuum delivery ( OR = 7.17 ; 95 % CI 5.43 - 10.25 ) , forceps delivery ( OR = 2.66 ; 95 % CI 1.78 - 5.18 ) , and birthweight ( OR = 2.20 ; 95 % CI 1.54 - 6.56 ) significantly influenced the occurrence of subgaleal haemorrhage . When the effects of prolonged second stage of labour , fetal distress , birthweight and gestational age were controlled for , the odds of harbouring subgaleal bleed following vacuum delivery were , respectively , OR = 7.80 ( 95 % CI 5.45 - 11.61 ) , OR = 6.15 ( 95 % CI 3.71 - 10.84 ) , OR = 5.01 ( 95 % CI 2.78 - 9.63 ) and OR = 7.65 ( 95 % CI 4.73 - 16.65 ) . Among the 69 newborns with subgaleal haemorrhage , ten ( 14 % ) died and twelve ( 20 % ) of the 59 survivors were lost to follow-up . Of the remaining 47 survivors , three ( 6 % ) died during follow-up of diseases unrelated to the bleed , leaving 44 survivors , none of whom had either neurological deficit or developmental delay . The study concludes that subgaleal haemorrhage in neonates is the result of birth trauma associated with difficult instrumental delivery . Newborns with subgaleal haemorrhage who survive the acute episode of the bleed show no evidence of subsequent long-term neurological deficit or developmental delay One hundred eighty-four patients were assessed prospect ively by uroflowmetry and postmicturition ultrasonography on a daily basis in the immediate postpartum period to assess the incidence of abnormal voiding parameters , their predisposing factors , and whether the combination of two screening tests was more helpful than either alone as a screening test of abnormal voiding in the puerperium . The incidence of abnormal voiding parameters was 43 % . The majority of these were asymptomatic . Of those patients who had an abnormality , 68 % had normal voiding parameters by the time they went home , and all of those who returned for follow-up had normal parameters . Operative delivery , perineal trauma , and epidural anaesthesia all increased the incidence of abnormal voiding parameters . Residual urine was a feature in 70 of the 79 patients found to be abnormal , and the incidence of an abnormal flow rate was not significantly greater than in the nonpregnant population . This suggests that the addition of uroflowmetry does not confer any benefit over postmicturition assessment of residual urine by ultrasonography in the detection of patients with postpartum voiding dysfunction Two groups of nulliparous women with fetuses in singleton vertex presentation received continuous infusion epidural analgesia ( EDA ) with bupivacaine : group A ( 90 parturients ) without infusion analgesia in the second stage of labor and group B ( 90 parturients ) with infusion analgesia throughout delivery . The groups were compared regarding pain relief , duration of the second stage , persistent malrotation of the fetal head , and rate of instrumental vaginal delivery . The continuous infusion EDA gave satisfactory pain relief in 93.3 % of the parturients in group A and 97.8 % in group B. The duration of second stage was the same in both groups . There were more persistent mal‐rotations of the fetal head in group A , but the malrotation did not affect the mode of deli : very . The rate of instrumental vaginal delivery was 25.5 % in both groups . The main cause of operative intervention was delay in the second stage . When the continuous infusion technique is used , it seems unreasonable to discontinue the EDA and thereby deprive the parturient of analgesia during the second stage BACKGROUND In the hierarchy of research design s , the results of r and omized , controlled trials are considered to be evidence of the highest grade , whereas observational studies are viewed as having less validity because they reportedly overestimate treatment effects . We used published meta-analyses to identify r and omized clinical trials and observational studies that examined the same clinical topics . We then compared the results of the original reports according to the type of research design . METHODS A search of the Medline data base for articles published in five major medical journals from 1991 to 1995 identified meta-analyses of r and omized , controlled trials and meta-analyses of either cohort or case-control studies that assessed the same intervention . For each of five topics , summary estimates and 95 percent confidence intervals were calculated on the basis of data from the individual r and omized , controlled trials and the individual observational studies . RESULTS For the five clinical topics and 99 reports evaluated , the average results of the observational studies were remarkably similar to those of the r and omized , controlled trials . For example , analysis of 13 r and omized , controlled trials of the effectiveness of bacille Calmette-Guérin vaccine in preventing active tuberculosis yielded a relative risk of 0.49 ( 95 percent confidence interval , 0.34 to 0.70 ) among vaccinated patients , as compared with an odds ratio of 0.50 ( 95 percent confidence interval , 0.39 to 0.65 ) from 10 case-control studies . In addition , the range of the point estimates for the effect of vaccination was wider for the r and omized , controlled trials ( 0.20 to 1.56 ) than for the observational studies ( 0.17 to 0.84 ) . CONCLUSIONS The results of well- design ed observational studies ( with either a cohort or a case-control design ) do not systematic ally overestimate the magnitude of the effects of treatment as compared with those in r and omized , controlled trials on the same topic A r and omized double-blind study evaluated the analgesic efficacy and influence of maintaining a continuous epidural infusion of 0.75 % lidocaine during the second stage of labor in nulliparous women . When the cervix was 8 cm or more dilated , unidentified study solution was substituted for the known 0.75 % lidocaine solution and continued until delivery . The study solution for 26 patients was 0.75 % lidocaine ; 27 subjects received saline . During the first stage of labor , 88 % of women in the lidocaine group and 81 % of women in the saline group had analgesia of excellent or good quality , a nonsignificant difference . During the second stage , there was a tendency ( not statistically significant ) toward improved analgesia quality in the lidocaine patients , but there was no significant difference in the frequency of perineal anesthesia ( 23 % lidocaine , 7 % saline ) . There was no difference between the groups in the duration of the second stage of labor ( 73 ± 63 versus 76 ± 48 minutes ) . Operative delivery frequency was similar ( 31 and 37 % ) , as were umbilical cord blood acid-base values . It is concluded that maintenance of the continuous epidural infusion of 0.75 % lidocaine did not prolong the second stage of labor , but it also did not significantly differ from saline in quality of second stage analgesia or frequency of perineal anesthesia This study compares a continuous infusion technique with intermittent " top-up " doses using 0.25 per cent bupivacaine for epidural analgesia for labour and delivery in healthy primiparous patients . Sixty women were r and omized into two groups , A ( continuous ) and B ( intermittent ) . Twenty-eight patients in Group A and 29 in Group B completed the study . We compared the groups with regard to satisfaction with pain relief for both labour and delivery as measured by a Visual Analogue Scale on five occasions during and after parturition . There was no difference between groups at any of the five stages . The difference in pain scores before the epidural and after the epidural was significant for both groups ( p less than 0.001 ) . The incidence of missed segments , degrees of motor block , height of sensory block , length of labour and fetal outcome were similar in both groups . Plasma bupivacaine levels were measured in six patients in each group . Mothers in Group A received more drug than those in Group B ( p less than 0.01 ) but plasma bupivacaine levels remained low in the mother and the umbilical cord sample s in the sub-set from this group . More women in Group A required outlet forceps ( p less than 0.05 ) whereas mid-forceps and Caesarean section rates were similar in the two groups . Fewer mothers in the infusion group had spontaneous vaginal delivery . We conclude that infusion techniques are as effective as intermittent top-up epidurals and are well received by mothers in labour BACKGROUND Changes in basal temperature of > or = 1 degree C ( e.g. , fever-induced hyperthermia or anesthesia-related hypothermia ) are a common occurrence in neurologically impaired patients . The current study tested the hypothesis that temperature changes as small as 1 degree C or 2 degrees C would significantly alter post-ischemic functional neurologic outcome and cerebral histopathology . The hypothesis was tested in a canine model of transient , complete cerebral ischemia . METHODS After institutional approval , 21 dogs were r and omly assigned to one of three temperature-specific groups : ( 1 ) a reference group maintained at 37.0 + /- 0.3 degree C ( target temperature + /- range ) ; ( 2 ) a 38.0 + /- 0.3 degree C group ; or ( 3 ) a 39.0 + /- 0.3 degree C group ( n = 7 per group ) . Complete cerebral ischemia 12.5 min in duration was produced using an established model of arterial hypotension plus intracranial hypertension . Right atrial and cranial ( beneath the temporalis muscles ) temperatures were maintained at the target value , beginning 20 min before ischemia and ceasing 1 h postischemia . Thereafter , temperatures were returned to 37.0 + /- 0.3 degree C in all dogs . After discharge from the intensive care environment , all dogs were placed in a temperature-controlled recovery area . Neurologic assessment was performed by a blinded observer at 24 , 48 , and 72 h postischemia using a 100-point scoring scale . After the 72 h examination ( with the dogs anesthetized ) or at the time of ischemia-related death , the brains were excised and preserved . The brains subsequently were histologically scored by a neuropathologist who was unaware of the treatment groups . All 21 dogs were included in the analysis of neurologic function ; however , only dogs that survived for > or = 24 h postischemia were included in the histopathology analysis . RESULTS Dogs were well matched for systemic physiologic variables throughout the study , with the exception of temperature . During the 72 h postischemic examination , dogs maintained at 37 degrees C were either normal or near normal . In contrast , dogs maintained at 39 degrees C were either comatose or died from ischemia-related causes . Dogs maintained at 38 degrees C were intermediate between 37 degrees C and 39 degrees C dogs . When compared with the reference group , both 38 degrees C and 39 degrees C dogs had significantly worse neurologic function scores ( P < 0.01 and < 0.001 , respectively ) and histopathology scores ( P < 0.01 for both ) . There also was a significant correlation between neurologic function and histopathology rank scores ( rs = 0.96 ; P < 0.001 ) . CONCLUSIONS Small , clinical ly relevant changes in temperature ( 1 degree C or 2 degrees C ) result ed in significant alterations in both postischemic neurologic function and cerebral histopathology . Assuming that our results are transferable to humans , the results suggest that , in patients at imminent risk for ischemic neurologic injury , body temperature should be closely monitored . Further , the clinician should aggressively treat all episodes of hyperthermia until the patient is no longer at risk for ischemic neurologic injury OBJECTIVE To assess whether epidural analgesia is associated with fever , independent of maternal infection , by evaluating the relationship between epidural analgesia and inflammation of the placenta . METHODS Placentas collected prospect ively from women with singleton gestations , who delivered 6 hours or more after membrane rupture , were evaluated systematic ally for histologic inflammation by an investigator blinded to all clinical information . Maternal and neonatal markers of infection were assessed in the cohorts who did and did not receive epidural analgesia . RESULTS One hundred forty-nine consecutive placentas were analyzed , and 80 ( 54 % ) of these women received epidural analgesia . On univariate analysis , significant differences between epidural and no epidural groups were found with respect to maternal fever 38C or greater ( 46 % versus 26 % , P = .01 ) , placenta inflammation ( 61 % versus 36 % , P = .002 ) , and length of labor ( 11.8 hours versus 9.6 hours , P = .03 ) . The combination of maternal fever plus placental inflammation was significantly more common in the epidural group ( 35 % versus 17 % P = .02 ) . However , maternal fever in the absence of supporting evidence of infection , in the form of placental inflammation , was not increased after epidural analgesia ( 11 % versus 9 % , P = .61 ) . CONCLUSION Epidural analgesia is associated with intrapartum fever , but only in the presence of placental inflammation . This suggests that the fever reported with epidural analgesia is due to infection rather than the analgesia itself STUDY OBJECTIVE To analyze the effects of epidural analgesia for labor when dystocia occurs . DESIGN Retrospective cohort study . SETTING Academic health center . PATIENTS 641 low risk , nulliparous women in spontaneous labor . INTERVENTIONS 406 ( 63 % ) women received epidurals analgesia and 253 ( 37 % ) did not . Sixty women ( 9.4 % ) required an abdominal delivery for dystocia . MEASUREMENTS AND MAIN RESULTS Women receiving epidural analgesia were more likely to be white , receive care from an attending physician , need labor augmentation , and deliver a heavier infant . Multivariate analysis identified five variables predictive of dystocia and abdominal delivery : pitocin augmentation odds ratio ( O.R. ) = 3.9 ( 2.0 to 7.6 ) , duration of labor more than 20 hours O.R. = 2.4 ( 1.3 to 4.4 ) , high epidural dose O.R. = 2.2 ( 1.2 to 4.1 ) , birthweight over 4,000 grams O.R. = 2.0 ( 1.0 to 4.2 ) , and early placement of epidural O.R. = 1 . 9 ( 1.0 to 3.5 ) . Repeating the regression after excluding the 20 women who developed abnormal labor prior to epidural placement ( 18 of 20 women had protracted dilatation ) demonstrated that pitocin augmentation O.R. = 4.0 ( 1.8 to 4 . ) , high epidural dose O.R. = 3.0 ( 1.9 to 6.2 ) , duration of labor greater than 20 hours O.R. = 2.7 ( 1.3 to 5.7 ) , and birthweight over 4,000 grams O.R. = 2.1 ( 0 . 9 to 4.8 ) were associated with dystocia . CONCLUSION Epidural analgesia appears to be a marker of abnormal labor rather than a cause of dystocia . High concentration anesthetics and epinephrine should be avoided , as they may influence labor . R and omized , controlled trials of this technique will be difficult to do ; our work should reassure patients and their clinicians that epidural analgesia does not adversely affect labor Background and Objectives Over 100 papers in the medical literature suggest pro or con that epidural analgesia is associated with an increase in the incidence of instrument delivery . This two-component study was performed to evaluate the influence of epidural labor analgesia on the incidence of instrument delivery . Methods Component 1 was a retrospective analysis of the medical records of 14,804 mothers having a vaginal delivery before and after implementation of an active epidural service . Component 2 was a case control study design ed to determine factors , in addition to epidural analgesia , associated with an increase in instrument delivery . In component 2 11 factors describing maternal , fetal , anesthetic , and obstetric factors were analyzed for each of 609 consecutive patients having an instrument delivery and 246 controls having a spontaneous vaginal delivery . Results In component 1 , despite a tenfold increase in the use of epidural analgesia , there was a similar association between epidural use and instrument delivery in both time periods . Additionally , the epidural-forceps association was twice as strong for parous patients as for nulliparous patients ( odds-ratios 9.74 and 4.52 , respectively ) . In component 2 , five factors were significantly ( P > .0001 ) associated with instrument delivery conclusions . Conclusions While epidural analgesia was one factor , the others were gestational age > 41 weeks , a second stage of labor > 2 hours , an occiput posterior or transverse fetal position , and previous cesarean section . These four factors are individually and independently associated with an increase in the incidence of instrument delivery independent of epidural use The aim of the study was to investigate the effect of epidural analgesia on blood pressure , duration of the second stage and mode of delivery . In a prospect i ve controlled study carried out in a district general hospital , 122 parturients made up the study population ; 81 had epidural blocks and 41 had other forms of analgesia during labour . Data were collated using question naires within 48 hours of delivery : 58/81 ( 71.6 % ) of those who chose epidural were primigravidae compared with 14/41 ( 34 % ) in the non-epidural group ( p < 0.001 ) . During labour , minimum diastolic blood pressure was significantly lower in the epidural group : 65.8 versus 72.4 mmHg ( p = 0.003 ) . Mean duration of the second stage of labour was significantly longer in the epidural group : 108.3 versus 41.6 minutes ( p < 0.0001 ) ; 28/81 ( 34.6 % ) of the epidural group had operative vaginal deliveries compared with 6/41 ( 14.6 % ) of the non-epidural group ( p = 0.0004 ) . Epidural analgesia provides an effective form of pain relief in labour , which has a particularly strong appeal to primigravidae . It has a hypotensive effect which can be put to beneficial effect in hypertensive disease of pregnancy , but is significantly associated with a lengthened second stage of labour , result ing in an increased operative vaginal delivery rate Summary : We investigated the maternal characteristics , labour performance and delivery mode of 497 nulliparas entering labour spontaneously at term to identify the obstetric factors which influenced their choice of analgesia ; 51.7 % of these women used epidural analgesia . They were shorter ( 163 versus 165 cm , p=0.002 ) and the mean gestation was 3 days greater than those not using epidural analgesia ( 40.2 versus 39.6 weeks , p=0.0007 ) . Median birth‐weight in the epidural group was greater by 155 g ( 3,450 versus 3,295 gs , p=0.0001 ) . Analysis of the labour characteristics showed a lesser cervical dilatation on admission , significantly longer latent and active phases of labour and second stage length in the epidural cohort . The need for oxytocin augmentation was significantly greater in the epidural group , both prior to and after insertion . Oxytocin augmentation was strongly associated with an increased risk of operative intervention regardless of analgesia . Selection of intrapartum analgesia is not a r and om event and epidural analgesia appears to be an indicator of abnormal labour patterns . To further investigate the impact of analgesic methods on nulliparous labour we are currently conducting a prospect i ve r and omized controlled trial A prospect i ve r and omized study was performed to evaluate the influence of epidural analgesia compared to parenteral pethidine in parturients with pain in the first stage of labour on the progress of labour and the frequency of instrumental deliveries . There was no significant difference in the two groups in the duration of either the first or second stage of labour . The overall instrumental delivery rate was 25 % , with no difference between the groups . The analgesic efficacy of the epidural blockade was significantly better than that of parenteral pethidine . We conclude that epidural bupivacaine with our technique and obstetric practice did neither prolong labour nor increase the frequency of instrumental delivery Eighty normal primigravidae received an extradural dose of 0.25 % bupivacaine and were then allocated r and omly to receive " top-ups " of 0.25 % bupivacaine ( group A ) or an infusion of 0.125 % bupivacaine ( group B ) . Group B received supplementary top-ups if required . Group A required more top-ups ( 147 vs 80 ) ( P < 0.01 ) . No maternal advantage was demonstrated from each regimen . Fetal state was assessed by analysis of the cardiotocograph during labour and the condition of the fetus at delivery . Three different patterns of late deceleratory episodes were identified ( grade s 1 - 3 ) . Total numbers of episodes per group were similar ( group A , 71 ; group B , 69 ) . More episodes in group A were related to top-ups ( 42/71 vs 18/69 ; P < 0.01 ) but the incidence of episodes after a top-up was similar ( group A , 42/147 ( 28.6 % ) ; group B , 18/80 ( 22.5 % ) ) . In group A , 31/42 events ( 73.8 % ) were transient compared with 11/18 persistent episodes ( 61.1 % ) ( > 10 min duration ) in group B. However , the difference in the deceleratory patterns did not influence the condition of the fetuses at delivery BACKGROUND : For many years it has been cl aim ed that observational studies find stronger treatment effects than r and omized , controlled trials . We compared the results of observational studies with those of r and omized , controlled trials . METHODS : We search ed the Abridged Index Medicus and Cochrane data bases to identify observational studies reported between 1985 and 1998 that compared two or more treatments or interventions for the same condition . We then search ed the Medline and Cochrane data bases to identify all the r and omized , controlled trials and observational studies comparing the same treatments for these conditions . For each treatment , the magnitudes of the effects in the various observational studies were combined by the Mantel-Haenszel or weighted analysis -of-variance procedure and then compared with the combined magnitude of the effects in the r and omized , controlled trials that evaluated the same treatment . RESULTS : There were 136 reports about 19 diverse treatments , such as calcium-channel-blocker therapy for coronary artery disease , appendectomy , and interventions for subfertility . In most cases , the estimates of the treatment effects from observational studies and r and omized , controlled trials were similar . In only 2 of the 19 analyses of treatment effects did the combined magnitude of the effect in observational studies lie outside the 95 percent confidence interval for the combined magnitude in the r and omized , controlled trials . CONCLUSIONS : We found little evidence that estimates of treatment effects in observational studies reported after 1984 are either consistently larger than or qualitatively different from those obtained in r and omized , controlled trials One hundred primigravidae were allocated r and omly to receive either an extradural infusion of 0.125 % bupivacaine ( Marcain ) 10 ml ( 12.5 mg ) per hour during labour , or no infusion . Both groups had intermittent " top-ups " of 0.5 % bupivacaine when indicated . The mean interval between top-ups was significantly longer in the infusion group ( 218 min v. 152 min ) . Seventy-six percent of the mothers in the infusion group required no or only one top-up . Although the infusion patients received a higher mean dose of bupivacaine ( 178 mg v. 130 mg ) , there was no difference between the groups with respect to mode of delivery , need for urinary catheterization , adverse cardiovascular effects on mother or fetus , or the time taken after delivery to recover sensation and motor power . The only real disadvantage was that the infusion group had an increased incidence of lower limb weakness ( 64 % v. 44 % ) . The neonates had similar Apgar scores , times to sustained respiration and requirements for resuscitation . The technique , therefore , should be safe if coupled with testing of sensory level , as no block extended higher than T6 OBJECTIVE To compare station and cervical dilation at the time of epidural placement for predicting cesarean delivery risk . METHODS This prospect i ve cohort study included 275 women in labor with live , singleton fetuses at term in vertex presentations . We excluded women with preeclampsia or previous cesarean deliveries . A multiple logistic regression model evaluated demographic and labor-related variables ' associations with cesarean risk . RESULTS Fifty-nine of the 275 patients receiving epidural analgesia ( 21.5 % ) were delivered by cesarean , whereas 216 ( 78.5 % ) delivered vaginally . Variables that proved to be statistically significant in increasing the likelihood of cesarean were station at time of epidural placement ( odds ratio [ OR ] 5.3 ; 95 % confidence interval [ CI ] 2.6 , 11.0 ; P < .001 ) and nulliparity ( OR 3.8 , 95 % CI 1.8 , 8.0 ; P < .001 ) . Cervical dilation at the time of epidural placement was not a statistically significant predictor ( OR 1.2 , 95 % CI 0.9 , 1.6 ; P = .26 ) . Cesareans were performed in 43 of 129 women ( 33.3 % ) who received epidurals with the vertex at a -1 station or higher , whereas only 16 of 146 women ( 11.0 % ) had cesareans if placement of the epidural was done after the vertex had reached at least a zero station . CONCLUSION Station at the time of epidural placement was more accurate predicting cesarean risk than cervical dilation . Placement of the epidural after the fetal vertex has become engaged in the pelvis ( at least a zero station ) result ed in a substantially lower cesarean risk OBJECTIVE Our purpose was to determine the effect of epidural analgesia on nulliparous labor and delivery . STUDY DESIGN Normal term nulliparous women in early spontaneous labor were r and omized to receive either narcotic or epidural analgesia . RESULTS When compared with the group receiving narcotic analgesia ( n = 45 ) , the group receiving epidural analgesia ( n = 48 ) had a significant prolongation in the first and second stages of labor , an increased requirement for oxytocin augmentation , and a significant slowing in the rate of cervical dilatation . Epidural analgesia was associated with a significant increase in malposition ( 4.4 % vs 18.8 % , p < 0.05 ) . Cesarean delivery occurred more frequently in the epidural group ( 2.2 % vs 25 % , p < 0.05 ) , primarily related to an increase in cesarean section for dystocia ( 2.2 % vs 16.7 % , p < 0.05 ) . CONCLUSIONS In a r and omized , controlled , prospect i ve trial epidural analgesia result ed in a significant prolongation in the first and second stages of labor and a significant increase in the frequency of cesarean delivery , primarily related to dystocia To assess the safety and effect of epidural analgesia on the course of labour and delivery in Pakistani women , a retrospective case control study was conducted from November , 1986 to November , 1991 ( 5 years ) at the Aga Khan University Medical Centre , Karachi . All patients ( n = 64 ) who received epidural analgesia for labour ( cases ) were compared with r and omly selected patients ( n = 18 ) who did not receive epidural analgesia during labour ( controls ) . The cases and controls were matched for age , height , body mass index , parity , use of oxytocin , presentation and weight of the foetus . There was no significant difference ( P > 0.05 ) between the two groups in duration of labour , caesarean section rate and foetal apgar scores at 1 and 5 minutes after birth . The incidence of malposition of foetal vertex at delivery and that of instrumental ( forceps ) deliveries was significantly higher ( P < 0.05 and < 0.01 respectively ) in the epidural group as compared to controls . The incidence of complications was low and the acceptance and tolerance of epidural analgesia was good in our patients OBJECTIVE To assess whether the station of the fetal head when lumbar epidural analgesia is administered influences the duration or the mode of delivery in low-risk laboring women . METHODS We prospect ively evaluated 131 consecutive cases of low-risk parturients at term who requested intrapartum epidural analgesia . Obstetric outcome of 65 parturients who underwent epidural analgesia when the fetal head was low in the birth canal was compared to 66 patients whose fetal head station was above the ischial spine . RESULTS Both groups were similar in their obstetric characteristics . Cervical dilatation when performing the epidural analgesia was similar in both groups . The duration of labor and mode of delivery , as well as percentage of malpositions , were not significantly different in the two groups . CONCLUSIONS The station of the fetal head while initiating epidural analgesia does not influence the duration of labor or the mode of delivery . Therefore , there is no justification to delay epidural analgesia in labor until the presenting fetal part is engaged Background Some studies suggest that epidural analgesia prolongs labor and increases the incidence of cesarean section , especially if it is administered before 5 cm cervical dilation . The purpose of the current study was to determine whether early administration of epidural analgesia affects obstetric outcome in nulliparous women who are in spontaneous labor . Methods Informed consent was obtained from 344 healthy nulliparous women with a singleton fetus in a vertex presentation , who requested epidural analgesia during spontaneous labor at at least 36 weeks ' gestation . Each patient was r and omized to receive either early or late epidural analgesia . R and omization occurred only after the following conditions were met : ( 1 ) the patient requested pain relief at that moment , ( 2 ) a lumbar epidural catheter had been placed , and ( 3 ) the cervix was at least 3 cm but less than 5 cm dilated . Patients in the early group immediately received epidural bupivacaine analgesia . Patients in the late group received 10 mg nalbuphlne intravenously . Late-group patients did not receive epidural analgesia until they achieved a cervical dilation of at least 5 cm or until at least 1 h had elapsed after a second dose of nalbuphine . Ten of the 344 patients were excluded because of a protocol violation or voluntary withdrawal from the study . Results Early administration of epidural analgesia did not increase the incidence of oxytocin augmentation , prolong the interval between r and omization and the diagnosis of complete cervical dilation , or increase the incidence of malposition of the vertex at delivery . Also , early administration of epidural analgesia did not result in an increased incidence of cesarean section or instrumental vaginal delivery . Seventeen ( 10 % ) of 172 women in the early group and 13 ( 8 % ) of 162 women in the late group underwent cesarean section ( relative risk for the early group 1.22 ; 95 % confidence interval 0.62–2.40 ) . Patients in the early group had lower pain scores between 30 and 150 min after r and omization . Infants in the late group had lower umbilical arterial and venous blood pH and higher umbilical venous blood carbon dioxide tension measurements at delivery . Conclusions Early administration of epidural analgesia did not prolong labor , increase the incidence of oxytocin augmentation , or increase the incidence of operative delivery , when compared with intravenous nalbuphlne followed by late administration of epidural analgesia , in nulliparous women who were in spontaneous labor at term Objective To compare the effects of epidural analgesia with intravenous ( IV ) analgesia on the outcome of labor . Methods Thirteen hundred thirty women with uncomplicated term pregnancies and in spontaneous labor were r and omized to be offered epidural bupivacaine-fentanyl or IV meperidine analgesia during labor . Results Comparison of the allocation groups by intent to treat revealed a significant association between epidural allocation and operative delivery for dystocia . However , only 65 % of each r and omization group accepted the allocated treatment . Four hundred thirty-seven women accepted and received meperidine as allocated , and they were compared with 432 women accepting epidural allocation . Significant associations result ed between epidural administration and prolongation of labor , increased rate of oxytocin administration , chorioamnionitis , low forceps , and cesarean delivery . Because of the high rate of noncompliance with treatment allocation , a multifactorial regression analysis was performed on the entire cohort , and a twofold relative risk of cesarean delivery persisted in association with epidural treatment . The impact of epidural treatment on cesarean delivery was significant for both nulliparous and parous women ( risk ratios 2.55 and 3.81 , respectively ) . Epidural analgesia provided significantly better pain relief in labor than did parenteral meperidine . Conclusion Although labor epidural analgesia is superior to meperidine for pain relief , labor is prolonged , uterine infection is increased , and the number of operative deliveries are increased . A two- to fourfold increased risk of cesarean delivery is associated with epidural treatment in both nulliparous and parous women BACKGROUND Among nulliparous women , there appears to be an association between the use of epidural analgesia during labor and an increased risk of dystocia . We tested the hypothesis that combined spinal-epidural analgesia , which permits ambulation during labor , is associated with a lower incidence of dystocia than continuous lumbar epidural analgesia . METHODS Between July 1995 and September 1996 , we r and omly assigned 761 nulliparous women in spontaneous labor at term who requested epidural analgesia to receive either continuous lumbar epidural analgesia or a combination of spinal and epidural analgesia . Among the women who received combined spinal-epidural analgesia , some were discouraged from walking and others were encouraged to walk . Maternal and neonatal outcomes , the incidence of dystocia necessitating cesarean section , and measures of patients ' satisfaction were compared in the two groups . RESULTS There were no significant differences in the overall rate of cesarean section , the incidence of dystocia , the frequency of maternal or fetal complications , the patients ' or nursing staff 's assessment of the adequacy of analgesia , or the degree of overall satisfaction between the two groups . Significantly more women receiving combined spinal-epidural analgesia had pruritus ( P<0.001 ) and requested additional epidural bolus doses of local anesthetic ( P=0.01 ) . For all the women , dystocia necessitating cesarean section was significantly more likely when analgesia was administered with the fetal vertex at a negative station ( odds ratio , 2.5 ; P<0.001 ) or at less than 4 cm of cervical dilatation ( odds ratio , 2.2 ; P<0.001 ) . CONCLUSIONS As compared with continuous lumbar epidural analgesia , the combination of spinal and epidural analgesia is not associated with an overall decrease in the incidence of cesarean delivery OBJECTIVE We analyzed the delivery statistics from our institution to describe a successful program of cesarean section delivery reduction and to help us underst and what factors explained the reduction . STUDY DESIGN A retrospective analysis of various cesarean section rates and risk factors from a prospect ively collected delivery data base of all patients delivered between May 15 , 1988 , and June 30 , 1994 . During the study period we instituted a program of increasing awareness , confidential provider feedback , more aggressive laboring techniques , and other clinical guidelines . The delivery data were divided into 6-month intervals and analyzed by chi 2 tables . RESULTS The overall cesarean section rate fell from 31.1 % to 15.4 % . Similar reductions were noted in the primary ( 17.9 % to 9.8 % ) and repeat cesarean section rates ( 13.2 % to 5.7 % ) . The primary cesarean section rate fall was accompanied by a drop in abdominal delivery for cephalopelvic disproportion and fetal distress . The repeat cesarean section rate is explained by a significant increase in trial and successful vaginal birth after cesarean delivery . No increase in maternal , fetal , or neonatal morbidity or mortality was observed . CONCLUSIONS We have demonstrated that the cesarean delivery rate can be safely lowered in a private hospital without m and ated clinical changes . Our data suggest that careful and detailed feedback can lead to improved clinical practice The effects on mature newborn have been compared at 0.5 , 4 , 8 12 24 and 48 hr after birth , of maternally administered epidural bupivacaine ( 11 babies ) or pethidine ( 18 babies ) or pethidine reversed by naloxone administered intramuscularly to the newborn ( 15 babies ) . Bupivacaine ( mean dose 130 mg ) had less effect that pethidine ( mean dose 183.3 mg ) on alveolar carbon dioxide tension ( PACO2 ) at 0.5 hr after birth , but had a similar effect to pethidine on feeding , elicited reflexes and produced more depression of muscle tone up to 48 hr . Bupivacaine had more effect on PACO2 feeding measures , elicited reflexes and muscle tone at almost all examination periods than pethidine ( mean dose 157.0 mg ) reversed by naloxone ( 200 micrograms intramuscularly ) . Except at delivery , the effects of bupivacaine or pethidine on respiration and feeding up to 48 hr after birth were similar . There were more signs of depression with both drugs than when pethidine had been reversed by naloxone We have studied the effect of analgesia on maternal temperature ( oral and tympanic membrane ) progression in 53 women during normal spontaneous labour . Three groups were studied : two received extradural analgesia with a continuous infusion of 0.25 % bupivacaine with or without the addition of fentanyl ; the third group received only parenteral opioid analgesia . All patients were afebrile and without clinical evidence of infection at the beginning of the study . Both groups of patients receiving extradural analgesia had a consistent and significant increase in temperature after approximately 5 h of analgesia ; no such trend was observed in the parenteral opioid group . Alterations in mechanisms of heat dissipation may explain these findings OBJECTIVE We sought to examine the relationship between epidural analgesia and cesarean and instrumental vaginal delivery rates . STUDY DESIGN This is a retrospective analysis of the first 1000 nulliparous pregnancies in women with a cephalic presentation in spontaneous labor at term in each of 3 different years , over which the epidural rate increased from 10 % to 57 % . RESULTS Cesarean and instrumental vaginal delivery rates were similar in all 3 years . Demographic characteristics remained unchanged or altered in a manner that has previously been associated with an increase in intervention . Electronic fetal monitoring and first-stage oxytocin use remained unchanged , but oxytocin use in the second stage increased considerably . CONCLUSIONS Increased use of epidural analgesia had no effect on cesarean delivery rates . Although r and omized trials have suggested that it increases instrumental vaginal delivery rates , this might be overcome by active management of labor or judicious use of oxytocin in the second stage Seventy-three women who requested epidural analgesia during labour were r and omly allocated in a prospect i ve study to receive either a continuous epidural infusion of 0.075 % bupivacaine at a rate of 12 - 18 ml/hour ( 38 mothers ) or intermittent top-ups of 0.5 % bupivacaine ( 35 mothers ) . Both groups received an initial dose of 6 - 8 ml bupivacaine 0.5 % . Patients were asked to score their pain using a 10-cm linear scale prior to insertion of the epidural , 30 minutes after its insertion and hourly thereafter . The quality of analgesia in the continuous infusion group was significantly better than in the intermittent top-up group ( p less than 0.025 ) . There was no significant difference in the total dose of bupivacaine given to the two groups OBJECTIVE Our purpose was to compare maternal and fetal factors that influence the route of delivery with active management of labor and a traditional labor management protocol . STUDY DESIGN Data were collected prospect ively on 346 consecutive patients receiving active management of labor and 354 patients who were managed traditionally . Within each group demographic and labor characteristics of patients undergoing cesarean section were compared with those of patients having vaginal deliveries by means of the Student t test , chi 2 analysis , and stepwise logistic regression . RESULTS With both active management of labor and traditional labor management success in achieving vaginal delivery was related to the station of the fetal vertex at admission , the need for oxytocin augmentation of labor , the uterine response to oxytocin , the use of epidural anesthesia , and the development of chorioamnionitis . By means of multiple logistic regression analysis maternal age , height , payor status , and birth weight were also identified as risk factors for cesarean section with traditional labor management but not with active management of labor . CONCLUSIONS Differences were identified in risk factors for cesarean section between active management and traditional labor management . Active management of labor may diminish or eliminate some patient characteristics as risk factors for cesarean birth Two groups of parturients who had received selective extradural analgesia were studied . In Group A patients the regional block was allowed to wear off for the second stage of labour whereas in Group B patients ' analgesia was maintained throughout labour Analgesic effect , labor outcome , safety and consumer satisfaction were compared in 170 primigravid women ; 50 using TENS initially for pain relief , 20 using entonox , 50 pethidine + promazine and 50 lumbar epidural . 88 % choosing epidural related it fully effective . 90 % using entonox , 96 % using TENS and 54 % given pethidine + promazine found partial relief . 82 % of patients given TENS and 80 % given pethidine + promazine required additional analgesia . This was also needed by one of the 20 patients choosing entonox . Women using entonox alone had the shortest labors and women using lumbar epidural , the longest . Operative delivery was significantly more common in women receiving lumbar epidural . No significant intergroup differences were noted in cord pH or Apgar scores . Parturients and midwives both gave high consumer satisfaction ratings to all methods — except for pethidine + promazine , whose use must therefore be question ed . The analgesic efficacy of lumbar epidural outweighs any possible side effects . Entonox appears suited to those able to cope with the earlier part of labor , drug‐free . Realization of the potential of TENS requires the design of machines specifically to cope with the quality of the pain of labor The objective of this study was to compare the incidence of intrapartum fetal heart tracing ( FHT ) abnormalities and the obstetric outcome after intrathecal sufentanil ( ITS ) versus epidural bupivacaine ( EB ) . During the period from April to September 1994 , 129 patients who met inclusion criteria were prospect ively identified during labor at a single university-affiliated hospital . Inclusion criteria included : singleton , gestational age > or = 36 wk , and cephalic presentation . In the ITS group , epidural anesthesia was not administered before 60 min after ITS . Sixty-five consecutive ITS patients were compared to 64 consecutive EB patients . Each FHT was review ed independently by two obstetricians blinded to the type of analgesia . The FHT characteristics evaluated included baseline rate , variability , and periodic changes . No differences in the incidence of clinical ly significant FHT abnormalities ( recurrent late decelerations and /or bradycardia ) were observed between the two groups ( ITS 21.5 % versus EB 23.4 % ) . The rates of clinical ly significant FHT abnormalities in both groups was not different when patients with hypotension and medical complications were excluded ( 16.9 % vs 17.1 % ) . In addition , equal rates of hypotension ( 18.5 % vs 17.2 % ) were noted between the groups . In both groups there was a significantly higher risk of cesarean section in patients whose previously normal FHT became abnormal postanalgesia when compared to patients without a new onset FHT abnormality ( ITS 28.6 % [ 4/14 ] versus 2.0 % [ 1/51 ] , P < 0.01 ; EB 33.3 % [ 5/15 ] versus 8.2 % [ 4/49 ] , P < 0.05 ) . This increased risk was associated with an increase in cesarean section for nonreassuring FHT in both groups ( ITS 14.3 % [ 2/14 ] versus 0 % [ 0/51 ] , P = 0.04 ; EB 13.3 % [ 2/15 ] versus 0 % [ 0/49 ] , P = 0.05 ) . These results support the conclusion that the incidence of clinical ly significant FHT abnormalities and hypotension is equivalent in patients receiving ITS when compared to EB within the first hour of administration . During this period , patients should have continuous FHT monitoring since a new onset FHT abnormality unveils and alerts the physicians to a possible compromised fetal condition and a corresponding increased risk of cesarean section Background and Objectives The purpose of this investigation was to evaluate the effectiveness and side effects of combined spinal-epidural ( CSE ) injection of a bupivacaine-sufentanil-epinephrine mixture during labor as compared with epidural analgesia alone . Methods In a r and omized trial , 63 parturients presenting for vaginal delivery received either epidural analgesia ( 10 mL ) with 12.5 mg bupivacaine plus 10 μg sufentanil and 12.5 μg epinephrine or CSE analgesia with a single subarachnoid injection of 1 mg bupivacaine plus 5 μg sufentanil and 25 μg epinephrine ( total volume , 2.5 mL ) . For this purpose a 29-gauge BD-Quincke spinal needle was used . All subsequent top-ups consisted of 10 mL of the mixture , as used for the patients who received epidural analgesia only . Results Thirteen patients delivered without requesting a second injection . The time required to obtain satisfactory analgesia ( visual analog score ≤ 2.5 and /or > 50 % improvement ) was significantly shorter for those who received the subarachnoid mixture than for the epidural analgesia group ( 4.0 ± 0.4 vs 10.4 ± 0.5 minutes , respectively , P < .001 ) . The duration of analgesia was longer for the CSE group ( 137.4 ± 11.5 vs 106.4 ± 11.8 minutes , P < .05 ) , with more patients being pain-free for longer than 150 minutes ( 40 vs 8 % , P < .05 ) . Less bupivacaine was consumed in the group receiving the subarachnoid mixture ( 21.6 ± 2.0 vs 30.7 ± 2.1 mg , P < .01 ) . Pruritus was more common following subarachnoid than following epidural injection of sufentanil ( 53.1 vs 25.8 % , P < .05 ) . Other side effects related to the injected drugs , such as motor impairment , hypotension , or nausea or vomiting , were not observed . Although all blocks were uneventful , moderate headache compatible with postdural puncture headache occurred in two patients of the CSE group , which necessitated a blood patch after 5 days . Conclusions The CSE mixture induced long-lasting analgesia , with fast onset and without motor block or hypotension . Pruritus and headache were the major drawbacks of this technique OBJECTIVE To determine if epidural analgesia is associated with differences in rates of severe perineal trauma during vaginal deliveries . METHODS We studied 1942 consecutive , low-risk , term , vaginal deliveries in nulliparas , including spontaneous and induced labors , at a single institution from December 1994 to August 1995 . The rate of third- and fourth-degree lacerations was compared for women who had and did not have epidural analgesia for labor-pain relief . Statistical significance was determined using chi2 . Logistic regression analyses were used to evaluate associations while controlling for possible confounding variables . RESULTS Overall rates of third- and fourth-degree lacerations were 10.8 % ( n = 210 ) and 3.4 % ( n = 63 ) , respectively . Epidural analgesia was given to 1376 ( 70.9 % ) women . Among women who had epidurals , 16.1 % ( 221 of 1376 ) had severe perineal lacerations compared with 9.7 % ( n = 55 ) of the 566 women who did not have epidurals ( P < .001 ; odds ratio [ OR ] 1.8 , 95 % confidence interval [ CI ] 1.3 , 2.4 ) . When controlling for birth weight , use of oxytocin , and maternal age in logistic regression analysis , epidural remained a significant predictor of severe perineal injury ( OR 1.4 , 95 % CI 1.0 , 2.0 ) . Epidural use is consistently associated with increased operative vaginal deliveries and consequent episiotomies , so we constructed a logistic regression model to evaluate whether the higher rates of those procedures were responsible for the effect of epidurals on severe perineal traumas . With operative vaginal delivery and episiotomy in the model , epidural was no longer an independent predictor of perineal injury ( OR 0.9 , 95 % CI 0.6 , 1.3 ) . CONCLUSION Epidural analgesia is associated with an increase in the rate of severe perineal trauma because of the more frequent use of operative vaginal delivery and episiotomy Labouring women were r and omly allocated to receive epidural infusions during labour of either 0.125 % plain bupivacaine ( n = 200 ) or a combination of 0.0625 % bupivacaine with either 2.5μg.ml‐1 fentanyl or 0.25μg.ml‐1 sufentanil ( n = 199 ) each starting at 12 ml.h‐1 and adjusted as necessary to maintain analgesia . The dose of bupivacaine , both hourly ( p < 0.001 ) and total ( p < 0.001 ) , was significantly lower in the group receiving the combination . Motor block was significantly less common and less severe in the combination group ( p < 0.001 ) . These reductions did not result in a significant increase in spontaneous deliveries . Maternal satisfaction with first ( p < 0.001 ) and second stage analgesia ( p < 0.001 ) was significantly increased in the combination group . The addition of opioid to the epidural infusion did not reduce the incidence of perineal pain . There were no significant differences between the groups in neonatal outcome or the incidence of early postnatal symptoms BACKGROUND The combined spinal-epidural technique provides rapid onset of labor analgesia and , anecdotally , is associated with labors of shorter duration . Epidural analgesia , by contrast , has been suggested to prolong labor modestly . It is unclear , however , whether more rapid cervical dilation in patients who receive combined spinal-epidural analgesia is a physiologic effect of the technique or an artifact of patient selection . The authors hypothesized that anesthetic technique may influence the rate of cervical dilation , and we compared the effects of combined spinalepidural with those of epidural analgesia on the rate of cervical dilation . METHODS One hundred healthy nulliparous parturients in spontaneous labor with singleton , vertex , full-term fetuses were enrolled in a double-blinded manner when their cervical dilation was less than 5 cm . The patients were r and omly assigned to receive analgesia via a st and ardized combined spinal-epidural ( n = 50 ) or epidural ( n = 50 ) technique . Data were collected on cervical dilation , pain , sensory level , and motor blockade . RESULTS When regional analgesia was induced in comparable groups at a mean of 3 cm cervical dilation , the mean initial cervical dilation rates were significantly faster in the combined spinal-epidural group ( mean values , 2.1 + /- 2.1 cm/h vs. 1 + /- 1 cm/h ; P = 0.0008 ) . Five parturients in the combined spinal-epidural group had a very rapid ( > 5 cm/h ) rate of mean initial cervical dilation , compared with none of the women in the epidural group . Overall mean cervical dilation rates in patients who achieved full cervical dilation were 2.3 + /- 2.6 cm/h and 1.3 + /- 0.71 cm/h ( P = 0.0154 ) in the combined spinal-epidural and epidural groups , respectively . CONCLUSIONS In healthy nulliparous parturients in early labor , combined spinal-epidural analgesia is associated with more rapid cervical dilation compared with epidural analgesia . Further study is needed to elicit the cause and overall effect of this difference BACKGROUND Epidural analgesia has been associated in previous research with an increase in maternal temperature . METHODS Three studies were done : a retrospective chart review of women in labor , a prospect i ve cohort study of women in labor , and a case-control study of newborns with fever . The prospect i ve study enrolled 28 women , 14 of whom received epidural analgesia . Maternal temperature was measured hourly with a tympanic membrane thermometer . Other variables examined included duration of labor , duration of ruptured membranes , and room temperature . To further explore the possible association between maternal epidural exposure and newborn fever , a case-control study of newborns with fever at birth was carried out . RESULTS In both the retrospective and prospect i ve studies of women in labor , the duration of epidural analgesia was correlated with maximum maternal temperature during labor , with an increase , in the prospect i ve study , of 0.07 degrees C per hour of exposure to epidural analgesia ( P = .002 ) . Controlling for other variables did not change the magnitude of this effect or its statistical significance . Similar trends were seen in the newborn 's first temperature in both the prospect i ve study of women in labor and the case-control study of newborns , but the associations were not significant ( P = .07 and .08 , respectively ) . CONCLUSIONS Epidural analgesia is associated with an increase in maternal temperature during labor and possibly with an elevation of newborns ' first temperatures |
10,433 | 27,113,639 | Moderate- quality evidence indicates that use of a vapocoolant immediately before intravenous cannulation reduces pain during the procedure .
Use of vapocoolant does not increase the difficulty of cannulation nor cause serious adverse effects but is associated with mild discomfort during application | BACKGROUND Intravenous cannulation is a painful procedure that can provoke anxiety and stress .
Injecting local anaesthetic can provide analgesia at the time of cannulation , but it is a painful procedure .
Topical anaesthetic creams take between 30 and 90 minutes to produce an effect .
A quicker acting analgesic allows more timely investigation and treatment .
Vapocoolants have been used in this setting , but studies have reported mixed results .
OBJECTIVES To determine effects of vapocoolants on pain associated with intravenous cannulation in adults and children .
To explore variables that might affect the performance of vapocoolants , including time required for application , distance from the skin when applied and time to cannulation .
To look at adverse effects associated with the use of vapocoolants . | Objective To assess the efficacy , acceptability , and safety of a topical alkane vapocoolant in reducing pain during intravenous cannulation in adults . Design R and omised double blind placebo controlled trial . Setting Emergency department of a metropolitan teaching hospital . Participants 201 adult patients ( 54 % male ) , mean ( SD ) age 58.2 ( 19.5 ) years , who required intravenous cannulation . Interventions Less than 15 seconds before cannulation , the skin area was sprayed with either water ( control , n=98 ) or vapocoolant ( intervention , n=103 ) , from a distance of 12 cm for 2 seconds . The intervention spray was a blend of propane , butane , and pentane . Main outcome measures Pain with cannulation and discomfort with spray , measured with a 100 mm visual analogue scale . Results Groups did not differ significantly in age , sex , indication for or site of cannulation , cannula size , or who cannulated the patient ( P>0.05 ) . Median ( interquartile range ) pain scores for cannulation in the control and intervention groups were 36 ( 19 - 51 ) and 12 ( 5 - 40 ) mm , respectively ( P<0.001 ) , and 59 ( 60 % ) and 33 ( 32 % ) reported pain scores ≥30 mm ( P<0.001 ) . Scores for spray discomfort also differed significantly ( P<0.001 ) because of skewing to the right within the intervention group . The median discomfort scores , however , were 0 mm in both groups . Success rates for first cannulation attempt did not differ between groups ( P=0.39 ) . Thirty four ( 39 % ) and 62 ( 62 % ) patients said they would choose the spray they received for analgesia in the future ( P=0.002 ) . At follow-up at five days , two patients in the intervention group reported transient skin redness . Conclusions Topical alkane vapocoolant spray is effective , acceptable , and safe in reducing pain with peripheral intravenous cannulation in adults in the emergency department . Trial registration Australian Clinical Trials ACTRN12607000470493 Objectives Mechanoreceptor and noxious thermal inhibitory stimulation modulate pain conduction but have not been clinical ly tested in combination . Our objectives were to determine whether a vibrating cold device decreased adult venipuncture pain on a 10 cm visual analog scale more than no intervention , and compared with vapocoolant analgesia versus no intervention . Methods The design was a prospect i ve r and omized crossover clinical trial . Thirty healthy adult volunteers were r and omized to the study device or vapocoolant intervention . One nurse attempted cannulation on both intervention and control h and s with a 22 gauge intravenous catheter . Vapocoolant was applied to the cannulation site , or the device was applied 5 to 10 cm proximally throughout the intervention attempt . Visual analog scale assessed needle fear and the primary outcome of self-reported pain . Results Sixteen device and 14 vapocoolant participants were included in this study . One participant felt discomfort from device prongs before the needle stick and was excluded . Compared with no intervention , the device reduced pain significantly ( mean 9.9 mm , 95 % confidence interval 0.82 - 19 , P=0.035 , SD 16 ) whereas vapocoolant did not ( mean 7.9 mm , 95 % confidence interval −1.8 - 17.7 , P=0.1 , SD 16.9 ) . Mean pain reduction for device group participants was not significantly different from vapocoolant participants . Each 20 mm of prior anxiety increased the likelihood of intervention pain relief ( odds ratio 2 , P=0.043 ) . One venipuncture failure occurred in the vapocoolant intervention . Discussion The combination of cold and vibration gave significant venipuncture pain relief without affecting cannulation success . Interventions were more helpful for those with greater preprocedural fear . Larger sample sizes and a prongless device could better compare equivalence or superiority to existing pain relief modalities STUDY OBJECTIVE The J-Tip ( National Medical Products Inc , Irvine , CA ) uses air instead of a needle to push lidocaine into the skin . To our knowledge , no studies have investigated its use for venipuncture in young children . We determine whether the J-Tip decreased venipuncture pain in young children compared with vapocoolant spray . METHODS Children aged 1 to 6 years were r and omized into 3 groups : intervention ( J-Tip ) , control ( vapocoolant spray ) , and sham ( vapocoolant spray and pop of an empty J-Tip ) . The procedure was videotaped and scored with the Face , Legs , Activity , Cry and Consolability ( FLACC ) tool at 3 points ; baseline , before approach ; device , at J-Tip deployment ; and at venipuncture . The FLACC tool was scored 0 ( none ) to 10 ( severe ) . Comparisons of pain scores over time were made with the generalized estimating equation . Venipuncture success and adverse effects were assessed and compared with χ(2 ) . RESULTS Two hundred five children enrolled : intervention 96 , control 53 , and sham 56 . There were no between-group differences in baseline characteristics . There was no mean change in pain scores from device to venipuncture in the intervention group ( 0.26 ; 95 % confidence interval [ CI ] -0.31 to 0.82 ) , but there was an increase in pain in the control ( 2.82 ; 95 % CI 1.91 to 3.74 ) and sham ( 1.68 ; 95 % CI 0.83 to 2.52 ) groups . This change was greater for the control and sham compared to the intervention group . There was no difference in venipuncture success between groups . No severe adverse events occurred . Minor adverse events were the same between groups . CONCLUSION Use of the J-Tip for children aged 1 to 6 years reduced venipuncture pain compared with vapocoolant spray or sham treatment Objective : Although intravenous ( IV ) line placement is a common procedure in the emergency department ( ED ) , it is an uncomfortable experience for many patients . Topical analgesic agents are rarely used because they have long onsets of action and thereby cause unacceptable treatment delays . Cryoanaesthesia , the use of cooling agents to reduce pain , has been recognised for many years as a potential pain management strategy . The purpose of this study was to determine whether an instantaneous topical skin coolant spray reduces patient ’s pain during IV cannulation and represents a feasible alternative for cutaneous analgesia in the ED setting . Methods : We conducted an unblinded , r and omised , controlled study , in a convenience sample of ED patients . Utilising a r and om number generator to assign patients to the control or study group , patients over the age of 18 years who required IV cannulation as part of their evaluation were enrolled at two tertiary care hospitals . In both groups , IV lines were placed in accordance with accepted clinical st and ards of practice , with the single addition of the coolant spray delivered to the IV site before needle insertion in the study group . All study participants answered question naires before and after IV placement and rated pain during procedure on a 100 mm visual analogue scale . Results : Of the 92 patients enrolled in the study , 47 ( 51.1 % ) were r and omised to the study group and received the anaesthetic spray , and 45 ( 48.9 % ) were r and omised to the control group and had their IV placed in a st and ard method . 66 patients were female ( 71.8 % ) and 26 ( 28.2 % ) were males . The mean pain score in the study group was 27 mm ( 95 % confidence interval ( CI ) 19.9 to 34.1 mm ) and 28 mm ( 95 % CI 20.4 to 35.6 m ) in the control group ( p = 0.934 ) . Subgroup analysis of female and male patients did not show significance . Conclusions : Our study failed to detect a difference in pain perception result ing from the pre-procedural application of a skin coolant associated with IV placement in the ED setting Introduction : Ethyl chloride can be used as a cryoanalgesic , but with the availability of alternative and relatively safer topical analgesics , its use has decreased . However , it still has the advantage of being quicker to apply compared with other topical analgesics , making it ideal for use in the outpatient departments . We wanted to compare the effectiveness of ethyl chloride as an analgesic during venipuncture in children . Methods : Venipuncture was carried out using either no analgesia ( NO ) , ethyl chloride spray ( EC ) , or application of the topical anesthetic Ametop ( TA ) on children attending the phlebotomy outpatient service by experienced pediatric phlebotomists . A pain score was recorded using either the Faces scoring system or the Faces , Legs , Activity , Cry Consolability scoring system . Results : A total of 55 patients were included in the study , 18 from group EC , 18 from group TA , and 19 from group NO . Thirteen patients from both groups EC and TA and 17 from group NO scored 2 or less on the pain scores . Discussion : The use of ethyl chloride was as effective as topical anesthetics in preventing distress to children in venipuncture . However , in the appropriate situations , the use of NO could also be comfortable to the child if venipuncture was done by specialist pediatric phlebotomists Background : Established noninvasive pharmacologic means of alleviating pain and anxiety in children undergoing intravenous cannulation are time-consuming , and thus impractical for routine use in the emergency department . Vapocoolant sprays provide transient skin anesthesia within seconds of application . We compared the effect of a new vapocoolant spray to placebo on pain due to intravenous cannulation in children . Methods : In this double-blind r and omized controlled trial , which we conducted between June 1 and Sept. 12 , 2006 , 80 children aged 6–12 years received either vapocoolant spray or placebo before cannulation . Children rated their pain using a 100-mm colour visual analogue scale . Secondary outcomes included success rate on first attempt at cannulation and pain ratings by the children 's parents , nurses and child life specialists . Results : We found a modest but significant reduction in pain with the use of vapocoolant spray ( mean difference 19 mm , 95 % confidence interval [ CI ] 6–32 mm ; p < 0.01 ) . Cannulation on first attempt was more often successful with the use of vapocoolant spray ( 85.0 % ) than with placebo ( 62.5 % ) ( mean difference 22.5 % , 95 % CI 3.2%–39.9 % ; p = 0.03 ) . The number needed to treat to prevent 1 cannulation failure was 5 ( 95 % CI 3–32 ) . Parents ( p = 0.04 ) , nurses ( p = 0.01 ) and child life specialists ( p < 0.01 ) considered the children 's pain to be reduced with the use of vapocoolant spray . Interpretation : The vapocoolant spray in our study quickly and effectively reduced pain due to intravenous cannulation in children and improved the success rate of cannulation . It is an important option to reduce childhood procedural pain in emergency situations , especially when time precludes traditional interventions . ( http:// Clinical Trials.gov trial register no. NCT00130650 . The purpose of this study was to evaluate the effect of ethyl chloride spray on the anxiety and pain associated with placing an intravenous catheter in patients se date d with nitrous oxide . Eighty-eight patients scheduled for dental surgery with a combination of intravenous and nitrous oxide sedation were r and omly assigned to have ethyl chloride spray or a placebo , water spray , applied before cannulation of a vein . Anxiety and pain were reported using a 10.0-cm visual analog scale before nitrous oxide administration , after nitrous oxide sedation , following application of the spray , and following venous cannulation . The first 2 assessment s measured overall levels of patient anxiety and pain and confirmed that nitrous oxide sedation reduced anxiety without changing already low levels of pain . The second 2 assessment s of anxiety and pain measured the reaction toward the spray and cannulation . The application of ethyl chloride spray produced significantly more anxiety and pain than did the placebo . The results of this study demonstrate that ethyl chloride spray does not significantly reduce the anxiety and pain associated with venous cannulation in patients se date d with nitrous oxide One hundred and twenty unpremedicated patients undergoing gynaecological surgery were r and omly allocated to one of three equal treatment groups to assess the effectiveness of ethyl chloride in producing instant skin anaesthesia to prevent the pain of venepuncture from a 20 G cannula . They received either no anaesthetic , 0.2 ml one per cent lidocaine plain intradermally or a ten-second spray of ethyl chloride at the cannulation site . Ethyl chloride produced skin anaesthesia that significantly reduced the pain of venepuncture . However , it was not as effective as intradermal lidocaine . It had no effect on vein visualisation or ease of cannulation . Ethyl chloride can be recommended as a method of producing instant skin anaesthesia . RésuméAfin d’évaluer l’anesthésie cutanée produite par le chlorure d’éthyl , nous avons r and omisé en trois groupes , 120 c and i date s à une chirurgie gynécologique n’ayant pas reçu de prémédication . Avant l’insertion percutanée d’une canule de calibre 20 , nous n’utilisions soil aucun agent , soil une injection intradermique de 0,2 ml de lidocaïne une pour cent , soil une vaporisation de chlorure d’éthyl de dix secondes au site d’insertion . Le chlorure d’éthyl produit alors une anesthésie cutanée capable de diminuer la douleur lors de l’insertion d’une canule veineuse ( mais pas de façon aussi marquée que la lidocaïne ) sans en compliquer la technique ni entraver la visualisation de la veine . Il s’agit done là d’une technique acceptable d’anesthésie cutanée presque instantanée Three commonly available local anaesthetics were compared , in a controlled trial , for use before venous cannulation . The pain of application of the local anaesthetic , the pain of cannulation , and the rate of successful cannulations were compared . The value of EMLA cream applied for 5 min was question ed . Venous cannulation with a 20 G venflon was found to be significantly more painful than the application of any of the local anaesthetics ( P < 0.01 ) . Lignocaine 1 % , injected subcutaneously , and ethyl chloride spray significantly reduced the pain of venous cannulation ( P < 0.01 ) . The use of lignocaine did not result in significantly more failed cannulations than the control group . It was concluded that local anaesthesia should be used before venous cannulation , even for 20 G cannulae The purpose of the study was to determine the effect of ethyl vinyl chloride vapocoolant spray on pain reported by children undergoing intravenous cannulation . A r and omized , double-blinded , placebo-controlled trial was conducted on eligible children between the ages of 9 and 18 years seen in a pediatric emergency department and requiring intravenous cannulation . Informed consent was obtained , and children were r and omized to receive ethyl vinyl chloride spray , isopropyl alcohol spray , or no spray ( control group ) . Patient demographics and information pertaining to each intravenous cannulation were recorded . Children indicated the degree of pain associated with intravenous cannulation on a 100-mm visual analog scale ( VAS ) compared to a baseline pain score of “ zero . ” Statistical analysis was performed by using Stata version 7 . One hundred twenty-seven subjects were enrolled : 37 received ethyl vinyl chloride vapocoolant spray , 48 received isopropyl alcohol spray ( placebo ) , and 42 received no pretreatment . Mean VAS scores for pain experienced during cannulation were 34 , 33 , and 31 mL for each group , respectively . Ethyl vinyl chloride vapocoolant spray failed to measurably reduce pain associated with intravenous cannulation when compared to those pretreated with isopropyl alcohol spray or receiving no intervention OBJECTIVE . The Comparison of Venipuncture and Venous Cannulation Pain After Fast-Onset Needle-Free Powder Lidocaine or Placebo Treatment trial was a r and omized , single-dose , double-blind , phase 3 study investigating whether a needle-free powder lidocaine delivery system ( a sterile , prefilled , disposable system that delivers lidocaine powder into the epidermis ) produces effective local analgesia within 1 to 3 minutes for venipuncture and peripheral venous cannulation procedures in children . METHODS . Pediatric patients ( 3–18 years of age ) were r and omly assigned to treatment with the needle-free powder lidocaine delivery system ( 0.5 mg of lidocaine and 21 ± 1 bar of pressure ; n = 292 ) or a sham placebo system ( n = 287 ) at the antecubital fossa or the back of the h and 1 to 3 minutes before venipuncture or cannulation . All patients rated the administration comfort of the needle-free systems and the pain of the subsequent venous access procedures with the Wong-Baker Faces Pain Rating Scale ( from 0 to 5 ) . Patients 8 to 18 years of age also provided self-reports with a visual analog scale , and parents provided observational visual analog scale scores for their child 's venous access pain . Safety also was assessed . RESULTS . Immediately after administration , mean Wong-Baker Faces scale scores were 0.54 and 0.24 in the active system and sham placebo system groups , respectively . After venipuncture or cannulation , mean Wong-Baker Faces scale scores were 1.77 ± 0.09 and 2.10 ± 0.09 and mean visual analog scale scores were 22.62 ± 1.80 mm and 31.97 ± 1.82 mm in the active system and sham placebo system groups , respectively . Parents ' assessment s of their child 's procedural pain were also lower in the active system group ( 21.35 ± 1.43 vs 28.67 ± 1.66 ) . Treatment-related adverse events were generally mild and resolved without sequelae . Erythema and petechiae were more frequent in the active system group . CONCLUSIONS . The needle-free powder lidocaine delivery system was well tolerated and produced significant analgesia within 1 to 3 minutes BACKGROUND Comprehensive international travel preparation often requires several vaccines . Up to 90 % of adults have some fear of injections , mostly due to injection-related pain . Pediatric studies with routine vaccines have shown topical anesthetic EMLA cream ( lidocaine and prilocaine , Astra Pharmaceuticals , Inc. ) and the topical vapocoolant Fluori-Methane ( dichlorodifluoromethane and trichlorodifluoromethane , Gebauer Co. ) to be equally effective in reducing pain from vaccinations . EMLA cream is expensive and requires a 60-min application , while Fluori-Methane ( FM ) is immediate in onset of action and inexpensive . Skin anesthesia begins at 10 degrees C. Fluori-Methane can briefly cool the skin to 0 degrees C. METHODS We studied the effectiveness of topical vapocoolant on adult clients at our international travel clinic in a r and omized , controlled trial of topical FM vs. cold ( 4 degrees C ) saline placebo . Using a preset r and omization table , participants served as their own controls , receiving placebo/control or active agent ( participant blinded ) in one arm ( left or right ) , and a similar number of vaccines in the untreated arm . Vaccines were administered according to a set protocol per arm to minimize the risk of bias . Pain was measured using a modified McGill present pain intensity ( PPI ) pain index . Subjects rated their pain immediately and at 5 min on a six-level scale , noting treated and untreated arms separately . A question naire was completed on intervention preferences . Sample size was predetermined to achieve 90 % statistical power estimating 25 % efficacy ( minimum n=172 ) . RESULTS One hundred and eighty-five participants were enrolled ; 93 FM and 92 cold saline placebo . FM-treated arms had a significant reduction in immediate pain compared to untreated arms ( pain scale mean 2.2 vs. 3.1 ; p<.0001 ) , and compared to placebo ( mean 2.2 vs. 2.8 ; p<.01 ) . Delayed pain at 5 min was not affected by FM or control ( mean 1.9 vs. 2.0 ) compared to no intervention ( pain scale 1.9 ) . The intervention preference question naire indicated that participants did not find FM therapy uncomfortable . They would choose FM therapy in the future , over a cream , especially if a wait was involved . CONCLUSION The topical vapocoolant Fluori-Methane is an effective , quick , preferred , inexpensive agent for reducing vaccine-associated injection pain for international travel clients Objective : To determine whether brief , focal pretreatment of children 's skin with low-frequency ultrasound followed by a 5-minute application of a 4 % lidocaine topical anesthetic decreases the pain of intravenous ( IV ) catheter placement . Methods : A r and omized , double-blind , placebo-controlled trial enrolling children 8 to 18 years of age undergoing IV placement as part of their care in a pediatric emergency department . Thirty-eight children received pretreatment followed by 5-minute application of a topical anesthetic . Thirty-nine children received pretreatment followed by 5-minute application of a placebo cream . Children and parents rated the pain associated with IV placement using the visual analog scale ( VAS ) . Results : There were no significant differences in demographics between the 2 groups . Children in the treatment group had significantly lower VAS scores ( mean , 2.29 ) than children in the control group ( mean , 3.23 ) ( P = 0.023 ; 95 % confidence interval of the mean difference , −1.87 to −0.02 ) . The parents ' VAS scores of the child 's pain were also lower for the treatment group ( mean , 2.47 vs 3.39 ; P = 0.038 ; confidence interval , −1.97 to 0.11 ) . Conclusions : Visual analog scale scores measuring children 's pain and parents ' perception of the child 's pain were lower in those who were pretreated with brief focal ultrasound and 5 minutes of 4 % lidocaine cream when compared with those pretreated with ultrasound and placebo STUDY OBJECTIVE To determine the amount of change in pain severity , as measured by a visual analog scale , that constitutes a minimum clinical ly significant difference . METHODS Patients 18 years of age or older who presented with acute pain result ing from trauma were enrolled in this prospect i ve , descriptive study . The setting was an urban county hospital emergency department with a Level 1 trauma center . In the course of a brief interview , patients were asked to indicate their current pain severity with a single mark through a st and ard 100-mm visual analog scale . At intervals of 20 minutes for the next 2 hours , patients were asked to repeat this measurement and , in addition , to contrast their present pain severity with that at the time of the previous measurement . They were to indicate whether they had " much less , " " a little less , " " about the same , " " a little more , " or " much more " pain . All contrasts were made without reference to prior visual analog scale measurements . A maximum of six measurements of pain change were recorded per patient . Measurements ended when the patient left the ED or when the patient reported a pain score of zero . The minimum clinical ly significant change in visual analog scale pain score was defined as the mean difference between current and preceding visual analog scale scores when the subject noted a little less or a little more pain . RESULTS Forty-eight subjects were enrolled , and 248 pain contrasts were recorded . Of these contrasts , 41 were rated as a little less and 39 as a little more pain . The mean difference between current and preceding visual analog scale scores in these 80 contrasts was 13 mm ( 95 % confidence interval , 10 to 17 mm ) . CONCLUSION The minimum clinical ly significant change in patient pain severity measured with a 100-mm visual analog scale was 13 mm . Studies of pain experience that report less than a 13-mm change in pain severity , although statistically significant , may have no clinical importance |
10,434 | 19,366,942 | Metformin decreases the rate of conversion from prediabetes to diabetes . | OBJECTIVE To determine if the use of metformin in people with prediabetes ( impaired glucose tolerance or impaired fasting glucose ) would prevent or delay the onset of frank type 2 diabetes mellitus . | Patients with insulin resistance often manifest increased intramyocellular lipid ( IMCL ) along with increased visceral adipose tissue . This study was design ed to determine whether the insulin sensitizer drugs pioglitazone and metformin would improve glucose intolerance and insulin sensitivity by decreasing IMCL . In this study , 23 generally healthy subjects with impaired glucose tolerance were r and omized to receive either pioglitazone 45 mg/day or metformin 2,000 mg/day for 10 wk . Before and after treatment , we measured insulin sensitivity and abdominal subcutaneous and visceral adipose tissue with CT scanning . In addition , muscle biopsies were performed for measurement of IMCL and muscle oxidative enzymes . After treatment with pioglitazone , 2-h glucose fell from 9.6 mmol/l ( 172 mg/dl ) to 6.1 mmol/l ( 119 mg/dl ) , whereas there was no change in 2-h glucose with metformin . With pioglitazone treatment , there was a 65 % increase in insulin sensitivity along with a 34 % decrease in IMCL ( both P < or = 0.002 ) . This decrease in IMCL was not due to increased muscle lipid oxidation , as there were no changes in muscle lipid oxidative enzymes . However , pioglitazone result ed in a 2.6-kg weight gain along with a significant decrease in the visceral-to-subcutaneous adipose tissue ratio . In contrast , metformin treatment result ed in no change in insulin sensitivity , IMCL , oxidative enzymes , or adipose tissue volumes . Pioglitazone improved glucose tolerance and insulin sensitivity by reducing IMCL . This reduction in IMCL was not due to an increase in muscle lipid oxidation but to a diversion of lipid from ectopic sites into subcutaneous adipose tissue OBJECTIVE The Diabetes Prevention Program demonstrated the ability to delay or prevent type 2 diabetes in participants with impaired glucose tolerance ( IGT ) . Participants with IGT are at high risk for cardiovascular disease ( CVD ) , with a marked increase in the number and severity of CVD risk factors . We prospect ively assessed the impact of our interventions on hypertension , dyslipidemia , and CVD events . RESEARCH DESIGN AND METHODS The study group consisted of 3,234 individuals with IGT r and omly assigned to receive intensive lifestyle intervention , metformin , or placebo . Annual assessment of blood pressure , lipids , electrocardiogram , and CVD events was undertaken . RESULTS Hypertension was present in 30 % of participants at study entry and then increased in the placebo and metformin groups , although it significantly decreased with intensive lifestyle intervention . Triglyceride levels fell in all treatment groups , but fell significantly more with intensive lifestyle intervention . Total cholesterol and LDL cholesterol levels were similar among treatment groups . Intensive lifestyle intervention significantly increased the HDL cholesterol level and reduced the cumulative incidence of the proatherogenic LDL phenotype B. At 3 years of follow-up , the use for pharmacologic therapy to achieve established goals in the intensive lifestyle group was 27 - 28 % less for hypertension and 25 % less for hyperlipidemia compared with placebo and metformin groups . Over an average of 3 years , 89 CVD events from 64 participants were positively adjudicated study wide , with no differences among treatment groups . CONCLUSIONS Lifestyle intervention improves CVD risk factor status compared with placebo and metformin therapy . Although no differences in CVD events were noted after 3 years , achieved risk factor modifications suggest that longer intervention may reduce CVD event rates AIMS This study was initiated to test the hypothesis that metformin treatment leads to enhanced glucose disposal at ambient insulin concentrations . METHODS Nineteen obese patients with impaired glucose tolerance ( IGT ) were treated with either metformin or placebo in a r and omized , double-blind , placebo-controlled , cross-over study . Insulin secretion and insulin resistance were quantified using the homeostasis model assessment ( HOMA ) and insulin-stimulated glucose disposal were measured by determining the steady-state plasma glucose ( SSPG ) . RESULTS The average benefit of metformin was 0.6 mmol/l for glucose ( 95 % confidence interval ( CI ) 0.2 - 0.9 P = 0.002 ) , 2.8 pmol/l for insulin ( 95 % CI 0.2 - 5.4 , P = 0.019 ) . Insulin resistance , as quantified by HOMA , was improved by 1.1 ( 95 % CI 0.2 - 2.0 , P = 0.004 ) , without any change in insulin secretion . Basal and insulin-stimulated glucose oxidation were comparable in the placebo and metformin-treated groups at the end of each treatment period , as was the SSPG concentration . However , both systolic and diastolic blood pressures fell significantly following metformin administration as compared to treatment with placebo . CONCLUSIONS These results indicate that metformin administration to patients with IGT is associated with enhanced glucose disposal at baseline insulin concentrations and a fall in blood pressure . In contrast , neither glucose oxidation nor glucose disposal were increased in association with metformin treatment under conditions of physiological hyperinsulinaemia Several studies have demonstrated that type 2 diabetes mellitus ( DM ) can be prevented/delayed in subjects with impaired glucose tolerance ( IGT ) by using pharmacologic agents and /or lifestyle interventions . However , a number of challenges remain , including the translation of lifestyle programmes to the general population and the need to achieve greater risk reductions by using pharmacologic approaches . IGT , like DM , is characterized by insulin resistance , β‐cell dysfunction and increased hepatic glucose production . We believe that the use of combination diabetes therapy would be a particularly effective diabetes prevention strategy . In this context , we initiated the Canadian Normoglycemia Outcomes Evaluation ( CANOE ) study , a moderately sized , r and omized , double‐blind , controlled trial . The primary objective of CANOE is to determine whether treatment with metformin plus rosiglitazone , in addition to a healthy living lifestyle programme , will prevent the development of DM . The secondary objective of CANOE is to determine whether this treatment approach will improve cardiovascular risk factors associated with IGT . A total of 200 patients will be recruited in Toronto and London , Ontario , and followed for an average of 4 years ( range 3–5 years ) . Active treatment with metformin ( 500 mg ) plus rosiglitazone ( 2 mg ) , administered as one capsule twice daily , will be compared to matched placebo . Subjects will be eligible for r and omization if they have IGT and are between the ages of 30–75 years . The primary outcome will be the development of new‐onset DM , diagnosed by either two fasting plasma glucose values of ≥7 mmol/l or one positive oral glucose tolerance test with a 2‐h plasma glucose value of > 11.0 mmol/l during the active drug phase of the trial . With a sample size of 100 participants per group , we will be able to detect a relative risk reduction of 45 % , with a two‐sided log‐rank test with a significance level of 0.05 and 80 % power , assuming that the median time to progression is 8 years in the control group and that participants will be recruited over 2 years and followed for an average of 4 years . In conclusion , the CANOE study will determine whether combination pharmacological therapy combined with a lifestyle intervention programme can significantly modify the development of diabetes in high‐risk Canadians The research ers conducted this study to test the hypothesis that risk of type 2 diabetes is less following reductions in body size and central adiposity . The Diabetes Prevention Program ( DPP ) recruited and r and omized individuals with impaired glucose tolerance to treatment with placebo , metformin , or lifestyle modification . Height , weight , waist circumference , and subcutaneous and visceral fat at L2-L3 and L4-L5 by computed tomography were measured at baseline and at 1 year . Cox proportional hazards models assessed by sex the effect of change in these variables over the 1st year of intervention upon development of diabetes over subsequent follow-up in a subset of 758 participants . Lifestyle reduced visceral fat at L2-L3 ( men −24.3 % , women −18.2 % ) and at L4-L5 ( men −22.4 % , women −17.8 % ) , subcutaneous fat at L2-L3 ( men −15.7 % , women −11.4 % ) and at L4-L5 ( men −16.7 % , women −11.9 % ) , weight ( men −8.2 % , women −7.8 % ) , BMI ( men −8.2 % , women −7.8 % ) , and waist circumference ( men −7.5 % , women −6.1 % ) . Metformin reduced weight ( −2.9 % ) and BMI ( −2.9 % ) in men and subcutaneous fat ( −3.6 % at L2-L3 and −4.7 % at L4-L5 ) , weight ( −3.3 % ) , BMI ( −3.3 % ) , and waist circumference ( −2.8 % ) in women . Decreased diabetes risk by lifestyle intervention was associated with reductions of body weight , BMI , and central body fat distribution after adjustment for age and self-reported ethnicity . Reduced diabetes risk with lifestyle intervention may have been through effects upon both overall body fat and central body fat but with metformin appeared to be independent of body fat The effect of metformin ( 1000 mg twice a day ) on markers of endothelial activation , inflammation , and coagulation was investigated in subjects with impaired glucose tolerance ( IGT ) in a 16-wk , r and omized , placebo-controlled , double-blind study . Soluble intercellular adhesion molecule , soluble vascular cell adhesion molecule , C-reactive protein , TNFalpha , von Willebr and factor , and tissue plasminogen activator were measured at baseline and at the end of the trial . Subjects with IGT ( n = 55 , 14 males and 41 females ) , aged 48.4 + /- 9.6 yr with a body mass index of 31.4 + /- 5.6 kg/m(2 ) , were studied . All participants followed a 1-month stabilization period in their diet and physical activity . Afterward , 29 subjects were assigned to the treatment group and 26 to the control group . A significant reduction in weight , fasting plasma glucose , soluble intercellular adhesion molecule ( 306 + /- 75 vs. 268 + /- 61 ng/ml , P = 0.029 ) , soluble vascular cell adhesion molecule ( 595 + /- 114 vs. 508 + /- 126 ng/ml , P = 0.006 ) , and von Willebr and factor ( 124 + /- 34 vs. 94 + /- 34 % , P = 0.001 ) was seen in the treatment group , whereas tissue plasminogen activator , TNFalpha , and C-reactive protein levels did not change . No change was seen in the control group . Thus , metformin improves the plasma levels of some markers of endothelial activation and coagulation in subjects with IGT , whereas it has no effect on markers of inflammation AIMS To evaluate the effect of metformin on glucose metabolism , insulin sensitivity and rate of conversion diabetes in people with impaired glucose tolerance ( IGT ) . METHODS Seventy subjects with IGT were r and omized under double-blind conditions to receive either placebo ( n = 37 ) or metformin ( n = 33 ) at a dosage of 250 mg three times daily for a duration of 12 months . Glycaemic control , plasma insulin and other biochemical indexes were assessed before and after 3 , 6 and 12 months . RESULT At 12 months the conversion rate to diabetes was 16.2 % in the placebo group compared to 3.0 % for the metformin group ( P = 0.011 ) . Of subjects treated with metformin for 12 months , 84.9 % became normoglycaemic compared to 51.4 % of those receiving the placebo . Significant improvements in fasting glucose , glucose tolerance and insulin sensitivity were found at 12 months and at intermediate clinic assessment s. CONCLUSIONS Metformin can improve glucose metabolism in IGT patients and may be a treatment option in their management of IGT subjects Aims /hypothesisLifestyle modification helps in the primary prevention of diabetes in multiethnic American , Finnish and Chinese population s. In a prospect i ve community-based study , we tested whether the progression to diabetes could be influenced by interventions in native Asian Indians with IGT who were younger , leaner and more insulin resistant than the above population s. Methods We r and omised 531 ( 421 men 110 women ) subjects with IGT ( mean age 45.9±5.7 years , BMI 25.8±3.5 kg/m2 ) into four groups . Group 1 was the control , Group 2 was given advice on lifestyle modification ( LSM ) , Group 3 was treated with metformin ( MET ) and Group 4 was given LSM plus MET . The primary outcome measure was type 2 diabetes as diagnosed using World Health Organization criteria . Results The median follow-up period was 30 months , and the 3-year cumulative incidences of diabetes were 55.0 % , 39.3 % , 40.5 % and 39.5 % in Groups 1–4 , respectively . The relative risk reduction was 28.5 % with LSM ( 95 % CI 20.5–37.3 , p=0.018 ) , 26.4 % with MET ( 95 % CI 19.1–35.1 , p=0.029 ) and 28.2 % with LSM + MET ( 95 % CI 20.3–37.0 , p=0.022 ) , as compared with the control group . The number needed to treat to prevent one incident case of diabetes was 6.4 for LSM , 6.9 for MET and 6.5 for LSM + MET . Conclusions /interpretationProgression of IGT to diabetes is high in native Asian Indians . Both LSM and MET significantly reduced the incidence of diabetes in Asian Indians with IGT ; there was no added benefit from combining them Impaired glucose tolerance ( IGT ) is associated with cardiovascular risk factors , but the effects of pioglitazone and metformin on IGT are not well described . We tested the hypothesis that each drug would exhibit antiatherogenic and anti-inflammatory effects in subjects with IGT and early diabetes . The study design was a prospect i ve , r and omized , open label , cross-over study . Blood tests , including a 75-g oral glucose tolerance test ( OGTT ) , were performed at baseline and after each treatment . Pioglitazone 15 mg/day or metformin 500–750 mg/day was given for 3 months . Biochemical markers to assess insulin resistance as well as lipid , inflammatory , neurohumoral , and hemostatic factors were included . Twenty-five subjects ( 17 male , 8 female ; age [ mean±SD ] : 61±9 years ; 84 % hypertensive ) completed the protocol . Of 25 subjects , 14 were diagnosed as IGT and 11 as diabetes with 75-g OGTT . Pioglitazone significantly reduced fasting glucose ( p<0.05 ) , and homeotasis model assessment of insulin resistance ( HOMA-IR ) ( p<0.05 ) and metformin ( p<0.01 ) reduced cholesterol . Both drugs significantly reduced aldosterone ( both p<0.05 ) and von Willebr and factor ( vWF ) ( both p<0.05 ) . Plasma adiponectin was increased only by pioglitazone ( p<0.001 ) . Neither drug affected BP levels . In conclusion , pioglitazone was superior to metformin for the improvement of insulin resistance and adiponectin , and both drugs were equally effective in reducing vWF and aldosterone in subjects with IGT and early diabetes . Early intervention with pioglitazone or metformin therapy may reduce the incidence of future cardiovascular disease in subjects with impaired glucose tolerance or early diabetes Summary Background Data : Hyperglycemia and accelerated muscle catabolism have been shown to adversely affect immune response and survival . The purpose of this study was to determine the effect of metformin on glucose kinetics and muscle protein metabolism in severely burned patients and assess any potential benefit of metformin in this clinical setting . Methods : In a double-blind , r and omized manner , 8 adult burn patients received metformin ( 850 mg every 8 hours × 7 days ) , while 5 burn patients received placebo . Infusions of 6,6d2 glucose , d5 phenylalanine , sequential muscle biopsies , and femoral arterial , venous blood sampling allowed determination of glucose and muscle protein kinetics . Measurements were obtained immediately prior and at the conclusion of 7 days of treatment ( metformin versus placebo ) . All patients received enteral feeds of comparable amounts during study . Results : Patients receiving metformin had a significant decrease in their plasma glucose concentration , the rate of glucose production , and an increase in glucose clearance . Metformin administration was also associated with a significant increase in the fractional synthetic rate of muscle protein and improvement in net muscle protein balance . Glucose kinetics and muscle protein metabolism were not significantly altered in the patients receiving placebo . Conclusions : Metformin attenuates hyperglycemia and increases muscle protein synthesis in severely burned patients , thereby indicating a metabolic link between hyperglycemia and muscle loss following severe injury . Therefore , therapies that improve glucose tolerance such as metformin may be of clinical value in ameliorating muscle catabolism in critically injured patients BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States . Some risk factors -- elevated plasma glucose concentrations in the fasting state and after an oral glucose load , overweight , and a sedentary lifestyle -- are potentially reversible . We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes . METHODS We r and omly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week . The mean age of the participants was 51 years , and the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 34.0 ; 68 percent were women , and 45 percent were members of minority groups . RESULTS The average follow-up was 2.8 years . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence by 58 percent ( 95 percent confidence interval , 48 to 66 percent ) and metformin by 31 percent ( 95 percent confidence interval , 17 to 43 percent ) , as compared with placebo ; the lifestyle intervention was significantly more effective than metformin . To prevent one case of diabetes during a period of three years , 6.9 persons would have to participate in the lifestyle-intervention program , and 13.9 would have to receive metformin . CONCLUSIONS Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk . The lifestyle intervention was more effective than metformin The Diabetes Prevention Program is a new , 150 million dollar , NIH-sponsored study design ed to determine whether non-insulin-dependent diabetes mellitus can be prevented or delayed in persons with impaired glucose tolerance . Four thous and subjects will be r and omly assigned to one of four study groups and followed for 4.5 years . Study groups include intensive lifestyle intervention with diet and exercise ; metformin ( Glucophage ) or troglitazone ( an investigational drug ) with st and ard diet and exercise ; and a control group . Insulin resistance is an important pathogenic factor in impaired glucose tolerance . Trivalent chromium , a dietary supplement that potentiates the action of insulin , was not included in the program . Like metformin and troglitazone , trivalent chromium decreases insulin resistance and has an acceptable side-effect profile ; furthermore , it is available at a fraction of their cost . Trivalent chromium should have been included in the Diabetes Prevention Program ; it is unfortunate that it was omitted In a double-blind , r and omized , cross-over study , the metabolic effects of a short treatment with metformin ( 2 x 850 mg day-1 for 2 days and 850 mg 1 h before evaluation ) were compared to those of placebo in 15 obese subjects ( BMI : 33.2 + /- 0.9 kg m-2 ) , with abdominal distribution of adipose tissue and impaired glucose tolerance . An intravenous glucose tolerance test ( 0.3 g glucose kg-1 ) was performed after each period of treatment . Areas under the curve ( AUC0 - 180 min ) were calculated for plasma glucose , insulin , and C-peptide levels . Glucose tolerance was estimated by the coefficient of glucose assimilation ( KG ) . Insulin sensitivity ( SI ) and glucose effectiveness ( SG ) indices were calculated using Bergman 's minimal model . Insulin secretion rate ( ISR ) was determined by deconvolution of plasma C-peptide levels and insulin metabolic clearance rate ( MCR ) was estimated by dividing AUC 1SR by AUC insulin . Fasting plasma insulin levels were reduced after metformin ( 89.3 + /- 15.9 vs 112.4 + /- 24.3 pmol l-1 ; p = 0.04 ) . AUC glucose , KG and SG were similar in both tests . However , AUC insulin was reduced ( 39.7 + /- 6.5 vs 51.8 + /- 10.4 nmol min l-1 ; p = 0.02 ) , while SI ( 6.98 + /- 1.14 vs 4.61 + /- 0.42 10(-5 ) min-1 pmol-1 l ; p = 0.03 ) and insulin MCR ( 715 + /- 116 vs 617 + /- 94 ml min-1 m-2 ; p = 0.03 ) were increased after metformin . The demonstration that metformin rapidly improves insulin sensitivity should encourage further research to evaluate the long-term effects of metformin in and roid obese subjects with impaired oral glucose tolerance |
10,435 | 19,730,018 | Although neurophysiological studies have not shown great differences result ing from the application of corticosteroids , the symptomatic benefit provided by such drugs is clear .
In the short term , local infiltration provides better results than systemic administration of corticosteroids .
Over a 1-year period , however , this difference does not persist . | The purpose of this study was to evaluate anti-inflammatory drugs in the medium- and long-term management of mild to moderate carpal tunnel syndrome ( CTS ) . | Orthodromic SNAPs were recorded over the median nerve using needle electrodes at the wrist and elbow after stimulation of the thumb and middle fingers . CMAPs were recorded with concentric needle electrodes placed in the endplate zone of the APB after stimulation at the wrist and elbow . NCVs were determined for 28 male and 20 female normal subjects aged 16 to 62 years . There was no significant difference in NCV between male and female subjects . There was a decrease in NCV with increasing age . No CTS patients were studied . 186 . Occupational Disease Surveillance . Carpal tunnel syndrome . MMWR Morb Mortal Wkly Rep 1989;38:485 - 489 . Background Reference Source : Baker , 1990 . 187 . * Osborn JB , Newell KJ , Rudney JD , Stoltenberg JL . Carpal tunnel syndrome among Minnesota dental hygienists . J Dent Hyg 1990;64(2):79 - 85 . Criteria Met ( 2/6 : 1,2 ) Source : Medline Search . 188 . Padua L , Lo Monaco M , Valente EM , Tonali PA . A useful electrophysiologic parameter for diagnosis of carpal tunnel syndrome . Muscle Nerve 1996;19:48 - 53 . Criteria Met ( 6/6 : 1,2,3,4,5,6 ) . Source : Medline Search . Abstract : In 43 patients ( 50 h and s ) with clinical manifestations of mild-moderate CTS and 36 healthy volunteers ( 40 h and s ) , orthodromic sensory nerve conduction velocity ( SNCV ) was measured with surface electrodes in the median nerve between the third digit and palm and between the palm and wrist . These figures were used to calculate the ratio of distal to proximal conduction ( distoproximal ratio ) . All 90 h and s were also subjected to other nerve conduction studies used for diagnosis of CTS . All control h and s presented distoproximal ratios less than 1.0 reflecting higher conduction rates in the proximal segment . In contrast , 49 of 50 CTS h and s ( 98 % ) presented reversed ratios ( > 1.0 ) indicating compromised proximal conduction . The sensitivity of this test was significantly greater than that of other methods evaluated , including comparative studies and segmental study of the palm-wrist portion of the median nerve . Segmental study of median SNCV with calculation of the distoproximal ratio is a sensitive technique for diagnosis of CTS in patients with normal findings in st and ard nerve conduction studies . Note : The author indicated by correspondence that the mean ± SD for the Control DML in Table 1 should read 3.2 ± 0.4 and not 3.2 ± 0.8 as published . 189 . Padua L , LoMonaco M , Gregori B , Valente EM , Padua R , Tonali P. Neurophysiological classification and sensitivity in 500 carpal tunnel syndrome h and s. Acta Neurol Sc and 1997;96:211 - 217 . Criteria Med ( 6/6 : 1,2,3,4,5,6 ) Source : Medline Search . Abstract : Prospect i ve study of 500 h and s ( 379 patients ) with clinical diagnosis of CTS symptoms . Normal values from the same laboratory previously published ( Padua , 1996 ) . In the 500 CTS patients , DML was prolonged ( 55 % ) , median orthodromic sensory latency was prolonged ( D2 , 74 % ; D3 , 67 % ) . Of the remaining 117 patients with normal DML and median orthodromic sensory studies over 14 cm , the median sensory palmwrist NCV over 8 cm was abnormal in 21 % and the distoproximo ratio of the median palm and digit segments was abnormal in 87 % . 190 . Palliyath SK , Holden L. Refractory studies in early detection of carpal tunnel syndrome . Electromyogr Clin Neurophysiol 1990;30:307 - 309 . Criteria Met ( 5/6 : 1,3,4,5,6 ) Source : Medline Search . Abstract : Using paired stimuli and varying the inter-stimulus interval , the absolute refractory period ( ARP ) and relative refractory period ( RRP ) , were determined in 10 patients with mild electrophysiologic changes suggestive of CTS . They found that the sensory RRP was sensitive in diagnosing early CTS . 191 . * Pavesi G , Olivieri MF , Misk A , Mancia D. Clinical electrophysiological correlations in the carpal tunnel syndrome . Ital J Neurol Sci 1986;7:93 - 96 . Criteria Met ( 3/6 : 2,3,5 ) Source : Medline Search . 192 . Pease WS , Cannell CD , Johnson EW . Median to radial latency difference test in mild carpal tunnel syndrome . Muscle Nerve 1989;12:905 - 909 . Criteria Met ( 4/6 : 1,3,5,6 ) Source : Medline Search . Abstract : The following techniques were studied : ( a ) antidromic DSL median radial differences to the thumb , ( b ) antidromic DSL after stimulation at the wrist and recording from the third digit , ( c ) median mid-palmar DSL compared as a ratio of the wrist to middle finger DSL , ( d ) median ulnar DSL latency difference between the ulnar Practice Parameter : Carpal Tunnel Syndrome Muscle & Nerve Supplement X 2002 S971 SNAP recorded from the little finger after stimulation at the wrist and the median DSL after stimulation at the wrist and recording from the middle finger , and ( e ) median motor DML after recording from the APB after stimulation at the wrist . Three hundred thirty-three symptomatic h and s in 262 patients were initially evaluated with subgroups of patients with CTS evaluated with different tests . The median radial DSL difference and median ulnar DSL difference were most likely to be abnormal followed by median DSL then the palmto-wrist DSL latency ratio and lastly the DML . 193 . Pease WS , Cunningham ML , Walsh WE , Johnson EW . Determining neurapraxia in carpal tunnel syndrome . Am J Phys Med Rehabil 1988;67:117 - 119 . Criteria Met ( 5/6 : 1,3,4,5,6 ) Source : Medline Search . Abstract : With needle stimulation at the wrist and midpalm , CMAPs were recorded over the APB in 25 CTS patients and 23 healthy asymptomatic persons . They found a significant difference in the amplitude of the CMAP in the CTS group when compared to the control group . They propose that this is evidence for conduction block ( neurapraxia ) in CTS . 194 . Pease WS , Lee HH , Johnson EW . Forearm median nerve conduction velocity in carpal tunnel syndrome . Electromyogr Clin Neurophysiol 1990;30:299 - 302 . Criteria Met ( 4/6 : 1,3,4,5 ) Source : Medline Search . Abstract : The NCV of the median nerve in the forearm was determined by 2 methods : ( a ) stimulation in the forearm and recording the nerve action potential at the wrist , and ( b ) stimulation at the wrist and elbow with recording over the APB , in 21 CTS patients and 16 control subjects . They found that the forearm NCV was slowed in the CTS group using either technique . The authors have proposed that this suggest that there is proximal nerve dysfunction as a result of median nerve compression in the carpal tunnel . 195 . * Peterson GW , Will AD . Newer electrodiagnostic techniques in peripheral nerve injuries . Orthop Clin North Am 1988;19:13 - 25 . Criteria Met ( 0/6 ) Source : Narkis , 1990 . 196 . * Phalen GS . The carpal tunnel syndrome : clinical evaluation of 598 h and s. Clin Orthop 1972;83:29 - 40 . Background Reference . Source : Katz 1990 ( J Rheumatology ) . 197 . * Phalen GS . The carpal tunnel syndrome : seventeen years ’ experience in diagnosis and treatment of 654 h and s. J Bone Joint Surg 1966;48:211 - 228 . Criteria Met ( 1/6 : 2 ) Source : Meyers , 1989 . 198 . Phalen GS , Gardner WJ , LaLonde AA . Neuropathy of the median nerve due to compression beneath the transverse carpal ligament . J Bone Joint Surg 1950;32-A:109 - 112 . Background Reference . Source : Braun , 1989 . 199 . Plaja J. Comparative value of different electrodiagnostic methods in carpal tunnel syndrome . Scan J Rehabil Med 1971;3:101 - 108 . Criteria Met ( 4/6 : 1,3,5,6 ) Source : Joynt , 1989 . Abstract : The following techniques were studied : ( a ) CMAP potentials were recorded after stimulation at the wrist and recording with coaxial needle electrodes , ( b ) orthodromic SNAPs with stimulation over the index finger and recording with surface electrodes at the wrist , ( c ) needle EMG using a coaxial needle , ( d ) strength/ duration curves and chronaxy . Fifty-six cases of CTS and 20 normal subjects were evaluated . Sensory latencies were more likely to be abnormal than the other techniques measured . 200 . Preston DC , Logigian EL . Lumbrical and interossei recording in carpal tunnel syndrome [ see comments ] . Muscle Nerve 1992 ; 15 : 1253 - 1257 . Criteria Met ( 5/6 : 1,3,4,5,6 ) Source : Medline Search . Abstract : Median motor studies are commonly “ normal ” in mild carpal tunnel syndrome ( CTS ) . This reflects either the sparing of motor compared to sensory fibers , or the inability of conventional studies to detect an abnormality . A novel approach to demonstrate early motor fiber involvement in CTS is the placement of the same active electrode lateral to the third metacarpal , allowing recording from the second lumbrical or the deeper interossei , when stimulating the median or ulnar nerves at the wrist , respectively . We compared the difference between these latencies in 51 normal control h and s to 107 consecutive patient h and s referred with symptoms and signs suggestive of CTS , who were subsequently proven to have electrophysiologic CTS by st and ard nerve conduction criteria . A prolonged lumbrical-interossei latency difference ( > 0.4 ms ) was found to be a sensitive indicator of CTS in all patient groups . It was also helpful in patients with coexistent polyneuropathy , where localization of median nerve pathology at the wrist was otherwise difficult . 201 . * Preston DC , Ross MH , Kothari MJ , Plotkin GM , Venkatesh S , Logigian EL . The median-ulnar latency difference studies are comparable in mild carpal tunnel syndrome . Muscle Nerve 1994 ; 17 : 1469 - 1471 . Criteria Met ( 2/6 : 1,3 ) . Source : Medline Search . Abstract : Compares sensitivity 159 patients of orthodromic palm-wrist mixed palmar median-ulnar peak latency difference with normal < 0.4 ms , antidromic wrist-D4 sensory median-ulnar onset latency difference with normal < 0.5 ms , and the second lumbrical/interossei motor with normal < 0.5 ms . See discussion of benefits of techniques and diagrams of electrode placements and line drawings of electrode and stimulator placement . 202 . Preswick G. The effect of stimulus intensity in motor latency in carpal tunnel syndrome . J Neurol Neurosurg Psychiatry 1963;26:398 - 401 . Criteria Met ( 4/6 : 1,3,5,6 ) Source : Loong , 1971 . Abstract : With stimulation at the wrist and coaxial needle electrode recording from the APB , DMLs were recorded at super-maximal stimulation and threshold stimulation in 29 CTS h and s The purpose of this study was to investigate the long-term prognosis of patients with carpal tunnel syndrome ( CTS ) . We prospect ively followed-up patients with CTS for 80 weeks . Thirty cases had been treated with a single injection of methylprednisolone acetate and another 30 with a 10-day course of prednisolone . At the end of the follow-up period , there were no significant differences in symptoms as measured by global symptom score and in the proportion of patients who progressed to decompressive surgery . Few patients who were not operated on ( 11.4 % ) remain asymptomatic Objectives : To determine the efficacy of a two week and a four week course of oral steroids in the conservative treatment of carpal tunnel syndrome . Methods : 109 patients with carpal tunnel syndrome were r and omly divided into two treatment groups : ( 1 ) two weeks of prednisolone 20 mg daily followed by two weeks of prednisolone 10 mg daily ( n = 53 ) ; ( 2 ) two weeks of prednisolone 20 mg daily and two weeks of placebo ( n = 56 ) . A symptom question naire was used to rate the five major symptoms of carpal tunnel syndrome ( numbness , pain , weakness/clumsiness , tingling , and nocturnal awakening ) on a scale of 0 ( nil ) to 10 ( severe ) ; the result ing global symptom score was used to evaluate the efficacy of treatment . Assessment s were made at baseline and at one , three , six , nine , and 12 months . Electrodiagnosis was repeated at the end of the study to vali date improvement . Results : In an intention to treat analysis at the end of the study , improvement in the four week treatment group was achieved in 66.0 % of the patients after one month and in 49.0 % at the end of the study ; in the two week treatment group , the respective values were 48.2 % and 35.7 % . In the four week treatment group , 51 % were considered treatment failures ( including those lost to follow up , receiving surgery , or with mild or no improvement ) , compared with 64.3 % for the two week group . Though the percentage improvement was higher in the four week group , the difference did not reach a statistical significance . Persistence of improvement was 74.2 % in the four week group v 74.1 % in the two week group , suggesting no difference in the long term effect . Efficacy analysis showed no significant difference in global symptom score reduction between the two groups . Follow up electrodiagnosis showed significant improvement in all measured variables except for the amplitude of compound muscle action potentials . Conclusions : Short term low dose oral steroid are effective treatment for carpal tunnel syndrome . The dose of steroids and the duration treatment are not key determinants of efficacy The authors compared the effectiveness of low-dose , short-term oral prednisolone vs local methylprednisolone injection in a prospect i ve , double-blinded , parallel treatment study of carpal tunnel syndrome ( CTS ) . A single injection of 15 mg methylprednisolone result ed in significant improvement in global symptom scores over a 12-week period . This study demonstrated the superiority of local steroid injection to oral steroid in the treatment of CTS Çeliker R , Arslan Ş , İnanıcı F : Corticosteroid injection vs. nonsteroidal antiinflammatory drug and splinting in carpal tunnel syndrome . Am J Phys Med Rehabil 2002;81:182–186 . Objective To compare the efficacy of local corticosteroid injection to a nonsteroidal antiinflammatory drug and splinting for the treatment of carpal tunnel syndrome . Design This study was a prospect i ve , unblinded , r and omized clinical trial with an 8-wk follow-up . Thirty-three h and s of 23 patients were r and omly treated with acemetacine and splinting ( group A ) or with corticosteroid injection ( group B ) . Clinical ( symptom severity scale , visual analog scale , Tinel and Phalen tests ) and electromyographic evaluations were performed on initial visit and after 8 wk . Results Clinical and electromyographic parameters , which were similar at baseline , were improved in both groups after treatment . Improvement was also similar when both groups were compared at 8 wk . Conclusion Both splinting combined with the use of a nonsteroidal antiinflammatory drug and steroid injection into the carpal tunnel result ed in significant improvement in carpal tunnel syndrome Objective : To assess the course of untreated carpal tunnel syndrome ( CTS ) . Methods : The Italian CTS Study Group prospect ively followed up ( 10 to 15 months ) 196 untreated patients ( 274 h and s ) with idiopathic CTS with multiple measurements of CTS . Baseline factors were used to predict the evolution of untreated CTS in multiple regression analysis . Results : Comparison of baseline and follow-up data showed a significant spontaneous improvement of patient-oriented and neurophysiologic measurements . A significant correlation between evolution and initial severity of CTS was observed . CTS measurements improved in patients with more severe initial impairment whereas they worsened in patients with milder initial impairment . The main positive prognostic factor was short duration of symptoms . Similarly , spontaneous improvement was more frequently associated with young age . Conversely , baseline bilateral symptoms and positive Phalen predicted a poor prognosis . Conclusions : Some patients with CTS improve spontaneously without surgical treatment Background : Conservative treatment of mild to moderate carpal tunnel syndrome ( CTS ) is variable . Objective : To evaluate the effectiveness of commonly used oral medications such as diuretics , nonsteroid anti-inflammatory drugs ( NSAIDs ) , and steroids in the treatment of CTS . Methods : Prospect i ve , r and omized , double-blind and placebo-controlled study of patients with clinical symptoms and signs of CTS , confirmed by st and ard electrodiagnosis . Baseline assessment s included a st and ardized symptom question naire , rating five categories of symptoms ( pain , numbness , paresthesia , weakness/clumsiness , and nocturnal awakening ) on a scale from 0(no symptoms ) to 10 ( severe ) . The total score in each of the five categories was termed the global symptom score ( GSS ) . After baseline assessment , patients were r and omized to the following treatment arms : 1 ) 4 weeks of placebo ( N = 16 ) ; 2 ) 4 weeks of diuretic ( trichlormethiazide , 2 mg daily ; n = 16 ) ; 3 ) 4 weeks of NSAID-slow release ( SR ) ( tenoxicam-SR , mg daily ; n = 18 ) ; and 4 ) 2 weeks of prednisolone , 20 mg daily , followed by another 2-week dosage of 10 mg daily ( n = 23 ) . Results of follow-up assessment s in the second and the fourth weeks were identical to baseline scores . The changes in GSS were analyzed to determine the statistical difference . Results : No significant reduction from baseline GSS was seen at second , and fourth weeks in the placebo , NSAID-SR , and diuretic groups . However , the mean score at 4 weeks in the steroid group decreased significantly from a baseline of 27.9 ± 6.9 to 10 ± 7.4 . Conclusion : For patients with mild to moderate CTS who opt for conservative treatment , corticosteroids are of greater benefit A clinical and electrophysiological study evaluated the usefulness of local steroid therapy for carpal tunnel syndrome ( CTS ) . To evaluate the efficacy of local steroid therapy 32 patients ( 53 nerves ) were r and omly assigned to one of two groups : one ( 27 nerves ) received 15 mg methylprednisolone acetate injected locally and the other ( 26 nerves ) received the same amount of saline solution . The injections were repeated after a week . Clinical and electrophysiological findings were evaluated , double blind , at regular intervals . A clear-cut efficacy of steroid treatment was found . Only 8 % of nerves were not benefitted while a marked early improvement was observed in most of the nerves . In order to appraise the long-term effect of local steroid treatment on CTS , 53 patients ( 91 nerves ) were studied and followed up by means of clinical and electrophysiological examinations performed every 2 months for 2 years . The benefit of steroid treatment was transient . About 50 % of the nerves became worse within 6 months and 90 % within 18 months . Only a small percentage ( 8 % ) of the nerves remained improved at the 2-years follow-up . The clinical features were not useful in foretelling the duration of the improvement , which appeared to be related to the antidromic SAP latency The objective of the study was to compare the favorable response rate , time duration , and pain level of local corticosteroid injection using a novel approach for the treatment of carpal tunnel syndrome vs a classic approach . Patients with symptomatic carpal tunnel syndrome of less than 1-year duration were r and omized for local corticosteroid injection using either the classic approach or a novel approach . In our approach ( novel ) , we used a 29 gauge × 1/2-in . needle and a 1-ml insulin syringe containing 12 mg of methylprednisolone mixed with 0.15 ml of lidocaine 2 % , and the site of the injection was 2–3 cm distal to the middle of wrist crease . In the classic approach , we used a 25 gauge × 3-cm needle and a 2-ml syringe injecting 35 mg of methylprednisolone mixed with 0.5 ml of lidocaine 2 % , 3–4 cm proximal to the wrist crease and just ulnar to the tendon of the flexor carpi radialis muscle . Response rate was evaluated 1 , 3 , 6 , and 12 weeks after the injection , and also the duration of time of the procedure and the level of pain using the visual analogue scale were compared between the two groups . Forty-two patients signed the consent form , and all of them completed the study [ 21 patients in the classic approach group ( group 1 ) and 21 patients in the novel approach group ( group 2 ) ] . The favorable response rates were 100 , 81 , 71 , and 57 % in group 1 and 100 , 71 , 67 , and 57 % in group 2 after 1 , 3 , 6 , and 12 weeks , respectively . There was no significant difference in the favorable response rate between the two groups ( p=0.468 , 95 % CI=−12–31 % , after 3 weeks ) . The average duration of time of the procedure in group 1 was 26.71±32.83 s compared to 8.48±1.123 s ( p=0.021 ) in group 2 . The average grade of pain expressed by the patients in group 1 was 4.38±1.523 compared to 3.62±1.071 in group 2 ( p=0.065 ) . In conclusion , local corticosteroid injection using the novel approach for the treatment of carpal tunnel syndrome is helpful , and the favorable response rates are comparable to those using the classic approach after 1 , 3 , 6 , and 12 weeks . The novel approach is much less time consuming and is not more painful We evaluated the effectiveness of low-dose , short-term oral prednisone in ameliorating the pain and other symptoms of carpal tunnel syndrome ( CTS ) in a r and omized , double-blind , placebo-controlled study of patients with mild to moderate CTS . Prednisone , in doses of 20 mg daily for the first week and 10 mg daily for the second week , result ed in significant improvement in global symptom scores . The effect was rapid , but gradually waned over 8 weeks of observation . This approach may provide a treatment alternative in the short-term , conservative management of CTS . NEUROLOGY 1995;45 : 1923 - Abstract .To evaluate the long-term efficacy of non-surgical treatment methods for mild and moderate carpal tunnel syndrome , 120 patients with clinical symptoms and electrophysiologic evidence were included in a prospect i ve , r and omized and blinded trial : 60 patients were instructed to wear splints every night , 30 received injections of betamethasone 4 cm proximal to the carpal tunnel , and 30 received injections distal to the carpal tunnel . After approximately 1 year ( mean , 11 months ; range , 9–14 ) , 108 patients were available for final evaluation . We assessed clinical symptom severity and performed detailed electrophysiologic examinations before and after treatment . Splinting provided symptomatic relief and improved sensory and motor nerve conduction velocities at the long-term follow-up when the splints were worn almost every night . Proximal and distal injections of steroids were ineffective on the basis of both clinical symptoms and electrophysiologic findings We investigated the efficacy of a single vs. double steroid injections in the treatment of carpal tunnel syndrome ( CTS ) in a r and omised double-blind controlled trial . Patients with idiopathic CTS were r and omised into ( i ) one group receiving a baseline methylprednisolone acetate injection plus a saline injection 8 weeks later and ( ii ) a second group receiving methylprednisolone acetate injection at baseline and at 8 weeks . The primary outcome was the Global Symptom Score ( GSS ) . Forty patients were recruited . By 40 weeks , the mean GSS improved from 25.6 to 14.1 in the single-injection group whereas from 26.7 to 12.6 in the reinjection group , but there was no significant difference in GSS between the two groups ( p = 0.26 ) . There were also no significant differences in terms of electrophysiological and functional outcomes . The results suggest that an additional steroid injection confers no added benefit to a single injection in terms of symptom relief Abstract Objective : To assess the effect of a 40 mg methylprednisolone injection proximal to the carpal tunnel in patients with the carpal tunnel syndrome . Design : R and omised double blind placebo controlled trial . Fig 1 . Site for injecting corticosteroid to treat carpal tunnel syndrome Setting : Outpatient neurology clinic in a district general hospital . Participants : Patients with symptoms of the carpal tunnel syndrome for more than 3 months , confirmed by electrophysiological tests and aged over 18 years . Intervention : Injection with 10 mg lignocaine ( lidocaine ) or 10 mg lignocaine and 40 mg methylprednisolone Non-responders who had received lignocaine received 40 mg methylprednisolone and 10 mg lignocaine and were followed in an open study . Main outcome measures : Participants were scored as having improved or not improved . Improved was defined as no symptoms or minor symptoms requiring no further treatment . Results : At 1 month 6 ( 20 % ) of 30 patients in the control group had improved compared with 23 ( 77 % ) of 30 patients the intervention group ( difference 57 % ( 95 % confidence interval 36 % to 77 % ) ) . After 1 year , 2 of 6 improved patients in the control group did not need a second treatment , compared with 15 of 23 improved patients in the intervention group ( difference 43 % ( 23 % to 63 % ) . Of the 28 non-responders in the control group , 24 ( 86 % ) improved after methylprednisolone . Of these 24 patients , 12 needed surgical treatment within one year . Conclusion : A single injection with steroids close to the carpal tunnel may result in long term improvement and should be considered before surgical decompression . Key messages Corticosteroid injections into the carpal tunnel may damage the nerve , and any treatment benefits may be of short duration A single injection with steroids proximal to the carpal tunnel improves 77 % of patients with the carpal tunnel syndrome at one month after treatment This single injection is still effective at one year in half of the patients Injections proximal to the carpal tunnel have no side effects and are easier to carry out than injections into the carpal A double-blinded placebo-controlled trial was performed to evaluate the use of steroid injections beneath the transverse carpal ligament in the treatment of carpal tunnel syndrome ( CTS ) refractory to nonsurgical therapy . Forty-three patients received 6 mg betamethasone and lidocaine and 38 patients received 1 ml saline placebo and lidocaine . The primary outcome measure was satisfaction with symptom relief . Thirty patients ( 70 % ) in the steroid-treated group were satisfied or highly satisfied compared with 13 ( 34 % ) of placebo-treated patients ( P < 0.001 ) . Patients receiving steroids also showed significant improvement in median nerve conduction parameters and scores on vali date d symptom/function question naires . Forty-six patients were treated with serial injections for recurrent CTS symptoms . After 18 months , 17 patients reported adequate symptom relief with steroid injection , and 18 patients with unsatisfactory symptom relief were referred for carpal tunnel release surgery . We conclude that although steroid injections are safe and effective for temporary relief of CTS , most patients will eventually require surgery for long-term control of their symptoms |
10,436 | 29,912,621 | A meta-regression suggested that interventions using larger numbers of BCTs produced the greatest effects .
This paper highlights the potential for digital interventions to improve rates of smoking cessation in pregnancy | ABSTRACT Smoking in pregnancy remains a global public health issue due to foetal health risks and potential maternal complications .
The aims of this systematic review and meta- analysis were to explore : ( 1 ) whether digital interventions for pregnancy smoking cessation are effective , ( 2 ) the impact of intervention platform on smoking cessation , ( 3 ) the associations between specific Behaviour Change Techniques ( BCTs ) delivered within interventions and smoking cessation and ( 4 ) the association between the total number of BCTs delivered and smoking cessation . | Objectives : To evaluate the effectiveness in helping pregnant women stop smoking of two interventions ( Pro-Change for a healthy pregnancy ) based on the transtheoretical model of behaviour change ( TTM ) compared to current st and ard care . Design : Cluster r and omised trial . Setting : Antenatal clinics in West Midl and s , UK general practice s. Participants : 918 pregnant smokers Interventions : 100 general practice s were r and omised into the three trial arms . Midwives in these practice s delivered three interventions : A ( st and ard care ) , B ( TTM based self help manuals ) , and C ( TTM based self help manuals plus sessions with an interactive computer program giving individualised smoking cessation advice ) . Main outcome measures : Biochemically confirmed smoking cessation for 10 weeks previously , and point prevalence abstinence , both measured at 30 weeks of pregnancy and 10 days after delivery . Results : There were small differences between the TTM arms . Combining the two arms , the odds ratios at 30 weeks were 2.09 ( 95 % confidence interval ( CI ) 0.90 to 4.85 ) for 10 week sustained abstinence and 2.92 ( 95 % CI 1.42 to 6.03 ) for point prevalence abstinence relative to controls . At 10 days after delivery , the odds ratios were 2.81 ( 95 % CI 1.11 to 7.13 ) and 1.85 ( 95 % CI 1.00 to 3.41 ) for 10 week and point prevalence abstinence respectively . Conclusions : While there is a small borderline significant increase in quitting in the combined intervention arms compared with the controls , the effect of the intervention is small . At 30 weeks gestation and at 10 days postnatal , only about 3 % of the intervention groups achieved sustained cessation , with numbers needed to treat of 67 ( 30 weeks of gestation ) and 53 ( 10 weeks postnatal ) for one additional woman to achieve sustained confirmed cessation . Given also that the intervention was re source intensive , it is of doubtful benefit Background Behavioural support for smoking cessation in pregnancy can be effective ; however , many pregnant women face barriers to seeking support to stop smoking . Some digital interventions have been found to be effective for smoking cessation in the general population and may be effective for supporting cessation in pregnancy due to their flexibility and the potential for personalisation . To date , there is limited evidence of the effectiveness of digital interventions for smoking cessation in pregnancy . This review aims to assess the following : ( 1 ) whether digital interventions are effective at promoting smoking cessation among pregnant women ; ( 2 ) which behaviour change techniques ( BCTs ) or combinations of BCTs are associated with the effectiveness of digital interventions for smoking cessation in pregnancy ; and ( 3 ) whether the number of BCTs used is associated with the effectiveness of digital interventions for smoking cessation in pregnancy . Methods This review will include digital interventions delivered largely through computer ( PC or laptop ) , video/DVD , mobile phone ( including smartphones ) or portable h and held device ( e.g. tablet , iPad ) and include websites , mobile or tablet applications and SMS text messages . Interventions must be r and omised or quasi-r and omised controlled trials aim ed at women who smoke in pregnancy , with smoking cessation as a measured outcome ( preferably the latest available point prevalence smoking status measure taken during pregnancy , biochemically verified if available ) . Electronic bibliographic data bases will be search ed to identify suitable studies indexed in the following : Academic Search Complete , ASSIA , CINAHL , The Cochrane Library , EMBASE , Medline , PsycINFO , Scopus , and Web of Science . The search strategy will include key words and data base-specific subject headings relating to ‘ pregnancy ’ and ‘ smoking ’ and synonyms for the terms ‘ digital ’ and ‘ r and omised controlled trial ’ . Where required and where possible , the first and second authors will independently code interventions and control groups for BCTs . If data allows , meta-analyses will be used to assess intervention effectiveness and the effectiveness of BCTs . Discussion This systematic review will provide a detailed synthesis of the effectiveness of current research using digital interventions for smoking cessation in pregnancy , to build on the evidence base and guide the development of future research in this area . Systematic review registration PROSPERO Abstract Aims To estimate the effectiveness of pregnancy smoking cessation support delivered by short message service ( SMS ) text message and key parameters needed to plan a definitive trial . Design Multi‐centre , parallel‐group , single‐blinded , individual r and omized controlled trial . Setting Sixteen antenatal clinics in Engl and . Participants Four hundred and seven participants were r and omized to the intervention ( n = 203 ) or usual care ( n = 204 ) . Eligible women were < 25 weeks gestation , smoked at least one daily cigarette ( > 5 pre‐pregnancy ) , were able to receive and underst and English SMS texts and were not already using text‐based cessation support . Intervention All participants received a smoking cessation leaflet ; intervention participants also received a 12‐week programme of individually tailored , automated , interactive , self‐help smoking cessation text messages ( MiQuit ) . Outcome measurements Seven smoking outcomes , including vali date d continuous abstinence from 4 weeks post‐r and omization until 36 weeks gestation , design parameters for a future trial and cost‐per‐quitter . Findings Using the vali date d , continuous abstinence outcome , 5.4 % ( 11 of 203 ) of MiQuit participants were abstinent versus 2.0 % ( four of 204 ) of usual care participants [ odds ratio ( OR ) = 2.7 , 95 % confidence interval ( CI ) = 0.93–9.35 ] . The Bayes factor for this outcome was 2.23 . Completeness of follow‐up at 36 weeks gestation was similar in both groups ; provision of self‐report smoking data was 64 % ( MiQuit ) and 65 % ( usual care ) and abstinence validation rates were 56 % ( MiQuit ) and 61 % ( usual care ) . The incremental cost‐per‐quitter was £ 133.53 ( 95 % CI = –£395.78 to 843.62 ) . Conclusions There was some evidence , although not conclusive , that a text‐messaging programme may increase cessation rates in pregnant smokers when provided alongside routine NHS cessation care This study examined smoking cessation and cigarette reduction of indigent inner city pregnant women ( n = 193 ) who completed one of three interventions : a special videoprogram based on their perceptions of the effects of smoking during pregnancy , the American Lung Association 's “ Freedom From Smoking For You and Your Baby ” program , or the usual physician 's advice . Six percent of the women quit smoking , and 43 % reduced the number of cigarettes they smoked . There were no significant differences among the three groups for either the number who quit smoking or who reduced the number of cigarettes smoked INTRODUCTION Implementation of evidence -based interventions for smoking during pregnancy is challenging . We developed 2 highly replicable interventions for smoking during pregnancy : ( a ) a computer-delivered 5As-based brief intervention ( CD-5As ) and ( b ) a computer-assisted , simplified , and low-intensity contingency management ( CM-Lite ) . METHODS A sample of 110 primarily Black pregnant women reporting smoking in the past week were recruited from prenatal care clinics and r and omly assigned to CD-5As ( n = 26 ) , CM-Lite ( n = 28 ) , CD-5As plus CM-Lite ( n = 30 ) , or treatment as usual ( n = 26 ) . Self-report of smoking , urine cotinine , and breath CO were measured 10 weeks following r and omization . RESULTS Participants rated both interventions highly ( e.g. , 87.5 % of CD-5As participants reported increases in likelihood of quitting ) , but most CM-Lite participants did not initiate reinforcement sessions and did not show increased abstinence . CD-5As led to increased abstinence as measured by cotinine ( 43.5 % cotinine negative vs. 17.4 % ; odds ratio [ OR ] = 10.1 , p = .02 ) but not for CO-confirmed 7-day point prevalence ( 30.4 % abstinent vs. 8.7 % ; OR = 5.7 , p = .06 ) . Collapsing across CM-Lite status , participants receiving the CD-5As intervention were more likely to talk to a doctor or nurse about their smoking ( 60.5 % vs. 30.8 % ; OR = 3.0 , p = .02 ) . CONCLUSIONS Low-intensity participant-initiated CM did not affect smoking in this sample , but the CD-5As intervention was successful in increasing abstinence during pregnancy . Further research should seek to replicate these results in larger and more diverse sample s. Should CD-5As continue to prove efficacious , it could greatly increase the proportion of pregnant smokers who receive an evidence -based brief intervention Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVE To evaluate a web-based contingency management program ( CM ) and a phone-delivered cessation counseling program ( Smoking Cessation for Healthy Births [ SCHB ] ) with pregnant smokers in rural Appalachia who were ≤12 weeks gestation at enrollment . DESIGN Two group r and omized design . SETTING Home-based cessation programs in rural Appalachia Ohio and Kentucky . PARTICIPANTS A community sample of pregnant smokers ( N = 17 ) . METHODS Participants completed demographic and smoking-related question naires and were assigned to CM ( n = 7 ) or SCHB ( n = 10 ) conditions . Smoking status was assessed monthly using breath carbon monoxide and urinary cotinine . RESULTS For CM , two of seven ( 28.57 % ) of the participants achieved abstinence , and three of 10 ( 30 % ) of those enrolled in SCHB were abstinent by late in pregnancy . Participants in CM attained abstinence more rapidly than those in SCHB . However , those in SCHB experienced less relapse to smoking , and a greater percentage of these participants reduced their smoking by at least 50 % . CONCLUSION Based on this initial evaluation , the web-based CM and SCHB programs appeared to be feasible for use with rural pregnant smokers with acceptable program adherence for both approaches . Future research ers could explore combining these programs to capitalize on the strengths of each , for example , rapid smoking cessation based on CM incentives and better sustained cessation or reductions in smoking facilitated by the counseling support of SCHB Smoking during pregnancy is a plausible risk factor for childhood cancer , yet previous studies have yielded conflicting results , and few prospect i ve studies have been published . Data on maternal smoking were obtained from California birth certificates . We linked California birth certificates ( births 2007 - 2011 ) with California Cancer Registry records for childhood cancer cases ( diagnosed January 2007-September 2013 ) that were ages 5 or younger at diagnosis ( N cases = 2,021 ) . Controls ( N = 40,356 ) were frequency-matched by birth year and r and omly selected from birth certificate records . We used unconditional logistic regression to obtain odds ratios ( OR ) and 95 % confidence intervals ( CI ) to assess the association between smoking during pregnancy and childhood cancer . We observed positive associations for gliomas ( OR = 1.8 , 95 % CI : 1.0 - 3.4 ) and retinoblastoma ( OR = 3.0 , 95 % CI : 1.4 - 6.6 ) , particularly bilateral retinoblastoma ( OR = 9.4 , 95 % CI 3.6 - 24.7 ) with maternal smoking in pregnancy . Maternal smoking during pregnancy may be a risk factor for retinoblastoma and certain types of childhood brain tumors INTRODUCTION There is a need for innovation in both the enrollment of pregnant smokers in smoking cessation treatment programs and in the types of treatments offered . The study tests whether an interactive and intensive text messaging program , Quit4baby , can promote smoking cessation for pregnant women already enrolled in a health text messaging program , Text4baby . METHODS Between July 2015 and February 2016 , a total of 35,957 recruitment text messages were sent to Text4baby subscribers . Eligible pregnant smokers were enrolled and r and omized to receive Text4baby ( control ) or Text4baby and Quit4baby ( intervention ; N=497 ) . Participants were surveyed at 1 month , 3 months , and 6 months post-enrollment , and saliva sample s were collected at 3 months for biochemical verification of smoking status . Data were collected from 2015 to 2016 and analyzed in 2016 . RESULTS Using an intention-to-treat analysis , 28.80 % of the intervention group and 15.79 % of the control group reported not smoking in the past 7 days at 1 month ( p<0.01 ) , and 35.20 % of the intervention group and 22.67 % of the control group reported not smoking in the past 7 days at 3 months ( p<0.01 ) . Biochemical verification of smoking status at 3 months indicated no significant differences between groups ( 15.60 % in the intervention group and 10.93 % in the control group [ p=0.13 ] ) , although significant differences favoring the intervention were found for older smokers ( p<0.05 ) and for those who enrolled in their second or third trimester of pregnancy ( p<0.05 ) . Self-report of late pregnancy 7- and 30-day point prevalence abstinence favored the intervention group ( p<0.001 , p<0.01 ) . No significant differences were observed at the 6-month follow-up or in the postpartum period . CONCLUSIONS Results provide limited support of the efficacy of the Quit4baby text messaging program in the short term and late in pregnancy , but not in the postpartum period This exploratory study examined the acceptability and efficacy of a videotape modeling smoking cessation as an adjunct to smoking cessation advice delivered during prenatal care . In a r and omized controlled trial involving 60 women , we compared the delivery of brief smoking cessation advice and a tipsheet to the same advice and tipsheet plus provision of the videotape . Outcomes included opinions about content and acceptability of the videotape , and smoking behavior change during pregnancy . The most highly endorsed features of the videotape were seeing other women quitting smoking ( 77 % ) , dealing with stress and bad feelings ( 69 % ) , talking about what to do with urges to smoke ( 69 % ) , and discussing ways to get support from families and friends ( 54 % ) . The reported quit rate in the last month of pregnancy , vali date d by exhaled carbon monoxide levels , and including women lost to follow-up as smokers , was 19.2 % in the intervention group and 0 % in the comparison group ( p = .02 ) . This study suggests that the use of videotapes modeling smoking behavior change may increase the effectiveness of the assistance in quitting smoking that is generally available in obstetric and family practice s or public maternity clinics BACKGROUND Internet-based interventions for smoking cessation could help millions of people stop smoking at very low unit costs ; however , long-term biochemically verified evidence is scarce and such interventions might be less effective for smokers with low socioeconomic status than for those with high status because of lower online literacy to engage with websites . We aim ed to assess a new interactive internet-based intervention ( StopAdvisor ) for smoking cessation that was design ed with particular attention directed to people with low socioeconomic status . METHODS We did this online r and omised controlled trial between Dec 6 , 2011 , and Oct 11 , 2013 , in the UK . Participants aged 18 years and older who smoked every day were r and omly assigned ( 1:1 ) to receive treatment with StopAdvisor or an information-only website . R and omisation was automated with an unseen r and om number function embedded in the website to establish which treatment was revealed after the online baseline assessment . Recruitment continued until the required sample size had been achieved from both high and low socioeconomic status sub population s. Participants , and research ers who obtained data and did laboratory analyses , were masked to treatment allocation . The primary outcome was 6 month sustained , biochemically verified abstinence . The main secondary outcome was 6 month , 7 day biochemically verified point prevalence . Analysis was by intention to treat . Homogeneity of intervention effect across the socioeconomic sub sample s was first assessed to establish whether overall or separate sub sample analyses were appropriate . The study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N99820519 . FINDINGS We r and omly assigned 4613 participants to the StopAdvisor group ( n=2321 ) or the control group ( n=2292 ) ; 2142 participants were of low socioeconomic status and 2471 participants were of high status . The overall rate of smoking cessation was similar between participants in the StopAdvisor and control groups for the primary ( 237 [ 10 % ] vs 220 [ 10 % ] participants ; relative risk [ RR ] 1·06 , 95 % CI 0·89 - 1·27 ; p=0·49 ) and the secondary ( 358 [ 15 % ] vs 332 [ 15 % ] participants ; 1·06 , 0·93 - 1·22 ; p=0·37 ) outcomes ; however , the intervention effect differed across socioeconomic status sub sample s ( 1·44 , 0·99 - 2·09 ; p=0·0562 and 1·37 , 1·02 - 1·84 ; p=0·0360 , respectively ) . StopAdvisor helped participants with low socioeconomic status stop smoking compared with the information-only website ( primary outcome : 90 [ 8 % ] of 1088 vs 64 [ 6 % ] of 1054 participants ; RR 1·36 , 95 % CI 1·00 - 1·86 ; p=0·0499 ; secondary outcome : 136 [ 13 % ] vs 100 [ 10 % ] participants ; 1·32 , 1·03 - 1·68 , p=0·0267 ) , but did not improve cessation rates in those with high socioeconomic status ( 147 [ 12 % ] of 1233 vs 156 [ 13 % ] of 1238 participants ; 0·95 , 0·77 - 1·17 ; p=0·61 and 222 [ 18 % ] vs 232 [ 19 % ] participants ; 0·96 , 0·81 - 1·13 , p=0·64 , respectively ) . INTERPRETATION StopAdvisor was more effective than an information-only website in smokers of low , but not high , socioeconomic status . StopAdvisor could be implemented easily and made freely available , which would probably improve the success rates of smokers with low socioeconomic status who are seeking online support . FUNDING National Prevention Research Initiative INTRODUCTION Study aims were to assess the feasibility and acceptability of a tailored self-help smoking cessation intervention for pregnant smokers ( MiQuit ) . Secondary aims were to assess whether MiQuit affected cognitive determinants of quitting and to provide a range of potential effect sizes of the intervention effect on smoking abstinence . METHODS A r and omized controlled trial was undertaken in which pregnant smokers were allocated to either receive MiQuit , a tailored self-help leaflet followed by an 11-week program of tailored text messages , or to a control group , receiving a nontailored self-help leaflet . Participants were 207 pregnant smokers identified by community midwives across 7 NHS Trusts ( United Kingdom ) . At 3-month follow-up , intervention acceptability , cognitive determinants of quitting , and smoking outcomes ( self-reported and cotinine-vali date d 7-day point prevalence abstinence ) were assessed . RESULTS Feasibility : 94 % ( 95 % CI 89%-99 % ) of MiQuit participants reported receiving both intervention components . Acceptability : 9 % ( 95 % CI 4%-15 % ) of MiQuit participants opted to discontinue the text messages . Mechanism : compared with controls , MiQuit participants were more likely to set a quit date ( p = .049 ) and reported higher levels of self-efficacy ( p = .024 ) , harm beliefs ( p = .052 ) , and determination to quit ( p = .019 ) . Potential efficacy : self-reported abstinence-MiQuit 22.9 % , control 19.6 % ; odds ratio ( OR ) = 1.22 , 95 % CI 0.62 - 2.41 ; cotinine-vali date d abstinence-MiQuit 12.5 % , control 7.8 % ; OR = 1.68 , 95 % CI 0.66 - 4.31 . CONCLUSIONS Delivering tailored smoking cessation support to pregnant smokers via leaflet and text message is feasible and acceptable . The positive effects of MiQuit on cognitive determinants and the likelihood of setting a quit date are encouraging . A larger efficacy trial is warranted |
10,437 | 31,258,649 | Based on the meta- analysis , NBI , FICE and AFI were significantly better compared with SDWL at detecting patients with adenoma . | A colonoscopy is considered to be the st and ard diagnostic test used to detect early colorectal lesions .
Detection rates are expected to improve with optimised visualisation .
A systematic review and network meta- analysis was conducted to evaluate detection efficiency in several colonoscopic modalities . | Purpose The purpose of this study is to evaluate an endoscopic trimodal imaging ( ETMI ) system ( high resolution , autofluorescence , and NBI ) in the detection and differentiation of colorectal adenomas . Methods A prospect i ve r and omised trial of t and em colonoscopies was carried out using the Olympus XCF-FH260AZI system . Each colonic segment was examined twice for lesions , once with HRE and once with AFI , in r and om order per patient . All detected lesions were assessed with NBI for pit pattern and with AFI for colour . All lesions were removed and sent for histology . Any lesion identified on the second examination was considered as missed by the first examination . Outcome measures are adenoma miss rates of AFI and HRE , and diagnostic accuracy of NBI and AFI for differentiating neoplastic from non-neoplastic lesions . Results Ninety-four patients underwent colonoscopy with ETMI ( 47 in each group ) . Among 47 patients examined with AFI first , 31 adenomas in 15 patients were detected initially [ detection rate 0.66 ( 0.52–0.75 ) ] . Subsequent HRE inspection identified six additional adenomas . Among 47 patients examined with HRE first , 29 adenomas in 14 patients were detected initially [ detection rate 0.62 ( 0.53–0.79 ) ] . Successive AFI yielded seven additional adenomas . Adenoma miss rates of AFI and HRE were 14 % and 16.2 % , respectively ( p = 0.29 ) . Accuracy of AFI alone for differentiation was lower than NBI ( 63 % vs. 80 % , p < 0.001 ) . Combined use of AFI and NBI achieved improved accuracy for differentiation ( 84 % ) , showing a trend for superiority compared with NBI alone ( p = 0.064 ) . Conclusions AFI did not significantly reduce the adenoma miss rate compared with HRE . AFI alone had a disappointing accuracy for adenoma differentiation , which could be improved by combination of AFI and NBI Objective : Colonoscopy is the accepted gold st and ard for screening of neoplastic colorectal lesions , but the substantial miss rate remains a challenge . Computed virtual chromoendoscopy with the Fujinon intelligent colour enhancement ( FICE ) system is a new dyeless imaging technique that might allow higher rates of adenoma detection . Methods : This is a prospect i ve r and omised five tertiary care centre trial of colonoscopy in the FICE mode versus st and ard colonoscopy with targeted indigocarmine chromoscopy ( control group ) in consecutive patients attending for routine colonoscopy . Histopathology of detected lesions was confirmed by evaluation of endoscopic resection or biopsy specimens . Results : 871 patients were enrolled , and 764 patients ( 344 female , mean age 64 years ) were subjected to final analysis ( 368 in the FICE group , 396 in the control group ) . In total , 236 adenomas ( mean of 0.64 per case ) were detected in the FICE group and 271 adenomas ( mean of 0.68 per case ) in the control group ( p = 0.92 ) . There was no statistically significant difference in the percentage of patients with ⩾1 adenoma between the control group ( 35.4 % ) and the FICE group ( 35.6 % ) ( p = 1.0 ) . For the differential diagnosis of adenomas and non-neoplastic polyps , the sensitivity of FICE ( 92.7 % ) was comparable with that of indigocarmine ( 90.4 % ) ( p = 0.44 ) . Conclusions : At colonoscopy , adenoma detection rates are not improved by virtual chromoendoscopy with the FICE system compared with white light endoscopy with targeted indigocarmine spraying . However , FICE can effectively substitute for chromoscopy concerning the differentiation of neoplastic and non-neoplastic lesions Background : Diminutive and flat colorectal lesions can be difficult to detect using conventional colonoscopic techniques . Previous data have suggested that pan-chromoscopy may improve detection rates . No r and omised control trial has been performed examining detection rates of such lesions while controlling for extubation time and lavage effect . Aim : We conducted a r and omised controlled trial of pan-colonic chromoscopic colonoscopy for the detection of diminutive and flat colorectal lesions while controlling for extubation time and lavage effect . Methods : Consecutive patients attending for routine colonoscopy were r and omised to either pan-chromoscopy using 0.5 % indigo carmine ( IC ) or targeted chromoscopy ( control group ) . A minimum diagnostic extubation time was set at eight minutes with controls undergoing a matched volume of saline wash . Results : A total of 260 patients were r and omised ; 132 controls and 128 to pan-colonic chromoscopy . Extubation times did not differ significantly between the control ( median 15 minutes ( range 8–41 ) ) and chromoscopy ( median 17 minutes ( range 8–39 ) ) groups . The volume of IC used in the pan-chromoscopy group ( median 68 ml ( range 65–90 ) ) and normal saline used in the control group ( 69 ml ( range 60–93 ) ) did not differ significantly . There was a statistically significant difference between the groups regarding the total number of adenomas detected ( p<0.05 ) with significantly more diminutive ( < 4 mm ) adenomas detected in the pan-chromoscopy group ( p = 0.03 ) . Pan-chromoscopy diagnosed more diminutive and flat lesions in the right colon compared with controls ( p<0.05 ) , with more patients with multiple adenomas ( > 3 ) detected using pan-chromoscopy ( p<0.01 ) . Hyperplastic lesions were more commonly detected in the pan-chromoscopy group compared with controls ( p<0.001 ) . More hyperplastic polyps were detected in the left colon ( 86 % rectosigmoid ) using chromoscopy compared with controls . Conclusion : Chromoscopy improves the total number of adenomas detected and enhances the detection of diminutive and flat lesions . Importantly , eight diminutive lesions had foci of high grade dysplasia . Chromoscopy may benefit patients , assuming a high risk of colorectal cancer , and help in risk stratification and planning follow up colonoscopy intervals Background and aims : Colonoscopy is an established method of colorectal cancer screening , but has an adenoma miss rate of 10–20 % . Detection rates are expected to improve with optimised visualisation methods . This prospect i ve r and omised study evaluated narrow-b and imaging ( NBI ) , a new technique that may enhance image contrast in colon adenoma detection . Methods : Eligible patients presenting for diagnostic colonoscopy were r and omly assigned to undergo wide-angle colonoscopy using either conventional high-resolution imaging or NBI during instrument withdrawal . The primary outcome parameter was the difference in the adenoma detection rate between the two techniques . Results : A total of 401 patients were included ( mean age 59.4 years , 52.6 % men ) . Adenomas were detected more frequently in the NBI group ( 23 % ) than in the control group ( 17 % ) with a number of 17 colonoscopies needed to find one additional adenoma patient ; however , the difference was not statistically significant ( p = 0.129 ) . When the two techniques were compared in consecutive subgroups of 100 study patients , adenoma rates in the NBI group remained fairly stable , whereas these rates steadily increased in the control group ( 8 % , 15 % , 17 % , and 26.5 % , respectively ) . Significant differences in the first 100 cases ( 26.5 % versus 8 % ; p = 0.02 ) could not be maintained in the last 100 cases ( 25.5 % versus 26.5 % , p = 0.91 ) . Conclusions : The increased adenoma detection rate means of NBI colonoscopy were statistically not significant . It remains speculative as to whether the increasing adenoma rate in the conventional group may have been caused by a training effect of better polyp recognition on NBI BACKGROUND AND STUDY AIMS Hyperplastic polyposis syndrome ( HPS ) is associated with colorectal cancer and is characterized by multiple hyperplastic polyps , sessile serrated adenomas ( SSAs ) and adenomas . Narrow b and imaging ( NBI ) may improve the detection of polyps in HPS . We aim ed to compare polyp miss rates with NBI with those of high resolution endoscopy ( HRE ) . PATIENTS AND METHODS In a single center , r and omized crossover study consecutive HPS patients underwent t and em colonoscopy with HRE and NBI , in r and omized order with removal of all detected polyps . RESULTS In 22 patients with HPS , 209 polyps were detected , including 27 with normal histology , 116 hyperplastic polyps , 42 SSAs , and 24 adenomas . Among patients assigned to HRE first ( n = 11 ) a total of 78 polyps was detected ; subsequent NBI added 44 polyps . In patients examined with NBI first , 78 polyps were detected and subsequent HRE added 9 . Polyp miss rates of HRE and NBI were 36 % and 10 % ( OR 0.21 ; 0.09 - 0.45 ) . Flat polyp shape was independently associated with increased miss rate . CONCLUSION NBI significantly reduces polyp miss rates in HPS patients . We recommend using either NBI or chromoendoscopy for colonoscopic surveillance of HPS patients with removal of all detected polyps BACKGROUND Missing adenomas and the inability to accurately differentiate between polyp histology remain the main limitations of st and ard-definition white-light ( SD-WL ) colonoscopy . OBJECTIVE To compare the adenoma detection rates of SD-WL with those of high-definition white-light ( HD-WL ) and narrow-b and imaging ( NBI ) as well as the accuracy of predicting polyp histology . DESIGN Multicenter , prospect i ve , r and omized , controlled trial . SETTING Two academic medical centers in the United States . PATIENTS Subjects undergoing screening or surveillance colonoscopy . INTERVENTION Subjects were r and omized to undergo colonoscopy with one of the following : SD-WL , HD-WL , or NBI . MAIN OUTCOME MEASUREMENTS The proportion of subjects detected with adenomas , adenomas detected per subject , and the accuracy of predicting polyp histology real time . RESULTS A total of 630 subjects were included . The proportion of subjects with adenomas was 38.6 % with SD-WL compared with 45.7 % with HD-WL and 46.2 % with NBI ( P = .17 and P = .14 , respectively ) . Adenomas detected per subject were 0.69 with SD-WL compared with 1.12 with HD-WL and 1.13 with NBI ( P = .016 and P = .014 , respectively ) . HD-WL and NBI detected more subjects with flat and right-sided adenomas compared with SD-WL ( all P values < .005 ) . NBI had a superior sensitivity ( 90 % ) and accuracy ( 82 % ) to predict adenomas compared with SD-WL and HD-WL ( all P values < .005 ) . LIMITATIONS Academic medical centers with experienced endoscopists . CONCLUSIONS There was no difference in the proportion of subjects with adenomas detected with SD-WL , HD-WL , and NBI . However , HD-WL and NBI detected significantly more adenomas per subject ( > 60 % ) compared with SD-WL . NBI had the highest accuracy in predicting adenomas in real time during colonoscopy . ( CLINICAL TRIAL REGISTRATION NUMBER NCT 00614770 . ) Background Some patients under close colonoscopic surveillance still develop colorectal cancer , thus suggesting the overlook of colorectal adenoma by endoscopists . AFI detects colorectal adenoma as a clear magenta , therefore the efficacy of AFI is expected to improve the detection ability of colorectal adenoma . The aim of this study is to determine the efficacy of AFI in detecting colorectal adenoma . Methods This study enrolled 88 patients who underwent colonoscopy at Asahikawa Medical University and Kushiro Medical Association Hospital . A r and omly selected colonoscopist first observed the sigmoid colon and rectum with conventional high resolution endosopy ( HRE ) . Then the colonoscopist changed the mode to AFI and h and ed to the scope to another colonoscopist who knew no information about the HRE . Then the second colonoscopist observed the sigmoid colon and rectum . Each colonoscopist separately recorded the findings . The detection rate , miss rate and procedural time were assessed in prospect i ve manner . Results The detection rate of flat and depressed adenoma , but not elevated adenoma , by AFI is significantly higher than that by HRE . In less-experienced endoscopists , AFI dramatically increased the detection rate ( 30.3 % ) and reduced miss rate ( 0 % ) of colorectal adenoma in comparison to those of HRE ( 7.7 % , 50.0 % ) , but not for experienced endoscopists . The procedural time of HRE was significantly shorter than that of AFI . Conclusions AFI increased the detection rate and reduced the miss rate of flat and depressed adenomas . These advantages of AFI were limited to less-experienced endoscopists because experienced endoscopists exhibited a substantially high detection rate for colorectal adenoma with HRE Introduction . To compare the accuracy of digital and real-time chromoendoscopy for the differential diagnosis of diminutive ( < 5 mm ) neoplastic and nonneoplastic colorectal lesions . Material s and Methods . This is a prospect i ve r and omized study comparing the Fujinon intelligent color enhancement ( FICE ) system ( 65 patients /95 lesions ) and indigo carmine ( 69 patients /120 lesions ) in the analysis of capillary meshwork and pit pattern , respectively . All lesions were less than 5 mm in diameter , and magnification was used in both groups . Histopathology was the gold st and ard examination . Results . Of 215 colorectal lesions , 153 ( 71.2 % ) were adenomas , and 62 were hyperplastic polyps ( 28.8 % ) . Morphological analysis revealed 132 ( 61.4 % ) superficial lesions , with 7 ( 3.3 % ) depressed lesions , and 83 ( 38.6 % ) protruding lesions . Vascular meshwork analysis using FICE and magnification result ed in 91.7 % sensitivity , 95.7 % specificity , and 92.6 % accuracy in differentiating neoplastic from nonneoplastic lesions . Pit pattern analysis with indigo carmine and magnification showed 96.5 % sensitivity , 88.2 % specificity , and 94.2 % accuracy for the same purpose . Conclusion . Both magnifying virtual chromoendoscopy and indigo carmine chromoendoscopy showed high accuracy in the histopathological diagnosis of colorectal lesions less than 5 mm in diameter Conventional colonoscopy misses some neoplastic lesions . We compared the sensitivity of chromoendoscopy and colonoscopy with intensive inspection for detecting adenomatous polyps missed by conventional colonoscopy . Fifty subjects with a history of colorectal cancer or adenomas underwent t and em colonoscopies at one of five centers of the Great Lakes New Engl and Clinical Epidemiology and Validation Center of the Early Detection Research Network . The first exam was a conventional colonoscopy with removal of all visualized polyps . The second exam was r and omly assigned as either pan-colonic indigocarmine chromoendoscopy or st and ard colonoscopy with intensive inspection lasting > 20 minutes . Size , histology , and numbers of polyps detected on each exam were recorded . Twenty-seven subjects were r and omized to a second exam with chromoendoscopy and 23 underwent intensive inspection . Forty adenomas were identified on the first st and ard colonoscopies . The second colonoscopies detected 24 additional adenomas : 19 were found using chromoendoscopy and 5 were found using intensive inspection . Chromoendoscopy found additional adenomas in more subjects than did intensive inspection ( 44 % versus 17 % ) and identified significantly more missed adenomas per subject ( 0.7 versus 0.2 , P < 0.01 ) . Adenomas detected with chromoendoscopy were significantly smaller ( mean size 2.66 ± 0.97 mm ) and were more often right-sided . Chromoendoscopy was associated with more normal tissue biopsies and longer procedure times than intensive inspection . After controlling for procedure time , chromoendoscopy detected more adenomas and hyperplastic polyps compared with colonoscopy using intensive inspection alone . Chromoendoscopy detected more polyps missed by st and ard colonoscopy than did intensive inspection . The clinical significance of these small missed lesions warrants further study The aim of this pilot study was to assess the feasibility of using computed virtual chromoendoscopy with the flexible spectral imaging color enhancement ( FICE ) for colon neoplasia screening . A modified back-to-back colonoscopy using FICE and white light in the right-sided colon was conducted prospect ively for the consecutive patients attending for the postoperative ( sigmoidectomy or anterior resection ) follow-up colonoscopy . Histopathology of detected lesions was confirmed by evaluation of endoscopic resection or biopsy specimens . One-hundred and two patients were enrolled , and 100 patients ( 61 males and mean age 63 years ) were finally analyzed . The total number of polyps detected by FICE and white light colonoscopy was 65 and 45 , respectively . The miss rate for all polyps with FICE ( 24 % ) was significantly less than that with white light ( 46 % ) ( P = 0.03 ) . Colonoscopy using FICE could beneficially enhance the detection of neoplastic lesions in the right-sided colon compared to white light colonoscopy Objective . Previous data suggest that routine chromoendoscopy may increase detection rates of diminutive or flat lesions . The aim of this study was to evaluate the usefulness of chromoendoscopy in the ascending colon and cecum , where the incidence of diminutive or flat lesions is high . Material and methods . Between June 2006 and September 2006 , a total of 316 consecutive patients were prospect ively enrolled in this study . The patients were r and omly divided into two groups ( control group : 158 patients , chromoendoscopy group : 158 patients ) . If the quality of bowel preparation was poor or cecal intubation was not achieved , the patient was excluded from the study . In the control group , the ascending colon and cecum were observed twice without chromoendoscopy . In the chromoendoscopy group , the cecum and ascending colon were reinspected following staining with indigocarmine solution after conventional examination of the cecum and ascending colon . Finally , a total of 151 and 149 patients were enrolled in the control and chromoendoscopy groups , respectively . Results . The chromoendoscopy group differed significantly from the control group in the number of additionally detected polyps ( control : 14 versus chromoendoscopy : 62 , p<0.001 ) and in the number of patients with additionally detected polyps ( control : 12 versus chromoendoscopy : 50 , p<0.001 ) . Multivariate analysis revealed that detection of polyps after indigocarmine spraying was independently associated with a high body mass index and older age ( p = 0.045 and p = 0.006 , respectively ) . Conclusions . With chromoendoscopy using indigocarmine , more polyps can be detected in the ascending colon and cecum as compared with using conventional colonoscopy BACKGROUND & AIMS It is essential to optimize st and ard colonoscopy technique to be able to increase polyp detection . We sought to compare the performance of colonoscopy using a high-definition , wide-angle endoscope ( HDE ) versus a st and ard colonoscope ( SC ) for the detection of colorectal neoplasia . PATIENTS AND METHODS All consecutive consenting adult patients referred from primary care centers were included and r and omly assigned at a 1:1 ratio to undergo HDE or SC . Times to reach and withdraw from the cecum were measured . Morphology , size , location , and pathologic diagnosis of each polyp were recorded . Sample size calculation result ed in a total of 682 patients needed . RESULTS A total of 693 consecutive patients fulfilled all inclusion criteria ( 73 excluded owing to insufficient bowel preparation ) . Each arm included 310 patients with no baseline characteristic differences . Time to reach the cecum was slightly superior for SC ( 8.9 + /- 4.8 minutes vs 8.2 + /- 4.5 minutes ; P = .055 ) . Pathology examination was feasible in 418 lesions ( 272 adenomas , 109 hyperplastic polyps , and 37 inflammatory lesions ) . Both techniques detected a similar number and type of lesions , and there were no differences in the distribution along the colon , in the degree of dysplasia , or morphology of adenomas . The per-patient basis analyses demonstrated that there were no differences between the 2 arms of the study in the detection rates of polyps ( SC , 0.84 + /- 1.59 ; HDE , 0.83 + /- 1.30 ) , adenomas ( 0.45 + /- 1.07 vs 0.43 + /- 0.87 ) , small adenomas ( 0.22 + /- 0.71 vs 0.28 + /- 0.78 ) , flat adenomas ( 0.30 + /- 0.91 vs 0.21 + /- 0.63 ) , or hyperplastic polyps ( 0.16 + /- 0.50 vs 0.18 + /- 0.54 ) . CONCLUSION HDE did not detect significantly more colorectal neoplasia than SC Background Previous studies have yielded conflicting results on the adenoma detection rate with narrow b and imaging ( NBI ) compared with white light imaging ( WLI ) . To overcome the confounding factors of these studies , we aim ed to evaluate the colonic adenoma detection rate with primary NBI versus that with primary WLI by using consistent NBI system , endoscope , and imaging setting s , and experienced colonoscopists . Methods In this multicenter prospect i ve trial , 813 patients were r and omized to undergo high-definition , t and em colonoscopy in the right colon with either NBI followed by WLI ( NBI – WLI group ) or WLI followed by NBI ( WLI – NBI group ) . The NBI setting s were fixed at surface structure enhancement level A-5 and adaptive index of hemoglobin color enhancement level 3 . All detected polyps were resected or biopsied for histopathological analysis . The primary and secondary outcome measures were the adenoma detection rates and miss rates , respectively , with primary imaging . Results The NBI – WLI and WLI – NBI groups comprised 389 and 393 patients , respectively , who met the inclusion criteria . The groups did not differ significantly in age , gender , institution , indication for colonoscopy , bowel preparation , or observation time . The adenoma detection rates of primary NBI and WLI were 42.3 and 42.5 % , respectively [ difference not significant ( NS ) ] . The adenoma miss rate was significantly less with primary NBI than with primary WLI ( 21.3 vs. 27.8 % ; p = 0.03 ) . Conclusions NBI does not improve the adenoma detection rate during primary colonoscopy ; however , it has a lower miss rate for adenoma lesions in the proximal colon than WLI BACKGROUND & AIMS High-resolution colonoscopy with chromoscopy ( HRC ) is a technique design ed to improve the detection of colonic neoplasias . We prospect ively compared st and ard colonoscopy ( SC ) and HRC in a r and omized multicenter trial . METHODS Patients ( n = 203 ; age , 58 + /- 10 years ; sex ratio , 1 ) were recruited according to the following criteria : ( 1 ) a history of either familial or personal colonic neoplasia or ( 2 ) alarm symptoms after the age of 60 years . After r and omization , an SC was performed in 100 patients ( resolution , < or = 410,000 pixels ) and a HRC in 103 patients ( Fujinon EC485ZW , 850,000 pixels ) . In the HRC group , each colonic segment was examined before and after spraying with indigo carmine 0.4 % . RESULTS Two hundred seventy-six polyps were detected in 198 patients . One hundred sixty of them were hyperplastic polyps , 116 were adenomas , and 2 were carcinomas . The numbers of hyperplastic polyps and purely flat adenomas were significantly higher in the HRC group than in the SC group ( 1.1 + /- 1.6 vs 0.5 + /- 1.4 and 0.22 + /- 0.68 vs 0.07 + /- 0.29 , respectively ; P = .01 and P = .04 ) , but there was no significant difference in the total number of adenomas per patient ( primary end point ) detected between the HRC and the SC groups ( 0.6 + /- 1.0 vs 0.5 + /- 0.9 , respectively ) . CONCLUSIONS Although HRC improves detection of purely flat adenomas and hyperplastic polyps , the overall detection of colonic adenomas in a population at increased risk of neoplasia is not significantly improved . These findings do not support the routine use of HRC in clinical practice BACKGROUND AND STUDY AIMS Colonoscopy is still considered the st and ard investigation for the detection of colorectal adenomas , but the miss rate , especially for small and flat lesions , remains unacceptably high . Chromoscopy has been shown to increase the yield for lesion detection in inflammatory bowel disease . The aim of this r and omized prospect i ve study was to determine whether a combination of chromoscopy and structure enhancement could increase the adenoma detection rate in high-risk patients . PATIENTS AND METHODS All patients included in the trial had a personal history of colorectal adenomas and /or a family history of colorectal cancer ( but excluding genetic syndromes ) . They were r and omized to one of two t and em colonoscopy groups , with the first pass consisting of conventional colonoscopy for both groups , followed by either chromoscopy and structure enhancement ( the " study " group ) or a second conventional colonoscopy ( the control group ) for the second-pass colonoscopy . All detected lesions was examined histopathologically after endoscopic resection or biopsy . The principal outcome parameter was the adenoma detection rate ; the number , histopathology , and location of lesions was also recorded . RESULTS A total of 292 patients were included in the study ( 146 patients in each group ) . The patients ' demographic characteristics , the indications for colonoscopy , and the quality of bowel preparation were similar in the two groups . There was a significant difference between the two groups with respect to the median duration of the examination ( 18.9 minutes in the control group vs. 27.1 minutes for the study group , P < 0.001 ) . Although more hyperplastic lesions were detected throughout the colon in the study group ( P = 0.033 ) , there was no difference between the two groups in either the proportion of patients with at least one adenoma or in the total number of adenomas detected . Chromoscopy and structure enhancement diagnosed significantly more diminutive adenomas ( < 5 mm ) in the right colon , compared with controls ( P = 0.039 ) . CONCLUSIONS On the basis of our results we can not generally recommend the systematic use of chromoscopy and structure enhancement in a high-risk patient population , although the detection of small adenomas in the proximal colon was improved BACKGROUND & AIMS Narrow b and imaging ( NBI ) is an imaging technique that allows a better definition of capillary pattern and improves the contrast between adenomas and the surrounding mucosa . Conflicting data exist on the ability of NBI to improve detection of colonic neoplasm ; the impact of NBI is being tested in several screening scenarios . We evaluated whether the routine use of NBI , compared with white light ( WL ) , during the withdrawal phase of screening colonoscopy improved adenoma detection . METHODS This r and omized controlled study included consecutive 50- to 69-year-old patients with positive immunologic fecal occult blood tests . They were r and omly assigned to groups that were examined with WL ( n = 108 ) or NBI ( n = 103 ) during the withdrawal phase of their colonoscopies . The primary end point was the adenoma detection rate . The prevalence of non-polypoid and the total number of adenomas were also evaluated . RESULTS The number of total and mean per-patient adenomas were 201 ( 1.95 + /- 2.3 ) and 198 ( 1.83 + /- 2.1 ) in the NBI and WL groups , respectively ( P = .69 ) . The adenoma detection rates were 57.3 % for patients examined by NBI and 58.3 % for those examined by WL ( P = .88 ) . A total of 41 non-polypoid adenomas were identified ( 26 in the NBI and 15 in the WL groups , P = .16 ) . The flat adenoma detection rates were 21.4 % and 9.3 % in the NBI and WL groups , respectively ( P = .019 ) . CONCLUSIONS The routine use of NBI in screening colonoscopy did not increase the adenoma detection rate . NBI seems to improve the detection of flat adenomas , although additional studies are necessary BACKGROUND AND AIMS Most studies have not reported an improvement in the detection of adenomas with the use of image-enhanced colonoscopy methods , possibly because of the darkness of the images . To overcome this limitation , a new-generation endoscopic system has been developed . This system has 2 blue-laser imaging ( BLI ) observation modes . The BLI observation was set to BLI-bright mode to detect lesions . We aim ed to evaluate the efficacy of BLI in detecting lesions . METHODS This study was design ed as a r and omized controlled trial with participants from 8 institutions . We enrolled patients aged ≥40 years . The participants were r and omly assigned to 2 groups : observation by using white-light imaging ( WLI ) with a conventional xenon light source ( WLI group ) or observation by using BLI-bright mode with a laser light source ( BLI group ) . All of the detected lesions were resected or had a biopsy taken for histopathologic analysis . The primary outcome was the mean number of adenomas per patient ( MAP ) that were detected per procedure . RESULTS The WLI and BLI groups consisted of 474 and 489 patients , respectively . The MAP was significantly higher in the BLI group than in the WLI group ( mean ± st and ard deviation [ SD ] WLI 1.01 ± 1.36 , BLI 1.27 ± 1.73 ; P = .008 ) . Adenoma detection rate in the BLI group was not significantly higher than in the WLI group . Observation times differed significantly , with BLI ( 9.48 minutes ) being longer than WLI ( 8.42 ; P < .001 ) . The mean ( ± SD ) number of polyps per patient was significantly higher in the BLI group compared with the WLI group ( WLI 1.43 ± 1.64 , BLI 1.84 ± 2.09 ; P = .001 ) . CONCLUSIONS A newly developed system that uses BLI improves the detection of adenomatous lesions compared with WLI . ( Clinical trial registration number : UMIN 000014555 . ) OBJECTIVES : Colonoscopy is considered the gold st and ard for the detection of colorectal polyps ; however , polyps can be missed with conventional white light ( WL ) colonoscopy . The aim of this pilot study was to evaluate whether a newly developed autofluorescence imaging ( AFI ) system can detect more colorectal polyps than WL . METHODS : A modified back-to-back colonoscopy using AFI and WL was conducted for 167 patients in the right-sided colon including cecum , ascending and transverse colon by a single experienced colonoscopist . The patient was r and omized to undergo the first colonoscopy with either AFI or WL ( group A : AFI-WL , group B : WL-AFI ) . The time needed for both insertion and examination for withdrawal and all lesions detected in the right-sided colon were recorded . RESULTS : Eighty-three patients were r and omized to group A and 84 to group B. The total number of polyps detected by AFI and WL colonoscopy was 100 and 73 , respectively . The miss rate for all polyps with AFI ( 30 % ) was significantly less than that with WL ( 49 % ) ( P= 0.01 ) . CONCLUSIONS : AFI detects more polyps in the right-sided colon compared to WL colonoscopy Objective : Colonoscopy , the “ gold st and ard ” screening test for colorectal cancer ( CRC ) , has known diagnostic limitations . Advances in endoscope technology have focused on improving mucosal visualisation . In addition to increased angle of view and resolution features , recent colonoscopes have non-white-light optics , such as narrow b and imaging ( NBI ) , to enhance image contrast . We aim ed to study the neoplasia diagnostic characteristics of NBI , by comparing the neoplasm miss rate when the colonoscopy was performed under NBI versus white light ( WL ) . Design : R and omised controlled trial . Setting : US Veterans hospital . Patients : Elective colonoscopy adults . Intervention : We r and omly assigned patients to undergo a colonoscopic examination using NBI or WL . All patients underwent a second examination using WL , as the reference st and ard . Main outcome measures : The primary end point was the difference in the neoplasm miss rate , and secondary outcome was the neoplasm detection rate . Results : In 276 t and em colonoscopy patients , there was no significant difference of miss or detection rates between NBI or WL colonoscopy techniques . Of the 135 patients in the NBI group , 17 patients ( 12.6 % ; 95 % confidence interval ( CI ) 7.5 to 19.4 % ) had a missed neoplasm , as compared with 17 of the 141 patients ( 12.1 % ; 95 % CI 7.2 to 18.6 % ) in the WL group , with a miss rate risk difference of 0.5 % ( 95 % CI −7.2 to 8.3 ) . 130 patients ( 47 % ) had at least one neoplasm . Missed lesions with NBI showed similar characteristics to those missed with WL . All missed neoplasms were tubular adenomas , the majority ( 78 % ) was ⩽5 mm and none were larger than 1 cm ( one-sided 95 % CI up to 1 % ) . Nonpolypoid lesions represented 35 % ( 13/37 ) of missed neoplasms . Interpretation : NBI did not improve the colorectal neoplasm miss rate compared to WL ; the miss rate for advanced adenomas was less than 1 % and for all adenomas was 12 % . The neoplasm detection rates were similar high using NBI or WL ; almost a half the study patients had at least one adenoma . Clinical trials.gov identifier : Background The benefits of narrow b and imaging ( NBI ) in colorectal polyp detection remain question able . Previous NBI has poorer brightness and resolution than white light ( WL ) . However , recently these factors were improved by the new-generation video processor system ( EVIS LUCERA ELITE ) in comparison with the previous system ( EVIS LUCERA SPECTRUM ) . The aim of this study was to investigate whether NBI with EVIS LUCERA ELITE could improve the visibility of colorectal polyps compared to WL . Methods We analyzed prospect ively 240 colorectal polyps ( group 1 : ELITE with CF-HQ290 scope , 80 polyps ; group 2 : ELITE with PCF-Q260AZI scope , 80 polyps ; group 3 : SPECTRUM with PCF-Q260AZI scope , 80 polyps ) whose videos were recorded using NBI and WL at Kyoto Prefectural University of Medicine . The videos were evaluated in a r and omized order by three experts and three non-experts . Each polyp was assigned a polyp visibility score from 4 ( excellent visibility ) to 1 ( poor visibility ) . The polyp visibility scores in each mode and their relationship to the clinical characteristics were analyzed . Results The mean polyp visibility scores of NBI with ELITE system were significantly higher than those of WL ( ELITE with CF-HQ290 : 3.14 ± 0.87 vs. 2.75 ± 0.98 , p < 0.0001 , ELITE with PCF-Q260AZI : 3.03 ± 0.92 vs. 2.83 ± 0.93 , p = 0.0006 ) . Conversely , the mean polyp visibility score of NBI using SPECTRUM system with PCF-Q260AZI was significantly lower than WL ( 2.75 ± 1.06 vs. 3.05 ± 0.92 , p < 0.0001 ) . Conclusions Our study showed that NBI using EVIS LUCERA ELITE improved polyp visibility Background Colonoscopy is considered to be the st and ard diagnostic test for detecting colonic neoplasia , particularly for small lesions . However , recent publications have suggested that 15–27 % of small adenomas might be missed during conventional colonoscopy . Aims To determine whether computed virtual chromoendoscopy ( CVC ) can improve the detection of small adenomas as compared to conventional colonoscopy . Methods We examined 135 consecutive patients by total colonoscopy and 128 patients were r and omized to compare white-light colonoscopy ( 65 patients ) and CVC-mode colonoscopy ( 63 patients ) after the exclusion of seven patients because of poor bowel preparation ( n = 4 ) or other causes ( one sigmoid colon cancer , two intestinal tuberculosis ) . Results There were no differences between the patient characteristics for the two study groups , i.e. , age , sex , body mass index , quality of bowel preparations , indications for the procedure , conscious sedation , and examination times — both insertion time and withdrawal time . The groups did not differ in the number of patients with all polyps , adenomas , or hyperplastic polyps . In the patients with adenomas , however , there was a significant difference in the detection rate for the patients with small adenomas less than 5 mm in size ( P = 0.006 ) . Conclusions Colonoscopy with the CVC mode identified more patients with small colorectal adenomas than conventional white-light colonoscopy . Therefore , CVC might be a supplementary tool aiding the colonoscopist in the detection of small adenomas ; however , further studies will need to demonstrate whether these results are reproducible across patients in varied clinical setting BACKGROUND & AIMS Endoscopic trimodal imaging ( ETMI ) incorporates high-resolution endoscopy ( HRE ) and autofluorescence imaging ( AFI ) for adenoma detection , and narrow-b and imaging ( NBI ) for differentiation of adenomas from nonneoplastic polyps . The aim of this study was to compare AFI with HRE for adenoma detection and to assess the diagnostic accuracy of NBI for differentiation of polyps . This was a r and omized trial of t and em colonoscopies . The study was performed at the Academic Medical Center in Amsterdam . METHODS One hundred patients underwent colonoscopy with ETMI . Each colonic segment was examined twice for polyps , once with HRE and once with AFI , in r and om order per patient . All detected polyps were assessed with NBI for pit pattern and with AFI for color , and subsequently removed . Histopathology served as the gold st and ard for diagnosis . The main outcome measures of this study were adenoma miss-rates of AFI and HRE , and diagnostic accuracy of NBI and AFI for differentiating adenomas from nonneoplastic polyps . RESULTS Among 50 patients examined with AFI first , 32 adenomas were detected initially . Subsequent inspection with HRE identified 8 additional adenomas . Among 50 patients examined with HRE first , 35 adenomas were detected initially . Successive AFI yielded 14 additional adenomas . The adenoma miss-rates of AFI and HRE therefore were 20 % and 29 % , respectively ( P = .351 ) . The sensitivity , specificity , and overall accuracy of NBI for differentiation were 90 % , 70 % , and 79 % , respectively ; corresponding figures for AFI were 99 % , 35 % , and 63 % , respectively . CONCLUSIONS The overall adenoma miss-rate was 25 % ; AFI did not significantly reduce the adenoma miss-rate compared with HRE . Both NBI and AFI had a disappointing diagnostic accuracy for polyp differentiation , although AFI had a high sensitivity Purpose It remains controversial whether chromocolonoscopy using indigocarmine increases the detection of colorectal polyps . We aim ed to assess the impact of indigocarmine dye spray on the detection rate of adenomas and the feasibility of learning the technique in a Western practice . Methods 400 patients were prospect ively allocated into 2 groups ; A ( n = 200 ) : indigocarmine chromocolonoscopy was performed by a Japanese colonoscopist with expertise in chromoscopy ; B ( n = 200 ) : initial 100 patients ( B-1 ) , a Western colonoscopist with no previous experience of chromoscopy performed conventional colonoscopy , but with at least 10 min observation during colonoscopy withdrawal . In the next 100 patients ( B-2 ) , he performed chromocolonoscopy . All polyps found were resected . Regression analysis was used to compare the numbers of polyps detected in groups A , B-1 and B-2 , whilst controlling for gender , age , indication and history of colorectal cancer . Results There were significant differences in the numbers of neoplastic polyps and flat adenomas between groups A and B-1 as well as between B-1 and B-2 , but not between A and B-2 . There was no significant difference in numbers of advanced lesions . Chromocolonoscopy ( A and B-2 ) detected more neoplastic polyps of ≤5 mm . Conclusion Chromocolonoscopy increases the detection of neoplastic polyps and flat adenomas , particularly diminutive polyps , but does not increase the detection of advanced lesions BACKGROUND The newly developed i-SCAN application can theoretically maximize the effectiveness of colonoscopy . However , the practical usefulness of the i-SCAN application during screening colonoscopy has not been assessed . OBJECTIVE To assess the efficacy of the i-SCAN application during screening colonoscopy . DESIGN A prospect i ve , r and omized trial that used a modified , back-to-back colonoscopy . SETTING Academic hospital . PATIENTS This study involved 389 asymptomatic , consecutive , average-risk patients who underwent screening colonoscopy . INTERVENTION The patients were r and omized to the first withdrawal with either conventional high-definition white light ( HDWL group ; n = 119 ) , i-SCAN contrast/surface enhancement ( CE/SE ) mode ( i-SCAN1 group ; n = 115 ) , or i-SCAN CE/SE/tone enhancement-colorectal mode ( i-SCAN2 group ; n = 118 ) . All patients underwent a second examination with HDWL as the criterion st and ard . MAIN OUTCOME MEASUREMENTS The primary outcome measurement was the adenoma detection rate and adenoma miss rate . The secondary outcome measurement was the accuracy of the histologic prediction of neoplastic and nonneoplastic polyps . RESULTS The adenoma detection rates during the first withdrawal of HDWL , i-SCAN1 , and i-SCAN2 were 31.9 % , 36.5 % , and 33.1 % , respectively ( P = .742 ) , and the adenoma miss rates of each group were 22.9 % , 19.3 % , and 15.9 % , respectively ( P = .513 ) . Based on the multivariate analysis , the application of i-SCAN was not associated with an improvement in adenoma detection and the prevention of missed polyps . However , the prediction of neoplastic and nonneoplastic colorectal lesions was more precise in the i-SCAN2 group compared with the HDWL group ( accuracy 79.3 % vs 75.5 % , P = .029 ; sensitivity 86.5 % vs 72.6 % , P = .020 ; and specificity 91.4 % vs 80.6 % , P = .040 ) . LIMITATIONS Single-center trial . CONCLUSION i-SCAN during the screening colonoscopy may fail to improve adenoma detection and the prevention of missed polyps , but i-SCAN appears to be effective for real-time histologic prediction of polyps compared with conventional HDWL colonoscopy . ( CLINICAL TRIAL REGISTRATION NUMBER NCT01417611 . ) BACKGROUND In the National Polyp Study ( NPS ) , colorectal cancer was prevented by colonoscopic removal of adenomatous polyps . We evaluated the long-term effect of colonoscopic polypectomy in a study on mortality from colorectal cancer . METHODS We included in this analysis all patients prospect ively referred for initial colonoscopy ( between 1980 and 1990 ) at NPS clinical centers who had polyps ( adenomas and nonadenomas ) . The National Death Index was used to identify deaths and to determine the cause of death ; follow-up time was as long as 23 years . Mortality from colorectal cancer among patients with adenomas removed was compared with the expected incidence-based mortality from colorectal cancer in the general population , as estimated from the Surveillance Epidemiology and End Results ( SEER ) Program , and with the observed mortality from colorectal cancer among patients with nonadenomatous polyps ( internal control group ) . RESULTS Among 2602 patients who had adenomas removed during participation in the study , after a median of 15.8 years , 1246 patients had died from any cause and 12 had died from colorectal cancer . Given an estimated 25.4 expected deaths from colorectal cancer in the general population , the st and ardized incidence-based mortality ratio was 0.47 ( 95 % confidence interval [ CI ] , 0.26 to 0.80 ) with colonoscopic polypectomy , suggesting a 53 % reduction in mortality . Mortality from colorectal cancer was similar among patients with adenomas and those with nonadenomatous polyps during the first 10 years after polypectomy ( relative risk , 1.2 ; 95 % CI , 0.1 to 10.6 ) . CONCLUSIONS These findings support the hypothesis that colonoscopic removal of adenomatous polyps prevents death from colorectal cancer . ( Funded by the National Cancer Institute and others . ) Background . Detection and removal of adenomas by colonoscopy is an important means for preventing cancer ; however , small adenomas may be missed during colonoscopy . The narrow-b and imaging ( NBI ) system clearly enhances the microvasculature in neoplastic lesions , making it appear as a dark complex . Therefore , the NBI system may improve the detection of colonic neoplasias . However , no r and omized , controlled trials have evaluated the efficacy of a pan-colonic NBI system in adenoma detection . We conducted a r and omized , controlled trial to determine the efficacy of the pancolonic NBI system in adenoma detection . Methods . Two hundred forty-three patients were r and omized , 121 to conventional colonoscopy and 122 to pan-colonic NBI system . Demographics , indication for colonoscopy , and quality of preparation were similar between groups . Results . Extubation time was not significantly different between the conventional colonoscopy and pan-colonic NBI system . The proportions of patients with at least one adenoma and those with multiple adenomas were not significantly different between groups . However , the pan-colonic NBI system significantly increased the total number of adenomas detected ( P < 0.05 ) and the number of diminutive ( < 5 mm ) adenomas detected ( P < 0.05 ) . The pan-colonic NBI system allowed detection of more diminutive adenomas in the distal colon than did conventional colonoscopy ( P < 0.01 ) , and more patients in the NBI group had at least one diminutive adenoma than in the control group ( P < 0.05 ) . Conclusions . The pan-colonic NBI system improves the total number of adenomas detected , including significantly more diminutive adenomas , without prolongation of extubation time . These results indicate that routine use of the NBI system for surveillance of diminutive adenomas may be recommended BACKGROUND Colonoscopy is the criterion st and ard for screening of colorectal neoplasms . Nonetheless , a substantial miss rate with conventional , white-light colonoscopy ( WL ) remains a challenge . OBJECTIVE To assess whether Fuji Intelligent Color Enhancement ( FICE ) can detect more adenomas than WL in screening colonoscopy . DESIGN Prospect i ve , r and omized trial of t and em colonoscopy adjusted for withdrawal time and lavage effect . SETTING Seoul National University Hospital Healthcare System Gangnam Center , Korea . PATIENTS This study involved 359 average-risk adults undergoing screening colonoscopy . INTERVENTION Patients were r and omized to the first withdrawal with either FICE ( FICE-WL group ) or WL ( WL-FICE group ) . MAIN OUTCOME MEASUREMENTS The primary end point measure was the difference in adenoma miss rates , and the secondary outcome measure was the adenoma detection rate . RESULTS We enrolled 359 patients ( mean age 50.6 years , male 66.9 % ) and r and omly assigned 181 to the WL-FICE group and 178 to the FICE-WL group . The number of adenomas detected by FICE and WL was 123 and 107 , respectively . The adenoma miss rate with FICE showed no significant difference compared with that of WL ( 6.6 % vs 8.3 % , P = .59 ) . Characteristics of lesions missed by use of FICE were similar to those missed by use of WL ; 93 % of overall missed polyps were < or = 5 mm , and none were > or = 1 cm . All missed adenomas were low grade and nonpedunculated . There was no significant difference between FICE and WL in adenoma detection rate ( mean 0.64 vs 0.55 per patient , P = .65 ) nor percentage of patients with > or = 1 adenoma ( 33.7 % vs 30.4 % , P = .74 ) . LIMITATIONS Single-center study . CONCLUSION FICE at screening colonoscopy did not improve the adenoma miss rate or detection rate compared with WL BACKGROUND AND STUDY AIMS Colonoscopy is widely used to detect and remove precancerous polyps , but fails to detect some polyps . Recent studies evaluating different image-enhanced methods have revealed conflicting results . The efficacy of colonoscopy imaging with simultaneous use of commercially available improvements , including high definition narrow b and imaging ( HD-NBI ) , and monochromatic charge-coupled device ( CCD ) video , was compared with a widely used st and ard definition white light ( SDWL ) colonoscopy system for detecting colorectal polyps . The primary aim was to determine whether the combination of image-enhanced colonoscopy systems result ed in fewer missed polyps compared with conventional colonoscopy . PATIENTS AND METHODS In a r and omized controlled trial ( Clinical trials.gov . study number NCT00825292 ) patients having routine screening and surveillance underwent t and em colonoscopies with SDWL and image-enhanced ( HD-NBI ) colonoscopy . The main outcome measurement was the per-polyp false-negative ( " miss " ) rate . Secondary outcomes were adenoma miss rate , and per-patient polyp and adenoma miss rates . RESULTS 100 patients were r and omized and 96 were included in the analysis . In total , 177 polyps were detected ; of these , 72 ( 41 % ) were adenomatous . Polyp and adenoma miss rates for SDWL colonoscopy were 57 % ( 60/105 ) and 49 % ( 19/39 ) ; those for image-enhanced colonoscopy were 31 % ( 22/72 ) and 27 % ( 9/33 ) ( P = 0.005 and P = 0.036 for polyps and adenomas , respectively ) . Image-enhanced and SDWL approaches had similar per-patient miss rates for polyps ( 6/35 vs. 9/32 , P = 0.27 ) and adenomas ( 4/22 vs. 8/20 , P = 0.11 ) . CONCLUSIONS Utilization of multiple recent improvements in image-enhanced colonoscopy was associated with a reduced miss rate for all polyps and for adenomatous polyps . It is not known which individual feature or combination of image-enhancement features led to the improvement BACKGROUND Small adenomas may be missed during colonoscopy , but chromoscopy has been reported to enhance detection . The aim of this r and omized-controlled trial was to determine the effect of total colonic dye spray on adenoma detection during routine colonoscopy . METHODS Consecutive out patients undergoing routine colonoscopy were r and omized to a dye-spray group ( 0.1 % indigo carmine used to coat the entire colon during withdrawal from the cecum ) or control group ( no dye ) . RESULTS Two hundred fifty-nine patients were r and omized , 124 to the dye-spray and 135 to the control group ; demographics , indication for colonoscopy , and quality of the preparation were similar between the groups . Extubation from the cecum took a median of 9:05 minutes ( range : 2:48 - 24:44 min ) in the dye-spray group versus 4:52 minutes ( range : 1:42 - 15:21 min ) in the control group ( p < 0.0001 ) . The proportion of patients with at least 1 adenoma and the total number of adenomas were not different between groups . However , in the dye-spray group significantly more diminutive adenomas ( < 5 mm ) were detected proximal to the sigmoid colon ( p = 0.026 ) and more patients were identified with 3 or more adenomas ( p = 0.002 ) . More non-neoplastic polyps were detected throughout the colon in the dye-spray group ( p = 0.003 ) . There were no complications . CONCLUSIONS Dye-spray increases the detection of small adenomas in the proximal colon and patients with multiple adenomas , but long-term outcomes should be studied to determine the clinical value of these findings BACKGROUND & AIMS Detection of adenomas is an important goal of colonoscopy . Narrow b and imaging ( NBI ) might highlight adenomas and lead to higher rates of adenoma detection . METHODS This was a r and omized controlled trial of colonoscopy withdrawal in white light versus NBI in 434 patients aged 50 years or older with intact colons . All examinations were performed by a single experienced endoscopist with a known high detection rate of adenomas using high-definition , wide-angle ( 170 degrees field of view ) colonoscopes . RESULTS There was no difference in the percent of patients with > or=1 adenoma for the entire cohort in white light ( 67 % ) versus NBI ( 65 % ) ( P = .61 ) or in the subset of 257 patients with indication screening ( 58 % vs 57 % ; P = .91 ) . Both the prevalences of adenomas and the numbers of adenomas per colonoscopy are the highest ever reported in colonoscopy studies . The high prevalence rates of adenomas were accounted for by detection of large numbers of adenomas , including flat adenomas , which were < or=5 mm . CONCLUSIONS NBI did not result in better detection of adenomas by an endoscopist with a known high detection rate using white light . This result does not exclude a possible benefit of NBI in reducing variation between endoscopists in detection of adenomas . The very high adenoma detection rate in this study suggests that high definition should be directly tested for its effect on detection of adenomas BACKGROUND & AIMS Endoscopic trimodal imaging ( ETMI ) is a novel endoscopic technique that combines high-resolution endoscopy ( HRE ) , autofluorescence imaging ( AFI ) , and narrow-b and imaging ( NBI ) that has only been studied in academic setting s. We performed a r and omized , controlled trial in a nonacademic setting to compare ETMI with st and ard video endoscopy ( SVE ) in the detection and differentiation of colorectal lesions . METHODS The study included 234 patients scheduled to receive colonoscopy who were r and omly assigned to undergo a colonoscopy in t and em with either ETMI or SVE . In the ETMI group ( n=118 ) , first examination was performed using HRE , followed by AFI . In the other group , both examinations were performed using SVE ( n=116 ) . In the ETMI group , detected lesions were differentiated using AFI and NBI . RESULTS In the ETMI group , 87 adenomas were detected in the first examination ( with HRE ) , and then 34 adenomas were detected during second inspection ( with AFI ) . In the SVE group , 79 adenomas were detected during the first inspection , and then 33 adenomas were detected during the second inspection . Adenoma detection rates did not differ significantly between the 2 groups ( ETMI : 1.03 vs SVE : 0.97 , P=.360 ) . The adenoma miss-rate was 29 % for HRE and 28 % for SVE . The sensitivity , specificity , and accuracy of NBI in differentiating adenomas from nonadenomatous lesions were 87 % , 63 % , and 75 % , respectively ; corresponding values for AFI were 90 % , 37 % , and 62 % , respectively . CONCLUSIONS In a nonacademic setting , ETMI did not improve the detection rate for adenomas compared with SVE . NBI and AFI each differentiated colonic lesions with high levels of sensitivity but low levels of specificity Objective To compare the sensitivity of autofluorescence endoscopy ( AFE ) and white light video endoscopy ( WLE ) for the detection of colorectal adenomas in high-risk patients belonging to Lynch syndrome ( LS ) or familial colorectal cancer ( CRC ) families . Methods This was a prospect i ve single-centre study carried out in a tertiary referral centre . The subjects were 75 asymptomatic patients originating from LS or familial CRC families . Patients were examined with either WLE followed by AFE or AFE followed by WLE . Back-to-back colonoscopy was performed by two blinded endoscopists . All lesions were removed during the second endoscopic procedure . Lesions missed during the second procedure were identified and removed on third pass . The sensitivity calculations for colorectal adenomas were based on histology results . The main outcome measures were the difference in sensitivity between WLE and AFE for the detection of adenomas in patients with LS or familial CRC . Results At least one adenoma was detected in 41 ( 55 % ) patients . WLE identified adenomas in 28/41 patients and AFE in 37/41 patients , corresponding to a 32 % increase . In total 95 adenomas were detected , 65 by WLE and 87 by AFE , result ing in a significantly higher sensitivity of AFE compared with WLE ( 92 % vs 68 % ; p=0.001 ) . The additionally detected adenomas with AFE were significantly smaller than the adenomas detected by WLE ( mean 3.0 mm vs 4.9 mm , p<0.01 ) . Conclusions AFE improves the detection of colorectal adenomas in patients with LS or familial CRC . The results of this study suggest that AFE may be preferable for surveillance of these high-risk patients Objective Virtual chromoendoscopy ( CE ) is expected to enhance adenoma yield and reduce variation in performance between colonoscopists . This study aim ed to compare the efficacy of narrow b and imaging ( NBI ) , flexible spectral imaging CE ( FICE ) and white light ( WL ) colonoscopy and their impact for less experienced endoscopists . Methods We performed a r and omised t and em colonoscopy trial controlling for withdrawal time and bowel preparation . Average-risk adults undergoing screening colonoscopy were enrolled and r and omly assigned to first withdrawal with one of the three imaging modalities ( NBI ( NBI-WL group ) , FICE ( FICE-WL group ) and WL ( WL-WL group ) ) . Eight colonoscopists were categorised into expert and non-expert subgroups . Results 1650 subjects ( mean age 51.4 years , 63.9 % men ) were included ( 550 in each group ) . Compared with WL , neither NBI nor FICE increased the mean number of adenomas detected per patient ( 0.37 vs 0.35 and 0.36 ; p=0.591 ) or the percentage of patients with adenoma ( 25.3 % vs 24.5 % and 23.6 % ; p=0.753 ) . For all three modalities , expert subgroups had higher yields of adenomas than non-expert subgroups . Learning curves were observed only for non-expert subgroups with all three modalities . The percentage of missed adenomas did not differ between the three groups ( 20.8 % by WL vs 22.9 % by NBI and 26.0 % by FICE , p=0.300 ) and was not affected by endoscopists ’ expertise . Conclusions Neither NBI nor FICE improved adenoma detection or miss rates , with no difference in diagnostic efficacy between the two systems . Virtual CE had no additional benefits over WL for non-experts . Clinical trial registration number : KCT0000570 |
10,438 | 31,222,450 | Conclusions Among patients with hormone receptor-positive breast cancer , patients with either ER+PR− tumours or ER−PR+ tumours have a higher risk of recurrence and a shorter survival time than those with ER+PR+ tumours . | Background The prognostic and clinical significance of single hormone receptor expression in breast cancer has not been clearly established .
The goal of this study was to conduct a meta- analysis to compare the clinical outcomes of patients with ER+PR− tumours and ER−PR+ tumours to those of patients with ER+PR+ tumours . | Initial clinical studies in 32 Senegalese subjects have demonstrated the efficacy of ivermectin in Onchocerca volvulus infection ( river blindness ) . Although O. volvulus microfilariae in skin snips were not reduced in number after single oral doses of 5 micrograms or 10 micrograms/kg body-weight , they were greatly reduced in all subjects after single oral doses of 30 micrograms or 50 micrograms/kg and were eliminated completely in 6 of th 8 subjects who received the 50 micrograms/kg dose . All subjects tolerated the drug well . Transient pruritus which did not require treatment was observed on the day the dose was given in 2 of the 8 subjects after the 30 micrograms/kg dose and in 4 of the 8 who received the 50 micrograms/kg dose . Ivermectin produced no abnormal laboratory results Background : Progesterone receptor ( PR ) expression assessment in early invasive breast cancer remains controversial . This study sought to re-evaluate PR expression as a potential therapeutic guide in early breast cancer ; particularly in oestrogen receptor (ER)-positive , lymph node (LN)-negative disease . Methods : A population cohort of 1074 patients presenting to a single Cancer Centre over 4 years ( 2000–2004 ) underwent surgery for primary invasive breast cancer with curative intent . Prospect i ve data collection included patient demographics , pathology , ER and PR expression , HER2 status , adjuvant chemotherapy and endocrine therapy . Progesterone receptor expression was compared with ( all causes ) overall survival ( OS ) , breast cancer-specific survival ( BCSS ) and disease-free survival ( DFS ) . Results : Overall survival was 71.0 % and BCSS was 83.0 % at median follow-up of 8.34 years . Absent PR expression was significantly associated with poorer prognosis for OS , BCSS and DFS ( P<0.0001 , log-rank ) , even within the ER-positive , LN-negative group ( hazard ratio for BCSS 3.17 , 95 % CI 1.43–7.01 ) and was not influenced by endocrine therapy . Cox ’s regression analysis demonstrated that PR expression was an independent prognostic variable . Conclusion : Absence of PR expression is a powerful , independent prognostic variable in operable , primary breast cancer even in ER-positive , LN-negative patients receiving endocrine therapy . Absence of PR expression should be re-evaluated as a biomarker for poor prognosis in ER-positive breast cancer and such patients considered for additional systemic therapy BACKGROUND Evaluations of epidemiologic risk factors in relation to breast cancer classified jointly by estrogen receptor ( ER ) and progesterone receptor ( PR ) status have been inconsistent . To address this issue , we conducted a prospect i ve evaluation of risk factors for breast cancer classified according to receptor status . METHODS During 1 029 414 person-years of follow-up of 66 145 women participating in the Nurses ' Health Study from 1980 through 2000 , we identified 2096 incident cases of breast cancer for which information on ER/PR status was available : 1281 were ER+/PR+ , 318 were ER+/PR- , 80 were ER-/PR+ , and 417 were ER-/PR- . We fit a log-incidence model of breast cancer and used polychotomous logistic regression to compare coefficients for breast cancer risk factors in patients with different ER/PR status . To test for differences in risk factor odds ratios based on marginal ER/PR categories , we evaluated ER status controlling for PR status and vice versa . The predictive ability of our log-incidence model to discriminate between women who would develop ER+/PR+ breast cancer and those who would not ( and similarly for ER-/PR- breast cancer ) was evaluated by using receiver operator characteristic curve analysis . All statistical tests were two-sided . RESULTS We observed statistically significant heterogeneity among the four ER/PR categories for some risk factors ( age , menopausal status , body mass index [ BMI ] after menopause , the one-time adverse effect of first pregnancy , and past use of postmenopausal hormones ) but not for others ( benign breast disease , family history of breast cancer , alcohol use , and height ) . The one-time adverse association of first pregnancy with incidence was present for PR- but not for PR+ tumors after controlling for ER status ( P = .007 ) . However , the association of BMI after menopause with incidence was present for PR+ but not PR- tumors ( P = .005 ) . Statistically significant differences in the incidence of ER+ and ER- tumors were seen with age , both before and after menopause ( P = .003 ) , and with past use of postmenopausal hormones ( P = .01 ) . Area under the receiver operator characteristic curve , adjusted for age , was 0.64 ( 95 % confidence interval [ CI ] = 0.63 to 0.66 ) for ER+/PR+ tumors and 0.61 ( 95 % CI = 0.58 to 0.64 ) for ER-/PR- tumors . CONCLUSIONS Incidence rates and risk factors for breast cancer differ according to ER and PR status . Thus , to accurately estimate breast cancer risk , breast cancer cases should be divided according to the ER and PR status of the tumor PURPOSE Uncertainty about the relative worth of doxorubicin/cyclophosphamide ( AC ) and cyclophosphamide/methotrexate/fluorouracil ( CMF ) , as well as doubt about the propriety of giving tamoxifen ( TAM ) with chemotherapy to patients with estrogen receptor-negative tumors and negative axillary nodes , prompted the National Surgical Adjuvant Breast and Bowel Project to initiate the B-23 study . PATIENTS AND METHODS Patients ( n = 2,008 ) were r and omly assigned to CMF plus placebo , CMF plus TAM , AC plus placebo , or AC plus TAM . Six cycles of CMF were given for 6 months ; four cycles of AC were administered for 63 days . TAM was given daily for 5 years . Relapse-free survival ( RFS ) , event-free survival ( EFS ) , and survival ( S ) were determined by using life-table estimates . Tests for heterogeneity of outcome used log-rank statistics and Cox proportional hazards models to detect differences across all groups and according to chemotherapy and hormonal therapy status . RESULTS No significant difference in RFS , EFS , or S was observed among the four groups through 5 years ( P = .96,.8 , and .8 , respectively ) , for those aged < or = 49 years ( P = .97,.5 , and .9 , respectively ) , or for those aged > or = 50 years ( P = .7,.6 , and .6 , respectively ) . A comparison between all CMF- and all AC-treated patients demonstrated no significant differences in RFS ( 87 % at 5 years in both groups , P = .9 ) , EFS ( 83 % and 82 % , P = .6 ) , or S ( 89 % and 90 % , P = .4 ) . There were no significant differences in RFS , EFS , or S between CMF and AC in patients aged < or = 49 or > or = 50 years . No significant difference in any outcome was observed when chemotherapy-treated patients who received placebo were compared with those given TAM . RFS in both groups was 87 % ( P = .6 ) , 87 % in patients aged < or = 49 ( P = .9 ) , and 88 % and 87 % , respectively ( P = .4 ) , in those aged > or = 50 years . CONCLUSION There was no significant difference in the outcome of patients who received AC or CMF . TAM with either regimen result ed in no significant advantage over that achieved from chemotherapy alone |
10,439 | 22,371,919 | Initial stent implantation for stable CAD shows no evidence of benefit compared with initial medical therapy for prevention of death , nonfatal MI , unplanned revascularization , or angina | BACKGROUND Prior meta-analyses have yielded conflicting results regarding the outcomes of treatment of stable coronary artery disease ( CAD ) with initial percutaneous coronary intervention ( PCI ) vs medical therapy .
However , most of the studies in prior systematic review s used balloon angioplasty as well as medical therapies that do not reflect current interventional or medical practice s. We therefore performed a meta- analysis of all r and omized clinical trials comparing initial coronary stent implantation with medical therapy to determine the effect on death , nonfatal myocardial infa rct ion ( MI ) , unplanned revascularization , and persistent angina . | CONTEXT Many patients with chronic angina experience anginal episodes despite revascularization and antianginal medications . In a previous trial , antianginal monotherapy with ranolazine , a drug believed to partially inhibit fatty acid oxidation , increased treadmill exercise performance ; however , its long-term efficacy and safety have not been studied in combination with beta-blockers or calcium antagonists in a large patient population with severe chronic angina . OBJECTIVES To determine whether , at trough levels , ranolazine improves the total exercise time of patients who have symptoms of chronic angina and who experience angina and ischemia at low workloads despite taking st and ard doses of atenolol , amlodipine , or diltiazem and to determine times to angina onset and to electrocardiographic evidence of myocardial ischemia , effect on angina attacks and nitroglycerin use , and effect on long-term survival in an open-label observational study extension . DESIGN , SETTING , AND PATIENTS A r and omized , 3-group parallel , double-blind , placebo-controlled trial of 823 eligible adults with symptomatic chronic angina who were r and omly assigned to receive placebo or 1 of 2 doses of ranolazine . Patients treated at the 118 participating ambulatory outpatient setting s in several countries were enrolled in the Combination Assessment of Ranolazine In Stable Angina ( CARISA ) trial from July 1999 to August 2001 and followed up through October 31 , 2002 . INTERVENTION Patients received twice-daily placebo or 750 mg or 1000 mg of ranolazine . Treadmill exercise 12 hours ( trough ) and 4 hours ( peak ) after dosing was assessed after 2 , 6 ( trough only ) , and 12 weeks of treatment . MAIN OUTCOME MEASURES Change in exercise duration , time to onset of angina , time to onset of ischemia , nitroglycerin use , and number of angina attacks . RESULTS Trough exercise duration increased by 115.6 seconds from baseline in both ranolazine groups ( pooled ) vs 91.7 seconds in the placebo group ( P = .01 ) . The times to angina and to electrocardiographic ischemia also increased in the ranolazine groups , at peak more than at trough . The increases did not depend on changes in blood pressure , heart rate , or background antianginal therapy and persisted throughout 12 weeks . Ranolazine reduced angina attacks and nitroglycerin use by about 1 per week vs placebo ( P<.02 ) . Survival of 750 patients taking ranolazine during the CARISA trial or its associated long-term open-label study was 98.4 % in the first year and 95.9 % in the second year . CONCLUSION Twice-daily doses of ranolazine increased exercise capacity and provided additional antianginal relief to symptomatic patients with severe chronic angina taking st and ard doses of atenolol , amlodipine , or diltiazem , without evident adverse , long-term survival consequences over 1 to 2 years of therapy BACKGROUND Optimal treatment for patients with both type 2 diabetes mellitus and stable ischemic heart disease has not been established . METHODS We r and omly assigned 2368 patients with both type 2 diabetes and heart disease to undergo either prompt revascularization with intensive medical therapy or intensive medical therapy alone and to undergo either insulin-sensitization or insulin-provision therapy . Primary end points were the rate of death and a composite of death , myocardial infa rct ion , or stroke ( major cardiovascular events ) . R and omization was stratified according to the choice of percutaneous coronary intervention ( PCI ) or coronary-artery bypass grafting ( CABG ) as the more appropriate intervention . RESULTS At 5 years , rates of survival did not differ significantly between the revascularization group ( 88.3 % ) and the medical-therapy group ( 87.8 % , P=0.97 ) or between the insulin-sensitization group ( 88.2 % ) and the insulin-provision group ( 87.9 % , P=0.89 ) . The rates of freedom from major cardiovascular events also did not differ significantly among the groups : 77.2 % in the revascularization group and 75.9 % in the medical-treatment group ( P=0.70 ) and 77.7 % in the insulin-sensitization group and 75.4 % in the insulin-provision group ( P=0.13 ) . In the PCI stratum , there was no significant difference in primary end points between the revascularization group and the medical-therapy group . In the CABG stratum , the rate of major cardiovascular events was significantly lower in the revascularization group ( 22.4 % ) than in the medical-therapy group ( 30.5 % , P=0.01 ; P=0.002 for interaction between stratum and study group ) . Adverse events and serious adverse events were generally similar among the groups , although severe hypoglycemia was more frequent in the insulin-provision group ( 9.2 % ) than in the insulin-sensitization group ( 5.9 % , P=0.003 ) . CONCLUSIONS Overall , there was no significant difference in the rates of death and major cardiovascular events between patients undergoing prompt revascularization and those undergoing medical therapy or between strategies of insulin sensitization and insulin provision . ( Clinical Trials.gov number , NCT00006305 . OBJECTIVES This study sought to determine whether initial medical therapy ( MT ) only or percutaneous coronary intervention plus medical therapy ( PCI+MT ) is better for patients with low-risk stable coronary artery disease ( CAD ) indicated for intervention in Japan . BACKGROUND Several multicenter studies have suggested that in the above patients , an initial management strategy of PCI+MT does not reduce the long-term risk of cardiovascular events more effectively than initial MT only . METHODS We conducted a r and omized comparative study ( JSAP [ Japanese Stable Angina Pectoris ] study ) in the previously mentioned patients . RESULTS The patients were r and omized to PCI+MT ( n = 192 ) or initial MT only group ( n = 192 ) , and the patient characteristics were very similar in the 2 groups . During the 3.3-year follow-up , there was no significant difference in the cumulative death rate between PCI+MT ( 2.9 % ) and MT ( 3.9 % ) . However , the cumulative risk of death plus acute coronary syndrome was significantly smaller in PCI+MT . CONCLUSIONS In stable low-risk CAD , PCI+MT may improve long-term prognosis more effectively than MT OBJECTIVE We sought to conduct a r and omized trial comparing late revascularization with conservative therapy in symptom-free patients after acute myocardial infa rct ion ( AMI ) . BACKGROUND In the absence of ischemia , the benefits of reperfusion late after AMI remain controversial . However , the possibility exists that an open infa rct related artery benefits healing post AMI . METHODS Of 223 patients enrolled with Q-wave anterior AMI , 66 with isolated persistent occlusion of the left anterior descending coronary artery ( LAD ) were r and omized to the following treatments : 1 ) medical therapy ( closed artery group ; n = 34 ) or 2 ) late intervention and stent to the LAD + medical therapy ( open artery group ; n = 32 ) . The study was powered to compare left ventricular ( LV ) end-systolic volume between the two groups 12 months post AMI . RESULTS Late intervention 26 + /- 18 days post AMI result ed in significantly greater LV end-systolic and end-diastolic volumes at 12 months than medical therapy alone ( 106.6 + /- 37.5 ml vs. 79.7 + /- 34.4 ml , p < 0.01 and 162.0 + /- 51.4 ml vs. 130.1 + /- 46.1 ml , p < 0.01 , respectively ) . Exercise duration and peak workload significantly increased in both groups from 6 weeks to 12 months post AMI , although absolute values were greater in the open artery group . Quality of life scores tended to deteriorate during this time interval in the closed artery patients but remained unchanged in the open artery patients . Coronary angiography at 1 year documented a low incidence of intergroup cross-over ( spontaneous recanalization in 19 % and closure in 11 % ) . CONCLUSIONS In the present study , recanalization of occluded infa rct -related arteries in symptom-free patients approximately 1 month post AMI had an adverse effect on remodeling but tended to increase exercise tolerance and improve quality of life Background — Extent and severity of myocardial ischemia are determinants of risk for patients with coronary artery disease , and ischemia reduction is an important therapeutic goal . The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation ( COURAGE ) nuclear sub study compared the effectiveness of percutaneous coronary intervention ( PCI ) for ischemia reduction added to optimal medical therapy ( OMT ) with the use of myocardial perfusion single photon emission computed tomography ( MPS ) . Methods and Results — Of the 2287 COURAGE patients , 314 were enrolled in this sub study of serial rest/stress MPS performed before treatment and 6 to 18 months ( mean=374±50 days ) after r and omization using paired exercise ( n=84 ) or vasodilator stress ( n=230 ) . A blinded core laboratory analyzed quantitative MPS measures of percent ischemic myocardium . Moderate to severe ischemia encumbered ≥10 % myocardium . The primary end point was ≥5 % reduction in ischemic myocardium at follow-up . Treatment groups had similar baseline characteristics . At follow-up , the reduction in ischemic myocardium was greater with PCI+OMT ( −2.7 % ; 95 % confidence interval , −1.7 % , −3.8 % ) than with OMT ( −0.5 % ; 95 % confidence interval , −1.6 % , 0.6 % ; P<0.0001 ) . More PCI+OMT patients exhibited significant ischemia reduction ( 33 % versus 19 % ; P=0.0004 ) , especially patients with moderate to severe pretreatment ischemia ( 78 % versus 52 % ; P=0.007 ) . Patients with ischemia reduction had lower unadjusted risk for death or myocardial infa rct ion ( P=0.037 [ risk-adjusted P=0.26 ] ) , particularly if baseline ischemia was moderate to severe ( P=0.001 [ risk-adjusted P=0.08 ] ) . Death or myocardial infa rct ion rates ranged from 0 % to 39 % for patients with no residual ischemia to ≥10 % residual ischemia on follow-up MPS ( P=0.002 [ risk-adjusted P=0.09 ] ) . Conclusions — In COURAGE patients who underwent serial MPS , adding PCI to OMT result ed in greater reduction in ischemia compared with OMT alone . Our findings suggest a treatment target of ≥5 % ischemia reduction with OMT with or without coronary revascularization BACKGROUND It has not been clearly established whether percutaneous coronary intervention ( PCI ) can provide an incremental benefit in quality of life over that provided by optimal medical therapy among patients with chronic coronary artery disease . METHODS We r and omly assigned 2287 patients with stable coronary disease to PCI plus optimal medical therapy or to optimal medical therapy alone . We assessed angina-specific health status ( with the use of the Seattle Angina Question naire ) and overall physical and mental function ( with the use of the R AND 36-item health survey [ R AND -36 ] ) . RESULTS At baseline , 22 % of the patients were free of angina . At 3 months , 53 % of the patients in the PCI group and 42 % in the medical-therapy group were angina-free ( P<0.001 ) . Baseline mean ( + /-SD ) Seattle Angina Question naire scores ( which range from 0 to 100 , with higher scores indicating better health status ) were 66+/-25 for physical limitations , 54+/-32 for angina stability , 69+/-26 for angina frequency , 87+/-16 for treatment satisfaction , and 51+/-25 for quality of life . By 3 months , these scores had increased in the PCI group , as compared with the medical-therapy group , to 76+/-24 versus 72+/-23 for physical limitation ( P=0.004 ) , 77+/-28 versus 73+/-27 for angina stability ( P=0.002 ) , 85+/-22 versus 80+/-23 for angina frequency ( P<0.001 ) , 92+/-12 versus 90+/-14 for treatment satisfaction ( P<0.001 ) , and 73+/-22 versus 68+/-23 for quality of life ( P<0.001 ) . In general , patients had an incremental benefit from PCI for 6 to 24 months ; patients with more severe angina had a greater benefit from PCI . Similar incremental benefits from PCI were seen in some but not all R AND -36 domains . By 36 months , there was no significant difference in health status between the treatment groups . CONCLUSIONS Among patients with stable angina , both those treated with PCI and those treated with optimal medical therapy alone had marked improvements in health status during follow-up . The PCI group had small , but significant , incremental benefits that disappeared by 36 months . ( Clinical Trials.gov number , NCT00007657 . Background —Regular exercise in patients with stable coronary artery disease has been shown to improve myocardial perfusion and to retard disease progression . We therefore conducted a r and omized study to compare the effects of exercise training versus st and ard percutaneous coronary intervention ( PCI ) with stenting on clinical symptoms , angina-free exercise capacity , myocardial perfusion , cost-effectiveness , and frequency of a combined clinical end point ( death of cardiac cause , stroke , CABG , angioplasty , acute myocardial infa rct ion , and worsening angina with objective evidence result ing in hospitalization ) . Methods and Results —A total of 101 male patients aged ≤70 years were recruited after routine coronary angiography and r and omized to 12 months of exercise training ( 20 minutes of bicycle ergometry per day ) or to PCI . Cost efficiency was calculated as the average expense ( in US dollars ) needed to improve the Canadian Cardiovascular Society class by 1 class . Exercise training was associated with a higher event-free survival ( 88 % versus 70 % in the PCI group , P = 0.023 ) and increased maximal oxygen uptake ( + 16 % , from 22.7±0.7 to 26.2±0.8 mL O2/kg , P < 0.001 versus baseline , P < 0.001 versus PCI group after 12 months ) . To gain 1 Canadian Cardiovascular Society class , $ 6956 was spent in the PCI group versus $ 3429 in the training group ( P < 0.001 ) . Conclusions —Compared with PCI , a 12-month program of regular physical exercise in selected patients with stable coronary artery disease result ed in superior event-free survival and exercise capacity at lower costs , notably owing to reduced rehospitalizations and repeat revascularizations BACKGROUND Percutaneous coronary revascularization is widely used in improving symptoms and exercise performance in patients with ischemic heart disease and stable angina pectoris . In this study , we compared percutaneous coronary revascularization with lipid-lowering treatment for reducing the incidence of ischemic events . METHODS We studied 341 patients with stable coronary artery disease , relatively normal left ventricular function , asymptomatic or mild-to-moderate angina , and a serum level of low-density lipoprotein ( LDL ) cholesterol of at least 115 mg per deciliter ( 3.0 mmol per liter ) who were referred for percutaneous revascularization . We r and omly assigned the patients either to receive medical treatment with atorvastatin , at 80 mg per day ( 164 patients ) , or to undergo the recommended percutaneous revascularization procedure ( angioplasty ) followed by usual care , which could include lipid-lowering treatment ( 177 patients ) . The follow-up period was 18 months . RESULTS Twenty-two ( 13 percent ) of the patients who received aggressive lipid-lowering treatment with atorvastatin ( result ing in a 46 percent reduction in the mean serum LDL cholesterol level , to 77 mg per deciliter [ 2.0 mmol per liter ] ) had ischemic events , as compared with 37 ( 21 percent ) of the patients who underwent angioplasty ( who had an 18 percent reduction in the mean serum LDL cholesterol level , to 119 mg per deciliter [ 3.0 mmol per liter ] ) . The incidence of ischemic events was thus 36 percent lower in the atorvastatin group over an 18-month period ( P=0.048 , which was not statistically significant after adjustment for interim analyses ) . This reduction in events was due to a smaller number of angioplasty procedures , coronary-artery bypass operations , and hospitalizations for worsening angina . As compared with the patients who were treated with angioplasty and usual care , the patients who received atorvastatin had a significantly longer time to the first ischemic event ( P=0.03 ) . CONCLUSIONS In low-risk patients with stable coronary artery disease , aggressive lipid-lowering therapy is at least as effective as angioplasty and usual care in reducing the incidence of ischemic events Percutaneous coronary intervention ( PCI ) has played an integral role in the therapeutic management strategies for patients who present with either acute coronary syndromes or stable angina pectoris . The COURAGE ( Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation ) trial enrolled patients with chronic stable angina and at least 1 significant ( > or = 70 % ) angiographic coronary stenosis who were r and omly assigned to an initial treatment of either PCI in conjunction with optimal medical therapy or optimal medical therapy alone . Although the initial management strategy of PCI did not reduce the risk of death , myocardial infa rct ion , or other major cardiovascular events , improvement in angina-free status and a reduction in the requirement for subsequent revascularization was observed . An in-depth analysis of the COURAGE trial design and execution is provided BACKGROUND It is unclear whether stable , high-risk patients with persistent total occlusion of the infa rct -related coronary artery identified after the currently accepted period for myocardial salvage has passed should undergo percutaneous coronary intervention ( PCI ) in addition to receiving optimal medical therapy to reduce the risk of subsequent events . METHODS We conducted a r and omized study involving 2166 stable patients who had total occlusion of the infa rct -related artery 3 to 28 days after myocardial infa rct ion and who met a high-risk criterion ( an ejection fraction of < 50 % or proximal occlusion ) . Of these patients , 1082 were assigned to routine PCI and stenting with optimal medical therapy , and 1084 were assigned to optimal medical therapy alone . The primary end point was a composite of death , myocardial reinfa rct ion , or New York Heart Association ( NYHA ) class IV heart failure . RESULTS The 4-year cumulative primary event rate was 17.2 % in the PCI group and 15.6 % in the medical therapy group ( hazard ratio for death , reinfa rct ion , or heart failure in the PCI group as compared with the medical therapy group , 1.16 ; 95 % confidence interval [ CI ] , 0.92 to 1.45 ; P=0.20 ) . Rates of myocardial reinfa rct ion ( fatal and nonfatal ) were 7.0 % and 5.3 % in the two groups , respectively ( hazard ratio , 1.36 ; 95 % CI , 0.92 to 2.00 ; P=0.13 ) . Rates of nonfatal reinfa rct ion were 6.9 % and 5.0 % , respectively ( hazard ratio , 1.44 ; 95 % CI , 0.96 to 2.16 ; P=0.08 ) ; only six reinfa rct ions ( 0.6 % ) were related to assigned PCI procedures . Rates of NYHA class IV heart failure ( 4.4 % vs. 4.5 % ) and death ( 9.1 % vs. 9.4 % ) were similar . There was no interaction between treatment effect and any subgroup variable ( age , sex , race or ethnic group , infa rct -related artery , ejection fraction , diabetes , Killip class , and the time from myocardial infa rct ion to r and omization ) . CONCLUSIONS PCI did not reduce the occurrence of death , reinfa rct ion , or heart failure , and there was a trend toward excess reinfa rct ion during 4 years of follow-up in stable patients with occlusion of the infa rct -related artery 3 to 28 days after myocardial infa rct ion . ( Clinical Trials.gov number , NCT00004562 [ Clinical Trials.gov ] . ) BACKGROUND In patients with stable coronary artery disease , it remains unclear whether an initial management strategy of percutaneous coronary intervention ( PCI ) with intensive pharmacologic therapy and lifestyle intervention ( optimal medical therapy ) is superior to optimal medical therapy alone in reducing the risk of cardiovascular events . METHODS We conducted a r and omized trial involving 2287 patients who had objective evidence of myocardial ischemia and significant coronary artery disease at 50 U.S. and Canadian centers . Between 1999 and 2004 , we assigned 1149 patients to undergo PCI with optimal medical therapy ( PCI group ) and 1138 to receive optimal medical therapy alone ( medical-therapy group ) . The primary outcome was death from any cause and nonfatal myocardial infa rct ion during a follow-up period of 2.5 to 7.0 years ( median , 4.6 ) . RESULTS There were 211 primary events in the PCI group and 202 events in the medical-therapy group . The 4.6-year cumulative primary -event rates were 19.0 % in the PCI group and 18.5 % in the medical-therapy group ( hazard ratio for the PCI group , 1.05 ; 95 % confidence interval [ CI ] , 0.87 to 1.27 ; P=0.62 ) . There were no significant differences between the PCI group and the medical-therapy group in the composite of death , myocardial infa rct ion , and stroke ( 20.0 % vs. 19.5 % ; hazard ratio , 1.05 ; 95 % CI , 0.87 to 1.27 ; P=0.62 ) ; hospitalization for acute coronary syndrome ( 12.4 % vs. 11.8 % ; hazard ratio , 1.07 ; 95 % CI , 0.84 to 1.37 ; P=0.56 ) ; or myocardial infa rct ion ( 13.2 % vs. 12.3 % ; hazard ratio , 1.13 ; 95 % CI , 0.89 to 1.43 ; P=0.33 ) . CONCLUSIONS As an initial management strategy in patients with stable coronary artery disease , PCI did not reduce the risk of death , myocardial infa rct ion , or other major cardiovascular events when added to optimal medical therapy . ( Clinical Trials.gov number , NCT00007657 [ Clinical Trials.gov ] . ) Background — In the Bypass Angioplasty Revascularization Investigation 2 Diabetes ( BARI 2D ) trial , an initial strategy of coronary revascularization and optimal medical treatment ( REV ) compared with an initial optimal medical treatment with the option of subsequent revascularization ( MED ) did not reduce all-cause mortality or the composite of cardiovascular death , myocardial infa rct ion , and stroke in patients with type 2 diabetes mellitus and stable ischemic heart disease . In the same population , we tested whether the REV strategy was superior to the MED strategy in preventing worsening and new angina and subsequent coronary revascularizations . Methods and Results — Among the 2364 men and women ( mean age , 62.4 years ) with type 2 diabetes mellitus , documented coronary artery disease , and myocardial ischemia , 1191 were r and omized to the MED and 1173 to the REV strategy preselected in the percutaneous coronary intervention ( 796 ) and coronary artery bypass graft ( 377 ) strata . Compared with the MED strategy , the REV strategy at the 3-year follow-up had a lower rate of worsening angina ( 8 % versus 13 % ; P<0.001 ) , new angina ( 37 % versus 51 % ; P=0.001 ) , and subsequent coronary revascularizations ( 18 % versus 33 % ; P<0.001 ) and a higher rate of angina-free status ( 66 % versus 58 % ; P=0.003 ) . The coronary artery bypass graft stratum patients were at higher risk than those in the percutaneous coronary intervention stratum , and had the greatest benefits from REV . Conclusions — In these patients , the REV strategy reduced the occurrence of worsening angina , new angina , and subsequent coronary revascularizations more than the MED strategy . The symptomatic benefits were observed particularly for high-risk patients . Clinical Trial Registration — URL : http://www . Clinical Trials.gov . Unique identifier : NCT00006305 |
10,440 | 19,370,563 | Asthma education aim ed at children and their carers who present to the emergency department for acute exacerbations can result in lower risk of future emergency department presentation and hospital admission .
There remains uncertainty as to the long-term effect of education on other markers of asthma morbidity such as quality of life , symptoms and lung function .
It remains unclear as to what type , duration and intensity of educational packages are the most effective in reducing acute care utilisation | BACKGROUND Asthma is the most common chronic childhood illness and is a leading cause for paediatric admission to hospital .
Asthma management for children results in substantial costs .
There is evidence to suggest that hospital admissions could be reduced with effective education for parents and children about asthma and its management .
OBJECTIVES To conduct a systematic review of the literature and up date the previous review as to whether asthma education leads to improved health outcomes in children who have attended the emergency room for asthma . | Asthma self-management programmes have been shown to increase children 's knowledge about asthma and improve their management practice s and health status . However , existing programmes have rarely addressed the unique learning needs of very young children . This study aim ed to develop and assess the effectiveness of a video tape and picture book design ed to teach children about the prevention and management of acute episodes of asthma . The information content of the educational re sources was determined by analysis of relevant medical information and asthma management skills . Social Learning Theory and consideration of the developmental stage of the target population informed the format and style of presentation of the re sources . Eighty children aged between 2 and 5 years who had been diagnosed with asthma by their medical practitioner and who required daily asthma medication participated in a controlled experimental study . The study evaluated the impact of the asthma education re sources on children 's knowledge about asthma , compliance with medication regimens and health status . Children were r and omly allocated to one of three experimental groups . Children in these groups were exposed to either the video tape alone , the book alone or both the video tape and book , or to a control group who viewed material s unrelated to asthma . The results for the three experimental groups were compared with the control group who did not receive exposure to any of the asthma education re sources . The results showed that children in each experimental group had significantly greater gains in asthma-related knowledge than children in the control group and children exposed to both re sources showed the greatest increases in knowledge . Children in each of the three experimental groups also had better compliance and health than children in the control group . These findings indicate that carefully design ed asthma education re sources are useful for providing even the youngest children with information about asthma and its management Background : Until now , care provided by asthma nurses has been additional to care provided by paediatricians . A study was undertaken to compare nurse led outpatient management of childhood asthma with follow up by a paediatrician . Methods : Seventy four children referred because of insufficient control of persistent asthma were r and omly allocated to 1 year follow up by a paediatrician or asthma nurse . The main outcome measure was the percentage of symptom-free days . Additional outcome measures were airway hyperresponsiveness , lung function , daily dose of inhaled corticosteroids ( ICS ) , number of exacerbations , number of additional visits to the general practitioner , absence from school , functional health status , and disease specific quality of life . Results : There were no significant differences at the end of the 1 year study period between the two treatment groups in percentage of symptom-free days ( mean difference 2.5 % ; 95 % CI −8.8 to 13.8 ) , airway hyperresponsiveness ( log10 PD20 0.06 ; −0.19 to 0.32 ) , functional health status ( 10.1 ; −0.3 to 19.8 ) , disease specific quality of life of patients ( 0.08 ; −0.9 to 0.7 ) , and disease specific quality of life of caregivers ( 0.09 ; −0.2 to 0.3 ) , nor in any other outcome parameters . Most outcome parameters improved considerably over the 1 year study period . These improvements were achieved although the daily dose of ICS was reduced by a mean of 26 % compared with the dose received by children at referral . All parents were satisfied with the asthma care received . Conclusions : After initial assessment in a multidisciplinary clinic , childhood asthma can be successfully managed by an asthma nurse in close cooperation with a paediatrician . During close follow up by paediatrician or asthma nurse , asthma control improved despite a reduction in ICS dose BACKGROUND Children with asthma who live in the inner city are exposed to multiple indoor allergens and environmental tobacco smoke in their homes . Reductions in these triggers of asthma have been difficult to achieve and have seldom been associated with decreased morbidity from asthma . The objective of this study was to determine whether an environmental intervention tailored to each child 's allergic sensitization and environmental risk factors could improve asthma-related outcomes . METHODS We enrolled 937 children with atopic asthma ( age , 5 to 11 years ) in seven major U.S. cities in a r and omized , controlled trial of an environmental intervention that lasted one year ( intervention year ) and included education and remediation for exposure to both allergens and environmental tobacco smoke . Home environmental exposures were assessed every six months , and asthma-related complications were assessed every two months during the intervention and for one year after the intervention . RESULTS For every 2-week period , the intervention group had fewer days with symptoms than did the control group both during the intervention year ( 3.39 vs. 4.20 days , P<0.001 ) and the year afterward ( 2.62 vs. 3.21 days , P<0.001 ) , as well as greater declines in the levels of allergens at home , such as Dermatophagoides farinae ( Der f1 ) allergen in the bed ( P<0.001 ) and on the bedroom floor ( P=0.004 ) , D. pteronyssinus in the bed ( P=0.007 ) , and cockroach allergen on the bedroom floor ( P<0.001 ) . Reductions in the levels of cockroach allergen and dust-mite allergen ( Der f1 ) on the bedroom floor were significantly correlated with reduced complications of asthma ( P<0.001 ) . CONCLUSIONS Among inner-city children with atopic asthma , an individualized , home-based , comprehensive environmental intervention decreases exposure to indoor allergens , including cockroach and dust-mite allergens , result ing in reduced asthma-associated morbidity STUDY OBJECTIVE We determined whether a simple emergency department intervention improves the likelihood of primary care provider ( PCP ) follow-up after ED discharge for an acute asthma exacerbation . METHODS This r and omized , controlled clinical trial was conducted in an urban university-based ED . Participants were patients with asthma between the ages of 16 and 45 years who were treated and discharged from the ED . The study intervention was usual care or an intervention that consisted of a free 5-day course of prednisone , vouchers for transportation to and from their PCP , and a 48-hour telephone reminder to make an appointment with their PCP . The main outcome was whether the patient received follow-up care as determined by PCP contact at 4 weeks . RESULTS One hundred ninety-two patients with asthma were enrolled over 8 months ; 178 ( 93 % ) had complete follow-up . The intervention and control groups were similar with regard to age , sex , ethnicity , or years of education . The 2 groups were also comparable with respect to multiple measures of baseline access/barriers to care and severity of ED exacerbation . Patients receiving the intervention were significantly more likely to follow up with their PCP than control patients ( relative risk 1.6 ; 95 % confidence interval [ CI ] 1.1 , 2.4 ) . When adjusted for other factors influencing PCP follow-up care ( ethnicity , prior PCP relationship , insurance status , regular car access ) , intervention patients were more likely to follow up with their PCP ( odds ratio 3.1 ; 95 % CI 1.5 , 6.3 ) . CONCLUSION Providing medication , transportation vouchers , and a telephone reminder to make an appointment increased the likelihood that discharged patients with asthma obtained PCP follow-up BACKGROUND Diagnosis information from existing data sources is used commonly for epidemiologic , administrative , and research purpose s. The quality of such data for emergency department ( ED ) visits is unknown . OBJECTIVES To determine the agreement on final diagnoses between two sources , electronic administrative sources and manually abstract ed medical records , for pediatric ED visits , in a multicenter network . METHODS This was a cross sectional study at 19 EDs nationwide . The authors obtained data from two sources at each ED during a three-month period in 2003 : administrative sources for all visits and abstract ed records for r and omly selected visits during ten days over the study period . Records were matched using unique identifiers and probabilistic linkage . The authors recorded up to three diagnoses from each abstract ed medical record and up to ten for the administrative data source . Diagnoses were grouped into 104 groups using a modification of the Clinical Classification System . RESULTS A total of 8,860 abstract ed records had at least one valid diagnosis code ( with a total of 12,895 diagnoses ) and were successfully matched to records in the administrative source . Overall , 67 % ( 95 % confidence interval = 66 % to 68 % ) of diagnoses from the administrative and abstract ed sources were within the same diagnosis group . Agreement varied by site , ranging from 54 % to 77 % . Agreement varied substantially by diagnosis group ; there was no difference by method of linkage . Clustering clinical ly similar diagnosis groups improved agreement between administrative and abstract ed data sources . CONCLUSIONS ED diagnoses retrieved from electronic administrative sources and manual chart review frequently disagree , even if similar diagnosis codes are grouped . Agreement varies by institution and by diagnosis . Further work is needed to improve the accuracy of diagnosis coding ; development of a grouping system specific to pediatric emergency care may be beneficial The parents of asthmatic children treated in the pediatric respiratory service of Wolfson Hospital were r and omly divided into two groups . One group compromised 26 parents who voluntarily attended a teaching session . After completion of the course , a question naire was completed by parents who had attended the course and parents who had not . The first group showed greater knowledge of all aspects of the disease and , after a year 's follow up , it was noted that there was a statistically significant lower hospitalization rate of their asthmatic child BACKGROUND Asthma continues to be a substantial cause of morbidity in pediatric population s. New strategies are needed to provide cost-effective educational interventions for children with asthma , particularly those in the inner city . OBJECTIVE To assess the effectiveness of a multimedia educational software program about asthma . SETTING A hospital-based primary care clinic and an affiliated neighborhood health center . DESIGN R and omized , controlled trial . POPULATION Children 3 to 12 years old with physician-diagnosed asthma . INTERVENTION An interactive educational computer program , Asthma Control , design ed to teach children about asthma and its management . Using a graphic display of a child going through simulated daily events , the game emphasizes : 1 ) monitoring ; 2 ) allergen identification ; 3 ) use of medications ; 4 ) use of health services ; and 5 ) maintenance of normal activity . Control group participants review ed printed educational material s with a research assistant . OUTCOMES Acute health care use ( emergency department and outpatient ) was the primary outcome . Secondary outcome measures included maternal report of asthma symptom severity , child functional status and school absences , satisfaction with care , and parental and child knowledge of asthma . RESULTS A total of 137 families were enrolled in the study ( 76 intervention , 61 control ) . Both intervention and control groups showed substantial improvement in all outcomes during the 12-month follow-up period . Aside from improvement in knowledge after use of the computer program , no differences were demonstrated between the 2 groups in primary or secondary outcome measures . Children reported enjoyment of program use . CONCLUSIONS This trial of an educational software program found that it did not produce greater improvement than occurred with review of traditional written material s. Because both groups showed substantial improvement over baseline , computer-based education may be more cost-effective . Alternatively , improvements in illness severity over time may overshadow the effects of such interventions . Rigorous comprehensive evaluations such as this are necessary to assess new interventions intended to improve management and outcomes of asthma Background : The effects on morbidity were examined of providing an educational intervention and a written guided self-management plan to the parents of pre-school children following a recent attendance at hospital for asthma or wheeze . Methods : A prospect i ve , r and omised , partially blinded , controlled trial was design ed at two secondary care centres . Over a 13 month period 200 children aged 18 months to 5 years at the time of admission to a children 's ward or attendance at an accident and emergency department or children 's ( emergency ) assessment unit ( A&E/CAU ) with a primary diagnosis of acute severe asthma or wheezing were recruited . 101 children were r and omised into the control group and received usual care and 99 were assigned to the intervention group and received : ( 1 ) a pre-school asthma booklet ; ( 2 ) a written guided self-management plan ; and ( 3 ) two 20 minute structured educational sessions between a specialist respiratory nurse and the parent(s ) and child . Subjects were assessed at 3 , 6 , and 12 months . The main outcomes were GP consultation rates , hospital re-admissions , and attendances at A&E/CAU . Secondary outcomes included disability score , caregivers ' quality of life , and parental knowledge of asthma . Results : There were no statistically significant differences between the two groups during the 12 month follow up period for any of the main or secondary outcome measures . Conclusions : These results do not support the hypothesis that the introduction of an educational package and a written guided self-management plan to the parents of pre-school children with asthma who had recently attended hospital for troublesome asthma or wheeze reduces morbidity over the subsequent 12 months This study was conducted to test the efficacy of AIR WISE , an individually administered asthma self-management program . Subjects were paired and r and omly assigned to either an experimental group ( N = 7 ) or a control group ( N = 7 ) . The frequency of experimental group emergency visits , analyzed over a 12-month posttreatment period , was substantially less than those of the control group , supporting the hypothesis that AIR WISE is effective in high-utilizer children through improved self-management This article describes the evaluation of a comprehensive school-based asthma management program in an inner-city , largely African-American school system . All 54 elementary schools ( combined enrollment 13,247 students ) from a single urban school system participated in this study . Schools were r and omly divided between immediate and delayed intervention programs . The intervention consisted of 3 separate educational programs ( for school faculty/staff , students with asthma , and peers without asthma ) and medical management for the children with asthma ( including an Individual Asthma Action Plan , medications , and peakflow meters ) . Children with asthma were identified using a case detection program and 736 were enrolled into the intervention study . No significant differences were observed in school absences , grade point average , emergency room visits , or hospitalizations between the immediate and delayed intervention groups . Significant increases in knowledge were observed in the immediate intervention group . This study of a school-based asthma management education and medical intervention program did not show any differences between the intervention and control groups on morbidity outcomes . Our experience leads us to believe that such measures are difficult to impact and are not always reliable . Future research ers should be aware of the problems associated with using such measures . In addition , connecting children with a regular source of health care in this population was difficult . More intensive methods of medical management , such as school-based health centers or supervised asthma therapy , might prove more effective in inner-city schools PURPOSE Written asthma action plans ( WAAPs ) have become a core component of asthma management in Australia . We investigated ownership , utilisation and factors associated with ownership of asthma action plans by caregivers . METHODS 443/776 ( 57 % ) caregivers of children aged 2 - 14 years with asthma were identified from 32 GP clinics as part of a r and omised controlled trial ( RCT ) , and completed self-administered question naires . RESULTS Only 29 % of participants owned a WAAP , while 13 % possessed verbal instructions , and 56 % had no plan . An asthma action plan for children , which was developed by a general practitioner ( GP ) was more likely to comprise verbal instructions ( p = 0.001 ) , while action plans developed by paediatricians were more likely to be written ( p < 0.001 ) . Just over one half of caregivers ( 59 % ) reported discussing their child 's action plan the last time they visited their doctor for asthma . Factors associated with WAAP ownership included nights waking ( p = 0.013 ) , self reported severity ( p = 0.001 ) , and days lost from school ( p = 0.037 ) . Children who had seen a GP in the last 3 months for asthma , or who had been to the Emergency Department ( ED ) or hospital were more likely to possess a WAAP ( p < 0.001 ) . Caregivers who were less satisfied with their child 's asthma control were more likely to own a WAAP ( p = 0.037 ) . Caregivers with any action plan found it useful and 82 % reported using their action plan for management of an acute attack . However , caregivers with a WAAP were more likely to adhere to the plan for an acute attack compared to caregivers with verbal instructions ( OR = 4.5 , p < 0.05 ) . Caregivers with a WAAP were more knowledgeable about asthma ( p = 0.002 ) , better able to recognise the difference between preventer and reliever medications ( p = 0.01 ) , and better able to recognise an asthma attack ( p = 0.006 ) . CONCLUSIONS Ownership of WAAPs in this group was still too low . Importantly , caregivers with written instructions were more knowledgeable about asthma and more likely to report following the action plan during an asthma attack A r and omized , controlled trial was conducted to assess the effectiveness of Blue Angel for Asthma Kids , an Internet-based interactive asthma educational and monitoring program , used in the management of asthmatic children . One hundred sixty-four ( n = 164 ) pediatric patients with persistent asthma were enrolled and r and omized into two study groups for a 12-week controlled trial . The intervention group had 88 participants who were taught to monitor their peak expiratory flows ( PEF ) and asthma symptoms daily on the Internet . They also received an interactive response consisting of a self-management plan from the Blue Angel monitoring program . The control group had 76 participants who received a traditional asthma care plan consisting of a written asthma diary supplemented with instructions for self-management . Disease control was assessed by weekly averaged PEF values , symptom scores , and asthma control tests . Adherence measures were assessed by therapeutic and diagnostic monitoring . Outcome was assessed by examining quality of life and retention of asthma knowledge . The data were analyzed by comparing results before and after the trial . At the end of trial , the intervention group decreased nighttime ( -0.08 + /- 0.33 vs. 0.00 + /- 0.20 , p = 0.028 ) and daytime symptoms ( -0.08 + /- 0.33 vs. 0.01 + /- 0.18 , p = 0.009 ) ; improved morning ( 241.9 + /- 81.4 vs. 223.1 + /- 55.5 , p = 0.017 ) and night PEF ( 255.6 + /- 86.7 vs. 232.5 + /- 55.3 , p = 0.010 ) ; increased adherence rates ( p < 0.05 ) ; improved well-controlled rates ( 70.4 % vs. 55.3 % , p < 0.05 ) ; improved knowledge regarding self-management ( 93.2 % vs. 70.3 % , p < 0.05 ) ; and improved quality of life ( 6.5 + /- 0.5 vs. 4.3 + /- 1.2 on a 7-point scale , p < 0.05 ) when compared with conventional management . The Internet-based asthma telemonitoring program increases selfmanagement skills , improves asthma outcomes , and appears to be an effective and well-accepted technology for the care of children with asthma and their caregivers BACKGROUND The aim of this study was to compare the effectiveness of an intensive asthma education program ( group B ) with that of a st and ard asthma education program ( group A ) . METHODS A prospect i ve r and omized single blinded study was conducted in the pediatric department of a public hospital in Hong Kong . Children aged 2 - 15 years admitted to the pediatric department with an acute attack of asthma were recruited . A st and ard asthma education program ( group A ) or an intensive asthma education program ( group B ) for children were offered . The main outcome measures include the number of visits to the emergency department and the number of hospitalization for asthma during the 3 month follow-up period . RESULTS A total of 45 children were in group A and 55 in group B. Group B had statistically significant reductions in the number of visits to the emergency department and the number of hospitalizations . Drug compliance was also significantly improved in group B. Parents ' satisfaction rate was also higher in group B. CONCLUSION The intensive asthma education program might be more cost effective than the st and ard asthma education program in the management of asthmatic children admitted to hospital in Hong Kong An educational training program for children with asthma , aged between 8 and 13 years , was evaluated in an 18-month r and omized , controlled experiment , including three follow-up evaluations . The objective of the program is to improve coping with asthma in daily life . The program , ten 1-hour sessions , is a combination of self-management training and cognitive behaviour therapy in a group , using games and learning material s specifically design ed for this age group . From 195 asthmatic children , 112 with inadequate self-management abilities were selected ; these children were r and omly divided into an experimental group and two control groups . The results indicated highly significant differences in favor of the experimental group on the psychological and medical variables . There were no drop-outs during the program . The conclusion is that this multi-faceted program is an effective method of teaching children how to cope with their asthma and helping them to achieve a less anxious and more realistic attitude towards their illness An interactive multimedia computer game to enhance self-management skills and thereby improve asthma outcomes in inner city children with asthma was evaluated . Subjects aged 6 - 17 were recruited from four pediatric practice s and r and omly assigned to the computer intervention condition or to the usual-care comparison . The main character in the game could match the subject on gender and ethnicity . Characteristics of the protagonist 's asthma were tailored to be like those of the subject . Subjects played the computer game as part of regular asthma visits . Time between pre- and post-test varied from 4 to 15.6 months ( mean , 7.6 months ) . Analysis of covariance , with pre-test scores , age , and asthma severity as covariates , found that the intervention was associated with fewer hospitalizations , better symptom scores , increased functional status , greater knowledge of asthma management , and better child self-management behavior for those in the intervention condition . Interactions with covariates were found and discussed in terms of variable efficacy of the intervention OBJECTIVES To test the hypothesis that reinforcement of the advice given at the time of discharge from the emergency department by telephone consultation would improve asthma outcomes . METHODS A r and omized controlled trial of the parents of 310 children who had been discharged from the emergency department with asthma was undertaken . The parents were r and omized to receive either st and ard care ( 155 children ) or st and ard care plus education by telephone ( 155 children ) from a trained asthma educator . Symptoms , parental asthma knowledge , parental quality of life and use of asthma action plans and preventer therapy were collected at baseline and 6 months later . The primary measure was days of wheeze in last 3 months ; intermediate measures were regular use of preventer medications , possession and use of written asthma action plan , parental asthma knowledge scores and parental quality of life scores . RESULTS A total of 266 parents ( 136 intervention ) completed the follow-up question naires after 6 months . Both groups showed similar symptoms and process measures at baseline , apart from more regular use of preventer medication in the control children . At follow up , the intervention group children were significantly more likely than controls to possess ( 87.5 % vs 72.3 % ; P = 0.002 ) a written asthma action plan . Possession of action plans increased from baseline in the intervention group but tended to decrease in the control group . Use of action plans was greater in the intervention group but decreased from baseline in both groups . Both intervention and control groups showed significant decreases in asthma symptoms . CONCLUSIONS Reinforcement by telephone consultation did not improve the primary outcome of wheeze in the last 3 months . However , it increased the possession and regular use of written asthma action plans in the intervention group Twenty children with severe asthma using continual oral beta 2 agonists were r and omized equally into either a behavioral intervention group or a control group . The behavioral intervention consisted of : symptom discrimination of asthma signals , self-management techniques of breathlessness , and contingency management of asthma-related behavior . The purpose of the study was to evaluate the effects of the behavioral treatment when superimposed on a regular medical treatment . The design consisted of a four-week baseline period , a four-week intervention period , and a four-week follow-up period . Results showed that the group receiving the behavioral intervention significantly reduced their use of beta 2 agonist spray doses and days of school absenteeism without increasing the number of asthma symptoms compared with the control group . It was concluded that children with severe asthma may benefit substantially from a behavioral program in addition to their regular medical treatment & NA ; The issue of whether nursing instruction efforts could improve asthma knowledge and quality of life among schoolchildren was investigated using a quasi-experimental design . The key instruments were the Asthmatic Knowledge Question naire and the Childhood Asthma Question naire-Form B. Asthmatic knowledge increased among children who received instruction from nurses ( Mean pre/post= 22.20/31.87 , p < .05 ) . These children also experienced significant improvements in their active quality of life ( Mean pre/post = 27.53/30.20 , p < .05 ) , and decreased distress ( Mean pre/post= 24.04/10.86 , p < .05 ) and asthma severity ( Mean pre/post= 13.27/8.3 , p < .05 ) . This study finds nursing instruction helpful in improving asthma knowledge . However , in terms of quality of life , elevated knowledge has a marked ( negative ) correlation only with levels of distress and severity . It shows no detectable relationship with active or passive life quality . Therefore , though nursing instruction can improve schoolchildren 's knowledge about asthma , the improvement in knowledge only relates to reducing distress and severity and thus improving quality of life . This result can provide guidance for nursing personnel in developing nursing instruction to improve active quality of life in child patients OBJECTIVE To determine the effectiveness of a home-based asthma education intervention in increasing appropriate nebulizer use and reducing symptom frequency , emergency department ( ED ) visits , and hospitalizations over 12 months . DESIGN A r and omized clinical trial . Setting s Pediatric primary care , pulmonary/allergy , and ED practice s associated with the University of Maryl and Medical System and The Johns Hopkins Hospital , Baltimore . PARTICIPANTS Children with persistent asthma , aged 2 to 9 years , with regular nebulizer use and an ED visit or hospitalization within the past 12 months . Children were r and omized into the intervention ( n = 110 ) or control ( n = 111 ) group . Follow-up data were available for 95 intervention and 86 control children . INTERVENTION Home-based asthma education , including symptom recognition , home treatment of acute symptoms , appropriate asthma medication , and nebulizer practice . MAIN OUTCOME MEASURES Estimates of mean differences in asthma symptom frequency , number of ED visits and hospitalizations and appropriate quick relief , controller medication , and nebulizer practice over 12 months . RESULTS Of the 221 children , 181 ( 81.9 % ) completed the study . There were no significant differences in home nebulizer practice , asthma morbidity , ED visits , or hospitalizations between groups ( P range , .11-.79 ) . Although most children received appropriate nonurgent asthma care ( mean , 2 visits per 6 months ) , more than one third of all children received at least 6 quick-relief medication prescriptions during 12 months , with no difference by group . CONCLUSIONS A nebulizer education intervention had no effect on asthma severity or health care use . Of concern is the high quick-relief and low controller medication use in young children with asthma seen nearly every 3 months for nonurgent care This study describes a self-treatment program for parents of children with asthma . The aim was to prevent asthma exacerbations by learning to recognise prodromal signs and acting upon them by increasing inhaled corticosteroids ( ICS ) . The study questions were : ( 1 ) can we teach parents and children to recognise prodromal signs ? ( 2 ) are instructions to increase inhalation medication followed ? ( 3 ) will frequency and severity of asthma attacks diminish subsequently ? Due to physicians ' changed attitude towards prescription of ICS , fewer children could be recruited who were " ICS-naive " than expected . Twenty-nine children of the age of 4 - 11 years with moderate asthma , participated in a one year prospect i ve r and omised study . Structured information was given to all patients on asthma , symptoms and medication . The experimental group received additional information on recognising prodromal signs and doubling ICS during one week . Only in 25 % of the patients who recognised prodromal signs the dose of ICS was doubled ( as prescribed ) , in 75 % inadequately or not at all . Recognition of prodromal signs was poor as well as compliance to increase as-needed medication . No significant decrease of asthma symptoms occurred in the experimental group . Clinical implication s are important for self-treatment instructions : an individually tailored and multi-component program should be offered by health care providers in order to help the patient to recognise early alarm symptoms , comply to self-treatment instructions and to make adaptations for continuous self-regulation OBJECTIVE To establish the efficacy in terms of morbidity and quality of life of a group education program on asthma aim ed at children and caregivers . METHODS An open , r and omized , controlled trial was undertaken in 13 primary health care centers in Spain , Cuba , and Uruguay and involved 245 children with active asthma aged 9 to 13 years and their caregivers . The intervention consisted of 3 educational sessions lasting 45 to 60 minutes each and was performed with 3 intervention groups : children alone , caregivers alone , and both children and caregivers . The outcome measures were difference between intervention and control groups in the rate of asthma attacks and hospital admission , as well as the quality of life of children and caregivers in the 6 months following the intervention . RESULTS The rate of asthma attacks per patient-year decreased when the intervention was given only to children ( mean difference , -1.61 ; 95 % confidence interval [ CI ] , -2.87 to -0.34 ) or to both children and caregivers ( -1.60 ; 95 % CI , -2.88 to -0.31 ) . Hospital admissions per patient-year decreased in the intervention groups children alone ( -0.28 ; 95 % CI , -0.51 to -0.05 ) and both children and caregivers ( -0.25 ; 95 % CI , -0.49 to -0.02 ) . Education provided to caregivers alone was not associated with any changes in morbidity . No differences were observed in terms of quality of life between controls and any of the intervention groups . CONCLUSIONS Group education on asthma reduces morbidity but does not improve quality of life . The benefits are apparent when education is aim ed at children but no additional benefit is obtained if the intervention is also aim ed at their caregivers . Finally , group education for adult caregivers alone is not effective OBJECTIVE . Many children are brought to the pediatric emergency department ( ED ) with acute asthma symptoms . Emergency asthma care is costly , and many ED visits may be preventable . Families often do not have written asthma action plans and lack asthma self-managment skills . This study tests a tailored self-managment intervention delivered in the ED for families of children with asthma . The primary hypotheses were that the intervention group would have greater confidence to manage asthma 14 days postintervention and more well-asthma visits and fewer urgent care/ED visits at 9 and 12 months . METHODS . This r and omized intervention/usual-care study was part of a larger ED asthma surveillance project in 4 urban pediatric ED sites . Asthma educators used a computer-based re source to tailor the intervention messages and provide a customized asthma action plan and educational summary . Children with acute asthma were enrolled during an ED visit , and follow-up telephone interviews were conducted during the next 9 months . The ED clinician classified the child ’s acute and chronic severity . RESULTS . To date , 464 subjects aged 1 to 18 years have been enrolled . The ED clinicians reported that 46 % had intermittent and 54 % had persistent chronic severity with 51 % having mild acute severity episodes . The confidence level to prevent asthma episodes and keep them from getting worse was significantly higher in the intervention group at 14 days postintervention . More subjects in the intervention group reported well-asthma visits by 9 months . Return ED visits were significantly lower in the intervention group in those with intermittent asthma . Twelve-month follow-up is in process . CONCLUSIONS . The tailored ED self-management intervention demonstrates significant effects on caregiver self-confidence and well-visit follow-up . Additional evaluation is needed to determine what impact this intervention has long-term OBJECTIVE To evaluate Watch , Discover , Think and Act ( WDTA ) , a theory-based application of CD-ROM educational technology for pediatric asthma self-management education . DESIGN A prospect i ve pretest posttest r and omized intervention trial was used to assess the motivational appeal of the computer-assisted instructional program and evaluate the impact of the program in eliciting change in knowledge , self-efficacy , and attributions of children with asthma . Subjects were recruited from large urban asthma clinics , community clinics , and schools . Seventy-six children 9 to 13 years old were recruited for the evaluation . RESULTS Repeated- measures analysis of covariance showed that knowledge scores increased significantly for both groups , but no between-group differences were found ( P : = 0.55 ) ; children using the program scored significantly higher ( P : < 0.01 ) on questions about steps of self-regulation , prevention strategies , and treatment strategies . These children also demonstrated greater self-efficacy ( P : < 0.05 ) and more efficacy building attribution classification of asthma self-management behaviors ( P : < 0.05 ) than those children who did not use the program . CONCLUSION The WDTA is an intrinsically motivating educational program that has the ability to effect determinants of asthma self-management behavior in 9- to 13-year-old children with asthma . This , coupled with its reported effectiveness in enhancing patient outcomes in clinical setting s , indicates that this program has application in pediatric asthma education Care of asthmatic children is often episodic and more therapeutic than preventive . A 2-year r and omized , controlled trial involving 95 children measured the impact of a comprehensive home and ambulatory program for pediatric asthma management using objective outcome measures . Interventions for the study group during the first year included 3-month clinic visits , education , and home visits by a specially trained research nurse . Control subjects continued to receive regular care from a family physician or pediatrician . Eight-nine subjects ( 93 % ) completed the study . Study subjects had less school absenteeism than control subjects ( 10.7 vs. 16.0 days , P = .04 ) and showed significantly better small airway function after 1 year . Asthma severity improved in 13 study subjects and worsened in 5 . The reverse was true for control subjects . Study subjects exhibited better metered aerosol technique than control subjects ( P = .0005 ) . Fewer days were spent in hospital by the study subjects admitted compared with control subjects ( 3.67 vs 11.2 days , P = .02 ) . After 1 year , more study than control families ( 72.1 % vs 33.1 % , P = .006 ) reported that their asthmatic child took responsibility for the asthma management . The intervention failed to reduce exposure to secondh and smoke or to household pets . There were no significant differences in medical visits , theophylline levels , or records of asthma symptoms . One year after discontinuing the intervention , a marked " washout " effect was observed . Comprehensive ambulatory programs of childhood asthma management can improve objective measures of illness severity but must be sustained Background . It is often difficult to predict the timing and frequency of asthma attacks . In addition to interrupting the daily life of both the affected child and his/her family , asthma can also pose sudden danger to a child . Based on clinical observations , many asthma‐affected children and their parents must constantly adjust themselves to the uncertainty of the disease , which leads to increased stress on the family . The use of care maps has demonstrated increased efficiency and effectiveness in the care of asthma patients from a variety of setting s. Objective . We design ed this study to construct and evaluate a care map for asthmatic children in Taiwan . Specific attention was placed on comparing the study and control subjects by parental knowledge of asthma , medication used for asthma , hospital readmission , and health care re source usage . Subjects and Methods . The care map was constructed by in‐depth interviews with eight sets of parents of children with asthma . Forty‐four parents of 42 asthma children were r and omized into two groups in the Allergic Clinic of the Chang Gung Children 's Hospital . The experimental group of 22 parents received individual instruction and training sessions in addition to the regular care provided to the control group of 22 parents . Results . Forty‐two children with asthma were surveyed in this study . To examine the reliability and validity of a care map for children with asthma , a quantitative survey was conducted with 42 outpatient parents with asthmatic children . There was less emergency room attending rate in experimental group ( 6/month ; p < 0.05 ) The underst and ing of the disease was much improved in parents of experimental group ( 13.85 ± 1.04 vs. 10.91 ± 2.14 ; p < 0.01 ) . Furthermore , parents acquired a more positive attitude to asthma , and almost all of the control group had irregular follow‐ups by a physician and had irregular use of medication . Conclusion . This study emphasizes that a care map in children with asthma ( CACM ) can be used to educate parents in how to provide the best treatment plan for their children . This study also shows how a CACM can help parents train their children in the best behaviors during asthma attacks . Empathetic assessment and elimination of cultural barriers , a well‐ design ed educational program , and a mutually developed treatment plan could significantly improve the quality of life for families and specific asthma outcomes A r and omised controlled study of an educational programme for children with asthma and their families was carried out by community child health nurses . Three hundred and sixty eight children aged 2 to 14 years were enrolled in the study after admission to hospital for asthma . The intervention group was visited monthly by a nurse for six months . The subjects were assessed six months later by a postal , self administered question naire . European children in the intervention group were taking significantly more drugs for the treatment of asthma six months after the index admission to hospital than those in the control group ( mean ( SD ) intake 2.7 ( 1.1 ) v 2.1 ( 1.0 ) , respectively ) . In particular , they were using more theophylline ( 56.6 % v 37.0 % ) and inhaled steroids ( 34.9 % v 21.0 % ) . There was no difference between the groups for parental reports of improvement , of missed schooling , and in severe attacks of asthma of not responding to the usual treatment at home . European children in the intervention group used the hospital services for severe attacks of asthma more than controls ( 34.2 % v 10.5 % ) . There were more re-admissions in the European intervention group in the subsequent six months after the index admission than in the control group ( mean ( SD ) 0.51 ( 0.97 ) v 0.29 ( 0.65 ) . Re-admission continued to be higher in the 12 months after the nurse had stopped visiting ( 0.81 ( 1.65 ) v 0.25 ( 0.65 ] . There was no difference in the duration of hospital stay between the intervention and control groups . For Polynesian children there was no difference between the groups for any outcome measures The effectiveness of community health workers ( CHWs ) assisting families in reducing exposure to indoor asthma triggers has not been studied . In all , 274 low-income asthmatic children were r and omly assigned to high- or low-intensity groups . CHWs visited all homes to assess exposures , develop action plans and provide bedding encasements . The higher-intensity group also received cleaning equipment and five to nine visits over a year focusing on asthma trigger reduction . The asthma trigger composite score decreased from 1.56 to 1.19 ( Δ=−0.37 , 95 % CI 0.13 , 0.61 ) in the higher-intensity group and from 1.63 to 1.43 in the low-intensity group ( Δ=−0.20 , 95 % CI 0.004 , 0.4 ) . The difference in this measure due to the intervention was significant at the P=0.096 level . The higher-intensity group also showed improvement during the intervention year in measurements of condensation , roaches , moisture , cleaning behavior , dust weight , dust mite antigen , and total antigens above a cut point , effects not demonstrated in the low-intensity group . CHWs are effective in reducing asthma trigger exposure in low-income children . Further research is needed to determine the effectiveness of specific interventions and structural improvements on asthma trigger exposure and health The purpose of this study was to assess the impact of asthma Self Management Training on the health status and re source use of patients with chronic asthma . The study consisted of a r and omized control design of chronic asthmatic patients in a tertiary care center in India . The intervention group ( 153 patients ) received four training sessions in addition to the regular care provided to the control group ( 150 patients ) . Health status and re source use were measured at baseline and over a one year follow-up period . The intervention group had significantly better health status ( measured by breathing ability ) , fewer productive days lost , and lower re source use ( hospitalizations and emergency room visits ) than the control group . Total annual costs ( direct and indirect ) were also lower , though physician costs were not included in the assessment . Therefore , incorporation of asthma Self Management Training as part of clinical management of asthma can result in improvements in health status and reductions in hospital use A r and omized control trial of a curriculum , A.C.T. ( Asthma Care Training ) for Kids , was conducted . Seventy-six children between the ages of 8 and 12 years , whose asthma required treatment with medications at least 25 % of the days per month , were r and omly assigned to control and experimental groups . The control group received 4 1/2 hours of lecture presentations on asthma and its management . The experimental groups ( consisting of four to seven children and their parents ) received five 1-hour sessions comprising " the treatment . " Children and their parents were interviewed before the sessions and 3 , 6 , and 12 months after the completion of the experimental treatment . Use of emergency rooms and hospitals was determined by review ing the records of these patients ( all members of the Los Angeles Kaiser Permanente health care system ) for the period of 1 year before and 1 year after the treatment . Results include ( 1 ) equivalent increases in knowledge and changes in beliefs in both groups , ( 2 ) significant changes in the self-reported compliance behaviors of the experimental group only , and ( 3 ) significant reductions in emergency room visits and days of hospitalization among those receiving the experimental treatment , compared with the control group . These changes represent an estimated savings of approximately $ 180 per child per year for those in the experimental group The aim of the present study was to evaluate long-term efficacy of a patient education programme in an asthma out-patient clinic . The study included two groups . Educational group consisted of 25 patients who were given special education for one year . Usual care group included 27 patients who were not given special education . All patients were evaluated after 3 years follow-up period . Mean per cent asthma knowledge score ( KS% ) , mean per cent demonstration score ( DS% ) , daytime and nighttime symptom scores , Aas score , and pulmonary function tests were measured . The asthma- quality -of-life assessment was performed . The rate of application to emergency room and admission to hospital for last 1 year had been calculated . KS% was higher in educational group than in usual care group ( P < 0.001 ) . Daytime score was 0.3 + /- 0.6 in educational group and was 0.8 + /- 1.2 in usual care group ( P = 0.08 ) . Nighttime symptom score was found to be 0.5 + /- 0.9 and 0.9 + /- 1.3 , respectively ( P = 0.07 ) . Usual care group had higher Aas score compared to educational group ( P = 0.048 ) . The total score of quality of life was 197.1 + /- 17.8 in educational group and was 176.7 + /- 33.7 in usual care group ( P = 0.009 ) . While none of the patients had emergency room application and hospital admission in educational group , seven patients had 21 emergency room application ( P = 0.01 ) and four patients had four hospital admissions in usual care group . Additional short-acting inhaled beta-2 agonist usage was found lower in the educational group ( P = 0.068 ) . In conclusion , proper drug use and usual care of patients are not sufficient for asthma treatment . Patient education is an important component of therapy in asthma patients . For a life with optimum st and ards , in addition to these factors , patient education must be accepted first by doctors and then by patients Optimal home self-management in young children with asthma includes accurate symptom identification followed by timely and appropriate treatment . The objective of this study was to evaluate a home-based asthma educational intervention targeting symptom identification for parents of children with asthma . Two hundred twenty-one children with asthma were enrolled into an ongoing home-based clinical trial and r and omized into either a st and ard asthma education ( SAE ) or a symptom/nebulizer education intervention ( SNEI ) . Data included home visit records and parent 's self-report on question naires . Symptom identification and self-management skills significantly improved from preintervention to postintervention for parents in both groups with the exception of checking medications for expiration date s and the frequency of cleaning nebulizer device and equipment . However , significantly more parents of children in the SNEI group reported treating cough symptoms as compared with the SAE group ( p = 0.05 ) . Of concern is that only 38 % of all parents reported having an asthma action plan in the home . A targeted home-based asthma education intervention can be effective for improving symptom identification and appropriate use of medications in children with asthma . Home asthma educational programs should address accurate symptom identification and a demonstration of asthma medication delivery devices AIM To compare a nurse-led clinic in schools versus care in general practice for adolescents with asthma . DESIGN OF STUDY R and omised controlled trial in four schools ; parallel observational study in two schools . SETTING Six comprehensive schools . METHOD In the r and omised trial , pupils were invited to attend asthma review at a nurse-led clinic either in school , or in general practice . The parallel observational study compared pupils invited to practice care within and outside the r and omised trial . Primary outcome measures were attendance for asthma review , symptom control , and quality of life . Secondary outcomes were knowledge , attitudes , inhaler technique , use of steroids , school absence , peak flow rate , preference for future care , health service utilisation , and costs . RESULTS School clinic pupils were more likely to attend an asthma review than those r and omised to practice care ( 90.8 % versus 51.0 % overall [ P < 0.001 , not consistent across schools ] ) . No differences were observed in symptom control ( P = 0.42 ) or quality of life ( P = 0.63 ) . Pupils attending school clinics had greater knowledge of asthma ( difference = + 0.38 , 95 % CI = 0.19 to 0.56 ) , more positive attitudes ( difference = + 0.21 , 95 % CI = 0.05 to 0.36 ) , and better inhaler technique ( P < 0.001 , not consistent across all schools ) . No differences were observed in school absence or peak flow rate . A majority ( 63 % ) of those who had received care at school preferred this model in future . Median costs of providing care at school and at the practice were 32.10 Pounds and 19.80 Pounds , respectively . No differences were observed between the groups in the observational comparison on any outcome . CONCLUSIONS The schools asthma clinic increased uptake of asthma review s. There were improvements in various process measures , but not in clinical outcomes Children with asthma are at special risk for problems in psychological functioning , as are children with other chronic illnesses . We conducted a controlled trial of a combined education and stress management program among children ages 6 to 14 years with asthma . Eighty-one children were r and omly assigned to an intervention or a control group ; 56 children completed data collection , 29 intervention and 27 control . Psychological status was assessed by the Child Behavior Checklist ( CBCL ) before and after the intervention , as were children 's knowledge of asthma , stress ( as measured by children 's life events ) , and functional status ( as indicated by such activities as school attendance , time playing with friends , and daily chore performance ) . Children in the intervention group had a significant improvement in the total Behavior Problems score ( p < .04 ) and Internalizing scale ( p < .01 ) on the CBCL and a significant increase in daily chores ( p < .04 ) compared with the control group . Before intervention , the two groups had statistically significant positive relationships between negative life events and behavior problem scores . After intervention , children in the control group still demonstrated a significant relationship between negative life events and total and Internalizing Behavior Problem scores , although participation in the intervention group negated that relationship . Children in the intervention group whose knowledge of asthma increased were more likely to report an increase in daily chores ( p < .02 ) . We conclude that the intervention had a beneficial effect on psychological status and on children 's daily activities . The effect may have occurred in part by decreasing the likelihood that perceived stress from negative life events led to poorer adjustment Objective : Asthma is the most common chronic illness in childhood . Recruiting children and their parents into a research study in a busy urban emergency department ( ED ) is challenging . The purpose of this manuscript is to describe the recruitment process and the results of our recruitment in soliciting children and their parents to participate in an ED‐based asthma research study . Methods : The data for this manuscript came from a National Heart , Lung , and Blood Institute‐funded study : Study of Asthma Follow‐up from the Emergency Department ( SAFE ) . SAFE evaluated an ED‐based intervention to link low‐income urban children with asthma to their primary care providers . Two persons were assigned specifically to enrolling , which was done from 0700 to 2300 hours Monday through Friday . Data for the analysis come from the web‐based data base , the master log , and the hospital 's patient data base . A computerized r and omization scheme chose 512 patients from all patients in the master log for more detailed demographic analyses . Results : Five hundred twenty‐seven subjects were enrolled between February 1999 and May 2001 . There were 9188 children who presented for treatment of an acute asthma exacerbation during this interval . Chart review s were conducted on a subset of patients presenting to the ED to ensure that the recruitment strategy did not bias the patients enrolled . Comparison of patients who were enrolled with those who were not enrolled indicated no differences by gender , race , insurance status , age , or socioeconomic status of neighborhood residence . Discussion : The high rate of enrollment was primarily due to the two dedicated enrollers . The enrollers quickly learned how to function within the ED and how to interact with both families and ED staff . Strategies identified by the enrollers as helpful in r and omizing subjects included visits with the parents shortly after the physician had initiated treatment so that stability of the child had been achieved . Interacting with the child and showing concern for the comfort of both the child and parent during the ED stay were important as well . Conclusion : Recruiting subjects into long‐term follow‐up studies in the ED setting is a departure from traditional ED studies . The ED enrollment offers the distinct advantage of capturing subjects who are unlikely to present for care in other locations . We were able to successfully recruit low‐income urban parents of children with asthma for study of both short‐term and long‐term outcomes . The enrollment process successfully captured the subjects of interest without bias The present study investigated schools as an appropriate context for an intervention design ed to produce clinical and psychological benefits for children with asthma . A total of 193 out of 219 ( 88.1 % ) children with asthma ( aged 7–9 yrs ) from 23 out of 24 ( 95.8 % ) schools completed the study . Intervention schools received a staff asthma-training session , advice on asthma policy , an emergency β2-agonist inhaler with spacer and whole-class asthma workshops . Nonintervention schools received no asthma-related input . Intervention children required less general practitioner-prescribed preventer medication despite no differences in symptom control compared with the nonintervention asthmatic group . Increased peer knowledge of asthma may have mediated improved active quality of life in the intervention group , together with increased self-esteem in young females . Those females not receiving the intervention , but identified as being asthmatic within the classroom , and thus possibly stigmatised , reported decreased self-esteem . Lower self-esteem in young males was associated with pet ownership . No change was found in staff knowledge , the establishment of asthma policies or school absences which were low even before intervention . In conclusion , a whole-school intervention can improve the health of children with asthma when followed with support for all children but effects are likely to be modified by sex and the home environment To evaluate a health education program to improve family management of asthma , 310 children with asthma and their 290 parents were r and omly assigned to a program or control group . Program families participated in health education design ed to resolve specific management problems and build self-confidence in the ability to manage asthma . Following education , program parents scored better on an asthma self-management index than parents in the control group ( + 1.57 versus -0.83 , P less than 0.0001 ) . Program parents also scored better on two subindices of the self-management index : attack management ( + 0.87 vs. + 0.42 , P less than 0.05 ) and preventive measures ( + 0.42 vs. -0.35 , P less than 0.05 ) . Also , program parents reported significantly more use of guidelines to determine appropriate levels of physical activity for children . Following education , program children reported more use of three management steps than control children : productive cough or postural drainage ( 59 % vs. 35 % , P less than 0.004 ) , breathing and relaxation exercises ( 80 % vs. 65 % , P less than 0.05 ) , and attempts to stay calm ( 12 % vs. 2 % , P less than 0.05 ) . Program children reported significantly less worry than control children about the limitations asthma imposes and about making mistakes at school OBJECTIVE To conduct a controlled trial of a home-based education program for low-income caregivers of young children with asthma . METHODS Participants were r and omized to treatment-eight weekly asthma education sessions adapted from the Wee Wheezers program ( n = 49)-or usual care ( n = 46 ) . Baseline and 3- and 12-month follow-up data were gathered from caregivers and from children 's medical records . RESULTS Treatment was associated with less bother from asthma symptoms , more symptom-free days , and better caregiver quality of life at follow-up for children 1 - 3 , but not those 4 - 6 , years of age . Treatment and control groups did not differ in caregiver asthma management behavior or children 's acute care utilization . CONCLUSIONS This home-based asthma education program was most effective with younger children ; perhaps their caregivers were more motivated to learn about asthma management . Targeting psychosocial factors associated with asthma morbidity might also enhance the efficacy of asthma education for these families OBJECTIVES To evaluate health care and financial outcomes in a population of Medicaid-insured asthmatic children after a comprehensive asthma intervention program . DESIGN Controlled clinical trial . SETTING Pediatric allergy clinic in an urban , tertiary care children 's hospital . SUBJECTS Eighty children , 2 to 16 years old , with a history of frequent use of emergent health care services for asthma . Intervention . Children in the intervention group received asthma education and medical treatment in the setting of a tertiary care pediatric allergy clinic . An asthma outreach nurse maintained monthly contact with the families enrolled in the intervention group . OUTCOME MEASURES Emergency department ( ED ) visits , hospitalizations , and health care charges per patient in the year after enrollment . RESULTS Baseline demographics did not differ significantly between the 2 groups . In the year before the study , there were no significant differences between intervention and control children in ED visits ( mean , 3.5 per patient ) , hospitalizations ( mean,.6 per patient ) or health care charges ( $ 2969 per patient ) . During the study year , ED visits decreased to a mean of 1.7 per patient in the intervention group and 2.4 in controls , while hospitalizations decreased to a mean of.2 per patient in the intervention group and .5 in the controls . Average asthma health care charges decreased by $ 721/child/year in the intervention group and by $ 178/patient/year in the control group . CONCLUSIONS A comprehensive asthma intervention program for Medicaid-insured asthmatic children can significantly improve health outcomes while reducing health care costs.asthma education , health care outcomes , Medicaid , asthma outreach , utilization A r and omized trial of an instructional method was conducted in which school nurses taught children asthma self-management principles and skills , including peak flow monitoring , in 20-min , individual sessions over an 8-week period . Thirty-six children participated . An intervention group of 18 children received the teaching sessions . A control group of 18 children received regular care by the nurses , but no teaching sessions . The sample included 64 % boys , 69 % African-Americans , and 69 % Medicaid recipients . The average age of subjects was 10.2 years . The two groups were demographically similar , but despite r and om assignment , the control group had a significantly earlier age of onset of asthma and tended to have had more asthma attacks in the preceding year . These factors were statistically controlled in outcome analyses . Results of group comparisons showed no significant differences in the number of postintervention emergency room visits and days absent from school . However , nurses reported that children who practice d breathing exercises had less anxiety during exacerbations , and the nurses ' knowledge of the children 's baseline peak expiratory flow rates facilitated care of the children . Nurses expressed the opinion that the individual sessions with students might be useful in motivating them to participate effectively in later group sessions . The intervention was well accepted by students , parents , and nurses . We believe that this intervention is promising as a practical , low-cost approach to enhancing children 's asthma self-management skills and warrants further testing in a larger sample , with the intervention conducted over a longer period BACKGROUND Since most smoker parents of children with asthma are unable to quit , an alternative measure that would reduce their children 's exposure to environmental tobacco smoke ( ETS ) is to ban smoking in the home . METHODS Compared with 136 usual-care controls , 128 intervention-group parents recruited from South Australian pediatric hospital outpatient waiting rooms were given written and verbal feedback about their 1- to 11-year-old child 's urinary cotinine-to-creatinine level , information booklets , and two telephone calls encouraging a ban on smoking at home . RESULTS At 6 months , 49.2 % of the intervention group reported having banned smoking in the home compared with 41.9 % of controls , but the differential rate of change from baseline was not significant ( P = 0.40 ) . At follow-up , there were no significant differences between groups in the percentage reporting bans on smoking in the car , the mean reduction from baseline in total daily consumption or consumption in front of the child , children 's urinary cotinine level , or parental smoking cessation . CONCLUSIONS The intervention did not change parents ' propensity to create or maintain bans on smoking in their homes or otherwise change smoking habits to reduce their children 's exposure to ETS . More intensive interventions may be required to achieve change among low-income smoker parents of children with asthma This study was design ed to answer three main questions : 1 ) Does asthma self-management education reduce asthma morbidity ? 2 ) Are the two programmes " Living With Asthma " and " Open Airways " equally effective in doing so ? 3 ) Is a shortened version of these programmes ( 4 weeks ) as effective as the longer original programme ( 8 weeks ) ? Twelve Italian centres of paediatric bronchopneumology selected 312 children with asthma , who were stratified by disease severity , gender and age , and then r and omly assigned to an Experimental group which received an educational programme or to a Comparison group , which did not . Of the 312 children selected , 209 ( 114 Experimental and 95 Comparison ) completed the educational protocol and a 1 year follow-up . Data recorded during the last 2 months of follow-up , 10 months after the educational intervention , showed that the Experimental group required significantly fewer emergency treatments : this reduction was more evident in the more severe asthma cases . In the Experimental , but not in the Comparison group , patients with more severe asthma consumed more medications than patients with milder asthma " Open Airways " yielded , in some cases , better results than " Living with Asthma " : but a type 2 error is possible . The st and ard and the shortened programmes proved equally effective . In conclusion , following education , regardless of receiving a short or long educational programme , asthma patients use emergency care services less and use medications more appropriately in comparison with st and ard care without education . This suggests that short educational programmes can be highly cost-effective in children with asthma BACKGROUND Despite significant medical advances , many ethnic and racial minority children who live in inner cities continue to experience disproportionately high levels of asthma morbidity and mortality compared with white children . As a result , a growing number of psychosocial asthma management interventions are being developed to address their needs ; however , only a few of these interventions have incorporated cultural variables into their treatments and have had their efficacy evaluated . OBJECTIVE To examine the efficacy of the Multifamily Asthma Group Treatment ( MFAGT ) , design ed to enhance asthma management and reduce emergency department ( ED ) visits among African American and Hispanic families . METHODS Twenty-four African American and Hispanic families who have children with asthma were r and omly assigned to either the MFAGT or the St and ard Psychoeducational Asthma Intervention . Differences in the number of ED visits and the level of asthma management in both groups were compared 1 year before and 1 year after the intervention . In addition , these groups were contrasted to a control group that did not receive any psychoeducational intervention . RESULTS The MFAGT was significantly ( P = .04 ) more effective than the St and ard Psychoeducational Asthma Intervention and the control in decreasing ED visits and increasing parental asthma knowledge . CONCLUSIONS These preliminary results suggest that the MFAGT is efficacious in enhancing asthma management and in reducing ED visits in inner-city African American and Hispanic children from a lower socioeconomic background Pediatric asthma rates are reaching epidemic proportions , adversely affecting children 's quality of life , educational potential , and health care costs , especially those in the inner city . This study evaluated the effectiveness of a school-based asthma case management ( CM ) approach with medically underserved inner-city children attending Memphis City schools . Fourteen elementary schools with high rates of asthma-related hospital utilization were grouped according to school size , percentage of children with asthma enrolled , and percentage of children eligible for free or reduced-price lunch . Schools were r and omized to either a nurse CM intervention or a usual care ( UC ) condition . The CM group included 115 students ; 128 students were in the UC group . A longitudinal design was used to follow students ' progress . Students were primarily African-American children diagnosed with asthma . In CM schools , nurse case managers conducted weekly group sessions incorporating the Open Airways curriculum , followed up on students ' school absences , and coordinated students ' asthma care with families , school personnel , and medical providers . In UC schools , students received routine school nursing services . CM students had fewer school absences than their counterparts in UC schools ( mean 4.38 vs 8.18 days , respectively ) and experienced significantly fewer emergency department visits ( p < .0001 ) and fewer hospital days ( p < .05 ) than UC students . No such differences existed before program initiation . Replication and follow-up in year 2 showed continued significant improvements . School-based nurse CM can achieve significant improvements in school attendance and medical utilization OBJECTIVE To measure the effect of an asthma intervention on the functional status and morbidity of children with undiagnosed asthma . STUDY DESIGN Data from a r and omized trial were used to compare outcomes at baseline and follow-up for children with undiagnosed and diagnosed asthma . We studied 510 symptomatic children with diagnosed asthma ( diagnosed ) and 299 children with symptoms but no diagnosis ( undiagnosed ) . Baseline functioning and morbidity were similar for undiagnosed and diagnosed patients classified as moderate-severe . RESULTS There were fewer undiagnosed reported allergies , seasonal symptoms , and other respiratory diagnoses ( all P < 0.01 ) . Among the moderate-severe , functional status , for example , symptom-days ( P = .02 ) , symptom-nights ( P < .01 ) , and days of restricted activity ( P < .01 ) , was significantly reduced at follow-up for the undiagnosed in the intervention group but not for undiagnosed control subjects . Findings were similar for children with diagnosed asthma . CONCLUSIONS Children with undiagnosed asthma were generally nonatopic , although some had symptoms at a level comparable to children with a diagnosis . The intervention successfully improved functional status for children with undiagnosed asthma as well as for children with diagnosed asthma . These results can be applied to ongoing discussion s related to case detection BACKGROUND Re-admissions to hospital in childhood asthma are common with studies reporting that 25 % or more of children will be re-admitted within a year . There is a need for strategies to reduce re-admissions . METHODS A prospect i ve r and omised control study of an asthma home management training programme was performed in children aged two years or over admitted with acute asthma . Two hundred and one children were r and omised at admission to either an intervention group ( n = 96 ) which received the teaching programme or a control group ( n = 105 ) . A nurse-led teaching programme used the current attack as a model for the management of future attacks and included discussion , written information , subsequent follow up and telephone advice aim ed at developing and reinforcing individualised asthma management plans . Parents were also provided with a course of oral steroids and guidance on when to start them . RESULTS The groups were similar in degree of social deprivation , length of stay , number of previous admissions , acute asthma treatment , and asthma treatment at discharge . Subsequent re-admissions were significantly reduced in the intervention group from 25 % to 8 % in individual follow up periods that ranged from two to 14 months ( chi 2 = 9.63 ; p = 0.002 ) . This reduction was not accompanied by any increase in subsequent emergency room attendances nor , in the short term , by any increase in urgent community asthma treatment . The intervention group also showed significant reductions in day and night morbidity 3 - 4 weeks after admission to hospital . CONCLUSIONS A nurse-led asthma home management training programme administered during a hospital admission can significantly reduce subsequent admissions to hospital for asthma . Acute hospitalisation may be a particularly effective time to deliver home management training STUDY OBJECTIVE To determine the effect of a symptom-based and a peak flow-based action plan in preventing acute exacerbations in subjects with poorly controlled asthma . DESIGN A r and omized controlled trial in which subjects who had required urgent treatment for their asthma were allocated to receive no action plan , a symptom-based plan , or a peak flow-based action plan . SETTING A university hospital asthma clinic . POPULATION One hundred fifty subjects were recruited after attending an emergency department or a clinic for urgent treatment of asthma . INTERVENTIONS All subjects received evaluation and education for asthma before being r and omly allocated to receive no action plan , a symptom-based action plan , or a peak flowmeter and a peak flow-based action plan . MEASUREMENTS Subjects were assessed by question naire at 3 and 6 months after enrollment with questions relating to their asthma control and their need for urgent treatment or hospital admission for asthma . RESULTS At 6 months after enrollment , although all three intervention groups experienced improvement in their asthma control , there was a striking reduction in emergency department visits for asthma only in the peak flow-based action plan group ( p=0.006 ) . No significant difference in emergency visits was apparent between the symptom-based action plan and no action plan groups . CONCLUSIONS We conclude that a peak flow-based action plan is effective , at least in the short term , in protecting patients with asthma against severe exacerbations of their disease BACKGROUND --Peak flow based asthma self-management plans have been strongly advocated in consensus statements , but convincing evidence for the effectiveness of this approach has been largely lacking . METHODS --A r and omised controlled trial was conducted in 25 general practice s comparing an asthma self-management programme based on home peak flow monitoring and surgery review by a general practitioner or practice nurse with a programme of planned visits for surgery review only over a six month period . RESULTS --Seventy two subjects ( 33 in the self-management group and 39 in the planned visit group ) completed the study protocol , but diary card data for at least three months were available on a total of 84 ( 39 in the self-management group and 45 in the planned visit group ) . Teaching self-management took longer than the planned visit review . In the self-management group home peak flow monitoring was felt to be useful by doctors and patients in 28 ( 85 % ) and 27 ( 82 % ) cases , respectively . There were no between group differences during the study period in terms of lung function , symptoms , quality of life , and prescribing costs . Only within the self-management group were improvements noted in disturbance of daily activities and quality of life . Possible explanations for these negative results include small numbers of subjects , the mild nature of their asthma , and inappropriate self-management strategies for such patients . CONCLUSIONS -- Rigid adherence to long term daily peak flow measurement in the management of mild asthma in general practice does not appear to produce large changes in outcomes . Self-management and the use of prescribed peak flow meters need to be tailored to individual circumstances Abstract Objective : To investigate whether parents of asthmatic children would stop smoking or alter their smoking habits to protect their children from environmental tobacco smoke . Design : R and omised controlled trial . Setting : Tayside and Fife , Scotl and . Participants : 501 families with an asthmatic child aged 2 - 12 years living with a parent who smoked . Intervention : Parents were told about the impact of passive smoking on asthma and were advised to stop smoking or change their smoking habits to protect their child 's health . Main outcome measures : Salivary cotinine concentrations in children , and changes in reported smoking habits of the parents 1 year after the intervention . Results : At the second visit , about 1 year after the baseline visit , a small decrease in salivary cotinine concentrations was found in both groups of children : the mean decrease in the intervention group ( 0.70 ng/ml ) was slightly smaller than that of the control group ( 0.88 ng/ml ) , but the net difference of 0.19 ng/ml had a wide 95 % confidence interval ( −0.86 to 0.48 ) . Overall , 98 % of parents in both groups still smoked at follow up . However , there was a non-significant tendency for parents in the intervention group to report smoking more at follow up and to having a reduced desire to stop smoking . Conclusions : A brief intervention to advise parents of asthmatic children about the risks from passive smoking was ineffective in reducing their children 's exposure to environmental tobacco smoke . The intervention may have made some parents less inclined to stop smoking . If a clinician believes that a child 's health is being affected by parental smoking , the parent 's smoking needs to be addressed as a separate issue from the child 's health . Key messages Many asthmatic children are exposed to high levels of environmental tobacco smoke A brief intervention informing parents of asthmatic children on the harmful effects of passive smoking did not lead to a reduction in exposure of their children to tobacco smoke Low rates of smoking cessation were found in both the intervention group and the control group Some parents may have been less inclined to stop smoking after the intervention Brief interventions requesting smokers to stop for another person 's health seem Abstract Objective : To determine the effect of a peer led programme for asthma education on quality of life and related morbidity in adolescents with asthma . Design : Cluster r and omised controlled trial . Setting : Six high schools in rural Australia . Participants : 272 students with recent wheeze , recruited from a cohort of 1515 students from two school years ( mean age 12.5 and 15.5 years ) ; 251 ( 92.3 % ) completed the study . Intervention : A structured education programme for peers comprising three steps ( the “ Triple A Program ” ) . Main outcome measures : Quality of life , school absenteeism , asthma attacks , and lung function . Results : When adjusted for year and sex , mean total quality of life scores showed significant improvement in the intervention than control group . Clinical ly important improvement in quality of life ( > 0.5 units ) occurred in 25 % of students with asthma in the intervention group compared with 12 % in the control group ( P=0.01 ) . The number needed to treat was 8 ( 95 % confidence interval 4.5 to 35.7 ) . The effect of the intervention was greatest in students in year 10 and in females . Significant improvements occurred in the activities domain ( 41 % v 28 % ) and in the emotions domain ( 39 % v 19 % ) in males in the intervention group . School absenteeism significantly decreased in the intervention group only . Asthma attacks at school increased in the control group only . Conclusion : The triple A programme leads to a clinical ly relevant improvement in quality of life and related morbidity in students with asthma . Wider dissemination of this programme in schools could play an important part in reducing the burden of asthma in OBJECTIVES To operationalize a comprehensive description of attrition , including pre- inclusion , dropout , and attrition due to intermittent missing data , and to test a predictive model of attrition using a data set from a r and omized controlled intervention in pediatric asthma . METHODS Participants included children , ages 4 - 12 , diagnosed with asthma and their caregivers . Demographic variables and outcome measures of asthma morbidity were examined in 327 families to determine their association with attrition . RESULTS Families who did not complete r and omization and the intervention tended to have younger caregivers than did completers . Caregiver age emerged as the most consistent predictor of pre- inclusion and dropout attrition . There were no significant predictors of attrition due to intermittent missing data . CONCLUSION Younger caregivers may be at particular risk for attrition in pediatric asthma intervention studies and warrant special attention by investigators BACKGROUND Airborne pollutants and indoor allergens increase asthma morbidity in inner-city children ; therefore , reducing exposure , if feasible , should improve asthma morbidity . OBJECTIVE To conduct a r and omized controlled trial of methods to reduce environmental pollutant and allergen exposure in the homes of asthmatic children living in the inner city . METHODS After the completion of question naires , spirometry and allergen skin tests , home inspection , and measurement of home air pollutant and allergen levels , 100 asthmatic children aged 6 to 12 years were r and omized to the treatment group ( home-based education , cockroach and rodent extermination , mattress and pillow encasings , and high-efficiency particulate air cleaner ) or to the control group ( treated at the end of the 1-year trial ) . Outcomes were evaluated by home evaluations at 6 and 12 months , clinic evaluation at 12 months , and multiple telephone interviews . RESULTS In the treatment group , 84 % received cockroach extermination and 75 % used the air cleaner . Levels of particulate matter 10 microm or smaller declined by up to 39 % in the treatment group but increased in the control group ( P < .001 ) . Cockroach allergen levels decreased by 51 % in the treatment group . Daytime symptoms increased in the control group and decreased in the treatment group ( P = .04 ) . Other measures of morbidity , such as spirometry findings , nighttime symptoms , and emergency department use , were not significantly changed . CONCLUSIONS A tailored , multifaceted environmental treatment reduced airborne particulate matter and indoor allergen levels in inner-city homes , which , in turn , had a modest effect on morbidity The largest portion of the cost for asthma healthcare is due to hospitalizations . Improved methods of healthcare delivery for patients with asthma are needed to prevent readmissions . From 1996 to 1999 , 96 adult subjects ( predominantly young African American women ) hospitalized with an asthma exacerbation , who had a history of frequent healthcare use , were r and omized to an asthma nurse specialist intervention ( n = 50 ) or a usual care group ( n = 46 ) for 6 months . Our aim was to decrease rates of readmissions within 6 months of hospital discharge , to reduce cost , and to improve health-related quality of life . Our results demonstrate a 60 % reduction in total hospitalizations ( 31 readmissions in the intervention group and 71 in the control group , p = 0.04 ) , with no significant change in emergency department visits . Readmissions for asthma were reduced by 54 % ( 21 vs. 42 in the control group ; p = 0.04 ) . We found a marked reduction in lost work or school days : 246 versus 1040 days in the control group ( p = 0.02 ) . The intervention result ed in a substantial reduction in direct and indirect healthcare costs , saving US dollars 6462 per patient ( p = 0.03 ) . A brief intervention program focusing on high healthcare users with asthma can result in improved asthma control and reduced hospital use with substantial cost savings BACKGROUND Traditional primary care practice change approaches have not led to full implementation of national asthma guidelines . OBJECTIVE To evaluate the effectiveness of 2 asthma care improvement strategies in primary care . DESIGN Two-year r and omized controlled clinical trial . SETTING Forty-two primary care pediatric practice s affiliated with 4 managed care organizations . PARTICIPANTS Children aged 3 to 17 years with mild to moderate persistent asthma enrolled in primary care practice s affiliated with managed care organizations . INTERVENTIONS Peer leader education consisted of training 1 physician per practice in asthma guidelines and peer teaching methods . Planned care combined the peer leader program with nurse-mediated organizational change through planned visits with assessment s , care planning , and self-management support , in collaboration with physicians . Analyses compared each intervention with usual care . MAIN OUTCOME MEASURES Annualized asthma symptom days , asthma-specific functional health status ( Children 's Health Survey for Asthma ) , and frequency of brief oral steroid courses ( bursts ) . RESULTS Six hundred thirty-eight children completed baseline evaluations , representing 64 % of those screened and eligible . Mean + /- SD age was 9.4 + /- 3.5 years ; 60 % were boys . Three hundred fifty ( 55 % ) were taking controller medication . Mean + /- SD annualized asthma symptom days was 107.4 + /- 122 days . Children in the peer leader arm had 6.5 fewer symptom days per year ( 95 % confidence interval [ CI ] , - 16.9 to 3.6 ) , a nonsignificant difference , but had a 36 % ( 95 % CI , 11 % to 54 % ) lower oral steroid burst rate per year compared with children receiving usual care . Children in the planned care arm had 13.3 ( 95 % CI , - 24.7 to -2.1 ) fewer symptom days annually ( -12 % from baseline ; P = .02 ) and a 39 % ( 95 % CI , 11 % to 58 % ) lower oral steroid burst rate per year relative to usual care . Both interventions showed small , statistically significant effects for 2 of 5 Children 's Health Survey for Asthma scales . Planned care subjects had greater controller adherence ( parent report ) compared with usual care subjects ( rate ratio , 1.05 [ 95 % CI , 1.00 to 1.09 ] ) . CONCLUSIONS Planned care ( nurse-mediated organizational change plus peer leader education ) is an effective model for improving asthma care in the primary care setting . Peer leader education on its own may also serve as a useful model for improving asthma care , although it is less comprehensive and the treatment effect less pronounced We have assessed the effects of intervention on medication compliance in asthmatic children . The intervention comprised both written information about the medications and behavioural strategies effected by the physician . Children were assigned at r and om to either control ( received no intervention ) or test ( received the intervention ) groups . Compliance was assessed by question naire . The mean compliance for the test ( 78.0 % ; n = 93 ) and for the control ( 54.5 % ; n = 103 ) groups differed significantly ( P less than 0.001 ; Mann-Whitney U-test ) . The test group had a better knowledge of asthma and of the medications , and was more satisfied with the physician and with the regimen than was the control group . These variables were also related to good compliance . This study demonstrates that a programme of intervention can significantly improve medication compliance and can be accompanied by increases in the knowledge of , and satisfaction with , treatment BACKGROUND Asthma is an important cause of morbidity , absence from school , and use of health services among children . Computer-based educational programs can be design ed to enhance children 's self-management skills and to reduce adverse outcomes . OBJECTIVE To assess the effectiveness of an interactive device programmed for the management of pediatric asthma . DESIGN A r and omized controlled trial ( 66 participants were in the intervention group and 68 were in the control group ) . SETTING Interventions conducted at home and in an outpatient hospital clinic . PARTICIPANTS Inner-city children aged 8 to 16 years diagnosed as having asthma by a physician . INTERVENTION An asthma self-management and education program , the Health Buddy , design ed to enable children to assess and monitor their asthma symptoms and quality of life and to transmit this information to health care providers ( physicians , nurses , or other case managers ) through a secure Web site . Control group participants used an asthma diary . MAIN OUTCOME MEASURES Any limitation in activity was the primary outcome . Secondary outcomes included perceived asthma symptoms , absence from school , any peak flow reading in the yellow or red zone , and use of health services . RESULTS After adjusting for covariates , the odds of having any limitation in activity during the 90-day trial were significantly ( P = .03 ) lower for children r and omized to the Health Buddy . The intervention group also was significantly ( P = .01 ) less likely to report peak flow readings in the yellow or red zone or to make urgent calls to the hospital ( P = .05 ) . Self-care behaviors , which were important correlates of asthma outcomes , also improved far more for the intervention group . CONCLUSION Compared with the asthma diary , monitoring asthma symptoms and functional status with the Health Buddy increases self-management skills and improves asthma outcomes PURPOSE To determine the relationships of adherence to daily peak expiratory flow rate ( PEFR ) monitoring , recommended for asthma self-management , with self-concept and health locus of control in a sample of 42 children , ages 7 through 11 . DESIGN / METHODS Secondary analysis was conducted on data collected as part of our 5-week r and omized , controlled asthma self-management clinical trial . During the study , the Piers-Harris Children 's Self-Concept Scale ( PHCSC ) and Children 's Health Locus of Control Scale ( CHLOC ) were administered at baseline ( Week 1 ) and Week 5 for comparison , while adherence to electronically-measured peak flow monitor ( PFM ) was evaluated during Week 5 . RESULTS Adherence was positively correlated with higher self-concept ( r(s ) = .33 , p = .03 ) and internal health locus of control ( r(s ) = .30 , p = .05 ) . Adherence to PFM and the intellectual and anxiety subscales of the PHCSC also were positively associated ( r(s ) = .38 , p = .01 , in both cases ) . CONCLUSIONS Children who have a positive self-concept , particularly in the areas of intellect and anxiety , are more adherent to their recommended asthma regimen . Similarly , those who perceive their ability to control their health more positively adhere better to daily PEFR monitoring . These results suggest that children 's adherence interventions may need to include components aim ed at enhancing self-concept and health locus of control OBJECTIVES To determine the ability of children and adolescents with acute asthma exacerbations to adhere to national guidelines for proper metered-dose inhaler ( MDI ) and peak flow meter ( PFM ) technique and to define characteristics associated with improper use . DESIGN A prospect i ve study in which the patients were instructed to use a placebo MDI or a PFM in the emergency department exactly as at home . Technique was grade d on the basis of performance of specific steps recommended by national guidelines . SETTING AND PARTICIPANTS Children and adolescents ( aged 2 - 18 years ) with acute asthma exacerbations in the emergency department of an urban children 's hospital with acute asthma . RESULTS Thirty-three ( 45.2 % ) of 73 patients using an MDI ( MDI group ) demonstrated multiple steps improperly compared with 60 ( 44.4 % ) of 135 using an MDI with a holding chamber ( MDI-HC group ; P = .92 ) . In the MDI group , young ages of the patients ( P<.008 ) and the parents ( P<.003 ) were associated with improper use . In the MDI-HC group , factors independently and significantly associated with improper use were no hospitalizations within the past year , parent assistance of the patient with MDI-HC use , and nondaily use of the MDI-HC . Also , 165 ( 82.9 % ) of 199 children who , per national guidelines , should be using a PFM at home , did not . Eighty-two ( 73.9 % ) of 111 patients demonstrated perfect performance of all PFM steps . CONCLUSIONS Among children with acute asthma , we found high rates of improper MDI use and PFM underuse . A greater emphasis must be placed on teaching methods to optimize drug delivery and to instruct patients about the importance of self-monitoring of disease severity Objective . To compare three pediatric asthma interventions for their impact on improving the health status of inner-city asthmatic children and in achieving cost savings . Study Design . A total of 212 children 1 to 16 years of age were r and omized into three groups : group 1 ( n = 74 ) received one individualized asthma education session ; group 2 ( n = 68 ) received reinforced asthma education ; group 3 ( n = 70 ) received reinforced asthma education plus case management . Asthma-related health re source utilization and cost were primary outcomes . The cost-benefit analysis sought to estimate the expected cost savings to the Illinois Department of Healthcare and Family Services ( Medicaid administrator ) associated with the intervention . Results . Participants in all three groups used significantly fewer emergency health care services in the follow-up year . Averaged across all three groups , the magnitudes of declines were substantial : 81 % for hospitalizations , 69 % for hospital days , 64 % for emergency department visits , and 58 % for clinic visits . Although there were no statistically significant differences between study groups for three of the four main outcome measures , group 3 participants consistently improved to the greatest degree . All three interventions were associated with considerable cost savings ranging from $ 4,021/child/year for group 1 to $ 4,503/child/year for group 3 . Conclusion . Asthma education with or without case management services enhances the health of children with asthma thereby reducing associated costs OBJECTIVES . Factors predictive of future asthma must be identified among young inner-city children , who suffer disproportionately from asthma . We investigated whether current asthma control predicts future asthma-related health care use among inner-city preschool-aged children with asthma . METHODS . A total of 150 inner-city preschool-aged children with asthma were followed prospect ively for 6 months . At baseline , symptom frequency and reliever-medication use were assessed to classify children into National Asthma Education and Prevention Program – derived control categories . Long-term controller-medication use was also assessed , as well as asthma-related health care use at baseline and at 3 and 6 months . RESULTS . The mean age was 4.4 years , 92 % were black , and 39 % reported long-term controller use . At baseline , 37 % were classified as having mild-intermittent , 17 % had mild-persistent , 21 % had moderate-persistent , and 25 % had severe-persistent asthma control . Significant changes in asthma control were observed over time , including 46 % of children originally categorized with mild-intermittent asthma who had worsened asthma control by 3 months . Asthma control significantly predicted future health care use 3 months later but not 6 months later . Multivariate analyses showed that , once control status was known , reported use of long-term controller medication added little additional predictive value . CONCLUSIONS . Among inner-city preschool-aged children , significant fluctuations in asthma control occur as early as 3 months after assessment . Poor control but not long-term controller-medication use is an independent predictor of future asthma-related health care use at 3 months but is not significantly predictive of 6-month outcomes . Therefore , clinicians caring for inner-city children with asthma should consider reassessing asthma control at least every 3 months to identify those at highest future risk and to provide early interventions BACKGROUND Although allergy is central to the pathophysiology of asthma , little is known about the benefits of a structured approach to allergen diagnosis and management in primary care asthma patients . OBJECTIVES We studied effects of a structured allergen evaluation and allergen avoidance advice combined with or without additional allergy skin testing on health status , illness perception , and lung function of asthma patients treated in general practice . METHOD Fifty-four asthma patients were r and omly assigned to three groups : ( i ) St and ard asthma care with information on the stepwise treatment approach , a written action plan , and inhaler technique training ; ( ii ) Additional structured allergen evaluation and avoidance advice ; ( iii ) Additional structured allergen evaluation and avoidance advice based on skin prick test results . Patients were seen for one initial appointment at a primary care asthma clinic and a follow-up examination 3 months later . On both occasions , question naire measures of symptoms , illness perception , and the perceived control of asthma were administered . Lung function was measured by spirometry ( PEF , FEV1 ) . Perceived allergic asthma triggers , the trigger impact , and the trigger control were assessed in both intervention groups . RESULTS Following intervention , a decrease in beta-adrenergic inhaler use , an increase in the perceived control of asthma , and a decrease in the bothering from asthma symptoms were observed for all three groups . Intervention groups showed a higher awareness of animal-allergic triggers , and the perceived control of asthma triggers was increased in the group receiving no skin tests . FEV1 showed an improvement in both intervention groups . CONCLUSION Structured allergy evaluation and avoidance advice can improve lung function and the control of asthma in primary care . Further research is needed on the additional benefits of allergy skin testing Aim : To evaluate the effectiveness of a programme of asthma clubs in improving quality of life in primary school children with asthma . Methods : A cluster r and omised intervention trial was undertaken in 22 primary schools within the urban area of south and east Belfast , Northern Irel and . Schools were r and omised in pairs to immediate or delayed groups . The study subjects comprised 173 children aged 7–11 years whose parents had notified the school of their asthma diagnosis . Children attended school based weekly clubs over an 8 week period . The main outcome measures were the interview administered Paediatric Quality of Life Question naire scores , ranging from 1 ( worst ) to 7 ( best ) , spirometry , and inhaler technique . Results : Over 15 weeks , small but non-significant improvements in the overall quality of life score ( mean 0.20 ; 95 % confidence interval ( CI ) −0.20 to 0.61 ) and in each of its three components , activity limitation ( 0.20 ; −0.43 to 0.84 ) , symptoms ( 0.23 ; −0.23 to 0.70 ) , and emotional function ( 0.17 ; −0.18 to 0.52 ) , were observed in the immediate compared with the delayed group . Inhaler technique at week 16 was markedly better in the immediate group , with 56 % having correct technique compared with 15 % in the delayed group . No significant effect of the intervention on spirometry results could be demonstrated . Conclusion : This primary school based asthma education programme result ed in sustained improvements in inhaler technique , but changes in quality of life scores were not significant BACKGROUND Asthma is common and is often poorly controlled in adolescent subjects . OBJECTIVE To determine the impact of an age-specific asthma program on asthma control , particularly on exacerbations of asthma requiring emergency department treatment , and on the quality of life of adolescents with asthma . METHODS The present r and omized , controlled trial included patients who were 15 to 20 years of age and had visited emergency departments for management of their asthma . The interventional group attended an age-specific asthma program that included assessment , education and management by a team of asthma educators , respiratory therapists and respiratory physicians . In the control group , spirometry was performed , and the patients continued to receive usual care from their regular physicians . The outcomes were assessed by a question naire six months after entry into the study . RESULTS Ninety-three subjects entered the study and were r and omly assigned to the intervention or control group . Of these , only 62 patients were available for review after six months . Subjects in both the control and the intervention groups showed a marked improvement in their level of asthma control , reflected primarily by a 73 % reduction in the rate of emergency department attendance for asthma . Other indexes of disease control , including disease-specific quality of life , as assessed by question naires , were improved . There was , however , no discernible difference between the subjects in the two groups , with the exception of an improvement in favour of the intervention group in the symptom ( actual difference 0.7 , P=0.048 ) and emotional ( actual difference 0.8 , P=0.028 ) domains of the asthma quality of life question naire . The overall quality of life score favoured the intervention group by a clinical ly relevant difference of 0.6 , but this difference did not reach statistical significance ( P=0.06 ) . CONCLUSIONS Although all subjects demonstrated a significant improvement in asthma control and quality of life , the improvement attributable to this intervention was limited to two domains in disease-specific quality of life OBJECTIVE . We sought to study the impact of emergency department (ED)–based intensive primary care linkage and initiation of asthma case management on long-term , patient-oriented outcomes for children with an asthma exacerbation . METHODS . Our study was a r and omized , 3-arm , parallel-group , single-blind clinical trial . Children aged 2 through 17 years treated in a pediatric ED for acute asthma were r and omly assigned to st and ard care ( group 1 ) , including patient education , a written care plan , and instructions to follow up with the primary care provider within 7 days , or 1 of 2 interventions . Group 2 received st and ard care plus assistance with scheduling follow-up , while group 3 received the above interventions , plus enrollment in a case management program . OUTCOMES . The primary outcome was the proportion of children having an ED visit for asthma within 6 months . Other outcomes included change in quality -of-life score and controller-medication use . RESULTS . Three hundred fifty-two children were enrolled ; 78 % completed follow-up , 69 % were black , and 70 % had persistent asthma . Of the children , 37.8 % had a subsequent ED visit for asthma , with no difference among the treatment groups ( group 1 : 38.4 % ; group 2 , 39.2 % ; group 3 , 35.8 % ) . Children in all groups had a substantial , but similar , increase in their quality -of-life score . Controller-medication use increased from 69.4 % to 81.4 % , with no difference among the groups . CONCLUSION . ED-based attempts to improve primary care linkage or initiate case management are no more effective than our st and ard ED care in improving subsequent asthma outcomes over a 6-month period OBJECTIVE To evaluate the efficacy of a comprehensive asthma program on emergency department ( ED ) visits and hospital admission rates in an inner-city pediatric population . DESIGN A12-month prospect i ve r and omized trial . METHODS Three hundred asthma patients , ages 2 to 17 years , were recruited and r and omized in an inner-city pediatric ED , to obtain asthma care in a specialty clinic or to continue receiving care by other health re sources . The specialty clinic provided intensive medical and environmental control , education , close monitoring , and 24-hour availability . For the prospect i ve study , monthly question naires were sent to the caregivers of these children to evaluate use of hospital facilities for asthma care . For the retrospective study , use of hospital re sources by the study participants was analyzed using a hospital data base . RESULTS One hundred twenty-nine patients ( 60 in the treatment group and 69 in the control group ) were included in the final analysis . Asthma severity index was significantly higher for the patients in the treatment versus the control group ( 35 % versus 16.2 % , P = .05 ) . Fewer patients in the treatment group visited the ED at least once during the first study year , 32 versus 46 , ( P = .11 ) , and they made fewer visits , 73 versus 269 . The mean number of ED visits of the patients who used the ED was 0.1 versus 0.326 for the control group ( P = .01 ) . There were also fewer admissions in the treatment group , 22 versus 29 ( P < .59 ) . The 53 patients remaining in the treatment group in the second study year made fewer visits to the ED versus the control group ( P < .03 ) . In comparison to the first year , fewer patients in the treatment group visited the ED or were hospitalized in the second year ( P = .007 and P = .04 , respectively ) . CONCLUSIONS A comprehensive asthma care program is efficacious in reducing hospital utilization BACKGROUND Patients with asthma who visit the emergency department ( ED ) may benefit from education that optimizes self-management and treatment . OBJECTIVE To conduct a r and omized trial of asthma education ( AE ) after an ED visit . METHODS Patients who present with acute asthma and history consistent with moderate to severe persistent asthma or recent ED visits were stratified by age ( adult , child ) and r and omly assigned to intervention or usual care during the ED visit . The intervention was conducted by trained asthma educators and included a facilitated office visit with the primary care physician followed by a home visit . Intention-to-treat analysis was conducted , with time to first asthma relapse ( either ED or unscheduled urgent office visit ) during the 6-month follow-up period used as the primary outcome . RESULTS Of the 239 patients analyzed , 46 % were adults , 46 % were male , 30 % were African American , and 56 % had moderate to severe persistent asthma . Follow-up information was obtained on 191 patients ( 80 % ) at 6 months ; 23.1 % of the intervention group vs 31.1 % of the usual care group had an urgent asthma visit ( hazard ratio [ HR ] , 0.79 ; 95 % confidence interval [ CI ] , 0.48 - 1.29 ) . Overall , 39 % of the 117 patients assigned to the intervention group did not comply with any of the post-ED activities . Subgroup analysis suggested greater benefit among children ( HR , 0.62 ; 95 % CI , 0.33 - 1.19 ) than adults ( HR , 1.08 ; 95 % CI , 0.50 - 2.33 ) . CONCLUSIONS Delivery of a comprehensive AE program after an ED visit was ineffective in adult patients ; however , it may be effective in children . Further research on alternative AE delivery strategies appears warranted to reduce the burden of asthma visits to the ED CONTEXT . Barriers impede translating recommendations for asthma treatment into practice , particularly in inner cities where asthma morbidity is highest . METHODS . The purpose of this study was to test the effectiveness of timely patient feedback in the form of a letter providing recent patient-specific symptoms , medication , and health service use combined with guideline -based recommendations for changes in therapy on improving the quality of asthma care by inner-city primary care providers and on result ant asthma morbidity . This was a r and omized , controlled clinical trial in 5- to 11-year-old children ( n = 937 ) with moderate to severe asthma receiving health care in hospital- and community-based clinics and private practice s in 7 inner-city urban areas . The caretaker of each child received a bimonthly telephone call to collect clinical information about the child 's asthma . For a full year , the providers of intervention group children received bimonthly computer-generated letters based on these calls summarizing the child 's asthma symptoms , health service use , and medication use with a corresponding recommendation to step up or step down medications . We measured the number and proportion of scheduled visits result ing in stepping up of medications , asthma symptoms ( 2-week recall ) , and health care use ( 2-month recall ) . RESULTS . In this population , only a modest proportion of children whose symptoms warranted a medication increase actually had a scheduled visit to reevaluate their asthma treatment . However , in the 2-month interval after receipt of a step-up letter , 17.1 % of the letters were followed by scheduled visits in the intervention group compared with scheduled visits 12.3 % of the time by the control children with comparable clinical symptoms . Asthma medications were stepped up when indicated after 46.0 % of these visits in the intervention group compared with 35.6 % in the control group , and when asthma symptoms warranted a step up in therapy , medication changes occurred earlier among the intervention children . Among children whose medications were stepped up at any time during the 12-month study period , those in the intervention group experienced 22.1 % fewer symptom days and 37.9 % fewer school days missed . The intention-to-treat analysis showed no difference over the intervention year in the number of symptom days , yet there was a trend toward fewer days of limited activity and a significant decrease in emergency department visits by the intervention group compared with controls . This 24 % drop in emergency department visits result ed in an intervention that was cost saving in its first year . CONCLUSIONS . Patient-specific feedback to inner-city providers increased scheduled asthma visits , increased asthma visits in which medications were stepped up when clinical ly indicated , and reduced emergency department visits BACKGROUND Cockroach allergen is important in asthma . Practical methods to reduce exposure are needed . OBJECTIVE We sought to evaluate the effectiveness of house cleaning and professional extermination on lowering cockroach antigen levels in inner-city dwellings . METHODS As part of the National Cooperative Inner-City Asthma Study intervention , 265 of 331 families with asthmatic children who had positive skin test responses to cockroach allergen consented to a professional home extermination with 2 applications of a cockroach insecticide ( Abamectin , Avert ) combined with directed education on cockroach allergen removal . On a r and om subset of 48 homes undergoing cockroach extermination in the intervention group , Bla g 1 was measured in settled dust from the kitchen , bedroom , and TV/living room . The first sample was collected 1 week before extermination , with additional sample s after the exterminations at approximately 2 , 6 , and 12 months after the first sample . Self-reported problems with cockroaches were collected at baseline and after 12 months of follow-up in both the intervention and control group . RESULTS The geometric mean kitchen level of Bla g 1 decreased at 2 months ( 33.6 U/g ) relative to preextermination levels ( 68.7 U/g , P < .05 ) . The percent of kitchens with over 8 U/g of Bla g 1 followed a similar pattern , but only the decrease from preextermination to 6-month levels was significant ( 86.8 % vs 64.3 % , P < .05 ) . By the 12-month visit , the allergen burden had returned to or exceeded baseline levels . Except for an increase in the bedroom at 2 months ( 8.9 U/g vs 11.1 U/g , P < .05 ) , no other significant change was seen . Only about 50 % of the families followed the cleaning instructions ; no greater effect was found in these homes . Self-reported problems with cockroaches showed no difference between the intervention and control group after 1 year of follow-up . CONCLUSIONS Despite a significant , but short-lived , decrease the cockroach allergen burden remained well above levels previously found to be clinical ly significant The objective of the present study was to evaluate the effects of a self-management educational program on 29 children between 6 and 14 years old and their parents implemented in an office setting in Venezuela . Children were r and omly assigned to experimental and control group . Children 's asthma knowledge , self-management abilities , index morbidity , parents ' asthma knowledge and management abilities were measured . The program consisted of six sessions of information giving and cognitive-behavioral strategies for the children , and two talks and an informative brochure for the parents . Results of t tests indicate that the experimental group experienced a statistical significant effects on children 's asthma knowledge ( P < 0.001 ) and practice of self-management abilities ( P < 0.000 ) and in parents ' knowledge ( P < 0.008 ) compared to the control group . The educational Self-management program had a significant impact on the Morbidity Index of the study group at post-test ( P < 0.05 ) . Younger children benefited more from the program compared to older ones ( P < 0.09 ) . Children 's age is highlighted as a critical variable in design ing asthma educational programs . Results suggest the effectiveness on these programs independently of the cultural context AIM To investigate if an intervention with extra information and support in a group setting to parents of preschool children could improve adherence and clinical outcome . METHODS This is a controlled , prospect i ve study where the parents of 60 newly diagnosed preschool asthmatic children aged 3 mo-6 y were r and omized to either a control group or to an intervention that consisted of four group sessions in close connection with the diagnosis . The basic education on asthma and the written treatment plan were the same in both groups . The outcome measures were question naires to the parents and classification of the children according to symptoms and medication . The adherence rate and the burden of asthma were calculated with the help of diaries and weighing of the MDIs used between 12 and 18 mo after inclusion . RESULTS The follow-up rate was 85 % after 18 mo . The parents ' presence in the sessions was around 70 % , with no gender difference . The parents ' view on adherence issues improved significantly in the intervention group . In the control group , 30 % had poor adherence compared to 8 % in the intervention group ( p=0.015 ) . Both the parents and the paediatricians underestimated the number of children with poor adherence . The children in the intervention group had significantly fewer exacerbation days during the last 6 mo-2.1 compared to 3.9 d/child-although they had lower inhaled steroid doses after 18 mo . An economic calculation showed that the intervention was profitable . CONCLUSION This intervention result ed in an improvement in the parents ' view on adherence , in the measured adherence rates and in the clinical outcome OBJECTIVE . The purpose of this study was to evaluate the impact and acceptability of an educational multimedia program design ed to promote self-management skills in children with asthma . METHODS . We conducted a r and omized , controlled trial with measures at baseline and 1- and 6-month follow-up . The trial was conducted in pediatric outpatient respiratory clinics in 3 United Kingdom hospitals . Participants included 101 children aged 7 to 14 years under the care of hospital-based asthma services . The children were r and omly assigned to receive an asthma information booklet alone or the booklet plus The Asthma Files , an interactive CD-ROM for children with asthma . Asthma knowledge was the primary outcome measure . Other measures included asthma locus of control , lung function , use of oral steroids , and school absence . RESULTS . At the 1-month follow-up ( n = 99 ) , children in the computer group had improved knowledge compared with the control group and a more internal locus of control . There were no differences in objective lung-function measures , hospitalizations , or oral steroid use . The study participants were positive in their evaluation of the intervention . At the 6-month follow-up ( n = 90 ) , significantly fewer children in the intervention group had required oral steroids and had had time off school for asthma in the previous 6 months . The difference did not reach statistical significance in the intention-to-treat analysis for both steroid use and school absence . CONCLUSION . The Asthma Files was found to be an effective and popular health education tool for promoting asthma self-management skills within pediatric care Objectives Childhood asthma is a growing public health concern in low-income urban communities . Indoor exposure to asthma triggers has emerged as an important cause of asthma exacerbations . We describe indoor environmental conditions related to asthma triggers among a low-income urban population in Seattle/King County , Washington , as well as caregiver knowledge and re sources related to control of these triggers . Methods Data are obtained from in-person , structured , closed-end interviews with the caretakers of children aged 4–12 years with persistent asthma living in households with incomes less than 200 % of poverty . Additional information is collected during a home inspection . The children and their caregivers are participants in the ongoing Seattle-King County Healthy Homes Project , a r and omized controlled trial of an intervention to empower low-income families to reduce exposure to indoor asthma triggers . We report findings on the conditions of the homes prior to this intervention among the first 112 enrolled households . Results A smoker was present in 37.5 % of homes . Mold was visible in 26.8 % of homes , water damage was present in 18.6 % of homes , and damp conditions occurred in 64.8 % of households , while 39.6 % of caregivers were aware that excessive moisture can increase exposures to allergens . Dust-trapping reservoirs were common ; 76.8 % of children 's bedrooms had carpeting . Cockroach infestation in the past 3 months was reported by 23.4 % of caregivers , while 57.1 % were unaware of the association of roaches and asthma . Only 19.8 % of the children had allergy-control mattress covers . Conclusions Many low-income urban children with asthma in King County live in indoor environments that place them at substantial risk of ongoing exposure to asthma triggers . Subst and ard housing and lack of re sources often underlie these exposures . Initiatives involving health educators , outreach workers , medical providers , health care insurers , housing agencies , and elected officials are needed to reduce these exposures BACKGROUND Asthma control may be assisted by educating patients to use peak expiratory flow meters ( PEFMs ) . AIMS To find out the sociodemographic and clinical characteristics of asthmatics attending an Emergency Room ( ER ) who owned PEFMs . METHODS We undertook a study of 352 asthmatics aged seven to 55 years who attended an ER . The following were analysed : their pattern of peak flow monitoring ( PFM ) , the factors associated with ' appropriate ' or daily PFM on entry to the study and then prospect ively ; whether asthma education influenced utilisation and whether there was a reduction in ER use or admissions in those who acquired a PEFM . RESULTS Those owning a PEFM at entry to the study ( 54 % ) had more asthma morbidity ( p = 0.0001 ) , had had asthma for longer ( p = 0.0001 ) , had seen their medical practitioners more often in the previous nine months ( p = 0.0001 ) , were on more asthma medications ( p = 0.0001 ) and were more likely to have been to an Asthma Clinic ( p = 0.0001 ) . Those not owning a PEFM were more likely to be of lower social class ( p = 0.016 ) and of Pacific Isl and origin ( p = 0.0001 ) suggesting that distribution is not ideal and is influenced by disease severity , amount of health care use and sociodemographics . Patients with a self-management plan ( 35 % of PEFM owners ) and those receiving ' good care ' or management , were more likely to use PFM ' appropriately ' and to mention PFM in a scenario evaluating their response to worsening asthma control and argues for PEFMs to be distributed only in conjunction with a self-management plan , and therefore in close association with the patients ' medical practitioners . Most patients ( 75 % ) appeared to prefer making management decisions based on symptoms rather than on their peak expiratory flow ( PEF ) and few ( 16 % ) performed daily PFM at entry to the study and fewer ( 6 % ) nine months later . There was an improvement in the pattern of PFM after education , but the acquisition of a PEFM made no difference to the frequency of ER use or admission . CONCLUSION More realistic goals need to be defined in relationship to PFM which may improve patients ' acceptance of the strategy , and therefore , hopefully their compliance . Such strategies need to be consistently reinforced over time for them to have an impact on asthma morbidity Asthma is a very common chronic disease among preschool children in primary health care . Research has shown that planned and systematic patient education positively affects the management of asthma by parents . This study focuses on the question of whether an asthma patient education protocol that is used by general practitioners ( GPs ) has an effect on medical care consumption . The treatment group consisted of 28 GPs , representing 47 asthmatic infants . The control group contained 18 GPs , representing 38 patients . Data were collected from medical records ( with a written instrument ) for a 12-month period preceding and after the intervention period in which the education protocol was tested . Results indicated that sociodemographic variables and pretest data on asthma severity and medical care utilization were largely comparable for patients in both study groups . Furthermore , the treatment group showed a significantly greater decrease than the control group from pre- to post-test measurement in the number of contacts with the GP and the number of emergency visits to the physician 's office The effectiveness of an educational program to increase compliance with cromolyn sodium was assessed in 31 children and adolescents 6 to 17 years of age . Patients were r and omly assigned to an education or noneducation group . A st and ard education program regarding asthma and asthma medications was provided to the education group during four monthly visits . At each visit , all patients were assessed in terms of knowledge of asthma and medications , asthma-related symptoms , and pulmonary function . Patients were also asked to self-rate their compliance . The education program increased the patients ' knowledge of cromolyn , and appeared to result in increased cromolyn compliance . Post-hoc analyses , however , suggested that increased compliance did not correspond to improved medical status unless the quality of management ( by physician and parents ) of the child 's asthma was taken into account . These results suggest that inadequate management of asthma in children may be a more serious problem than patient noncompliance Parent education has proven to be effective in improving parents coping with their child 's asthma . Little is known about its effectiveness neither during inpatient rehabilitation nor about the different effectiveness of different approaches . A controlled clinical trial was conducted with 242 parents of asthmatic children aged less than 8 years . The aims were to develop a cognitive-behavioral training program for parents and compare its differential effectiveness with an information-centered st and ard-program as part of rehabilitation . Both groups reported a highly significant increase in their knowledge , self-efficacy and quality of life over time in a follow-up just after the end of their inpatient stay . There was a further increase from discharge to the 6-month follow-up for self-efficacy and quality of life . In respect to the functional severity of asthma , children of both groups showed a significant improvement . Whether these effects have long-term stability and which parents benefit from which type of intervention will be the objective of an ongoing 12-month follow-up Abstract Several behavioral medicine interventions ( eg , relaxation training and written emotional expression ) have been proposed as effective supplemental treatments for individuals with chronic illnesses such as asthma . Whether these treatments are feasible or effective in a manual-based , self-administered format is unclear , and few studies have examined the effectiveness of such treatments presented in a complementary format . We examined the feasibility and effectiveness of a 4 week stress management treatment compared with a matched placebo intervention in young adults with asthma . Both groups considered the workbooks credible treatment interventions and completed them conscientiously . The treatment group showed significant improvement in measures of lung function compared with the placebo group , but analysis revealed no differences in measures of perceived stress . These findings provide initial support for the feasibility of self-administered manual-based interventions and some evidence that they can produce health benefits in individuals with asthma and , perhaps other chronic conditions STUDY OBJECTIVES To examine the effectiveness of an interdisciplinary intervention for pediatric asthma . DESIGN R and omized , controlled study . SETTING Urban tertiary-referral pediatric hospital . PARTICIPANTS One hundred seventy-five patients with asthma lacking written treatment plans and presenting with asthma-related emergency department visits ( two or more ) and /or hospitalizations ( one or more ) in the past year were r and omized to a comparison group receiving medical care alone ( n = 86 ) or to an interdisciplinary intervention group receiving medical care , asthma education , and problem-solving therapy ( n = 89 ) INTERVENTION All participants received written asthma management plans , peak flow meters , and spacer devices . The intervention group also received asthma education , an asthma risk profile assessment , brief problem-solving therapy , and access to a 24-h nurse advice line . The primary outcome measure was change in asthma symptoms , and secondary outcomes included health-care utilization and asthma-related quality of life . RESULTS Both groups demonstrated significant reductions in asthma symptoms and improvements in quality of life without any between-group differences identified over the course of follow-up . In contrast , the intervention group demonstrated less frequent health-care utilization than the comparison group , with 28 % of the intervention group requiring emergency department or inpatient services for asthma compared to 41 % of the comparison group ( adjusted odds ratio , 1.92 ; 95 % confidence interval , 1.00 to 3.69 ) over the 12-month follow-up period . CONCLUSIONS This study examined the effectiveness of an interdisciplinary intervention for undertreated asthma . The intervention did not result in improvements in asthma symptoms , but accomplished modest reductions in the utilization of acute medical care OBJECTIVES We assessed the effectiveness of a community health worker intervention focused on reducing exposure to indoor asthma triggers . METHODS We conducted a r and omized controlled trial with 1-year follow-up among 274 low-income households containing a child aged 4 - 12 years who had asthma . Community health workers provided in-home environmental assessment s , education , support for behavior change , and re sources . Participants were assigned to either a high-intensity group receiving 7 visits and a full set of re sources or a low-intensity group receiving a single visit and limited re sources . RESULTS The high-intensity group improved significantly more than the low-intensity group in its pediatric asthma caregiver quality -of-life score ( P=.005 ) and asthma-related urgent health services use ( P=.026 ) . Asthma symptom days declined more in the high-intensity group , although the across-group difference did not reach statistical significance ( P=.138 ) . Participant actions to reduce triggers generally increased in the high-intensity group . The projected 4-year net savings per participant among the high-intensity group relative to the low-intensity group were 189 - 721 dollars . CONCLUSIONS Community health workers reduced asthma symptom days and urgent health services use while improving caregiver quality -of-life score . Improvement was greater with a higher-intensity intervention OBJECTIVE --To compare a peak flow self management plan for asthma with a symptoms only plan . DESIGN --R and omisation to one of the self management plans and follow up for a year . SETTING --Four partner , rural training practice in Norfolk . SUBJECTS--115 Patients ( 46 children and 69 adults ) with asthma who were having prophylactic treatment for asthma and attending a nurse run asthma clinic . MAIN OUTCOME MEASURES --The number of doctor consultations , courses of oral steroids , and short term nebulised salbutamol treatments and the number of patients who required doctor consultations , courses of oral steroids , and short term nebulised salbutamol . RESULTS --Both self management plans produced significant reductions in the outcome measures but there were no significant differences in the degree of improvement between the groups . The results were similar for children and adults . The proportions of patients requiring a doctor consultation fell from 98 % ( 50/51 ) to 66 % ( 34/51 ) in the peak flow group and from 97 % ( 62/64 ) to 53 % ( 34/64 ) in the symptoms only group and the proportions requiring oral steroids from 73 % ( 34/46 ) to 47 % ( 21/46 ) and 52 % ( 31/60 ) to 12 % ( 7/60 ) . The median number of doctor consultations was reduced from 8.0 to 2.0 in the peak flow group and from 4.5 to 1.0 in the symptoms only group . CONCLUSIONS --The peak flow meter was not the crucial ingredient in the improved illness of the two groups . Teaching patients the importance of their symptoms and the appropriate action to take when their asthma deteriorates is the key to effective management of asthma . Simply prescribing peak flow meters without a system of self management and regular review will be unlikely to improve patient care INTRODUCTION Asthma is the most prevalent chronic illness , affecting more than 7 million children younger than 17 years . Asthma has become a leading public health concern because of the dramatic rise in the incidence of this disease during the past 15 years , particularly in minority population s. This study tested a two-part intervention on selected psychosocial and health outcomes of 8- to 13-year-old inner city minority students with asthma . METHOD The intervention consisted of participation in an asthma education program ( Open Airways ) followed by 5 monthly visits with a nurse practitioner . The total sample of 52 children was composed of 28 children in the treatment group who received the intervention and 24 children who served as a control group . RESULTS Students in the treatment group scored significantly higher than the control group over time on measures of asthma knowledge , asthma self-efficacy , general self-care practice s , and asthma self-care practice s. No significant differences were found between the two groups on health outcomes . DISCUSSION A school-based intervention program can improve psychosocial outcomes for inner-city minority children with asthma . Recommendations for future research and clinical practice are discussed A clinic supervised by a nurse , using principles originally developed in general practice , was established in the paediatric department of a district general hospital . A r and omised controlled study was conducted comparing children admitted with asthma or attending out patients who were given a patient education programme and self management plan ( intervention group ) with a control group . The study comprised 91 patients aged 3 - 14 years admitted for asthma or attending a hospital outpatient department from November 1989 to November 1990 . Seventy seven patients completed the study and kept diaries for a median of 283 days . Patients in the intervention group had significantly less restriction of activity ( 95 % confidence interval ( CI ) -0.27 to -0.01 ) and fewer episodes of peak flow below 30 % of best ( 95 % CI 0.03 to 1.17 ) . Patients in the intervention group were more likely to make the correct response to an acute exacerbation of their asthma than the control group ( 71 % v 47 % , 95 % CI 9.51 to 39.1 ) . The intervention group had fewer school absences and fewer home visits by a general practitioner . There was an increase in the readmission rate for the intervention group . A subgroup of patients who self managed by doubling their use of inhaled steroids during an exacerbation performed better than those patients who only increased their bronchodilator or were managed on salbutamol or sodium cromoglycate alone . Improvements in patient follow up and the structure of the self management plans used , particularly changing the peak flow level at which inhaled steroids are doubled , may further improve the outcome of patients attending the asthma clinic OBJECTIVES Asthma continues to cause significant morbidity in children . We hypothesized that many children still do not use recommended preventive medications , or they have ineffective symptom control despite preventive medication use . The aim of this study was 1 ) to describe the use of preventive medications among children with persistent asthma , 2 ) to determine whether children using preventive medications have adequate asthma control , and 3 ) to identify factors associated with poor control . METHODS The State and Local Area Integrated Telephone Survey ( SLAITS ) Asthma Survey provided parent-reported data for children aged < 18 years with asthma from a r and om-digit dial survey implemented in Alabama , California , Illinois , and Texas . We focused this analysis on children with persistent symptoms and /or children using preventive asthma medications ( N = 975 ) . Children with inadequate therapy had persistent symptoms and no preventive medication use . Children with suboptimal control had persistent symptoms or > 1 attack in the previous 3 months despite preventive medication use ; children in optimal control had intermittent symptoms , < or = 1 attack , and reported using preventive medication . Demographic and asthma-related variables were compared across groups . RESULTS Among children with persistent asthma , 37 per cent had inadequate therapy , 42.9 per cent had suboptimal control , and only 20.1 per cent had optimal control . In multivariate regression , black race ( odds ratio [ OR ] , 2.0 ; 95 percent confidence interval [ CI ] 1.1 - 3.5 ) , Hispanic ethnicity ( OR , 1.8 ; 95 per cent CI , 1.1 - 2.9 ) , and discontinuous insurance status ( OR , 2.4 ; 95 per cent CI , 1.4 - 4.3 ) were associated with inadequate therapy . Potential explanations for poor control included poor adherence , exposure to smoke and other triggers , and lack of written action plans . CONCLUSIONS Inadequate asthma therapy remains a significant problem . A newly highlighted concern is the substantial number of children experiencing poor symptom control despite reported use of preventive medications The Self-Care Rehabilitation in Pediatric Asthma ( SCRPA ) project was design ed to ascertain ( 1 ) the level to which children with asthma are able to acquire the asthma knowledge and skills presented in a self-management training program conducted by the American Lung Association of Utah and ( 2 ) the effect of such training on the asthma experience . The preschool SCRPA Curriculum ( ages 2 - 5 ) consisted of six 1-hour classes scheduled twice a week for 3 weeks . The first and last classes were for one or both parents only , and the middle four sessions were for the child and parent(s ) . The school-age SCRPA curriculum ( ages 6 - 14 ) consisted of eight 90-minute classes for both child and parent(s ) scheduled twice a week for 4 weeks . Private physicians referred 21 preschool children and 38 school-age children into the program . The school-age children were r and omly assigned to a study or control group , and the preschool children served as their own controls . A comparison of asthma episodes during the 3 months before and after training showed a statistically significant decrease in the number of episodes but no change in severity in the preschool , school study , and school control groups . The decrease in episodes for the control groups suggest that the family record keeping required of all subjects may have a beneficial effect , a phenomenon worth further investigation . Also , the school-age group , in pre- and posttesting , demonstrated that the SCRPA curriculum increased knowledge and skills in the study group , changes not found in the control group Pediatric asthma is a growing public health issue , disproportionately affecting low-income people and people of color . Exposure to indoor asthma triggers plays an important role in the development and exacerbation of asthma . We describe the implementation of the Seattle-King County Healthy Homes Project , a r and omized , controlled trial of an outreach/education intervention to improve asthma-related health status by reducing exposure to allergens and irritants in the home . We r and omly assigned 274 low-income children with asthma ages 4 - 12 to either a high- or a low-intensity group . In the high-intensity group , community health workers called Community Home Environmental Specialists ( CHES ) conducted initial home environmental assessment s , provided individualized action plans , and made additional visits over a 12-month period to provide education and social support , encouragement of participant actions , provision of material s to reduce exposures ( including bedding encasements ) , assistance with roach and rodent eradication , and advocacy for improved housing conditions . Members of the low-intensity group received the initial assessment , home action plan , limited education during the assessment visit , and bedding encasements . We describe the recruitment and training of CHES and challenges they faced and explain the assessment and exposure reduction protocol s addressing dust mites , mold , tobacco smoke , pets , cockroaches , rodents , dust , moisture , and toxic or hazardous chemicals . We also discuss the gap between the practice s recommended in the literature and what is feasible in the home . We accomplished home interventions and participants found the project very useful . The project was limited in resolving structural housing quality issues that contributed to exposure to indoor triggers BACKGROUND --Previous work has indicated a high rate of non-attendance at hospital based clinics among young , multiracial asthmatic patients of lower socioeconomic class . The efficacy of delivering asthma education from a community health centre established in a multiracial working class neighbourhood was evaluated . METHODS --A prospect i ve controlled study was performed in which asthmatic subjects aged between two and 55 years attending a hospital emergency room with acute asthma and living within a defined geographical area of high emergency room users were r and omised to the usual follow up or the education centre plus usual follow up . Measurements were taken at entry into the study and again nine months later . RESULTS --At nine months patients r and omised to the education centre had more preventive medications , more peak expiratory flow meters and better flow meter technique , more self-management plans , better knowledge of appropriate action to take when confronted with worsening asthma , less nocturnal awakening , and better self-reported asthma control than the control group . There was no difference between the study groups in measurements of compliance , hospital admission , days lost from school or work , or emergency room use . CONCLUSIONS --The main effects of education were on asthma knowledge and self-management skills , whilst improvements in asthma morbidity were small . Potential reasons for this include heterogeneous study population ( in terms of baseline self-management skills , asthma severity , ethnicity and age ) , pragmatic study design , insensitivity of many of the measurements of morbidity , the modest effectiveness of a single time limited education programme , and inability to limit the effects of such a large community based study to the intervention group ( there was a 67 % reduction in asthma admissions during the study period from the geographical area targeted compared with a 22 % reduction for the rest of Auckl and ) OBJECTIVES Coaching and monetary incentives have been used to modify medical behavior of individuals with several chronic diseases , including asthma . The authors performed a r and omized , controlled trial of an intervention combining asthma coaching during an emergency department ( ED ) visit for asthma , and monetary incentive to improve follow-up with primary care providers ( PCP ) . METHODS Subjects were parents of children 2 - 12 years of age , with Medicaid or no medical insurance , receiving treatment for asthma in the ED . The primary outcome was a verified PCP visit for asthma within two weeks of the index ED visit . All parents received 15 dollars for their time in the ED . Parents in the intervention group were told that they would receive an additional 15 dollars monetary incentive if a PCP visit was completed . The coach engaged in a dialogue with the parent during the ED visit , and discussed the importance and advantages of seeking follow-up care with the child 's PCP . All parents received the usual discharge instructions , including advice to see the PCP within three days . RESULTS The authors enrolled 92 parents ; outcome data were available for 86 ( 42 controls , 50 intervention ) . Demographic characteristics were similar in both groups . There was no significant difference in the proportion of patients who had follow-up PCP visits between the intervention ( 22.0 % ; 95 % confidence interval [ 95 % CI ] = 11.5 % to 36.0 % ) and control ( 23.8 % ; 95 % CI = 12.0 % to 39.4 % ) groups ( p = 0.99 ) . CONCLUSIONS An intervention combining asthma coaching during acute ED visits and a monetary incentive to return for a PCP visit does not appear to increase follow-up with the PCP STUDY OBJECTIVES To determine the effectiveness of a cotinine-feedback , behaviorally based education intervention in reducing environmental tobacco smoke ( ETS ) exposure and health-care utilization of children with asthma . DESIGN R and omized controlled trial of educational intervention vs usual care . SETTING The pediatric pulmonary service of a regional pediatric hospital . PARTICIPANTS ETS-exposed , Medicaid/Medi-Cal-eligible , predominantly minority children who were 3 to 12 years old and who were seen for asthma in the hospital 's emergency , inpatient , and outpatient services departments ( n = 87 ) . INTERVENTION Three nurse-led sessions employing behavior-changing strategies and basic asthma education and that incorporated repeated feedback on the child 's urinary cotinine level . MEASUREMENTS The primary measurements were the urinary cotinine/creatinine ratio ( CCR ) and the number of acute asthma medical visits . The secondary measurements were number of hospitalizations , smoking restrictions in home , amount smoked , reported exposures of children , and asthma control . RESULTS The intervention was associated with a significantly lower odds ratio ( OR ) for more than one acute asthma medical visit in the follow-up year , after adjusting for baseline visits ( total visits , 87 ; OR , 0.32 ; p = 0.03 ) , and a comparably sized but nonsignificant OR for one or more hospitalization ( OR , 0.34 ; p = 0.14 ) . The follow-up CCR measurement and the determination of whether smoking was prohibited inside the home strongly favored the intervention group ( n = 51 ) ( mean difference in CCR adjusted for baseline , -0.38 ; p = 0.26 ; n = 51 ) ( 60 ; OR [ for proportion of subjects prohibiting smoking ] , 0.24 ; p = 0.11 ; n = 60 ) . CONCLUSIONS This intervention significantly reduced asthma health-care utilization in ETS-exposed , low-income , minority children . Effects sizes for urine cotinine and proportion prohibiting smoking were moderate to large but not statistically significant , possibly the result of reduced precision due to the loss of patients to active follow-up . Improving ETS reduction interventions and underst and ing their mechanism of action on asthma outcomes requires further controlled trials that measure ETS exposure and behavioral and disease outcomes concurrently OBJECTIVE To identify and educate members of ConnectiCare , Inc & Affiliates , a regional managed care organization , who were not using asthma medications as recommended by the National Heart , Lung , and Blood Institute , by means of a nurse-administered 6-month telephonic case management intervention called the Asthma Treatment Awareness Project . STUDY DESIGN A r and omized controlled design was used to evaluate intervention and control groups . Self-selected members who opted in , opted out , or did not respond to an invitation to participate were included in the analysis . METHODS Changes in asthma medication use , physician office visits , emergency department visits , hospitalizations , and quality of life were measured . A change in asthma medication use was measured using an asthma medication index ranging from 0 to 1.00 , with a higher score indicating a better prescribing pattern . RESULTS There was significant improvement in asthma medication use for all groups , but the asthma medication index increase of 0.176 for the intervention group was nearly 2 times the 0.091 increase for the control group . This difference remained significant ( P = .04 ) after using analysis of variance to control for age and the preintervention asthma medication index . There was also a significant increase in overall quality of life for the intervention group ( P = .04 ) but not for the control group . CONCLUSION Individualized telephonic case management from a specially trained registered nurse may be effective in improving asthma medication use and quality of life in subjects that do not use asthma medications according to National Heart , Lung , and Blood Institute guidelines BACKGROUND Improving asthma knowledge and self-management is a common focus of asthma educational programs , but most programs have had little influence on morbidity outcomes . We developed a novel multiple-component intervention that included the use of an asthma education video game intended to promote adoption of asthma self-management behaviors and appropriate asthma care . OBJECTIVE To determine the effectiveness of an asthma education video game in reducing morbidity among high-risk , school-aged children with asthma . METHODS We enrolled 119 children aged 5 to 12 years from low-income , urban areas in and around San Francisco , CA , and San Jose , CA . Children with moderate-to-severe asthma and parental reports of significant asthma health care utilization were r and omized to participate in the disease management intervention or to receive their usual care ( control group ) . Patients were evaluated for clinical and quality -of-life outcomes at weeks 8 , 32 , and 52 of the study . RESULTS Compared with controls , the intervention group had significant improvements in the physical domain ( P = .04 and P = .01 at 32 and 52 weeks , respectively ) and social activity domain ( P = .02 and P = .05 at 32 and 52 weeks , respectively ) of asthma quality of life on the Child Health Survey for Asthma and child ( P = .02 at 8 weeks ) and parent ( P = .04 and .004 at 32 and 52 weeks , respectively ) asthma self-management knowledge . There were no significant differences between groups on clinical outcome variables . CONCLUSIONS A multicomponent educational , behavioral , and medical intervention targeted at high-risk , inner-city children with asthma can improve asthma knowledge and quality of life OBJECTIVE To improve follow-up with primary care providers after acute Emergency Department ( ED ) asthma visits for children from low-income urban families . STUDY DESIGN A prospect i ve , r and omized , controlled trial evaluated combined telephone asthma coaching and monetary incentive . The primary outcome was asthma-planning visits with primary care providers within 15 days of index ED visits . The subjects were urban parents whose children were treated for asthma in the ED and had Medicaid or no insurance . RESULTS We enrolled 527 parents ( 264 control and 263 intervention ) . There was a significant difference ( P < .0001 ) between the intervention ( 35.7 % ) and control ( 18.9 % ) groups in the proportion of children who had asthma-planning visits and decreased mean nights/days with asthma symptoms by 4.36 intervention and 3.31 control at 2 weeks . The proportions of children with asthma-planning visits and acute asthma care visits during the 16-day to 6-month period were similar for both groups . CONCLUSIONS Telephone coaching and a monetary incentive significantly increased the proportion of low-income urban parents who brought their children for asthma-planning visits , and decreased asthma symptoms shortly after asthma ED visits . The intervention did not increase subsequent asthma-planning visits or decrease ED visits or hospitalizations OBJECTIVE To determine if an emergency department-based asthma follow-up clinic could improve outcomes within a high-morbidity pediatric population . DESIGN Prospect i ve , r and omized clinical trial with 6 months of follow-up . SETTING Emergency department of an urban pediatric medical center . PARTICIPANTS Convenience sample of 488 patients aged 12 months to 17 years , inclusive , with prior physician-diagnosed asthma and 1 or more other unscheduled visits in the previous 6 months and /or 1 or more hospitalizations in the prior 12 months . INTERVENTION Single follow-up clinic visit focusing on 3 domains : asthma self-monitoring and management , environmental modification and trigger control , and linkages and referrals to ongoing care . MAIN OUTCOME MEASURES The primary outcome measure was unscheduled visits for acute asthma care . Secondary outcomes included compliance with a medical plan and asthma quality of life . Analysis was by intention to treat with adjustment for baseline differences . RESULTS Of those r and omized to the clinic visit , 172 ( 70.5 % ) of 244 attended . The intervention group had significantly fewer mean unscheduled visits for asthma care during follow-up ( 1.39 vs 2.34 ; relative risk [ RR ] = 0.60 [ 95 % confidence interval ( CI ) , 0.46 - 0.77 ] ) . At 6 months , significantly more patients in the intervention group reported use of inhaled corticosteroids in the prior 2 days ( 49.3 % vs 26.5 % ; RR = 2.03 [ 95 % CI , 1.57 - 2.62 ] ) , no limitation in daytime quality of life ( 43.8 % vs 34.4 % ; RR = 1.36 [ 95 % CI , 1.06 - 1.73 ] ) , and no functional limitations in quality of life ( 49.8 % vs 40.8 % ; RR = 1.33 [ 95 % CI , 1.08 - 1.63 ] ) . CONCLUSION Attendance in the follow-up clinic was high . The intervention decreased subsequent unscheduled health care use while improving compliance and quality of life The administration of antiasthmatic drugs by pressurised aerosols is limited by the difficulties of the inhalation technique . The development of teaching aids may help their use . The aim of this study was to assess and to compare 2 educational methods of inhalation : a st and ardised inhalation card and a video film . Forty five asthmatic patients who were poor coordinators were separated r and omly into 3 groups : education by card , education by video film and a third group served as a positive control and had been educated by video film and also an additional education in a room set aside for teaching inhalation techniques . The FEV1 ( VEMS ) had been read before the education session and 15 days after , and on each occasion before and after inhalation of a beta-2-mimetic . An inhalation score was measured on the same date . The 2 educational methods enabled an improvement in the score to be shown which was more marked in the video group than in the card group . The VEMS ( mean + or - one st and ard deviation ) before inhalation of beta-2-mimetics was significantly superior to J15 in relation to J1 in the video group ( 2.38 + /- 0.84 and 1.89 + /- 0.61 respectively ) and in the control group ( 2.05 + /- 0.81 and 1.71 + /- 0.66 respectively ) whilst the values did not differ in the card group ( 2.09 + /- 0.63 and 2.01 + /- 0.7 respectively ) . This study suggests the value of education of these patients and the superiority of video education in relation to reading a st and ardised card in the optimisation of treatment administered by the inhaled route BACKGROUND Comprehensive management efforts to reduce asthma morbidity among children in urban areas with high levels of poverty and large minority population s have been inconclusive . The National Cooperative Inner-City Asthma Study ( NCICAS ) demonstrated improved symptom outcomes but did not evaluate cost-effectiveness in this population . OBJECTIVE We sought to examine the incremental cost-effectiveness of a comprehensive social worker-based education program and environmental control in children with asthma stratified by baseline level of asthma control . METHODS We performed a prospect i ve cost-effectiveness analysis alongside a r and omized trial . A total of 1033 children and their families residing in 8 inner-city urban areas in the United States were enrolled in the NCICAS . Outcomes included symptom-free days , cost per symptom-free day gained , and annual costs of asthma morbidity compared by baseline symptom control , previous hospitalization , and previous unscheduled physician visits . RESULTS The NCICAS intervention significantly reduced asthma symptoms . First-year intervention costs were 245 US dollars higher for the intervention children compared with those receiving usual care . There were no additional intervention-related costs during the second year . When compared with usual care , the intervention improved outcomes at an average additional cost of 9.20 US dollars per symptom-free day gained ( 95 % CI , -12.56 to 55.29 US dollars ) . The intervention was cost saving in 3 strata of children with increasing asthma severity . CONCLUSIONS A multifaceted asthma intervention program reduced symptom days and was cost-effective for inner-city children with asthma . In children with more severe disease , the intervention was substantially more effective and reduced costs compared with that seen in control children . Organizations serving this population should consider this strategy as part of a comprehensive disease-management program for asthma To address the recent rise in asthma morbidity and mortality in Russia , an intervention study was conducted to improve asthma diagnosis , treatment and prevention . US recommendations for asthma management were adapted for use in educating Moscow families with children with asthma . Two hundred and fifty-two children with asthma aged 4 - 14 years receiving health care in eight Moscow public health clinics together with their parents were enrolled in the study to see whether US teaching manuals for asthma management would be acceptable and effective in Russia . Children at four of the clinics with recent asthma attacks were r and omly assigned to either the education or control group to test if patient education and guided asthma care would improve outcomes for patients . Modern medications were made available to both groups to see if training in the US guidelines was necessary to get physicians to use the medications . Children with recent asthma attacks at the other four clinics were defined as comparison group 1 to control for the possible effect of medication availability . All children at the eight clinics who had no asthma attacks composed comparison group 2 to see if the outcomes for these children would change over time . One-year follow-up results showed significant improvement in asthma self-management skills of children and parents , in terms of asthma treatment , only among those in the education group . Significant increases were observed in the subgroup of children in the education group using anti-inflammatory drugs for asthma control . Children in the education group had markedly increased peak flow rates and reduced daily peak flow variability as compared to control and comparison groups . There was a significantly greater reduction in doctor visits by the education group of children compared to control . Presumably , changes in parents ' and children 's behaviour in terms of asthma treatment and prevention skills , proper treatment of the disease and access to medications could be responsible for reducing asthma morbidity in children OBJECTIVE To evaluate the impact of a multifaceted environmental and educational intervention on the indoor environment and health in 5 - 12-year-old children with asthma living in urban environments . DESIGN Changes in indoor allergen levels and asthma severity measurements were compared between children who were r and omized to intervention and delayed intervention groups in a 14-month prospect i ve field trial . Intervention group households received dust mite covers , a professional house cleaning , and had roach bait and trays placed in their houses . RESULTS Of 981 eligible children , 410 ( 42 % ) were enrolled ; 161 ( 40 % ) completed baseline activities and were r and omized : 84 to intervention and 77 to delayed intervention groups . At the study 's end , dust mite levels were 163 % higher than at baseline for the delayed intervention group . Overall asthma severity scores did not change . However , the median functional severity score ( FSS ) component of the severity score improved more in the intervention group ( 33 % vs. 20 % ) than in the delayed intervention group . At the study 's end , the median FSSs for the intervention group improved 25 % compared with the delayed intervention group , ( p<0.01 ) . Differences between groups for medication use , emergency department ( ED ) visits or hospitalization were not significant . CONCLUSIONS Despite low retention , the intervention result ed in decreased dust mite allergen levels and increased FSSs among the intervention group . The interventions probably contributed to the improvements , especially among the more severely affected children . This study highlights the complexities of design ing and assessing the outcomes from a multifaceted asthma intervention We asked whether the addition of PEF recordings to a symptom-based self-management plan improved outcome in school children with asthma . In an open-r and omized , parallel-group , controlled trial , we studied children aged 7 - 14 years with moderate asthma . After a 4-week run-in , 90 children were r and omized to receive either PEF plus symptom-based management or symptom-based management alone for 12 weeks . Thresholds for action based on PEF were 70 % of best ( for increasing inhaled steroids ) and 50 % of best ( for commencing prednisolone ) . Children were asked to perform twice-daily spirometry at home ( using an electronic recording spirometer that revealed only PEF to the study group alone ) and to record a symptom diary . The mean daily symptom score was the main outcome . There were no differences between groups in mean symptom score or in spirometric lung function , PEF , quality of life score , or reported use of health services over 12 weeks . During acute episodes , children responded to changes in symptoms by increasing their inhaled steroids at a mean value of PEF of greater than 70 % of best so that overall PEF did not contribute to this important self-management decision . Knowledge of PEF did not enhance self-management even during acute exacerbations To affect asthma-related knowledge , behavior , and morbidity , research ers tested a new educational intervention for children with asthma : an asthma-specific computer game called Asthma Comm and , which was specifically design ed for this study . Sixty-five children with moderately severe asthma were r and omly assigned to one of two groups , and 54 completed the study . Both groups were seen approximately six times during the 1 year of the study . Control subjects ( n = 29 ) played routine computer games . Experimental subjects ( n = 25 ) played Asthma Comm and . Compared with children in the control group , experimental subjects showed improvement in knowledge about asthma ( P less than .001 ) , behavior related to the management of asthma ( P less than .008 ) , and a trend toward the reduction of acute visits due to asthma ( P less than .13 ) . Children in the experimental group also scored higher on the assessment of behaviors related to the management of asthma that were specifically addressed by the intervention provided by Asthma Comm and ( P less than .01 ) . Differences between the control and experimental groups showed a greater improvement in the experimental group in 21 ( 84 % ) of the 25 outcome variables in the study ( P = .004 , Sign test ) . The study indicates that an asthma-specific computer game can significantly affect knowledge and behavior and may potentially affect morbidity in childhood asthma OBJECTIVE To investigate racial/ethnic differences in acute asthma among children who present to the emergency department ( ED ) . METHOD We analyzed data from 2 prospect i ve cohort studies performed during 1997 - 1998 as part of the Multicenter Airway Research Collaboration . Using a st and ardized protocol , research ers at 40 EDs in 18 US states provided 24-hour-per-day coverage for a median of 2 weeks per year . Children with acute asthma were interviewed in the ED and by telephone 2 weeks after discharge . RESULTS Among 1095 patients , 679 ( 62 % ) were black , 256 ( 23 % ) were Hispanic , and 160 ( 15 % ) were white . Black and Hispanic children had greater histories of lifetime ( 63 % , 64 % , 46 % ) and past-year ( 34 % , 31 % , 14 % ) hospitalization and more ED visits in the past year ( medians : 2 , 3 , 1 ) . Asthma severity at ED presentation , ED management and course , hospitalization during the index visit , discharge prescriptions , and postdischarge outcomes were equivalent among all race/ethnic groups . CONCLUSION Despite pronounced race/ethnicity-based differences in chronic asthma , all racial/ethnic groups exhibited similar acute asthma severity , ED management , and course . However , given that black and Hispanic children exhibited much higher admission histories and past ED use , the equivalence in inhaled corticosteroid prescriptions on discharge is a disconcerting pattern that mirrors previous literature on outpatient prescription practice s. In addition to barriers attributable to socioeconomic factors , health care providers and policy makers should target equalizing deficiencies in preventive medication prescription practice Asthma prevalence is increasing among poor and minority children . We examined the effectiveness of a novel interactive device programmed for self-management of pediatric asthma in reducing asthma control problems and hospitalizations . A r and omized controlled trial ( 66 children in the intervention group and 68 in the control group ) was conducted at home and in an outpatient hospital clinic with 8 - 16-year-old inner-city children with physician-diagnosed asthma . During a 12-week period , children in the experimental group received an asthma self-management and education program , the Health Buddy ( Health Hero Network ) , design ed to enable them to monitor their symptoms and transmit this information to a case manager through a secure website . Control group participants used an asthma diary . After adjusting for baseline asthma control problems , asthma severity , and seasonality , children r and omized to automated self-management had a significantly lower mean number of asthma control problems at 6 weeks ( 2.0 , SD = 1.6 ) as compared to children assigned to the asthma diary ( 2.7 , SD = 1.6 ) ( p = 0.03 ) . By 12 weeks , after adjusting for time and the other covariates , asthma control problems dropped markedly in both groups , and did not differ by intervention modality ( p = .07 ) . The intervention modality was not a significant predictor of hospitalization . Educational interventions that encourage children 's active involvement in their own care and symptom monitoring would help children increase their control of asthma problems . Compared to the asthma diary , the automated self-management had a significant short-term impact on asthma control problems . Its initial effectiveness and more consistent use suggest that remote monitoring may be successfully used in short-term interventions and in setting s where staffing for case management is weak RATIONALE Urban African-American youth , aged 15 - 19 years , have asthma fatality rates that are higher than in whites and younger children , yet few programs target this population . Traditionally , urban youth are believed to be difficult to engage in health-related programs , both in terms of connecting and convincing . OBJECTIVES Develop and evaluate a multimedia , web-based asthma management program to specifically target urban high school students . The program uses " tailoring , " in conjunction with theory-based models , to alter behavior through individualized health messages based on the user 's beliefs , attitudes , and personal barriers to change . METHODS High school students reporting asthma symptoms were r and omized to receive the tailored program ( treatment ) or to access generic asthma websites ( control ) . The program was made available on school computers . MEASUREMENTS AND MAIN RESULTS Functional status and medical care use were measured at study initiation and 12 months postbaseline , as were selected management behaviors . The intervention period was 180 days ( calculated from baseline ) . A total of 314 students were r and omized ( 98 % African American , 49 % Medicaid enrollees ; mean age , 15.2 yr ) . At 12 months , treatment students reported fewer symptom-days , symptom-nights , school days missed , restricted-activity days , and hospitalizations for asthma when compared with control students ; adjusted relative risk and 95 % confidence intervals were as follows : 0.5 ( 0.4 - 0.8 ) , p = 0.003 ; 0.4 ( 0.2 - 0.8 ) , p = 0.009 ; 0.3 ( 0.1 - 0.7 ) , p = 0.006 ; 0.5 ( 0.3 - 0.8 ) , p = 0.02 ; and 0.2 ( 0.2 - 0.9 ) , p = 0.01 , respectively . Positive behaviors were more frequently noted among treatment students compared with control students . Cost estimates for program delivery were $ 6.66 per participating treatment group student . CONCLUSIONS A web-based , tailored approach to changing negative asthma management behaviors is economical , feasible , and effective in improving asthma outcomes in a traditionally hard-to-reach population Background Cockroach allergy is common among inner city children with asthma , and exposure to cockroach allergen is associated with more severe disease . However , there has been little evaluation of educational approaches for controlling cockroach infestations and reducing allergen exposure OBJECTIVE Caring for a child with asthma can affect the parent 's coping and well-being and coping strategies . This study examined the influence of a home-based asthma health education program on parental coping and quality of life . DESIGN R and omized controlled non-blinded clinical trial . SETTING Northern community pediatrician 's office . PATIENTS Families whose children , under the age of 11 , had chronic stable asthma , and who presented to the pediatrician 's office for continuing care ; those with an acute exacerbation of asthma were excluded . INTERVENTIONS Families were r and omly assigned to receive either a single two-hour , st and ardized home-based asthma health education session or a booklet representing conventional care . MAIN OUTCOME MEASURES One and three-months following the intervention , assessment s were obtained for coping measured by Hymovich 's Parent Perception Inventory ( PPI ) , quality of life measured by the Pediatric Asthma Caregiver Quality of Life Question naire ( PACQLQ ) and change in asthma measured by the Caregiver Perception of Change ( CPC ) survey . RESULTS Forty families were recruited and r and omized ; baseline characteristics were similar between groups . At the final follow-up , reduction in parental need for asthma information ( p = 0.04 ) , reduction in parental concerns ( p = 0.02 ) and increased use of coping strategies ( p = 0.04 ) were observed in the home-based care group . Improvement was noted in the parent 's perception of their child 's asthma in the home-based asthma education group ( p = 0.01 ) . Quality of life as measured by the PACQLQ remained unchanged over the intervention period ( p > 0.05 ) . CONCLUSIONS These results suggest the use of a one-time , flexible , home-based intervention to assist families caring for children with asthma should be considered and appears effective OBJECTIVE To assess the effect of a structured program of pharmaceutical care on changes in disease control , functional status , and health services utilization for pediatric and adolescent patients with moderate-to-severe asthma . DESIGN R and omized , controlled trial . SETTING Community and clinic pharmacies ( 14 intervention and 18 usual care pharmacies ) in western Washington State . PATIENTS Three hundred thirty children , aged 6 to 17 years , with asthma . INTERVENTION Structured training for the intervention group pharmacists to provide individualized asthma management services during patient-pharmacist encounters for up to 1 year following the patient 's enrollment into the study . MAIN OUTCOME MEASURES The primary outcome measure was change in pulmonary function as measured by peak expiratory flow rate and spirometry . Secondary outcome measures included changes in functional status and use of asthma-related health care services . RESULTS The intervention had no significant effect on the health or health services use outcomes of study subjects . When compared with the usual care group , there was no evidence that patients from the intervention group experienced improvements in pulmonary function , functional status , quality of life , asthma management , or satisfaction with care . In addition , there were no differences between groups in use of anti-inflammatory medications , total or asthma-related medical care utilization , or total or asthma-related school days lost . CONCLUSION This pharmaceutical care intervention had no significant effect on the health or health services use outcomes of pediatric patients with asthma . The intervention may not have been powerful enough to significantly affect pharmacists ' behaviors and asthma patients ' outcomes in community pharmacy setting s , and there is evidence that the pharmacists ' compliance with the study protocol was low due , in part , to patient- and practice -related obstacles Objectives : This study examined the effectiveness in children in China of an asthma education programme adapted from a model developed in the USA . Methods : Six hundred and thirty-nine children in 21 elementary schools in one agricultural and one industrial area participated in a r and omized , controlled trial . Data were collected at baseline and 1 year subsequently . The self-regulation-based programme addressed topics including preventing and managing symptoms , using medicines , and identifying and controlling triggers . Results : Positive effects on treatment children v. control children were noted in school performance ( 0.21 v. -0.06 , p=0.04 ) , absences ( -0.55 v . -0.32 , p=0.02 ) , and home environment ( 1.78 v. 4.75 , p=0.009 ) . Industrial-area children additionally benefited from fewer hospitalizations ( odds ratio=1.96 , p=0.05 ) and asthma-related concerns of parents ( -0.63 v. -0.34 , p=0.001 ) . Agricultural-area parents showed greater improvement in asthma management ( 0.93 v. 0.26 , p=0.0001 ) , and expressed more negative feelings about asthma ( -0.13 v. -0.58 , p=0.04 ) and asthma concerns ( -0.31 v. -0.63 , p=0.0001 ) . Discussion : The programme provided overall benefits related to school performance , absences , and home environment . In the agricultural area , where fewer re sources were available , benefits were fewer and concerns greater . In the industrial area , where education and income were higher , additional benefits related to healthcare use and parents ' quality of life were realized OBJECTIVE Emergency department ( ED ) visits for asthma are frequent and may indicate increased morbidity and poor primary care access . Our objective was to compare the effect of two interventions on primary care follow-up after ED treatment for asthma exacerbations . METHODS We performed a r and omized controlled trial of patients 2 to 54 years old who were judged safe for discharge receiving prednisone , and who were available for contact at 2 days and 30 days . Patients were excluded if they were previously enrolled or did not speak English . Patients received usual discharge care ( group A ) ; free prednisone , vouchers for transport to and from a primary care visit , and either a telephone reminder to schedule a visit ( group B ) ; or a prior scheduled appointment ( group C ) . Follow-up with a primary care provider for asthma within 30 days was the main outcome . Secondary outcomes were recurrent ED visits , subsequent hospitalizations , quality of life , and use of inhaled corticosteroids 1 year later . RESULTS Three hundred eighty-four patients were enrolled . Baseline demographics , chronic asthma severity , and access to care were similar across groups . Primary care follow-up was higher in group C ( 65 % ) vs group A ( 42 % ) or group B ( 48 % ) [ p = 0.002 ] . Group C intervention remained significant ( odds ratio , 2.8 ; 95 % confidence interval , 1.5 to 5.1 ) when adjusted for other factors influencing follow-up ( prior primary care relationship , insurance status ) . There were no differences in ED , hospitalizations , quality of life , or inhaled corticosteroid use at 1 year after the index ED visit . CONCLUSION An intervention including free medication , transportation vouchers , and appointment assistance significantly increased the likelihood that discharged asthma patients obtained primary care follow-up but did not impact long-term outcomes OBJECTIVE To determine whether health outcomes of children who have asthma can be improved through the use of an Internet-enabled interactive multimedia asthma education program . METHODS Two hundred twenty-eight children with asthma visiting a pediatric pulmonary clinic were r and omly assigned to control and intervention groups . Children and caregivers in both groups received traditional patient education based on the National Asthma Education and Prevention Program . Intervention group participants received additional self-management education through the Interactive Multimedia Program for Asthma Control and Tracking . Pediatric Asthma Care Knowledge Survey , Pediatric Asthma Caregiver 's Quality of Life Question naire , asthma symptom history , spirometry , and health services utilization data were collected at the initial visit and at 3 and 12 months . RESULTS Interactive Multimedia Program for Asthma Control and Tracking significantly increased asthma knowledge of children and caregivers , decreased asthma symptom days ( 81 vs 51 per year ) , and decreased number of emergency department visits ( 1.93 vs 0.62 per year ) among the intervention group participants . The intervention group children were also using a significantly lower average daily dose of inhaled corticosteroids ( 434 vs 754 micro g [ beclomethasone equivalents ] ) at visit 3 . Asthma knowledge of all 7- to 17-year-old children correlated with fewer urgent physician visits ( r = 0.37 ) and less frequent use of quick-relief medicines ( r = 0.30 ) . CONCLUSIONS Supplementing conventional asthma care with interactive multimedia education can significantly improve asthma knowledge and reduce the burden of childhood asthma BACKGROUND Management of asthma involves adherence to medication regimens . Assessing adherence is difficult for health care providers and research ers . Self-reported medication use is subjective , so objective methods of data collection for medication use are frequently used in asthma research . The aim of this project is to examine the concordance between asthma medication pharmacy data culled from Medicaid cl aims data ( " Medicaid pharmacy data ") and patient pharmacy record data obtained from individual pharmacies ( " pharmacy record data ") . METHODS Medicaid pharmacy data and pharmacy record data were obtained from inner-city children enrolled in a prospect i ve study of children with persistent asthma . A subject level comparison of pharmacy records and Medicaid pharmacy data pharmacy records was done to determine concordance between the 2 data collection methods . RESULTS Of 513 children recruited for inclusion , 221 were consented and r and omized . Medicaid cl aims data were collected on 72.8 % ( n=161 ) of the 221 enrolled subjects . Pharmacy record data were available on 96.8 % ( n=214 ) of the 221 subjects . Data presented represent the 159 subjects who had both Medicaid cl aims data and pharmacy records data available throughout the study period . There was complete agreement between Medicaid pharmacy data and pharmacy record for 26 % ( n=42 ) of subjects . A total of 1858 asthma medication cl aims were captured by the Medicaid pharmacy data . Medicaid pharmacy data missed 149 cl aims that were capture by the pharmacy record data . Medicaid pharmacy data failed to capture a single cl aim on 4.4 % ( n=7 ) of subjects . The pharmacy record data captured a total of 1627 asthma medication cl aims and missed 371 cl aims that were captured by the Medicaid pharmacy data . Pharmacy record data failed to capture a single cl aim in 1.9 % ( n=3 ) of subjects . CONCLUSIONS There was overlap between the pharmacy data captured by the Medicaid pharmacy data set and pharmacy record data set , but the overall concordance between the two data collection methods was low . Pharmacy records collected directly from the pharmacy included data on more subjects and pharmacy data culled from Medicaid cl aims captured more total number of cl aims . In spite of the differences in the methods used to collect data , pharmacy fill records are a rich source of data with both clinical and research applications . Clinicians and research ers must weigh the benefits and limitations of each method used to collect pharmacy data BACKGROUND Discharge planning is becoming an important part of the management of childhood asthma in hospital . Readmission to hospital , although often inevitable , might represent a failure of the opportunity for intervention presented by a brief period of supervised care in hospital . AIM To examine the impact of a structured , nurse-led discharge package for children admitted to hospital with acute asthma on readmission to hospital , reattendance at the accident and emergency ( A&E ) department , and general practitioner consultations for asthma . METHODS A structured nurse-led discharge package , consisting of a 20 minute patient education programme and self management plan for children with asthma was developed on the wards of a busy children ’s hospital . A r and omised controlled trial was conducted involving 160 children aged 2–16 years admitted for asthma over a 12 month period . Readmission and A&E reattendance ’s over the six months after discharge from hospital were obtained from the hospital computerised information system and general practitioner consultations from practice records . RESULTS Children in the intervention group were significantly less likely to be readmitted to hospital in the next six months than those in the control group ( 12 of 80 v30 of 80 patients ) , and significantly less likely to attend the A&E department ( 6 of 80 v 31 of 80 ) . Significantly fewer children in the intervention group had visits to their general practitioner for problematic asthma ( 31 of 78v 72 of 77 for whom data were available ) . CONCLUSION By delivering the simplest form of education and support during a child ’s stay in hospital , readmissions over a six month period were reduced . The programme was design ed to be suitable for administration by nursing staff on the children ’s wards after a brief period of training The increased prevalence , morbidity , mortality , and health costs associated with asthma among children suggest the need for accessible asthma education . This study examined the effect of telepharmacy counseling , using interactive compressed video , on metered-dose inhaler ( MDI ) technique and patient satisfaction among adolescents with asthma in rural Arkansas . The telepharmacy counseling provided accessible education regarding MDI technique for adolescents in this study . Twenty percent of the adolescents who participated had never been shown the appropriate use of an MDI . The study used an experimental design with r and om assignment of participants to a telepharmacy counseling group ( n = 15 ) or a control group ( n = 21 ) . Both groups participated in pre-test , post-test , and 2- to 4-week follow-up assessment s for MDI technique and patients satisfaction ( follow-up assessment only ) via interactive compressed video . Results indicated that from pre-test to follow-up the telepharmacy counseling group showed more improvement in MDI technique than participants in the control group ( p < 0.001 ) . There was no significant difference between the telepharmacy counseling group and control group in satisfaction with the instructional sessions ( p = 0.132 ) . Both groups had high levels of satisfaction with the telepharmacy sessions . The study findings demonstrated that patient education provided by pharmacists via interactive compressed video was superior to education provided via written instructions on an inhaler package insert . Interactive compressed video is an effective medium for teaching and improving MDI technique in this rural , adolescent , predominantly African-American population The Healthy Learners Asthma Initiative ( HLAI ) involved collaboration between Minneapolis Public Schools ( MPS ) , local health care providers/payors , parents , and other partners . The intervention included development of enhanced asthma care in school health offices and clinic performance improvement projects to foster adoption of National Institutes of Health asthma guidelines . Goals were to improve asthma management among school children and reduce asthma-related school absences , hospitalizations , and emergency department visits . The effectiveness evaluation utilized a r and omized community trial design with 16 elementary and middle schools matched and r and omly assigned to either an intervention or a control group . Outcomes investigated were ( a ) school health office impacts and ( b ) school attendance . Data sources included school health office records , district attendance , enrollment , and demographics files . Following implementation of the HLAI , asthma visits to health offices were significantly lower in intervention schools compared to control schools ( 91 vs 121 visits per 100 students with asthma per month ) , and intervention schools had greater availability of medication and asthma action plans and more peakflow measurements , asthma education , and parent communication . Clinics initiated significantly more asthma action plans and sent them to MPS . Attendance differences between groups were limited to students who received asthma care through the school health office . Monitoring of asthma management activities provided through school health offices from 2002 to 2005 indicates sustained implementation of enhanced asthma care in schools and increased asthma communication between school , parents , and health care providers OBJECTIVE To compare the effects on asthma morbidity of asthma clinics based in general practice with st and ard general practice care . DESIGN AND SETTING A r and omised controlled trial in eight general practice s. Patients , general practitioners and outcomes assessors were not blinded to treatment allocation . PARTICIPANTS 195 patients with asthma aged 5 - 64 years ; 191 completed the trial . INTERVENTION Three asthma clinic sessions over six months involving nurse counselling , education about asthma management , spirometry and consultation with the general practitioner . MAIN OUTCOME MEASURES Patients reporting days lost from work or school , number of days lost , the presence of morning or nocturnal asthma symptoms , use of an action plan , medication use , current smoking , hospitalisation , and emergency visits . RESULTS Asthma clinics were associated with a greater reduction in nocturnal symptoms , an increase in the ownership of peak flow meters and an increase in the number of patients commencing or resuming smoking . Both control and intervention groups showed similar improvement in days lost from work or school , the presence of symptoms , use of an action plan and taking reliever medication . CONCLUSION Our study does not show that asthma clinics are more effective than st and ard general practice care in reducing asthma morbidity . It is uncertain how much of the improvement in outcomes was due to the asthma clinic , the influence of the study itself upon patients and practitioners , or other factors , such as the tendency for a patient 's asthma management to improve over time OBJECTIVE To highlight the unique challenges of evaluative research on practice behavior change in the " real world " setting s of contemporary managed-care organizations , using the experience of the Pediatric Asthma Care PORT ( Patient Outcomes Research Team ) . STUDY SETTING The Pediatric Asthma Care PORT is a five-year initiative funded by the Agency for Healthcare Research and Quality to study strategies for asthma care improvement in three managed-care plans in Chicago , Seattle , and Boston . At its core is a r and omized trial of two care improvement strategies compared with usual care : ( 1 ) a targeted physician education program using practice based Peer Leaders ( PL ) as change agents , ( 2 ) adding to the PL intervention a " Planned Asthma Care Intervention " incorporating joint " asthma check-tips " by nurse-physician teams . During the trial , each of the participating organizations viewed asthma care improvement as an immediate priority and had their own corporate improvement programs underway . DATA COLLECTION Investigators at each health plan described the organizational and implementation challenges in conducting the PAC PORT r and omized trial . These experiences were review ed for common themes and " lessons " that might be useful to investigators planning interventional research in similar care-delivery setting s. CONCLUSIONS R and omized trials in " real world " setting s represent the most robust design available to test care improvement strategies . In complex , rapidly changing managed-care organizations , blinding is not feasible , corporate initiatives may complicate implementation , and the assumption that a " usual care " arm will be static is highly likely to be mistaken . Investigators must be prepared to use innovative strategies to maintain the integrity of the study design , including : continuous improvement within the intervention arms , comanagement by research ers and health plan managers of condition-related quality improvement initiatives , procedures for avoiding respondent burden in health plan enrollees , and anticipation and minimization of risks from experimental arm contamination and major organizational change . With attention to these delivery system issues , as well as the usual design features of r and omized trials , we believe managed-care organizations can serve as important laboratories to test care improvement strategies Asthma training programs for parents and children have been developed to increase both the self-management skills of asthmatic children and compliance with medical regimes . In order to evaluate two training programs for asthmatic children aged 7 - 14 , 81 patients were r and omly assigned to three groups . Group 1 consisted of 27 patients and their parents who participated in a five-day st and ardized family-oriented clinical asthma training program . They had monthly follow-up meetings with the training team for a period of six months . Group 2 ( n = 29 ) had the same clinical training without follow-up interventions ; a control group ( n = 25 ) received regular medical treatment according to the international guidelines at the asthma clinics without a training program and served as control group . Question naires regarding self-management aspects , coping and anxiety were filled out by patients , parents , family doctors and the training team prior to as well as twelve months after the training . The results indicate that Training group 1 benefitted most with respect to active asthma self-management , Training group 2 to some degree while the control group showed no significant effects . The differences after one year between the three groups regarding physical parameters such as lung-function and days missed in school did not reach the level of significance . Our results indicate that the long-term efficacy of self management courses for asthmatic children is enhanced by regular follow-up training sessions BACKGROUND Previous studies have shown that asthma education and case management may reduce asthma emergency care , hospitalizations , and expenditures . OBJECTIVE We sought to study the effect of an asthma outreach program ( AOP ) , a team-based , case-management intervention , on emergency ward ( EW ) and hospital use . METHODS Fifty-seven patients aged 1 to 15 years with the diagnosis of asthma based on the usual clinical practice criteria who were continuously enrolled in a staff-model health maintenance organization for a period of at least 2 consecutive years were r and omized into 2 intervention groups . The control group received a single intensive asthma education intervention , and the AOP group received the same initial education but then was followed-up by an asthma case management nurse throughout the intervention period . RESULTS EW visits , hospitalizations , and total outside-of-health-plan expenditures ( consisting of EW and hospital expenses , as well as miscellaneous costs , such as ambulance , durable medical equipment , tertiary referrals , and home care ) were assessed from cl aims filed for a year before and after enrollment . Control group patients experienced significant reductions in EW visits ( 39 % ) , hospitalizations ( 43 % ) , and outside-of-health-plan costs ( 28 % ) , possibly as a result of the baseline educational intervention received by all enrolled patients , in conjunction with regression to the mean . AOP group patients experienced significant reductions in EW visits , ( 73 % , P = .0002 ) , hospitalizations ( 84 % , P = .0012 ) , and outside-of-health-plan use ( 82 % , P < .0001 ) . When compared with the control group , AOP group patients demonstrated additional significant reductions in EW visits ( 57 % , P < .05 ) , hospitalizations ( 75 % , P < .05 ) , and outside-of-health-plan use ( 71 % , P < .001 ) . Estimates of direct savings to the health plan ranged from $ 7.69 to $ 11.67 for every dollar spent on the AOP nurse 's salary , depending on assumptions . CONCLUSIONS Asthma patients in a staff-model health maintenance organization decreased their re source use between 57 % to 75 % by participation in an AOP as compared with a r and omized control group receiving only an educational intervention . Substantial savings were achieved compared with the cost of the AOP nurse A research project , which looks at the value of health education in the prevention of childhood asthma , is described . The project was a controlled trial by a health visitor focused within the community . This exploratory research looked at three groups of children over a 2-year period , and compared the effect of : ( a ) individual health education , and ( b ) group health education . During the first year , two groups were active , one receiving individual health education , the other collecting data of the same type . During the second year , a third group was involved in health education sessions . The findings have been similar in both cases , in that both groups have demonstrated a good improvement in knowledge of asthma and its treatment . Through the active involvement of using a peakflow meter and diary records in the health education programme , both groups receiving health education have shown a significant improvement in the morbidity indicators related to night symptoms and restricted activities . The qualitative analysis of the research also highlighted the value parents of asthmatic children place on counselling Our purpose was to examine school‐age children 's self‐reports of characteristics of their asthma episodes including the precipitating events , symptoms experienced during the episodes , and interventions used to resolve the episodes . Children 's self‐reports of their asthma episodes were assessed over a 6‐week period for 42 children with persistent asthma who participated in a r and omized , controlled clinical trial to evaluate the efficacy of an asthma self‐management program on adherence to recommended daily peak expiratory flow rate monitoring . Children were instructed to answer the following questions on the Asthma Report Form each time they experienced an asthma episode : 1 ) What were you doing ; 2 ) How did you feel ; and 3 ) What did you do to help your breathing ? Of the children , 71 % experienced at least one asthma episode during the 6 weeks . There were a total of 206 episodes . Physical activity ( 51 % ) was the most cited trigger , cough alone or combined with other symptoms ( 84 % ) was the predominant symptom , and rescue asthma medication ( 59 % ) was identified most often as the intervention used by the children to resolve the asthma episode . Children 's self‐reports provided valuable information about their asthma episodes . The finding that most of the children experienced at least one asthma episode during the 6‐week period underscores the importance of family education on how to h and le asthma episodes effectively at home . Because physical activity was cited most often as a trigger for asthma episodes , families should receive education on preventive steps for averting an asthma episode prior to the child engaging in physical activity AIMS To determine the effect of introducing an action plan to children with mild to moderate asthma , who have never used a plan before . METHODS Children were recruited from general practitioner records with a diagnosis of asthma , and who agreed to participate , having identified that they had not used an action plan before and that they had mild or moderate asthma based upon symptoms , acute episodes and the need for preventative medication . The families were given a plan , and its use was explained to them by their general practitioner . A symptom diary was kept , and , where appropriate , peak flow measurements were recorded . A number of outcomes were measured to determine changes that could be attributed to the introduction of the plan . RESULTS Following the introduction of the plan , the percentage of nights woken for asthma fell from 18.2 % to 12.2 % ( P<0.001 ) and the number of days out of action fell from 6.4 to 4.1 ( P<0.001 ) . The requirement for acute medical treatment also fell during the intervention period with general practitioner visits falling from 129 to 42 ( p<0.001 ) . Most participants commented favourably about the usefulness of the plan in giving them a better idea of the state of their asthma at any time , and in knowing what to do about it . CONCLUSIONS The children 's action plan , when introduced into a group of asthmatic children was effective and acceptable in the self management of asthma BACKGROUND A decision to implement innovative disease management interventions in health plans often requires evidence of clinical benefit and financial impact . The Pediatric Asthma Care Patient Outcomes Research Team II trial evaluated 2 asthma care strategies : a peer leader-based physician behavior change intervention ( PLE ) and a practice -based re design called the planned asthma care intervention ( PACI ) . OBJECTIVE To estimate the cost-effectiveness of the interventions . METHODS This was a 3-arm , cluster r and omized trial conducted in 42 primary care practice s. A total of 638 children ( age range , 3 - 17 years ) with mild to moderate persistent asthma were followed up for 2 years . Practice s were r and omized to PLE ( n = 226 ) , PACI ( n = 213 ) , or usual care ( n = 199 ) . The primary outcome was symptom-free days ( SFDs ) . Costs included asthma-related health care utilization and intervention costs . RESULTS Annual costs per patient were as follows : PACI , USD 1292 ; PLE , USD 504 ; and usual care , USD 385 . The difference in annual SFDs was 6.5 days ( 95 % confidence interval [ CI ] , -3.6 to 16.9 days ) for PLE vs usual care and 13.3 days ( 95 % CI , 2.1 - 24.7 days ) for PACI vs usual care . Compared with usual care , the incremental cost-effectiveness ratio was USD 18 per SFD gained for PLE ( 95 % CI , USD 5.21-dominated ) and USD 68 per SFD gained for PACI ( 95 % CI , USD 37.36 - 361.16 ) . CONCLUSIONS Results of this study show that it is possible to increase SFDs in children and move organizations toward guideline recommendations on asthma control in setting s where most children are receiving controller medications at baseline . However , the improvements were realized with an increase in the costs associated with asthma care A sample of 310 low income urban children with asthma from 290 families was r and omized into a control group and an experimental group that received health education to improve asthma management at home . No significant decreases in subsequent health care use were observed when the experimental group was compared to the control group without regard to previous hospitalization . When the comparison was restricted to children who had been hospitalized during the preceding year , however , the experimental group was found to have decreased its use of the emergency room significantly more than the control group ( p less than 0.05 ) and to have experienced a significantly greater reduction in the mean number of hospitalizations ( p less than 0.05 ) during the year of follow-up . The program reduced health care costs for children with one or more hospitalizations , saving $ 11.22 for every $ 1.00 spent to deliver health education OBJECTIVE To assess the impact of an asthma management program on the dispensing of inhaled corticosteroids , hospitalizations , and emergency department ( ED ) visits on children , adolescents , and young adults . DESIGN We used medical record and pharmacy data for the 18 months after initiation of a pilot asthma management program . Two intervention offices were matched with 2 control offices on pediatric volume , number of pediatricians or family practitioners , and specialist availability . SETTING Primary care offices at Kaiser Permanente Colorado , in Denver and Boulder . PATIENTS We identified 298 patients , 18 years or younger , who were listed in an asthma registry between February 1 and July 31 , 1997 , as having moderate or severe asthma . INTERVENTION The Kaiser Permanente Colorado Asthma Care Management Program is an outpatient-based program that provides comprehensive evaluation , education , and follow-up to patients identified from an asthma registry or referred by providers . MAIN OUTCOME MEASURES The proportion of patients who received more than 1 dispensing of inhaled corticosteroid during the observation period . Additional outcomes measured the proportion of patients with 1 or more hospitalizations or ED visits . RESULTS A significantly greater proportion of patients from the intervention group received more than 1 dispensing of inhaled corticosteroid compared with controls ( relative risk [ RR ] , 1.41 ; 95 % confidence interval [ CI ] , 1.08 - 1.72 ) . We found no significant difference in the proportion of patients who were hospitalized ( RR , 1.37 ; 95 % CI , 0.48 - 3.71 ) or visited the ED ( RR , 0.86 ; 95 % CI , 0.49 - 1.40 ) . CONCLUSIONS The presence of an asthma management program may improve dispensing of inhaled corticosteroids to young patients with moderate or severe asthma , as recommended by national guidelines . This type of program may not have an effect on hospitalizations or ED visits OBJECTIVE To evaluate a family-focused asthma intervention design ed for inner-city children 5 to 11 years old with moderate to severe asthma . STUDY DESIGN R and omized , multisite , controlled trial to minimize symptom days ( wheeze , loss of sleep , reduction in play activity ) measured by a 2-week recall assessed at 2-month intervals over a 2-year follow-up period . The intervention was tailored to each family 's individual asthma risk profile assessed at baseline . RESULTS Averaged over the first 12 months , participants in the intervention group ( n = 515 ) reported 3.51 symptom days in the 2 weeks before each follow-up interview compared with 4.06 symptom days for the control group ( n = 518 ) , a difference of 0.55 ( 95 % CI , 0.18 to 0.92 , P = .004 ) . The reduction among children with severe asthma was approximately 3 times greater ( 1.54 d/2 wk ) . More children in the control group ( 18.9 % ) were hospitalized during the intervention compared with children in the intervention group ( 14 . 8 % ) , a decrease of 4.19 % ( CI , -8.75 to 0.36 , P = .071 ) . These improvements were maintained in the intervention group during the second year of follow-up , during which they did not have access to the asthma counselor . CONCLUSIONS We demonstrated that an individually tailored , multifaceted intervention carried out by Masters-level social workers trained in asthma management can reduce asthma symptoms among children in the inner city An educational program for children with asthma design ed to reduce emergency room ( ER ) use enrolled all eligible children ( n = 253 primarily low-income Black ) within a health maintenance organization ( HMO ) who had used the hospital or ER for asthma during the pre-enrollment period and r and omized them into two groups . Twenty-four of the experimental group patients had 55 ER visits and 18 of the control patients had 39 ER visits during the first 12 months post-intervention . This program did not achieve its goal PURPOSE Adherence to peak expiratory flow rate monitoring by children with asthma was evaluated , and a behavioral strategy to enhance adherence to daily monitoring was tested . DESIGN AND METHODS Forty-two 7- through 11-year-old children with persistent asthma were recruited into a 5-week r and omized , controlled clinical trial . Adherence data were collected electronically by PeakLog and the self-report Asthma Diary . RESULTS Adherence declined over time . At week 5 , intervention group adherence ( Median = 79 % ) was higher than the usual care group adherence ( Median = 64 % ) , but the difference was not statistically significant . The effect size did suggest that differences between groups were present . CONCLUSIONS Even small improvements in adherence to asthma treatment may be clinical ly significant in light of the alarming increases in asthma morbidity and mortality . Contingency management shows promise for improving adherence outcomes . Future research should engage larger sample sizes and increase the number and intensity of sessions to teach behavioral strategies Asthma care management programs may improve outcomes , but it is not clear which aspects of such management are responsible for the improvement . We performed a r and omized controlled trial of a limited intervention ( one visit with asthma self-management education and provision of inhaled budesonide ) compared to this visit plus regular asthma care manager follow-up . Quality of life , symptom-free days , emergency hospital care , and beta-agonist dispensings did not differ between groups at 12 months . Patients who entered the study did receive significantly less beta-agonists in the follow-up year than patients who did not enter the study . These data suggest that the limited intervention in our setting improved outcomes but that regular care manager follow-up thereafter did not add significantly to this intervention Computer-based education in schools is not novel . However , only a few computer games have been introduced into school-based health education programs . This study describes inclusion of an asthma education space adventure game into fourth- grade classrooms . Using the game improved asthma knowledge in the intervention classes . Children in the active participation classroom gained significantly more asthma knowledge over the observation period compared to the classroom that did not play the computer game . Knowledge gained was retained over a four-week period and the addition of physician-led talks appeared to add little to the knowledge gained . " Air Academy : The Quest for Airtopia " is an easy and successful tool for elementary grade asthma-related health education in schools BACKGROUND Inhaled medications are the mainstay of asthma therapy , but significant deficiencies exist in the knowledge and skills of physicians regarding use of metered-dose inhalers ( MDI ) and spacer devices . OBJECTIVE We developed , implemented , and evaluated the effects of a physician-targeted educational program on inhaled therapy in a group of pediatric residents in our institution . METHODS Patient-directed instruction sheets on aerosol therapy were developed on the basis of literature review and expert guidelines . These served to establish a consistent foundation for the educational curriculum . The program was delivered through one-on-two teaching sessions ( 45 minutes ) . Residents were provided with a summary of theoretical and practical information and with devices for practice ( a placebo MDI , InspirEase and AeroChamber holding chambers , and the AeroChamber device with mask ) . Each session included review of an educational monograph , demonstration of proper technique , and practice with the different devices . The program was evaluated by a r and omized-control design . Assessment of practical skills included number of correct steps for the use of MDI ( maximum score , 7 ) , InspirEase ( maximum , 7 ) and AeroChamber ( maximum , 6 ) . Theoretical knowledge was assessed with 25 multiple-choice questions . RESULTS Pretest scores in the experimental group ( n = 24 ) were 3.7 of 7 , 1.9 of 7 , and 0.3 of 6 steps correct for MDI , InspirEase , and AeroChamber devices , respectively , and 13 of 25 for the theoretical knowledge assessment . The control group ( n = 26 ) had similar pretest scores . After the program the experimental group significantly improved in all parameters : 6.3 of 7 , 5.9 of 7 , and 4.5 of 6 steps correct for MDI , InspirEase , and AeroChamber devices , respectively , and 18 of 25 questions correct ( p < 0.01 for all parameters ) . CONCLUSIONS Implementation of a simple educational program among pediatric residents can significantly increase their skills in the use of inhalational therapy We hypothesized that an educational intervention based on a readiness model would lead to improved health outcomes among patients with asthma . Within a r and omized control design in an urban Latino and African-American community , we conducted an intensive three-month pediatric intervention . A Family Coordinator provided patient education based on a readiness-to-learn model , and facilitated improved interactions between the patient and the doctor . Family education addressed the most basic learning needs of patients with asthma by improving their perception of asthma symptom persistence using asthma diaries and peak flow measures . The physician intervention focused clinicians ’ attention on patients ’ diary records and peak flow measures , and encouraged physicians to use stepped action plans . Patients were also tested for allergic sensitization and provided strategies to reduce contact with allergens and other asthma triggers . The results showed significant improvements by intervention group families on measures of knowledge , health beliefs , self-efficacy , self- regulatory skill , and adherence ; decreases in symptom persistence and activity restriction ; and increased prescription of anti-inflammatory medication by the physicians of the intervention group families OBJECTIVE --To determine whether an intervention programme based on existing school and community re sources can reduce school absence and improve participation in games lessons and sport in children with unrecognised or undertreated asthma . DESIGN --Parallel group controlled intervention study . SETTING --102 primary schools in Nottingham : 49 were r and omised to receive the intervention and 53 to be control schools . SUBJECTS -- All children aged 5 to 10 years with parent reported absence from school because of wheezing in the previous year and taking no treatment or beta agonists only . INTERVENTIONS --Children with asthma were referred to their general practitioner for assessment of symptoms and treatment . Teachers were given education on asthma by the school nurse in 44 of the 49 intervention schools . MAIN OUTCOME MEASURES --Changes in school absence and missed games and swimming lessons because of wheezing , and schools ' policy towards management of asthma in school . RESULTS --Of 17,432 children screened , 451 met the entry criteria --228 in intervention schools and 223 in control schools . 152 ( 67 % ) children in intervention schools visited their general practitioner , of whom 39 ( 26 % ) were given a new diagnosis of asthma and 58 ( 38 % ) had treatment for asthma increased or changed . Over the next academic year mean ( SE ) parent reported school absence due to wheezing fell significantly , but to a similar extent , in both intervention and control schools ( 0.82 ( 0.11 ) and 1.09 ( 0.21 ) weeks respectively ) . There was little change in school recorded absence or participation in games lessons and swimming lessons in either group . At the end of the study intervention schools were more likely to have improved aspects of management of asthma in school . CONCLUSION --The intervention result ed in a majority of children being assessed by their general practitioner and improved teachers ' underst and ing and management of asthma , but it did not result in any appreciable reduction in morbidity Abstract Twenty-one asthmatic children , aged 15 months to 13 years and from low-income families , who used the emergency room as their primary source of asthma care , were evaluated by the physicians of the Pediatric Allergy Division at baseline . These children were then r and omly assigned to either a control group or a clinical nurse specialist group . All children were scheduled for follow-up in the hospital clinic with pediatric residents and staff ( control group ) or with the clinical nurse specialist ( CNS ) . After assessing individual family needs , the CNS counseled each family regarding preventive health measures , focusing on early recognition of asthma exacerbations and self-care . During the 12-month study period , the frequency of allergy physician contacts and the total number of outpatient department visits were similar in both groups . However , compared with the 12-month period prior to enrollment , the CNS group subjects demonstrated a significant reduction in the frequency of emergency room ( ER ) visits ( 2.6 ± 1.1 versus 0.6 ± 0.9 ER visits per patient ; Asthma is a common , costly , and chronic disease that has a significant impact on children , their families , and the health care system . This study investigated whether formal asthma education can reduce asthma severity and morbidity and further question ed whether the method of education is an important factor in this process . Study subjects were recruited from the emergency department of the Royal Children 's Hospital , Melbourne ( RCHM ) , and controls were recruited from the neighboring Western Hospital , Sunshine ( WHS ) . Subject parents were r and omized to receive face-to-face education , group education , or home-based video education . Controls had similar medical treatment but received no formal asthma education . Subject and control parents were asked to complete question naires before the intervention and at 1 , 6 , and 12 months . These question naires measured demographics , the levels of parent asthma knowledge , anxiety , child asthma severity , and morbidity . Results showed that any method of education increased parent asthma knowledge and immediately decreased their anxiety and child asthma morbidity scores . Despite this , asthma severity was reduced only when knowledge was imparted in an interactive , face-to-face setting . When this happened , asthma severity scores were significantly reduced in both the short- and long-term . These findings call into question mass asthma education campaigns and have important implication s for the design of future asthma education programs OBJECTIVE To assess whether efforts to actively involve General Practitioners ( GPs ) in the postdischarge care of their paediatric asthma patients improved their satisfaction with communication with hospital staff . METHODOLOGY R and omized controlled trial involving 60 patients admitted to the Royal Children 's Hospital , Melbourne , with acute asthma and an identifiable GP . The GPs of the intervention patients were telephoned during the admission . Intervention patients and their GPs received printed information detailing the care the patient received in hospital and the recommended postdischarge care , as well as st and ardized educational booklets about asthma . Follow-up appointments were made for intervention patients to attend their GPs . RESULTS The GPs of intervention patients were more satisfied when compared to the GPs receiving a st and ard level of communication ( 96.4 % vs 48.3 % of the intervention and control GPs , respectively , described the communication as good or extremely good , P = 0.0001 ) . The intervention group GPs believed they were more involved after discharge ( 75.0 % vs 44.8 % , P = 0.005 ) and had greater underst and ing of their patient 's hospitalisation ( 96.4 % vs 62.1 % , P = 0.005 ) . These differences were noted despite there being no difference in the rate of follow-up attendance with GPs for intervention and control patients ( 85.7 % vs 72.4 % , P = 0.2 ) . Qualitative data supported these findings with GPs expressing approval of the intervention used . CONCLUSION Efforts to actively involve GPs in the postdischarge care of their paediatric patients with asthma result ed in a marked improvement in their satisfaction with the communication with medical staff at the Royal Children 's Hospital , Melbourne . The study had insufficient power to demonstrate a difference in morbidity Although airway disease in preschool children is common , st and ard spirometry is limited by the level of cooperation . We evaluated a computer-animated system ( SpiroGame ) aim ed at improving children 's performance in spirometry . SpiroGame includes a commercial pneumotachograph ( ZAN100 ; ZAN Messgeraete GmbH , Oberthulba , Germany ) and games teaching tidal breathing and all steps of an FVC maneuver . SpiroGame was compared with commercial flow-targeted c and le-blowing software ( MasterLab , Jaeger , Germany ) , and with extrapolated predicted values . Of 112 children aged 3 to 6 yr , 10 refused spirometry and 102 proceeded to FVC games and were r and omized to initially perform either SpiroGame or c and le-blowing . Training lasted 5 to 10 min for SpiroGame and 3 to 7 min for c and le-blowing . Acceptable spirometry was performed by 69 of 102 children with SpiroGame and 48 of 102 with c and le-blowing ( p = 0.005 ) . Order did not affect success . Acceptable FEV(1 ) maneuvers were achieved by 55 children with SpiroGame and two children with c and le-blowing . The intrasubject coefficient of variation was 4.0 % for FVC and 3.3 % for FEV(1 ) with SpiroGame . A premature expiratory break occurred in 41 subjects with c and le-blowing and in six with SpiroGame . FEV(0.5 ) could be measured with both systems . FVC and maximal midexpiratory flow at 50 % of FVC ( MMEF(50 ) ) values were similar , whereas peak expiratory flow was higher with c and le-blowing . In 39 healthy children , most parameters with SpiroGame were similar to extrapolated normal values . We conclude that an interactive computer-animated system facilitates successful spirometry in preschool children Background : The management of childhood asthma necessitates a comprehensive approach including pharmacological treatment as well as education about self‐evaluation and home management of the condition . Aim : To evaluate the efficacy of adding an individualized written home‐management plan in the control of moderate persistent asthma . Methods : Children with moderate persistent asthma were r and omized to receive either an individualized written home‐management plan or no plan , in addition to st and ard asthma therapy including education . They were followed up with serial measurement of outcome variables . Results : Children receiving an individualized written home‐management plan had fewer acute asthma events , fewer lost school days , lower symptom score and less nocturnal awakening than those who did not receive a written plan A r and omized control trial of the Wee Wheezers asthma education program was conducted with 76 children < 7 years of age , 31 % of whom were on a medication regimen consistent with mild , 51 % with moderate , and 18 % with moderately severe/severe asthma . Treatment children showed improved morbidity at 3-month follow-up relative to the changes in the controls : increased symptom-free days in the preceding 2 weeks ( mean change of + 2.2 vs. -2.6 in the controls ; p = .004 ) and month ( + 2.0 vs. -3.8 ; p < .02 ) , fewer nights of parental sleep interruption in a typical week ( + 0.7 vs. + 1.8 ; p < or = .05 ) , and a trend toward fewer asthma sick days ( -0.2 vs + 0.7 ; p = ns ) . These improvements were accompanied by significantly better parental asthma management compared with controls ( more consistent use of preventive medications , p < or = .01 ; early symptom intervention , [ corrected ] p < or = .05 ) and trends toward more restrictions on smoking in the home ( p < .07 ) and decreased parental confusion about asthma treatment ( p < .11 ) . This study provides evidence that a multisession program of asthma education for parents can improve parental asthma management and clinical outcomes in very young children and provides information on the validity and sensitivity of various asthma outcome measures in this age group This study evaluated the benefits produced by " Superstuff " , a self-help program for asthmatic children aged 7 - 12 . Forty-three children with a confirmed diagnosis of moderate to severe asthma were r and omly assigned to either the totally self-administered Superstuff condition or to a nocontact Control condition . Self-report , parental , physician , and school data were collected at pre-intervention , and two , six , and twelve months post-intervention . Children receiving Superstuff reported increased asthma self-control skills , but no gains in general self-control abilities or self-esteem . Superstuff subjects also evidence d fewer interruptions of parents , greater improvement in the progression of asthma as reported by physicians ( but not in the severity of the disease or intensity of average attack ) , and tended toward decreased school absenteeism . Superstuff did not reduce scheduled or emergency medical contacts . The demonstration of important , but modest , benefits from a low-cost , easily disseminated , self-administered intervention is discussed in the context of self-help treatment in general To evaluate the effectiveness of a comprehensive asthma management education program for 7- to 12-year-old children with asthma , entitled Roaring Adventures of Puff ( RAP ) , 18 elementary schools in Edmonton were r and omized to intervention and control groups . Participating in the program were 76 students with asthma in the intervention schools and 86 in the control schools . Children in the intervention schools had statistically significant improvements in unscheduled doctor visits , missed school days , moderate-to-severe parent rating of severity , severity of shortness of breath , limitations in the kind of play , and correct use of medications . Unscheduled doctor visits and missed school days were the only significant improvements in the control group ; however , improvements were about half that of the intervention group . The results showed that a comprehensive , school-based asthma education program is feasible and improves outcomes OBJECTIVES Follow-up with a primary care provider ( PCP ) is recommended after an emergency department ( ED ) visit for asthma to assess clinical status and develop a management plan to improve future care . However , previous ED-based studies of urban children with asthma have reported low follow-up rates . The objective of this study was to determine whether scheduling an appointment at the time of an ED visit improves PCP follow-up for urban children . A secondary goal was to assess the effect of this intervention on short-term health outcomes and the use of recommended preventive controller medications . METHODS This r and omized trial enrolled a convenience sample of children who were 2 to 18 years old and discharged after treatment for acute asthma in an urban children 's hospital ED . Both intervention and control subjects were instructed to follow up with their PCP within 3 to 5 days . Study staff assisted intervention subjects to call their PCP from the ED and schedule an appointment . When follow-up could not be scheduled , assistance continued after ED discharge by telephone until an appointment date was confirmed . Study outcomes included PCP visits , asthma-related morbidity , and daily use of preventive medication 4 weeks after the ED visit . Outcomes were assessed by telephone interview and confirmed by PCP record review . RESULTS A total of 278 eligible subjects were enrolled over 8 months ; intervention and control groups were similar by demographic variables and PCP type as well as by asthma history , symptoms , and previous medication use . Only 38 % of subjects reported using a daily controller medication , although 70 % described persistent asthma symptoms for which these are recommended . For the intervention group , follow-up appointments were successfully obtained during the ED visit for 24 % of subjects ; when unsuccessful , a median of 3 telephone calls ( range : 1 - 14 ) were needed to confirm that an appointment had been scheduled . During the 4 weeks after the ED visit , intervention subjects were more likely than controls to follow up with their PCP ( 64 % vs 46 % ; relative probability for follow-up : 1.4 ; 95 % confidence interval : 1.1 - 1.7 ) . Study groups did not differ in return ED visits , missed school or work , or the percentage reporting daily use of a controller medication ( 58 % vs 54 % ) 4 weeks after the ED visit . The median time to the next PCP visit was shorter among intervention subjects ( 13 vs 54 days ) . CONCLUSIONS Scheduling an appointment after an ED visit increased the likelihood that urban children with asthma would follow up with a PCP . An appointment could not be obtained during the ED visit for most children . Other interventions are needed to improve linkage between ED and primary care for asthma and to improve the use of controller medications OBJECTIVE To determine whether an integrated care pathway ( ICP ) could improve care delivered to patients coming to an emergency department only or to patients who were subsequently admitted . STUDY DESIGN Children ( age , 2 - 16 years ; n = 298 ) coming to the ED with acute asthma/wheeze , were r and omized by using a cluster design to either st and ard care or care delivered by an ICP . RESULTS Children discharged from the ED who received care with an ICP ( n = 118 ) received more prednisolone ( 81 % ; st and ard , 63 % ; P = .03 ) and increased advice to obtain primary care review ( 72 % ; st and ard , 33 % ; P < .0001 ) . A total of 180 children were admitted ( 94 ICP , 86 st and ard ) . The rate of recovery was unchanged by ICP . The mean ICP length of stay ( 37.6 hours ; range , 33.5 - 42.4 hours ) , was 93 % of the mean st and ard length of care ( 40.7 hours ; range , 35.9 - 46 ; P = .36 ) . When a discharge checklist was completed ( 60 of 94 cases ) , the mean ICP length of stay was 34.2 hours ( range , 30.5 - 38.4 hours ; P = .07 versus st and ard ) . An ICP result ed in a 30 % reduction in prescribing errors ( mean , 10.4 ; st and ard , 14.8 ; P = .002 ) . Eighty-four of 94 children with an ICP received a 48-hour discharge plan ( 89 % ) versus 35 of 86 children with st and ard care ( 41 % ) . More clinical contacts were observed in children receiving care by an ICP ( mean , 22 , versus st and ard , 19.2 : P = .0004 ) . CONCLUSION An acute asthma/wheeze ICP improved education and prescribing errors , modestly reduced the length of stay when discharge criteria were adhered to , but did not influence recovery time . Further consideration of the effect on staff workload is required BACKGROUND . Uninsured children with asthma are known to face barriers to asthma care , but little is known about the impact of health insurance on asthma care . OBJECTIVES . We sought to assess the impact of New York 's State Children 's Health Insurance Program ( SCHIP ) on health care for children with asthma . DESIGN . Parents of a stratified r and om sample of new enrollees in New York 's SCHIP were interviewed by telephone shortly after enrollment ( baseline , n = 2644 [ 74 % of eligible children ] ) and 1 year later ( follow-up , n = 2310 [ 87 % ] ) . Asthma was defined by parent report using questions based on National Heart , Lung , and Blood Institute criteria . A comparison group ( n = 401 ) who enrolled in SCHIP 1 year later was interviewed as a test for secular trends . MAIN OUTCOME MEASURES . Access ( having a usual source of care [ USC ] , unmet health needs , problems receiving acute asthma care ) , asthma-related medical visits , quality ( continuity of care at the USC , problems receiving chronic asthma care , use of antiinflammatory medications ) , and asthma outcomes ( change in asthma care or severity ) were the main outcome measures used . Bivariate and multivariate analyses compared measures at baseline ( year before SCHIP ) versus follow-up ( year during SCHIP ) . RESULTS . Three-hundred eighty-three children ( 14 % ) had asthma at baseline , and 364 had asthma at follow-up ( 16 % ) . No secular trends were detected between the baseline study group and the comparison group . After enrollment in SCHIP , improvements were noted in access : lacking a USC ( decrease from 5 % to 1 % ) , unmet health needs ( 48 % to 21 % ) , and problems getting to the USC for asthma ( 13 to 4 % ) . Children had fewer asthma-related attacks and medical visits after SCHIP ( mean number of attacks : 9.5 to 3.8 : mean number of asthma visits : 3.0 to 1.5 ; hospitalizations : 11 % to 3 % ) . Quality of asthma care improved for general measures ( most/all visits to USC : 53 % to 94 % ; mean rating of provider : 7.9 to 8.8 of 10 ) and asthma-specific measures ( problems getting to the USC for asthma care when child was well : 13 % to 1 % ) . More than two thirds of the parents at follow-up reported that both quality of asthma care and asthma severity were “ better or much better ” than at baseline , generally because of insurance coverage or lower costs of medications and medical care . CONCLUSIONS . Enrollment in New York 's SCHIP was associated with improvements in access to asthma care , quality of asthma care , and asthma-specific outcomes . These findings suggest that health insurance improves the health of children with asthma OBJECTIVE Recent studies have shown that lack of continuing primary care for asthma is associated with increased levels of morbidity in low-income minority children . Although effective preventive therapy is available , many African-American and Latino children receive episodic treatment for asthma that does not follow current guidelines for care . To see if access , continuity , and quality of care could be improved in pediatric clinics serving low-income children in New York City , we trained staff in New York City Bureau of Child Health clinics to provide continuing , preventive care for asthma . METHODS We evaluated the impact of the intervention over a 2-year period in a controlled study of 22 clinics . Training for intervention clinic staff was based on National Asthma Education and Prevention Program guidelines for the diagnosis and management of asthma , and included screening to identify new cases and health education to improve family management . The intervention included strong administrative support by the Bureau of Child Health to promote staff behavior change . We hypothesized that after the intervention , clinics that received the intervention would , compared with control clinics , have increased numbers of children with asthma receiving continuing care in the clinics and increased staff use of new pharmacologic and educational treatment methods . RESULTS In both the first and second follow-up years , the intervention clinics had greater positive changes than control clinics on measures of access , continuity , and quality of care . For second year follow-up data these include : for access , greater rate of new asthma patients ( 40/1000 vs 16/1000 ; P < .01 ) ; for continuity , greater percentage of asthma patients returning for treatment 2 years in a row ( 42 % vs 12 % ; P < .001 ) and greater annual frequency of scheduled visits for asthma per patient ( 1.85 vs .88 ; P < .001 ) ; and for quality , greater percentage of patients receiving inhaled beta agonists ( 52 % vs 15 % ; P < .001 ) and inhaled antiinflammatory drugs ( 25 % vs 2 % ; P < .001 ) , and greater percentages of parents who reported receiving patient education on 12 topics from Bureau of Child Health physicians ( 71 % vs 58 % ; P < .01 ) and nurses ( 61 % vs 44 % ; P < .05 ) . CONCLUSION We conclude that the intervention substantially increased the Bureau of Child Health staff 's ability to identify children with asthma , involve them in continuing care , and provide them with state-of-the-art care for asthma |
10,441 | 25,907,504 | Simvastatin is contraindicated in the setting of protease inhibitor use because of toxic drug-drug interactions when the 2 drugs are taken concomitantly .
Meanwhile , atorvastatin appears to be relatively safe at submaximal doses if monitored .
Pravastatin , rosuvastatin , and pitavastatin appear to have the most benign safety profiles among statins when co-administered with ART and may not require dose adjustment . | HIV-infected patients have a greater prevalence of dyslipidemia , earlier incidence and progression of atherosclerosis , and a nearly twofold increased risk for myocardial infa rct ion compared with those not infected with HIV .
Pre-existing cardiovascular risk factors , viral replication , and antiviral treatments all contribute to this accelerated and increased risk for cardiovascular disease in HIV-infected subjects .
Given this risk and the proven benefit of statins reducing cardiovascular events across numerous patient groups , statin therapy might be particularly beneficial for patients with HIV .
However , safety concerns and a dearth of quality trial data evaluating clinical outcomes in HIV-infected patients on simultaneous antiretroviral therapy ( ART ) and statin therapy have likely limited statin use in HIV-infected patients chronically taking ART . | We conducted a pilot study to assess the effect of atorvastatin on HIV replication . Patients with stable HAART-controlled infection interrupted therapy and were r and omly assigned to a control group or to start atorvastatin 40 or 80 mg/day . Statin groups showed lower serum cholesterol but similar viral loads and CD4 T-cell counts to the control group at weeks 4 and 12 . Paradoxically , baseline serum cholesterol , but not atorvastatin , influenced viral rebound at week 4 OBJECTIVES Statins and fibrates alter lipids , apolipoproteins and inflammatory markers in persons without HIV . The objective of this study was to evaluate changes in lipoproteins , apolipoproteins and other markers of inflammation with the use of pravastatin and fenofibrate . DESIGN Evaluation of participants in ACTG A5087 , a r and omized trial of pravastatin 40 mg/day or fenofibrate 200 mg/day for the treatment of dyslipidemia . Participants that failed single-agent therapy at week 12 were given the combination . METHODS Participants with available specimens were tested for apolipoproteins A1 and B , adiponectin , plasminogen-activator inhibitor type 1 ( PAI-1 ) , P-selectin , and high-sensitivity C-reactive protein ( hs-CRP ) . RESULTS 74 participants ( 37 per r and omized arm ) received either pravastatin or fenofibrate for 12 weeks with 60 receiving combination treatment from weeks 12 - 48 . There were no significant changes in hs-CRP , PAI-1 , and P-selectin . From baseline to week 12 , the median Apo B levels (-8 mg/dL , P=0.01 for fenofibrate and -27 mg/dL , P<0.01 for pravastatin ) and ApoB/A1 ratios ( -0.16 , P<0.01 for both arms ) significantly decreased . From baseline to week 48 , median adiponectin ( -1 ng/dL , P<0.01 ) , Apo B ( -22 mg/dL , P<0.01 ) and Apo B/A1 ratios ( -0.2 , P<0.01 ) all decreased in those who went on combination therapy , whereas Apo A1 ( 9.5 mg/dL , P=0.01 ) levels increased . CONCLUSION Treatment with pravastatin or fenofibrate improves the atherogenic lipid profile within the first 12 weeks and is sustained through 48 weeks with combination therapy . Adiponectin levels decrease with lipid-lowering therapy . However , markers of inflammation and platelet activation were not appreciably changed suggesting that the biologic properties of these agents differ in persons with HIV infection Recent studies have shown that rosuvastatin significantly decreases serum levels of inflammatory biomarkers and slows progression of carotid atherosclerosis in the general population . However , there are no data about its effect on progression of atherosclerosis in HIV-infected patients . Adult patients with HIV infection , on stable antiretroviral therapy , with asymptomatic carotid atherosclerosis and hypercholesterolemia , who started a rosuvastatin treatment at 10 mg daily during the period 2007 - 2009 were enrolled and followed-up for 24 months . Thirty-six patients ( 30 males ) were enrolled , with a mean age of 49 years , a mean duration of current antiretroviral therapy of 38 months , and a mean 10-year risk of myocardial infa rct ion of 18.5 % . Rosuvastatin led to a significant decrease in mean values of intima-media thickness in all extracranial carotid arteries , with the greatest magnitude observed in carotid bifurcations ( a mean decrease of 18.7 % in the right artery and of 21.4 % in the left artery ) and in internal carotid arteries ( a mean decrease of 23.7 % in the right artery and of 25.6 % in the left artery ) . Moreover , there was a significant reduction in mean levels of total cholesterol , low-density lipoprotein ( LDL ) cholesterol , and triglycerides versus respective baseline values associated with a significantly decreased mean cardiovascular risk . The treatment with rosuvastatin was well tolerated , and serious adverse events were not reported . A 24-month treatment with rosuvastatin in HIV-infected patients on highly active antiretroviral therapy ( HAART ) with sub clinical atherosclerosis and a moderate cardiovascular risk seems to promote significantly favorable changes in carotid atherosclerosis , associated with a favorable effect on serum lipid levels and a good tolerability profile BACKGROUND Lipoatrophy can complicate thymidine analogue nucleoside reverse transcriptase inhibitor (tNRTI)-based antiretroviral therapy ( ART ) . Lipoatrophy may be less likely with ART including ritonavir-boosted lopinavir ( LPV/r ) . Small , placebo-controlled studies found that uridine ( in tNRTI recipients ) and pravastatin improved HIV lipoatrophy over 12 weeks . Today , most patients with lipoatrophy receive non-tNRTI-based ART ; the effect of uridine in such patients is unknown . METHODS We performed a prospect i ve , r and omized trial in lipoatrophic adults with plasma HIV RNA<50 HIV-1 RNA copies/mL on tNRTI-sparing ART including LPV/r . Patients received uridine [ 36 g three times a day ( tid ) on 10 consecutive days per month ; n=10 ] , pravastatin [ 40 mg every night ( nocte ) ; n=12 ] , uridine plus pravastatin ( n=11 ) or neither ( n=12 ) for 24 weeks . The primary endpoint was mean change in limb fat mass as assessed by dual-energy X-ray absorptiometry ( DEXA ) . With 20 patients per intervention , the study had 80 % power to detect a mean difference between a treatment and the control of 0.5 kg , assuming a st and ard deviation of 0.9 and an alpha threshold equal to 5 % ( two-sided ) . RESULTS Of 45 participants ( all men , with median age 49.5 years and median limb fat 2.6 kg ) , two discontinued pravastatin and one participant stopped both pravastatin and uridine . The difference between the mean changes in limb fat mass for uridine vs. no uridine was 0.03 kg [ 95 % confidence interval ( CI ) -0.35 , + 0.28 ; P=0.79 ] . The respective difference for pravastatin was -0.03 kg ( 95 % CI -0.29 , + 0.34 ; P=0.84 ) . Pravastatin slightly decreased total cholesterol ( 0.44 mmol/L ; P=0.099 ) . Visceral adipose tissue measured by computed tomography did not change significantly . CONCLUSION In this population and at the doses used , neither uridine nor pravastatin for 24 weeks significantly increased limb fat mass BACKGROUND AND OBJECTIVE We investigated atorvastatin effectiveness and tolerance in HIV patients with hypercholesterolemia related to antiretroviral treatment . PATIENTS AND METHOD Prospect i ve study that included HIV+ patients under antiretroviral treatment who displayed secondary dyslipemia and medical treatment criteria ( according to NCEP-III ) . These patients were given 10 mg/day atorvastatin and hygienic-dietetic measures . If the therapeutic objectives were not achieved , the dose of atorvastatin was increased to 20 mg/day . Patients were followed up for 6 months . RESULTS 32 patients were included . In 5 cases it was necessary to increase the dose from 10 mg atorvastatin to 20 mg . The therapeutic objective was obtained in 62 % cases , with a good clinical tolerance . Only one adverse effect was noticed , which forced the removal of the drug . CONCLUSION In our study atorvastatin was effective for the treatment of dyslipemia in HIV patients , and it was safe and well tolerated Efavirenz ( EFV ) is associated with hyperlipidemia when used in combination with other antiretroviral drugs . EFV is a mixed inducer/inhibitor of cytochrome P450 ( CYP ) 3A4 isozyme and may interact with hydroxymethylglutaryl coenzyme A ( HMG-CoA ) reductase inhibitors that are primarily metabolized via CYP3A4 . To assess the drug-drug interaction of EFV used in combination with simvastatin ( SIM ) , atorvastatin ( ATR ) , or pravastatin ( PRA ) , an open-label trial was conducted in 52 healthy adult HIV-seronegative subjects across AIDS Clinical Trials Group sites in the United States . Subjects received 40 mg of SIM , 10 mg of ATR , or 40 mg of PRA daily on days 0 through 3 and days 15 through 18 . EFV was administered daily at a dose of 600 mg on days 4 through 18 . SIM , ATR , and PRA concentrations were determined before and after EFV , and EFV concentrations were determined before and after statins . EFV reduced SIM acid exposure ( area under the curve at 0 to 24 hours [ AUC0 - 24h ] ) by 58 % ( Wilcoxon signed rank test , P = 0.003 ) and active HMG-CoA reductase inhibitory activity by 60 % ( P < 0.001 ) . EFV reduced ATR exposure by 43 % ( P < 0.001 ) and the total active ATR exposure by 34 % ( P = 0.005 ) . EFV administration result ed in a 40 % decrease in PRA exposure ( P = 0.005 ) . SIM , ATR , and PRA had no effect on non-steady-state EFV concentrations . In conclusion , EFV , when administered with SIM , ATR , or PRA , can result in significant induction of statin metabolism . The reduced inhibition of HMG-CoA reductase activity during coadministration of EFV may result in diminished antilipid efficacy at usual doses of SIM , ATR , and PRA Background Treatments that reduce inflammation and cardiovascular disease ( CVD ) risk among individuals with HIV infection receiving effective antiretroviral therapy ( ART ) are needed . Design and Methods We conducted a 2 × 2 factorial feasibility study of lisinopril ( L ) ( 10 mg daily ) vs L-placebo in combination with pravastatin ( P ) ( 20 mg daily ) vs P-placebo among participants receiving ART with undetectable HIV RNA levels , a Framingham 10 year risk score ( FRS ) ≥3 % , and no indication for ACE-I or statin therapy . Tolerability and adherence were evaluated . Longitudinal mixed models assessed changes in blood pressure ( BP ) , blood lipids , and inflammatory biomarkers from baseline through months 1 and 4 . Results Thirty-seven participants were r and omized and 34 [ lisinopril/pravastatin ( n = 9 ) , lisinopril/P-placebo ( n = 8) , L-placebo/pravastatin ( n = 9 ) , L-placebo/P-placebo ( n = 8) ] attended at least one follow-up visit . Participants were 97 % male , 41 % white , 67 % were current smokers , and 65 % were taking a protease inhibitor . Median age was 48 years , CD4 count 483 cells/mm3 , FRS 7.79 % , total cholesterol 184 mg/dL , and LDL-C 95 mg/dL. There was no treatment difference for pravastatin vs P-placebo in total cholesterol , LDL-C , or any of the inflammatory biomarkers . Participants r and omized to lisinopril vs. L-placebo had significant declines in diastolic BP ( −3.3 mmHg , p = 0.05 ) , hsCRP ( −0.61 µg/mL , p = 0.02 ) and TNF-α ( −0.17 pg/mL , p = 0.04 ) . Participants taking lisinopril vs L-placebo were more likely to report missed doses ( 88 vs 35 % ; p = 0.001 ) and have adherence < 90 % by pill count ( 42 vs. 0 % ; p = 0.02 ) . Few participants from either group reported side effects ( n = 3 vs. n = 1 ) . Conclusions The modest BP changes and decreased adherence with lisinopril and absence of lipid differences with pravastatin suggest future studies of these drug classes should consider a run-in period to assess adherence and use a different statin . Our results also indicate that ACE-I therapy may have anti-inflammatory benefits for ART-treated persons with HIV infection and this should be further evaluated . Trial Registration Clinical Trials.gov Background : Ezetimibe inhibits intestinal absorption of cholesterol . Methods : Multicentered double-blind , r and omized , placebo-controlled , crossover study to determine the short-term safety , efficacy , and tolerability of ezetimibe in combination with ongoing statin therapy in HIV-infected adults with elevated low-density lipoprotein cholesterol ( LDL-C ) . Participants on stable HAART with fasting LDL-C at least 130 mg/dl and stable statin were r and omized to ezetimibe 10 mg daily or placebo for 12 weeks followed by 4 weeks of washout and then 12 weeks with alternative study assignment . Percentage and absolute change in LDL-C ( primary endpoint ) , total cholesterol , triglyceride , high-density lipoprotein cholesterol ( HDL-C ) , apolipoprotein B , and high sensitivity C-reactive protein were compared . Changes in clinical symptoms and safety laboratory measurements were assessed . Results : Forty-four participants enrolled : 70 % men , median age 49 years , 43 % White/Non-Hispanic , median CD4 cell count 547 cells/μl , and 95 % HIV RNA less than 50 copies/ml . Median ( interquartile range ) percentage change in LDL-C was −20.8 % ( −25.4 , −10.7 ) with ezetimibe and −0.7 % ( −10.3,18.6 ) with placebo ; the median within-participant effect of ezetimibe was −14.1 % ( −33.0 , −5.0 ; P < 0.0001 ) . Median difference in absolute LDL-C values between ezetimibe and placebo was −32 mg/dl ( −58 , −6 , P < 0.0001 ) . Significant differences in within-participant effect of ezetimibe were noted for total cholesterol −18.60 % ( −27.22 , −11.67 , P < 0.001 ) , non-HDL-C −23.18 % ( −33.14 , −14.36 , P < 0.0001 ) , and apolipoprotein B −8.73 % ( −18.75 , 1.99 , P = 0.02 ) . No significant changes seen in HDL-C , triglyceride , or high sensitivity C-reactive protein . Ezetimibe was well tolerated . Adverse events were similar between phases . Conclusion : The present short-term study found adding ezetimibe to ongoing statin therapy was well tolerated and effective in reducing LDL-C , total cholesterol , non-HDL-C , and apolipoprotein B. Adding ezetimibe to statin therapy offers reasonable treatment option for HIV-infected patients with elevated ABSTRACT 3-Hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase inhibitors are effective agents in lowering cholesterol and triglycerides and are being used by human immunodeficiency virus-positive patients to treat the lipid elevation that may be associated with antiretroviral therapy . Many HMG-CoA reductase inhibitors and protease inhibitors are metabolized by the same cytochrome P450 enzyme 3A4 ( CYP3A4 ) . In addition , many protease inhibitors are potent inhibitors of CYP3A4 . Therefore , coadministration of these two classes of drugs may cause significant drug interactions . This open-label , multiple-dose study was performed to determine the interactions between nelfinavir , a protease inhibitor , and two HMG-CoA reductase inhibitors , atorvastatin and simvastatin , in healthy volunteers . Thirty-two healthy subjects received either atorvastatin calcium ( 10 mg once a day ) or simvastatin ( 20 mg once a day ) for the first 14 days of the study . Nelfinavir ( 1,250 mg twice a day ) was added on days 15 to 28 . Pharmacokinetic assessment was performed on days 14 and 28 . The study drugs were well tolerated . Nelfinavir increased the steady-state area under the plasma concentration-time curve during one dosing period ( AUCτ ) of atorvastatin 74 % and the maximum concentration ( Cmax ) of atorvastatin 122 % and increased the AUCτ of simvastatin 505 % and theCmax of simvastatin 517 % . Neither atorvastatin nor simvastatin appeared to alter the pharmacokinetics of nelfinavir . It is recommended that coadministration of simvastatin with nelfinavir should be avoided , whereas atorvastatin should be used with nelfinavir with caution Recent data suggest that statins block HIV-1 replication , which may have important implication s for an alternative treatment for AIDS . We tested different statins in cell culture against HIV and conducted a pilot study in HIV-positive patients receiving simvastatin . No anti-HIV activity was detected at subtoxic concentrations and simvastatin did not induce a significant change in the mean viral load or CD4 cell count in study patients . We caution on the use of statins as antiretroviral agents Background : Despite suppressive antiretroviral therapy ( ART ) , increased levels of immune activation persist in HIV-infected subjects . Statins have anti-inflammatory effects and may reduce immune activation in HIV disease . Methods : Stopping Atherosclerosis and Treating Unhealthy bone with RosuvastatiN in HIV ( SATURN-HIV ) is a r and omized , double-blind placebo-controlled trial assessing the effect of rosuvastatin ( 10 mg daily ) on markers of cardiovascular risk and immune activation in ART-treated patients . T-cell activation was measured by expression of CD38 , HLA-DR , and PD1 . Monocyte activation was measured with soluble markers ( sCD14 and sCD163 ) and by enumeration of monocyte sub population s and tissue factor expression . Markers of systemic and vascular inflammation and coagulation were also measured . SATURN-HIV is registered on clinical trials.gov ( identifier : NCT01218802 ) . Results : Rosuvastatin , compared with placebo , reduced sCD14 ( −10.4 % vs 0.5 % , P = 0.006 ) , lipoprotein-associated phospholipase A2 ( −12.2 % vs −1.7 % , P = 0.0007 ) , and IP-10 ( −27.5 vs −8.2 % , P = 0.03 ) levels after 48 weeks . The proportion of tissue factor-positive patrolling ( CD14DimCD16 + ) monocytes was also reduced by rosuvastatin ( −41.6 % ) compared with placebo ( −18.8 % , P = 0.005 ) . There was also a greater decrease in the proportions of activated ( CD38+HLA-DR+ ) T cells between the arms ( −38.1 % vs −17.8 % , P = 0.009 for CD4 + cells , and −44.8 % vs −27.4 % , P = 0.003 for CD8 + cells ) . Conclusions : Forty-eight weeks of rosuvastatin treatment reduced significantly several markers of inflammation and lymphocyte and monocyte activation in ART-treated subjects Abstract . Background : Lipoprotein disorders in HIV-positive patients receiving highly active antiretroviral therapy ( HAART ) are becoming a major concern in HIV treatment , since there is growing evidence for an association between HAART-induced hyperlipidemia and increased cardiovascular risk . Yet relatively few data are available on the possible interactions of HAART and treatment with statins . Patients and Methods : In this prospect i ve study , 25 HIV-positive , treatment-experienced patients ( five female , 20 male , all Caucasian ) were treated with either fluvastatin or pravastatin . Total cholesterol , low density lipoprotein ( LDL ) and high density lipoprotein ( HDL ) levels , and serum triglycerides were determined at regular intervals , as well as therapeutic drug monitoring to assess possible drug interactions . Results : In 13 pravastatin-treated patients , a decrease in total cholesterol levels ( from 7.12 mmol/l to 6.29 mmol/l ) after 12 weeks of therapy was seen . In 12 patients treated with fluvastatin , a permanent reduction of total cholesterol ( from 6.46 mmol/l to 5.31 mmol/l ) after 12 weeks was observed . The reduction of LDL levels was 30.2 % in the fluvastatin group and 14.4 % in the pravastatin group . In eight patients receiving an indinavir-containing HAART , indinavir plasma levels were not significantly influenced . No effect on triglycerides or HDL was observed . Conclusion : Fluvastatin and pravastatin are efficient in lowering total and LDL cholesterol levels in HIV-positive patients receiving HAART . Furthermore , no influence on indinavir plasma levels could be observed . Therefore , both compounds seem to be a viable treatment option in HAART-induced hypercholesterolemia There is a paucity of information on the safety and efficacy of lipid-lowering therapy for dyslipidemia associated with human immunodeficiency virus ( HIV ) and antiretroviral therapy . Our objective was to determine whether fenofibrate and pravastatin were equivalent for the treatment of combined dyslipidemia in HIV as measured by a composite of the National Cholesterol Education Project ( NCEP ) goals based on absolute values for low-density lipoprotein ( LDL ) , triglycerides ( TG ) , and high-density lipoprotein ( HDL ) and to compare the safety of these agents through 48 weeks . This was a r and omized , open-label trial with subjects assigned to fenofibrate 200 mg ( n = 88 ) or pravastatin 40 mg ( n = 86 ) daily . Subjects who failed to reach the NCEP composite goal on monotherapy by week 12 received both drugs . The composite goal at week 12 was achieved in 1 % of fenofibrate and 5 % of pravastatin subjects . At week 16 , 69/88 subjects on fenofibrate added pravastatin ( FP ) and 67/86 subjects on pravastatin added fenofibrate ( PF ) . At week 48 , 7 % FP subjects and 3 % PF subjects achieved the composite goal . Median changes in LDL/HDL/TG/non-HDL were -8/+5/-144/+50 and -14/+2/-66/+34 mg/dl in subjects receiving FP and PF , respectively . There were few adverse events and no rhabdomyolysis reported . Combination therapy with fenofibrate and pravastatin for HIV-related dyslipidemia provides substantial improvements in lipid parameters and appears safe , but is unlikely to achieve all NCEP targets for lipid levels Highly active antiretroviral therapy ( HAART ) including protease inhibitors ( PIs ) has been independently associated with an abnormal lipid profile , and recent studies have shown an increased risk of cardiovascular complications in patients with prolonged exposure to HAART . Aim of our open-label , r and omized , prospect i ve study is to evaluate the role of different statins in the management of PI-associated hypercholesterolaemia . Ninety-four adult patients on a stable PI-based antiretroviral therapy since at least 12 months , and presenting hypercholesterolaemia ( total cholesterol level > 250 mg/dL ) of at least 3-month duration and unresponsive to a hypolipidaemic diet and physical exercise , were r and omized to a hypolipidaemic treatment with rosuvastatin ( 10 mg once daily ) , pravastatin ( 20 mg once daily ) or atorvastatin ( 10 mg once daily ) , and were followed-up for 12 months . Among the 85 subjects who completed the study , rosuvastatin was employed in 26 cases , pravastatin in 31 , and atorvastatin in 28 . At the close of 1-year follow-up , statins led to a mean reduction of 21.2 % and 23.6 % versus baseline total cholesterol and LDL cholesterol levels , respectively ( p=0.002 ) . Mean decrease in total cholesterol concentration was significantly greater with rosuvastatin ( 25.2 % ) than with pravastatin ( 17.6 % ; p=0.01 ) and atorvastatin ( 19.8 % ; p=0.03 ) . During these 12 months , all administered statins showed a favourable tolerability profile , and patients ' plasma HIV viral load did not present any variation . All used statins showed a significant efficacy and a good tolerability in the treatment of diet-resistant hyperlipidaemia , but rosuvastatin was found to be more effective in reducing total and LDL cholesterol levels We tested the security and efficacy of ezetimibe in the treatment of HIV-associated dyslipemia . Twenty HIV-infected patients were r and omly assigned to receive ezetimibe 10 mg/day or fluvastatin 80 mg/day . Patients receiving ezetimibe experienced a statistically significant ( P = 0.003 ) 20 % reduction in the concentration of LDL-cholesterol , similar to that observed with fluvastatin ( 24 % , P between groups 0.70 ) . We concluded that ezetimibe monotherapy effectively decreases LDL-cholesterol in HIV-infected patients Objectives : To determine the effect of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor , pravastatin , on markers of cardiovascular risk and lipodystrophy in HIV-infected , protease inhibitor (PI)-treated men with hypercholesterolaemia . Methods : A r and omized , placebo-controlled , 16-week study was carried out on 33 HIV-infected , hypercholesterolaemic men ( fasting total cholesterol > 6.5mmol/L ) on PI-containing therapy . Patients commenced dietary assessment and advice at week 0 and were r and omized to 12 weeks pravastatin ( 40 mg each night ) or placebo from week 4 . The primary endpoint was the time-weighted change ( TWAUC ) in total cholesterol from week 0 . Secondary endpoints included TWAUC cholesterol from week 4 ( start of pravastatin ) , total and regional body fat , fasting lipids , glucose , insulin , and markers of cardiovascular risk . Results : Of 33 men r and omized ( pravastatin n = 16 , mean age 48 years ) , 31 completed the study . Groups were matched for baseline cholesterol and body composition . Although there was no significant between-group difference in TWAUC cholesterol from week 0 ( pravastatin −0.6 ± 1.0 versus placebo −0.4 ± 1.0 mmol/L/week ; P = 0.8 ) , TWAUC cholesterol from week 4 decreased more in the pravastatin group ( −0.8 ± 1.0 versus −0.3 ± 0.9 mmol/L/week ; P = 0.04 ) . Neither triglycerides nor dietary intake changed . Subcutaneous fat increased significantly with pravastatin ( + 0.72 ± 1.55 versus + 0.19 ± 0.48 kg change in limb fat , P < 0.04 ; + 5.2 ± 8.7 versus −1.3 ± 13.7 cm2 change in abdominal subcutaneous fat , P = 0.02 ) . Apart from homocystine , which decreased in the pravastatin group , there were no significant differences in other cardiovascular , lipid or glucose parameters . Conclusions : Despite limited effects on cholesterol , 12 weeks use of pravastatin 40 mg each night in HIV-infected men with hypercholesterolaemia result ed in significant increases in subcutaneous fat The authors investigated whether SLCO1B1 polymorphisms contribute to variability in pravastatin pharmacokinetics when pravastatin is administered alone versus with darunavir/ritonavir . HIV-negative healthy participants were prospect ively enrolled on the basis of SLCO1B1 diplotype : group 1 ( * 1A/*1A , n = 9 ) ; group 2 ( * 1A/*1B , n = 10 ; or * 1B/*1B , n = 2 ) ; and group 3 ( * 1A/*15 , n = 1 ; * 1B/*15 , n = 5 ; or * 1B/*17 , n = 1 ) . Participants received pravastatin ( 40 mg ) daily on days 1 through 4 , washout on days 5 through 11 , darunavir/ritonavir ( 600/100 mg ) twice daily on days 12 through 18 , with pravastatin 40 mg added back on days 15 through 18 . Pharmacokinetic studies were conducted on day 4 ( pravastatin alone ) and day 18 ( pravastatin + darunavir/ritonavir ) . Pravastatin area under the plasma concentration-time curve ( AUC(tau ) ) was 21 % higher during administration with darunavir/ritonavir compared with pravastatin alone ; however , this difference was not statistically significant ( P = .11 ) . Group 3 variants had 96 % higher pravastatin AUC(tau ) on day 4 and 113 % higher pravastatin AUC(tau ) on day 18 compared with group 1 . The relative change in pravastatin pharmacokinetics was largest in group 3 but did not differ significantly between diplotype groups . In sum , the influence of SLCO1B1 * 15 and * 17 haplotypes on pravastatin pharmacokinetics was maintained in the presence of darunavir/ritonavir . Because OATP1B1 inhibition would be expected to be greater in carriers of normal or high-functioning SLCO1B1 haplotypes , these findings suggest that darunavir/ritonavir is not a potent inhibitor of OATP1B1-mediated pravastatin transport in vivo Background : HIV infection and its treatment with protease inhibitors , especially when boosted with ritonavir , can cause lipid disorders . Statins , with the exception of fluvastatin , pravastatin and rosuvastatin , interact with protease inhibitor metabolism via CYP450 . Pravastatin is recommended for patients with protease inhibitor-associated dyslipidemia . Rosuvastatin is the statin most effective on low-density lipoprotein cholesterol ( LDL-c ) in non-HIV patients . Methods : HIV-1-infected patients treated with boosted protease inhibitor were r and omized to receive either rosuvastatin 10 mg/day or pravastatin 40 mg/day for dyslipidemia ( LDL-c > 4.1 mmol/l and triglycerides < 8.8 mmol/l ) . The percentage change in LDL-c , triglyceride and high-density lipoprotein-cholesterol levels , measured in a central laboratory , was determined after 45 days of statin treatment . Results : Eighty-eight patients were r and omized and 83 took the study drugs , 41 rosuvastatin and 42 pravastatin . The median duration of prior antiretroviral treatment was 9 years . At baseline , the median LDL-c level was 4.93 mmol/l , the triglyceride level 2.29 mmol/l , and the high-density lipoprotein-cholesterol level 1.27 mmol/l . The median percentage changes in the rosuvastatin and pravastatin arms were −37 and −19 % for LDL-c ( P < 0.001 ) , respectively , and −19 and −7 % for triglycerides ( P = 0.035 ) , respectively . The change in the high-density lipoprotein-cholesterol level was not significantly different between the two arms . None of the four severe adverse events was attributed to the statins ; in particular , there were no renal , hepatic or muscular events . Conclusion : Rosuvastatin 10 mg/day was more effective than pravastatin 40 mg/day on LDL-c and triglyceride levels in HIV-1-infected patients receiving a boosted protease inhibitor OBJECTIVE To assess whether statin administration for HIV-associated hyperlipidemia has long-term effects on immune recovery ( as expressed by the trend of mean CD4 + lymphocyte count ) , in patients on a virologically-active HAART regimen since 12 months or more . METHODS Single-centre , open-label , prospect i ve study of 301 hyperlipidemic patients treated with statins ( 99 cases , with a predominant hypercholesterolemia ) , fibrates ( 116 subjects , when hypertriglyceridemia prevailed ) , or a isolated dietary/exercise program ( 86 patients , used as a control group ) . Neither epidemiological nor clinical , virological , or immunological differences were detected among the three study groups at baseline . During the subsequent follow-up , patients were excluded from evaluation should virological efficacy was not maintained , and /or initial hypolipidemic therapy was modified or interrupted for any reason . RESULTS The quarterly assessment of mean CD4 + lymphocyte count did not disclose any statistically significant difference among the three study groups , since baseline and until at least 24 consecutive months of follow-up . Our data tend to exclude relevant in vivo negative activities of statins on immune system recovery of HIV-infected individuals who undergo a virologically effective HAART treatment . CONCLUSIONS Multiple , pleiotropic features have been attributed to both statins and fibrates , and also apparently significant effects on laboratory markers of HIV disease progression have been recently cl aim ed or expected . Despite some preliminary in vitro and ex-vivo models , both the main hypolipidemic classes administered for the management of HIV-related dyslipidemia ( both statins and fibrates ) do not seem to act significantly on clinical immune response of patients successfully treated with HAART . Multifactorial pathways are expected to interact with the cell-mediated immune system of HIV-infected patients undergoing successful HAART , and further studies are needed to eluci date whether more subtle immune effects might be prompted by a long-term administration of hypolipidemic drugs in this speciasl setting Background : The drug – drug interactions between pitavastatin and darunavir/ritonavir ( DRV/r ) as well as pitavastatin and efavirenz ( EFV ) were examined in an open-label , parallel-arm , pharmacokinetic ( PK ) study in HIV-uninfected healthy volunteers . Methods : Subjects received a pitavastatin dose of 2 mg for 4 days , followed by either EFV 600 mg ( n = 14 ) or DRV/r 800/100 mg ( n = 14 ) daily for 10 days , and pitavastatin 2 mg coadministered with EFV 600 mg or DRV/r 800/100 mg for 4 days . Full PK profiles were determined for pitavastatin and its lactone metabolite on days 4 and 18 and for EFV or DRV on days 14 and 18 . Results : In the EFV arm , the geometric mean area under the concentration time curve ( AUC0-&tgr ; ) and Cmax of pitavastatin were 85.3 ng·h·mL−1 and 15.6 ng/mL , respectively , when given alone , versus 76 ng·h·mL−1 and 18.8 ng/mL when coadministered with EFV . The geometric mean ratio for pitavastatin with EFV versus alone was 0.89 [ 90 % confidence interval ( CI ) : 0.73 to 1.09 ] for AUC0-&tgr ; and 1.20 ( 90 % CI : 0.79 to 1.83 ) for Cmax . In the DRV/r arm , AUC0-&tgr ; and Cmax were 62.8 ng·h·mL−1 and 24.0 ng/mL , respectively , when pitavastatin was administered alone , versus 56.9 ng·h·mL−1 and 23.2 ng/mL when coadministered with DRV/r . The geometric mean ratio for pitavastatin with DRV/r versus alone was 0.91 ( 90 % CI : 0.78 to 1.06 ) for AUC0-&tgr ; and 0.93 ( 90 % CI : 0.72 to 1.19 ) for Cmax . Conclusions : There were no significant PK interactions between pitavastatin and EFV or DRV/r . No significant safety issues or lipid changes were noted Background : Traditional cardiovascular disease risk factors ( CVDRFs ) increase the risk of acute myocardial infa rct ion ( AMI ) among HIV-infected ( HIV+ ) participants . We assessed the association between HIV and incident AMI within CVDRF strata . Methods : Cohort—81,322 participants ( 33 % HIV+ ) without prevalent CVD from the Veterans Aging Cohort Study Virtual Cohort ( prospect i ve study of HIV+ and matched HIV− veterans ) participated in this study . Veterans were followed from first clinical encounter on/after April 1 , 2003 , until AMI/death/last follow-up date ( December 31 , 2009 ) . Predictors — HIV , CVDRFs ( total cholesterol , cholesterol-lowering agents , blood pressure , blood pressure medication , smoking , diabetes ) used to create 6 mutually exclusive profiles : all CVDRFs optimal , 1 + nonoptimal CVDRFs , 1 + elevated CVDRFs , and 1 , 2 , 3 + major CVDRFs . Outcome —Incident AMI [ defined using enzyme , electrocardiogram ( EKG ) clinical data , 410 inpatient ICD-9 ( Medicare ) , and /or death certificates ] . Statistics — Cox models adjusted for demographics , comorbidity , and substance use . Results : Of note , 858 AMIs ( 42 % HIV+ ) occurred over 5.9 years ( median ) . Prevalence of optimal cardiac health was < 2 % . Optimal CVDRF profile was associated with the lowest adjusted AMI rates . Compared with HIV− veterans , AMI rates among HIV+ veterans with similar CVDRF profiles were higher . Compared with HIV− veterans without major CVDRFs , HIV+ veterans without major CVDRFs had a 2-fold increased risk of AMI ( HR : 2.0 ; 95 % confidence interval : 1.0 to 3.9 ; P = 0.044 ) . Conclusions : The prevalence of optimal cardiac health is low in this cohort . Among those without major CVDRFs , HIV+ veterans have twice the AMI risk . Compared with HIV− veterans with high CVDRF burden , AMI rates were still higher in HIV+ veterans . Preventing/reducing CVDRF burden may reduce excess AMI risk among HIV+ people |
10,442 | 31,982,601 | The results of our meta-analyses suggest that three baseline demographic and clinical features are associated with better clozapine response , i.e. relatively young age , few negative symptoms and paranoid schizophrenia subtype . | OBJECTIVES Clozapine ( CLZ ) is prescribed to ( relatively ) treatment-resistant patients with schizophrenia spectrum disorders .
Currently , it is unknown what factors predict response to CLZ .
Therefore , we performed meta-analyses to identify predictors of CLZ response , hence aim ing to facilitate timely and efficient prescribing of CLZ . | OBJECTIVES A growing number of atypical antipsychotics are available for clinicians to choose from in the treatment of psychotic disorders . However , a number of important questions concerning medication selection , dosing and dose equivalence , and the management of inadequate response , compliance problems , and relapse have not been adequately addressed by clinical trials . To aid clinical decision-making , a consensus survey of expert opinion on the pharmacologic treatment of psychotic disorders was undertaken to address questions not definitively answered in the research literature . METHOD Based on a literature review , a written survey was developed with 60 questions and 994 options . Approximately half of the options were scored using a modified version of the R AND 9-point scale for rating the appropriateness of medical decisions . For the other options , the experts were asked to write in answers ( e.g. , average doses ) or check a box to indicate their preferred answer . The survey was sent to 50 national experts on the pharmacologic treatment of psychotic disorders , 47 ( 94 % ) of whom completed it . In analyzing the responses to items rated on the 9-point scale , consensus on each option was defined as a non r and om distribution of scores by chi-square " goodness-of-fit"test . We assigned a categorical rank ( first line/preferred choice , second line/alternate choice , third line/usually inappropriate ) to each option based on the 95 % confidence interval around the mean rating . Guideline tables indicating preferred treatment strategies were then developed for key clinical situations . RESULTS The expert panel reached consensus on 88 % of the options rated on the 9-point scale . The experts overwhelmingly endorsed the atypical antipsychotics for the treatment of psychotic disorders . Risperidone was the top choice for first-episode and multi-episode patients , with the other newer atypicals rated first line or high second line depending on the clinical situation . Clozapine and a long-acting injectable atypical ( when available)were other high second line options for multi-episode patients . The expert 's dosing recommendations agreed closely with the package inserts for the drugs , and their estimates of dose equivalence among the antipsychotics followed a linear pattern . The experts considered 3 - 6 weeks an adequate antipsychotic trial , but would wait a little longer ( 4 - 10 weeks ) before making a major change in treatment regimen if there is a partial response . The experts recommended trying to improve response by increasing the dose of atypical and depot antipsychotics before switching to a different agent ; there was less agreement about increasing the dose of conventional antipsychotics before switching , probably because of concern about side effects at higher doses . If it is decided to switch because of inadequate response , risperidone was the expert 's first choice to switch to , no matter what drug was initially tried . Although there was some disparity in the expert 's recommendations concerning how many agents to try before switching to clozapine , the expert 's responses suggest that switching to clozapine should be Clozapine was also the antipsychotic of choice for patients with suicidal behavior . When switching oral antipsychotics , the experts considered cross-titration the preferred strategy . When switching to an injectable antipsychotic , the experts stressed the importance of continuing the oral antipsychotic until therapeutic levels of the injectable agent are achieved . The experts considered psychosocial interventions the first choice strategy for partially compliant patients , with pharmacologic interventions the first choice for patients with clear evidence of noncompliance . However , because it can be difficult to distinguish partially compliant from noncompliant patients , the editors recommended combining psychosocial and pharmacologic interventions to improve compliance whenever possible . When patients relapse because of compliance problems or if there is any doubt about compliance , the experts recommended the use of a long-acting injectable antipsychotic and would select an injectable atypical when this option becomes available . The experts would also consider using an injectable atypical antipsychotic ( when available ) in many clinical situations that do not involve compliance problems . The experts stressed the importance of monitoring for health problems-especially obesity , diabetes , cardiovascular problems , HIV risk behaviors , medical complications of substance abuse , heavy smoking and its effects , hypertension , and amenorrhea-in patients being treated with antipsychotics . Although many patients are prescribed adjunctive treatments , multiple antipsychotics , and combinations of different classes of drugs ( e.g. , antipsychotics plus mood stabilizers or antidepressants ) in an effort to enhance response , the experts gave little support to any of these strategies , with the exception of antidepressants for patients with dysphoria/depression , antidepressants or ECT for patients with suicidal behavior , and mood stabilizers for patients with aggression/violence . When asked about indicators of remission and recovery , the experts considered acute improvement in psychotic symptoms the most important indicator of remission , whereas they considered more sustained improvement in multiple outcome domains ( e.g. , occupational/educational functioning , peer relationships , independent living ) important in assessing recovery . CONCLUSIONS The experts reached a high level of consensus on many of the key treatment questions in the survey . Within the limits of expert opinion and with the expectation that future research data will take precedence , these guidelines provide direction for addressing common clinical dilemmas that arise in the pharmacologic treatment of psychotic disorders . They can be used to inform clinicians and educate patients regarding the relative merits of a variety of interventions . Clinicians should keep in mind that no guidelines can address the complexities involved in the care of each individual patient and that sound clinical judgment based on clinical experience should be used in applying these recommendations Clozapine is the only available therapy for about 30 % of schizophrenia patients otherwise refractory to antipsychotics . Unfortunately , the mechanism of action of the drug is still unknown and there are no biomarkers that can predict a positive response to clozapine . We aim ed to examine serum neurotrophins and glutamate levels as putative biomarkers for clozapine response based on the hypothesized mode-of-action of the compound . Blood sample s of 89 chronic schizophrenia patients maintained on clozapine were analyzed in a cross-sectional design . Serum brain derived neurotrophic factor ( BDNF ) , vascular endothelial growth factor ( VEGF ) , neurotrophic growth factor ( NGF ) , glial derived neurotrophic factor ( GDNF ) and glutamate were determined . Differences between responders and non-responders to clozapine and correlation between clinical and biological measures were analyzed . Our sample consisted of 54 ( 61 % ) responders and 35 ( 39 % ) non-responders . Responders had higher mean BDNF levels than non-responders ( 2066±814 vs. 1668±820pg/ml , p<0.05 . respectively ) and higher serum glutamate levels ( 1.61±2.2 vs. 0.66±0.9pg/ml , respectively , p<0.05 ) . Furthermore , there was a significant correlation between serum glutamate levels and positive symptoms among the clozapine-responder group ( rho=0.47 , p<0.005 ) . High serum levels of BDNF and glutamate were associated with response to clozapine , while glutamate levels correlated with the psychosis severity in clozapine responders only . Large-scale , prospect i ve longitudinal studies are needed to support these findings and the assumption that serum glutamate and BDNF can discriminate between clozapine responders and non-responders OBJECTIVE Maintenance treatment of schizophrenia with antipsychotic medications has become a st and ard for the prevention of psychotic relapse . However , little is known about the effectiveness of antipsychotic drugs for maintenance treatment in " real-world " population s with schizophrenia . We carried out a prospect i ve study to assess the effectiveness of the most frequently prescribed antipsychotic drugs in the maintenance treatment of schizophrenia from 2 community setting s. METHODS This study was conducted from October 2011 to December 2014 . All participants were diagnosed with schizophrenia according to DSM-IV , were treated with an antipsychotic monotherapy , and were registered in a case management program with monthly monitoring for 24 months . The primary outcome measure , Positive and Negative Syndrome Scale ( PANSS ) , and the Clinical Global Impressions-Severity of Illness ( CGI-S ) and -Improvement ( CGI-I ) scales were used to evaluate symptom severity and treatment response . The Personal and Social Performance scale ( PSP ) was used to evaluate the patients ' social functioning . The Medication Adherence Rating Scale ( MARS ) was used to assess medication adherence behavior . On the basis of antipsychotic used at baseline , patients were clustered into 7 groups : aripiprazole ( n = 21 ) , clozapine ( n = 84 ) , chlorpromazine ( n = 61 ) , olanzapine ( n = 34 ) , perphenazine ( n = 21 ) , quetiapine ( n = 27 ) , and risperidone ( n = 99 ) . RESULTS Of the 347 patients enrolled in the study , 312 completed the 24-month follow-up . There were no significant differences among the treatment groups in the PANSS total and subscale scores or the CGI-S and CGI-I scores over 24 months ( all P values > .05 ) . There were also no significant differences in interactions between PSP scores and antipsychotic drugs ( P = .17 ) . The remission rates increased as the follow-time lapsed in all groups , but no significant difference was observed in remission rates at each time point among the 7 groups ( P values > .05 ) . At the endpoint , MARS total scores were over 6 , but did not significantly differ among the studied drugs ( P = .24 ) . CONCLUSIONS These findings suggest that antipsychotic drugs can achieve equivalent effectiveness in maintenance treatment of first-episode schizophrenia through a well-organized case management program and family participation OBJECTIVE To assess the relation between plasma concentrations of clozapine and its 2 main metabolites desmethyl clozapine and clozapine N-oxide , and clinical change in a sample of in patients with schizophrenia who were resistant to conventional neuroleptics . METHOD Thirty-seven patients ( 27 men and 10 women , mean age 34.8 yr ) with treatment-resistant schizophrenia were treated with clozapine for 18 weeks ; dosage was adjusted according to clinical response , and plasma concentrations of clozapine and of its metabolites were measured weekly by high-performance liquid chromatography . Clinical status was also assessed weekly with the Positive and Negative Syndrome Scale ( PANSS ) . Patients were considered " responsive " if they showed at least a 20 % improvement over their baseline PANSS ratings . RESULTS The mean endpoint clozapine dosage was 486.5 mg/day . There was a significant correlation between the daily dosage of clozapine and the plasma levels of clozapine and of its metabolites ( p < 0.05 ) . There was no correlation between the clozapine plasma level and the percent improvement on the PANSS . Clozapine plasma levels were not significantly different between those who responded to clozapine ( n = 19 ) and those who did not ( n = 18 ) and were not significantly different between patients who smoked ( n = 28 ) and those who did not ( n = 9 ) . Receiver operating characteristic ( ROC ) curve analysis determined the plasma level threshold ( above which a better clinical response was obtained ) to be 550 ng/mL. Using the total of plasma levels of clozapine and its metabolites did not lead to a better sensitivity and specificity . CONCLUSIONS Our calculated plasma clozapine threshold was higher than that reported by others , but this may be related to the severity of symptoms of our patient sample . Monitoring plasma rates remains a useful tool , together with clinical evaluation , to establish the clozapine dosage for an optimum benefit-risk ratio Here we report the results of a pilot study investigating the relative and combined effects of a 12 week course of clozapine and CBT in first-episode psychosis patients with prominent ongoing positive symptoms following their initial treatment . Patients from our early psychosis service who met the inclusion criteria ( n = 48 ) were r and omized to one of four treatment groups : clozapine , clozapine plus CBT , thioridazine , or thioridazine plus CBT . The degree of psychopathology and functionality of all participants was measured at baseline then again at 6 , 12 and 24 weeks , and the treatment outcomes for each group determined by statistical analysis . A substantial proportion ( 52 % ) of those treated with clozapine achieved symptomatic remission , as compared to 35 % of those who were treated with thioridazine . Overall , those who received clozapine responded more rapidly to treatment than those receiving the alternative treatments . Interestingly , during the early treatment phase CBT appeared to reduce the intensity of both positive and negative symptoms and thus the time taken to respond to treatment , as well having as a stabilizing effect over time This study compared the time course to clinical improvement with clozapine and with conventional antipsychotic medications . A double-blind trial compared clozapine and haloperidol in patients with schizophrenia who were refractory to conventional antipsychotic medication and were hospitalized for 30 to 364 days at 15 Veteran Affairs medical centers during the year before study entry . Patients in the original study were r and omly assigned to haloperidol or clozapine and followed for 12 months , at maximum tolerable doses . Patients who completed a full year of treatment with clozapine ( n = 122 ) , or with either haloperidol or another conventional antipsychotic medication ( n = 123 ) and who also completed the 9- or 12-month assessment were included . Response to treatment was defined as 20 percent improvement on st and ard scales of symptoms and quality of life at the latter of the 9- or 12-month interviews . More patients assigned to clozapine achieved 20 percent improvement in symptoms at each followup . Among patients who did not improve at 6 weeks , 3 months , or 6 months , there were no significant differences between clozapine and comparison patients in outcomes at 1 year . Among patients who did improve , maintenance of that improvement also did not differ between the groups at 1 year on symptom measures . Maintenance of improvement in quality of life at 1 year was significantly greater for clozapine patients who had improved at 6 months ( p < 0.04 ) . Significant differential symptom response to clozapine occurred exclusively during the first 6 weeks of treatment BACKGROUND Despite the advent of new atypical antipsychotics , clozapine remains an important option in the treatment of patients with poor response to conventional antipsychotics . Clinicians would be well served if clinical characteristics could be identified that predict a favorable response to clozapine . A few studies addressing this issue have reported inconsistent results . METHOD The association of clinical characteristics with a sustained response was investigated in 37 partially treatment-refractory out patients with a DSM-III-R diagnosis of chronic schizophrenia who had been assigned to clozapine treatment in a double-blind , haloperidol-controlled , long-term ( 29-week ) study of clozapine . Response was defined as a 20 % decrease of the Brief Psychiatric Rating Scale ( BPRS ) psychosis factor score sustained over 2 consecutive ratings . Differences between responders and nonresponders with regard to selected baseline variables were analyzed with t tests and chi2 tests . In addition , Cox regression analyses were performed to identify variables that best predicted a response to clozapine treatment . RESULTS Clozapine responders were rated as less severely ill , showed a lesser degree of negative symptoms , and demonstrated fewer extrapyramidal side effects at baseline as compared with nonresponders . In addition , higher BPRS total scores -- after controlling for the effects of the other variables -- were associated with a response . CONCLUSION In a cohort of partially treatment-refractory out patients , a favorable response to clozapine was associated with characteristics describing less severely ill patients . The history of patients did not affect their response to clozapine The treatment of schizophrenic patients who fail to respond to adequate trials of neuroleptics is a major challenge . Clozapine , an atypical antipsychotic drug , has long been of scientific interest , but its clinical development has been delayed because of an associated risk of agranulocytosis . This report describes a multicenter clinical trial to assess clozapine 's efficacy in the treatment of patients who are refractory to neuroleptics . DSM-III schizophrenics who had failed to respond to at least three different neuroleptics underwent a prospect i ve , single-blind trial of haloperidol ( mean dosage , 61 + /- 14 mg/d ) for six weeks . Patients whose condition remained unimproved were then r and omly assigned , in a double-blind manner , to clozapine ( up to 900 mg/d ) or chlorpromazine ( up to 1800 mg/d ) for six weeks . Two hundred sixty-eight patients were entered in the double-blind comparison . When a priori criteria were used , 30 % of the clozapine-treated patients were categorized as responders compared with 4 % of chlorpromazine-treated patients . Clozapine produced significantly greater improvement on the Brief Psychiatric Rating Scale , Clinical Global Impression Scale , and Nurses ' Observation Scale for Inpatient Evaluation ; this improvement included " negative " as well as positive symptom areas . Although no cases of agranulocytosis occurred during this relatively brief study , in our view , the apparently increased comparative risk requires that the use of clozapine be limited to selected treatment-resistant patients In first-episode patients with psychosis , clozapine may be potentially valuable as an initial treatment seeking to limit early on clinical and cognitive deterioration . Nevertheless , until recently its restricted use has limited the study of this possibility . Our research group is developing a non-commercial , multicentric and open label study on the differential efficacy between clozapine and risperidone in first-episode schizophrenia . In this paper , we present the results related to clinical variables after a one-year follow-up . So far , we have recruited 30 patients diagnosed with schizophrenia or schizophreniform disorder with illness duration of less than two years . The patients had not received any previous treatment and they were r and omized to treatment with clozapine or risperidone . Our results indicate that on average , patients on clozapine adhered to their original treatment for a longer time period than patients on risperidone . By last observation carried forward ( LOCF ) analysis , patients on clozapine and risperidone displayed similar clinical improvements , although marginally greater improvements in positive and total symptoms scores were found in the clozapine group . At the 12-month point we observed a marginal improvement in negative symptom scores in patients on clozapine . Subjective secondary effects , as measured with the Udvalg for KliniskeUndersøgelser ( UKU ) scale , correlated negatively with negative symptoms at follow-up . Our data , although preliminary , suggest that clozapine may have a slightly superior efficacy in the initial year of treatment of first-episode treatment-naïve patients with schizophrenia , and this can be explained for the most part by greater adherence to this treatment Schizophrenic out patients ( n=102 ) whose condition had stabilized with clozapine ( CLZ ) therapy and were being maintained on CLZ were followed for 1 year . Clinical status and concentrations of serum clozapine ( CLZ ) and its metabolite norclozapine ( NCLZ ) were evaluated periodically or when relapse occurred . Relapse was defined as a significant exacerbation of psychotic symptoms or hospitalization . Thirty-three patients relapsed and 69 did not . Relapse patients displayed significantly lower serum concentrations of CLZ and a sum of CLZ and NCLZ at endpoint than non-relapses ( CLZ : 162 ng/ml vs. 237 ng/ml , p<0.001 ; CLZ+NCLZ : 225 ng/ml vs. 301 ng/ml , p<0.001 ) . When all subjects were pooled together , a significant inverse correlation was observed between percent increase in the total score on the Brief Psychiatric Rating Scale ( BPRS ) from baseline and serum levels of CLZ alone ( r=0.404 , p<0.001 ) and the sum of CLZ and NCLZ ( r=0.364 , p<0.001 ) . Relapses and non-relapses were well separated by a threshold CLZ serum concentration of 200 ng/ml with a sensitivity of 73 % and a specificity of 80 % . The threshold value represented about a 40 % lower serum CLZ level than concentration achieved in acute treatment . Survival analysis showed a similarity of the relapse risk over time defined by the CLZ serum threshold and by symptomatic criteria . These results suggest that effective relapse prevention may require maintenance of patients at CLZ serum concentrations above 200 ng/ml and above 60 % of the acute-phase level during long-term maintenance treatment of schizophrenia BACKGROUND Clozapine , despite its side-effect burden , has been considered to be the drug of choice for patients with schizophrenia whose psychotic symptoms fail to respond adequately to other anti-psychotic drugs . There are conflicting data concerning the potential utility of olanzapine in treatment-resistant schizophrenia at doses beyond the 10- to 20-mg/day range that has proven to be effective for most nonrefractory patients with schizophrenia . OBJECTIVE The main objective of this study was to compare the efficacy and tolerability of high-dose olanzapine ( target dose , 25 - 45 mg/day ) and clozapine ( 300 - 900 mg/day ) in patients with schizophrenia or schizoaffective disorder who had failed to respond adequately to prior treatment with other antipsychotic drugs . STUDY DESIGN / METHOD This 6-month , r and omized , double-blind , parallel-group study compared the efficacy and tolerability of olanzapine ( mean dose , 34 mg/day ; N = 19 ) or clozapine ( mean dose , 564 mg/day ; N = 21 ) in patients with treatment-resistant schizophrenia or schizoaffective disorder , diagnosed according to DSM-IV criteria . Outcome measures included psychopathology , cognitive performance ( as assessed with a comprehensive neuropsychological test battery ) , and tolerability . The study was conducted between May 2000 and December 2003 . RESULTS Robust and significant ( mostly p < .001 ) improvement in multiple measures of psychopathology , mainly between 6 weeks and 6 months of treatment , was found in both treatment groups , with no significant difference between the 2 treatments except for the Global Assessment of Functioning score , which favored clozapine ( p = .01 ) . Improvement in some domains of cognition was significant- and equivalent for both drugs , as well . Nonsignificantly different improvement in Verbal List Learning-Immediate Recall ( p < .05 ) , Controlled Word Association Test ( p < .05 ) , and Digit Symbol Substitution Test ( p < .001 ) was found . There were no significant differences in extrapyramidal symptoms . Weight gain was significantly ( p = .01 ) greater with olanzapine . CONCLUSIONS Olanzapine , at higher than customary doses , demonstrated similar efficacy to clozapine in treatment-resistant schizophrenia and schizoaffective disorder in this study . However , the small sample size precludes definitively concluding that the 2 treatments are equivalent , at these doses , in treatment-resistant schizophrenia . The metabolic side effects of olanzapine are a limitation in its use . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00179231 The relationship between the time course of clinical response to clozapine and the time course of clozapine plasma levels has never been investigated . In the present study , we assessed prospect ively the clinical response to clozapine and the plasma levels of the drug and its major metabolites in 32 drug-resistant patients with schizophrenia kept on a fixed dose of 600 mg/day for 1 year Four of the patients met response criteria at week 4 of treatment . At weeks 8 , 12 , and 24 , new responders were 7 , 6 , and 6 , respectively . Nine patients never achieved clinical response . In responders at week 4 , clozapine and clozapine-N-oxide plasma levels were significantly higher than in both new responders at weeks 8 , 12 , and 24 and nonresponders . In new responders at weeks 8 , 12 , and 24 , in spite of a fixed clozapine daily dose , mean drug plasma levels progressively rose up to when clinical response occurred ; then , the levels remained stable over time . Nonresponders exhibited mean clozapine plasma levels constantly below the value of 260 ng/ml , with N-demethylation as the preferred metabolic route . The present findings show , for the first time , that the time course of the clinical response to clozapine may be linked to the time course of plasma levels of clozapine and its major metabolites Concentrations in plasma of clozapine and norclozapine , the major metabolite of clozapine , were measured in 59 treatment-resistant schizophrenic patients at a r and om time period during the course of treatment . A lower sum of the concentrations of clozapine and norclozapine or either alone predicted less improvement in the Brief Psychiatric Rating Scale ( BPRS ) Total and Positive symptoms in a multivariate analysis that controlled for baseline BPRS rating and dose . The mean doses of clozapine after 6 months of treatment and at the time of blood sampling were not significantly different in 30 responders and 29 nonresponders to clozapine , on the basis of the decrease in BPRS Total scores , whereas the concentrations in plasma in clozapine of norclozapine and the sum of their concentrations were significantly higher in responders . Clozapine and norclozapine concentrations in plasma correlated both with dose at the time of sampling and with dose at 6 months . A clozapine concentration of 370 ng/ml was the optimal cutoff for distinguishing responders from nonresponders . Clozapine and norclozapine concentrations did not differ in male smokers and nonsmokers The purported advantages of second-generation or ‘ atypical ’ antipsychotics relative to first-generation antipsychotics have not been examined in patients with a first episode of schizophrenia . This flexible-dose study examined efficacy and safety in a r and omized , double-blind , 52-week trial , comparing chlorpromazine ( CPZ ) and clozapine ( CLZ ) in treatment naive patients experiencing their first episode of schizophrenia . In all , 160 in patients with first-episode schizophrenia or schizophreniform disorder were r and omized to CPZ or CLZ and followed them for 52 weeks or until dropout . The primary efficacy measure was time to first remission and proportion of time remaining in remission . The analysis was supplemented by comparisons on a profile of clinical symptoms and side effects . Of these first-episode patients , 80 % achieved remission within 1 year ( 79 % CPZ , 81 % CLZ ) . The Kaplan – Meier estimated median time to first remission was 8 weeks for CLZ vs 12 weeks for CPZ ( χ2(1)=5.56 , p=0.02 ) . Both the rate of first achieving remission and the odds for being in remission during the trial were almost doubled for the CLZ group in comparison with the CPZ group . At 12 weeks , CLZ was superior on many rating scale measures of symptom severity while CPZ was not superior on any . These symptom differences remained significant when controlling for EPS differences . By 52 weeks many of the symptom differences between groups were no longer significantly different . Generally , CLZ produced fewer side effects than CPZ , particularly extrapyramidal side effects . There was no significant difference between treatments in weight change or glucose metabolism . For each prior year of untreated psychosis , there was a 15 % decrease in the odds of achieving remission ( OR=0.85 ; CI 0.75–0.95 ) . A high proportion of first-episode patients remitted within 1 year . We detected no difference in the proportion of first-episode patients receiving CLZ or CPZ that achieved remission . However , first-episode patients receiving CLZ remitted significantly faster and remained in remission longer than subjects receiving CPZ . While the CLZ group showed significantly less symptomatology on some measures and fewer side effects at 12 weeks , the two treatment groups seemed to converge by 1 year . Longer duration of untreated psychosis was associated with lower odds of achieving remission Abstract Previous studies have suggested the utility of nonlinear complexity measures of heart rate variability ( HRV ) in evaluating the regulatory capacity of the neuroautonomic system . The purpose of the present study was to investigate the effects of clozapine on the nonlinear complexity measures of HRV in patients with treatment-resistant schizophrenia to find novel electrophysiological markers that indicate response to clozapine treatment . Forty patients with treatment-resistant schizophrenia were evaluated during 8 weeks of clozapine monotherapy . For nonlinear complexity measures of HRV , the approximate entropy ( ApEn ) and sample entropy ( SampEn ) values were obtained . The response rate to clozapine was 37.5 % . The results of multivariate analysis of covariance revealed that the ApEn and the SampEn values of HRV at week 8 were significantly higher in the responders than in the nonresponders . Repeated- measures analysis of covariance showed a significant group by time interaction effect in the ApEn and SampEn indices . The responder group showed an increasing pattern of change in these complexity measures after administration of clozapine , whereas the nonresponder group showed a decreasing pattern of change . These results suggest that the nonlinear dynamic complexity measures of HRV , which indicate the irregularity and complexity of the biosystem , may be useful in evaluating the therapeutic changes of neuroautonomic function in schizophrenia . The response to clozapine treatment is expected to be more favorable when the plasticity of the neuroautonomic system reflected in the nonlinear complexity measures is high OBJECTIVE The authors sought to determine the time to clozapine response in treatment-refractory patients with schizophrenia . METHOD Antipsychotic response to a clozapine trial was examined in 50 treatment-refractory schizophrenic in patients . Subjects were treated with clozapine for at least 12 months , regardless of response status , according to a st and ardized , increasing dose protocol . Behavioral changes were measured through monthly assessment s with the Brief Psychiatric Rating Scale . RESULTS Thirty-four subjects ( 68 % ) met clinical response criteria by the end of the trial . Response was achieved at a mean dose of 468 mg/day ( SD = 168 ) . The dose of 30 ( 88 % ) of the responding patients was 600 mg/day or less . The mean time to response was 82 days ( SD = 100 , range = 10 - 401 ) . It took an average of 60 days ( SD = 87 ) for subjects to reach the dose at which clozapine response was achieved . Once this dose was reached , the average response time was 17 days ( SD = 14 , range = 2 - 56 ) . All 34 subjects who responded met criteria within 8 weeks of a clozapine dose escalation . No late response was found in the remaining 16 subjects despite a mean follow-up period of 75 weeks ( SD = 50 ) . CONCLUSIONS In this study , all patients who responded to clozapine did so within 8 weeks of a change in dose . Thus , there appears to be little clinical gain in prolonging exposure to clozapine beyond 8 weeks at any particular dose if no response is seen OBJECTIVE : To evaluate clozapine in a field trial for hospitalized patients with treatment-resistant schizophrenia . METHOD : The setting consisted of a large , state-operated , public psychiatric system . The protocol called for the treating psychiatrist to provide symptom- and adverse-effect ratings at four times following the start of drug therapy . The outcome criteria included the S and oz study outcome measure of symptom improvement as well as discharge status for one year of follow-up . To assess the validity of the ratings , several measures of internal consistency were determined . Clozapine therapy was started in 227 patients , and symptom data are available for 202 . RESULTS : Overall , 33 percent ( n=66 ) of the patients were improved at the end of one year of treatment ; 12 percent ( n=24 ) maintained symptom improvement at all three evaluation times . Modest , statistically significant improvement after 12 weeks compared with baseline Brief Psychiatric Rating Scale ( BPRS ) total scores was observed for the patients continuing medication ( n=152 ) ; the emergence of a previously unimproved group ( n=26 ) explains this modest improvement . However , in the analysis of all patients ( n=202 ) , ( including dropouts ) , there was no significant symptom improvement after 12 weeks . Lower baseline BPRS scores predicted significant symptom improvement after 12 weeks of treatment . Among those medicated for one year , the pattern of symptom improvement showed that the probability of late improvement was 0.26 for those previously unimproved , and the probability of a 12-week responder losing improvement was 0.23 , result ing in a net group gain of 3 cases in 100 . By the end of one year , 8 percent ( n=17 ) of the cohort was discharged , and 3 percent ( n=7 ) was transferred to another facility while continuing to receive clozapine . Of the 227 original patients started on clozapine therapy , medication was discontinued for adverse effects in 11 percent ( n=25 ) : white blood cell count ( WBC ) decrease ( but no agranulocytosis ) in 5 percent ( n=12 ) , seizures in 1 percent ( n=3 ) , one patient with seizures and decreased WBC count , and other events ( e.g. , cardiovascular changes , fever , or possible neuroleptic malignant syndrome ) in 4 percent ( n=9 ) . Patient refusal was reported for 6 percent ( n=13 ) of those starting treatment . CONCLUSIONS : Although only 19 percent of the patients exhibited improvement at 6 weeks , the response rate at 12 weeks ( 29 percent ) for this naturalistic study cohort was similar to that in the major , double-blind , six-week , controlled , clinical trial of clozapine . The impersistence of response as symptoms were followed for up to one year is a finding that deserves rigorous evaluation A prospect i ve study in treatment-resistant schizophrenic patients was performed over 10 years to evaluate the therapeutic response to clozapine and the variables related to this treatment . Eighty schizophrenic and schizoaffective patients ( according to Diagnostic and Statistical Manual [DSM]-IIIR criteria ) , considered as refractory ( previously resistant to at least two different typical neuroleptics ) , were studied . The average dose of clozapine was 267 mg/d . The clinical variables considered were : Brief Psychiatric Rating Scale ( BPRS ) , number of admissions before and after clozapine treatment and the Strauss-Carpenter scale as measures of efficacy ; Premorbid Adjustment Scale ( PAS ) , to assess personal and social adjustment before illness ; Karolinska Personality Scale ( KPS ) to assess stable traits of personality ; and the Simpson-Angus scale as a measure of extrapyramidal symptoms . Sixty percent of patients showed a significant improvement after clozapine treatment . Side-effects were mild and well tolerated , with no cases of haematological disturbance and only five withdrawals because of adverse events . The severity of the episode , according to BPRS score and anxiety as a personal trait , are related to good prognosis . Other relationships between improvement and clinical and demographic variables are discussed Clozapine has been shown to have superior effectiveness compared with classic neuroleptics in treating refractory schizophrenia in Caucasians , but its efficacy and safety in Chinese have not been adequately studied . Forty Chinese schizophrenic patients were recruited in a 12-week , double-blind , comparative trial . Twenty-one patients were r and omly assigned to clozapine treatment and 19 to chlorpromazine treatment . The average dose was 543 ± 157 and 1163 ± 228 mg/day for clozapine and chlorpromazine , respectively . The results showed that six clozapine-treated patients ( 28.6 % ) had more than 20 % improvement in Brief Psychiatric Rating Scale score and were classified as responders , whereas none of the chlor-promazine-treated patients was classified as a responder . The degree of improvement in positive symptoms , negative symptoms and Brief Psychiatric Rating Scale scores in the clozapine group was inversely correlated with the severity of negative symptoms at entry into the trial . Two clozapine-treated patients were withdrawn from the study , one because of leukopenia and nausea , and the other because of vomiting and hypotension . Chlorpromazine treatment was prematurely discontinued in two patients , because of jaundice and over sedation in one , and because of severe weight loss in the other ( 9 kg ) . The rate of moderate-to-severe sialorrhea was high in clozapine-treated patients ( 28.6 % ) . Two clozapine-treated patients and two chlorpromazine-treated patients showed significant improvement in previously existing tardive dyskinesia and one chlorpromazine-treated patient exhibited aggravation of tardive dyskinesia . The results of this study indicate that clozapine treatment might have advantages over chlorpromazine for Chinese schizophrenic patients who are refractory to typical neuroleptic treatment OBJECTIVE In a preliminary report , the authors observed that clozapine was superior to haloperidol in the treatment of positive and negative symptoms in stable out patients with schizophrenia . In this final report , they examine the effects of clozapine on positive and negative symptoms in patients with and without the deficit syndrome to determine which patients receive the positive symptom advantage of clozapine and the extent of clozapine 's therapeutic effects on negative symptoms . In addition , they examine the long-term effects of clozapine on positive , negative , and affective symptoms , social and occupational functioning , and quality of life . METHOD Seventy-five out patients with schizophrenia , who met retrospective and prospect i ve criteria for residual positive or negative symptoms , were entered into a 10-week double-blind , parallel-groups comparison of clozapine and haloperidol . Patients who completed the double-blind study were then entered into a 1-year open-label clozapine study . RESULTS For patients who completed the 10-week double-blind study , clozapine was superior to haloperidol in treating positive symptoms . This effect was not observed in the intent-to-treat analyses . There was no evidence of any superior efficacy or long-term effect of clozapine on primary or secondary negative symptoms . Long-term clozapine treatment was associated with significant improvements in social and occupational functioning but not in overall quality of life . CONCLUSIONS For schizophrenic patients who are able to tolerate clozapine therapy , clozapine has superior efficacy for positive symptoms but not negative symptoms and is associated with long-term improvements in social and occupational functioning for patients with and without the deficit syndrome OBJECTIVE The purpose of the study was to examine the effects of clozapine in treating moderately ill schizophrenic out patients and to determine the length of medication trial needed to identify responders and nonresponders . METHODS Rates of clinical responses , relapses and hospitalizations , and levels of symptomatology and functioning were assessed for 30 chronic schizophrenic out patients who received clozapine for one year . For some patients , data on relapse and hospitalization during treatment were compared with data from the year before treatment . RESULTS Eighteen of the 30 patients met criteria for sustained response ; 17 of the responders were identified within the first four months of treatment . Patients experienced significantly fewer relapses and hospitalizations during treatment than in the previous year . Improvement in positive symptoms , general symptomatology , and levels of functioning reached a plateau during the first six months of treatment and remained at that level during the second six months . Negative symptoms and quality of life showed nonsignificant improvements at 12 months . CONCLUSIONS Results support the use of clozapine in treating chronic , residually symptomatic schizophrenic out patients . A four-month clozapine trial may be adequate to detect clinical responders in this population Background & objectives : Clozapine may be more useful in treatment-naive patients with first-episode schizophrenia for better symptoms control and improving quality of life . The current study was carried out to compare the efficacy and tolerability of clozapine versus risperidone in treatment-naive , first-episode patients of schizophrenia . Methods : This was a comparative , open-label , six months prospect i ve study of treatment-naive , first-episode patients with schizophrenia between the age group of 18 and 40 yr diagnosed as per the International Classification of Diseases-10 ( ICD-10 ) criteria . A total of 63 patients were recruited and r and omly assigned to clozapine group or risperidone group using computer-generated r and om number tables . Eight patients were lost to follow up . The dosages of the respective drugs were kept in therapeutic range of 200 - 600 mg/day and 4 - 8 mg/day orally for clozapine and risperidone , respectively . Results : On general psychopathology score , after six months of intervention , clozapine led to 60.32 per cent mean reduction in Positive and Negative Syndrome Scale ( PANSS ) for Schizophrenia total score while risperidone led to 56.35 per cent mean reduction in PANSS total score , which meant more improvement with clozapine . Clozapine group was found to have significant improvement in quality of life ( P = 0.04339 ) . On Glasgow Antipsychotic Side-effect Scale , clozapine was superior to risperidone . The most common side effects observed in clozapine group were oversedation ( 78.96 % ) and dizziness ( 55.23 % ) , and in risperidone group , common side effects were rigidity ( 62.36 % ) , sedation ( 38.69 % ) , tremors ( 65.69 % ) and menstrual irregularities in 80.25 per cent of female patients . Interpretation & conclusions : The findings of this preliminary study showed clozapine as a better choice than risperidone in terms of efficacy , tolerability and better quality of life in treatment-naive , first-episode schizophrenia . However , further studies need to be done on a larger group of patients to confirm the findings Preliminary results of a non-blinded prospect i ve study of the effect of clozapine on symptomatology and social function in 51 treatment-resistant schizophrenic patients are reported . The mean duration of treatment at the time of this report was 10.3±8.1 months , median 7.6 months . Overall , 3/51 patients ( 60.8 % ) showed at least a 20 % decrease in total BPRS , a criterion of improvement in the study of Kane et al. ( 1988 ) . Four of 51 ( 7.8 % ) had at least a 50 % decrease in total BPRS . Improvements in both positive and negative symptoms were noted . Marked improvements in social function were noted within the first 6 months of treatment . Improvement was first noted at all time points , with only 45.2 % of improvers being identified after 6 weeks of treatment . These results suggest a 6–12-month trial may be desirable before deciding to discontinue clozapine because of insufficient response . Higher total Brief Psychiatric Rating Scale ( BPRS ) score and higher ratings on the Paranoid Disturbance subscales of the BPRS were factors which discriminated clozapine responders from non-responders BACKGROUND Several lines of evidence suggest that clozapine is more effective than both first- and second-generation antipsychotic drugs in treatment-resistant schizophrenia ( TRS ) . However , clinicians appear to be hesitant to prescribe this drug . It would therefore be extremely valuable if predictors of response to clozapine could be identified . The aim of this study was to evaluate the predictive factors of clinical responses to clozapine in a group of Turkish patients with TRS . METHODS This was a 16-week uncontrolled open study carried out among 97 TRS patients ( 80 males and 17 females ; DSM-IV diagnosis ) . All patients fulfilled the criteria for refractory schizophrenia according to the UK guidelines for the National Institute of Clinical Excellence ( NICE ) . After all previous antipsychotic medications had run their course , the patients were started on clozapine according to a st and ardized titration and dosage schedule . Psychopathology was evaluated before the initiation of clozapine therapy and once every 4 weeks using the Brief Psychiatric Rating Scale ( BPRS ) , the Scale for the Assessment for Positive Symptoms , and the Scale for the Assessment of Negative Symptoms . RESULTS Of the TRS patients on clozapine , 55.7 % achieved a clinical response , defined as at least a 20 % decrease in BPRS . We observed a favorable effect of clozapine on both positive and negative symptoms . Logistic regression analysis showed that a good clozapine response was more likely when schizophrenia began at a later age , when negative symptoms were severe , and when patients had an early response at 4 weeks . CONCLUSION A combination of demographic , baseline clinical , and acute treatment response variables may accurately predict response to clozapine in TRS . Priority should be given to initiating clozapine at the earliest phase of TRS , especially for patients with evident negative symptoms Purpose / Background For approximately one third of individuals treated for psychosis or schizophrenia , antipsychotic medications will have little or no therapeutic benefit . Clozapine remains the sole medication approved for treatment-resistant schizophrenia , and studies have demonstrated its superior efficacy in reducing psychotic symptoms . Methods / Procedures Data were collected from the medical records of people who originally presented with a first-episode psychosis between 1995 and 1999 ( N = 171 ) . Data were obtained from first presentation up to December 31 , 2013 or until the patient was discharged or transferred . Information on service use and physical health was gathered using a data collection template design ed specifically for this audit . Findings / Results Twenty-eight ( 16.3 % ) of the cohort were prescribed clozapine . Data were available for 24 individuals . Of this clozapine sub sample , the mean age at baseline was 23.11 ( SD = 4.58 ) ; 82.14 % ( n = 23 ) were male ; and 82.14 % ( n = 23 ) had a baseline diagnosis of schizophrenia . The mean time to first trial of clozapine was 6.7 years . The mean number of antipsychotics prescribed before clozapine trial was 4.85 . After the initiation of clozapine , the mean number of hospital admissions reduced from 6.04 per year to 0.88 per year . Implication s/ Conclusions Nearly 1 in 5 of the original cohort was considered to have a suboptimal response to trials of antipsychotic medication . The use of clozapine for treatment-resistant schizophrenia is underutilized , and better underst and ing of the barriers to prescribing clozapine is necessary given the implication s for patient 's quality of life and hospital admission rates . Physical health data further emphasizes the importance of physical health monitoring in this vulnerable population BACKGROUND Treatment-resistance in schizophrenia remains a public health problem . Clozapine has been shown to be effective in about one third of this population , but carries with it medical risks and weekly blood draws . As olanzapine is a drug with a very similar biochemical profile to clozapine , it is important to evaluate whether non-response to olanzapine predicts clozapine non-response . METHODS Forty-four treatment-resistant patients received eight weeks of olanzapine , either in a double-blind trial or subsequent open treatment at a mean daily dose of 25 mg/day . Two of 44 patients ( 5 % ) responded to olanzapine treatment . Patients who did not respond could then receive clozapine . Twenty-seven subsequently received an 8-week open trial of clozapine . RESULTS Patients who did and did not receive clozapine did not differ demographically or in psychopathology . Eleven of 27 ( 41 % ) met a priori response criteria during clozapine treatment ( mean dose 693 mg/day ) after failing to respond to olanzapine . CONCLUSIONS This study demonstrates that failure to respond to olanzapine treatment does not predict failure to clozapine . Treatment-resistant patients who fail on olanzapine may benefit from a subsequent trial of clozapine This study focused on the symptomatic and cognitive effects of the atypical antipsychotic clozapine in chronic hospitalized schizophrenia patients . Further , it explored how these effects might be related to discharge , an important functional outcome . Patients were assessed at baseline and at regular intervals with clinical instruments and a cognitive battery . Clozapine treatment produced symptomatic and cognitive improvements , positive changes that appeared to occur independently of one another . Baseline cognitive performance , as well as cognitive change with treatment , predicted discharge . Further investigation of the effects of clozapine and other atypical antipsychotics on cognition and functional outcome is warranted OBJECTIVE Clozapine is an atypical neuroleptic with superior efficacy in severely ill , treatment-resistant in patients with schizophrenia . To determine if clozapine 's differential efficacy generalizes to less ill , out patients population s , the authors examined the effects of clozapine on positive and negative symptoms in out patients with schizophrenia . METHOD Out patients with schizophrenia who had histories of partial response to conventional neuroleptics and who had not responded to a prospect i ve 6-week trial of fluphenazine participated in a 10-week , double-blind , parallel-groups comparison of clozapine and haloperidol . Thirteen men and six women were given clozapine , and 15 men and five women were given haloperidol . Clinical response rates were determined and effects on primary versus secondary negative symptoms were addressed . Doses of clozapine and haloperidol at the end of the 10-week trial were 410.5 mg/day ( SD = 45.8 ) and 24.8 mg/day ( SD = 5.5 ) , respectively . RESULTS Clozapine was superior to haloperidol for treating positive symptoms . In addition , eight of the patients given clozapine and only one of the patients given haloperidol fulfilled clinical responder criteria . Clozapine was also superior to haloperidol for treating negative symptoms , although these effects were relatively minor . Negative symptoms were significantly affected in the subgroup of patients with nondeficit schizophrenia but not in the subgroup with deficit schizophrenia . Overall , clozapine was well tolerated . CONCLUSIONS Clozapine has superior efficacy for treating positive symptoms in partially responsive out patients with chronic schizophrenia , suggesting that it has utility for a broad spectrum of patients with schizophrenia beyond the most severely ill Background : Clozapine is the recommended antipsychotic for treatment-resistant schizophrenia ( TRS ) but there is significant variability between patients in the degree to which clozapine will improve symptoms . The biological basis of this variability is unknown . Although clozapine has efficacy in TRS , it can elicit adverse effects and initiation is often delayed . Identification of predictive biomarkers of clozapine response may aid initiation of clozapine treatment , as well as underst and ing of its mechanism of action . In this article we systematic ally review prospect i ve or genetic studies of biological predictors of response to clozapine . Methods : We search ed the PubMed data base until 20th January 2018 for studies investigating “ clozapine ” AND ( “ response ” OR “ outcome ” ) AND “ schizophrenia . ” Inclusion required that studies examined a biological variable in relation to symptomatic response to clozapine . For all studies except genetic- studies , inclusion required that biological variables were measured before clozapine initiation . Results : Ninety-eight studies met the eligibility criteria and were included in the review , including neuroimaging , blood-based , cerebrospinal fluid (CSF)-based , and genetic predictors . The majority ( 70 ) are genetic studies , collectively investigating 379 different gene variants , however only three genetic variants ( DRD3 Ser9Gly , HTR2A His452Tyr , and C825 T GNB3 ) have independently replicated significant findings . Of the non-genetic variables , the most consistent predictors of a good response to clozapine are higher prefrontal cortical structural integrity and activity , and a lower ratio of the dopamine and serotonin metabolites , homovanillic acid ( HVA ) : 5-hydroxyindoleacetic acid ( 5-HIAA ) in CSF . Conclusions : Recommendations include that future studies should ensure adequate clozapine trial length and clozapine plasma concentrations , and may include multivariate models to increase predictive accuracy Importance It has remained unclear whether there are clinical ly meaningful differences between antipsychotic treatments with regard to preventing relapse of schizophrenia , owing to the impossibility of including large unselected patient population s in r and omized clinical trials , as well as residual confounding from selection biases in observational studies . Objective To study the comparative real-world effectiveness of antipsychotic treatments for patients with schizophrenia . Design , Setting , and Participants Prospect ively gathered nationwide data bases were linked to study the risk of rehospitalization and treatment failure from July 1 , 2006 , to December 31 , 2013 , among all patients in Sweden with a schizophrenia diagnosis who were 16 to 64 years of age in 2006 ( 29 823 patients in the total prevalent cohort ; 4603 in the incident cohort of newly diagnosed patients ) . Within-individual analyses were used for primary analyses , in which each individual was used as his or her own control to eliminate selection bias . Traditional Cox proportional hazards multivariate regression was used for secondary analyses . Main Outcomes and Measures Risk of rehospitalization and treatment failure ( defined as psychiatric rehospitalization , suicide attempt , discontinuation or switch to other medication , or death ) . Results There were 29 823 patients ( 12 822 women and 17 001 men ; mean [ SD ] age , 44.9 [ 12.0 ] years ) . During follow-up , 13 042 of 29 823 patients ( 43.7 % ) were rehospitalized , and 20 225 of 28 189 patients ( 71.7 % ) experienced treatment failure . The risk of psychiatric rehospitalization was the lowest during monotherapy with once-monthly long-acting injectable paliperidone ( hazard ratio [ HR ] , 0.51 ; 95 % CI , 0.41 - 0.64 ) , long-acting injectable zuclopenthixol ( HR , 0.53 ; 95 % CI , 0.48 - 0.57 ) , clozapine ( HR , 0.53 ; 95 % CI , 0.48 - 0.58 ) , long-acting injectable perphenazine ( HR , 0.58 ; 95 % CI , 0.52 - 0.65 ) , and long-acting injectable olanzapine ( HR , 0.58 ; 95 % CI , 0.44 - 0.77 ) compared with no use of antipsychotic medication . Oral flupentixol ( HR , 0.92 ; 95 % CI , 0.74 - 1.14 ) , quetiapine ( HR , 0.91 ; 95 % CI , 0.83 - 1.00 ) , and oral perphenazine ( HR , 0.86 ; 95 % CI , 0.77 - 0.97 ) were associated with the highest risk of rehospitalization . Long-acting injectable antipsychotic medications were associated with substantially lower risk of rehospitalization compared with equivalent oral formulations ( HR , 0.78 ; 95 % CI , 0.72 - 0.84 in the total cohort ; HR , 0.68 ; 95 % CI , 0.53 - 0.86 in the incident cohort ) . Clozapine ( HR , 0.58 ; 95 % CI , 0.53 - 0.63 ) and all long-acting injectable antipsychotic medications ( HRs 0.65 - 0.80 ) were associated with the lowest rates of treatment failure compared with the most widely used medication , oral olanzapine . The results of several sensitivity analyses were consistent with those of the primary analyses . Conclusions and Relevance Clozapine and long-acting injectable antipsychotic medications were the pharmacologic treatments with the highest rates of prevention of relapse in schizophrenia . The risk of rehospitalization is about 20 % to 30 % lower during long-acting injectable treatments compared with equivalent oral formulations |
10,443 | 21,884,954 | Treatment with beta-blockers improved all-cause mortality in patients with CKD and chronic systolic heart failure .
There is insufficient evidence to conclude whether people with CKD who are not known to have heart failure derive benefit from beta-blockers | OBJECTIVES The aim of this systematic review was to study the benefits and risks of beta-adrenergic antagonists ( beta-blockers ) in patients with chronic kidney disease ( CKD ) .
BACKGROUND There is an excess burden of cardiovascular disease and death in people with CKD .
Despite their potential benefits , the effects of beta-blockers in this population are uncertain . | BACKGROUND There have been no r and omized trials of cardioprotective therapy after acute myocardial infa rct ion in patients with chronic kidney disease who should be largely eligible for aspirin ( acetylsalicylic acid ; ASA ) and beta-blockers ( BB ) as a base of therapy . METHODS We analyzed a prospect i ve coronary care unit registry of 1724 patients with ST-segment elevation myocardial infa rct ion . RESULTS Usage rates were 52.3 % , 19.0 % , 15.2 % , and 13.5 % for ASA and BB ( ASA+BB ) , BB alone , ASA alone , and no ASA or BB therapy . Patients who received ASA+BB were more likely to be male , free of earlier cardiac disease , and recipients of thrombolysis . Conversely , the absence of ASA+BB was observed in patients with heart failure on admission , left bundle branch block , atrial and ventricular arrhythmias , and shock . The combination of ASA+BB was used in 63.9 % , 55.8 % , 48.2 % , and 35.5 % of patients with corrected creatinine clearance values of > 81.5 , 81.5 to 63.1 , 63.1 to 46.2 , and < 46.2 mL/min/72 kg ( P < .0001 ) . ASA+BB was used in 40.4 % of patients undergoing dialysis . The age-adjusted relative risk reduction for the inhospital mortality rate was similar among all renal groups and ranged from 64.3 % to 80.0 % ( all P < .0001 ) . CONCLUSION ASA+BB is an underused therapy in patients with acute myocardial infa rct ion who have underlying kidney disease Cardiovascular events ( CVEs ) are the leading cause of death in chronic hemodialysis patients . Results of trials in non-end-stage renal disease ( ESRD ) patients can not be extrapolated to patients with ESRD . It is critical to test cardiovascular therapies in these high-risk patients who are usually excluded from major cardiovascular trials . The study objective was to evaluate the effect of fosinopril on CVEs in patients with ESRD . Eligible patients were r and omized to fosinopril 5 mg titrated to 20 mg daily ( n=196 ) or placebo ( n=201 ) plus conventional therapy for 24 months . The primary end point was combined fatal and nonfatal first major CVEs ( cardiovascular death , resuscitated death , nonfatal stroke , heart failure , myocardial infa rct ion , or revascularization ) . No significant benefit for fosinopril was observed in the intent to treat analysis ( n=397 ) after adjusting for independent predictors of CVEs ( RR=0.93 , 95 % confidence interval ( CI ) 0.68 - 1.26 , P=0.35 ) . The per protocol secondary supportive analysis ( n=380 ) found a trend towards benefit for fosinopril ( adjusted RR=0.79 ( 95 % CI 0.59 - 1.1 , P=0.099 ) ) . In the patients who were hypertensive at baseline , systolic and diastolic blood pressures were significantly decreased in the fosinopril as compared to the placebo group . After adjustment for risk factors , trends were observed suggesting fosinopril may be associated with a lower risk of CVEs . These trends may have become statistically significant had the sample size been larger , and these findings warrant further study OBJECTIVES We sought to evaluate the effects of carvedilol on mortality and morbidity in dialysis patients with dilated cardiomyopathy . BACKGROUND Several lines of evidence support the concept that therapy with beta-blocking agents reduces morbidity and mortality in patients with congestive heart failure ( HF ) , but the demonstration of such a survival benefit in dialysis patients with dilated cardiomyopathy is still lacking . METHODS A total of 114 dialysis patients with dilated cardiomyopathy were r and omized to receive either carvedilol or placebo in addition to st and ard therapy . A first analysis was performed at one year and was followed by an additional follow-up period of 12 months . RESULTS Two-year echocardiographic data revealed a significant attenuation of pathologic remodeling , with smaller cavity diameters and higher ejection fractions in the active treatment group than in the placebo group . At two years , 51.7 % of the patients died in the carvedilol group , compared with 73.2 % in the placebo group ( p < 0.01 ) . Furthermore , there were significantly fewer cardiovascular deaths ( 29.3 % ) and hospital admissions ( 34.5 % ) among patients receiving carvedilol than among those receiving a placebo ( 67.9 % and 58.9 % , respectively ; p < 0.00001 ) . The exploratory analyses revealed that fatal myocardial infa rct ions , fatal strokes , and hospital admissions for worsening HF were lower in the carvedilol group than in the placebo group . A reduction in sudden deaths and pump-failure deaths was also observed , though it did not reach statistical significance . CONCLUSIONS Carvedilol reduced morbidity and mortality in dialysis patients with dilated cardiomyopathy . These data suggest the use of carvedilol in all dialysis patients with chronic HF Aim To determine the safety and efficacy of nebivolol in elderly heart failure ( HF ) patients with renal dysfunction . Methods and results SENIORS recruited patients aged 70 years or older with symptomatic HF , irrespective of ejection fraction , and r and omized them to nebivolol or placebo . Patients ( n = 2112 ) were divided by tertile of estimated glomerular filtration rate ( eGFR ) . Mean age of patients was 76.1 years , 35 % of patients had an ejection fraction of > 35 % , and 37 % were women result ing in a unique cohort , far more representative of clinical practice than previous trials . eGFR was strongly associated with outcomes and nebivolol was similarly efficacious across eGFR tertiles . The primary outcome rate ( all-cause mortality or cardiovascular hospital admission ) and adjusted hazard ratio for nebivolol use in those with low eGFR was 40 % and 0.84 ( 95 % CI 0.67–1.07 ) , 31 % and 0.79 ( 0.60–1.04 ) in the middle tertile , and 29 % and 0.86 ( 0.65–1.14 ) in the highest eGFR tertile . There was no interaction noted between renal function and the treatment effect ( P = 0.442 ) . Nebivolol use in patients with moderate renal impairment ( eGFR < 60 ) was not associated with major safety concerns , apart from higher rates of drug-discontinuation due to bradycardia . Conclusion Nebivolol is safe and has a similar effect in elderly HF patients with mild or moderate renal impairment Given the high prevalence of cardiovascular disease in people with chronic kidney disease ( CKD ) and the clear benefits of mortality reduction observed for most β−blockers in clinical trials , they are relatively underused in CKD patients [ 1,2 ] . The rationale for use of β-blockers in patients with CKD is review ed in detail elsewhere [ 2,3 ] but is summarized in this editorial . Alterations in β- and α-receptor responsiveness are associated with sympathetic over-activity in CKD . This increased sympathetic activity is involved in the genesis of hypertension , and contributes to cardiac complications seen in CKD [ 2,3 ] . The contribution of the sympathetic nervous system to nephropathy progression is documented in sub-totally nephrectomized rats where non-hypotensive doses of β-blockers ameliorate development of glomerulosclerosis and cardiac injury [ 4 ] . In men , sympathetic over-activity , as assessed by sural nerve microneurography , was present in patients on haemodialysis [ 5 ] , stage 4 nephropathy [ 6 ] and in early stage 2 nephropathy among patients with polycystic kidney disease [ 7 ] . The role of the damaged kidney in causing sympathetic over-activity is illustrated by normalization of sympathetic over-activity in haemodialysis patients following bilateral nephrectomy [ 5 ] and in renal allograft recipients when their shrunken native kidneys are removed [ 8 ] . The most common cause of death in stage 3 and higher CKD results from complications of cardiovascular disease . This may be due , in part , to inadequate treatment of blood pressure , where blood pressure goals were not attained and agents known to reduce mortality secondary to cardiovascular causes , i.e. aspirin , ACE inhibitors and β-blockers were not used [ 9 ] . In a separate study , β-blockers were used in fewer than 30 % of haemodialysis patients [ 10 ] . This is surprising , since β-blockers are well-established , evidence -based therapy for reducing cardiovascular risk in hypertension associated with diabetes and after myocardial infa rct ion [ 11,12 ] . Observational studies support definite survival benefits derived from β-blocker use in patients with advanced CKD [ 13,14 ] . Furthermore , a prospect i ve CONTEXT Hypertension is a leading cause of end-stage renal disease ( ESRD ) in the United States , with no known treatment to prevent progressive declines leading to ESRD . OBJECTIVE To compare the effects of 2 levels of blood pressure ( BP ) control and 3 antihypertensive drug classes on glomerular filtration rate ( GFR ) decline in hypertension . DESIGN R and omized 3 x 2 factorial trial with enrollment from February 1995 to September 1998 . SETTING AND PARTICIPANTS A total of 1094 African Americans aged 18 to 70 years with hypertensive renal disease ( GFR , 20 - 65 mL/min per 1.73 m(2 ) ) were recruited from 21 clinical centers throughout the United States and followed up for 3 to 6.4 years . INTERVENTIONS Participants were r and omly assigned to 1 of 2 mean arterial pressure goals , 102 to 107 mm Hg ( usual ; n = 554 ) or 92 mm Hg or less ( lower ; n = 540 ) , and to initial treatment with either a beta-blocker ( metoprolol 50 - 200 mg/d ; n = 441 ) , an angiotensin-converting enzyme inhibitor ( ramipril 2.5 - 10 mg/d ; n = 436 ) or a dihydropyridine calcium channel blocker , ( amlodipine 5 - 10 mg/d ; n = 217 ) . Open-label agents were added to achieve the assigned BP goals . MAIN OUTCOME MEASURES Rate of change in GFR ( GFR slope ) ; clinical composite outcome of reduction in GFR by 50 % or more ( or > or = 25 mL/min per 1.73 m2 ) from baseline , ESRD , or death . Three primary treatment comparisons were specified : lower vs usual BP goal ; ramipril vs metoprolol ; and amlodipine vs metoprolol . RESULTS Achieved BP averaged ( SD ) 128/78 ( 12/8 ) mm Hg in the lower BP group and 141/85 ( 12/7 ) mm Hg in the usual BP group . The mean ( SE ) GFR slope from baseline through 4 years did not differ significantly between the lower BP group ( -2.21 [ 0.17 ] mL/min per 1.73 m2 per year ) and the usual BP group ( -1.95 [ 0.17 ] mL/min per 1.73 m2 per year ; P = .24 ) , and the lower BP goal did not significantly reduce the rate of the clinical composite outcome ( risk reduction for lower BP group = 2 % ; 95 % confidence interval [ CI ] , -22 % to 21 % ; P = .85 ) . None of the drug group comparisons showed consistent significant differences in the GFR slope . However , compared with the metoprolol and amlodipine groups , the ramipril group manifested risk reductions in the clinical composite outcome of 22 % ( 95 % CI , 1%-38 % ; P = .04 ) and 38 % ( 95 % CI , 14%-56 % ; P = .004 ) , respectively . There was no significant difference in the clinical composite outcome between the amlodipine and metoprolol groups . CONCLUSIONS No additional benefit of slowing progression of hypertensive nephrosclerosis was observed with the lower BP goal . Angiotensin-converting enzyme inhibitors appear to be more effective than beta-blockers or dihydropyridine calcium channel blockers in slowing GFR decline Abstract Objective : To compare the ability of angiotensin converting enzyme inhibitors and β blockers to slow the development of end stage renal failure in non-diabetic patients with chronic renal failure . Design : Open r and omised multicentre trial with three year follow up . Setting : Outpatient departments of six French hospitals . Patients : 100 hypertensive patients with chronic renal failure ( initial serum creatinine 200 - 400 μmol/l ) . 52 r and omised to enalapril and 48 to β blockers ( conventional treatment ) . Interventions : Enalapril or β blocker was combined with frusemide and , if necessary , a calcium blocker or central ly acting drug in patients whose diastolic pressure remained above 90 mm Hg . Results : 17 patients receiving conventional treatment and 10 receiving enalapril developed end stage renal failure . The cumulative renal survival rate was significantly better in the enalapril group than in the conventional group ( P<0.05 ) . The slope of the reciprocal serum creatinine concentration was steeper in the conventionally treated patients ( - 6.89x10 - 5l/μmol/month ) than in the enalapril group ( -4.17x10 - 5l/μmol/month ; P<0.05 ) . No difference in blood pressure was found between groups . Conclusion : In hypertensive patients with chronic renal failure enalapril slows progression towards end stage renal failure compared with β blockers . This effect was probably not mediated through controlling blood pressure BACKGROUND Limited information is available on the risk and impact of renal dysfunction on the response to beta-blockade and mode of death in systolic heart failure ( HF ) . METHODS AND RESULTS Renal function was estimated with glomerular filtration rate ( eGFR ) using the simplified Modification of Diet in Renal Disease ( MDRD ) equation . Patients from the Metoprolol CR/XL Controlled R and omized Intervention Trial in Chronic HF ( MERIT-HF ) were divided into 3 renal function subgroups ( MDRD formula ) : eGFR(MDRD ) > 60 ( n = 2496 ) , eGFR(MDRD ) 45 to 60 ( n = 976 ) , and eGFR(MDRD ) < 45 mL/min per 1.73 m(2 ) body surface area ( n = 493 ) . Hazard ratio ( HR ) was estimated with Cox proportional hazards models adjusted for prespecified risk factors . Placebo patients with eGFR < 45 had significantly higher risk than those with eGFR > 60 : HR for all-cause mortality , 1.90 ( 95 % confidence interval [ CI ] , 1.28 to 2.81 ) comparing placebo patients with eGFR < 45 and eGFR > 60 , and for the combined end point of all-cause mortality/hospitalization for worsening HF ( time to first event ) : HR , 1.91 ( 95 % CI , 1.44 to 2.53 ) . No significant increase in risk with deceased renal function was observed for those r and omized to metoprolol controlled release (CR)/extended release ( XL ) due to a highly significant decrease in risk on metoprolol CR/XL in those with eGFR < 45 . For total mortality , metoprolol CR/XL vs placebo : HR , 0.41 ( 95 % CI . 0.25 to 0.68 ; P < .001 ) in those with eGFR < 45 compared with HR , 0.71 ( 95 % CI , 0.54 to 0.95 ; P < .021 ) for those with eGFR > 60 ; corresponding data for the combined end point was HR , 0.44 ( 95 % CI , 0.31 to 0.63 ; P < .0001 ) and HR , 0.75 ( 0.62 to 0.92 ; P = .005 , respectively ; P = .095 for interaction by treatment for total mortality ; P = .011 for combined end point ) . Metoprolol CR/XL was well tolerated in all 3 renal function subgroups . CONCLUSIONS Renal function as estimated by eGFR was a powerful predictor of death and hospitalizations from worsening HF . Metoprolol CR/XL was at least as effective in reducing death and hospitalizations for worsening HF in patients with eGFR < 45 as in those with eGFR > 60 BACKGROUND Cardiac disease is a common cause of death in chronic hemodialysis patients . A sub analysis of the data on cardiac diseases in the Hemodialysis ( HEMO ) Study was performed . The specific objectives were : ( 1 ) to analyze the prevalence of cardiac disease at baseline ; ( 2 ) to characterize the incidence of various types of cardiac events during follow-up ; ( 3 ) to examine the association of cardiac events during follow-up with baseline cardiac diseases ; and ( 4 ) to examine the effect of dose and flux interventions on various types of cardiac events . METHODS The HEMO Study is a r and omized multi-center trial on 1846 chronic hemodialysis patients at 15 clinical centers comprising 72 dialysis units . The scheduled maximum follow-up duration was 0.9 to 6.6 years , with the mean actual follow-up of 2.84 years . The interventions were st and ard-dose versus high-dose and low-flux versus high-flux hemodialysis in a 2 x 2 factorial design . RESULTS At baseline , 80 % of patients had cardiac diseases , including ischemic heart disease ( IHD ) ( 39 % ) , congestive heart failure ( 40 % ) , arrhythmia ( 31 % ) , and other heart diseases ( 63 % ) . There were a total of 1685 cardiac hospitalizations , with angina and acute myocardial infa rct ion accounting for 42.7 % of these hospitalizations . There were 343 cardiac deaths during follow-up , accounting for 39.4 % of all deaths . IHD was implicated in 61.5 % of the cardiac deaths . Any cardiac disease at baseline was highly predictive of cardiac death during follow-up [ relative risk ( RR ) 2.57 ; 95 % CI 1.73 - 3.83 ] . There were no significant effects of dose or flux assignments on the primary outcome of all-cause mortality or the main secondary cardiac composite outcome of first cardiac hospitalization or all-cause mortality . Assignment to high-flux dialysis was , however , associated with decreased cardiac mortality and the composite outcome of first cardiac hospitalization or death from cardiac causes . CONCLUSION The HEMO Study identified IHD to be a major cause of cardiac hospitalizations and cardiac deaths . Future strategies for the prevention of cardiac diseases in the maintenance hemodialysis population should focus on this entity . Although high-flux dialysis did not reduce all-cause mortality , it might improve cardiac outcomes . This hypothesis needs to be further examined BACKGROUND The presence of coexisting conditions has a substantial effect on the outcome of acute myocardial infa rct ion . Renal failure is associated with one of the highest risks , but the influence of milder degrees of renal impairment is less well defined . METHODS As part of the Valsartan in Acute Myocardial Infa rct ion Trial ( VALIANT ) , we identified 14,527 patients with acute myocardial infa rct ion complicated by clinical or radiologic signs of heart failure , left ventricular dysfunction , or both , and a documented serum creatinine measurement . Patients were r and omly assigned to receive captopril , valsartan , or both . The glomerular filtration rate ( GFR ) was estimated by means of the four-component Modification of Diet in Renal Disease equation , and the patients were grouped according to their estimated GFR . We used a 70-c and i date variable model to adjust and compare overall mortality and composite cardiovascular events among four GFR groups . RESULTS The distribution of estimated GFR was wide and normally shaped , with a mean ( + /-SD ) value of 70+/-21 ml per minute per 1.73 m2 of body-surface area . The prevalence of coexisting risk factors , prior cardiovascular disease , and a Killip class of more than I was greatest among patients with a reduced estimated GFR ( less than 45.0 ml per minute per 1.73 m2 ) , and the use of aspirin , beta-blockers , statins , or coronary-revascularization procedures was lowest in this group . The risk of death or the composite end point of death from cardiovascular causes , reinfa rct ion , congestive heart failure , stroke , or resuscitation after cardiac arrest increased with declining estimated GFRs . Although the rate of renal events increased with declining estimated GFRs , the adverse outcomes were predominantly cardiovascular . Below 81.0 ml per minute per 1.73 m2 , each reduction of the estimated GFR by 10 units was associated with a hazard ratio for death and nonfatal cardiovascular outcomes of 1.10 ( 95 percent confidence interval , 1.08 to 1.12 ) , which was independent of the treatment assignment . CONCLUSIONS Even mild renal disease , as assessed by the estimated GFR , should be considered a major risk factor for cardiovascular complications after a myocardial infa rct ion Echocardiographic abnormalities are the rule in patients starting dialysis therapy and are associated with the development of cardiac failure and death . It is unknown , however , whether regression of these abnormalities is associated with an improvement in prognosis . As part of a prospect i ve cohort study with mean follow-up of 41 mo , 227 patients had echocardiography at inception and after 1 yr of dialysis therapy . Improvements in left ventricular ( LV ) mass index , volume index , and fractional shortening were seen in 48 , 48 , and 46 % , respectively . Ninety patients had developed cardiac failure by 1 yr of dialysis therapy . Twenty-six percent of the remaining 137 patients subsequently developed new-onset cardiac failure . The mean changes in LV mass index were 17 g/m(2 ) in those who subsequently developed cardiac failure compared with 0 g/m(2 ) among those who did not ( P = 0.05 ) . The corresponding values were -8 versus 0 % for fractional shortening ( P < 0.0001 ) . The associations between serial change in both LV mass index and fractional shortening and subsequent cardiac failure persisted after adjusting for baseline age , diabetes , ischemic heart disease , and the corresponding baseline echocardiographic parameter . Regression of LV abnormalities is associated with an improved cardiac outcome in dialysis patients . Serial echocardiography adds prognostic information to one performed at baseline BACKGROUND beta-Blockers have been shown to be beneficial in the treatment and prevention of heart failure ( HF ) in the general population , but they have not been assessed for their association with nonfatal HF in a nationally representative population of long-term dialysis patients . METHODS We conducted a retrospective cohort study of 2550 patients enrolled in the US Renal Data System ( USRDS ) Wave 2 who were Medicare eligible at the start of the study . Analysis was stratified by the presence or absence of a known diagnosis of HF , and patients followed up until December 31 , 2000 . Cox regression analysis , including propensity scores , was used to model adjusted hazard ratios for beta-blocker use ( assessed separately by cardioselective activity and lipid solubility ) with time to the first Medicare institutional cl aim for HF , cardiovascular-related death , or death from any cause . RESULTS In patients without a previous history of HF , beta-blocker use was significantly associated with a lower adjusted risk of HF ( adjusted hazard ratio , 0.69 ; 95 % confidence interval , 0.52 - 0.91 ; P=.008 ) , with a similar reduction in risk of cardiac-related and all-cause death . beta-Blocker use had no statistically significant associations with outcomes in patients with previous HF . CONCLUSIONS In dialysis patients without a previous documented history of HF , beta-blocker use was associated with a lower risk of new HF , cardiovascular death , and death from any cause . No such associations were seen for dialysis patients with a previous history of HF . These results are hypothesis generating only and should be confirmed in r and omized trials Chronic kidney disease ( CKD ) is associated with a high risk of cardiovascular disease , but evidence regarding the effectiveness of interventions to reduce that risk is lacking . The Perindopril Protection against Recurrent Stroke Study ( PROGRESS ) study enrolled 6105 participants with cerebrovascular disease and r and omly allocated them to perindopril-based blood pressure-lowering therapy or placebo . Individuals with CKD were at approximately 1.5-fold greater risk of major vascular events , stroke , and coronary heart disease , and were more than twice as likely to die ( all P < or = 0.002 ) . Perindopril-based treatment reduced the risk of major vascular events by 30 % and stroke by 35 % among subjects with CKD , and the absolute effects of treatment were 1.7-fold greater for those with CKD than for those without . Considering patients with CKD and a history of cerebrovascular disease , perindopril prevented one stroke or other cardiovascular event among every 11 patients treated over five years . In conclusion , kidney function should be considered when determining the need for blood pressure lowering therapy in patients with cerebrovascular disease Chronic kidney disease ( CKD ) is associated with a high risk of death from coronary artery disease and may modify the response to st and ard cardiovascular therapies . Treatment of subjects with CKD should ideally be based on evidence from r and omized , clinical trials , but how often subjects with CKD have been excluded from these trials is uncertain . We undertook this study in order to quantify how often subjects with moderate to advanced CKD were excluded from large cardiovascular trials . MEDLINE and the reference list of selected articles were search ed in order to identify large , r and omized , controlled trials of five different coronary artery disease therapies published between 1998 and 2005 . Exclusion criteria and reported clinical characteristics of subjects were abstract ed . Rates of exclusion and reporting of baseline characteristics of study participants were compared for CKD , diabetes , history of smoking , and hypertension . Eighty-six trials r and omizing 411 653 patients were identified . More than 80 % of trials excluded subjects with end-stage renal disease and 75.0 % excluded patients with CKD . Subjects with diabetes , hypertension , or a history of smoking were excluded less than 4 % of the time . Baseline renal function of study participant was reported in only 7 % of trials . Patients with CKD are frequently excluded from coronary artery disease trials and renal function of r and omized subjects is rarely reported . These findings reinforce the notion that available data on the treatment of coronary artery disease in subjects with CKD have significant limitations and should be generalized to the treatment of subjects with CKD cautiously The incidence of ESRD is increasing dramatically . Progression to end-stage may be halted or slowed when kidney damage is detected at an early stage . Kidney damage is frequently asymptomatic but is indicated by the presence of proteinuria , hematuria , or reduced GFR . Population -based studies relating to the prevalence of kidney damage in the community are limited , particularly outside of the United States . Therefore , the prevalence of proteinuria , hematuria , and reduced GFR in the Australian adult population was determined using a cross-sectional study of 11,247 noninstitutionalized Australians aged 25 yr or over , r and omly selected using a stratified , cluster method . Subjects were interviewed and tested for proteinuria-spot urine protein to creatinine ratio ( abnormal : > /=0.20 mg/mg ) ; hematuria-spot urine dipstick ( abnormal : 1 + or greater ) confirmed by urine microscopy ( abnormal : > 10,000 red blood cells per milliliter ) or dipstick ( abnormal : 1 + or greater ) on midstream urine sample ; and reduced GFR-Cockcroft-Gault estimated GFR ( abnormal : < 60 ml/min per 1.73 m(2 ) ) . The associations between age , gender , diabetes mellitus , and hypertension , and indicators of kidney damage were examined . Proteinuria was detected in 2.4 % of cases ( 95 % CI : 1.6 % , 3.1 % ) , hematuria in 4.6 % ( 95 % CI : 3.8 % , 5.4 % ) , and reduced GFR in 11.2 % ( 95 % CI : 8.6 % , 13.8 % ) . Approximately 16 % had at least one indicator of kidney damage . Age , diabetes mellitus , and hypertension were independently associated with proteinuria ; age , gender , and hypertension with hematuria ; and age , gender , and hypertension with reduced GFR . Approximately 16 % of the Australian adult population has either proteinuria , hematuria , and /or reduced GFR , indicating the presence of kidney damage . Identifying and targeting this section of the population may provide a means to reduce the burden of ESRD BACKGROUND Statins reduce the incidence of cardiovascular events in patients at high cardiovascular risk . However , a benefit of statins in such patients who are undergoing hemodialysis has not been proved . METHODS We conducted an international , multicenter , r and omized , double-blind , prospect i ve trial involving 2776 patients , 50 to 80 years of age , who were undergoing maintenance hemodialysis . We r and omly assigned patients to receive rosuvastatin , 10 mg daily , or placebo . The combined primary end point was death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . Secondary end points included death from all causes and individual cardiac and vascular events . RESULTS After 3 months , the mean reduction in low-density lipoprotein ( LDL ) cholesterol levels was 43 % in patients receiving rosuvastatin , from a mean baseline level of 100 mg per deciliter ( 2.6 mmol per liter ) . During a median follow-up period of 3.8 years , 396 patients in the rosuvastatin group and 408 patients in the placebo group reached the primary end point ( 9.2 and 9.5 events per 100 patient-years , respectively ; hazard ratio for the combined end point in the rosuvastatin group vs. the placebo group , 0.96 ; 95 % confidence interval [ CI ] , 0.84 to 1.11 ; P=0.59 ) . Rosuvastatin had no effect on individual components of the primary end point . There was also no significant effect on all-cause mortality ( 13.5 vs. 14.0 events per 100 patient-years ; hazard ratio , 0.96 ; 95 % CI , 0.86 to 1.07 ; P=0.51 ) . CONCLUSIONS In patients undergoing hemodialysis , the initiation of treatment with rosuvastatin lowered the LDL cholesterol level but had no significant effect on the composite primary end point of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . ( Clinical Trials.gov number , NCT00240331 . Patients with end-stage renal disease ( ESRD ) are at high risk for heart failure , but the prevalence and the prognostic value of asymptomatic systolic dysfunction in these patients are unknown . In this prospect i ve cohort study , the authors have therefore assessed by echocardiography the prevalence and the prognostic value of systolic function as estimated by ejection fraction ( EF ) , fractional shortening at endocardial level ( endoFS ) , and at midwall ( mwFS ) , in a cohort of 254 asymptomatic dialysis patients . Systolic dysfunction had a prevalence rate of 26 % by endoFS and of 48 % by mwFS . During the follow-up period , 125 patients had one or more fatal and nonfatal CV events . On multivariate COX regression analysis , the three LV systolic function indicators were independently associated with incident fatal and nonfatal CV events , and there were no differences in the predictive power of these indicators ( P > 0.30 ) . The prediction power of LV function indicators was largely independent of traditional and novel risk factors in ESRD such as C-reactive protein and asymmetric dimethyl arginine ( ADMA ) . ADMA was significantly related with LV function indicators as well as with mortality and incident CV events , but these links were much reduced ( P = NS ) in models including LV function indicators . Of note , the risk of CV events was minimal in patients with normal LV mass and function , intermediate in patients with either LVH or systolic dysfunction , and maximal in patients displaying both alterations . The study of myocardial contractility by echocardiography provides prognostic information independently of LV mass and other risk factors in ESRD . Risk stratification by simple systolic function parameters may prove useful in secondary prevention strategies in these patients End-stage renal disease ( ESRD ) patients have a high cardiovascular mortality rate . Precise estimates of the prevalence , risk factors and prognosis of different manifestations of cardiac disease are unavailable . In this study a prospect i ve cohort of 433 ESRD patients was followed from the start of ESRD therapy for a mean of 41 months . Baseline clinical assessment and echocardiography were performed on all patients . The major outcome measure was death while on dialysis therapy . Clinical manifestations of cardiovascular disease were highly prevalent at the start of ESRD therapy : 14 % had coronary artery disease , 19 % angina pectoris , 31 % cardiac failure , 7 % dysrhythmia and 8 % peripheral vascular disease . On echocardiography 15 % had systolic dysfunction , 32 % left ventricular dilatation and 74 % left ventricular hypertrophy . The overall median survival time was 50 months . Age , diabetes mellitus , cardiac failure , peripheral vascular disease and systolic dysfunction independently predicted death in all time frames . Coronary artery disease was associated with a worse prognosis in patients with cardiac failure at baseline . High left ventricular cavity volume and mass index were independently associated with death after two years . The independent associations of the different echocardiographic abnormalities were : systolic dysfunction-older age and coronary artery disease ; left ventricular dilatation-male gender , anemia , hypocalcemia and hyperphosphatemia ; left ventricular hypertrophy-older age , female gender , wide arterial pulse pressure , low blood urea and hypoalbuminemia . We conclude that clinical and echocardiographic cardiovascular disease are already present in a very high proportion of patients starting ESRD therapy and are independent mortality factors The future rate of cardiovascular events can be predicted by several well-established risk factors . Even in the absence of classic risk factors , patients with renal disease have an elevated risk for cardiovascular disease ( 1 , 2 ) . This renalcardiovascular association is well established in patients with advanced renal insufficiency ( 2 ) . It has also been reported in patients in the Hypertension Detection and Follow-up Program ( HDFP ) ( 3 ) , in which a serum creatinine concentration greater than 133 mol/L ( 1.5 mg/dL ) was a strong predictor of cardiovascular disease . However , HDFP included only patients with hypertension . In contrast , a recent analysis of data from the Framingham Study did not detect a relationship between mild renal insufficiency ( defined as a serum creatinine concentration of 124 to 265 mol/L [ 1.4 to 3.0 mg/dL ] ) and cardiovascular events ( 4 ) . The Heart Outcomes and Prevention Evaluation ( HOPE ) study investigated the effects of ramipril and vitamin E on major cardiovascular outcomes in 9297 patients at high risk , including those with serum creatinine concentrations up to 200 mol/L ( 2.3 mg/dL ) ( 5 - 7 ) . Our study examined the hypothesis that previous evidence of renal disease ( that is , an elevated serum creatinine concentration 124 mol/L [ 1.4 mg/dL ] ) would independently predict future cardiovascular disease . Since the connection between renal and cardiovascular disease is known to exist in patients with diabetes mellitus and those with hypertension , we analyzed nondiabetic and normotensive patients separately . We also examined whether ramipril continued to be effective in patients with impaired renal function . This was done to determine whether the common clinical practice of withholding angiotensin-converting enzyme ( ACE ) inhibitors in patients with impaired renal excretory function is justified . Methods Patients The design and primary outcomes of the HOPE study have been described elsewhere ( 5 - 7 ) . Briefly , men and women at least 55 years of age from 267 centers were included if they had objective evidence of vascular disease or diabetes combined with another cardiovascular risk factor . The main exclusion criteria were heart failure , intolerance of ACE inhibitors or vitamin E , a serum creatinine concentration greater than 200 mol/L ( 2.3 mg/dL ) , or dipstick-positive proteinuria ( > 1 + ) . Patients were treated with ramipril , vitamin E , or placebo in a double-blind , 2 2 factorial design . Follow-up was 3.5 to 5.5 years ( median , 4.5 years ) , and the primary outcome measure was the incidence of cardiovascular death , myocardial infa rct ion , or stroke . Secondary outcome measures included total mortality , hospitalization for heart failure , and revascularization . At the time of r and omization , urine albumin level and creatinine concentration were measured once in all patients at four central laboratories . The ratio of urine albumin to creatinine was calculated , and a value of at least 2 mg/mmol was defined as microalbuminuria . Serum creatinine concentration was measured in all patients at local laboratories at the time of r and omization . Renal Insufficiency Recent data suggest that in patients older than 55 years of age , a serum creatinine concentration of at least 124 mol/L ( 1.4 mg/dL ) is a good indicator of a glomerular filtration rate less than 80 mL/min ( 8) . Therefore , before beginning this post hoc analysis , we used a serum creatinine concentration of at least 124 mol/L ( 1.4 mg/dL ) to differentiate between patients with and those without renal insufficiency . We also estimated creatinine clearance from serum creatinine concentrations by using the CockcroftGault formula ( 8) , which derives the value from creatinine concentration , age , and body weight ( 140 age [ in years ] body weight [ in kg]/serum creatinine concentration [ in mg/dL ] 72 [ in men ] or 0.85 [ in women ] ) . For calculated creatinine clearance , an a priori value of 65 mL/min was arbitrarily chosen as a definite indicator of renal insufficiency . Statistical Analysis Baseline serum creatinine values were missing in 10 of 9297 patients who were r and omly assigned to receive ramipril , 10 mg/d , or placebo . Only data from the original intention-to-treat analysis ( 5 ) were included in our study . We compared baseline characteristics in patients with and those without renal insufficiency by using chi-square tests for discrete variables and t-tests for continuous variables . Because the ratio of albumin to creatinine was not normally distributed , it was compared by using a Wilcoxon test . In the final analysis , time-to-event in each group was estimated by using Cox regression stratified by center ; this was done because rates of renal insufficiency varied significantly by center ( P=0.006 ) but event rates did not . Association by center was tested by using logistic regression for renal insufficiency and Cox regression for events . Center was treated as a fixed effect in these models ( 9 ) . Multivariate models to predict events were developed by using Cox regression and a backward elimination technique , beginning with univariate significant risk factors , including age ; sex ; waist-to-hip ratio ; body mass index ; and history of hypertension , diabetes , coronary artery disease , peripheral vascular disease , smoking , ramipril use , and renal insufficiency . Age , body mass index , waist-to-hip ratio , and blood pressure were treated as continuous variables . All covariates were tested for possible confounding with renal insufficiency , but no such pattern was found . We used Cox regression models to assess the effect of r and omization to ramipril after controlling for serum creatinine concentration . Statistical tests for interaction were done in the Cox regression analysis to determine whether the effect of ramipril differed in patients with and those without renal insufficiency . We classified patients according to quartiles of serum creatinine concentration and then determined the effect of renal insufficiency on risk for the primary outcome . To do this , we analyzed the rate of the primary outcome across quartiles using Cox regression and testing linearity of the hazard ratios ( HRs ) . Creatinine clearance was also estimated from serum creatinine concentration by using the CockcroftGault formula ( 8) . Because age is used to calculate this value , age was excluded from all multivariate analyses that included creatinine clearance as a variable . All analyses were done by using SAS software for Unix , version 6.12 ( SAS Institute , Inc. , Cary , North Carolina ) . Role of the Funding Sources The funding sources had no role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results Baseline Characteristics of Patients with Renal Disease As shown in Table 1 , 980 patients had a serum creatinine concentration at least 124 mol/L ( 1.4 mg/dL ) and 8307 patients did not . Baseline variables did not differ between the placebo and ramipril subgroups . Compared with patients who had no evidence of renal insufficiency , those with renal insufficiency were older ; were more likely to be male ; and had a higher baseline prevalence of hypertension , coronary artery disease , peripheral vascular disease , low high-density lipoprotein cholesterol level , and use of antiplatelet and antihypertensive agents . Systolic blood pressure , urine albumin level , and waist-to-hip ratio were also higher in this group . Table 1 . Baseline Characteristics of Patients with and Those without Renal Insufficiency Event Rates in Patients with Renal Insufficiency Renal insufficiency was an important predictor of the primary outcome for all patients , as well as for the ramipril and placebo groups separately . The extent to which renal insufficiency was associated with the primary outcome is shown in Figure 1 and Table 2 . Most impressive is the fact that cardiovascular and all-cause mortality rates were nearly twice as high in patients with renal insufficiency ( HR , 1.90 [ 95 % CI , 1.53 to 2.36 ] and 1.83 [ CI , 1.54 to 2.17 ] , respectively , by Cox regression controlling for ramipril use ; P<0.001 for both comparisons ) , as were hospitalizations for heart failure ( HR , 2.11 [ CI , 1.56 to 2.81 ] ; P<0.001 ) . This effect of renal insufficiency was also observed when calculated creatinine clearance was used instead of serum creatinine concentration ( Table 3 ) . Figure 1 . Primary outcome , myocardial infa rct ion , cardiovascular death , and all death for patients with a serum creatinine concentration less than 1.4 mg/dL ( < 124 mol/L ) or at least 1.4 mg/dL ( 124 mol/L ) . Table 2 . Outcomes in Patients with and Those without Renal Insufficiency Table 3 . Outcomes in Patients with a Creatinine Clearance 65 mL/min or > 65 mL/min Analysis of the group risk for the primary outcome clearly showed that as serum creatinine concentration increases , so does cardiovascular risk . As shown in Figure 2 , the incidence of the primary outcome increased with each quartile of serum creatinine concentration ( P<0.001 for linear trend of HR across quartiles ) . Figure 2 . Primary outcome according to quartiles of serum creatinine concentration . P P We performed a multivariate analysis to determine whether the observed relationship between the incidence of the primary outcome and renal insufficiency could be explained by the association of impaired renal function with the variables identified in Table 1 . In this analysis , an elevated serum creatinine concentration and microalbuminuria were highly significant , independent renal risk factors for the aggregate primary outcome of cardiovascular death , myocardial infa rct ion , or stroke ( HR , 1.40 [ CI , 1.16 to 1.69 ] and 1.59 [ CI , 1.37 to 1.84 ] , respectively ; P<0.001 for both comparisons ) . Other factors that independently and significantly predicted the primary outcome measure were coronary artery disease ( HR , 1.51 [ CI , 1.22 to 1.85 ] ) , peripheral vascular disease ( HR , 1.49 [ CI , 1.29 to 1.70 ] ) , diabetes mellitus ( HR , 1.42 [ CI , 1.23 to 1.65 ] ) , male sex ( HR , 1.20 [ CI , 1.01 to 1.43 ] ) , 1-year increase in age ( OBJECTIVES The aim of this study was to investigate in dialysis patients with symptomatic heart failure New York Heart Association ( NYHA ) functional class II or III whether the addition of carvedilol to conventional therapy is associated with beneficial effects on cardiac architecture , function and clinical status . BACKGROUND Congestive heart failure ( CHF ) in chronic hemodialyzed patients , particularly when associated with dilated cardiomyopathy , represents an ominous complication and is an independent risk factor for cardiac mortality . METHODS We enrolled 114 dialysis patients with dilated cardiomyopathy . All patients were treated with carvedilol for 12 months in a double-blind , placebo-controlled , r and omized trial . The patients underwent M-mode and two-dimensional echocardiography at baseline , 1 , 6 and 12 months after the r and omization . Each patient 's clinical status was assessed using an NYHA functional classification that was determined after 6 and 12 months of treatment . RESULTS Carvedilol treatment improved left ventricular ( LV ) function . In the active-treatment group , the increase in LV ejection fraction ( from 26.3 % to 34.8 % , p < 0.05 vs. basal and placebo group ) and the reduction of both LV end-diastolic volume ( from 100 ml/m2 to 94 ml/m2 , p < 0.05 vs. basal and placebo group ) and end-systolic volume ( from 74 ml/m2 to 62 ml/m2 , p < 0.05 vs. basal and placebo group ) reached statistical significance after six months of therapy , compared with baseline and corresponding placebo values , and they remained constant at one year of treatment ( p < 0.05 vs. basal and placebo group ) . The clinical status of patients , assessed by NYHA functional classification , improved during the treatment period . Moreover , at the end of the trial , there were no patients in NYHA functional class IV in the carvedilol group , compared with 5.9 % of the patients in the placebo arm . CONCLUSIONS One year of therapy with carvedilol in dialysis patients with CHF and dilated cardiomyopathy reduces LV volumes and improves LV function and clinical status |
10,444 | 23,937,858 | Conclusions Across the RCTs , pazopanib over placebo , gemcitabine-dacarbazine over dacarbazine , and trabectedin 3-weekly over weekly regimen clearly demonstrated a PFS advantage in the second- and later-line treatment of advanced STS . | Background Current guidelines recommend anthracycline-based chemotherapy primarily with doxorubicin either as monotherapy or in combination with ifosfamide as the first-line treatment for most advanced STS subtypes .
Therapeutic options after failure of doxorubicin and /or ifosfamide are limited .
This study aim ed to comprehensively review available data on the activity and safety of interventions in second- or later-line treatment of advanced STS . | PURPOSE This nonr and omized multicenter phase II study was performed to evaluate the activity and safety of Ecteinascidin ( ET-743 ) administered at a dose of 1.5 mg/m(2 ) as a 24-hour continuous infusion every 3 weeks in patients with pretreated advanced soft tissue sarcoma . PATIENTS AND METHODS Patients with documented progressive advanced soft tissue sarcoma received ET-743 as second- or third-line chemotherapy . Antitumor activity was evaluated every 6 weeks until progression , excessive toxicity , or patient refusal . RESULTS One hundred four patients from eight European institutions were included in the study ( March 1999 to November 2000 ) . A total of 410 cycles were administered in 99 assessable patients . Toxicity mainly involved reversible grade 3 to 4 asymptomatic elevation of transaminases in 40 % of patients , and grade 3 to 4 neutropenia was observed in 52 % of patients . There were eight partial responses ( PR ; objective regression rate , 8 % ) , 45 no change ( NC ; > 6 months in 26 % of patients ) , and 39 progressive disease . A progression arrest rate ( PR + NC ) of 56 % was observed in leiomyosarcoma and 61 % in synovialosarcoma . The median duration of the time to progression was 105 days , and the 6-month progression-free survival was 29 % . The median duration of survival was 9.2 months . CONCLUSION ET-743 seems to be a promising active agent in advanced soft tissue sarcoma , with no cumulative toxicities . The 6-months progression-free survival observed in advanced soft tissue sarcoma compares favorably with those obtained with other active drugs tested in second-line chemotherapy in previous European Organisation for the Research and Treatment of Cancer trials . The median overall survival was unusually long in these heavily pretreated patients mainly due to the high number of patients who benefit from the drug in terms of tumor control Purpose and Methods : Bone and soft tissue sarcomas currently comprise 1 % of adult malignancies and 15 % of pediatric malignancies [ 1 ] . While doxorubicin and ifosfamide are active agents , no significant impact on survival has been observed . More active regimes are required in sarcoma . This trial studied cisplatin and a 5 day continuous infusion of vinblastine for patients who had had disease progression of advanced soft tissue sarcoma after a doxorubicin based regimen . Results : Between July 1983 and October 1986 , 20 patients entered the study . There were no treatment related deaths . Seven patients required dose adjustment for neutropenia . No responses were observed In this phase II study the effect of high-dose ifosfamide ( HDI ) given as a 3-day continuous infusion at a dose of 12 g/m2 repeated every 4 weeks with adequate mesna protection and hydration was evaluated in patients with advanced soft tissue sarcomas . A total of 124 patients entered the trial of which 10 were ineligible . HDI was given both as first-line and second-line chemotherapy . Median age was 46 years ( 19 - 66 years ) . Median World Health Organization ( WHO ) performance status was 1 ( 0 - 1 ) . Fifty two per cent of the patients were males . The predominant histology was leiomyosarcoma ( 33 % ) . A maximum of six cycles was given . At the time of analysis 55 patients have died . The partial response ( PR ) rate was 16 % . The median time to progression was 15 weeks . 8 of the 18 responding patients ( 44 % ) had synovial sarcomas , whereas only 5 % of the patients having leiomyosarcomas responded . The grade 3 + 4 haematological toxicity encountered was neutrophils in 78 % and platelets in 12 % . The major grade 3 + 4 non-haematological toxicities encountered were febrile neutropenia in 39 % , infection in 20 % , and acute renal failure in 4 % . In conclusion , it is possible to administer HDI on a multicentre basis , but the toxicity is substantial . HDI given as a continuous infusion at this dose can not be recommended as the st and ard treatment of advanced soft tissue sarcomas , even in selected patients Purpose : Based on the promising results of a Phase I study with a combination of gemcitabine and DTIC performed in advanced soft tissue sarcoma ( ASTS ) patients , and due to the limited efficacy of second or third line therapies in those patients , we design ed a Phase II study to determine the activity of this new regimen . Methods : Patients with ASTS , measurable disease , pretreated with chemotherapy , received gemcitabine 1,800 mg/m2 infused over 180 min followed by DTIC 500 mg/m2 ( one cycle ) , every 2 weeks . The pharmacokinetics ( PK ) of gemcitabine and 2′,2′-difluorodeoxyuridine ( dFdU ) , and the accumulation of gemcitabine triphosphate ( dFdCTP ) by peripheral blood mononuclear cells were studied . The influence of the sequence of administration on those parameters was examined to exclude potential drug interactions . Results : Twenty-six patients received a total of 158 cycles ( mean four cycles , range 1–18 ) . Grade 3–4 anemia ( 23 % of patients ) , granulocytopenia ( 46 % ) or thrombocytopenia ( 12 % ) , and grade 3 increase in AST ( 18 % ) , ALT ( 21 % ) , or γ-glutamyl-transferase ( 9 % ) were noted . Response rate in 23 patients was 4 % ( 95 % CI : 0–24 % ) , and in 8 of 11 patients stable disease lasted > 6 months . Progression-free rate ( PFR ) at 3 and 6 months was , respectively , 48 and 28 % , and median overall survival 37 weeks . Pooled data from the Phase I and Phase II studies showed clinical benefit in patients with leiomyosarcomas ( LMS ) ( 57 % ) and malignant fibrous histiocytomas ( MFH ) ( 33 % ) . The sequence of administration did not influence PK of gemcitabine or dFdU. There was a trend ( P = 0.11 ) toward a lower accumulation of dFdCTP when DTIC preceded gemcitabine . Conclusions : Although the remission rate was low , PFR figures indicate that this regimen has activity in patients with ASTS . It should be compared with DTIC , or other gemcitabine-containing combinations , in patients with LMS or MFH , to determine whether this combination offers advantages in PFR or in overall activity 10529 Background : Dacarbazine ( D ) and gemcitabine ( G ) are active as single agents in the treatment of patients ( pts ) with advanced soft tissue sarcoma ( STS ) resistant to st and ard chemotherapy . The purpose of this study was to assess if the combination of D and G ( Buesa et al. Cancer . 2004;101:2261 ) improved clinical outcome compared with st and ard D. METHODS Pts with advanced STS progressing after doxorubicin and ifosfamide , PS 0 - 2 , no prior G or D , measurable disease and adequate organ function , were r and omized to receive G 1,800 mg/m2 as a fixed dose infusion rate ( 10 mg/m2/min ) and D 500 mg/m2 every 2 weeks , or D 1,200 mg/m2 alone every 3 weeks . Pts were stratified by PS and interval since the initial diagnosis . The primary endpoint was progression-free rate ( PFR ) at 3 months , based on EORTC reference values . A one- sample binomial design was used . To detect an increase in PFR at 3 months from 40 % to 60 % with a power of 80 % and a two-sided alpha of 0.05 , 49 pts had to be accrued per arm ( an additional 10 % was permitted , to allow for pts who could not be evaluated ) . RESULTS From November 2005 to September 2008 , 113 pts from 18 centers were r and omized . 3 pts were ineligible . Baseline characteristics were well-balanced between both arms . The median number of cycles administered of D+G and D were 6 ( 2 - 13 ) and 2 ( 1 - 10 ) , respectively . PR and SD > 12 weeks rates were 9 % and 38 % ( D+G ) vs. 4 % and 19 % ( D ) respectively ( p=.01 ) . PFR at 3 months was 59 % ( D+G ) vs. 35 % ( D ) ( p=.001 ) . 29 pts were free of progression at 3 months among the first 49 pts in the D+G arm ( 26 required to be the study positive ) . Median progression-free survival was 4.4 ( D+G ) vs. 1.9 ( D ) months ( p=.002 ) . Median overall survival was 17.1 ( D+G ) vs. 9.9 ( D ) months ( p=.007 ) . Asthenia , emesis and stomatitis were the most common nonhematologic effects . Severe anemia and thrombocytopenia were more frequent with D and granulocytopenia with D+G. CONCLUSIONS The combination of D plus G is active and well-tolerated in pts with pretreated STS , yielding significant improvement in survival . No significant financial relationships to disclose Summary Background : The number of effective cytotoxic agents for the treatment of patients with metastatic adult type soft tissue sarcoma ( STS ) is limited , when patients have failed anthracyline-based chemotherapy . The aim of this trial was to evaluate the efficacy of gemcitabine in this setting . Methods : Between August 2001 and March 2003 19 patients were eligible to enter . Gemcitabine was administered as a 30-minutes infusion at a dosage of 1 g/m2 on day 1 , 8 and 15 every 4 weeks . All patients had progressive disease during ( n = 12 ) or shortly after an anthracycline-based regimen ( n = 3 ) . Results : Four of 19 patients did not start study treatment because of fulminant progression . Fifteen patients with a median age 47 years ( 32–72 ) were assessable . All patients had received at least one prior treatment regimen ( range , 1–6 ) for metastatic disease containing anthracyclines ( n = 15 ) and ifosfamide ( n = 11 ) . To date , a total of 72 + cycles have been applied ( median ; 3 , 1–28 + ) . Seven patients ( 47 % ) had progressive disease after completion of two cycles at the first response assessment . One patient ( 6 % ) attained a partial remission , and 7 patients ( 47 % ) achieved disease stabilisations . One patient is still on treatment after more than 2.5 years . The calculated progression-free rate at 3 and 6 months was 46.7 % ( CI95 % , 21.4–71.9 ) and 13.3 % ( CI95 % , ( 0–30.5 ) . 95 % of the cycles have been applied without any dose modification or treatment delay . Conclusions : Considering response and progression-free rate as the primary endpoints for phase II trials in pretreated STS , gemcitabine has moderate efficacy RATIONALE Advanced synovial sarcomas ( SyS ) refractory to doxorubicin and ifosfamide are highly resistant to the currently available cytotoxic agents . Based on a report showing a specific overexpression of HER-1 in SyS , we investigated an HER-1 inhibitor , gefitinib , in refractory SyS. SUBJECTS AND METHODS To establish the efficacy and safety of gefitinib in HER-1 - positive SyS refractory to one or two lines of doxorubicin- and ifosfamide-based chemotherapy , a phase II study was conducted from December 2002 to October 2005 by 12 centers of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group . Gefitinib was given at a 500-mg/day oral dose until progression or intolerance . RESULTS Forty-eight patients were included ( 46 eligible ) . All patients had previously received chemotherapy for metastatic disease , with a median number of two lines ( range , 1 - 4 ) . The most frequent metastatic sites were the lungs ( n = 44 , 92 % ) , lymph nodes ( n = 11 , 23 % ) , and soft tissues ( n = 10 , 21 % ) . The median duration of treatment was 43 days ( range , 13 - 315 ) . Treatment was interrupted in five patients ( 10 % ) . Treatment was halted for progression in 45 ( 94 % ) patients . The best response was stable disease in 10 patients ( 21 % ) . Disease progression occurred in 32 patients ( 70 % ) , with a median time to disease progression of 6 weeks . Progression-free survival at 4 and 6 months was 21 % and 6 % , respectively . CONCLUSION The results show that gefitinib monotherapy in advanced SyS refractory to conventional chemotherapy did not demonstrate sufficient activity to warrant further investigation in this setting . This may suggest that HER-1 is not a critical protein in tumor progression in this disease PURPOSE To assess the activity and toxicity of the combination of gemcitabine plus dacarbazine ( DTIC ) in patients with advanced soft tissue sarcoma ( STS ) in a r and omized , multicenter , phase II study using DTIC alone as a control arm . PATIENTS AND METHODS Patients with previously treated advanced STS were r and omly assigned to receive either fixed-dose rate gemcitabine ( 10 mg/m2/min ) at 1800 mg/m2 followed by DTIC at 500 mg/m2 every 2 weeks , or DTIC alone at 1200 mg/m2 every 3 weeks . The primary end point of the study was progression-free rate ( PFR ) at 3 months . RESULTS From November 2005 to September 2008 , 113 patients were included . PFR at 3 months was 56 % for gemcitabine plus DTIC versus 37 % for DTIC alone ( P = .001 ) . Median progression-free survival was 4.2 months versus 2 months ( hazard ratio [ HR ] , 0.58 ; 95 % CI , 0.39 to 0.86 ; P = .005 ) , and median overall survival was 16.8 months versus 8.2 months ( HR , 0.56 ; 95 % CI , 0.36 to 0.90 ; P = .014 ) ; both favored the arm of gemcitabine plus DTIC . Gemcitabine plus DTIC was also associated with a higher objective response or higher stable disease rate than was DTIC alone ( 49 % v 25 % ; P = .009 ) . Severe toxicities were uncommon , and treatment discontinuation for toxicity was rare . Granulocytopenia was the more common serious adverse event , but febrile neutropenia was uncommon . Asthenia , emesis , and stomatitis were the most frequent nonhematologic effects . CONCLUSION The combination of gemcitabine and DTIC is active and well tolerated in patients with STS , providing in this phase II r and omized trial superior progression-free survival and overall survival than DTIC alone . This regimen constitutes a valuable therapeutic alternative for these patients 10509 Background : This prospect i ve , international r and omized study evaluated two trabectedin dosing regimens [ 1.5 mg/m2 24-hour i.v . infusion once every 3 weeks ( q3wk 24-h ) vs. 0.58 mg/m2 3-hour i.v . infusion every week for 3 weeks of a 4-week cycle ( qwk 3-h ) ] in adult patients ( pts ) with unresectable and /or metastatic liposarcoma or leiomyosarcoma following failure of at least prior anthracycline and ifosfamide chemotherapy . METHODS Pts were treated and continuously followed in this trial , and we now present final OS data with long-term follow-up ( median = 41 mo ) . With 234 deaths , the study would have > 80 % power to detect a minimum 45 % improvement in median overall survival ( OS ) ( 2-sided 5 % significance level ) . RESULTS The primary efficacy endpoint ( time to progression , TTP ) was superior for the q3wk 24-h arm , as previously reported [ Morgan , et al. J Clin Oncol : 25(18S June 20 Suppl . ) 10060 ( 2007 ) ] . At cutoff , 235 deaths had occurred ( 13 % censored ) . This final OS analysis confirms the previously reported trend towards improved survival with trabectedin q3wk 24-h despite crossover of 32 % of pts from qwk 3-h to the q3wk 24-h dosing regimen . Pts treated with q3wk 24-h had a 16 % reduction in the relative risk of death ( HR=0.843 ; p=0.1931 ) . Median ( 95%CI ) OS were 13.9 mo ( 12.5 - 18.6 ; q3wk 24-h ) and 11.8 mo ( 9.9 - 14.9 ; qwk 3-h ) ( log-rank p=0.1920 ) . OS rates at 12 mo were 60 % ( q3wk 24-h ) and 50 % ( qwk 3-h ) . Sensitivity analyses censoring at crossover further highlighted this favorable trend in survival with trabectedin q3wk 24-h . With longer follow-up , up date d median TTP ( investigator assessment , 223 progression events ) was 4.2 vs. 2.5 mo [ HR : 0.658 ; p=0.0032 ] , favoring the q3wk 24-h arm . With 59 additional cycles ( for a total of 1,532 cycles ) and longer exposure , trabectedin safety profile was consistent with that previously reported . CONCLUSIONS Final survival data reinforce the internal consistency of all efficacy-related endpoints showing improved outcomes associated with the trabectedin q3wk 24-h regimen with an acceptable safety profile in this population of patients with advanced , previously-treated leiomyosarcomas and liposarcomas . [ Table : see text ] Purpose To explore the clinical activity and toxicity of gemcitabine infused at the fixed dose of 10 mg/m2/min over 100 min in patients with soft tissue sarcomas ( STSs ) . Patients and methods Fourteen patients with advanced locally unresectable and /or metastatic , pretreated STSs ( seven leiomyosarcoma , three malignant schwannoma , one synovialsarcoma , one malignant fibrous histiocytoma , one endometrial stromal cell sarcoma , one undifferentiated ) were treated with gemcitabine 10 mg/m2/min/week over 100 min given for 3 weeks out of 4 . The median age was 52 years ( range 27–77 ) , male/female ratio was 3/11 , and the median WHO performance status was 0 ( range 0–1 ) . The median number of previous medical treatments for advanced disease was 1 ( range 1–2 ) . Results A median number of three cycles ( range 1–10 cycles ) and a total of 151 weekly administrations ( median 9 , range 3–27 ) of gemcitabine were administered . Treatment was well tolerated and the main causes of dose-reduction or omission/delay were hematological and liver toxicities . One patient ( 7 % ; 95 % confidence interval : 0.2–33.9 % ) with a metastatic uterine leiomyosarcoma obtained a partial response that lasted for 6.5 months . Three patients ( two leiomyosarcoma and one schwannoma ) ( 21 % ) obtained a stabilization of disease . The median time to progression was 3.1 months ( range 1.0–9.5 ) . The median overall survival was 11.8 months ( range 1.0–54.5 + ) . Conclusions Gemcitabine infused at the fixed dose of 10 mg/m2/min over 100 min shows a good tolerability but an overall modest activity in unselected STSs histotypes . Nevertheless , an interesting tumor growth control rate was observed in specific histological variants ( i.e. , leiomyosarcoma ) , thus confirming data from recent controlled clinical trials Ifosfamide ( 5 g/m2 ) was compared with its parent analogue cyclophosphamide ( 1.5 g/m2 ) in a r and omized phase II study . Both drugs were given by 24-h intravenous ( i.v . ) infusion every 3 weeks along with i.v . bolus infusions of mesna ( 400 mg/m2 ) , which was given every 4 h for nine administrations . Eligibility criteria included an age of 15 - 75 years , biopsy-proven advanced metastatic soft-tissue sarcoma , and a World Health Organization performance status of 0 - 2 . Exclusion criteria were prior treatment with classic alkylating agents , a creatinine level of > 150 mumol/l , a bilirubin level of > 20 mumol/l , a leukocyte cell count of < 3.5 x 10(9)/l , and a platelet count of < 100 x 10(9)/l . A total of 171 patients were entered , 24 of whom were ineligible and 12 , inevaluable , leaving 135 patients evaluable . In all , 67 patients were treated with cyclophosphamide , and the overall response rate was 7.5 % . All responders to cyclophosphamide were patients who had not received prior chemotherapy ( 13 % of 38 patients ) . Another 68 patients were given ifosfamide , 18 % of whom responded to treatment . Of the 28 ifosfamide-treated patients who had received prior chemotherapy , 7 % were responders . The response rate for the remaining 40 patients was 25 % . The higher overall response rate ( P = 0.13 ) obtained with less myelosuppression in ifosfamide-treated patients suggests that this agent may have advantages over cyclophosphamide in combination therapy Ifosfamide ( IFOS ) 5 g/m2 and its parent analog Cyclophosphamide ( CYCLO ) 1.5 g/m2 were studied in a r and omized phase II study , accruing 171 patients with advanced soft tissue sarcoma . Both drugs were administered as 24 hr infusions , every 3 weeks , with comcomitant Mesna 400 mg/m2 i.v . bolus 4 hourly X 9 doses . Twenty-four patients were ineligible and 12 were not evaluable . The groups were well matched for age , previous chemotherapy ( 42 % of the total ) or radiotherapy , the presence of distant metastases and performance status , but there were more females ( 59 % vs. 45 % ) in the IFOS arm . Among the 68 evaluable patients receiving IFOS , there were 2 CR , 10 PR ( overall response 18 % ) , 27 SD and 29 PD . For CYCLO , the corresponding results in 67 patients were 1 CR , 4 PR ( overall response 8 % ) , 23 SD and 39 PD . Using the chi-square test the P values for response rate and linear trend were 0.13 and 0.04 respectively . Response rates were higher for females ( 20 % vs. 5 % , P = 0.01 ) and patients who had not received previous chemotherapy ( 19 % vs. 4 % , P = 0.01 ) . Fourteen of the 17 responses came from a group of 43 females , who had not received previous chemotherapy , for whom the overall response rate was 37.5 % . Remissions were noted in only 4 histological subtypes ( central ly review ed material ) , i.e. , 5 of 17 synovial sarcomas , 7 of 13 mixed mesodermal sarcomas and 2 of 7 fibrosarcomas . One of the 31 leiomyosarcomas responded to Cyclophosphamide . Duration s of response did not differ significantly between the 2 arms -- median 26 , range 10 - 81 + weeks . Leucopenia was significantly more severe on CYCLO , particularly in patients who had received previous chemotherapy ( P = 0.007 ) . Serious infections occurred in approx . 7 % of patients with no difference between the two drugs , although there was one toxic death on CYCLO . Nausea and vomiting were significantly worse on IFOS and alopecia , related in extent to dose , was seen in both arms . Other side-effects , such as hematuria or rises in serum creatinine and encephalopathy , were infrequent and mild . A higher response rate with less myelosuppression suggests that IFOS may have advantages over CYCLO in combination therapy OBJECTIVE To determine the antitumor activity and toxicity profile of gemcitabine as second-line chemotherapy in patients with recurrent or persistent uterine leiomyosarcoma ( LMS ) . METHODS Intravenous gemcitabine was administered over 30 min at a dose of 1000 mg/m(2 ) on days 1 , 8 , 15 , with cycles repeated every 28 days . Eligibility criteria included measurable disease , performance status 0 - 2 , adequate bone marrow function , creatinine < 1.5 mg% , bilirubin < 1.5x institutional normal , SGOT/alkaline phosphatase < 3x institutional normal , and signed informed consent . St and ard Gynecologic Oncology Group ( GOG ) toxicity and response criteria were utilized . RESULTS Forty-eight patients were enrolled on the study . Three were deemed ineligible upon central pathology review , another received an inadequate course of protocol treatment , and two others were not reassessed for response ; thus 44 patients were evaluable for toxicity and 42 for toxicity and response . The median age was 52.5 ( range : 31 - 82 ) years . Thirty-five patients had received prior chemotherapy and 11 had undergone prior radiotherapy . Sites of measurable disease were pelvic ( n = 9 ) and extrapelvic ( n = 35 ) . A median of two ( range : 1 - 13 ) cycles was received . The schedule was well tolerated ; there were no treatment-related deaths . The only grade 4 toxicities included neutropenia ( n = 7 ) , nausea and vomiting ( n = 2 ) , and dermatologic ( n = 1 ) . One ( 2.3 % ) patient achieved a complete response and eight ( 18.2 % ) experienced a partial response , for an overall response rate of 20.5 % . CONCLUSION Gemcitabine demonstrates activity in patients with persistent or recurrent uterine LMS and should be considered in multiagent regimens treating this patient population PURPOSE To evaluate the efficacy and feasibility of high-dose ifosfamide ( HDI ) at a total dose of 14 g/m2 per cycle with mesna in combination with granulocyte colony-stimulating factor ( G-CSF ) in adult patients with sarcomas . PATIENTS AND METHODS Between July 1991 and February 1994 , 74 patients with sarcomas ( 37 bone and 37 soft tissue ) were treated on two simultaneous phase II studies that evaluated HDI given as a continuous infusion over 74 hours . G-CSF was started on day 5 at 5 microg/kg/d until recovery of granulocyte count . Additionally , between March 1993 and March 1994 , 15 similar patients with previously treated bone or soft tissue sarcomas were treated on a pilot study in which the same total dose of ifosfamide was administered by a bolus schedule , along with mesna and G-CSF . Patients were treated until maximal response , and where possible , surgical resection of gross disease was performed . RESULTS Seventy-two patients from the phase II study using continuous infusion are assessable for response . Four complete responses ( CRs ) and 17 partial responses ( PRs ) were noted , for an overall response rate of 29 % ( 95 % confidence interval [ CI ] , 19 % to 39 % ) . The response rate was 40 % ( 95 % CI , 24 % to 56 % ) for bone sarcomas and 19 % ( 95 % CI , 6 % to 32 % ) for soft tissue sarcomas . Fourteen patients from the pilot study that used a bolus schedule are assessable for response . One CR and seven PRs were noted , for an overall response rate of 57 % ( 95 % CI , 31 % to 83 % ) and a response rate of 45 % for soft tissue sarcomas . Two patients developed grade 3 to 4 renal toxicity , three developed grade 3 CNS toxicity , one had possible grade 3 cardiac toxicity , and two developed severe painful peripheral neuropathy . There were no treatment-related deaths . CONCLUSION HDI at 14 g/m2 with mesna and G-CSF is an active salvage regimen for patients with bone and soft tissue sarcomas . There is a definite positive dose-response curve , and bolus administration appears to be more active than continuous infusion OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity Advanced soft-tissue sarcomas are usually resistant to cytotoxic agents such as doxorubicin and ifosfamide . Antitumor activity has been observed for gemcitabine and docetaxel combination . We conducted a retrospective study on 133 patients ( 58 males/75 females ) with unresectable or metastatic soft-tissue sarcoma . The median age at diagnosis was 51.7 ( 18 - 82 ) , with 76 patients with leiomoyosarcoma and 57 patients with other histological subtypes . The initial localizations were limb ( 44 ) , uterine ( 32 ) , retroperitoneal ( 23 ) and organs or bone ( 34 ) . Patients received 900 mg/m2 of gemcitabine ( days 1 and 8) over 90 min plus 100 mg/m2 of docetaxel ( day 8) , intravenously every 21 days . Gemcitabine/docetaxel combination was well tolerated with an overall response of 18.4 % and with no clear statistical difference between leiomyosarcomas and other histological subtypes ( 24.2 % versus 10.4 % ( p=0.06 ) ) . No difference was found between uterine soft-tissue sarcomas versus others . The median overall survival was 12.1 months ( 1 - 28 ) . Better overall survival was correlated with leiomyosarcoma ( p=0.01 ) and with the quality of the response , even for patients with stable disease ( p<10(-4 ) ) . No statistical difference was found for the initial localization . Response to treatment and overall survival were better for patients in World Health Organization ( WHO ) performance status classification ( PS ) 0 at baseline versus patients in WHO PS-1 , 2 or 3 ( p=0.023 and p<10(-4 ) , respectively ) . Gemcitabine/docetaxel combination was tolerable and demonstrated better response and survival for leiomyosarcoma , especially for patients in WHO PS-0 at baseline . For the other histological subtypes , the response was not encouraging , but the survival for patients in response or stable suggests further investigation PURPOSE Given the importance of angiogenesis in soft tissue sarcoma ( STS ) , pazopanib , an oral angiogenesis inhibitor that targets vascular endothelial growth factor receptor and platelet-derived growth factor receptor , was explored in patients with advanced STS . PATIENTS AND METHODS Patients with intermediate- or high- grade advanced STS who were ineligible for chemotherapy or who had received no more than two prior cytotoxic agents for advanced disease , who had documented progression , who had adequate performance status , and who had good organ function were eligible . Pazopanib 800 mg was given daily . The primary end point was progression-free rate at 12 weeks ( PFR(12 weeks ) ) . Secondary end points were response , safety , and overall survival . Four different strata were studied : adipocytic STS , leiomyosarcomas , synovial sarcomas , and other STS types . A Simon two-stage design was applied ( P1 = 40 % ; P0 = 20 % ; alpha = beta = .1 ) for each stratum . Results One hundred forty-two patients were enrolled . The adipocytic STS stratum was closed after the first stage , given insufficient activity ( PFR(12 weeks ) , five [ 26 % ] of19 ) . PFR(12 weeks ) was 18 ( 44 % ) of 41 patients in the leiomyosarcoma cohort , 18 ( 49 % ) of 37 in the synovial sarcomas , and 16 ( 39 % ) of 41 in the other STS types . Compared with historical controls who were treated with second-line chemotherapy , progression-free and overall survivals were prolonged in the three cohorts in which the primary end point was reached . The most frequent drug-related toxicities were hypertension , fatigue , hypopigmentation , and nausea . Other toxicities included liver enzyme elevations , myelosuppression , and proteinuria , all of which were mostly grade s 1 to 2 . The most frequent grade s 3 to 4 toxicities were hyperbilirubinemia ( 6.3 % ) , hypertension ( 7.7 % ) , and fatigue ( 7.7 % ) . CONCLUSION Pazopanib is well tolerated in patients with relapsed , advanced STS and demonstrates interesting activity that warrants additional study in patients with leiomyosarcomas , synovial sarcomas , and other STS types In the current study , the authors set out to determine the dose‐limiting toxicity ( DLT ) and maximum tolerated dose ( MTD ) associated with a combination of gemcitabine and dacarbazine ( DTIC ) in patients with advanced soft tissue sarcoma ( ASTS ) , to obtain preliminary information on the activity of this combination , and to explore possible pharmacodynamic interactions between gemcitabine and DTIC Chemotherapy options in patients with advanced soft tissue sarcomas ( STS ) remain presently inadequate . In this phase II study the activity and toxicity of a combined alternating VAC/IE regimen in advanced and /or metastatic STS was evaluated . VAC ( vincristine , total dose of 2 mg , adriamycin 70 mg/m2 and cyclophosphamide 600 mg/m2 ) was given as intravenous bolus infusion on day 1 , followed after 21 days by IE ( ifosfamide , 1.8 g/m2 infused over 1 h , daily for 5 consecutive days , with mesna uroprotection , plus etoposide at 500 mg/m2 infused over 2 h on the first day ) . Courses were repeated every 3 weeks . Twenty patients were treated , 12 of whom had previously been given chemotherapy for advanced and /or metastatic disease . Treatment was feasible in ambulatory setting , with good patient compliance . Myelosuppression , overall acceptable , was the major dose-limiting toxicity , while non-hematological side effects were minimal . An overall response rate of 45 % was observed ( 95 % CI , 26%-66 % ) , with 2 complete and 7 partial remissions , achieving 75 % in the subset of untreated patients . Median survival time was 10 months in the whole group ( range , 4 - 26 + months ) and 14 months in responder patients ( range , 9 - 26 + months ) Forty-four of 50 adult patients with advanced soft-tissue sarcoma who had received previous chemotherapy were evaluable for response after treatment with DTIC . The therapeutic schedule consisted of DTIC 1.2 g/m2 infused over 20 minutes , and repeated every 3 weeks . There were 1 complete and 7 partial remissions ( objective activity 18 % , 95 % C.I. 7%-29 % ) , with a median duration of 8 weeks ( range 5 - 19 ) , with the complete remission lasting 1 yr . Hematologic toxicity was dose-limiting ; W.H.O. greater than or equal to 3 values were observed for WBC in 36 % , and for platelets in 26 % of patients . The non-hematologic toxicity included nausea and vomiting ( 90 % ) , a flu-like syndrome ( 49 % ) , diarrhea ( 35 % ) , pain in the infused vein ( 28 % ) and hypotensive episodes ( 4 % ) . Intermittent high-dose DTIC is active in advanced soft-tissue sarcoma and should be considered for inclusion in combination regimens PURPOSE Few chemotherapy agents are active in leiomyosarcoma ( LMS ) , particularly LMS that has progressed after doxorubicin treatment . We sought to determine the response to gemcitabine plus docetaxel among patients with LMS . PATIENTS AND METHODS Patients with unresectable LMS of uterine ( n = 29 ) or other ( n = 5 ) primary sites who did not respond to zero to two prior chemotherapy regimens were enrolled onto a phase II study of gemcitabine 900 mg/m(2 ) intravenously ( i.v . ) on days 1 and 8 plus docetaxel 100 mg/m(2 ) i.v . on day 8 with granulocyte colony-stimulating factor given subcutaneously on days 9 to 15 , delivered every 21 days . Patients with prior pelvic radiation received 25 % lower doses of both agents . Gemcitabine was delivered over 30 or 90 minutes in cycles 1 and 2 and by 90-minute infusion in all subsequent cycles . Pharmacokinetic studies assessed in vivo differences in gemcitabine concentrations with different rates of infusion . RESULTS Thirty-four patients ( median age , 55 years ; range , 32 to 74 years ) have enrolled . Fourteen had received prior pelvic radiation . Sixteen of 34 patients had progressed after doxorubicin-based therapy ; 18 had no prior chemotherapy . Among 34 patients , complete response was observed in three patients and partial response in 15 , for an overall response rate of 53 % ( 95 % confidence interval , 35 % to 70 % ) . Seven patients had stable disease . Fifty percent of patients previously treated with doxorubicin responded . Hematologic toxicity was common ( neutropenia : grade 3 , 15 % ; grade 4 , 6 % ; thrombocytopenia : grade 3 , 26 % ; grade 4 , 3 % ) , but neutropenic fever ( 6 % ) and bleeding events ( 0 % ) were rare . The median time to progression was 5.6 months ( range , 4 to 10 months ) . CONCLUSION Gemcitabine plus docetaxel is tolerable and highly active in treated and untreated patients with LMS Summary Aim Phase II multi-disease r and omized discontinuation trial to assess the safety and efficacy of sorafenib including patients with advanced soft tissue sarcoma ( STS ) . Methods Sorafenib ( 400 mg twice daily ) was initially administered for 12 weeks . Patients with : ≥25 % tumour shrinkage continued sorafenib ; ≥25 % tumour growth discontinued ; other patients were r and omized and received sorafenib or placebo . Results Twenty-six patients ( median age 55 years ) were enrolled . Common drug-related adverse events , including fatigue , h and –foot skin reaction , rash or gastrointestinal disturbances , were manageable , reversible and generally low grade . Fatigue , skin toxicity , nausea , diarrhoea and hypertension occurred at grade ≥3 in 19 % of patients . After 12 weeks eight ( 31 % ) patients had not progressed . Three patients who experienced tumour shrinkage and continued on sorafenib , and five ( 19 % ) were r and omized either to continue sorafenib or to receive placebo . Of the three patients r and omized to sorafenib , one achieved a partial response and two had SD . Overall one patient achieved a partial response and three further patients achieved minor responses . Conclusions There was evidence of disease activity in STS as defined by tumor regressions including one objective partial response . Further investigation in STS is warranted PURPOSE The study was design ed to assess the toxicity and activity of high-dose ifosfamide ( HDI ) administered by continuous infusion at a dose of 4 g/m2/d over 3 days every 4 weeks in adult patients with advanced soft tissue sarcomas ( ASTS ) pretreated with doxorubicin and /or a st and ard-dose ifosfamide (SDI)-containing regimen . PATIENTS AND METHODS Between January 1991 and November 1993 , 40 patients with progressive ASTS were entered onto the study . Twenty-eight patients had been pretreated with a multidrug regimen that contained SDI and were classified as follows : SDI-refractory ( n = 21 ) , SDI-resistant ( n = 2 ) , and indeterminate SDI-sensitive ( n = 5 ) . Patients were treated until progression or major toxicity . RESULTS One hundred forty-seven cycles of HDI were administered . Neutropenia was dose-limiting , with 100 % of patients experiencing grade 3 to 4 toxicity and 12 admissions for febrile neutropenia ( 30 % of patients ) . Neurotoxicity ( 17 % of patients ) was significantly associated with acute renal failure ( n = 4 ) ( P < .001 ) , grade 4 thrombocytopenia ( P < .01 ) and febrile neutropenia ( P = .048 ) . Chronic renal toxicity ( n = 4 ) was significantly associated with retroperitoneal masses and /or prior nephrectomy ( P = .008 ) . Partial responses ( PRs ) were observed in 12 of 36 assessable patients ( 33 % ) and eight patients ( 22 % ) experienced disease stabilization . All but one response occurred in patients pretreated with SDI , with five PRs among SDI-refractory patients . Leiomyosarcomas appear resistant to HDI . The median response duration was 8 months ( range , 6 to 13 + ) and the median overall survival time was 12 months . CONCLUSION The activity of HDI in these pretreated ASTS patients and the apparent circumvention of SDI resistance suggest a real dose-response relationship for ifosfamide and deserve further evaluation . Although toxic , this treatment appears feasible and manageable using routine clinical support . Since prophylaxis of ifosfamide-induced renal damage remains unknown , frequent monitoring of renal and tubular functions during therapy is highly recommended Results are summarized for two phase II studies of docetaxel as first-line therapy for advanced squamous cell carcinoma of the head and neck ( SCCHN ) and one study of docetaxel as second-line therapy for advanced soft tissue sarcomas . In all three studies , docetaxel was administered at a dose of 100 mg/m2 by intravenous infusion over 1 h every 3 weeks . A total of 62 patients were enrolled in the SCCHN trials , of whom 57 were evaluable for response . The combined overall response rate in the SCCHN patients was 35 % . Median duration of overall response was 6.5 months in the EORTCECTG study . In the DFCI study , median duration s of complete and partial remission were 6.75 months and 4.45 months , respectively . These results are at least comparable to those achieved with other single-agent therapies in this setting . In the soft tissue sarcoma study , 29 of the 31 patients enrolled were evaluable for response . Five patients ( 17 % ) achieved a partial response to docetaxel as second-line therapy and a further nine ( 31 % ) had stable disease . Median duration of response in these patients with soft tissue sarcomas was 5 months . Again , these results are similar to those seen with the three most active single agents in soft tissue sarcomas when used as second-line therapy . Docetaxel may therefore represent a useful drug in both advanced SCCHN and soft tissue sarcomas Based on the likelihood of antitumor interactions between cytokines and cytotoxic drugs , we design ed a pilot study to evaluate feasibility , clinical , pharmacologic , and immunologic effects of concomitantly administered subcutaneous ( SQ ) recombinant interleukin-2 ( r-IL-2 ) and doxorubicin ( ADR ) in patients with advanced solid tumors ( AST ) . Patients received one injection of ADR alone ( 70 mg/m2 ) and 3 weeks later a combination of r-IL-2 ( 18 MIU/m2 days 1 - 5 s.q . ) and ADR at the same dose either 3 - 4 h after the first r-IL-2 injection ( arm 1 ) or 2 days after the last r-IL-2 injection ( arm 2 ) . The same combination was repeated every 4 weeks according to the evolution of the disease . Pharmacokinetics were assessed over 48 h after injection of ADR alone and after the first ADR-IL-2 cycle and immunologic monitoring at days 1 and 8 of the first ADR-IL-2 cycle . Tumors were measured at baseline , after ADR alone , and after each ADR-IL-2 cycle until progression . Twenty-one adult patients with various AST including 14 soft-tissue sarcomas ( STS ) entered the study , 11 in arm 1 and 10 in arm 2 . All patients were heavily pretreated ; 16 had received an anthracycline-containing chemotherapy regimen . Eleven patients were ADR refractory and 1 ADR resistant . Grade 4 neutropenia occurred in 28 , 82 , and 40 % of patients after ADR alone , ADR-IL-2 in arm 1 and ADR-IL-2 in arm 2 , respectively . Mucitis was higher in arm 1 ( 7 of 11 patients ) compared with arm 2 ( 0 of 10 ) and ADR alone ( 0 of 21 ) . SQ injections of r-IL-2 did not affect ADR pharmacokinetics . ADR injection in arm 1 prevented IL-2-induced lymphocyte rebounds in all patients but did not alter qualitatively non-major histocompatibility complex-restricted cytotoxicity . There was no response after ADR alone . Two patients , one in each arm , experienced a prolonged ( 8 and 5 months ) objective response after ADR-IL-2 . Both had ADR-refractory STS with a local relapse and metastatic metastases . Interestingly , both patients had unusually elevated TNF-alpha levels before and after the first ADR cycle . Combination ADR-IL-2 , although toxic , is feasible and manageable with routine clinical support . r-IL-2 enhanced ADR hematologic and extrahematologic toxicities . The two objective responses observed in these heavily pretreated patients refractory to ADR supports the hypothesis of a modulation of ADR resistance , possibly mediated by means of a mechanism involving TNF-alpha . Elevated baseline TNF-alpha levels could be predictive of response to ADR-IL-2 and deserves further investigation Because of the low number of active cytotoxic drugs and their limited activity , the evaluation of new anti-cancer agents for their activity in soft tissue sarcomas is a continuing need . The objectives of this prospect i ve phase II trial of gemcitabine were to estimate the response rate and to define the toxicities of prolonged infusions of low-dose gemcitabine in patients with pretreated advanced soft tissue sarcomas . Patients were eligible if they had a histologic diagnosis of unresectable , recurrent or metastatic , progressive soft tissue sarcoma , and if they had been treated with at least one prior chemotherapy consisting of an anthracycline- and /or ifosfamide-containing regimen . Gemcitabine was administered as a 360 min infusion on days 1 , 8 and 15 of a 28 day cycle . The initial dose of gemcitabine was 200 mg/m2 in all patients . Dose escalation to 250 mg/m2 was allowed in the case of stable disease and good tolerability of the drug . All 18 patients ( median age 58 years ) who enrolled were treated with gemcitabine , and all were assessable for toxicity , response and survival . Only two of these 18 patients had an objective response to a previous palliative chemotherapy . A median of 3 cycles ( range 1 - 7 ) of gemcitabicin were administered . Two ( 11 % ) of the patients had a partial response lasting 5 and 6 months , respectively . Both of these patients had only lung metastases . Whereas one of these patients had a transient partial response to the foregoing chemotherapy ( consisting of ifosfamide and doxorubicin ) , the other patient has been progressive on these drugs . One additional patient , progressive on ifosfamide and doxorubicin , had an objective response of greater than 50 % confined to the lungs and stable local recurrence for 6 months . Six patients had stable disease for 3 - 6 months and nine patients had disease progression . The median survival was 8 months . Treatment generally was well tolerated with six patients having transient grade 3 non-hematologic toxicity , four having grade 3 neutropenia , and one having grade 4 neutropenia and thrombocytopenia . Gemcitabine , given as a prolonged infusion at a low dose level , has a favorable toxicity profile and displays antitumor activity in patients with intensively pretreated , advanced soft tissue sarcomas Background . Chemotherapy given by continuous infusion may have different toxicity profiles and different degrees of therapeutic efficacy than when given by bolus administration . The potential therapeutic benefits of continuous infusion chemotherapy and the advantages of outpatient treatment led us to study a continuous infusion of ifosfamide with mesna and oral etoposide PURPOSE To assess the efficacy of the marine-derived alkaloid ecteinascidin 743 ( ET-743 ) in patients with soft tissue sarcomas that progressed despite prior conventional chemotherapy and to characterize the pharmacokinetic profiles of ET-743 in this patient population . PATIENTS AND METHODS Thirty-six previously treated soft tissue sarcoma patients from three institutions received ET-743 as a 24-hour continuous intravenous ( IV ) infusion at a dose of 1,500 microg/m(2 ) every 3 weeks . Pharmacokinetic studies were also performed . Patients were restaged every two cycles for response by objective criteria . RESULTS Objective responses were observed in three patients , with one complete response and two partial responses , for an overall response rate of 8 % ( 95 % CI , 2 % to 23 % ) . Responses were durable for up to 20 months . Two minor responses ( 43 % and 47 % tumor reduction ) were observed , for an overall clinical benefit rate of 14 % . The predominant toxicities were neutropenia and self-limited transaminitis of grade 3 to 4 severity in 34 % and 26 % of patients , respectively . The estimated 1-year time to progression and overall survival rates were 9 % ( 95 % CI , 3 % to 27 % ) and 53 % ( 95 % CI , 39 % to 73 % ) , respectively . The maximum observed plasma concentration and total plasma clearance of ET-743 ( mean + /- st and ard deviation ) , 1.04 + /- 0.48 ng/mL and 35.6 + /- 16.2 L/h/m(2 ) , respectively , were consistent with previously reported values from phase I studies of the drug given as a 24-hour IV infusion . CONCLUSION ET-743 is a promising new option for the management of several histologic subtypes of sarcoma . Durable objective responses were obtained in a subset of sarcoma patients with disease progression despite prior chemotherapy . Additionally , the relatively high survival rate noted in this series of previously treated patients further justifies development of this agent The aim of this phase II study was to evaluate the efficacy and toxicity of two regimens of ifosfamide in metastatic soft tissue sarcoma patients given as first- and second-line chemotherapy . Two different schedules of ifosfamide were investigated in a r and omised manner : Ifosfamide was given either at a dose of 5 g/m(2 ) over 24 h ( 5 g/m(2)/1 day ) , every 3 weeks or at a dose of 3 g/m(2 ) per day , administered over 4 h on three consecutive days ( 3 g/m(2)/3 days ) , every 3 weeks . Both schedules were given as first-line or second-line chemotherapy . A total of 182 patients was entered , 103 in first- and 79 in second-line , of whom 8 patients were ineligible , 5 in the first- and 3 in the second-line study . Most patients had a leiomyosarcoma , 46 of the 98 in the first-line and 34 of the 76 in the second-line . The two study arms were well balanced in both the first- and second-lines with respect to sex , age and performance status . In first-line treatment , 5 g/m(2)/1 day yielded five partial responses ( PR ) ( Response Rate ( RR ) 10 % ) , versus 12 PR ( RR 25 % ) for the 3 g/m(2)/3 days . As second-line treatment , the 24-h infusion yielded : one CR and one PR ( RR 6 % ) and the 3-day schedule one CR and two PR ( RR 8 % ) . Survival did not differ between the two regimens . The major World Health Organization ( WHO ) grade 3 and 4 toxicities encountered were : leucopenia in 19 % of all courses in the first-line and 32 % in the second-line with the 5 g/m(2)/1 day , while for the 3 g/m(2)/3 days schedule the rates were 57 and 63 % respectively . Grade 3 or 4 infections were seen in 4 % of patients treated with 5 g/m(2)/1 day first-line and 10 % of patients given 3 g/m(2)/3 days , both as first- and second-lines . No such infections were seen in patients receiving 5 g/m(2)/1 day as second line treatment . In advanced soft-tissue sarcomas in the first-line , ifosfamide 3 g/m(2 ) , given over 4 h on three consecutive days , is an active regimen with acceptable toxicity while the 5 g/m(2 ) over 24 hours schedule result ed in a disappointing response rate The objective of this r and omized phase II/phase III study was to investigate the efficacy and toxicity of equimolar doses of adriamycin ( ADM ) and 4-epiadriamycin ( EPI ) in patients with locally advanced and /or metastatic soft tissue sarcoma . Doses of ADM and EPI were 75 mg/m2 given as an i.v . bolus injection every 3 weeks . Two hundred and ten patients were entered into the study by 18 institutions . Twenty-eight patients were ineligible and 15 were non-evaluable , leaving 167 evaluable patients . The two treatment groups were well balanced for sex , performance status , age , prior radiotherapy , extent and site of disease . Rates of response were similar , 25 % in the ADM group compared to 18 % in the EPI group ( P = 0.33 ) , and there were no significant differences between the ADM and EPI groups with respect to median duration of response ( 45 weeks vs. 77 weeks , P = 0.08 ) , time to progression ( 15 weeks vs. 12 weeks , P = 0.945 ) , and median survival ( 41 weeks vs. 48 weeks , P = 0.363 ) . Myelotoxicity as shown by leucopenia was significantly more pronounced in the ADM treated patients ( P = 0.002 ) . Other toxicities such as alopecia and nausea/vomiting were also more severe in the ADM group ( P = 0.02 and 0.06 , respectively ) . In conclusion , the use of equimolar doses of ADM and EPI in advanced soft tissue sarcoma produced response rates which did not differ significantly and were only slightly in favour of ADM . However , this was achieved at the expense of higher toxicity LBA10002 Background : Pazopanib , a multi targeted angiogenesis inhibitor , has demonstrated single-agent activity in pts with advanced STS . The efficacy and safety of pazopanib versus placebo as second or later line treatment were evaluated in pts with metastatic STS in a multi-center , international , double-blind , placebo-controlled phase III trial . METHODS Pts ≥18 years of age with angiogenesis inhibitor-naïve , histologically proven , metastatic STS , who failed at least one anthracycline containing regimen , could enter the study . They should have ≥1 measurable baseline lesion ( per RECIST v1.0 ) , WHO PS 0 - 1 , adequate bone marrow , coagulation , hepatic and renal function , no poorly controlled hypertension , no bleeding diathesis , and no CNS involvement . The study has been conducted by EORTC and GSK in collaboration with 72 sarcoma centers worldwide . Pts were r and omized 2:1 to receive either pazopanib 800 mg once daily or placebo until tumor progression , unacceptable toxicity , death , or pt 's request . RESULTS A total of 369 r and omized pts ( 246 pazopanib , 123 placebo ) , median age of 56 years , participated in the study ( EORTC 45 % , other 55 % ) . Median duration of follow-up at clinical cut-off date is 15 months . The primary endpoint of progression-free survival ( PFS ) per independent review is significantly prolonged with pazopanib ( median : 20 vs 7 weeks ; HR=0.31 , 95 % CI 0.24 - 0.40 ; P<0.0001 ) . The interim analysis for overall survival shows a statistically non-significant improvement of pazopanib vs placebo ( median : 11.9 vs 10.4 months , HR=0.83 , 95 % CI 0.62 - 1.09 ) . Main on-therapy grade 3 - 4 toxicities in the pazopanib vs placebo arm respectively : fatigue ( 13 % , 6 % ) , hypertension ( 7 % , nil ) , anorexia ( 6 % , nil ) , and diarrhea ( 5 % , 1 % ) . Similarly , thromboembolic events ( grade 3 - 5 ) ( 3 % , 2 % ) , LVEF drop of > 15 % ( 8 % , 3 % ) . Median relative dose intensity of pazopanib was 768 mg daily . CONCLUSIONS Pazopanib is an active drug in anthracycline pretreated metastatic STS pts with an increase in median PFS of 13 weeks BACKGROUND Doxorubicin remains one of the few drugs with consistent single agent activity in advanced Soft Tissue Sarcomas ( STS ) , with a demonstrated dose-response relationship . Liposomal-encapsulated Doxorubicin ( LED ) has been shown to be at least as active as free doxorubicin in experimental models , and phase I and II human studies indicate that this novel strategy of drug delivery my have less myocardial toxicity . Few clinical trials in adult STS have been published until now , with disappointing and often contrasting results . PATIENTS AND METHODS Twenty-five consecutive patients with measurable advanced and /or metastatic STS , previously pretreated with anthracycline-based chemotherapy , were enrolled into the trial . LED ( Caelyx ) was administered over 1-hour intravenous infusion at the dose of 30 mg/m2 in the first 5 patients , then at the fixed dose of 50 mg/m2 in the subsequent 20 patients . Treatment was given on ambulatory basis , at 3-week intervals . Antiemetics were generally not required and only used if indicated . RESULTS A total of 98 courses of chemotherapy were given ( median 4 per patient , range 2 to 5 ) . Amongst the 25 evaluable patients , there were 3 partial responses ( 12 % , 95 % confidence interval 4.2 % to 29.9 % ) lasting 3 - 9 + months and all occurring in patients treated at 50 mg/m2/cycle . In addition , 2 minor responses ( 4 + months ) and 17 stable disease ( 2 - 7 + months ) were observed ; the remaining 3 patients progressed while on therapy . The median delivered drug dose-intensity was 13.3 mg/m2/week ( range 10 to 16.6 mg/m2/week ) . Treatment was well tolerated , with no patient requiring dose reduction or therapy delay because of toxicity . Only 2 cases of WHO grade 3 toxicity occurred , consisting of neutropenia and scrotal skin toxicity ; respectively ; no cardiotoxicity was seen . CONCLUSIONS This study shows that Caelyx has some activity in advanced , anthracycline-pretreated STS , with favourable toxic profile . From the analysis of available experiences it emerges that liposomal doxorubicin has not been tested at doses adequate to exploit the antitumor effects of the drug , being the reached dose-intensity being even lower than those deemed critical for obtaining optimal responses to free doxorubicin . We suggest that further and better addressed studies be performed in STS , including patients with less advanced stages of disease , focused on attempting to delivery the drug at optimal doses PURPOSE A multicenter phase II study evaluating efficacy , safety , and pharmacokinetics of ecteinascidin-743 ( ET-743 ) in pretreated advanced soft tissue sarcoma patients . PATIENTS AND METHODS Patients received ET-743 1,500 microg/m(2 ) ( 24-hour intravenous infusion ) every 3 weeks ( group 1 , 26 patients with one to two prior single agents or one previous combination chemotherapy ; group 2 , 28 patients with three or more prior single agents or two or more previous combination chemotherapies ) . Results Patients ( 30 women , 24 men ) had a median age of 48 years ( range , 22 to 71 years ) ; 41 % had leiomyosarcoma ( eight of 22 of uterine origin ) , a median of two involved organs ( range , one to four ) , and 93 % had documented progressive disease at study entry . Patients received a median of three cycles ( range , one to 20 ) ; 28 % received six or more cycles . Fifty-two patients were assessable for response ( WHO criteria ): two partial responses , four minor responses , and nine with stable disease ( > or = 6 months ) . Three patients were rendered tumor free after surgery . Median progression-free survival was 1.9 months ( range , 0.69 to 17.90 months ) ; 24 % of patients were progression free at 6 months . Median survival was 12.8 months , with 30 % of patients alive at 2 years . Four patients withdrew because of treatment-related toxicity . Two treatment-related deaths occurred ( renal failure and febrile neutropenia , and rhabdomyolysis and decompensated cirrhosis , respectively ) that were probably related to protocol eligibility violations . Reversible grade 3 to 4 AST or ALT occurred in 50 % of patients and grade 3 to 4 neutropenia occurred in 61 % of patients , with six episodes of febrile neutropenia . Nausea , vomiting , and asthenia were prevalent but mild and manageable . CONCLUSION With a 4 % overall response rate ( 95 % CI , 0.5 to 12.8 ) and an 11 % rate of third-party-verified tumor regression ( overall response rate + minor response ) , ET-743 has a 24 % 6-month disease progression control rate , confirming evidence of antitumoral activity and a manageable safety profile in patients experiencing disease progression with pretreated soft tissue sarcoma PURPOSE Incel ( biricodar , VX-710 ) restores drug sensitivity to P-glycoprotein and multidrug resistance-associated protein-1-expressing cells . This Phase I/II study evaluated the safety/tolerability , pharmacokinetics , and efficacy of VX-710 plus doxorubicin in patients with inoperable , locally advanced or metastatic , anthracycline-resistant/refractory , soft tissue sarcoma . EXPERIMENTAL DESIGN In Phase I , i.v . bolus doxorubicin at 60 , 75 , or 67.5 mg/m(2 ) was administered 8 h after initiation of a 72-h continuous i.v . ( CIV ) infusion of VX-710 ( 120 mg/m(2)/h ) to cohorts of patients to establish a maximum tolerated dose . For efficacy evaluations in Phase II , eligible patients had inoperable , locally advanced or metastatic , anthracycline-resistant/refractory soft tissue sarcoma ; < or = 225 mg/m(2 ) cumulative prior doxorubicin ; and adequate hematological , liver , and kidney function . Cycles were repeated every 3 weeks . RESULTS Fourteen patients were enrolled in Phase I. Myelosuppression was the dose-limiting toxicity with 75 and then 67.5 mg/m(2 ) doxorubicin , and the maximum tolerated dose was established at 60 mg/m(2 ) with VX-710 , 120 mg/m(2)/h , 72-h CIV . VX-710 had no apparent effect on doxorubicin pharmacokinetics . Twenty-nine patients enrolled in Phase II were treated with VX-710 , 120 mg/m(2)/h 72-h CIV , and 60 mg/m(2 ) doxorubicin . Among 26 evaluable patients , minimal activity was noted among 11 patients with gastrointestinal stromal tumors ( GISTs ) ; however , in 15 patients with anthracycline-resistant sarcomas of other histologies , 2 achieved partial responses and 7 patients had disease stabilization with an overall median progression-free interval of 3.4 months . CONCLUSION Anthracycline resistance in GISTs appears to be independent of P-glycoprotein or multidrug resistance-associated protein-1 resistance mechanisms . However , the combination of VX-710 and doxorubicin result ed in objective responses or disease stabilization in patients with strictly defined anthracycline-refractory non-GIST sarcomas , which warrants further evaluation Ifosfamide , an oxazaphosphorine analogue , is now commonly used in first-line anthracycline-containing regimens for advanced soft tissue sarcomas , based on its demonstrated single-agent activity in previously treated patients . At the Institut Gustave-Roussy , we performed a phase II study of high-dose ifosfamide without hematopoietic support in patients with adult advanced soft tissue sarcomas previously treated with a doxorubicin-based regimen . Our goal was to confirm a dose-response relationship for ifosfamide in soft tissue sarcoma . Ifosfamide was given at a dose of 4 g/m2/d over 3 days by continuous infusion with an equivalent dose of mesna ; an additional 4 g/m2 of mesna was given on day 4 . Among 36 evaluable patients , we observed no complete responses and 12 partial responses , for an overall response rate of 33 % . No patients with leiomyosarcoma responded to treatment , and some histologic subtypes clearly showed better chemosensitivity than others . The major dose-limiting toxicities were hematologic . Our results confirm a dose-response effect for high-dose ifosfamide in soft tissue sarcomas , with a threshold of approximately 10 g/m2 |
10,445 | 25,231,081 | Conclusion The considerable morbidity of ileostomy reversal reduces the overall benefit of temporary fecal diversion .
However , ileostomy creation is still recommended , as it effectively reduces the risk of pouch-related septic complications | Background Temporary loop ileostomy is a routine procedure to reduce the morbidity of restorative proctocolectomy .
However , morbidity of ileostomy closure could reduce the benefit of this concept .
The objective of this systematic review was to assess the risks of ileostomy closure after restorative proctocolectomy for ulcerative colitis or familial adenomatous polyposis . | The results of the pelvic pouch procedure were review ed to assess the surgical complication rate and outcome of patients who had had the procedure performed with a stapled ileo-anal anastomosis with and without a defunctioning ilcostomy . Between December 1982 and March 1992 , 483 patients underwent a pelvic pouch ( PP ) procedure . Patients were divided into three groups : group I consisted of 325 patients ( 178 men and boys and 147 women and girls ) who underwent a PP procedure with a h and sewn ileoanal anastomosis ( IAA ) with a defunctioning loop ileostomy . In group II , there were 87 patients ( 47 men and boys and 40 women and girls ) who had a stapled IAA with a defunctioning ileostomy . Group III patients consisted of 71 patients ( 43 men and boys and 28 women and girls ) who had a stapled IAA with no covering ileostomy . Assessment was made of the IAA leak rate , the surgical complications , the reoperation rate , and functional outcome . Early surgical complications included 40 ( 12 % ) IAA leaks in group I patients compared with only six ( 7 % ) leaks in group II patients who had a stapled IAA ( p < 0.05 ) . In group III patients , who had a stapled IAA but no covering ileostomy , there were 13 leaks ( 18 % ) . Eleven of these 13 leaks healed spontaneously with tube drainage ; one patient remains with a rectal tube in place 6 weeks after operation , and only one patient has required a reoperation ( defunctioning ileostomy ) . Functionally , all patients with a healed IAA after a leak have had an excellent result comparable to those without a leak . Patients who were male , older than age 40 , on steroids , and had had a true one-stage PP procedure , had a greater risk of developing an IAA leak . In two patients , there was intraoperative difficulty , and one of these patients had an IAA leak after operation . Disease activity at the resection margin and patient weight did not affect the leak rate . Our results suggest that the IAA leak rate is significantly reduced in patients with a stapled IAA with an ileostomy compared with those with a h and sewn IAA . Omission of the defunctioning ileostomy is associated with a higher IAA leak rate , but spontaneous healing occurs in almost all patients without impairment of functional results . In patients in whom the ileostomy is omitted , the IAA leak rate is greatest in male patients who have undergone a true one-stage PP procedure , are on steroids , and are older than age 40 Purpose Defunctioning ileostomies are widely performed in order to prevent or treat anastomotic leakage after colorectal surgery . The aim of the present study was to determine morbidity related to stoma closure and to identify predictive factors of a complicated postoperative course . Methods A consecutive series of 138 patients were retrospectively analyzed after stoma reversal . Data collection included general demographics and surgery-related aspects . Morbidity related to stoma closure was retrieved from our prospect ively collected registry of complications . Results In 74 of 138 patients , defunctioning ileostomy was performed after restorative proctocolectomy and ileal pouch-anal anastomosis ( IPAA ) . The remaining ileostomies ( n = 64 ) were constructed after a low colorectal or coloanal anastomosis . A total of 46 complications were recorded in 28 patients result ing in an overall complication rate of 20.3 % . Anastomotic leakage rate was 4.3 % , and reoperation rate was 8.0 % . The number of complications according to the Clavien – Dindo classification was 5 for grade I ( 10.9 % ) , 26 for grade II ( 56.5 % ) , 13 for grade III ( 28.3 % ) , 1 for grade IV ( 2.2 % ) , and 1 for grade V ( 2.2 % ) . Multivariate analysis revealed a significantly higher ASA score in the complicated group ( P = 0.015 , odds ratio 2.6 , 95 % confidence interval 1.2–5.6 ) . Conclusions Closure of a defunctioning ileostomy is associated with 20 % morbidity and a reoperation rate of 8 % . There is an urgent need for criteria on which a more selective use of a defunctioning ileostomy after low colonic anastomosis or IPAA can be based given its associated morbidity Purpose This study analyzes the impact of a temporary loop ileostomy on postoperative outcome after restorative proctocolectomy for ulcerative colitis in terms of complications and reoperations including ileostomy closure . Methods The records of 122 consecutive patients undergoing restorative proctocolectomy for ulcerative colitis during a 12-year period were review ed . In 89 patients , a defunctioning ileostomy was created , while 33 patients had no ileostomy . Statistics were done with Chi-square test and Mann – Whitney U test , p < 0.05 considered significant . Results Both study groups were comparable concerning age , colitis activity , previous diseases , previous surgery , use of steroids , and immunosuppressives . Pouch-related septic complications ( anastomotic dehiscence , pouch leakage , pelvic abscess ) were significantly lower in the ileostomy group ( 5.6 % vs. 18.2 % , p = 0.031 ) , result ing in a lower rate of emergency laparotomies following restorative proctocolectomy ( 4.5 % vs. 30.3 % , p < 0.001 ) . Including all complications associated with scheduled closure of ileostomy , the cumulative frequency of emergency laparotomies was significantly lower in the ileostomy group ( 13.5 % vs. 30.3 % , p = 0.032 ) . The cumulative duration of hospitalization , including all hospital stays for complications or closure of the ileostomy , was significantly longer in the ileostomy group [ median 22 days ( 11–92 ) vs. 14 days ( 9–109 ) , p < 0.001 ] . During long-term follow-up , a stricture at the pouch-anal anastomosis was more common in the ileostomy group ( 24.7 % vs. 6.1 % , p = 0.021 ) , whereas only one stricture necessitated surgical therapy . Conclusions Creation of a defunctioning loop ileostomy reduces pouch-related septic complications and the frequency of emergency second laparotomies after restorative proctocolectomy for ulcerative colitis Purpose Controversy exists regarding the safety for omission of diverting ileostomy in restorative proctocolectomy because of fears of increased septic complications . This study was design ed to evaluate the outcomes of restorative proctocolectomy in a consecutive series of patients by comparing postoperative complications , functional results , and quality of life in patients with and without diverting ileostomy . Methods Data regarding demographics , length of stay , surgical characteristics , and complications were review ed and recorded according to the presence ( n= 1,725 ) or absence ( n = 277 ) of a diverting ileostomy at the time of pelvic pouch surgery . Criteria for omission of ileostomy included : stapled anastomosis , tension-free anastomosis , intact tissue rings , good hemostasis , absence of airleaks , malnutrition , toxicity , anemia , and prolonged consumption of steroids . Functional outcome and quality of lifeindicators were prospect ively recorded and compared . Results Patients in the ileostomy group had greater body surface area and older mean age at time of surgery , were taking greater doses of steroids preoperatively , and required more blood transfusions at the time of surgery compared with the one-stage ( P < 0.05 ) . There were no differences between the two groups in septic complications ( P > 0.05 ) . Early postoperative ileus was more common in the one-stage group ( P < 0.001 ) . There were no differences between the groups in quality of life and functional outcomes . Conclusions For carefully selected patients undergoing restorative proctocolectomy with ileal pouch-anal anastomosis , omission of diverting ileostomy is a safe procedure that does not lead to an increase inseptic complications or mortality . Quality of life and functional results are similar to those who undergo ileal pouch-anal anastomosis with diversion , provided that certain selection factors are considered Background : Ileal pouch anal anastomosis ( IPAA ) is the treatment of choice for chronic , medically refractory mucosal ulcerative colitis , indeterminate colitis , familial adenomatous polyposis ( FAP ) , and a select group of patients with Crohn 's disease . Aim : We report outcomes , complications , and quality of life ( QOL ) in a cohort of 3707 patients treated at our institution from January 1984 to March 2010 . Methods : Data were collected from a prospect ively maintained data base and chart review of 3707 consecutive primary IPAA cases . Patient demographics , postoperative complications , functional outcomes , and QOL data were available . Follow-up consisted of clinical examination with assessment of pouch function and QOL . Results : A total of 3707 patients underwent primary pouch and 328 underwent redo pouch surgery . Postoperative histopathological diagnoses were mucosal ulcerative colitis ( n = 2953 , 79.7 % ) , indeterminate colitis ( n = 63 , 1.7 % ) , FAP ( n = 223 , 6 % ) , Crohn 's disease ( n = 150 , 4 % ) , cancer/dysplasia ( n = 97 , 2.6 % ) , and others ( n = 221 , 6.0 % ) . Early perioperative complications were encountered in 33.5 % of patients with a mortality rate of 0.1 % . Excluding pouchitis , late complications were experienced by 29.1 % of patients . Of those patients who had IPAA at our institution , pouch failure occurred in 197 patients ( 5.3 % ) . During a median follow-up of 84 months , 119 patients ( 3.2 % ) required excision of the pouch , 32 ( 0.8 % ) had a nonfunctioning pouch , and 46 patients ( 1.2 % ) had redo IPAA . Functional outcomes and QOL were good or excellent in 95 % of patients and similar in each histopathological subgroup . Conclusions : IPAA is an excellent option for patients with MUC , IC , FAP , and select patients with Crohn 's disease Restorative proctocolectomy and ileal pouch‐anal anastomosis ( IPAA ) has been carried out on 88 patients since 1982 . Three different pouch design s ( J , S and W ) were used . Ten pouches had to be removed . Detailed analysis was performed on 61 patients ( J = 23 , S = 15 , W = 23 ) whose pouches had been functioning for at least 6 months . There was no significant difference in surgical complications before or after ileostomy closure between pouch design s but the hospital stay was greater after construction of an S pouch ( P<0.05 ) . There were no significant differences in stool frequency , degree of continence or urgency between the three types . Twelve patients with J pouches required antidiarrhoeal medication compared with only one with S and five with W pouches . Only seven patients with S pouches could defaecate spontaneously compared with 22 with W pouches and all patients with J pouches ( P<0.001 ) . Twenty‐five of 29 patients who had preservation of the anal transition zone had perfect continence compared with 23 of 32 with a mucosal proctectomy ( P = n.s . ) . Pouchitis occurred in 13 patients , all of whom had ulcerative colitis . In a subgroup of 23 patients , pouch evacuation was assessed scintigraphically . There was no difference in pouch capacity or total volume evacuated , but spontaneous evacuation was better in J and W pouches compared with S pouches Objective : Few studies have evaluated factors that may be associated with the development of septic complications after restorative proctocolectomy . Therefore , the aim of this study is to evaluate preoperative and operative factors that might be associated with septic complications after restorative proctocolectomy . Methods : Patients developing abdominal and pelvic septic complications after restorative proctocolectomy were identified from a prospect i ve data base . Patients with sub clinical leaks and ileostomy closure leak were not included in the septic complication group . A multivariable logistic regression model for sepsis was constructed using a forward stepwise selection with entry criterion of P < 0.05 . Results : From 1983 to 2007 , 3233 patients ( 56 % male ) were included in the data base . Eight-four percent ( 2597 ) of patients underwent proximal diversion . Two hundred patients ( 6.2 % ) developed septic complications within 3 months of restorative proctocolectomy or within 3 months of ileostomy closure . On multivariate analysis , body mass index > 30 ( P = 0.02 , OR = 1.77 ) , final pathologic diagnosis of ulcerative/indeterminate colitis ( P = 0.02 , OR = 2 ) or Crohn 's disease ( P = 0.02 , OR = 3.6 ) , intraoperative ( P = 0.02 , OR = 1.6 ) , and postoperative transfusions ( P = 0.01 , OR = 1.9 ) were all independently associated with septic complications . We also demonstrated an independent association among individual surgeons ( P = 0.04 ) with decreased septic complications . Conclusions : Body mass index greater than 30 , final pathologic diagnosis of ulcerative/indeterminate colitis or Crohn 's disease , intraoperative and postoperative transfusions , and surgeon were all independent factors associated with septic complications after restorative proctocolectomy Objectives : The objective of the HASTA trial was to compare h and suture versus stapling loop ileostomy closure in a r and omized controlled trial . Background : Bowel obstruction is one of the main and the clinical ly and economically most relevant complication following closure of loop ileostomy after low anterior resection . The best surgical technique for closure of loop ileostomy has not been defined yet . Methods : HASTA trial is a multicenter pragmatic r and omized controlled surgical trial with 2 parallel groups to compare h and suture versus stapling for closure of loop ileostomy . The primary endpoint was the rate of bowel obstruction within 30 days after ileostomy closure . Results : A total of 337 r and omized patients undergoing closure of loop ileostomy after low anterior resection because of rectal cancer in 27 centers were included . The overall rate of postoperative ileus after ileostomy closure was 13.4 % . Seventeen of 165 ( 10.3 % ) patients in the stapler group and 27 of 163 ( 16.6 % ) in the h and suture group developed bowel obstruction within 30 days postoperatively [ odds ratio ( OR ) = 1.72 ; 95 % confidence interval ( CI ) : 0.89–3.31 = 0.10 ] . Duration of surgical intervention was significantly shorter in the stapler group ( 15 minutes ; P < 0.001 ) . Multivariable analysis of potential risk factors did not reveal any significant correlation with development of postoperative ileus . Rate of anastomotic leakage ( stapler : 3.0 % , h and suture : 1.8 % , P = 0.48 ) did not differ significantly as well as all other secondary endpoints . Conclusions : H and -sewn anastomosis versus stapler ileo-ileostomy for ileostomy closure are equally effective in terms of postoperative bowel obstruction , with stapler anastomosis leading to a shorter operation time . Postoperative ileus after ileostomy reversal remains a relevant complication Ileal pouch-anal anastomosis ( IPAA ) has become the procedure of choice for surgical treatment of intractable ulcerative colitis ( UC ) . Surgical complications occurring in the short-term , like pelvic sepsis , are responsible for pouch dysfunction . We prospect ively evaluated 118 patients with IPAA for UC operated on between 1987 and 2002 . Follow-up intervals were at 3 , 6 , and 12 months in the first year , then every year for at least 5 years . Patients answered a question naire 1 and 5 years after ileostomy closure . One hundred and seventeen patients completed the early follow-up . Nine patients developed early pelvic sepsis ( 7.69 % ) ; six required pouch salvage procedure . In about 33.3 per cent of cases more than one procedure was necessary . Eighty-eight patients were available for 5-year functional evaluation . Patients developing early sepsis ( n = 9 ) showed worse long-term functional results compared with the remaining study population ( n = 79 ) : stool frequency ; night evacuation ; perfect day/night continence ; discrimination ; antidiarrhoeals need ; pad usage ; and sexual restriction were significantly different ( P < 0.05 ) . Quality of life and satisfaction after surgery were good in all patients . This observation did not correlate with function . Eighty-eight and 97 per cent would undergo IPAA again and would recommend it to others respectively , in septic group and controls . Functional outcome after IPAA may be influenced by early septic complications . Overall quality of life and satisfaction with surgery are comparable with those of controls A r and omized controlled trial was performed to assess the role of loop ileostomy in totally stapled restorative proctocolectomy . Entry criteria included all patients who were not on corticosteroids in whom on‐table testing revealed a watertight pouch with intact ileoanal anastomosis . Of 59 patients undergoing restorative proctocolectomy over 36 months , 45 were eligible and were r and omized to loop ileostomy ( n = 23 ) or no ileostomy ( n = 22 ) . The age and diagnosis of the groups were similar . There were no deaths ; two ileoanal anastomotic leaks occurred , one in each group . Ileoanal stenosis occurred in five patients with and one without an ileostomy . The incidences of wound and pelvic sepsis , bowel obstruction and pouchitis were similar . Twelve patients ( 52 per cent ) developed ileostomy‐related complications . The median total hospital stay was 23 ( range 13–75 ) days with ileostomy and 13 ( range 7–119 ) days without ( P < 0.001 ) . This study indicates that there is a low risk of pelvic sepsis which is not increased by avoiding a protective ileostomy . Loop ileostomy was associated with a high incidence of complications PURPOSE : This study was design ed to measure the impact of pelvic abscess on eventual pouch failure and functional outcome after ileal pouch-anal anastomosis in patients with chronic ulcerative colitis . PATIENTS AND METHODS : The outcome of 1,508 patients who underwent ileal pouch-anal anastomosis for chronic ulcerative colitis at the Mayo Clinic was determined from a central patient registry ; data were collected prospect ively . RESULTS : Seventy-three patients developed a pelvic abscess as a complication of ileal pouch-anal anastomosis . Pouch failure occurred in 19 ( 26 percent ) . Forty-eight patients ( 55 percent ) required transabdominal salvage surgery , 6 ( 8 percent ) underwent local surgery , and the remaining 27 ( 37 percent ) were treated nonsurgically . Wound infection was more common in patients who experienced pelvic abscess . The majority of pouch failures secondary to pelvic abscess formation occurred within two years of ileal pouch-anal anastomosis . Daytime incontinence , the use of a protective pad , and the need for constipating or bulking medication were significantly more common among patients who had an abscess but kept their reservoir . Ability to perform work and domestic activities and to undertake recreational activities were significantly more restricted among these patients . CONCLUSIONS : Pouch failure occurs in one-fourth of patients who retain their pouch despite pelvic abscess after ileal pouch-anal anastomosis . Among patients who retain their pouch despite postoperative pelvic abscess , functional outcome and quality of life are significantly poorer than in patients in whom no sepsis occurred BACKGROUND Restorative proctocolectomy with ileal pouch-anal anastomosis ( IPAA ) is the treatment of choice for patients with ulcerative colitis and familial adenomatous . This study examined the impact of the surgical approach ( laparoscopic versus open ) to IPAA on short-term outcomes and time to ileostomy closure in 2-stage restorative proctocolectomies . STUDY DESIGN A retrospective review was performed on a prospect ively maintained data base at Washington University School of Medicine for patients undergoing elective 2-stage restorative proctocolectomy and IPAA from April of 1999 through July of 2008 . Outcomes for patients were analyzed according to laparoscopic versus open technique . RESULTS A total of 124 patients ( 55 laparoscopy , 69 open ) were included in this study . Laparoscopic IPAA took , on average , 79.2 minutes longer to complete than open IPAA ( p < 0.0001 ) and required significantly more intravenous fluid administration ( p = 0.0004 ) . There was no significant difference between laparoscopic and open IPAA with respect to estimated blood loss , blood transfusions , postoperative narcotic usage , return of bowel function , length of stay , and hospital readmission rates . Total complications were not statistically significant between the 2 groups . Patients in the laparoscopic IPAA group underwent ileostomy closure an average of 24.1 days sooner than patients in the open group ( p = 0.045 ) . Multivariate analysis revealed that surgical approach ( p = 0.018 ) and length of stay ( p = 0.004 ) were associated with faster time to closure of loop ileostomy . CONCLUSIONS Laparoscopic IPAA is safe , with postoperative morbidity comparable with open IPAA . Laparoscopic IPAA can lead to faster recovery and result in faster progression to restoration of intestinal continuity in patients undergoing 2-stage restorative proctocolectomy The aim was to compare reversal and laparoscopy with st and ard reversal of loop ileostomy in terms of hospital stay and morbidity in a r and omized study Twenty consecutive stapled loop ileostomy closures in patients treated by restorative proctocolectomy were compared with the previous 20 sutured loop ileostomy closures in a non-r and omised audit . Complications occurred in six of 20 stapled closures compared with seven of 20 sutured closures . Operating time and hospital stay were similar . The additional expense of stapling does not seem justified as complication rates , operating time and hospital stay are similar to sutured closures BACKGROUND Diverting loop ileostomy is used to mitigate the sequelae of anastomotic dehiscence . OBJECTIVE To report the rate of complications after ileostomy reversal using st and ardized definitions to aid physicians who are deciding whether to divert anastomoses . METHODS Patients who underwent diverting loop ileostomy closure from January 1 , 2005 , through February 28 , 2010 , were identified using a prospect i ve data base . Perioperative variables and 30-day outcomes were review ed . Complications were grade d according to the Clavien-Dindo Classification , in which grade III , IV , or V represents major complications . Univariate analysis assessed the relationship between operative variables and surgical outcomes . RESULTS A total of 944 patients underwent reversal : 43.1 % were women , the mean age was 47.2 years , the mean body mass index ( calculated as weight in kilograms divided by height in meters squared ) was 25.7 , and 18.5 % were American Society of Anesthesiologists class III or IV . Indications for the initial operation were ulcerative colitis ( 49.5 % ) , rectal cancer ( 27.5 % ) , diverticular disease ( 6.8 % ) , and other ( 16.1 % ) . Anastomotic technique for reversal was sutured fold-over in 466 patients ( 49.4 % ) , stapled in 315 ( 33.4 % ) , and h and sewn end to end in 163 ( 17.3 % ) . After reversal , the mean time to first bowel movement , tolerance of soft diet , and discharge from hospital was 2.6 , 3.7 , and 5.2 days , respectively . H and sewn cases had longer operative times and longer times to bowel movement , soft diet , and discharge . Overall , complications occurred in 203 patients ( 21.5 % ) , including 45 patients ( 4.8 % ) who experienced a major complication ; there were no deaths within 30 days . CONCLUSION Ileostomy closure is associated with a low rate of major grade III and IV complications and should be reserved for patients who have a predicted postoperative major complication rate of 5 % or more without diversion BACKGROUND Total proctocolectomy with ileal pouch-anal anastomosis ( IPAA ) is the gold st and ard surgical treatment for chronic ulcerative colitis . More recently , this procedure is being performed laparoscopically assisted . Postoperatively , small bowel obstruction ( SBO ) is one of the more common associated complications . However , it is unknown whether the addition of a laparoscopic approach has changed this risk . This study aims to assess and compare the incidence of SBOs after both open and laparoscopic restorative proctocolectomy . METHODS All subjects who underwent restorative proctocolectomy from 1998 - 2008 were identified from a prospect i ve Colorectal Surgery Data base . Medical records were review ed for all cases of SBO , confirmed by a combination of clinical symptoms and radiologic evidence . Comparisons were made between laparoscopic and open approaches . The incidence of SBO was also subdivided into pre-ileostomy takedown , early post-ileostomy takedown ( 30 d post ) , and late post-ileostomy takedown ( 30 d to 1 y post ) . Several potential risk factors were also evaluated . Statistical analysis was performed utilizing Fisher 's exact ( for incidence ) or t-tests ( for means ) . Significance was defined as P < 0.05 RESULTS A total of 290 open cases and 100 laparoscopic cases were identified during this time period . The overall incidence of SBO at 1 y post-ileostomy takedown was 14 % ( n = 42 ) in the open group and 16 % ( n = 16 ) laparoscopic ( P = NS ) . In the pre-ileostomy takedown period the incidence of SBO was 7 % ( n = 21 ) open and 13 % ( n = 13 ) laparoscopic ( P = NS ) . While in the post-takedown period , the early incidence was 4 % ( n = 12 ) open and 1 % ( n = 1 ) laparoscopic and late incidence was 3 % ( n = 9 ) open and 2 % ( n = 2 ) laparoscopic ( P = NS ) . Factors associated with an increased risk of SBO include coronary artery disease , prior appendectomy and W and J pouch configurations . CONCLUSIONS The burden of postoperative small bowel obstruction after restorative proctocolectomy is not changed with a laparoscopic approach . Most cases occur in the early postoperative period , especially prior to ileostomy reversal The aim of this study was to prospect ively assess the morbidity of creating and closing loop ileostomies in a consecutive series of patients having an ileoanal pouch procedure . Between 1983 and 1991 , 203 patients had loop ileostomies created for temporary fecal diversion after an ileoanal pouch procedure . There was one death as a result of liver failure . One patient developed a persistent pouch-vaginal fistula that result ed in pouch excision . The remaining 201 patients had their ileostomies closed at a mean time of 10 weeks after the primary procedure . Only 7 % needed surgery to correct ileostomy-related problems . After ileostomy closure , complications were noted in only 2 % of patients . Loop ileostomy is easy to create and provides highly effective fecal diversion , which decreases the incidence of and mitigates the serious sequelae of pouch sepsis . Closure is simple , does not require a laparotomy , and is associated with few complications . Our experience with loop ileostomy for temporary fecal diversion after an ileoanal pouch procedure has been favorable . The loop ileostomy may be the stoma of choice for most clinical situations in which temporary fecal diversion is indicated |
10,446 | 28,824,994 | Conclusions and Relevance There is emerging , albeit low- quality , evidence in favor of combination CHG and PVI preoperative antisepsis . | Importance Effective preoperative antisepsis is recognized to prevent surgical site infection ( SSI ) , although the definitive method is unclear .
Many have compared chlorhexidine ( CHG ) with povidone-iodine ( PVI ) , but there is emerging evidence for combination usage .
Objective To conduct a systematic review and meta- analysis to evaluate if combination skin preparation ( 1 ) reduces colonization at the operative site and ( 2 ) prevents SSI compared with single-agent use . | BACKGROUND --Pacemaker pocket infection is a potentially serious problem after permanent pacemaker implantation . Antibiotic prophylaxis is commonly prescribed to reduce the incidence of this complication , but current trial evidence of its efficacy is conflicting . A large prospect i ve r and omised trial was therefore performed of antibiotic prophylaxis in permanent pacemaker implantation . The intention was firstly to determine whether antibiotic prophylaxis is efficacious in these patients and secondly to identify which patients are at the highest risk of infection . METHODS --A prospect i ve r and omised open trial of flucloxacillin ( clindamycin if the patient was allergic to penicillin ) v no antibiotic was performed in a cohort of patients undergoing first implantation of a permanent pacing system over a 17 month period . Intravenous antibiotics were started at the time of implantation and continued for 48 hours . The trial endpoint was a repeat operation for an infective complication . RESULTS --473 patients were entered into a r and omised trial . 224 received antibiotic prophylaxis and 249 received no antibiotics . A further 183 patients were not r and omised but were treated according to the operator 's preference ( 64 antibiotics , 119 no antibiotics ) ; these patients are included only in the analysis of predictors of infection . Patients were followed up for a mean ( SD ) of 19(5 ) months . Among the patients in the r and omised group there were nine infections requiring a repeat operation , all in the group not receiving antibiotic ( P = 0.003 ) . In the total patient cohort there were 13 infections , all but one in the non-antibiotic group ( P = 0.006 ) . Nine of the infections presented as erosion of the pulse generator or electrode , three as septicaemia secondary to Staphylococcus aureus , and one as a pocket abscess secondary to Staphylococcus epidermidis . Infections were significantly more common when the operator was inexperienced ( < or = 100 previous patients ) , the operation was prolonged , or after a repeat operation for non-infective complications ( principally lead displacement ) . Infection was not significantly more common in patients identified preoperatively as being at high risk ( for example patients with diabetes mellitus , patients receiving long term steroid treatment ) , although there was a trend in this direction . CONCLUSIONS --Antibiotic prophylaxis significantly reduced the incidence of infective complications requiring a repeat operation after permanent pacemaker implantation . It is suggested that antibiotics should be used routinely Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more To investigate the usefulness of a st and ard surgical preparation in prevention of surgical site contamination , 49 consecutive patients undergoing foot or ankle surgery were r and omly assigned to st and ard preparation with chlorhexidine gluconate home scrubs and preoperative povidone-iodine or to st and ard preparation plus preoperative preparation with 70 % alcohol . Results were available for all 49 patients . Cultures were positive for normal aerobic bacteria from the toes of nine of 26 patients ( 35 % ) receiving st and ard surgical preparation and from the toes of 13 of 23 patients ( 57 % ) receiving st and ard preparation plus alcohol ( P=0.12 ) . No patient had a positive culture for anaerobic organisms or clinical evidence of infection or wound problems . St and ard surgical preparation did not provide a completely sterile field , and the inclusion of alcohol added no benefit BACKGROUND Currently , there are various antiseptics used for cleaning the skin before surgery , but there is no st and ard procedure in practice . Chlorhexidine and povidone-iodine are the most preferred compounds among antiseptics . Both are proved to be safe and effective for skin disinfection . In this study , our aim was to investigate the combined effects of chlorhexidine and povidone-iodine on the skin 's flora before neurosurgical intervention , consecutively . METHODS R and omly , 50 cranial and 50 spine neurosurgery cases were assigned to the study . The first culture was obtained after hair removal and before cleaning the skin with any antiseptic . The second culture was obtained after the skin had been cleaned with chlorhexidine for 3 minutes . Then , the skin was cleaned twice with povidone-iodine for 30 seconds , and the third and fourth cultures were taken from the skin incision area . Bacteria were identified by means of st and ard laboratory identification methods . Positive culture results were compared statistically among order of cultures obtained . RESULTS In the first culture evaluation , 39 ( 33 cnS , 6 Stapylococcus aureus ) of 50 cranial sample s and 37 ( 33 cnS , 4 S aureus ) of 50 spine sample s showed reproduction . In the second culture , 9 cranial and 5 spine sample s showed reproduction of cnS. In the third and fourth cultures , no growth was observed ( P < .001 ) . CONCLUSION Three minutes ' cleaning of the incision area with chlorhexidine , followed by 30-second cleaning with povidone-iodine , could be a sufficient disinfection procedure for preoperative preparation of the skin in patients undergoing a neurosurgical procedure BACKGROUND Treatment of Staphylococcus aureus colonization before surgery reduces risk of surgical site infection ( SSI ) . The regimen of nasal mupirocin ointment and topical chlorhexidine gluconate is effective , but cost and patient compliance may be a barrier . Nasal povidone-iodine solution may provide an alternative to mupirocin . METHODS We conducted an investigator-initiated , open-label , r and omized trial comparing SSI after arthroplasty or spine fusion in patients receiving topical chlorhexidine wipes in combination with either twice daily application of nasal mupirocin ointment during the 5 days before surgery or 2 applications of povidone-iodine solution into each nostril within 2 hours of surgical incision . The primary study end point was deep SSI within the 3 months after surgery . RESULTS In the modified intent-to-treat analysis , a deep SSI developed after 14 of 855 surgical procedures in the mupirocin group and 6 of 842 surgical procedures in the povidone-iodine group ( P = .1 ) ; S. aureus deep SSI developed after 5 surgical procedures in the mupirocin group and 1 surgical procedure in the povidone-iodine group ( P = .2 ) . In the per protocol analysis , S. aureus deep SSI developed in 5 of 763 surgical procedures in the mupirocin group and 0 of 776 surgical procedures in the povidone-iodine group ( P = .03 ) . CONCLUSIONS Nasal povidone-iodine may be considered as an alternative to mupirocin in a multifaceted approach to reduce SSI . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01313182 Introduction Surgical site infection ( SSI ) is a significant cause of postoperative morbidity and mortality . Effective preoperative antisepsis is a recognised prophylactic , with commonly used agents including chlorhexidine ( CHG ) and povidone-iodine ( PVI ) . However , there is emerging evidence to suggest an additional benefit when they are used in combination . Methods We analysed data from our prospect i ve SSI data base on patients undergoing clean cranial neurosurgery between October 2011 and April 2014 . We compared the case-mix adjusted odds of developing a SSI in patients undergoing skin preparation with CGH or PVI alone or in combination . Results SSIs were detected in 2.6 % of 1146 cases . Antisepsis with PVI alone was performed in 654 ( 57 % ) procedures , while 276 ( 24 % ) had CHG alone and 216 ( 19 % ) CHG and PVI together . SSIs were associated with longer operating time ( p<0.001 ) and younger age ( p=0.03 ) . Surgery type ( p<0.001 ) and length of operation ( p<0.001 ) were significantly different between antisepsis groups . In a binary logistic regression model , CHG and PVI was associated with a significant reduction in the likelihood of developing an SSI ( adjusted odds ratio [ AOR ] 0.12 , 95 % confidence interval [ CI ] 0.02 - 0.63 ) than either agent alone . There was no difference in SSI rates between CHG and PVI alone ( AOR 0.60 , 95 % CI 0.24 - 1.5 ) . Conclusions Combination skin preparation with CHG and PVI significantly reduced SSI rates compared to CHG or PVI alone . A prospect i ve , r and omized study validating these findings is now warranted Objective Central venous catheter (CVC)-related infections may be caused by micro-organisms introduced from the skin surface into deeper tissue at the time of CVC insertion . The optimal disinfection regimen to avoid catheter-related infections has not yet been defined . This study compares three different approaches . Design Prospect i ve r and omised trial . Setting A tertiary care hospital . Patients and participants One hundred nineteen patients scheduled electively to receive 140 CVCs . Interventions Skin disinfection was performed with either povidone-iodine 10 % ( PVP-iodine ) , chlorhexidine 0.5%/propanol 70 % , or chlorhexidine 0.5%/propanol 70 % followed by PVP-iodine 10 % . Prior to disinfection , a swab from the site of insertion was taken for culture . CVCs were removed if no longer needed or infection was suspected . All catheters were cultured quantitatively after removal . Measurement and results Bacteria could be isolated from 20.7 % of the catheter tips . Bacterial growth was found in 30.8 % of the catheters placed after skin disinfection with povidone-iodine , in 24.4 % after disinfection with propanol/chlorhexidine and in 4.7 % after disinfection with propanol/chlorhexidine followed by povidone-iodine ( p=0.006 ) . In 15 cases , the same organism was isolated from the skin swab and the catheter tip . Ten of these paired isolates showed the same pattern in a pulsed-field gel electrophoresis analysis . Conclusions Skin disinfection with propanol/chlorhexidine followed by PVP-iodine was superior in the prevention of microbial CVC colonisation compared to either of the regimens alone . These results support the concept that catheter infections can originate from bacterial translocation at the time of catheter insertion A prospect i ve study was performed to describe the density of bacterial counts on the skin of neurosurgical patients and examine the association between total colony-forming unit ( cfu ) counts of skin flora at the operative site and surgical site infection ( SSI ) . Two skin cultures were obtained , immediately before and after skin preparation , from the operative sites of 609 neurosurgical patients . SSI surveillance that used Centers for Disease Control/National Nosocomial Infection Surveillance definitions was performed . Predictors for high bacterial counts and SSI among craniotomies were analyzed by means of logistic regression . Neither pre- nor postpreparation counts were associated with SSI . Other SSI risk factors were obesity ( relative risk [ RR ] , 2.5 ) , duration of surgery ( RR , 1.3 for every additional 30 minutes ) and age ( RR , 0.7 for each additional 10 years ) . Duration of skin preparation was not correlated with postpreparation cfu counts . We were unable to detect an association between preoperative bacterial skin counts and SSI Eradication of bacterial flora from the foot , especially the nailfolds and toe webspaces , through surgical preparation remains a challenge . All previous studies have involved healthy patients undergoing elective foot and ankle surgery or healthy volunteers . However , the patient with diabetes is considered an immunocompromised host with decreased ability to combat invasive bacterial infections . The use of an efficacious surgical preparation is therefore of paramount importance . The author conducted a prospect i ve study involving patients with diabetes with and without ulceration who underwent the current " best evidence available " surgical preparation ( i.e. , chlorhexidine gluconate [ 4 % ] scrub followed by alcohol impregnated with iodine [ 1 % ] solution ) . Qualitative aerobic cultures before and after completion of this surgical preparation technique were obtained from the hallux nailfold ; second , third , and fourth toe webspaces ( as one culture ) ; and distal anterior tibia . A total of 120 organisms were cultured before surgical preparation with 64 in the elective group and 56 in the ulcerated group . The most commonly isolated organism was methicillin-resistant Staphylococcus epidermidis , which was identified in 46 pre-preparation cultures ( 38.3 % ) . This was followed by methicillin-sensitive S. epidermidis ( 16.7 % ) and " other " organisms ( 10.0 % ) . There was a significant reduction for both numbers of organisms identified and positive cultures for the 3 most commonly isolated organisms after surgical preparation . Based on the results of this study , the surgical preparation used here appears to be an efficacious surgical preparation technique for eradicating aerobic bacterial pathogens from the foot in patients with diabetes both with and without ulceration . The high incidence of methicillin-sensitive and methicillin-resistant S. epidermidis found in this patient population is a cause for concern , especially when metallic fixation is intended to be implanted Fifty patients undergoing foot or ankle surgery were r and omized into two groups for the purpose s of toe preparation . Twenty-four patients underwent a st and ard preparation which included placing antiseptic between the toes while 26 were additionally cleaned by sliding a gauze swab soaked in topical antiseptic back and forth several times . Povidone iodine followed by chlorhexidine in alcohol was used in both groups . All toes were covered by a sterile glove during surgery unless the toes themselves were to be operated upon . Bacteria were cultured from the toe clefts in 4 % of all patients immediately following preoperative disinfection . Significantly fewer patients whose toes had been additionally scrubbed ( group 1 ) showed bacterial recolonization at the end of surgery compared with those undergoing a st and ard prep ( group 2 ) ( 7.7 % vs 20.8 % ) . We conclude that additional scrubbing of toe clefts prior to surgery reduces the incidence of recolonization of bacteria during the surgical procedure BACKGROUND Preventing surgical site infection ( SSI ) after total joint arthroplasty ( TJA ) is a high priority and is partly linked to the efficacy of surgical site preparation solutions ( SPSs ) in reducing the number of pathogens on the skin before incision . The aim of this study is to investigate the effectiveness of SRS reapplication after draping to reduce the incidence of SSI after TJA . METHODS Six hundred patients undergoing primary TJA between 2010 and 2011 at a single institution were recruited and r and omly assigned to one of 2 groups . The patients in the intervention group ( n = 300 ) received SPS that included alcohol and povidone-iodine before draping and an additional SPS by iodine povacrylex and isopropyl alcohol before application of the final adhesive drape , whereas the patients in the control group ( n = 300 ) received a single SPS with alcohol and povidone-iodine before draping . R and omization was performed by an opaque envelope , and the rates of SSI and blistering were compared between groups . RESULTS Five seventy-seven patients completed the study and were included in the final analysis . There was a significant reduction in the incidence of superficial SSI for the intervention group ( 1.8 % , 5 of 283 ) compared to the control group ( 6.5 % , 19 of 294 , P = .02 ) . There were 2 ( 0.7 % , 2 of 294 ) deep incisional SSIs in the control group , and 2 ( 0.7 % , 2 of 283 ) organ-space SSIs in the intervention group ( P = 1.00 ) . In addition , skin blistering was lower in the intervention group ( 3.5 % , 10 of 283 ) vs the control group ( 6.5 % , 19 of 294 ) , but this difference also did not reach statistical significance ( P = .13 ) . CONCLUSION Reapplication of an SPS after draping and before the application of iodophor-impregnated incisive draping result ed in a significant reduction in the rate of SSI in patients undergoing elective TJA Objective : We studied the impact of residual bacteria at the incision site after disinfection with polyvinylpyrrolidone ( PVP or povidone)-iodine-alcohol and the correlation with postoperative surgical site infections ( SSIs ) . Background : Chlorhexidine-based preparations are significantly more effective for catheter insertion care than povidone-iodine solutions to prevent catheter-associated infections , suggesting that the use of PVP-iodine should be reevaluated for disinfection of the surgical site . In the majority of European hospitals PVP-iodine-alcohol is still st and ard of care to prepare the preoperative site . Methods : We consecutively and prospect ively enrolled 1005 patients from representative surgical disciplines . Skin cultures to determine skin microbial counts were taken after disinfection with PVP-iodine-alcohol , immediately before incision . Disinfection of the surgical site was performed using st and ardized procedure under supervision . Criteria for SSI were based on guidelines issued by the Centers for Disease Control including appropriate follow-up of 30 days and 1 year . Results : A total of 1014 skin cultures from surgical sites were analyzed from 1005 patients , of which 36 ( 3.6 % ) revealed significant colonization of the preoperative site , and 41 SSIs were detected , accounting for an SSI rate of 4.04 % ; residual bacteria before incision were completely unrelated to the incidence of SSI , even after adjustment for multiple potentially confounding variables . Conclusions : A low rate of SSIs of 4.04 % was achieved when using PVP-iodine-alcohol for disinfection of the preoperative site . Remaining bacteria after st and ardized 3-step disinfection did not at all correlate with the development of an SSI . Our data provide clear evidence that PVP-iodine-alcohol is effective for preparation of the preoperative site OBJECT Quality improvement methods are being implemented in various areas of medicine . In an effort to reduce the complex ( instrumented ) spine infection rate in pediatric patients , a st and ardized protocol was developed and implemented at an institution with a high case volume of instrumented spine fusion procedures in the pediatric age group . METHODS Members of the Texas Children 's Hospital Spine Study Group developed the protocol incrementally by using the current literature and prior institutional experience until consensus was obtained . The protocol was prospect ively applied to all children undergoing complex spine surgery starting August 21 , 2012 . Acute infections were defined as positive wound cultures within 12 weeks of surgery , defined in alignment with current hospital infection control criteria . Procedures and infections were measured before and after protocol implementation . This protocol received full review and approval of the Baylor College of Medicine institutional review board . RESULTS Nine spine surgeons performed 267 procedures between August 21 , 2012 , and September 30 , 2013 . The minimum follow-up was 12 weeks . The annual institutional infection rate prior to the protocol ( 2007 - 2011 ) ranged from 3.4 % to 8.9 % , with an average of 5.8 % . After introducing the protocol , the infection rate decreased to 2.2 % ( 6 infections of 267 cases ) ( p = 0.0362 ; absolute risk reduction 3.6 % ; relative risk 0.41 [ 95 % CI 0.18 - 0.94 ] ) . Overall compliance with data form completion was 63.7 % . In 4 of the 6 cases of infection , noncompliance with completion of the data collection form was documented ; moreover , 2 of the 4 spine surgeons whose patients experienced infections had the lowest compliance rates in the study group . CONCLUSIONS The st and ardized protocol for complex spine surgery significantly reduced surgical site infection at the authors ' institution . The overall compliance with entry into the protocol was good . Identification of factors associated with post-spine surgery wound infection will allow further protocol refinement in the future |
10,447 | 25,268,290 | The meta-analyses determined that there were no differences in the effectiveness of linear vs. undulating periodization on upper-body or lower-body strength .
The results suggest that novelty or training variety are important for stimulating further strength development .
Few studies have examined the effect of periodization approaches in adolescent or athletic population | Periodization is known to improve training adaptations but the most effective periodization approach for muscular strength development for a wide variety of population s is yet to be determined . | Summary A 28-week resistance training with linear periodization was compared with an undulating model in 27 premenopausal women . In both groups , bone mineral density ( BMD ) was not changed but muscle strength increased , and there were changes in anthropometrical and muscle damage parameters , indicating that in this population , these models are similar concerning these variables . Introduction This study seeks to compare the effects of resistance training with undulating versus linear periodization on BMD , muscle strength , anthropometrical variables , and muscle damage parameters in premenopausal women . Methods Twenty-seven females ( 39.6 ± 0.41 years , mean ± st and ard error ) , without osteopenia or osteoporosis and without calcium supplementation , were r and omly assigned either to a linear periodization group ( LPG , n = 14 ) or to an undulating periodization group ( UPG , n = 13 ) . The subjects were trained three times a week for 28 weeks . Lumbar spine and femoral neck BMDs were measured through dual-energy X-ray absorptiometry . Maximal and submaximal dynamic muscle strengths were measured through the 1-RM and 20-RM tests , respectively . Anthropometrical ( body mass , skinfolds , and perimeters ) and muscle damage parameters were assessed through serum creatine kinase ( CK ) and delayed-onset muscle soreness ( DOMS ) . Results BMD remained unchanged in both groups , despite significant increases in maximal ( LPG , 37–73 % ; UPG , 40–70 % ) and submaximal ( LPG , 82–114 % ; UPG , 70–102 % ) muscle strength . The perimeter of the distal thigh was increased ( about 1.7 cm ) in both groups . CK and DOMS were greater in the first mesocycle than in the subsequent ones . After the 1st training session in each mesocycle , 24 and 48 h CK was increased as compared to pretraining values . Conclusions The resistance training of 28 weeks increased muscle strength in both training groups with no difference in BMD or in the occurrence of muscle damage The purpose of the present investigation was to determine if significant differences exist among 3 different periodization programs in eliciting changes in strength . Twenty-eight recreationally trained college-aged volunteers ( mean = SD ; 22.29 = 3.98 ) of both genders were tested for bench press , leg press , body fat percentage , chest circumference , and thigh circumference during initial testing . After initial testing , subjects were r and omly assigned to 1 of 3 training groups : ( a ) linear periodization ( n = 9 ) , ( b ) daily undulating periodization ( n = 10 ) , or ( c ) weekly undulating periodization ( n = 9 ) . The training regimen for each group consisted of a 9-week , 3-day-per-week program . Training loads were assigned as heavy ( 90 % , 4 repetition maximum [ 4RM ] ) , medium ( 85 % , 6RM ) , or light ( 80 % , 8RM ) for bench press and leg press exercises . Subjects were familiarized with the CR-10 rated perceived exertion scale and instructed to achieve an 8 or 9 on the final repetition of each set for all other exercises . Subjects were then retested after 4 weeks of training . Training loads were then adjusted according to the new 1RM . Subjects were then retested after 5 more weeks of exercise . For all subjects , significant ( p < 0.05 ) increases in bench press and leg press strength were demonstrated at all time points ( T1–T3 ) . No significant differences ( p > 0.05 ) were observed between groups for bench press , leg press , body fat percentage , chest circumference , or thigh circumference at all time points . These results indicate that no separation based on periodization model is seen in early-phase training Recently , the comparison of " periodized " strength training methods has been a focus of both exercise and sport science . Daily undulating periodization ( DUP ) , using daily alterations in repetitions , has been developed and touted as a superior method of training , while block forms of programming for periodization have been question ed . Therefore , the purpose of this study is to compare block to DUP in Division I track and field athletes . Thirty-one athletes were assigned to either a 10-wk block or DUP training group in which sex , year , and event were matched . Over the course of the study , there were 4 testing sessions , which were used to evaluate a variety of strength characteristics . Although performance trends favored the block group for strength and rate of force development , no statistically significant differences were found between the 2 training groups . However , statistically different ( P ≤ .05 ) values were found for estimated volume of work ( volume load ) and the amount of improvement per volume load between block and DUP groups . Based on calculated training efficiency scores , these data indicate that a block training model is more efficient than a DUP model in producing strength gains Abstract Simão , R , Spineti , J , de Salles , BF , Matta , T , Fern and es , L , Fleck , SJ , Rhea , MR , and Strom-Olsen , HE . Comparison between nonlinear and linear periodized resistance training : hypertrophic and strength effects . J Strength Cond Res 26(5 ) : 1389–1395 , 2012—The aim of this study was to investigate the effects of nonlinear periodized ( NLP ) and linear periodized ( LP ) resistance training ( RT ) on muscle thickness ( MT ) and strength , measured by an ultrasound technique and 1 repetition maximum ( 1RM ) , respectively . Thirty untrained men were r and omly assigned to 3 groups : NLP ( n = 11 , age : 30.2 ± 1.1 years , height : 173.6 ± 7.2 cm , weight : 79.5 ± 13.1 kg ) , LP ( n = 10 , age : 29.8 ± 1.9 years , height : 172.0 ± 6.8 cm , weight : 79.9 ± 10.6 kg ) , and control group ( CG ; n = 9 , age : 25.9 ± 3.6 years , height : 171.2 ± 6.3 cm , weight : 73.9 ± 9.9 kg ) . The right biceps and triceps MT and 1RM strength for the exercises bench press ( BP ) , lat-pull down , triceps extension , and biceps curl ( BC ) were assessed before and after 12 weeks of training . The NLP program varied training biweekly during weeks 1–6 and on a daily basis during weeks 7–12 . The LP program followed a pattern of intensity and volume changes every 4 weeks . The CG did not engage in any RT . Posttraining , both trained groups presented significant 1RM strength gains in all exercises ( with the exception of the BP in LP ) . The 1RM of the NLP group was significantly higher than LP for BP and BC posttraining . There were no significant differences in biceps and triceps MT between baseline and posttraining for any group ; however , posttraining , there were significant differences in biceps and triceps MT between NLP and the CG . The effect sizes were higher in NLP for the majority of observed variables . In conclusion , both LP and NLP are effective , but NLP may lead to greater gains in 1RM and MT over a 12-week training period Apel , JM , Lacy , RM , and Kell , RT . A comparison of traditional and weekly undulating periodized strength training programs with total volume and intensity equated . J Strength Cond Res 25(3 ) : 694 - 703 , 2011-The purpose of this study was to compare the training adaptations attained during 12 weeks of traditional ( TD ) and weekly undulating ( WUD ) periodized strength training . Forty-two recreationally active men ( age = 22 ± 2.3 years ) were r and omly assigned to 1 of 3 groups : control ( C ) ( n = 14 ) , TD ( n = 14 ) , or WUD ( n = 14 ) . Ten-repetition maximum ( 10RM ) laboratory testing was carried out for the free weight back squat and the free weight flat bench press at baseline , week 8 , and week 12 . The subjects trained 3 d·wk−1 ( approximately 135 min·wk−1 ) from weeks 1 to 2 and 4 d·wk−1 from week 3 to week 12 ( approximately 180 min·wk−1 ) . The TD and WUD groups trained using a periodized strength program with all program variables controlled ( e.g. , volume and intensity ) . The independent variable was the manipulation of intensity . The TD group used a linear increase in intensity , whereas the WUD group had a varied intensity . The results showed that both the TD and WUD groups made significant ( p ≤ 0.05 ) increases in strength at weeks 8 and 12 , but by week 12 , the TD group was significantly ( p ≤ 0.05 ) stronger than the WUD group . These results indicate that TD periodization with a linear increase in intensity was more effective at eliciting strength gains than WUD periodization with a varied intensity . The differences in strength gains between the TD and WUD groups may be related to extended periods of muscle soreness and fatigue that were present in the WUD group but not in the TD group . Thus , during long-term training , individuals may benefit more from TD periodized programs because there may be less muscle soreness and fatigue to disrupt practice and training Monteiro , AG , Aoki , MS , Evangelista , AL , Alveno , DA , Monteiro , GA , Piçarro , IDC , and Ugrinowitsch , C. Nonlinear periodization maximizes strength gains in split resistance training routines . J Strength Cond Res 23(4 ) : 1321 - 1326 , 2009-The purpose of our study was to compare strength gains after 12 weeks of nonperiodized ( NP ) , linear periodized ( LP ) , and nonlinear periodized ( NLP ) resistance training models using split training routines . Twenty-seven strength-trained men were recruited and r and omly assigned to one of 3 balanced groups : NP , LP , and NLP . Strength gains in the leg press and in the bench press exercises were assessed . There were no differences between the training groups in the exercise pre-tests ( p > 0.05 ) ( i.e. , bench press and leg press ) . The NLP group was the only group to significantly increase maximum strength in the bench press throughout the 12-week training period . In this group , upper-body strength increased significantly from pre-training to 4 weeks ( p < 0.0001 ) , from 4 to 8 weeks ( p = 0.004 ) , and from 8 weeks to the post-training ( p < 0.02 ) . The NLP group also exhibited an increase in leg press 1 repetition maximum at each time point ( pre-training to 4 weeks , 4 - 8 week , and 8 weeks to post-training , p < 0.0001 ) . The LP group demonstrated strength increases only after the eight training week ( p = 0.02 ) . There were no further strength increases from the 8-week to the post-training test . The NP group showed no strength increments after the 12-week training period . No differences were observed in the anthropometric profiles among the training models . In summary , our data suggest that NLP was more effective in increasing both upper- and lower-body strength for trained subjects using split routines The purpose of this study was to compare linear periodization ( LP ) and daily undulating periodization ( DUP ) for strength gains . Twenty men ( age = 21 ± 2.3 years ) were r and omly assigned to LP ( n = 10 ) or DUP ( n = 10 ) groups . One repetition maximum ( 1RM ) was recorded for bench press and leg press as a pre- , mid- , and posttest . Training involved 3 sets ( bench press and leg press ) , 3 days per week . The LP group performed sets of 8 RM during weeks 1–4 , 6 RM during weeks 4–8 , and 4 RM during weeks 9–12 . The DUP group altered training on a daily basis ( Monday , 8 RM ; Wednesday , 6 RM ; Friday , 4 RM ) . Analysis of variance with repeated measures revealed statistically significant differences favoring the DUP group between T1 to T2 and T1 to T3 . Making program alterations on a daily basis was more effective in eliciting strength gains than doing so every 4 weeks The purpose of this study was to compare linear periodi-zation ( LP ) , daily undulating periodization ( DUP ) , and reverse linear periodization ( RLP ) for gains in local muscular endurance and strength . Sixty subjects ( 30 men , 30 women ) were r and omly assigned to LP , DUP , or RLP groups . Maximal repetitions at 50 % of the subject 's body weight were recorded for leg extensions as a pretest , midtest , and post-test . Training involved 3 sets ( leg extensions ) 2 days per week . The LP group performed sets of 25 repetition maximum ( RM ) , 20RM , and 15RM changing every 5 weeks . The RLP group progressed in reverse order ( 15RM , 20RM , 25RM ) , changing every 5 weeks . The DUP group adjusted training variables between each workout ( 25RM , 20RM , 15RM repeated for the 15 weeks ) . Volume and intensity were equated for each training program . No significant differences were measured in endurance gains between groups ( RLP = 73 % , LP = 56 % , DUP = 55 % ; p = 0.58 ) . But effect sizes ( ES ) demonstrated that the RLP treatment ( ES = 0.27 ) was more effective than the LP treatment ( control ) and the DUP treatment ( ES = -0.02 ) at increasing muscular endurance . Therefore , it was concluded that making gradual increases in volume and gradual decreases in intensity was the most effective program for increasing muscular endurance Hoffman , JR , Ratamess , NA , Klatt , M , Faigenbaum , AD , Ross , RE , Tranchina , NM , McCurley , RC , Kang , J , and Kraemer , WJ . Comparison between different off-season resistance training programs in Division III American college football players . J Strength Cond Res 23(1 ) : 11 - 19 , 2009-The purpose of this study was to examine the efficacy of periodization and to compare different periodization models in resistance trained American football players . Fifty-one experienced resistance trained American football players of an NCAA Division III football team ( after 10 weeks of active rest ) were r and omly assigned to 1 of 3 groups that differed only in the manipulation of the intensity and volume of training during a 15-week off-season resistance training program . Group 1 participated in a nonperiodized ( NP ) training program , group 2 participated in a traditional periodized linear ( PL ) training program , and group 3 participated in a planned nonlinear periodized ( PNL ) training program . Strength and power testing occurred before training ( PRE ) , after 7 weeks of training ( MID ) , and at the end of the training program ( POST ) . Significant increases in maximal ( 1-repetition maximum [ 1RM ] ) squat , 1RM bench press , and vertical jump were observed from PRE to MID for all groups ; these increases were still significantly greater at POST ; however , no MID to POST changes were seen . Significant PRE to POST improvements in the medicine ball throw ( MBT ) were seen for PL group only . The results do not provide a clear indication as to the most effective training program for strength and power enhancements in already trained football players . Interestingly , recovery of training-related performances was achieved after only 7 weeks of training , yet further gains were not observed . These data indicate that longer periods of training may be needed after a long-term active recovery period and that active recovery may need to be dramatically shortened to better optimize strength and power in previously trained football players The aim of this r and omized controlled study was to verify the impact of a 12-weeks muscular endurance ( ME ) training of high repetitions ( i. e. , 15 - 30 ) with 2 different periodization models on body composition , maximal strength , muscular endurance and cardiorespiratory fitness . Twenty eight sedentary women aged 20 - 35 years were r and omly assigned to : control ( CON ) ( n=8 ) , linear periodization ( LP ) ( n=10 ) and daily undulating periodization ( DUP ) ( n=10 ) . LP and DUP models significantly improved body composition , maximal strength and ME . However , no significant changes were detected for cardiorespiratory fitness . LP showed a higher body fat loss ( - 12.73 % ) compared to DUP ( - 9.93 % ) ( p=0.049 ) , and systematic ally higher effect sizes ( ES ) when compared with DUP for maximal strength and cardiorespiratory fitness parameters ( e. g. ES=0.53 for ventilatory threshold ) . In contrast , DUP exhibited a significantly ( p=0.002 ) greater ME gain ( 129.43 % ) compared to LP ( 70.72 % ) in bench press , and greater ES in all exercises . It may be suggested that LP performed with a high number of repetitions may be considered an appropriate periodization model for untrained young women that would likely lead to the improvement of body composition and maximum strength performance , whereas DUP is more effective for the development of ME Mir and a , F , Simão , R , Rhea , M , Bunker , D , Prestes , J , Leite , RD , Mir and a , H , de Salles , BF , and Novaes , J. Effects of linear vs. daily undulatory periodized resistance training on maximal and submaximal strength gains . J Strength Cond Res 25(7 ) : 1824 - 1830 , 2011—The objective of this study was to verify the effect of 2 periodized resistance training ( RT ) methods on the evolution of 1-repetition maximum ( 1RM ) and 8RM loads . Twenty resistance trained men were r and omly assigned to 2 training groups : linear periodization ( LP ) group and daily undulating periodization ( DUP ) group . The subjects were tested at baseline and after 12 weeks for 1RM and 8RM loads in leg press ( LEG ) and bench press ( BP ) exercises . The training program was performed in alternated sessions for upper ( session A : chest , shoulder and triceps ) and lower body ( session B : leg , back and biceps ) . The 12-week periodized training was applied only in the tested exercises , and in the other exercises , 3 sets of 6 - 8RM were performed . Both groups exhibited significant increases in 1RM loads on LEG and BP , but no statistically significant difference between groups was observed . The same occurred in 8RM loads on LEG and BP . However , DUP group presented superior effect size ( ES ) in 1RM and 8RM loads for LEG and BP exercises when compared to the LP group . In conclusion , periodized RT can be an efficient method for increasing the strength and muscular endurance in trained individuals . Although there was no statistically significant difference between periodization models , DUP promoted superior ES gains in muscular maximal and submaximal strength |
10,448 | 12,917,949 | MAIN RESULTS The additional analyses conducted revealed a statistically significant treatment effect in favour of the aroma therapy intervention on measures of agitation and neuropsychiatric symptoms . | BACKGROUND Complementary therapies have become more commonly used over the last decade and have been applied to a range of health problems , including dementia .
Of these , aroma therapy is reported to be the most widely used in the British National Health Service ( Lundie 1994 ) and might be of use for people with dementia for whom verbal interaction may be difficult and conventional medicine of only marginal benefit .
Aroma therapy has been used for people with dementia to reduce disturbed behaviour ( e.g. Brooker 1997 ) , promote sleep ( e.g. Wolfe 1996 ) , and stimulate motivational behaviour ( e.g. MacMahon 1998 ) .
OBJECTIVES To assess the efficacy of aroma therapy as an intervention for people with dementia . | OBJECTIVES Two controlled trials of aromatherapy to decrease agitation in persons with dementia have recently produced promising results . However , both studies combined the use of essential oils with massage . Thus , it is unclear if the effect of the aromatherapy intervention was the result of smelling or the cutaneous absorption of the oils . The purpose of this study was to determine whether smelling lavender oil decreases the frequency of agitated behaviors in patients with dementia . DESIGN The study design was within-subjects ABCBA ( A = lavender oil , B = thyme oil , C = unscented grapeseed oil ) : 4 weeks of baseline measurement , 2 weeks for each of the five treatment conditions ( 10-week total intervention time ) , and 2 weeks of postintervention measurement . Oil was placed every 3 hours on an absorbent fabric sachet pinned near the collarbone of each participant 's shirt . SETTING A long-term care facility specifically for persons with dementia . PARTICIPANTS Seven agitated nursing home residents with advanced dementia . MEASUREMENTS Agitation was assessed every 2 days using a modified Cohen-Mansfield Agitation Inventory . Olfactory functioning was assessed with structured olfactory identification and discrimination tasks , and with qualitative behavioral observation during those tasks . RESULTS Split-middle analyses conducted separately for each patient revealed no treatment effects specific to lavender , no treatment effects nonspecific to pleasant smelling substances , and no treatment effects dependent on order of treatment administration . There were no differences between participants with more and less intact olfactory abilities . CONCLUSION There is significant evidence in the neurologic and neuropsychologic literature that persons with dementia have impaired olfactory abilities . Concordant with this literature , this study found no support for the use of a purely olfactory form of aromatherapy to decrease agitation in severely demented patients . Cutaneous application of the essential oil may be necessary to achieve the effects reported in previous controlled studies This study was design ed to assess the olfactory impact of the essential oils of lavender ( Lav and ula angustifolia ) and rosemary ( Rosmarlnus officinalis ) on cognitive performance and mood in healthy volunteers . One hundred and forty-four participants were r and omly assigned to one of three independent groups , and subsequently performed the Cognitive Drug Research ( CDR ) computerized cognitive assessment battery in a cubicle containing either one of the two odors or no odor ( control ) . Visual analogue mood question naires were completed prior to exposure to the odor , and subsequently after completion of the test battery . The participants were deceived as to the genuine aim of the study until the completion of testing to prevent expectancy effects from possibly influencing the data . The outcome variables from the nine tasks that constitute the CDR core battery feed into six factors that represent different aspects of cognitive functioning . Analysis of performance revealed that lavender produced a significant decrement in performance of working memory , and impaired reaction times for both memory and attention based tasks compared to controls . In contrast , rosemary produced a significant enhancement of performance for overall quality of memory and secondary memory factors , but also produced an impairment of speed of memory compared to controls . With regard to mood , comparisons of the change in ratings from baseline to post-test revealed that following the completion of the cognitive assessment battery , both the control and lavender groups were significantly less alert than the rosemary condition ; however , the control group was significantly less content than both rosemary and lavender conditions . These findings indicate that the olfactory properties of these essential oils can produce objective effects on cognitive performance , as well as subjective effects on mood BACKGROUND Behavioral and psychological symptoms in dementia are frequent and are a major management problem , especially for patients with severe cognitive impairment . Preliminary reports have indicated positive effects of aromatherapy using select essential oils , but there are no adequately powered placebo-controlled trials . We conducted a placebo-controlled trial to determine the value of aromatherapy with essential oil of Melissa officinalis ( lemon balm ) for agitation in people with severe dementia . METHOD Seventy-two people residing in National Health Service ( U.K. ) care facilities who had clinical ly significant agitation in the context of severe dementia were r and omly assigned to aromatherapy with Melissa essential oil ( N = 36 ) or placebo ( sunflower oil ) ( N = 36 ) . The active treatment or placebo oil was combined with a base lotion and applied to patients ' faces and arms twice a day by caregiving staff . Changes in clinical ly significant agitation ( Cohen-Mansfield Agitation Inventory [ CMAI ] ) and quality of life indices ( percentage of time spent socially withdrawn and percentage of time engaged in constructive activities , measured with Dementia Care Mapping ) were compared between the 2 groups over a 4-week period of treatment . RESULTS Seventy-one patients completed the trial . No significant side effects were observed . Sixty percent ( 21/35 ) of the active treatment group and 14 % ( 5/36 ) of the placebo-treated group experienced a 30 % reduction of CMAI score , with an overall improvement in agitation ( mean reduction in CMAI score ) of 35 % in patients receiving Melissa balm essential oil and 11 % in those treated with placebo ( Mann-Whitney U test ; Z = 4.1 , p < .0001 ) . Quality of life indices also improved significantly more in people receiving essential balm oil ( Mann-Whitney U test ; percentage of time spent socially withdrawn : Z = 2.6 , p = .005 ; percentage of time engaged in constructive activities : Z = 3.5 , p = .001 ) . CONCLUSION The finding that aromatherapy with essential balm oil is a safe and effective treatment for clinical ly significant agitation in people with severe dementia , with additional benefits for key quality of life parameters , indicates the need for further controlled trials OBJECTIVE To determine the effectiveness of a brief agitation rating scale ( BARS ) derived from the Cohen-Mansfield Agitation Inventory ( CMAI ) . DESIGN Test of reliability and validity of a new test . SETTING The Lieberman Geriatric Health Centre , a skilled nursing facility . PARTICIPANTS Forty members of the Lieberman Geriatric Health Centre nursing staff , 232 residents , and a sample of 40 r and omly selected residents . MEASUREMENTS Observational agitation ratings by registered nurses and certified nurses ' assistants ; item to total correlations for the CMAI on each of the three shifts ; Pearson correlations between the 10-item BARS and the BEHAVE-AD and the BSSAD scales . RESULTS Internal consistency reliability for the BARS was .74 ( for the day shift ) , .82 ( evening shift ) , and .80 ( night shift ) , compared with .86 , .91 , and .87 for the full CMAI . Each of the 232 residents ' scores on the BARS was correlated with a total score from the CMAI separately on each shift . Correlations were of .95 , .94 , and .95 . Thus , across all shifts , the BARS accounted for approximately 90 percent of the variance of the total score of the CMAI . Concurrent validity of the BARS was supported by significant correlation with BEHAVE-AD and BSSD . CONCLUSIONS The BARS represents a brief and effective mechanism to assess the presence and severity of physically aggressive , physically non-aggressive , and verbally agitated behaviors in elderly nursing home residents Aromatherapy and massage could provide a useful addition to psychological therapeutic interventions with clients suffering from dementia . The effects of aromatherapy and massage on disturbed behaviour in four individuals with severe dementia were evaluated using a single-case research design . Each participant received 10 treatment sessions of aromatherapy , aromatherapy and massage combined , and massage alone . The effects on each individual 's behaviour in the hour following treatment were assessed against 10 ' no treatment ' control sessions . Reliable individualized disturbed behaviour scales were design ed . The effects of the treatments were mixed . The opinion of the staff providing treatment was that all participants benefited . On close scrutiny , only one of the participants benefited from the aromatherapy and massage to a degree that reached statistical significance . In two of the cases aromatherapy and massage led to an increase in agitated behaviour . The importance of the single case study approach with this client group is discussed Accurate clinical staging of dementia in older subjects has not previously been achieved despite the use of such methods as psychometric testing , behavioural rating , and various combinations of simpler psychometric and behavioural evaluations . The Clinical Dementia Rating ( CRD ) , a global rating device , was developed for a prospect i ve study of mild senile dementia -- Alzheimer type ( SDAT ) . Reliability , validity , and correlational data are discussed . The CRD was found to distinguish unambiguously among older subjects with a wide range of cognitive function , from healthy to severely impaired A r and om controlled trial of the relaxing effects of an aromatherapy massage on disordered behaviour in dementia was conducted . Twenty‐one patients were r and omly allocated into one of three conditions , aromatherapy and massage ( AM ) , conversation and aromatherapy ( CA ) and massage only ( M ) . AM showed the greatest reduction in the frequency of excessive motor behaviour of all three conditions . This reached statistical significance between the hours of three and four pm ( p < 0.05 ) . Post hoc analysis suggested that at this time of day the AM consistently reduced motor behaviour when compared with CA ( p = 0.05 ) . This provides preliminary evidence of a measurable sedative effect of aromatherapy massage on dementia within a robust scientific paradigm . Further research is recommended with an exp and ed sample size . Copyright © 2001 John Wiley & Sons , Thirteen older persons ( seven men and six women ) in residential care participated as subjects in this study . All participants had histories of confusion due to dementia and were identified by staff as being consistently resistant to medication administration as indicated by vocal outbursts , moving away , or physical combativeness . Subjects were exposed to four aroma interventions during medication administration : 1 ) lavender vera ( lavendula officinalis ) ; 2 ) sweet orange ( citrus aurantium ) ; 3 ) tea tree ( malaleuca alternifolia ) ; and 4 ) no aroma ( control ) . All medication administrations were videotaped for later data collection . Observers were trained to record frequency and duration of resistive behaviors during medication administration in all four interventions for each subject . Reliability between two observers was extremely high . Results showed no statistically significant differences across all aroma conditions for either resistive behavior or duration of administration . Also , there were no statistically significant differences based on gender . This study indicates that aromatherapy does not reduce combative , resistive behaviors in individuals with dementia . Research with a larger sample in future studies may yield other results |
10,449 | 12,917,945 | The choice of epidural agents may also influence the extent to which epidural analgesia differs from systemic analgesia .
REVIEW ER 'S CONCLUSIONS Epidural analgesia may be useful for postoperative pain relief following major lower limb joint replacements .
However , the benefits may be limited to the early ( four to six hours ) postoperative period .
An epidural infusion of local anesthetic or local anesthetic-narcotic mixture may be better than epidural narcotic alone .
The current evidence is insufficient to draw conclusions on the frequency of rare complications from epidural analgesia , postoperative morbidity or mortality , functional outcomes , or length of hospital stay | BACKGROUND Hip and knee replacement are common operative procedures to improve mobility and quality of life .
Adequate pain relief is essential in the postoperative period to enable ambulation and initiation of physiotherapy .
Lumbar epidural analgesia is a common modality for pain relief following these procedures .
However , there is no systematic review of the evidence comparing the efficacy of epidural analgesia with other postoperative analgesic modalities .
As the use of epidural analgesia may delay the initiation of anticoagulant thromboprophylaxis due to the potential risk of epidural hematoma , a synthesis of the evidence is necessary to determine whether or not alternative analgesic modalities are worse , equivalent , or better than epidural analgesia .
OBJECTIVES Our objective is to answer the question : " Is lumbar epidural analgesia more efficacious than systemic analgesia or long-acting spinal analgesia for postoperative pain relief in patients after elective hip or knee replacement ? " | Tissue damage during surgery induces coagulation factors and activates platelets . Surgical pain may provoke release of catecholamines , leading to hypercoagulability . We have investigated the effect of surgical pain on blood coagulability and fibrinolysis in orthopaedic operations using tourniquets in 22 patients undergoing total knee replacement . Patients were allocated to one of two groups to receive extradural anaesthesia ( EA ; n = 11 ) or general anaesthesia ( GA ; n = 11 ) . The EA group received lumbar extradural block with lidocaine . The GA group received only general anaesthesia , maintained with 1.5 - 2.5 % sevoflurane and 66 % nitrous oxide in oxygen . Using a thrombelastogram technique , blood coagulability and fibrinolysis were measured . Mean maximum amplitude ( MA ) , which reflects coagulability , increased after tourniquet inflation ( 11 % ) in group GA whereas MA in group EA did not change . After tourniquet deflation , MA values in both GA and EA groups increased significantly ( 10 % and 20 % , respectively ) ( P < 0.05 ) , and there was also a significant difference in MA between groups ( P < 0.05 ) . The fibrinolytic rate did not change in either group during tourniquet inflation , but increased significantly ( 160 % ) after tourniquet deflation . There was no significant difference in fibrinolytic rate between the groups . We conclude that the hypercoagulability seen in group GA could have been caused by surgical or tourniquet pain , or both , and that extradural anaesthesia is a useful technique to prevent hypercoagulability This study compared the effects of general and regional anesthesia on cognitive and psychosocial functioning in elderly persons . Sixty-four patients between 60 and 86 yr of age undergoing knee arthroplasty were r and omly assigned to receive either general or regional anesthesia . A battery of psychometric tests , including the Satz-Mogel form of the Wechsler Adult Intelligence Scale-Revised , the Wechsler Memory Scale-Revised and the Sickness Impact Profile , and various neuropsychological measures were administered by a blinded observer just before surgery and again 3 months later . Analyses of covariance revealed improvements in most measures that were equivalent between groups . The results indicated that there were no cognitive or psychosocial effects of general or regional anesthesia after 3 months in elderly persons undergoing knee arthroplasty . In this patient population , general anesthesia poses no more risk to long-term mental function than regional anesthesia We have studied the effect of extradural analgesia on postoperative venous thrombosis in patients undergoing knee arthroplasty . Forty-eight patients were allocated r and omly to receive either general anaesthesia or extradural analgesia with local anaesthetics for 3 days . All patients wore compressive elastic stockings and no anticoagulant drugs were administered . Bilateral venography was performed 10 days after surgery . Continuous extradural analgesia did not impede mobilization of the patients . One case of nonfatal pulmonary embolism occurred in a patient who received general anaesthesia . The use of continuous extradural analgesia result ed in a significant difference in the total incidence of deep vein thrombosis ( 18 % compared with 59 % after general anaesthesia ( P = 0.02 ] . The incidence of calf vein thrombosis was 12 % compared with 45 % after general anaesthesia ( P = 0.05 ) Seventy-two patients were r and omized into a prospect i ve clinical trial to evaluate the effects of epidural ( EA ) versus general anesthesia ( GA ) on the incidence of thromboembolic disease ( TED ) following total knee arthroplasty ( TKA ) . Males received aspirin 650 mg po bid and females low-dose warfarin daily to maintain the prothrombin time at 15 to 16 seconds for pharmacologic prophylaxis against TED . Thirty-four patients had EA and 38 GA for their primary TKA . Contrast venography and ventilation-perfusion scanning were performed on the sixth , seventh , and eighth postoperative days , and these were interpreted in a blinded fashion . The mean age of the 45 males and 27 females was 64 years ( range , 42 - 84 years ) . There were no significant differences between the two groups with respect to hematocrit , operative time , blood loss , number of units transfused , or hospital stay . Twelve of the 34 patients ( 35 % ) receiving an EA and 10 of the 38 patients ( 26 % ) receiving GA developed TED , an overall incidence of 31 % ( p greater than 0.05 ) Fifty-three percent of the clots were located in the popliteal vein above the trifurcation or more proximal . However , the incidence of proximal vein thrombosis was significantly less in patients receiving an EA ( 46 % ) rather than a GA ( 64 % ) . The incidence and distribution of clots was not affected by the type of pharmacologic prophylaxis , gender , or use of methylmethacrylate . Ten percent of the patients had a positive scan by strict criteria and were thought to have a pulmonary embolism ( PE ) . In patients with a femoral vein clot , the incidence of PE was 67 % . One bleeding complication occurred in a patient who took double the appropriate warfarin dose . ( ABSTRACT TRUNCATED AT 250 WORDS Background Mood states during epidural opioids are not known . The authors studied the change in mood during the 48‐h period of epidural morphine and epidural fentanyl in 47 patients after elective hip or knee joint arthroplasty . Methods An epidural catheter was inserted at the L2‐L3 or L3‐L4 interspace . Anesthesia was induced with thiopenthal and maintained with isoflurane and nitrous oxide . One hour before the conclusion of the operation , patients received an epidural bolus injection of 2 mg morphine ( n = 23 ) or 100 micro gram fentanyl ( n = 24 ) , followed by the same opiate ( 125 micro gram/ml morphine or 25 micro gram/ml fentanyl ) epidurally delivered by a patient‐controlled analgesia ( PCA ) pump in the postoperative period for 48 h. Mood was assessed using the bipolar form of the Profile of Mood States before operation and 24 h , 48 h , and 72 h after operation . Results There was no significant difference in pain intensity between the groups during epidural PCA . Mood states became more positive over time in the patients who received morphine ( P < 0.01 at 48 h ) and negative in those who were given fentanyl ( P < 0.01 at 24 and 48 h , respectively ) compared with those before the operation , and they were more positive in the morphine than in the fentanyl group at 24 h , 48 h ( P < 0.05 ) , and 72 h ( P < 0.01 ) . Patients in the morphine group were more composed , agreeable , elated , confident , energetic , and clearheaded than were those in the fentanyl group ( P < 0.05 ) . There was no correlation between mood scores and pain scores in either group . There was an inverse correlation at 48 h between mood scores and plasma fentanyl concentrations ( r = ‐0.58 , P < 0.05 ) . Conclusion Mood states are significantly more positive during epidural morphine PCA than they are during epidural fentanyl PCA Background : Both epidural analgesia and intravenous patient‐controlled analgesia ( PCA ) have been found efficacious after various types of surgery . We compared the efficacy , safety , side effects and patient satisfaction of these methods in a r and omized double‐blind fashion after elective anterior cruciate ligament reconstruction of the knee The purpose of this study was to determine if intra-articular injection of morphine or bupivacaine significantly decreased postoperative pain as well as the use of intravenous narcotics for pain relief in patients undergoing total knee arthroplasty ( TKA ) . In a prospect i ve , double-blind , r and omized fashion , 105 patients undergoing TKA were divided into the following 4 groups defined by the intra-articular injection they received : group 1 ( n = 27 ) received saline solution , group 2 ( n = 26 ) received morphine sulfate ( 5 mg ) , group 3 ( n = 24 ) received bupivacaine ( 50 mg ) , and group 4 ( n = 28 ) received a combination of morphine sulfate and bupivacaine . The injections were administered immediately after wound closure by the Hemovac drainage tubing that remained clamped for 45 minutes after surgery to allow for absorption . Before surgery and at 2 , 4 , 6 , 24 , and 48 hours after surgery , pain intensity was recorded using a visual analog scale . Postoperative supplemental intravenous morphine and /or meperidine was administered via a patient-controlled analgesia device , and 24-hour drug usage was tabulated . Results were suggestive of a modest short-term reduction in pain scores in the morphine and bupivacaine treatment groups compared with placebo ( saline ) ; however , results were statistically significant only at 4 hours because of the great variability in the pain score data . The total amount of postoperative pain medication used in the first 24 hours after surgery was not statistically significant between the 4 treatment groups . Thus , the results put into question the benefit of postoperative intra-articular administration of morphine or bupivacaine in patients undergoing TKA Postoperative analgesia after two extradural tramadol regimens was compared with that obtained using a st and ard extradural morphine regimen in patients undergoing total knee replacement . Extradural anaesthesia with light general anaesthesia was used . Patients received extradurally either : tramadol 50 mg by bolus injection followed by infusion ( 5mg.h‐1 for 12 h and 2.5mg.h‐1 for a further 12 h ) ( group T50 ) , tramadol 100 mg by bolus injection followed by infusion ( 10 mg.h‐1 for 12 h and 5mg.h‐1 for a further 12 h ) ( group T100 ) or morphine sulphate 2 mg by bolus injection followed by infusion ( 0.2 mg.h‐1 for 12 h and at 0.1 mg.h‐1 for a further 12 h ) ( group M ) . Analgesia was allocated according to a controlled double‐blind design . Visual analogue pain scores were markedly poorer ( p < 0.05 ) and patient‐controlled analgesic consumption was significantly greater ( p < 0.01 ) in the two tramadol groups when compared with the morphine group . The study was discontinued after recruitment of 12 patients , as analgesia was deemed inadequate in those receiving tramadol extradurally . However , further study of this drug may be warranted to examine its effectiveness where postoperative pain is expected to be less severe , and to assess the effect of larger extradural doses and of co‐administration of tramadol and morphine by this route OBJECTIVE --To evaluate the efficacy and safety of two subcutaneous prophylactic regimens for postoperative deep vein thrombosis after total hip replacement . DESIGN -- Prospect i ve open r and omised multicentre trial . SETTING --28 European departments of orthopaedic surgery . INTERVENTION -- All patients had bilateral phlebography 10 days after surgery . 31 patients receiving low molecular weight heparin and 29 receiving unfractionated heparin were excluded from the efficacy analysis for various reasons . PATIENTS --349 patients undergoing total hip replacement between September 1988 and May 1989 . 174 patients received subcutaneously a low molecular weight heparin ( Fraxiparine ) with anti-factor Xa activity of 41 IU/kg/day for three days , then 62 IU/kg/day from day 4 to day 10 . 175 patients received subcutaneous unfractionated heparin at intervals of eight hours ; doses were adjusted to maintain the activated thromboplastin time at two to five seconds above control values . MAIN OUTCOME MEASURE -- Total incidence of deep vein thrombosis and incidence of proximal deep vein thrombosis on bilateral phlebography . RESULTS --The total incidence of deep vein thrombosis was 16 % in patients receiving unfractionated heparin and 12.6 % in patients receiving low molecular weight heparin ( p = 0.45 ) , and the incidence of thrombosis of the proximal veins was 13.1 % and 2.9 % respectively ( p less than 0.001 ) . Four patients receiving unfractionated heparin and one receiving low molecular weight heparin developed pulmonary embolism . The incidence of bleeding complications was low and comparable in the two groups . CONCLUSION --Low molecular weight heparin is at least as effective as unfractionated heparin in preventing deep vein thrombosis and is more effective at preventing thrombosis of the proximal veins in patients undergoing hip replacement . Low molecular weight heparin is not more likely to cause bleeding complications and is simpler to give than unfractionated heparin This prospect i ve , r and omized , double-blind trial evaluated the efficacy of rectal indomethacin as an adjunct to morphine for controlling postoperative pain . Fifty healthy patients undergoing elective hip arthroplasty were investigated . Group 1 ( n = 25 ) received placebo suppositories . Group 2 ( n = 25 ) received indomethacin suppositories , 100 mg q8hr for five doses , starting at the end of the procedure . Both groups received morphine via a PCA pump , which recorded the amount of morphine delivered each hour . After a st and ardized general anaesthetic , PCA was begun in the recovery room . Pain was measured with a st and ard 100 mm VAS at 2 , 6 , 20 , 28 , 42 hr after surgery and the morphine consumption recorded . Over the 42-hr study period , patients in Group 2 required less morphine than those in Group 1 ( 34.8 ± 21.8 mg vs 89.6 ± 43.7 , P < 0.01 ) . Pain scores were lower in Group 2 at 20 , 28 , 42 hr postoperatively . The incidence of side-effects did not differ between groups and no patient had excessive postoperative bleeding . The combination of indomethacin and morphine provided superior pain relief to morphine alone even though the control group had liberal access to morphine . This synergistic effect would make indomethacin a useful adjunct to intramuscular or epidural narcotics . RésuméCette étude prospect i ve r and omisée et à double insu a évalué l’efficacité de l’indométhacine par voie rectale comme adjuvant à la morphine pour contrôler la douleur postopératoire . Cinquante patients en bonne samé devant subir une arthroplastie de la hanche élective furent investigués . Le Groupe 1 ( n = 25 ) a reçu des suppositoires de placebo le Groupe ( n = 25 ) a reçu des suppositoires d’indométhacine , 100 mg q8hre pour cinq doses debutant à la fin de la procédure . Les deux groupes ont reçu de la morphine à travers une pompe PCA qui a enregistre la quantité de morphine délivrée à chaque heure . Après st and ardisation de l’anesthésie générate , le PCA fut commencé en salle de réveil . La douleur fut mesurée avec un VAS st and ard 100 mm en 2 , 6 , 20 , 28 , 42 heures après la chirurgie et la consommation générate de morphine fut enregistrée . Pour une période d’étude de 42 heures , les patients du Groupe 2 ont requis moins de morphine que ceux du Groupe 1 ( 34.8 ± 21.8 mg vs 89.6 ± 43,7 , P < 0.01 ) . Les échelles de douleur étaient plus basses dans le Groupe 2 avant 20 , 28 , 42 heures après la chirurgie . L’incidence des effets secondaires n’était pas différente entre les deux groupes et aucun patient n’a demontré de saignement postoperatoire excessif . La combinaison de l’indométhacine et de la morphine a fourni un soulagement de la douleur supérieur à la morphine seule même si le groupe contrôle avait accès d’une manière libérate à la morphine . Les effets sénergétiques pourraient rendre à l’indométhacine une addition utile aux narcotiques intramusculaires ou une injection épidurale Extradural anaesthesia is associated with lower incidences of deep vein thrombosis after total knee arthroplasty . It is not known if the type of anaesthesia influences thrombogenesis or fibrinolysis during knee surgery performed under tourniquet . We studied 31 patients allocated r and omly to receive either extradural or general anaesthesia for primary unilateral total knee arthroplasty performed under tourniquet . Radial artery blood sample s were obtained before surgery , during surgery with the tourniquet inflated and on deflation of the tourniquet . Plasma sample s were assayed for markers of thrombin generation and fibrinolysis . Two of the circulating indices of thrombin generation , fibrinopeptide A and thrombin-antithrombin complexes , increased to a similar degree in the perioperative period in both groups . Fibrinolytic activity was similar in both groups , as measured by tissue plasminogen activator ( t-PA ) antigen , t-PA activity , t-PA-plasminogen activator inhibitor complexes , alpha 2-plasmin inhibitor-plasmin complexes and D-dimer . Extradural and general anaesthesia did not result in significant differences in either thrombin generation or fibrinolytic activity during total knee arthroplasty performed under tourniquet BACKGROUND Intrathecal neostigmine produces analgesia in volunteers and patients . However , the use of epidural neostigmine has not been investigated . The purpose of the current study was to define the analgesic effectiveness of epidural neostigmine coadministered with lidocaine and side effects in patients after minor orthopedic procedures . METHODS After Institutional Review Board approval and informed consent , 48 patients ( n = 12 ) undergoing knee surgery were r and omly allocated to one of four groups and studied in a prospect i ve way . After 0.05 - 0.1 mg/kg intravenous midazolam premedication , patients were r and omized to receive 20 mg intrathecal bupivacaine plus epidural lidocaine ( 85 mg ) with saline ( control group ) ; 1 microg/kg epidural neostigmine ( 1 microg group ) ; 2 microg/kg epidural neostigmine ( 2 microg group ) ; or 4 microg/kg epidural neostigmine ( 4 microg group ) . The concept of the visual analog scale , which consisted of a 10-cm line with 0 equaling " no pain at all " and 10 equaling " the worst possible pain " was introduced . Postoperatively , pain was assessed using the visual analog scale , and intramuscular 75 mg diclofenac was available at patient request . RESULTS Groups were demographically the same and did not differ in intraoperative characteristics ( blood pressure , heart rate , ephedrine consumption , oxyhemoglobin saturation , sensory loss before start of surgery , or duration of sensory motor block ) . The visual analog scale score at first rescue analgesic and the incidence of adverse effects were similar among groups ( P > 0.05 ) . The time ( min + /- SD ) to first rescue analgesic was as follows : control group : 205+/-48 ; 1-microg group : 529+/-314 ; 2-microg group : 504+/-284 ; 4-microg group : 547+/-263 ( P < 0.05 ) . The analgesic consumption ( number of intramuscular diclofenac injections [ mean , 25th-75th percentile ] ) in 24 h was as follows : control group : 3 [ 3 or 4 ] ; 1-microg group : 1 [ 1 or 2 ] ; 2-microg group : 2 [ 1 or 2 ] ; 4-microg group : 2 [ 1 - 3 ] ( P < 0.05 ) . The 24-h-pain visual analog scale score ( cm + /- SD ) that represents the overall impression for the last 24 h was as follows : control group : 5+/-1.6 ; 1-microg group : 1.6+/-1.8 ; 2-microg group : 1.4+/-1.6 ; 4-microg group : 2.2+/-1.9 ( P < 0.005 ) . The incidence of adverse effects was similar among groups ( P > 0.05 ) . CONCLUSION Epidural neostigmine ( 1 , 2 , or 4 microg/kg ) in lidocaine produced a dose-independent analgesic effect ( approximately 8 h ) compared to the control group ( approximately 3.5 h ) , and a reduction in postoperative rescue analgesic consumption without increasing the incidence of adverse effects OBJECTIVE To evaluate both effectiveness and incidence of side effects of two techniques of postoperative pain treatment : intravenous and epidural PCA . DESIGN Prospect i ve analysis of data from two groups of r and omized patients . SETTING S Orthopedic and trauma center . PATIENTS Figty ASA class II-III patients undergoing total hip replacement under combined Spinal-Epidural Anesthesia . METHODS Patients were divided into 2 groups who received different postoperative pain treatment . One group ( group PCA ) received a patient-controlled intravenous analgesia with morphine 30 mg and ketorolac 90 mg in 100 ml of saline ( back-ground infusion 2 - 4 ml , according to body weith , bolus 1 ml , lockout 5 min , 4 h dose limit 40 ml ) . PCEA group received a patient-controlled epidural analgesia with morphine 4 mg and bupivacaine 0.125 % 100 ml , ( background infusion 3 - 4 ml , according to patient ' height , bolus 1 ml , lockout 10 min , 4 h dose limit 25 ml ) . Postoperative pain intensity was evaluated , through 24 postoperative hours , by a verbal analogue scale ( VPS = 0 to 3 ) and a total pain score ( TOTPAR ) was calculated for each patient at 6 and 24 postoperative hours . Side effects were recorded and their incidence was obtained for each group . Statistical data analysis was performed by one-way ANOVA and non-parametric tests for ordinal data . Nominal data were analyzed by chi 2 test . p < 0.05 was considered significant . RESULTS Patient receiving PCEA showed a significant ( p < 0.005 ) decrease of incident pain , while VPS at rest was similar in the two groups . TOTPAR VPS was lower ( p < 0.05 ) in PCEA group both at 6 and 24 postoperative hours . Somnolence was observed more often in PCA patients ( 8 % vs 2 % ; p 0.05 ) , while no significant differences were noted among other side effects incidence . CONCLUSIONS Our data show a better control of postoperative pain arising from total hip replacement during PCEA when compared to PCA . It should be emphasized that incident pain is far more decreased by PCEA , so that this technique is particularly indicated when an early postoperative mobilization is required We have compared 0.5 % bupivacaine 75 mg ( group A ; n = 15 ) with three 0.5 % bupivacaine 75 mg-ketamine mixtures for extradural block in 59 ASA I-III patients undergoing total knee replacement in a r and omized , double-blind study . The following doses of preservative-free 1 % ketamine were used : 0.3 mg kg-1 ( group B : n = 14 ) ; 0.5 mg kg-1 ( group C : n = 5 ) ; and 0.67 mg kg-1 ( group D : n = 15 ) . Level of sensory block , degree of motor weakness and sedation scores were recorded before and after operation . Duration of postoperative analgesia was also noted . There was no difference between groups in median maximum level of sensory block ( group A : T4 ( range T10-T2 ) ; group B : T4 ( T10-T2 ) ; group C : T4 ( T8-T2 ) ; and group D : T3 ( T8-C3 ) ) or in the degree of motor block . Thirty-three of the 44 patients who received ketamine showed signs of systemic absorption ( blurred vision , sedation ) within 10 min of injection . There was no significant difference between groups in median duration of analgesia ( group A : 240 ( range 115 - 340 ) min ; group B : 198 ( 97 - 460 ) min ; group C : 150 ( 122 - 448 ) min ; and group D : 210 ( 130 - 390 ) min ) . No patient suffered any adverse psychomimetic effects . We conclude that at the doses used , addition of ketamine to extradural bupivacaine did not improve extradural block in adult patients undergoing total knee replacement BACKGROUND Continuous passive motion after major knee surgery optimizes the functional prognosis but causes severe pain . The authors tested the hypothesis that postoperative analgesic techniques influence surgical outcome and the duration of convalescence . METHODS Before st and ardized general anesthesia , 56 adult scheduled for major knee surgery were r and omly assigned to one of three groups , each to receive a different postoperative analgesic technique for 72 h : continuous epidural infusion , continuous femoral block , or intravenous patient-controlled morphine ( dose , 1 mg ; lockout interval , 7 min ; maximum dose , 30 mg/4 h ) . The first two techniques were performed using a solution of 1 % lidocaine , 0.03 mg/ml morphine , and 2 microg/ml clonidine administered at 0.1 ml x kg(-1 ) x h(-1 ) . Pain was assessed at rest and during continuous passive motion using a visual analog scale . The early postoperative maximal amplitude of knee flexion was measured during continuous passive motion at 24 h and 48 h and compared with the target levels prescribed by the surgeon . To evaluate functional outcome , the maximal amplitudes were measured again on postoperative day 5 , at hospital discharge ( day 7 ) , and at 1- and 3-month follow-up examinations . When the patients left the surgical ward , they were admitted to a rehabilitation center , where their length of stay depended on prospect ively determined discharge criteria RESULTS The continuous epidural infusion and continuous femoral block groups showed significantly lower visual analog scale scores at rest and during continuous passive motion compared with the patient-controlled morphine group . The early postoperative knee mobilization levels in both continuous epidural infusion and continuous femoral block groups were significantly closer to the target levels prescribed by the surgeon than in the patient-controlled morphine group . On postoperative day 7 , these values were 90 degrees ( 60 - 100 degrees)(median and 25th-75th percentiles ) in the continuous epidural infusion group , 90 degrees ( 60 - 100 degrees ) in the continuous femoral block group , and 80 degrees ( 60 - 100 degrees ) in the patient-controlled morphine group ( P < 0.05 ) . The duration s of stay in the rehabilitation center were significantly shorter : 37 days ( range , 30 - 45 days ) in the continuous epidural infusion group , 40 days ( range , 31 - 60 days ) in the continuous femoral block group , and 50 days ( range , 30 - 80 days ) in the patient-controlled morphine group ( P < 0.05 ) . Side effects were encountered more frequently in the continuous epidural infusion group . CONCLUSION Regional analgesic techniques improve early rehabilitation after major knee surgery by effectively controlling pain during continuous passive motion , thereby hastening convalescence We have examined the effect of prophylactic treatment with i.v . fluid 1000 ml , ephedrine 24 mg or methoxamine 4 mg on cardiovascular responses to both extradural and combined extradural and general isoflurane anaesthesia in 45 adult patients undergoing knee arthroplasty . Heart rate ( HR ) and systemic arterial pressure ( AP ) were measured using automated oscillotonometry and cardiac output was measured using continuous wave suprasternal Doppler ultrasonography . After lumbar extradural anaesthesia ( LEA ) there were no significant differences in arterial pressure between treatments , although cardiac index was significantly greater after fluid preloading ( mean 4.3 ( 95 % confidence interval 3.7 - 4.9 ) litre min-1 m-2 ) than after ephedrine ( 3.1 ( 2.6 - 3.6 ) litre min-1 m-2 ) or methoxamine ( 2.6 ( 2.0 - 3.2 ) litre min-1 m-2 ) . During combined LEA and general anaesthesia , systolic AP was significantly greater after ephedrine ( 114 ( 103 - 125 ) mm Hg ) than after either preloading ( 98 ( 88 - 107 ) mm Hg ) or methoxamine ( 97 ( 89 - 105 ) mm Hg ) . The reduction in AP after induction of general anaesthesia was associated with a decrease in cardiac index after fluid preloading and a decrease in vascular resistance after methoxamine Evidence of pre‐emptive analgetic effect of opioid would offer great potential benefit to patients with postoperative pain , a better pain relief with less opioid . The aim of this double blind r and omised trial was to study the effect of intramuscular morphine premedication on postoperative pain We have examined the effectiveness of extradural clonidine infusions for postoperative analgesia and the effect of clonidine on extradural morphine . In a double-blind , controlled study , patients , undergoing total hip replacement were allocated r and omly to receive one of two doses of extradural clonidine ( 25 micrograms h-1 or 50 micrograms h-1 ) , low dose extradural morphine or a combination of morphine and clonidine . Pain scores in the morphine group were significantly greater than in the clonidine groups ( P less than 0.01 ) and the combination group ( P less than 0.05 ) during the first 1 h after surgery . The requirements for systemic analgesia were least in the combination and larger dose clonidine group , and the duration of effect of the initial bolus dose was significantly longer compared with the morphine and low dose clonidine groups ( P less than 0.05 ) . Arterial pressure was reduced in the clonidine groups , although the incidence of clinical hypotension was low . There were no significant differences between the groups in emetic symptoms or urinary retention UNLABELLED Levobupivacaine , the isolated S(- ) isomer of bupivacaine , is less cardiotoxic than racemic bupivacaine in animal studies . We studied the effectiveness of patient-controlled epidural analgesia ( PCEA ) with either levobupivacaine 0.125 % or fentanyl 4 microg/mL alone , or a combination of levobupivacaine and fentanyl in 65 patients after total joint arthroplasty in a prospect i ve , r and om , double-blinded fashion . Intraoperatively , all patients received 20 mL of 0.75 % levobupivacaine . Study medication was infused at an initial rate of 4 mL/h , with additional medication available on patient dem and ( 2 mL/10 min ) . The combination of levobupivacaine and fentanyl produced better analgesia ( longer time to first PCEA request ; P = 0.007 combination versus fentanyl and P = 0.006 combination versus levobupivacaine ) than either drug alone . Patients in the levobupivacaine groups had appreciable sensory blockade to pinprick with minimal motor impairment . Resting and dynamic visual analog scale pain scores were lower in the combination group than in the plain fentanyl group at 6 ( P = 0.022 and 0.036 ) and 12 h ( P = 0.002 and 0.001 ) . The 24-h overall patient- and investigator-rated visual analog scale pain scores were also lower in the combination group ( resting P = 0.007 , dynamic P = 0.005 ) . There was no significant difference among the groups in the incidence of postoperative nausea ( 26.2 % ) , pruritus ( 9.2 % ) , hypotension ( 23.1 % ) , or sedation ( 0 % ) . We conclude that the analgesic effects of levobupivacaine 0.125 % and fentanyl ( 4 microg/mL ) are additive and beneficial for the management of orthopedic surgical pain by the PCEA method . Patients in this study began dem and -dosing later , reported lower pain scores , and had no greater risk of adverse events than those who were given either levobupivacaine or fentanyl alone . IMPLICATION S We demonstrated a significant additive effect of the combination of levobupivacaine ( 0.125 % ) and fentanyl ( 4 microg/mL ) , compared with either drug alone , when using patient-controlled epidural analgesia in patients after total joint arthroplasty Epidural analgesia with local anaesthetic minimizes the catabolic response to surgery . To determine whether this could enhance the rate of recovery following orthopaedic surgery , 51 patients undergoing bilateral one-stage total knee arthroplasty were allocated to receive infusions of either continuous epidural bupivacaine/fentanyl or continuous intravenous fentanyl to compare the efficacy of these modes of pain relief on postoperative clinical outcomes and rates of rehabilitation . Infusions were maintained for 36 to 48 hours in a post-anaesthesia care unit ( PACU ) . Postoperatively , pain relief ( visual analogue scale ) , attainment of physical therapy goals and cardiopulmonary complications were measured daily for 7 days . Epidural analgesia with a combination of bupivacaine and fentanyl did not result in any measurable improvement in rehabilitation milestones or reduction in postoperative complications following bilateral total knee arthroplasty than with fentanyl infusions alone OBJECTIVE To compare the effect of post-operative analgesia using epidural versus intravenous infusions on the incidence of delirium after bilateral knee replacement surgery in elderly patients . Additional risk factors and impact on post-operative recovery were also assessed . DESIGN Prospect i ve r and omized controlled trial . SETTING Urban referral hospital specializing in elective orthopedic surgery . PATIENTS 60 consecutive patients undergoing bilateral knee replacement surgery with epidural anesthesia were approached ; 51 patients were eligible and consented . The mean age was 68 , 55 % were women , and there was a high prevalence of comorbid medical disease . No patient was demented pre-operatively . INTERVENTION R and om allocation to either continuous epidural infusion of bupivacaine and fentanyl or continuous intravenous infusion of fentanyl . Infusions were initiated at the first complaint of pain and continued through the 36- to 48-hour stay in the recovery room . MAIN OUTCOME MEASURE Acute post-operative delirium defined using an algorithm based on DSM III criteria . RESULTS The overall incidence of acute delirium was 41 % , with no difference between types of post-operative analgesia . Predictors of delirium were age , gender , and pre-operative alcohol use . All cases resolved within 1 week , and length of stay and achievement of physical therapy goals were the same for delirious and non-delirious patients . CONCLUSIONS There is a high incidence of post-operative delirium in elderly non-demented patients following bilateral knee replacement , regardless of whether post-operative analgesia is administered by the epidural or intravenous route Background : Tramadol is an analgesic with combined opioid agonist and monoamine reuptake blocker properties , which may be useful as a perioperative analgesic and antinociceptive adjuvant Both continuous spinal anaesthesia and continuous epidural anaesthesia are supposed to provide adequate post-operative pain relief . The purpose of this r and omized , prospect i ve study was to compare the quality of analgesia , occurrence of side effects and patient satisfaction between spinal and epidural administration of bupivacaine during the first post-operative 72 h. One hundred and two patients scheduled for hip arthroplasty were r and omly assigned to one of two groups : Group 1 received continuous spinal anaesthesia for intra-operative and post-operative management , Group 2 received continuous epidural anaesthesia . Immediately after surgery , the continuous spinal anaesthesia-group received a 1-mL bolus ( bupivacaine 0.25 % ) , followed by a continuous infusion of 10 mL over 24 h. The continuous epidural anaesthesia-group received a 10-mL bolus ( bupivacaine 0.25 % ) , followed by 2 mL h-1 . The level of pain was gauged from a verbal rating score and from a visual analogue scale ; the degree of motor blockade was recorded using the Bromage score . In the continuous spinal anaesthesia-group 90.2 % reported complete analgesia on the verbal rating scale , but only 21.6 % of the continuous epidural anaesthesia-group did . The visual analogue scale scores given by the continuous spinal anaesthesia-group were significantly lower than those of the continuous epidural anaesthesia-group . The percentage of patients with a motor block was significantly higher in the continuous spinal anaesthesia-group on the day of surgery and at the first post-operative day . During the first 24 h , nausea and vomiting occurred more often in the continuous epidural anaesthesia-group . The satisfaction was considered excellent in 92.2 % of the continuous spinal anaesthesia-group and in 70.6 % of the continuous epidural anaesthesia-group . It is concluded that continuous spinal anaesthesia and continuous epidural anaesthesia are effective and safe for post-operative pain relief after hip replacement . Compared with continuous epidural anaesthesia , continuous spinal anaesthesia provides faster onset of pain relief , ensures better analgesia and results in more satisfied patients UNLABELLED The aim of our study was to compare epidural anesthesia and analgesia ( EDA ) with ropivacaine versus general anesthesia followed by IV patient-controlled analgesia with morphine ( GA/PCA ) after hip replacement regarding pain , side effects , and discharge from the postanesthesia care unit . After ethics committee approval , r and omization , and informed consent , 90 patients were enrolled . In Group EDA , epidural anesthesia ( ropivacaine 10 mg/mL , 15 - 25 mL ) was followed by an epidural infusion ( 2 mg/mL , 4 - 6 mL/h for 24 h , plus top-up doses of 6 - 10 mL for 48 h ) . GA/PCA patients received general anesthesia ( isoflurane/N2O/fentanyl ) followed by IV patient-controlled analgesia with morphine postoperatively . Pain was assessed by using visual analog scales ( 0 - 100 mm ) at rest and during physiotherapy . Pain at rest was less in the EDA ( n = 43 ) group than in the GA/PCA ( n = 45 ) group ( at 10 h : 11.8+/-12.9 vs. 28.4+/-17.1 [ P < 0.001 ] ; at 24 h : 14.3+/-11.7 vs. 24.0+/-17 [ P<0.01 ] ; in 48 h : 14.3+/-9.3 vs. 21.1+/-17.4 [ P = 0.1 ] ) . Whereas EDA patients were deemed ready for discharge from the postanesthesia care unit earlier than GA/PCA patients ( 5.6+/-8.9 vs. 39.7+/-41.5 min ) , the actual discharge time was comparable . The median time for first passage of flatus was shorter in the EDA group than in the GA/PCA group ( 26 vs. 47 h ) . Nausea and vomiting were more common in the GA/PCA group than in the EDA group ( 16 % vs. 28 % and 11 % vs. 22 % , respectively ) , whereas hypotension ( 11 % vs. 4 % ) and bradycardia ( 14 % vs. 2 % ) were less frequent . Under the conditions of the present study , EDA with ropivacaine provided pain control after hip replacement superior to that provided by IV patient-controlled analgesia with morphine , particularly during the first 24 h. Both approaches to pain management were equally safe . IMPLICATION S Compared with general anesthesia and postoperative IV patient-controlled analgesia with morphine , epidural anesthesia and analgesia with the new local anesthetic ropivacaine enables patients to be discharged sooner from a postanesthesia care unit and provides superior pain relief during the first 24 h after hip replacement Forty – two patients scheduled for total knee arthroplasty ( n = 20 ) or hip arthroplasty ( n = 22 ) were r and omly allocated to receive either continuous epidural bupivacaine/morphine for 48 h postoperatively plus oral piroxicam , or general anaesthesia followed by a conventional intramuscular opioid and acetaminophen regimen . Patients undergoing knee– or hip arthroplasty treated with epidural analgesia had significantly lower pain scores during mobilization under the 48 h epidural infusion compared with patients receiving conventional treatment , while no important differences were observed after cessation of the epidural regimen . However , the achieved pain relief had no impact on postoperative convalescence parameters , such as ambulation , patient activity including need for nursing care , fatigue or hospital stay . Late postoperative pain , fatigue and conservative attitudes and routines in the postoperative care , were the most important reasons limiting mobilization and activity . We conclude that effective early ( 48 h ) postoperative pain relief with balanced analgesia does not per se lead to important improvements in convalescence and hospital stay A double blind r and omized trial comparing subcutaneous enoxaparin ( 40 mg once daily ) with st and ard unfractionated calcium heparin administered at a dose of 5,000 units every 8 hours in patients undergoing elective hip replacement has been performed . Treatment regimens began 12 hours preoperatively with enoxaparin , 2 hours preoperatively with st and ard unfractionated calcium heparin , and were continued for 15 days or until discharge . Venography was performed in all patients . Two hundred thirty-seven patients were included in the study : 113 received unfractionated heparin and 124 received enoxaparin . The incidence of proximal deep vein thrombosis was reduced from 18.5 % in the unfractionated heparin group to 7.5 % in the enoxaparin group ( p = 0.014 ) , and the incidence of total deep vein thrombosis was similarly reduced from 25 % to 12.5 % ( p = 0.03 ) . There were two major bleeding episodes and one minor bleed in the enoxaparin group compared to two minor bleeds in the unfractionated heparin group . Patients who received enoxaparin required fewer red blood cell transfusions and had a significantly higher hemoglobin on postoperative days 3 and 4 . Thus prophylaxis with enoxaparin , 40 mg once daily , is simple , safe and more effective than st and ard low dose unfractionated heparin in preventing deep vein thrombosis in patients undergoing elective hip replacement Summary Twenty-one patients who had undergone total hip replacement were r and omly assigned to one of three groups in order to compare a single dose of 1 mg/kg of pethidine i m ( I ) and 20 mg ( II ) or 60 mg of extradural pethidine ( III ) in a double-blind design .The degree of analgesia , the adverse effects , and the kinetics were studied for 18 h. Pain was monitored using a visual analogue scale ( VAS ) . Supplementary doses of oxycodone if required were given no earlier than 0.75 h after pethidine . Plasma concentrations of pethidine were measured with gas chromatography mass spectrometry ( GCMS ) . Hypoalgesia to pin prick test was evaluated . Low pain scores were observed in the extradural groups between 0.25 and 1.5 h after the dose . A significant difference in pain score compared with the i m group was found after the higher extradural dose only between 0.5 and 1 h (p<0.05).The area under the curve ( AUC ) of pain score versus time ( 0–18 h ) was not significantly different between groups . The recorded adverse effects were minor in all three groups . The terminal half-lives and plasma clearances of pethidine , and the time to peak concentration were not different between the groups . Single patients in the extradural groups showed hypoalgesia to pin prick in parallel to the effect . The present study shows that extradural pethidine produces shortlived analgesia , in contrast to the long-lasting effect of morphine found in other studies The authors studied the use of epidural anesthesia prolonged to 48 hours of epidural analgesia in 120 total hip arthroplasty patients in a case-control fashion . One half of the patients received prolonged epidural anesthesia , while the other matched half received general endotracheal anesthesia . Venograms were obtained after surgery and grade d in blind fashion by a single radiologist . The overall incidence of deep venous thrombosis in the epidural versus general anesthetic groups was 23 ( 14 of 60 patients ) versus 40 % ( 24 of 60 ) ( P < .05 ) . There was an identical incidence--8.3 % ( 5 of 60 patients ) --of proximal thrombosis in the two groups , and all of the difference in the overall rates of thrombosis occurred in the calf . Fifteen percent ( 9 of 60 patients ) of the epidural patients and 31.6 % ( 19 of 60 ) of the general anesthetic patients demonstrated this finding ( P < .05 ) . Of the 10 proximal clots , 8 ( 80 % ) were found in the operative leg , while only 29 ( 59.2 % ) of the 49 calf clots were found in the operative leg . Prolonged epidural anesthesia significantly decreases the incidence of deep venous thrombosis after total hip arthroplasty , with its most apparent benefit on calf vein thrombosis secondary to its hyperkinetic effect on lower limb blood flow . The observation that it has no demonstrable effect on the prevention of proximal thrombosis and our finding that the majority of proximal clots are in the operative leg suggest that thrombi in the thigh may be the result of a different primary pathogenic mechanism that is more related to endothelial injury than to changes in viscosity or blood flow . ( ABSTRACT TRUNCATED AT 250 WORDS Background : After total knee arthroplasty , patients regularly suffer from severe pain . It is unclear whether epidural or systemic pain therapy is superior in terms of postoperative pain relief , patients ’ comfort and side effects . A new therapeutic approach , intraarticular opioids , has been suggested with the detection of opioid receptors in inflamed tissue . This method has proven suitable for clinical use in small operations ( e.g. knee arthroscopy ) . In this study , we compared epidural analgesia and intraarticular application of morphine plus “ on‐dem and ” intravenous analgesia to “ on‐dem and ” intravenous analgesia alone UNLABELLED We assessed the analgesic efficacy of postoperative epidural ropivacaine 0.1 % with and without sufentanil 1 microgram/mL in this prospect i ve , r and omized , single-blinded study of 30 ASA physical status I-III patients undergoing elective total hip replacement . Lumbar epidural block using 0.75 % ropivacaine was combined with either propofol sedation or general anesthesia for surgery . After surgery , the epidural infusion was commenced . Fifteen patients in each group received either an epidural infusion of 0.1 % ropivacaine with 1 microgram/mL sufentanil ( R + S ) or 0.1 % ropivacaine without sufentanil ( R ) at a rate of 5 - 9 mL/h . All patients had access to i.v . piritramide via a patient-controlled analgesia device . The R + S group consumed six times less piritramide over a 48-h infusion period than the R group ( median 12.7 vs 73.0 mg ; P < 0.001 ) . Motor block was negligible for the study duration in both groups . Patient satisfaction was excellent . The incidence of adverse events , such as nausea , was similar . We conclude that a continuous epidural infusion of 0.1 % ropivacaine with 1 microgram/mL sufentanil is more effective than ropivacaine alone in treating pain after elective hip replacement without motor block . IMPLICATION S This is the first r and omized study comparing the efficacy of the epidural combination of ropivacaine 0.1 % and sufentanil 1 microgram/mL versus plain ropivacaine 0.1 % in treating pain after hip replacement . We found that ropivacaine 0.1 % and sufentanil 1 microgram/mL led to a sixfold reduction in opioid requirements after total hip replacement by producing a negligible motor block In a r and omised controlled trial , epidural buprenorphine was compared with intramuscular morphine for postoperative analgesia in patients after hip surgery . Analgesia was given on dem and and consisted of epidural boluses of 60 μg of buprenorphine in 10 ml of normal saline or intramuscular morphine 0.15 mg/kg . Both forms of analgesia produced excellent pain relief as assessed by the linear analogue scoring system . In both quality and duration of pain relief , no significant difference was found between the two forms of analgesia , but the total dose of epidural buprenorphine required was Jive times less than the equivalent dose of intramuscular morphine . No side effects attributable to epidural buprenorphine administration were found . The authors conclude that low dose epidural buprenorphine provides an excellent alternative to intramuscular opiates for pain relief after hip surgery In this prospect i ve , r and omised , double-blind study , we investigated the effect of epidural anaesthesia and an antifibrinolytic agent , Aprotinin ( 500,000 KIU in bolus before surgery and 500,000 KIU h-1 in drip form during surgery ) , on intra and postoperative blood loss and transfusion requirements in total hip arthroplasty . Sixty patients were allocated r and omly to four groups ( A : epidural + general anesthesia + Aprotinin , B : epidural + general anesthesia + placebo ( equal volume ) , C : general anaesthesia + Aprotinin , D : general anaesthesia + placebo ) . Postoperative analgesia : epidural analgesia in groups A and B , systemic analgesia with opiates in groups C and D. Blood loss during surgery was monitored and salvaged with the Compact-A Dideco , and postoperative blood loss with the BT 797 Recovery Dideco for the first 24 hours . Perioperative blood loss , frequency and quantity of transfusions were significantly higher in group D ( p < 0.0001 ) . Total blood loss was reduced by 31.3 % by epidural anaesthesia , 20.4 % by Aprotinin and 51.4 % using a combination of the two techiniques OBJECTIVE The aim of the present study was to show the influence of the parameters of gas exchange ( arterial oxygen pressure paO2 , arterial oxygen saturation SatO2 ) and haemodynamics ( arterial systolic and mean blood pressure RRs and MAP ) on the restitution of cognitive functions in geriatric patients scheduled for elective hip arthroplasty . METHODS A total of 30 patients ( 70 years , ASA II ) were r and omized to be operated either in regional anaesthesia ( n = 15 ) or general anaesthesia ( n = 15 ) . PaO2 ( by capillary blood gas analysis ) , RRs and MAP ( by oscillometry ) were measured 15 and 90 minutes after arrival in the recovery unit ( t1 and t2 ) , 24 and 72 hours postoperatively ( t3 and t4 ) , and cognitive functions were tested . Intraoperatively , throughout the day and the first night after surgery we measured satO2 by continuous pulse oximetry . We recorded MAP and RRs by oscillometry every 3 minutes during the operation and every 15 minutes for the rest of that day and night . RESULTS The parameters of gas exchange and haemodynamics did not differ among the groups . PaO2 was significantly reduced in both groups compared to baseline 24 hours postoperatively ( t3 ) and remained low until 72 hours postoperatively ( t4 ) . Nearly all cognitive functions were significantly reduced in both groups compared to baseline 15 and 90 minutes after arrival in the recovery unit ( t1 and t2 ) , but recovered on the first postoperative day ( t3 ) . Both groups kept deficits in verbal memory and reading capacity up to the third postoperative day ( t4 ) . There was no correlation between the physiological parameters and the restitution of the tested cognitive functions . CONCLUSION The restitution of cognitive functions during the first three postoperative days in geriatric patients scheduled for elective hip surgery does not depend on the anaesthetic technique . According to our results regional anaesthesia does not show any advantage for geriatric patients undergoing elective hip arthroplasty OBJECTIVE To determine the relative efficacy and safety of low molecular weight ( LMW ) heparin ( Enoxaparin ) compared with st and ard calcium heparin for the prevention of postoperative deep vein thrombosis in patients undergoing elective hip surgery . DESIGN A double-blind , r and omized , controlled trial . PATIENTS Six hundred sixty-five consecutive patients undergoing hip replacement at five participating hospitals . INTERVENTIONS Patients received either fixed-dose LMW heparin , 30 mg subcutaneously twice daily , or fixed-dose st and ard calcium heparin , 7500 units subcutaneously twice daily ; both regimens were started 12 to 24 hours after surgery and continued for 14 days or until discharge if sooner . MEASUREMENTS All patients had postoperative I-125-fibrinogen leg scanning and impedance plethysmography . If results of one or both tests were positive , then venography was done . Otherwise , venography was done between day 10 and day 14 , or sooner if the patient was ready for discharge . RESULTS Evaluable venograms were obtained in 258 of the 333 patients r and omly assigned to receive LMW heparin and in 263 of the 332 patients assigned to receive calcium heparin . For patients with evaluable venograms , thrombosis was detected in 50 patients ( 19.4 % ) who received LMW heparin compared with 61 patients ( 23.2 % ) who received st and ard heparin ( difference , -3.8 % ; 95 % CI , -11.1 % to 3.6 % ) ( P greater than 0.2 ) . Proximal deep vein thrombosis was detected in 5.4 % of the patients receiving LMW heparin and in 6.5 % of the patients receiving st and ard heparin ( difference , -1.1 % ; CI , - 5.2 % to 3.3 % ) ( P greater than 0.2 ) . For the entire group of 665 patients , venous thrombosis occurred in 17.1 % given LMW heparin and in 19.0 % given st and ard heparin . Hemorrhagic complications occurred in 31 patients ( 9.3 % ) given st and ard heparin and in 17 patients ( 5.1 % ) given LMW heparin ( difference , 4.2 % ; CI , 0.3 % to 8.2 % ) ( P = 0.035 ) . The relative risk reduction was 45 % . The rate of major bleeding in the st and ard heparin group was 5.7 % compared with 3.3 % in the LMW heparin group ( difference , 2.4 % ; CI , -1.0 % to 5.4 % ) ( P = 0.13 ) . The relative risk reduction was 42 % . CONCLUSION Low molecular weight heparin is significantly less hemorrhagic than st and ard unfractionated heparin ; the difference in the rate of deep vein thrombosis , although not statistically significant ( P greater than 0.2 ) , favors the use of LMW heparin The effects of postoperative epidural infusions using local anesthetic and narcotic were assessed in reference to lower extremity blood flow . Nineteen patients who underwent unilateral total hip arthroplasty were r and omly assigned to receive a postoperative epidural infusion of either 5 microg/ml fentanyl or 5 microg/ml fentanyl plus 0.125 % bupivacaine at a rate of 10 ml per hour . The infusions were started after complete resolution of the operative epidural blockade . Femoral venous blood flow volume and velocity were measured above and below the saphenous vein bifurcation using an Acuson # 128XP/10 computed sonography system ( duplex ultrasound ) and proprietary software . Femoral venous blood flow was not affected by the type of infusion and did not increase during the study period . However , femoral venous blood flow volume increased 50 % after active flexion and extension of the foot , 10 times in quick succession . The addition of bupivacaine ( a local anesthetic that blocks sympathetic afferent nerves ) to a postoperative epidural infusion does not augment blood flow from the deep veins of the leg after total hip arthroplasty . Alternatively , lower extremity skeletal muscle activity significantly enhances femoral venous blood flow and may be a useful adjunct in deep venous thrombosis prevention Parkinson 's disease , a progressive neurodegenerative disorder , affects about 1 % of the population over the age of 50 . While it has no cure , it is the only neurodegenerative disorder with a range of medical and neurosurgical treatments that substantially reduce clinical symptoms.1 However , medical management of early Parkinson 's disease is controversial because of the potential risks and benefits to patients . Some clinicians prefer to use levodopa , a dopamine precursor , since it promptly relieves symptoms . Others prescribe dopamine agonists and withhold levodopa because of its long term complications , namely abnormal involuntary movements and potential neurotoxicity . Inevitably , managing the side effects of antiparkinsonian drugs becomes a therapeutic focus along with treating the primary motor abnormalities.1 Extended controlled clinical trials are the only means of obtaining evidence based guidance on the use of dopamine agonists or levodopa for the management of early Parkinson 's disease . The results of a recent multisite , five year , r and omised , double blind study comparing the incidence of dyskinesia with levodopa or ropinirole , a dopamine D2 receptor agonist,2 should sway practitioners towards initial treatment with agonists for early Parkinson 's disease . In contrast to the hypokinesis that characterises Parkinson 's disease , dyskinesias related to antiparkinsonian drugs involve hyperkinetic choreoathetoid , lurching , and jerky movements . These movements are thought Oral controlled release morphine ( CRM ) was compared in a double-blind study with epidural morphine ( EM ) for postoperative pain relief in 20 patients undergoing knee arthrotomy under epidural anesthesia . Ten patients received 30 mg CRM orally and saline epidurally ( CRM group ) , and ten patients received placebo tablets orally and 4 mg morphine epidurally ( EM group ) , both at the time of skin incision and then every 8 hr for 48 hr during which patients evaluated pain intensity using a visual analog scale . Nine of the ten patients in the EM group had good relief of pain throughout the study period . Seven of the ten patients in the CRM group needed rescue analgesics within 6 hr of the initiation of the study ( P < 0.01 ) . We conclude that CRM is not suitable for the control of early postoperative pain , whereas epidural morphine is excellent Fifty-five patients undergoing hip arthroplasty under spinal anaesthesia ( 4 ml of 0.5 % plain bupivacaine ) were r and omized to receive post-operative analgesia either using an intrathecal or an epidural catheter . Associated technical problems and side effects were studied . In both groups per-operative analgesia was achieved with intrathecal 0.5 % plain bupivacaine , 4 ml . In the intrathecal infusion group a bolus dose of 100 micrograms morphine was injected through a spinal 28 gauge catheter followed by a 24 h infusion of 200 micrograms morphine ( 8.3 micrograms h-1 ) . In the epidural infusion group a bolus dose of 2 mg of morphine was injected before the epidural 24 h infusion was started ( morphine 200 micrograms h-1 + 0.25 % bupivacaine 4 ml h-1 ) . There were 10 catheter failures ( two could not be inserted ) in the intrathecal group and one in the epidural group . Three epidural catheter infusions failed due to other technical problems . The number of side effects was 21 in the remaining spinal group ( n = 20 ) and 18 in the 20 epidural group patients with successful infusions . One patient in the spinal catheter group developed postdural puncture headache . For post-operative pain relief the patients in the epidural group needed less supplementary intramuscular oxycodone ( five doses/four patients ) than the spinal group ( 17 doses/nine patients ) ( P < 0.05 ) Despite modern surgical techniques and early patient mobilization , venous thromboembolism remains a major complication of knee arthroplasty [ 1 - 3 ] . Without prophylaxis , the reported incidences of venographically verified deep venous thrombosis and proximal venous thrombosis have ranged from 55 % to 70 % and from 10 % to 30 % , respectively [ 2 , 4 - 8 ] . Fatal pulmonary embolism , allegedly uncommon ( incidence less than 1 % [ 9 ] ) , remains an avoidable cause of perioperative death in these patients . The burden of postoperative venous thromboembolism must also be assessed in terms of the morbidity from the acute event , the risk for long-term postphlebitic complications [ 10 , 11 ] , and the effect of venous thromboembolism on the cost of health care delivery [ 12 , 13 ] . Preventing venous thromboembolism after knee arthroplasty is difficult because of the relative resistance of this type of surgery to the effects of most thromboprophylaxis options [ 6 , 14 - 18 ] , the substantial hemorrhagic risk associated with the surgical procedure [ 19 ] , and the lack of consensus on the safest and most effective method . The main hemorrhagic threat of thromboprophylaxis in knee surgery is hemarthrosis , which may require surgical drainage or may compromise the result of the reconstruction . Less intense warfarin and low-molecular-weight heparins have been evaluated as prophylaxis after knee surgery [ 8 , 20 - 24 ] . Warfarin has the advantage of oral administration , and low-molecular-weight heparins do not require laboratory monitoring . In previous studies comparing warfarin with low-molecular-weight heparins , patients having either hip or knee surgery were evaluated together [ 20 , 21 ] , interventions were unblinded [ 21 , 22 ] , or unilateral venography was done [ 21 - 23 ] . We thus conducted a double-blind , r and omized trial with bilateral venographic assessment of the effectiveness and safety of postoperative , adjusted-dose warfarin compared with those of postoperative , fixed-dose enoxaparin in patients having knee arthroplasty . Methods Patients Eight hundred sixty-five consecutive adult patients having knee arthroplasty at eight hospitals were evaluated . Sixty-eight patients were excluded for the following reasons : allergy to contrast material ( 20 patients ) ; need for oral anticoagulant or antiplatelet agents ( 18 patients ) ; bleeding diathesis ( 9 patients ) ; gastrointestinal hemorrhage within 3 months of surgery ( 7 patients ) ; renal or hepatic insufficiency ( 4 patients ) ; uncontrolled hypertension ( 3 patients ) ; illicit drug use or alcohol abuse ( 3 patients ) ; participation in the present study within the last 3 months ( 1 patient ) ; hemorrhagic stroke within 3 months of surgery ( 1 patient ) ; receipt of other investigational drugs in the past month ( 1 patient ) ; and warfarin allergy ( 1 patient ) . Of the 797 patients eligible for the study , 670 ( 84 % ) gave informed consent . Interventions The 670 eligible and consenting patients were r and omly allocated after surgery to receive either warfarin sodium ( 334 patients ) or enoxaparin ( 336 patients ) in a 1:1 ratio in blocks of four . A computer generated the r and omization schedule . We stratified r and omization by study center , history of venous thromboembolism , and use of a cemented or uncemented prosthesis . Patients in the warfarin group also received subcutaneous saline placebo every 12 hours . The treatment goal was to maintain the international normalized ratio between 2.0 and 3.0 using a prespecified nomogram . Patients in the enoxaparin group received 30 mg of enoxaparin subcutaneously every 12 hours and warfarin placebo once daily . Therapy with oral medications began on the evening of the day on which surgery was done ( day 1 ) , and therapy with subcutaneous medications began on the morning of the first day after surgery ( day 2 ) . Study medications were administered for 14 days or until hospital discharge , whichever occurred first . No other thromboprophylactic agents or antiembolic stockings were used . Patient Surveillance and Outcome Measures The primary end point was the incidence of deep venous thrombosis in patients with adequate bilateral venograms and symptomatic pulmonary embolism . Venography was done on day 14 or earlier if the patient was discharged or if patients developing clinical ly suspected deep venous thrombosis had abnormal noninvasive test results . The diagnostic criterion for thrombosis was a constant intraluminal filling defect seen on two or more views . Venograms were considered adequate if the entire deep venous system could be seen to at least the level of the common femoral vein . Bilateral compression ultrasonography of the tibioperoneal trunk , popliteal vein , superficial femoral vein in at least two sites , and common femoral vein was routinely done before venography . A positive venous ultrasound was defined as the noncompressibility of a vein segment . Patients with clinical ly suspected venous thrombosis had either compression ultrasonography or impedance plethysmography when symptoms developed . Venography was done immediately if the noninvasive test result was abnormal . Symptomatic patients with a normal noninvasive test result had repeated testing every other day until predischarge venography was done . Patients with suspected pulmonary embolism had lung scanning . Pulmonary embolism was excluded on the basis of a normal perfusion scan and was confirmed by a high-probability scan ; the latter was defined as showing one or more segmental perfusion defects with normal or near-normal ventilation . Patients with abnormal lung scans that did not show a high probability of embolism subsequently had pulmonary angiography . Patients with proven venous thromboembolism received heparin treatment followed by oral anticoagulant agents as per local practice . Patients who did not develop venous thromboembolism received no further thromboprophylaxis after hospital discharge . Secondary end points were clinical ly overt hemorrhage and postoperative blood loss . Major hemorrhage was defined as overt bleeding that 1 ) decreased the hemoglobin level by 20 g/L or more or 2 ) necessitated transfusion of 2 or more units of packed red cells , hemarthrosis requiring evacuation , discontinuation of prophylaxis , or interruption of physiotherapy for at least 24 hours . Minor hemorrhage was defined as overt bleeding that did not meet the criteria for major hemorrhage . All patients were followed for 6 months . During this interval , patients were instructed to contact the investigator if they developed symptoms suggestive of venous thromboembolism . Blinding Oral medications were monitored by an independent physician who was aware of the r and omization schedule but was not otherwise involved in the study . Dosage adjustments were based on the measured international normalized ratios in patients receiving warfarin and on phantom international normalized ratios , generated a priori , in patients receiving warfarin placebo . Patients receiving warfarin placebo also had daily blood sampling for sham measurements of the international normalized ratio . International normalized ratios were not recorded in the patients ' charts . All diagnostic tests and bleeding episodes were adjudicated by a central committee that was unaware of treatment allocation or clinical findings . Statistical Analysis The rates of deep venous thrombosis in the two treatment groups were compared using the chi-square test with Yates correction . Blood loss was analyzed using one-way analysis of variance . The rates of pulmonary embolism and the proportion of patients receiving packed red cells were analyzed using the Fisher exact test . We used the statistical package S-PLUS version 3.1 ( StatSci , Seattle , Washington ) . Estimation of Sample Size On the basis of the assumption that the incidence of deep venous thrombosis in enoxaparin recipients would be approximately 20 % [ 8 ] and with an value of 0.05 ( two-tailed ) and a value of 0.20 , we determined that 200 patients with adequate venograms per group would be required to show at least a 50 % reduction in the rate of thrombosis in the enoxaparin group compared with the warfarin group . Interim Analysis We did a preplanned interim analysis after 200 patients with adequate venograms were enrolled . An independent committee review ed the results without breaking the code . We formally used an O'Brien-Fleming stopping boundary [ 25 ] but also analyzed the overall rate of thrombosis and bleeding complications to arrive at a conclusion . We decided to continue the trial until 400 patients had adequate venograms . Study Logistics The investigators independently design ed the study and interpreted the results . The research coordinators at each site collected the data , and the sponsoring pharmaceutical firm monitored the quality of the data at each study center . Biostatisticians from the Division of Clinical Epidemiology of the Montreal General Hospital design ed the data base , and the clinical research firm Biopharmaceutical Research Consultants ( Ann Arbor , Michigan ) independently analyzed the data . Results The two treatment groups had similar important baseline characteristics ( Table 1 ) . Adequate venographic outcomes were obtained in 417 of 670 patients ( 62 % ) . Adequate venograms were not obtained in the remaining patients for the following reasons : technically inadequate venogram ( 129 patients ) , failed venous access ( 94 patients ) , refusal of the patient ( 24 patients ) , pulmonary embolism ( 3 patients ) , refusal of the treating physician ( 2 patients ) , and unavailable films ( 1 patient ) . These reasons were equally balanced between the two groups . All technically inadequate venograms result ed from incomplete opacification of the deep venous system . In many instances , radiologists were uncomfortable administering additional contrast material , particularly because the protocol required bilateral venography . An additional complicating factor was the overshadowing of the popliteal vein by the knee prosthesis , despite the protocol requirement to obtain lateral views of this area . The BACKGROUND Deep-vein thrombosis is a potentially life-threatening complication of total hip or knee replacement . There are few data on the effectiveness and safety of warfarin as compared with low-molecular-weight heparin as prophylaxis against this problem . METHODS We therefore performed a r and omized , double-blind trial in 1436 patients to evaluate the effectiveness and safety of low-molecular-weight heparin ( given subcutaneously once daily ) as compared with adjusted-dose warfarin to prevent venous thrombosis after hip or knee replacement . Treatment with the drugs was started postoperatively . The primary end point was deep-vein thrombosis as detected by contrast venography ( performed a mean of 9.4 days after surgery in each group ) . RESULTS Among the 1207 patients with interpretable venograms , 231 of 617 patients ( 37.4 percent ) in the warfarin group and 185 of 590 patients ( 31.4 percent ) in the low-molecular-weight-heparin group had deep-vein thrombosis ( P = 0.03 ) . The reduction in risk with low-molecular-weight heparin as compared with warfarin was 16 percent , and the absolute difference in the incidence of venous thrombosis was 6 percent in favor of low-molecular-weight heparin ( 95 percent confidence interval , 0.8 to 11.4 percent ) . The incidence of major bleeding was 1.2 percent ( 9 of 721 patients ) in the warfarin group and 2.8 percent ( 20 of 715 patients ) in the low-molecular-weight-heparin group ( P = 0.04 ) , and the absolute difference was 1.5 percent in favor of warfarin ( 95 percent confidence interval , 0.1 to 3.0 percent ) . CONCLUSIONS Our data demonstrate that the small reduction in the incidence of venous thrombosis with low-molecular-weight heparin , as compared with warfarin , was offset by an increase in bleeding complications . Although the use of low-molecular-weight heparin is simpler , because it is administered subcutaneously without the need for monitoring , it may be more costly than warfarin . Warfarin is inexpensive , but the overall cost of its use is increased by the need to monitor the intensity of anticoagulation . At this time it is unclear which of these approaches is the most cost effective Epidural analgesia for total knee replacement ( TKR ) surgery has been proposed as a means of enhancing patient comfort , thereby expediting rehabilitation and reducing hospital stay . This study was done to determine differences in rehabilitation parameters of range of motion and mobility in patients receiving epidural vs. conventional ( intravenous ) analgesia following TKR surgery . Chart review s were done of 52 patients who underwent consecutive unilateral TKR , with 26 patients in each analgesia group . There were 21 males and 31 females , ages 24 - 88 years ( median 65 ) , with diagnoses of osteoarthritis ( 45 ) , rheumatoid arthritis ( 4 ) , and other ( 3 ) . The surgeon , procedure , type of prosthesis , and physical therapy protocol were the same for all subjects . Demographics , range of motion , distance walked , assistance required for gait and transfers , assistive device , and exercise competence data were studied at the first postoperative day and at time of discharge . No significant difference was found in the length of stay at the p < .05 level . Significant differences at the first postoperative day favored the epidural group : in knee flexion range -- median difference was 0.26 rad [ 95 % confidence interval ( CI ) : 0.09 - 0.52 , p < .05 ] ie . , 15 degrees ( 95 % CI : 5 - 30 ) ; in total range of motion -- median difference was 0.30 rad ( 95 % CI : 0.09 - 0.58 , p < .05 ) , ie . , 17 degrees ( 95 % CI : 5 - 33 ) ; and in assistance required for gait and transfers ( p < .05 ) . At discharge , the epidural group required significantly less assistance ( p < .05 ) . There was a trend toward greater walking distance in the epidural group , who walked a median of 15.2 m farther than the conventional analgesia group . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Sufentanil is a potent but short-acting spinal analgesic used to manage perioperative pain . This study evaluated the influence of transdermal nitroglycerine on the analgesic action of spinal sufentanil in patients undergoing orthopedic surgery . METHODS Fifty-six patients were r and omized to one of four groups . Patients were premedicated with 0.05 - 0.1 mg/kg intravenous midazolam and received 15 mg bupivacaine plus 2 ml of the test drug intrathecally ( saline or 10 microg sufentanil ) . Twenty to 30 min after the spinal puncture , a transdermal patch of either 5 mg nitroglycerin or placebo was applied . The control group received spinal saline and transdermal placebo . The sufentanil group received spinal sufentanil and transdermal placebo . The nitroglycerin group received spinal saline and transdermal nitroglycerine patch . Finally , the sufentanil-nitroglycerin group received spinal sufentanil and transdermal nitroglycerine . Pain and adverse effects were evaluated using a 10-cm visual analog scale . RESULTS The time to first rescue analgesic medication was longer for the sufentanil-nitroglycerin group ( 785+/-483 min ) compared with the other groups ( P<0.005 ) . The time to first rescue analgesics was also longer for the sufentanil group compared with the control group ( P<0.05 ) . The sufentanil-nitroglycerin group group required less rescue analgesics in 24 h compared with the other groups ( P<0.02 ) and had lesser 24-h pain visual analog scale scores compared with the control group ( P<0.005 ) , although these scores were similar to the sufentanil and nitroglycerin groups ( P>0.05 ) . The incidence of perioperative adverse effects was similar among groups ( P>0.05 ) . CONCLUSIONS Transdermal nitroglycerine alone ( 5 mg/day ) , a nitric oxide generator , did not result in postoperative analgesia itself , but it prolonged the analgesic effect of spinal sufentanil ( 10 microg ) and provided 13 h of effective postoperative analgesia after knee surgery Venous thrombosis rates were compared in 200 patients undergoing total hip arthroplasty and r and omized to receive either fixed mini-dose warfarin ( 1 mg daily ) or adjusted-dose warfarin to maintain an international normalized prothrombin ratio ( INR ) of 2.0 - 4.0 . Bilateral lower limb venography was performed between days 11 and 13 inclusive . Fixed mini-dose warfarin was associated with a significantly higher rate of total thrombosis ( P less than 0.05 ) . General anaesthesia was associated with a significantly higher rate of thrombosis than spinal anaesthesia ( P less than 0.05 ) . Adjusted-dose warfarin was associated with more bleeding complications than mini-dose warfarin although these were not attributable to excessive anticoagulation . A single death from pulmonary embolus occurred in the early postoperative period in a patient receiving adjusted-dose warfarin The purpose of this study was to compare neutrophil cidal activity during general or spinal anaesthesia . Assays were performed on neutrophils extracted from the blood of patients after surgery had been under way for one hour . First , the ability of the neutrophils to kill a st and ard laboratory strain of S. aureus was examined . Neutrophils extracted from the blood during surgery in the spinal anaesthetic group and incubated with the staphylococci for one hour killed twice as many bacteria than those from two groups of patients that received halothane or isoflurane general anaesthesia ( P < 0.05 ) . This effect persisted , to a lesser extent , in the spinal group neutrophils after two hours of incubation with the bacteria . Second , neutrophils from patients under the same conditions of surgery and anaesthesia were tested to examine the effect of the different anaesthetic techniques on neutrophil biocidal mechanisms . Neutrophils extracted during surgery in the spinal group released more superoxide in response to phorbol-12-myristate-13-acetate ( PMA ) than those from both groups of patients that received general anaesthesia ( P < 0.05 ) . It is concluded that there is an increased state of reactivity of the neutrophil cell membrane NADPH oxidase system in patients receiving spinal anaesthesia than in patients receiving general anaesthesia . RésuméCette étude vise à comparer l’activité bactéricide des neutrophiles pendant l’anesthésie générale ou rachidienne . Les analyses sont effectuées à partir de neutrophiles extraits du sang de patients une heure après le début de la chirurgie . D’abord , l’habileté des neutrophiles à tuer une colonie st and ard de S. aureus est éxaminée . Les neutrophiles extraits de patients sous rachianesthésie et incubés avec des neutrophiles pendant une heure tuent deux fois plus de bactéries que le sang se patients sous anesthésie générale à l’halothane ou à l’isoflurane ( P < 0,05 ) . Cet effet persiste , mais à un degré moindre , dans le sang du groupe rachianesthésie après un contact de deux heures avec les bactéries . Ensuite , on a examiné sous les mêmes conditions d’anesthésie et de chirurgie les neutrophiles de patients anesthésiés avec les différentes techniques pour en déterminer le mécanisme bactéricide . Les neutrophiles extraits pendant la rachianesthésie libèrent plus de superoxyde en réponse au phorbol-12-myristate-13-acétate ( PMA ) que ceux des deux groupes de patients sous générale ( P < 0,05 ) . En conclusion , on constate une augmentation de l’état réactif du système NADPH oxydase de la membrane cellulaire du neutrophile chez les patients sous rachianesthésie comparativement à ceux qui sont sous anesthésie générale Continuous bupivacaine epidural analgesia was compared with conventional methods of systemic analgesic administration in the management of postoperative pain in 30 patients for 3 days following total knee replacement surgery . Patients given continuous epidural analgesia had significantly better pain relief ( visual analogue scale , global evaluation ) , needed significantly fewer supplementary analgesics , and had significantly fewer side effects . In the epidural group , sensory block averaged six dermatomes on day 1 and four dermatomes on day 3 . The number of patients with complete ( or almost complete ) motor block of the lower limbs decreased from eight on day 1 to five on day 3 . The mean dosage of bupivacaine decreased from 21.0 ± 5.7 ( SD ) mg/hr on day 1 to 15.1 ± 8.5 mg/hr on day 3 . No signs of accumulation of or toxic reactions to bupivacaine were seen STUDY OBJECTIVES To determine whether lumbar epidural anesthesia , when combined with general anesthesia , decreases perioperative blood loss , the incidence of postoperative deep vein thrombosis ( DVT ) , cardiac dysrhythmias , and ischemia in patients undergoing total hip arthroplasty ( THA ) . DESIGN R and omized , controlled study . SETTING A university hospital . PATIENTS 37 ASA physical status I , II , and III patients , undergoing elective THA . INTERVENTION Patients were divided into two statistically comparable groups : Group GA = general anesthesia ; Group CEGA = general anesthesia plus lumbar epidural anesthesia . All patients had 48-hour perioperative Holter monitoring , applied on admission , the day prior to surgery . In both groups , general anesthesia was induced with thiopental sodium and muscle relaxant , and maintained with oxygen , nitrous oxide , isoflurane , opioid , and muscle relaxant . Group B received lumbar epidural anesthesia with 10 ml 0.5 % bupivacaine with 1:200,000 epinephrine prior to anesthesia induction . Blood loss was measured by suction bottle contents , sponge weights , and collection drainage . DVT was assessed with postoperative leg scanning , plethysmography , and venogram . MEASUREMENTS AND MAIN RESULTS Intraoperative blood loss was less after combined epidural-general anesthesia ( 663.8 ml + /- 299.0 ml ) than after general anesthesia alone ( 1,259.2 ml + /- 366.0 ml ) . The difference was found to be statistically significant ( p < 0.00005 ) . No difference was found between the two groups in postoperative blood loss , incidence of DVT , cardiac dysrhythmias , or ischemia . CONCLUSION Combined regional-general anesthesia decreases intraoperative blood loss in THA , and thereby offers an advantage over general anesthesia alone STUDY OBJECTIVE To assess the most appropriate postoperative analgesic technique after hip surgery . DESIGN Prospect i ve , nonr and omized study . SETTING University hospital . PATIENTS 1,338 ASA physical status I , II , and III patients scheduled for elective unilateral total hip arthroplasty ( THA ) . INTERVENTIONS During the first 48 postoperative hours , pain relief was provided by intravenous ( i.v . ) patient-controlled analgesia ( PCA ) with morphine ( Group 1 ) , continuous " 3-in-1 " block ( Group 2 ) , or patient-controlled epidural analgesia ( PCEA ) ( Group 3 ) . MEASUREMENTS AND MAIN RESULTS During a 7.5-year period , pain scores , supplemental analgesia , satisfaction score , technical problems , and side effects were collected by our acute pain service . Postoperative pain relief was comparable in the three groups . More paracetamol was required in Group 2 ( 1.0 + /- 1.2 g/48 h ) and Group 3 ( 0.9 + /- 1.3 g/48 h ) than in Group 1 ( 0.5 + /- 1.1 g/48 h ) ( p < 0.01 ) . However , only 8 % of patients in Group 2 and 12 % of patients in Group 3 needed an opioid . A higher incidence of technical problems was noted in Group 3 ( 23.4 % ) than in Group 1 ( 2.3 % ) or Group 2 ( 5.5 % ) ( p < 0.001 ) . A lower incidence of side effects was observed in Group 2 ( 23.5 % ) when compared with Group 1 ( 58.8 % ) and Group 3 ( 71.9 % ) ( p < 0.001 ) . Satisfaction score was significantly higher in Group 2 than in the other two groups [ 80 + /- 16 vs. 87 + /- 14 vs. 81 + /- 14 in Groups 1 , 2 , and 3 respectively ( p = 0.003 ) ] . CONCLUSION After THA , i.v . PCA with morphine , continuous " 3-in-1 " block , and PCEA provided comparable pain relief . Because it induces the fewest technical problems and side effects , continuous " 3-in-1 " block is the preferred technique & NA ; A r and omized double‐blind study compared the dose‐response relationship of epidural morphine for postoperative pain relief in two groups of patients whose surgical procedures would result in either moderate ( femoral‐popliteal bypass ) or severe ( total knee replacement ) postoperative pain . Preservative‐ free morphine sulphate in doses of 0 , 2 , 5 , or 10 mg in a volume of 10 ml saline were administered via lumbar epidural catheters . The epidural morphine was administered 1 hr after the last dose of intraoperative local epidural anesthetic in an effort to achieve a pain‐free postoperative course . A significant relationship existed between the dose of epi‐ dural morphine and both time to first required pain medication and 24‐hr weighted pain score . Five mg epidural morphine provided significant improvement in postoperative analgesia compared with the control in both groups . Further enhancement of analgesia occurred with 10 mg ; however , late respiratory depression , demonstrated by an increased resting PaCO2 10 hr after administration , was seen only with the 10‐mg dose in both surgical groups . Minor complications such as nausea , vomiting , pruritus , and urinary retention were uncommon and did not appear to be related to dose . We found that 5 mg epidural morphine provided long‐lasting postoperative analgesia without serious adverse effects after peripheral vascular and orthopedic surgery We studied 151 patients undergoing total hip or knee arthroplasty , or cruciate ligament reconstruction in a multicentre study in Australia and New Zeal and . Patients were openly allocated r and omly to one of five treatment groups or to a control group . General anaesthesia was induced after introduction of extradural block with 0.5 % ropivacaine . After surgery , patients received an extradural infusion of 0.2 % ropivacaine at 6 , 8 , 10 , 12 or 14 ml h-1 or received no postoperative extradural infusion ( control group ) . All patients had access to i.v . PCA morphine for supplementary analgesia . Morphine consumption was lower in all treatment groups compared with the control group , decreasing with increasing ropivacaine infusion rate . Median VAS scores were lower in all ropivacaine infusion groups compared with the control group for the first 10 h of the study ; however by the end of the study , VAS scores were similar in all groups . The higher ropivacaine infusion rates caused a slower convergence of spread of the initial sensory block and a higher degree of motor block . The overall incidence of side effects was similar , with the exception of a higher incidence of urinary retention and hypotension in the groups receiving the higher rates of ropivacaine . The quality of treatment scores were similar for all treatment groups ( Br . J. Anaesth . 1996 ; 76 : 606 - 610 ) In this study , we assessed the influence of three analgesic techniques on postoperative knee rehabilitation after total knee arthroplasty (TKA).Forty-five patients scheduled for elective TKA under general anesthesia were r and omly divided into three groups . Postoperative analgesia was provided with IV patient-controlled analgesia ( PCA ) with morphine in Group A , continuous 3-in-1 block in Group B , and epidural analgesia in Group C. Immediately after surgery , the three groups started identical physical therapy regimens . Pain scores , supplemental analgesia , side effects , degree of maximal knee flexion , day of first walk , and duration of hospital stay were recorded . Patients in Groups B and C reported significantly lower pain scores than those in Group A. Supplemental analgesia was comparable in the three groups . Compared with Groups A and C , a significantly lower incidence of side effects was noted in Group B. Significantly better knee flexion ( until 6 wk after surgery ) , faster ambulation , and shorter hospital stay were noted in Groups B and C. However , these benefits did not affect outcome at 3 mo . We conclude that , after TKA , continuous 3-in-1 block and epidural analgesia provide better pain relief and faster knee rehabilitation than IV PCA with morphine . Because it induces fewer side effects , continuous 3-in-1 block should be considered the technique of choice . Implication s : In this study , we determined that , after total knee arthroplasty , loco-regional analgesic techniques ( epidural analgesia or continuous 3-in-1 block ) provide better pain relief and faster postoperative knee rehabilitation than IV patient-controlled analgesia with morphine . Because it causes fewer side effects than epidural analgesia , continuous 3-in-1 block is the technique of choice . ( Anesth Analg 1998;87:88 - 92 We have studied the anaesthetic and analgesic properties of intrathecal clonidine and intrathecal morphine in patients undergoing total hip replacement under spinal anaesthesia . After routine spinal anaesthesia with 0.5 % plain bupivacaine 2.75 ml , patients were allocated r and omly to receive intrathecal clonidine , morphine or saline ( control ) as adjuvant to the bupivacaine . Postoperative analgesic effects were measured by consumption of morphine via patient-controlled analgesia and visual analogue pain scores . Both intrathecal clonidine and intrathecal morphine prolonged the time to first analgesia compared with saline ( mean 278 ( SD 93.2 ) min , 498 ( 282.4 ) min and 54 ( 61.9 ) min , respectively ) ( P < 0.001 ) . Total morphine consumption on the first night after operation was significantly less in the intrathecal morphine group . There were no differences between the clonidine and the control group . Intrathecal clonidine prolonged the duration of spinal analgesia , but was markedly inferior to the intrathecal morphine in providing subsequent postoperative analgesia Thirty-six patients scheduled for knee arthroplasty were r and omized to general or epidural anesthesia that was prolonged into the postoperative period . All the patients wore grade d compression stockings until full ambulation . No other thrombo-prophylactic treatment was given . In diagnosing deep venous thrombosis , bilateral ascending venography was performed 9 - 11 days after surgery . The incidence of thrombosis was 2/13 in the epidural group versus 10/16 in the general anesthesia group ( P less than 0.05 ) In a double-blind , r and omized study , we have compared the effects of i.v . ketoprofen 200 mg followed by 12.5 mg h-1 over 13 h , with those of extradural morphine 4 mg in 32 patients after hip and knee arthroplasty . A visual analogue scale was used to score pain before analgesic administration ( first complaint after operation ) , 1 h after and every 2 h subsequently . Pain reduction 1 h after the start of analgesia was mean 44 % ( SEM 17 % ) in the extradural morphine group and 54 % ( 9 % ) in the ketoprofen group ( ns ) . There were no significant differences between groups in pain scores , pain reduction and additional analgesia requirement ( i.v . paracetamol ) . Naloxone 5 micrograms kg-1 h-1 was required for hypercapnia exceeding 6.0 kPa in three patients in the extradural morphine group ( vs none in the ketoprofen group ; ns ) . There were no differences between groups in side effects , except for urinary retention , which was more frequent in the extradural morphine group ( P < 0.05 ) . As there were few differences between i.v . ketoprofen and extradural morphine , we conclude that ketoprofen may be an efficient alternative to extradural morphine after hip and knee arthroplasty The efficacy of highdose aprotinin in reducing pen-operative blood loss has long been reported in surgery of the hem and main vessels [ 1 - 4 ] and in liver transplants [ 5 , 61 . Even in orthopaedic surgery there is the problem of perioperative bleeding at times causing serious complications [ 7 ] . Epidural anaesthesia per and postoperatively can reduce peri-operative bleeding [ 8-lo ] . The aim of this prospect i ve , r and omised and double-blind study was to assess interactions between epidural anaesthesia and postoperative epidural analgesia and the use of high-dose aprotinin in orthopaedic surgery on peri-operative bleeding |
10,450 | 30,738,757 | The studies examined PPE use in hospital ( n=7 ) , dental ( n=4 ) or laboratory ( n=2 ) setting s. Policies and practice s on PPE use were inconsistent .
Face masks and gloves were the most commonly used PPE to protect from respiratory and other infections .
PPE was not available in many facilities and its use was limited to high-risk situations .
Compliance with PPE use was low among healthcare workers , and reuse of PPE was reported . | Abstract Like other low-income countries , limited data are available on the use of personal protective equipment ( PPE ) in Pakistan .
We conducted a systematic review of studies on PPE use for respiratory infections in healthcare setting s in Pakistan . | Please cite this paper as : MacIntyre et al. ( 2011 ) A cluster r and omized clinical trial comparing fit‐tested and non‐fit‐tested N95 respirators to medical masks to prevent respiratory virus infection in health care workers . Influenza and Other Respiratory Viruses DOI : 10.1111/j.1750‐2659.2010.00198.x . Background We compared the efficacy of medical masks , N95 respirators ( fit tested and non fit tested ) , in health care workers ( HCWs ) . Methods A cluster r and omized clinical trial ( RCT ) of 1441 HCWs in 15 Beijing hospitals was performed during the 2008/2009 winter . Participants wore masks or respirators during the entire work shift for 4 weeks . Outcomes included clinical respiratory illness ( CRI ) , influenza‐like illness ( ILI ) , laboratory‐confirmed respiratory virus infection and influenza . A convenience no‐mask/respirator group of 481 health workers from nine hospitals was compared . Findings The rates of CRI ( 3·9 % versus 6·7 % ) , ILI ( 0·3 % versus 0·6 % ) , laboratory‐confirmed respiratory virus ( 1·4 % versus 2·6 % ) and influenza ( 0·3 % versus 1 % ) infection were consistently lower for the N95 group compared to medical masks . By intention‐to‐treat analysis , when P values were adjusted for clustering , non‐fit‐tested N95 respirators were significantly more protective than medical masks against CRI , but no other outcomes were significant . The rates of all outcomes were higher in the convenience no‐mask group compared to the intervention arms . There was no significant difference in outcomes between the N95 arms with and without fit testing . Rates of fit test failure were low . In a post hoc analysis adjusted for potential confounders , N95 masks and hospital level were significant , but medical masks , vaccination , h and washing and high‐risk procedures were not . Interpretation Rates of infection in the medical mask group were double that in the N95 group . A benefit of respirators is suggested but would need to be confirmed by a larger trial , as this study may have been underpowered . The finding on fit testing is specific to the type of respirator used in the study and can not be generalized to other respirators . Trial registration Australian New Zeal and Clinical Trials Registry ( ANZCTR ) , ACTRN : ACTRN12609000257268 ( http://www.anzctr.org.au ) BACKGROUND Certain emerging infections , such as severe acute respiratory syndrome and avian influenza , represent a great risk to healthcare workers ( HCWs ) . There are few data about the epidemiology of H1N1 influenza among HCWs . METHODS We conducted a prospect i ve surveillance study for all HCWs at King Abdulaziz Medical City ( Riyadh , Saudi Arabia ) who were confirmed positive for H1N1 influenza by polymerase chain reaction ( PCR ) from June 1 through November 30 , 2009 . RESULTS During 6 months of surveillance , 526 HCWs were confirmed positive for H1N1 influenza . The distribution of these cases showed 2 clear outbreaks : an initial outbreak ( peak at early August ) and a shorter second wave ( peak at end of October ) . Among all PCR-confirmed cases , the attack rate was significantly higher in clinical HCWs than in non clinical HCWs ( 6.0 % vs 4.3 % ; P < .001 ) and in HCWs in emergency departments than in HCWs in other hospital locations ( 17.4 % vs 5.0 % , P < .001 ) . The percentage of HCWs who received regular influenza vaccination was greater for clinical HCWs than for non clinical HCWs ( 46.2 % vs 24.6 % ; P < .001 ) . The majority of HCWs with confirmed H1N1 influenza were young ( mean age + or - st and ard deviation , 34.5 + or - 9.5 years ) , not Saudi ( 58.4 % ) , female ( 55.1 % ) , and nurses ( 36.1 % ) . Approximately 4 % of women who were less than 50 years old were pregnant . Reported exposures included contact with a case ( 41.0 % ) , contact with a sick household member ( 23.8 % ) , and recent travel history ( 13.3 % ) . Respiratory symptoms ( 98.0 % ) , including cough ( 90.1 % ) , were the most frequently reported symptoms , followed by muscle aches ( 66.2 % ) , fever ( 62.5 % ) , headache ( 57.9 % ) , diarrhea ( 16.5 % ) , and vomiting ( 9.8 % ) . None of these HCWs died , and all recovered fully without hospital admission . CONCLUSIONS The results confirm the vulnerability of HCWs , whether clinical or non clinical , to emerging H1N1 influenza Abstract Purpose To explore factors relating to the practice of habitual and volitional health behaviors against the severe acute respiratory syndrome ( SARS ) among Chinese adolescents in Hong Kong . Methods A community telephone survey was conducted with 230 Chinese adolescents . R and om-digit dialing of the local residential telephone directory was used to select respondents , who were asked to provide information on their practice of SARS preventive health behaviors and associated factors as specified by the Health Belief Model . These factors included perceived threat of SARS , perceived benefits and barriers in practicing SARS preventive health behaviors , cues to action , knowledge of SARS , and self-efficacy . Hierarchical regression analyses were conducted to determine salient correlates of habitual and volitional health behaviors against SARS . Results About 54.8 % of respondents reported practicing all three recommended habitual health behaviors . Another 47.8 % indicated consistent practice of volitional health behavior of facemask-wearing to prevent SARS . Results of hierarchical regression analyses showed that habitual health behaviors against SARS were related to perceived health threat and environmental cues . For facemask-wearing , salient correlates were environmental cues , rates of SARS habitual health behaviors , younger age , and perceived health threat . Conclusions The Health Belief Model is useful in underst and ing Chinese adolescents ’ practice of health behaviors , especially volitional health behaviors OBJECTIVE To evaluate healthcare worker ( HCW ) risk of self-contamination when donning and doffing personal protective equipment ( PPE ) using fluorescence and MS2 bacteriophage . DESIGN Prospect i ve pilot study . SETTING Tertiary-care hospital . PARTICIPANTS A total of 36 HCWs were included in this study : 18 donned/doffed contact pre caution ( CP ) PPE and 18 donned/doffed Ebola virus disease ( EVD ) PPE . INTERVENTIONS HCWs donned PPE according to st and ard protocol s. Fluorescent liquid and MS2 bacteriophage were applied to HCWs . HCWs then doffed their PPE . After doffing , HCWs were scanned for fluorescence and swabbed for MS2 . MS2 detection was performed using reverse transcriptase PCR . The donning and doffing processes were videotaped , and protocol deviations were recorded . RESULTS Overall , 27 % of EVD PPE HCWs and 50 % of CP PPE HCWs made ≥1 protocol deviation while donning , and 100 % of EVD PPE HCWs and 67 % of CP PPE HCWs made ≥1 protocol deviation while doffing ( P=.02 ) . The median number of doffing protocol deviations among EVD PPE HCWs was 4 , versus 1 among CP PPE HCWs . Also , 15 EVD PPE protocol deviations were committed by doffing assistants and /or trained observers . Fluorescence was detected on 8 EVD PPE HCWs ( 44 % ) and 5 CP PPE HCWs ( 28 % ) , most commonly on h and s. MS2 was recovered from 2 EVD PPE HCWs ( 11 % ) and 3 CP PPE HCWs ( 17 % ) . CONCLUSIONS Protocol deviations were common during both EVD and CP PPE doffing , and some deviations during EVD PPE doffing were committed by the HCW doffing assistant and /or the trained observer . Self-contamination was common . PPE donning/doffing are complex and deserve additional study . Infect Control Hosp Epidemiol 2017;38:1077 - 1083 BACKGROUND Masks are often worn in healthcare setting s to prevent the spread of infection from healthcare workers ( HCWs ) to patients . Masks are also used to protect the employee from patient-generated infectious organisms but poor compliance can reduce efficacy . The aim of this study was to examine the factors influencing compliance with the use of medical and cloth masks amongst hospital HCWs . METHODS HCWs compliance with the use of medical and cloth masks was measured over a 4-week period in a r and omized controlled trial in Vietnam . HCWs were instructed to record their daily activities in diary cards . Demographic , clinical , and diary card data were used to determine the predictors of compliance and the relationship of compliance with infection outcomes . RESULTS Compliance rates for both medical and cloth masks decreased during the 4 weeks : medical mask use decreased from 77 to 68 % ( P < 0.001 ) and cloth masks from 78 to 69 % ( P < 0.001 ) . The presence of adverse events ( adjusted RR 0.90 , 95 % CI 0.85 - 0.95 ) , and performing aerosol-generating procedures ( adjusted RR 0.78 , 95 % CI 0.73 - 0.82 ) were negatively associated with compliance , while contact with febrile respiratory illness patients was positively associated ( adjusted RR 1.14 , 95 % CI 1.07 - 1.20 ) . Being compliant with medical or cloth masks use ( average use ≥70 % of working time ) was not associated with clinical respiratory illness , influenza-like illness , and laboratory-confirmed viral infection . CONCLUSION Underst and ing the factors that affect compliance is important for the occupational health and safety of HCWs . New strategies and tools should be developed to increase compliance of HCWs . The presence of adverse events such as discomfort and breathing problems may be the main reasons for the low compliance with mask use and further studies should be conducted to improve the design / material of masks to improve comfort for the wearer This study investigated provincial and territorial differences in dentists ' compliance with recommended infection control practice s in Canada ( 1995 ) . Question naires were mailed to a stratified r and om sample of 6,444 dentists , of whom 66.4 % responded . Weighted analyses included Pearson 's chi-square test and multiple logistic regression . Significant provincial and territorial differences included testing for immune response after hepatitis B virus ( HBV ) vaccination , HBV vaccination for all clinical staff , use of infection control manuals and post-exposure protocol s , biological monitoring of heat sterilizers , h and washing before treating patients , using gloves and changing them after each patient , heat-sterilizing h and pieces between patients , and using masks and uniforms to protect against splatter of blood and saliva . Excellent compliance ( compliance with a combination of 18 recommended infection control procedures ) ranged from 0 % to 10 % ; the best predictors were more hours of continuing education on infection control in the last two years , practice location in larger cities ( > 500,000 ) and sex ( female ) . Clearly , improvements in infection control are desirable for dentists in all provinces and territories . Extending m and atory continuing education initiatives to include infection control may promote better compliance with current recommendations The nature of discomfort and level of exertion associated with wearing respiratory protection in the health care workplace are not well understood . Although a few studies have assessed these topics in a laboratory setting , little is known about the magnitude of discomfort and the level of exertion experienced by workers while they deliver health care to patients for prolonged periods . The purpose of this study was to determine the magnitude of discomfort and level of exertion experienced by health care workers while wearing respiratory protection for periods up to 8 hr when performing their typical occupational duties . This project was a multiple cross-over field trial of 27 health care workers , aged 24–65 , performing their typical , hospital-based occupational duties . Each participant served as his/her own control and wore one of seven respirators or a medical mask for 8 hr ( or as long as tolerable ) with interposed doffing periods every 2 hr . Self-perceived discomfort and exertion were quantified before each doffing : self-perceived level of discomfort using a visual analog scale , and self-perceived level of exertion using a Borg scale . Overall , and as would be expected , discomfort increased over time with continual respirator use over an 8-hr period . Interestingly , exertion increased only marginally over the same time period . The relatively low level of exertion associated with eight respiratory protective devices , including models commonly used in the U.S. health care workplace , is not likely to substantially influence workers ’ tolerability or occupational productivity . However , the magnitude of discomfort does appear to increase significantly over time with prolonged wear . These results suggest that respirator-related discomfort , but not exertion , negatively influences respirator tolerance over prolonged periods . Discomfort may also interfere with the occupational duties of workers Background : The aim of this study was to describe the risk of self‐contamination associated with doffing of personal protective equipment ( PPE ) and to compare self‐contamination with various PPE protocol s. Methods : We tested 10 different PPE donning and doffing protocol s , recommended by various health organizations for Ebola . Ten participants were recruited for this study and r and omly assigned to use 3 different PPE protocol s. After donning of PPE , fluorescent lotion and spray were applied on the external surface of the PPE to simulate contamination , and ultraviolet light was used to count fluorescent patches on the skin . Results : After testing 30 PPE sequences , large fluorescent patches were recorded after using “ WHO coverall and 95 ” and “ North Carolina coverall and N95 ” sequences , and small patches were recorded after using “ CDC coverall and N95 ” and “ Health Canada gown and N95 ” sequences . Commonly reported problems with PPE use were breathing difficulty , suffocation , heat stress , and fogging‐up glasses . Most participants rated PPE high ( 18/30 ) or medium ( 11/30 ) for ease of donning/doffing and comfort . PPE sequences with powered air‐purifying respirators ( PAPRs ) and assisted doffing were generally associated with fewer problems and were rated the highest . Conclusion : This study confirmed the risk of self‐contamination associated with the doffing of PPE . PAPR‐containing protocol s and assisted doffing should be preferred whenever possible during the outbreak of highly infectious pathogens |
10,451 | 28,390,069 | This review demonstrates that pre/peri-operative intravenous vancomycin may reduce the risk of early peritonitis and that antifungal prophylaxis with oral nystatin or fluconazole reduces the risk of fungal peritonitis following an antibiotic course .
However , no other antimicrobial interventions have proven efficacy .
In particular , the use of nasal antibiotic to eradicate Staphylococcus aureus , had an uncertain effect on the risk of peritonitis and raises questions about the usefulness of this approach . | BACKGROUND Peritoneal dialysis ( PD ) is an important therapy for patients with end-stage kidney disease and is used in more than 200,000 such patients globally .
However , its value is often limited by the development of infections such as peritonitis and exit-site and tunnel infections .
Multiple strategies have been developed to reduce the risk of peritonitis including antibiotics , topical disinfectants to the exit site and antifungal agents .
However , the effectiveness of these strategies has been variable and are based on a small number of r and omised controlled trials ( RCTs ) .
The optimal preventive strategies to reduce the occurrence of peritonitis remain unclear .
This is an up date of a Cochrane review first published in 2004 .
OBJECTIVES To evaluate the benefits and harms of antimicrobial strategies used to prevent peritonitis in PD patients . | The efficacy of cephalothin sodium , added to dialysis fluids , as prophylaxis against infection during peritoneal dialysis was tested in a r and om double-blind study of 95 dialyses performed in 36 patients . Although the two cases of clinical peritonitis observed occurred in the placebo group , this observation was not statistically significant . The number of positive cultures obtained from the dialysate returns , however , was significantly greater in the placebo group . The duration of the dialysis did not correlate with the finding of bacteria in the dialysate returns or with the development of clinical peritonitis Infection is the Achilles heel of peritoneal dialysis . Exit site mupirocin prevents Staphylococcus aureus peritoneal dialysis ( PD ) infections but does not reduce Pseudomonas aeruginosa or other Gram-negative infections , which are associated with considerable morbidity and sometimes death . Patients from three centers ( 53 % incident to PD and 47 % prevalent ) were r and omized in a double-blinded manner to daily mupirocin or gentamicin cream to the catheter exit site . Infections were tracked prospect ively by organism and expressed as episodes per dialysis-year at risk . A total of 133 patients were r and omized , 67 to gentamicin and 66 to mupirocin cream . Catheter infection rates were 0.23/yr with gentamicin cream versus 0.54/yr with mupirocin ( P = 0.005 ) . Time to first catheter infection was longer using gentamicin ( P = 0.03 ) . There were no P. aeruginosa catheter infections using gentamicin compared with 0.11/yr using mupirocin ( P < 0.003 ) . S. aureus exit site infections were infrequent in both groups ( 0.06 and 0.08/yr ; P = 0.44 ) . Peritonitis rates were 0.34/yr versus 0.52/yr ( P = 0.03 ) , with a striking decrease in Gram-negative peritonitis ( 0.02/yr versus 0.15/yr ; P = 0.003 ) using gentamicin compared with mupirocin cream , respectively . Gentamicin use was a significant predictor of lower peritonitis rates ( relative risk , 0.52 ; 95 % confidence interval , 0.29 to 0.93 ; P < 0.03 ) , controlling for center and incident versus prevalent patients . Gentamicin cream applied daily to the peritoneal catheter exit site reduced P. aeruginosa and other Gram-negative catheter infections and reduced peritonitis by 35 % , particularly Gram-negative organisms . Gentamicin cream was as effective as mupirocin in preventing S. aureus infections . Daily gentamicin cream at the exit site should be the prophylaxis of choice for PD patients We have studied the efficacy of topical Mupirocin for elimination of Staphylococcus aureus ( Staph . aureus ) nasal carriage in CAPD patients . Staph . aureus nasal carriers in our CAPD program were r and omized to one of two groups : Group 1 , treated with Mupirocin , and Group 2 , treated with neomycin sulphate nasal ointment . The prevalence of Staph . aureus nasal colonization was 44 % for patients ( 24/54 ) and 17 % for dialysis partners ( 5/29 ) . Group 1 included 11 patients and 1 partner , and Group 2 , 8 patients and 2 partners . In Group 1 , the eradication rate was 100 % , and the recolonization rate was 0 , 8 , 41 , 55 and 66 % at 1 , 2 , 3 , 6 and 10 months . In Group 2 , the eradication rate was 40 % , with a recolonization rate of 0.25 and 75 % at 1 , 2 and 3 months . Re-treatment with mupirocin was successful in 66 % of the cases , compared to 20 % for neomycin . The MIC90 of mupirocin for Staph . aureus was 0.5 mcg/mL , with an increase to 4 mcg/mL towards the end of the study . During the study period , there was a very low incidence of Staph . aureus peritonitis or catheter-related infections in patients treated with mupirocin . Secondary effects of mupirocin were negligible . Mupirocin is more effective than neomycin sulphate for the elimination of Staph . aureus nasal colonization in patients undergoing CAPD . Periodic re-treatment is frequently necessary , given the significant recolonization rate This study evaluates the dialysis-related infection rate in children receiving peritoneal dialysis with Staphylococcus aureus nasal carriage . Children with S. aureus nasal carriage were r and omized to treatment with rifampin and bacitracin or no treatment . The children were observed for one month after r and omization for evidence of a S. aureus dialysis-related infection . Individuals with nasal carriage had a higher incidence of S. aureus dialysis-related infection than those patients without carriage ( p < 0.05 ) . Those children treated for nasal carriage had a lower dialysis-related infection rate than those who were untreated ( p < 0.05 ) . We conclude that children receiving peritoneal dialysis with nasal carriage of S. aureus are at a greater risk of developing a S. aureus dialysis-related infection . The treatment of nasal carriage in this population decreased the risk of a S. aureus dialysis-related infection ♦ Background : The HONEYPOT study is a multicenter , open-label , blinded- outcome , r and omized controlled trial design ed to determine whether , compared with st and ard topical application of mupirocin for nasal staphylococcal carriage , exit-site application of antibacterial honey reduces the rate of catheter-associated infections in peritoneal dialysis patients . ♦ Objective : To make public the pre-specified statistical analysis principles to be adhered to and the procedures to be performed by statisticians who will analyze the data for the HONEYPOT trial . ♦ Methods : Statisticians and clinical investigators who were blinded to treatment allocation and treatment-related study results and who will remain blinded until the central data base is locked for final data extraction and analysis determined the statistical methods and procedures to be used for analysis and wrote the statistical analysis plan . The plan describes basic analysis principles , methods for dealing with a range of commonly encountered data analysis issues , and the specific statistical procedures for analyzing the primary , secondary , and safety outcomes . ♦ Results : A statistical analysis plan containing the pre-specified principles , methods , and procedures to be adhered to in the analysis of the data from the HONEYPOT trial was developed in accordance with international guidelines . The structure and content of the plan provide sufficient detail to meet the guidelines on statistical principles for clinical trials produced by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use . ♦ Conclusions : Making public the pre-specified statistical analysis plan for the HONEYPOT trial minimizes the potential for bias in the analysis of trial data and the interpretation and reporting of trial results Exit site infection is a major risk factor for the development of peritonitis in continuous ambulatory peritoneal dialysis . The frequency of infection can be reduced by scrupulous exit site care with or without topical antiseptics . A r and omized trial was performed of 149 catheters in 130 patients to assess any additional benefits conferred by the use of povidine iodine dry powder spray at dressing changes over an existing strict protocol of exit care . Exit infections occurred in 14 ( 18 % ) of 77 patients using spray and in 15 ( 21 % ) of 72 patients not using spray . The risk of peritonitis was also similar in each group . The proportion of infections caused by Staphylococcus aureus was reduced in the spray group , but those caused by Pseudomonas aeruginosa were increased . Rash occurred in 6 % of those using the spray . The use of the spray did not therefore seem justified Over a three-year period , 217 episodes of bacterial peritonitis occurred in 183 patient years . Thirty-seven episodes were due to Staphylococcus aureus and 19 ( 51 % ) of these required removal of the catheter to eradicate infection . This compared with catheter loss in 4/63 ( 6.3 % ) coagulase negative staphylococci infections ( p < 0.001 ) ; 7/67 ( 9.5 % ) culture negative peritonitis ( p < 0.001 ) ; and 10/30 ( 33.3 % ) episodes due to gram-negative organisms ( p < 0.05 ) . Over half ( 51.3 % ) the episodes due to S. aureus were associated with exit-site infections , and this rose to 100 % ( 10/10 ) with recurrent peritonitis ( p < 0.01 ) . A prospect i ve analysis of nasal carriage and exit-site infections due to S. aureus was carried out in 87 patients . Exit-site infections were present in 21 ( 24 % ) , almost entirely due to different strains as judged by sensitivity patterns and phage typing . Nasal carriage , defined as two positive swabs within the study period , was present in 20 ( 23 % ) patients . Fourteen ( 70 % ) of these had exit site infections due to the same strain as that isolated from the nose , whereas no patient grew different strains from either site . Nasal carriage increased the risk of infection sixfold ( p < 0.001 ) Background The use of peritoneal dialysis ( PD ) has declined in the United States over the past decade and technique failure is also reportedly higher in PD compared to hemodialysis ( HD ) , but there are little data in the United States addressing the factors and outcomes associated with switching modalities from PD to HD . Methods In a prospect i ve cohort study of 262 PD patients enrolled from 28 peritoneal dialysis clinics in 13 U.S. states , we examined potential predictors of switching from PD to HD ( including demographics , clinical factors , and laboratory values ) and the association of switching with mortality . Cox proportional hazards regression was used to assess relative hazards ( RH ) of switching and of mortality in PD patients who switched to HD . Results Among 262 PD patients , 24.8 % switched to HD ; with more than 70 % switching within the first 2 years . Infectious peritonitis was the leading cause of switching . Patients of black race and with higher body mass index were significantly more likely to switch from PD to HD , RH ( 95 % CI ) of 5.01 ( 1.15–21.8 ) for black versus white and 1.09 ( 1.03–1.16 ) per 1 kg/m2 increase in BMI , respectively . There was no difference in survival between switchers and non-switchers , RH ( 95 % CI ) of 0.89 ( 0.41–1.93 ) . ConclusionS witching from PD to HD occurs early and the rate is high , threatening long-term viability of PD programs . Several patient characteristics were associated with the risk of switching . However , there was no survival difference between switchers and non-switchers , reassuring providers and patients that PD technique failure is not necessarily associated with poor prognosis ♦ Background : One of the most common and severe complications affecting peritoneal dialysis ( PD ) patients is exit-site infection of the peritoneal catheter ; it is therefore of vital importance to prevent it . This complication has a negative impact on the success of the technique . In spite of this , there are no clear guidelines concerning how to take care of the exit site . The objective of this study was to assess the efficacy of polyhexanide in preventing exit-site infection over a 12-month period . ♦ Methods : We design ed a single-center , prospect i ve , open-labeled , r and omized controlled clinical trial with parallel groups . Requirements for participation in the study included implantation of the peritoneal catheter at least six weeks before entering the study and no infectious complications requiring either hospital admission or antibiotic treatment for at least three months before entering into the study . Patients were r and omized to be daily cured as follows : Group A : traditional care with saline serum and povidone-iodine ; and Group B : polyhexanide solution . Exit sites were evaluated at baseline and every four to six weeks or if any event occurred , according to the Twardowski criteria . ♦ Results : Of the 60 included patients , 46 completed the 12-month follow-up period . Six underwent transplantation , five died and three were transferred to hemodialysis ( HD ) . The treatment was well tolerated , with no side effects nor ab and onments due to such effects . Throughout the study period , six patients ( 20 % ) undergoing traditional care and only two ( 6,7 % ) receiving polyhexanide developed an exit-site infection ( p = 0.032 ) . There were a total number of 12 infections ; nine occurred in patients following the traditional approach and only three in patients treated with polyhexanide ( p = 0.037 ) . The germs responsible for the infections were : S. aureus ( six cases ) , Corynebacterium jeikeium ( two cases ) and P. aeruginosa ( one case ) in the saline serum and povidone-iodine group and P. aeruginosa ( three cases ) in the polyhexanide group . The mean rate of exit-site infection was 1 episode/36.6 patient-months for the traditional care group and 1 episode/102.7 patient-months for the polyhexanide group ( p = 0.017 ) . Patients following the traditional treatment required fewer days to get infected than those using polyhexanide ( p = 0.033 ; log rank : 4.2 ) . ♦ Conclusions : These results show that using polyhexanide is efficient for the prevention of exit-site infections . Patients treated with this product suffer from fewer infections and need more time to become infected . Polyhexanide application is painless , no allergies have been described and it is well tolerated by patients . We therefore propose that it may be used routinely from now on for the care of healthy exit site A prospect i ve r and omized study of the prevention of c and ida peritonitis ( CP ) in continuous ambulatory peritoneal dialysis patients using oral nystatin given concomitantly with antibiotic therapy was carried out for 2 years . Patients were r and omized into two groups . Nystatin tablets 500,000 units four times a day were given to group 1 but not group 2 patients whenever antibiotics were prescribed . There were 199 patients at risk ( mean follow-up , 18.0 months ) in group 1 and 198 patients at risk ( mean follow-up , 16.6 months ) in group 2 . The peritonitis and antibiotic prescription rates were comparable between the two groups . There were four episodes of CP in four patients in group 1 and 12 episodes in 11 patients in group 2 . The probability of CP-free survival at 2 years was higher in group 1 compared with group 2 ( 0.974 v 0.915 ; P < 0.05 ) . However , only three ( 75 % ) CP episodes in group 1 and six ( 50 % ) in group 2 were considered " antibiotics related . " The incidence of antibiotics-related CP was 1.39 and 3.19 per 100 peritonitis episodes and 0.66 and 1.43 per 100 antibiotic prescriptions in groups 1 and 2 , respectively ( P = NS ) . We conclude that oral nystatin prophylaxis with each antibiotic prescription reduced the rate of CP in patients on continuous ambulatory peritoneal dialysis irrespective of its apparent temporal relationship to antibiotic prescription Staphylococcal infections are a major cause of catheter infections and peritonitis in peritoneal dialysis patients . Since catheter-related infections are associated with nasal carriage of Staphylococcus aureus in this population , we studied the effect of intermittent rifampin , an antibiotic known to decrease S aureus nasal carriage , on catheter-related infections and peritonitis . We r and omly assigned 64 patients to receive either rifampin 300 mg twice daily for 5 days every 3 months or no treatment . The rifampin-treated patients had a significant delay in time to first catheter-related infection ( P less than 0.015 ) and significantly fewer catheter-related infections overall ( P less than 0.001 ) . The catheter-related infection rate in rifampin-treated patients was .26 per patient-year versus .93 per patient-year in untreated patients . Multivariate analysis defined baseline colonization of nares or catheter exit-site and prior renal transplant as risk factors for catheter-related infections . There was no significant difference in peritonitis rates between groups , although the trend was for a delayed time to first episodes and fewer episodes in rifampin-treated patients . Adverse effects necessitated withdrawal of rifampin in four patients . We conclude that intermittent rifampin administration is effective in decreasing catheter-related infections in a peritoneal dialysis population Objective We evaluated the effectiveness of local application of mupirocin ointment at the catheter exit site in preventing exit-site infection and peritonitis attributable to gram-positive organisms in continuous ambulatory peritoneal dialysis patients . Methods This prospect i ve r and omized controlled trial included 154 patients . They were r and omly allocated to a mupirocin-treated group ( group M ) and a control group ( group C ) . Group M included 73 patients ( 47.4 % ) who were instructed to apply mupirocin ointment to the catheter exit site once daily after the routine daily exit-site dressing . Group C included 81 patients ( 52.6 % ) who continued their usual daily exit-site care without applying mupirocin . The two groups were followed to see whether there would be any difference in the frequency of exit-site infection and peritonitis or in the infecting organisms . Results Interim data were collected at 5 months after the start of the study . Those data showed a significantly lower incidence of exit-site infection and peritonitis attributable to gram-positive organisms in group M as compared with group C. The incidence of gram-positive exit-site infection in group C was 1 episode per 36.8 patient – months ; in group M , the incidence was 1 episode per ∞ patient – months ( 0 incidence in 5 months , p < 0.05 ) . The incidence of gram-positive peritonitis in group C was 1 episode per 40.5 patient – months ; in group M , the incidence was 1 episode per 365 patient – months ( p < 0.05 ) . Mupirocin treatment had no significant effect on the incidence of exit-site infection and peritonitis attributable to other organisms . Before mupirocin treatment , we saw a trend toward higher infection rates in diabetic patients and nasal carriers of Staphylococcus aureus as compared with non diabetic patients and nasal non carriers , although the differences were not statistically significant . Mupirocin brought the infection rate attributable to gram-positive organisms to an equally low level in diabetic and non-diabetic patients , and in nasal carriers and nasal non carriers of S. aureus . No adverse effect of local application of mupirocin was reported . Conclusion Local application of mupirocin ointment at the catheter exit site is a safe and effective method of preventing exit-site infection and peritonitis involving gram-positive organisms BACKGROUND When a peritoneal dialysis catheter is inserted intra-abdominally in a patient starting peritoneal dialysis ( PD ) there is always a risk for postoperative wound infection and peritonitis . At our centre , PD is started immediately after the dialysis catheter is inserted . This may increase the postoperative risk for peritonitis and wound infection . The aim of this prospect i ve , r and omized , study was to evaluate whether the incidence of microbial growth postoperatively ( within 10 days ) after catheter insertion could be reduced by prophylactic antibiotic therapy . SUBJECTS AND METHODS During a period of 27 months , 38 patients , who consecutively entered the PD programme , ( 11 women and 27 men , mean age 57 years ) were included in the study . Eighteen patients were given cefuroxime 1.5 g i.v . preoperatively and 250 mg i.p . in the first dialysis bag ( containing 1 litre fluid ) as prophylaxis . Twenty patients were not given prophylactic antibiotics ( control group ) . All catheter insertions were performed in an operating theatre by the same surgeons using the same technique . RESULTS In the test group , none of the patients showed microbial growth in the dialysis fluid during the post-operative period , while in the control group six of 20 patients ( 30 % ) suffered from such growth ( P = 0.021 ) . CONCLUSION Prophylactic treatment by cefuroxime i.v . pre- and i.p . perioperatively may reduce the risk for microbial growth and peritonitis after insertion of a Tenckhoff catheter Ciprofloxacin is increasingly used to treat peritoneal dialysis related peritonitis . We studied the pharmacokinetics of intraperitoneally administered ciprofloxacin in six uninfected CCPD patients . In a r and omized cross-over setting ciprofloxacin was added either to a long dwell exchange ( lastbag ) or to four short dwell exchanges ( dwell time 1.5 h ) . Addition of ciprofloxacin ( 25 mg/l ) during the four short dwell exchanges result ed in dialysate levels of 21.1 - 13.3 mg/l during these exchanges . In the subsequent last bag devoid of ciprofloxacin a dialysate Cmax , D of 1.38 mg/l was observed at 30 min . Mean + /- SD serum Cmax , S was 0.59 + /- 0.29 mg/l after 5.4 h. Instillation of 100 mg/l ciprofloxacin in the last-bag yielded Cmax , D of 99.1 mg/l , falling with a t1/2 of 3.3 h towards levels < 2 mg/l at 19.8 h. A mean + /- SD serum Cmax , S of 0.69 + /- 0.19 was reached after 4 h. During four subsequent 1.5h exchanges without ciprofloxacin dialysate levels were < 0.1 mg/l . Instillation of 25 mg/l ciprofloxacin in the last-bag yielded a Cmax , D of 21.7 mg/l , falling towards levels < 2 mg/l at 15 h with a t1/2 of 3.85 h. A mean + /- SD serum Cmax , S of 0.26 + /- 0.03 was reached after 8 h. We conclude that the rapid absorption of ciprofloxacin from the dialysate into the tissues requires ciprofloxacin to be administered to all CCPD bags to ensure bactericidal dialysate levels . When therapeutic serum levels are required higher intraperitoneal doses or an oral or i.v . loading dose is warranted A total of 127 patients from 8 hospitals were r and omized into 1 of 2 exit-site care regimes to evaluate their effect on rate of exit-site infection ( ESI ) . Group 1 used povidone iodine and nonocclusive dressings changed 2 to 3 times weekly ; Group 2 simply cleansed the exit site with nondisinfectant soap and water . Incidence , cause , duration , and treatment of ESI and peritonitis ( P ) were noted . Groups were analysed for age , sex , end-stage renal disease ( ESRD ) , catheter , and systems . Total cumulative follow up time was 95.6 years . There was a significantly higher rate ( p = 0.0183 ) of ESI in Group 2 ( soap and water ) . The mean rate of ESI was 0.27 episodes/patient year for Group 1 versus 0.71 episodes/patient year for Group 2 . Rates of P for the two groups were not significantly different ( p greater than 0.50 ) : 0.446 episodes/year for Group 1 versus 0.574 episodes/year for Group 2 . S. aureus was responsible for 83 % of ESI in Group 1 and 67 % of ESI in Group 2 . Protective dressing with a disinfectant is associated with significantly less ESI than minimum care . However , further research in exit-site care aim ed specifically at reducing S. aureus infection is still required The role of vancomycin and other antibiotics in treatment of acute peritonitis in peritoneal dialysis patients is well established . However , the role of preoperative vancomycin or cephalosporins in preventing early infection in newly placed peritoneal dialysis catheters remains controversial . We performed a prospect i ve r and omized study to examine the role of vancomycin or cefazolin prophylaxis in decreasing the incidence of postoperative peritonitis . Over 8-year period , 265 patients undergoing 305 permanent peritoneal catheter placement procedures were r and omized into three groups . Group I ( 103 procedures ) received a single intravenous ( i.v . ) dose of 1000 mg vancomycin 12 hours before the peritoneal catheter placement procedure . Group II ( 102 procedures ) received a single i.v . dose of 1000 mg of Ancef ( cefazolin ) 3 hours before the procedure . Group III ( 100 procedures ) received no antibiotics preoperatively for a least one week before the procedure . Patients were monitored for peritonitis during the following 14 days . Peritonitis developed in 1 patient ( 1 % ) in Group I ( vancomycin group ) compared to 12 patients ( 12 % ) in Group III ( control group ) , p = 0.002 , and in 9 patients ( 9 % ) in Group II ( cefazolin group ) compared to Group III , p = 0.68 . We conclude that the use of preoperative single-dose i.v . vancomycin prophylaxis for permanent peritoneal dialysis catheter placement reduces the risk of postoperative peritonitis . Cefazolin did not achieve a statistically significant difference from the control group and may not provide adequate prophylaxis The enrollment of Mexican continuous ambulatory peritoneal dialysis ( CAPD ) patients in a r and omized controlled study began in June 1998 ( 1 ) . A prescription of 4 × 2 L exchanges was compared to an increased dose , achieved by increasing the exchange volume and /or adding an extra nighttime exchange by use of a device . The study included incident and prevalent patients that were between 18 and 70 years of age and had a peritoneal clearance of less than 60 L/ week/1.73 m2 . Patients that were on immunosuppression , had active malignancies , abdominal hernias , cardiac failure , or were positive for hepatitis B or HIV were excluded . Almost 1000 patients were enrolled , 484 to the control group and 481 to the intervention group . The clinical characteristics of the groups were not different . A substantial proportion of the patients in each group were anuric ( 56 % control , 54 % intervention ) . The mean peritoneal Kt/V and creatinine clearances were identical at the start in the two groups but , as planned in the intervention , were well separated for the period of the trial . Total creatinine clearance , averaged across the study duration , was 54.1 versus 62.9 L/week/1.73 m2 ( p < 0.001 ) , and total Kt/V was 1.80 and 2.27 per week ( p < 0.001 ) , for control and intervention groups , respectively . To the surprise of the PD community , there was absolutely no difference in survival between the two groups ( Table 1 ) . Furthermore , subgroup analyses ( based on serum albumin , nPNA , prevalent or incident , diabetic or not , age , and anuria ) were done . No difference in survival was found between the two groups in any of these subgroup analyses . What does this study mean ? Should we change our practice of PD and reduce the dose of dialysis ? Emphatically , the answer to this is NO ! ! The Adequacy of Peritoneal Dialysis in Mexico ( ADEMEX ) study looked at one primary outcome : death . Secondary outcomes included hospitalization ( no difference in the two groups ) , therapy-related complications , correction of anemia , and effects on nutritional status . Quality of life was measured but the results were not included in the presented paper . Therefore , the study did not , nor was it intended to answer the question of what level of small molecule clearance is needed to prevent uremic symptoms . What is adequate dialysis ? Adequate dialysis is that level of dialysis at which the patient feels well and is free of symptoms such as nausea , anorexia , fatigue , sleeplessness , and difficulty concentrating . The welldialyzed patient , ideally , should be fully functional and have a good quality of life with minimal hospitalizations . What do we know about the results of the ADEMEX trial ? If we examine reasons for dropout , we see that 5 % of patients in the control arm ( 4 × 2 L/ day ) dropped out due to uremia , compared to zero in the treated , higher dose group ( Figure 1 ) . Why then was technique failure no different in the two groups ? Dropout from the study due to “ discomfort , ” hernia development , and peritonitis ( despite no increase in the rate of peritonitis ) was more common in the treated group . Except for the last reason , these results are easy to underst and , since the study was not blinded . A 5 % dropout rate due to uremia suggests that , for some patients , a prescription of 4 × 2 L is not enough . What were the causes of death in the two groups ? The patients with the increased prescription were Nasal carriage of Staphylococcus aureus is a risk factor for catheter-related infections with S. aureus in patients on chronic peritoneal dialysis ( CPD ) . In children , S. aureus may transmitted to the catheter either from the patients ' nares , or from the nares of caregiving carriers . As part of a prospect i ve trial on the efficacy of mupirocin prophylaxis in children on CPD and their caregivers , we evaluated the prevalence of S. aureus carriage in 92 families of pediatric CPD patients . Patients and their caregivers ( usually both parents ) were screened by three nasal cultures obtained within four weeks . In 62 % of the families , neither the patients nor any caregiver carried S. aureus . In 23 % , the patient or at least one caregiver ( sometimes both ) was identified as a carrier . In 15 % , at least one caregiver , but not the patient , was colonized with S. aureus . During further follow-up by once-monthly nasal cultures , 5 of the 57 initially negative patients developed S. aureus colonization , and in two families , at least one caregiver turned positive . Including these " occasional " carriers , the cumulative likelihood of one or several family members carrying S. aureus gradually increased to a plateau of about 55 % after 6 observation months . Susceptibility rates of cultured S. aureus were 100 % for vancomycin , 99 % for aminoglycosides , 95 % for piperacillin/tazobactam , 94 % for cephalosporins , and 15 % for ampicillin . In two patients and two caregivers ( four different families ) , methicillin-resistant S. aureus was found . Three isolates from three different families were resistant to mupirocin . We conclude that S. aureus colonization is common in families of children on CPD . While 85 % of carrier families are detected by 3 sequential nose cultures in patient and caregivers , up to 9 cultures may be required in " occasional " carriers Introduction . The application of mupirocin to the exit-site in peritoneal dialysis ( PD ) patients decreases peritonitis and exit-site infection ( ESI ) considerably . However , long-term application of mupirocin may result in the development of methicillin- and mupirocin-resistant strains . In this study , we aim ed to investigate the effect of once-a-week vs. thrice-a-week application of mupirocin on mupirocin and methicillin resistance in PD patients . Patients and methods . Thirty-six patients were divided into two groups based on frequency of weekly mupirocin application at the catheter exit-site . In group 1 , patients were r and omly assigned to apply mupirocin once a week ( n = 18 ) , while patients in group 2 applied mupirocin three times a week ( n = 18 ) . We obtained cultures from the nares , inguinal area , axillae , and the exit site . The microorganisms reproduced , and the resistance to mupirocin and methicillin were recorded . Three years of follow-up of these patients were also recorded . Results . During the three-year follow-up period , seven episodes ( 0.26 episodes/patient-years ) of ESI and 13 episodes ( 0.36 episodes/patient-years ) of peritonitis were determined in group 1 , and one episode of ESI ( 0.11 episodes/patient-years ) and six episodes ( 0.24 episodes/patient-years ) of peritonitis were determined in group 2 . The rate of peritonitis and ESI were , respectively , 56 % and 92 % lower in group 2 when compared to group I ( p = 0.041 and p = 0.038 , respectively ) . Throughout three years , a total of 1852 sample s were analyzed . In group 1 , S. aureus reproduction rate and mupirocin resistance were 2.11 % and 0.2 % , respectively . In group 2 , S. aureus reproduction rate was 0.93 % , and no mupirocin resistance was observed . Methicillin-resistant S. aureus was not observed in both groups . Coagulase-negative staphylococcus ( CNS ) reproduction rate was 70.56 % ( mupirocin resistance : 59.87 % and methicillin resistance : 33.7 % ) and 72.56 % ( mupirocin resistance : 64.7 % and methicillin resistance : 33.3 % ) in groups 1 and 2 , respectively . No peritonitis and ESI secondary to S. aureus and fungal agents were observed in both groups . Conclusion . The thrice-a-week application of mupirocin seems to be more efficient when compared to once-a-week application of mupirocin . Long-term application of mupirocin may cause the development of mupirocin- and methicillin-resistant strains , especially in CNS , which results in a difficulty for struggling against infections The study objective was to measure the benefits of elimination of nasal carriage of Staphylococcus aureus by calcium mupirocin ointment in patients undergoing continuous ambulatory peritoneal dialysis . The design was a prospect i ve , placebo-controlled , r and omized clinical trial . The subjects were 267 patients recruited from nine renal units in Belgium , France and the UK . The main outcome measures were the rate of catheter exit site infection ( ESI ) , rates of other infections and healthcare costs from the perspective of a hospital budget-holder . The rate of ESI caused by S. aureus was significantly reduced from one in 28.1 patient months to one in 99.3 patient months ( P = 0.006 ) and there were also non-significant trends towards lower rates of ESI caused by any organism and peritonitis caused by S. aureus . In comparison with the placebo group , patients in the mupirocin group with ESI had lower antibiotic ( P = 0.02 ) and hospitalization costs ( P = 0.065 ) . However , overall costs of antibiotic treatment , for all infections combined , were not significantly different ( P = 0.2 ) and total antibiotic costs ( including mupirocin ) were significantly higher in the mupirocin group ( P = 0.001 ) . Mupirocin prophylaxis would have been cost-neutral if the rate of ESI increased to > 75 % in the placebo group , or if all healthcare costs increased by 40 % , or if the cost of screening was reduced from Pound Sterling 15 to Pound Sterling 3 per patient , or if the cost of mupirocin treatment was reduced from Pound Sterling 93 to Pound Sterling 40 per patient year . In conclusion , savings in healthcare costs are unlikely to be sufficiently great to offset the cost of mupirocin and screening for nasal carriage of S. aureus . The decision about whether or not to implement mupirocin should depend on a local analysis of the value of preventing ESIs caused by S. aureus sixty-one new continuous ambulatory peritoneal dialysis ( CAPD ) patients were allocated to a Y connector disinfectant ( Amuchina , Italy ) and 63 to st and ard systems ( Baxter Systems II & III ) in a r and omized clinical trial addressing peritonitis rates in 8 CAPD programs in 6 Canadian cities . In the Y connector-disinfectant group , 15 patients experienced 21 episodes of peritonitis in 452 patient-months or 1 per 21.53 patient-months . In the st and ard systems group , 30 patients experienced 47 episodes of peritonitis in 467 patient-months or 1 per 9.93 patient-months ( p = 0.009 ) . The peritonitis risk reduction was 61 % ( 95 % confidence limits 27–79 % ) . Exit-site infections occurred in 36 % of each group . Prior to the development of exit -site infection , the monthly risk for peritonitis was 3.12 % for the Y connector disinfectant system and 7.37 % for the st and ard system . After an exit -site infection , these probabilities increased to 6.15 % and 15.47 % , respectively . Skin organisms were responsible for peritonitis in 8/21 ( 38 % ) in the Y connector-disinfectant group and 30/47 ( 64 % ) in the st and ard group . There were 75 days hospitalized for peritonitis in the Y connector-disinfectant group compared to 257 days for the st and ard group . The Y connector disinfectant system decreases the peritonitis rate through its effect on skin organisms . Exit -site infections are a major source of organisms responsible for peritonitis Catheter-related infections remain a significant cause of method failure in chronic peritoneal dialysis ( PD ) therapy . Given the increasing antibiotic resistance , such nonpharmacological strategies as local silver devices attract more interest . To establish whether a silver ring device ( design ed by Grosse-Siestrup in 1992 ) mounted onto the PD catheter and placed at the exit site at skin level is effective in preventing exit-site and other catheter-related infections , a prospect i ve 12-month , multicenter , controlled study stratified by diabetes status was conducted . The study subjects were assessed by an extensive structured inventory , including a broad spectrum of control variables , such as age , body mass index ( BMI ) , Staphylococcus aureus carrier status , catheter features , mode and quality of PD therapy , comorbidity , and psychosocial rehabilitation . Ten experienced German outpatient dialysis centers ( seven adult , three pediatric ) participated in the trial . All eligible patients ( n=195 ) from the study area without catheter-related infections during the ascertainment period were included ( incidental subjects undergoing PD therapy for at least 3 months ) . The main outcome measures were the occurrence of first exit-site infections ( primary study end point ) , sinus tract/tunnel infection , and peritonitis . Ninety-seven patients were assigned to the silver ring and 98 patients to the control group . Baseline characteristics of age , sex , proportion of pediatric and incidental patients , S aureus carrier status , and other variables were similar in both groups . The incidence of infections in the silver ring group versus the control group was as follows : 23 of 97 versus 16 of 98 patients had exit-site infections , 12 of 97 versus 12 of 98 patients had sinus tract/tunnel infections , 16 of 97 versus 18 of 98 patients had peritonitis , respectively . Kaplan-Meier analysis for the probability of an infection-free interval showed no statistical difference ( log-rank test ) between the two groups . Displacement of the silver ring contributed to study termination in 6 % of the study group patients , including two patients with catheter loss . Univariate analysis and multiple logistic regression identified younger age ( < 50 years ) , low serum albumin level ( < 35 g/L ) , number of previously placed PD catheters , short cuff-exit distance ( < 2 cm ) , and S aureus nasal carriage as risk factors for the development of exit-site infections . In conclusion , our study does not show any benefit of the silver ring in preventing catheter-related infections in PD patients . Thus , prevention of infection-related method failure in PD still has to rely on conventional antibiotic treatment strategies and less so on alternative methods BACKGROUND There is a paucity of evidence to guide the best strategy for prevention of peritoneal-dialysis-related infections . Antibacterial honey has shown promise as a novel , cheap , effective , topical prophylactic agent without inducing microbial resistance . We therefore assessed whether daily application of honey at the exit site would increase the time to peritoneal-dialysis-related infections compared with st and ard exit-site care plus intranasal mupirocin prophylaxis for nasal carriers of Staphylococcus aureus . METHODS In this open-label trial undertaken in 26 centres in Australia and New Zeal and , participants undergoing peritoneal dialysis were r and omly assigned in a 1:1 ratio with an adaptive allocation algorithm to daily topical exit-site application of antibacterial honey plus st and ard exit-site care or intranasal mupirocin prophylaxis ( only in carriers of nasal S aureus ) plus st and ard exit-site care ( control group ) . The primary endpoint was time to first infection related to peritoneal dialysis ( exit-site infection , tunnel infection , or peritonitis ) . The trial is registered with the Australian New Zeal and Clinical Trials Registry , number 12607000537459 . FINDINGS Of 371 participants , 186 were assigned to the honey group and 185 to the control group . The median peritoneal-dialysis-related infection-free survival times were not significantly different in the honey ( 16·0 months [ IQR not estimable ] ) and control groups ( 17·7 months [ not estimable ] ; unadjusted hazard ratio 1·12 , 95 % CI 0·83 - 1·51 ; p=0·47 ) . In the subgroup analyses , honey increased the risks of both the primary endpoint ( 1·85 , 1·05 - 3·24 ; p=0·03 ) and peritonitis ( 2·25 , 1·16 - 4·36 ) in participants with diabetes . The incidences of serious adverse events ( 298 vs 327 , respectively ; p=0·1 ) and deaths ( 14 vs 18 , respectively ; p=0·9 ) were not significantly different in the honey and control groups . 11 ( 6 % ) participants in the honey group had local skin reactions . INTERPRETATION The findings of this trial show that honey can not be recommended routinely for the prevention of peritoneal-dialysis-related infections . FUNDING Baxter Healthcare , Queensl and Government , Comvita , and Gambro In a prospect i ve cohort study of 680 incident continuous peritoneal dialysis ( PD ) patients in North America , dialysis in the United States compared with Canada was associated with a relative risk ( RR ) of death of 1.93 ( 95 % confidence interval [ CI ] , 1.14 to 3.28 ) . The 2-yr survival probability was 79.7 % in Canada and 63.2 % in the United States . This difference was not explained by race , age , gender , functional status , insulin-dependent diabetes mellitus , history of cardiovascular disease ( CVD ) , nutritional status , or adequacy of dialysis . Other potential explanatory variables were further evaluated . These included severity of CVD , residual renal function , race , differential transfer to hemodialysis or transplantation , patient compliance , modality selection bias , and incidence of endstage renal disease requiring dialysis . Cardiovascular morbidity and peritonitis probabilities were compared . The CVD severity index was not different between countries ; the RR risk associated with dialysis in the United States remained high at 1.87 ( 95 % CI , 1.09 to 3.19 ) . Residual renal function at initiation of dialysis was not different between countries . The 2-yr survival for Caucasians was 77 % in Canada and 55 % in the United States . There was no difference in the probability of transfer to hemodialysis or transplantation . The RR of a nonfatal cardiovascular event in the United States compared with Canada was 1.80 ( 95 % CI , 1.21 to 2.67 ) . There was no difference in time to first peritonitis . The observed to predicted creatinine ratio , as an estimate of compliance , was 1.13 in Canada and 1.00 in the United States . The prevalence of PD in the study centers was 48 % in Canada and 22 % in the United States . The incidence of new dialysis patients in 1992 was 100/million population in Canada compared with 211/ million in the United States . The survival difference is not explained by age , gender , insulin-dependent diabetes mellitus , nutritional status , or adequacy of dialysis . Neither is it explained by race , severity of CVD , transfer to hemodialysis , transplantation , or an estimate of compliance . The lower proportion of patients receiving PD in the United States may represent a selection bias of uncertain direction . The higher acceptance rate for dialysis in the United States may explain , in part , the greater cardiovascular morbidity and the decreased survival observed 124 stable CAPD patients from 8 Australian and 3 New Zeal and centers were r and omly assigned in a blinded fashion to one of two groups to study the effect of vaccination using commercial preparations consisting of a combined staphylococcus toxoid and whole killed staphylococci ( SB ) or normal saline solution ( SS ) on the incidence of peritonitis and exit site infection and S. aureus nasal carriage over a 12-month prospect i ve period . In addition , levels of IgG , IgA , IgM , C3 and C4 were monitored during the trial period in serum and dialysate ; serum levels of anti-alpha hemolysin and dialysate levels of fibronectin and specific antistaphylococcal antibodies were also measured . Over the period , treatment with SB or SS did not affect the incidence of peritonitis , catheter-related infection or S. aureus nasal carriage . However , vaccination with SB elicited a significant increase in the level of serum anti-alpha hemolysin throughout the 12 month duration of the study , although the level of increase was unrelated to the subsequent rate of peritonitis . Vaccination with SB but not SS elicited a significant increase in the dialysate level of specific antibodies against S. aureus . Serum levels of IgG , IgA , IgM , complement C3 and C4 were within the normal range in the CAPD patients studied and remained unaffected by vaccination with SB . In addition , dialysate levels of IgG , IgA , IgM , complement C3 and C4 were 50 - 100 times lower than corresponding serum levels and remained unaffected by vaccination . In summary , immunisation with an anti-staphylococcal agent was not successful in reducing peritonitis or exit site infection in CAPD patients Some studies have demonstrated the efficacy and safety of intraperitoneal ( i.p . ) urokinase in the resolution of recurrent or relapsing peritonitis , while others have not . Most studies were small , and they varied in methodology . Furthermore , the role of i.p . urokinase in shortening the duration of peritonitis or in preventing recurrence after initial peritonitis has not been examined . In addition , no previous studies have examined the role of i.p . urokinase in preventing , after first infection , catheter loss due to unresolving ( resistant ) peritonitis . Over a period of 3 years , we prospect ively r and omized into two groups all peritoneal dialysis ( PD ) patients who developed a first episode of peritonitis . Group I ( n = 40 ) received i.p . urokinase on the first day of diagnosis ( 5000 IU intraluminally in the peritoneal catheter and left for 4 hours before next exchange ) . Group II ( n = 40 ) received no urokinase . The duration of peritonitis was assessed by daily PD fluid white blood cell ( WBC ) count . Indications for catheter removal were : persistent peritonitis after four days from initiation of antibiotic therapy , or peritonitis with multiple organisms , suggesting bowel perforation . No statistically significant difference was seen between the two groups in regard to primary cause of end-stage renal disease ( ESRD ) , age , sex , race , weight , type of dialysis [ continuous ambulatory peritoneal dialysis ( CAPD ) , automated peritoneal dialysis ( APD ) , continuous cycling peritoneal dialysis ( CCPD ) ] , or duration of dialysis prior to first peritonitis . No statistically significant difference was seen between the two groups in the duration of peritonitis or in the severity of symptoms and signs of peritonitis . Neither was any difference seen in the peritonitis recurrence or relapse rate ( 10 % in the urokinase group vs 7.5 % in the control group ) . Nine patients lost their catheters ( 3 in the urokinase group : 1 Pseudomonas aeruginosa and 2 C and ida tropicalis ; 6 in the control group : 1 Klebsiella pneumonia , 1 enterococcus , 2 Pseudomonas aeruginosa , and 2 C and ida tropicalis ) . The difference in the rate of catheter loss between the two groups was not statistically significant ; it appeared to relate to the type of organism rather than to the response to urokinase . In conclusion , i.p . urokinase plays no significant role in shortening the course of peritonitis or in preventing recurrence or loss of the PD catheter . Loss of PD catheters in patients having their first peritonitis appears to be related primarily to the type of organism causing the infection BACKGROUND Dialysis-related infections are the commonest cause of catheter loss and transfer to hemodialysis . Surface modifications of the catheter that reduce infections are of major importance . OBJECTIVE The efficacy of silver-ion treated catheters in reducing dialysis-related infections was tested . METHODS The study design was a prospect i ve , r and omized controlled trial . Patients were implanted with either a silver-treated study catheter or a control catheter . Prospect i ve collection of data included infectious complications and catheter survival . RESULTS The subject groups were comprised of 67 silver-treated catheters and 72 control catheters . Demographic characteristics of the study and control groups were equal . Exit-site infection rates for the study group and control group ( 0.52 and 0.45 episodes/patient-year of dialysis respectively ) were not different by Poisson regression analysis ( p > 0.4 ) . Peritonitis rates were identical for the two groups ( 0.37 episodes/patient-year ) and were not different by Poisson analysis ( p > 0.9 ) . Antibiotic-free intervals between infections for the study and control groups were not significantly different for exit-site infections ( p = 0.58 ) , peritonitis ( p = 0.44 ) , or both infections combined ( p = 0.47 ) . Actuarial analyses showed no differences between the groups in the probability of remaining free of exit-site infection ( p > 0.2 ) or peritonitis ( p > 0.7 ) . Similarly , catheter survival was not significantly different between the groups ( p > 0.6 ) . CONCLUSION Surface modification of catheters with ion beam implantation of silver produced no clinical effect with respect to reducing dialysis-related infections The objective of this study was to compare prophylaxis for Staphylococcus aureus infections in peritoneal dialysis patients using 600 mg cyclic oral rifampin for 5 days every 3 months versus mupirocin calcium ointment 2 % applied daily to the exit site . The study design was a prospect i ve r and omized trial , controlling for S aureus nasal carriage . Eighty-two continuous ambulatory and continuous cyclic peritoneal dialysis patients ( 54 % male , 71 % white , 34 % insulin-dependent , mean pre study time on peritoneal dialysis 1.2 years ) were r and omly assigned to cyclic rifampin ( n = 41 patients ) or daily exit site mupirocin prophylaxis ( n = 41 patients ) . Mean follow-up was 1 year . S aureus catheter infection rates were 0.13/yr with mupirocin and 0.15/yr with rifampin ( P = NS ) . Both rates were significantly lower than the center 's historical rate ( the period between 1983 and 1992 ) of 0.46/yr prior to the study ( P < 0.001 ) . S aureus peritonitis rates were 0.04/yr with mupirocin and 0.02/yr with rifampin ( P = NS ) , both significantly lower than the center 's historical rate of 0.16/yr ( P < 0.02 ) . Catheter loss due to S aureus infections was 0.02/yr with mupirocin and 0/yr with rifampin ( P = NS ) , both significantly lower than the center 's historical rate of 0.12/yr ( P < 0.001 ) . There were no side effects in patients using mupirocin , but 12 % were unable to continue rifampin due to side effects . We conclude that mupirocin ointment at the exit site and cyclic oral rifampin are equally effective in reducing S aureus catheter infections . In addition , rifampin or mupirocin significantly reduced S aureus peritonitis and catheter loss due to S aureus infections . Mupirocin at the exit site provides an excellent alternative prophylaxis for S aureus infections , particularly in patients who can not tolerate oral rifampin therapy Background Peritonitis remains the most serious complication of peritoneal dialysis ( PD ) . Gram-positive organisms are among the most common causes of PD peritonitis ; however , recent trends show increasing rates of gram-negative and fungal infections . Strategies to prevent peritonitis include the use of prophylactic topical mupirocin at the site where the PD catheter exits from the abdominal wall ; however , mupirocin does not afford protection against gram-negative or fungal infections . The aim of this study is to determine if the incidence of catheter-related infections ( exit-site infection , tunnel infection , or peritonitis ) is significantly reduced by the routine application of Polysporin Triple antibiotic ointment ( Pfizer Canada , Markham , Ontario , Canada ) in comparison to mupirocin ointment . Methods and Design The Mupirocin Versus Polysporin Triple Study ( MP3 ) is a multicenter , r and omized , double-blinded controlled study comparing Polysporin Triple ( P3 ) against the current st and ard of care . The aim of the study is to recruit 200 patients being treated with or starting on PD and r and omize them to receive either mupirocin or P3 at the catheter exit site . Patients will be followed for 18 months or until death or transfer from PD to an alternate treatment modality . The primary outcome will be the time to first catheter-related infection . Catheter-related infections will be strictly defined using current guidelines and categorized into exit-site infections , infective peritonitis , or tunnel infections . The primary analysis will be an intention-to-treat analysis . Discussion The results of this study will help determine if the use of P3 is superior to mupirocin ointment in the prevention of catheter-related infections and will help guide evidence -based best practice In a study in seven large renal units in Engl and , the morbidity and mortality of all patients starting continuous ambulatory peritoneal dialysis ( CAPD ) and haemodialysis during 1983 - 85 were monitored prospect ively over a 4-year period and related to reasons for choice of therapy and potential risk factors . 610 new patients ( median age 52 years , range 3 - 80 years ) started CAPD ; 16 % had diabetes mellitus and 21 % cerebrovascular or cardiovascular disease . 329 patients ( median age 48 years , range 5 - 77 years ) started haemodialysis ; 7 % had diabetes mellitus and 17 % cerebrovascular or cardiovascular disease . The Kaplan-Meier patient survival estimates at 4 years were 74 % for haemodialysis and 62 % for CAPD ; technique survival figures for the same period were 91 % for haemodialysis and 61 % for CAPD . Cox 's proportional hazards regression analysis showed that cerebrovascular/cardiovascular disease , age over 60 years , and diabetes mellitus were important predictors for survival in CAPD patients ; there were no risk factors associated with permanent change to haemodialysis . In the haemodialysis group early change to CAPD was associated with presence of cerebrovascular or cardiovascular disease . The major cause of drop-out in both groups was transplantation . The mean length of hospital admission was 14.8 days per patient-year for CAPD and 12.4 days per patient-year for haemodialysis Objectives The primary objective of this study is to determine whether daily exit-site application of st and ardized antibacterial honey ( Medihoney Antibacterial Wound Gel ; Comvita , Te Puke , New Zeal and ) results in a reduced risk of catheter-associated infections in peritoneal dialysis ( PD ) patients compared with st and ard topical mupirocin prophylaxis of nasal staphylococcal carriers . Design Multicenter , prospect i ve , open label , r and omized controlled trial . Setting PD units throughout Australia and New Zeal and . Participants The study will include both incident and prevalent PD patients ( adults and children ) for whom informed consent can be provided . Patients will be excluded if they have had ( 1 ) a history of psychological illness or condition that interferes with their ability to underst and or comply with the requirements of the study ; ( 2 ) recent ( within 1 month ) exit-site infection , peritonitis , or tunnel infection ; ( 3 ) known hypersensitivity to , or intolerance of , honey or mupirocin ; ( 4 ) current or recent ( within 4 weeks ) treatment with an antibiotic administered by any route ; or ( 5 ) nasal carriage of mupirocin-resistant Staphylococcus aureus . Methods 370 subjects will be r and omized 1:1 to receive either daily topical exit-site application of Medihoney Antibacterial Wound Gel ( all patients ) or nasal application of mupirocin if staphylococcal nasal carriage is demonstrated . All patients in the control and intervention groups will perform their usual exit-site care according to local practice . The study will continue until 12 months after the last patient is recruited ( anticipated recruitment time is 24 months ) . Main Outcome Measures The primary outcome measure will be time to first episode of exit-site infection , tunnel infection , or peritonitis , whichever comes first . Secondary outcome measures will include time to first exit-site infection , time to first tunnel infection , time to first peritonitis , time to infection-associated catheter removal , catheter-associated infection rates , causative organisms , incidence of mupirocin-resistant microbial isolates , and other adverse reactions . Conclusions This multicenter Australian and New Zeal and study has been design ed to provide evidence to help nephrologists and their PD patients determine the optimal strategy for preventing PD catheter-associated infections . Demonstration of a significant improvement in PD catheter-associated infections with topical Medihoney will provide clinicians with an important new prophylactic strategy with a low propensity for promoting antimicrobial resistance In the interest of study ing the prevention of chronic peritoneal dialysis infections , serial studies of the bacterial epidemiology in peritonitis and of antibiotic prophylaxis , respectively , were carried out . For 18 months , prospect i ve evaluation of catheter exist site cultures , performed at the time patients developed acute peritonitis , showed that Staphylococcus aureus peritonitis was associated with concordant S. aureus at the exist site in 85 % of cases , significantly more frequent than that for other organisms ( P less than 0.02 ) . Furthermore , active inflammation along with concordant culture results at the exit site characterized more than 60 % of S. aureus peritonitis cases , also significantly more than that for other organisms ( P less than 0.01 ) . Over the ensuing 2 yr , patients beginning chronic peritoneal dialysis with a new percutaneously placed catheter were prospect ively entered into a r and omized , controlled trial of long-term antibiotic prophylaxis with trimethoprim-sulfamethoxasole . Patients receiving prophylaxis tended to have fewer episodes of peritonitis ; however , the lower rate of peritonitis reached statistical significance only comparing patients who were S. aureus carriers at entry into the study to patients who were not S. aureus carriers . In particular , the prophylaxis trial seemed to reduce the specific incidence of S. aureus peritonitis overall , with S. aureus appearing in only 2 of 28 total peritonitis episodes among treated patients as compared with 11 of 37 total episodes among non-treated patients ( P less than 0.01 ) . Further analysis of the time to first peritonitis suggests that the effect of prophylaxis was most prominent during the first 3 months of therapy ( P less than 0.02 ) rather than later in the course of treatment . ( ABSTRACT TRUNCATED AT 250 WORDS Objective To determine if the rate of peritoneal dialysis (PD)-related infections in our large Native population was higher than in non-Natives . Design Prospect i ve study of PD-related infections , 1987 to 1993 . Patients Forty-eight Natives and 136 non-Natives were studied . Comparisons of infection rates were made as well as determinations of the effect of diabetes and of dialysis techniques on infection rate . Results The chance of remaining free of peritonitis was far lower at 6 and 12 months in Natives versus nonNatives , 40 % versus 76 % at 6 months , and 24 % versus 54 % at 12 months ( p < 0.01 ) . Having diabetes or adding intraperitoneal insulin did not confer additional risk of peritonitis . The Y-Iine reduced the risk of peritonitis in non-Natives only . Exit-site infection ( ESI ) was significantly higher in Natives versus non-Natives , 0.42 versus 0.19 episodes per patient year ( p < 0.01 ) mainly due to Staph . aureus . However , less than 30 % of episodes of peritonitis were due to that organism . Staph . epidermidis peritonitis episodes were not more common in Native patients , whereas infections due to most other organisms were . Conclusion The susceptibility to both peritonitis and exit-site infection is increased in Native Canadians compared to non-Natives . The non protective effect of the Yline combined with increased peritonitis due to most organisms except Staph . epidermidis in Natives suggests that host factors could be important in these patients We compared the survival of 842 patients on centre haemodialysis to 272 patients on continuous ambulatory peritoneal dialysis ( CAPD ) . All patients selected had begun treatment between 1 January 1984 and 30 June 1988 and were from six centres which participate in a regional renal patients registry . Patients on CAPD were older and had a greater proportion of diabetes and other associated diseases . Age , diabetes , and cardiovascular diseases were associated with a shorter survival on treatment in all the patients studied . Without adjustment for risk factors , patient 3-year survival was higher in centre haemodialysis than in CAPD , 80 % versus 64 % respectively . However , no significant differences could be shown in the survival rates of the two treatment modalities after accounting for the heterogeneity of the patients in the two groups , either by stratification or by multivariate analysis ( Cox ) . Age was the main predictive factor for CAPD patient survival , while the influence of diabetes and cardiovascular diseases was less clear . Technique survival was much better in centre haemodialysis ( 94 % versus 56 % in CAPD , 3-year survival ) . Older age and diabetes mellitus were associated with a greater risk of switching from centre haemodialysis to CAPD and a trend to retain those patients on CAPD In the present study , we prospect ively investigated the effects of once- or thrice-weekly prophylactic application of mupirocin to catheter exit sites on Staphylococcus aureus carriage , methicillin and mupirocin resistance , and catheter-related infections in continuous ambulatory peritoneal dialysis ( CAPD ) patients . We enrolled 36 CAPD patients ( men/women : 21/ 15 ; mean age : 55.1 + /- 1.4 years ) in the study . At the start of the study , patients had been on once-weekly mupirocin treatment for 3.1 + /- 2.0 years . They were then r and omly assigned to use mupirocin either once weekly ( group I ; n = 18 ; men/women : 10/8 ; age : 55.3 + /- 1.8 years ) or thrice weekly ( group II ; n = 18 ; men/women : 11/7 ; age : 55.0 + /- 2.3 years ) . During the study period , swabs were taken monthly from nares , axillae , the inguinal area , and the catheter exit site . We evaluated a total of 806 sample s in the first 6 months of the study . The two study groups were similar in terms of age and sex . In group I , 5 isolations of S. aureus in 3 patients came from initial S. aureus carriers . During the first 6 months of the study , only 2 new S. aureus carriers were detected in group I , for a total of 7 isolations . Mupirocin resistance ( MuR ) was present in only 1 isolate and methicillin resistance ( MeR ) was not observed . In group II , no S. aureus carriers were present at the initial evaluation , and we encountered only 1 new S. aureus carrier during the first 6 months of the study . During the same period , MuR and MeR were absent in group II . During the 6 months , we observed 1 exit-site infection and 1 peritonitis episode attributable to coagulase-negative staphylococcus ( CNS ) in group I. In group II , we observed 1 exit-site infection attributable to CNS . During the first 6 months of the study , once- or thrice-weekly application of mupirocin to the catheter exit site has not led to any significant change in S. aureus carriage , MeR and MuR , or catheter-related infection in our CAPD patients BACKGROUND Depression is the most common psychological disorder among patients with end-stage renal disease and has been associated with mortality in patients maintained on hemodialysis therapy . Peritonitis is the leading cause of technique failure among long-term peritoneal dialysis ( PD ) patients . This prospect i ve study is design ed to examine the relationship between depression and peritonitis . METHODS All patients on long-term PD therapy in our unit between January 1 , 1997 , and January 31 , 2002 , completed a Beck Depression Inventory ( BDI ) assessment at 6-month intervals . BDI scores were analyzed 2 ways . First , patients were placed into either group I ( BDI score < 10 ) or group II ( BDI score > or = 11 ) and were reclassified based on subsequent scores . Second , multivariable analysis was performed looking at initial BDI score as a risk factor for peritonitis , adjusting for age older than 65 years , diabetes , coronary artery disease , and race . RESULTS One hundred sixty-two patients were enrolled , and 281 individual BDI assessment s were completed . There was a significantly greater incidence of diabetes and coronary artery disease in group II . Rates for overall and gram-positive peritonitis were significantly greater in group II patients compared with group I patients . Using Cox regression , only BDI score of 11 or greater was associated with the development of peritonitis ( hazard ratio , 2.7 ; 95 % confidence interval , 1.2 to 6.0 ) . CONCLUSION There is an association between BDI score of 11 or greater and the development of peritonitis . Whether treatment of depression can impact on the rate of peritonitis remains to be examined ♦ Objectives : To determine whether oral administration of the antifungal fluconazole during the entire period of treatment of bacterial peritonitis ( BP ) , exit-site infection ( ESI ) , or tunnel infection ( TI ) prevents later appearance of fungal peritonitis ( called secondary ) in patients with chronic kidney disease stage 5 in a peritoneal dialysis ( PD ) program . ♦ Patients and Methods : All patients treated in the PD program in RTS Ltda Sucursal Caldas , during the period 1 June 2004 to 30 October 2007 were screened . Patients that had infectious bacterial complications ( BP , ESI , TI ) were included in a prospect i ve r and omized trial to receive or not receive oral fluconazole ( 200 mg every 48 hours ) throughout the time period required by the administration of therapeutic antibiotics via any route . It was evaluated whether the fungal peritonitis complication appeared within 30 – 150 days following the end of antibacterial treatment . Based on local results , the sample size necessary to obtain statistically significant results was determined to be 434 episodes of peritonitis . ♦ Results : The 434 episodes of peritonitis presented between the previously specified date s and during this same period there were 174 ESI or TI , of which only 52 received oral antibiotic treatment . Information in relation to consumption of antibiotics for purpose s other than BP , ESI , and TI was not reliable and thus this variable was excluded . Among the episodes of peritonitis , 402 ( 92.6 % ) were of bacterial origin and 32 ( 7.3 % ) were mycotic , mainly C and ida species [ 30 ( 93.75 % ) ] . Of the fungal peritonitis , 14 ( 43.73 % ) were primary ( without prior use of antibiotics ) and 18 ( 56.25 % ) were secondary . In the group of patients that received prophylaxis with fluconazole ( 210 for BP and 26 for ESI or TI ) , only 3 occurrences of fungal peritonitis were observed within 30 – 150 days of its administration , which is opposite to the group without prophylaxis ( 210 for BP and 26 for ESI or TI ) , in which 15 occurrences of fungal peritonitis were detected . Statistical analysis of the group of patients with BP found comparisons of the proportions of those receiving fluconazole ( 0.92 % ) or not ( 6.45 % ) presented a highly significant difference in favor of prophylaxis ( p = 0.0051 , Z = 2.8021 ) . Given that only 1 patient in each group with ESI or TI , with or without prophylaxis , presented the complication fungal peritonitis , it was concluded that this result was not statistically significant . During laparoscopic surgery attempting re introduction of the peritoneal catheter , it was found that 11 patients had severe adhesions or peritoneal fibrosis leading to obliteration of the peritoneal cavity . In 19 patients , re introduction of the catheter was possible and the patients returned to PD without consequence . ♦ Conclusion : In patients with bacterial peritonitis , administration of prophylactic oral fluconazole throughout the time they received antibiotics significantly prevented the appearance of secondary fungal peritonitis Objective To determine if black patients in our peritoneal dialysis ( PD ) program had higher rates of PD-related infections . The outcomes of black patients versus white patients were also review ed . Design A review of prospect ively collected patient demographic and PD-related infection data and out comes , from 1979 to 1991 . Patients The 68 black patients in our PD program were matched with white control patients for age , sex , insulin dependence , time on dialysis , and mode of dialysis ( CAPD or CCPD ) . The infection , demographic , and outcome data from the two groups were compared . Results Black patients had higher peritonitis rates ( 1.10 vs 0.82 episodeslyear , p=0.001 ) and exit-site infection rates ( 1.13 vs 0.95 episodeslyear , p=0.02 ) than the white control patients . Tunnel infection rates were 0.21 episodeslyear in both groups . S. epidermidis peritonitis was more common in black patients ( 48 % of episodes vs 21 % of episodes in whites , p=0.005 ) , and S. aureus peritonitis was more common in white patients ( 29 % vs 11 % in blacks , p=0.005 ) . The subset of black patients ( n=13 ) on a disconnect system ( Y-set ) had a peritonitis rate similar to their white controls on the Y-set ( 0.41 vs 0.74 episodes/year , p=0.27 ) . There were no episodes of S. epidermidis peritonitis in this subset of black patients . Black patients had fewer S. aureus exit-site infections than white patients ( 21 % vs 41 % , p=0.005 ) . Peritonitis was the leading cause of transfer to hemodialysis in the black patients but not in the white patients . Conclusion The susceptibility to S. aureus and S. epidermidis infections differs in black and white patients on peritoneal dialysis for unclear reasons . Peritonitis rates in black patients can be reduced to that of white patients if a disconnect system is used This paper describes a preliminary investigation into the efficacy of dressings in preventing catheter exit site infections in patients undergoing continuous ambulatory peritoneal dialysis ( CAPD ) . It has been carried out in the form of a pilot study . The background to the study is described and the literature is review ed . This revealed that it is an important field of research . Exit site infections are the main cause of morbidity and treatment failure in CAPD patients . The rationale for carrying the study out , the findings and the implication s for further study are reported and discussed . There is little guidance in current literature for clinicians on the prevention of catheter exit site infection . Patients are difficult to recruit to research studies . Practising nurses need training and careful management as data collectors We present the clinical results of a prospect i ve protocol of the treatment of Staphylococcus aureus nasal carriers ( SANCs ) in our continuous ambulatory peritoneal dialysis unit with mupirocin ( Bactroban , SmithKline Beecham Pharmaceuticals , Philadelphia , PA ) . We monitored the incidence of peritonitis and catheter exit-site infection , the rate of infection-related catheter loss , and the degree of association between SANC state and S aureus infection . The study group included 94 patients with a follow-up of 1,097 patient-months ( phase B ) . The same information was retrospectively collected among 74 continuous ambulatory peritoneal dialysis patients treated during the 24 months preceding the study period ( follow-up of 1,043 patient-months ) ( phase A ) . S aureus nasal carriage was observed in 47.5 % of the patients . Mupirocin was very effective in eradicating S aureus from the nares , but most patients required periodic retreatment . The incidence of S aureus peritonitis decreased from 1 episode/58 patient-months in phase A to 1 episode/548 patient-months in phase B , and the incidence of exit-site infection decreased from one episode/55 patient-months in phase A to 1 episode/137 patient-months in phase B. However , there was a simultaneous increase in the incidence of infections by other gram-positive and -negative bacteria . The rate of catheter loss after peritonitis ( P = not significant ) or exit-site infection ( P < 0.05 ) tended to decrease from phase A to phase B. Seventy-seven percent of the peritonitis infections and 74 % of the exit-site infections by S aureus occurred in SANCs . ( ABSTRACT TRUNCATED AT 250 WORDS The effectiveness of sodium fusi date and ofloxacin to eliminate nasal and catheter exit-site Staphylococcus aureus colonization and to prevent infections was compared in 31 patients on continuous ambulatory peritoneal dialysis ( CAPD ) . In a prospect i ve r and omized study , 9 patients were treated with topical 2 % sodium fusi date ointment applied in the anterior nares and in the pericatheter skin twice daily for 5 days ; 9 subjects received oral ofloxacin 200 mg taken every 48 hours for 5 days and 13 subjects were in the control group . Treatment courses were repeated at one-month intervals . Mean duration of follow-up was 7.8 months ( 242 patients -month ) . Follow-up sample s from the nares and the catheter exit-site were obtained every month from all participants to determine the presence of S. aureus . Development of S. aureus exit-site infection and peritonitis were assessed . During the study , S. aureus was recovered from 45 % , 59 % and 52 % of the sample s from the nares and /or exit-site in the sodium fusi date , ofloxacin and control groups , respectively ( p = 0.13 ) . S. aureus grew less frequently ( p < 0.01 ) in sample s from the exit-site in the sodium fusi date than in the other two groups . Eradication of nasal colonization ( two negative cultures within one month ) was observed in 43 % , 40 % and 33 % of the cases in the sodium fusi date , ofloxacin and control groups , respectively ( p > 0.50 ) . The corresponding figures for exit-site eradication were 43 % , 33 % and 11 % , respectively ( p = 0.34 ) . Twenty-four S. aureus-associated infection episodes ( 12 of exit-site and 12 of peritonitis ) were diagnosed in 16 of the 31 patients . ( ABSTRACT TRUNCATED AT 250 WORDS To compare the efficacy of the st and ard Oreopoulos CAPD system with that of a new method consisting of a Y-shaped set filled with sodium hypochlorite during the dwelling time , a r and omised controlled study was performed in 62 new CAPD patients . Life table analysis showed a significantly ( p less than 0.001 ) less frequent incidence of peritonitis in the group treated with the Y connector system . This study shows that the Y system appears to be effective in reducing the incidence of peritonitis , as compared with the st and ard technique , in patients on the CAPD programme . The method is simple and economical and the incidence and the severity of side effects appear to be acceptable Previous in vitro , in vivo , and a preliminary clinical report have demonstrated efficacy of noncovalently bonding antibiotics to the surface of continuous ambulatory peritoneal dialysis ( CAPO ) catheters in decreasing infectious complications . A larger prospect i ve r and omized clinical trial was completed . Eighty-six patients with chronic renal failure were enrolled in the study and r and omized to receive either a surfactant treated or untreated control catheter . All catheters were soaked in cefoxitin at the time of insertion . Groups were comparable in terms of pre-existing illnesses , age , and gender . No differences were shown in the incidence of cathetertract infections , peritonitis or mechanical complications . There was also no differences in microbiologic culture results . Therefore , it is concluded that this clinical trial did not demonstrate a reduction in catheter-related infectious complications by antibiotic bonding Objective To evaluate the potential superiority of either oral or intraperitoneal treatment of catheter tunnel infections ( TI ) , using clindamycin as a first-Iine antibiotic and ultrasound as a diagnostic tool . Design This was a prospect i ve , r and omized study in continuous ambulatory peritoneal dialysis patients . From August 1993 until August 1995 , 16 clinical ly and ultrasound-proven episodes of TI were r and omly assigned to either an oral or an intraperitoneal ( IP ) treatment ( 100 patients , 1414 patient-months ) . Main criteria for TI diagnosis were purulent drainage from the exit site and /or a positive ultrasound ( pericatheter fluid collection of at least 2 mm , 7.5 MHz transducer ) . Initially , clindamycin ( 20 mg/kg body weight ) was given via the oral ( three times per day ) or intraperitoneal route ( four times per day ) . In the case of incompatibility or resistance to clindamycin , either oxacillin orciprofloxacin were used orally or IP . Results Based on ultrasound criteria , the mean time until a ≥50 % reduction of pericatheter abscess diameter was 26 days ( median ) ( range : 8 28 days ) in the oral , and 15 days ( 8 27 days ) in the IP group ( p ≤ 0.05 ) . Showing no significant difference of pericatheter fluid at study entry with 4 mm ( median ) ( range : 2 -6 mm ) in the oral group and 4 mm ( 2 -4 mm ) in the IP group , the IP treatment result ed in a decrease to 0 mm ( 0 2 mm ) after 28 days ( p < 0.05 ) , while the diameter was still 2 mm ( 0 10 mm ) ( NS ) in the oral group . Disappearance of exit-site infection was also somewhat earlier in the intraperitoneal group ( 51 vs 15 days , NS ) . Catheter removal had to be done once in the IP group and twice in the oral group within 6 months after study entry . Conclusions The results give evidence for greater efficacy of the IP application of clindamycin as a first -Iine antibiotic compared to the oral route for the treatment of tunnel infections BACKGROUND AND OBJECTIVES Infectious complications remain a significant cause of peritoneal dialysis ( PD ) technique failure . Topical ointments seem to reduce peritonitis ; however , concerns over resistance have led to a quest for alternative agents . This study examined the effectiveness of applying topical Polysporin Triple ointment ( P(3 ) ) against mupirocin in a multi-centered , double-blind , r and omized controlled trial . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS PD patients routinely applied either P(3 ) or mupirocin ointment to their exit site . Patients were followed for 18 months or until death or catheter removal . The primary study outcome was a composite endpoint of exit-site infection ( ESI ) , tunnel infection , or peritonitis . RESULTS Seventy-five of 201 r and omized patients experienced a primary outcome event ( 51 peritonitis episodes , 24 ESIs ) . No difference was seen in the time to first event for P(3 ) ( 13.2 months ; 95 % confidence interval , 11.9 - 14.5 ) and mupirocin ( 14.0 months ; 95 % confidence interval , 12.7 - 15.4 ) ( P=0.41 ) . Twice as many patients reported redness at the exit site in the P(3 ) group ( 14 versus 6 , P=0.10 ) . Over the complete study period , a higher rate per year of fungal ESIs was seen in patients using P(3 ) ( 0.07 versus 0.01 ; P=0.02 ) with a corresponding increase in fungal peritonitis ( 0.04 versus 0.00 , respectively ; P<0.05 ) . CONCLUSIONS This study shows that P(3 ) is not superior to mupirocin in the prophylaxis of PD-related infections . Colonization of the exit site with fungal organisms is of concern and warrants further study . As such , the use of P(3 ) over mupirocin is not advocated in the prophylaxis of PD-related infections Background Peritoneal dialysis (PD)-related infections are the major cause of technique failure . Exit-site infections ( ESI ) can be prevented by local application of antibiotics . Mupirocin ( M ) is the most extensively studied drug for this application . Long-term use can result in the development of resistance . Gentamicin ( G ) is an attractive alternative , with both gram-positive and gram-negative activities . We studied the comparative efficacy of G cream versus M ointment in the prevention of PD-related infections in a Chinese cohort . Methods This was a prospect i ve study of adult PD patients of the Princess Margaret Hospital , Hong Kong . Patients were excluded if they had active infection , recent ESI or peritonitis , history of allergy to either drug , or were unable to apply the drug or give consent . Patients were taught to apply the drug daily to the exit site after routine exit-site care . Records were tracked prospect ively during hospital admissions and clinic follow-ups . Results 95 patients were recruited ; 14 discontinued the study . The ESI rates were 0.38 and 0.20 episodes/patient-year for the G group and the M group respectively ( p = 0.36 ) . Gram-positive ESI rates were 0.18 and 0 episodes/patient-year for the G group and the M group respectively . Gram-negative ESI rates were 0.20 episodes/patient-year for both groups ( p = 0.62 ) . The overall peritonitis rates were similar in the two groups ( p = 0.91 ) . Discussion In addition to good perioperative care and strict exit-site care , local antibiotic application can prevent ESI . Mupirocin has been extensively studied and shown to be effective . Similar if not superior effects of G cream have been demonstrated . In this study , neither antibiotic gave significantly better results in the prevention of either ESI or peritonitis . Conclusions Both gentamicin and mupirocin were effective as prophylaxis for ESI . Longer study is required to determine the long-term efficacy and the potential beneficial effect on the prevention of peritonitis A controlled study in two centres compared the efficacy of the st and ard continuous ambulatory peritoneal dialysis ( CAPD ) system with that of a new method consisting of a Y-shaped set filled with sodium hypochlorite during the dwelling time . 62 new CAPD patients were r and omly allocated to the st and ard method ( group A : 30 patients ; age 55.5 + /- 17.5 years ) or to the Y-system ( group B : 32 patients ; age 55.1 + /- 14.3 years ) . In group A , there were 31 peritonitis episodes in 17 patients ( 57 % ) during a cumulative period of 351 months--1 episode every 11.3 patient-months . In group B , there were 11 peritonitis episodes in 10 patients ( 31 % ) during 363 months--1 episode every 33 patient-months . Life-table analysis showed a significant difference between the incidence of peritonitis in the two groups . The Y-system method is simple and economical and the frequency and the severity of side-effects appears to be acceptable The objective of this study was to evaluate the effectiveness of mupirocin on Staphylococcus aureus with regard to peritoneal dialysis (PD)-catheter exit-site infections ( ESI ) , tunnel infections ( TI ) , and peritonitis episodes ( PE ) . The study was performed on 42 continuous ambulatory peritoneal dialysis ( CAPD ) patients ( group I ) treated from April 1998 to July 1999 . These patients were instructed to apply mupirocin daily at the catheter exit site as part of their exit-site care . The control was the same group 's historical infection data . Results were also recorded for a second group of 16 patients ( group II ) with newly implanted PD catheters were also instructed to apply mupirocin at the exit site daily . During the control period ( before daily mupirocin application ) , group I recorded 16 episodes of ESI ( 0.30 episodes per patient-year ) , 6 episodes of TI ( 0.11 episodes per patient-year ) , 15 episodes of PE ( 0.28 episodes per patient-year ) , and one case of catheter removal ( 0.019 episodes per patient-year ) owing to S. aureus exit-site infection coexisting with peritonitis . The rate of S. aureus exit-site infection during this period was 0.11 episodes per patient-year ; of S. aureus tunnel infection , 0.057 episodes per patient-year ; and of S. aureus peritonitis , 0.076 episodes per patient-year . During the mupirocin period , infections and peritonitis owing to S. aureus dramatically decreased ( p < 0.01 and p < 0.001 respectively ) . The rate of S. aureus exit-site infection was 0.02 episodes per patient-year , with no S. aureus tunnel infections , and no catheter removals owing to S. aureus peritonitis . Similarly , in group II , no episodes were recorded of any ESI , TI , or PE owing to S. aureus , although 4 episodes of ESI ( 0.37 episodes per patient-year , 2 with other gram-positive bacteria , and 2 with gram-negative bacteria ) and 8 PEs ( 0.75 episodes per patient-year ) were seen . We conclude that mupirocin application provides excellent prophylaxis for catheter-related infections owing to S. aureus , and that reduction of these infections may improve the long-term survival of patients on CAPD The role of vancomycin and other antibiotics in the treatment of acute peritonitis in peritoneal dialysis ( PD ) patients is well established . However , the role of preoperative vancomycin or cephalosporins in preventing early infection in newly placed PD catheters remains controversial . We performed a prospect i ve r and omized study to examine the role of vancomycin or cefazolin prophylaxis in decreasing the incidence of postoperative peritonitis . Over a 6-year period , 221 patients undergoing 254 permanent peritoneal catheter placement procedures were r and omized into three groups . Group I patients ( 86 procedures ) were administered a single intravenous ( IV ) dose of vancomycin , 1,000 mg , 12 hours before peritoneal catheter placement procedures , whereas group II patients ( 85 procedures ) were administered a single IV dose of cefazolin , 1,000 mg , 3 hours before the procedure . Group III patients ( 83 procedures ) were not administered antibiotics preoperatively for at least 1 week before the procedure . Patients were monitored for peritonitis in the following 14 days . Peritonitis developed in 1 patient ( 1 % ) in group I ( vancomycin group ) and 6 patients ( 7 % ) in group II ( cefazolin group ) compared with 10 patients ( 12 % ) in group III ( control group ) ; P = 0.02 . We conclude that the use of preoperative single-dose IV vancomycin prophylaxis for permanent PD catheter placement reduces the risk for postoperative peritonitis . Single-dose vancomycin is superior to single-dose cefazolin in reducing the risk for postoperative peritonitis . Absence of prophylaxis is associated with a high risk for developing postoperative peritonitis Infections are the main complications of peritoneal dialysis , and currently there is no established method for prevention . A prospect i ve , r and omized , single-blind study was performed to evaluate the efficacy of regular application of povidone-iodine ointment at the catheter site ( during the entire time on the study ) in peritoneal dialysis . One hundred twenty patients were r and omized ; three were excluded for not completing the study . Sixty-one patients received application of povidone-iodine and 56 patients received st and ard care . Povidone-iodine ointment was effective in delaying infectious complications , with a lower proportion of treated patients having infections ( exit site and peritonitis ) within 140 days of starting dialysis compared with the controls ( P = 0.04 , Wilcoxon test ) . This protective benefit was lost after 140 days on dialysis . Staphylococcus aureus infections developed in only two ( 3.3 % ) of the treated patients compared with 10 ( 21.4 % ) of the controls ( P = 0.009 ) , despite the higher rate of S aureus nasal carriage in the treated group ( 22 of 61 patients [ 36 % ] v 14 of 56 patients [ 25 % ] ) To determine the value of oral neomycin in preventing peritonitis during peritoneal dialysis , 95 consecutive dialyses were r and omly assigned to two groups . One group received neomycin 0.5 gm in suspension every six hours for 48 hours ; the other , placebo . The incidence of peritonitis was 8.3 per cent in the neomycin group and 9.7 per cent in the placebo group . The incidence of significant asymptomatic infection , as evaluated by colony counts , was 14.6 per cent and 17 per cent , respectively . It was concluded that oral neomycin in the dosages employed did not prevent peritonitis during dialysis Although , decreasing in incidence with the disconnection systems , the first complication is still peritonitis in patients with chronic renal failure and the second is infection of Tenckhoff catheter exit-site . All efforts made to diminish the frequency of exit-site infection lower the possibility of peritonitis . The pediatric population is well-known to have a major risk of infectious complications , and making easy and safe the care of the exit-site will prevent the peritonitis that follows . The aim of the study was to evaluate the efficacy of the Amuchina 10 % solution vs. pH neutral soap in children with chronic renal failure , on preventing exit-site infection . There were 60 patients who were assigned r and omly to one of two groups . One group used Amuchina 10 % solution for the daily cleaning of the exit-site , and the other used pH neutral soap , with 14 months of follow-up . Before the study they have to be free of infection for at least 30 days . All were taught by the same nurse how to clean their exit-site . Groups were almost identical in years , sex , and time on dialysis . We had nine infections in the soap group and none in the Amuchina 10 % solution group , with an OR : 17 ( p = 0.004 ) . From these nine infections , the bacteria isolated were : 4 ( 13 % ) were caused by Pseudomona aeruginosa , 1 ( 3.3 % ) by Staphylococcus aureus , coagulase-positive staphylococci in 2 ( 6.6 % ) and Serratia marcensens in 1 ( 3.3 % ) . In conclusion , Amuchina 10 % solution is effective in preventing infection on the exit-site , without any secondary topical reaction BACKGROUND AND OBJECTIVES Peritonitis is the most common infectious complication seen in peritoneal dialysis ( PD ) . Traditionally , exit site infection ( ESI ) has been thought to predispose PD patients to peritonitis , although the risks have not been quantified . This study aim ed to quantify the risk of PD peritonitis after ESI . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Data from 203 clinical ly stable PD patients > 18 years of age who were followed as part of a r and omized controlled trial over 18 months were used to estimate the risk of developing peritonitis within 30 days of an ESI compared with individuals who did not have a recent ESI . Sensitivity analyses were performed at 15 , 45 , and 60 days . RESULTS Patients were mostly male ( 64.5 % ) and Caucasian , with a mean age of 60.5 ± 14.4 years . There were 44 ESIs and 87 peritonitis episodes during the 18-month study . Seven patients had an ESI followed by peritonitis within 30 days . Using a frailty model , patients who had an ESI had a significantly higher risk of developing peritonitis within 30 days , even if the ESI was appropriately treated . This risk was maximal early on and diminished with time , with hazard ratios ( 95 % confidence interval ) of 11.1 at 15 days ( HR=11.1 , 95 % CI=4.9 - 25.1 ) , 5.3 at 45 days ( 2.5 - 11.3 ) , and 4.9 at 60 days ( 2.4 - 9.9 ) . In 2.3 % of patients , subsequent peritonitis was caused by the same organism as the previous ESI . CONCLUSIONS A strong association between a treated ESI and subsequent PD peritonitis was present up to 60 days after initial diagnosis ♦ Background : The HONEYPOT study recently reported that daily exit-site application of antibacterial honey was not superior to nasal mupirocin prophylaxis for preventing overall peritoneal dialysis (PD)-related infection . This paper reports a secondary outcome analysis of the HONEYPOT study with respect to exit-site infection ( ESI ) and peritonitis microbiology , infectious hospitalization and technique failure . ♦ Methods : A total of 371 PD patients were r and omized to daily exit-site application of antibacterial honey plus usual exit-site care ( N = 186 ) or intranasal mupirocin prophylaxis ( in nasal Staphylococcus aureus carriers only ) plus usual exit-site care ( control , N = 185 ) . Groups were compared on rates of organism-specific ESI and peritonitis , peritonitis- and infection-associated hospitalization , and technique failure ( PD withdrawal ) . ♦ Results : The mean peritonitis rates in the honey and control groups were 0.41 ( 95 % confidence interval [ CI ] 0.32 – 0.50 ) and 0.41 ( 95 % CI 0.33 – 0.49 ) episodes per patient-year , respectively ( incidence rate ratio [ IRR ] 1.01 , 95 % CI 0.75 – 1.35 ) . When specific causative organisms were examined , no differences were observed between the groups for gram-positive ( IRR 0.99 , 95 % CI 0.66 – 1.49 ) , gram-negative ( IRR 0.71 , 95 % CI 0.39 – 1.29 ) , culture-negative ( IRR 2.01 , 95 % CI 0.91 – 4.42 ) , or polymicrobial peritonitis ( IRR 1.08 , 95 % CI 0.36 – 3.20 ) . Exit-site infection rates were 0.37 ( 95 % CI 0.28 – 0.45 ) and 0.33 ( 95 % CI 0.26 – 0.40 ) episodes per patient-year for the honey and control groups , respectively ( IRR 1.12 , 95 % CI 0.81 – 1.53 ) . No significant differences were observed between the groups for gram-positive ( IRR 1.10 , 95 % CI 0.70 – 1.72 ) , gram-negative ( IRR : 0.85 , 95 % CI 0.46 – 1.58 ) , culture-negative ( IRR 1.88 , 95 % CI 0.67 – 5.29 ) , or polymicrobial ESI ( IRR 1.00 , 95 % CI 0.40 – 2.54 ) . Times to first peritonitis-associated and first infection-associated hospitalization were similar in the honey and control groups . The rates of technique failure ( PD withdrawal ) due to PD-related infection were not significantly different between the groups . ♦ Conclusion : Compared with st and ard nasal mupirocin prophylaxis , daily topical exit-site application of antibacterial honey result ed in comparable rates of organism-specific peritonitis and ESI , infection-associated hospitalization , and infection-associated technique failure in PD patients |
10,452 | 23,955,506 | There was also a significant improvement in the clinical pregnancy rate with use of LMWH ( OR 1.61 , 95 % CI 1.03 to 2.53 , three studies , 386 women , I(2 ) = 29 % , very low quality evidence with low heterogeneity).However these findings should be interpreted with extreme caution as they were dependent upon the choice of statistical method : they were no longer statistically significant when a r and om-effects model was used .
Adverse events were poorly reported in all included studies , with no comparative data available .
However , LMWH did cause adverse effects including bruising , ecchymosis , bleeding , thrombocytopenia and allergic reactions .
It appeared that these adverse effects were increased if heparin therapy was used over a longer duration .
The results of this Cochrane review of three r and omised controlled trials with a total of 386 women suggested that peri-implantation LMWH in assisted reproduction treatment ( ART ) cycles may improve the live birth rate in women undergoing assisted reproduction .
However , these results were dependent on small low quality studies with substantial heterogeneity , and were sensitive to the choice of statistical model .
There were side effects reported with use of heparin , including bruising and bleeding , and no reliable data on long-term effects . | BACKGROUND Heparin as an adjunct in assisted reproduction ( peri-implantation heparin ) is given at or after egg collection or at embryo transfer during assisted reproduction .
Heparin has been advocated to improve embryo implantation and clinical outcomes .
It has been proposed that heparin enhances the intra-uterine environment by improving decidualisation with an associated activation of growth factors and a cytokine expression profile in the endometrium that is favourable to pregnancy .
OBJECTIVES To investigate whether the administration of heparin around the time of implantation ( peri-implantation heparin ) improves clinical outcomes in subfertile women undergoing assisted reproduction . | This study evaluated whether heparin administration could affect IVF outcome . A total of 172 women , aged < 40years , without laboratory findings of thrombophilia and undergoing their first IVF cycle , were r and omly allocated to treatment ( n=86 ) and control ( n=86 ) groups . Patients allocated to the treatment group received low-molecular-weight heparin dalteparin sodium 2500IU s.c . daily , in addition to routine luteal phase support , from oocyte retrieval up to the day of the pregnancy test or up to the ninth week of pregnancy in the cases of positive human chorionic gonadotrophin . From the day after the oocyte retrieval , all patients began st and ard supplementation with vaginal progesterone 200 mg twice a day . At the sixth week of pregnancy , patients underwent an ultrasound scan to assess the number/viability of gestational sacs . Implantation rates were 15 % and 12 % in the dalteparin and control groups , respectively . The clinical pregnancy rates/embryo transfers were 26 % ( 19/73 ) and 20 % ( 16/80 ) , in the dalteparin and control groups , respectively , with live birth rates/embryo transfer of 21 % ( 15/73 ) and 16 % ( 13/80 ) . Despite the lack of statistical significance , the increase in pregnancies observed in the treatment group may be considered as an important clinical point in the optimization of IVF clinical outcome PROBLEM : The effect of mini‐dose heparin/aspirin ( H/A ) alone vs. combined intravenous immunoglobulin G ( IVIg ) and H/A on in vitro fertilization ( IVF ) birthrates in women who test seropositive for antiphospholipid antibodies ( APA+ ) was evaluated , as was the question of whether outcome is influenced by the gammaglobulin isotype(s ) or the phospholipid ( PL ) epitope(s ) to which the APAs are directed BACKGROUND Heparin and low molecular weight heparin ( LMWH ) are used widely to improve the pregnancy outcome in women with thrombophilia , miscarriage , recurrent miscarriage and fetal death . This study was design ed to investigate the effects of heparin and LMWHs , enoxaparin and tinzaparin , on E-cadherin and laminin expression in placental and decidual tissues in rat pregnancy . METHODS Wistar albino female rats ( n = 48 ) were r and omly assigned to four study groups ( normal saline , heparin , enoxaparin and tinzaparin ) in the preconceptional period . Tissue sections of placenta and decidua were immunohistochemically examined for the expression of E-cadherin and laminin . RESULTS E-cadherin placental staining score of heparin group was significantly lower and E-cadherin decidual staining score of heparin and enoxaparin groups were significantly lower than control group . There were no significant differences in placental and decidual laminin staining scores among the study groups . CONCLUSIONS Heparin and enoxaparin can reduce E-cadherin expression but not laminin expression in rat pregnancy . They might modulate trophoblast invasion . We suggest that this is the possible underlying mechanism involving in improvement of trophoblast invasion by the use of heparin and LMWH in patients with the history of miscarriage This study evaluated the results of a management protocol combining a number of investigations and interventions , previously proven beneficial in r and omized controlled trials in IVF/intracytoplasmic sperm injection ( ICSI ) patients with apparently unexplained recurrent implantation failure ( defined as two or more previous failed cycles , during which at least six good- quality embryos were transferred ) . It was a prospect i ve cohort study and included 273 couples with previous recurrent implantation failure . Each patient ( all under 40 ) underwent a pre-treatment work-up , consisting of pelvic ultrasound scan for hydrosalpinx , hysteroscopy and screening for acquired and congenital thrombophilia . Detected abnormalities were dealt with accordingly : proximal occlusion for hydrosalpinx , hysteroscopic management for intrauterine pathology and thromboprophylaxis with daily low-molecular weight heparin from the day of embryo transfer for thrombophilia . The patients then underwent IVF/ICSI with laser-assisted hatching . 112 patients ( 41 % ; group 1 ) had abnormalities detected ( 17 hydrosalpinx , 11 intrauterine pathology , 63 congenital thrombophilia , 21 acquired thrombophilia ) and the remaining 161 ( 59 % ; group 2 ) had normal work-up . The pregnancy rates per cycle started for all patients , group 1 and group 2 were 47 % , 55 % and 41 % , respectively . This suggests that using the described management protocol in couples with previous recurrent implantation failure leads to a favourable chance of success OBJECTIVE To investigate whether heparin and low-dose aspirin increase the pregnancy rate in antiphospholipid antibody or antinuclear antibody-seropositive women with IVF implantation failure . DESIGN A double-blind , r and omized , transfer-by-transfer of fresh or cryopreserved embryos , crossover trial . A hospital infertility clinic and associated IVF service . PATIENT(S ) Women seropositive for at least one antiphospholipid ( APA ) , antinuclear ( ANA ) , or beta(2 ) glycoprotein I autoantibody and > or=10 embryos transferred without achieving pregnancy ( n = 143 ) . INTERVENTION(S ) Subcutaneous unfractionated heparin ( 5000 IU b.i.d . ) and aspirin ( 100 mg daily ) ( 158 transfers of 296 embryos ) or placebo ( 142 transfers of 259 embryos ) from the day of embryo transfer . MAIN OUTCOME MEASURE(S ) Fetal heart per embryo transferred ( implantation rate ) . RESULT ( S ) There was no significant difference in pregnancy rates or implantation rates between treated and placebo cycles ; for example , fetal hearts per embryo transferred implantation rates were 6.8 % ( 20/296 ) and 8.5 % ( 22/259 ) , respectively , and the generalized estimating equation covariate adjusted relative pregnancy rate was 0.65 ( 95 % confidence interval , 0.33 - 1.28 ) . The implantation rate for seropositive trial participants ( 42/555 , 7.6 % ) compared favorably with that for IVF implantation-failure patients continuing treatment outside the trial ( 147/3237 , 4.5 % ) . CONCLUSION ( S ) Heparin and aspirin did not improve pregnancy or implantation rates for APA-positive or ANA-positive patients with IVF implantation failure OBJECTIVE To evaluate the expression of syndecan-1 , -2 , -3 , and -4 in different phases of eutopic endometrium of normal cycling women . DESIGN Prospect i ve observational study . SETTING University-based research center for reproductive medicine . PATIENT(S ) Twenty-nine healthy ovulatory volunteers . INTERVENTION(S ) mRNA and protein expression of syndecan-1 to -4 in human endometrium . MAIN OUTCOME MEASURE(S ) Real-time polymerase chain reaction of syndecan members and further characterization of mRNA expression of syndecan-1 and -4 with multiprobe RNase protection assays of epithelial and stromal cells after purification with antibody-coated magnetic beads . For confirmation of results , protein expression and localization using immunohistochemistry for syndecan-1 and -4 was performed . RESULT ( S ) All syndecans were expressed within human endometrium . Syndecan-1 and -4 proved to be significantly upregulated in whole endometrium during the secretory phase ( 2.73-fold and 2.85-fold , respectively ) . Using multiprobe RNase protection assays , a significant upregulation of mRNA was noted in epithelial cells during the secretory phase for both syndecan-1 and -4 ( 7.46-fold and 2.52-fold , respectively ) and confirmed by immunohistochemistry . CONCLUSION ( S ) Cycle-dependent expression of syndecan-1 and -4 suggests that these adhesion proteins are involved in the regulation of the cycling endometrium BACKGROUND The quality of clinical trials has received increasing attention with the growth of evidence -based medicine and systematic review s. We aim ed to identify whether errors and omissions commonly encountered when undertaking Cochrane review s in this field are still passing peer review . METHODS We undertook a review of trials published in 2001 by two major journals . We selected from Medline only trials in which authors compared pregnancy rates under two interventions by allocating women to different groups . RESULTS We identified 39 trials meeting our criteria . Six trials were fatally flawed by design , either by inappropriate use of a cross-over design or by systematic allocation described by the authors as ' r and om ' . Only six reports cl aim ed to apply the intention-to-treat principle , and the principle was misunderstood by four of these . Only five trials reported live birth rates sufficiently to allow valid meta- analysis . Most trials ( 82 % ) included at least one ' unit of analysis ' error . CONCLUSIONS We selected simple trials from respected journals , assuming that our sample would represent trials of highest method ological quality in the field . Nevertheless , the st and ards of design , analysis and reporting of many subfertility trials are not sufficient to allow reliable interpretation of results , or inclusion in meta-analyses BACKGROUND The pathology underlying recurrent implantation failures ( RIF ) is not clear and treatment options proposed are generally not evidence based . Although the effect of heparin on trophoblast biology has not been studied extensively , given the available data suggesting a possible beneficial effect of heparin on embryo implantation , we decided to undertake this pilot study . METHODS One hundred and fifty women with > or = 2 failed assisted reproduction treatment cycles were included in this r and omized open-label pilot trial . Participants underwent controlled ovarian stimulation with the long protocol and were r and omly allocated to receive 1 mg/kg/day low molecular weight heparin ( LMWH ) or no treatment in addition to routine luteal phase support ( LPS ) on the day after oocyte retrieval . LPS and LMWH was continued up to the 12th gestational week in pregnant participants . RESULTS There were 26 ( 34.7 % ) live births in the LMWH group , and 20 ( 26.7 % ) in the control group ( absolute difference 8.0 % , 95 % CI -4.2 to 24.9 % , P = 0.29 ) . There were 34 ( 45.3 % ) and 29 ( 38.7 % ) clinical pregnancies in the LMWH and control groups , respectively ( absolute difference 6.6 % , 95 % CI -9.0 to 21.8 % , P = 0.41 ) . Implantation rates were 24.5 and 19.8 % in the LMWH and control groups , respectively ( absolute difference 4.7 % , 95 % CI -4.7 to 14.1 % , P = 0.33 ) . CONCLUSION Despite lack of statistical significance , observed relative increase by 30 % in live birth rates with LMWH may be regarded as a clinical ly significant trend necessitating further research on the use of empirical LMWH in women with RIF and possibly in all women undergoing assisted reproduction treatment . Failure to demonstrate statistical significance of the observed treatment difference may be due to limited sample size of this pilot study Background Introduction : Recently , thrombophilia ( acquired and inherited ) has been implicated in recurrent IVF – ET failure . The objective of this study was to determine the effect and safety of thromboprophylaxis using low-molecular-weight heparin ( LMWH ) in women with recurrent in vitro fertilization (IVF)–embryo transfer ( ET ) failure and thrombophilia . Methods : Eighty-three women with history of three or more previous IVF failures and who had at least one thrombophilic defect were eligible for this study . Patients were r and omly allocated into two groups : Group A ( n = 42 ) received enoxaparin 40 mg/day , and group B ( n = 41 ) received placebo ( NaCl 0.9 % ) . Both treatments started on the day of ET and continued until delivery or foetal demise was diagnosed . The primary outcomes were the implantation , pregnancy and live birth rates . Results : Patients who received LMWH for thromboprophylaxis had a significant increase in the implantation and pregnancy rates compared with the placebo group ( 20.9 % vs. 6.1 % and 31 % vs. 9.6 % , respectively ; p < 0.001 and p < 0.05 , respectively ) . A significant increase in the live birth rate was observed in the heparin-treated group compared with placebo ( 23.8 % vs. 2.8 % , respectively ; p < 0.05 ) . The abortion rate was significantly higher in the placebo-treated group compared to the heparin-treated group ( p < 0.05 ) . The frequency of treatment complications did not differ between the two study groups . Conclusions : LMWH is a safe and effective thromboprophylactic treatment for women with thrombophilia and recurrent IVF – ET failures . The implantation rate , pregnancy and live birth rates are significantly increased with such treatment To describe the prevalence of antiphospholipid antibodies in women undergoing in-vitro fertilization ( IVF ) and to determine if heparin and aspirin affect implantation rates , 191 women with a history of infertility undergoing IVF were prospect ively tested for antiphospholipid antibodies . This was a two-centre , non-r and omized comparison of women with positive antiphospholipid antibodies receiving heparin and aspirin versus st and ard treatment . An enzyme-linked immunosorbent assay , with referenced st and ards and known positive and negative sera on each plate , was utilized to measure antibodies to cardiolipin , phosphatidylinositol , phosphatidylglycerol , phosphatidylserine and phosphatidylethanolamine . Statistical analyses of results included analysis of variance and Fisher 's two-tailed exact test . Antiphospholipid antibodies were detected in 18.8 % of patients undergoing IVF compared with only 5.5 % in the 200 normal controls , 26 % in 200 women with recurrent pregnancy loss , and 32 % in 200 women with systemic lupus erythematosus . In conclusion , antiphospholipid antibodies were found more frequently in women undergoing IVF than in the normal control population . Although implantation rates appeared higher in the group of women treated with heparin and aspirin , no statistically significant differences were detected in implantation , pregnancy and ongoing pregnancy rates between those who received st and ard therapy and those treated with heparin and aspirin |
10,453 | 28,447,766 | AUTHORS ' CONCLUSIONS Take-home medication strategies are attractive to treatment services due to lower costs , and place less restrictions on clients , but it is unknown whether they may be associated with increased risk of diversion and unsanctioned use of medication . | BACKGROUND Opioid dependence ( OD ) is an increasing clinical and public health problem worldwide .
International guidelines recommend opioid substitution treatment ( OST ) , such as methadone and buprenorphine , as first-line medication treatment for OD .
A negative aspect of OST is that the medication used can be diverted both through sale on the black market , and the unsanctioned use of medications .
Daily supervised administration of medications used in OST has the advantage of reducing the risk of diversion , and may promote therapeutic engagement , potentially enhancing the psychosocial aspect of OST , but costs more and is more restrictive on the client than dispensing for off-site consumption .
OBJECTIVES The objective of this systematic review is to compare the effectiveness of OST with supervised dosing relative to dispensing of medication for off-site consumption . | BACKGROUND Heroin-assisted treatment has been found to be effective for people with severe opioid dependence who are not interested in or do poorly on methadone maintenance . AIMS To study heroin-assisted treatment in people on methadone who continue intravenous heroin and in those who are heroin dependent but currently not in treatment . METHOD In an open-label multicentre r and omised controlled trial , 1015 people with heroin dependence received a variable dose of injectable heroin ( n=515 ) or oral methadone ( n=500 ) for 12 months . Two response criteria , improvement of physical and /or mental health and decrease in illicit drug use , were evaluated in an intent-to-treat analysis . RESULTS Retention was higher in the heroin ( 67.2 % ) than in the methadone group ( 40.0 % ) and the heroin group showed a significantly greater response on both primary outcome measures . More serious adverse events were found in the heroin group , and were mainly associated with intravenous use . CONCLUSIONS Heroin-assisted treatment is more effective for people with opioid dependence who continue intravenous heroin while on methadone maintenance or who are not enrolled in treatment . Despite a higher risk , it should be considered for treatment resistance under medical supervision AIM Supervised consumption of opioid maintenance treatment ( OMT ) is st and ard in many drug centres reducing drug diversion , but is costly . We aim ed to determine whether supervised consumption of OMT improved retention and other measures of drug use . DESIGN Pragmatic r and omized controlled trial comparing 3 months of daily supervised consumption of OMT with 1 month or less of daily supervised OMT , then daily unsupervised consumption . SETTING Four community drug services in the United Kingdom . PARTICIPANTS A total of 293 opioid-dependent patients entering OMT . MEASUREMENTS PRIMARY OUTCOME retention in treatment at 12 weeks . Secondary : retention at 6 months ; illicit drug use [ Maudsley Addiction Profile ( MAP ) ] ; quality of life ( SF-12 and MAP ) ; criminality ( MAP ) ; and social functioning . FINDINGS No significant between-group difference was observed for the primary outcome : 69 % ( 100 of 145 ) supervised and 74 % ( 109 of 148 ) unsupervised were retained [ odds ratio ( OR ) = 0.74 , 95 % confidence interval ( CI ) = 0.43 - 1.27 ] . Per protocol survival analysis suggested that supervised patients were less well retained ( hazard ratio for retention = 0.71 , 95 % CI = 0.51 - 1.00 ) . Illicit opioid use reduced in both groups and , while not statistically significant by intention-to-treat analysis , favoured unsupervised patients in per protocol analysis ( odds of positive opioid screen for supervised versus unsupervised = 2.07 , 95 % CI = 1.05 - 4.06 ) . Data on criminal activity also favoured unsupervised patients with 21 % supervised patients committing crime versus 9 % unsupervised ( OR = 3.37 , 95 % CI = 1.28 - 8.86 ) . CONCLUSIONS There was no evidence of a difference in treatment retention or opioid use rates between patients whose consumption of opioid maintenance treatment was supervised for 3 months daily ( except Saturdays ) compared with supervision for 1 month . There was some evidence that longer periods of supervised consumption were associated with higher levels of criminality BACKGROUND The partial opiate-receptor agonist buprenorphine has been suggested for treatment of heroin dependence , but there are few long-term and placebo-controlled studies of its effectiveness . We aim ed to assess the 1-year efficacy of buprenorphine in combination with intensive psychosocial therapy for treatment of heroin dependence . METHODS 40 individuals aged older than 20 years , who met DSM-IV criteria for opiate dependence for at least 1 year , but did not fulfil Swedish legal criteria for methadone maintenance treatment were r and omly allocated either to daily buprenorphine ( fixed dose 16 mg sublingually for 12 months ; supervised daily administration for a least 6 months , possible take-home doses thereafter ) or a tapered 6 day regimen of buprenorphine , thereafter followed by placebo . All patients participated in cognitive-behavioural group therapy to prevent relapse , received weekly individual counselling sessions , and su bmi tted thrice weekly supervised urine sample s for analysis to detect illicit drug use . Our primary endpoint was 1-year retention in treatment and analysis was by intention to treat . FINDINGS 1-year retention in treatment was 75 % and 0 % in the buprenorphine and placebo groups , respectively ( p=0.0001 ; risk ratio 58.7 [ 95 % CI 7.4 - 467.4 ] ) . Urine screens were about 75 % negative for illicit opiates , central stimulants , cannabinoids , and benzodiazepines in the patients remaining in treatment . INTERPRETATION The combination of buprenorphine and intensive psychosocial treatment is safe and highly efficacious , and should be added to the treatment options available for individuals who are dependent on heroin BACKGROUND The registration of combination buprenorphine/naloxone , a formulation design ed to reduce risk of diversion , has led some Australian jurisdictional authorities to allow treatment without direct observation of dosing for stable , opioid-dependent patients . AIM To compare two approaches ( 1 ) initiating treatment with observed dosing , then allowing patients who demonstrate stability to change to unobserved dosing ; or ( 2 ) initiating patients with unobserved dosing , subsequently requiring those who fail to stabilize to change to observed treatment . METHODS This study builds on an RCT comparing efficacy of observed and unobserved treatment at 3 months . At the conclusion of the RCT , clinical ly " stable " subjects were allocated to continue without observed dosing , while those who did not demonstrate stability were allocated to observed dosing . Subjects were followed for a further 3 months . Primary end-point was retention in treatment . RESULTS Of 119 subjects r and omised , 70 were retained in treatment to 3 months . Forty-five stable subjects were allocated to unobserved dosing , 25 to observation . Unstable subjects allocated to observed treatment were more likely to drop out thereafter ( OR 2.14 , 95 % CI 1.09 - 4.19 ) . There was a non-significant trend for people initiated with observed dosing to be better retained during the allocation phase ; at 6 months , 13 subjects ( 22 % ) from the original unobserved group , and 22 ( 34 % ) from the observed group , were retained in treatment ( chi2=2.10 , 1 df , p=0.15 ) . CONCLUSIONS Withdrawal of unobserved doses led to marked attrition from treatment . If access to unobserved dosing is to be restricted to stable patients , it appears preferable to initiate dosing with observation and allow unobserved doses for people who successfully stabilize , than to initiate with unobserved doses and transfer unstable patients to observation AIMS This study aim ed to determine the relative effectiveness of 12 months of interim methadone ( IM ; supervised methadone with emergency counseling only for the first 4 months of treatment ) , st and ard methadone treatment ( SM ; with routine counseling ) and restored methadone treatment ( RM : routine counseling with smaller case-loads ) . DESIGN A r and omized controlled trial was conducted comparing IM , SM and RM treatment . IM lasted for 4 months , after which participants were transferred to SM . SETTING The study was conducted in two methadone treatment programs in Baltimore , MD , USA . PARTICIPANTS The study included 230 adult methadone patients newly admitted through waiting-lists . MEASUREMENTS We administered the Addiction Severity Index and a supplemental question naire at baseline , 4 and 12 months post- baseline . Measurements included retention in treatment , self-reported days of heroin and cocaine use , criminal behavior and arrests and urine tests for heroin and cocaine metabolites . FINDINGS At 12 months , on an intent-to-treat basis , there were no significant differences in retention in treatment among the IM , SM and RM groups ( 60.6 % , 54.8 % and 37.0 % , respectively ) . Positive urine tests for the three groups declined significantly from baseline ( Ps < 0.001 and 0.003 , for heroin and cocaine metabolites , respectively ) but there were no significant group x time interactions for these measures . At least one arrest was reported by 30.6 % of the sample during the year , but there were no significant between-group effects . CONCLUSIONS Limited availability of drug counseling services should not be a barrier to providing supervised methadone to adults dependent on heroin -- at least for the first 4 months of treatment Abstract Objective To determine whether supervised medical prescription of heroin can successfully treat addicts who do not sufficiently benefit from methadone maintenance treatment . Design Two open label r and omised controlled trials . Setting Methadone maintenance programmes in six cities in the Netherl and s. Participants 549 heroin addicts . Interventions Inhalable heroin ( n = 375 ) or injectable heroin ( n = 174 ) prescribed over 12 months . Heroin ( maximum 1000 mg per day ) plus methadone ( maximum 150 mg per day ) compared with methadone alone ( maximum 150 mg per day ) . Psychosocial treatment was offered throughout . Main outcome measures Dichotomous , multidomain response index , including vali date d indicators of physical health , mental status , and social functioning . Results Adherence was excellent with 12 month outcome data available for 94 % of the r and omised participants . With intention to treat analysis , 12 month treatment with heroin plus methadone was significantly more effective than treatment with methadone alone in the trial of inhalable heroin ( response rate 49.7 % v 26.9 % ; difference 22.8 % , 95 % confidence interval 11.0 % to 34.6 % ) and in the trial of injectable heroin ( 55.5 % v 31.2 % ; difference 24.3 % , 9.6 % to 39.0 % ) . Discontinuation of the coprescribed heroin result ed in a rapid deterioration in 82 % ( 94/115 ) of those who responded to the coprescribed heroin . The incidence of serious adverse events was similar across treatment conditions . Conclusions Supervised coprescription of heroin is feasible , more effective , and probably as safe as methadone alone in reducing the many physical , mental , and social problems of treatment resistant heroin addicts Whilst unsupervised injectable methadone and diamorphine treatment has been part of the British treatment system for decades , the numbers receiving injectable opioid treatment ( IOT ) has been steadily diminishing in recent years . In contrast , there has been a recent expansion of supervised injectable diamorphine programs under trial conditions in a number of European and North American cities , although the evidence regarding the safety , efficacy and cost effectiveness of this treatment approach remains equivocal . Recent British clinical guidance indicates that IOT should be a second-line treatment for those patients in high- quality oral methadone treatment who continue to regularly inject heroin , and that treatment be initiated in newly-developed supervised injecting clinics . The R and omised Injectable Opioid Treatment Trial ( RIOTT ) is a multisite , prospect i ve open-label r and omised controlled trial ( RCT ) examining the role of treatment with injected opioids ( methadone and heroin ) for the management of heroin dependence in patients not responding to conventional substitution treatment . Specifically , the study examines whether efforts should be made to optimise methadone treatment for such patients ( e.g. regular attendance , supervised dosing , high oral doses , access to psychosocial services ) , or whether such patients should be treated with injected methadone or heroin . Eligible patients ( in oral substitution treatment and injecting illicit heroin on a regular basis ) are r and omised to one of three conditions : ( 1 ) optimized oral methadone treatment ( Control group ) ; ( 2 ) injected methadone treatment ; or ( 3 ) injected heroin treatment ( with access to oral methadone doses ) . Subjects are followed up for 6-months , with between-group comparisons on an intention-to-treat basis across a range of outcome measures . The primary outcome is the proportion of patients who discontinue regular illicit heroin use ( operationalised as providing > 50 % urine drug screens negative for markers of illicit heroin in months 4 to 6 ) . Secondary outcomes include measures of other drug use , injecting practice s , health and psychosocial functioning , criminal activity , patient satisfaction and incremental cost effectiveness . The study aims to recruit 150 subjects , with 50 patients per group , and is to be conducted in supervised injecting clinics across Engl and OBJECTIVE The objective of this secondary analysis was to explore differences in baseline clinical characteristics and opioid replacement therapy treatment outcomes by type ( heroin , opioid analgesic [ OA ] , or combined [ heroin and OA ] ) and route ( injector or non-injector ) of opioid use . METHOD A total of 1,269 participants ( 32.2 % female ) were r and omized to receive one of two study medications ( methadone or buprenorphine/naloxone [ BUP ] ) . Of these , 731 participants completed the 24-week active medication phase . Treatment outcomes were opioid use during the final 30 days of treatment ( among treatment completers ) and treatment attrition . RESULTS Non-opioid substance dependence diagnoses and injecting differentiated heroin and combined users from OA users . Non-opioid substance dependence diagnoses and greater heroin use differentiated injectors from non-injectors . Further , injectors were more likely to be using at end of treatment compared with non-injectors . OA users were more likely to complete treatment compared with heroin users and combined users . Non-injectors were more likely than injectors to complete treatment . There were no interactions between type of opioid used or injection status and treatment assignment ( methadone or BUP ) on either opioid use or treatment attrition . CONCLUSIONS Findings indicate that substance use severity differentiates heroin users from OA users and injectors from non-injectors . Irrespective of medication , heroin use and injecting are associated with treatment attrition and opioid misuse during treatment . These results have particular clinical interest , as there is no evidence of superiority of BUP over methadone for treating OA users versus heroin users AIMS To compare the effectiveness and cost-effectiveness of unobserved versus observed dosing of patients seeking treatment of heroin dependence . DESIGN R and omized controlled trial and cost-effectiveness analysis . Setting Specialist out-patient drug treatment centres in Australia . PARTICIPANTS Heroin users seeking maintenance treatment . INTERVENTION Participants were allocated r and omly to observed or unobserved dosing for 3 months . All subjects received buprenorphine-naloxone and weekly clinical review s. MEASUREMENTS Primary end-points were retention in treatment and heroin use at 3 months . Costs of treatment were measured ( in Australian dollars , AU$ ) and cost-effectiveness compared . Secondary outcomes included quality of life , psychological symptoms and use of non-opioid drugs . FINDINGS A total of 119 subjects were r and omized and analysed . At 3 months , 33/58 ( 57 % ) r and omized to unobserved treatment , and 37/61 ( 61 % ) observed were retained ( log-rank chi2 = 0.04 , df = 1 , P = 0.84 ) . On an intention-to-treat analysis , reductions in days of heroin use in the preceding month , from baseline to 3 months , did not differ significantly ; 18.5 days ( 95 % CI : 21.8 - 15.3 ) and 22.0 days ( 95 % CI : 24.3 - 19.7 ) , respectively ( Mann-Whitney U = 807.5 , P = 0.13 ) . The mean cost for the unobserved group was AU$1,663 ( 95 % CI 1308 - 2017 ) per treatment episode , significantly less than the mean cost for the observed group at AU$2,138 ( 95 % CI 1713 - 2562 ) . CONCLUSIONS Retention and heroin use was not significantly different between observed and unobserved dosing groups . Attendance for observed dosing was not associated with worse retention . Treatment with close clinical monitoring , but no observation of dosing , was significantly cheaper and therefore significantly more cost-effective BACKGROUND Buprenorphine-naloxone sublingual film was introduced in 2011 in Australia as an alternative to tablets . This study compared the two formulations on subjective dose effects and equivalence , trough plasma levels , adverse events , patient satisfaction , supervised dosing time , and impact upon treatment outcomes ( substance use , psychosocial function ) . METHODS 92 buprenorphine-naloxone tablet patients were recruited to this outpatient multi-site double-blind double-dummy parallel group trial . Patients were r and omised to either tablets or film , without dose changes , over a 31 day period . RESULTS No significant group differences were observed for subjective dose effects , trough plasma buprenorphine or norbuprenorphine levels , adverse events and treatment outcomes . Buprenorphine-naloxone film took significantly less time to dissolve than tablets ( 173±71 versus 242±141s , p=0.007 , F=7.67 ) . CONCLUSIONS The study demonstrated dose equivalence and comparable clinical outcomes between the buprenorphine-naloxone film and tablet preparations , whilst showing improved dispensing times and patient ratings of satisfaction with the film Objective Methadone coverage is poor in many countries due in part to methadone induction being possible only in specialized care ( SC ) . This multicenter pragmatic trial compared the effectiveness of methadone treatment between two induction models : primary care ( PC ) and SC . Methods In this study , registered at Clinical Trials . Gov ( NCT00657397 ) , opioid-dependent individuals not on methadone treatment for at least one month or receiving buprenorphine but needing to switch were r and omly assigned to start methadone in PC ( N = 155 ) or in SC ( N = 66 ) in 10 sites in France . Visits were scheduled at months M0 , M3 , M6 and M12 . The primary outcome was self-reported abstinence from street-opioids at 12 months ( M12 ) ( with an underlying 15 % non-inferiority hypothesis for PC ) . Secondary outcomes were abstinence during follow-up , engagement in treatment ( i.e. completing the induction period ) , retention and satisfaction with the explanations provided by the physician . Primary analysis used intention to treat ( ITT ) . Mixed models and the log-rank test were used to assess the arm effect ( PC vs. SC ) on the course of abstinence and retention , respectively . Results In the ITT analysis ( n = 155 in PC , 66 in SC ) , which compared the proportions of street-opioid abstinent participants , 85/155 ( 55 % ) and 22/66 ( 33 % ) of the participants were classified as street-opioid abstinent at M12 in PC and SC , respectively . This ITT analysis showed the non-inferiority of PC ( 21.5 [ 7.7 ; 35.3 ] ) . Engagement in treatment and satisfaction with the explanations provided by the physician were significantly higher in PC than SC . Retention in methadone and abstinence during follow-up were comparable in both arms ( p = 0.47 , p = 0.39 , respectively ) . Conclusions Under appropriate conditions , methadone induction in primary care is feasible and acceptable to both physicians and patients . It is as effective as induction in specialized care in reducing street-opioid use and ensuring engagement and retention in treatment for opioid dependence . Trial registration Number Eudract 2008 - 001338 - 28 ; Clinical Trials.gov : NCT00657397 ; International St and ard R and omized Controlled Trial Number Register IS RCT Methadone Maintenance Treatment ( MMT ) is among the most widely studied treatments for opiate dependence with proven benefits for patients and society . When misused , however , methadone can also be lethal . The issue of methadone diversion is a major concern for all MMT programs . A potential source for such diversion is from those MMT patients who receive daily take home methadone doses . Using a reverse phase high performance liquid chromatography method , seven of the nine patients who were r and omly selected to have all of their remaining methadone take home doses ( within a 24 hour period ) analyzed , returned lower than expected quantities of methadone . This finding suggests the possibility that such patients may have tampered with their daily take home doses . Larger prospect i ve observational studies are clearly needed to test the supposition of this pilot study Methadone maintenance therapy ( MMT ) has been found effective in treating heroin addiction . Serious consideration should be given to the modality of methadone distribution , as it influences not only treatment outcome but the attitudes of policy makers and the community , too . On one h and , the choice of take-home methadone removes the need for daily attendance at a methadone clinic , which seems to improve patients ' quality of life . On the other , this method , because of its lack of supervision and the absence of strict consumption monitoring , runs the risk of methadone misuse and diversion . In this study , we compared A ) supervised daily consumption , B ) contingent take-home incentives and C ) non-contingent take-home in methadone maintenance in three groups of heroin-addicted patients attending three different MMT programmes . Retention rates at 12 months were significantly higher in contingent take-home patients ( group B ) than in those with supervised daily consumption ( group A ) and the non-contingent take-home ( group C ) . Retention rates were higher in group A than in group C patients . Compared to patients in groups A and B , those in group C showed fewer negative urinalyses and higher rates of self-reported diversion and episodes of crime or violence . Results indicate a more positive outcomes following take-home methadone associated with behavioural incentives and other measures that aim to facilitate treatment compliance than those following daily supervised consumption . By contrast , non-contingent take-home methadone given to non-stabilized patients is associated with a high rate of diversion , along with more crime episodes and maladaptive behaviours AIMS The R and omized Injectable Opioid Treatment Trial ( RIOTT ) compared supervised injectable heroin ( SIH ) and supervised injectable methadone ( SIM ) with optimized oral methadone ( OOM ) ( IS RCT N0133807 ) . Heroin addicts ( previously unresponsive to treatment ) made significant reductions in street heroin use at 6 months when treated with SIH . We now examine secondary outcomes . DESIGN Multi-site r and omized controlled trial ( RCT ) comparing SIH versus OOM and SIM versus OOM . SETTING Three supervised injectable opiate clinics in Engl and . PARTICIPANTS Chronic refractory heroin addicts continuing to inject street heroin virtually daily despite oral substitution treatment ( n = 127 ) , r and omized to either SIH(n = 43 ) , SIM(n = 42 ) or OOM(n = 42 ) . All received high levels of medical and psychosocial support . MEASUREMENTS SECONDARY OUTCOMES wider drug use , crime , health and social functioning at 6 months . FINDINGS At 6 months , no significant differences were found between treatment groups in wider drug use ( crack/cocaine , benzodiazepines , alcohol ) , physical and mental health ( SF-36 ) or social functioning . Within each treatment group , significant reductions were observed in crime [ SIH = odds ratio ( OR ) 0.05 ; P < 0.001 ; SIM = OR 0.11 ; P = 0.002 ; OOM = OR 0.11 ; P = 0.003 ] and money spent per week on illicit drugs ( SIH = mean change £ -289.43 ; P < 0.001 ; SIM = mean change £ -183.41 ; P < 0.001 ; OOM = mean change £ -162.80 ; P < 0.001 ) , with SIH significantly more likely to have reduced money spent on illicit drugs versus OOM ( mean difference £ -92.04 ; P < 0.001 ) . Significant improvements were seen in physical health for SIH and SIM ( SIH = mean change 3.97 ; P = 0.008 ; SIM = mean change 4.73 ; P = 0.002 ) and mental health for OOM ( mean change 6.04 ; P = 0.013 ) . CONCLUSIONS Supervised injectable heroin treatment and supervised injectable methadone treatment showed no clearly identified benefit over optimized oral methadone in terms of wider drug use , crime , physical and mental health within a 6-month period , despite reducing street heroin use to a greater extent . However , all interventions were associated with improvements in these outcomes INTRODUCTION AND AIMS Supervised consumption of opiate substitution treatment is st and ard practice in the UK yet little is known about the patient experience of this treatment modality . This study aim ed to assess the patient experience of receiving supervised compared with unsupervised consumption of methadone or buprenorphine . DESIGN AND METHODS A qualitative study utilising a grounded theory approach to analysis . Participants ( 29 ) were theoretically sample d from 293 opioid-dependent patients entering a r and omised controlled trial of opiate substitution treatment across four urban and community drug treatment services in Engl and . Multidisciplinary staff were recruited for interviews and focus groups ( 55 ) . RESULTS Supervised consumption was accepted by patients , despite causing practical limitations and raising issues of privacy and stigma . Patients recognised that establishing a daily routine away from illicit drugs was useful early in treatment . However , having flexibility to move away from supervision was important . Unsupervised patients reported that they ultimately preferred this treatment approach and appreciated the trust and sense of reward that unsupervised treatment bought . Clinicians expressed confidence in supervised prescribing and reduced risk for their patients , but also concern that a minority of individuals may remain inappropriately supervised for lengthy time periods . DISCUSSION AND CONCLUSIONS This study provides an important patient perspective and is the first in-depth qualitative investigation directly comparing supervision with unsupervised treatment to consider both patient and professional perspectives . Overall , our qualitative findings suggest that flexibly timed discontinuation of supervision may have positive benefits OBJECTIVE To implement a collaborative care management program with buprenorphine in a primary care clinic . DESIGN Prospect i ve observational study . SETTING A busy urban academic primary care clinic affiliated with a tertiary care hospital . PARTICIPANTS Opioid-dependent patients or patients with chronic pain using opioids nonmedically were recruited for the study . A total of 45 participants enrolled . INTERVENTIONS Patients were treated with buprenorphine and managed by a supervising psychiatrist , pharmacist care manager , and health coaches . The care manager conducted buprenorphine inductions and all follow-up visits . Health coaches offered telephonic support . The psychiatrist supervised both the care manager and health coaches . MAIN OUTCOME MEASURES Primary outcomes were treatment retention at 6 months , and change in the proportion of aberrant toxicology results and opioid craving scores from baseline to 6 months . After data collection , clinical outcomes were compared between opioid-dependent patients and patients with chronic pain using opioids nonmedically . Overall , 55.0 percent of participants ( 25/45 ) remained in treatment at 6 months . Primary care physicians ( PCPs ) ' attitudes about opioid dependence treatment were surveyed at baseline and at 18 months . RESULTS Forty-three patients ( 95.6 percent ) accepted treatment and 25 ( 55.0 percent ) remained in treatment at 6 months . The proportion of aberrant urine toxicology results decreased significantly from baseline to 6 months ( p < 0.01 ) . Craving scores significantly decreased from baseline to 6 months ( p < 0.01 ) . Opioid-dependent patients , as opposed to patients with chronic pain using opioids nonmedically , were significantly more likely to complete 6 months of treatment ( p < 0.05 ) . PCPs ' confidence in treating opioid dependence in primary care increased significantly from baseline to 18 months postimplementation ( p < 0.01 ) . CONCLUSION Collaborative care management for opioid dependence with buprenorphine may be feasible in a primary care clinic . More research is needed to underst and the role of buprenorphine in managing patients with chronic pain using opioids nonmedically OBJECTIVE To document trends in : ( i ) prescribing of morphine and oxycodone ; ( ii ) hospital separations for overdose ; ( iii ) presentations for treatment of problems associated with these drugs ; and ( iv ) oxycodone-related mortality data in Australia . DESIGN AND SETTING Cross-sectional study analysing prescriptions for morphine and oxycodone based on figures adjusted using Australian Bureau of Statistics estimated resident population and prospect ively collected data from : ( i ) the National Hospital Morbidity Data base on hospital separations primarily attributed to poisoning with opioids other than heroin ( " other opioids " ) ; ( ii ) the Alcohol and Other Drug Treatment National Minimum Data Set for treatment episodes where morphine or oxycodone were the primary or other drugs of concern ; ( iii ) the National Coronial Information System on deaths where oxycodone was the underlying cause of death or a contributory factor . MAIN OUTCOME MEASURES Population -adjusted numbers of ( i ) prescriptions for morphine and oxycodone by 10-year age group , ( ii ) hospital separations for " other opioid " poisoning , and ( iii ) treatment episodes related to morphine or oxycodone ; and ( iv ) number of oxycodone-related deaths . RESULTS Prescriptions for morphine declined , while those for oxycodone increased . Prescriptions for both were highest among older Australians . Hospital separations for " other opioid " poisoning doubled between the financial years 2005 - 06 and 2006 - 07 . Treatment episodes for morphine remained stable , while those for oxycodone increased . There were 465 oxycodone-related deaths recorded during 2001 - 2009 . CONCLUSIONS Oxycodone prescriptions in Australia have increased , particularly among older Australians . The increase may , in part , reflect appropriate prescribing for pain among an ageing population . However we are unable to differentiate non-medical use from appropriate prescribing from this data . In comparison to heroin , the morbidity and mortality associated with oxycodone is relatively low in Australia . There is a continued need for comprehensive training of general practitioners in assessing patients with chronic non-malignant pain and prescribing of opioids for these patients , to minimise the potential for harms associated with use of these medications AIMS To evaluate whether buprenorphine . even without additional control and psychosocial treatment and support , alleviates the problems faced by patients waiting for medication assisted rehabilitation ( MAR ) . DESIGN A r and omized , double-blind , 12-week study of Subutex versus placebo without additional support as an interim therapy . PARTICIPANTS One hundred and six patients , 70 males and 36 females , waiting for MAR in Oslo . The average age was 38 years with an average history of heroin use of 20 years . Fifty-five patients were assigned to buprenorphine and 51 to a placebo . INTERVENTION Subutex or placebo sublingual tablets were given under supervision in a daily dose of 16 mg with the exception of a double dose on Saturday and no dose on Sunday . MEASUREMENT Retention , compliance , self-reported drug-abuse , wellbeing and mental health . FINDINGS The average number of days of participation was significantly higher in the buprenorphine group , 42 ( median : 29 ) compared to 14 ( median : 11 ) for the placebo group ( P < 0.001 ) . The retention of patients after 12 weeks was 16 patients in the buprenorphine group and one patient in the placebo group . The buprenorphine group had a larger decrease in reported opioid use ( p < 0.001 ) and in reported use of other drugs , tablets and alcohol abuse ( p < 0.01 ) . The group also showed a stronger increase in wellbeing ( p < 0.01 ) and life satisfaction ( p < 0.05 ) . None of the participants died . CONCLUSION The patients waiting for MAR benefited significantly from the buprenorphine as an interim therapy according to retention , self-reported use of drugs and wellbeing . However , the patients had difficulties in remaining in treatment over time without psychosocial support BACKGROUND In the multi-site Prescription Opioid Addiction Treatment Study ( POATS ) , conducted within the National Drug Abuse Clinical Trials Network , participants r and omly assigned to receive individual drug counseling in addition to buprenorphine-naloxone and medical management did not have superior opioid use outcomes . However , research with other substance-dependent population s shows that subgroups of participants may benefit from a treatment although the entire population does not . METHOD We conducted a secondary analysis of POATS data to determine whether a subgroup of participants benefited from drug counseling in addition to buprenorphine-naloxone and medical management , either due to greater problem severity or more exposure to counseling as a result of greater treatment adherence . Problem severity was measured by a history of heroin use , higher Addiction Severity Index drug composite score , and chronic pain . Adequate treatment adherence was defined a priori as attending at least 60 % of all offered sessions . RESULTS Patients who had ever used heroin and received drug counseling were more likely to be successful ( i.e. , abstinent or nearly abstinent from opioids ) than heroin users who received medical management alone , but only if they were adherent to treatment and thus received adequate exposure to counseling ( OR=3.7 , 95 % CI=1.1 - 11.8 , p=0.03 ) . The association between severity and outcome did not vary by treatment condition for chronic pain or ASI drug severity score . CONCLUSIONS These findings emphasize the importance of treatment adherence , and suggest that patients with prescription opioid dependence are a heterogeneous group , with different optimal treatment strategies for different subgroups INTRODUCTION AND AIMS Methadone maintenance remains the mainstay of treatment for opiate dependence in Scotl and . Guidelines recommend supervised self-administration for at least 3 months , yet this is often interpreted as long-term supervision . However , there is no evidence base for deciding the optimal period of supervision . We tested the feasibility of conducting a r and omised controlled trial ( RCT ) of different supervision models . DESIGN AND METHODS Three armed pilot RCT , set in three Scottish treatment areas , recruited opiate-dependent patients who had received methadone treatment for 3 months . Participants were r and omised to : ( i ) no supervision ; ( ii ) twice weekly supervision ; or ( iii ) daily supervision for further 3 months . As a pilot , key process measures were : recruitment rates , follow-up rates and treatment fidelity . We also wanted to estimate effect sizes of two co- primary outcomes for a full RCT : treatment retention and illicit heroin use . The recruitment target was 60 participants . RESULTS One hundred and two eligible patients were identified , 60 ( 59 % ) participated , and 46 followed up ( 77 % ) . Study fidelity was good with two participants moving group . Those r and omised to no supervision were significantly happier with their group allocation . No significant differences were found in primary outcomes , although retention decreased with increased supervision , while illicit heroin use was least in those most supervised . DISCUSSION AND CONCLUSIONS It is possible to recruit and r and omise participants to an RCT comparing different forms of supervised consumption . Pilot data suggest increased supervision may reduce illicit heroin use , but may decrease retention . This should now be tested in a large-scale multicentre RCT INTRODUCTION AND AIMS The study investigates patients ' pre-treatment expectations of , and post-treatment satisfaction with , supervised injectable opiate treatment delivered within UK 's first such clinics within the R and omised Injectable Opiate Treatment Trial ( RIOTT ) ( IS RCT N0133807 ) . DESIGN AND METHODS Data were collected from 127 chronic heroin addicts recruited to RIOTT and r and omised to receive supervised injectable ( heroin or methadone ) treatment or optimised oral maintenance treatment at supervised injectable maintenance clinics in London , Darlington and Brighton . RESULTS Of 127 RIOTT patients , 113 ( 89 % ) provided responses to structured enquiry about treatment expectations , and 94 ( 74 % ) subsequent responses about treatment satisfaction ( at six months ) . Patients were hoping that injectable heroin treatment would : reduce substance misuse ( 81 % ) ; help achieve normality , routine and structure ( 16 % ) ; and increase education and work prospect s ( 15 % ) . At six months , an area of treatment satisfaction most commonly reported by all three trial groups was reduced substance misuse ( supervised injectable heroin 59 % , supervised injectable methadone 56 % , optimised oral methadone 54 % ) . Most found supervision acceptable , but some desired modifications were also identified . DISCUSSION AND CONCLUSIONS Patients previously considered non-responsive to treatment appear to have similar treatment expectations and aspirations as other drug users in treatment . Supervised injectable opioid treatment patients consistently reported treatment satisfaction but also that more could be done to optimise aspects of current arrangement . This raised the challenging issue of the extent to which opinions of patients need to be taken into consideration in shaping future treatment provision . Future research may need to examine the extent of expectations ' fit ' and the relationship between treatment sought and received Objectives To determine ( 1 ) the natural history of prescription opioid use , ( 2 ) the predictors of long-term opioid use , and ( 3 ) the association between opioid dose and pain and function in a large cohort of workers with recent back injuries . Methods Prospect i ve cohort of workers with back injuries ( N=1883 ) interviewed 18 days ( median ) and 1 year after cl aim su bmi ssion . Detailed pharmacy data were obtained from computerized records of paid bills . Results Forty-two percent of workers ( 781/1843 ) received an opioid in the year after injury , most ( 694/781 , 89 % ) at or shortly after the first medical visit for the injury . Of these , most ( 410/694 , 59 % ) received opioids only within the first quarter after injury , whereas 16 % ( 111/694 ) received opioids for 4 quarters . Among these long-term users , total morphine equivalent dose ( MED ) increased significantly ( P<0.01 ) from the first ( mean , 2364 mg ; st and ard deviation , 4019 mg ) to the fourth ( mean , 3824 mg ; st and ard deviation , 5998 mg ) quarter . Improvement by at least 30 % in pain and function measure scores occurred in only 26 % ( 95 % confidence interval 18%-36 % ) and 16 % ( 95 % confidence interval 10%-25 % ) , respectively , of long-term users . Opioid doses increased substantially over time in all but those in whom function improved . After adjustment for baseline pain , function , and injury severity , the strongest predictor of longer term opioid prescription was total MED in the first quarter . Workers receiving at least 40 mg MED per day in the first quarter had 6-fold odds of receiving longer-term opioids . Discussion sFor the small group of workers with compensable back injuries who receive opioids longer-term ( 111/1843 , 6 % ) , opioid doses increase substantially and only a minority shows clinical ly important improvement in pain and function . The amount of prescribed opioid received early after injury strongly predicts long-term use . More research is needed to underst and clinical decisions to continue or increase opioid therapy after back injury BACKGROUND Some heroin addicts persistently fail to benefit from conventional treatments . We aim ed to compare the effectiveness of supervised injectable treatment with medicinal heroin ( diamorphine or diacetylmorphine ) or supervised injectable methadone versus optimised oral methadone for chronic heroin addiction . METHODS In this multisite , open-label , r and omised controlled trial , we enrolled chronic heroin addicts who were receiving conventional oral treatment ( > or=6 months ) , but continued to inject street heroin regularly ( > or=50 % of days in preceding 3 months ) . R and omisation by minimisation was used to assign patients to receive supervised injectable methadone , supervised injectable heroin , or optimised oral methadone . Treatment was provided for 26 weeks in three supervised injecting clinics in Engl and . Primary outcome was 50 % or more of negative specimens for street heroin on weekly urinalysis during weeks 14 - 26 . Primary analysis was by intention to treat ; data were adjusted for centre , regular crack use at baseline , and treatment with optimised oral methadone at baseline . Percentages were calculated with Rubin 's rules and were then used to estimate numbers of patients in the multiple imputed sample s. This study is registered , IS RCT N01338071 . FINDINGS Of 301 patients screened , 127 were enrolled and r and omly allocated to receive injectable methadone ( n=42 patients ) , injectable heroin ( n=43 ) , or oral methadone ( n=42 ) ; all patients were included in the primary analysis . At 26 weeks , 80 % ( n=101 ) patients remained in assigned treatment : 81 % ( n=34 ) on injectable methadone , 88 % ( n=38 ) on injectable heroin , and 69 % ( n=29 ) on oral methadone . Patients on injectable heroin were significantly more likely to have achieved the primary outcome ( 72 % [ n=31 ] ) than were those on oral methadone ( 27 % [ n=11 ] , OR 7.42 , 95 % CI 2.69 - 20.46 , p<0.0001 ; adjusted : 66 % [ n=28 ] vs 19 % [ n=8 ] , 8.17 , 2.88 - 23.16 , p<0.0001 ) , with number needed to treat of 2.17 ( 95 % CI 1.60 - 3.97 ) . For injectable methadone ( 39 % [ n=16 ] ; adjusted : 30 % [ n=14 ] ) versus oral methadone , the difference was not significant ( OR 1.74 , 95 % CI 0.66 - 4.60 , p=0.264 ; adjusted : 1.79 , 0.67 - 4.82 , p=0.249 ) . For injectable heroin versus injectable methadone , a significant difference was recorded ( 4.26 , 1.63 - 11.14 , p=0.003 ; adjusted : 4.57 , 1.71 - 12.19 , p=0.002 ) , but the study was not powered for this comparison . Differences were evident within the first 6 weeks of treatment . INTERPRETATION Treatment with supervised injectable heroin leads to significantly lower use of street heroin than does supervised injectable methadone or optimised oral methadone . UK Government proposals should be rolled out to support the positive response that can be achieved with heroin maintenance treatment for previously unresponsive chronic heroin addicts . FUNDING Community Fund ( Big Lottery ) Research section , through Action on Addiction Background For the past 30 years , opioids have been used to treat chronic nonmalignant pain . This study tests the following hypotheses : ( 1 ) there is no strong evidence -based foundation for the conclusion that long-term opioid treatment of chronic nonmalignant pain is effective ; and ( 2 ) the main problem associated with the safety of such treatment – assessment of the risk of addiction – has been neglected . Methods Scientometric analysis of the articles representing clinical research in this area was performed to assess ( 1 ) the quality of presented evidence ( type of study ) ; and ( 2 ) the duration of the treatment phase . The sufficiency of representation of addiction was assessed by counting the number of articles that represent ( 1 ) editorials ; ( 2 ) articles in the top specialty journals ; and ( 3 ) articles with titles clearly indicating that the addiction-related safety is involved ( topic-in-title articles ) . Results Not a single r and omized controlled trial with opioid treatment lasting > 3 months was found . All studies with a duration of opioid treatment ≥6 months ( n = 16 ) were conducted without a proper control group . Such studies can not provide the consistent good- quality evidence necessary for a strong clinical recommendation . There were profound differences in the number of addiction articles related specifically to chronic nonmalignant pain patients and to opioid addiction in general . An inadequate number of chronic pain-related publications were observed with all three types of counted articles : editorials , articles in the top specialty journals , and topic-in-title articles . Conclusion There is no strong evidence -based foundation for the conclusion that long-term opioid treatment of chronic nonmalignant pain is effective . The above identified signs indicating neglect of addiction associated with the opioid treatment of chronic nonmalignant pain were present |
10,454 | 23,338,775 | Risk assessment and behavioral interventions in pediatric clinics reduced abuse and neglect outcomes for young children .
Early childhood home visitation also reduced abuse and neglect , but results were inconsistent . | BACKGROUND In 2004 , the U.S. Preventive Services Task Force determined that evidence was insufficient to recommend behavioral interventions and counseling to prevent child abuse and neglect .
PURPOSE To review new evidence on the effectiveness of behavioral interventions and counseling in health care setting s for reducing child abuse and neglect and related health outcomes , as well as adverse effects of interventions . | OBJECTIVE : To estimate the efficacy of a psycho-behavioral intervention in reducing intimate partner violence recurrence during pregnancy and postpartum and in improving birth outcomes in African-American women . METHODS : We conducted a r and omized controlled trial for which 1,044 women were recruited . Women were r and omly assigned to receive either intervention ( n=521 ) or usual care ( n=523 ) . Individually tailored counseling sessions were adapted from evidence -based interventions for intimate partner violence and other risks . Logistic regression was used to model intimate partner violence victimization recurrence and to predict minor , severe , physical , and sexual intimate partner violence . RESULTS : Women r and omly assigned to the intervention group were less likely to have recurrent episodes of intimate partner violence victimization ( odds ratio [ OR ] 0.48 , 95 % confidence interval [ CI ] 0.29–0.80 ) . Women with minor intimate partner violence were significantly less likely to experience further episodes during pregnancy ( OR 0.48 , 95 % CI 0.26–0.86 , OR 0.53 , 95 % CI 0.28–0.99 ) and postpartum ( OR 0.56 , 95 % CI 0.34–0.93 ) . Numbers needed to treat were 17 , 12 , and 22 , respectively , as compared with the usual care group . Women with severe intimate partner violence showed significantly reduced episodes postpartum ( OR 0.39 , 95 % CI 0.18–0.82 ) ; the number needed to treat was 27 . Women who experienced physical intimate partner violence showed significant reduction at the first follow-up ( OR 0.49 , 95 % CI 0.27–0.91 ) and postpartum ( OR 0.47 , 95 % CI 0.27–0.82 ) ; the numbers needed to treat were 18 and 20 , respectively . Women in the intervention group had significantly fewer very preterm neonates ( 1.5 % intervention group , 6.6 % usual care group ; P=.03 ) and an increased mean gestational age ( 38.2±3.3 intervention group , 36.9±5.9 usual care group ; P=.016 ) . CONCLUSION : A relatively brief intervention during pregnancy had discernible effects on intimate partner violence and pregnancy outcomes . Screening for intimate partner violence as well as other psychosocial and behavioral risks and incorporating similar interventions in prenatal care is strongly recommended . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00381823 . LEVEL OF EVIDENCE : OBJECTIVE To compare the behaviors of black , white , and Hispanic children who were 18 months to 18 years of age and exposed to intimate partner violence with an age- and ethnically similar sample of children who were not exposed to violence and to compare both exposed and nonexposed children to normative sample s. METHODS As part of a study on treatments for abused women in primary care public health clinics and Women , Infants and Children clinics in a large urban area , 258 abused mothers completed the Child Behavior Checklist ( CBCL ) on 1 of their r and omly selected children between the ages of 18 months and 18 years . An ethnically similar sample of 72 nonabused mothers also completed the CBCL . The CBCL is a st and ardized instrument that provides a parental report of the extent of a child 's behavioral problems and social competencies . The CBCL consists of a form for children 18 months to 5 years and a version for ages 6 to 18 years . The CBCL is orally administered to a parent , who rates the presence and frequency of certain behaviors on a 3-point scale ( 0 = not true , 1 = somewhat or sometimes true , and 2 = very true or often true ) . The time period is the last 6 months for the child 6 to 18 years of age and 2 months for the child 18 months to 5 years of age . Examples of behaviors for the child age 6 to 18 years include " gets in many fights , " " truancy , skips school . " Examples of behaviors for the child 18 months to 5 years of age include " cruel to animals , " " physically attacks people , " and " does n't want to sleep alone . " Both forms of the CBCL consist of 2 broadb and factors of behavioral problems : internalizing and externalizing with mean scale scores for national normative sample s as well as clinical ly referred and nonreferred sample s of children . Internalizing behaviors include anxiety/depression , withdrawal , and somatic complaints . Externalizing behaviors include attention problems , aggressive behavior , and rule-breaking actions . Behavior scales yield a score of total behavioral problems . Scores are summed and then converted to normalized T scores . T scores > or=60 are within the borderline/ clinical referral range-higher scores represent more deviant behavior . Multivariate analyses of variance ( MANOVAs ) were used to determine whether children from abused mothers differed significantly in their internalizing behaviors , externalizing behaviors , and total behavior problems from children of nonabused mothers . One sample t tests were used to compare children from abused and nonabused mothers to the matched clinical ly referred and nonreferred normative sample . Four pair-wise comparisons were considered : 1 ) children from abused women to referred norm , 2 ) children from abused women to nonreferred norm , 3 ) children from nonabused women to referred norm , and 4 ) children from nonabused to nonreferred norm . The internal , external , and total behavior problem T scores were dichotomized into a referral status : nonreferred = T score < 60 , referred = T score > or= 60 . Frequencies and percentages were used to describe the distribution of referral status among the children from the abused and nonabused women , and chi(2 ) tests of independence were used to determine whether the groups were significantly different . RESULTS No significant differences in demographic characteristics between children from the abused women and nonabused women were observed . The sample consisted of a large number of Hispanic children ( 68.9 % ) and slightly more girls ( 53.6 % ) , and nearly half ( 45.2 % ) had annual household incomes < 10,000 dollars . Means , st and ard deviations , and results from the MANOVAs performed on internal , external , and total behavior problem scores between children from abused and nonabused women revealed no significant differences ( F[3,139 ] = 1.21 ) for children ages 18 months through 5 years . Results from the MANOVA performed for ages 6 through 18 years revealed a significant group difference ( F[3,183 ] = 3.13 ) . Univariate tests revealed significant group differences for internalizing behavior ( F[1,185 ] = 6.81 ) , externalizing behav = 6.81 ) , externalizing behavior ( F[1,185 ] = 7.84 ) , and total behavior problems ( F[1,185 ] = 9.45 ) . Overall , children of abused mothers had significantly higher internalizing ( 58.5 + /- 12.1 ) , externalizing ( 55.5 + /- 12.4 ) , and total behavior problems ( 57.6 + /- 12.3 ) scores than the internalizing ( 52.9 + /- 13.7 ) , externalizing ( 49.7 + /- 10.6 ) , and total behavior problems ( 51.0 + /- 13.0 ) scores exhibited for children of nonabused mothers . Most comparisons of children from the abused women to the referred and nonreferred norms are significant . The mean internal , external , and total behavior problem scores from children of abused women were significantly higher than the nonreferred norms and significantly lower than the referred norms . In contrast , all comparisons for children from nonabused women were not significantly different from the nonreferred norms . CONCLUSIONS Children , ages 6 to 18 years , of abused mothers exhibit significantly more internalizing , externalizing , and total behavior problems than children for the same age and sex of nonabused mothers . In addition , the mean internalizing behavior score for boys 6 to 11 years of age as well as girls and boys 12 to 18 years of age of abused mothers were not significantly different from the clinical referral norms . Internalizing behaviors of anxiety , withdrawal , and depression are consistent with suicidal risk . The association of a child 's exposure to intimate partner violence and subsequent attempted and /or completed suicide dem and s research . Our data demonstrate that children of abused mothers have significantly more behavioral problems than the non clinical ly referred norm children but also , for most children , display significantly fewer problems than the clinical ly referred children . These children of abused mothers are clearly suspended above normal and below deviant , with children ages 6 to 18 being at the greatest risk . If abused mothers can be identified and treated , then perhaps behavior problems of their children can be arrested and behavioral scores improved . The American Academy of Pediatrics Committee on Child Abuse and Neglect recommends routine screening of all women for abuse at the time of the well-child visit and implementation of a protocol that includes a safety plan for the entire family . Clinicians can use this research information to assess for intimate partner violence during child health visits and inform abused mothers of the potential effects on their children 's behavior . Early detection and treatment for intimate partner violence against women has the potential to interrupt and prevent behavioral problems for their children CONTEXT Home visitation to families with young children has been promoted as an effective way to prevent child maltreatment , but few studies have examined the conditions under which such programs meet this goal . OBJECTIVE To investigate whether the presence of domestic violence limits the effects of nurse home visitation interventions in reducing substantiated reports of child abuse and neglect . DESIGN Fifteen-year follow-up study of a r and omized trial . SETTING Semirural community in upstate New York . PARTICIPANTS Of 400 socially disadvantaged pregnant women with no previous live births enrolled consecutively between April 1978 and September 1980 , 324 mothers and their children participated in the follow-up study . INTERVENTIONS Families were r and omly assigned to receive routine perinatal care ( control group ; n = 184 participated in follow-up ) , routine care plus nurse home visits during pregnancy only ( n = 100 ) , or routine care plus nurse home visits during pregnancy and through the child 's second birthday ( n = 116 ) . MAIN OUTCOME MEASURES Number of substantiated reports over the entire 15-year period involving the study child as subject regardless of the identity of the perpetrator or involving the mother as perpetrator regardless of the identity of the child abstract ed from state records and analyzed by treatment group and level of domestic violence in the home as measured by the Conflict Tactics Scale . RESULTS Families receiving home visitation during pregnancy and infancy had significantly fewer child maltreatment reports involving the mother as perpetrator ( P = . 01 ) or the study child as subject ( P = .04 ) than families not receiving home visitation . The number of maltreatment reports for mothers who received home visitation during pregnancy only was not different from the control group . For mothers who received visits through the child 's second birthday , the treatment effect decreased as the level of domestic violence increased . Of women who reported 28 or fewer incidents of domestic violence ( 79 % of sample ) , home-visited mothers had significantly fewer child maltreatment reports during the 15-year period than mothers not receiving the longer-term intervention ( P = .01 ) . However , this intervention did not significantly reduce child maltreatment among mothers reporting more than 28 incidents of domestic violence ( 21 % of sample ) . CONCLUSIONS The presence of domestic violence may limit the effectiveness of interventions to reduce incidence of child abuse and neglect . JAMA . 2000;284:1385 - 1391 OBJECTIVE . Our goal was to test the effect of prenatal and infancy home visits by nurses on mothers ' fertility and children 's functioning 7 years after the program ended at child age 2 . METHODS . We conducted a r and omized , controlled trial in a public system of obstetric and pediatric care . A total of 743 primarily black women < 29 weeks ' gestation , with previous live births and at least 2 sociodemographic risk characteristics ( unmarried , < 12 years of education , unemployed ) , were r and omly assigned to receive nurse home visits or comparison services . Primary outcomes consisted of intervals between births of first and second children and number of children born per year ; mothers ' stability of relationships with partners and relationships with the biological father of the child ; mothers ' use of welfare , food stamps , and Medicaid ; mothers ' use of substances ; mothers ' arrests and incarcerations ; and children 's academic achievement , school conduct , and mental disorders . Secondary outcomes were the sequelae of subsequent pregnancies , women 's employment , experience of domestic violence , and children 's mortality . RESULTS . Nurse-visited women had longer intervals between births of first and second children , fewer cumulative subsequent births per year , and longer relationships with current partners . From birth through child age 9 , nurse-visited women used welfare and food stamps for fewer months . Nurse-visited children born to mothers with low psychological re sources , compared with control-group counterparts , had better grade -point averages and achievement test scores in math and reading in grade s 1 through 3 . Nurse-visited children , as a trend , were less likely to die from birth through age 9 , an effect accounted for by deaths that were attributable to potentially preventable causes . CONCLUSIONS . By child age 9 , the program reduced women 's rates of subsequent births , increased the intervals between the births of first and second children , increased the stability of their relationships with partners , facilitated children 's academic adjustment to elementary school , and seems to have reduced childhood mortality from preventable causes This study examines whether an integrated behavioral intervention with proven efficacy in reducing psycho-behavioral risks ( smoking , environmental tobacco smoke exposure ( ETSE ) , depression , and intimate partner violence ( IPV ) ) in African-Americans is associated with improved pregnancy outcomes . A r and omized controlled trial targeting risks during pregnancy was conducted in the District of Columbia . African-American women were recruited if reporting at least one of the risks mentioned above . R and omization to intervention or usual care was site and risk specific . Sociodemographic , health risk and pregnancy outcome data were collected . Data on 819 women , and their singleton live born infants were analyzed using an intent-to-treat approach . Bivariate analyses preceded a reduced logistical model approach to eluci date the effect of the intervention on the reduction of prematurity and low birth weight . The incidence of low birthweight ( LBW ) was 12 % and very low birthweight ( VLBW ) was 1.6 % . Multivariate logistic regression results showed that depression was associated with LBW ( OR = 1.71 , 95 % CI = 1.12–2.62 ) . IPV was associated with preterm birth ( PTB ) and very preterm birth ( VPTB ) ( OR 1.64 , 95 % CI = 1.07–2.51 , OR = 2.94 , 95 % CI = 1.40–6.16 , respectively ) . The occurrence of VPTB was significantly reduced in the intervention compared to the usual care group ( OR = 0.42 , 95 % CI = 0.19 - 0.93 ) . Our study confirms the significant associations between multiple psycho-behavioral risks and poor pregnancy outcomes , including LBW and PTB . Our behavioral intervention with demonstrated efficacy in addressing multiple risk factors simultaneously reduced VPTB within an urban minority population OBJECTIVES To assess the impact of a home visiting program in reducing malleable parental risk factors for child abuse in families of newborns identified , through population -based screening , as at-risk of child abuse . METHODS This r and omized trial focused on Healthy Start Program ( HSP ) sites operated by three community-based organizations on Oahu , HI , USA . From 11/94 to 12/95 , 643 families were enrolled and r and omly assigned to intervention and control groups . Mothers in both groups were interviewed annually for 3 years ( 88 % follow-up each year ) to measure mental health , substance use , and partner violence . HSP records were review ed to measure home visiting services provided . Home visitors were surveyed annually to measure their perceived competence . RESULTS Malleable parental risks for child abuse were common at baseline . There was no significant overall program effect on any risk or on at-risk mothers ' desire for and use of community services to address risks . There was a significant reduction in one measure of poor mental health at one agency and a significant reduction in maternal problem alcohol use and repeated incidents of physical partner violence for families receiving > or = 75 % of visits called for in the model . Home visitors often failed to recognize parental risks and seldom linked families with community re sources . HSP training programs were under-developed in preparing staff to address risks and to link families with community re sources . CONCLUSIONS Overall , the home visiting program did not reduce major risk factors for child abuse that made families eligible for service . Research is needed to develop and test strategies to improve home visiting effectiveness in reducing parental risks for child abuse OBJECTIVE To determine if a community-based intervention program focusing on parenting education will have an impact on preventive health care utilization behaviors among low-income , minority mothers in Washington , DC . DESIGN The experimental design was a r and omized , controlled study in which 286 mother-infant dyads were assigned to either the st and ard social services ( control ) group or to the intervention group . Women and their newborn infants were recruited during the immediate postpartum period in 4 Washington , DC , hospital sites from April 1995 to April 1997 . The year-long multicomponent intervention included home visits and hospital-based group sessions in addition to the st and ard social services available at the hospital sites . A total of 286 postpartum women with inadequate prenatal care were assigned r and omly to the control or the intervention group . Women and their infants were followed for 1 full year . Outcome measures included usage of preventive health care services including well care infant visits and adherence to immunization schedules during the first year of the infant 's life . RESULTS Infants in the intervention group initiated well care at an earlier age than controls ( by 6 weeks , 62.5 % vs 50 % had received their first well infant visit ) . Infants in the intervention group had more frequent well visits ( by 12 months of age , 3.5 vs 2.7 visits ) . Multivariate analyses showed infants in the intervention group to be more likely to complete their scheduled immunizations ( by 9 months , odds ratio = 2.2 , 95 % confidence interval : 1.09 - 4.53 ) . Those in the intervention group with more frequent contacts ( 30 + visits ) with study personnel were most likely to have followed age-appropriate immunization schedules when compared with controls ( at 9 months odds ratio = 3.63 , 95 % confidence interval : 1.58 - 8.33 ) . CONCLUSIONS It is possible to influence health care usage patterns of high-risk minority population s through public health interventions that are global in their perspective . Focusing on parental knowledge and beliefs regarding health-related issues and life skills in a self-efficacy model is associated with improved usage of infant health care re sources OBJECTIVE : To examine whether the Safe Environment for Every Kid ( SEEK ) model of enhanced primary care would improve the attitudes , knowledge , comfort , competence , and behavior of child health care professionals ( HPs ) regarding addressing major risk factors for child maltreatment ( CM ) . METHODS : In a cluster r and omized controlled trial , 18 private practice s were assigned to intervention ( SEEK ) or control groups . SEEK HPs received training on CM risk factors ( eg , maternal depression ) . The SEEK model included the parent screening question naire and the participation of a social worker . SEEK 's impact was evaluated in 3 ways : ( 1 ) the health professional question naire ( HPQ ) , which assessed HPs ' attitudes and practice regarding the targeted problems ; ( 2 ) observations of HPs conducting checkups ; and ( 3 ) review of children 's medical records . RESULTS : The 102 HPs averaged 45 years of age ; 68 % were female , and 74 % were in suburban practice s. Comparing baseline scores with 6- , 18- , and 36-month follow-up data , the HPQ revealed significant ( P < .05 ) improvement in the SEEK group compared with controls on addressing depression ( 6 months ) , substance abuse ( 18 months ) , intimate partner violence ( 6 and 18 months ) , and stress ( 6 , 18 , and 36 months ) , and in their comfort level and perceived competence ( both at 6 , 18 , and 36 months ) . SEEK HPs screened for targeted problems more often than did controls based on observations 24 months after the initial training and the medical records ( P < .001 ) . CONCLUSIONS : The SEEK model led to significant and sustained improvement in several areas . This is a crucial first step in helping HPs address major psychosocial problems that confront many families . SEEK offers a modest yet promising enhancement of primary care Objectives : To examine the association of chronic pain in young adults with childhood exposure to maltreatment and to determine whether depressive symptoms mediate such an association . Design : A total of 649 members of a r and omly selected cohort of young adults from a multiwave , multi-informant epidemiological study were interviewed with regard to chronic pain and symptoms of major depressive disorder . Maltreatment was measured both by retrospective self-report and by official records of substantiated child maltreatment . Outcome Measures : Current complaints of frequent pain and functionally impairing chronic pain were assessed in young adult interviews at mean age 22 . Results : Net of demographic factors , adult chronic pain was associated with self-reported sexual abuse . This association persisted after the contribution of concurrent depression was statistically controlled . Elevations of pain attributable to documented maltreatment were comparatively modest and below the threshold of statistical significance . Pain complaints in participants who self-reported physical abuse were not significantly elevated . Conclusions : Overall , results show an association between self-reported sexual abuse history and adult pain complaints in this general population sample , which was not attributable to symptoms of depression at the time of such reports OBJECTIVE To examine the effectiveness of home visiting by paraprofessionals and by nurses as separate means of improving maternal and child health when both types of visitors are trained in a program model that has demonstrated effectiveness when delivered by nurses . METHODS A r and omized , controlled trial was conducted in public- and private-care setting s in Denver , Colorado . One thous and one hundred seventy-eight consecutive pregnant women with no previous live births who were eligible for Medicaid or who had no private health insurance were invited to participate . Seven hundred thirty-five women were r and omized to control , paraprofessional , or nurse conditions . Nurses completed an average of 6.5 home visits during pregnancy and 21 visits from birth to the children 's second birthdays . Paraprofessionals completed an average of 6.3 home visits during pregnancy and 16 visits from birth to the children 's second birthdays . The main outcomes consisted of changes in women 's urine cotinine over the course of pregnancy ; women 's use of ancillary services during pregnancy ; subsequent pregnancies and births , educational achievement , workforce participation , and use of welfare ; mother-infant responsive interaction ; families ' home environments ; infants ' emotional vulnerability in response to fear stimuli and low emotional vitality in response to joy and anger stimuli ; and children 's language and mental development , temperament , and behavioral problems . RESULTS Paraprofessional-visited mother-child pairs in which the mother had low psychological re sources interacted with one another more responsively than their control-group counterparts ( 99.45 vs 97.54 st and ard score points ) . There were no other statistically significant paraprofessional effects . In contrast to their control-group counterparts , nurse-visited smokers had greater reductions in cotinine levels from intake to the end of pregnancy ( 259.0 vs 12.32 ng/mL ) ; by the study child 's second birthday , women visited by nurses had fewer subsequent pregnancies ( 29 % vs 41 % ) and births ( 12 % vs 19 % ) ; they delayed subsequent pregnancies for longer intervals ; and during the second year after the birth of their first child , they worked more than women in the control group ( 6.83 vs 5.65 months ) . Nurse-visited mother-child pairs interacted with one another more responsively than those in the control group ( 100.31 vs 98.99 st and ard score points ) . At 6 months of age , nurse-visited infants , in contrast to their control-group counterparts , were less likely to exhibit emotional vulnerability in response to fear stimuli ( 16 % vs 25 % ) and nurse-visited infants born to women with low psychological re sources were less likely to exhibit low emotional vitality in response to joy and anger stimuli ( 24 % vs 40 % and 13 % vs 33 % ) . At 21 months , nurse-visited children born to women with low psychological re sources were less likely to exhibit language delays ( 7 % vs 18 % ) ; and at 24 months , they exhibited superior mental development ( 90.18 vs 86.20 Mental Development Index scores ) than their control-group counterparts . There were no statistically significant program effects for the nurses on women 's use of ancillary prenatal services , educational achievement , use of welfare , or their children 's temperament or behavior problems . For most outcomes on which either visitor produced significant effects , the paraprofessionals typically had effects that were about half the size of those produced by nurses . CONCLUSIONS When trained in a model program of prenatal and infancy home visiting , paraprofessionals produced small effects that rarely achieved statistical or clinical significance ; the absence of statistical significance for some outcomes is probably attributable to limited statistical power to detect small effects . Nurses produced significant effects on a wide range of maternal and child outcomes In this experiment , 123 sixth and seventh grade classrooms from Clevel and area schools were r and omly assigned to one of two five-session curricula addressing gender violence/sexual harassment ( GV/SH ) or to a no-treatment control . Three-student surveys were administered . Students in the law and justice curricula , compared to the control group , had significantly improved outcomes in awareness of their abusive behaviors , attitudes toward GV/SH and personal space , and knowledge . Students in the interaction curricula experienced lower rates of victimization , increased awareness of abusive behaviors , and improved attitudes toward personal space . Neither curricula affected perpetration or victimization of sexual harassment . While the intervention appeared to reduce peer violence victimization and perpetration , a conflicting finding emerged — the intervention may have increased dating violence perpetration ( or at least the reporting of it ) but not dating violence victimization Objective . To evaluate the extent to which a program of home visitation ( Early Start ) , targeted at families who are facing stress and difficulty , had beneficial consequences for child health , preschool education , service utilization , parenting , child abuse and neglect , and behavioral adjustment . Methods . The study used a r and omized , controlled trial design in which 220 families who were participating in the Early Start program were contrasted with a control series of 223 families who were not participating in the program . Families were enrolled in the program after population screening that was conducted by community health nurses . Families were enrolled in the program for up to 36 months . Outcomes were assessed at 6 , 12 , 24 , and 36 months after trial entry . Results . Families in the Early Start series received a mean of 24 months of service . Comparisons between the Early Start and control series over the 36-month follow-up period revealed that families in the Early Start program showed significant benefits in the areas of improved utilization of child health services , reduced rates of hospital attendance for injury/poisoning , increased preschool education , increased positive and nonpunitive parenting , reduced rates of severe parent/child assaults , and reduced rates of early problem behaviors . Effect sizes ( Cohen 's “ d ” ) were found to be in the small to moderate range , with d ranging from .03 to .31 ( median : .22 ) . Conclusions . The Early Start program was associated with small to moderate benefits in a wide range of areas relating to child health , preschool education , parenting , child abuse , and early behavioral adjustment . Comparisons with other studies are made , and threats to validity are considered The authors assessed the effectiveness of a home visitation program in enhancing the early parenting history of infants born at medical risk -- a population that is at risk for mistreatment . A r and omized clinical trial design was used to compare the effects of a cognitively based extension of the Healthy Start home visitation program ( HV+ ) with a visitation condition that did not include this component ( HV ) . In the HV+ condition , they observed ( a ) a lower use of corporal punishment , ( b ) greater safety maintenance in the home , and ( c ) fewer reported child injuries . The sample ( N = 102 ) was primarily Latino ; however , the effects of the intervention were not qualified by ethnicity , maternal education , or immigration status OBJECTIVES One of the greatest method ological problems in the study of childhood maltreatment is the discrepancy in methods by which cases of child maltreatment are identified . The current study compared incidents of maltreatment identified prospect ively , retrospectively , or through a combination of both methods . METHOD Within a cohort of 170 participants followed from birth to age 19 , incidents of maltreatment which occurred prior to age 17.5 were identified via prospect i ve case review and interviewer ratings of retrospective self-reports . Multi-informant measures of behavior problems were obtained at age 16 , and diagnostic assessment s of psychopathology were completed at age 17.5 . RESULTS While the maximal number of maltreatment cases was identified by using a combination of all available identification methods , the prospect i ve method was the single most comprehensive method for identifying the most cases of childhood physical abuse , sexual abuse , and neglect . Those who were identified as maltreated by a combination of both prospect i ve and self-report methods experienced the greatest number of incidences of maltreatment ( i.e. , 49 % of this group experienced more than one type of maltreatment ) and displayed the most emotional and behavioral problems in late adolescence ( i.e. , 74 % met diagnostic criteria for a clinical disorder ) . CONCLUSIONS This study emphasizes the variability in the incidence rates of maltreatment and the psychological outcomes that result from utilizing different methods of identification . The most severe cases of maltreatment are likely to be identified by both prospect i ve and retrospective methods ; however , cases that are identified solely through retrospective self-report may have unique relations to psychopathology in late adolescence . PRACTICE IMPLICATION S Reliance on a single method to identify childhood maltreatment incidents often overlooks many cases . Comparing both prospect i ve case review s and retrospective self-reports in late adolescence , the most severe cases of multiple incidents of abuse were most likely to be identified by both method ologies . The less severe maltreatment incidents were more likely to be missed , either by prospect i ve methods or , more frequently , by self-report methods . Practitioners must be continually sensitive to possible abuse histories among their clients , seeking out information from multiple sources whenever feasible . Additionally , the potential effects of abuse disclosure on pre-existing or developing psychopathology should be considered Diagnosis is a critical component of health care , and clinicians , policymakers , and patients routinely face a range of questions regarding diagnostic tests . They want to know whether testing improves outcome ; what test to use , purchase , or recommend in practice guidelines ; and how to interpret test results . Well- design ed diagnostic test accuracy studies can help in making these decisions , provided that they transparently and fully report their participants , tests , methods , and results as facilitated , for example , by the STARD ( St and ards for Reporting of Diagnostic Accuracy ) statement ( 1 ) . That 25-item checklist was published in many journals and is now adopted by more than 200 scientific journals worldwide . As in other areas of science , systematic review s and meta- analysis of accuracy studies can be used to obtain more precise estimates when small studies addressing the same test and patients in the same setting are available . Review s can also be useful to establish whether and how scientific findings vary by particular subgroups , and may provide summary estimates with a stronger generalizability than estimates from a single study . Systematic review s may help identify the risk for bias that may be present in the original studies and can be used to address questions that were not directly considered in the primary studies , such as comparisons between tests . The Cochrane Collaboration is the largest international organization preparing , maintaining , and promoting systematic review s to help people make well-informed decisions about health care ( 2 ) . The Collaboration decided in 2003 to make preparations for including systematic review s of diagnostic test accuracy in their Cochrane Data base of Systematic Review s. To enable this , a working group ( Appendix ) . was formed to develop methodology , software , and a h and book The first diagnostic test accuracy review was published in the Cochrane Data base in October 2008 . In this paper , we review recent method ological developments concerning problem formulation , location of literature , quality assessment , and meta- analysis of diagnostic accuracy studies by using our experience from the work on the Cochrane H and book . The information presented here is based on the recent literature and up date s previously published guidelines by Irwig and colleagues ( 3 ) . Definition of the Objectives of the Review Diagnostic test accuracy refers to the ability of a test to distinguish between patients with disease ( or more generally , a specified target condition ) and those without . In a study of test accuracy , the results of the test under evaluation , the index test , are compared with those of the reference st and ard determined in the same patients . The reference st and ard is an agreed-on and accurate method for identifying patients who have the target condition . Test results are typically categorized as positive or negative for the target condition . By using such binary test outcomes , the accuracy is most often expressed as the test 's sensitivity ( the proportion of patients with positive results on the reference st and ard that are also positive on the index test ) and specificity ( the proportion of patients with negative results on the reference st and ard that are also negative on the index test ) . Other measures have been proposed and are in use ( 46 ) . It has long been recognized that test accuracy is not a fixed property of a test . It can vary between patient subgroups , with their spectrum of disease , with the clinical setting , or with the test interpreters and may depend on the results of previous testing . For this reason , inclusion of these elements in the study question is essential . In order to make a policy decision to promote use of a new index test , evidence is required that using the new test increases test accuracy over other testing options , including current practice , or that the new test has equivalent accuracy but offers other advantages ( 79 ) . As with the evaluation of interventions , systematic review s need to include comparative analyses between alternative testing strategies and should not focus solely on evaluating the performance of a test in isolation . In relation to the existing situation , 3 possible roles for a new test can be defined : replacement , triage , and add-on ( 7 ) . If a new test is to replace an existing test , then comparing the accuracy of both tests on the same population and with the same reference st and ard provides the most direct evidence . In triage , the new test is used before the existing test or testing pathway , and only patients with a particular result on the triage test continue the testing pathway . When a test is needed to rule out disease in patients who then need no further testing , a test that gives a minimal proportion of falsenegative results and thus a relatively high sensitivity should be used . Triage tests may be less accurate than existing ones , but they have other advantages , such as simplicity or low cost . A third possible role of a new test is add-on . The new test is then positioned after the existing testing pathway to identify false-positive or false-negative results after the existing pathway . The review should provide data to assess the incremental change in accuracy made by adding the new test . An example of a replacement question can be found in a systematic review of the diagnostic accuracy of urinary markers for primary bladder cancer ( 10 ) . Clinicians may use cytology to triage patients before they undergo invasive cystoscopy , the reference st and ard for bladder cancer . Because cytology combines high specificity with low sensitivity ( 11 ) , the goal of the review was to identify a tumor marker with sufficient accuracy to either replace cytology or be used in addition to cytology . For a marker to replace cytology , it has to achieve equally high specificity with improved sensitivity . New markers that are sensitive but not specific may have roles as adjuncts to conventional testing . The review included studies in which the test under evaluation ( several different tumor markers and cytology ) was evaluated against cystoscopy or histopathology . Included studies compared 1 or more of the markers , cytology only , or a combination of markers and cytology . Although information on accuracy can help clinicians make decisions about tests , good diagnostic accuracy is a desirable but not sufficient condition for the effectiveness of a test ( 8) . To demonstrate that using a new test does more good than harm to patients tested , r and omized trials of test- and -treatment strategies and review s of such trials may be necessary . However , with the possible exception of screening , in most cases , such r and omized trials are not available and systematic review s of test accuracy may provide the most useful evidence available to guide clinical and health policy decision making and use as input for decision and cost-effectiveness analysis ( 12 ) . Identification and Selection of Studies Identifying test accuracy studies is more difficult than search ing for r and omized trials ( 13 ) . There is not a clear , unequivocal keyword or indexing term for an accuracy study in literature data bases comparable with the term r and omized , controlled trial . The Medical Subject Heading sensitivity and specificity may look suitable but is inconsistently applied in most electronic bibliographic data bases . Furthermore , data on diagnostic test accuracy may be hidden in studies that did not have test accuracy estimation as their primary objective . This complicates the efficient identification of diagnostic test accuracy studies in electronic data bases , such as MEDLINE . Until indexing systems properly code studies of test accuracy , search ing for them will remain challenging and may require additional manual search es , such as screening reference lists . In the development of a comprehensive search strategy , review authors can use search strings that refer to the test(s ) under evaluation , the target condition , and the patient description or a subset of these . For tests with a clear name that are used for a single purpose , search ing for publications in which those tests are mentioned may suffice . For other review s , adding the patient description may be necessary , although this is also often poorly indexed . A search strategy in MEDLINE should contain both Medical Subject Headings and free text words . A search strategy for articles about tests for bladder cancer , for example , should include as many synonyms for bladder cancer as possible in the search strategy , including neoplasm , carcinoma , transitional cell , and hematuria . Several method ological electronic search filters for diagnostic test accuracy studies have been developed , each attempting to restrict the search to articles that are most likely to be test accuracy studies ( 1316 ) . These filters rely on indexing terms for research methodology and text words used in reporting results , but they often miss relevant studies and are unlikely to decrease the number of articles one needs to screen . Therefore , they are not recommended for systematic review s ( 17 , 18 ) . The incremental value of search ing in language s other than English and in the gray literature has not yet been fully investigated . In systematic review s of intervention studies , publication bias is an important and well-studied form of bias in which the decision to report and publish studies is linked to their findings . For clinical trials , the magnitude and determinants of publication bias have been identified by tracing the publication history of cohorts of trials review ed by ethics committees and research boards ( 19 ) . A consistent observation has been that studies with significant results are more likely to be published than studies with nonsignificant findings ( 19 ) . Investigating publication bias for diagnostic tests is problematic , because many studies are done without ethical review or study registration ; therefore , identification of cohorts of studies from registration to final publication status OBJECTIVES To assess the impact of home visiting in preventing child abuse and neglect in the first 3 years of life in families identified as at-risk of child abuse through population -based screening at the child 's birth . METHODS This experimental study focused on Hawaii Healthy Start Program ( HSP ) sites operated by three community-based agencies . From 11/94 to 12/95 , 643 families were enrolled and r and omly assigned to intervention and control groups . Child abuse and neglect were measured by observed and self-reported parenting behaviors , all hospitalizations for trauma and for conditions where hospitalization might have been avoided with adequate preventive care , maternal relinquishment of her role as primary caregiver , and substantiated CPS reports . Data were collected through annual maternal interviews ( 88 % follow-up each year of all families with baseline interviews ) ; observation of the home environment ; and review of CPS , HSP , and pediatric medical records . RESULTS HSP records rarely noted home visitor concern about possible abuse . The HSP and control groups were similar on most measures of maltreatment . HSP group mothers were less likely to use common corporal/verbal punishment ( AOR=.59 , p=.01 ) but this was attributable to one agency 's reduction in threatening to spank the child . HSP group mothers reported less neglectful behavior ( AOR=.72 , .02 ) , related to a trend toward decreased maternal preoccupation with problems and to improved access to medical care for intervention families at one agency . CONCLUSIONS The program did not prevent child abuse or promote use of nonviolent discipline ; it had a modest impact in preventing neglect . Possible targets for improved effectiveness include the program 's implementation system and model OBJECTIVE To evaluate the effects of a home visiting program modeled after Healthy Families America on parenting behaviors in the first 2 years of life . METHODS A sample of 1173 families at risk for child abuse and neglect who met the criteria for Healthy Families New York ( HFNY ) was r and omly assigned to either an intervention group that was offered HFNY or a control group that was given information and referrals to other services . Data were collected through a review of CPS records , and maternal interviews at baseline and the child 's first birthday ( 90 % re-interviewed ) and second birthday ( 85 % re-interviewed ) . RESULTS HFNY mothers reported committing one-quarter as many acts of serious abuse at age 2 as control mothers ( .01 versus .04 , p<.05 ) . Two sets of interactions were tested and found to have significant effects ( p<.05 ) . At age 2 , young , first-time mothers in the HFNY group who were r and omly assigned at 30 weeks of pregnancy or less were less likely than counterparts in the control group to engage in minor physical aggression in the past year ( 51 % versus 70 % ) and harsh parenting in the past week ( 41 % versus 62 % ) . Among women who were " psychologically vulnerable , " HFNY mothers were one-quarter as likely to report engaging in serious abuse and neglect as control mothers ( 5 % versus 19 % ) at age 2 . CONCLUSIONS These findings suggest that who is offered home visitation may be an important factor in explaining the differential effectiveness of home visitation programs . Improved effects may be realized by prioritizing the population s served or by enhancing the model to meet program objectives for hard-to-serve families OBJECTIVE To determine the rate and risk of clinical and personality disorders diagnosed in childhood and adulthood in those known to have been sexually abused during childhood . METHODS Forensic medical records of 2,759 sexually abused children assessed between 1964 and 1995 were linked with a public psychiatric data base between 12 and 43 years later . Cases were compared to control subjects matched on gender and age groupings drawn from the general population through a r and om sample of the national electoral data base . RESULTS A lifetime record of contact with public mental health services was found in 23.3 % of cases compared to 7.7 % of controls . The rate of contact among child sexual abuse victims was 3.65 times higher ( 95 % CI , 3.09 - 4.32 , p<0.001 ) . It was estimated that child sexual abuse accounted for approximately 7.83 % of mental health contact . Exposure to sexual abuse increased risks for the majority of outcomes including psychosis , affective , anxiety , substance abuse , and personality disorders . Rates of clinical disorders diagnosed in adulthood and childhood remained significantly higher among child sexual abuse cases . Older age at sexual abuse and those exposed to severe abuse involving penetration or multiple offenders were associated with greater risk for psychopathology . CONCLUSIONS This study confirms that child sexual abuse is a substantial risk factor for a range of mental disorders in both childhood and adulthood . PRACTICE IMPLICATION S Those treating victims of sexual abuse must assess not only disorders commonly associated with trauma , but also low prevalence disorders such as psychosis OBJECTIVE : We tested the efficacy of a cognitive-behavioral intervention in reducing environmental tobacco smoke exposure ( ETSE ) and improving pregnancy outcomes among black women . METHODS : We recruited 1044 women to a r and omized , controlled trial during 2001–2004 in Washington , DC . Data on 691 women with self-reported ETSE were analyzed . A subset of 520 women with ETSE and salivary cotinine levels ( SCLs ) of < 20 ng/mL were also analyzed . Individually tailored counseling sessions , adapted from evidence -based interventions for ETSE and other risks , were delivered to the intervention group . The usual-care group received routine prenatal care as determined by their provider . Logistic regression models were used to predict ETSE before delivery and adverse pregnancy outcomes . RESULTS : Women in the intervention were less likely to self-report ETSE before delivery when controlling for other covariates ( odds ratio [ OR ] : 0.50 [ 95 % confidence interval ( CI ) : 0.35–0.71 ] ) . Medicaid recipients were more likely to have ETSE ( OR : 1.97 [ 95 % CI : 1.31–2.96 ] ) . With advancing maternal age , the likelihood of ETSE was less ( OR : 0.96 [ 95 % CI : 0.93–0.99 ] ) . For women in the intervention , the rates of very low birth weight ( VLBW ) and very preterm birth ( VPTB ) were significantly improved ( OR : 0.11 [ 95 % CI : 0.01–0.86 ] and OR : 0.22 [ 95 % CI : 0.07–0.68 ] , respectively ) . For women with an SCL of < 20 ng/mL , maternal age was not significant . Intimate partner violence at baseline significantly increased the chances of VLBW and VPTB ( OR : 3.75 [ 95 % CI : 1.02–13.81 ] and 2.71 [ 95 % CI : 1.11–6.62 ] , respectively ) . These results were true for mothers who reported ETSE overall and for those with an SCL of < 20 ng/mL. CONCLUSIONS : This is the first r and omized clinical trial demonstrating efficacy of a cognitive-behavioral intervention targeting ETSE in pregnancy . We significantly reduced ETSE as well as VPTB and VLBW , leading causes of neonatal mortality and morbidity in minority population s. This intervention may reduce health disparities in reproductive outcomes BACKGROUND The goal of this investigation was to determine the association between self-reported childhood trauma and physical disorders among adults in the United States . METHOD Data were drawn from the National Comorbidity Survey ( N=5877 ) . Multiple logistic regression analyses were used to determine the associations between childhood physical abuse , sexual abuse , and childhood neglect and the likelihood of specific physical disorders among adults . RESULTS Childhood physical abuse , sexual abuse and neglect were associated with a statistically significantly increased risk of a wide range of physical illnesses during adulthood . After adjusting for demographic characteristics , lifetime anxiety and depressive disorders , alcohol and substance dependence , and all types of trauma : results showed that childhood physical abuse was associated with increased risk of lung disease ( OR= 1.5 ( 1.1 , 2.2 ) ) , peptic ulcer ( OR= 1.5 ( 1.03 , 2.2 ) ) and arthritic disorders ( OR= 1.5 ( 1.1 , 2.2 ) ) ; childhood sexual abuse was associated with increased risk of cardiac disease ( OR = 3.7 ( 1.5 , 9.4 ) ) ; and childhood neglect was associated with increased risk of diabetes ( OR=2 2 ( 1.1 , 4.4 ) ) and autoimmune disorders ( OR = 4.4 ( 1.7 , 11.6 ) ) . CONCLUSIONS Consistent with previous work , these results suggest that self-reported childhood trauma is associated with increased risk of a range of physical illnesses during adulthood . Future research that includes replication of these findings using prospect ively assessed physical and mental disorders with objective ly measured biological data using a longitudinal design , including other known risk factors for these diseases and more detailed information on specific forms of abuse , is needed to underst and the potential mechanisms of these links OBJECTIVES To assess the impact of a voluntary , paraprofessional home visiting program in preventing child maltreatment and reducing the multiple , malleable psychosocial risks for maltreatment for which families had been targeted . METHODS This collaborative , experimental study focused on 6 Healthy Families Alaska ( HFAK ) programs ; 325 families were enrolled in 2000 - 2001 , r and omized to intervention and control groups , and interviewed to measure baseline attributes . Follow-up data were collected when children were 2 years old ( 85 % follow-up rate ) . Outcomes included maltreatment reports , measures of potential maltreatment and parental risks , for example , poor mental health , substance use , and partner violence . HFAK records were review ed to measure home visiting services . Home visitors were surveyed to measure perceived effectiveness and training adequacy . RESULTS Parental risks were common at baseline , and one-sixth of families had a substantiated child protective services report in the child 's first 2 years of life . There was no overall program effect on maltreatment reports , and most measures of potential maltreatment . Home visited mothers reported using mild forms of physical discipline less often than control mothers . The groups were similar in their use of more severe forms of physical discipline . There was no program impact on parental risks . There was no impact on outcomes for families with a ' high dose ' of home visiting . Home visitors often failed to address parental risks and seldom linked families with community re sources . Contradictions in the model compromised effectiveness . CONCLUSIONS The program did not prevent child maltreatment , nor reduce the parental risks that had made families eligible for service . Research is needed to develop and test strategies to improve the effectiveness of home visiting OBJECTIVE To examine , during the 3rd and 4th years of life , the health , development , rates of child maltreatment , and living conditions of children who had been enrolled in a r and omized trial of nurse home visitation during pregnancy and first 2 years of their lives . DESIGN Prospect i ve follow-up of families who had been r and omly assigned to nurse-visited and comparison conditions . SETTING Study conducted in semirural community in upstate New York . Families dispersed among 14 other states during 2-year period after children 's second birthdays . PARTICIPANTS Four hundred women were recruited through a health department antepartum clinic and offices of private obstetricians and were registered before 30th week of pregnancy . All women had no previous live births and 85 % were either teenaged ( < 18 years at registration ) , unmarried , or from Hollingshead social classes IV or V. Analysis focused on whites , who comprised 89 % of sample . INTERVENTION Nurse home visitation from pregnancy through second year of the child 's life . MAIN RESULTS There were no treatment differences in the rates of child abuse and neglect or children 's intellectual functioning from 25 to 48 months of age . Nurse-visited children , nevertheless , lived in homes with fewer hazards for children ; they had 40 % fewer injuries and ingestions and 45 % fewer behavioral and parental coping problems noted in the physician record ; and they made 35 % fewer visits to the emergency department than did children in the comparison group . Nurse-visited mothers were observed to be more involved with and to punish their children to a greater extent than were mothers in the comparison group . The functional meaning of punishment differed between the nurse-visited and comparison families . CONCLUSIONS The program does have enduring effects on certain aspects of parental caregiving , safety of the home , and children 's use of the health care system , but it may be necessary to extend the length of the program for families at highest risk to produce lasting reductions in child abuse and neglect This r and omized , controlled trial was design ed to document the effectiveness of Child FIRST ( Child and Family Interagency , Re source , Support , and Training ) , a home-based , psychotherapeutic , parent-child intervention embedded in a system of care . Multirisk urban mothers and children , ages 6 - 36 months ( N = 157 ) participated . At the 12-month follow-up , Child FIRST children had improved language ( odds ratio [ OR ] = 4.4 ) and externalizing symptoms ( OR= 4.7 ) compared to Usual Care children . Child FIRST mothers had less parenting stress at the 6-month follow-up ( OR = 3.0 ) , lower psychopathology symptoms at 12-month follow-up ( OR = 4.0 ) , and less protective service involvement at 3 years postbaseline ( OR = 2.1 ) relative to Usual Care mothers . Intervention families accessed 91 % of wanted services relative to 33 % among Usual Care . Thus , Child FIRST is effective with multirisk families raising young children across multiple child and parent outcomes OBJECTIVE . Inflicted traumatic brain injury ( iTBI ) is the leading cause of death from TBI in infants . Misdiagnosis of iTBI is common and results in increased morbidity and mortality . Biomarkers may be able to assist in screening infants who are at high risk for iTBI and whose injury might otherwise be missed . We investigated whether serum and /or cerebrospinal fluid ( CSF ) concentrations of neuron-specific enolase ( NSE ) , S100B , and myelin-basic protein ( MBP ) are sensitive and specific for iTBI in high-risk infants . METHODS . A prospect i ve case-control study was conducted of 98 well-appearing infants who presented with nonspecific symptoms and no history of trauma . Serum or CSF was collected . NSE , S100B , and MBP concentrations were measured by enzyme-linked immunosorbent assay . Abnormal marker concentrations were defined a priori . Patients were followed for 12 months to assess for subsequent abuse . RESULTS . Fourteen patients received a clinical diagnosis of iTBI . Using preestablished cutoffs , NSE was 77 % sensitive and 66 % specific and MBP was 36 % sensitive and 100 % specific for iTBI . S100B was neither sensitive nor specific for iTBI . Five patients who were not identified with iTBI at enrollment were identified at follow-up as being possible victims of abuse ; 4 had an increased NSE concentration at enrollment . CONCLUSIONS . Serum and /or CSF concentrations of NSE and MBP may be useful as a screening test to identify infants who are at increased risk for iTBI and may benefit from additional evaluation with a head computed tomography scan . S100B is neither sensitive nor specific for iTBI in this study population . The ability to identify iTBI that might otherwise be missed has important implication s for decreasing the morbidity and the mortality from iTBI CONTEXT . Effective strategies for preventing child maltreatment are needed . Few primary care – based programs have been developed , and most have not been well evaluated . OBJECTIVE . Our goal was to evaluate the efficacy of the Safe Environment for Every Kid model of pediatric primary care in reducing the occurrence of child maltreatment . METHODS . A r and omized trial was conducted from June 2002 to November 2005 in a university-based resident continuity clinic in Baltimore , Maryl and . The study population consisted of English-speaking parents of children ( 0–5 years ) brought in for child health supervision . Of the 1118 participants approached , 729 agreed to participate , and 558 of them completed the study protocol . Resident continuity clinics were cluster r and omized by day of the week to the model ( intervention ) or st and ard care ( control ) groups . Model care consisted of ( 1 ) residents who received special training , ( 2 ) the Parent Screening Question naire , and ( 3 ) a social worker . Risk factors for child maltreatment were identified and addressed by the resident physician and /or social worker . St and ard care involved routine pediatric primary care . A subset of the clinic population was sample d for the evaluation . Child maltreatment was measured in 3 ways : ( 1 ) child protective services reports using state agency data ; ( 2 ) medical chart documentation of possible abuse or neglect ; and ( 3 ) parental report of harsh punishment via the Parent-Child Conflict Tactics scale . RESULTS . Model care result ed in significantly lower rates of child maltreatment in all the outcome measures : fewer child protective services reports , fewer instances of possible medical neglect documented as treatment nonadherence , fewer children with delayed immunizations , and less harsh punishment reported by parents . One-tailed testing was conducted in accordance with the study hypothesis . CONCLUSIONS . The Safe Environment for Every Kid ( SEEK ) model of pediatric primary care seems promising as a practical strategy for helping prevent child maltreatment . Replication and additional evaluation of the model are recommended CONTEXT Interest in home-visitation services as a way of improving maternal and child outcomes has grown out of the favorable results of a trial in semirural New York . The findings have not been replicated in other population s. OBJECTIVE To test the effect of prenatal and infancy home visits by nurses on pregnancy-induced hypertension , preterm delivery , and low birth weight ; on children 's injuries , immunizations , mental development , and behavioral problems ; and on maternal life course . DESIGN R and omized controlled trial . SETTING Public system of obstetric care in Memphis , Tenn. PARTICIPANTS A total of 1139 primarily African-American women at less than 29 weeks ' gestation , with no previous live births , and with at least 2 sociodemographic risk characteristics ( unmarried , < 12 years of education , unemployed ) . INTERVENTION Nurses made an average of 7 ( range , 0 - 18 ) home visits during pregnancy and 26 ( range , 0 - 71 ) visits from birth to the children 's second birthdays . MAIN OUTCOME MEASURES Pregnancy-induced hypertension , preterm delivery , low birth weight , children 's injuries , ingestions , and immunizations abstract ed from medical records ; mothers ' reports of children 's behavioral problems ; tests of children 's mental development ; mothers ' reports of subsequent pregnancy , educational achievement , and labor-force participation ; and use of welfare derived from state records . MAIN RESULTS In contrast to counterparts assigned to the comparison condition , fewer women visited by nurses during pregnancy had pregnancy-induced hypertension ( 13 % vs 20 % ; P=.009 ) . During the first 2 years after delivery , women visited by nurses during pregnancy and the first 2 years of the child 's life had fewer health care encounters for children in which injuries or ingestions were detected ( 0.43 vs 0.55 ; P=.05 ) ; days that children were hospitalized with injuries or ingestions ( 0.03 vs 0.16 ; P<.001 ) ; and second pregnancies ( 36 % vs 47 % ; P=.006 ) . There were no program effects on preterm delivery or low birth weight ; children 's immunization rates , mental development , or behavioral problems ; or mothers ' education and employment . CONCLUSION This program of home visitation by nurses can reduce pregnancy-induced hypertension , childhood injuries , and subsequent pregnancies among low-income women with no previous live births This article addresses the relationship between childhood sexual abuse and the long-term physical health and healthcare utilization of 148 female participants in an eight-year prospect i ve study . Five factors of physical health emerged : General Health ; Vegetative Health Symptoms ; Colds and Flu ; Gastrointestinal/Gynecological ; and Healthcare Utilization . Abused females scored higher on the healthcare utilization and gastrointestinal/gynecological factors than comparison females . Abused females experiencing multiple perpetrators , violence , longer duration and older age at onset endorsed significantly more gastrointestinal/gynecological problems than did the other abused females and the comparison group . Findings suggest that : ( 1 ) sexual abuse affects long-term health outcomes and healthcare utilization ; and ( 2 ) physical health sequelae of abuse may differentially affect females , depending upon the pattern of abuse characteristics A program of prenatal and infancy home visitation by nurses was tested as a method of preventing a wide range of health and developmental problems in children born to primiparas who were either teenagers , unmarried , or of low socioeconomic status . Among the women at highest risk for care-giving dysfunction , those who were visited by a nurse had fewer instances of verified child abuse and neglect during the first 2 years of their children 's lives ( P = .07 ) ; they were observed in their homes to restrict and punish their children less frequently , and they provided more appropriate play material s ; their babies were seen in the emergency room less frequently during the first year of life . During the second year of life , the babies of all nurse-visited women , regardless of the families ' risk status , were seen in the emergency room fewer times , and they were seen by physicians less frequently for accidents and poisonings than comparison group babies ( P less than or equal to .05 for all findings , except where indicated . ) Treatment differences for child abuse and neglect and emergency room visits were more significant among women who had a lower sense of control over their lives |
10,455 | 32,227,599 | Manual therapy may make little or no difference to the change in trunk deformity compared to usual care ( low- quality evidence ) .
Due to method ological limitations in the included trials , and in addition to the very low to low quality of the current evidence , there is limited evidence about the benefits of physical therapies on postural abnormalities in people with CF . | BACKGROUND Cystic fibrosis ( CF ) is the most common life-threatening , inherited disease in white population s which causes several dysfunctions , including postural abnormalities .
Physical therapy may help in some consequences of these postural abnormalities , such as pain , trunk deformity and quality of life .
OBJECTIVES To determine the effects of a range of physical therapies for managing postural abnormalities in people with cystic fibrosis , specifically on quality of life , pain and trunk deformity . | BACKGROUND : Regular aerobic exercise in patients with cystic fibrosis ( CF ) improves aerobic conditioning and delays disease progression , result ing in better quality of life . The purpose of this study was to evaluate the effect of an aerobic exercise program based on verbal and written guidelines on maximum exercise capacity using a cardiopulmonary exercise test , quality of life , and the self-reported aerobic exercise practice of children and adolescents with CF . METHODS : This r and omized controlled trial followed guidelines for physical exercise in a CF center . Subjects were assigned to 2 groups : intervention ( group 1 ) , with 17 subjects ; and control ( group 2 ) , also with 17 subjects . Data were collected from October 2010 to October 2011 , and the study population comprised 7–20-y-old children and adolescents with CF . The intervention consisted of h and ing out a manual with guidelines for aerobic physical exercises and reinforcing recommendations in telephone calls every 2 weeks . RESULTS : Thirty-four subjects were included in the study , 20 of whom were boys ( 58.5 % ) . The groups were similar at baseline . In group 1 , 6 subjects ( 35.2 % ) reported practicing physical exercises regularly . The mean age was 13.4 ± 2.8 y , the mean percent-of-predicted FEV1 was 95.5 ± 17.9 % , and the mean peak oxygen uptake ( V̇O2 ) relative to body mass was 34.9 ± 9.0 mL/kg/min . In group 2 , 4 subjects ( 23.5 % ) reported practicing physical exercises regularly . The mean age was 12.7 ± 3.3 y , the mean percent-of-predicted FEV1 was 100.1 ± 21.2 % , and the mean peak V̇O2 was 33.2 ± 8.2 mL/kg/min . In group 1 , there was a significant increase in physical exercise practice as reported by subjects after 3 months of intervention compared with group 2 ( P = .01 ) . No statistically significant differences were found for the other variables . CONCLUSIONS : Verbal and written guidelines for aerobic exercise , together with supervision over the telephone , had a positive impact on the self-reported regular physical exercise practice of children and adolescents . However , no improvement was found in lung function and maximum exercise capacity or domains of the quality of life question naire AIMS To assess the sensitivity of selected outcome measures to any change result ing from treatment of adults with cystic fibrosis with physiotherapy musculoskeletal techniques , use the data for sample size calculations for future studies and assess the acceptability of the methods to potential participants . DESIGN Preliminary , prospect i ve , single-blind , r and omised controlled trial . SETTING Specialist cystic fibrosis centre . PARTICIPANTS Adults recruited from a cystic fibrosis outpatient clinic . INTERVENTIONS The control group received normal optimal physiotherapy care and the intervention group received weekly musculoskeletal treatment for 6 weeks in addition to normal optimal physiotherapy care . OUTCOME MEASURES Recorded at baseline , 3 , 6 and 12 weeks . The outcome measures were posture ( thoracic index ) , chest wall excursion , forced expiratory volume in 1 second ( FEV₁ ) , visual analogue scale for pain , modified shuttle test and Cystic Fibrosis Quality of Life Question naire -- Section One ( physical functioning ) . STATISTICAL ANALYSIS Descriptive statistics [ using medians and interquartile ranges ( IQRs ) ] and linear regression mixed model . RESULTS From a total of 20 subjects , 10 were r and omised to each group . Fifty percent of subjects were male , with a median age of 27 years ( IQR 25 to 34 ) , median FEV(1 ) of 1.75 l ( IQR 1.4 to 2.4 ) and median body mass index of 20.8 ( IQR 20.0 to 23.5 ) . Baseline differences between groups in thoracic index and modified shuttle test made any differences difficult to interpret , but the results for thoracic index and chest wall excursion at the third rib in the treatment group showed a trend towards improvement . The usefulness of FEV₁ , the visual analogue scale for pain and the Cystic Fibrosis Quality of Life Question naire as measures is unclear . CONCLUSION Further musculoskeletal studies in people with cystic fibrosis should consider using thoracic index and a measure of lung function in addition to FEV₁. The musculoskeletal techniques appear to be acceptable to people with cystic fibrosis , and do not seem to have associated adverse effects Objective . Comparing global postural reeducation ( GPR ) to a st and ard physiotherapy treatment ( PT ) based on active exercises , stretching , and massaging for improving pain and function in chronic low back pain ( CLBP ) patients . Design . Prospect i ve controlled study . Setting . Outpatient rehabilitation facility . Participants . Adult patients with diagnosis of nonspecific , chronic ( > 6 months ) low back pain . Interventions . Both treatments consisted of 15 sessions of one hour each , twice a week including patient education . Measures . Rol and Morris Disability Question naire to evaluate disability , and Numeric Analog Scale for pain . A score change > 30 % was considered clinical ly significant . Past treatments , use of medications , smoking habits , height , weight , profession , and physical activity were also recorded on baseline , on discharge , and 1 year after discharge ( resp . , T0 , T1 , and T2 ) . Results . At T0 103 patients with cLBP ( 51 cases and 52 controls ) were recruited . The treatment ( T1 ) has been completed by 79 ( T1 ) of which 60 then carried out the 1-year follow-up ( T2 ) . Both GPR and PT at T1 were associated with a significant statistical and clinical improvement in pain and function , compared to T0 . At T2 , only pain in GPR still registered a statistically significant improvement DESIGN R and omized controlled study . SETTING Laboratory . PARTICIPANTS 26 healthy swimmers r and omly assigned to an exercise ( n = 13 ; Ex ) or control group ( n = 13 ; Cont ) . INTERVENTION The Ex group performed respiratory-muscle exercises for 10 min thrice a week for 4 wk . CONTEXT Respiratory-muscle exercises are used not only in the rehabilitation of patients with respiratory disease but also in endurance training for athletes . Respiration involves the back and abdominal muscles . These muscles are 1 of the elements responsible for posture control , which is integral to injury prevention and physical performance . However , the effects of respiratory-muscle exercise on posture remain unclear . OBJECTIVE To examine the potential of respiratory-muscle exercise for improving posture . MAIN OUTCOME MEASURES Spinal curvature , pulmonary function , and trunk-muscle strength were measured for both the groups at baseline and after 4 wk . The data were compared between the Ex and Cont groups with Mann-Whitney U test and preintervention and postintervention within groups with a Wilcoxon signed rank-sum test . RESULTS AND CONCLUSION The spinal curvature was significantly different in the Ex group , indicating a decrease in the thoracic ( -13.1 % , P < .01 ) and lumbar ( -17.7 % , P < .05 ) angles . The Ex group presented with lower thoracic ( -8.6 % ) and lumbar ( -20.9 % ) angles at postexercise than the Cont group ( P < .05 ) . With respect to trunk-muscle strength , only trunk-flexion strength significantly increased from pretest to posttest in the Ex group ( P < .05 ) . For pulmonary function , forced vital capacity and forced expiratory volume in 1.0 s were significantly increased after 4 wk in the Ex group ( P < .05 ) . The results suggest that respiratory-muscle exercise straightened the spine , leading to good posture control , possibly because of contraction of abdominal muscles OBJECTIVE To evaluate postural changes and the distribution of plantar pressures in patients with cystic fibrosis ( CF ) . We also sought to evaluate the effects of an educational guideline for physical activity on body posture in children and adolescents with CF . STUDY DESIGN This was a 2-phase study of individuals between age 7 and 20 years . Phase I was a cross-sectional study in which healthy subjects were selected for postural evaluation and baropodometry , aim ing to perform a later comparison with patients with CF . In phase II , we performed a r and omized controlled clinical trial to assess the influence of the exercise guideline on the postural changes . Patients were assigned to 2 groups : control and intervention . The intervention consisted of a h and book with instructions for aerobic exercise and stretching . Main outcomes were postural abnormalities , plantar pressure distribution , and lung function . RESULTS In phase I , 34 patients with CF and 34 healthy matched individuals were included . No significant baseline differences were identified . Children with CF presented more postural deviations compared with healthy subjects ( P < .05 ) , as to alignment of the head , shoulder girdle , and pelvis , increased cervical lordosis , and lateral chest distance . In phase II ( n = 34 ) , there were no baseline differences between groups . The intervention caused ( P < .05 ) a decrease in cervical lordosis , thoracic kyphosis , lumbar lordosis , lateral chest distance , and abdominal protrusion , as well as in the baropodometric mean pressure and contact area . CONCLUSIONS Children and adolescents with CF present postural changes when compared with healthy individuals . The educational guideline for exercise practice helped to improve posture , preventing the progression of some postural disorders Virtual healthcare is fast entering medical practice . Research into the feasibility of using it to teach treatment regimens such as exercise has not been explored . Maintaining an exercise regime can be difficult in cystic fibrosis : group classes risk potential infection , yet motivation is hard to maintain when alone . Tai Chi is a low-impact exercise and involves gentle , dem and ing movements . This study aim ed to assess the feasibility , safety and acceptability of learning Tai Chi via an internet-based approach and compared patient-reported outcomes . Children and adults with cystic fibrosis were recruited to a r and omised , comparative effectiveness trial . Participants learnt eight Tai Chi movements ; teaching was delivered in eight lessons over 3 months : delivered either via the internet or face-to-face . Assessment s were at 3-monthly intervals over 9 months . Outcomes included health status , quality of life , sleep , mindfulness and instructor-led questions . 40 adults and children completed the eight sets of Tai Chi lessons . The median age was 22.8 years ( range 6.1–51.5 years ) ; 27 patients were female . The cohort comprised 26 adults ( aged > 16 years ) , six teenagers and eight children ( aged < 12 years ) . The groups were well matched . Feasibility and safety were demonstrated . Participants showed significant improvements in self-reported sleep , cough ( both daytime and night-time ) , stomach ache and breathing . No differences in lung function , health status , quality of life , sleep or mindfulness was shown before or after completing the lessons . Tai Chi was safe and well tolerated ; it was feasible to deliver individual lessons via the internet , reducing concerns regarding cross-infection , and appeared to improve self-reported symptoms . R and omised controlled trial of Tai Chi in cystic fibrosis |
10,456 | 22,116,540 | Conclusion There is some evidence to suggest that ACEI or ARB use may be associated with improved outcomes in cancer patients . | Objective To investigate the association between angiotensin-converting enzyme inhibitors ( ACEIs ) and angiotensin receptor blockers ( ARBs ) and disease progression and survival in cancer patients . | Background : The renin – angiotensin system ( RAS ) is thought to have a role in carcinogenesis , and RAS inhibition may prevent tumour growth . Methods : We retrospectively investigated the impact of angiotensin I-converting enzyme inhibitors ( ACEIs ) and angiotensin II type-1 receptor blockers ( ARBs ) in 155 patients with pancreatic cancer receiving gemcitabine monotherapy . Patients were divided into three groups : the ACEI/ARB group ( 27 patients receiving an ACEI or ARB for hypertension ( HT ) ) , the non-ACEI/ARB with HT group ( 25 patients receiving antihypertensive drugs other than ACEIs or ARBs ) , and the non-HT group ( 103 patients receiving no antihypertensive drugs ) . Results : Patient characteristics were not different , except for age and HT medications . Progression-free survival ( PFS ) was 8.7 months in the ACEI/ARB group , 4.5 months in the non-ACEI/ARB with HT group , and 3.6 months in the non-HT group . Overall survival ( OS ) was 15.1 months in the ACEI/ARB group , 8.9 months in the non-ACEI/ARB with HT group , and 9.5 months in the non-HT group . The use of ACEIs/ARBs was a significant prognostic factor for both PFS ( P=0.032 ) and OS ( P=0.014 ) in the multivariate analysis . Conclusions : The ACEIs/ARBs in combination with gemcitabine might improve clinical outcomes in patients with advanced pancreatic cancer . Prospect i ve trials are needed to test this hypothesis In a retrospective study we have sought to determine whether the administration of angiotensin-I-converting enzyme inhibitors ( ACEI ) influences the outcome of patients with multiple myeloma ( MM ) . Patients with MM who underwent autologous peripheral blood stem cell transplantation ( PBSCT ) ( n=168 ) were studied . Patients taking ACEI alone or in combination with other antihypertensive agents during the hospital admission for PBSCT were allocated to the ACEI group ( n=25 ; 15 % ) . Patients from the non-ACEI group ( n=143 ; 85 % ) were taking other or no antihypertensive medication . Patients taking ACEI had worse overall survival ( OS ) compared to patients not taking ACEI ( 38.7 versus 73.3 months after diagnosis ; P=0.025 ) . Among patients with hypertension , both OS and progression-free survival were significantly shorter in patients taking ACEI . There were no significant differences between the studied groups in st and ard prognostic parameters for MM ( age , albumin , beta 2-microglobulin , IPI and Durie-Salmon stage , LDH , CRP , performance status ) or in engraftment . The mortality in our study has been mostly myeloma related . In conclusion , according to our findings , ACEI administered during PBSCT have adverse effect on survival of patients with MM BACKGROUND The influence of excess body weight on the risk of death from cancer has not been fully characterized . METHODS In a prospect ively studied population of more than 900,000 U.S. adults ( 404,576 men and 495,477 women ) who were free of cancer at enrollment in 1982 , there were 57,145 deaths from cancer during 16 years of follow-up . We examined the relation in men and women between the body-mass index in 1982 and the risk of death from all cancers and from cancers at individual sites , while controlling for other risk factors in multivariate proportional-hazards models . We calculated the proportion of all deaths from cancer that was attributable to overweight and obesity in the U.S. population on the basis of risk estimates from the current study and national estimates of the prevalence of overweight and obesity in the U.S. adult population . RESULTS The heaviest members of this cohort ( those with a body-mass index [ the weight in kilograms divided by the square of the height in meters ] of at least 40 ) had death rates from all cancers combined that were 52 percent higher ( for men ) and 62 percent higher ( for women ) than the rates in men and women of normal weight . For men , the relative risk of death was 1.52 ( 95 percent confidence interval , 1.13 to 2.05 ) ; for women , the relative risk was 1.62 ( 95 percent confidence interval , 1.40 to 1.87 ) . In both men and women , body-mass index was also significantly associated with higher rates of death due to cancer of the esophagus , colon and rectum , liver , gallbladder , pancreas , and kidney ; the same was true for death due to non-Hodgkin 's lymphoma and multiple myeloma . Significant trends of increasing risk with higher body-mass-index values were observed for death from cancers of the stomach and prostate in men and for death from cancers of the breast , uterus , cervix , and ovary in women . On the basis of associations observed in this study , we estimate that current patterns of overweight and obesity in the United States could account for 14 percent of all deaths from cancer in men and 20 percent of those in women . CONCLUSIONS Increased body weight was associated with increased death rates for all cancers combined and for cancers at multiple specific sites Objective . A prior report suggested that individuals medicated with captopril showed a decreased incidence of prostate cancer . This study therefore investigated whether captopril given postoperatively had any preventive effect on biochemical recurrence for patients treated with radical prostatectomy . Material and methods . Data were prospect ively review ed for 62 men subjected to radical retropubic prostatectomy due to biopsy-confirmed , clinical ly localized prostate cancer and comparisons were made between two groups , those receiving captopril postoperatively ( 12.5 mg twice daily ; captopril group , n=32 ) and those not receiving any captopril ( control group , n=30 ) . One surgeon carried out the surgery . Results . The two groups were comparable as regards age at surgery , prostate volume , preoperative prostate-specific antigen values , pathological stage , Gleason score , organ-confined disease , occurrence of positive surgical margins and extraprostatic extension . The incidence of biochemical failure was three out of 32 patients in the captopril group and 10 out of 30 in the control group ( p=0.034 ) during a mean observational time of 29 months . Conclusions . A lower rate of biochemical recurrence was observed in men subjected to radical prostatectomy treated with captopril postoperatively than in those not receiving captopril . These results were based on only 32 observations ; a larger study may show no evidence of an association BACKGROUND Is cancer related to hypertension and blood pressure ? Do antihypertensive drugs promote cancer ? Do antihypertensive drugs protect against cancer ? We previously analysed the frequency of cardiovascular mortality and morbidity in elderly people who participated in the Swedish Trial in Old Patients with Hypertension 2 ( STOP-Hypertension-2 ) . We have also looked at the frequency of cancer in these patients . METHODS We r and omly assigned 6614 elderly patients with hypertension ( mean age 76 years , median time of follow-up 5.3 years ) to one of three treatment strategies : conventional drugs ( diuretics or b-blockers ) , calcium antagonists , or ACE inhibitors . We matched the patients to the Swedish Cancer Registry and compared our findings with expected values based on age , sex , and calendar-year-specific reference frequencies for the general Swedish population . We also compared the number of cancers between the three treatment groups . FINDINGS At baseline , 607 ( 9 % ) patients had previous malignant disease . Diagnoses were closely similar to the distribution of cancer types that might be seen in elderly patients . During follow-up , there were 625 new cases of cancer in 590 patients . The frequency of cancer did not differ significantly between the treatment strategies , including all cancers and those at individual sites . The st and ardised incidence ratios ( SIRs ) for all cancers were also close to unity : 0.92 ( 95 % CI 0.80 - 1.06 ) for conventional drugs , 0.96 ( 0.83 - 1.10 ) for calcium antagonists , and 0.99 ( 0.86 - 1.13 ) for ACE inhibitors . INTERPRETATIONS No difference in cancer risk was seen between patients r and omly assigned to conventional drugs , calcium antagonists , or ACE inhibitors . Thus , the general message to the practising physician is that more attention should be given to getting the blood pressure down than to the risk of cancer Background Modifiable behavioural risk factors — including exercise , obesity and smoking — have been causally associated with colorectal cancer mortality . However , results have been inconsistent and undiagnosed cancers may affect baseline risk factors , distorting the temporal relationship that is observed between them . Objective To determine whether risk factors for colorectal cancers available in the Whitehall I study were predictive of colonic or rectal cancer mortality . Methods Prospect i ve cohort study over 40 years on Whitehall I men aged 40–69 on entry between 1967 and 1970 . Associations between baseline risk factors and cause-specific mortality were tested with Cox proportional hazards models . Events within the first 10 years of follow-up were excluded to minimise ‘ reverse causality . ’ Results 329 colon and 121 rectal cancer deaths occurred among 17 949 men followed up for a total of 472 523 person-years . Age and smoking were associated with increased mortality from colorectal cancers . Compared with never-smokers , current smoking was associated with age-adjusted HRs for colon and rectal cancers of 1.45 ( 95 % CI 1.03 to 2.03 ) and 1.97 ( 95 % CI 1.02 to 3.80 ) , respectively . A significant effect of current smoking on rectal cancer mortality was only apparent after events in the first 10 years of follow-up were excluded . No convincing evidence was found that body mass index , diabetes mellitus , blood pressure or physical activity were associated with colorectal cancer mortality . Conclusion Smoking significantly increases mortality from colorectal cancer and its decreasing prevalence in the UK may partly explain falling mortality from the disease . Changes in health behaviours in response to early cancer symptoms may result in differential misclassification or ‘ reverse causality ’ unless early events are excluded . Although many individual cohort studies have not shown significant relationships between behavioural risk factors and colorectal cancer mortality , their contribution to meta-analyses remains important BACKGROUND Previous studies have reported an increased risk of cancer with calcium-channel blockers in man . Other work in animals suggests that inhibitors of angiotensin-I-converting enzyme ( ACE ) protect against cancer . We aim ed to assess the risk of cancer in hypertensive patients receiving ACE inhibitors or other antihypertensive drugs . METHODS Our retrospective cohort study was based on the records of 5207 patients who attended the Glasgow Blood Pressure Clinic between Jan 1 , 1980 , and Dec 31 , 1995 . The patients ' records are linked with the Registrar General Scotl and and the West of Scotl and Cancer Registry . FINDINGS Compared with the West of Scotl and controls , the relative risks of incident and fatal cancer among the 1559 patients receiving ACE inhibitors were 0.72 ( 95 % CI 0.55 - 0.92 ) and 0.65 ( 0.44 - 0.93 ) . Among the 3648 patients receiving antihypertensive drugs other than ACE inhibitors ( calcium-channel blockers 1416 , diuretics 2099 , beta-blockers 2681 ) , the corresponding relative risks were 110 ( 0.97 - 1.22 ) and 1.03 ( 0.87 - 1.20 ) . The relative risk of cancer was lowest in women on ACE inhibitors : 0.63 ( 0.41 - 0.93 ) for incident cancer ; 0.48 ( 0.23 - 0.88 ) for fatal cancer ; and 0.37 ( 0.12 - 0.87 ) for female-specific cancers . The reduced relative risk of cancer in patients on ACE inhibitors was greatest with follow-up of longer than 3 years . Calcium-channel blockers , diuretics , and beta-blockers had no apparent effect on risk of cancer . INTERPRETATION Long-term use of ACE inhibitors may protect against cancer . The status of this finding is more that of hypothesis generation than of hypothesis testing ; r and omised controlled trials are needed BACKGROUND & AIMS There are contradictory results regarding the association between angiotensin-converting enzyme ( ACE ) inhibitors and cancer . We aim ed to investigate whether ACE inhibitors protect against esophageal and gastric cancer . METHODS We conducted a population -based case-control study nested within the General Practitioners ' Research Data base in the United Kingdom . All individuals in the General Practitioners ' Research Data base aged 40 - 84 years between 1994 and 2001 were followed up until detection of an esophageal or gastric cancer ( cases ) , other cancer , age of 85 years , death , or end of study period . RESULTS Among 4.34 million person-years , 909 cases of esophageal and 1023 cases of gastric cancer were identified , and 10,000 matched controls were selected at r and om . Adjustments included smoking , body mass index , concurrent medication , and gastrointestinal disorders . Current use of ACE inhibitors decreased the risk of esophageal adenocarcinoma by 29 % ( odds ratio [ OR ] , 0.71 ; 95 % confidence interval [ CI ] , 0.43 - 1.17 ) , but not of squamous-cell carcinoma ( OR , 1.27 ; 95 % CI , 0.71 - 2.28 ) compared with nonusers . A high daily dose of ACE inhibitors decreased the risk of both adenocarcinoma and squamous-cell cancer of the esophagus and rendered a 45 % decrease of total esophageal cancer ( OR , 0.55 ; 95 % CI , 0.33 - 0.93 ) . Our data showed no clear association between the use of ACE inhibitors and risk of gastric cancer ( OR , 1.07 ; 95 % CI , 0.84 - 1.36 ) . CONCLUSIONS The use of ACE inhibitors may decrease the risk of developing esophageal cancer , particularly among users with a high daily dose . No association was found between gastric cancer and ACE inhibitors BACKGROUND The use of angiotensin-converting enzyme ( ACE ) inhibitors has been linked to a decreased risk of developing cancer , and longer-term use of calcium channel blockers ( CCBs ) has been associated with an increased risk of developing cancer in general and breast cancer in particular . METHODS Using data from the General Practice Research Data base , we conducted a large case-control analysis . Previous exposure to ACE inhibitors , CCBs , and beta-blockers was compared between 3706 postmenopausal women who were diagnosed with incident breast cancer between 1992 and 1997 and 14155 matched-control women . RESULTS Compared with nonusers of antihypertensive drugs , women who used ACE inhibitors ( odds ratio [ OR ] , 1.0 ; 95 % confidence interval [ CI ] , 0.7 - 1.5 ) , CCBs ( OR , 0.9 ; 95 % CI , 0.7 - 1.2 ) , or beta-blockers ( OR , 1.0 ; 95 % CI , 0.8 - 1.2 ) for 5 or more years were not at an increased or decreased risk of developing breast cancer ( adjusted for smoking and body mass index [ calculated as weight in kilograms divided by the square of height in meters ] ) . The risk of breast cancer did not differ between users of different ACE inhibitors or different CCBs ( dihydropyridines , diltiazem hydrochloride , and verapamil hydrochloride ) or between users of short-acting ( OR , 1.0 ; 95 % CI , 0.7 - 1.4 ) or sustained-release ( OR , 1.0 ; 95 % CI , 0.8 - 1.3 ) nifedipine preparations . CONCLUSION The findings of this large case-control analysis do not support the hypothesis that longer-term use of ACE inhibitors or CCBs affects the risk of developing breast cancer |
10,457 | 25,381,346 | Conclusion : None of the existing instruments fulfils all criteria . | Objective : To review systematic ally studies investigating the convergent , criterion , and predictive validity of multi-domain cognitive screening instruments in the first four weeks after stroke . | Background and Purpose — Determining cognitive dysfunctioning ( CDF ) after stroke is an important issue because it influences choices for management in terms of return to previous activities . Because previous research in subacute stroke has shown important variations in CDF rates , we aim ed to describe the frequency and neuropsychological profile of CDF in subacute stroke outside dementia . We used a large battery of tests to screen any potentially hidden CDF . Methods — Patients with Mini-Mental State Examination scores ≥23 were prospect ively and consecutively included 2 weeks after a first-ever ischemic brain infa rct . Stroke features were based on MRI . Four domains were evaluated : instrumental and executive functions , episodic memory , and working memory ( WM ) . Patients were scored using means and compared with education- and age-matched control subjects . Then we attributed Z-scores for each test and each domain . The most relevant cognitive tests characterizing CDF were determined using logistic regression . Results — Among 177 patients ( mean age , 50.6 years ) , 91.5 % failed in at least one cognitive domain . WM was the most impaired domain ( 87.6 % ) with executive functions ( 64.4 % ) , episodic memory ( 64.4 % ) , and instrumental functions ( 24.9 % ) being relatively preserved . CDF was associated with age , education , depression , neurological deficit , and leukoaraiosis in bivariate analysis . Using logistic regression , WM tests and age predicted CDF ( Modified Paced Auditorial Serial Addition Test : OR=0.96 CI=0.93 to 0.98 ; Owen-spatial-WM : OR=1.07 CI=1.02 to 1.12 ; age : OR=0.96 CI=0.93 to 0.98 ) . Conclusion — CDF appears to be almost constant , although underestimated , in subacute stroke . WM could reflect some hidden dysfunctioning , which may interfere with rehabilitation and return to work . Clinical routine may include WM tests in young patients with mild stroke Objectives To investigate the prognostic value of the neurocognitive status measured by screening instruments , the Montreal Cognitive Assessment ( MoCA ) and Mini-Mental State Examination ( MMSE ) , individually and in combination with the stroke severity scale , the National Institute of Health Stroke Scale ( NIHSS ) , obtained at the subacute stroke phase or the baseline ( ≤2 weeks ) , for functional outcome 3–6 months later . Design Prospect i ve observational study . Setting Tertiary stroke neurology service . Participants 400 patients with a recent ischaemic stroke or transient ischaemic attack ( TIA ) received NIHSS , MoCA and MMSE at baseline and were followed up 3–6 months later . Primary outcome measures At 3–6 months following the index event , functional outcome was measured by the modified Rankin Scale ( mRS ) scores . Results Most patients ( 79.8 % ) had a mild ischaemic stroke and less disability ( median NIHSS=2 , median mRS=2 and median premorbid mRS=0 ) , while a minority of patients had TIA ( 20.3 % ) . Baseline NIHSS , MMSE and MoCA scores individually predicted mRS scores at 3–6 months , with NIHSS being the strongest predictor ( NIHSS : R2 change=0.043 , p<0.001 ) . Moreover , baseline MMSE scores had a small but statistically significant incremental predictive value to the baseline NIHSS for mRS scores at 3–6 months , while baseline MoCA scores did not ( MMSE : R2 changes=0.006 , p=0.03 ; MoCA : R2 changes=0.004 , p=0.083 ) . However , in patients with more severe stroke at baseline ( defined as NIHSS>2 ) , baseline MoCA and MMSE had a significant and moderately large incremental predictive value to the baseline NIHSS for mRS scores at 3–6 months ( MMSE : R2 changes=0.021 , p=0.010 ; MoCA : R2 changes=0.017 , p=0.021 ) . Conclusions Cognitive screening at the subacute stroke phase can predict functional outcome independently and improve the predictive value of stroke severity scores for functional outcome 3–6 months later , particularly in patients with more severe stroke Objective : To evaluate the prognostic value of domain-specific cognitive abilities in acute stroke with respect to long-term cognitive and functional outcome in addition to neurologic and demographic predictors . Methods : The authors evaluated 168 patients within the first 3 weeks after first-ever stroke . The prevalence of neuropsychological impairment was calculated vs 75 matched healthy controls . The authors also recorded demographic data , vascular risk factors , lesion characteristics , and clinical factors at admission . Independent predictor variables associated with long-term cognitive impairment ( assessed with a follow-up neuropsychological examination ) and functional impairment ( assessed with the modified Barthel Index and the Frenchay Activities Index ) were identified with stepwise multiple logistic regression . Areas under receiver operator characteristic curves were used to compare the predictive value of three models , i.e. , a st and ard medical model , a purely cognitive model , and a model consisting of both medical and cognitive predictors . Results : Thirty-one percent of patients showed long-term cognitive impairment . Basic and instrumental ADL disturbances remained present in 19 % and 24 % of patients . Domain-specific cognitive functioning predicted cognitive and functional outcome better than any other variable . Moreover , the prediction of instrumental ADL functioning improved when cognitive predictors were added to the st and ard medical model ( p < 0.05 ) . Impairments in abstract reasoning and executive functioning were independent predictors of long-term cognitive impairment . Inattention and perceptual disorders were more important in predicting long-term functional impairment . Conclusion : Domain-specific cognitive abilities in the early phase of stroke are excellent independent predictors of long-term cognitive and functional outcome While the Mini-Mental State Examination ( MMSE ) was originally developed to screen for dementia and delirium , many neurologists use this measure as a screening instrument for ' cognitive impairment ' in hospitalized stroke patients . However , the validity of the MMSE as such has never been evaluated in acute stroke . We administered the MMSE in addition to a neuropsychological examination covering six cognitive domains to 34 stroke patients ( mean interval between stroke and examination , 6.5+/-2.9 days ) and 34 healthy controls . The area under the receiver operating characteristic curve ( AUC ) was calculated in addition to the sensitivity and specificity for various cut-off points on the MMSE . Seventy percent of the patients were impaired in at least one cognitive domain . The accuracy of the MMSE in detecting cognitive impairment was no better than chance ( AUC = 0.67 ; p = 0.13 ) . No optimum MMSE cut-off value could be identified . The MMSE is particularly insensitive to impairments in abstract reasoning , executive functioning , and visual perception/construction Objectives To determine the prognostic value of brief cognitive screening tests administered in the subacute stroke phase ( initial 2 weeks ) for the detection of significant cognitive impairment 3–6 months after stroke , the authors compared the Montreal Cognitive Assessment ( MoCA ) and the Mini-Mental State Examination ( MMSE ) . Methods Patients with ischaemic stroke and transient ischaemic attack were assessed with both MoCA and MMSE within 14 days after index stroke , followed by a formal neuropsychological evaluation of seven cognitive domains 3–6 months later . Cognitive outcomes were dichotomised as either no – mild ( impairment in ≤2 cognitive domains ) or moderate – severe ( impairment in ≥3 cognitive domains ) vascular cognitive impairment . Area under the receiver operating characteristic ( ROC ) curve analysis was used to compare discriminatory ability . Results 300 patients were recruited , of whom 239 received formal neuropsychological assessment 3–6 months after the stroke . 60 ( 25 % ) patients had moderate – severe VCI . The overall discriminant validity for detection of moderate – severe cognitive impairment was similar for MoCA ( ROC 0.85 ( 95 % CI 0.79 to 0.90 ) and MMSE ( ROC 0.83 ( 95 % CI 0.77 to 0.89 ) ) , p=0.96 ) . Both MoCA ( 21/22 ) and MMSE ( 25/26 ) had similar discriminant indices at their optimal cutoff points ; sensitivity 0.88 versus 0.88 ; specificity 0.64 versus 0.67 ; 70 % versus 72 % correctly classified . Moreover , both tests had similar discriminant indices in detecting impaired cognitive domains . Conclusions Brief screening tests during acute admission in patients with mild stroke are predictive of significant vascular cognitive impairment 3–6 months after stroke OBJECTIVE To assess whether , and to what extent , cognitive outcome relates to overall functional outcome among elderly stroke patients . DESIGN Nonconcurrent prospect i ve study . SETTING Geriatric rehabilitation division at a large , urban , academic , freest and ing hospital in Israel . PARTICIPANTS Three hundred thirty-six patients aged 60 years and older admitted consecutively for rehabilitation after first acute stroke . Inclusion criteria were met by 315 patients , who were included in the final analysis . Average age was 75.3 years . The stroke was right sided in 44.1 % . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES The motor subscale of the FIM instrument assessed functional status . Absolute functional gain was determined by the FIM motor gain . Relative functional gain was calculated according to the Montebello Rehabilitation Factor Score . Cognitive status was assessed with the Mini-Mental State Examination ( MMSE ) and the FIM cognitive subscale . RESULTS FIM scores increased significantly during rehabilitation , mainly due to improvement in motor functioning . A strong association was found between the cognitive scales ( r=.853 , P<.001 ) . Better rehabilitation outcomes were observed in patients with higher admission cognitive status , adjusting for the effect of age , sex , onset to admission interval , length of stay , and severity of stroke ( odds ratio = 2.0 ; 95 % confidence interval , 1.5 - 2.5 ) . CONCLUSIONS Impaired cognitive status at admission negatively affects the rehabilitation outcome of elderly stroke patients . The utility of routinely using a cognitive test for all patients before admission to rehabilitation , preferably the MMSE , is emphasized . The time , cost , and effort involved in performing such a test are negligible , and the potential benefits are considerable Background and aim : Social functioning is impaired in approximately two-thirds of stroke patients of vocational age , even several months after a first ever mild to moderate stroke . The known predictors of social functioning are initial stroke severity , anxiety and depression , and the Mini-Mental State Evaluation , suggesting that cognitive deficits contribute to post-stroke social dysfunctioning . The aim of this study was to evaluate whether cognitive domains correlated with social functioning and to determine the cognitive predictors of social dysfunctioning . Methods : 74 patients were prospect ively included 6 months after a first ever stroke . National Institutes of Health Stroke Scale ( NIHSS ) , modified Rankin scale , depression and anxiety were recorded . Social functioning was recorded using the Work and Social Adjustment Scale ( WSAS ) . An extensive neuropsychological test battery explored general cognitive functioning , episodic memory , instrumental functions , executive functions and working memory . Univariate comparisons assessed the relationships between the neuropsychological tests and scores on the WSAS . Predicting factors for WSAS were determined using ordinal logistic regression . Results : 52 patients ( 70 % ; 95 % confidence interval 58 % to 80 % ) complained of significant perturbations in work and social functioning . In univariate comparisons , general cognitive functioning , memory , instrumental functions , executive functions and working memory significantly correlated with social functioning . Working memory was the most affected domain . With multivariate modelling , the NIHSS at admission , Hospital Anxiety Depression scale and Owen ’s Spatial Working Memory test were independent predictors of WSAS . Conclusions : All cognitive domains were associated with social functioning , working memory being the main cognitive determinant . Our results suggest that cognitive impairment impacts on social dysfunctioning , which is known to be a component of quality of life OBJECTIVES To assess the sensitivity and specificity of a screening battery for detecting cognitive impairment after stroke . DESIGN A r and omized controlled trial . METHODS Stroke patients were recruited from hospitals in three centres . Patients were screened for cognitive impairment on the Mini-Mental State Examination , the Sheffield Screening Test for Acquired Language Disorders and Raven 's Coloured Progressive Matrices and received a further battery of assessment s of cognitive function . Sensitivity and specificity values were calculated for the three screening measures for overall conclusions regarding cognitive impairment reached from a comprehensive assessment . Receiver Operating Characteristic Curves were plotted . CONCLUSION The Mini-Mental State Examination was not a useful screen for memory problems or overall cognitive impairment after stroke . The Sheffield Screening Test for Acquired Language Disorders was an appropriate screen for language problems . The Raven 's Coloured Progressive Matrices was appropriate as a screen for perceptual problems and visual inattention but not for executive deficits OBJECTIVES To determine whether cognitive impairment affects access to , or quality of , rehabilitation services , and to examine the effects of functional outcomes in stroke patients . DESIGN Secondary analysis of prospect i ve cohort of stroke patients followed for 6 months after stroke . SETTING S Eleven large-volume US Department of Veterans Affairs hospitals nationwide . PARTICIPANTS Stroke patients ( N=272 ) who were c and i date s for rehabilitation . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Rehabilitation process variables were examined for patients assessed as cognitively impaired or unimpaired according to education-adjusted Mini-Mental State Examination score . Functional outcomes were performance of activities of daily living ( ADLs ) , measured by the FonFIM , and instrumental activities of daily living ( IADLs ) , measured by Lawton , at 6-month follow-up . RESULTS Compliance with guidelines and receipt of and interval to postacute treatment initiation did not differ between cognitively impaired and unimpaired patients . Although most cognition-related treatment elements were similar for both groups , cognitive goals were more frequently charted in impaired patients . Controlling for baseline function and rehabilitation process , cognitively impaired patients had worse IADL performance at 6 months than did unimpaired patients ; cognition did not significantly influence ADL performance . CONCLUSIONS Quality of , and access to , rehabilitative care was equivalent for patients with and without cognitive impairment . Despite a similar rehabilitation process , cognitively impaired stroke patients experienced worse recovery of IADLs Background / Aims : Even mild stroke survivors may sometimes experience residual cognitive damage . No consensus has emerged about which cognitive test is most appropriate for the diagnosis of poststroke cognitive impairment . We aim to compare a computerized battery of neuropsychological tests for memory , attention and executive functions ( MindStreams ® ) with the Montreal Cognitive Assessment ( MoCA ) to detect mild-to-moderate cognitive impairments in poststroke patients . Methods : Subjects enrolled to the TABASCO ( Tel Aviv Brain Acute Stroke Cohort ) study , a prospect i ve study which includes consecutive first-ever mild-to-moderate stroke patients , were included . All participants underwent neurological and cognitive evaluations . Results : A total of 454 patients with transient ischemic attack ( TIA ) or stroke are reported . Their mean MoCA and MindStreams scores were lower than normal ; however , the TIA group presented significantly better scores using either method . The correlation between the MoCA and the computerized global score was 0.6 ( p < 0.001 ) . A significant correlation was found between the subcategory scores ( executive function , memory and attention ) . However , the MoCA identified many more subjects with low scores ( < 26 ) compared to the MindStreams ( 70.6 vs. 15.7 % ) . Conclusion : Our results demonstrate that either of the modalities alone is sensitive enough for identifying subtle cognitive impairment and none picks up substantially more cognitive losses than the other in patients with cerebrovascular disease Purpose . The ability to balance is no longer automatic after stroke in patients with motor impairment and needs to be relearned . Learning requires cognitive and executive abilities . It is well known that cognitive and executive impairments are common after stroke , but how these are related to balance has not yet been fully studied . We , therefore , wanted to explore the impact of pre-stroke cognitive impairment , global and selective cognitive and executive impairment in the early phase after stroke and at the 1-year follow-up on balance and on the improvement of balance during the first year after stroke . Method . Seventy-four patients were included consecutively on admission following stroke to a geriatric stroke unit and followed prospect ively for 1 year . Balance was assessed using the Berg Balance Scale on admission , on discharge and 1 year after stroke . Results . Cognitive impairment before stroke , measured using the Cognitive Impairment Question naire , was found to lead to poor balance on discharge and 1 year after stroke . Patients with impaired logical deductive ability and executive function , measured using a neuropsychological test battery both in the early phase and 1 year after stroke , also had significantly poorer balance 1 year after stroke than patients with intact functions . Most importantly , only patients with intact cognitive function , before stroke , on admission and at the 1-year follow-up , significantly improved their balance after discharge . Conclusions . Our results show that cognitive status , both before and after stroke , is important for balance and improvement of balance after stroke Abstract : Few well‐ design ed descriptive studies focus exclusively on patients after motor stroke . This study describes a cohort of participants after motor stroke and assesses the extent to which five key variables explain the variation in functional recovery 3 months after stroke . Prospect i ve data were collected ( N = 100 ) on age , lesion volume , motor strength , cognition , and poststroke function during the acute care hospital admission . Instruments included magnetic resonance imaging ( MRI ) to provide a measure of lesion volume , the Mini‐Mental State Examination ( MMSE ) and the Neurobehavioral Cognitive Status Examination ( NCSE ) to measure cognitive status , and the National Institutes of Health Stroke Scale ( NIHSS ) to measure motor strength . The Functional Independence Measure ( FIMTM ) was used to measure baseline function and functional recovery 3 months after stroke . Descriptive and hierarchical multiple regression analyses were used to describe the cohort and predict functional recovery . The means for key variables during acute care were 65 ( ±15 ) years of age , lesion volume 21.5 ( ±44.7 ) cm3 , NIHSS 6.34 ( ±3.55 ) , MMSE 24.38 ( ±4.82 ) , NCSE 64.33 ( ±13 ) , and FIMTM 94.05 ( ±19.31 ) . Age , cognitive status , and initial function accounted for 42 % of the variance in functional recovery 3 months after stroke . Results indicate that neuroscience nurses need to add cognition to their focus during the fast‐paced acute phase of care following motor stroke Purpose : To identify predictors of outcome after 12 months in elderly stroke patients rehabilitated in a geriatric ward . Design : Prospect i ve with evaluation in the subacute phase and after 12 months . Setting : Geriatric ward and outpatient clinic . Subjects : All stroke patients admitted from the acute unit to a geriatric ward for rehabilitation during a 16-month period ( n = 171 ) . Main outcome measures : Place of living , mortality and social functioning ( Frenchay Activities Index ) 12 months following stroke . Results : Age , urinary incontinence and cognitive function were significantly associated with place of living ( home versus nursing home ) 12 months post stroke in bivariate analyses . However , using multivariate logistic regression analyses , only age ( p = 0.005 ) and urinary incontinence at baseline ( p = 0.028 ) remained independent predictors of place of living . Mortality during the first year was significantly predicted by urinary incontinence and gender ( men doing worse ) , whereas the Barthel Activities of Daily Living ( ADL ) Index sumscore was the only significant independent predictor of social activities . Conclusion : Urinary incontinence at baseline seems to be a most important predictor of outcome 12 months post stroke in geriatric patients . However , with regard to social activities ( Frenchay Activities Index ) , functional impairment in the initial phase as reflected by the Barthel ADL Index supersedes other predictors BACKGROUND The relationship between the amount of rehabilitation therapy and functional outcome in stroke patients has not been established . OBJECTIVES To evaluate the effectiveness of inpatient rehabilitation for post-acute stroke , and examine the relationship between intensity of therapies and functional status at discharge . METHODS We evaluated 50 first-stroke patients , average age 63 years , in a prospect i ve descriptive study . The impairment and Functional Independence Measurement were assessed both at admission to rehabilitation and at discharge . Patients were monitored weekly during their stay by means of discipline-specific measures of activity level . Predictor variables included intensity of physical , occupational and speech therapies ; demographic characteristics ; length of stay ; and time since the stroke . RESULTS A significant reduction in impairment was observed at discharge . The predictors of gains and activity level at discharge as well as motor vs. cognitive components of the FIM were neither consistent nor did they occur in the same trend of functional improvement . Greater FIM motor level at discharge was associated with younger age , higher admission motor and cognitive level , and receipt of any speech therapy , while greater FIM cognitive level was associated with higher cognitive level at admission , shorter interval from onset to admission , and more intense occupational therapy . More intense OT was associated with greater and more cognitive improvement during the hospitalization . CONCLUSION Since the sample was relatively small and heterogenous in terms of the patients ' functional abilities , the findings can not be generalized to the whole population of stroke patients . Further efforts to identify the best timing , modalities , intensity and frequency of the various treatments are needed to improve the cost-benefit equation of rehabilitation in stroke patients Neuropsychological assessment of older individuals with dementing illnesses has suffered from a lack of appropriately design ed test instruments . The Repeatable Battery for the Assessment of Neuropsychological Status ( RBANS ) was developed for the dual purpose s of identifying and characterizing abnormal cognitive decline in the older adult and as a neuropsychological screening battery for younger patients . The entire battery takes less than 30 minutes to administer , and yields scaled scores for five cognitive domains . The current study reports preliminary clinical validity results with the RBANS , comparing very mildly demented patients with a diagnosis of probable Alzheimer 's disease ( n = 20 ) to patients with Huntington 's disease ( n = 20 ) and normal controls ( n = 40 ) . Although the patient groups had essentially identical total scores on the RBANS , they exhibited opposite profiles , differing significantly on four of the five subsections . The AD patients performed most poorly on Language , and Delayed Memory subsections , while the HD patients obtained their lowest scaled scores on the Attention and the Visuospatial/Constructional subsections . These results are consistent with the neuropsychological profiles of these dementing disorders derived from lengthier st and ardized tests and experimental investigations . In addition , even those patients who performed above the suggested cut-off points on the MMSE and the Dementia Rating Scale scored significantly below their controls on the RBANS . These data suggest that the RBANS is effective at both detecting and characterizing dementia of different etiologies Objective : To investigate prospect ively the frequency and clinical determinants of poststroke dementia ( PSD ) in a cohort of consecutive ischemic stroke in patients in southern Taiwan . Methods : A st and ard stroke evaluation protocol was conducted at admission and 3 months after an ischemic stroke . The protocol included clinical , neurologic , neurobehavioral , and functional assessment s as well as neuroimaging examinations . Diagnoses were made according to the Neurologic Adaptation of the 10th edition of the International Classification of Diseases criteria for dementia . Results : Excluding patients with prestroke dementia , a total of 283 patients were surveyed at 3 months after stroke ; 26 ( 9.2 % ) of them met the criteria for PSD . The correlates of PSD in logistic regression analyses were age 65 years or older ( odds ratio [ OR ] 6.6 ) vs < 65 years , previous occupation as a laborer ( OR 3.3 ) , prior stroke ( OR 3.1 ) , left carotid vascular territory ( OR 12.5 ) vs vertebrobasilar and unknown territories , moderate to severe stroke severity ( OR 3.4 ) , and cognitive impairment ( OR 4.5 ) and poorer functional status at admission ( OR 4.5 ) . Based on the significant predictors identified , the logistic regression model correctly classified PSD in 93.4 % of subjects . Conclusion : The lower frequency of PSD in this study from Taiwan compared with previous studies from Western countries may have been due to the relatively younger age of the elderly population and the use of stricter diagnostic criteria |
10,458 | 25,537,782 | Finding information relating to the number of studies in the meta- analysis , and locating the number of studies in the entire systematic review were revealed as areas needing attention during the usability evaluation .
Iterative testing combined with a multifaceted approach to usability testing offered essential insight into aspects of the prototypes that required modifications . | OBJECTIVE The aim of this study was to evaluate the usability of two formats of a shortened systematic review for clinicians . | The current evidence -based practice ( EBP ) movement in healthcare emphasizes that clinical decision making should be based on the " best evidence " available , preferably the findings of r and omized clinical trials . Within this context qualitative research findings are considered to have little value and the old debate in nursing has been re-ignited related to whether qualitative versus quantitative research findings provides the best empirical evidence for nursing practice . In response to this crisis qualitative scholars have been called upon by leaders in the field to clarify for outsiders what qualitative research is and to be more explicit in pointing out the utility of qualitative research findings . In addition , attention to " quality " in qualitative research has been identified as an area worthy of renewed focus . Within this paper two key problems related to addressing these issues are review ed : disagreement not only among " outsiders " but also some nursing scholars related to the definition of " qualitative research " , and a lack of consensus related how to best address " rigor " in this type of inquiry . Based on this review a set of st and ard requirements for qualitative research published in nursing journals is proposed that reflects a uniform definition of qualitative research and an enlarged yet clearly articulated conceptualization of quality . The approach suggested provides a framework for developing and evaluating qualitative research that would have both defensible scholarly merit and heuristic value . This will help solidify the argument in favor of incorporating qualitative research findings as part of the empirical " evidence " upon which evidence -based nursing is founded This is a prospect i ve study of clinical questions generated in primary care consultations and a comparison of two approaches to answering those clinical questions . Twenty-one doctors in a university-based primary care clinic su bmi tted 78 clinical questions arising from patient consultations during 24 clinic days ( 0.01 question per patient encounter ) . These doctors subsequently found answers to 40 % of their questions but were satisfied with only 67 % of these answers . The investigators were able to provide answers for 95 % of the questions asked and the doctors rated these answers as satisfactory in 86 % of instances . Answers obtained by investigators had significantly higher satisfaction score than those obtained by doctors ' search ( p = 0.002 ) . The two main findings of this study are ( 1 ) almost all questions arising in clinic setting could be answered by intensive search ; ( 2 ) answers found by intensive search es were judged to be more satisfactory than those found routinely by doctors . Provision of an information retrieval service in addition to training in the search ing and appraisal of medical literature are possible solutions to the information needs of busy clinicians BACKGROUND No professional society or group recommends routine ovarian cancer screening , yet physicians ' enthusiasm for several cancer screening tests before benefit has been proven suggests that some women may be exposed to potential harms . OBJECTIVE To provide nationally representative estimates of physicians ' reported nonadherence to recommendations against ovarian cancer screening . DESIGN Cross-sectional survey of physicians offering women 's primary care . The 12-page question naire contained a woman 's annual examination vignette and questions about offers or orders for transvaginal ultrasonography ( TVU ) and cancer antigen 125 ( CA-125 ) . SETTING United States . PARTICIPANTS 3200 physicians r and omly sample d equally from the 2008 American Medical Association Physician Masterfile lists of family physicians , general internists , and obstetrician-gynecologists ; 61.7 % responded . After exclusions , 1088 respondents were included ; their responses were weighted to represent the specialty distribution of practicing U.S. physicians nationally . MEASUREMENTS Reported nonadherence to screening recommendations ( defined as sometimes or almost always ordering screening TVU or CA-125 or both ) . RESULTS Twenty-eight percent ( 95 % CI , 24.5 % to 32.9 % ) of physicians reported nonadherence to screening recommendations for women at low risk for ovarian cancer ; 65.4 % ( CI , 61.1 % to 69.4 % ) did so for women at medium risk for ovarian cancer . Six percent ( CI , 4.4 % to 8.9 % ) reported routinely ordering or offering ovarian cancer screening for low-risk women , as did 24.0 % ( CI , 20.5 % to 28.0 % ) for medium-risk women ( P ≤ 0.001 ) . Thirty-three percent believed TVU or CA-125 was an effective screening test . In adjusted analysis , actual and physician-perceived patient risk , patient request for ovarian cancer screening , and physician belief that TVU or CA-125 was an effective screening test were the strongest predictors of physician-reported nonadherence to published recommendations . LIMITATION The results are limited by their reliance on survey methods ; there may be respondent-nonrespondent bias . CONCLUSION One in 3 physicians believed that ovarian cancer screening was effective , despite evidence to the contrary . Substantial proportions of physicians reported routinely offering or ordering ovarian cancer screening , thereby exposing women to the documented risks of these tests . PRIMARY FUNDING SOURCE Centers for Disease Control and Prevention and the National Cancer Institute BACKGROUND Unlike reduced mortality rates , improved survival rates and increased early detection do not prove that cancer screening tests save lives . Nevertheless , these 2 statistics are often used to promote screening . OBJECTIVE To learn whether primary care physicians underst and which statistics provide evidence about whether screening saves lives . DESIGN Parallel-group , r and omized trial ( r and omization controlled for order effect only ) , conducted by Internet survey . ( Clinical Trials.gov registration number : NCT00981019 ) SETTING National sample of U.S. primary care physicians from a research panel maintained by Harris Interactive ( 79 % cooperation rate ) . PARTICIPANTS 297 physicians who practice d both inpatient and outpatient medicine were surveyed in 2010 , and 115 physicians who practice d exclusively outpatient medicine were surveyed in 2011 . INTERVENTION Physicians received scenarios about the effect of 2 hypothetical screening tests : The effect was described as improved 5-year survival and increased early detection in one scenario and as decreased cancer mortality and increased incidence in the other . MEASUREMENTS Physicians ' recommendation of screening and perception of its benefit in the scenarios and general knowledge of screening statistics . RESULTS Primary care physicians were more enthusiastic about the screening test supported by irrelevant evidence ( 5-year survival increased from 68 % to 99 % ) than about the test supported by relevant evidence ( cancer mortality reduced from 2 to 1.6 in 1000 persons ) . When presented with irrelevant evidence , 69 % of physicians recommended the test , compared with 23 % when presented with relevant evidence ( P < 0.001 ) . When asked general knowledge questions about screening statistics , many physicians did not distinguish between irrelevant and relevant screening evidence ; 76 % versus 81 % , respectively , stated that each of these statistics proves that screening saves lives ( P = 0.39 ) . About one half ( 47 % ) of the physicians incorrectly said that finding more cases of cancer in screened as opposed to unscreened population s " proves that screening saves lives . " LIMITATION Physicians ' recommendations for screening were based on hypothetical scenarios , not actual practice . CONCLUSION Most primary care physicians mistakenly interpreted improved survival and increased detection with screening as evidence that screening saves lives . Few correctly recognized that only reduced mortality in a r and omized trial constitutes evidence of the benefit of screening . PRIMARY FUNDING SOURCE Harding Center for Risk Literacy , Max Planck Institute for Human Development OBJECTIVE Usage of computer re sources at the point of care has a positive effect on physician decision making . Pediatricians ' information-seeking behaviors are not well characterized . The goal of this study was to characterize quantitatively the information-seeking behaviors of general pediatricians and specifically compare their use of computers , including digital libraries , before and after an educational intervention . METHODS General pediatric residents and faculty at a US Midwest children 's hospital participated . A control ( year 1 ) versus intervention group ( year 2 ) research design was implemented . Eligible pediatrician pools overlapped , such that some participated first in the control group and later as part of the intervention . The intervention group received a 10-minute individual training session and h and out on how to use a pediatric digital library to answer professional questions . A general medical digital library was also available . Pediatricians in both the control and the intervention groups were surveyed using the critical incident technique during 2 6-month time periods . Both groups were telephoned for 1- to 2-minute interviews and were asked , " What pediatric question ( s ) did you have that you needed additional information to answer ? " The main outcome measures were the differences between the proportion of pediatricians who use computers and digital libraries and a comparison of the number of times that pediatricians use these re sources before and after intervention . RESULTS A total of 58 pediatricians were eligible , and 52 participated ( 89.6 % ) . Participant demographics between control ( N = 41 ; 89.1 % ) and intervention ( N = 31 ; 70.4 % ) were not statistically different . Twenty pediatricians were in both groups . Pediatricians were slightly less likely to pursue answers after the intervention ( 94.7 % vs 89.2 % ) ; the primary reason cited for both groups was a lack of time . The pediatricians were as successful in finding answers in each group ( 95.7 % vs 92.7 % ) , but the intervention group took significantly less time ( 8.3 minutes vs 19.6 minutes ) . After the intervention , pediatricians used computers and digital libraries more to answer their questions and spent less time using them . CONCLUSION This study showed higher rates of physician questions pursued and answered and higher rates of computer use at baseline and after intervention compared with previous studies . Pediatricians who seek answers at the point of care therefore should begin to shift their information-seeking behaviors toward computer re sources , as they are as effective but more time-efficient OBJECTIVE To measure the effects of a summary -of- findings ( SoF ) table on user satisfaction , underst and ing , and time spent finding key results in a Cochrane review . STUDY DESIGN AND SETTING We r and omized participants in an evidence -based practice workshop ( r and omized controlled trial [ RCT ] I ) and a Cochrane Collaboration entities meeting ( RCT II ) to receive a Cochrane review with or without an SoF table . In RCT I , we measured user satisfaction . In RCT II , we measured correct comprehension and time spent finding key results . RESULTS RCT I : Participants with the SoF table ( n=47 ) were more likely to " agree " or " strongly agree " that it was easy to find results for important outcomes than ( n=25 ) participants without the SoF table-68 % vs. 40 % ( P=0.021 ) . RCT II : Participants with the SoF table ( n=18 ) were more likely to correctly answer two questions regarding results than ( n=15 ) those without the SoF table : 93 % vs. 44 % ( P=0.003 ) and 87 % vs. 11 % ( P<0.001 ) . Participants with the SoF table spent an average of 90 seconds to find key information compared with 4 minutes for participants without the SoF table ( P=0.002 ) . CONCLUSION In two small trials , we found that inclusion of an SoF table in a review improved underst and ing and rapid retrieval of key findings compared with review s with no SoF table RATIONALE AND AIM Over the past 12 years , thous and s of authors working with the Cochrane Collaboration around the world have produced systematic review s to reduce uncertainty in health care decision making . We evaluated the conclusions from Cochrane systematic review s of r and omized controlled trials in terms of their recommendations for clinical practice and research . METHODS In our cross-sectional study of systematic review s published in the Cochrane Library , we r and omly selected and analysed completed systematic review s published across all 50 Cochrane Collaborative Review Groups . RESULTS We analysed 1016 completed systematic review s. Of these , 44 % concluded that the interventions studied were likely to be beneficial , of which 1 % recommended no further research and 43 % recommended additional research . Also , 7 % of the review s concluded that the interventions were likely to be harmful , of which 2 % did not recommend further studies and 5 % recommended additional studies . In total , 49 % of the review s reported that the evidence did not support either benefit or harm , of which 1 % did not recommend further studies and 48 % recommended additional studies . Overall , 96 % of the review s recommended further research . CONCLUSIONS Cochrane systematic review s were about evenly split between those in which the authors concluded that at least one of the interventions was beneficial and those in which the evidence neither supported nor refuted the intervention tested . The Cochrane Collaboration needs to include clinical trial protocol summaries with a study design optimized to answer the relevant research questions |
10,459 | 20,360,221 | None of these six tests was ( sufficiently ) studied in primary care .
Conclusions Although combinations of symptom and results of immunochemical faeces tests showed good diagnostic performance for colorectal cancer , evidence from primary care is lacking . | Objective To summarise available evidence on diagnostic tests that might help primary care physicians to identify patients with an increased risk for colorectal cancer among those consulting for non-acute lower abdominal symptoms . | Abstract Screening for fecal occult blood by means of guaiac tests has an unsatisfactory sensitivity for the detection of colorectal neoplasms . The immunological determination of human hemoglobin in feces has a higher sensitivity and specificity , but hemoglobin is de grade d during its transport through the gastrointestinal tract . We compared the hemoglobin test to a newly developed immuno-chemiluminometric ( ILMA ) assay for quantifying the hemoglobin-haptoglobin complex in feces which shows high stability against degradation . From each of 621 patients with gastrointestinal complaints before scheduled colonoscopy we collected two 1-ml sample s from a single stool ; there were no dietary restrictions . The sensitivity for detecting colorectal carcinomas proved 87 % with hemoglobin . With the hemoglobin-haptoglobin complex it was 87 % at a cutoff level of 1.5 µg/g feces , 83 % at 2.0 µg/g feces , and 78 % at 2.5 and 3.0 µg/g feces . The sensitivity for detecting large adenomatous polyps was 54 % with hemoglobin , 76 % with the hemoglobin-haptoglobin complex at a cutoff point of 1.5 µg/g feces , 73 % with the hemoglobin-haptoglobin complex at 2.0 and 2.5 µg/g feces , and 65 % with the hemoglobin-haptoglobin complex at 3.0 µg/g feces . The optimal cutoff point for the hemoglobin-haptoglobin complex was estimated to be 2.0 µg/g stool . The specificity for hemoglobin ( 99 % ) was significantly higher than that for the hemoglobin-haptoglobin complex at 2.0 µg/g feces ( 96 % ) . Immunological determination of the hemoglobin-haptoglobin complex in feces has a comparable sensitivity as the fecal hemoglobin assay for colorectal carcinomas and a significantly higher sensitivity for adenomatous polyps but a significantly lower specificity . Its use for colorectal cancer prevention is currently being evaluated in a screening study This article is one of a series of statements discussing the use of gastrointestinal endoscopy in common clinical situations . The St and ards of Practice Committee of the American Society for Gastrointestinal Endoscopy prepared this text . In preparing this guideline , a MEDLINE literature search was performed , and additional references were obtained from the bibliographies of the identified articles and from recommendations of expert consultants . When little or no data exist from well design ed prospect i ve trials , emphasis is given to results from large series and reports from recognized experts . Guidelines for appropriate use of endoscopy are based on a critical review of the available data and expert consensus . Further controlled clinical studies are needed to clarify aspects of this statement , and revision may be necessary as new data appear . Clinical consideration may justify a course of action at variance to these recommendations . This guideline replaces and supplements our previous document on colorectal cancer screening and surveillance BACKGROUND Rectal bleeding is common , but it is still unclear which patients require investigation to exclude serious pathology , although it is known that colectoral cancer is very rare under the age of 40 years . Few studies have examined all patients presenting to their primary health physician rather than screening whole population s. AIM The aim of this study was to investigate the view that all patients over the age of 40 who present to their general practitioner with rectal bleeding should undergo investigation by colonoscopy to rule out serious pathology , regardless of symptomatology . METHOD A prospect i ve study was carried out of 99 consecutive patients over 40 years presenting with rectal bleeding to 17 general practice s in Newcastle upon Tyne . RESULTS Serious pathology was detected by colonoscopy in 44.4 % of patients . The diagnoses were : colorectal carcinoma , eight cases ( two Dukes ' grade A , two Dukes ' grade B , four Dukes ' grade C ) ; one or more polyps , 25 cases ( in 17 cases at least one polyp was 5 mm or greater in diameter ) ; inflammatory bowel disease , 11 cases . In the remaining 55 patients , bleeding was associated with diverticular disease ( 16 cases ) and haemorrhoids ( 28 cases ) . No cause was found in 11 patients . This high rate of pathology may be partly caused by selection of cases for referral by the general practitioner , despite efforts to minimize this . Three symptoms as elicited by the colonoscopist were found to be significantly associated with serious disease : blood mixed with stool ( P < 0.001 ) ; change in bowel habit ( P < 0.005 ) ; and the presence of abdominal pain ( P < 0.025 ) . However , symptoms elicited on primary presentation were less helpful and symptoms changed significantly between consultation with the general practitioner and colonoscopy . CONCLUSION All patients over the age of 40 years presenting with rectal bleeding should be referred for flexible sigmoidoscopy or colonoscopy . Symptoms are unhelpful in deciding who requires investigation Hemoccult faecal occult blood testing is widely advocated as a screening test for colorectal cancer but few studies have shown its correlation with conventional methods of investigation for colorectal disease . In a prospect i ve study of 802 symptomatic patients with suspected colorectal disease there was good patient compliance ( 92.5 % ) and a high specificity for colorectal cancer ( 85.4 % ) . The false positive rate was 8.6 % ( 12 of 140 patients with positive results ) , and while the test result was positive in 22 of 26 colonic cancers the false negative rate for rectal cancer ( 45.4 % ) should not detract from its value as a screening test if proper digital anorectal and proctosigmoidoscopic examination are widely practised . A positive Hemoccult test result is a useful indicator for the need to proceed to full colorectal investigation , including colonoscopy A combination guaiac and immunological test Fecatwin/Feca EIA for the detection of faecal occult blood was used in the investigation of 535 symptomatic patients in order to assess the value of this combined test in the detection of colorectal neoplasia . The addition of the immunological part of the test led to an improvement in specificity for colorectal cancer from 80 % to 91 % and an increase in the positive predictive value of the test for colorectal cancer from 14 % to 24 % . However , there was a fall in sensitivity from 75 % to 67 % . There was no substantial advantage in the addition of the immunological part of the test to justify the extra laboratory workload incurred Over a 3‐year period , all patients referred for barium enema examination had a double‐contrast barium enema and flexible sigmoidoscopy performed on the same day . A total of 462 joint examinations were performed . Abnormalities were found in 193 patients by the use of barium enema , 164 patients by using sigmoidoscopy and 294 by the use of both methods of investigation . Sigmoidoscopy was superior to barium enema in the detection of polyps and inflammatory bowel disease but barium enema was more sensitive for diverticular disease . The presenting symptoms had no predictive value in distinguishing carcinoma , polyps and diverticular disease . Diverticular disease did not reduce the sensitivity of barium enema examination to polyps in the sigmoid colon . Fibreoptic sigmoidoscopy immediately before barium enema was well tolerated by patients . The investigations were complementary in the diagnosis of colonic polyps , inflammatory bowel disease and diverticular disease Objective . A diagnostic strategy implemented in Denmark in 2002 recommends selective use of colonoscopy in out patients without known colorectal cancer ( CRC ) risk factors who are referred with symptoms consistent with possible CRC . Selection of patients for colonoscopy was based on the presenting symptom(s ) and findings at the initial examination ( flexible sigmoidoscopy/faecal occult blood test ) . The aim of this study was to evaluate the strategy by assessing the prevalence of patients with diagnosed CRC , the frequency of patients with missed CRC , the adherence to the strategy and the number of examinations performed . Material and methods . We prospect ively studied patients aged 40 years and older without known risk factors for CRC , referred to two surgical outpatient clinics during a period of 15–16 months . Examinations , findings at the examinations , the final diagnoses and date of discharge were recorded . Missed CRCs were identified by follow-up in hospital discharge registries . Results . CRC was diagnosed in 126 ( 5.3 % ; 95 % CI : 4.5–6.3 % ) of the 2361 patients included during the diagnostic work-up . Two additional cancers identified at follow-up were both missed during colonoscopy ( 1.5 % ; 95 % CI : 0.2–5.4 % ) . The adherence to the strategy was 75.7 % , and 125 of the 126 patients with a CRC were examined in conformity with the recommended strategy . Almost 60 % of the patients underwent colonoscopy and almost 50 % underwent both flexible sigmoidoscopy and colonoscopy . Conclusions . The diagnostic strategy is an acceptable alternative to initial colonoscopy , with a low probability of missing a CRC ; however , a considerable proportion of the patients undergo colonoscopy and multiple examinations Although most cases of rectal bleeding are due to local conditions , this symptom is a major sign of colorectal cancer . Little research exists on whether to refer a patient with rectal bleeding for further evaluation.1 - 3 We therefore studied the diagnostic value of rectal bleeding in relation to a subsequent diagnosis of colorectal cancer . In Belgium , a network of sentinel practice s , covering 1 % of the population , registers epidemiological data .4 The methods used to estimate the denominator ( in patient years ) have been published.4 We analysed data on all patients with colorectal cancer diagnosed in 1993–4 to evaluate sensitivity ( retrospective study ) . We chose rectal bleeding as the reason for visiting a general practitioner before colorectal cancer was diagnosed as the main outcome measure . To obtain a positive predictive value ( prospect i ve part of study ) , we included all patients presenting with rectal bleeding in 1993 - 4 . Our reference st and ard was colorectal cancer diagnosed AIM To estimate the prevalence of colorectal cancer ( CRC ) in patients with long lasting colonic symptoms undergoing total colonoscopy ; and to establish clinical features predicting its occurrence . METHODS This prospect i ve study was carried out in Imam Hospital , Tabriz University of medical sciences , Iran . Continuous patients with long lasting lower gastrointestinal tract symptoms who had the criteria of a colonoscopy were included . The endoscopist visualized the caecum documented by a photo and /or a specimen from terminal ileum . RESULTS Four hundred and eighty consecutive symptomatic patients [ mean age ( SD ) : 42.73 ( 16.21 ) ] were included . The prevalence of colorectal neoplasia was 15.3 % ( 34 subjects ) and 37.7 % ( 181 subjects ) had a completely normal colon . Adenomatous polyps were detected in 56 ( 11.7 % ) patients , in 12.3 % of men and 10.9 % of women . The mean age of the patients with a polyp was significantly higher than the others ( 49.53 + /- 14.16 vs 41.85 + /- 16.26 , P = 0.001 ) . Most of the adenomatous polyps were left sided and tubular ; only 22.5 % of polyps were more than 10 mm . Cancer was detected in 16 ( 3.6 % ) of our study population , which was mostly right sided ( 57.2 % ) . The mean age of patients with cancer was significantly higher than the others ( 60.25 + /- 8.26 vs 42.13 + /- 16.08 , P < 0.005 ) and higher than patients with polyps [ 60.25 ( 8.26 ) vs 49.53 ( 1.91 ) ( P < 0.0005 ) ] . None of the symptoms ( diarrhea , abdominal pain , rectal bleeding , constipation , altering diarrhea and constipation , history of cancer , known irritable bowel disease , history of polyp and fissure or family history of cancer ) were predictors for cancer or polyps , but the age of the patient and unexplained anemia independently predicted cancer . CONCLUSION Less advanced patterns and smaller sizes of adenomas in Iran is compatible with other data from Asia and the Middle East , but in contrast to western countries . Prevalence of colonic neoplasia in our community seems to be lower than that in western population . Colonic symptoms are not predictors for polyps or cancer but unexplained anemia and elder age can predict CRC Objectives : To determine the impact of novel invitation strategies on population participation in faecal immunochemical test (FIT)-based colorectal cancer ( CRC ) screening . Setting A community screening programme in Adelaide , South Australia . Methods : In total , 2400 people aged 50–74 years were r and omly allocated to one of four CRC screening invitation strategies : ( a ) Control : st and ard invitation-to-screen letter explaining risk of CRC and the concept , value and method of screening ; ( b ) Risk : invitation with additional messages related to CRC risk ; ( c ) Advocacy : invitation with additional messages related to advocacy for screening from previous screening programme participants and ( d ) Advance Notification : first , a letter introducing Control letter messages followed by the st and ard invitation-to-screen . Invitations included an FIT kit . Programme participation rates were determined for each strategy relative to control . Associations between participation and sociodemographic variables were explored . Results : At 12 weeks after invitation , participation was : Control : 237/600 ( 39.5 % ) ; Risk : 242/600 ( 40.3 % ) ; Advocacy : 216/600 ( 36.0 % ) and Advance Notification : 290/600 ( 48.3 % ) . Participation was significantly greater than Control only in the Advance Notification group ( Relative risk [ RR ] 1.23 , 95 % confidence interval [ CI ] 1.06–1.43 ) . This effect was apparent as early as two weeks from date of offer ; Advance Notification : 151/600 ( 25.2 % ) versus Control : 109/600 ( 18.2 % , RR 1.38 , 95 % CI 1.11–1.73 ) . Conclusions : Advance notification significantly increased screening participation . The effect may be due to a population shift in readiness to undertake screening , and is consistent with the Transtheoretical Model of behaviour change . Risk or lay advocacy strategies did not improve screening participation . Organized screening programmes should consider using advance notification letters to improve programme participation OBJECTIVES : The immunological fecal occult blood test ( IFOBT ) has established itself as a more precise marker for colorectal cancer ( CRC ) screening than traditional guaiac-based FOBT . The simpler , cheaper , and more convenient newer office-based IFOBTs have been vali date d for diagnosing CRC . Dimeric isoenzyme of pyruvate kinase , M2-PK , expressed by tumor cells , has as well been proposed as a screening tool for CRC . This is the first study comparing fecal M2-PK as a screening biomarker for CRC against previously evaluated office-based IFOBT and colonoscopy . METHODS : Six hundred forty consecutive subjects ( symptomatic , as well as for CRC screening ) referred for colonoscopy for various indications across five centers in Germany provided the stool sample s for performing M2-PK and an immunochemical FOB strip test . The IFOBT used was a rapid immunochromatographic assay for detection of fecal hemoglobin . For M2-PK , a commercially available s and wich enzyme-linked immunosorbent assay ( ELISA ) was used . The M2-PK test needs 6 h , while the office-based test can be read in just 10 min and is five times cheaper . RESULTS : Office-based IFOBT had sensitivity , specificity , positive predictive value ( PPV ) , negative predictive value ( NPV ) , and positive and negative likelihood ratios ( LR ) of 64.5 , 96.3 , 72.0 , 94.9 , 17.5 , and 0.4 for diagnosing colorectal neoplasia ( CRN ) , while the above performance characteristics for M2-PK at a cutoff value of 4U/mL were 72.4 , 73.8 , 29.0 , 94.8 , 2.8 , and 0.8 respectively . CONCLUSIONS : This office-based IFOBT was found to have significantly higher specificity , PPV , and positive LR as compared with M2-PK . IFOBT proved to be a convenient , noncumbersome , quick , and cheap tool in patients with above-average risk for detection of CRN The aim of the study is to determine the diagnostic value of ( combinations of ) signs , symptoms and simple laboratory test results for colorectal cancer in patients with rectal bleeding presenting in general practice . Initial complaints and findings were compared with the final diagnoses based on clinical follow-up after at least 1 year . Patients studied were those presenting overt rectal bleeding to the general practitioner ( 83 GPs in the South of the Netherl and s ) . Outcome measures are sensitivity , specificity , predictive values , odds ratios and a prediction model derived from multiple logistic regression analysis . Age , change in bowel habit and blood mixed with or on stool show a statistically significant independent value in the discrimination between patients with a low and those with a high probability of colorectal cancer . Many other variables did not show predictive value . The prediction model has a sensitivitiy of 100 % and a specificity of 90 % . Although the number of patients with colorectal cancer is small ( n = 9 ) it was possible to identify three characteristics which can be helpful in the prediction of presence or absence of colorectal cancer in general practice . Application of the model presented might prevent 90 % of ' unnecessary ' invasive diagnostic procedures for patients with rectal bleeding who do not have colorectal cancer ( true negative ) . Testing the performance of the model in other general practice population s is recommended OBJECTIVE In this study the sensitivity and specificity of immunochemical tests for colorectal neoplasia were evaluated in retrospective and prospect i ve studies . METHODS Four types of fecal blood tests -- a chemical test ( Hemoccult II ) and three different immunochemical tests including a test which detects hemoglobin and transferrin- were performed in the retrospective study . In the prospect i ve study the test for hemoglobin and transferrin was used for all patients that underwent total colonoscopy . PATIENTS One hundred seven patients with colorectal neoplasia , 57 with gastroduodenal bleeding , and 62 with normal digestive tracts were examined retrospectively . One thous and two hundred and ninety-eight nonspecifically symptomatic patients whose endoscopic examination was negative for hemorrhagic lesions in the upper digestive tract were examined prospect ively . RESULTS In the retrospective study , sensitivities for the detection of colorectal cancers and adenomas with diameters > or = 10 mm using the tests which detect hemoglobin and transferrin were 98 % and 89 % , respectively . These were the highest sensitivity among the four tests . The specificity of this test was 97 % , which was higher than that of the Hemoccult II test . In the prospect i ve study , the sensitivities of the tests for hemoglobin and transferrin for the detection of colorectal cancers and adenomas with diameters > or = 10 mm were 79 % and 33 % , respectively . The specificity was 95 % . CONCLUSIONS The test for hemoglobin and transferrin showed the highest sensitivity and specificity for colorectal neoplasia in the retrospective study . The sensitivity and specificity of this test were not so high in the prospect i ve study , but they may be clinical ly applicable in the evaluation of patients with various nonspecific symptoms INTRODUCTION The aim of this study was to develop a system to compare and vali date cancer referral guidelines , identifying the pitfalls in their development and provide a mechanism to evaluate their efficacy . PATIENTS AND METHODS 3302 patients referred from primary care with colorectal symptoms over a 3-year period were assessed . All participants had a comprehensive history obtained via a question naire that incorporated all colorectal symptoms . The question naires were completed prior to assessment at the hospital . All patients were then assessed at the Colorectal One Stop Clinic ( CROSC ) , underwent investigation and diagnosis achieved . All data were entered into a data bank . Current prioritisation guidelines and tools that are used to assess colorectal referrals were applied to this colorectal data bank to test their efficacy for cancer detection and referral prioritisation . Sensitivity and specificity for cancer detection and referral rates were assessed . RESULTS Cancer was detected in 156 patients ( 4.7 % ) . All prioritisation models ( NHS guidelines , Weighted Numerical Score [ WNS ] , Netherl and s , Harvard , Mersey , and Somerset ) differentiated cancer from non-cancer patients . The use of a few symptoms as risk predictors ( e.g. NHS guidelines ) causes a decrease in specificity in contrast to a comprehensive risk tool , for example , the WNS at a score of 50 ( NHS 54.1 % , WNS 62.9 % ) . This results in a significantly higher referral rate ( NHS 47.6 % , WNS 39.4 % ) and identifies fewer cancers ( NHS 80.1 % , WNS 85.9 % ) . Non- evidence based modifications of the NHS guidelines ( Somerset and Mersey ) caused a further deterioration in specificity , which was reflected in an increased referral rate . Using the WNS , which is objective and a continuous scale , allows adaptation of the referral threshold , balancing sensitivity and specificity to the re sources available within a hospital . For example , the WNS of > or = 40 has a sensitivity of 96.8 % for cancer detection . CONCLUSIONS Accurate prospect i ve data collection into a data bank allows testing of referral guidelines as well as providing an adjunct to guideline construction BACKGROUND Although many patients are evaluated initially by their general practitioner , clinicians ' accuracy at diagnosing organic gastrointestinal disease has not been studied in a primary care setting . Different spectra of severity of disease in general practice and hospital population s may lead to different values for diagnostic tests in these two population s. AIM This study set out to determine the diagnostic value of history and physical and laboratory items for organic and neoplastic disease in general practice patients with nonacute abdominal complaints . METHOD The one-year prospect i ve , observational study was carried out in 1989 in 80 general practice s in Limburg , the Netherl and s. The study subjects were 933 patients ( aged 18 - 75 years ) presenting to their general practitioner with new non-acute abdominal complaints of minimum duration two weeks , and with whom the doctor had a diagnostic problem . Patients were physically examined by their general practitioner and asked to complete pre-structured question naires . Basic laboratory tests were carried out . Patients were followed up for at least one year by research ers and then a diagnosis was determined by an independent panel of three general practitioners using patient records , blinded for the results of the question naires . Sensitivity , specificity and odds ratios were calculated for clinical items . Stepwise forward logistic regression analysis was undertaken to identify independent predictors of organic gastrointestinal disease . RESULTS Of the 933 patients 14 % had organic gastrointestinal disease . No clinical item had both high sensitivity and specificity . Logistic regression analysis showed only eight independent predictors of organic disease : male sex , greater age , epigastric pain , no specific character to pain , pain affecting sleep , history of blood in stool , no pain relief after defecation and abnormal white blood cell count . When the model was programmed to predict neoplasms five items were found : male sex , greater age , no specific character to pain , weight loss and erythrocyte sedimentation rate greater than 20 mm hour-1 . CONCLUSION In a general practice population with non-acute abdominal complaints some clinical findings can be used as predictors for organic and neoplastic gastrointestinal disease Objective : To determine the effectiveness and efficiency of the Department of Health ’s new general practitioner referral guidelines for bowel cancer . Design : One year prospect i ve audit . Setting : District general hospital serving a population of 550 000 . Subjects : All patients with bowel cancer ; all patients referred on the basis of the two week st and ard and to a routine colorectal surgical outpatient clinic . Main outcome measures : Proportion of cancers referred on the basis of the two week st and ard and to other colorectal clinics ; the proportion with the higher risk criteria and their diagnostic yields ; stage of cancers diagnosed in outpatient clinics ; and time to treatment . Results : A total of 249 cancers were diagnosed in the index year . Sixty five ( 26.1 % ) were referred to two week st and ard clinics , 40 ( 16.1 % ) to routine colorectal surgical outpatient clinics , 54 ( 22 % ) to other clinics , and 88 ( 35.3 % ) were emergencies . Thirteen patients per week were referred to the two week st and ard clinics and 85 % ( 54/65 ) of cancers so referred were seen within two weeks . The diagnostic yield of cancer in the two week st and ard clinic was 9.4 % ( 65/695 ) compared with 2.2 % ( 40/1815 ) in the routine colorectal surgical outpatient clinic ( p<0.0001 ) . Eighty five per cent of patients with cancer referred to out patients matched the guidelines for the two week st and ard clinics . Only 46 % of this group were so referred . Overall , delay to treatment and Dukes ’ stage were not improved in patients diagnosed in the two week st and ard clinics . Conclusions : Most patients with bowel cancer were not referred on the basis of the two week st and ard although most fulfilled the referral criteria , which had higher diagnostic yields . The two week st and ard clinics did not shorten the overall time to treatment or improve the stage of disease because the time lags before referral and after the outpatient appointment are the major causes of delay in the bowel cancer patient ’s journey BACKGROUND The majority of colorectal cancers are still diagnosed in patients who present with symptoms especially in countries where colorectal screening programs are not practised . The aim of our study was to determine the predictive factors for colorectal cancer in patients referred for colonoscopy . METHODS A prospect i ve study of 485 consecutive patients who underwent colonoscopy during a 22-month period was performed . All patients answered a detailed question naire . Indications for colonoscopy and the findings were recorded . RESULTS The mean age of the study population was 55.7 + /- 14.7 years . There were 221 ( 45.6 % ) males and 264 ( 54.4 % ) females . Sixty-five ( 13.4 % ) were Malays , 298 ( 61.4 % ) were Chinese and 112 ( 23.1 % ) were Indians . Multiple backward stepwise regression analysis revealed that independent predictors for colorectal cancer ( odds ratio [ 95 % CI ] ) were the presence of rectal bleeding ( 4.3 [ 4.0 - 8.0 ] ) and iron deficiency anemia ( 4.0 [ 3.6 - 10.2 ] ) . In those aged 50 and over , male gender ( 4.5 [ 2.2 - 9.3 ] ) and abdominal pain ( 3.1 [ 1.4 - 6.7 ] ) were also significant positive predictors of cancer . CONCLUSIONS With the ever-increasing dem and for gastrointestinal endoscopy , the appropriate utilization of colonoscopy is essential to afford prompt patient evaluation . Our study supports the need to prioritize the use of colonoscopy in patients with rectal bleeding and iron deficiency anemia . In the older patient where the background prevalence of colorectal cancer is higher , referral for colonoscopy is also justified Purpose Full diagnostic colonoscopy often is performed to exclude significant pathology in patients presenting with rectal bleeding . In patients with classic “ outlet ” bleeding , defined as bright red blood after or during defecation , with no family history of colorectal neoplasia or change in bowel habits , we hypothesize that the diagnostic yield of complete colonoscopy will be low . The purpose of this study was to determine whether complete colonoscopy is necessary in the evaluation of patients with “ outlet ” rectal bleeding . Methods Information for all patients undergoing colonoscopy by a single endoscopist was prospect ively recorded . Before each colonoscopy , a complete history , including indication for the examination , was obtained . Using st and ard definitions , patients with outlet bleeding , suspicious bleeding , hemorrhage , and occult bleeding were accessed and the findings of their colonoscopies were analyzed . Institutional permission was obtained . Results A total of 9,098 patients had colonoscopy recorded in the data base , and 703 had the indication of outlet bleeding , 251 suspicious bleeding , 204 occult bleeding , and 67 hemorrhage . Of the patients with outlet bleeding , only 47 ( 6.7 percent ) had significant lesions on colonoscopy ( adenomas > 1 cm , villous adenomas , cancer in situ , or invasive cancer ) . By contrast a greater number of significant lesions were present in patients with all other types of bleeding ( 17.2 percent ; P < 0.001 ) . The incidence of invasive cancer was significantly lower in the outlet bleeding group compared with other types of bleeding ( 1 vs. 3.6 percent ; P < 0.01 ) . Patients with outlet bleeding were much less likely than patients with other bleeding to have isolated right-sided colonic pathology . Younger patients with outlet bleeding have a particularly low yield on colonoscopy . In 182 patients younger than aged 50 years with outlet bleeding , only 3 ( 1.6 percent ) had adenomas > 1 cm and no invasive cancers were detected . Conclusions In patients with classic outlet bleeding , the yield of a complete diagnostic colonoscopy is low . If the history is classic for outlet bleeding and no other indication for colonoscopy exists , flexible sigmoidoscopy is enough to exclude significant pathology BACKGROUND Rectal bleeding is a common symptom . The ability to distinguish those patients having serious underlying pathology from those with self-limiting conditions is a continuing dilemma in general practice . AIM To determine the factors affecting the predictive and diagnostic value of rectal bleeding for bowel cancer in primary care . DESIGN OF STUDY One-year prospect i ve observational study . SETTING Three large general practice s. METHOD Three hundred and nineteen consecutive patients over the age of 34 years consulting their GPs with rectal bleeding were included in the study . Investigation was by flexible sigmoidoscopy or a question naire and review of all patients took place after 18 months . The main outcome measures were consultation rates ; the prevalence of cancer , colitis and significant polyps in patients presenting with rectal bleeding ; its diagnostic value when occurring with or without a change in bowel habit , perianal symptoms and abdominal pain . RESULTS The consultation rate for rectal bleeding in patients over the age of 34 years was 15 per 1000 per year ; 3.4 % had colorectal cancer . The prevalence of cancer increased to 9.2 % when the rectal bleeding was associated with a change in bowel habit , and to 11.1 % when it was without perianal symptoms . Thirty-six per cent of cancer patients had a palpable rectal mass . CONCLUSION Over 96 % of the patients who present to their GPs with rectal bleeding do not have cancer . Greater awareness of the diagnostic value of the different symptom combinations of rectal bleeding could help GPs adopt different management strategies for patients at higher and very low risk of cancer RATIONALE AND OBJECTIVES Quality Assessment of Diagnostic Accuracy Studies ( QUADAS ) is a new tool to measure the method ological quality of diagnostic accuracy studies in systematic review s. We used data from a systematic review of magnetic resonance spectroscopy ( MRS ) in the characterization of suspected brain tumors to provide a preliminary evaluation of the inter-rater reliability of QUADAS . MATERIAL S AND METHODS A structured literature search identified 19 diagnostic accuracy studies . These publications were distributed r and omly to primary and secondary review ers for dual independent assessment . Review ers recorded method ological quality by using QUADAS on a custom- design ed spreadsheet . We calculated correlation , percentage of agreement , and kappa statistic to assess inter-rater reliability . RESULTS Most studies in our review were judged to have used an accurate reference st and ard . Conversely , the MRS literature frequently failed to specify the length of time between index and reference tests or that the clinicians were unaware of the index test findings when reporting the reference st and ard . There was good correlation ( rho = 0.78 ) between review ers in assessment of the overall number of quality criteria met . However , mean agreement for individual QUADAS questions was only fair ( kappa = 0.22 ) and ranged from no agreement beyond chance ( kappa < 0 ) to moderate agreement ( kappa = 0.58 ) . CONCLUSION Inter-rater reliability in our study was relatively low . Nevertheless , we believe that QUADAS potentially is a useful tool for highlighting the strengths and weaknesses of existing diagnostic accuracy studies . Low reliability suggests that different review ers will reach different conclusions if QUADAS is used to exclude " low- quality " articles from meta-analyses . We discuss methods for improving the validity and reliability of QUADAS |
10,460 | 20,070,141 | Topical calcineurin inhibitors provide targeted anti-inflammatory activity without the local or systemic side-effects seen with topical corticosteroids . | BACKGROUND Atopic dermatitis ( AD ) is a chronic , pruritic , inflammatory skin disease with a wide range of severity , and is usually the first manifestation of atopic disease .
It is one of the most common skin disorders in developed countries , affecting approximately 20 % of children and 1 - 3 % of adults .
Symptoms such as eczematous papules , plaques , and itch , and their associated consequences , such as sleep disturbance , can significantly impact the quality of life of the patient and family .
SCOPE This is a broad-based review focusing on clinical practice for primary care physicians treating patients with AD .
FINDINGS Emollients have long been used to maintain the skin barrier function in patients with AD .
Topical corticosteroids have been the pillar of medicated therapy for AD since their introduction nearly 50 years ago .
The introduction of topical calcineurin inhibitors more than 8 years ago represented the first new class of medication approved for the treatment of AD since topical corticosteroids .
CONCLUSION Multiple topical therapies have been successfully used to treat patients with AD . | Abstract Objective To explore the efficacy and safety of fluticasone propionate , cream and ointment , applied twice weekly in addition to maintenance treatment with emollients , in reducing the risk of relapse of chronic recurrent atopic dermatitis . Design R and omised , double blind , parallel group study of 20 weeks ' duration . Setting Dermatology outpatient clinics ( 6 countries , 39 centres ) . Participants Adult ( aged 12 - 65 ) patients with moderate to severe atopic dermatitis who were experiencing a flare . Methods Participants applied fluticasone propionate ( 0.05 % cream or 0.005 % ointment ; once or twice daily ) regularly for four weeks to stabilise their condition . The patients whose disease was brought under control then continued into a 16 week maintenance phase , applying emollient on a daily basis with a bath oil as needed and either the same formulation of fluticasone propionate or its placebo base ( emollient alone ) twice weekly to the areas that were usually affected . Main outcome measure Time to relapse of atopic dermatitis during maintenance phase . Results 376 patients entered the stabilisation phase , and 295 continued into the maintenance phase . After 16 weeks in the maintenance phase , the disease remained under control in 133 patients ( 87 using fluticasone propionate twice weekly , 46 using emollient alone ) , 135 ( 40 fluticasone propionate , 95 emollient ) had experienced a relapse , and 27 had discontinued . Median time to relapse was six weeks for emollient alone compared with more than 16 weeks for additional fluticasone propionate . Patients who applied fluticasone propionate cream twice weekly were 5.8 times less likely ( 95 % confidence interval 3.1 to 10.8 , P < 0.001 ) and patients using fluticasone propionate ointment 1.9 times less likely ( 1.2 to 3.2 , P=0.010 ) to have a relapse than patients applying emollient alone . The groups showed no differences in adverse events . Conclusion After atopic dermatitis had been stabilised the addition of fluticasone propionate twice weekly to maintenance treatment with emollients significantly reduced the risk of relapse BACKGROUND Intermittent dosing of a topical calcineurin inhibitor for preventing atopic dermatitis ( AD ) disease relapse in patients with stabilized AD has not been evaluated . OBJECTIVE We sought to evaluate the long-term efficacy and safety of 3-times-weekly use of tacrolimus ointment in preventing AD disease relapse . METHODS Adult and pediatric patients with moderate to severe AD who were clear of disease after up to 16 weeks of treatment with tacrolimus ointment were r and omized in a double-blind fashion to 3-times-weekly treatment with either tacrolimus ointment ( 0.03 % or 0.1 % ) or vehicle for 40 weeks . The primary end point was the number of flare-free treatment days . RESULTS A total of 125 patients were r and omized to tacrolimus and 72 patients to vehicle . The mean number of flare-free treatment days was 177 for tacrolimus and 134 for vehicle ( P = .003 ) . Median time to first relapse was 169 days for tacrolimus and 43 for vehicle ( P = .037 ) . LIMITATIONS Generalizability to all patients seen in clinic may be limited because only patients who responded to tacrolimus ointment in the stabilization phase were r and omized into the maintenance phase of the trial . CONCLUSIONS Maintenance therapy with tacrolimus ointment was associated with significantly more flare-free days compared with vehicle , and a significantly longer time until first disease relapse Tacrolimus ointment is a nonsteroidal topical immunomodulator that was formulated specifically for the treatment of atopic dermatitis . A total of 255 children , 2 to 15 years of age , with moderate to severe atopic dermatitis applied 0.1 % tacrolimus ointment twice daily for up to 12 months to assess long-term safety and efficacy . Patients on average were treated with tacrolimus ointment for 279 days or 87 % of study days . Substantial improvements in the signs and symptoms of atopic dermatitis , percent body surface area affected , and the patient 's or parent 's assessment of pruritus were observed during the first week of treatment and were maintained throughout the study . Transient skin burning and itching were the most common drug application site adverse events . Occurrence of these symptoms decreased after the first few days of treatment . There was no increased incidence of infections or other significant adverse events . Effectiveness of tacrolimus was maintained with prolonged daily use . Tacrolimus ointment ( 0.1 % ) is safe and effective for long-term treatment of atopic dermatitis in children BACKGROUND Little is known about the prevalence of atopic eczema outside Northern Europe . OBJECTIVES We sought to describe the magnitude and variation in the prevalence of atopic eczema symptoms throughout the world . METHODS A cross-sectional question naire survey was conducted on r and om sample s of schoolchildren aged 6 to 7 years and 13 to 14 years from centers in 56 countries throughout the world . Those children with a positive response to being question ed about the presence of an itchy relapsing skin rash in the last 12 months that had affected their skin creases were considered to have atopic eczema . Children whose atopic eczema symptoms result ed in sleep disturbance for 1 or more nights per week were considered to have severe atopic eczema . RESULTS Complete data was available for 256,410 children aged 6 to 7 years in 90 centers and 458,623 children aged 13 to 14 years in 153 centers . The prevalence range for symptoms of atopic eczema was from less than 2 % in Iran to over 16 % in Japan and Sweden in the 6 to 7 year age range and less than 1 % in Albania to over 17 % in Nigeria for the 13 to 14 year age range . Higher prevalences of atopic eczema symptoms were reported in Australasia and Northern Europe , and lower prevalences were reported in Eastern and Central Europe and Asia . Similar patterns were seen for symptoms of severe atopic eczema . CONCLUSIONS Atopic eczema is a common health problem for children and adolescents throughout the world . Symptoms of atopic eczema exhibit wide variations in prevalence both within and between countries inhabited by similar ethnic groups , suggesting that environmental factors may be critical in determining disease expression . Studies that include objective skin examinations are required to confirm these findings BACKGROUND For long-term management of atopic eczema , the use of skin care creams is recommended , but effectiveness of this treatment is not well established . OBJECTIVE The objective of this study was to yield data on the skin care properties of a cream with a unique lamellar matrix containing N-palmitoylethanolamine ( PEA ) and to assess quality -of-life variables in patients with mild to moderate atopic eczema . SETTING In this multinational , multicentre , observational , non-controlled , prospect i ve cohort study , patients between 2 and 70 years of age were enrolled . All patients were supplied with the study product sufficient for treatment over the entire study period . Outcome was followed in periods between 3 and 7 days and 4 and 6 weeks after study start . Data were gathered from doctor reports and patient self- assessment s via patient question naires . RESULTS Data from 2456 patients entered the data base . The mean examination intervals were 6 days for the 3- to 7-day period and 38 days for the 4- to 6-week period . At study end , intensities of erythema , pruritus , excoriation , scaling , lichenification and dryness were significantly reduced with a combined score reduction of 58.6 % in the entire population ( 57.7 % in adults > 12 years and 60.5 % in children < /= 12 years ) according to doctors ' reports . Patients reported a reduction of pruritus on visual analogue scales from 4.9 + /- 2.6 to 2.7 + /- 2.4 6 days after treatment start and a further reduction to 2.0 + /- 2.3 at study end ( P < 0.001 each ) . Likewise , sleep quality improved significantly during the study period . Earlier-used topical corticosteroids were omitted by 56 % of all patients ( 53.4 % in adults and 62.5 % in children ) at study end , and the average weekly application rate decreased by 62 % from 7.9 + /- 6.0 to 3.0 + /- 5.1 ( P < 0.001 ) . The tolerance was assessed as very good or good in 92 % of cases by both patients and doctors . CONCLUSION This study showed substantial relief of objective and subjective symptoms of atopic eczema after regular skin care with the study cream . The patient-related effectiveness ( decline of pruritus and loss of sleep ) indicated a gain in quality of life in these patients . The reduced use of topical corticosteroids is important in view of safety and pharmacoeconomic implication s in the treatment of atopic eczema Patients with atopic skin show a defective barrier function both in rough and in clinical ly normal skin , with an increasing risk of developing contact dermatitis . Moisturizing creams are often used in the treatment of dry skin . The purpose of this study was to investigate the influence of treatment with a urea‐containing moisturizer on the barrier properties of atopic skin . Fifteen patients with atopic dermatitis treated one of their forearms twice daily for 20 days with a moisturizing cream . Skin capacitance and transepidermal water loss ( TEWL ) were measured at the start of the study and after 10 and 20 days . On day 21 the skin was exposed to sodium lauryl sulphate ( SLS ) and on day 22 the irritant reaction was measured non‐invasively . Skin capacitance was significantly increased by the treatment , indicating increased skin hydration . The water barrier function , as reflected by TEWL values , tended to improve ( P = 0.07 ) , and the skin susceptibility to SLS was significantly reduced , as measured by TEWL and superficial skin blood flow ( P < 0.05 ) . Thus , it seems that certain moisturizers could improve skin barrier function in atopics and reduce skin susceptibility to irritants . The mechanism and the clinical relevance need further investigation Moisturizers are used daily by many people to alleviate symptoms of clinical ly and subjectively dry skin . Recent studies suggest that certain ingredients in creams may accelerate the recovery of a disrupted barrier and decrease the skin susceptibility to irritant stimuli . In the present single‐blind study , a moisturizing cream was tested for its influence both on barrier recovery in surfuctant‐damaged skin and on the susceptibility of normal skin to exposure to the irritant sodium lauryl sulphate ( SLS ) . Parameters measured were transepidermal water loss ( TEWL ) and skin corneometer values , indicating degree of hydration . Treatment of surfactant‐damaged skin with the test cream for 14 days promoted barrier recovery , as observed as a decrease in TEWL . Skin corneometer values also normalized more rapidly during the treatment . In normal skin , use or the test cream significantly reduced TFWL after 14 days of treatment , and irritant reactions to SLS were , significantly decreased . Skin corneometer values increased after only 1 application and remained elevated after 14 days . In conclusion , the accelerated rate of recovery of surfactant‐damaged skin and the lower degree of SLS‐induced irritation in normal skin treated with the test cream may be of clinical relevance in attempts to reduce contact dermatitis due to irritant stimuli BACKGROUND MAS063DP cream has received marketing authorization in the US and the European Union for symptom relief of atopic dermatitis ( eczema ) and contact dermatitis . DESIGN A multicenter , r and omized , vehicle-controlled , phase IV study was completed in the US . METHODS 218 patients aged 18 to 84 years joined this 50-day study . Patients self-administered MAS063DP cream ( N=145 ) or vehicle cream ( N=73 ) 3 times per day to affected areas and those areas prone to be affected . The primary endpoint for efficacy was the change in EASI at Day 22 of treatment , comparing the 2 treatment groups . Secondary outcomes included EASI scores at other time points , IGA , pruritus ( 100 mm VAS ) , % BSA , and the need for rescue medication . RESULTS MAS063DP was statistically ( p<.0001 ) more effective than vehicle in all outcomes at all time points . The incidence of rash was 2.1 % in the MAS063DP group versus 5.5 % in the vehicle group . Only 2 patients discontinued MAS063DP due to an adverse event . CONCLUSION MAS063DP cream was confirmed to be a safe and effective treatment for mild to moderate atopic dermatitis in adults The effectiveness of an emollient as an adjunct to topical corticosteroid therapy for the treatment of mild to moderate atopic dermatitis was studied for 3 weeks in 25 children 3 to 15 years of age in comparison with corticosteroid therapy alone . The adjunctive regimen of a once-daily application each of hydrocortisone 2.5 % cream and of a water-in-oil cream was equivalent in efficacy to the comparative regimen of twice-daily applications of hydrocortisone 2.5 % cream . Both treatment regimens elicited significant improvement in skin condition by day 7 ( p < 0.005 ) and further significant improvement by day 14 ( p < 0.005 ) . No significant differences between the two treatment regimens were observed in the rates of improvement ( p > 0.545 ) or in the reductions in mean lesion size ( p > 0.98 ) . No differences were observed in parental evaluations , except for ease of application where a slight preference was expressed for the hydrocortisone 2.5 % cream preparation ( p < 0.038 ) . We conclude that emollient adjunctive therapy offers a steroid-sparing alternative to topical corticosteroids alone in the treatment of mild to moderate atopic dermatitis OBJECTIVE This study was design ed to evaluate the long-term safety and efficacy of 0.1 % tacrolimus ointment in adult and pediatric patients with atopic dermatitis ( AD ) . METHODS A total of 408 adult and 391 pediatric patients with AD who had participated in a previous clinical trial of tacrolimus ointment were enrolled in this long-term , open-label , noncomparative trial . Tacrolimus ointment 0.1 % was applied twice daily either intermittently or continuously to the affected areas . Efficacy and safety assessment s included percent body surface area affected , Eczema Area and Severity Index score , individual signs of AD , and the incidence of adverse events . RESULTS A total of 799 patients were evaluated , of whom 300 ( 37.5 % ) were followed for more than 3 years ( maximum 49 months ) . Improvements in efficacy parameters were observed within 1 week of treatment and continued for the duration of the study . Common adverse events included skin burning , pruritus , skin infection , skin erythema , flu-like symptoms , and headache . The incidence of adverse events , including cutaneous infections , did not increase with time on study . CONCLUSION Tacrolimus ointment therapy is a rapidly effective and safe treatment for the management of AD in pediatric and adult patients for up to 4 years Moisturizing creams have beneficial effects in the treatment of dry , scaly skin , but they may induce adverse skin reactions . In a r and omized double-blind study , 197 patients with atopic dermatitis were treated with one of the following : a new moisturizing cream with 20 % glycerin , its cream base without glycerin as placebo , or a cream with 4 % urea and 4 % sodium chloride . The patients were asked to apply the cream at least once daily for 30 days . Adverse skin reactions and changes in skin dryness were assessed by the patient and a dermatologist . Adverse skin reactions such as smarting ( a sharp local superficial sensation ) were felt significantly less among patients using the 20 % glycerin cream compared with the urea-saline cream , because 10 % of the patients judged the smarting as severe or moderate when using glycerin cream , whereas 24 % did so using urea-saline cream ( p < 0.0006 ) . No differences were found regarding skin reactions such as stinging , itching and dryness/irritation . The study showed equal effects on skin dryness as judged by the patients and the dermatologist . In conclusion , a glycerin containing cream appears to be a suitable alternative to urea/sodium chloride in the treatment of atopic dry skin BACKGROUND The efficacy of topical medications is limited by non-adherence . Interventions to improve adherence to topical treatments are not well characterized . OBJECTIVE To assess the impact of office visits on patients ' adherence to topical treatment . METHODS Twenty-nine subjects enrolled in a clinical trial for psoriasis and were followed for up to 8 weeks . Subjects were told to apply 6 % salicylic acid gel twice daily . Electronic monitors were used to assess adherence . Results were compared to adherence in clinical trials of h and dermatitis and atopic dermatitis . RESULTS Adherence rates were significantly higher around the time of office visits ( P < .05 ) . LIMITATIONS This is a small study in a limited patient population . The study was observational and not a r and omized trial of the effect of increased office visits . CONCLUSION Frequent follow-up visits in clinical trials increase patients ' adherence to medications . The use of a follow-up visit shortly after initiating treatment may be an effective way to boost patients ' use of their medication and achieve better treatment outcomes BACKGROUND / AIMS Moisturising creams are useful treatment adjuncts in inflammatory dermatoses and have beneficial effects in the treatment of dry , scaly skin . The effects on dryness and skin permeability of a new moisturising cream with 20 % glycerine was compared with its placebo and with a medicinally authorised cream with 4 % urea ( combined with 4 % sodium chloride ) in the treatment of dry skin . METHODS Patients ( n=109 ) with atopic dermatitis were treated for 30 days with a moisturiser in a r and omised , parallel and double-blind fashion . Transepidermal water loss ( TEWL ) and skin capacitance were assessed instrumentally , and changes in the dryness of the skin were assessed by the dermatologist . RESULTS No difference in TEWL was found between glycerine treatment and its placebo , whereas a lower value was found in the urea-treated area compared to the glycerine-treated area . No difference in skin capacitance was found . The clinical assessment of dryness showed urea to be superior to glycerine in treating the condition . CONCLUSIONS Moisturising creams are different , not only with respect to composition but also with respect to their influence on skin as a barrier to water in patients with atopic dermatitis The cutaneous permeability barrier is localized to the stratum corneum interstices and is mediated by lamellar bilayers enriched in cholesterol , free fatty acids and ceramides . Topically applied lipids may interfere with the skin barrier function and formulations containing " skin-identical lipids " have been suggested to facilitate normalization of damaged skin . The aim of the present study was to compare the ability of " skin-identical lipids " in a petrolatum-rich cream base and pure petrolatum to facilitate barrier repair in detergent- and tape-stripped-perturbed human skin . Barrier recovery and inflammation were instrumentally monitored for 14 days as transepidermal water loss and skin blood flow , using an Evaporimeter and a laser Doppler flowmeter , respectively . Treatment with the 2 different products gave no indication that " skin-identical lipids " in a cream base are more efficient than pure petrolatum at promoting normalization in either of the 2 experimentally perturbed areas . This finding may support the hypothesis that different types of skin abnormality should be treated according to the underlying damage Data were review ed on the beneficial responses and adverse reactions among 2,849 patients in 14 paired-comparison studies with eight unoccluded topical corticosteroids in six steroid-responsive dermatoses . Adverse reactions were found to be mild , transient , and , for the most part , rare . Of 5,698 treatment exposures , 249 ( 4.39 % ) adverse reactions were reported , including irritation ( 1.3 % ) , itching ( 0.95 % ) , burning ( 0.81 % ) , dryness ( 0.46 % ) , scaling ( 0.30 % ) , and vesicle formation ( 0.16 % ) . Other reactions occurred in less than one in 1,000 treatment exposures . No severe reactions were observed . Five subjects ( 0.17 % ) terminated treatment early because of adverse reactions . The incidence of adverse reactions to vehicle alone was 6.7 % . The benefit-risk ratio for mild reactions was 17:1 . Therefore , long lists of adverse reactions are inappropriate in written consent forms for prospect i ve volunteers for clinical trials . Al alternative warning statement is proposed The aim of the study was to investigate whether adding emollients to the st and ard topical corticosteroid therapy influences the outcome of children with atopic dermatitis . Fifty-two children aged between 2 and 12 yr were divided r and omly in two subgroups consisting of 26 children each . Both groups applied 0.1 % methylprednisolone aceponate cream on lesional atopic skin once daily for 2 wk and were observed for another 4 wk after treatment discontinuation . Group B used additionally emollients for the whole study period . Patients were evaluated at days 0 ( baseline ) , 7 , 14 ( end of therapy ) , 28 and 42 ( follow-up ) . Both groups demonstrated significant improvement of disease severity according to EASI ( Eczema Area and Severity Index ) scale ( group A : 6.8 + /- 3.59 before and 0.87 + /- 1.25 after therapy , p < 0.001 ; group B : 9.6 + /- 8.39 before and 1.11 + /- 2.37 after therapy , p < 0.001 ) . Xerosis improved significantly better in group B compared to group A , both clinical ly ( group A : 1.38 + /- 0.57 scores before and 1.5 + /- 0.58 scores after therapy , p = 0.11 ; group B : 1.62 + /- 0.64 scores before and 0.12 + /- 0.33 scores after therapy , p < 0.001 ) , and by corneometry assessment ( group A : 41.7 + /- 9.1 units before and 51.3 + /- 11.3 units after therapy , p < 0.001 ; group B : 38.9 + /- 12.9 units before and 58.2 + /- 13.5 units after therapy , p < 0.001 ) . A trend towards faster resolving of pruritus in group B ( group A : 5.44 + /- 2.6 scores before and 3.22 + /- 2.31 scores after therapy , p = 0.001 ; group B : 5.87 + /- 2.79 scores before and 2.24 + /- 1.59 scores after therapy , p < 0.001 ) was also observed . In group B , the improvement was maintained for couple of weeks after treatment discontinuation , while in group A recurrence of the disease was noted ( EASI at day 42 in group A vs. group B : 5.29 + /- 5.6 vs. 1.25 + /- 1.4 , p = 0.01 ) . Similar results were also observed for xerosis ( p < 0.001 ) and pruritus ( p = 0.002 ) . Concomitant usage of emollients significantly improves xerosis and pruritus during corticosteroid treatment of atopic dermatitis and enables to maintain clinical improvement after therapy discontinuation A multicenter , r and omized , double-blind , vehicle-controlled clinical study was conducted to evaluate the efficacy and safety of MAS063DP in 60 paediatric patients affected by atopic dermatitis ( AD ) , aged between 2 and 17 years . Using the Investigator 's Global Assessment ( IGA ) score for AD , patients with a score of 2 ( mild ) or 3 ( moderate ) were enrolled in the study . Patients were r and omly selected to receive MAS063DP ( 20 patients ) , MAS060 ( 20 patients , a similar formulation with lower key ingredients ' concentration and no preservatives ) or vehicle ( 20 patients ) .The study consisted in a treatment period of 43 days , with clinical evaluations at baseline ( day 1 ) , days 8 , 15 , 22 , 29 and 43 , at which time the treatment was stopped . MAS063DP showed nearly 80 % improvement in IGA score at day 22 , compared with 16.6 % and 26.3 % with the MAS060 and vehicle respectively . A statistically significant difference was found by comparing MAS063DP with MAS060 ( p < 0.0001 ) ; a similar result was evidence d comparing MAS063DP and vehicle ( p = 0.001 ) . By contrast , no significant difference was found between MAS060 and vehicle . A statistically significant difference was sustained until the end of the study . MAS063DP may therefore be considered as one of the available regimens effective in the treatment of mild-to-moderate AD in children and adolescents |
10,461 | 28,122,035 | There was no significant sex difference in CV mortality | In the United States ( US ) , cardiovascular ( CV ) disease accounts for nearly 20 % of national health care expenses .
Since costs are expected to increase with the aging population , informative research is necessary to address the growing burden of CV disease and sex-related differences in diagnosis , treatment , and outcomes .
Hypertension is a major risk factor for CV disease and mortality .
To evaluate whether there are sex-related differences in the effect of systolic blood pressure ( SBP ) on the risk of CV disease and mortality , we performed a systematic review and meta- analysis . | We compared systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , pulse pressure ( PP ) , and mean arterial pressure ( MAP ) in predicting the risk of cardiovascular disease ( CVD ) , stratifying results at age 60 years , when DBP decreases while SBP continues to increase . We prospect ively followed 11 150 male physicians with no history of CVD or antihypertensive treatment through the 2-year question naire , after which follow-up began . Reported blood pressure was averaged from both the baseline and 2-year question naires . During a median follow-up of 10.8 years , there were 905 cases of incident CVD . For men aged < 60 years ( n=8743 ) , those in the highest versus lowest quartiles of average SBP ( ≥130 versus < 116 mm Hg ) , DBP ( ≥81 versus < 73 mm Hg ) , and MAP ( ≥97 versus < 88 mm Hg ) had relative risks ( RRs ) of CVD of 2.16 , 2.23 , and 2.52 , respectively . Models with average MAP and PP did not add information compared with models with MAP alone ( P > 0.05 ) . For men aged ≥60 years ( n=2407 ) , those in the highest versus lowest quartiles of average SBP ( ≥135 versus < 120 mm Hg ) , PP ( ≥55 versus < 44 mm Hg ) , and MAP ( ≥99 versus < 91 mm Hg ) had RRs of CVD of 1.69 , 1.83 , and 1.43 , respectively . The addition of other blood pressure measures did not add information compared with average SBP or PP alone ( all P > 0.05 ) . These data suggest that average SBP , DBP , and MAP strongly predict CVD among younger men , whereas either average SBP or PP predicts CVD among older men . More research should distinguish whether MAP , highly correlated with SBP and DBP , better predicts CVD Background An effect of diet in determining blood pressure is suggested by epidemiological studies , but the role of specific nutrients is still unsettled . Methods and Results The relation of various nutritional factors with hypertension was examined prospect ively among 30,681 predominantly white US male health professionals , 40–75 years old , without diagnosed hypertension . During 4 years of follow-up , 1,248 men reported a diagnosis of hypertension . Age , relative weight , and alcohol consumption were the strongest predictors for the development of hypertension . Dietary fiber , potassium , and magnesium were each significantly associated with lower risk of hypertension when considered individually and after adjustment for age , relative weight , alcohol consumption , and energy intake . When these nutrients were considered simultaneously , only dietary fiber had an independent inverse association with hypertension . For men with a fiber intake of < 12 g/day , the relative risk of hypertension was 1.57 ( 95 % confidence interval , 1.20–2.05 ) compared with an intake of > 24 g/day . Calcium was significantly associated with lower risk of hypertension only in lean men . Dietary fiber , potassium , and magnesium were also inversely related to baseline systolic and diastolic blood pressure and to change in blood pressure during the follow-up among men who did not develop hypertension . Calcium was inversely associated with baseline blood pressure but not with change in blood pressure . No significant associations with hypertension were observed for sodium , total fat , or saturated , transunsaturated , and polyunsaturated fatty acids . Fruit fiber but not vegetable or cereal fiber was inversely associated with incidence of hypertension . Conclusions These results support hypotheses that an increased intake of fiber and magnesium may contribute to the prevention of hypertension CONTEXT For women , impact of cardiovascular risk factors measured in young adulthood , particularly favorable ( low-risk ) profile , on mortality has been difficult to assess due to low short-term death rates . OBJECTIVE To assess the relationship of baseline coronary risk factor status to mortality from coronary heart disease ( CHD ) , cardiovascular diseases ( CVDs ) , and all causes in young women . DESIGN Prospect i ve cohort study . SETTING AND PARTICIPANTS A total of 7302 women aged 18 to 39 years without prior CHD or major electrocardiographic abnormalities screened between 1967 and 1973 for the Chicago Heart Association Detection Project in Industry . Risk groups were defined using national guidelines for values of systolic and diastolic blood pressure , serum cholesterol level , body mass index , presence of diabetes , and smoking status . Participants were divided into 4 groups : low risk , 0 risk factors high but 1 or more unfavorable , 1 only risk factor high , and 2 or more risk factors high . MAIN OUTCOME MEASURES All-cause mortality , CHD mortality , and CVD mortality ; hazard ratio of outcome measures comparing low-risk group with other groups . RESULTS Only 20 % met low-risk criteria ; 59 % had high levels of 1 or more risk factors . During an average follow-up of 31 years , there were 47 CHD deaths , 94 CVD deaths , and 469 deaths from all causes . The age-adjusted CVD death rate per 10,000 person-years was lowest for low-risk women and increased with the number of risk factors , ie , 1.5 , 1.7 , 5.0 , and 9.1 for low-risk ; 0 , 1 , and 2 or more risk factors high , respectively . Multivariate-adjusted CVD mortality hazard ratio for low-risk women was 0.19 ( 95 % confidence interval , 0.08 - 0.45 ) compared with women with 2 or more risk factors high . Similar patterns were observed for CHD and all-cause mortality and for both blacks and whites . CONCLUSION For women with favorable levels for all 5 major risk factors at younger ages , CHD and CVD are rare ; long-term and all-cause mortality are much lower compared with others Background —Low systolic blood pressure ( SBP ) is a risk factor for adverse outcomes in patients with heart failure ( HF ) . Valsartan improved morbidity rates in the Valsartan Heart Failure Trial ( Val-HeFT ) despite a reduction in SBP . The aim of the present study was to investigate the relationship between the SBP-lowering effects of valsartan and its cardiovascular protective effects in this population . Methods and Results —Baseline measurements and changes in SBP at 4 months were related to mortality and morbidity rates . The effects of valsartan on these end points were compared in quartiles of baseline SBP with multivariable Cox proportional hazards regression models that included a test for interaction between the effects of valsartan treatment and baseline SBP and examined the effects of changes in SBP on the valsartan effect . The mean±SD baseline SBP in all patients ( n=5010 ) was 124±18 mm Hg . Patients in the lowest quartile of SBP ( SBP ≤110 mm Hg ; mean SBP 102 mm Hg ; n=940 ) had more severe HF and a significantly increased adjusted risk of death ( hazard ratio [ HR ] , 1.21 ; 95 % confidence interval [ CI ] , 1.03 to 1.43 ; P=0.02 ) , first morbid event ( HR , 1.25 ; 95 % CI , 1.10 to 1.40 ; P=0.001 ) , and hospitalization for HF ( HR , 1.45 ; 95 % CI , 1.22 to 1.73 ; P<0.001 ) than did patients in the upper 3 quartiles of baseline SBP ( mean SBP 130 mm Hg ; n=3260 ) . Valsartan reduced SBP in patients in the upper 3 quartiles but not in patients in the lowest quartile who had a baseline SBP < 110 mm Hg . Valsartan was associated with decreases in the risks of first morbid event ( HR , 0.74 ; 95 % CI , 0.60 to 0.91 ; P=0.005 ) and hospitalization for HF ( HR , 0.60 ; 95 % CI , 0.45 to 0.79 ; P<0.001 ) in the lowest quartile that were not significantly different than the valsartan effects in the other 3 quartiles combined ( first morbid event HR , 0.90 ; 95 % CI , 0.79 to 1.02 ; P=0.10 ; and HF hospitalization HR , 0.77 ; 95 % CI , 0.64 to 0.93 ; P=0.006 ; nonsignificant interactions ) . The decrease in SBP from baseline to 4 months was an independent risk factor for subsequent events . When changes in SBP were added to the regression model , the effects of valsartan in the lowest quartile and in the other 3 quartiles combined did not change substantially . Conclusion —Baseline SBP and a decrease in SBP over time were risk factors for adverse events in HF . Valsartan reduced SBP but not in the high-risk group of patients who had a baseline SBP < 110 mm Hg . The beneficial effects of valsartan did not vary significantly with baseline SBP , and decreases in SBP did not counteract the beneficial effects on HF morbidity rates We compared the relations of 4 blood pressure ( BP ) indexes ( pulse pressure [ PP ] , systolic BP [ SBP ] , diastolic BP [ DBP ] , and mean arterial pressure [ MAP ] ) with 25-year mortality rates for coronary heart disease ( CHD ) , cardiovascular disease ( CVD ) , and all causes in younger , middle-aged , and older men and women by using data from a long-term prospect i ve epidemiological study of employed persons who were screened between 1967 and 1973 . A single supine BP measurement was obtained at baseline . Vital status was determined through 1995 . We report on 5 groups ( total , 28 360 participants ) consisting of men age 18 to 39 , 40 to 59 , and 60 to 74 years and of women age 40 to 59 and 60 to 74 years who were not receiving antihypertensive treatment , had no history of CHD , and did not have diabetes . Cox proportional hazards analyses were used to determine multivariate-adjusted hazard ratios with a 1-SD higher value for each BP index ; Wald & khgr;2 tests were used to compare the strength of relations . Relations of PP were less strong than were those of SBP for all end points in all age/gender groups . SBP or MAP showed the strongest relations to all end points in all age/gender groups ( hazard ratio , 1.17 to 1.36 ) . The relations of SBP to death were stronger than were those of DBP , except for middle-aged men and for CVD in women . DBP showed significant positive associations with death , after control for SBP , in middle-aged participants . In conclusion , these data indicate that the long-term risk of high BP should be assessed mainly on the basis of SBP or of SBP and DBP together , not on the basis of PP , in apparently healthy adults OBJECTIVES This study sought to 1 ) determine the effect of gender on early and late infa rct -related artery patency and reocclusion after thrombolytic therapy for acute myocardial infa rct ion ; 2 ) examine the effect of gender on left ventricular function in response to injury/reperfusion ; and 3 ) assess the independent contribution of gender to early ( 30-day ) mortality after acute myocardial infa rct ion . BACKGROUND Women have a higher mortality rate than men after myocardial infa rct ion . However , the effect of gender on infa rct -related coronary artery patency and left ventricular response to injury/reperfusion have not been fully defined in the thrombolytic era . METHODS Patency rates and global and regional left ventricular function were determined in patients at 90 min and 5 to 7 days after thrombolytic therapy for acute myocardial infa rct ion . The effect of gender on infa rct -related artery patency and left ventricular function was determined . Thirty-day mortality differences between women and men were compared . RESULTS Women were significantly older and had more hypertension , diabetes , hypercholesterolemia , heart failure and shock . They were less likely to have had a previous myocardial infa rct ion , history of smoking or previous bypass surgery . Ninety-minute patency rates ( Thrombolysis in Myocardial Infa rct ion [ TIMI ] flow grade 3 ) in women and men were 39 % and 38 % , respectively ( p = 0.5 ) . Reocclusion rates were 8.7 % in women versus 5.1 % in men ( p = 0.14 ) . Women had more recurrent ischemia than men ( 21.4 % vs. 17.0 % , respectively , p = 0.01 ) . Ninety-minute ejection fraction and regional ventricular function were clinical ly similar in women and men with TIMI 2 or 3 flow ( ejection fraction [ mean + /- SD ] : 63.4 + /- 6 % vs. 59.4 + /- 0.7 % , p = 0.02 ; number of chords : 21.4 + /- 0.9 vs. 21.0 + /- 1.9 , p = 0.7 ; SD/chord : -2.4 + /- 08 vs. -2.4 + /- 0.2 , p = 0.9 , respectively ) . No clinical ly significant differences in left ventricular function were noted at 5- to 7-day follow-up . Women had a greater hyperkinetic response than men in the noninfa rct zone ( SD/chord : 2.4 + /- 0.2 vs. 1.7 + /- 0.1 , p = 0.005 ) . The 30-day mortality rate was 13.1 % in women versus 4.8 % in men ( p < or = 0.0001 ) . After adjustment for other clinical and angiographic variables , gender remained an independent determinant of 30-day mortality . CONCLUSIONS Women do not differ significantly from men with regard to either early infa rct -related artery patency rates or reocclusion after thrombolytic therapy or ventricular functional response to injury/reperfusion . Gender was an independent determinant of 30-day mortality after acute myocardial infa rct ion BACKGROUND Elevated blood pressure ( BP ) is a risk factor for cardiovascular disease ( CVD ) , but it remains unclear which component-alone or in combination-is the best predictor . We sought to determine which BP parameters are important predictors of CVD death across a wide age range . METHODS We used a prospect i ve cohort study design with 53,163 men followed for cause-specific death during a median of 5.7 years in the Physicians ' Health Study enrollment cohort . Baseline age , systolic BP and diastolic BP were collected . We calculated relative risks ( RRs ) and their 95 % confidence intervals using Cox proportional hazard models adjusting for major risk factors for CVD , and then stratified by age ( 39 to 49 , 50 to 59 , 60 to 69 , and 70 to 84 years ) . RESULTS There were 459 CVD deaths during follow-up . For each 10 mm Hg increase in systolic BP , the multivariable RRs by ascending age group were 1.46 , 1.43 , 1.24 , and 1.13 . The multivariable RRs for each 10 mm Hg increase in diastolic BP were 1.25 , 1.20 , 1.28 , and 1.07 . Compared with systolic BP , pulse pressure and mean arterial pressure were not consistent predictors across age ranges , and combining systolic BP with another parameter did not improve the model compared with using systolic BP alone in any age group ( all P > .05 ) . CONCLUSIONS In this large cohort of healthy men with no history of hypertension , systolic BP was the most consistent and significant predictor of CVD death across all ages . Diastolic BP was not as strongly associated with risk . Our results support the continuing emphasis on using systolic BP in predicting cardiovascular risk BACKGROUND Pulse pressure ( PP ) has been shown to predict risk for cardiovascular events in men ; however , this association has not been well established in women . Hormone replacement therapy may improve arterial compliance , but findings from cross-sectional and prospect i ve studies report inconsistent results . We sought to examine the relationship between PP and risk for cardiovascular events , and to determine the effect of hormone therapy on PP in postmenopausal women with coronary heart disease ( CHD ) . METHODS AND RESULTS A total of 2,763 postmenopausal women ( mean age , 66 + /- 7 years [ + /- SD ] ) with CHD in the Heart and Estrogen/Progestin Replacement Study , a r and omized , placebo-controlled , secondary CHD prevention trial of estrogen plus progestin , were followed up on average for 4.1 years . BP was measured at baseline and annually . Mean baseline PP was 62 + /- 16 mm Hg . There were 361 myocardial infa rct ions ( MIs ) or CHD deaths , 265 hospitalizations for congestive heart failure ( CHF ) , and 215 strokes or transient ischemic attacks ( TIAs ) . Women in the highest quartile of PP at baseline had a 47 % increase in risk for MI or CHD death and more than a twofold increase in risk for stroke and TIA events or hospitalization for CHF ( p < 0.01 for each outcome ) . After adjustment for other cardiovascular risk factors and mean arterial pressure , PP remained significantly associated with incident stroke or TIA events ( odds ratio , 1.25 ; p = 0.02 ) and hospitalizations for CHF ( odds ratio , 1.31 ; p < 0.01 ) but not with MI or CHD death . After adjustment for diastolic BP , systolic BP was similarly associated with stroke or TIA ( odds ratio , 1.30 ; p < 0.01 ) and hospitalized CHF ( odds ratio , 1.30 ; p < 0.01 ) and was also weakly associated with risk for MI and CHD death ( odds ratio , 1.18 ; p = 0.02 ) . Mean PP was 1- to 2-mm Hg higher in women r and omized to hormone replacement therapy vs those receiving placebo ( p < 0.01 ) . CONCLUSIONS PP had predictive value for CHF and stroke or TIA , but not MI or CHD death in this cohort of postmenopausal women with CHD . Use of hormone replacement therapy produced a small , statistically significant increase in PP . Further research is necessary to determine the clinical utility of PP as a potential therapeutic target BACKGROUND Currently recognized risk factors for coronary artery disease have been identified primarily from investigations of white population s. In this investigation , we estimated mortality rates for coronary disease and for any cause and identified risk factors for death from coronary disease among whites and blacks . METHODS Data collected over a 30-year period in the Charleston Heart Study were used to estimate mortality rates and quantify associations with risk factors assessed at the base-line examination in 1960 and 1961 of 653 white men , 333 black men , 741 white women , and 454 black women . RESULTS There were no significant racial differences in the rate ratios for death from coronary disease ; however , women had significantly lower death rates than men . Over the 30-year period , the mortality rates for coronary disease per 1000 person-years were 5.2 for white men ( 95 percent confidence interval , 4.1 to 6.3 ) , 4.6 for black men ( 3.0 to 6.2 ) , 2.1 for white women ( 1.6 to 2.6 ) , and 3.2 for black women ( 2.3 to 4.0 ) . Significant , or nearly significant , predictors of mortality due to coronary disease were systolic blood pressure in all four groups ; serum cholesterol level among white men , white women , and black women ; and smoking among white men , white women , and black men . Although the difference was not statistically significant , the risk of death from coronary disease was consistently increased among diabetics in all four groups . A higher level of education was predictive of lower rates of death due to coronary disease among white men and black women . For all causes of death taken together , the rates for blacks were higher than the rates for whites . The presence of hypertension , a history of smoking , and a history of diabetes were significant or nearly significant predictors of mortality from any cause in all four groups . CONCLUSIONS Although the rates of death from coronary disease were somewhat lower among black men than white men and higher among black women than white women , the black : white mortality rate ratios were not statistically significant , and the major risk factors for mortality from coronary disease were similar in blacks and whites in the 30-year follow-up of the Charleston Heart Study OBJECTIVE To explore the relationship of one versus two postload plasma glucose measurements to 19-yr mortality in men in the Chicago Peoples Gas Company Study . RESEARCH DESIGN AND METHODS One-hour postload plasma glucose was measured twice ( 1.4 yr apart , 1965–1967 ) for 873 nondiabetic men 34–65 yr of age . Serum cholesterol , blood pressure , height , and weight were measured . Data on smoking habits were obtained . Mortality follow-up was complete through July 1986 , 19 yr after second glucose load . RESULTS In prospect i ve analyses , with each of three glucose values — first , second , and mean of first and second — coronary , cardiovascular , and all-cause age-adjusted mortality rates were higher in quintiles 3 , 4 , and 5 compared with quintile 1 , with a significant linear trend . Multivariate analyses with glycemia as a continuous variable confirmed a positive independent association between plasma glucose and mortality endpoints with first measurement and mean of two values but not with second . With dichotomization of plasma glucose ( ≥ 11.2 mM [ ≥ 200 mg/dl ] ) for 30 men hyperglycemic both times , CHD and CVD death rates were significantly higher ( odds ratios 2.3–2.7 ) compared with those for 758 men consistently nonhyperglycemic . In contrast , for those hyperglycemic once only , death rates were not significantly higher . Results of multivariate analyses were consistent with these findings . CONCLUSIONS These data indicate a significant relationship of asymptomatic hyperglycemia on repeat examinations to coronary and cardiovascular mortality independent of other factors measured in the study Background : High blood pressure is an important public health concern because it is highly prevalent and a risk factor for adverse health outcomes , including coronary heart disease , stroke , decompensated heart failure , chronic kidney disease , and decline in cognitive function . Observational studies show a progressive increase in risk associated with blood pressure above 115/75 mm Hg . Prior research has shown that reducing elevated systolic blood pressure lowers the risk of subsequent clinical complications from cardiovascular disease . However , the optimal systolic blood pressure to reduce blood pressure – related adverse outcomes is unclear , and the benefit of treating to a level of systolic blood pressure well below 140 mm Hg has not been proven in a large , definitive clinical trial . Purpose : To describe the design considerations of the Systolic Blood Pressure Intervention Trial ( SPRINT ) and the baseline characteristics of trial participants . Methods : The Systolic Blood Pressure Intervention Trial is a multicenter , r and omized , controlled trial that compares two strategies for treating systolic blood pressure : one targets the st and ard target of < 140 mm Hg , and the other targets a more intensive target of < 120 mm Hg . Enrollment focused on volunteers of age ≥50 years ( no upper limit ) with an average baseline systolic blood pressure ≥130 mm Hg and evidence of cardiovascular disease , chronic kidney disease , 10-year Framingham cardiovascular disease risk score ≥15 % , or age ≥75 years . The Systolic Blood Pressure Intervention Trial recruitment also targeted three pre-specified subgroups : participants with chronic kidney disease ( estimated glomerular filtration rate < 60 mL/min/1.73 m2 ) , participants with a history of cardiovascular disease , and participants 75 years of age or older . The primary outcome is first the occurrence of a myocardial infa rct ion ( MI ) , acute coronary syndrome , stroke , heart failure , or cardiovascular disease death . Secondary outcomes include all-cause mortality , decline in kidney function or development of end-stage renal disease , incident dementia , decline in cognitive function , and small-vessel cerebral ischemic disease . Results : Between 8 November 2010 and 15 March 2013 , Systolic Blood Pressure Intervention Trial recruited and r and omized 9361 people at 102 clinics , including 3331 women , 2648 with chronic kidney disease , 1877 with a history of cardiovascular disease , 3962 minorities , and 2636 ≥75 years of age . Limitations : Although the overall recruitment target was met , the numbers recruited in the high-risk subgroups were lower than planned . Conclusions : The Systolic Blood Pressure Intervention Trial will provide important information on the risks and benefits of intensive blood pressure treatment targets in a diverse sample of high-risk participants , including those with prior cardiovascular disease , chronic kidney disease , and those aged ≥75 years |
10,462 | 18,639,476 | Several potential biomarkers were identified .
The strongest association with AAA was obtained with serum elastin peptides ( SEP ) and plasmin-antiplasmin ( PAP ) complexes .
Matrix-degrading metalloproteinase 9 ( MMP9 ) and interferon-gamma ( IFN-gamma ) could have clinical potential while many putative biomarkers showed poor association .
Several circulating agents in peripheral blood may predict AAA size , expansion rate or rupture . | BACKGROUND The maximal diameter of abdominal aortic aneurysms ( AAAs ) is the dominating indication for repair .
However half of the AAAs repaired would never have ruptured if left unrepaired , although small AAAs occasionally rupture .
Earlier surgery may be associated with a lower mortality .
More precise indicators for surgery are warranted .
This systematic review identifies potential systemic biomarkers for AAA rupture or expansion . | Background Abdominal aortic aneurysm is a multifactorial disorder in which inflammation is an important pathophysiological feature . In explant culture , aneurysm biopsies secrete large amounts of interleukin-6 ( IL-6 ) , and among aneurysm patients , the circulating concentration of IL-6 appears to be increased . Methods and Results We investigated , in 19 patients , whether aneurysm wall was an important source of circulating IL-6 . We also tested the hypotheses , in 466 patients with a small aneurysm , that ( 1 ) high concentrations of circulating IL-6 signaled rapid aneurysm growth and ( 2 ) the −174 G→C polymorphism in the IL-6 promoter predicted survival . For 19 patients with large or inflammatory aneurysms , the concentration of IL-6 was higher in the iliac arteries than the brachial arteries ( median difference 26.5 pg/mL , this difference increasing with aneurysm diameter , P = 0.01 ) . In 466 patients with small aneurysms , the frequency of the −174 C allele ( 0.40 ) was similar to that in a normal healthy population . Patients of GG genotype had lower plasma concentrations of IL-6 than patients of GC and CC genotypes ( medians 1.9 , 4.8 , and 15.6 pg/mL , respectively , Kruskal-Wallis P = 0.047 ) . Cardiovascular and all-cause mortalities were lower for patients of GG genotype than for patients of GC and CC genotype : hazard ratios 0.32 ( 95 % CI 0.12 to 0.93 ) , P = 0.036 , and 0.51 ( 95 % CI 0.25 to 1.00 ) , P = 0.05 , respectively . There was no association between plasma IL-6 or IL-6 genotype and aneurysm growth . Conclusions Aortic aneurysms appear to be an important source of circulating IL-6 , the concentration being influenced by genotype . For patients with small aneurysms , the −174 G→C IL-6 genotype predicts future cardiovascular mortality CONTEXT Among patients with abdominal aortic aneurysm ( AAA ) who have high operative risk , repair is usually deferred until the AAA reaches a diameter at which rupture risk is thought to outweigh operative risk , but few data exist on rupture risk of large AAA . OBJECTIVE To determine the incidence of rupture in patients with large AAA . DESIGN AND SETTING Prospect i ve cohort study in 47 Veterans Affairs medical centers . PATIENTS Veterans ( n = 198 ) with AAA of at least 5.5 cm for whom elective AAA repair was not planned because of medical contraindication or patient refusal . Patients were enrolled between April 1995 and April 2000 and followed up through July 2000 ( mean , 1.52 years ) . MAIN OUTCOME MEASURE Incidence of AAA rupture by strata of initial and attained diameter . RESULTS Outcome ascertainment was complete for all patients . There were 112 deaths ( 57 % ) and the autopsy rate was 46 % . Forty-five patients had probable AAA rupture . The 1-year incidence of probable rupture by initial AAA diameter was 9.4 % for AAA of 5.5 to 5.9 cm , 10.2 % for AAA of 6.0 to 6.9 cm ( 19.1 % for the subgroup of 6.5 - 6.9 cm ) , and 32.5 % for AAA of 7.0 cm or more . Much of the increased risk of rupture associated with initial AAA diameters of 6.5 - 7.9 cm was related to the likelihood that the AAA diameter would reach 8.0 cm during follow-up , after which 25.7 % ruptured within 6 months . CONCLUSION The rupture rate is substantial in high-operative-risk patients with AAA of at least 5.5 cm in diameter and increases with larger diameter PURPOSE Chlamydia Pneumoniae has been shown to be associated with atherosclerosis , myocardial infa rct ion , and abdominal aortic aneurysms ( AAAs ) . The possible association between AAA expansion and C pneumoniae infection was therefore assessed . METHODS Blood sample s were taken from patients with an AAA that was considered for surgical repair after having been diagnosed by means of the Chichester aneurysm screening program ( UK ) as having an initially infrarenal aortic diameter of 3.0 to 5.9 cm . The patients were examined prospect ively for as long as 11.5 years ( mean , 4.1 years ) with ultrasound scanning . Of 110 patients considered for surgery , 90 men and 10 women had blood sample s taken . Their IgG and IgA antibodies against C pneumoniae were measured by means of a microimmunofluorescence test . Unpaired t tests , multiple linear regression analyses , and logistic regression analyses were used for statistical analysis . RESULTS A total of 44 % ( 95 % CI , 31%-55 % ) of the men with an AAA had an IgA titer of 64 or more , an IgG titer of 128 or more , or both , compared with 10 % of the women with an AAA ( OR = 7.2 ; 95 % CI , 1.05 - 160.8 ) . A titer of IgG of 128 or more was significantly associated with higher expansion ( 5.3 vs 2.6 mm per year ) , even after adjustment for initial AAA size and age . A significant positive correlation between both IgA and IgG titers and mean annual expansion was observed ( r = 0.28 ; 95 % CI , 0.05 - 0.49 ; and r = 0.45 ; 95 % CI , 0.24 - 0.62 , respectively ) , persisting after adjusting for initial AAA size and age . An IgG titer of 128 or more was present significantly more often in cases with an expansion greater than 1 cm annually ( adjusted OR = 12.6 ; 95 % CI , 1.37 - 293 ) . CONCLUSION A high proportion of men with an AAA has signs of infection with C pneumoniae . The progression of their AAAs was positively correlated with the presence of indicators of C pneumoniae infection OBJECTIVES endothelin 1,2 plays a significant role in the process of atherogenesis and vascular wall injury . The aim of this study was to assess whether plasma endothelin 1,2 levels were elevated in patients with large or symptomatic abdominal aortic aneurysms ( AAAs ) . DESIGN a prospect i ve open study . MATERIAL S AND METHODS plasma endothelin 1,2 levels were measured in 65 consecutive patients with infrarenal aortic aneurysms and compared with the levels in 44 healthy volunteer controls . The data for abdominal aneurysm patients was analysed in four subgroups : ( i ) small aneurysms ( < 5 cm ) , ( ii ) large aneurysms ( > /=5 cm ) , ( iii ) asymptomatic aneurysms and ( iv ) symptomatic aneurysms . Comparisons were made between endothelin 1,2 levels in aneurysm patients and controls and between the different aneurysm subgroups . RESULTS a highly significant difference ( p<0.0001 ) was found between aneurysm patients and controls . Patients with large aneurysms had significantly higher levels than patients with small aneurysms ( p<0.01 ) . There was no statistical difference in endothelin 1,2 levels between symptomatic and asymptomatic patients ; however , the highest levels were found in large , symptomatic aneurysms and the lowest in small , asymptomatic aneurysms . CONCLUSIONS plasma endothelin 1,2 is an endogenous marker of aneurysm diameter . Further studies are required to determine whether it relates to the rate of growth of aneurysms Abstract The pathogenesis of abdominal aortic aneurysms ( AAA ) is a complex process in which atherosclerosis and inflammation play a leading role . Cytokines are important mediators of both processes . The aim of our study was to determine whether plasma levels of cytokines which are most involved in AAA pathogenesis can be used as endogenous markers of AAA development , and thus to facilitate the decision on surgical intervention in cases when this is clinical ly unclear ( e.g. small AAA ) . In the prospect i ve study a total of 90 patients with AAA were examined . These patients were divided into the following groups according to symptoms and AAA diameter : symptomatic AAAs , including ruptures ( n=16 ) ; asymptomatic AAAs ( n=74 ) ; AAAs with a diameter of up to 5 cm ( n=30 ) , AAAs of 5–8 cm ( n=38 ) , and AAAs with a diameter over 8 cm ( n=22 ) . The average age of the patients was 70.7 ( 56–82 ) years . The male to female ratio was 4:1 ( 71:19 ) . A control group consisted of 30 healthy individuals of similar age and sex presentation with no manifestation of atherosclerosis . Plasma levels of cytokines were assessed in venous blood by means of radio- or enzymo-immunoassay . Statistical processing of the results was conducted with ANOVA and Wilcoxon tests with Spearman correlation , where p<0.05 was considered to be statistically significant . Plasma concentrations of cytokines were significantly higher in AAA patients than in healthy individuals . In AAA patients the tumour necrosis factor-α ( TNF-α ) and interleukin ( IL-8 ) levels were low in large and in symptomatic AAAs . IL-6 levels were increased with increasing AAA diameter and symptoms . IL-8 levels ( p<0.05 ) showed a statistically significant correlation with the diameter , and TNF-α ( p<0.05 ) with the symptoms of AAA . IL-1β , IL-2 and IL-6 did not show any significant changes with different AAA diameter or symptomatology . In Conclusion : IL-8 and TNF-α can be used as endogenous markers of the process of AAA development , in deciding for either surgical or endovascular treatment of patients when the clinical indication is not entirely clear BACKGROUND Serum C-reactive protein ( CRP ) has proven to be an independent marker of the extent of atherosclerosis in patients with coronary , cerebrovascular , and peripheral arterial disease . In this prospect i ve observational study , we wanted to assess the relationship between serum CRP and extent of disease transversely and longitudinally in time , as well as future cardiovascular complications in patients with peripheral arterial disease ( PAD ) . Hypothesizing that CRP not only is a marker of but also actively participates in atherogenesis , we explored the possibility of CRP production by femoral atherosclerotic plaques . METHODS Serum CRP was measured as highly sensitive ( hsCRP ) in 387 patients with PAD attending the vascular clinic of a university and 2 affiliated teaching hospitals . Serum hsCRP was related to the ankle-brachial pressure index ( ABPI ) as an indication of severity of disease at inclusion and at 12 months ' follow-up and to future events ( death and coronary , cerebral , and peripheral arterial events ) . In femoral plaques , the production of CRP was analyzed with reverse transcription-polymerase chain reaction , and CRP plaque localization was assessed with immunostaining on serial tissue sections with antibodies toward CRP , smooth muscle cells , T cells , and macrophages . RESULTS The hsCRP ( average + /- SD ) was 3.26 + /- 2.41 mg/L. Serum hsCRP showed a correlation with baseline and 12-month follow-up ABPI ( Spearman rank correlation ; P < .05 for both correlations ) . When the patients were divided into three equally sized groups according to baseline serum hsCRP , the ABPI at baseline and at 12 months decreased significantly from the low- to the high-hsCRP group ( baseline ABPI : 0.70 , 0.65 , and 0.57 , P < .01 ; 12-month follow-up ABPI : 0.78 , 0.70 , and 0.65 , P < .01 ) . These associations persisted after correction for conventional risk factors . Furthermore , serum hsCRP was related to the combined end point " death and /or any cardiovascular event " ( log-rank test ; P = .04 ) during a median 24-month follow-up period . Reverse transcription-polymerase chain reaction analysis showed CRP production in 4 of 14 femoral plaques . CRP was detected in all femoral plaques , but not in healthy brachial arteries . Immunoreactivity for CRP was observed in smooth muscle cells , macrophages , and T cells . CONCLUSIONS Serum hsCRP was related to the severity of PAD , showing a relation to future hemodynamic function and cardiovascular events in PAD patients . In addition to coronary plaques , aneurysmal aortas , and failed venous coronary bypasses , femoral plaques also produce CRP , thus illustrating that the production of CRP may represent a universal response to vascular injury and suggesting that vascular CRP may contribute to plaque development OBJECTIVE plasmin is a common activator of the known proteolytic systems involved in the aneurysmal degradation , and is reported to be associated with the expansion of abdominal aortic aneurysms ( AAA ) . The aim of this study was to study the activating pathways of plasminogen as predictors of the progression of AAA . MATERIAL S AND METHODS one hundred and twelve of 122 male patients with a small AAA ( def . : + 3 cm ) were interviewed , examined , had blood sample s taken at diagnosis , and scanned annually for 1 - 5 years ( mean 3.5 years ) , and referred for surgery if the AAA exceeded 5 cm in diameter . A r and om sample of 70 of the 112 cases had plasma levels of urokinase-like-plasminogen activator ( uPA ) , tissue-type-plasminogen activator ( tPA ) , plasminogen-activator-inhibitor-1 ( PAI-1 ) , macrophage inhibiting factor ( MIF ) , tumour-growth-factor-beta1 ( TGF-beta1 ) , homocysteine , and serum levels of IgA-antibodies against Chlamydia pneumoniae ( IgA-CP ) and Cotinine ( a nicotine metabolite ) measured . Spearmans correlation analysis was used for statistics . RESULTS the annual expansion rate correlated positively with tPA , IgA-CP and S-Cotinine ; r = 0.37 ( p=0.002 ) , 0.29 ( p=0.006 ) and 0.24 ( p=0.038 ) , while PAI1 , uPA , TGF-beta1 , homocysteine , and MIF did not . S-Cotinine did also correlate positively with tPA , r=0.24 ( p=0.049 ) . CONCLUSION the aortic matrix degradation in AAA may be partly caused by an activation of plasminogen by tPA , but apparently not by uPA , which usually dominates matrix degradation . Smoking seems to be a factor for this pathway , while the pathways of IgA-CP and MIF , a new marker of aneurysmal progression , seem different . The latter observations suggest that other proteolytic pathways are involved in the aortic wall degradation in AAA Chronic Chlamydophila pneumoniae infection has been suggested as a possible contributing factor for the development and expansion of abdominal aortic aneurysm ( AAA ) . The relevance of C pneumoniae involved in the processes underlying aneurysmal rupture is unknown . The aim of this study was to examine the relationship between C pneumoniae seropositivity and AAA rupture . In a case-control study , 119 patients with AAA and 36 matched controls were prospect ively investigated with C pneumoniae serology . Patients with ruptured AAA have similar levels of IgG antibodies against C pneumoniae as patients with an electively operated AAA , a small AAA , and controls . In conclusion , this study fails to demonstrate a connection between C pneumoniae seropositivity and AAA rupture BACKGROUND To study the levels of the aminoterminal propeptide of type III(PIIINP ) and carboxyterminal propeptide of type I procollagen ( PICP ) in plasma and in the wall of abdominal aortic aneurysms in relation to their size and symptomatology . PIIINP serves as a marker of turnover and PICP as a marker of the synthesis of the corresponding collagens . METHODS EXPERIMENTAL DESIGN A prospect i ve non-r and omised study . SETTING University Hospital , Plzen , Czech Republic . PATIENTS Eighty-six patients who underwent resection of abdominal aortic aneurysms , average age 70.1 years ( range 45 to 91 years ) , men to women ratio 5:1 . The indication for resection was its symptomatology without relation to its diameter , and diameter over 5 cm in asymptomatic patients . Twenty patients ( with similar age and gender distribution ) scheduled for hernia repair or laparoscopic cholecystectomy were examined as a control group . MAIN OUTCOME MEASURES The plasma and tissue PICP and PIIINP concentrations were evaluated using radioimmunoassay methods . The plasma sample s were taken from the cubital vein without the use of a tourniquet . Full-thickness sections of the anterior abdominal aortic aneurysm wall at the site of the largest aneurysm diameter were taken at the time of operation . RESULTS A significant difference between plasma PIIINP levels in patients with abdominal aortic aneurysms and the control group was observed ( p<0.01 ) . No correlation of PICP , PIIINP plasma levels with diameter and symptomatology of abdominal aortic aneurysms was found . The increase in PHIIINP tissue concentration was significant in patients with increasing diameter and positive symptomatology ( p<0.01 ) . No statistically significant correlation between plasma and tissue PICP and PIIINP concentrations was observed . CONCLUSIONS The metabolism of type III collagen is increased in patients with abdominal aortic aneurysm , in contrast to type I collagen . The result is a degradation of collagen in the aneurysmal wall . The turnover of type III collagen increases with the enlargement of the aneurysm diameter and with the positive symptomatology . Degradation of type III collagen in the aneurysmal wall has therefore a fundamental significance for abdominal aortic aneurysm rupture . Because no correlation between plasma and tissue levels of PIIINP was found , the plasma levels of PIIINP can not be used as the plasma markers of this process BACKGROUND We previously reported the prevalence and associations of abdominal aortic aneurysm ( AAA ) in 73451 veterans aged 50 to 79 years who underwent ultrasound screening . OBJECTIVE To underst and the prevalence of and principal positive and negative risk factors for AAA , and to assess reproducibility of our previous findings . METHODS In the new cohort of veterans undergoing screening , 52 745 subjects aged 50 to 79 without history of AAA underwent successful ultrasound screening for AAA , after completing a question naire on demographics and potential risk factors . RESULTS We detected AAA of 4.0 cm or larger in 613 participants ( 1.2 % ; compared with 1.4 % in the earlier cohort ) . The direction and magnitude of the important associations reported in the first cohort were confirmed . Respective odds ratios for the major associations with AAA for the second and for the combined cohorts were as follows : 1.81 and 1.71 for age ( per 7 years ) , 0.12 and 0 . 18 for female sex , 0.59 and 0.53 for black race , 1.94 and 1.94 for family history of AAA , 4.45 and 5.07 for smoking , 0.50 and 0.52 for diabetes , and 1.60 and 1.66 for atherosclerotic diseases . The excess prevalence associated with smoking accounted for 75 % of all AAAs of 4.0 cm or larger in the total population of 126 196 . Associations for AAA of 3.0 to 3.9 cm were similar but tended to be somewhat weaker . CONCLUSIONS Our findings confirm our previous cohort findings . Age , smoking , family history of AAA , and atherosclerotic diseases remained the principal positive associations with AAA , and female sex , diabetes , and black race remained the principal negative associations OBJECTIVE Three proteolytic systems seem involved in the aneurysmal degradation of the aortic wall . Plasmin is a common activator of the systems and could thus be predictive for the progression of abdominal aortic aneurysms ( AAAs ) . METHODS AND MATERIAL S In 1994 , 112 of 141 male patients with AAA diagnosed through population screening ( defined as 3 cm or more ) were interviewed and examined and had blood sample s taken . One hundred twelve cases were scanned annually for 1 to 5 years ( mean , 2.5 years ) and referred for surgery if the AAA exceeded 5 cm in diameter . A r and om sample of 70 of the 112 cases had P-plasmin-antiplasmin-complexes ( PAPs ) , P-plasminogen , and S-elastin-peptides ( SEPs ) . RESULTS PAP was positively correlated with annual expansion rate ( r = 0.39 , 0.16 - 0.56 ) , persisting after adjustment for initial AAA size , SEP , age , and smoking . However , PAP levels did not correlate with the initial AAA size or SEP . Furthermore , PAP levels were significantly predictive for cases exp and ing to operation-recommendable AAA sizes . Combined with the initial AAA size , both optimal sensitivity and specificity were 82 % , increasing to 95 % and 96 % , respectively , excluding those lost to follow-up and accepting 2 mm of interobserver variation . CONCLUSION The progression of AAA is correlated with the PAP level , which seems to have a predictive value similar to the best serologic predictor known , serum-elastin-peptides The cysteine protease inhibitor cystatin C may play a role in the development and progression of abdominal aortic aneurysms ( AAAs ) |
10,463 | 28,889,119 | Using a r and om-effects model , meta- analysis of a-tDCS , c-tDCS , tACS , tRNS and tPCS studies showed statistically non-significant pre-post effects of sham interventions on CSE .
This review found evidence for statically non-significant effects of sham tES on CSE | Abstract Sham stimulation is used in r and omized controlled trials ( RCTs ) to assess the efficacy of active stimulation and placebo effects .
It should mimic the characteristics of active stimulation to achieve blinding integrity . | Transcranial direct current stimulation ( tDCS ) uses a weak electric current to modulate neuronal activity . A neurophysiologic outcome measure to demonstrate reliable tDCS modulation at the group level is transcranial magnetic stimulation engendered motor evoked potentials ( MEPs ) . Here , we conduct a study testing the reliability of individual MEP response patterns following a common tDCS protocol . Fourteen participants ( 7m/7f ) each underwent nine r and omized sessions of 1 mA , 10 min tDCS ( 3 anode ; 3 cathode ; 3 sham ) delivered using an M1/orbito-frontal electrode montage ( sessions separated by an average of ~5.5 days ) . Fifteen MEPs were obtained prior to , immediately following and in 5 min intervals for 30 min following tDCS . TMS was delivered at 130 % resting motor threshold using neuronavigation to ensure consistent coil localization . A number of non-experimental variables were collected during each session . At the individual level , considerable variability was seen among different testing sessions . No participant demonstrated an excitatory response ≥20 % to all three anodal sessions , and no participant demonstrated an inhibitory response ≥20 % to all three cathodal sessions . Intra-class correlation revealed poor anodal and cathodal test – retest reliability [ anode : ICC(2,1 ) = 0.062 ; cathode : ICC(2,1 ) = 0.055 ] and moderate sham test – retest reliability [ ICC(2,1 ) = 0.433 ] . Results also revealed no significant effect of tDCS at the group level . Using this common protocol , we found the effects of tDCS on MEP amplitudes to be highly variable at the individual level . In addition , no significant effects of tDCS on MEP amplitude were found at the group level . Future studies should consider utilizing a more strict experimental protocol to potentially account for intra-individual response variations Transcranial direct current stimulation ( tDCS ) is a representative non-invasive brain stimulation method ( NIBS ) . tDCS increases cortical excitability not only in healthy individuals , but also in stroke patients where it contributes to motor function improvement . Recently , two additional types of transcranial electrical stimulation ( tES ) methods have been introduced that may also prove beneficial for stimulating cortical excitability ; these are transcranial r and om noise stimulation ( tRNS ) and transcranial alternating current stimulation ( tACS ) . However , comparison of tDCS with tRNS and tACS , in terms of efficacy in cortical excitability alteration , has not been reported thus far . We compared the efficacy of the three different tES methods for increasing cortical excitability using the same subject population and same current intensity . Fifteen healthy subjects participated in this study . Similar stimulation patterns ( 1.0 mA and 10 min ) were used for the three conditions of stimulation ( tDCS , tRNS , and tACS ) . Cortical excitability was explored via single-pulse TMS elicited motor evoked potentials ( MEPs ) . Compared with pre- measurements , MEPs significantly increased with tDCS , tACS , and tRNS ( p < 0.05 ) . Compared with sham measurements , significant increases in MEPs were also observed with tRNS and tACS ( p < 0.05 ) , but not with tDCS . In addition , a significant correlation of the mean stimulation effect was observed between tRNS and tACS ( p = 0.019 , r = 0.598 ) . tRNS induced a significant increase in MEP compared with the Pre or Sham at all time points . tRNS result ed in the largest significant increase in MEPs . These findings suggest that tRNS is the most effective tES method and should be considered as part of a treatment plan for improving motor function in stroke patients PURPOSE Transcranial direct current stimulation ( tDCS ) has proven to be a useful tool for fundamental brain research as well as for attempts in therapy of neurological and psychiatric diseases by modulating neuronal plasticity . Little is understood about the effects of tDCS are influenced by hemispheric dominance , even less in terms of h and edness . The aim of our pilot study was to investigate whether tDCS induced neuroplastic changes may be different in right- and left-h and ed individuals due to existing differences in hemispheric lateralisation . METHODS We measured changes in motor evoked potentials ( MEPs ) after application of tDCS in 8 right-h and ers , 8 left-h and ers and 8 mixed-h and ers according to the Edinburgh H and edness Inventory ( EHI ) . In double-blind sessions , we applied either anodal or cathodal tDCS for 5 minutes for each hemisphere . RESULTS While motor thresholds ( MT ) seem to be not influenced by h and edness significantly , in right-h and ed subjects we reproduced the well-known effects of tDCS : anodal stimulation increased while cathodal stimulation decreased MEP amplitudes . However , left- and mixed-h and ed subjects differed from right-h and ed subjects . After anodal stimulation of the left hemisphere the increase of the MEP amplitudes was stronger in right h and ed subjects than in left and mixed h and ed subjects . Interestingly , after cathodal stimulation of the left hemisphere this difference was less marked . The stimulation of the right hemisphere showed the same tendency , but results were not significant . CONCLUSIONS For the first time , we are able to demonstrate that the modulating effects of tDCS on corticospinal excitability differ moderately in the left- and mixed-h and ed population compared to right-h and ed subjects . The shown differences according to h and edness should be taken into account in further studies The common aim of transcranial stimulation methods is the induction or alterations of cortical excitability in a controlled way . Significant effects of each individual stimulation method have been published ; however , conclusive direct comparisons of many of these methods are rare . The aim of the present study was to compare the efficacy of three widely applied stimulation methods inducing excitability enhancement in the motor cortex : 1 mA anodal transcranial direct current stimulation ( atDCS ) , intermittent theta burst stimulation ( iTBS ) , and 1 mA transcranial r and om noise stimulation ( tRNS ) within one subject group . The effect of each stimulation condition was quantified by evaluating motor-evoked-potential amplitudes ( MEPs ) in a fixed time sequence after stimulation . The analyses confirmed a significant enhancement of the M1 excitability caused by all three types of active stimulations compared to sham stimulation . There was no significant difference between the types of active stimulations , although the time course of the excitatory effects slightly differed . Among the stimulation methods , tRNS result ed in the strongest and atDCS significantly longest MEP increase compared to sham . Different time courses of the applied stimulation methods suggest different underlying mechanisms of action . Better underst and ing may be useful for better targeting of different transcranial stimulation techniques Previous research ers have approved the ability of anodal transcranial direct current stimulation ( a-tDCS ) of the primary motor cortex ( M1 ) to enhance corticospinal excitability ( CSE ) . The primary aim of the current study was to investigate the effect of concurrent stimulation of M1 and a functionally connected cortical site of M1 on CSE modulation . This new technique is called unihemispheric concurrent dual-site a-tDCS ( a-tDCSUHCDS ) . The secondary aim was to investigate the mechanisms underlying the efficacy of this new approach in healthy individuals . In a r and omized crossover study , 12 healthy right-h and ed volunteers received a-tDCS under five conditions : a-tDCS of M1 , a-tDCSUHCDS of M1-dorsolateral prefrontal cortex ( DLPFC ) , a-tDCSUHCDS of M1- primary sensory cortex ( S1 ) , a-tDCSUHCDS of M1- primary visual cortex ( V1 ) , and sham a-tDCSUHCDS . Peak-to-peak amplitude of transcranial magnetic stimulation ( TMS ) induced MEPs , short-interval intracortical inhibition ( SICI ) and intracortical facilitation ( ICF ) were assessed before and four times after each condition . A-tDCSUHCDS conditions induced larger MEPs than conventional a-tDCS . The level of M1 CSE was significantly higher following a-tDCSUHCDS of M1-DLPFC than other a-tDCSUHCDS conditions ( p < 0.001 ) , and lasted for over 24 h. The paired-pulse TMS results after a-tDCS of M1-DLPFC showed significant facilitatory increase and inhibitory change . A-tDCSUHCDS of M1-DLPFC increases M1 CSE twofold that of conventional a-tDCS . A-tDCSUHCDS of M1-DLPFC enhances the activity of glutamergic mechanisms for at least 24 h. Such long-lasting M1 CSE enhancement induced by a-tDCSUHCDS of M1-DLPFC could be a valuable finding in clinical scenarios such as learning , motor performance , or pain management . The present study has been registered on the Australian New Zeal and Clinical Trial at http://www.anzctr.org.au/ with registry number of ACTRN12614000817640 Background Transcranial direct current stimulation ( tDCS ) is a non-invasive technique that modulates the excitability of neurons within the primary motor cortex ( M1 ) . Research shows that anodal-tDCS applied over the non-dominant M1 ( i.e. unilateral stimulation ) improves motor function of the non-dominant h and . Similarly , previous studies also show that applying cathodal tDCS over the dominant M1 improves motor function of the non-dominant h and , presumably by reducing interhemispheric inhibition . In the present study , one condition involved anodal-tDCS over the non-dominant M1 ( unilateral stimulation ) whilst a second condition involved applying cathodal-tDCS over the dominant M1 and anodal-tDCS over non-dominant M1 ( bilateral stimulation ) to determine if unilateral or bilateral stimulation differentially modulates motor function of the non-dominant h and . Using a r and omized , cross-over design , 11 right-h and ed participants underwent three stimulation conditions : 1 ) unilateral stimulation , that involved anodal-tDCS applied over the non-dominant M1 , 2 ) bilateral stimulation , whereby anodal-tDCS was applied over the non-dominant M1 , and cathodal-tDCS over the dominant M1 , and 3 ) sham stimulation . Transcranial magnetic stimulation ( TMS ) was performed before , immediately after , 30 and 60 minutes after stimulation to eluci date the neural mechanisms underlying any potential after-effects on motor performance . Motor function was evaluated by the Purdue pegboard test . Results There were significant improvements in motor function following unilateral and bilateral stimulation when compared to sham stimulation at all-time points ( all P < 0.05 ) ; however there was no difference across time points between unilateral and bilateral stimulation . There was also a similar significant increase in corticomotor excitability with both unilateral and bilateral stimulation immediately post , 30 minutes and 60 minutes compared to sham stimulation ( all P < 0.05 ) . Unilateral and bilateral stimulation reduced short-interval intracortical inhibition ( SICI ) immediately post and at 30 minutes ( all P < 0.05 ) , but returned to baseline in both conditions at 60 minutes . There was no difference between unilateral and bilateral stimulation for SICI ( P > 0.05 ) . Furthermore , changes in corticomotor plasticity were not related to changes in motor performance . Conclusion These results indicate that tDCS induced behavioural changes in the non-dominant h and as a consequence of mechanisms associated with use-dependant cortical plasticity that is independent of the electrode arrangement Background Premotor cortical regions ( PMC ) play an important role in the orchestration of motor function , yet their role in compensatory mechanisms in a disturbed motor system is largely unclear . Previous studies are consistent in describing pronounced anatomical and functional connectivity between the PMC and the primary motor cortex ( M1 ) . Lesion studies consistently show compensatory adaptive changes in PMC neural activity following an M1 lesion . Non-invasive brain modification of PMC neural activity has shown compensatory neurophysiological aftereffects in M1 . These studies have contributed to our underst and ing of how M1 responds to changes in PMC neural activity . Yet , the way in which the PMC responds to artificial inhibition of M1 neural activity is unclear . Here we investigate the neurophysiological consequences in the PMC and the behavioral consequences for motor performance of stimulation mediated M1 inhibition by cathodal transcranial direct current stimulation ( tDCS ) . Purpose The primary goal was to determine how electrophysiological measures of PMC excitability change in order to compensate for inhibited M1 neural excitability and attenuated motor performance . Hypothesis Cathodal inhibition of M1 excitability leads to a compensatory increase of ipsilateral PMC excitability . Methods We enrolled 16 healthy participants in this r and omized , double-blind , sham-controlled , crossover design study . All participants underwent navigated transcranial magnetic stimulation ( nTMS ) to identify PMC and M1 corticospinal projections as well as to evaluate electrophysiological measures of cortical , intracortical and interhemispheric excitability . Cortical M1 excitability was inhibited using cathodal tDCS . Finger-tapping speeds were used to examine motor function . Results Cathodal tDCS successfully reduced M1 excitability and motor performance speed . PMC excitability was increased for longer and was the only significant predictor of motor performance . Conclusion The PMC compensates for attenuated M1 excitability and contributes to motor performance maintenance The aim is to investigate the effects of pulse duration ( PD ) on the modulatory effects of transcranial pulsed current ( tPCS ) on corticospinal excitability ( CSE ) . CSE of the dominant primary motor cortex ( M1 ) of right first dorsal interosseous muscle was assessed by motor evoked potentials , before , immediately , 10 , 20 and 30 minutes after application of five experimental conditions : 1 ) anodal transcranial direct current stimulation ( a-tDCS ) , 2 ) a-tPCS with 125 ms pulse duartion ( a-tPCSPD = 125 ) , 3 ) a-tPCS with 250 ms pulse duration ( a-tPCSPD = 250 ) , 4 ) a-tPCS with 500 ms pulse duration ( a-tPCSPD = 500 ) and 5 ) sham a-tPCS . The total charges were kept constant in all experimental conditions except sham condition . Post-hoc comparisons indicated that a-tPCSPD = 500 produced larger CSE compared to a-tPCSPD = 125 ( P<0.0001 ) , a-tPCSPD = 250 ( P = 0.009 ) and a-tDCS ( P = 0.008 ) . Also , there was no significant difference between a-tPCSPD = 250 and a-tDCS on CSE changes ( P>0.05 ) . All conditions except a-tPCSPD = 125 showed a significant difference to the sham group ( P<0.006 ) . All participants tolerated the applied currents . It could be concluded that a-tPCS with a PD of 500ms induces largest CSE changes , however further studies are required to identify optimal values A 10-minute application of highfrequency ( 100–640 Hz ) transcranial r and om noise stimulation ( tRNS ) over the primary motor cortex ( M1 ) increases baseline levels of cortical excitability , lasting around 1 hr poststimulation Terney et al. ( 2008 ) . We have extended previous work demonstrating this effect by decreasing the stimulation duration to 4 , 5 , and 6 minutes to assess whether a shorter duration of tRNS can also induce a change in cortical excitability . Single-pulse monophasic transcranial magnetic stimulation ( TMS ) was used to measure baseline levels of cortical excitability before and after tRNS . A 5- and 6-minute tRNS application induced a significant facilitation . 4-minute tRNS produced no significant aftereffects on corticospinal excitability . Plastic after effects after tRNS on corticospinal excitability require a minimal stimulation duration of 5 minutes . However , the duration of the aftereffect of 5-min tRNS is very short compared to previous studies using tRNS . Developing different transcranial stimulation techniques may be fundamental in underst and ing how excitatory and inhibitory networks in the human brain can be modulated and how each technique can be optimised for a controlled and effective application Background Many double-blind clinical trials of transcranial direct current stimulation ( tDCS ) use stimulus intensities of 2 mA despite the fact that blinding has not been formally vali date d under these conditions . The aim of this study was to test the assumption that sham 2 mA tDCS achieves effective blinding . Methods A r and omised double blind crossover trial . 100 tDCS-naïve healthy volunteers were incorrectly advised that they there were taking part in a trial of tDCS on word memory . Participants attended for two separate sessions . In each session , they completed a word memory task , then received active or sham tDCS ( order r and omised ) at 2 mA stimulation intensity for 20 minutes and then repeated the word memory task . They then judged whether they believed they had received active stimulation and rated their confidence in that judgement . The blinded assessor noted when red marks were observed at the electrode sites post-stimulation . Results tDCS at 2 mA was not effectively blinded . That is , participants correctly judged the stimulation condition greater than would be expected to by chance at both the first session ( kappa level of agreement ( κ ) 0.28 , 95 % confidence interval ( CI ) 0.09 to 0.47 p = 0.005 ) and the second session ( κ = 0.77 , 95%CI 0.64 to 0.90 ) , p = < 0.001 ) indicating inadequate participant blinding . Redness at the reference electrode site was noticeable following active stimulation more than sham stimulation ( session one , κ = 0.512 , 95%CI 0.363 to 0.66 , p<0.001 ; session two , κ = 0.677 , 95%CI 0.534 to 0.82 ) indicating inadequate assessor blinding . Conclusions Our results suggest that blinding in studies using tDCS at intensities of 2 mA is inadequate . Positive results from such studies should be interpreted with caution Objective The objective of this study was to examine the effect of transcranial r and om noise stimulation ( tRNS ) with and without a direct current ( DC ) offset on motor cortical excitability and compare results to transcranial DC stimulation ( tDCS ) . Methods Fifteen healthy participants were tested in a within-subjects design . Motor-evoked potentials were measured before and up to 90 minutes after stimulation using transcranial magnetic stimulation . Five stimulation conditions were examined : sham , 1-mA tDCS , 2-mA tDCS , 2-mA tRNS ( with no DC offset ) , and 2-mA tRNS + 1-mA DC offset . Results There were no significant differences between the stimulation conditions . An analysis of individual stimulation conditions found that there was a significant increase in motor-evoked potential amplitudes after 1-mA tDCS , 2-mA tDCS , and 2-mA tRNS + DC offset when compared with baseline . Sham and 2-mA tRNS did not result in changes in cortical excitability . Conclusions Although differences between the stimulation conditions did not reach a statistical significance , the findings suggest that stimulation involving a DC ( tDCS and tRNS + DC offset ) but not solely tRNS is more likely to lead to increases in cortical excitability BACKGROUND Transcranial direct current stimulation ( tDCS ) has been investigated as therapeutic intervention in various psychiatric and neurologic disorders . As placebo responses to technical interventions may be pronounced in many clinical conditions , it is important to thoroughly develop placebo conditions which meet the requirements for application in r and omized double-blind controlled trials . OBJECTIVE The two-part experiment reported here aims at evaluating a new sham tDCS condition in healthy subjects and device operators . Sham or active tDCS is delivered after entering a number code to the device and allows blinding of the operator before and during tDCS . The sham mode has no short stimulation period . METHODS The experimental sequence was as follows : 1 ) Evaluation of successful blinding by comparing placebo to active stimulation at prefrontal sites based on the rating of subjects undergoing tDCS , 2 ) Evaluation of successful blinding by comparing placebo to active stimulation at prefrontal sites based on the operator/observer ratings . RESULTS Subjects were not able to distinguish between active and sham tDCS for prefrontal stimulation . Overall there was no relevant discomfort and tDCS was well tolerated . Operators/observers were able to identify sham stimulation based on skin reddening after active , but not after sham tDCS . CONCLUSIONS The tDCS sham condition investigated here may be suitable for placebo-controlled trials keeping subjects blind to treatment conditions . However , operators can easily be aware of the condition applied and they should not get involved in rating outcome measures during the course of high st and ard placebo-controlled trials OBJECTIVE Brain polarization in the form of transcranial direct current stimulation ( tDCS ) , which influences motor function and learning processes , has been proposed as an adjuvant strategy to enhance training effects in Neurorehabilitation . Proper testing in Neurorehabilitation requires double-blind sham-controlled study design s. Here , we evaluated the effects of tDCS and sham stimulation ( SHAM ) on healthy subjects and stroke patients ' self-report measures of attention , fatigue , duration of elicited sensations and discomfort . METHODS tDCS or SHAM was in all cases applied over the motor cortex . Attention , fatigue , and discomfort were self rated by study participants using visual analog scales . Duration of perceived sensations and the ability to distinguish tDCS from Sham sessions were determined . Investigators question ing the patients were blind to the intervention type . RESULTS tDCS and SHAM elicited comparably minimal discomfort and duration of sensations in the absence of differences in attention or fatigue , and could not be distinguished from SHAM by study participants nor investigators . CONCLUSIONS Successful blinding of subjects and investigators and ease of application simultaneously with training protocol s supports the feasibility of using tDCS in double-blind , sham-controlled r and omized trials in clinical Neurorehabilitation . SIGNIFICANCE tDCS could evolve into a useful tool , in addition to TMS , to modulate cortical activity in Neurorehabilitation Alleviating the symptoms of neurological diseases by increasing cortical excitability through transcranial stimulation is an ongoing scientific challenge . Here , we tackle this issue by interfering with high frequency oscillations ( 80–250 Hz ) via external application of transcranial alternating current stimulation ( tACS ) over the human motor cortex ( M1 ) . Twenty-one subjects participated in three different experimental studies and they received on separate days tACS at three frequencies ( 80 Hz , 140 Hz and 250 Hz ) and sham stimulation in a r and omized order . tACS with 140 Hz frequency increased M1 excitability as measured by transcranial magnetic stimulation-generated motor evoked potentials ( MEPs ) during and for up to 1 h after stimulation . Control experiments with sham and 80 Hz stimulation were without any effect , and 250 Hz stimulation was less efficient with a delayed excitability induction and reduced duration . After-effects elicited by 140 Hz stimulation were robust against inversion of test MEP amplitudes seen normally under activation . Stimulation at 140 Hz reduced short interval intracortical inhibition , but left intracortical facilitation , long interval cortical inhibition and cortical silent period unchanged . Implicit motor learning was not facilitated by 140 Hz stimulation . High frequency stimulation in the ripple range is a new promising non-invasive brain stimulation protocol to increase human cortical excitability during and after the end of stimulation BACKGROUND Recently we have shown that transcranial r and om noise ( tRNS ) and 140 Hz transcranial alternating current stimulations ( tACS ) , applied over the primary motor cortex ( M1 ) and using 10 min stimulation duration and 1 mA intensity , significantly increases cortical excitability as measured by motor evoked potentials at rest before and after stimulation . OBJECTIVE /HYPOTHESIS Here , by decreasing the stimulation intensity in 0.2 mA steps from 1.0 mA , we investigate to what extent intensity depends on the induced after-effects . METHODS All twenty-five subjects participated in two different experimental sessions each . They received tACS using 140 Hz frequency and full spectrum tRNS at five different intensities on separate days . Sham stimulation was used as a control . RESULTS Instead of receiving a simple threshold , unexpectedly , in these two independent data sets at threshold intensities of 0.4 mA we found a switch of the already known excitation achieved with an intensity of 1 mA to inhibition . The intermediate intensity ranges of 0.6 and 0.8 mA had no effect at all . Interestingly , the inhibition produced by 140 Hz tACS was stronger than that induced by tRNS . CONCLUSIONS In summary , we have shown here the possibility of selectively controlling the enhancement or reduction of M1 excitability by applying different intensities of high frequency transcranial electrical stimulation In this paper we demonstrate in the intact human the possibility of a non-invasive modulation of motor cortex excitability by the application of weak direct current through the scalp . Excitability changes of up to 40 % , revealed by transcranial magnetic stimulation , were accomplished and lasted for several minutes after the end of current stimulation . Excitation could be achieved selectively by anodal stimulation , and inhibition by cathodal stimulation . By varying the current intensity and duration , the strength and duration of the after-effects could be controlled . The effects were probably induced by modification of membrane polarisation . Functional alterations related to post-tetanic potentiation , short-term potentiation and processes similar to postexcitatory central inhibition are the likely c and i date s for the excitability changes after the end of stimulation . Transcranial electrical stimulation using weak current may thus be a promising tool to modulate cerebral excitability in a non-invasive , painless , reversible , selective and focal way Transcranial direct current stimulation ( tDCS ) of the human motor cortex at an intensity of 1 mA with an electrode size of 35 cm(2 ) has been shown to induce shifts of cortical excitability during and after stimulation . These shifts are polarity-specific with cathodal tDCS result ing in a decrease and anodal stimulation in an increase of cortical excitability . In clinical and cognitive studies , stronger stimulation intensities are used frequently , but their physiological effects on cortical excitability have not yet been explored . Therefore , here we aim ed to explore the effects of 2 mA tDCS on cortical excitability . We applied 2 mA anodal or cathodal tDCS for 20 min on the left primary motor cortex of 14 healthy subjects . Cathodal tDCS at 1 mA and sham tDCS for 20 min was administered as control session in nine and eight healthy subjects , respectively . Motor cortical excitability was monitored by transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials ( MEPs ) from the right first dorsal interosseous muscle . Global corticospinal excitability was explored via single TMS pulse-elicited MEP amplitudes , and motor thresholds . Intracortical effects of stimulation were obtained by cortical silent period ( CSP ) , short latency intracortical inhibition ( SICI ) and facilitation ( ICF ) , and I wave facilitation . The above-mentioned protocol s were recorded both before and immediately after tDCS in r and omized order . Additionally , single-pulse MEPs , motor thresholds , SICI and ICF were recorded every 30 min up to 2 h after stimulation end , evening of the same day , next morning , next noon and next evening . Anodal as well as cathodal tDCS at 2 mA result ed in a significant increase of MEP amplitudes , whereas 1 mA cathodal tDCS decreased corticospinal excitability . A significant shift of SICI and ICF towards excitability enhancement after both 2 mA cathodal and anodal tDCS was observed . At 1 mA , cathodal tDCS reduced single-pulse TMS-elicited MEP amplitudes and shifted SICI and ICF towards inhibition . No significant changes were observed in the other protocol s. Sham tDCS did not induce significant MEP alterations . These results suggest that an enhancement of tDCS intensity does not necessarily increase efficacy of stimulation , but might also shift the direction of excitability alterations . This should be taken into account for applications of the stimulation technique using different intensities and duration s in order to achieve stronger or longer lasting after-effects |
10,464 | 26,501,537 | Although 10-year probabilities of false-positive biopsy results were similar for women beginning screening at age 50 years , indirect estimates of lifetime probability of false-positive results were lower .
AND RELEVANCE For women of all ages at average risk , screening was associated with a reduction in breast cancer mortality of approximately 20 % , although there was uncertainty about quantitative estimates of outcomes for different breast cancer screening strategies in the United States . | IMPORTANCE Patients need to consider both benefits and harms of breast cancer screening .
OBJECTIVE To systematic ally synthesize available evidence on the association of mammographic screening and clinical breast examination ( CBE ) at different ages and intervals with breast cancer mortality , overdiagnosis , false-positive biopsy findings , life expectancy , and quality -adjusted life expectancy . | 12,987 invasive breast cancer cases were diagnosed in women aged 50 - 69 upto the year 2001 in nine Italian areas where a screening programme was active . Cases were followed up in 2005 for a total of 1921 breast cancer failures . The 10-year survival rates were 85.3 % for the invited group against 75.6 % for the non-invited . A time dependent analysis was performed using 5-year intervals . Crude hazard ratios for the invited group in comparison to the not invited group were 0.52 and 0.64 respectively in the ( 0 - 5 ) year and [ 5 - 10 ] year time windows . Hazard ratio adjusted for tumour characteristics was 0.96 in the [ 5 - 10 ] year time window , suggesting minimal or any length bias . Consistent with the results of r and omised trials , these analyses of service screening data document a mortality reduction of 36 % at 5 - 10 years after diagnosis Objective To evaluate the effectiveness of contemporary mammography screening using individual information about screening history and breast cancer mortality from public screening programmes . Design Prospect i ve cohort study of Norwegian women who were followed between 1986 and 2009 . Within that period ( 1995 - 2005 ) , a national mammography screening programme was gradually implemented , with biennial invitations sent to women aged 50 - 69 years . Participants All Norwegian women aged 50 - 79 between 1986 and 2009 . Main outcome measures Multiple Poisson regression analysis was used to estimate breast cancer mortality rate ratios comparing women who were invited to screening ( intention to screen ) with women who were not invited , with a clear distinction between cases of breast cancer diagnosed before ( without potential for screening effect ) and after ( with potential for screening effect ) the first invitation for screening . We took competing causes of death into account by censoring women from further follow-up who died from other causes . Based on the observed mortality reduction combined with the all cause and breast cancer specific mortality in Norway in 2009 , we used the CISNET ( Cancer Intervention and Surveillance Modeling Network ) Stanford simulation model to estimate how many women would need to be invited to biennial mammography screening in the age group 50 - 69 years to prevent one breast cancer death during their lifetime . Results During 15 193 034 person years of observation ( 1986 - 2009 ) , deaths from breast cancer occurred in 1175 women with a diagnosis after being invited to screening and 8996 women who had not been invited before diagnosis . After adjustment for age , birth cohort , county of residence , and national trends in deaths from breast cancer , the mortality rate ratio associated with being invited to mammography screening was 0.72 ( 95 % confidence interval 0.64 to 0.79 ) . To prevent one death from breast cancer , 368 ( 95 % confidence interval 266 to 508 ) women would need to be invited to screening . Conclusion Invitation to modern mammography screening may reduce deaths from breast cancer by about 28 % Abstract Objectives To compare double readings when interpreting full field digital mammography ( 2D ) and tomo synthesis ( 3D ) during mammographic screening . Methods A prospect i ve , Ethical Committee approved screening study is underway . During the first year 12,621 consenting women underwent both 2D and 3D imaging . Each examination was independently interpreted by four radiologists under four reading modes : Arm A—2D ; Arm B—2D + CAD ; Arm C—2D + 3D ; Arm D— synthesis ed 2D + 3D . Examinations with a positive score by at least one reader were discussed at an arbitration meeting before a final management decision . Paired double reading of 2D ( Arm A + B ) and 2D + 3D ( Arm C + D ) were analysed . Performance measures were compared using generalised linear mixed models , accounting for inter-reader performance heterogeneity ( P < 0.05 ) . Results Pre-arbitration false-positive scores were 10.3 % ( 1,286/12,501 ) and 8.5 % ( 1,057/12,501 ) for 2D and 2D + 3D , respectively ( P < 0.001 ) . Recall rates were 2.9 % ( 365/12,621 ) and 3.7 % ( 463/12,621 ) , respectively ( P = 0.005 ) . Cancer detection was 7.1 ( 90/12,621 ) and 9.4 ( 119/12,621 ) per 1,000 examinations , respectively ( 30 % increase , P < 0.001 ) ; positive predictive values ( detected cancer patients per 100 recalls ) were 24.7 % and 25.5 % , respectively ( P = 0.97 ) . Using 2D + 3D , double-reading radiologists detected 27 additional invasive cancers ( P < 0.001 ) . Conclusion Double reading of 2D + 3D significantly improves the cancer detection rate in mammography screening . Key Points• Tomo synthesis -based screening was successfully implemented in a large prospect i ve screening trial . • Double reading of tomo synthesis -based examinations significantly reduced false-positive interpretations . • Double reading of tomo synthesis significantly increased the detection of invasive cancers Background . Imprecision in estimates of benefits and harms around treatment choices is rarely described to patients . Variation in sampling error between treatment alternatives ( e.g. , treatments have similar average risks , but one treatment has a larger confidence interval ) can result in patients failing to choose the option that is best for them . The aim of this study is to use a discrete choice experiment to describe how 2 methods for conveying imprecision in risk influence people ’s treatment decisions . Methods . We r and omized a representative sample of the Canadian general population to 1 of 3 surveys that sought choices between hypothetical treatments for rheumatoid arthritis based on different levels of 7 attributes : route and frequency of administration , chance of benefit , serious and minor side effects and life expectancy , and imprecision in benefit and side-effect estimates . The surveys differed in the way imprecision was described : 1 ) no imprecision , 2 ) quantitative description based on a range with a visual graphic , and 3 ) qualitative description simply describing the confidence in the evidence . Results . The analyzed data were from 2663 respondents . Results suggested that more people understood imprecision when it was described qualitatively ( 88 % ) versus quantitatively ( 68 % ) . Respondents who appeared to underst and imprecision descriptions placed high value on increased precision regarding the actual benefits and harms of treatment , equivalent to the value placed on the information about the probability of serious side effects . Both qualitative and quantitative methods led to small but significant increases in decision uncertainty for choosing any treatment . Limitations included some issues in defining underst and ing of imprecision and the use of an internet survey of panel members . Conclusions . These findings provide insight into how conveying imprecision information influences patient treatment choices Background Efficacy of breast screening may differ in practice from the results of r and omized trials . We report one of the largest case – control evaluations of a screening service . Methods Subjects included 491 breast-cancer deaths affecting 45–80-year-old South Australian females during 2002–2005 ( diagnosed after BreastScreen commencement ) and 1,473 live controls ( three per death ) r and omly selected from the State Electoral Roll after birth- date matching . Cancer Registry and BreastScreen records provided cancer and screening details . Risk estimates were calculated by BreastScreen participation , using conditional logistic regression . Interpretation was assisted by a population survey of risk factor prevalence by BreastScreen participation in 1,684 females aged ≥40 years . Results The relative odds ( OR ) ( 95 % confidence limits ) of breast-cancer death in BreastScreen participants compared with non- participants were 0.59 ( 0.47 , 0.74 ) . Compared with non- participants , the OR was 0.70 ( 0.47 , 1.05 ) for women last screened through BreastScreen more than 3 years before diagnosis of the index case , and 0.57 ( 0.44 , 0.72 ) for women screened more recently . The OR of 0.47 ( 0.34 , 0.65 ) for women screened more frequently in the pre-diagnosis phase was lower than the 0.64 ( 0.50 , 0.82 ) for other screened women . The overall OR of 0.59 approximated 0.70 when corrected for the screening self- selection bias observed in five r and omized trials . However , multivariable analysis of survey data did not indicate a lower prevalence of breast-cancer risk factors among BreastScreen participants , suggesting that this correction may be inappropriate . Conclusions Participation in screening was associated with a breast-cancer mortality reduction of between 30 and 41 % , depending on assumptions about screening self- selection bias . A downward mortality risk by recency of last screen prior to cancer diagnosis , and frequency of recent screening , is consistent with a screening effect Background : False-positive recall is a recognized disadvantage of mammographic breast screening , and the rate of such recalls may be higher in younger women , potentially limiting the value of screening below age 50 . Methods : Attendance and screening outcome data for 53,884 women in the intervention arm of the U.K. Age trial were analyzed to report observed false-positive recall rates during 13 years of trial fieldwork . The Age trial was a r and omized controlled trial of the effect of mammographic screening from age 40 on breast cancer mortality , conducted in 23 National Health Service screening centers between 1991 and 2004 . Women r and omized to the intervention arm were offered annual invitation to mammography from age 40 or 41 to age 48 . Results : Overall , 7,893 women ( 14.6 % of women the intervention arm and 18.1 % of women attending at least one routine screen ) experienced one or more false-positive screen during the trial . The rates of false-positive mammography at first and subsequent routine screens were 4.9 % and 3.2 % , respectively . The cumulative false-positive rate over seven screens was 20.5 % . Eighty-nine percent of women who had a false-positive recall at their previous screen attended their next invitation to routine screening . Conclusions : The rates of false-positive recall in the Age trial were comparable with the national screening program ; however , the positive predictive value of referral was lower . Experiencing a false-positive screen did not seem to lessen the likelihood of re-attendance in the trial . Impact : The question of greatly increased false-positive rates in this age group and of their compromising re-attendance is refuted by the findings of this study . Cancer Epidemiol Biomarkers Prev ; 19(11 ) ; 2758–64 . © 2010 AACR Objectives To estimate the absolute numbers of breast cancer deaths prevented and the absolute numbers of tumours overdiagnosed in mammographic screening for breast cancer at ages 50–69 years . Setting The Swedish Two-County r and omized trial of mammographic screening for breast cancer , and the UK Breast Screening Programme in Engl and , ages 50–69 years . Methods We estimated the absolute numbers of deaths avoided and additional cases diagnosed in the study group ( active study population ) of the Swedish Two-County Trial , by comparison with the control group ( passive study population ) . We estimated the same quantities for the mortality and incidence rates in Engl and ( 1974–2004 and 1974–2003 , respectively ) . We used Poisson regression for statistical inference . Results A substantial and significant reduction in breast cancer mortality was associated with screening in both the Two-County Trial ( P < 0.001 ) and the screening programme in Engl and ( P < 0.001 ) . The absolute benefits were estimated as 8.8 and 5.7 breast cancer deaths prevented per 1000 women screened for 20 years starting at age 50 from the Two-County Trial and screening programme in Engl and , respectively . The corresponding estimated numbers of cases overdiagnosed per 1000 women screened for 20 years were , respectively , 4.3 and 2.3 per 1000 . Conclusions The benefit of mammographic screening in terms of lives saved is greater in absolute terms than the harm in terms of overdiagnosis . Between 2 and 2.5 lives are saved for every overdiagnosed case IMPORTANCE False-positive mammograms , a common occurrence in breast cancer screening programs , represent a potential screening harm that is currently being evaluated by the US Preventive Services Task Force . OBJECTIVE To measure the effect of false-positive mammograms on quality of life by measuring personal anxiety , health utility , and attitudes toward future screening . DESIGN , SETTING , AND PARTICIPANTS The Digital Mammographic Imaging Screening Trial ( DMIST ) quality -of-life sub study telephone survey was performed shortly after screening and 1 year later at 22 DMIST sites and included r and omly selected DMIST participants with positive and negative mammograms . EXPOSURE Mammogram requiring follow-up testing or referral without a cancer diagnosis . MAIN OUTCOMES AND MEASURES The 6- question short form of the Spielberger State-Trait Anxiety Inventory state scale ( STAI-6 ) and the EuroQol EQ-5D instrument with US scoring . Attitudes toward future screening as measured by women 's self-report of future intention to undergo mammographic screening and willingness to travel and stay overnight to undergo a hypothetical new type of mammography that would identify as many cancers with half the false-positive results . RESULTS Among 1450 eligible women invited to participate , 1226 ( 84.6 % ) were enrolled , with follow-up interviews obtained in 1028 ( 83.8 % ) . Anxiety was significantly higher for women with false-positive mammograms ( STAI-6 , 35.2 vs 32.7 ) , but health utility scores did not differ and there were no significant differences between groups at 1 year . Future screening intentions differed by group ( 25.7 % vs 14.2 % more likely in false-positive vs negative groups ) ; willingness to travel and stay overnight did not ( 9.9 % vs 10.5 % in false-positive vs negative groups ) . Future screening intention was significantly increased among women with false-positive mammograms ( odds ratio , 2.12 ; 95 % CI , 1.54 - 2.93 ) , younger age ( 2.78 ; 1.5 - 5.0 ) , and poorer health ( 1.63 ; 1.09 - 2.43 ) . Women 's anticipated high-level anxiety regarding future false-positive mammograms was associated with willingness to travel overnight ( odds ratio , 1.94 ; 95 % CI , 1.28 - 2.95 ) . CONCLUSIONS AND RELEVANCE False-positive mammograms were associated with increased short-term anxiety but not long-term anxiety , and there was no measurable health utility decrement . False-positive mammograms increased women 's intention to undergo future breast cancer screening and did not increase their stated willingness to travel to avoid a false-positive result . Our finding of time-limited harm after false-positive screening mammograms is relevant for clinicians who counsel women on mammographic screening and for screening guideline development groups The aim of the study was to develop a model for estimating the effect of the nation-wide service screening program with mammography on breast cancer mortality in Sweden . In 1997 , the introduction of population -based service screening had been completed in all 26 counties . In approximately half of the counties suitable for evaluation , the lower age limit for invitation was 40 years ( study population ) and in the other half the age limit was 50 years ( control population ) . The numbers of females aged 40 49 years for the two population s were 202,152 and 237,279 , respectively ( 1988 ) . The study and control population s were compared for the period 1986 - 1996 with regard to refined breast cancer mortality . To adjust for geographical differences , the period 1976 1986 was used as reference . With a mean follow-up time of 8 years , the estimated relative risk of breast cancer death in relation to invitation to service screening among women aged 40 - 49 years at breast cancer diagnosis was 0.91 ( 95 % confidence interval 0.72 - 1.15 ) . These findings were compatible with those presented in the previous overview of the Swedish r and omized studies BACKGROUND Age-specific effects of mammographic screening , and the timing of such effects , are a matter of debate . The results of the UK Age trial , which compared the effect of invitation to annual mammographic screening from age 40 years with commencement of screening at age 50 years on breast cancer mortality , have been reported at 10 years of follow-up and showed no significant difference in mortality between the trial groups . Here , we report the results of the UK Age trial after 17 years of follow-up . METHODS Women aged 39 - 41 from 23 UK NHS Breast Screening Programme units years were r and omly assigned by individual r and omisation ( 1:2 ) to either an intervention group offered annual screening by mammography up to and including the calendar year of their 48th birthday or to a control group receiving usual medical care ( invited for screening at age 50 years and every 3 years thereafter ) . Both groups were stratified by general practice . We compared breast cancer incidence and mortality by time since r and omisation . Analyses included all women r and omly assigned who could be traced with the National Health Service Central Register and who had not died or emigrated before entry . The primary outcome measures were mortality from breast cancer ( defined as deaths with breast cancer coded as the underlying cause of death ) and breast cancer incidence , including in-situ , invasive , and total incidence . Because there is an interest in the timing of the mortality effect , we analysed the results in different follow-up periods . This trial is registered , number IS RCT N24647151 . FINDINGS Between Oct 14 , 1990 , and Sept 25 , 1997 , 160 921 participants were r and omly assigned ; 53 883 women in the intervention group and 106 953 assigned to usual medical care were included in this analysis . After a median follow-up of 17 years ( IQR 16·8 - 18·8 ) , the rate ratio ( RR ) for breast cancer mortality was 0·88 ( 95 % CI 0·74 - 1·04 ) from tumours diagnosed during the intervention phase . A significant reduction in breast cancer mortality was noted in the intervention group compared with the control group in the first 10 years after diagnosis ( RR 0·75 , 0·58 - 0·97 ) but not thereafter ( RR 1·02 , 0·80 - 1·30 ) from tumours diagnosed during the intervention phase . The overall breast cancer incidence during 17 year follow-up was similar between the intervention group and the control group ( RR 0·98 , 0·93 - 1·04 ) . INTERPRETATION Our results support an early reduction in mortality from breast cancer with annual mammography screening in women aged 40 - 49 years . Further data are needed to fully underst and long-term effects . Cumulative incidence figures suggest at worst a small amount of overdiagnosis . FUNDING National Institute for Health Research Health Technology Assessment programme and the American Cancer Society . Past funding was received from the Medical Research Council , Cancer Research UK , the UK Department of Health , and the US National Cancer Institute Ductal carcinoma in situ ( DCIS ) is a condition in which abnormal cells line the milk ducts of the breast but have not invaded the underlying breast tissue . Approximately 55000 new cases of DCIS were expected to occur among U.S. women in 2013 , which accounted for approximately 24 % of all new breast cancer diagnoses ( 1 ) . Although the annual incidence of DCIS is less than that of invasive breast cancer , exp and ed use of screening mammography has led to a dramatic increase in the diagnosis of DCIS ( 32.5 cases per 100000 women ) ( 2 ) . There is considerable uncertainty about the optimal clinical management of DCIS because of the lack of reliable methods for distinguishing DCIS that would never become symptomatic from DCIS that is likely to progress to life-threatening invasive cancer ( 3 ) . Current treatment options for DCIS include mastectomy , breast-conserving surgery ( BCS ) , and BCS plus radiation therapy ( 2 , 46 ) . There are limited r and omized , controlled trials ( RCTs ) on which to base decisions about the tradeoffs among DCIS treatment options , and the existing trials may not capture all relevant patient-centered outcomes . For example , 4 large RCTs comparing BCS alone with BCS plus radiation therapy all show similar , very high overall survival regardless of treatment ( 710 ) . The addition of radiation therapy significantly reduces the risk for local recurrence ; approximately one half of all recurrences are DCIS rather than invasive cancer ( 5 , 11 ) . The long-term benefit of preventing the recurrence of an asymptomatic condition that may or may not progress to cancer is difficult to quantify . In other conditions where screening may detect early cancer or cancer precursors that may not progress to a life-threatening stage , such as early-stage prostate cancer , active surveillance or watchful waiting ( an observation strategy ) is an acceptable option for some patients . A similar strategy may be acceptable for some women diagnosed with DCIS , although no studies have compared management strategies that involve no immediate treatment ( that is , observation or active surveillance ) versus immediate treatments . The most important potential benefit of treatment of DCIS is the reduction in the number of deaths due to invasive breast cancer . For many women with a DCIS diagnosis , this may be an unrealized benefit . Some proportion of DCIS may never progress to life-threatening invasive cancer , so these women only have the adverse outcomes of diagnosis and treatments . Both active management strategies and surveillance approaches present tradeoffs relevant to patient-centered outcomes , such as symptoms , function , and well-being . Given the clinical importance of DCIS , the diversity of available treatment strategies , variety of patient-centered outcomes of interest , and areas of uncertainty , we sought to create a prioritized research agenda for the Patient-Centered Outcomes Research Institute ( PCORI ) that would incorporate different stakeholders ' perspectives . A central goal of PCORI is to engage stakeholders in its work in a meaningful way . Between September 2012 and January 2013 , PCORI undertook a broad effort tosolicit research topics to consider for targeted funding from patients , caregivers , research ers , and results of previous prioritization processes by groups , such as the Institute of Medicine . In April 2013 , PCORI 's Assessment of Prevention , Diagnosis , and Treatment Options program , together with the program 's external advisory panel , have identified DCIS management as an important topic with unmet research needs . Then , PCORI tasked the Duke University Evidence Synthesis Group ( ESG ) to work with various stakeholders to identify and prioritize the future research that is most needed by patients and other decision makers on this topic . Methods Overview of Prioritization Approach Our approach to prioritizing future research and developing recommendations for targeted future funding by PCORI included several steps ( Figure 1 ) . These included appraisal s of recent systematic review s to preliminarily identify important evidence gaps , transformation of evidence gaps into research questions and organization of the questions within a comprehensive analytic framework , engagement of stakeholders to identify additional gaps and prioritize research needs or questions , scans of recently published and ongoing studies relevant to the stakeholders ' list of prioritized research needs , and identification of potential study design s to address prioritized research questions . Figure 1 . Overview of prioritization process Adapted from reference 12 . ESG = Evidence Synthesis Group ; PCORI = Patient-Centered Outcomes Research Institute . Identification of Evidence Gaps We used an iterative process to identify evidence gaps for DCIS management . First , we identified and appraised recent published systematic review s , clinical practice guidelines , and future research needs documents to develop an initial list of evidence gaps . This list was neither exhaustive nor prioritized . Next , we organized these gaps according to the population s , interventions , comparators , outcomes , timing , and setting of interest and transformed them into research questions informed by the criteria . Selection and Engagement of Stakeholders We convened a group of 9 stakeholders , including clinical experts and research ers in DCIS management strategies , representatives from federal and nongovernmental funding agencies , representatives from relevant professional societies , health care decision makers and policymakers , and representatives from related consumer and patient advocacy groups ( Table 1 of the Supplement ) . Within each of these categories , we sought to identify a person who was either familiar with the clinical area and its current uncertainties or brought a specific method ological expertise to the stakeholder panel . The University of Minnesota Evidence -based Practice Center , which did a comparative effectiveness review on DCIS management in 2009 ( 13 ) , and PCORI 's patient engagement group provided input on potential stakeholders . Each potential stakeholder completed a disclosure statement and was screened for conflicts of interest . We solicited and received stakeholder input at various points in the process through group discussion s via teleconferences detailing the process and outlining existing evidence gaps , Web-based surveys to obtain priority ranking of topics , and e-mail communications to solicit or provide further clarification of research gaps from teleconferences . Supplement . Supplementary Data for Prioritization of Research Addressing the Management of DCIS Development of an Analytic Framework On the basis of the exp and ed list of 30 evidence gaps and informed by an analytic framework in a recent evidence synthesis on DCIS ( 13 ) , we constructed an analytic framework that depicted the identified knowledge gaps within the context of the population s , interventions , comparators , outcomes , timing , and setting criteria ( Figure 2 ) . This framework shows that women diagnosed with DCIS may have pretreatment evaluations . After these evaluations , women may undergo several management strategies . These management strategies affect patient-centered outcomes ( such as development of comorbid conditions , DCIS recurrence , invasive cancer , and sexual functioning ) . Throughout the analytic framework , population factors ( such as socioeconomic , family history , and genetic factors ) and effects of decisional uncertainty about management strategies were highlighted as potential modifiers . Figure 2 . Analytic framework . DCIS = ductal carcinoma in situ ; FRN = future research need ; MRI = magnetic resonance imaging . Prioritization of Future Research After expansion of the identified research priorities , stakeholders were invited to rank the revised future research needs online . The survey used a forced-ranking prioritization method described by the Agency for Healthcare Research and Quality Evidence -based Practice Center 's Future Research Needs projects ( 14 ) , whereby participants were given 10 votes that could be allocated to any identified research priorities , with a maximum of 3 votes per item . The stakeholders were not given specific prioritization criteria to use but rather were told to decide , on the basis of their perspectives , which were the most important unanswered research questions in DCIS management . Only the priorities in the top tier ( n= 10 ) moved on to the final stage of horizon scan and study design determination . Stakeholders were informed of the final ranking of future research priorities . Horizon Scan of Studies Potentially Relevant to Top-Tier Research Questions We performed 2 data base search es to identify recently published and ongoing studies relevant to the top-tier future research questions result ing from the stakeholder forced-ranking prioritization exercise . We search ed PubMed to identify relevant literature published since 2008 and Clinical Trials.gov for ongoing studies . Members of the ESG team review ed the titles and abstract s identified by search ing PubMed for applicability to the top-tier research questions ; full texts were then obtained and screened for all citations passing the title- and - abstract screening . At both the title- and - abstract and full-text screening stages , articles were included if they met all of the following criteria : presented original data or secondary analysis of data from an RCT , prospect i ve or retrospective observational study , or relevant modeling study ; included data for a pretreatment evaluation or management strategy of interest ; included women with DCIS ; and had a stated objective that could be categorized according to our identified list of research priorities . We search ed Clinical Trials.gov using the keywords ductal carcinoma in situ and DCIS . A member of the ESG team review ed all study abstract s result ing from the search and coded them as potentially relevant to 1 or more of the identified research priorities . We then abstract ed study type ( such as BACKGROUND The efficacy of breast cancer screening in the community may differ from that suggested by the results of r and omized trials , and no data have been available on efficacy among women who have different levels of breast cancer risk . METHODS We conducted a matched case-control study among women enrolled in six health plans in Washington , Oregon , California , Massachusetts , and Minnesota . We examined the efficacy of screening by mammography and /or clinical breast examination among women in two age cohorts ( 40 - 49 years and 50 - 65 years ) and in two breast cancer risk levels ( average and increased risk ) . Women who died from breast cancer from January 1 , 1983 , through December 31 , 1998 , ( N = 1351 ; case subjects ) were matched to control subjects ( N = 2501 ) on age and risk level . Increased risk was defined as a family history of breast cancer or a breast biopsy noted in the medical records before the index date ( defined as date of first suspicion of breast abnormalities in case subjects , with the same date used for matched control subjects ) . Data on screening , risk status , and other variables were abstract ed from medical records . Conditional logistic regression was used to examine the association between breast cancer mortality and receipt of screening . All statistical tests were two-sided . RESULTS There were small , non-statistically significant associations between breast cancer mortality and receipt of screening during the 3 years prior to the index date for both the younger women [ odds ratio ( OR ) = 0.92 ; 95 % confidence interval ( CI ) = 0.76 to 1.13 ] and the older women ( OR = 0.87 ; 95 % CI = 0.68 to 1.12 ) . The association among women at increased risk ( OR = 0.74 ; 95 % CI = 0.50 to 1.03 ) was stronger than that among women at average risk ( OR = 0.96 ; 95 % CI = 0.80 to 1.14 ) , but the difference was not statistically significant ( P = .17 ) . CONCLUSIONS In this community-based study , screening history was not associated with breast cancer mortality . However , potential limitations of this study argue for a cautious interpretation of these findings Objective To compare breast cancer incidence and mortality up to 25 years in women aged 40 - 59 who did or did not undergo mammography screening . Design Follow-up of r and omised screening trial by centre coordinators , the study ’s central office , and linkage to cancer registries and vital statistics data bases . Setting 15 screening centres in six Canadian provinces,1980 - 85 ( Nova Scotia , Quebec , Ontario , Manitoba , Alberta , and British Columbia ) . Participants 89 835 women , aged 40 - 59 , r and omly assigned to mammography ( five annual mammography screens ) or control ( no mammography ) . Interventions Women aged 40 - 49 in the mammography arm and all women aged 50 - 59 in both arms received annual physical breast examinations . Women aged 40 - 49 in the control arm received a single examination followed by usual care in the community . Main outcome measure Deaths from breast cancer . Results During the five year screening period , 666 invasive breast cancers were diagnosed in the mammography arm ( n=44 925 participants ) and 524 in the controls ( n=44 910 ) , and of these , 180 women in the mammography arm and 171 women in the control arm died of breast cancer during the 25 year follow-up period . The overall hazard ratio for death from breast cancer diagnosed during the screening period associated with mammography was 1.05 ( 95 % confidence interval 0.85 to 1.30 ) . The findings for women aged 40 - 49 and 50 - 59 were almost identical . During the entire study period , 3250 women in the mammography arm and 3133 in the control arm had a diagnosis of breast cancer , and 500 and 505 , respectively , died of breast cancer . Thus the cumulative mortality from breast cancer was similar between women in the mammography arm and in the control arm ( hazard ratio 0.99 , 95 % confidence interval 0.88 to 1.12 ) . After 15 years of follow-up a residual excess of 106 cancers was observed in the mammography arm , attributable to over-diagnosis . Conclusion Annual mammography in women aged 40 - 59 does not reduce mortality from breast cancer beyond that of physical examination or usual care when adjuvant therapy for breast cancer is freely available . Overall , 22 % ( 106/484 ) of screen detected invasive breast cancers were over-diagnosed , representing one over-diagnosed breast cancer for every 424 women who received mammography screening in the trial PURPOSE To assess cancer detection rates , false-positive rates before arbitration , positive predictive values for women recalled after arbitration , and the type of cancers detected with use of digital mammography alone and combined with tomo synthesis in a large prospect i ve screening trial . MATERIAL S AND METHODS A prospect i ve , reader- and modality-balanced screening study of participants undergoing combined mammography plus tomo synthesis , the results of which were read independently by four different radiologists , is under way . The study was approved by a regional ethics committee , and all participants provided written informed consent . The authors performed a preplanned interim analysis of results from 12,631 examinations interpreted by using mammography alone and mammography plus tomo synthesis from November 22 , 2010 , to December 31 , 2011 . Analyses were based on marginal log-linear models for binary data , accounting for correlated interpretations and adjusting for reader-specific performance levels by using a two-sided significance level of .0294 . RESULTS Detection rates , including those for invasive and in situ cancers , were 6.1 per 1000 examinations for mammography alone and 8.0 per 1000 examinations for mammography plus tomo synthesis ( 27 % increase , adjusted for reader ; P = .001 ) . False-positive rates before arbitration were 61.1 per 1000 examinations with mammography alone and 53.1 per 1000 examinations with mammography plus tomo synthesis ( 15 % decrease , adjusted for reader ; P < .001 ) . After arbitration , positive predictive values for recalled patients with cancers verified later were comparable ( 29.1 % and 28.5 % , respectively , with mammography alone and mammography plus tomo synthesis ; P = .72 ) . Twenty-five additional invasive cancers were detected with mammography plus tomo synthesis ( 40 % increase , adjusted for reader ; P < .001 ) . The mean interpretation time was 45 seconds for mammography alone and 91 seconds for mammography plus tomo synthesis ( P < .001 ) . CONCLUSION The use of mammography plus tomo synthesis in a screening environment result ed in a significantly higher cancer detection rate and enabled the detection of more invasive cancers . Clinical trial registration no. NCT01248546 BACKGROUND Few studies have evaluated interventions to decrease a woman 's anxiety after she receives an abnormal mammogram ( i.e. , one with a recommendation for follow-up ) . We performed a controlled trial to compare the effects of both an immediate reading of mammograms ( i.e. , a radiology intervention ) and of an educational intervention that taught skills to cope with anxiety on the psychological status of women whose mammograms were normal or abnormal . METHODS Eligible women ( n = 8543 ) aged 39 years or older were recruited from seven mammography sites at the time of their scheduled mammography screening and assigned to receive no intervention , either the radiology or the educational intervention , or both interventions . We used the Impact of Events Scale ( IES ) and the Hopkins Symptom Checklist subscales for Anxiety ( HSC-A ) and Depression ( HSC-D ) in structured telephone interviews of 2844 women to assess the psychological status of all women with abnormal mammograms ( excluding women diagnosed with breast cancer ) and of a r and om sample of women with normal mammograms at 3 weeks and 3 months after their mammograms . All statistical tests were two-sided . RESULTS We obtained usable 3-week interviews for 2390 ( 84 % ) women . By the 3-week interview , 1037 ( 72.1 % ) of the 1439 interviewed women with abnormal mammograms had completed the recommended work-up and knew that their abnormal mammograms were false positives . Women with abnormal mammograms had higher IES and HSC-A scores ( i.e. , more anxiety ) than women with normal mammograms ( mean IES scores : 4.97 [ 95 % confidence interval [ CI ] = 4.47 to 5.50 ] and 1.82 [ 95 % CI = 1.51 to 2.14 ] , respectively ; P<.001 ; mean HSC-A scores : 1.14 [ 95 % CI = 1.12 to 1.15 ] and 1.11 [ 95 % CI = 1.09 to 1.13 ] , respectively , P=.002 ) . Among women with false-positive mammograms , those who had received the radiology intervention reported less anxiety than those who had not ( mean IES scores : 4.42 [ 95 % CI = 3.73 to 5.07 ] and 5.53 [ 95 % CI = 4.82 to 6.28 ] , respectively , P=.026 ) . The educational intervention was not associated with any difference in psychological outcomes . Three months after the mammogram , by which time more than 80 % of the women with abnormal results knew their mammograms to be false positives , anxiety levels of women with false-positive mammograms remained higher than those of women with normal mammograms ( mean IES scores : 2.34 [ 95 % CI = 1.99 to 2.69 ] and 1.15 [ 95 % CI = 0.87 to 1.47 ] , respectively , P<.001 ) . CONCLUSION Immediate reading of screening mammograms , but not an educational intervention targeting coping skills , was associated with less anxiety among women with false-positive mammograms 3 weeks after mammography A cluster r and omized controlled trial was initiated in the Triv and rum district ( Kerala , India ) on January 1 , 2006 , to evaluate whether three rounds of triennial clinical breast examination ( CBE ) can reduce the incidence rate of advanced disease incidence and breast cancer mortality . A total of 275 clusters that included 115,652 healthy women , aged 30 - 69 years , were r and omly allocated to intervention ( CBE ; 133 clusters ; 55,844 women ) or control ( no screening ; 142 clusters ; 59,808 women ) groups . Performance characteristics ( sensitivity , specificity , false-positive rate , and positive predictive value ) of CBE were evaluated . An intention-to-treat analysis was performed for comparison of incidence rates between the intervention and control groups . Preliminary results for incidence are based on follow-up until May 31 , 2009 , when the first round of screening was completed . Of the 50,366 women who underwent CBE , 30 breast cancers were detected among 2880 women with suspicious findings in CBE screening that warranted further investigations . Sensitivity , specificity , false-positive rate , and positive predictive value of CBE were 51.7 % ( 95 % confidence interval [ CI ] = 38.2 % to 65.0 % ) , 94.3 % ( 95 % CI = 94.1 % to 94.5 % ) , 5.7 % ( 95 % CI = 5.5 % to 5.9 % ) , and 1.0 % ( 95 % CI = 0.7 % to 1.5 % ) , respectively . The age-st and ardized incidence rates for early-stage ( stage IIA or lower ) breast cancer were 18.8 and 8.1 per 100,000 women and for advanced-stage ( stage IIB or higher ) breast cancer were 19.6 and 21.7 per 100,000 women , in the intervention and control groups , respectively Although breast cancer screening has been shown to work in r and omised trials , there is a need to evaluate service screening programmes to ensure that they are delivering the benefit indicated by the trials . We carried out a case – control study to investigate the effect of mammography service screening , in the NHS breast screening programme , on breast cancer mortality in the East Anglian region of the UK . Cases were deaths from breast cancer in women diagnosed between the ages of 50 and 70 years , following the instigation of the East Anglia Breast Screening Programme in 1989 . The controls were women ( two per case ) who had not died of breast cancer , from the same area , matched by date of birth to the cases . Each control was known to be alive at the time of death of her matched case . All women were known to the breast screening programme and were invited , at least once , to be screened . There were 284 cases and 568 controls . The odds ratio ( OR ) for risk of death from breast cancer in women who attended at least one routine screen compared to those who did not attend was 0.35 ( CI : 0.24 , 0.50 ) . Adjusting for self- selection bias gave an estimate of the breast cancer mortality reduction associated with invitation to screening of 35 % ( OR=0.65 , 95 % CI : 0.48 , 0.88 ) . The effect of actually being screened was a 48 % breast cancer mortality reduction ( OR=0.52 , 95 % CI : 0.32 , 0.84 ) . The results suggest that the National Breast Screening Programme in East Anglia is achieving a reduction in breast cancer deaths , which is at least consistent with the results from the r and omised controlled trials of mammographic screening Background Uncertainty exists about the appropriate use of screening mammography among older women because comorbid illnesses may diminish the benefit of screening . We examined the risk of adverse tumor characteristics and false positive rates according to screening interval , age , and comorbidity . Methods From January 1999 to December 2006 , data were collected prospect ively on 2993 older women with breast cancer and 137 949 older women without breast cancer who underwent mammography at facilities that participated in a data linkage between the Breast Cancer Surveillance Consortium and Medicare cl aims . Women were aged 66 to 89 years at study entry to allow for measurement of 1 year of preexisting illnesses . We used logistic regression analyses to calculate the odds of advanced ( IIb , III , IV ) stage , large ( > 20 millimeters ) tumors , and 10-year cumulative probability of false-positive mammography by screening frequency ( 1 vs 2 years ) , age , and comorbidity score . The comorbidity score was derived using the Klabunde approximation of the Charlson score . All statistical tests were two-sided . Results Adverse tumor characteristics did not differ statistically significantly by comorbidity , age , or interval . Cumulative probability of a false-positive mammography result was higher among annual screeners than biennial screeners irrespective of comorbidity : 48.0 % ( 95 % confidence interval [ CI ] = 46.1 % to 49.9 % ) of annual screeners aged 66 to 74 years had a false-positive result compared with 29.0 % ( 95 % CI = 28.1 % to 29.9 % ) of biennial screeners . Conclusion Women aged 66 to 89 years who undergo biennial screening mammography have similar risk of advanced-stage disease and lower cumulative risk of a false-positive recommendation than annual screeners , regardless of comorbidity PURPOSE To retrospectively determine the long-term risk of false-positive mammographic assessment s and to evaluate the effect of screening regularity on the risk of false-positive events . MATERIAL S AND METHODS Institutional review board approval was obtained , and informed consent was waived . Retrospective analysis was performed for the occurrence of false-positive assessment s among 83,511 women who underwent 314,185 mammographic examinations from January 1 , 1985 , to February 19 , 2002 . Data were collected from a data base that had been assembled prospect ively . Two categories of false-positive events were examined : biopsies that did not reveal cancer and false-positive mammographic assessment s. Rates of false-positive events were compared by using a chi2 analysis , and 95 % confidence limits were calculated . Because comparisons of multiple pairs were considered , all P values that demonstrated statistical significance exceeded the requirement of the Bonferroni correction . RESULTS While the overall rates of biopsies that did not reveal cancer and of false-positive mammographic assessment s were similar to those found in other studies , most of the burden of false-positive events was borne by women who underwent intermittent screening . Long-term rates of false-positive events were lower among women who underwent regular screening than among those who underwent intermittent screening . In the 5-year group , 2.9 % of women who underwent five mammographic examinations over the next 5 years had biopsy results that did not reveal cancer , whereas 4.6 % of women who underwent three mammographic examinations over the next 5 years had biopsy results that did not reveal cancer . For women who underwent regular screening , the risk of undergoing biopsies that did not reveal cancer declined over time to 0.25 % per year after several years of screening , a value that is lower than the risk of these events among women who did not undergo screening . The rate of false-positive mammographic assessment s was also lower for women who underwent regular screening than for those who underwent intermittent screening . CONCLUSION Prompt annual attendance for mammographic screening reduces the occurrence of false-positive mammographic results Although there is evidence for a reduction in breast carcinoma mortality with mammographic screening , some doubts have been expressed , and there is still uncertainty regarding the age specific effects AIM This prospect i ve double-blind study was design ed to assess ( i ) if primary breast screening by ultrasonography is capable of detecting breast cancer independent of tissue density and ( ii ) if the rate of unnecessary biopsies remains acceptable when diagnostics are based on ultrasonography . PATIENTS AND METHODS Bilateral breast ultrasonography was performed in 448 asymptomatic women as the initial diagnostic method . Sonograms were interpreted using a set of st and ardized diagnostic criteria . Subsequently , mammograms were obtained . The radiologists reading the mammograms were blinded to the sonographic results . RESULTS Overall , 3 non-palpable breast cancers were detected by ultrasound and mammography . All 3 ultrasonographically detected breast cancers were smaller than 1 cm ( 0.7 , 0.7 , 0.6 cm ) . All 3 carcinomas were correctly detected by both methods . For ultrasonography , the false positive rate was 1.1 % ( n=5 ) and for mammography 0.6 % ( n=3 ) . When both methods were combined , the rate of unnecessary open biopsies was 1.6 % ( n=7 ) . The ratio of benign to malignant lesions was 3.7/1 . CONCLUSION Without prior mammography , primary high-resolution breast ultrasonography is capable of detecting non-palpable breast carcinomas in asymptomatic women at an early stage . The rate of unnecessary open biopsies is low and the ratio of benign to malignant biopsies acceptable BACKGROUND Digital breast tomo synthesis with 3D images might overcome some of the limitations of conventional 2D mammography for detection of breast cancer . We investigated the effect of integrated 2D and 3D mammography in population breast-cancer screening . METHODS Screening with Tomo synthesis OR st and ard Mammography ( STORM ) was a prospect i ve comparative study . We recruited asymptomatic women aged 48 years or older who attended population -based breast-cancer screening through the Trento and Verona screening services ( Italy ) from August , 2011 , to June , 2012 . We did screen-reading in two sequential phases-2D only and integrated 2D and 3D mammography-yielding paired data for each screen . St and ard double-reading by breast radiologists determined whether to recall the participant based on positive mammography at either screen read . Outcomes were measured from final assessment or excision histology . Primary outcome measures were the number of detected cancers , the number of detected cancers per 1000 screens , the number and proportion of false positive recalls , and incremental cancer detection attributable to integrated 2D and 3D mammography . We compared paired binary data with McNemar 's test . FINDINGS 7292 women were screened ( median age 58 years [ IQR 54 - 63 ] ) . We detected 59 breast cancers ( including 52 invasive cancers ) in 57 women . Both 2D and integrated 2D and 3D screening detected 39 cancers . We detected 20 cancers with integrated 2D and 3D only versus none with 2D screening only ( p<0.0001 ) . Cancer detection rates were 5.3 cancers per 1000 screens ( 95 % CI 3.8 - 7.3 ) for 2D only , and 8.1 cancers per 1000 screens ( 6.2 - 10.4 ) for integrated 2D and 3D screening . The incremental cancer detection rate attributable to integrated 2D and 3D mammography was 2.7 cancers per 1000 screens ( 1.7 - 4.2 ) . 395 screens ( 5.5 % ; 95 % CI 5.0 - 6.0 ) result ed in false positive recalls : 181 at both screen reads , and 141 with 2D only versus 73 with integrated 2D and 3D screening ( p<0.0001 ) . We estimated that conditional recall ( positive integrated 2D and 3D mammography as a condition to recall ) could have reduced false positive recalls by 17.2 % ( 95 % CI 13.6 - 21.3 ) without missing any of the cancers detected in the study population . INTERPRETATION Integrated 2D and 3D mammography improves breast-cancer detection and has the potential to reduce false positive recalls . R and omised controlled trials are needed to compare integrated 2D and 3D mammography with 2D mammography for breast cancer screening . FUNDING National Breast Cancer Foundation , Australia ; National Health and Medical Research Council , Australia ; Hologic , USA ; Technologic , Italy BACKGROUND The Edinburgh r and omised trial of breast-cancer screening recruited women aged 45 - 64 years from 1978 to 1981 ( cohort 1 ) , and those aged 45 - 49 years during 1982 - 85 ( cohorts 2 and 3 ) . Results based on 14 years of follow-up and 270,000 woman-years of observation are reported . METHODS Breast-cancer mortality rates in the intervention group ( 28,628 women offered screening ) were compared with those in the control group ( 26,026 ) with adjustment for socioeconomic status ( SES ) of general medical practice s. Rate ratios were derived by means of logistic regression for the total trial population and for women first offered screening while younger than 50 years . Analyses were by intention to treat . FINDINGS Initial unadjusted results showed a difference of just 13 % in breast-cancer mortality rates between the intervention and control groups ( 156 deaths [ 5.18 per 10,000 ] vs 167 [ 6.04 per 10,000 ] ; rate ratio 0.87 [ 95 % CI 0.70 - 1.06 ] ) , but the results were influenced by differences in SES by trial group . After adjustment for SES , the rate ratio was 0.79 ( 95 % CI 0.60 - 1.02 ) . When deaths after diagnosis more than 3 years after the end of the study were censored the rate ratio became 0.71 ( 0.53 - 0.95 ) . There was no evidence of heterogeneity by age at entry and no evidence that younger entrants had smaller or delayed benefit ( rate ratio 0.70 [ 0.41 - 1.20 ] ) . No breast-cancer mortality benefit was observed for women whose breast cancers were diagnosed when they were younger than 50 years . Other-cause mortality rates did not differ by trial group when adjusted for SES . INTERPRETATION Our findings confirm results from r and omised trials in Sweden and the USA that screening for breast cancer lowers breast-cancer mortality . Similar results are reported by the UK geographical comparison , UK Trial of Early Detection of Breast Cancer . The results for younger women suggest benefit from introduction of screening before 50 years of age BACKGROUND Screening with mammography has been shown by r and omized controlled trials to reduce breast cancer mortality in women aged 40 to 74 years . Estimates from observational studies following screening implementation in different countries have produced varyied findings . We report findings for seven Canadian breast screening programs . METHODS Canadian breast screening programs were invited to participate in a study aim ed at comparing breast cancer mortality in participants and non participants . Seven of 12 programs , representing 85 % of the Canadian population , participated in the study . Data were obtained from the screening programs and corresponding cancer registries on screening mammograms and breast cancer diagnoses and deaths for the period between 1990 and 2009 . St and ardized mortality ratios were calculated comparing observed mortality in participants to that expected based upon nonparticipant rates . A sub study using data from British Columbia women aged 35 to 44 years was conducted to assess the potential effect of self- selection participation bias . All statistical tests were two-sided . RESULTS Data were obtained on 2796472 screening participants . The average breast cancer mortality among participants was 40 % ( 95 % confidence interval [ CI ] = 33 % to 48 % ) lower than expected , with a range across provinces of 27 % to 59 % . Age at entry into screening did not greatly affect the magnitude of the average reduction in mortality , which varied between 35 % and 44 % overall . The sub study found no evidence that self- selection biased the reported mortality results , although the confidence intervals of this assessment were wide . CONCLUSION Participation in mammography screening programs in Canada was associated with substantially reduced breast cancer mortality This article provides additional follow-up data of two cohorts from the Malmö Mammographic Screening Trial ( MMST ) . The first cohort , MMST I , contained 7,984 women under age 50 at entry into MMST who were born between 1927 and 1932 . Half were assigned to a control group and were not invited for examination until four years after the code was broken in the MMST in 1988 . The second cohort , MMST II , contained 17,786 women born between 1933 and 1945 . Fifty four percent of these women were r and omly invited to screening between 1978 and 1990 . The remaining 46%--the control group -- was invited to screening between 1991 and 1994 . Nine screening rounds were completed in MMST I , and a mean of five rounds were completed in MMST II ; the screening interval ranged from 18 to 24 months . The effect of screening on breast cancer mortality was assessed by pooling the two cohorts . At the end of follow-up -- December 1993 for MMST I and December 1995 for MMST II -- there was a statistically significant 36 % reduction in breast cancer mortality in the intervention groups ( relative risk = 0.64 ; 95 % CI : 0.45 - 0.89 ; P = 0.009 ) . A harm-benefit analysis showed , however , that for every two breast cancer deaths prevented , one clinical ly insignificant cancer was diagnosed ; for each breast cancer death prevented , 63 cancer-free women had been called back for further examinations ; and for every 20 lives saved , one radiation-induced breast cancer death may have occurred . Recommendations for screening must therefore weigh mortality benefits against these negative effects Results in the breast cancer screening project of the Health Insurance Plan of Greater New York that started the end of 1963 have been up date d through December 31 , 1975 . The HIP study is a r and omized trial design ed to test whether periodic screening with clinical examination and mammography results in reduced breast cancer mortality among women aged 40–64 years at the start . Study women were offered screening examinations ; 65 % appeared for initial examinations and a large majority of these women had at least one of the three additional screenings at annual intervals . The control group of women continued to receive their usual medical care . New data support earlier reported results on benefits . During the nine years following date of entry there were 128 breast cancer deaths in the control group as compared with 91 in the study group ( screenees plus refusers ) . The impact of the screening program continues to be confined to women 50 years of age and over with no benefit at ages 40–49 years . Seven‐year case fatality rates show similar relationships . Several issues related to screening benefit are considered . Of major importance is the observation of no reduction among women under 50 in breast cancer mortality . The possibility that under different screening conditions ( e.g. , with current mammography equipment ) a benefit would be found needs to be investigated . There is a clear need for rapidly determining whether a new r and omized trial is the only way to answer the question and whether experience in the 27 NCI‐ACS demonstration projects can provide useful data . Another critical issue concerns the incremental value of mammography in a screening program . Over an eight‐year period after diagnosis , breast cancer cases that were positive only on mammography when screened had a case fatality rate of 14 % ; this compares with 32 % for cases positive only in the clinical examination and 41 % for cases positive on both modalities . Excluding mammography would have reduced the benefit of screening by an estimated one‐third . With regard to risk associated with screening , it is concluded that the increment in risk result ing from radiation exposure in mammography does not offset the benefits of screening above 50 years of age . Below that age , although the risk increment is small , the risk‐benefit balance is negative because of the absence of a demonstrated benefit . Another source of risk is related to the possible increase in biopsies . Assessment of the HIP experience suggests that only timing of biopsies was affected , but the potential for considerable variation if screening is adopted widely exists . Based on current findings in the HIP study , there appears to be strong support for periodic screening at ages 50 years and over with clinical examination and mammography ; to justify screening under 50 , new information from other studies is required Since the benefit of mammography screening for women 70 years and older is unclear , the aim of the present study was to evaluate the effect on breast cancer mortality of the population -based service-screening program in Sweden inviting women 70 - 74 years . Among the counties with service-screening programs in Sweden which started 1986 - 1990 those with upper age limit 74 years were compared to counties with 69 years as upper age limit with respect to refined breast cancer mortality . Allowance was made for potential biases namely inclusion of cases diagnosed before invitation and lead time . Two methods for estimation of breast cancer mortality were used ; underlying cause of death ( UCD ) and excess mortality . With a mean follow-up of 10.1 years a reduction of the breast cancer excess mortality was estimated at 24 % . Using the underlying cause of death the corresponding result was 6 % . A non-significant reduction in breast cancer mortality was found in the counties with service-screening program including the age group 70 - 74 years in Sweden . The estimated reduction was larger when using excess mortality compared to the use of individual underlying cause of death This article presents up date d data on breast cancer mortality for women under age 50 from the Stockholm Mammographic Screening Trial , as well as a review of some side effects associated with screening in this age group . Approximately 40,000 women aged 40 - 64 ( 14,842 aged 40 - 49 years ) were r and omized to a trial of breast cancer screening by single-view mammography alone ; 20,000 women ( 7,103 aged 10 - 49 ) were r and omized to a control group . In the 40 - 49 age group , 24 and 12 breast cancer deaths were found in the study and control groups , respectively , after 11.4 years of follow-up . The relative risk of breast cancer death in screened to nonscreened women was 1.08 ( 95 % confidence interval : 0.54 - 2.17 ) . The rates of benign surgical biopsies , false positives , and follow-up costs were higher among women under age 50 . Large overview studies are needed , however , to determine whether mammography screening consistently reduces mortality in women 40 - 49 years of age . Side effects such as costs and public aspects of mammography screening in this age group also warrant further study Background : Because the efficacy of mammography screening had been shown in r and omized controlled trials , the focus has turned on its effectiveness within the daily practice . Using individual data of women invited to screening , we conducted a case – control study to assess the effectiveness of the Dutch population –based program of mammography screening . Methods : Cases were women who died from breast cancer between 1995 and 2003 and were closely matched to five controls on year of birth , year of first invitation , and number of invitations before case 's diagnosis . ORs and 95 % confidence intervals ( CI ) for the association between attending either of three screening examinations prior to diagnosis and the risk of breast cancer death were calculated using conditional logistic regression and corrected for self- selection bias . Results : We included 755 cases and 3,739 matched controls . Among the cases , 29.8 % was screen-detected , 34.3 % interval-detected , and 35.9 % never-screened . About 29.5 % of the never-screened cases had stage IV tumor compared with 5.3 % of the screen-detected and 15.1 % of the interval-detected cases . The OR ( 95 % CIs ) , all ages ( 49–75 years ) , was 0.51 ( 0.40–0.66 ) and for the age groups 50–69 , 50–75 , and 70–75 years were 0.61 ( 0.47–0.79 ) , 0.52 ( CI 0.41–0.67 ) , and 0.16 ( 0.09–0.29 ) , respectively . Conclusion : The study provides evidence for a beneficial effect of early detection by mammography screening in reducing the risk of breast cancer death among women invited to and who attended the screening . Impact : This is the first case – control study that accurately accounts for equal screening opportunity for both cases and matched controls by number of invitations before case 's diagnosis . Cancer Epidemiol Biomarkers Prev ; 21(1 ) ; 66–73 . © 2011 AACR This paper summarizes the findings of the first breast cancer screening trial , which was initiated in December 1963 to explore the efficacy of screening . Women aged 40 - 64 years were selected from enrollees in the Health Insurance Plan ( HIP ) of Greater New York and were r and omly assigned to study and control groups . Study group women were invited for screening , an initial examination , and three annual reexaminations . Screening consisted of film mammography ( cephalocaudal and lateral views of each breast ) and clinical examination of breasts . Breast cancer and mortality from breast cancer were examined by treatment group ( study vs. control ) and by entry-age subgroup . By the end of 18 years from entry , the study group had about a 25 % lower breast cancer mortality among women aged 40 - 49 and 50 - 59 at time of entry than did the control group . However , to a large extent the difference among the 40 - 49-year-olds occurred in the subgroup with breast cancer diagnosed after these women had passed their 50th birthday , and utility of screening women in their forties is question able OBJECTIVE The objective of this study was to determine the potential added contribution of clinical breast examination ( CBE ) to invasive breast cancer detection in a mammography screening program , by categories of age and breast density . SUBJECTS AND METHODS We prospect ively followed 61,688 women aged 40 years or older who had undergone at least one screening examination with mammography and CBE between January 1 , 1996 , and December 31 , 2000 , for 1 year after their mammogram for invasive cancer . We computed the incremental sensitivity , specificity , and positive predictive value of CBE over mammography alone for combinations of age and breast density ( predominantly fatty or dense ) . RESULTS Mammography sensitivity was 78 % and combined mammography-CBE sensitivity was 82 % , thus CBE detected an additional 4 % of invasive cancers . CBE detected a minority of invasive cancers compared with mammography for all age groups and all breast densities . Sensitivity increased from adding CBE to screening mammography for all ages , from 6.8 % in women ages 50 - 59 with dense breasts to 1.8 % in women ages 60 - 69 years with fatty breasts . CBE generally added incrementally more to sensitivity among women with dense breasts . Specificity and positive predictive value declined when CBE was used in conjunction with mammography , and this decrement was more pronounced in women with dense breasts . CONCLUSION CBE had modest incremental benefit to invasive cancer detection over mammography alone in a screening program , but also led to greater risk of false-positive results . These risks and benefits were greater in women with dense breasts . The balance of risks and benefits must be weighed carefully when evaluating the inclusion of CBE in a screening examination Abstract Objective : To evaluate the effectiveness of screening for breast cancer as a public health policy . Design : Follow up in 1987 - 92 of Finnish women invited to join the screening programme in 1987 - 9 and of the control women ( balanced by age and matched by municipality of residence ) , who were not invited to the service screening . Setting : Finl and . Subjects : Of the Finnish women born in 1927 - 39 , 89 893 women invited for screening and 68 862 controls were followed ; 1584 breast cancers were diagnosed . Main outcome measures : Rate ratio of deaths from breast cancer among the women invited for screening to deaths among those not invited . Results : There were 385 deaths from breast cancer , of which 127 were among the 1584 incident cases in 1987 - 92 . The rate ratio of death was 0.76 ( 95 % confidence interval 0.53 to 1.09 ) . The effect was larger and significant ( 0.56 ; 0.33 to 0.95 ) among women aged under 56 years at entry . 20 cancers were prevented ( one death prevented per 10 000 screens ) . Conclusions : A breast screening programme can achieve a similar effect on mortality as achieved by the trials for breast cancer screening . However , it may be difficult to justify a screening programme as a public health policy on the basis of the mortality reduction only . Whether to run a screening programme as a public health policy also depends on its effects on the quality of life of the target population and what the re sources would be used for if screening was not done . Given all the different dimensions in the effect , mammography based breast screening is probably justifiable as a public health policy . Key messages Several countries have a breast cancer screening programme , but none has yet reported this as result ing in a reduction of breast cancer mortality This study shows that a breast cancer screening programme can achieve similar reduction in mortality to that seen in r and omised trials Effects on quality of life , cost of breast cancer screening , and the alternative use of re sources should affect the decision whether to introduce a screening IMPORTANCE Controversy exists about the frequency women should undergo screening mammography and whether screening interval should vary according to risk factors beyond age . OBJECTIVE To compare the benefits and harms of screening mammography frequencies according to age , breast density , and postmenopausal hormone therapy ( HT ) use . DESIGN Prospect i ve cohort . SETTING Data collected January 1994 to December 2008 from mammography facilities in community practice that participate in the Breast Cancer Surveillance Consortium ( BCSC ) mammography registries . PARTICIPANTS Data were collected prospect ively on 11,474 women with breast cancer and 922,624 without breast cancer who underwent mammography at facilities that participate in the BCSC . MAIN OUTCOMES AND MEASURES We used logistic regression to calculate the odds of advanced stage ( IIb , III , or IV ) and large tumors ( > 20 mm in diameter ) and 10-year cumulative probability of a false-positive mammography result by screening frequency , age , breast density , and HT use . The main predictor was screening mammography interval . RESULTS Mammography biennially vs annually for women aged 50 to 74 years does not increase risk of tumors with advanced stage or large size regardless of women 's breast density or HT use . Among women aged 40 to 49 years with extremely dense breasts , biennial mammography vs annual is associated with increased risk of advanced-stage cancer ( odds ratio [ OR ] , 1.89 ; 95 % CI , 1.06 - 3.39 ) and large tumors ( OR , 2.39 ; 95 % CI , 1.37 - 4.18 ) . Cumulative probability of a false-positive mammography result was high among women undergoing annual mammography with extremely dense breasts who were either aged 40 to 49 years ( 65.5 % ) or used estrogen plus progestogen ( 65.8 % ) and was lower among women aged 50 to 74 years who underwent biennial or triennial mammography with scattered fibrogl and ular densities ( 30.7 % and 21.9 % , respectively ) or fatty breasts ( 17.4 % and 12.1 % , respectively ) . CONCLUSIONS AND RELEVANCE Women aged 50 to 74 years , even those with high breast density or HT use , who undergo biennial screening mammography have similar risk of advanced-stage disease and lower cumulative risk of false-positive results than those who undergo annual mammography . When deciding whether to undergo mammography , women aged 40 to 49 years who have extremely dense breasts should be informed that annual mammography may minimize their risk of advanced-stage disease but the cumulative risk of false-positive results is high BACKGROUND Mammography screening can reduce breast cancer mortality . However , most women are unaware that inconsequential disease can also be detected by screening , leading to overdiagnosis and overtreatment . We aim ed to investigate whether including information about overdetection of breast cancer in a decision aid would help women aged around 50 years to make an informed choice about breast screening . METHODS We did a community-based , parallel-group , r and omised controlled trial in New South Wales , Australia , using a r and om cohort of women aged 48 - 50 years . Recruitment to the study was done by telephone ; women were eligible if they had not had mammography in the past 2 years and did not have a personal or strong family history of breast cancer . With a computer program , we r and omly assigned 879 participants to either the intervention decision aid ( comprising evidence -based explanatory and quantitative information on overdetection , breast cancer mortality reduction , and false positives ) or a control decision aid ( including information on breast cancer mortality reduction and false positives ) . Participants and interviewers were masked to group assignment . The primary outcome was informed choice ( defined as adequate knowledge and consistency between attitudes and screening intentions ) , which we assessed by telephone interview about 3 weeks after r and om allocation . The primary outcome was analysed in all women who completed the relevant follow-up interview questions fully . This trial is registered with the Australian New Zeal and Clinical Trials Registry , number ACTRN12613001035718 . FINDINGS Between January , 2014 , and July , 2014 , 440 women were allocated to the intervention group and 439 were assigned to the control group . 21 women in the intervention group and 20 controls were lost to follow-up ; a further ten women assigned to the intervention and 11 controls did not answer all questions on attitudes . Therefore , 409 women in the intervention group and 408 controls were analysed for the primary outcome . 99 ( 24 % ) of 409 women in the intervention group made an informed choice compared with 63 ( 15 % ) of 408 in the control group ( difference 9 % , 95 % CI 3 - 14 ; p=0·0017 ) . Compared with controls , more women in the intervention group met the threshold for adequate overall knowledge ( 122/419 [ 29 % ] vs 71/419 [ 17 % ] ; difference 12 % , 95 % CI 6 - 18 ; p<0·0001 ) , fewer women expressed positive attitudes towards screening ( 282/409 [ 69 % ] vs 340/408 [ 83 % ] ; 14 % , 9 - 20 ; p<0·0001 ) , and fewer women intended to be screened ( 308/419 [ 74 % ] vs 363/419 [ 87 % ] ; 13 % , 8 - 19 ; p<0·0001 ) . When conceptual knowledge alone was considered , 203 ( 50 % ) of 409 women in the intervention group made an informed choice compared with 79 ( 19 % ) of 408 in the control group ( p<0·0001 ) . INTERPRETATION Information on overdetection of breast cancer provided within a decision aid increased the number of women making an informed choice about breast screening . Becoming better informed might mean women are less likely to choose screening . FUNDING Australian National Health and Medical Research Council |
10,465 | 24,100,287 | Intention-to-treat sensitivity analyses consistently revealed even more robust effect estimates .
Despite a few outlying studies , consistently favourable estimates were obtained for all injury prevention measures except for stretching .
Strength training reduced sports injuries to less than 1/3 and overuse injuries could be almost halved | BACKGROUND Physical activity is important in both prevention and treatment of many common diseases , but sports injuries can pose serious problems .
OBJECTIVE To determine whether physical activity exercises can reduce sports injuries and perform stratified analyses of strength training , stretching , proprioception and combinations of these , and provide separate acute and overuse injury estimates . | Abstract . This prospect i ve r and omized intervention investigated whether training on a balance board could reduce the amount of traumatic injuries of the lower extremities in female soccer players . A total of 221 female soccer players from 13 different teams playing in the second and third Swedish divisions volunteered to participate in the study . Seven teams ( n=121 ) were r and omized to an intervention group and six teams ( n=100 ) to a control group and were followed during one outdoor season ( April – October ) . Before and after the season muscle flexibility and balance/postural sway of the lower extremities were measured in the players . There were no significant differences in age , height , weight , muscle flexibility and balance/postural sway of the lower extremities between the intervention and the control group . During the season the players in the intervention group performed a special training program consisting of 10–15 min of balance board training in addition to their st and ard soccer practice and games . After a 37 % drop-out the intervention group consisted of 62 players and the control group of 78 players . The results showed no significant differences between the groups with respect either to the number , incidence , or type of traumatic injuries of the lower extremities . The incidence rate of " major " injuries was higher in the intervention group than in the control group . Four of five anterior cruciate ligament injuries occurred in the intervention group , which means that we could not prevent severe knee injuries in female soccer players with balance board training . However , among the players who had been injured during the 3-month period prior to this investigation there were significantly more players from the control group than from the intervention group who sustained new injuries during the study period Objective To evaluate the effectiveness of neuromuscular training in reducing the rate of acute knee injury in adolescent female football players . Design Stratified cluster r and omised controlled trial with clubs as the unit of r and omisation . Setting 230 Swedish football clubs ( 121 in the intervention group , 109 in the control group ) were followed for one season ( 2009 , seven months ) . Participants 4564 players aged 12 - 17 years ( 2479 in the intervention group , 2085 in the control group ) completed the study . Intervention 15 minute neuromuscular warm-up programme ( targeting core stability , balance , and proper knee alignment ) to be carried out twice a week throughout the season . Main outcome measures The primary outcome was rate of anterior cruciate ligament injury ; secondary outcomes were rates of severe knee injury ( > 4 weeks ’ absence ) and any acute knee injury . Results Seven players ( 0.28 % ) in the intervention group , and 14 ( 0.67 % ) in the control group had an anterior cruciate ligament injury . By Cox regression analysis according to intention to treat , a 64 % reduction in the rate of anterior cruciate ligament injury was seen in the intervention group ( rate ratio 0.36 , 95 % confidence interval 0.15 to 0.85 ) . The absolute rate difference was −0.07 ( 95 % confidence interval −0.13 to 0.001 ) per 1000 playing hours in favour of the intervention group . No significant rate reductions were seen for secondary outcomes . Conclusions A neuromuscular warm-up programme significantly reduced the rate of anterior cruciate ligament injury in adolescent female football players . However , the absolute rate difference did not reach statistical significance , possibly owing to the small number of events . Trial registration Clinical trials NCT00894595 Background : Anterior knee pain ( AKP ) is the most common activity-related injury of the knee . The authors investigated the effect of an exercise intervention on the incidence of AKP in UK army recruits undergoing a 14-week physically arduous training program . Hypothesis : Modifying military training to include targeted preventative exercises may reduce the incidence of AKP in a young recruit population . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : A single-blind cluster r and omized controlled trial was performed in 39 male and 11 female training groups ( median age : 19.7 years ; interquartile range , 17 - 25 ) undergoing phase 1 of army recruit training . Each group was r and omly assigned to either an intervention ( n = 759 ) or control ( n = 743 ) protocol . The intervention consisted of 4 strengthening and 4 stretching exercises completed during supervised physical training lessons ( 7 per week ) . The control group followed the existing training syllabus warm-up exercises . The primary outcome was a diagnosis of AKP during the 14-week training program . Results : Forty-six participants ( 3.1 % ; 95 % confidence interval [ CI ] , 2.3 - 4.1 ) were diagnosed with AKP . There were 36 ( 4.8 % ; 95%CI , 3.5 - 6.7 ) new cases of AKP in the control group and 10 ( 1.3 % ; 0.7 - 2.4 ) in the intervention group . There was a 75 % reduction in AKP risk in the intervention group ( unadjusted hazard ratio = 0.25 ; 95 % CI , 0.13 - 0.52 ; P < .001 ) . Three participants ( 0.4 % ) from the intervention group were discharged from the military for medical reasons compared to 25 ( 3.4 % ) in the control group . Conclusion : A simple set of lower limb stretching and strengthening exercises result ed in a substantial and safe reduction in the incidence of AKP in a young military population undertaking a physical conditioning program . Such exercises could also be beneficial for preventing this common injury among nonmilitary participants in recreational physical activity Background Participants ' compliance , attitudes and beliefs have the potential to influence the efficacy of an intervention greatly . Objective To characterise team and player compliance with a comprehensive injury prevention warm-up programme for football ( The 11 + ) , and to assess attitudes towards injury prevention among coaches and their association with compliance and injury risk . Study Design A prospect i ve cohort study and retrospective survey based on a cluster-r and omised controlled trial with teams as the unit of r and omisation . Methods Compliance , exposure and injuries were registered prospect ively in 65 of 125 football teams ( 1055 of 1892 female Norwegian players aged 13–17 years and 65 of 125 coaches ) throughout one football season ( March – October 2007 ) . St and ardised telephone interviews were conducted to assess coaches ' attitudes towards injury prevention . Results Teams completed the injury prevention programme in 77 % ( mean 1.3 sessions per week ) of all training and match sessions , and players in 79 % ( mean 0.8 sessions per week ) of the sessions they attended . Compared with players with intermediate compliance , players with high compliance with the programme had a 35 % lower risk of all injuries ( RR 0.65 , 95 % CI 0.46 to 0.91 , p=0.011 ) . Coaches who had previously utilised injury prevention training coached teams with a 46 % lower risk of injury ( OR 0.54 , 95 % CI 0.33 to 0.87 , p=0.011 ) . Conclusions Compliance with the injury prevention programme was high , and players with high compliance had significantly lower injury risk than players with intermediate compliance . Positive attitudes towards injury prevention correlated with high compliance and lower injury risk Background : Sport is the leading cause of injury requiring medical attention among adolescents . We studied the effectiveness of a home-based balance-training program using a wobble board in improving static and dynamic balance and reducing sports-related injuries among healthy adolescents . Methods : In this cluster r and omized controlled trial , we r and omly selected 10 of 15 high schools in Calgary to participate in the fall of 2001 . We then recruited students from physical education classes and r and omly assigned them , by school , to either the intervention ( n = 66 ) or the control ( n = 61 ) group . Students in the intervention group participated in a daily 6-week and then a weekly 6-month home-based balance-training program using a wobble board . Students at the control schools received testing only . The primary outcome measures were timed static and dynamic balance , 20-m shuttle run and vertical jump , which were measured at baseline and biweekly for 6 weeks . Self-reported injury data were collected over the 6-month follow-up period . Results : At 6 weeks , improvements in static and dynamic balance were observed in the intervention group but not in the control group ( difference in static balance 20.7 seconds , 95 % confidence interval [ CI ] 10.8 to 30.6 seconds ; difference in dynamic balance 2.3 seconds , 95 % CI 0.7 to 4.0 seconds ) . There was evidence of a protective effect of balance training in over 6 months ( relative risk of injury 0.2 , 95 % CI 0.05 to 0.88 ) . The number needed to treat to avoid 1 injury over 6 months was 8 ( 95 % CI 4 to 35 ) . Interpretation : Balance training using a wobble board is effective in improving static and dynamic balance and reducing sports-related injuries among healthy adolescents Young female players in European h and ball have a very high injury incidence , up to 50 injuries per 1000 hours of game . More than half of these injuries happen without any external cause . The aim of the study was to investigate the effect of an intervention programme design ed to reduce the number of injuries in young female players in European h and ball , with special emphasis on injuries in the lower extremities . The programme was created using elite athlete training programmes and those design ed for rehabilitation of injured athletes with functional instability of their ankles and rupture of the anterior cruciate ligament . It included the use of an ankle disk for 10 - 15 min at all practice sessions , for one 10-month season ( August 1995-May 1996 ) . Twenty-two teams participated in the study , and were r and omly assigned to the intervention or control group . Eleven teams with 111 players were r and omised to the intervention group and 11 teams with 126 players to the control group . Data were analysed using a t-test for continuous variables , chi2- analysis and Fisher 's exact test for dichotomous variables and multivariate methods to determine odds-ratios . The results indicated that using the intervention programme decreased the numbers of both traumatic and overuse injuries significantly . The differences in injuries between the groups were 80 % during games and 71 % during practice . In addition , the players in the control group had a 5.9 times higher risk of acquiring an injury than the players in the intervention group Groin injuries cause major problems in sports and particularly in football . Exercise is effective in treating adductor-related groin pain , but no trials have been published regarding the specific prevention of groin pain or prevention specifically targeting overuse injuries in sport using exercise programs . We performed a cluster-r and omized trial including 55 football clubs representing 1211 players . The clubs were r and omized to an exercise program aim ed at preventing groin injuries ( n=27 ) or to a control group training as usual ( n=28 ) . The intervention program consisted of six exercises including strengthening ( concentric and eccentric ) , coordination , and core stability exercises for the muscles related to the pelvis . Physiotherapists assigned to each club registered all groin injuries . Twenty-two clubs in each group completed the study , represented by 977 players . There was no significant effect of the intervention ( HR=0.69 , 95 % CI 0.40 - 1.19 ) . The risk of a groin injury was reduced by 31 % , but this reduction was not significant . A univariate analysis showed that having had a previous groin injury almost doubles the risk of developing a new groin injury and playing at a higher level almost triples the risk of developing a groin injury Background The incidence rate of soccer injuries is among the highest in sports , particularly for adult male soccer players . Purpose To investigate the effect of the ‘ The11 ’ injury prevention programme on injury incidence and injury severity in adult male amateur soccer players . Study design Cluster-r and omised controlled trial . Methods Teams from two high-level amateur soccer competitions were r and omly assigned to an intervention ( n=11 teams , 223 players ) or control group ( n=12 teams , 233 players ) . The intervention group was instructed to perform The11 in each practice session during one soccer season . The11 focuses on core stability , eccentric training of thigh muscles , proprioceptive training , dynamic stabilisation and plyometrics with straight leg alignment . All participants of the control group continued their practice sessions as usual . Results In total , 427 injuries were recorded , affecting 274 of 456 players ( 60.1 % ) . Compliance with the intervention programme was good ( team compliance=73 % , player compliance=71 % ) . Contrary to the hypothesis , injury incidences were almost equal between the two study groups : 9.6 per 1000 sports hours ( 8.4–11.0 ) for the intervention group and 9.7 ( 8.5–11.1 ) for the control group . No significant differences were found in injury severity , but a significant difference was observed in the location of the injuries : players in the intervention group sustained significantly less knee injuries . Conclusions This study did not find significant differences in the overall injury incidence or injury severity between the intervention and control group of adult male soccer players . More research is recommended , focusing on injury aetiology and risk factors in adult male amateur soccer players Background It is unknown whether an exercise program can prevent overuse injuries in the lower extremity . An often encountered and important risk factor for the development of lower extremity overuse injuries is an abrupt increase in activity level . Hypothesis A preventive training program based on a literature review of intrinsic risk factors , and performed concurrent with an increase in physical activity , can reduce the incidence of overuse knee injuries and medial tibial stress syndrome , as well as increase running distance . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods A total of 1020 soldiers aged 20.9 years ( range , 19–26 years ) undergoing 3 months of basic military training consecutively enrolled from December 2004 to December 2005 . The prevention program consisted of an exercise program of 15 minutes ’ duration 3 times a week , including 5 exercises for strength , flexibility , and coordination ; the placebo program consisted of 5 exercises for the upper body . Results During the observation period , 223 subjects sustained an injury , with 50 and 48 of these fulfilling the study criteria for overuse knee injuries or medial tibial stress syndrome , respectively . There were no significant differences in incidence of injury between the prevention group and the placebo group ( incidence , 0.22 vs 0.19 ; P = .162 ; relative risk = 1.05 [ range , 0.98–1.11 ] ) . The soldiers in the prevention group had the greater improvement in running distance in 12-minute run tests ( 82 vs 43 m ; P = .037 ) . Conclusion An exercise program with an emphasis on muscular strengthening , coordination , and flexibility based on intrinsic risk factors identified through a literature review did not influence the risk of developing overuse knee injuries or medial tibial stress syndrome in subjects undergoing an increase in physical activity . The program increased maximal running distance in a 12-minute test BACKGROUND The risk of musculoskeletal injury with the introduction of moderate-to-vigorous exercise in sedentary adults is not well established . The purpose of this report is to examine the effect of a 12-month exercise intervention on musculoskeletal injury and bodily pain in predominately overweight , sedentary men ( n = 102 ) and women ( n = 100 ) , ages 40 to 75 years . METHODS Participants were r and omized to a moderate-to-vigorous aerobic exercise intervention ( EX ) ( 6 d/wk , 60 min/d , 60 % to 85 % max . heart rate ) or usual lifestyle control ( CON ) . Participants completed a self-report of musculoskeletal injury and body pain at baseline and 12-months . RESULTS The number of individuals reporting an injury ( CON ; 28 % vs. EX ; 28 % , P = .95 ) did not differ by group . The most commonly injured site was lower leg/ankle/foot . The most common causes of injury were sports/physical activity , home maintenance , or " other . " In the control group , bodily pain increased over the 12 months compared with the exercise group ( CON -7.9 , EX -1.4 , P = .05 ) . Baseline demographics and volume of exercise were not associated with injury risk . CONCLUSIONS Previously sedentary men and women r and omized to a 12-month aerobic exercise intervention with a goal of 360 min/wk reported the same number of injuries as those in the control group and less bodily pain Abstract Objective To investigate the effect of a structured warm-up programme design ed to reduce the incidence of knee and ankle injuries in young people participating in sports . Design Cluster r and omised controlled trial with clubs as the unit of r and omisation . Setting 120 team h and ball clubs from central and eastern Norway ( 61 clubs in the intervention group , 59 in the control group ) followed for one league season ( eight months ) . Participants 1837 players aged 15 - 17 years ; 958 players ( 808 female and 150 male ) in the intervention group ; 879 players ( 778 female and 101 male ) in the control group . Intervention A structured warm-up programme to improve running , cutting , and l and ing technique as well as neuromuscular control , balance , and strength . Main outcome measure The rate of acute injuries to the knee or ankle . Results During the season , 129 acute knee or ankle injuries occurred , 81 injuries in the control group ( 0.9 ( SE 0.09 ) injuries per 1000 player hours ; 0.3 ( SE 0.17 ) in training v 5.3 ( SE 0.06 ) during matches ) and 48 injuries in the intervention group ( 0.5 ( SE 0.11 ) injuries per 1000 player hours ; 0.2 ( SE 0.18 ) in training v 2.5 ( SE 0.06 ) during matches ) . Fewer injured players were in the intervention group than in the control group ( 46 ( 4.8 % ) v ( 76 ( 8.6 % ) ; relative risk intervention group v control group 0.53 , 95 % confidence interval 0.35 to 0.81 ) . Conclusion A structured programme of warm-up exercises can prevent knee and ankle injuries in young people playing sports . Preventive training should therefore be introduced as an integral part of youth sports programmes PURPOSE To investigate the effectiveness of a multistation proprioceptive exercise program for the prevention of ankle injuries in basketball players using a prospect i ve r and omized controlled trial in combination with biomechanical tests of neuromuscular performance . METHODS A total of 232 players participated in the study and were r and omly assigned to a training or control group following the CONSORT statement . The training group performed a multistation proprioceptive exercise program , and the control group continued with their normal workout routines . During one competitive basketball season , the number of ankle injuries was counted and related to the number of sports participation sessions using logistic regression . Additional biomechanical pre – post tests ( angle reproduction and postural sway ) were performed in both groups to investigate the effects on neuromuscular performance . RESULTS In the control group , 21 injuries occurred , whereas in the training group , 7 injuries occurred . The risk for sustaining an ankle injury was significantly reduced in the training group by approximately 65 % . [ corrected ] The corresponding number needed to treat was 7 . Additional biomechanical tests revealed significant improvements in joint position sense and single-limb stance in the training group . CONCLUSIONS The multistation proprioceptive exercise program effectively prevented ankle injuries in basketball players . Analysis of number needed to treat clearly showed the relatively low prevention effort that is necessary to avoid an ankle injury . Additional biomechanical tests confirmed the neuromuscular effect and confirmed a relationship between injury prevention and altered neuromuscular performance . With this knowledge , proprioceptive training may be optimized to specifically address the dem and s in various athletic activities A set of exercises -- the " 11"--have been selected to prevent football injuries . The purpose of this cluster-r and omized controlled trial was to investigate the effect of the " 11 " on injury risk in female youth football . Teams were r and omized to an intervention ( n=59 teams , 1091 players ) or a control group ( n=54 teams , 1001 players ) . The intervention group was taught the " 11 , " exercises for core stability , lower extremity strength , neuromuscular control and agility , to be used as a 15-min warm-up program for football training over an 8-month season . A total of 396 players ( 20 % ) sustained 483 injuries . No difference was observed in the overall injury rate between the intervention ( 3.6 injuries/1000 h , confidence interval ( CI ) 3.2 - 4.1 ) and control group ( 3.7 , CI 3.2 - 4.1 ; RR=1.0 , CI 0.8 - 1.2 ; P=0.94 ) nor in the incidence for any type of injury . During the first 4 months of the season , the training program was used during 60 % of the football training sessions , but only 14 out of 58 intervention teams completed more than 20 prevention training sessions . In conclusion , we observed no effect of the injury prevention program on the injury rate , most likely because the compliance with the program was low Objective : To examine the effectiveness of a sport-specific balance training program in reducing injury in adolescent basketball . Design : Cluster r and omized controlled trial . Setting : Twenty-five high schools in Calgary and surrounding area . Subjects : Nine hundred and twenty high school basketball players ( ages 12 - 18 ) . Intervention : Subjects were r and omly allocated by school to the control ( n = 426 ) and training group ( n = 494 ) . Both groups were taught a st and ardized warm-up program . The training group was also taught an additional warm-up component and a home-based balance training program using a wobble board . Main Outcome Measures : All injuries occurring during basketball that required medical attention and /or caused a player to be removed from that current session and /or miss a subsequent session were then recorded and assessed by a team therapist who was blinded to training group allocation . Results : A basketball-specific balance training program was protective of acute-onset injuries in high school basketball [ RR = 0.71 ( 95 % CI ; 0.5 - 0.99 ) ] . The protective effect found with respect to all injury [ RR = 0.8 ( 95 % CI ; 0.57 - 1.11 ) ] , lower-extremity injury [ RR = 0.83 ( 95 % CI ; 0.57 - 1.19 ) ] , and ankle sprain injury [ RR = 0.71 ( 95 % CI ; 0.45 - 1.13 ) ] were not statistically significant . Self-reported compliance to the intended home-based training program was poor ( 298/494 or 60.3 % ) . Conclusions : A basketball-specific balance training program was effective in reducing acute-onset injuries in high school basketball . There was also a clinical ly relevant trend found with respect to the reduction of all , lower-extremity , and ankle sprain injury . Future research should include further development of neuromuscular prevention strategies in addition to further evaluation of methods to increase compliance to an injury-prevention training program in adolescents Objective : To ascertain the reasons behind players not participating in a sports safety research project . Methods : During the preseason , 10 Australian football clubs volunteered 23 teams to participate in a protective equipment r and omised controlled trial , the Australian Football Injury Prevention Project ( AFIPP ) . All players from these teams were invited to participate . Players who did not agree to participate in AFIPP were surveyed about their reasons for non-involvement . Results : 110 football players ( response rate 63.6 % ) completed the non-responder survey and cited the two main reasons behind non-involvement in the project as “ I did not know about the project ” ( 39.4 % ) and “ I was not at training when the research team visited ” ( 36.5 % ) . Conclusions and implication s : Preseason may not be the best time for maximal player recruitment in community based sports safety research . Enhanced communication between research ers and players at community level football clubs during the recruitment phase is likely to improve response rates A prospect i ve study of acute injuries from sports and physical exercise was carried out during 1 year in a total population of a municipality with 31,620 inhabitants . The medical treatment and the services required for the injuries have been calculated and related to the total consumption of medical care in the municipality . A total of 571 injuries ( 17 % of all injuries ) occurred in 28 different sports : 65 % of the injured were males . Sports injuries accounted for 3 % of all acute visits and there were altogether 1,083 outpatient visits , which yields a mean of 1.9 visits per injury . Related to the total consumption of outpatient visits to the five clinics in the municipality sports injuries also accounted for 3 % . Forty-four patients were hospitalized ; the proportion of inpatient care due to sports injuries was 0.7 % and the mean length of stay in hospital 3.9 days . The total amount of sick leave compensated for sports injuries ( 3,477 days ) was 1.2 % of all days compensated in 1984 . The overall mean cost per injury was US$ 335 . Individual sports ( motorcycling , downhill skiing and equine sport ) were by far the most costly in the Falköping survey , the dearest of the team sports ranking only fifth ( h and ball followed by soccer ) OBJECTIVE To determine the effectiveness of coach-led neuromuscular warm-up on reducing lower extremity ( LE ) injuries in female athletes in a mixed-ethnicity , predominantly low-income , urban population . DESIGN Cluster r and omized controlled trial . SETTING Chicago public high schools . PARTICIPANTS Of 258 coaches invited to participate , 95 ( 36.8 % ) enrolled ( 1558 athletes ) . Ninety coaches and 1492 athletes completed the study . INTERVENTIONS We r and omized schools to intervention and control groups . We trained intervention coaches to implement a 20-minute neuromuscular warm-up . Control coaches used their usual warm-up . MAIN OUTCOME MEASURES Coach compliance was tracked by self-report and direct observation . Coaches reported weekly athlete exposures ( AEs ) and LE injuries causing a missed practice or game . Research assistants interviewed injured athletes . Injury rates were compared between the control and intervention groups using χ(2 ) and Fisher exact tests . Significance was set at P < .05 . Poisson regression analysis adjusted for clustering and covariates in an athlete subset reporting personal information ( n = 855 ; 57.3 % ) . RESULTS There were 28 023 intervention AEs and 22 925 control AEs . Intervention coaches used prescribed warm-up in 1425 of 1773 practice s ( 80.4 % ) . Intervention athletes had lower rates per 1000 AEs of gradual-onset LE injuries ( 0.43 vs 1.22 , P < .01 ) , acute-onset noncontact LE injuries ( 0.71 vs 1.61 , P < .01 ) , noncontact ankle sprains ( 0.25 vs 0.74 , P = .01 ) , and LE injuries treated surgically ( 0 vs 0.17 , P = .04 ) . Regression analysis showed significant incidence rate ratios for acute-onset noncontact LE injuries ( 0.33 ; 95 % CI , 0.17 - 0.61 ) , noncontact ankle sprains ( 0.38 ; 95 % CI , 0.15 - 0.98 ) , noncontact knee sprains ( 0.30 ; 95 % CI , 0.10 - 0.86 ) , and noncontact anterior cruciate ligament injuries ( 0.20 ; 95 % CI , 0.04 - 0.95 ) . CONCLUSION Coach-led neuromuscular warm-up reduces noncontact LE injuries in female high school soccer and basketball athletes from a mixed-ethnicity , predominantly low-income , urban population . TRIAL REGISTRATION CLINICAL TRIALS.ORG IDENTIFIER : NCT01092286 Background : The incidence of acute hamstring injuries is high in several sports , including the different forms of football . Purpose : The authors investigated the preventive effect of eccentric strengthening of the hamstring muscles using the Nordic hamstring exercise compared with no additional hamstring exercise on the rate of acute hamstring injuries in male soccer players . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Fifty Danish male professional and amateur soccer teams ( 942 players ) were allocated to an intervention group ( 461 players ) or a control group ( 481 players ) . Players in the intervention group conducted a 10-week progressive eccentric training program followed by a weekly seasonal program , whereas players in the control group followed their usual training program . The main outcome measures were numbers of overall , new , and recurrent acute hamstring injuries during 1 full soccer season . Results : Fifty-two acute hamstring injuries in the control group compared with 15 injuries in the intervention group were registered . Comparing intervention versus the control group , overall acute hamstring injury rates per 100 player seasons were 3.8 versus 13.1 ( adjusted rate ratio [ RR ] , 0.293 ; 95 % confidence interval [ CI ] , 0.150 - 0.572 ; P < .001 ) . New injury rates per 100 player seasons were 3.1 versus 8.1 ( RR , 0.410 ; 95 % CI , 0.180 - 0.933 ; P = .034 ) , whereas recurrent injury rates per 100 player seasons were 7.1 versus 45.8 ( RR , 0.137 ; 95 % CI , 0.037 - 0.509 ; P = .003 ) . Number needed to treat [ NNT ] to prevent 1 acute hamstring injury ( new or recurrent ) is 13 ( 95 % CI , 9 - 23 ) players . The NNT to prevent 1 new injury is 25 ( 95 % CI , 15 - 72 ) players , and NNT to prevent 1 recurrent injury is 3 ( 95 % CI , 2 - 6 ) players . Conclusion : In male professional and amateur soccer players , additional eccentric hamstring exercise decreased the rate of overall , new , and recurrent acute hamstring injuries Background Neuromuscular and proprioceptive training programs can decrease noncontact anterior cruciate ligament injuries ; however , they may be difficult to implement within an entire team or the community at large . Hypothesis A simple on-field alternative warm-up program can reduce noncontact ACL injuries . Study Design R and omized controlled trial ( clustered ) ; Level of evidence , 1 . Methods Participating National Collegiate Athletic Association Division I women 's soccer teams were assigned r and omly to intervention or control groups . Intervention teams were asked to perform the program 3 times per week during the fall 2002 season . All teams reported athletes ’ participation in games and practice s and any knee injuries . Injury rates were calculated based on athlete exposures , expressed as rate per 1000 athlete exposures . A z statistic was used for rate ratio comparisons . Results Sixty-one teams with 1435 athletes completed the study ( 852 control athletes ; 583 intervention ) . The overall anterior cruciate ligament injury rate among intervention athletes was 1.7 times less than in control athletes ( 0.199 vs 0.340 ; P = .198 ; 41 % decrease ) . Noncontact anterior cruciate ligament injury rate among intervention athletes was 3.3 times less than in control athletes ( 0.057 vs 0.189 ; P = .066 ; 70 % decrease ) . No anterior cruciate ligament injuries occurred among intervention athletes during practice versus 6 among control athletes ( P = .014 ) . Game-related noncontact anterior cruciate ligament injury rates in intervention athletes were reduced by more than half ( 0.233 vs 0.564 ; P = .218 ) . Intervention athletes with a history of anterior cruciate ligament injury were significantly less likely to suffer another anterior cruciate ligament injury compared with control athletes with a similar history ( P = .046 for noncontact injuries ) . Conclusion This program , which focuses on neuromuscular control , appears to reduce the risk of anterior cruciate ligament injuries in collegiate female soccer players , especially those with a history of anterior cruciate ligament injury Background Ankle sprains are the most common musculoskeletal injuries that occur in athletes , and they have a profound impact on health care costs and re sources . Hypothesis A balance training program can reduce the risk of ankle sprains in high school athletes . Study Design R and omized controlled clinical trial ; Level of evidence , 1 . Methods Seven hundred and sixty-five high school soccer and basketball players ( 523 girls and 242 boys ) were r and omly assigned to either an intervention group ( 27 teams , 373 subjects ) that participated in a balance training program or to a control group ( 28 teams , 392 subjects ) that performed only st and ard conditioning exercises . On-site athletic trainers recorded athlete exposures and sprains . Results The rate of ankle sprains was significantly lower for subjects in the intervention group ( 6.1 % , 1.13 of 1000 exposures vs 9.9 % , 1.87 of 1000 exposures ; P = .04 ) . Athletes with a history of an ankle sprain had a 2-fold increased risk of sustaining a sprain ( risk ratio , 2.14 ) , whereas athletes who performed the intervention program decreased their risk of a sprain by one half ( risk ratio , 0.56 ) . The ankle sprain rate for athletes without previous sprains was 4.3 % in the intervention group and 7.7 % in the control group , but this difference was not significant ( P = .059 ) . Conclusion A balance training program will significantly reduce the risk of ankle sprains in high school soccer and basketball players Self-reported rates of participation in sport vary by country . In the UK , about 40 % of men and women aged 16 years or older participate in at least one sport every week . Although few data exist to assess trends for participation in sport , there is little evidence of change in the past decade among adults . Large cohort studies suggest that such participation in sport is associated with a 20 - 40 % reduction in all-cause mortality compared with non-participation . R and omised trials and crossover clinical studies suggest that playing sport is associated with specific health benefits . Some sports have relatively high injury risk although neuromuscular training programmes can prevent various lower extremity injuries . Clinicians can influence a large number of patients through brief interventions that promote physical activity , and encouragement toward participation in sport for some physically inactive patients qualifies as evidence -based therapy . Exercise might also be considered as a fifth vital sign and should be recorded in patients ' electronic medical records and routine histories This study investigated effects of ankle dorsiflexion range and pre-exercise calf muscle stretching on relative risk of selected injuries in 1093 male Army recruits undertaking 12 weeks of intensive training . Prior to training , ankle dorsiflexion range was measured and recruits were allocated to stretch and control groups using a quasi-r and om procedure . The stretch group stretched calf muscles under supervision prior to all intense exercise . The control group stretched upper limb muscles instead . Forty-eight injuries were recorded . Survival analysis indicated that ankle dorsiflexion range was a strong predictor of injury ( p = 0.03 ) . Definitive evidence of an effect of stretching on injury risk was not found ( p = 0.76 ) , but the sample size may have been insufficient to detect such an effect Background Soccer is a leading sport for participation and injury in youth . Objective To examine the effectiveness of a neuromuscular prevention strategy in reducing injury in youth soccer players . Design Cluster-r and omised controlled trial . Setting Calgary soccer clubs ( male or female , U13–U18 , tier 1–2 , indoor soccer ) . Participants Eighty-two soccer teams were approached for recruitment . Players from 60 teams completed the study ( 32 training ( n=380 ) , 28 control ( n=364 ) ) . Intervention The training programme was a soccer-specific neuromuscular training programme including dynamic stretching , eccentric strength , agility , jumping and balance ( including a home-based balance training programme using a wobble board ) . The control programme was a st and ardised warm-up ( static and dynamic stretching and aerobic components ) and a home-based stretching programme . Main outcome measures Previously vali date d injury surveillance included injury assessment by a study therapist . The injury definition was soccer injury result ing in medical attention and /or removal from a session and /or time loss . Results The injury rate in the training group was 2.08 injuries/1000 player-hours , and in the control group 3.35 injuries/1000 player-hours . Based on Poisson regression analysis , adjusted for clustering by team and covariates , the incidence rate ratios ( IRR ) for all injuries and acute onset injury were 0.62 ( 95 % CI 0.39 to 0.99 ) and 0.57 ( 95 % CI 0.35 to 0.91 ) . Point estimates also suggest protection of lower extremity , ankle and knee sprain injuries ( IRR=0.68 ( 95 % CI 0.42 to 1.11 ) , IRR=0.5 ( 95 % CI 0.24 to 1.04 ) and IRR=0.38 ( 95 % CI 0.08 to 1.75 ) ) . Conclusions A neuromuscular training programme is protective of all injuries and acute onset injury in youth soccer players The primary purpose of this study was to evaluate whether a preseason strength training programme for the hamstring muscle group - emphasising eccentric overloading - could affect the occurrence and severity of hamstring injuries during the subsequent competition season in elite male soccer players . Thirty players from two of the best premier-league division teams in Sweden were divided into two groups ; one group received additional specific hamstring training , whereas the other did not . The extra training was performed 1 - 2 times a week for 10 weeks by using a special device aim ing at specific eccentric overloading of the hamstrings . Isokinetic hamstring strength and maximal running speed were measured in both groups before and after the training period and all hamstring injuries were registered during the total observational period of 10 months . The results showed that the occurrence of hamstring strain injuries was clearly lower in the training group ( 3/15 ) than in the control group ( 10/15 ) . In addition , there were significant increases in strength and speed in the training group . However , there were no obvious coupling between performance parameters and injury occurrence . These results indicate that addition of specific preseason strength training for the hamstrings - including eccentric overloading - would be beneficial for elite soccer players , both from an injury prevention and from performance enhancement point of view PURPOSE This study investigated the effect of muscle stretching during warm-up on the risk of exercise-related injury . METHODS 1538 male army recruits were r and omly allocated to stretch or control groups . During the ensuing 12 wk of training , both groups performed active warm-up exercises before physical training sessions . In addition , the stretch group performed one 20-s static stretch under supervision for each of six major leg muscle groups during every warm-up . The control group did not stretch . RESULTS 333 lower-limb injuries were recorded during the training period , including 214 soft-tissue injuries . There were 158 injuries in the stretch group and 175 in the control group . There was no significant effect of preexercise stretching on all-injuries risk ( hazard ratio [ HR ] = 0.95 , 95 % CI 0.77 - 1.18 ) , soft-tissue injury risk ( HR = 0.83 , 95 % CI 0.63 - 1.09 ) , or bone injury risk ( HR = 1.22 , 95 % CI 0.86 - 1.76 ) . Fitness ( 20-m progressive shuttle run test score ) , age , and enlistment date all significantly predicted injury risk ( P < 0.01 for each ) , but height , weight , and body mass index did not . CONCLUSION A typical muscle stretching protocol performed during preexercise warm-ups does not produce clinical ly meaningful reductions in risk of exercise-related injury in army recruits . Fitness may be an important , modifiable risk factor OBJECTIVE To investigate estimated outcome effects of a sports injury prevention intervention when analysed by means of a per protocol ( PP ) analysis approach . DESIGN R and omised controlled trial ( RCT ) involving 522 athletes who sustained a lateral ankle sprain allocated to either an intervention ( received a preventive programme in addition to usual care ) or control group who were followed prospect ively for one year . METHODS Secondary analysis of data relating to registered ankle sprain recurrences , exposure and adherence to the allocated intervention using a PP analysis approach . RESULTS Twenty-three percent of the RCT intervention group indicated to have fully adhered with the neuromuscular training programme . A per protocol analysis only considering fully adherent athletes and control athletes , showed a Hazard Ratio of 0.18 ( 95 % CI : 0.07 - 0.43 ) . Significantly fewer recurrent ankle sprains were found in the fully adherent group compared to the group that was not adherent ( relative risk = 0.63 ; 95 % CI : 0.43 - 0.99 ) . CONCLUSIONS A PP analysis on fully adherent athletes versus control group athletes showed that the established intervention effect was over threefold higher compared to an earlier intention-to-treat based analysis approach . This shows that outcomes of intervention studies are heavily biased by adherence to the allocated intervention |
10,466 | 29,255,842 | For cognitively normal adults , moderate-strength evidence suggests that cognitive training in a particular domain improves performance in that domain compared with inactive or attention control population s. These results are driven largely by the results from the ACTIVE ( Advanced Cognitive Training for Independent and Vital Elderly ) trial .
Low-strength evidence suggests that for persons with MCI , cognitive training in a particular domain does not improve performance in that domain compared with controls .
The MCI trials have more limitations and are less precise than the studies conducted with cognitively normal participants .
Evidence is insufficient for incident MCI or ADRD outcomes .
At 2 years , ACTIVE participants showed improvement in the cognitive domains in which they were trained ( for example , those who received memory training improved on memory-related tasks compared with control participants ) , but no statistically significant differences were found among groups with regard to other cognitive outcomes ( for example , persons who received training in memory did not do better than control participants on reasoning tasks ) .
One year after training , both intervention groups showed statistically significant improvement in the primary outcome of the Useful Field of View test compared with the attention control group . | Fear of losing one 's cognitive ability to Alzheimer disease and related dementias ( ADRD ) and ultimately declining to a state considered by many to be worse than death ( 1 ) is driving a growing brain-training industry .
Cognitive training programs , marketed to otherwise healthy adults and persons with a recent diagnosis of mild cognitive impairment ( MCI ) , make bold cl aims for reversing brain aging .
Such cl aims include the ability to boost cognitive reserve in midlife ( with cognitive reserve referring to both the mismatch between clinical symptoms of dementia and pathologic brain lesion load at death and the repeatedly demonstrated association between educational achievement and dementia risk ) .
However , few studies have evaluated the effect of cognitive training programs on cognitive decline or the onset of dementia , which is the outcome of interest for most people who buy these programs .
This review systematic ally evaluates the existing literature on the effectiveness of cognitive training in preventing cognitive decline and ADRD .
It is part of a larger systematic review commissioned by the National Institute on Aging to address a range of potential interventions to slow cognitive decline and prevent or delay dementia . | Background Age-related cognitive decline is common and may lead to substantial difficulties and disabilities in everyday life . We hypothesized that 10 hours of visual speed of processing training would prevent age-related declines and potentially improve cognitive processing speed . Methods Within two age b and s ( 50–64 and ≥65 ) 681 patients were r and omized to ( a ) three computerized visual speed of processing training arms ( 10 hours on-site , 14 hours on-site , or 10 hours at-home ) or ( b ) an on-site attention control group using computerized crossword puzzles for 10 hours . The primary outcome was the Useful Field of View ( UFOV ) test , and the secondary outcomes were the Trail Making ( Trails ) A and B Tests , Symbol Digit Modalities Test ( SDMT ) , Stroop Color and Word Tests , Controlled Oral Word Association Test ( COWAT ) , and the Digit Vigilance Test ( DVT ) , which were assessed at baseline and at one year . 620 participants ( 91 % ) completed the study and were included in the analyses . Linear mixed models were used with Blom rank transformations within age b and s. Results All intervention groups had ( p<0.05 ) small to medium st and ardized effect size improvements on UFOV ( Cohen 's d = −0.322 to −0.579 , depending on intervention arm ) , Trails A ( d = −0.204 to −0.265 ) , Trails B ( d = −0.225 to −0.320 ) , SDMT ( d = 0.263 to 0.351 ) , and Stroop Word ( d = 0.240 to 0.271 ) . Converted to years of protection against age-related cognitive declines , these effects reflect 3.0 to 4.1 years on UFOV , 2.2 to 3.5 years on Trails A , 1.5 to 2.0 years on Trails B , 5.4 to 6.6 years on SDMT , and 2.3 to 2.7 years on Stroop Word . Conclusion Visual speed of processing training delivered on-site or at-home to middle-aged or older adults using st and ard home computers result ed in stabilization or improvement in several cognitive function tests . Widespread implementation of this intervention is feasible . Trial Registration Clinical Trials.gov CONTEXT Cognitive function in older adults is related to independent living and need for care . However , few studies have addressed whether improving cognitive functions might have short- or long-term effects on activities related to living independently . OBJECTIVE To evaluate whether 3 cognitive training interventions improve mental abilities and daily functioning in older , independent-living adults . DESIGN R and omized , controlled , single-blind trial with recruitment conducted from March 1998 to October 1999 and 2-year follow-up through December 2001 . SETTING AND PARTICIPANTS Volunteer sample of 2832 persons aged 65 to 94 years recruited from senior housing , community centers , and hospital/clinics in 6 metropolitan areas in the United States . INTERVENTIONS Participants were r and omly assigned to 1 of 4 groups : 10-session group training for memory ( verbal episodic memory ; n = 711 ) , or reasoning ( ability to solve problems that follow a serial pattern ; n = 705 ) , or speed of processing ( visual search and identification ; n = 712 ) ; or a no-contact control group ( n = 704 ) . For the 3 treatment groups , 4-session booster training was offered to a 60 % r and om sample 11 months later . MAIN OUTCOME MEASURES Cognitive function and cognitively dem and ing everyday functioning . RESULTS Thirty participants were incorrectly r and omized and were excluded from the analysis . Each intervention improved the targeted cognitive ability compared with baseline , durable to 2 years ( P<.001 for all ) . Eighty-seven percent of speed- , 74 % of reasoning- , and 26 % of memory-trained participants demonstrated reliable cognitive improvement immediately after the intervention period . Booster training enhanced training gains in speed ( P<.001 ) and reasoning ( P<.001 ) interventions ( speed booster , 92 % ; no booster , 68 % ; reasoning booster , 72 % ; no booster , 49 % ) , which were maintained at 2-year follow-up ( P<.001 for both ) . No training effects on everyday functioning were detected at 2 years . CONCLUSIONS Results support the effectiveness and durability of the cognitive training interventions in improving targeted cognitive abilities . Training effects were of a magnitude equivalent to the amount of decline expected in elderly persons without dementia over 7- to 14-year intervals . Because of minimal functional decline across all groups , longer follow-up is likely required to observe training effects on everyday function OBJECTIVES To determine the effects of cognitive training on cognitive abilities and everyday function over 10 years . DESIGN Ten-year follow-up of a r and omized , controlled single-blind trial ( Advanced Cognitive Training for Independent and Vital Elderly ( ACTIVE ) ) with three intervention groups and a no-contact control group . SETTING Six U.S. cities . PARTICIPANTS A volunteer sample of 2,832 persons ( mean baseline age 73.6 ; 26 % African American ) living independently . INTERVENTION Ten training sessions for memory , reasoning , or speed of processing ; four sessions of booster training 11 and 35 months after initial training . MEASUREMENTS Objective ly measured cognitive abilities and self-reported and performance-based measures of everyday function . RESULTS Participants in each intervention group reported less difficulty with instrumental activities of daily living ( IADLs ) ( memory : effect size = 0.48 , 99 % confidence interval ( CI ) = 0.12 - 0.84 ; reasoning : effect size = 0.38 , 99 % CI = 0.02 - 0.74 ; speed of processing : effect size = 0.36 , 99 % CI = 0.01 - 0.72 ) . At a mean age of 82 , approximately 60 % of trained participants , versus 50 % of controls ( P < .05 ) , were at or above their baseline level of self-reported IADL function at 10 years . The reasoning and speed-of-processing interventions maintained their effects on their targeted cognitive abilities at 10 years ( reasoning : effect size = 0.23 , 99 % CI = 0.09 - 0.38 ; speed of processing : effect size = 0.66 , 99 % CI = 0.43 - 0.88 ) . Memory training effects were no longer maintained for memory performance . Booster training produced additional and durable improvement for the reasoning intervention for reasoning performance ( effect size = 0.21 , 99 % CI = 0.01 - 0.41 ) and the speed-of-processing intervention for speed-of-processing performance ( effect size = 0.62 , 99 % CI = 0.31 - 0.93 ) . CONCLUSION Each Advanced Cognitive Training for Independent and Vital Elderly cognitive intervention result ed in less decline in self-reported IADL compared with the control group . Reasoning and speed , but not memory , training result ed in improved targeted cognitive abilities for 10 years OBJECTIVE The role of cognition-focused interventions in reducing cognitive decline in older people remains uncertain . This study aim ed to clarify whether a group cognitive activity ( CA ) strategy -training program would decrease the 2-year rate of cognitive decline of people with mild cognitive impairment ( MCI ) . DESIGN R and omized controlled trial . SETTING One study site . PARTICIPANTS 160 older adults with MCI ≥65 years of age ( mean : 75 , SD : 5.8 ) . INTERVENTION Five-week CA strategy training or a control nonspecific educational program . The primary outcome measure was change from baseline in the total score on the Cambridge Cognitive Examination-Revised ( CAMCOG-R ) . Secondary outcomes of interest included changes in memory , attention , executive functions , mood , and quality of life . Endpoints were collected 10 , 52 , and 104 weeks post baseline . RESULTS Intention to treat analysis identified no significant difference in CAMCOG-R scores over time between the two groups ( mean difference : -0.36 , 95 % CI : -1.02,0.29 ) or across secondary outcome measures . The exceptions were better performance of the CA group on immediate attention ( Digit Span Forwards , adjusted mean difference : 0.15 , 95 % CI : 0.01,0.30 ) and better quality of life ( adjusted mean difference : 0.57 , 95 % CI : 0.10,1.04 ) compared with controls . CONCLUSION The devised program of CA did not improve general cognitive performance of older adults with MCI over a period of 2 years . Although favorable , the beneficial effects of the intervention on attention and quality of life were small , and of uncertain significance OBJECTIVES Research indicates an association between stimulating mental activities and better memory performance as people age , but studies on computerized mental stimulation programs are limited . We explored whether computerized brain training exercises improved cognitive performance in older adults . METHODS In local retirement communities , a convenience sample was r and omized into an intervention group ( N = 36 ) , who used a computer program 5 days a week for 20 - 25 minutes each day , or a wait-list control group ( N = 33 ) . All were older adults without dementia ( mean age : 81.8 years ; SD : 6.1 ; 67 % female ) . Neuropsychological testing was completed at baseline ( Time 1 ) , 2 months ( Time 2 ) , and 6 months ( Time 3 ) . Three cognitive domains ( Immediate Memory , Delayed Memory , Language ) were compared in the two groups as a function of time using mixed models . RESULTS The intervention group used the computerized program ( Brain Fitness , Dakim Inc. , Santa Monica , CA ) for an average of 43 ( SD : 4.4 ) sessions by Time 2 and 81 ( SD : 37.5 ) sessions by Time 3 . Mixed models examining cognitive domains as function of time revealed significant group differences in Delayed Memory ( F(2,72 ) = 4.7 , p = 0.01 ) but not Immediate Memory and Language ; no significant improvements were noted for the control group . Among all participants , anyone playing at least 40 sessions over the 6 months improved in all three domains ( Immediate Memory , Delayed Memory , and Language ) . CONCLUSION Participating in a computerized brain exercise program over 6 months improves cognitive abilities in older adults . These results extend literature indicating the benefit of training exercises , whether in a classroom format or via a computerized self-paced program BACKGROUND Several reports suggest beneficial impacts of either physical or mental activity on cognitive function in old age . However , the differential effects of complex mental and physical activities on cognitive performance in humans remain to be clarified . METHODS This r and omized controlled trial evaluates a cognitive and a physical st and ardized 6-month activity intervention ( 3 x 1.5 h/wk ) conducted in Berlin ( Germany ) . Two hundred fifty nine healthy women aged 70 - 93 years were r and omized to a computer course ( n = 92 ) , an exercise course ( n = 91 ) , or a control group ( n = 76 ) , of whom 230 completed the 6-month assessment . Group differences in change over a period of 6 months in episodic memory ( story recall , possible range , 0 - 21 ; word recall , possible range , 0 - 16 ) , executive control ( working memory , ie , time quotient of Trail Making Tests B/A ) , and verbal fluency were evaluated by analyses of covariance ( intention to treat ) adjusting for baseline , fluid intelligence , and educational level . RESULTS In contrast to the control group , both the exercise group , DeltaM ( SD ) = 2.09 ( 2.66 ) , p < .001 , and the computer group , DeltaM ( SD ) = 1.89 ( 2.88 ) , p < .001 , showed improved delayed story recall . They maintained performance in delayed word recall and working memory ( time measure ) as opposed to the control group that showed a decline , DeltaM ( SD ) = -0.91 ( 2.15 ) , p = .001 , and DeltaM ( SD ) = 0.24 ( 0.68 ) , p = .04 , respectively . CONCLUSIONS In healthy older women , participation in new stimulating activities contributes to cognitive fitness and might delay cognitive decline . Exercise and computer classes seem to generate equivalent beneficial effects OBJECTIVE This study examines the short-term and long-term effects of a cognitive training ( CT ) program in enhancing cognitive function of older people with subjective memory complaints . METHODS A single-blind r and omized placebo-controlled trial was carried out in a sample of 223 older adults aged 65 years or above with subjective memory complaints in Hong Kong . They were r and omly assigned to either receive CT ( intervention group , N = 111 ) or attend health-related educational lectures only ( control group , N = 112 ) . Participants ' cognitive abilities were assessed by the Chinese version of Mattis Dementia Rating Scale at baseline , immediately after the training , and nine months after the training . RESULTS Significant interaction effect of CT and education was detected on participants ' CT gains at both T2 ( F(2 , 200 ) = 6.329 , p = 0.002 , η(2 ) = 0.060 ) and T3 ( F(2 , 189 ) = 3.294 , p = 0.039 , η(2 ) = 0.034 ) . CONCLUSIONS Cognitive training was effective in enhancing the overall cognitive functioning of less educated older adults with subjective memory complaints . The positive effect was durable for at least nine months in two cognitive areas , namely conceptualization and memory Previous research indicates that persons assigning values to ranges of health states consider some states to be worse than death . In a study of decisions regarding life-sustaining treat ments , the authors adapted and assessed existing methods for their ability to identify and quantify preferences for health states near to or worse than death in a population of well adults and nursing home residents . The cognitive burdens involved in these decisions were also evaluated . Hypothetical health states based on six attributes of functional status were constructed to describe severe constant pain , dementia , and coma . The methods of rank order , category scaling , time tradeoff , and st and ard gamble were adapted to quantify states worse than death . Cognitive burden was assessed using completion rates , interviewer as sessments , respondents ' self-reporting , and investigators ' evaluations . For both respondent groups , all methods showed similar degrees of cognitive burden for those able to complete the tasks and were similar in their ability to identify and quantify preferences . The majority of nursing home residents , however , were unable to complete or comprehend the mea surement tasks . Most respondents evaluated their current health and severe constant pain as better than death ; dementia and coma were more often considered equal to or worse than death . These results indicate that respondents can and do evaluate some health states as worse than death . The authors recommend systematic inclusion of states worse than death to describe a more complete range of preference values and routine assessment of the cognitive burdens of assessment techniques to evaluate method ologies . Keywords : health status measurement ; preference weights ; utility measurement ; health-state prefer ences ; cognitive burden . ( Med Decis Making 1994;14:9 - 18 While a training model of cognitive intervention targets the improvement of particular skills through instruction and practice , an engagement model is based on the idea that being embedded in an intellectually and socially complex environment can impact cognition , perhaps even broadly , without explicit instruction . We contrasted these 2 models of cognitive enrichment by r and omly assigning healthy older adults to a home-based inductive reasoning training program , a team-based competitive program in creative problem solving , or a wait-list control . As predicted , those in the training condition showed selective improvement in inductive reasoning . Those in the engagement condition , on the other h and , showed selective improvement in divergent thinking , a key ability exercised in creative problem solving . On average , then , both groups appeared to show ability-specific effects . However , moderators of change differed somewhat for those in the engagement and training interventions . Generally , those who started either intervention with a more positive cognitive profile showed more cognitive growth , suggesting that cognitive re sources enabled individuals to take advantage of environmental enrichment . Only in the engagement condition did initial levels of openness and social network size moderate intervention effects on cognition , suggesting that comfort with novelty and an ability to manage social re sources may be additional factors contributing to the capacity to take advantage of the environmental complexity associated with engagement . Collectively , these findings suggest that training and engagement models may offer alternative routes to cognitive resilience in late life ' Mild cognitive impairment ' ( MCI ) in older adults refers to a significant decline in memory function but not other cognitive functions . Pharmacological and non-pharmacological treatments for MCI are needed . The present r and omized clinical trial tests the efficacy of a cognitive and behavioral treatment to improve memory performance and participants ' attitudes about their memory . A multi-faceted intervention that included education about memory loss , relaxation training , memory skills training , and cognitive restructuring for memory-related beliefs was compared to a no-treatment control condition . Outcomes included memory performance and appraisal s of memory function and control . Results indicate that the treated group had significantly better memory appraisal s than controls at the end of treatment and at a six-month follow-up . There were no differences between groups on memory performance at post-test but at follow-up the trained individuals showed a trend toward better word list recall than controls . Findings suggest that individuals with MCI can benefit from multi-component memory enhancement training . Further development of such training programs and tests of their efficacy alone and in combination with medications are needed CONTEXT Cognitive training has been shown to improve cognitive abilities in older adults but the effects of cognitive training on everyday function have not been demonstrated . OBJECTIVE To determine the effects of cognitive training on daily function and durability of training on cognitive abilities . DESIGN , SETTING , AND PARTICIPANTS Five-year follow-up of a r and omized controlled single-blind trial with 4 treatment groups . A volunteer sample of 2832 persons ( mean age , 73.6 years ; 26 % black ) , living independently in 6 US cities , was recruited from senior housing , community centers , and hospitals and clinics . The study was conducted between April 1998 and December 2004 . Five-year follow-up was completed in 67 % of the sample . INTERVENTIONS Ten-session training for memory ( verbal episodic memory ) , reasoning ( inductive reasoning ) , or speed of processing ( visual search and identification ) ; 4-session booster training at 11 and 35 months after training in a r and om sample of those who completed training . MAIN OUTCOME MEASURES Self-reported and performance-based measures of daily function and cognitive abilities . RESULTS The reasoning group reported significantly less difficulty in the instrumental activities of daily living ( IADL ) than the control group ( effect size , 0.29 ; 99 % confidence interval [ CI ] , 0.03 - 0.55 ) . Neither speed of processing training ( effect size , 0.26 ; 99 % CI , -0.002 to 0.51 ) nor memory training ( effect size , 0.20 ; 99 % CI , -0.06 to 0.46 ) had a significant effect on IADL . The booster training for the speed of processing group , but not for the other 2 groups , showed a significant effect on the performance-based functional measure of everyday speed of processing ( effect size , 0.30 ; 99 % CI , 0.08 - 0.52 ) . No booster effects were seen for any of the groups for everyday problem-solving or self-reported difficulty in IADL . Each intervention maintained effects on its specific targeted cognitive ability through 5 years ( memory : effect size , 0.23 [ 99 % CI , 0.11 - 0.35 ] ; reasoning : effect size , 0.26 [ 99 % CI , 0.17 - 0.35 ] ; speed of processing : effect size , 0.76 [ 99 % CI , 0.62 - 0.90 ] ) . Booster training produced additional improvement with the reasoning intervention for reasoning performance ( effect size , 0.28 ; 99 % CI , 0.12 - 0.43 ) and the speed of processing intervention for speed of processing performance ( effect size , 0.85 ; 99 % CI , 0.61 - 1.09 ) . CONCLUSIONS Reasoning training result ed in less functional decline in self-reported IADL . Compared with the control group , cognitive training result ed in improved cognitive abilities specific to the abilities trained that continued 5 years after the initiation of the intervention . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00298558 |
10,467 | 28,954,794 | Results Moderate-level evidence suggests ( 1 ) no difference between focused ESWT and placebo ESWT at short and mid-term in PT and ( 2 ) radial ESWT is superior to conservative treatment at short , mid and long term in PHT .
Low-level evidence suggests that ESWT ( 1 ) is comparable to eccentric training , but superior to wait- and -see policy at 4 months in mid-portion AT ; ( 2 ) is superior to eccentric training at 4 months in insertional AT ; ( 3 ) less effective than corticosteroid injection at short term , but ESWT produced superior results at mid and long term in GTPS ; ( 4 ) produced comparable results to control treatment at long term in GTPS ; and ( 5 ) is superior to control conservative treatment at long term in PT .
Conclusion Low level of evidence suggests that ESWT may be effective for some lower limb conditions in all phases of the rehabilitation | Objective To evaluate extracorporeal shockwave therapy ( ESWT ) in treating Achilles tendinopathy ( AT ) , greater trochanteric pain syndrome ( GTPS ) , medial tibial stress syndrome ( MTSS ) , patellar tendinopathy ( PT ) and proximal hamstring tendinopathy ( PHT ) . | Background : Conservative treatment of patellar tendinopathy has been minimally investigated . Effective vali date d treatment protocol s are required . Objectives : To investigate the immediate ( 12 weeks ) and long term ( 12 months ) efficacy of two eccentric exercise programmes for the treatment of patellar tendinopathy . Methods : This was a prospect i ve r and omised controlled trial of 17 elite volleyball players with clinical ly diagnosed and imaging confirmed patellar tendinopathy . Participants were r and omly assigned to one of two treatment groups : a decline group and a step group . The decline group were required to perform single leg squats on a 25 ° decline board , exercising into tendon pain and progressing their exercises with load . The step group performed single leg squats on a 10 cm step , exercising without tendon pain and progressing their exercises with speed then load . All participants completed a 12 week intervention programme during their preseason . Outcome measures used were the Victorian Institute of Sport Assessment ( VISA ) score for knee function and 100 mm visual analogue scale ( VAS ) for tendon pain with activity . Measures were taken throughout the intervention period and at 12 months . Results : Both groups had improved significantly from baseline at 12 weeks and 12 months . Analysis of the likelihood of a 20 point improvement in VISA score at 12 months revealed a greater likelihood of clinical improvements in the decline group than the step group . VAS scores at 12 months did not differ between the groups . Conclusions : Both exercise protocol s improved pain and sporting function in volleyball players over 12 months . This study indicates that the decline squat protocol offers greater clinical gains during a rehabilitation programme for patellar tendinopathy in athletes who continue to train and play with pain Background —There is no disease specific , reliable , and valid clinical measure of Achilles tendinopathy . Objective —To develop and test a question naire based instrument that would serve as an index of severity of Achilles tendinopathy . Methods —Item generation , item reduction , item scaling , and pretesting were used to develop a question naire to assess the severity of Achilles tendinopathy . The final version consisted of eight questions that measured the domains of pain , function in daily living , and sporting activity . Results range from 0 to 100 , where 100 represents the perfect score . Its validity and reliability were then tested in a population of non-surgical patients with Achilles tendinopathy ( n = 45 ) , presurgical patients with Achilles tendinopathy ( n = 14 ) , and two normal control population s ( total n = 87 ) . Results —The VISA-A question naire had good test-retest ( r = 0.93 ) , intrarater ( three tests , r = 0.90 ) , and interrater ( r = 0.90 ) reliability as well as good stability when compared one week apart ( r = 0.81 ) . The mean ( 95 % confidence interval ) VISA-A score in the non-surgical patients was 64 ( 59–69 ) , in presurgical patients 44 ( 28–60 ) , and in control subjects it exceeded 96 ( 94–99 ) . Thus the VISA-A score was higher in non-surgical than presurgical patients ( p = 0.02 ) and higher in control subjects than in both patient population s ( p<0.001 ) . Conclusions —The VISA-A question naire is reliable and displayed construct validity when means were compared in patients with a range of severity of Achilles tendinopathy and control subjects . The continuous numerical result of the VISA-A question naire has the potential to provide utility in both the clinical setting and research . The test is not design ed to be diagnostic . Further studies are needed to determine whether the VISA-A score predicts prognosis BACKGROUND Extracorporeal shockwave therapy has been shown to be effective in the treatment of chronic tendon pathology in the elbow , shoulder , and plantar fascia . This prospect i ve study examines the efficacy of extracorporeal shockwave therapy in the treatment of chronic Achilles tendon disorders . METHODS Twenty-three patients ( 23 feet ) were treated with extracorporeal shockwave therapy for Achilles tendinosis , insertional tendonitis , or both . Indications for treatment were a minimum of 6 months of conservative care , and a visual analog pain score > 5 . The mean follow-up was 20 months ( range , 4 - 35 months ) . RESULTS Ninety-one percent ( 14 patients ) were satisfied or very satisfied ( 23 patients ) with treatment . Eighty-seven percent ( 20 patients ) stated that extracorporeal shockwave therapy improved their condition , 13 % ( 3 patients ) said it did not affect the condition , and none stated that it made them worse . Eighty-seven percent ( 20 patients ) stated they would have the procedure again if given the choice . Four months after extracorporeal shockwave therapy , the mean visual analog score for morning pain decreased from 7.0 to 2.3 , and activity pain decreased from 8.1 to 3.1 . CONCLUSION High-power extracorporeal shockwave therapy is safe , noninvasive , and effective , and it has a role in the treatment of chronic Achilles tendinopathy Introduction Extracorporeal shockwave therapy ( ESWT ) produces good results in the treatment of insertional Achilles tendinopathy . The efficacy of combined administration of dietary supplements with ESWT has not yet been studied . Methods In this prospect i ve , r and omized clinical trial , Shock Waves therapy and Arginine for Achilles Tendinopathy ( SWAAT ) , subjects affected by insertional Achilles tendinopathy were enrolled . Between January and October 2011 , all participants underwent three sessions of ESWT . In addition , the patients in the experimental group received a daily dietary supplement containing arginine , Vinitrox ( Bio Serae Laboratories SAS , Bram , France ) , collagen , methyl-sulfonyl-methane , vitamin C , and bromelain , while the control group patients received placebo . Results There was no statistically significant difference in the visual analog scale ( VAS ) score between the two groups at 2 months ( 3.9 vs. 5.1 ; P = 0.07 ) , whereas at 6 months the value was significantly lower in the experimental group ( 2.0 vs. 2.9 ; P = 0.04 ) . The difference in the Ankle-Hindfoot Scale score at 2 and 6 months of follow-up ( FU ) was significantly in favor of the experimental group ( 2 months : 85.4 vs. 72.1 ; P = 0.0035 ; 6 months : 92.4 vs. 76.5 ; P = 0.0002 ) . The Roles and Maudsley score also showed a statistically significant difference between the two groups in favor of the experimental arm as regards patient satisfaction ( at 2 months : 1.7 vs. 2.8 ; P < 0.0001 ; at 6 months : 1.5 vs. 2.3 ; P < 0.001 ) . There was a statistically significant reduction in tissue oximetry values compared to baseline in both treatment groups at 2 and 6 months of FU . Comparing the groups , only at the last FU , at 6 months , was a significantly lower oximetry value observed in the experimental group versus controls ( 60.2 vs. 66.0 ; P = 0.007 ) . Conclusion On the basis of the results obtained in this study , the authors conclude that in the treatment of insertional Achilles tendinopathy , ESWT induces a hemodynamic re-equilibrium with an in tendon trophism . The addition of specific dietary supplements could improve the therapeutic response Background : Patellar tendinopathy is a common overuse injury among jumping athletes . No evidence -based treatment guidelines exist . Extracorporeal shockwave therapy ( ESWT ) appears to be a promising treatment but its effectiveness has not been studied in athletes with patellar tendinopathy who have symptoms for 3 to 12 months and are still playing . Purpose : The TOPGAME study was created to determine the effectiveness of ESWT on pain , symptoms , and function in athletes with early symptomatic patellar tendinopathy who are still in training and competition . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Athletes playing volleyball , basketball , or h and ball with patellar tendinopathy for 3 to 12 months were r and omized into the ESWT or placebo group during the first half of the season . The ESWT group received 3 ESWT treatments while the placebo group received sham ESWT . In-season follow-up measurements were 1 , 12 , and 22 weeks after treatment . The primary outcome was severity of patellar tendinopathy determined with the Victorian Institute of Sport Assessment –Patella ( VISA-P ) question naire . Secondary outcome measures were pain during activities of daily living and sports and after functional knee-loading tests rated on a visual analog scale and subjective improvement . Multilevel analyses were performed to determine differences between groups over time . Results : Of the 127 symptomatic athletes invited to participate , 62 were eligible , gave consent , and were r and omized into the ESWT ( n = 31 ) or placebo group ( n = 31 ) . Mean VISA-P scores before and 1 , 12 , and 22 weeks after treatment were 59.4 ( ±11.7 ) , 66.8 ( ±16.2 ) , 66.7 ( ±17.5 ) , and 70.5 ( ±18.9 ) for the ESWT group and 62.4 ( ±13.4 ) , 66.3 ( ±19.0 ) , 68.9 ( ±20.3 ) , and 72.7 ( ±18.0 ) for the placebo group . For the VISA-P , there was a significant effect for time ( P < .01 ) but no treatment × time interaction effect ( P = .82 ) . The same pattern was seen in visual analog scale pain scores . One week after final treatment , significantly more athletes in the ESWT group reported subjective improvement ( 65 % vs 32 % ; χ2 = 6.46 , P = .01 ) . This was the only difference noted between the 2 groups . Conclusion : Extracorporeal shockwave therapy as a solitary treatment during the competitive season has no benefit over placebo treatment in the management of actively competing jumping athletes with patellar tendinopathy who have symptoms for less than 12 months Background Dealing with heterogeneity in meta-analyses is often tricky , and there is only limited advice for authors on what to do . We investigated how authors addressed different degrees of heterogeneity , in particular whether they used a fixed effect model , which assumes that all the included studies are estimating the same true effect , or a r and om effects model where this is not assumed . Methods We sample d r and omly 60 Cochrane review s from 2008 , which presented a result in its first meta- analysis with substantial heterogeneity ( I2 greater than 50 % , i.e. more than 50 % of the variation is due to heterogeneity rather than chance ) . We extracted information on choice of statistical model , how the authors had h and led the heterogeneity , and assessed the method ological quality of the review s in relation to this . Results The distribution of heterogeneity was rather uniform in the whole I2 interval , 50 - 100 % . A fixed effect model was used in 33 review s ( 55 % ) , but there was no correlation between I2 and choice of model ( P = 0.79 ) . We considered that 20 review s ( 33 % ) , 16 of which had used a fixed effect model , had major problems . The most common problems were : use of a fixed effect model and lack of rationale for choice of that model , lack of comment on even severe heterogeneity and of reservations and explanations of its likely causes . The problematic review s had significantly fewer included trials than other review s ( 4.3 vs. 8.0 , P = 0.024 ) . The problems became less pronounced with time , as those review s that were most recently up date d more often used a r and om effects model . Conclusion One-third of Cochrane review s with substantial heterogeneity had major problems in relation to their h and ling of heterogeneity . More attention is needed to this issue , as the problems we identified can be essential for the conclusions of the review Background Results of a previous r and omized controlled trial have shown comparable effectiveness of a st and ardized eccentric loading training and of repetitive low-energy shock-wave treatment ( SWT ) in patients suffering from chronic midportion Achilles tendinopathy . No r and omized controlled trials have tested whether a combined approach might lead to even better results . Purpose To compare the effectiveness of 2 management strategies — group 1 : eccentric loading and group 2 : eccentric loading plus repetitive low-energy shock-wave therapy . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods Sixty-eight patients with a chronic recalcitrant ( > 6 months ) noninsertional Achilles tendinopathy were enrolled in a r and omized controlled study . All patients had received unsuccessful management for > 3 months , including at least ( 1 ) peritendinous local injections , ( 2 ) nonsteroidal anti-inflammatory drugs , and ( 3 ) physiotherapy . A computerized r and om-number generator was used to draw up an allocation schedule . Analysis was on an intention-to-treat basis . Results At 4 months from baseline , the VISA-A score increased in both groups , from 50 to 73 points in group 1 ( eccentric loading ) and from 51 to 87 points in group 2 ( eccentric loading plus shock-wave treatment ) . Pain rating decreased in both groups , from 7 to 4 points in group 1 and from 7 to 2 points in group 2 . Nineteen of 34 patients in group 1 ( 56 % ) and 28 of 34 patients in group 2 ( 82 % ) reported a Likert scale of 1 or 2 points ( “ completely recovered ” or “ much improved ” ) . For all outcome measures , groups 1 and 2 differed significantly in favor of the combined approach at the 4-month follow-up . At 1 year from baseline , there was no difference any longer , with 15 failed patients of group 1 opting for having the combined therapy as cross-over and with 6 failed patients of group 2 having undergone surgery . Conclusion At 4-month follow-up , eccentric loading alone was less effective when compared with a combination of eccentric loading and repetitive low-energy shock-wave treatment Background : Chronic proximal hamstring tendinopathy is an overuse syndrome that is usually managed by nonoperative methods . Shockwave therapy has proved to be effective in many tendinopathies . Hypothesis : Shockwave therapy may be more effective than other nonoperative treatments for chronic proximal hamstring tendinopathy . Study Design : R and omized controlled clinical study ; Level of evidence , 1 . Methods : Forty professional athletes with chronic proximal hamstring tendinopathy were enrolled between February 1 , 2004 , and September 30 , 2006 . Patients were r and omly assigned to receive either shockwave therapy , consisting of 2500 impulses per session at a 0.18 mJ/mm2 energy flux density without anesthesia , for 4 weeks ( SWT group , n = 20 ) , or traditional conservative treatment consisting of nonsteroidal anti-inflammatory drugs , physiotherapy , and an exercise program for hamstring muscles ( TCT group , n = 20 ) . Patients were evaluated before treatment , and 1 week and 3 , 6 , and 12 months after the end of treatment . The visual analog scale ( VAS ) score for pain and Nirschl phase rating scale ( NPRS ) were used as primary outcome measures . Results : The patients were observed for a mean of 10.7 months ( range , 1 - 12 months ) . Six patients were lost to follow-up because they underwent a surgical intervention : 3 ( all in TCT group ) were lost at 3 months ; 2 ( 1 in each group ) , at 6 months ; and 1 ( in the TCT group ) , at 12 months . Primary follow-up was at 3 months after the beginning of treatment . The VAS scores in the SWT and TCT groups were 7 points before treatment ( P = .84 ) , and 2 points and 5 points , respectively , 3 months after treatment ( P < .001 ) . The NPRS scores in the SWT and TCT groups were 5 points in either group before treatment ( P = .48 ) , and 2 points and 6 points , respectively , 3 months after treatment ( P < .001 ) . At 3 months after treatment , 17 of the 20 patients ( 85 % ) in the SWT group and 2 of the 20 patients ( 10 % ) in the TCT group achieved a reduction of at least 50 % in pain ( P < .001 ) . There were no serious complications in the SWT group . Conclusion : Shockwave therapy is a safe and effective treatment for patients with chronic proximal hamstring tendinopathy BACKGROUND Although the surgical treatment of patellar tendinopathy ( jumper 's knee ) is a common procedure , there have been no r and omized , controlled trials comparing this treatment with forms of nonoperative treatment . The purpose of the present study was to compare the outcome of open patellar tenotomy with that of eccentric strength training in patients with patellar tendinopathy . METHODS Thirty-five patients ( forty knees ) who had been referred for the treatment of grade -IIIB patellar tendinopathy were r and omized to surgical treatment ( twenty knees ) or eccentric strength training ( twenty knees ) . The eccentric training group performed squats on a 25 degrees decline board as a home exercise program ( with three sets of fifteen repetitions being performed twice daily ) for a twelve-week intervention period . In the surgical treatment group , the abnormal tissue was removed by means of a wedge-shaped full-thickness excision , followed by a structured rehabilitation program with gradual progression to eccentric training . The primary outcome measure was the VISA ( Victorian Institute of Sport Assessment ) score ( possible range , 0 to 100 ) , which was calculated on the basis of answers to a symptom-based question naire that was developed specifically for patellar tendinopathy . The patients were evaluated after three , six , and twelve months of follow-up . RESULTS There was no difference between the groups with regard to the VISA score during the twelve-month follow-up period , but both groups had improvement ( p < 0.001 ) . The mean combined VISA score for the two groups increased from 30 ( 95 % confidence interval , 25 to 35 ) before the start of treatment to 49 ( 95 % confidence interval , 42 to 55 ) at three months , 58 ( 95 % confidence interval , 51 to 65 ) at six months , and 70 ( 95 % confidence interval , 62 to 78 ) at twelve months . In the surgical treatment group , five knees had no symptoms , twelve had improvement but were still symptomatic , two were unchanged , and one was worse after twelve months ( p = 0.49 compared with the eccentric training group ) . In the eccentric training group , five knees did not respond to treatment and underwent secondary surgery after three to six months . Of the remaining fifteen knees in the eccentric training group , seven had no symptoms and eight had improvement but were still symptomatic after twelve months . CONCLUSIONS No advantage was demonstrated for surgical treatment compared with eccentric strength training . Eccentric training should be tried for twelve weeks before open tenotomy is considered for the treatment of patellar tendinopathy & NA ; Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy , postherpetic neuralgia , chronic low back pain , fibromyalgia , and osteoarthritis were used . The studies had similar design s and measurement instruments , including the PI‐NRS , collected in a daily diary , and the st and ard seven‐point patient global impression of change ( PGIC ) , collected at the endpoint . The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject . Categories of ‘ much improved ’ and ‘ very much improved ’ were used as determinants of a clinical ly important difference and the relationship to the PI‐NRS was explored using graphs , box plots , and sensitivity/specificity analyses . A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study , disease type , age , sex , study result , or treatment group . On average , a reduction of approximately two points or a reduction of approximately 30 % in the PI‐NRS represented a clinical ly important difference . The relationship between percent change and the PGIC was also consistent regardless of baseline pain , while higher baseline scores required larger raw changes to represent a clinical ly important difference . The application of these results to future studies may provide a st and ard definition of clinical ly important improvement in clinical trials of chronic pain therapies . Use of a st and ard outcome across chronic pain studies would greatly enhance the comparability , validity , and clinical applicability of these studies Purpose The aim of the study was to compare the effectiveness of focused shockwave therapy ( FSWT ) and radial shockwave therapy ( RSWT ) for treating patellar tendinopathy . Methods Patients were r and omized into two groups . One group received three sessions of FSWT , and the other group received three sessions of RSWT . Both groups also received an eccentric training programme . Follow-up measurements took place 1 , 4 , 7 and 14 weeks after the final shockwave treatment . The primary outcome measure was the Victorian Institute of Sport Assessment -Patella ( VISA-P ) question naire . Secondary outcome measures were pain during ADL , sports activities and the decline squat . Results Forty-three subjects ( 57 tendons ) were included in the study . Twenty-one subjects ( 31 tendons ) received FSWT , and 22 subjects ( 26 tendons ) received RSWT . Both groups improved significantly on the VISA-P score , but there were no differences in improvement between the FSWT group ( 15 points on the VISA-P ) and the RSWT group ( 9.6 points , n.s . ) . This was also the case for the secondary outcome measures . Conclusion There were no statistically significant differences in effectiveness between FSWT and RSWT . It is therefore not possible to recommend one treatment over the other on grounds of outcome . Both groups improved significantly , although it is question able whether this difference is clinical ly relevant . Level of evidence II Background : Tendinopathies represent a serious challenge for orthopaedic surgeons involved in treatment of athletes . Purpose : To compare the effectiveness and safety of platelet-rich plasma ( PRP ) injections and focused extracorporeal shock wave therapy ( ESWT ) in athletes with jumper ’s knee . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Forty-six consecutive athletes with jumper ’s knee were selected for this study and r and omized into 2 treatment groups : 2 autologous PRP injections over 2 weeks under ultrasound guidance ( PRP group ; n = 23 ) , and 3 sessions of focused extracorporeal shock wave therapy ( 2.400 impulses at 0.17 - 0.25 mJ/mm2 per session ) ( ESWT group ; n = 23 ) . The outcome measures were Victorian Institute of Sports Assessment –Patella ( VISA-P ) question naire , pain visual analog scale ( VAS ) , and modified Blazina scale . A review er who was blinded as to the group allocation of participants performed outcome assessment s before treatment and at 2 , 6 , and 12 months after treatment . Nonparametric tests were used for within-group ( Friedman/Wilcoxon test ) and between-group ( Kruskal-Wallis/Fisher test ) testing , and the significance level was set at .05 . Results : The 2 groups were homogeneous in terms of age , sex , level of sports participation , and pretreatment clinical status . Patients in both groups showed statistically significant improvement of symptoms at all follow-up assessment s. The VISA-P , VAS , and modified Blazina scale scores showed no significant differences between groups at 2-month follow-up ( P = .635 , .360 , and .339 , respectively ) . The PRP group showed significantly better improvement than the ESWT group in VISA-P , VAS scores at 6- and 12-month follow-up , and modified Blazina scale score at 12-month follow-up ( P < .05 for all ) . Conclusion : Therapeutic injections of PRP lead to better midterm clinical results compared with focused ESWT in the treatment of jumper ’s knee in athletes Background There are no controlled studies testing the efficacy of various nonoperative strategies for treatment of greater trochanter pain syndrome . Hypothesis The null hypothesis was that local corticosteroid injection , home training , and repetitive low-energy shock wave therapy produce equivalent outcomes 4 months from baseline . Study Design R and omized controlled clinical trial ; Level of evidence , 2 . Methods Two hundred twenty-nine patients with refractory unilateral greater trochanter pain syndrome were assigned sequentially to a home training program , a single local corticosteroid injection ( 25 mg prednisolone ) , or a repetitive low-energy radial shock wave treatment . Subjects underwent outcome assessment s at baseline and at 1 , 4 , and 15 months . Primary outcome measures were degree of recovery , measured on a 6-point Likert scale ( subjects with rating completely recovered or much improved were rated as treatment success ) , and severity of pain over the past week ( 0–10 points ) at 4-month follow-up . Results One month from baseline , results after corticosteroid injection ( success rate , 75 % ; pain rating , 2.2 points ) were significantly better than those after home training ( 7 % ; 5.9 points ) or shock wave therapy ( 13 % ; 5.6 points ) . Regarding treatment success at 4 months , radial shock wave therapy led to significantly better results ( 68 % ; 3.1 points ) than did home training ( 41 % ; 5.2 points ) and corticosteroid injection ( 51 % ; 4.5 points ) . The null hypothesis was rejected . Fifteen months from baseline , radial shock wave therapy ( 74 % ; 2.4 points ) and home training ( 80 % ; 2.7 points ) were significantly more successful than was corticosteroid injection ( 48 % ; 5.3 points ) . Conclusion The role of corticosteroid injection for greater trochanter pain syndrome needs to be reconsidered . Subjects should be properly informed about the advantages and disadvantages of the treatment options , including the economic burden . The significant short-term superiority of a single corticosteroid injection over home training and shock wave therapy declined after 1 month . Both corticosteroid injection and home training were significantly less successful than was shock wave therapy at 4-month follow-up . Corticosteroid injection was significantly less successful than was home training or shock wave therapy at 15-month follow-up Objective The purpose of this study was to describe the results of two treatment regimens for medial tibial stress syndrome ( MTSS ) ; a grade d running programme and the same running programme with additional shockwave therapy ( extracorporeal shockwave therapy ; ESWT ) . Design A prospect i ve observational controlled trial . Setting Two different sports medicine departments . Participants 42 athletes with MTSS were included . Intervention Patients from one hospital were treated with a grade d running programme , while patients from the other hospital were treated with the same grade d running programme and focused ESWT ( five sessions in 9 weeks ) . Main Outcome Measures Time to full recovery ( the endpoint was being able to run 18 min consecutively without pain at a fixed intensity ) . Results The time to full recovery was significantly faster in the ESWT group compared with the patients who only performed a grade d running programme , respectively 59.7±25.8 and 91.6±43.0 days ( p=0.008 ) . Conclusions This prospect i ve observational study showed that MTSS patients may benefit from ESWT in addition to a grade d running programme . ESWT as an additional treatment warrants further investigation in a prospect i ve controlled trial with the addition of r and omisation and double blinding STUDY DESIGN Cohort study of subjects with insertional Achilles tendinopathy ( IAT ) . OBJECTIVES The purpose of this study was to establish the minimum clinical ly important difference ( MCID ) on the Victorian Institute of Sport Assessment - Achilles Question naire ( VISA-A ) and the Lower Extremity Functional Scale ( LEFS ) for patients with IAT . BACKGROUND The VISA-A and LEFS are two measures commonly utilized for patients with IAT . Previous authors have estimated the MCID for the VISA-A , but a MCID has not been formally established . The MCID for the LEFS has been established for patients with lower extremity conditions in general , but it is not clear if this MCID is applicable to patients with IAT . METHODS Fifteen subjects participating in a r and omized controlled trial study ing the effectiveness of intervention for IAT over a 12-week period were included in this study . Subjects completed the VISA-A and LEFS forms at baseline and 12 weeks after the initiation of treatment . All subjects also completed a 15-point global rating of change ( GROC ) question naire at 12 weeks after the initiation of treatment . Subjects were classified as improved or stable based on their GROC scores . RESULTS The area under the curve ( AUC ) for the VISA-A was 0.97 and a MCID of 6.5 points was identified . The AUC for the LEFS was 0.97 and a MCID of 12 points was identified . CONCLUSION The VISA-A and LEFS are both useful outcome measures to assess response in patients with IAT . LEVEL OF EVIDENCE 3 AIM Jumper 's knee affects more frequently athletes participating in jumping activities . This pathology is very difficult to treat : various therapeutic treatments are used , often based on the physician 's personal experience rather than clinical evidence . The aim of this prospect i ve study is to present our experience with the treatment of jumper 's knee using extracorporeal shock wave therapy ( ESWT ) in a group of patients followed up for 2 years after treatment . METHODS In this study , we included 73 sports patients ( 83 knees ) , 54 males and 19 females , aged between 15 and 69 years ( mean age : 32 years ) . All patients underwent clinical and instrumental diagnosis ( ultrasonography , magnetic resonance imaging and X-rays ) in order to identify presence , location and seriousness of the specific tendinopathy . The symptomatology was classified using the visual analogical scale and according to a 6-stage clinical evaluation range . Shock wave treatment was applied with an electromagnetic shock wave generator . The protocol consisted in an average of 4 sessions ( minimum 3 , maximum 5 ) , at a 2/7-day interval . In each sessions , 1,500 - 2,500 impulses were administered with an energy varying between 0.08 and 0.44 mJ/mm(2 ) . RESULTS We obtained satisfactory results in 73.5 % of cases ( 54.2 % excellent results and 19.3 good results ) . In performing athletes ( 16 tendons ) , treatment was satisfactory in 87.5 % of cases , with an average time of resuming sport of approximately 6 weeks . CONCLUSION The outcome of the described shock wave treatment appears to be satisfactory and confirms the role of this alternative treatment in the management of the tendon disorders OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity Although eccentric exercise training has shown favorable results in chronic mid-portion Achilles tendinopathy , the optimum dosage remains unknown . A systematic review of the literature was performed in accordance with the PRISMA guidelines , in order to describe different exercise protocol s and to determine the most effective training parameters . An extensive search in MEDLINE , EMBASE , CINAHL , and CENTRAL revealed 14 r and omized and clinical controlled trials . Strong evidence was found for the Alfredson exercise protocol . In this 12-week protocol , exercises are performed 3 × 15 repetitions twice daily , both with a straight and bent knee . Exercises are performed at slow speed , and load is increased when exercises are without pain . Strong evidence was also found for gradual onset of exercises during the first week of the Alfredson program , but no uniformity of protocol s exists . Other exercise protocol s did achieve similar results , but many studies had some method ological shortcomings or lacked a detailed description of their training parameters . Because of the heterogeneity of study population s and outcome measures , and lack of reporting of training compliance data , a definitive conclusion regarding the most effective training parameters could not be made . Further research comparing the content of different exercise protocol s is warranted Background Chronic patellar tendinopathy is an overuse syndrome with pathologic changes similar to tendinopathies of the shoulder , elbow , and heel . Extracorporeal shockwave was shown effective in many tendinopathies . Hypothesis Extracorporeal shockwave therapy may be more effective than conservative treatment for chronic patellar tendinopathy . Study Design R and omized controlled clinical trial ; Level of evidence , 2 . Methods This study consisted of 27 patients ( 30 knees ) in the study group and 23 patients ( 24 knees ) in the control group . In the study group , patients were treated with 1500 impulses of extracorporeal shockwave at 14 KV ( equivalent to 0.18 mJ/mm 2 energy flux density ) to the affected knee at a single session . Patients in the control group were treated with conservative treatments including nonsteroidal anti-inflammatory drugs , physiotherapy , exercise program , and the use of a knee strap . The evaluation parameters included pain score , Victorian Institute of Sports Assessment score , and ultrasonographic examination at 1 , 3 , 6 , and 12 months and then once a year . Results At the 2- to 3-year follow-up , the overall results for the study group were 43 % excellent , 47 % good , 10 % fair , and none poor . For the control group , the results were none excellent , 50 % good , 25 % fair , and 25 % poor . The mean Victorian Institute of Sports Assessment scores were 42.57 ± 10.22 and 39.25 ± 10.85 , respectively , before treatment ( P = .129 ) and 92.0 ± 10.17 and 41.04 ± 10.96 , respectively , after treatment ( P < .001 ) . Satisfactory results were observed in 90 % of the study group versus 50 % of the control group ( P < .001 ) . Recurrence of symptoms occurred in 13 % of the study group and 50 % of the control group ( P = .014 ) . Ultrasonographic examination showed a significant increase in the vascularity of the patellar tendon and a trend of reduction in the patellar tendon thickness after shockwave treatment compared with conservative treatments . However , no significant difference in the appearance , arrangement , and homogeneity of tendon fibers was noted between the 2 groups . There were no systemic or local complications or device-related problems . Conclusion Extracorporeal shockwave therapy appeared to be more effective and safer than traditional conservative treatments in the management of patients with chronic patellar tendinopathy Objective : To evaluate the effectiveness of a combined treatment of focused shockwave therapy ( ESWT ) and eccentric training compared with sham-shockwave therapy ( placebo ) and eccentric training in participants with patellar tendinopathy ( PT ) after 24 weeks . Design : R and omized controlled trial . Setting : Sports medicine departments of a university hospital and a general hospital in the Netherl and s. Participants : Fifty-two physically active male and female participants with a clinical diagnosis of PT ( mean age : 28.6 years ; range , 18 - 45 ) were r and omly allocated to the ESWT ( n = 22 ) or sham shockwave ( n = 30 ) . Interventions : Extracorporeal shockwave therapy and sham shockwave were applied in 3 sessions at 1-week intervals with a piezoelectric device . All participants were instructed to perform eccentric exercises ( 3 sets of 15 repetitions twice a day ) for 3 months on a decline board at home . Main Outcome Measures : The Victorian Institute of Sport Assessment -Patella ( VISA-P ) scores ( primary ) , pain scores during functional knee loading tests , and Likert score ( secondary ) were registered at baseline and at 6 , 12 , and 24 weeks after the start with the ESWT or sham-shockwave treatment . Results : No significant differences for the primary and secondary outcome measures were found between the groups . In the ESWT/eccentric group , the VISA-P increased from 54.5 ± 15.4 to 70.9 ± 17.8 , whereas the VISA-P in the sham-shockwave/eccentric group increased from 58.9 ± 14.6 to 78.2 ± 15.8 ( between-group change in VISA-P at 24 weeks −4.8 ; 95 % confidence interval , −12.7 to 3.0 , P = 0.150 ) . Conclusions : This study showed no additional effect of 3 sessions ESWT in participants with PT treated with eccentric exercises . The results should be interpreted with caution because of small sample size and considerable loss to follow-up , particularly in the ESWT group Background : Patient-reported outcomes ( PROs ) are considered the gold st and ard when evaluating outcomes in a surgical population . While the psychometric properties of some PROs have been tested , the properties of newer PROs in patients undergoing hip arthroscopic surgery remain somewhat unknown . Purpose : To evaluate the reliability , validity , responsiveness , and interpretability of 5 PROs ( Copenhagen Hip and Groin Outcome Score [ HAGOS ] , Hip Disability and Osteoarthritis Outcome Score [ HOOS ] , Hip Outcome Score [ HOS ] , International Hip Outcome Tool [ iHOT-33 ] , and Modified Harris Hip Score [ MHHS ] ) in a population undergoing hip arthroscopic surgery and also to provide a recommendation of the best PROs in patients undergoing hip arthroscopic surgery . Study Design : Cohort study ( diagnosis ) ; Level of evidence , 2 . Methods : Study participants were adults ( mean age , 37 ± 11 years ) who had undergone hip arthroscopic surgery 12 to 24 months previously and pain-free , healthy age-matched controls ( mean age , 35 ± 11 years ) . Baseline characteristics including age , height , weight , waist girth , physical activity , and occupation were collected for both groups . The hip arthroscopic surgery group completed the 5 PRO question naires on 3 occasions , while the healthy control group completed the PRO question naires on 1 occasion . The reliability ( test-retest reliability [ intraclass correlation coefficient , or ICC ] and minimal detectable change [ MDC ] ) , validity ( construct validity , ability to detect a difference between groups , acceptability including floor and ceiling effects ) , responsiveness , and interpretability ( minimal important change [ MIC ] ) of each measure were calculated . Results : The test-retest reliability of PROs was excellent ( ICC , 0.91 - 0.97 ) , with an MDC of < 20 % . The HOOS , HAGOS , and iHOT-33 had acceptable content validity . All PROs demonstrated construct validity and were able to detect a difference between the hip arthroscopic surgery and control groups . No measures demonstrated a floor effect ; however , the MHHS and subscales relating to activities of daily living of the HOOS , HOS , and HAGOS demonstrated a ceiling effect . The HOOS , iHOT-33 , and MHHS demonstrated adequate responsiveness , and the MIC for all measures was < 11 points of a possible 100 points . Conclusion : The PROs of the HOOS and iHOT-33 demonstrate psychometric properties that may enable research ers and clinicians to use them with confidence in a population undergoing hip arthroscopic surgery . The psychometric properties of the MHHS , HOS , and some subscales of the HAGOS are reduced , and these PROs may be less valuable in this group OBJECTIVE Various studies have shown the benefit of extracorporal shock wave therapy ( ESWT ) in the treatment of soft tissue pathologies . The aim of this prospect i ve study was to compare the results of ESWT with the operative treatment for achilleus tendopathy . Furthermore mechanical effects of the shock waves on the achilleus tendon were analysed by an in-vitro model . METHOD The achilleus tendons of common pigs treated with 1500 impulses twice using an energy varying from 0.23 - 0.54 mJ/mm ( 2 ) were histologically examined . The clinical results of two patient groups of which the first ( n = 28 ) was treated with 2000 impulses ( 0.23 mJ/mm ( 2 ) ) once and the second ( n = 26 ) underwent surgery for achilleus tendopathy were compared . RESULTS The in-vitro model demonstrated that an EFD of 0.42 and 0.54 mJ/mm ( 2 ) can lead to tendon lesions . One year follow-up showed good and excellent results in 69 % and satisfactory results in 15 % of the operated group and good and excellent results in 29 % and satisfactory results in 43 % of the ESWT group . We could show a time-dependent effect of the shock wave treatment on the clinical outcome . CONCLUSIONS Follow-ups show acceptable results with little side effects when an energy flow density ( EFD ) under 0.23 mJ/mm ( 2 ) is used . ESWT offers a non-invasive therapeutic concept that can seriously be contemplated before operative treatment , but lower success rates in comparison to the operative results can be expected BACKGROUND Nonoperative management of chronic tendinopathy of the Achilles tendon insertion has been poorly studied . With the recently demonstrated effectiveness of eccentric loading and of repetitive low-energy shock wave therapy in patients with midsubstance Achilles tendinopathy , the aim of the present r and omized , controlled trial was to verify the effectiveness of both procedures exclusively in patients with insertional Achilles tendinopathy . METHODS Fifty patients with chronic ( six months or more ) recalcitrant insertional Achilles tendinopathy were enrolled in a r and omized , controlled study . All patients had received treatment , including local injections of an anesthetic and /or corticosteroids , a prescription of nonsteroidal anti-inflammatory drugs , and physiotherapy , without success for at least three months . A computerized r and om-number generator was used to draw up an allocation schedule . Twenty-five patients were allocated to receive eccentric loading ( Group 1 ) , and twenty-five patients were allocated to treatment with repetitive low-energy shock wave therapy ( Group 2 ) . Analysis was on an intention-to-treat basis . Primary follow-up was at four months , and afterward patients were allowed to cross over . The last follow-up evaluation was at one year after completion of the initial treatment . The patients were assessed for pain , function , and activity with use of a vali date d question naire ( the Victorian Institute of Sport Assessment -Achilles [ VISA-A ] question naire ) . RESULTS At four months from baseline , the mean VISA-A score had increased in both groups , from 53 to 63 points in Group 1 and from 53 to 80 points in Group 2 . The mean pain rating decreased from 7 to 5 points in Group 1 and from 7 to 3 points in Group 2 . Seven patients ( 28 % ) in Group 1 and sixteen patients ( 64 % ) in Group 2 reported that they were completely recovered or much improved . For all outcome measures , the group that received shock wave therapy showed significantly more favorable results than the group treated with eccentric loading ( p = 0.002 through p = 0.04 ) . At four months , eighteen of the twenty-five patients from Group I had opted to cross over , as did eight of the twenty-five patients from Group 2 . The favorable results after shock wave therapy at four months were stable at the one-year follow-up evaluation . CONCLUSIONS Eccentric loading as applied in the present study showed inferior results to low-energy shock wave therapy as applied in patients with chronic recalcitrant tendinopathy of the insertion of the Achilles tendon at four months of follow-up . Further research is warranted to better define the indications for this treatment modality Background High-energy extracorporeal shock wave therapy has been shown to be an effective treatment for chronic insertions Achilles tendinopathy . The results of high-energy shock wave therapy for chronic noninsertional Achilles tendinopathy have not been determined . Hypothesis Shock wave therapy is an effective treatment for noninsertional Achilles tendinopathy . Study Design Case control study ; Level of evidence , 3 . Methods Thirty-four patients with chronic noninsertional Achilles tendinopathy were treated with a single dose of high-energy shock wave therapy ( shock wave therapy group ; 3000 shocks ; 0.21 mJ/mm2 ; total energy flux density , 604 mJ/mm2 ) . Thirty-four patients with chronic noninsertional Achilles tendinopathy were treated not with shock wave therapy but with additional forms of nonoperative therapy ( control group ) . All shock wave therapy procedures were performed using regional anesthesia . Evaluation was by change in visual analog score and by Roles and Maudsley score . Results One month , 3 months , and 12 months after treatment , the mean visual analog scores for the control and shock wave therapy groups were 8.4 and 4.4 ( P < .001 ) , 6.5 and 2.9 ( P < .001 ) , and 5.6 and 2.2 ( P < .001 ) , respectively . At final follow-up , the number of excellent , good , fair , and poor results for the shock wave therapy and control groups were 12 and 0 ( P < .001 ) , 17 and 9 ( P < .001 ) , 5 and 17 ( P < .001 ) , and 0 and 8 ( P < .001 ) , respectively . A χ2 analysis revealed that the percentage of patients with excellent ( “ 1 ” ) or good ( “ 2 ” ) Roles and Maudsley scores , that is , successful results , 12 months after treatment was statistically greater in the shock wave therapy group than in the control group ( P < .001 ) . Conclusion Shock wave therapy is an effective treatment for chronic noninsertional Achilles tendinopathy OBJECTIVE Achilles tendinopathy is prevalent in athletes , but can also affect sedentary patients . We studied the effects of eccentric exercises in sedentary non-athletic patients with Achilles tendinopathy . METHODS Thirty-four sedentary patients ( 18 males , average age 44 years , range 23 - 67 ; 16 females , average age 51 years , range 20 - 76 ; average BMI : 28.6+/-4.7 , range 22.1 - 35.4 ) with a clinical diagnosis of unilateral tendinopathy of the main body of the Achilles tendon completed the VISA-A question naire at first attendance ( 39+/-S.D. 22.8 ) and at their subsequent visits . The patients underwent a grade d progressive eccentric calf strengthening exercises programme for 12 weeks . RESULTS Fifteen patients ( 44 % ) did not improve with eccentric exercise regimen . Three patients improved after perintendinous injections aprotinin and local anaesthetic . Surgery was performed in seven patients as 6 months of conservative management failed to produce improvements . The overall average VISA-A scores at latest follow up was 50 ( S.D. 26.5 ) . CONCLUSIONS Eccentric exercises , though effective in nearly 60 % of our patients , may not benefit sedentary patients to the same extent reported in athletes Background and purpose Chronic Achilles tendinopathy is a painful condition and there are often unsatisfactory results with conservative treatment . Extracorporal shock-wave therapy ( ESWT ) has been introduced for the management of various soft tissue conditions . The objective of the study was to compare the effect of supplementing conservative treatment of chronic Achilles tendinopathy with ESWT or placebo . Patients and methods This was a r and omized , double-blind , placebo-controlled trial . Patients assigned to nonoperative treatment of chronic achilles tendinopathy were r and omized to receive either active ESWT or sham ESWT over 4 weeks . There were 48 patients ( 28 men ) with a mean age of 47 ( 19–80 ) years . American Orthopaedic Foot and Ankle Society ( AOFAS ) score and pain were assessed before treatment , during the 4-week treatment period , and at 4 , 8 , and 12 weeks of follow-up . Results Both groups improved during the treatment and follow-up period . The mean AOFAS score increased from 74 ( SD 12 ) to 81 ( 16 ) in the placebo group and from 70 ( 6.8 ) to 88 ( 10 ) in the intervention group ( p = 0.05 ) . Better results were seen in the intervention group at 8 and 12 weeks of follow-up ( p = 0.01 and p = 0.04 , respectively ) . Interpretation Extracorporal shock-wave therapy appears to be a supplement for the treatment of chronic Achilles tendinopathy Background Few r and omized controlled trials compare different methods of management in chronic tendinopathy of the main body of tendo Achillis . Purpose To compare the effectiveness of 3 management strategies — group 1 , eccentric loading ; group 2 , repetitive low-energy shock-wave therapy ( SWT ) ; and group 3 , wait and see — in patients with chronic tendinopathy of the main body of tendo Achillis . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods Seventy-five patients with a chronic recalcitrant ( > 6 months ) noninsertional Achilles tendinopathy were enrolled in a r and omized controlled study . All patients had received unsuccessful management for > 3 months , including at least ( 1 ) peritendinous local injections , ( 2 ) nonsteroidal anti-inflammatory drugs , and ( 3 ) physiotherapy . A computerized r and om-number generator was used to draw up an allocation schedule . Analysis was on intention-to-treat basis . Results At 4 months from baseline , the Victorian Institute of Sport Assessment (VISA)-A score increased in all groups , from 51 to 76 points in group 1 ( eccentric loading ) , from 50 to 70 points in group 2 ( repetitive low-energy SWT ) , and from 48 to 55 points in group 3 ( wait and see ) . Pain rating decreased in all groups , from 7 to 4 points in group 1 , from 7 to 4 points in group 2 , and from 8 to 6 points in group 3 . Fifteen of 25 patients in group 1 ( 60 % ) , 13 of 25 patients in group 2 ( 52 % ) , and 6 of 25 patients in Group 3 ( 24 % ) reported a Likert scale of 1 or 2 points ( “ completely recovered ” or “ much improved ” ) . For all outcome measures , groups 1 and 2 did not differ significantly . For all outcome measures , groups 1 and 2 showed significantly better results than group 3 . Conclusion At 4-month follow-up , eccentric loading and low-energy SWT showed comparable results . The wait- and -see strategy was ineffective for the management of chronic recalcitrant tendinopathy of the main body of the Achilles tendon OBJECTIVES Up to 35 % of runners develop medial tibial stress syndrome ( MTSS ) which often results in lengthy disruption to training and sometimes affects daily activities . There is currently no high quality evidence to support any particular intervention for MTSS . This study aims to investigate the effect of shockwave therapy for MTSS . DESIGN A r and omized , sham-controlled , pilot trial in a university-based health clinic including 28 active adults with MTSS . METHODS Intervention included st and ard dose shockwave therapy for the experimental group versus sham dose for the control group , delivered during Week 1 - 3 , 5 and 9 . Main outcome measures were pain measured during bone and muscle pressure as well as during running using a numerical rating scale ( 0 - 10 ) and running was measured as pain-limited distance ( m ) , at Week 1 ( baseline ) and Week 10 ( post-intervention ) . Self-perception of change was measured using the Global Rating of Change Scale ( -7 to + 7 ) at Week 10 ( post-intervention ) . RESULTS Pain ( palpation ) was reduced in the experimental group by 1.1 out of 10.0 ( 95 % CI -2.3 to 0.0 ) less than the control group . There were no other statistically significant differences between the groups . CONCLUSIONS St and ard dose shockwave therapy is not more effective than sham dose at improving pain or running distance in MTSS . However , the sham dose may have had a clinical effect . Further investigation including a no intervention control is warranted to evaluate the effect of shockwave therapy in the management of MTSS |
10,468 | 24,793,000 | Therefore , platinum-based combination therapy plus RT should be the preferred treatment over weekly CDDP plus RT for stage IB-IVA CC | BACKGROUND Treatment with weekly cisplatin ( CDDP ) plus radiotherapy ( RT ) is the st and ard regimen for stage IB to stage IVA cervical carcinoma ( CC ) .
We performed a systematic review and meta- analysis of published studies to evaluate whether CDDP-based doublet therapy improves survival compared to weekly CDDP plus RT in patients with CC . | Objective Concurrent chemoradiation therapy ( CCRT ) is the st and ard treatment for locally advanced cervical cancer . Although the optimal chemotherapeutic regimen is not yet defined , previous r and omized trials have demonstrated that 5-fluorouracil ( 5-FU ) plus cisplatin every 3 weeks and weekly cisplatin are the most popular regimens . The purpose of this study was to compare the outcomes of weekly CCRT with cisplatin and monthly CCRT with 5-FU plus cisplatin for locally advanced cervical cancer . Methods We retrospectively review ed data from 255 patients with FIGO stage IIB-IVA cervical cancer . Patients were classified into two CCRT groups according to the concurrent chemotherapy : weekly CCRT group , consisted of CCRT with weekly cisplatin for six cycles ; and monthly CCRT group , consisted of CCRT with cisplatin and 5-FU every 4 weeks for two cycles followed by additional consolidation chemotherapy for two cycles with the same regimen . Results Of 255 patients , 152 ( 59.6 % ) patients received weekly CCRT and 103 ( 40.4 % ) received monthly CCRT . The mean follow-up period was 39 months ( range , 1 to 186 months ) . Planned CCRT was given to 130 ( 85.5 % ) patients in weekly CCRT group and 84 ( 81.6 % ) patients in monthly CCRT group , respectively . Severe adverse effects were more common in the monthly CCRT group than in the weekly CCRT group . There were no statistically significant differences in progression-free survival and overall survival between the two groups ( p=0.715 and p=0.237 ) . Conclusion Both weekly CCRT and monthly CCRT seem to have similar efficacy for patients with locally advanced cervical cancer , but the weekly cisplatin is better tolerated BACKGROUND AND METHODS On behalf of the Gynecologic Oncology Group , we performed a r and omized trial of radiotherapy in combination with three concurrent chemotherapy regimens -- cisplatin alone ; cisplatin , fluorouracil , and hydroxyurea ; and hydroxyurea alone -- in patients with locally advanced cervical cancer . Women with primary untreated invasive squamous-cell carcinoma , adenosquamous carcinoma , or adenocarcinoma of the cervix of stage IIB , III , or IVA , without involvement of the para-aortic lymph nodes , were enrolled . The patients had to have a leukocyte count of at least 3000 per cubic millimeter , a platelet count of at least 100,000 per cubic millimeter , a serum creatinine level no higher than 2 mg per deciliter ( 177 micromol per liter ) , and adequate hepatic function . All patients received external-beam radiotherapy according to a strict protocol . Patients were r and omly assigned to receive one of three chemotherapy regimens : 40 mg of cisplatin per square meter of body-surface area per week for six weeks ( group 1 ) ; 50 mg of cisplatin per square meter on days 1 and 29 , followed by 4 g of fluorouracil per square meter given as a 96-hour infusion on days 1 and 29 , and 2 g of oral hydroxyurea per square meter twice weekly for six weeks ( group 2 ) ; or 3 g of oral hydroxyurea per square meter twice weekly for six weeks ( group 3 ) . RESULTS The analysis included 526 women . The median duration of follow-up was 35 months . Both groups that received cisplatin had a higher rate of progression-free survival than the group that received hydroxyurea alone ( P<0.001 for both comparisons ) . The relative risks of progression of disease or death were 0.57 ( 95 percent confidence interval , 0.42 to 0.78 ) in group 1 and 0.55 ( 95 percent confidence interval , 0.40 to 0.75 ) in group 2 , as compared with group 3 . The overall survival rate was significantly higher in groups 1 and 2 than in group 3 , with relative risks of death of 0.61 ( 95 percent confidence interval , 0.44 to 0.85 ) and 0.58 ( 95 percent confidence interval , 0.41 to 0.81 ) , respectively . CONCLUSIONS Regimens of radiotherapy and chemotherapy that contain cisplatin improve the rates of survival and progression-free survival among women with locally advanced cervical cancer Objectives : The objective of this study was to compare outcomes for patients with cervical cancer treated with radiation concurrently with cisplatin , cisplatin/5-fluorouracil ( 5-FU ) , or without chemotherapy . Material s and Methods : We review ed the records of eligible patients with locoregionally confined , stage IB1 through IVA , intact cervical cancer who were treated at Northwestern Memorial Hospital . All patients underwent definitive radiotherapy with combined external beam radiation — the majority with extended-field (62%)— and received low-dose rate brachytherapy . Results : A total of 236 patients were included : 99 had no concurrent chemotherapy , 95 were treated with concurrent cisplatin , and 42 were treated with cisplatin/5-FU . For all patients treated with or without chemotherapy , overall survival at 5 and 10 years was 64 % and 59 % , respectively . Patients treated with chemotherapy had a superior recurrence-free survival rate of 69 % at 5 years versus 49 % in patients who did not receive chemotherapy ( P=0.09 ) . Twenty-six percent of patients treated with cisplatin alone , 31 % of patients treated with cisplatin/5-FU , and 45 % of patients who did not receive chemotherapy experienced a disease recurrence . Adenosquamous histology conferred a higher rate of recurrence as compared with adenocarcinoma and squamous cell histologies ( 54 % vs. 34 % , respectively ; P=0.05 ) . Conclusions : Cisplatin-based concurrent chemoradiotherapy showed a trend toward improved recurrence-free survival survival in the definitive treatment of nonmetastatic cervical cancer . The addition of 5-FU to cisplatin did not appear to significantly impact survival or recurrence-free survival . Adenosquamous histology was associated with a higher risk of recurrence as compared with other histologic subtypes PURPOSE To compare gemcitabine and cisplatin ( GC ) with cisplatin ( C ) concurrent with radiotherapy in International Federation of Gynecology and Obstetrics Stage IB2 , IIA , and IIB cervical carcinoma in a preoperative setting . The main endpoints were the pathologic response rate and toxicity . METHODS AND MATERIAL S A total of 83 patients were r and omized to either C or GC . Treatment consisted of six doses of cisplatin at 40 mg/m(2 ) every week for Arm 1 ( C ) and six doses of gemcitabine at 125 mg/m(2 ) plus cisplatin at 40 mg/m(2 ) every week for or Arm 2 ( GC ) Both regimens were administered concurrent with 50 Gy of external beam radiotherapy in 2-Gy fractions for 5 weeks . After chemoradiotherapy , patients underwent radical hysterectomy . RESULTS All 83 patients were studied for toxicity and 80 for response . The complete pathologic response rate in the C arm and GC arm was 55 % ( 95 % confidence interval , 35.5 - 73 % ) and 77.5 % ( 95 % confidence interval , 57 - 90 % ; p = 0.0201 ) . Among those with a partial response , 7 patients each had high and intermediate-high risk factors for recurrence in their surgical specimens in the C arm vs. 2 and 3 patients , respectively , with these characteristics in the CG arm . The number of weekly doses and the dose intensity of GC were lower than for C. The time to complete external beam radiotherapy also favored the C arm . The CG combination produced greater GI and hematologic toxicity . CONCLUSION The radiosensitizing combination of GC achieved a greater pathologic response rate than C in the treatment of cervical cancer BACKGROUND Bulky stage IB cervical cancers have a poorer prognosis than smaller stage I cervical cancers . For the Gynecologic Oncology Group , we conducted a trial to determine whether weekly infusions of cisplatin during radiotherapy improve progression-free and overall survival among patients with bulky stage IB cervical cancer . METHODS Women with bulky stage IB cervical cancers ( tumor , > or = 4 cm in diameter ) were r and omly assigned to receive radiotherapy alone or in combination with cisplatin ( 40 mg per square meter of body-surface area once a week for up to six doses ; maximal weekly dose , 70 mg ) , followed in all patients by adjuvant hysterectomy . Women with evidence of lymphadenopathy on computed tomographic scanning or lymphangiography were ineligible unless histologic analysis showed that there was no lymph-node involvement . The cumulative dose of external pelvic and intracavitary radiation was 75 Gy to point A ( cervical parametrium ) and 55 Gy to point B ( pelvic wall ) . Cisplatin was given during external radiotherapy , and adjuvant hysterectomy was performed three to six weeks later . RESULTS The relative risks of progression of disease and death among the 183 women assigned to receive radiotherapy and chemotherapy with cisplatin , as compared with the 186 women assigned to receive radiotherapy alone , were 0.51 ( 95 percent confidence interval , 0.34 to 0.75 ) and 0.54 ( 95 percent confidence interval , 0.34 to 0.86 ) , respectively . The rates of both progression-free survival ( P<0.001 ) and overall survival ( P=0.008 ) were significantly higher in the combined-therapy group at four years . In the combined-therapy group there were higher frequencies of transient grade 3 ( moderate ) and grade 4 ( severe ) adverse hematologic effects ( 21 percent , vs. 2 percent in the radiotherapy group ) and adverse gastrointestinal effects ( 14 percent vs. 5 percent ) . CONCLUSIONS Adding weekly infusions of cisplatin to pelvic radiotherapy followed by hysterectomy significantly reduced the risk of disease recurrence and death in women with bulky stage IB cervical cancers PURPOSE In 1986 , a protocol comparing primary radiation therapy ( RT ) plus hydroxyurea ( HU ) to irradiation plus fluorouracil ( 5-FU ) and cisplatin ( CF ) was activated by the Gynecologic Oncology Group ( GOG ) for the treatment of patients with locally advanced cervical carcinoma . The goals were to determine the superior chemoradiation regimen and to quantitate the relative toxicities . METHODS All patients had biopsy-proven invasive squamous cell carcinoma , adenocarcinoma , or adenosquamous carcinoma of the uterine cervix . Patients underwent st and ard clinical staging studies and their tumors were found to be International Federation of Gynaecology and Obstetrics stages IIB , III , or IVA . Negative cytologic washings and para-aortic lymph nodes were required for entry . Patients were r and omized to receive either st and ard whole pelvic RT with concurrent 5-FU infusion and bolus CF or the same RT plus oral HU . RESULTS Of 388 r and omized patients , 368 were eligible ; 177 were r and omized to CF and 191 to HU . Adverse effects were predominantly hematologic or gastrointestinal in both regimens . Severe or life-threatening leukopenia was more common in the HU group ( 24 % ) than in the CF group ( 4 % ) . The difference in progression-free survival ( PFS ) was statistically significant in favor of the CF group ( P = .033 ) . The sites of progression in the two treatment groups were not substantially different . Survival was significantly better for the patients r and omized to CF ( P = .018 ) . CONCLUSION This study demonstrates that for patients with locally advanced carcinoma of the cervix , the combination of 5-FU and CF with RT offers patients better PFS and overall survival than HU , and with manageable toxicity PURPOSE Radiation Therapy Oncology Group 0417 was a phase II study that explored the safety and efficacy of the addition of bevacizumab to chemoradiation therapy . The safety results have been previously reported . Herein we report the secondary efficacy endpoints of overall survival ( OS ) , locoregional failure ( LRF ) , para-aortic nodal failure ( PAF ) , distant failure ( DF ) , and disease-free survival ( DFS ) . METHODS AND MATERIAL S Eligible patients with bulky Stage IB-IIIB disease were treated with once-weekly cisplatin ( 40 mg/m2 ) chemotherapy and st and ard pelvic radiation therapy and brachytherapy . Bevacizumab was administered at 10 mg/kg intravenously every 2 weeks for 3 cycles during chemoradiation . For OS , failure was defined as death of any cause and was measured from study entry to date of death . LRF was defined as any failure in the pelvis . PAF was defined as any para-aortic nodal failure . DF was analyzed both including and excluding PAF . DFS was measured from study entry to date of first LRF . DF was measured with or without PAF or death . OS and DFS were estimated by the Kaplan-Meier method , and LRF and DF rates were estimated by the cumulative incidence method . RESULTS 49 eligible patients from 28 institutions were enrolled between 2006 and 2009 . The median follow-up time was 3.8 years ( range , 0.8 - 6.0 years ) . The surviving patients had a median follow-up time of 3.9 years ( range , 2.1 - 6.0 years ) . Most patients had tumors of International Federation of Gynecology and Obstetrics Stage IIB ( 63 % ) , and 80 % were squamous . The 3-year OS , DFS , and LRF were 81.3 % ( 95 % confidence interval [ CI ] , 67.2%-89.8 % ) , 68.7 % ( 95 % CI , 53.5%-79.8 % ) , and 23.2 % ( 95 % CI , 11%-35.4 % ) , respectively . The PAF , DF without PAF , and DF with PAF at 3 years were 8.4 % ( 95 % CI , 0.4%-16.3 % ) , 14.7 % ( 95 % CI , 4.5%-24.9 % ) , and 23.1 % ( 95 % CI 11.0%-35.2 % ) , respectively . CONCLUSION In this study , bevacizumab in combination with st and ard pelvic chemoradiation therapy for locally advanced cervical cancer showed efficacy results that are promising and may warrant further investigation PURPOSE We report the long-term survival and toxicity of a r and omized phase III study comparing cisplatin alone with cisplatin , flurouracil , and hydroxyurea versus hydroxyurea concurrent with pelvic irradiation for patients with locally advanced cervical cancer with pathologically negative para-aortic nodes . PATIENTS AND METHODS Comparisons of progression-free ( PFS ) and overall survival ( OS ) between treatment arms utilized Kaplan-Meier and log-rank statistics . Relative risk estimates adjusting for prognostic factors were determined using the Cox proportional hazards regression model . Pearson 's 2 test was used to assess differences in adverse events . RESULTS The analysis included 526 patients . The median follow-up among surviving patients was 106 months . Consistent with the original report , improvement in PFS and OS was evident for both cisplatin-containing arms compared with hydroxyurea ( P < .001 ) . Analogous results were seen for stage IIB and for stage III disease ( each P < .025 ) . The relative risk of progression of disease or death was 0.57 ( 95 % CI , 0.43 to 0.75 ) with cisplatin and 0.51 ( 95 % CI , 0.38 to 0.67 ) with cisplatin-based combination chemotherapy compared with hydroxyurea . Among 518 patients who received radiation , acute ( grade 3 or 4 ) gastrointestinal or urologic toxicities occurred in 66 with cisplatin ( 19.1 % ) and 29 with hydroxyurea ( 16.8 % ) . Delayed radiation toxicity occurred in six patients who received cisplatin ( 1.7 % ) and two who received hydroxyurea ( 1.2 % ; P = .680 ) . CONCLUSION Cisplatin-based chemotherapy during pelvic radiation therapy improves long-term PFS and OS among locally advanced cervical cancer patients collectively and for stage IIB and III disease , individually . There was no observed increase in late toxicity with cisplatin-based chemoradiotherapy Background This study explored whether docetaxel/cisplatin and radiotherapy ( TP-R ) increases overall survival ( OS ) and recurrence-free survival ( RFS ) compared to single-agent cisplatin and radiotherapy ( C-R ) in patients with high-risk early-stage cervical cancer post surgery . Methods Patients with clinical stage IB and IIA carcinoma of the cervix , initially treated with radical hysterectomy and pelvic lymphadenectomy , and who had positive pelvic lymph nodes and /or positive margins and /or the diameter of the primary tumor ≥4 cm and /or depth of interstitial infiltration ≥1/2 and /or lymphovascular space invasion were eligible for this study . Patients were r and omized to receive C-R or TP-R. Radiotherapy in both groups was external radiation ( 46–54 Gy ) followed by high-dose rate brachytherapy ( 12–24 Gy ) . Patients were given cisplatin ( 40 mg/m2 ) every week for five cycles ( C-R group ) or docetaxel ( 30 mg/m2 ) and cisplatin ( 30 mg/m2 ) every week for five cycles ( TP-R group ) . Results Between 2003 and 2008 , 320 patients were entered onto the study . Final analyses included 285 patients . One hundred and forty patients comprised the C-R group and 145 were in the TP-R group . The 5-year OS were 74.3 % in the C-R group and 82.8 % in the TP-R group . The hazard ratio ( HR ) for death was 0.65 in the TP-R group ( 95 % CI : 0.39–1.09 , P = 0.098 ) . The RFS were 69.3 % in the C-R group and 79.3 % in the TP-R group , and the HR for recurrence was 0.64 in the TP-R group ( 95 % CI : 0.40–1.03 , P = 0.061 ) . Recurrence rates were similar in both groups ( 27 in the C-R group and 18 in the TP-R group , P = 0.112 ) . The seriousness of late side effects was similar in the two groups , with a higher rate of reversible hematological effects in the TP-R group . Conclusions Compared with single-agent cisplatin and radiotherapy , docetaxel/cisplatin in combination with radiotherapy does not increase OS but has the trend of increasing RFS in patients with high-risk early-stage cervical cancer . However , docetaxel/cisplatin in combination with radiotherapy is associated with a higher incidence of side effects , this effect was reversible , and the incidence of late side effects was similar in the two treatment groups PURPOSE To analyze recurrence patterns in patients with cancer of the esophagus or gastroesophageal junction treated with either preoperative chemoradiotherapy ( CRT ) plus surgery or surgery alone . PATIENTS AND METHODS Recurrence pattern was analyzed in patients from the previously published CROSS I and II trials in relation to radiation target volumes . CRT consisted of five weekly courses of paclitaxel and carboplatin combined with a concurrent radiation dose of 41.4 Gy in 1.8-Gy fractions to the tumor and pathologic lymph nodes with margin . RESULTS Of the 422 patients included from 2001 to 2008 , 418 were available for analysis . Histology was mostly adenocarcinoma ( 75 % ) . Of the 374 patients who underwent resection , 86 % were allocated to surgery and 92 % to CRT plus surgery . On January 1 , 2011 , after a minimum follow-up of 24 months ( median , 45 months ) , the overall recurrence rate in the surgery arm was 58 % versus 35 % in the CRT plus surgery arm . Preoperative CRT reduced locoregional recurrence ( LRR ) from 34 % to 14 % ( P < .001 ) and peritoneal carcinomatosis from 14 % to 4 % ( P < .001 ) . There was a small but significant effect on hematogenous dissemination in favor of the CRT group ( 35 % v 29 % ; P = .025 ) . LRR occurred in 5 % within the target volume , in 2 % in the margins , and in 6 % outside the radiation target volume . In 1 % , the exact site in relation to the target volume was unclear . Only 1 % had an isolated infield recurrence after CRT plus surgery . CONCLUSION Preoperative CRT in patients with esophageal cancer reduced LRR and peritoneal carcinomatosis . Recurrence within the radiation target volume occurred in only 5 % , mostly combined with outfield failures BACKGROUND AND METHODS We compared the effect of radiotherapy to a pelvic and para-aortic field with that of pelvic radiation and concurrent chemotherapy with fluorouracil and cisplatin in women with advanced cervical cancer . Between 1990 and 1997 , 403 women with advanced cervical cancer confined to the pelvis ( stages IIB through IVA or stage IB or IIa with a tumor diameter of at least 5 cm or involvement of pelvic lymph nodes ) were r and omly assigned to receive either 45 Gy of radiation to the pelvis and para-aortic lymph nodes or 45 Gy of radiation to the pelvis alone plus two cycles of fluorouracil and cisplatin ( days 1 through 5 and days 22 through 26 of radiation ) . Patients were then to receive one or two applications of low-dose-rate intracavitary radiation , with a third cycle of chemotherapy planned for the second intracavitary procedure in the combined-therapy group . RESULTS Of the 403 eligible patients , 193 in each group could be evaluated . The median duration of follow-up was 43 months . Estimated cumulative rates of survival at five years were 73 percent among patients treated with radiotherapy and chemotherapy and 58 percent among patients treated with radiotherapy alone ( P=0.004 ) . Cumulative rates of disease-free survival at five years were 67 percent among patients in the combined-therapy group and 40 percent among patients in the radiotherapy group ( P<0.001 ) . The rates of both distant metastases ( P<0.001 ) and locoregional recurrences ( P<0.001 ) were significantly higher among patients treated with radiotherapy alone . The seriousness of side effects was similar in the two groups , with a higher rate of reversible hematologic effects in the combined-therapy group . CONCLUSIONS The addition of chemotherapy with fluorouracil and cisplatin to treatment with external-beam and intracavitary radiation significantly improved survival among women with locally advanced cervical cancer PURPOSE This prospect i ve , r and omized phase III intergroup trial of the Gynecologic Oncology Group and National Cancer Institute of Canada Clinical Trials Group was design ed to test the effectiveness and safety of adding the hypoxic cell sensitizer tirapazamine ( TPZ ) to st and ard cisplatin ( CIS ) chemoradiotherapy in locally advanced cervix cancer . PATIENTS AND METHODS Patients with locally advanced cervix cancer were r and omly assigned to CIS chemoradiotherapy versus CIS/TPZ chemoradiotherapy . Primary end point was progression-free survival ( PFS ) . Secondary end points included overall survival ( OS ) and tolerability . RESULTS PFS was evaluable in 387 of 402 patients r and omly assigned over 36 months , with enrollment ending in September 2009 . Because of the lack of TPZ supply , the study did not reach its original target accrual goal . At median follow-up of 28.3 months , PFS and OS were similar in both arms . Three-year PFS for the TPZ/CIS/RT and CIS/RT arms were 63.0 % and 64.4 % , respectively ( log-rank P = .7869 ) . Three-year OS for the TPZ/CIS/RT and CIS/RT arms were 70.5 % and 70.6 % , respectively ( log-rank P = .8333 ) . A scheduled interim safety analysis led to a reduction in the starting dose for the TPZ/CIS arm , with result ing tolerance in both treatment arms . CONCLUSION TPZ/CIS chemoradiotherapy was not superior to CIS chemoradiotherapy in either PFS or OS , although definitive commentary was limited by an inadequate number of events ( progression or death ) . TPZ/CIS chemoradiotherapy was tolerable at a modified starting dose OBJECTIVE To compare monthly fluorouracil ( FU ) plus cisplatin and weekly cisplatin concurrent with radiotherapy for locally advanced cervical cancer . METHODS A total of 158 patients ( stages IIB through IVA ) without para-aortic lymph nodes were r and omized to receive 3 monthly cycles of FU ( 1000 mg/m2/day i.v . ) plus cisplatin ( 20 mg/m2/day i.v . ) for 5 days ( group I , n=79 ) or 6 cycles of weekly cisplatin ( 30 mg/m2 i.v . ) ( group II , n=79 ) , concurrent with definitive radiotherapy . Radiotherapy consisted of external irradiation to the whole pelvis of 41.4 - 50.4 Gy in 23 - 28 fractions plus high-dose rate ( HDR ) intracavitary brachytherapy ( 30 - 35 Gy in 6 - 7 fractions ) to point A , together with a parametrial boost . Compliance with treatment , toxicity , response , and survival was analyzed and compared . RESULTS Of the 158 women , 155 women were eligible for analysis ; the median follow-up of surviving patients was 39 months . Full planned chemoradiotherapy was delivered to 47 ( 60 % ) and 55 ( 71 % ) patients in groups I and II , respectively . The incidence of acute grade 3/4 hematologic toxicity was 43 % and 26 % ( p=0.037 ) . The complete response rate of each group was 91 % . Four-year overall and progression-free survival rates were 70 % and 67 % , respectively , in group I and 67 % and 66 % , respectively , in group II . CONCLUSIONS The regimen of chemoradiation using weekly cisplatin significantly improves compliance with treatment and reduces acute hematologic toxicity , while not affecting response and survival rates |
10,469 | 23,126,607 | Differences in health literacy level were consistently associated with increased hospitalizations , greater emergency care use , lower use of mammography , lower receipt of influenza vaccine , poorer ability to demonstrate taking medications appropriately , poorer ability to interpret labels and health messages , and , among seniors , poorer overall health status and higher mortality .
Health literacy level potentially mediates disparities between blacks and whites . | OBJECTIVES To up date a 2004 systematic review of health care service use and health outcomes related to differences in health literacy level and interventions design ed to improve these outcomes for individuals with low health literacy . | RATIONALE Although inadequate health literacy has been associated with lower asthma medication knowledge and worse metered-dose inhaler ( MDI ) technique , the relationship between health literacy and the capacity to learn asthma self-management skills is unknown . OBJECTIVES In this prospect i ve cohort study of adults hospitalized for severe asthma exacerbations at two inner-city hospitals , we examined the relationship between inadequate health literacy and difficulties learning and retaining instructions about discharge medications and appropriate MDI technique . METHODS At hospital discharge , participants received one-on-one , 30-min , guideline -based , written and oral instruction about their asthma discharge regimen as well as appropriate MDI technique . MEASUREMENTS AND MAIN RESULTS Seventy-three patients were enrolled . Inadequate health literacy was identified in 16 ( 22 % ) participants . Before instruction , inadequate health literacy was associated with lower asthma medication knowledge ( 5.2/10 vs. 7.2/10 , p < 0.001 ) and worse MDI technique ( 3.2/6 vs. 3.9/6 , p = 0.03 ) . However , inadequate health literacy was not associated with difficulty learning ( p = 0.33 ) or retaining ( p = 0.35 ) instructions about the discharge regimen . Similarly , inadequate health literacy was not associated with difficulty learning ( p = 0.26 ) or retaining ( p = 0.97 ) appropriate MDI technique . Results were similar in multivariable models adjusted for demographic characteristics and asthma severity indicators . CONCLUSIONS These findings suggest that inadequate health literacy is a surmountable barrier to learning and remembering key asthma self-management skills Objective To evaluate the effect of a video decision support tool on the preferences for future medical care in older people if they develop advanced dementia , and the stability of those preferences after six weeks . Design R and omised controlled trial conducted between 1 September 2007 and 30 May 2008 . Setting Four primary care clinics ( two geriatric and two adult medicine ) affiliated with three academic medical centres in Boston . Participants Convenience sample of 200 older people ( ≥65 years ) living in the community with previously scheduled appointments at one of the clinics . Mean age was 75 and 58 % were women . Intervention Verbal narrative alone ( n=106 ) or with a video decision support tool ( n=94 ) . Main outcome measures Preferred goal of care : life prolonging care ( cardiopulmonary resuscitation , mechanical ventilation ) , limited care ( admission to hospital , antibiotics , but not cardiopulmonary resuscitation ) , or comfort care ( treatment only to relieve symptoms ) . Preferences after six weeks . The principal category for analysis was the difference in proportions of participants in each group who preferred comfort care . Results Among participants receiving the verbal narrative alone , 68 ( 64 % ) chose comfort care , 20 ( 19 % ) chose limited care , 15 ( 14 % ) chose life prolonging care , and three ( 3 % ) were uncertain . In the video group , 81 ( 86 % ) chose comfort care , eight ( 9 % ) chose limited care , four ( 4 % ) chose life prolonging care , and one ( 1 % ) was uncertain ( χ2=13.0 , df=3 , P=0.003 ) . Among all participants the factors associated with a greater likelihood of opting for comfort care were being a college graduate or higher , good or better health status , greater health literacy , white race , and r and omisation to the video arm . In multivariable analysis , participants in the video group were more likely to prefer comfort care than those in the verbal group ( adjusted odds ratio 3.9 , 95 % confidence interval 1.8 to 8.6 ) . Participants were re-interviewed after six weeks . Among the 94/106 ( 89 % ) participants re-interviewed in the verbal group , 27 ( 29 % ) changed their preferences ( κ=0.35 ) . Among the 84/94 ( 89 % ) participants re-interviewed in the video group , five ( 6 % ) changed their preferences ( κ=0.79 ) ( P<0.001 for difference ) . Conclusion Older people who view a video depiction of a patient with advanced dementia after hearing a verbal description of the condition are more likely to opt for comfort as their goal of care compared with those who solely listen to a verbal description . They also have more stable preferences over time . Trial registration Clinical trials.gov NCT00704886 Background Insecticide-treated bed nets ( ITN ) provide real hope for the reduction of the malaria burden across Africa . Underst and ing factors that determine access to ITN is crucial to debates surrounding the optimal delivery systems . The influence of homestead wealth on use of nets purchased from the retail sector is well documented , however , the competing influence of mother 's education and physical access to net providers is less well understood . Methods Between December 2004 and January 2005 , a r and om sample of 72 rural communities was selected across four Kenyan districts . Demographic , assets , education and net use data were collected at homestead , mother and child ( aged < 5 years ) levels . An assets-based wealth index was developed using principal components analysis , travel time to net sources was modelled using geographic information systems , and factors influencing the use of retail sector nets explored using a multivariable logistic regression model . Results Homestead heads and guardians of 3,755 children < 5 years of age were interviewed . Approximately 15 % ( 562 ) of children slept under a net the night before the interview ; 58 % ( 327 ) of the nets used were purchased from the retail sector . Homestead wealth ( adjusted OR = 10.17 , 95 % CI = 5.45–18.98 ) , travel time to nearest market centres ( adjusted OR = 0.51 , 95 % CI = 0.37–0.72 ) and mother 's education ( adjusted OR = 2.92 , 95 % CI = 1.93–4.41 ) were significantly associated with use of retail sector nets by children aged less than 5 years . Conclusion Approaches to promoting access to nets through the retail sector disadvantage poor and remote communities where mothers are less well educated When using community-based participatory methods to develop health promotion programs for specific communities , it is important to determine if participation differs based on sociodemographics and the extent to which program participants are demographically representative of the target community , especially when non-r and om recruitment methods are used . We evaluated rates of participating in a health promotion program among African American residents in an urban community and determined if program participants were representative of community residents in terms of sociodemographic factors . While participation in the program was modest , participation did not differ based on psychological factors or body mass index . However , individuals who were unemployed were significantly more likely to participate in the program compared with those who were employed . Our sample included a greater proportion of individuals who only had a high school education compared with community residents but was similar to community residents in terms of gender , marital status and employment Background We examined independent influences of context ual variables on cardiovascular risk factors in Shilin county , Yunnan province , South-west China . Methods Three villages were selected from each of the ten townships based on probability proportional to size . In each selected village , 200 individuals aged ≥ 45 years were chosen based on simple r and om sampling method . From 6006 individuals , information on demographic characteristics , smoking and drinking status was obtained by interview . Blood pressure , height , weight , and waist and hip girth were measured . Fasting blood sugar was measured in a 10-percent sub sample . Context ual data were from official reports . Multi-level regression modelling with adjustment for individual and context ual variables was used . Results Context ual variables associated with CVD risk factors included : remoteness of village with higher blood pressure and fasting blood sugar , high proportion of Yi minority with drinking , high literacy rate with a lower rate of smoking and a lower mean waist-hip ratio , and high average income with lower systolic blood pressure and body mass index ( BMI ) but higher FBS . Conclusion While context ual SES is associated with a few CVD risk factors , villages with high level of income are worse off in fasting blood sugar . Strategies of economic development should be review ed to avoid adverse effects on health BACKGROUND Developmental impairments in children have been attributed to persistent middle-ear effusion in their early years of life . Previously , we reported that among children younger than 3 years of age with persistent middle-ear effusion , prompt as compared with delayed insertion of tympanostomy tubes did not result in improved cognitive , language , speech , or psychosocial development at 3 , 4 , or 6 years of age . However , other important components of development could not be assessed until the children were older . METHODS We enrolled 6350 infants soon after birth and evaluated them regularly for middle-ear effusion . Before 3 years of age , 429 children with persistent effusion were r and omly assigned to undergo the insertion of tympanostomy tubes either promptly or up to 9 months later if effusion persisted . We assessed literacy , attention , social skills , and academic achievement in 391 of these children at 9 to 11 years of age . RESULTS Mean ( + /-SD ) scores on 48 developmental measures in the group of children who were assigned to undergo early insertion of tympanostomy tubes did not differ significantly from the scores in the group that was assigned to undergo delayed insertion . These measures included the Passage Comprehension subtest of the Woodcock Reading Mastery Tests ( mean score , 98+/-12 in the early-treatment group and 99+/-12 in the delayed-treatment group ) ; the Spelling , Writing Sample s , and Calculation subtests of the Woodcock-Johnson III Tests of Achievement ( 96+/-13 and 97+/-16 ; 104+/-14 and 105+/-15 ; and 99+/-13 and 99+/-13 , respectively ) ; and inattention ratings on visual and auditory continuous performance tests . CONCLUSIONS In otherwise healthy young children who have persistent middle-ear effusion , as defined in our study , prompt insertion of tympanostomy tubes does not improve developmental outcomes up to 9 to 11 years of age . ( Clinical Trials.gov number , NCT00365092 [ Clinical Trials.gov ] . ) Current st and ard neuropsychology practice is to examine normative sample performance for systematic influences of demographic variables and then to correct for these influences . The most commonly examined demographic variables are age , gender , and years of education , and current normative data bases frequently take these into consideration . However , there is a literature to suggest that self-reported years of educational attainment may not be an accurate reflection of some patients ' level of performance and may actually overpredict grade estimates based on reading level . Many of these studies have focused on older sample s of individuals who were free of neurological or psychiatric symptoms . In this study , a younger sample ( average age = 44.5 ) of African American ( N = 62 ) and Caucasian ( N = 133 ) patients referred to an outpatient psychiatry unit was examined . Results suggest that the prior findings of a significant discrepancy between self-reported years of education and Wide Range Achievement Test-3rd Edition Reading Recognition performance hold for a younger sample with a broad range of clinical diagnoses . How these findings might influence clinical practice are discussed OBJECTIVE To determine whether or not limited caregiver health literacy is associated with adherence to a daily multi-vitamin with iron regimen in infants . METHODS 110 caregiver/infant dyads were enrolled in a prospect i ve study to assess the relationship between caregiver health literacy and adherence to a daily multi-vitamin with iron regimen for infants . Households were contacted biweekly over a 3-month period . Adherence was based upon caregiver report . High adherence , our primary outcome , was defined as the administration of the multi-vitamin with iron on 5 - 7 days over the past week . RESULTS As measured by the Short Test of Functional Health Literacy in Adults ( S-TOFHLA ) , 18 % of caregivers had limited health literacy skills . Caregivers with limited health literacy skills were more likely to have higher adherence than caregivers with adequate health literacy , after adjusting for a number of possible confounding variables ( AOR=2.13 ; 95 % 1.20 - 3.78 ) . CONCLUSION Caregivers with limited health literacy were twice as likely to report high adherence to a daily multi-vitamin with iron regimen in infants as caregivers with adequate health literacy in adjusted analysis . PRACTICE IMPLICATION S Health literacy may exert a differential influence on adherence depending upon the complexity of the desired health behavior The authors examined whether tailored self-management support ( SMS ) strategies reach patients in a safety net system and explored variation by language , literacy , and insurance . English- , Spanish- , and Cantonese-speaking diabetes patients were r and omized to weekly automated telephone disease management ( ATDM ) or monthly group medical visits . The SMS programs employ distinct communication methods but share common objectives , including behavioral “ action plans . ” Reach was measured using three complementary dimensions : ( a ) participation among clinics , clinicians , and patients ; ( b ) patient representativeness ; and ( c ) patient engagement with SMS . Participation rates were high across all levels and preferentially attracted Spanish- language speakers , uninsured , and Medicaid recipients . Although both programs engaged a significant proportion in action planning , ATDM yielded higher engagement , especially among those with limited English proficiency and limited literacy . These results provide important insights for health communication and translational research with respect to realizing the public health benefits of SMS and can inform system-level planning to reduce health disparities BACKGROUND Hearing loss is a prevalent and significant disability that impairs functional development and educational attainment of school children in developing countries . Lack of a simple and practical screening protocol often deters routine and systematic hearing screening at school entry . AIM To identify predictors of hearing loss for a practical screening model in school-aged children . SETTING S AND DESIGN Community-based , retrospective case-control study of school entrants in an inner city . METHODS Results from the audiologic and non-audiologic examination of 50 hearing impaired children in r and omly selected mainstream schools were compared with those of a control group of 150 normal hearing children , matched for age and sex from the same population . The non-audiologic evaluation consisted of medical history , general physical examination , anthropometry , motor skills , intelligence and visual acuity while the audiologic assessment consisted of otoscopy , audiometry and tympanometry . STATISTICAL ANALYSIS Multiple logistic regression analysis of significant variables derived from univariate analysis incorporating student t-test and chi-square . RESULTS Besides parental literacy ( OR:0.3 ; 95 % CI:0.16 - 0.68 ) , non-audiologic variables showed no association with hearing loss . In contrast , most audiologic indicators , enlarged nasal turbinate ( OR:3.3 ; 95 % CI:0.98 - 11.31 ) , debris or foreign bodies in the ear canal ( OR:5.4 ; 95 % CI:1.0 - 36.03 ) , impacted cerumen ( OR:6.2 ; 95 % CI:2.12 - 14.33 ) , dull tympanic membrane ( OR:2.2 ; 95 % CI:1.10 - 4.46 ) , perforated ear drum ( OR:24.3 ; 95 % CI:2.93 - 1100.17 ) and otitis media with effusion OME ( OR:14.2 ; 95 % CI:6.22 - 33.09 ) , were associated with hearing loss . However , only parental literacy ( OR:0.3 ; 95 % CI:0.16 - 0.69 ) , impacted cerumen ( OR:4.0 ; 95 % CI:1.66 - 9.43 ) and OME ( OR:11.0 ; 95 % CI:4.74 - 25.62 ) emerged as predictors . CONCLUSION Selective screening based on the identification of impacted cerumen and OME will facilitate the detection of a significant proportion of hearing impaired school entrants A r and om sample of directors of programs for the deaf in North America were surveyed to get their views about the skills that teacher education programs need to be teaching future teachers of students who are deaf or hard of hearing . The directors were queried about literacy practice s , classroom management strategies , and communication strategies used in their programs , and were encouraged to comment freely on the question naire items presented to them . Program directors predicted a need for more itinerant and re source teachers . The survey also revealed that programs for the deaf are highly behaviorist ( i.e. , You do this and you 'll get that ) in the way they induce students to learn and in how they manage student behavior OBJECTIVES To evaluate the effectiveness of a back school program in pain , functional status , quality of life , and in anxiety and depression in patients with non-specific low back pain . METHODS Sixty patients with low back pain were r and omized to an intervention and control group . The intervention group underwent a five-weekly back school program . The control group was seen in weekly medical visits , without educative approaches . Both groups took acetaminophen as analgesic medication . All subjects were evaluated by a blind physiotherapist after r and omization , 30 , 60 and 120 days . Roll and -Morris , SF-36 , STAI and Beck question naires , pain visual analogical scale and Schober 's test were applied . Non-steroidal anti-inflammatory drugs ( NSAID ) consumption was considered co-intervention . The statistical analyses were performed using Pearson 's Chi-Square analysis and Student 's t-test to compare the baseline characteristics of the groups and the analysis of variance ( ANOVA ) with repeated measures to assess changes inter/intra groups . RESULTS There were no significant differences in the baseline characteristics between the two groups . Fifty-five patients completed the study . The intervention group showed a significant improvement in the general health domain , assessed by SF-36 , and also in the reduction of acetaminophen and NSAID intake . There was no significant difference between the groups in pain , functional status , anxiety or depression . CONCLUSION The back school program was more effective than any educational intervention in general health status and in decreasing acetaminophen and NSAID intake . It was ineffective in the other quality of life domains , in pain , functional status , anxiety and depression Background Our underst and ing of social disparities in diabetes-related health behaviors is incomplete . The purpose of this study was to determine if having less education is associated with poorer diabetes-related health behaviors . Methods This observational study was based on a cohort of 8,763 survey respondents drawn from ~180,000 patients with diabetes receiving care from 68 provider groups in ten managed care health plans across the United States . Self-reported survey data included individual educational attainment ( " education " ) and five diabetes self-care behaviors among individuals for whom the behavior would clearly be indicated : foot exams ( among those with symptoms of peripheral neuropathy or a history of foot ulcers ) ; self-monitoring of blood glucose ( SMBG ; among insulin users only ) ; smoking ; exercise ; and certain diabetes-related health seeking behaviors ( use of diabetes health education , website , or support group in last 12 months ) . Predicted probabilities were modeled at each level of self-reported educational attainment using hierarchical logistic regression models with r and om effects for clustering within health plans . Results Patients with less education had significantly lower predicted probabilities of being a non-smoker and engaging in regular exercise and health-seeking behaviors , while SMBG and foot self-examination did not vary by education . Extensive adjustment for patient factors revealed no discernable confounding effect on the estimates or their significance , and most education-behavior relationships were similar across sex , race and other patient characteristics . The relationship between education and smoking varied significantly across age , with a strong inverse relationship in those aged 25–44 , modest for those ages 45–64 , but non-evident for those over 65 . Intensity of disease management by the health plan and provider communication did not alter the examined education-behavior relationships . Other measures of socioeconomic position yielded similar findings . Conclusion The relationship between educational attainment and health behaviors was modest in strength for most behaviors . Over the life course , the cumulative effect of reduced practice of multiple self-care behaviors among less educated patients may play an important part in shaping the social health gradient PURPOSE This study explores how diverse attitudes about health literacy are assessed by medical librarians and other health care professionals . PROCEDURES An online survey of thirty-six items was conducted using Q methodology in two phases in spring 2005 and winter 2006 . Respondents ( n = 51 ) were nonr and omly self-selected from a convenience sample of members of the Medical Library Association and a group of environmental health consultants to the National Library of Medicine . FINDINGS Three factors were identified . Factor 1 is optimistic and supportive of health literacy 's transformative sociocultural and professional potential , if clinical setting s become a launching point for health literacy activities . Factor 2 is less optimistic about health literacy 's potential to improve clinical or patient outcomes and prefers to focus health literacy initiatives on classroom education setting s. Factor 3 supports improving the nation 's health literacy but tends to support health literacy initiatives when people privately interact with health information material s. CONCLUSIONS Each factor 's attitudes about the appropriate educational venue to initiate health literacy activities are different and somewhat mutually exclusive . This suggests that health literacy is seen through different perceptual frameworks that represent a possible source of professional disagreement This study examines the applicability of the modified Location Learning Test ( mLLT ) as a test of spatial memory in neuropsychological patients . Three groups of participants were examined : stroke patients , patients with diabetes mellitus and healthy participants ( N=411 ) . Three error measures were computed , the Total Score ( index of overall performance ) , the Learning Index ( the learning curve over subsequent trials ) and the Delayed Recall Score , measuring decay over time . The Learning Index was the most sensitive measure , showing differences between the three groups as well as lateralization effects within the stroke group . Also , the mLLT correlated significantly with the Rey Auditory Verbal Learning Test , as well as with age and education level . Regression-based normative data were computed based on the healthy participants . In all , the mLLT appears to be a sensitive and valid test for the detection of object-location memory impairments in clinical groups Background . Over the past 30 years , numerous studies have reported that some individuals are willing to donate a kidney anonymously to a stranger ; however , intentions are poor predictors of behavior . We surveyed individuals interested in being living anonymous donors ( LADs ) , exposed them to an interview paralleling live-donor assessment , and measured their LAD commitment . Personality and donation decision factors were examined to corroborate cases of attitudinal and behavioral congruency . Methods . A telephone survey of 1,002 r and omly selected adults living in Vancouver , British Columbia , asked respondents how willing they were to donate a kidney , while alive , to particular individuals including a stranger . A sub sample participated in a follow-up , which involved completing a mailed question naire and taking part in an in-depth interview . Expert raters judged respondents ’ commitment to being a LAD on the basis of the interviews . Results . Two hundred fifty-eight ( 26 % ) of those surveyed stated they would probably or definitely be willing to donate a kidney to a stranger . Fifty-two completed the follow-up . Sixteen of the 52 ( 31 % ) were judged to be “ committed LADs . ” No demographic differences were found between the committed LADs and the 33 remaining “ noncommitted participants . ” The committed LADs differed significantly from the noncommitted participants on personality measures and donation decision factors . These differences underscore the latter group ’s anonymous donation commitment . Conclusions . This study brings into focus the potential for a significant number of individuals coming forward as potential LAD c and i date s if they are informed about the need and given unbiased information about the procedure . We believe there is ethical latitude in allowing the promotion of LAD donation by interested third parties such as patient advocacy groups and professional bodies . We advocate public awareness of LAD programs as a first step followed thereafter by more provocative measures to engage the public in this endeavor OBJECTIVE To assess the effects of a facilitator enhanced multifaceted intervention to implement a locally adapted guideline on the shared care for people with type 2 diabetes . METHODS During 1 year a cluster-r and omized trial was performed in 30 general practice s. In the intervention group , nurse facilitators enhanced guideline implementation by analysing barriers to change , introducing structured care , training practice staff and giving performance feedback . Targets for HbA1c% , systolic blood pressure as well as indications for angiotensin converting enzyme/angiotensin receptor blocking agent prescription differed from the national guidelines . In the control group , GPs were asked to continue the care for people with diabetes as usually . Generalized estimating equations were used to control for the clustered design of the study . RESULTS In the intervention group , more people were seen on a 3-monthly basis ( 88 % versus 69 % , P < 0.001 ) and more blood pressure and bodyweight measurements were performed every 3 months ( blood pressure 83 % versus 66 % , P < 0.001 and bodyweight 78.9 % versus 48.5 % , P < 0.001 ) . Apart from a marginal difference in mean cholesterol , differences in HbA1c% , blood pressure , body mass index and treatment satisfaction were not significant . CONCLUSION Multifaceted implementation of locally adapted shared care guidelines did improve the process of diabetes care but hardly changed intermediate outcomes . In the short term , local adaptation of shared care guidelines does not improve the cardiovascular risks of people with type 2 diabetes Measures of verbal fluency are common additions to neuropsychological evaluations . Due to the literature demonstrating the impact of demographic variables on these measures , corrective norms have recently been published . However , these norms have yet to be cross-vali date d. This study sought to cross-vali date these norms in a racially diverse psychiatric sample . In addition , this study sought to evaluate the utility of Wide Range Achievement Test , 3rd Edition ( WRAT3 ) Reading Recognition and Wechsler Adult Intelligence Scale-Third Edition ( WAIS-III ) Vocabulary in attenuating the effect of demographic variables on these measures of verbal fluency . Results supported the utility of Gladsjo et al. 's ( 1999 ) norms . Further analysis revealed that both WRAT3 Reading Recognition and WAIS-III Vocabulary scores also attenuated the impact of demographic variables on these measures and accounted for more of the variance . Together , these results suggest that , although the demographically corrected norms adequately attenuate the impact of these variables , norms corrected for WRAT3 Reading Recognition or WAIS-III Vocabulary may account for more of the variance and therefore might be more appropriate and universally applicable BACKGROUND Electronic health records ( EHRs ) allow for a variety of functions , ranging from visit documentation to laboratory test ordering , but little is known about physicians ' actual use of these functions . METHODS We surveyed a r and om sample of 1884 physicians in Massachusetts by mail and assessed availability and use of EHR functions , predictors of use , and the relationships between EHR use and physicians ' perceptions of medical practice . RESULTS A total of 1345 physicians responded to the survey ( 71.4 % response rate ) , and 387 ( 28.8 % ) reported that their practice had adopted EHRs . More than 80 % of physicians with EHRs reported having the ability to view laboratory reports ( 84.8 % ) and document visits electronically ( 84.0 % ) , but considerably fewer reported being able to order laboratory tests electronically ( 46.8 % ) or transmit prescriptions to a pharmacy electronically ( 44.7 % ) . Fewer than half of the physicians who had systems with clinical decision support , transmittal of electronic prescriptions , and radiology order entry actually used these functions most or all of the time . Compared with physicians who had not adopted EHRs , EHR users reported more positive views of the effects of computers on health care ; there were no significant differences in these attitudes between high and low users of EHRs . Overall , about 1 in 4 physicians reported dissatisfaction with medical practice ; there was no difference in this measure by EHR adoption or use . CONCLUSIONS There is considerable variability in the functions available in EHRs and in the extent to which physicians use them . Future work should emphasize factors that affect the use of available functions OBJECTIVES To investigate ability to distinguish simple analgesics , to document misconceptions about aspirin use , and to identify strategies to diminish potentially harmful aspirin use in Ethiopia . DESIGN Qualitative study ( eight focus group discussion s ) used to inform cross-sectional survey . SETTING Butajira , a small town in southern Ethiopia , and surrounding rural areas . PARTICIPANTS Purposively selected informants for focus groups ; r and om sample of urban and rural residents for cross-sectional survey . MAIN OUTCOME MEASURES Ability to distinguish aspirin from paracetamol ; proportion using aspirin ; proportion aware of common risks of aspirin . RESULTS Question naires were completed by 204 of the 250 residents sample d ( 82 % response ) . Three-quarters of survey participants knew the difference between aspirin and paracetamol . Aspirin was used by 7.3 % of respondents , and was mainly taken for headache and fever . In focus group discussion s there was a suggestion that aspirin was considered particularly useful for children . There was very low awareness of the risks of using aspirin in children ( 2.5 % unprompted , 18.6 % prompted ) or in people with asthma ( 1 % unprompted , 5.9 % prompted ) . Aspirin is cheap and widely available in urban and rural areas . CONCLUSION Awareness of the risks of aspirin use by children and in asthma is extremely low in this rural Ethiopian setting . Medications are purchased with minimal packaging by a population with low literacy . Drug dispensers and vendors must be trained to convey simple verbal warnings about aspirin use The recent increased number of conditions for which patients can undergo genetic carrier testing raises the question of how best to obtain pre-test informed consent . Clinical approaches vary from a minimalist model to a model where patients are given detailed information about all conditions to be screened for . Few data exist as to patient preferences , or how information impacts decision-making . Eight high-literacy focus groups were conducted to assess the knowledge and preferences of pregnant patients and their male partners . Most groups indicated that some balance between details and brevity was optimal , recognizing that anxiety can occur when patients are provided with too much information and that the wide range of tests offered during pregnancy often led to confusion . Critical areas for the informed consent process included ( 1 ) details about the conditions and risk of being a carrier , ( 2 ) logistics of testing , ( 3 ) next steps if the test is positive , and ( 4 ) prognosis , options and re sources if the child were to be affected with a disorder . It will be useful to develop model consent programs and prospect ively assess their impact on informed consent and patient satisfaction , both when positive and negative results are received OBJECTIVE The cohort consisted of 328 very low birth weight infants ( 600 - 1250 g birth weight ) who were enrolled in the low-dose prophylactic indomethacin prevention trial and were intraventricular hemorrhage ( IVH ) negative at 6 postnatal hours . The objective was to determine the effects of both IVH and indomethacin on cognitive , language , and achievement performance at 8 years of age . METHODS The cohort was divided into 4 subgroups for analysis : indomethacin plus IVH , indomethacin no IVH , saline plus IVH , and saline with no IVH . The children were evaluated prospect ively at 8 years of age with a neurologic assessment , history of school performance , and a battery of cognitive , academic , behavioral , and functional assessment s. RESULTS Children in both IVH groups had more cerebral palsy ; more hearing impairment ; lower daily living skills scores ; lower IQ , vocabulary , and reading and mathematics achievement test scores ; and greater educational re source needs . With logistic regression analyses grade 3 to 4 IVH , periventricular leukomalacia and /or ventriculomegaly , male gender , maternal education , and language spoken in the home contributed to outcomes . No effects of indomethacin or gestational age were identified . CONCLUSIONS Although biological factors including IVH , ventriculomegaly , and periventricular leukomalacia contribute significantly to school age outcomes among very low birth weight survivors at 8 years of age , social and environmental factors including maternal level of education and primary language spoken in the home are also important contributors to outcome BACKGROUND Vaginal discharge is a common complaint , particularly among women in Asia . Although presumed to be caused by reproductive tract infections ( RTIs ) , the association between the complaint and the presence of RTIs is weak . This study aim ed to investigate the risk factors of the complaint of vaginal discharge . METHODS We conducted a community-based survey of 3000 women aged 18 - 50 years , r and omly sample d from a population in Goa , India . Women who gave informed consent were invited to participate in a structured interview , which elicited data on the primary outcome ( the experience of current abnormal vaginal discharge ) and psychosocial exposures : gender adversity ; symptoms of somatoform disorders ; and common mental disorders ( CMD ) . All women were required to provide vaginal and /or urine sample s for diagnosis of RTIs using gold st and ard laboratory tests . Risk factors were analysed using logistic regression with the binary outcome of the complaint of vaginal discharge . RESULTS Of the 2494 women ( 83 % ) who agreed to participate , 14.5 % complained of having an abnormal vaginal discharge . Stress was the most common causal attribution for the complaint . The final multivariate model found that high scores for CMD ( OR 2.16 , 1.4 - 3.2 ) and somatoform disorders ( 6.23 , 4.0 - 9.7 ) and the use of an intrauterine contraceptive device ( 1.86 , 1.0 - 3.4 ) were independently associated with the complaint . Low literacy ( 0.54 , 0.4 - 0.8 ) and age > 40 years ( 0.29 , 0.2 - 0.4 ) were associated with a reduced risk . RTI were not associated with the complaint ( 1.24 , 0.9 - 1.6 ) . CONCLUSIONS Psychosocial factors have the strongest association with the complaint of vaginal discharge . Syndromic management algorithms need refinement so that women with complaints that are non-infectious in aetiology are offered psychosocial interventions BACKGROUND Organizations have invested in disease management programs to improve quality and to reduce costs , but little is known about the labor characteristics and the program costs necessary to implement a program . OBJECTIVE To examine the labor characteristics and the program costs of a successful diabetes disease management program . STUDY DESIGN We performed a labor and cost analysis within a r and omized controlled trial of a primary care-based diabetes disease management intervention . METHODS Participants included 217 patients with type 2 diabetes mellitus and poor glycemic control ( glycosylated hemoglobin levels , > or = 8.0 % ) . The intervention group received 12 months of intensive management from clinical pharmacists and a diabetes care coordinator who provided education , applied algorithms for medication management , and addressed barriers to care . The control group attended a single session led by pharmacists , followed by usual care from their primary providers . The process outcomes included the number of patient care-related activities , time spent per patient , and number of drug titrations or additions . The program costs were calculated based on Bureau of Labor Statistics wage data using a sensitivity analysis . RESULTS The disease management team performed a mean of 4.0 care-related activities for a mean of 38.6 minutes per patient per month for intervention patients and performed a mean of 1.1 care-related activities for a mean of 10.7 minutes per patient per month for control patients ( P < .001 ) . Intervention patients had a median of 7 drug titrations or additions during the study . The incremental program cost for the intervention was 36.97 dollars ( sensitivity analysis , 6.22 dollars-88.56 dollars ) per patient per month . CONCLUSION A successful diabetes disease management program can be integrated into an academic clinic for modest labor and cost Children with developmental dyslexia fail to develop age-appropriate reading skills despite adequate intelligence and education . It has been suggested that dyslexics ' various literacy , sensory and motor difficulties may be related to impaired cerebellar function . As the cerebellum is involved in motor learning , we measured serial reaction time performance in 40 adults ( 21 controls , 19 dyslexics ) . Dyslexic subjects performed comparably to controls during the r and omly-ordered reaction time blocks , indicating that the dyslexics were as able as controls to make appropriate stimulus-response associations . However , the dyslexics failed to show the reaction time reduction that the control group showed during the repeated sequences ( p = 0.018 ) and there was a significant group by condition effect when comparing the last two blocks of the sequence condition with the first two blocks of the final r and om condition ( p = 0.008 ) . Furthermore , there was a significant difference between good and poor readers on the degree of learning during the task ( p = 0.015 ) . This suggests that some dyslexics may suffer from an implicit motor learning deficit , which could generalize to non-motor learning The Brazilian Peritoneal Dialysis Multicenter Study ( BRAZPD ) was launched in December 2004 aim ing to collect data monthly and continuously from a representative cohort , allowing for a continuous snapshot of the peritoneal dialysis ( PD ) reality in the country . This is an observational study of PD patients comprising follow-up from December 2004 to February 2007 ( mean follow-up of 13.6 months-ranging from 1 to 26 months ) in 114 Brazilian centers . All centers report data through a central web-based data base . After an initial baseline retrospective data collection , all patients are followed prospect ively every month until they drop out from the PD program . Total number of patients recruited until February 2007 was 3226 ( 2094 incident patients ) . Mean age was 54+/-19 years ( 37 % above 65 years old ) , with 55 % females and 64 % Caucasians . The more frequent causes of renal failure were diabetic nephropathy ( 34 % ) , renal vascular disease associated with hypertension ( 26 % ) , and glomerulopathies ( 13 % ) . The most common comorbidities were hypertension ( 76 % ) , diabetes ( 36 % ) , and ischemic heart disease ( 23 % ) . Automated PD ( APD ) was the modality utilized in 53 % . The estimated overall peritonitis rate was 1 episode per 30 patient-months ( most frequently due to Staphylococcus aureus ) . The total dropout rate was 33 % , mainly due to deaths , whereas 20 % of dropouts were due to renal transplant . The gross mortality was 17.6 % and the main causes of mortality were cardiovascular diseases ( 40 % ) and infections ( 15 % ) . The initial results of this first Brazilian PD registry provide a unique opportunity to develop future clinical studies addressing specific PD questions in the Brazilian reality and context OBJECTIVE To evaluate a clinic-based multimedia intervention for diabetes education targeting individuals with low health literacy levels in a diverse population . RESEARCH DESIGN AND METHODS Five public clinics in Chicago , Illinois , participated in the study with computer kiosks installed in waiting room areas . Two hundred forty-four subjects with diabetes were r and omized to receive either supplemental computer multimedia use ( intervention ) or st and ard of care only ( control ) . The intervention includes audio/video sequences to communicate information , provide psychological support , and promote diabetes self-management skills without extensive text or complex navigation . HbA(1c ) ( A1C ) , BMI , blood pressure , diabetes knowledge , self-efficacy , self-reported medical care , and perceived susceptibility of complications were evaluated at baseline and 1 year . Computer usage patterns and implementation barriers were also examined . RESULTS Complete 1-year data were available for 183 subjects ( 75 % ) . Overall , there were no significant differences in change in A1C , weight , blood pressure , knowledge , self-efficacy , or self-reported medical care between intervention and control groups . However , there was an increase in perceived susceptibility to diabetes complications in the intervention group . This effect was greatest among subjects with lower health literacy . Within the intervention group , time spent on the computer was greater for subjects with higher health literacy . CONCLUSIONS Access to multimedia lessons result ed in an increase in perceived susceptibility to diabetes complications , particularly in subjects with lower health literacy . Despite measures to improve informational access for individuals with lower health literacy , there was relatively less use of the computer among these participants Lipid-lowering drugs are one of the most prescribed drugs worldwide . The aim was to compare 10-year all-cause mortality according to initial dyslipidemia status and lipid-lowering drug exposure . The PRIME study was a multicenter population -based prospect i ve cohort study of men recruited in 1991 to 1993 , aged 50 to 59 years at baseline , and followed up for 10 years . The 4 groups compared were normolipidemic , untreated dyslipidemic , and dyslipidemic subjects on fibrate or statin therapy . Data were analyzed using multivariate Cox models . The cohort included 7,722 French men ( statin group 4.0 % , fibrate group 7.9 % , untreated dyslipidemic subjects 19.0 % , and normolipidemic subjects 69.1 % ) . After 10 years , 4.8 % of the sample was lost to follow-up and 416 deaths occurred ( cancers 53.1 % , cardiovascular diseases 17.1 % , and other 29.8 % ) . After adjustment for center , age , educational level , cardiovascular risk factors , lipids , alcohol intake , and history of cardiovascular and severe chronic diseases , hazard ratios ( HRs ) for all-cause mortality were 0.49 ( 95 % confidence interval [ CI ] 0.26 to 0.94 , p = 0.031 ) for subjects treated with a statin , 0.65 ( 95 % CI 0.42 to 0.99 , p = 0.046 ) for those on fibrate therapy , and 0.76 ( 95 % CI 0.56 to 1.03 , p = 0.080 ) for normolipidemic men compared with untreated dyslipidemic subjects . In the statin group , HRs for death from cardiovascular disease , cancer , and other causes were 0.55 ( p = 0.348 ) , 0.41 ( p = 0.067 ) , and 0.68 ( p = 0.546 ) compared with dyslipidemic subjects , respectively . In the fibrate group , HRs were 0.76 ( p = 0.499 ) , 0.52 ( p = 0.041 ) , and 0.87 ( p = 0.746 ) . In conclusion , in this cohort study carried out in a real-life setting , all-cause mortality was significantly lower in dyslipidemic subjects on fibrate or statin therapy than in untreated dyslipidemic patients . No excess risk of noncardiovascular death was observed This was a large population -based study to develop and vali date the Iranian version of the Short Form Health Survey ( SF-36 ) for use in health related quality of life assessment in Iran . A culturally comparable question naire was developed and pilot tested . Then , the Iranian version of the SF-36 was administered to a r and om sample of 4163 healthy individuals aged 15 years and over in Tehran . The mean age of the respondents was 35.1 ( SD=16.0 ) years , 52 % were female , mostly married ( 58 % ) and the mean years of their formal education was 10.0 ( SD=4.5 ) . Reliability was estimated using the internal consistency and validity was assessed using known groups comparison and convergent validity . In addition factor analysis was performed . The internal consistency ( to test reliability ) showed that all eight SF-36 scales met the minimum reliability st and ard , the Cronbach ’s α coefficients ranging from 0.77 to 0.90 with the exception of the vitality scale ( α=0.65 ) . Known groups comparison showed that in all scales the SF-36 discriminated between men and women , and old and the young respondents as anticipated ( all p values less than 0.05 ) . Convergent validity ( to test scaling assumptions ) using each item correlation with its hypothesized scale showed satisfactory results ( all correlation above 0.40 ranging from 0.58 to 0.95 ) . Factor analysis identified two principal components that jointly accounted for 65.9 % of the variance . In general , the Iranian version of the SF-36 performed well and the findings suggest that it is a reliable and valid measure of health related quality of life among the general population The objective of this study was to assess the readability of a nationwide sample of alcohol and drug abuse treatment programs ' material s. Of 646 programs that were r and omly selected from the National Clearinghouse for Alcohol and Drug Information directory , 52 programs returned completed material s. The average readability grade level of material s was 11.84 ( SD = 0.94 ) . The program staff estimations were significantly lower than actual reading levels of material s , and no program characteristics correlated with readability levels . Thus , it was concluded that material s written at high readability levels may not be effective tools for all patients . Integrating knowledge regarding program material s ' readability level and literacy levels of different population s could be successful aides to substance abuse treatment OBJECTIVE To determine whether the presence , severity , or symmetry of growth restriction in term infants is an independent risk factor for learning , cognitive , and attentional problems in adolescence . METHODS A total of 7388 term infants have been followed prospect ively since birth . At 14 years , 5059 mothers completed a Child Behavior Checklist and provided information on their child 's school progress . A total of 5051 adolescents completed a Youth Self Report , with 3703 also undergoing psychometric testing with Ravens Progressive Matrices and Wide Range Achievement Test ( WRAT ) reading subtest . Outcomes were compared on the basis of birth weight groups and measures of body symmetry and were adjusted for the level of social risk at birth . RESULTS Adolescents who were born small for gestational age ( SGA ) , when compared with their appropriately grown counterparts ( > 10th percentile ) , were more likely to experience learning difficulties , with a higher prevalence in those of birth weight < or = 3rd percentile . Girls of birth weight < or = 3rd percentile were more likely to have attentional problems and low WRAT reading scores . There was no significant difference in Ravens IQ or mean WRAT reading scores between SGA and non-SGA groups . There was no association between body symmetry and any of the outcomes studied . CONCLUSIONS SGA status seems to have only modest independent effects on learning , cognition , and attention in adolescence . Severity but not symmetry of growth restriction predicted learning difficulties Background Self-management programs for patients with heart failure can reduce hospitalizations and mortality . However , no programs have analyzed their usefulness for patients with low literacy . We compared the efficacy of a heart failure self-management program design ed for patients with low literacy versus usual care . Methods We performed a 12-month r and omized controlled trial . From November 2001 to April 2003 , we enrolled participants aged 30–80 , who had heart failure and took furosemide . Intervention patients received education on self-care emphasizing daily weight measurement , diuretic dose self-adjustment , and symptom recognition and response . Picture-based educational material s , a digital scale , and scheduled telephone follow-up were provided to reinforce adherence . Control patients received a generic heart failure brochure and usual care . Primary outcomes were combined hospitalization or death , and heart failure-related quality of life . Results 123 patients ( 64 control , 59 intervention ) participated ; 41 % had inadequate literacy . Patients in the intervention group had a lower rate of hospitalization or death ( crude incidence rate ratio ( IRR ) = 0.69 ; CI 0.4 , 1.2 ; adjusted IRR = 0.53 ; CI 0.32 , 0.89 ) . This difference was larger for patients with low literacy ( IRR = 0.39 ; CI 0.16 , 0.91 ) than for higher literacy ( IRR = 0.56 ; CI 0.3 , 1.04 ) , but the interaction was not statistically significant . At 12 months , more patients in the intervention group reported monitoring weights daily ( 79 % vs. 29 % , p < 0.0001 ) . After adjusting for baseline demographic and treatment differences , we found no difference in heart failure-related quality of life at 12 months ( difference = -2 ; CI -5 , + 9 ) . Conclusion A primary care-based heart failure self-management program design ed for patients with low literacy reduces the risk of hospitalizations or death PURPOSE This study examined the role of literacy in patients with poorly controlled diabetes who were participating in a diabetes management program that included low-literacy-oriented interventions . METHODS A before-after analysis was performed of a pharmacist-led diabetes management program for 159 patients with type 2 diabetes and poor glycemic control ( hemoglobin A1c [ A1C ] > or = 8.0 % ) . Clinic-based pharmacists offered one-to-one education and medication management for these patients using techniques that did not require high literacy . Literacy was measured by the Rapid Estimate of Adult Literacy in Medicine ( REALM ) test and dichotomized at the 6th- grade level . The A1C values were collected prior to enrollment , at enrollment , and approximately 6 months after enrollment . RESULTS Of the 111 patients with follow-up data , 55 % had literacy levels at the 6th- grade level or below . Lower literacy was more common among African Americans , older patients , and patients who required medication assistance . There was no significant relationship between literacy status and A1C prior to enrollment or at enrollment . Over the 6-month study period , patients with low and high literacy had similar improvements in A1C . CONCLUSIONS This diabetes care program , which used individualized teaching with low-literacy techniques , significantly improved A1C values independent of literacy status BACKGROUND Reductions in iodine and zinc deficiencies and improvements in hemoglobin were achieved from a micronutrient-fortified seasoning powder consumed in school lunches by children in northeast Thail and . OBJECTIVE The objective was to determine whether fortification with 4 micronutrients in a school lunch results in changes in children 's growth , morbidity , and cognitive function compared with no fortification . DESIGN In a r and omized controlled trial of 569 children aged 5.5 - 13.4 y from 10 schools , we compared the efficacy of a seasoning powder fortified with or without 5 mg Fe , 5 mg Zn , 50 mug I , and 270 mug vitamin A per serving consumed with a school lunch 5 d/wk . Here we report on results of the secondary functional outcomes . RESULTS The groups were comparable concerning compliance and loss to follow-up . The intervention had no statistically significant effect on anthropometric measures over 31 wk , but reduced the incidence of respiratory-related illnesses [ rate ratio ( RR ) : 0.83 ; 95 % CI : 0.73 , 0.94 ] , symptoms of runny nose ( RR : 0.80 ; 95 % CI : 0.70 , 0.92 ) , cough ( RR : 0.80 ; 95 % CI : 0.66 , 0.96 ) , and diarrhea ( RR : 0.38 ; 95 % CI : 0.16 , 0.90 ) . For the visual recall test , those in the fortified group recalled 0.5 more items ( 95 % CI : 0.1 , 0.9 ) than did the controls . There were no statistically significant differences between groups in the results of the digits forward and backward tests or in school grade s at the conclusion of the 2 semesters . CONCLUSION The beneficial effects on morbidity and visual recall over a short period , in addition to some biochemical improvements , highlight the potential of this micronutrient-fortified seasoning powder supplied in a school lunch . This trial was registered at clinical trials.gov as ACTRN12605000341628 BACKGROUND Iron supplements improve hemoglobin status and reduce anemia due to iron deficiency . It is not known whether multiple micronutrient ( MM ) supplements are as efficacious as are iron supplements alone in improving hemoglobin concentrations . OBJECTIVE We conducted a r and omized , double-blind community trial in Mexico to compare the efficacy of MM supplements containing iron with that of iron alone in improving hemoglobin concentrations in nonpregnant women . DESIGN Nonpregnant women ( n = 158 ) were recruited from a semirural community in Mexico and were r and omly assigned to receive iron alone ( 60 mg ; Fe group ) or MM supplements ( vitamins A , B complex , C , D , E , and K and iron , zinc , and magnesium ; MM group ) 6 d/wk in their home for 12 wk . Hemoglobin concentrations were measured in capillary blood sample s at baseline and follow-up . RESULTS The treatment groups ( MM : n = 75 ; Fe : n = 77 ) did not differ significantly at recruitment in age , schooling , literacy , or socioeconomic status . There were no significant differences between groups in compliance ( median : 97.5 % ) , baseline hemoglobin concentrations , or prevalence of anemia ( 20 % ) . Losses to follow-up ( 4 % ) and mean ( + /-SD ) changes in hemoglobin ( MM group : 6.7 + /- 10.6 g/L ; Fe group : 7.1 + /- 13.6 g/L ) were not significantly different between groups . However , the change in hemoglobin in anemic subjects was greater in the Fe group than in the MM group ( P < 0.05 for interaction ) , and there was no significant difference in nonanemic subjects . CONCLUSIONS MM supplements may not be as efficacious as is iron alone in improving the hemoglobin status of anemic women Systematic review s ( SRs ) are an increasingly popular evidence -based tool and are often used to answer complex research questions across many different research domains . Early SR methodology was advanced by social scientists , and the term meta- analysis was coined by a social scientist who also conducted research in psychology . SRs have recently become popular in healthcare and are likely to be beneficial in any field . The aim of this report is to highlight issues in SR conduct with a focus on the field of nutrition and to make recommendations on improving SR conduct in this area . Development of the research question is probably the most important step in conducting an SR . The 4 main components of an answerable question are 1 ) the patient , population , or problem ; 2 ) the intervention , independent variable , or exposure ; 3 ) the comparators ; and 4 ) the dependent variables or outcomes of interest . The question will be used to determine the optimal methods for conducting the SR . SRs often include study design s beyond r and omized trials and do not always include a meta- analysis of the results . Other topics explored include underst and ing and interpreting discordant review s and the importance of reporting tools [ eg , QUality Of Reporting Of Meta-analyses ( QUOROM Statement ) or CONsoli date d St and ards Of Reporting of Trials ( CONSORT Statement ) ] . Recommendations are then provided , such as developing a capacity-building program , search ing the primary literature for research gaps , and extending reporting tools such as the QUOROM Statement to the field of nutrition OBJECTIVE This study evaluated the reach , initial effectiveness , and potential moderators and mediators of results of a smoking reduction program . DESIGN A generally representative sample of 320 adult smokers from an HMO , scheduled for outpatient surgery or a diagnostic procedure , were r and omized to enhanced usual care or a theory-based smoking reduction intervention that combined telephone counseling and tailored newsletters . MAIN OUTCOME MEASURES Self-reported number of cigarettes smoked and carbon monoxide levels . RESULTS The intervention enrolled 30 % of known eligible smokers and produced reductions of 3 cigarettes per day greater than enhanced usual care . Intervention participants were significantly more likely than control participants to achieve at least a 50 % reduction in self-reported number of cigarettes using complete cases , imputation analyses , and intent-to-treat procedures . Similar patterns were seen for carbon monoxide results but were significant only in complete case analyses . The intervention was generally robust across patient characteristics ( e.g. , education , ethnicity , health literacy , and dependence ) and phone counselors . CONCLUSION Initial results suggest that this program has potential to reach and assist smokers who may not participate in cessation programs . Additional research is indicated to enhance intervention effects , assess maintenance , and evaluate public health impact Advances in medical treatment combined with changes in the demographics of persons who are becoming infected with autoimmune deficiency syndrome ( AIDS ) have transformed this illness from a rapidly progressing to a chronically disabling condition in a short period of time . This paper describes the development , implementation , and outcomes of a program of vocational services for persons with AIDS . This program was studied using a single group design , in which participatory action research strategies were used to investigate and improve the program as it unfolded . In addition to examining the overall outcomes of services , the study aim ed to discover which components were most helpful to participants and which participants were most likely to benefit from the program . Of 129 participants of who initially enrolled , 39 dropped out before finishing the program . Sixty of the 90 participants who completed the program achieved employment , returned to school , or began a volunteer position or internship . Consequently , the overall success rate was 46.5 % and the success rate for program completers was 66.7 % . The occupational narrative , which participants told in their initial assessment interview , was closely associated with both program completion and successful outcomes . This association adds support to the importance of narrative for underst and ing participants and predicting future behavior , as well as for the therapy process The purpose of this study is to investigate the feasibility of developing e-learning and to examine reasons for adopting or rejecting e-learning as an alternative way to conduct continuing education ( CE ) for public health nurses ( PHNs ) . A nationwide-based cross-sectional study was conducted with a r and omly selected sample of 233 PHNs in Taiwan . A structured question naire was used to collect data by mailing methods . The majority of PHNs ( 88.84 % , n=207 ) showed an affirmative intention towards adopting e-learning as their one way of CE . Reasons for adopting e-learning included achieving life learning , fulfilling personal interests , time-saving , based on job needs , information diversity , flexible in time and space , self-regulatory learning , cost-effectiveness , less impact on family duties and life . Twenty-six PHNs ( 11.16 % ) who rejected e-learning as their way of CE indicated main reasons including poor computer competence , lack of personal computer and without internet access , heavy work load , heavy family duties , conflict with personal preference , heavy economic burden , lack of motivation , and low self-control . This study reveals a high feasibility of developing e-learning that coexists with other CE models ( e.g. traditional instruction ) . Reasons analyses provide directions for decreasing barriers for developing a learning model of this new medium for nurses ' CE This study is part of a broader project aim ed at developing cognitive and neurocognitive profiles of adolescent and young adult readers whose educational and occupational prospect s are constrained by their limited literacy skills . We explore the relationships among reading-related abilities in participants ages 16 to 24 years spanning a wide range of reading ability . Two specific questions are addressed : ( a ) Does the simple view of reading capture all nonr and om variation in reading comprehension ? ( b ) Does orally assessed vocabulary knowledge account for variance in reading comprehension , as predicted by the lexical quality hypothesis ? A comprehensive battery of cognitive and educational tests was employed to assess phonological awareness , decoding , verbal working memory , listening comprehension , reading comprehension , word knowledge , and experience with print . In this heterogeneous sample , decoding ability clearly played an important role in reading comprehension . The simple view of reading gave a reasonable fit to the data , although it did not capture all of the reliable variance in reading comprehension as predicted . Orally assessed vocabulary knowledge captured unique variance in reading comprehension even after listening comprehension and decoding skill were accounted for . We explore how a specific connectionist model of lexical representation and lexical access can account for these findings BACKGROUND Determinants of oral language comprehension , a complex skill , are not clearly established , but may include age , schooling , health condition , depression and quality of life . OBJECTIVE To assess oral comprehension skill among Brazilian elderly and identify factors explaining elderly variability in the Token test performance . METHODS A population -based r and om sample of 373 elderly ( > or = 60 years ) in Belo Horizonte , 2007 , answered st and ardized question naire including socio-demographic and health-related questions and performed the Token Test short version ( SVTT ) , Snellen Test , Mini Mental State Examination , General Health Question naire , and Health Survey Short Form ( SF12 ) . RESULTS Token Test scores ranged from 8 to 35 points ; 50 % of participants scored < or = 24 points with no sex variation . Age , schooling , literacy , cognitive status , hypertension , self-rated conversational underst and ing and SF12 mental component explained 62 % of SVTT variability . CONCLUSIONS Language comprehension disorder was quite common and test performance was highly influenced by education and cognitive status . Association between test performance and self-rated conversational comprehension indicated that elderly were aware of their difficulty We determined the factors associated with exacerbation of heart failure , using a cohort ( n = 192 ) nested within a r and omized trial at a university‐affiliated ambulatory practice . Factors associated with emergency or hospital care included left ventricular ejection fraction , hematocrit and serum sodium levels , refill adherence , and the ability to read a prescription label . Refill adherence of < 40 % was associated with a threefold higher incidence of hospitalization for heart failure than a refill adherence of ≥80 % ( P = 0.002 ) . In multivariable analysis , prescription label reading skills were associated with a lower incidence of heart failure – specific emergency care ( incidence rate ratio , 0.76 ; 95 % confidence interval ( CI ) , 0.19–0.69 ) , and participants with adequate health literacy had a lower risk of hospitalization for heart failure ( incidence rate ratio , 0.34 ; 95 % CI , 0.15–0.76 ) . We conclude that inadequate treatment adherence and health literacy skills are key factors in the exacerbation of heart failure . These findings emphasize the need for careful instruction of patients about their medications Background Opioid misuse can complicate chronic pain management , and the non-medical use of opioids is a growing public health problem . The incidence and risk factors for opioid misuse in patients with chronic pain , however , have not been well characterized . We conducted a prospect i ve cohort study to determine the one-year incidence and predictors of opioid misuse among patients enrolled in a chronic pain disease management program within an academic internal medicine practice . Methods One-hundred and ninety-six opioid-treated patients with chronic , non-cancer pain of at least three months duration were monitored for opioid misuse at pre-defined intervals . Opioid misuse was defined as : 1 . Negative urine toxicological screen ( UTS ) for prescribed opioids ; 2 . UTS positive for opioids or controlled substances not prescribed by our practice ; 3 . Evidence of procurement of opioids from multiple providers ; 4 . Diversion of opioids ; 5 . Prescription forgery ; or 6 . Stimulants ( cocaine or amphetamines ) on UTS . Results The mean patient age was 52 years , 55 % were male , and 75 % were white . Sixty-two of 196 ( 32 % ) patients committed opioid misuse . Detection of cocaine or amphetamines on UTS was the most common form of misuse ( 40.3 % of misusers ) . In bivariate analysis , misusers were more likely than non-misusers to be younger ( 48 years vs 54 years , p < 0.001 ) , male ( 59.6 % vs. 38 % ; p = 0.023 ) , have past alcohol abuse ( 44 % vs 23 % ; p = 0.004 ) , past cocaine abuse ( 68 % vs 21 % ; p < 0.001 ) , or have a previous drug or DUI conviction ( 40 % vs 11 % ; p < 0.001 % ) . In multivariate analyses , age , past cocaine abuse ( OR , 4.3 ) , drug or DUI conviction ( OR , 2.6 ) , and a past alcohol abuse ( OR , 2.6 ) persisted as predictors of misuse . Race , income , education , depression score , disability score , pain score , and literacy were not associated with misuse . No relationship between pain scores and misuse emerged . Conclusion Opioid misuse occurred frequently in chronic pain patients in a pain management program within an academic primary care practice . Patients with a history of alcohol or cocaine abuse and alcohol or drug related convictions should be carefully evaluated and followed for signs of misuse if opioids are prescribed . Structured monitoring for opioid misuse can potentially ensure the appropriate use of opioids in chronic pain management and mitigate adverse public health effects of diversion Health-related quality of life ( HRQoL ) is an important factor that can interfere with treatment outcomes . The aim of the present study was cultural adaptation , validation , and translation of the Kidney Disease Quality of Life-Short Form ( KDQoL-SF 1.3 ) question naire into Turkish for the Turkish population . The KDQOL-SF was translated into Turkish and back-translated into English . Patient difficulties in underst and ing the question naire were evaluated and solved by a panel of experts . Measurement properties such as reliability and validity were determined by applying the question naire to 82 patients on dialysis , who were r and omly selected from the dialysis units of 3 educational and research hospitals in Istanbul : 65 % were females ; mean patient age was 51 + /- 12 years . The most common primary causes of renal failure were glomerulonephritis ( 47 % ) , hypertension ( 31 % ) , and diabetes ( 7 % ) . The median time on dialysis among the patients was 3 years . Test and retest methods were used for reliability . The total test-retest reliability Cronbach alpha coefficient of the Turkish KDQOL-SF question naire was 0.84 to 0.91 . These coefficients were statistically significant ( P < .05 ) for 19 dimensions of the KDQOL-SF that ranged from 0.75 to 0.91 . The Cronbach alpha coefficient was higher than 0.80 for most components . To evaluate its construct validity , the KDQOL-SF was compared with the Turkish version of the 15D , an instrument for global assessment that contains 15 items divided into 5 dimensions . The scores range from 0 to 1 ( 0 = worse health status , 1 = better health status ) . Significant correlations were observed between the scores of the similar domains of the 15D and the KDQOL-SF . The best correlations were observed between physical functioning ( KDQOL-SF ) and mobility ( 15D ; r = -.810 ) and between emotional well-being of ( KDQOL-SF ) , and with the mental functions of 15D ; ( r = -.784 ) , sexual function ( KDQOL-SF ) and sexual activity ( 15D ; r = -.781 ) , and patient satisfaction and distress ( r = -.801 ) . These findings support the construct validity of the new Turkish adapted KDQOL-SF . This study is reporting the complete process of translation and validation of the KDQOL-SF in the literature . These results demonstrate the high reliability and validity of this question naire for Turkish patients on dialysis Background EPIC-Italy cohort study recruited subjects who voluntarily accepted to participate in the project . From the self-selected bases of the population sample , some bias could derive in the data interpretation when risk estimation for cancer disease related to life-style factors is the principal concern . Knowledge of the bias related to self-selected sampling is important for better directing the interpretation of the EPIC-Italy study results . Methods We investigated the characteristics of volunteer subjects recruited in the EPIC-Italy cohorts and compared them with those of the r and omly selected subjects recruited in the Multi purpose ISTAT Surveys realized in the same period ( 1993 - 1998 ) in which the Epic-cohorts were recruited . Results We found some differences , and in particular a different attitude towards cigarettes smoking and wine consumption , between the EPIC cohort and the Multi purpose ISTAT Surveys , as well as among geographical areas within the EPIC cohort . Conclusions The uneven distribution of some characteristics suggests that the self-selected subjects were characterized by an overall lower consumption of wine and cigarette smoking even when the educational level was considered . This could suggest a generally more healthy life-style among subjects recruited on a volountary bases AIM To examine the concurrence of motor impairment and academic underachievement in a group of very preterm children at 8 years of age . METHODS All surviving children with a gestational age less than 30 weeks , admitted to the neonatal intensive care unit between 1987 and 1997 , were prospect ively enrolled in developmental follow-up . Children with a neurosensory disability or a low intelligence score ( FSIQ < or = 75 points ) were excluded . At 8 years of age the Bruininks Oseretsky Test of Motor Proficiency and st and ardised tests of academic achievement were administered to a sample of 323 very preterm children . RESULTS One hundred and one ( 31.3 % ) of these very preterm children were identified as having Developmental Coordination Disorder ( DCD ) . Of the children with DCD , 54.4 % also had underachievement in literacy and /or numeracy . As the severity of motor impairment increased so too did the severity and complexity of underachievement . Significantly fewer children with motor impairments participated in after-school sporting activities . Children with DCD required more mechanical ventilation support during their hospital admission . CONCLUSIONS This study demonstrated that a significant proportion of children born very preterm find both motor and academic skills difficult in early school years Background Self-reported medical history data are frequently used in epidemiological studies . Self-reported diagnoses may differ from medical record diagnoses due to poor patient-clinician communication , self-diagnosis in the absence of a satisfactory explanation for symptoms , or the " health literacy " of the patient . Methods The US Department of Defense military health system offers a unique opportunity to evaluate electronic medical records with near complete ascertainment while on active duty . This study compared 38 self-reported medical conditions to electronic medical record data in a large population -based US military cohort . The objective of this study was to better underst and challenges and strengths in self-reporting of medical conditions . Results Using positive and negative agreement statistics for less-prevalent conditions , near-perfect negative agreement and moderate positive agreement were found for the 38 diagnoses . Conclusion This report highlights the challenges of using self-reported medical data and electronic medical records data , but illustrates that agreement between the two data sources increases with increased surveillance period of medical records . Self-reported medical data may be sufficient for ruling out history of a particular condition whereas prevalence studies may be best served by using an objective measure of medical conditions found in electronic healthcare records . Defining medical conditions from multiple sources in large , long-term prospect i ve cohorts will reinforce the value of the study , particularly during the initial years when prevalence for many conditions may still be low Background Adolescents ' access to health information on the Internet is partly a function of their ability to search for and find answers to their health-related questions . Adolescents may have unique health and computer literacy needs . Although many surveys , interviews , and focus groups have been utilized to underst and the information-seeking and information-retrieval behavior of adolescents looking for health information online , we were unable to locate observations of individual adolescents that have been conducted in this context . Objective This study was design ed to underst and how adolescents search for health information using the Internet and what implication s this may have on access to health information . Methods A convenience sample of 12 students ( age 12 - 17 years ) from 1 middle school and 2 high schools in southeast Michigan were provided with 6 health-related questions and asked to look for answers using the Internet . Research ers recorded 68 specific search es using software that captured screen images as well as synchronized audio recordings . Recordings were review ed later and specific search techniques and strategies were coded . A qualitative review of the verbal communication was also performed . Results Out of 68 observed search es , 47 ( 69 % ) were successful in that the adolescent found a correct and useful answer to the health question . The majority of sites that students attempted to access were retrieved directly from search engine results ( 77 % ) or a search engine 's recommended links ( 10 % ) ; only a small percentage were directly accessed ( 5 % ) or linked from another site ( 7 % ) . The majority ( 83 % ) of followed links from search engine results came from the first 9 results . Incorrect spelling ( 30 of 132 search terms ) , number of pages visited within a site ( ranging from 1 - 15 ) , and overall search strategy ( eg , using a search engine versus directly accessing a site ) , were each important determinants of success . Qualitative analysis revealed that participants used a trial- and -error approach to formulate search strings , scanned pages r and omly instead of systematic ally , and did not consider the source of the content when search ing for health information . Conclusions This study provides a useful snapshot of current adolescent search ing patterns . The results have implication s for constructing realistic simulations of adolescent search behavior , improving distribution and usefulness of Web sites with health information relevant to adolescents , and enhancing educators ' knowledge of what specific pitfalls students are likely to encounter OBJECTIVE : To describe pediatricians ' self-reported experiences with health literacy , use of basic and enhanced communication techniques , and perceived barriers to effective communication during office visits . DESIGN / METHODS : A national , r and om sample of 1605 nonretired , posttraining American Academy of Pediatrics members were surveyed in 2007 about health literacy and patient communication as part of the Periodic Survey of Fellows . The response rate was 56 % ( N = 900 ) . RESULTS : Eight-one percent of the pediatricians were aware of a situation in the previous 12 months in which a parent had not sufficiently understood health information that had been delivered to him or her . In addition , 44 % of all pediatricians were aware of a communication-related error in patient care within the previous 12 months . Using simple language ( 99 % ) , repeating key information ( 92 % ) , and presenting only 2 or 3 concepts at a time ( 76 % ) were the most commonly used communication strategies . Enhanced communication techniques recommended by health literacy experts such as teach-back and indicating key points on written educational material s were used less often ( 23 % and 28 % , respectively ) . The most common reported barriers to effective communication were limited time to discuss information ( 73 % ) , volume of information ( 65 % ) , and complexity of information ( 64 % ) . The majority of physicians rated themselves highly in their ability to identify caregiver underst and ing ( 64 % ) , but only 21 % rated themselves as very good or excellent in identifying a parent with a literacy problem . Fifty-seven percent of the respondents were interested in training to improve communication skills , and 58 % reported that they would be very likely to use easy-to-read written material s , if available from the American Academy of Pediatrics . CONCLUSIONS : Pediatricians are aware of health literacy – related problems and the need for good communication with families but struggle with time dem and s to implement these skills . Despite awareness of communication-related errors in patient care , pediatricians report underutilizing enhanced techniques known to improve communication Background : Evidence based planning has been the hallmark of the blindness control programme in India . A nationwide survey was undertaken in 1999–2001 to document the magnitude and causes of blindness . Methods : One district each in 15 populous states was covered . 25 clusters were r and omly selected in each district and all individuals aged 50 years and above were enumerated . Presenting and best corrected vision was recorded using retroilluminated logMAR tumbling E charts and detailed eye examination was offered . Results : The response rate was 89.3 % . Presenting vision < 6/60 , in the better eye , was observed in 8.5 % ( 95 % CI : 8.1 to 8.9 ) . Age , sex , residence , literacy , and working status were associated with blindness . The highest risk was among those aged 70 + and the illiterate . Cataract was responsible for 62.4 % of bilateral blindness . Prevalence of cataract blindness was 5.3 % ( 95 % CI : 4.97 to 5.62 ) . Reduction in blindness prevalence among people aged 50 years and above was observed compared to earlier studies . Conclusion : Blindness control efforts seem to have played a part in arresting the increasing prevalence of blindness in India and there is hope that the goals of the “ Vision 2020—right to sight ” initiative can be achieved if there is strong political will and prioritised action Cancellation tasks have been largely used to evaluate visuospatial function and attention . Cognitive evaluation of low literacy subjects remains a challenge in developing countries , when it becomes necessary to distinguish between what is pathological and what is biased by low education . Performance of river bank dwellers of the Amazon region was studied , in a structured nonverbal cancellation task , verifying their search ing strategies ( r and omized/organized ) , time of completion , number of correct cancelled targets and number of false-positive targets . A difference was observed in performance and search ing strategies between illiterates and literates with only a few years of schooling ( mean=0.8 , S.D.=1.6 years of education ) across all measures . There was a significant difference between literate groups in the search ing strategy , as well as between illiterates who had never attended school and those who had , showing that a minimal contact with graphic presentations and organization of writing was able to modify this cognitive function PURPOSE / OBJECTIVES To test a multi method approach design ed for rural healthcare providers to increase breast cancer screening among low-income , African American , and older women . DESIGN Two-year experimental pretest/post-test with r and om assignment by group . SETTING Primary healthcare providers ' offices . SAMPLE 224 nurses , physicians , and mammography technicians . METHODS St and ardized patients to observe and record healthcare providers ' performances , followed by direct feedback , newsletters , posters , pocket reminder cards , and lay literature about screening to use in clinics . MAIN RESEARCH VARIABLES Healthcare providers ' knowledge and attitudes as measured by survey responses , skills as measured by a checklist , and the provision of breast cancer screening as measured by mammography facilities ' data . FINDINGS Healthcare providers significantly improved in demonstration of breast cancer screening practice after the intervention . Nurses performed significantly better than physicians on the breast examination during the post-test . More women older than 50 received mammograms in the experimental counties than in the comparison counties . Culturally sensitive lay literature is needed for African American women with low literacy . CONCLUSIONS Successful interventions included use of st and ardized patients to teach healthcare providers in their office setting s , prompts such as posters and pocket reminder cards , and easy-to-read newsletters . IMPLICATION S FOR NURSING Physicians and nurses play a powerful role in motivating women to have mammograms and clinical breast examinations and to practice breast self-examination . Interventions that help these providers fulfill that role should be implemented Background Latinos comprise the largest racial/ethnic group in the United States and have 2–3 times the prevalence of type 2 diabetes mellitus as Caucasians . Methods and design The Lawrence Latino Diabetes Prevention Project ( LLDPP ) is a community-based translational research study which aims to reduce the risk of diabetes among Latinos who have a ≥ 30 % probability of developing diabetes in the next 7.5 years per a predictive equation . The project was conducted in Lawrence , Massachusetts , a predominantly Caribbean-origin urban Latino community . Individuals were identified primarily from a community health center 's patient panel , screened for study eligibility , r and omized to either a usual care or a lifestyle intervention condition , and followed for one year . Like the efficacious Diabetes Prevention Program ( DPP ) , the LLDPP intervention targeted weight loss through dietary change and increased physical activity . However , unlike the DPP , the LLDPP intervention was less intensive , tailored to literacy needs and cultural preferences , and delivered in Spanish . The group format of the intervention ( 13 group sessions over 1 year ) was complemented by 3 individual home visits and was implemented by individuals from the community with training and supervision by a clinical research nutritionist and a behavioral psychologist . Study measures included demographics , Stern predictive equation components ( age , gender , ethnicity , fasting glucose , systolic blood pressure , HDL-cholesterol , body mass index , and family history of diabetes ) , glycosylated hemoglobin , dietary intake , physical activity , depressive symptoms , social support , quality of life , and medication use . Body weight was measured at baseline , 6-months , and one-year ; all other measures were assessed at baseline and one-year . All surveys were orally administered in Spanish . Results A community-academic partnership enabled the successful recruitment , intervention , and assessment of Latinos at risk of diabetes with a one-year study retention rate of 93%.Trial registration Study Design . Prospect i ve observational cohort . Objective . To describe the baseline characteristics of patients with a diagnosis of intervertebral disc herniation who had different treatment preferences and the relationship of specific expectations with those preferences . Summary of Background Data . Data were gathered from the observational cohort of the Spine Patient Outcomes Research Trial ( SPORT ) . Patients in the observational cohort met eligibility requirements identical to those of the r and omized cohort , but declined r and omization , receiving instead the treatment of their choice . Methods . Baseline preference and expectation data were acquired at the time of enrollment of the patient , before exposure to the informed consent process . Univariate analyses were performed using a t test for continuous variables and & khgr;2 for categorical variables . Multivariate analyses were also performed with ANCOVA for continuous variables and logistic regression for categorical variables . Multiple logistic regression models were developed in a forward stepwise fashion using blocks of variables . Results . More patients preferred operative care : 67 % preferred surgery , 28 % preferred nonoperative treatment , and 6 % were unsure ; 53 % of those preferring surgery stated a definite preference , whereas only 18 % of those preferring nonoperative care had a definite preference . Patients preferring surgery were younger , had lower levels of education , and higher levels of unemployment/disability . This group also reported higher pain , worse physical and mental functioning , more back pain related disability , a longer duration of symptoms , and more opiate use . Gender , race , comorbidities , and use of other therapies did not differ significantly across preference groups . Patients ’ expectations regarding improvement with nonoperative care was the strongest predictor of preference . Conclusion . Patient expectations , particularly regarding the benefit of nonoperative treatment , are the primary determinant of surgery preference among patients with lumbar intervertebral disc herniation . Demographic , functional status , and prior treatment experience had significant associations with patients ’ expectations and preferences PURPOSE Low health literacy is a significant problem in the United States . At the same time written screening tools such as the American Urological Association symptom score are used more frequently at hospitals and clinics . We previously reported that many patients do not fully underst and this tool and often provide inaccurate information . To combat this problem we developed a novel multimedia version of the American Urological Association symptom score . MATERIAL S AND METHODS In this r and omized , controlled trial we divided 232 patients into a control arm that self-administered the traditional written version of the symptom score and an experimental arm that self-administered the new multimedia version . Patients in each arm were later administered the tool a second time by an interviewer for comparison . Using multivariate analysis we measured disagreement between the self-administered and interviewer administered scores , and compared the 2 arms . RESULTS Patients assigned the written and the multimedia version showed an average error of 3.48 and 1.97 , respectively ( p < 0.001 ) , for a 43 % decrease . Improvement was noted regardless of patient literacy . Errors by patients with low and high literacy decreased from 4.55 to 2.24 and 3.10 to 1.86 ( p = 0.03 and < 0.001 , respectively ) . CONCLUSIONS As a model , the American Urological Association symptom score multimedia version represents an exciting opportunity to improve many other written screening tools since it increased underst and ing and decreased scoring errors across all literacy levels , possibly allowing physicians to treat patients more effectively Purpose : Investigate the prevalence and vision-related outcomes of cataract surgery in an area of high cataract surgical rate . Methods : Cluster sampling was used in r and omly selecting individuals ≥ 50 years of age in 2007 . Participants were queried regarding year and place of previous cataract surgery . Cataract surgical procedures and evidence of surgical complications were recorded . The principal cause was identified for eyes presenting with visual acuity ( VA ) ≤ 20/40 . Results : A total of 4,738 persons were examined and 834 ( 17.6 % ) had cataract surgery . Intra-ocular lenses ( IOLs ) were used in 84.1 % of the 1,299 cataract-operated eyes , with more than half of these having manual small incision surgery . Surgical coverage among the cataract blind ( visual acuity [ VA ] < 20/200 ) was estimated as 72.2 % . Coverage was associated with older age , literacy , and urban residence ; gender was not significant . Among cataract-operated eyes , 18.7 % presented with VA ≥ 20/32 and 18.0 % were < 20/200 . With best-corrected acuity , the corresponding percentages were 55.7 % and 11.0 % . Presenting and best-corrected VA ≥ 20/63 were associated with young age , literacy , and IOL surgery ; urban residence and surgery in non-governmental organizations (NGO)/private facilities were also significant for presenting VA ; and recent surgery was significant for best-corrected VA . Refractive error was the main cause of vision impairment/blindness in cataract-operated eyes . Conclusions : Refractive error and posterior capsule opacification , easily treatable causes of visual impairment , are common among the operated . A greater emphasis on the quality of visual acuity outcomes along with sustained efforts to provide access to affordable surgery is needed OBJECTIVE To determine the prevalence of systemic and ocular toxoplasmosis among 1024 students in the city of Natal , Northeastern Brazil , and correlate it with demographic , socioeconomic and epidemiological risk factors . METHODS The study population was r and omly selected , asked to fill out a question naire , provide a blood sample for IgG and IgM ( MEIA ) serology and a hemogram , and undergo an eye examination . RESULTS The seroprevalence for IgG was 46 % ( 95 % CI = 42.9 - 49.2 % ) and that for IgM was 1.4 % ( 95 % CI = 0.8 - 2.4 % ) . The prevalence of ocular lesions was 1.15 % ( 95 % CI = 0.6 - 2.0 % ) . In the univariate analyses , confirmed by multivariate analysis , the socioeconomic conditions were determinants in the prevalence of systemic and ocular toxoplasmosis ( mother 's schooling = literacy/OR = 2.9 and p < 0.001 ) . CONCLUSIONS The prevalence of systemic toxoplasmosis , although high , was lower than that found in studies performed in the South and Southeast of Brazil , and the incidence of ocular lesions was totally different , being lower by a factor varying from 5 to 17 . Although important epidemiological variables , such as owning a cat , drinking unfiltered water or having had contact with lakes or rivers , were found to be correlated with toxoplasmosis in the preliminary analysis , they lost their influence when included in the logistic model . However , further studies must be undertaken to identify the reasons for these findings , including the determination of the strains of Toxoplasma gondii encountered in different regions of the country and the sources of the water utilized by these population BACKGROUND To improve medication adherence in cardiac patients , in partnership with a safety-net provider , this research team developed and evaluated a low-literacy medication education tool . METHODS Using principles of community-based participatory research , the team developed a prototype of a low-literacy hospital discharge medication education tool , customizable for each patient , featuring instruction-specific icons and pictures of pills . In 2007 , a r and omized controlled clinical trial was performed , testing the tool 's effect on posthospitalization self-reported medication adherence and knowledge , 2 weeks postdischarge in English- and Spanish-speaking safety-net in patients . To vali date the self-report measure , 4 weeks postdischarge , investigators collected self-reports of the number of pills remaining for each medication in a sub sample of participants . Nurses rated tool acceptability . RESULTS Among the 166/210 eligible participants ( 79 % ) completing the Week-2 interview , self-reported medication adherence was 70 % ( 95 % CI=62 % , 79 % ) in intervention participants and 78 % ( 95 % CI=72 % , 84 % ) in controls ( p=0.13 ) . Among the 85 participants ( 31 % ) completing the Week-4 interview , self-reported pill counts indicated high adherence ( greater than 90 % ) and did not differ between study arms . Self-reported adherence was correlated with self-reported pill count in intervention participants ( R=0.5 , p=0.004 ) but not in controls ( R=0.07 , p=0.65 ) . There were no differences by study arm in medication knowledge . The nurses rated the tool as highly acceptable . CONCLUSIONS Although the evaluation did not demonstrate the tool to have any effect on self-reported medication adherence , patients who received the schedule self-reported their medication adherence more accurately , perhaps indicating improved underst and ing of their medication regimen and awareness of non-adherence Summary Objectives : Patient empowerment through the Internet is seen as a chance to improve patient-physician communication . Studies on the prevalence of Internet use for health related purpose s and on how patients perceive those technologies are still rare . We therefore studied perception of and trends in health related Internet use . Methods : As part of a European survey 1.000 German individuals were interviewed using a computer-based telephone interview ( CATI : Gabler-Häder- Design , r and om-digit-dialing , last birthday method ) in October 2005 . Descriptive statistics and logistic regression models were applied for elaborating characteristics of the health Internet users . Results : Internet use in general ( 72.3 % ) and for health related purpose s ( 53.1 % ) is already quite high . Its importance , relative to other sources of health related information , was rated rather low . Younger citizens and people with paid work used the Internet more often for health related purpose s , nevertheless , assessing it as less important for health related purpose s than their counterparts . Conclusion : Despite booming of Internet use in Germany , consumers still value and use more the traditional sources of health information/communication with their doctors . Followup studies with a subsequent survey in 2007 will be pursued OBJECTIVE To determine whether children with attention-deficit hyperactivity disorder ( ADHD ) and learning disabilities respond differently to methylpheni date ( MPH ) compared with children with ADHD only . METHODS We conducted a prospect i ve , double-blind , placebo-controlled , r and omized , 2-week crossover trial of MPH , during which response to MPH was assessed . Learning ability was appraised using the Wide Range Achievement Test , Revised ( WRAT-R ) , for English-speaking students and the Test de rendement pour francophones for French-speaking students . The study was conducted at the Douglas Hospital , a McGill University-affiliated teaching hospital in Montréal . Ninety-five children , aged 6 - 12 years , who met the Diagnostic and Statistical Manual of Mental Disorders , fourth edition ( DSM-IV ) , criteria for ADHD participated in the study , which ran from 2001 to 2004 . The outcome measure used was the Consensus Clinical Response , an indicator of the degree of clinical improvement shown when taking MPH . RESULTS The proportion of children with learning disabilities who responded to MPH ( 55 % ) was significantly smaller ( chi(2)1 = 4.5 , p = 0.034 ) than the proportion of children without learning disabilities who responded adequately to MPH ( 75 % ) . This difference was mainly because of children with mathematics disability being particularly unresponsive to MPH ( chi(2)1 = 4.5 , p = 0.034 ) . Children with reading disability did not show this pattern of poor response ( chi(2)1 = 1.0 , p = 0.33 ) . CONCLUSION Children with ADHD and comorbid learning disability tended to respond more poorly to MPH . In particular , children with disability in mathematics responded less to MPH than those without disability in mathematics . Additional therapy may be indicated for this group of patients This study evaluated the current level of diabetes care in three county clinics serving an underserved minority population and determined if a low-literacy , diabetes reminder card would enhance certain diabetes process care measures . Patients from two intervention sites were given the low-literacy , diabetes reminder card . Two-hundred-nineteen patients ( 87 % ) showed the card to their provider , and 209 charts were review ed . American Diabetes Association guidelines had been met 37 % , 71 % , and 41 % for foot exam , and urine and lipid tests , respectively , at the time the card was given to the patients . Of the patients who needed a foot exam , urine test , and lipid panel that day ( based on ADA guidelines ) , 48 % , 67 % , and 35 % received them , respectively ( card effect ) . In the third ( nonintervention ) site , charts of 218 patients were review ed . Guidelines met were 95 % , 89 % , and 45 % for foot exam , urine and lipid tests , respectively . Interestingly , st and ardized progress notes containing the first two ( but not the third ) process measures were used at this site . We conclude that although low-literacy reminder cards did improve the ordering of process measures somewhat , they were not as effective as the utilization of progress forms with specific diabetes-related measures The aim of this study was to assess public attitudes toward the promotion of genomic studies related to medicine and to examine the relationship between public attitudes and the level of genomic literacy by analyzing data from a nationwide opinion survey . The participants comprised 4,000 people ( age , 20–69 ) selected from the Japanese general population by using the two‐step stratified r and om sampling method . They were queried on the following topics in a mail survey : ( 1 ) pros and cons of the promotion of genomic studies related to medicine , ( 2 ) level of scientific literacy in genomics , ( 3 ) demographic and socioeconomic background , and ( 4 ) knowledge and attitudes toward science in general and genetic testing in particular . We examined the relationship between the approval of promotion and literacy level , using logistic regression models stratified by gender . Our results showed the response rate was 54.3 % ( 2,171/4,000 ) , and 69.4 % participants favored the promotion of genomic studies related to medicine . Only 1.3 % participants expressed a negative attitude . Multivariate analysis revealed that approval of promotion was related to a high literacy score . This relationship was stronger in males than in females ( the highest quartile of score vs. the lowest : adjusted odds ratio , 3.36 for males and 1.86 for females ; 95 % confidence interval , 1.88–5.98 for males and 1.17–2.95 for females ) . We determined that a majority of the Japanese participants currently approved of the promotion of genomic studies related to medicine and that people with a high level of genomic literacy tended to approve the promotion . © 2008 Wiley‐Liss , Children born preterm and of very low birth weight have an increased incidence of learning difficulties , but little is known about the specific nature of their cognitive deficits and the underlying neuropathology . We hypothesized that their vulnerability to hypoxic , metabolic , and nutritional insults would lead to reduced hippocampal volumes and to deficits in memory because of the role of the hippocampus in this domain of cognition . Neuropsychological and magnetic resonance imaging methods were used to investigate this hypothesis in adolescents born preterm ( ≤30 wk gestation , n = 11 ) or full-term ( n = 8) . The preterm group had significantly smaller hippocampal volumes bilaterally , despite equivalent head size , and showed specific deficits in certain aspects of everyday memory , both on objective testing and as indicated by parental question naires . The preterm group also had a specific deficit in numeracy . The reduced hippocampal volumes and deficits in everyday memory have previously been unrecognized , but their prevalence in a group of neurologically normal children is striking BACKGROUND the relationship between anemia and development . AIM to compare the auditory and language development in anemic and non-anemic children , with ages ranging from three to six years , of a public daycare center in Belo Horizonte city . METHOD a transversal study ; blind case and control format . A digital puncture was performed in all children to detect iron-deficiency anemia ( hemoglobin = 11.3g/dL ) . The research group was composed of 19 anemic children and the control group of 38 healthy children , selected through r and omized paired sampling . The children 's hearing was evaluated through otoacoustic emissions , tympanometry and a simplified evaluation of the central auditory processing was performed . The language development of each child was observed using the behavior observation guidelines for children with ages from zero to six years . Performance indexes were created in order to classify the language responses of the children . RESULTS the groups did not differ in terms of age , gender , breast-feeding and mother 's literacy . The following variables presented statistically significant differences : hemoglobin values ( 10.6g/dL , 12.6g/dL ) ; presence of the acoustic reflex ( 63 % , 92 % ) ; reception performance indexes ( 72.8 , 90.1 ) ; emission ( 50.6 , 80.6 ) and cognitive aspects of language ( 47.8 , 76.0 ) in anemic and non-anemic children respectively . The hearing abilities in the verbal and non-verbal sequential memory and the sonorous localization were inadequate in most of the children , especially in those with anemia . CONCLUSION anemic children differed statically from non-anemic children in terms of alterations in the acoustic reflex and language development and also presented a higher prevalence of alterations in the hearing evaluation OBJECTIVE This paper presents an approach to usability evaluation of computer-based health care systems design ed for patient use in their homes . Although such devices are becoming more prevalent , there is very little known about their usability . DESIGN The theoretical foundations for the methods are discussed . The approach incorporates a cognitive walkthrough usability evaluation and new methods for usability testing that can be conducted in patient 's homes . The method was applied to the IDEATel intervention , a multi-institution r and omized controlled trial of the feasibility , acceptability , and clinical utility of a home-based telemedicine system for diabetic Medicare population . The usability study was design ed to assess barriers to optimal use of the system . The focus was both on dimensions of the interface and on dimensions of patient skills and competency . The usability field research involved testing 25 patients in their homes using the system . The analysis included a range of video-analytic methods of varying levels of granularity . RESULTS The usability evaluation revealed aspects of the interface that were sub-optimal and impeded the performance of certain tasks . It also found a range of patient-related factors such as numeracy and psychomotor skills that constituted barriers to productive use . CONCLUSIONS A multifaceted usability approach provided important insight regarding use of technology by an elderly chronic-care patient population and more generally , for underst and ing how home health initiatives can more effectively use such technology Background : Long-term follow-up in patients with a subarachnoid hemorrhage ( SAH ) can be important in patients care and for clinical research , but out patients ’ visits or telephone interviews are time consuming . Methods : We studied the feasibility of follow up through e-mail in a prospect ively collected series of patients with aneurysmal SAH . Results : Of the 97 patients who were discharged 58 ( 60 % ; 95 % CI 49–70 % ) had e-mail , and all 58 provided their e-mail address . At 1 year 37 patients ( 64 % ; 95 % CI 50–76 % ) responded to the first question naire sent by e-mail , 6 did so after an e-mail reminder . Fifteen responded after a telephone call , of which 12 had a new e-mail address . Conclusions : E-mail follow-up after SAH is feasible and for patients acceptable , but the proportion of patients with no or with changing e-mail address is considerable . The validity of the responses via e-mail has to be assessed in further studies PURPOSE The aims of this study were to investigate whether prostate cancer patients want to be involved in the choice of the radiation dose , and which patients want to be involved . METHODS AND MATERIAL S This prospect i ve study involved 150 patients with localized prostate cancer treated with three-dimensional conformal radiotherapy . A decision aid was used to explain the effects of two alternative radiation doses ( 70 and 74 Gy ) in terms of cure and side effects . Patients were then asked whether they wanted to choose their treatment ( accept choice ) , or leave the decision to the physician ( decline choice ) . The treatment preference was carried out . RESULTS Even in this older population ( mean age , 70 years ) , most patients ( 79 % ) accepted the option to choose . A lower score on the design ations Pre-existent bowel morbidity , Anxiety , Depression , Hopelessness and a higher score on Autonomy and Numeracy were associated with an increase in choice acceptance , of which only Hopelessness held up in multiple regression ( p < 0.03 ) . The uninformed participation preference at baseline was not significantly related to choice acceptance ( p = 0.10 ) . CONCLUSION Uninformed participation preference does not predict choice behavior . However , once the decision aid is provided , most patients want to choose their treatment . It should , therefore , be considered to inform patients first and ask participation preferences afterwards Study Design . Prospect i ve study with 6 weeks of follow-up . Objective . To examine the predictors of outcome for patients with (sub)acute low back pain ( LBP ) receiving usual care ( UC ) or a minimal intervention strategy ( MIS ) aim ed at psychosocial factors . Summary of Background Data . A r and omized controlled trial in general practice showed no differences in average effect between UC and MIS . Methods . Socio-demographic variables , characteristics of LBP , and psychosocial factors were included as potential predictors of outcome . The outcome clinical ly important improvement was defined as a reduction of at least 30 % on functional disability plus patient perceived recovery . Logistic regression analyses were used to study the associations between predictors and outcome at 6 weeks follow-up . Results . In the UC group ( n = 163 ) , the multivariable model included a shorter duration of the LBP episode , few previous episodes , less pain catastrophizing , and good perceived general health . The area under the curve ( AUC ) of the model was 0.77 ( 95 % confidence interval , 0.70–0.85 ) . In the MIS group ( n = 142 ) , the multivariable model included less somatizing symptoms , more solicitous responses by an important other , lower perceived risk for chronic LBP , more fear avoidance beliefs , higher level of education , and shorter duration of the LBP episode . This AUC was 0.78 ( 95 % confidence interval , 0.71–0.86 ) . Conclusions . As we found two different profiles , our approach may contribute to the important question : what intervention works for whom The impact of an adherence enhancement program for low income HIV-infected Spanish-speaking Latinos on health literacy , patient-provider relationships , and adherence to HAART was examined . Evaluations were conducted at baseline , 6 weeks , and 6 months for participants ( n = 85 ) r and omly assigned to either the intervention group or a comparison group ; 69 ( 81 % ) remained in the study for the entire 6-month duration . The intervention group scored significantly better than the comparison group on 3 of 5 measures of HIV health literacy at 6 weeks and on 2 of 5 measures , at 6 months . While there was a weak trend for the intervention group to report an increase in self-efficacy of medication adherence management , baseline to 6 weeks , no other changes were significant . Perceptions of the quality of relationship and communications with their HIV-treating physicians improved both at 6 weeks ( p = 0.04 ) and at 6 months ( p < 0.001 ) . The comparison group showed little change baseline to 6 weeks and baseline to 6 months . While there was a trend for the pilot group to report better medication adherence , these differences were not statistically significant . Further evaluation of the impact of this adherence enhancement program is needed Background Evidence suggests that truth telling and honest disclosure of cancer diagnosis could lead to improved outcomes in cancer patients . To examine such findings in Iran , this trial aim ed to study the various dimensions of quality of life in patients with gastrointestinal cancer and to compare these variables among those who knew their diagnosis and those who did not . Methods A consecutive sample of patients with gastrointestinal cancer being treated in Cancer Institute in Tehran , Iran was prospect ively evaluated . A psychologist interviewed patients using the Iranian version of the European Organization for Research and Treatment of Cancer Quality of Life Question naire ( EORTC QLQ-C30 ) . Patients were categorized into two groups : those who knew their diagnosis and those who did not . Independent sample t-test was used for group comparisons . Results In all 142 patients were interviewed . A significant proportion ( 52 % ) of patients did not know their cancer diagnosis and 48 % of patients were aware that they had cancer . They were quite similar in most characteristics . The comparison of quality of life between two groups indicated that those knew their diagnosis showed a significant lower degree of physical ( P = 0.001 ) , emotional ( P = 0.01 ) and social functioning ( P < 0.001 ) , whereas the global quality of life and other functional scales including role functioning and cognitive functioning did not show significant result . There were no statistically significant differences between symptoms scores between two groups , except for fatigue suggesting a higher score in patients who knew their diagnosis ( P = 0.01 ) . The financial difficulties were also significantly higher in patients who knew their cancer diagnosis ( P = 0.005 ) . Performing analysis of variance while controlling for age , educational status , cancer site , and knowledge of cancer diagnosis , the results showed that the knowledge of cancer diagnosis independently still contributed to the significant differences observed between two groups . Conclusion Contrary to expectation the findings indicated that patients who did not know their cancer diagnosis had a better physical , social and emotional quality of life . It seems that due to cultural differences between countries cancer disclosure guidelines perhaps should be differing Background As in any measurement process , a certain amount of error may be expected in routine population surveillance operations such as those in demographic surveillance sites ( DSSs ) . Vital events are likely to be missed and errors made no matter what method of data capture is used or what quality control procedures are in place . The extent to which r and om errors in large , longitudinal data sets affect overall health and demographic profiles has important implication s for the role of DSSs as platforms for public health research and clinical trials . Such knowledge is also of particular importance if the outputs of DSSs are to be extrapolated and aggregated with realistic margins of error and validity . Methods This study uses the first 10-year data set from the Butajira Rural Health Project ( BRHP ) DSS , Ethiopia , covering approximately 336,000 person-years of data . Simple programmes were written to introduce r and om errors and omissions into new versions of the definitive 10-year Butajira data set . Key parameters of sex , age , death , literacy and roof material ( an indicator of poverty ) were selected for the introduction of errors based on their obvious importance in demographic and health surveillance and their established significant associations with mortality . Defining the original 10-year data set as the ' gold st and ard ' for the purpose s of this investigation , population , age and sex compositions and Poisson regression models of mortality rate ratios were compared between each of the intentionally erroneous data sets and the original ' gold st and ard ' 10-year data . Results The composition of the Butajira population was well represented despite introducing r and om errors , and differences between population pyramids based on the derived data sets were subtle . Regression analyses of well-established mortality risk factors were largely unaffected even by relatively high levels of r and om errors in the data . Conclusion The low sensitivity of parameter estimates and regression analyses to significant amounts of r and omly introduced errors indicates a high level of robustness of the data set . This apparent inertia of population parameter estimates to simulated errors is largely due to the size of the data set . Tolerable margins of r and om error in DSS data may exceed 20 % . While this is not an argument in favour of poor quality data , reducing the time and valuable re sources spent on detecting and correcting r and om errors in routine DSS operations may be justifiable as the returns from such procedures diminish with increasing overall accuracy . The money and effort currently spent on endlessly correcting DSS data sets would perhaps be better spent on increasing the surveillance population size and geographic spread of DSSs and analysing and disseminating research findings Previous studies have shown a significant association between reading skills and the performance on visuo-motor tasks . In order to clarify whether reading and writing skills modulate non-linguistic domains , we investigated the performance of two literacy groups on a visuo-motor integration task with non-linguistic stimuli . Twenty-one illiterate participants and twenty matched literate controls were included in the experiment . Subjects were instructed to use the right or the left index finger to point to and touch a r and omly presented target on the right or left side of a touch screen . The results showed that the literate subjects were significantly faster in detecting and touching targets on the left compared to the right side of the screen . In contrast , the presentation side did not affect the performance of the illiterate group . These results lend support to the idea that having acquired reading and writing skills , and thus a preferred left-to-right reading direction , influences visual scanning INTRODUCTION This study aim ed to compare the clinical and epidemiological profiles of cases of complicated and uncomplicated chronic suppurative otitis media , based on their prognostic factors . MATERIAL S AND METHODS This was a prospect i ve , cross-sectional study conducted in a tertiary care medical college hospital over a period of two and a half years . The study group comprised 187 ears , out of which 62 had complications while 125 did not . The two groups were compared with respect to nine prognostic variables : age distribution , sex , patient 's domicile , literacy status , duration of ear discharge at presentation , ear pathology , predisposing disease focus in the nose or throat , ear swab microbiology , and hearing loss . RESULTS Patients in the complicated chronic suppurative otitis media group had a higher male predominance and were younger . Rural and illiterate patients had a higher risk of developing complications . Cholesteatoma and granulation tissue were potential risk factors in the complicated chronic suppurative otitis media group . Ears with complications were more prone to develop sensorineural hearing loss . Age , sex , duration of ear discharge , predisposing disease focus in nose or throat , and ear swab microbiology were all less useful prognostic indicators of complications . CONCLUSION Early detection and timely treatment of chronic suppurative otitis media in rural and illiterate patients may prevent life-threatening complications and reduce their incidence . Ears that harbour relatively large quantities of both cholesteatoma and granulation tissue together require more urgent surgical intervention and more extensive disease clearance in order to prevent complications BACKGROUND Awareness of individual phonemes in words is a late-acquired level of phonological awareness that usually develops in the early school years . It is generally agreed to have a close relationship with early literacy development , but its role in speech change is less well understood . Speech and language therapy for children with speech disorder involves tasks that appear , either implicitly or explicitly , to require a phonemic level of awareness . However , children typically attend for intervention at a pre-school , pre-literate stage , i.e. before they would be expected to have developed the relevant phoneme segmentation and manipulation skills . AIMS To investigate whether it is possible to teach phoneme awareness skills to pre-literate children with speech disorder . METHODS & PROCEDURES In a r and omized controlled trial design 42 children with speech disorder , aged 4;0 - 4;6 , were allocated to either a phonological awareness or a language stimulation programme . Children were assessed on four measures of phoneme awareness ( alliteration awareness , phoneme isolation , word segmentation and phoneme addition/deletion ) immediately before and after the programme and categorized as ' improved ' or ' not improved ' according to predetermined criteria . Fisher 's Exact test was used to compare outcome in the two groups . OUTCOMES & RESULTS Significantly more children improved in the phonological awareness group than in the language stimulation group for three out of the four measures ( all except alliteration awareness ) . However , for the two most advanced tasks ( segmentation and addition/deletion ) only a small minority of children showed improvement . A marked improvement in Phoneme Isolation was made by the majority of children in the phonological awareness group . CONCLUSIONS It is possible to teach some advanced phoneme awareness skills to some pre-literate children . Phoneme Isolation was the most easily learned and is a skill that appears very relevant to speech and language therapy . However , phoneme addition , deletion and word segmentation showed relatively limited improvement and only in a small number of cognitively able and older children . Whereas isolation of word initial consonants appears to be a skill that can be triggered at 4;0 - 4;6 by relevant activities , most children in the study were not cognitively ready for more advanced , abstract phoneme manipulation tasks . This raises questions about how speech and language therapists should tackle many common errors and the age at which we should aim to develop or draw on phoneme awareness to stimulate speech change PURPOSE The aim of this study was to examine the validity and reliability of the Com-DAS ( combined dental anxiety scale ) as an indicator for children 's perceived dental anxiety and to investigate the effect of age , gender and socio-economic factors on dental anxiety . MATERIAL S AND METHODS A total of 258 children aged between 8 and 12 years , who had not visited a dentist before , were r and omly selected from three different socio-economic status groups . A new scale was developed by combining the C-DAS ( Corah 's dental anxiety scale ) and FIS ( facial imaging scale ) , and named Com-DAS . Original C-DAS was used for validation . RESULTS There was a high correlation between C-DAS and Com-DAS ( r = 0.69 ) . The lowest correlation was in 8-year-old children ( r = 0.46 ) , however the mean difference between the scales in this age group was not statistically significant ( p > 0.05 ) . The Com-DAS scores showed no statistical difference according to gender , whereas there was a significant difference according to age and socio-economic status ( p = 0.001 in both cases ) . CONCLUSION The Com-DAS used in this study may be of use in those communities where the children and their families have limited literacy skills and their underst and ing of modern dental procedures may be influenced by non-qualified dental practice BACKGROUND . Very low birth weight survivors are at increased risk of developing emotional and behavioral problems and low social and academic competencies . Information on such problems in very low birth weight adolescents is still sparse . OBJECTIVES . Our purpose for this work was to study gender-specific emotional and behavioral problems and social and academic competencies in a cohort of very low birth weight adolescents in north Norway . METHODS . Families with very low birth weight adolescents aged 13 to 18 years , born between 1978 and 1989 ( n = 162 ) were addressed by mail and asked to complete the Child Behavior Check List and the Youth Self-Report . Data were compared with 2 normative adolescent population s ( Child Behavior Check List , n = 540 ; Youth Self-Report , n = 2522 ) . Scores given by very low birth weight adolescents and their parents on identical items in Child Behavior Check List and Youth Self-Report ( cross-informant syndrome constructs ) were compared in pairs . To explore predictive effects , demographic and early medical characteristics were entered into a hierarchical multiple regression analysis . RESULTS . There were 156 eligible families , and 99 ( 63.5 % ) responded . All completed the Child Behavior Check List , and 82 ( 52.6 % ) completed the Youth Self-Report . Very low birth weight boys reported less externalizing and internalizing behaviors and thought and attention problems and higher activity score , whereas very low birth weight girls reported less externalizing behavior and less social , thought , and attention problems and higher activity score compared with normative adolescents . Very low birth weight parents , however , reported more social and attention problems and less social and school competence in boys and more internalizing behavior and social and attention problems and less school competence in girls compared with normative parents . They scored high proportions of both genders within the borderline/ clinical range on all of the scales , except for externalizing behavior and social problems in girls . Female very low birth weight adolescents , in contrast to males , reported more problems than parents when compared in pairs , and externalizing problems in particular were not recognized by parents . CONCLUSIONS . From parents ' point of view , significant proportions of very low birth weight adolescents experience more emotional and behavioral problems and less competence than normative adolescents . In contrast , very low birth weight adolescents state less problems and similar or higher competence than normative adolescents . Very low birth weight adolescent girls report more emotional and behavioral problems compared with their parents than very low birth weight adolescent boys do . Externalizing problems in very low birth weight adolescent girls are often not recognized by parents . To better underst and these seemingly paradoxical findings and to develop adequate intervention programs , there is a need for prospect i ve longitudinal studies BACKGROUND Significant palliative care intervention has focused on physical pain and symptom control ; yet less empirical evidence supports efforts to address the psychosocial and spiritual dimensions of experience . OBJECTIVE To evaluate the impact of an intervention ( Outlook ) that promotes discussion s of end-of-life preparation and completion on health outcomes in dying persons , including pain and symptoms , physical function , emotional function ( anxiety and depression ) , spiritual well-being , and quality of life at the end of life . DESIGN A three-arm pilot r and omized control trial . Subjects were recruited from inpatient and outpatient hospital , palliative care , and hospice setting s. Intervention subjects met with a facilitator three times and discussed issues related to life review , forgiveness , and heritage and legacy . Attention control subjects met with a facilitator three times and listened to a nonguided relaxation CD . True control subjects received no intervention . MEASUREMENTS Pre outcomes and post outcomes included the Memorial Symptom Assessment Scale , QUAL-E , Rosow-Breslau ADL Scale , Profile of Mood States anxiety sub-scale , the CESD short version , and the Daily Spiritual Experience Scale . RESULTS Eighty-two hospice eligible patients enrolled in the study ; 38 were women , 35 were African American . Participants ' primary diagnoses included cancer ( 48 ) , heart disease ( 5 ) lung disease ( 10 ) , and other ( 19 ) Ages ranged from 28 - 96 . Participants in the active discussion intervention showed improvements in functional status , anxiety , depression , and preparation for end of life . CONCLUSIONS The Outlook intervention was acceptable to patients from a variety of educational and ethnic background s and offers a brief , manualized , intervention for emotional and spiritual concerns BACKGROUND Dietary behavior , specifically a low-fat , high-fiber diet , plays a role in the primary prevention of chronic diseases including cancer . DESIGN A community-based r and omized trial to assess the impact of a low-intensity , physician-endorsed , self-help dietary intervention that provided tailored dietary feedback , and was design ed to promote improved fat and fiber behavior in a rural , low-education/low-literacy , partly minority population . The data were collected from 1999 to 2003 . SETTING / PARTICIPANTS A total of 754 patients from three physician practice s in rural Virginia completed a baseline telephone survey assessing dietary and psychosocial information , and were then r and omly assigned to the intervention or control condition . Follow-up telephone evaluation was based on 522 participants at 1 month , 470 at 6 months , and 516 participants at 12 months . INTERVENTION A series of tailored feedback , followed by brief telephone counseling and theory-based nutritional education booklets , provided by staggered delivery to the home . MAIN OUTCOME MEASURES Dietary fat and fiber behavior , dietary intentions to change , self-efficacy for dietary change , and fat and fiber knowledge . RESULTS The intervention group demonstrated significant improvement in dietary fat and fiber behaviors and intentions to change fat and fiber intake ( p < 0.05 ) at 1 , 6 , and 12 months . CONCLUSIONS The Rural Physician Cancer Prevention Project provides an effective model for achieving public health-level dietary health behavior changes among a rural , minority , and low-literacy/low-education population PURPOSE Studies have documented that the majority of consent documents for medical diagnosis and treatment are written at a reading level above that of the majority of the U.S. population . This study hypothesized that use of an easy-to-read consent statement , when compared with a st and ard consent statement , will result in higher patient comprehension of the clinical treatment protocol , lower patient anxiety , higher patient satisfaction , and higher patient accrual . METHODS A r and omized controlled trial was conducted in 44 institutions that were members or affiliates of three cooperative oncology groups . Institutions were r and omly assigned to administer either an easy-to-read consent statement or the st and ard consent statement to patients being recruited to participate in selected cancer treatment trials . Telephone interviews were conducted with a total of 207 patients to assess study outcomes . RESULTS Patients in the intervention arm demonstrated significantly lower consent anxiety and higher satisfaction compared with patients in the control arm . Patient comprehension and state anxiety were not affected by the intervention . Accrual rates into the parent studies also did not differ significantly between the two study groups . CONCLUSION Clinical trial informed consent statements can be modified to be easier to read without omitting critical information . Patient anxiety and satisfaction can be affected by the consent document . The generalizability of these study results is limited by the characteristics of the patient sample . Ninety percent of the sample were white women , and the mean Rapid Estimate of Adult Literacy in Medicine score was approximately 64 , indicating a literacy level at or above the ninth grade OBJECTIVE This study was aim ed at evaluating whether a Life Review Group Program ( LRGP ) improved the self-esteem and life satisfaction in the elderly . METHODS This r and omized , controlled trial consisted of 75 elderly males from a Veterans ' Home in Northern Taiwan , 36 of whom were in the experimental group and 39 of whom were in the control group . The subjects in the experimental group participated in an 8-week LRGP . Data were collected before and after the LRGP and again 1 month after the end of the program . RESULTS The study subjects had a mean age of 78.13 years . The generalized estimating equation was used to compare alterations in the self-esteem and life satisfaction of the elderly before and after the intervention . The alterations in self-esteem and life satisfaction in the experimental group after the LRGP were significantly improved compared to the control group . One month after the LRGP was completed , the self-esteem and life satisfaction of the experimental group continued to improve when compared with pre-intervention levels . CONCLUSIONS Based on these results , the LRGP can potentially improve the self-affirmation , confidence , and self-esteem of the elderly and promote short-term life satisfaction . The results of this study provide a model for clinical evidence -based therapy , serving as a reference for related studies and evaluation of health-promoting programs , as well as improving the health and quality of care of the elderly Nutrition might induce , at some loci , epigenetic or other changes that could be transmitted to the next generation impacting on health . The slow growth period ( SGP ) before the prepubertal peak in growth velocity has emerged as a sensitive period where different food availability is followed by different transgenerational response ( TGR ) . The aim of this study is to investigate to what extent the prob and s own childhood circumstances are in fact the determinants of the findings . In the analysis , data from three r and om sample s , comprising 271 prob and s and their 1626 parents and gr and parents , left after exclusions because of missing data , were utilized . The availability of food during any given year was classified based on regional statistics . The ancestors ' SGP was set at the ages of 8–12 years and the availability of food during these years classified as good , intermediate or poor . The prob and s ' childhood circumstances were defined by the father 's ownership of l and , the number of siblings and order in the sibship , the death of parents and the parents ' level of literacy . An earlier finding of a sex-specific influence from the ancestors ' nutrition during the SGP , going from the paternal gr and mother to the female prob and and from the paternal gr and father to the male prob and , was confirmed . In addition , a response from father to son emerged when childhood social circumstances of the son were accounted for . Early social circumstances influenced longevity for the male prob and . TGRs to ancestors ' nutrition prevailed as the main influence on longevity Continuing advances in human ability to manipulate matter at the atomic and molecular levels ( i.e. nanoscale science and engineering ) offer many previously unimagined possibilities for scientific discovery and technological development . Paralleling these advances in the various science and engineering subdisciplines is the increasing realization that a number of associated social , ethical , environmental , economic and legal dimensions also need to be explored . An important component of such exploration entails the identification and analysis of the ways in which current and prospect i ve research ers in these fields conceptualize these dimensions of their work . Within the context of a National Science Foundation funded Research Experiences for Undergraduates ( REU ) program in nano material s processing and characterization at the University of Central Florida ( 2002–2004 ) , here I present for discussion ( i ) details of a “ nanotechnology ethics ” seminar series developed specifically for students participating in the program , and ( ii ) an analysis of students ’ and participating research faculty ’s perspectives concerning social and ethical issues associated with nanotechnology research . I conclude with a brief discussion of implication s presented by these issues for general scientific literacy and public science education policy BACKGROUND Primary care is a key step in young people 's pathway to mental health care . Despite the high prevalence of mental disorder in this age group , little is known about the factors that determine the identification of young people 's mental disorder in primary care . AIM To provide a detailed description of the factors associated with both ' correct ' and ' excessive ' identification of youth mental disorder in primary care . DESIGN OF THE STUDY Cross-sectional study . SETTING Twenty-six r and omly selected general practice s in Victoria , Australia . METHOD Consecutive young people ( 16 - 24 years ) were interviewed before their consultation , using a semi-structured interview . They completed Kessler 's scale of emotional distress ( K10 ) . GPs completed a question naire after the consultation . Multinomial logistic regression was used to examine the factors associated with GP identification of mental disorder in those with high and low probability of disorder on the K10 . RESULTS Altogether , 450/501 ( 90 % ) of approached young people participated ; 36.1 % ( 95 % confidence interval [ CI ] = 32.3 to 40.2 % ) had high probability of mental disorder on the K10 . Young people 's perception that they had a mental illness was highly associated with GP identification ( odds ratio [ OR ] = 62.6 , 95 % CI = 22.8 to 172.0 ) . Other significantly associated factors were : patient fears ( OR = 2.4 , 95 % CI = 1.1 to 5.1 ) , frequent consultations ( OR = 3.0 , 95 % CI = 1.0 to 8.4 ) , days out of role ( OR = 2.7 , 95 % CI = 1.2 to 5.7 ) , and continuity of care ( OR = 3.4 , 95 % CI = 1.6 to 6.9 ) . The latter two were also associated with ' over- identification ' of young people who had low probability of mental disorder . GP characteristics were not associated with identification . CONCLUSION These findings provide guidance for GPs in their clinical work and training . They should also inform the further development of mental health literacy programmes in the community OBJECTIVE To examine whether explanatory illustrations can improve older adults ' comprehension of written health information . METHODS Six short health-related texts were selected from websites and pamphlets . Young and older adults were r and omly assigned to read health-related texts alone or texts accompanied by explanatory illustrations . Eye movements were recorded while reading . Word recognition , text comprehension , and comprehension of the illustrations were assessed after reading . RESULTS Older adults performed as well as or better than young adults on the word recognition and text comprehension measures . However , older adults performed less well than young adults on the illustration comprehension measures . Analysis of readers ' eye movements showed that older adults spent more time reading illustration-related phrases and fixating on the illustrations than did young adults , yet had poorer comprehension of the illustrations . CONCLUSION Older adults might not benefit from text illustrations because illustrations can be difficult to integrate with the text . PRACTICE IMPLICATION S Health practitioners should not assume that illustrations will increase older adults ' comprehension of health information OBJECTIVE To determine whether an advance directive re design ed to meet most adults ' literacy needs ( fifth grade reading level with graphics ) was more useful for advance care planning than a st and ard form ( > 12th grade level ) . METHODS We enrolled 205 English and Spanish-speaking patients , aged > /=50 years from an urban , general medicine clinic . We r and omized participants to review either form . Main outcomes included acceptability and usefulness in advance care planning . Participants then review ed the alternate form ; we assessed form preference and six-month completion rates . RESULTS Forty percent of enrolled participants had limited literacy . Compared to the st and ard form , the re design ed form was rated higher for acceptability and usefulness in care planning , P</=0.03 , particularly for limited literacy participants ( P for interaction < /=0.07 ) . The re design ed form was preferred by 73 % of participants . More participants r and omized to the re design ed form completed an advance directive at six months ( 19 % vs. 8 % , P=0.03 ) ; of these , 95 % completed the re design ed form . CONCLUSIONS The re design ed advance directive was rated more acceptable and useful for advance care planning and was preferred over a st and ard form . It also result ed in higher six-month completion rates . PRACTICE IMPLICATION S An advance directive re design ed to meet most adults ' literacy needs may better enable patients to engage in advance care planning OBJECTIVE Increasing numbers of children in the United States ( ie , approximately 200 children per 100,000 population ) require intensive care annually , because of advances in pediatric therapeutic techniques and a changing spectrum of pediatric disease . These children are especially vulnerable to a multitude of short- and long-term negative emotional , behavioral , and academic outcomes , including a higher risk of posttraumatic stress disorder ( PTSD ) and a greater need for psychiatric treatment , compared with matched hospitalized children who do not require intensive care . In addition , the parents of these children are at risk for the development of PTSD , as well as other negative emotional outcomes ( eg , depression and anxiety disorders ) . There has been little research conducted to systematic ally determine the effects of interventions aim ed at improving psychosocial outcomes for critically ill children and their parents , despite recognition of the adverse effects of critical care hospitalization on the nonphysiologic well-being of patients and their families . The purpose of this study was to evaluate the effects of a preventive educational-behavioral intervention program , the Creating Opportunities for Parent Empowerment ( COPE ) program , initiated early in the intensive care unit hospitalization on the mental health/psychosocial outcomes of critically ill young children and their mothers . DESIGN A r and omized , controlled trial with follow-up assessment s 1 , 3 , 6 , and 12 months after hospitalization was conducted with 174 mothers and their 2- to 7-year-old children who were unexpectedly hospitalized in the pediatric intensive care units ( PICUs ) of 2 children 's hospitals . The final sample of 163 mothers ranged in age from 18 to 52 years , with a mean of 31.2 years . Among the mothers reporting race/ethnicity , the sample included 116 white ( 71.2 % ) , 33 African American ( 20.3 % ) , 3 Hispanic ( 1.8 % ) , and 2 Indian ( 1.2 % ) mothers . The mean age of the hospitalized children was 50.3 months . Ninety-nine children ( 60.7 % ) were male and 64 ( 39.3 % ) were female . The major reasons for hospitalization were respiratory problems , accidental trauma , neurologic problems , and infections . Fifty-seven percent ( n = 93 ) of the children had never been hospitalized overnight , and none had experienced a previous PICU hospitalization . INTERVENTIONS Mothers in the experimental ( COPE ) group received a 3-phase educational-behavioral intervention program 1 ) 6 to 16 hours after PICU admission , 2 ) 2 to 16 hours after transfer to the general pediatric unit , and 3 ) 2 to 3 days after their children were discharged from the hospital . Control mothers received a structurally equivalent control program . The COPE intervention was based on self-regulation theory , control theory , and the emotional contagion hypothesis . The COPE program , which was delivered with audiotapes and matching written information , as well as a parent-child activity workbook that facilitated implementing the audiotaped information , focused on increasing 1 ) parents ' knowledge and underst and ing of the range of behaviors and emotions that young children typically display during and after hospitalization and 2 ) direct parent participation in their children 's emotional and physical care . The COPE workbook , which was provided to parents and children after transfer from the PICU to the general pediatric unit , contained 3 activities to be completed before discharge from the hospital , ie , 1 ) puppet play to encourage expression of emotions in a nonthreatening manner , 2 ) therapeutic medical play to assist children in obtaining some sense of mastery and control over the hospital experience , and 3 ) reading and discussing Jenny 's Wish , a story about a young child who successfully copes with a stressful hospitalization . OUTCOME MEASURES Primary outcomes included maternal anxiety , negative mood state , depression , maternal beliefs , parental stress , and parent participation in their children 's care , as well as child adjustment , which was assessed with the Behavioral Assessment System for Children ( parent form ) . RESn ( parent form ) . RESULTS COPE mothers reported significantly less parental stress and participated more in their children 's physical and emotional care on the pediatric unit , compared with control mothers , as rated by nurses who were blinded with respect to study group . In comparison with control mothers , COPE mothers reported less negative mood state , less depression , and fewer PTSD symptoms at certain follow-up assessment s after hospitalization . In addition , COPE mothers reported stronger beliefs regarding their children 's likely responses to hospitalization and how they could enhance their children 's adjustment , compared with control mothers . COPE children , in comparison with control children , exhibited significantly fewer withdrawal symptoms 6 months after discharge , as well as fewer negative behavioral symptoms and externalizing behaviors at 12 months . COPE mothers also reported less hyperactivity and greater adaptability among their children at 12 months , compared with control mothers . One year after discharge , a significantly higher percentage of control group children ( 25.9 % ) exhibited clinical ly significant behavioral symptoms , compared with COPE children ( 2.3 % ) . In addition , 6 and 12 months after discharge , significantly higher percentages of control group children exhibited clinical ly significant externalizing symptoms ( 6 months , 14.3 % ; 12 months , 22.2 % ) , compared with COPE children ( 6 months , 1.8 % ; 12 months , 4.5 % ) . CONCLUSIONS The findings of this study indicated that mothers who received the COPE program experienced improved maternal functional and emotional coping outcomes , which result ed in significantly fewer child adjustment problems , in comparison with the control group . With the increasing prevalence of attention-deficit/hyperactivity disorder and externalizing problems among children and the documented lack of mental health screening and early intervention services for children in this country , the COPE intervention could help protect this high-risk population of children from developing these troublesome problems . As a result , the mental health status of children after critical care hospitalization could be improved . With routine provision of the COPE program in PICUs throughout the country , family burdens and costs associated with the mental health treatment of these problems might be substantially reduced STATEMENT OF PROBLEM Despite the availability of improved healthcare access , self-management programs , disease management protocol s , and advances in pharmacologic and immunotherapy therapy , the prevalence of asthma in the urban inner city remains one of the major health disparities in the United States . Additionally , sustainability of effective intervention programs after the funding has ended remains a significant issue for asthma programs . OBJECTIVE This study examines the effectiveness of a longitudinal intervention program that was design ed with the assumption that improved literacy plays a role in improving asthma-related health outcomes among high-risk children with the most severe forms of asthma . METHODS A longitudinal intervention over 6 months prospect ively addressed the literacy and asthma self-management skills of 110 minority children in South Los Angeles utilizing weekly Saturday-school format . RESULTS The results demonstrated that there was a statistically significant decrease in both hospitalization and emergency department ( ED ) visits during the intervention . In addition , all the children showed significant improvement in their reading level and self-efficacy . Multivariate logistic analysis demonstrated that enhanced self-efficacy was directly related to decreased hospitalizations and ED visits . CONCLUSION This intervention demonstrated that literacy enhancement is an important factor in improving self-efficacy and impacting asthma-related outcomes . Improved literacy is a sustainable factor that will not only improve asthma outcomes but will enhance the potential for educational success Objective . Public social policies in New Zeal and assume that there are fundamental differences between Maori views of health phenomena and non‐Maori perceptions . The biomedical model and a Maori model known as Te Whare Tapa Wha are commonly employed to characterise these differences . Using the categorical ethnicity demarcation ‘ Maori/non‐Maori ’ we investigate this cl aim with respect to mental health literacy about depression . Design . Participants were r and omly selected from the General and Maori Electoral Rolls and recruited by post ( N=205 ) . A vignette methodology was employed and involved the development of a fictional character as a target stimulus who exhibited the minimum DSM‐IV‐R criteria for a major depressive disorder . Participants responded to items regarding problem recognition , well‐being , causal attributions , treatment preferences , and likely prognosis . Results . The majority of Maori and non‐Maori participants correctly identified the problem the vignette character was experiencing and nominated congruent attributions for the causes of the problem . In relation to treatment strategies and likely prognosis , independent of self‐assigned ethnicity , participants rated professional treatments above alternative options . Overall the categorical ethnicity distinction ‘ Maori and non‐Maori ’ produced no systematic variation with regards to individual evaluative responses about a major depressive disorder . Conclusions . Contrary to the embedded assumption within New Zeal and 's public health strategies that there are essential differences between the way Maori and non‐Maori view health problems , and that the categorical ethnicity demarcation reliably reflects these differences , we found no evidence for the veracity of this cl aim using a major depressive disorder as a target for judgements . Alternative explanations are canvassed as to why this assumption about fundamental differences based on categorical ethnicity has gained ascendancy and prominence within the sphere of New Zeal and health Objective : To evaluate the long-term effects of joint protection on health status of people with early rheumatoid arthritis ( RA ) . Design : A four-year follow-up of a r and omized , controlled , assessor-blinded trial was conducted . Setting : Two rheumatology outpatient departments . Participants : People with rheumatoid arthritis less than five years since diagnosis . Interventions : Two 8-hour interventions were originally compared : a st and ard arthritis education programme , including 21/2 hours of joint protection based on typical UK occupational therapy practice ( plus 51/2 hours on RA , exercise , pain management , diet and foot care ) ; and a joint protection programme , using educational-behavioural training . Main measures : Adherence to joint protection , pain , h and pain on activity , Arthritis Impact Measurement Scales 2 and Arthritis Self-efficacy were recorded at 0 and 4 years . Results : Sixty-five people attended the joint protection and 62 the st and ard programmes . Groups at entry were similar in age ( 51 years ; 49 years ) , disease duration ( 21 months : 17.5 months ) and use of nonsteroidal anti-inflammatory and disease-modifying drugs . At four years , the joint protection group continued to have significantly better : joint protection adherence ( p=0.001 ) ; early morning stiffness ( p=0.01 ) ; AIMS 2 activities of daily living ( ADL ) scores ( p=0.04 ) compared with the st and ard group . The joint protection group also had significantly fewer h and deformities : metacarpophalangeal ( MCP ) ( p=0.02 ) and wrist joints ( p=0.04 ) . Conclusion : Attending an educational = behavioural joint protection programme significantly improves joint protection adherence and maintains functional ability long term . This approach is more effective than st and ard methods of training and should be more widely adopted Objective : Aim of the present study was to identify potential dietary , lifestyle , psychosocial and clinical correlates of underreporting in a population -based sample . Methods : Following a r and om multistage sampling , 1514 men ( 46±13 years old ) and 1528 women ( 45±13 years old ) from the Attica area , in Greece , participated in this study . All participants underwent a st and ard assessment procedure that included clinical , psychosocial and lifestyle parameters . Food consumption was assessed through a vali date d semi-quantitative food frequency question naire . The ratio of energy intake to estimated basal metabolic rate ( EI/BMR ) and the Goldberg cut-off points were used for the classification of subjects as low energy reporters ( LERs ) and non-LERs . Results : LERs represented 12.2 % of the sample . This percentage was higher in obese subjects compared to overweight or normal weight ( 20.6 % vs. 9.9 % vs. 10.6 % , p = 0.05 ) , as well as in women compared to men ( 14.6 % vs. 9.9 % , p<0.001 ) . Data analysis was stratified by gender , since a significant interaction was observed between gender and LER group on several dietary parameters . Female LERs had higher Med Diet Score compared to non-LERs ( 30.6 ± 8.2 , 95%CI 30.2–31.04 vs. 26.9 ± 6.3 , 95%CI 26.05–27.7 , p<0.001 ) . Multiple regression analysis revealed that lower EI/BMR values were associated with younger age ( p<0.001 ) , higher BMI ( p<0.001 ) , presence of diabetes mellitus ( p=0.012 ) and lower depression score ( p=0.056 ) in women , whereas with younger age ( p<0.001 ) , higher BMI ( p<0.001 ) , higher education level ( p=0.046 ) and higher anxiety score ( p=0.08 ) in men . Conclusion : Several psychosocial and clinical characteristics operate in low energy reporting in both genders . Nutrition-related professionals should be aware of these gender-specific trends in dietary assessment procedures PURPOSE To assess prospect ively language and speech ability in children with benign partial epilepsy with centro-temporal spikes ( BCECTS ) . To evaluate academic performance and social competencies both during the active disease and after remission . METHODS Right-h and ed school children with typical BCECTS and a control group matched by age , sex , h and edness and socioeconomic status were examined . The German version of WISC-R , the " Tübinger Luria Christensen Neuropsychological Test Set for children " ( TUKI ) , the " Verbal Learning Memory Test " ( VLMT ) , the " Heidelberger Speech Development Test-second edition " ( HSET ) , and the " Salzburger reading and writing test " ( SLRT ) were applied . The Child Behavior Checklist ( CBCL ) and a semi-structured interview were performed with the children 's teachers to gain insight into school performance , behavioral and emotional problems . RESULTS During the active phase , the patient group - despite normal global intellectual abilities - showed few , but significant impairments both in expressive speech and in receptive and expressive vocabulary . A significant deficit in the ability to recognize and express interpersonal relations was also found . Patients ' teachers stated deficits concerning academic performance and complained about disturbing behavior . Parents reported significantly more psycho-pathological features in the subscales " Aggressive Behavior " , " Attention Problems " and " Anxious/Depressed " of the CBCL . Results were independent of medication and spike localization . After complete recovery from BCECTS , these problems were not found any more . CONCLUSIONS Both deficits of speech-related abilities ( in both expressive and receptive vocabulary ) and behavioral disturbances can be detected in children with typical BCECTS , but are no longer apparent after remission of the seizure disorder Background The Internet is a major source of information for professionals and the general public , especially in the field of health . However , despite ever-increasing connection rates , a digital divide persists in the industrialised countries . The objective of this study was to assess the determinants involved in : 1 ) having or not having Internet access ; and 2 ) using or not using the Internet to obtain health information . Methods A cross-sectional survey of a representative r and om sample was conducted in the Paris metropolitan area , France , in the fall of 2005 ( n = 3023 ) . Results Close to 70 % of the adult population had Internet access , and 49 % of Internet users had previously search ed for medical information . Economic and social disparities observed in online health information seeking are reinforced by the economic and social disparities in Internet access , hence a double divide . While individuals who reported having a recent health problem were less likely to have Internet access ( odds ratio ( OR ) : 0.72 , 95 % confidence interval ( CI ) : 0.53–0.98 ) , it is they who , when they have Internet access , are the most likely to search for health information ( OR = 1.44 , 95 % CI = 1.11–1.87 ) . Conclusion In the French context of universal health insurance , access to the Internet varies according to social and socioeconomic status and health status , and its use for health information seeking varies also with health beliefs , but not to health insurance coverage or health-care utilisation . Certain economic and social inequalities seem to impact cumulatively on Internet access and on the use of the Internet for health information seeking . It is not obvious that the Internet is a special information tool for primary prevention in people who are the furthest removed from health concerns . However , the Internet appears to be a useful complement for secondary prevention , especially for better underst and ing health problems or enhancing therapeutic compliance OBJECTIVE The primary objective of this study was to assess and compare the knowledge of diabetes mellitus possessed by patients with diabetes and healthy adult volunteers in Penang , Malaysia . METHOD A cross-sectional study was conducted from 20 February 2006 to 31 March 2006 . We r and omly selected 120 patients with diabetes mellitus from a diabetic clinic at the General Hospital Penang , Malaysia and 120 healthy adults at a shopping complex in Penang . Each participant was interviewed face-to-face by a pharmacist using a vali date d question naire , and they were required to answer a total of 30 questions concerning knowledge about diabetes mellitus using Yes , No or Unsure as the only response . RESULTS The results showed that patients with diabetes mellitus were significantly more knowledgeable than the healthy volunteers about risk factors , symptoms , chronic complications , treatment and self-management , and monitoring parameters . Educational level was the best predictive factor for diabetes mellitus and public awareness . CONCLUSION Knowledge about diabetes mellitus should be improved among the general population . PRACTICE IMPLICATION S This study has major implication s for the design of an educational programme for diabetics and a health promotion programme as a primary prevention measure for the healthy population in general , and especially for those at high risk . The results could be useful in the design of future studies for evaluating patients ' and the general public 's knowledge about diabetes mellitus Background and Purpose — Diabetes mellitus is an independent risk factor for stroke and is associated with a 1.8- to ≈6-fold increased risk compared with nondiabetic subjects . Recent guidelines have classified diabetes as a coronary heart disease risk equivalent . Whether diabetes is a cardiovascular disease risk equivalent for stroke is not established . Methods — Data were pooled from 9 prospect i ve epidemiological studies in the United States . We followed up 27 269 women ( 8.5 % diabetic , 2.9 % with prior myocardial infa rct ion , 2.3 % with prior stroke ) for an average of 8.3 years , during which 238 stroke deaths were observed . Results — Both diabetic subjects without cardiovascular disease and nondiabetic subjects with history of prior stroke had a significantly increased risk of 10-year stroke mortality compared with nondiabetic subjects without prior cardiovascular disease ( hazard ratio [ HR ] , 6.77 ; 95 % confidence interval [ CI ] , 4.56 to 10.05 ; HR , 3.37 ; 95 % CI , 2.38 to 4.77 ) . History of prior myocardial infa rct ion was not associated with long-term stroke mortality ( HR , 0.66 ; 95 % CI , 0.27 to 1.61 ) . After adjustment for risk factors , diabetic subjects had similar risk compared with subjects with a history of prior stroke ( HR , 1.29 ; P = 0.43 ) . Conclusions — Diabetic subjects without cardiovascular disease have a fatal stroke risk similar to that of nondiabetic subjects with a history of prior stroke and similar risk factor profile . This suggests that diabetes mellitus may be classified as a stroke risk equivalent and may warrant more aggressive treatment strategies in the future prevention of stroke Self-reported health , a widely used measure of general health status in population studies , can be affected by certain demographic variables such as gender , race/ethnicity and education . This cross-sectional assessment of the current health status of older adult residents was conducted in an inner-city Houston neighborhood in May , 2007 . A survey instrument , with questions on chronic disease prevalence , health limitations /functional status , self-reported subjective health status in addition to demographic data on households was administered to a systematic r and om sample of residents . Older adults ( > 60 years of age ) were interviewed ( weighted N = 127 ) at their homes by trained interviewers . The results indicated that these residents , with low literacy levels , low household income and a high prevalence of frequently reported chronic diseases ( hypertension , diabetes and arthritis ) also reported non-participation in community activities , volunteerism and activities centered on organized religion , thus , potentially placing them at risk for social isolation . Women reported poorer self-reported health and appeared to fare worse in all health limitation indicators and reported greater structural barriers in involvement with their community . Blacks reported worse health outcomes on all indicators than other sub-groups , an indication that skills training in chronic disease self-management and in actively eliciting support from various sources may be beneficial for this group . Therefore , the use of self-reported health with a broad brush as an indicator of “ true ” population health status is not advisable . Sufficient consideration should be given to the racial/ethnic and gender differences and these should be accounted for Background The treatment guidelines for tuberculosis treatment under Directly Observed Treatment , Short-course ( DOTS ) have been a common strategy for TB treatment in Zambia . The study was carried out in Ndola , Zambia , to investigate factors contributing to treatment non-adherence and knowledge of TB transmission among patients on TB treatment , in order to design a community-based intervention , that would promote compliance . Methods A household-based survey was conducted in six r and omly selected catchment areas of Ndola , where 400 out of 736 patients receiving TB treatment within the six months period , were recruited through the District 's Health Management Board ( DHMB ) clinics . All patients were interviewed using a pre-tested structured question naire , consisting of i. Socio-demographic characteristics ii . Socio-economic factors iii . Knowledge about TB transmission and prevention iv . Patterns in health seeking behaviour and v. TB treatment practice s at household level . Results Most male TB patient respondents tended to be older and more educated than the female TB patient respondents . Overall , 29.8 % of the patients stopped taking their medication . There were 39.1 % of the females and 33.9 % of the males , who reported that TB patients stopped taking their medication within the first 2 months of commencing treatment . Age , marital status and educational levels were not significantly associated with compliance . The major factors leading to non-compliance included patients beginning to feel better ( 45.1 % and 38.6 % ) , lack of knowledge on the benefits of completing a course ( 25.7 % ) , running out of drugs at home ( 25.4 % ) and TB drugs too strong ( 20.1 % and 20.2 % ) . There was a significant difference [ OR = 1.66 , 95 % CI 1.23 , 2.26 ] in TB knowledge , with more males than females reporting sharing of cups as a means for TB transmission , after adjusting for age , marital status and educational levels . Significantly [ p = 0.016 ] more patients who had resided in the study for less than two years ( 59 % ) were more likely to report mother to child transmission of TB , compared to 41.2 % of those who had been in the area for more than 2 years . Conclusion This study established that 29.8 % of TB patients failed to comply with TB drug taking regimen once they started feeling better Background The increasing prevalence of type 2 diabetes poses a major public health challenge . Population -based screening and early treatment for type 2 diabetes could reduce this growing burden . However , the benefits of such a strategy remain uncertain . Methods and design The ADDITION-Cambridge study aims to evaluate the effectiveness and cost-effectiveness of ( i ) a stepwise screening strategy for type 2 diabetes ; and ( ii ) intensive multifactorial treatment for people with screen-detected diabetes in primary care . 63 practice s in the East Anglia region participated . Three undertook the pilot study , 33 were allocated to three groups : no screening ( control ) , screening followed by intensive treatment ( IT ) and screening plus routine care ( RC ) in an unbalanced ( 1:3:3 ) r and omisation . The remaining 27 practice s were r and omly allocated to IT and RC . A risk score incorporating routine practice data was used to identify people aged 40–69 years at high-risk of undiagnosed diabetes . In the screening practice s , high-risk individuals were invited to take part in a stepwise screening programme . In the IT group , diabetes treatment is optimised through guidelines , target-led multifactorial treatment , audit , feedback , and academic detailing for practice teams , alongside provision of educational material s for newly diagnosed participants . Primary endpoints are modelled cardiovascular risk at one year , and cardiovascular mortality and morbidity at five years after diagnosis of diabetes . Secondary endpoints include all-cause mortality , development of renal and visual impairment , peripheral neuropathy , health service costs , self-reported quality of life , functional status and health utility . Impact of the screening programme at the population level is also assessed through measures of mortality , cardiovascular morbidity , health status and health service use among high-risk individuals . Discussion ADDITION-Cambridge is conducted in a defined high-risk group accessible through primary care . It addresses the feasibility of population -based screening for diabetes , as well as the benefits and costs of screening and intensive multifactorial treatment early in the disease trajectory . The intensive treatment algorithm is based on evidence from studies including individuals with clinical ly diagnosed diabetes and the education material s are informed by psychological theory . ADDITION-Cambridge will provide timely evidence concerning the benefits of early intensive treatment and will inform policy decisions concerning screening for type 2 diabetes . Trial registration Current Controlled trials IS RCT Critical thinking is essential for professional nursing practice . Promoting critical thinking with teaching strategies has been a focus of nursing education and nursing research . Reading and writing assignments are teaching strategies for fostering critical thinking ability . We developed a course with the emphasis on critical reading and writing . The purpose s of this study were to explore the effect of the course and teaching strategies on promoting critical thinking and to underst and the learning experience and perception of nursing students as part of the course assessment plan . Quasi-experimental design and purposive sampling were used . 170 students of a two-year nursing program were grouped into an experimental and a control group depending on whether or not they took the course . The change in critical thinking ability was evaluated and determined based on performance in an article critique test before and after the course . Data was collected with an assessment tool developed for the purpose s of the research and was analyzed with descriptive statistics , paired t-test , and two-factor analysis of variance with repeated measures and content analysis . The findings were : ( 1 ) The scores on the critique test at the end of the course in both groups were significantly higher than before the course ( p<.001 ) . The improvement in score of the experimental group , however , was significantly higher than that of the control group ( p<.001 ) . ( 2 ) Changes in thinking pattern and learning attitude , as well as a feeling of growth and achievement , were found in content analysis of students ' self-evaluation of their learning experience and perception . Critical thinking skills were applied while learning the course . The results not only provide evidence to support the positive effect of reading and writing assignments on critical thinking ability but also confirm the teaching and learning activity design for the course The aim of the present study was to assess the long-term impact on hospitalisation of a self-management programme for chronic obstructive pulmonary disease ( COPD ) patients . A multicentre , r and omised clinical trial was carried out involving 191 COPD patients from seven hospitals . Patients who had one or more hospitalisations in the year preceding study enrolment were assigned to a self-management programme “ Living Well with COPD TM ” or to st and ard care . Hospitalisations from all causes were the primary outcome and were documented from the provincial hospitalisation data base ; emergency visits were recorded from the provincial health insurance data base . Most patients were elderly , not highly educated , had advanced COPD ( reflected by a mean forced expiratory volume in one second of 1 L ) , and almost half reported a dyspnoea score of 5/5 ( modified Medical Research Council ) . At 2 years , there was a statistically significant and clinical ly relevant reduction in all-cause hospitalisations of 26.9 % and in all-cause emergency visits of 21.1 % in the intervention group as compared to the st and ard-care group . After adjustment for the self-management intervention effect , the predictive factors for reduced hospitalisations included younger age , sex ( female ) , higher education , increased health status and exercise capacity . In conclusion , in this study , patients with chronic obstructive pulmonary disease who received educational intervention with supervision and support based on disease-specific self-management maintained a significant reduction in hospitalisations after a 2-year period The objective of this study was to evaluate the efficacy of a home-based intervention targeted to parents with intellectual disability to promote child health and home safety in the preschool years . A total of 63 parents were recruited for the study with 45 parents ( 40 mothers and 5 fathers ) from 40 families completing the project . The research design permitted comparison between the intervention and three alternative conditions with all parents receiving the intervention in an alternating sequence over the life of the project . The intervention consisted of 10 weekly lessons carried out in the parent 's home focusing on child health and home safety . The program was adapted to suit the Australian context from the UCLA Parent -- Child Health and Wellness Project ( Tymchuk , Groen , & Dolyniuk , 2000 ) . Outcome measures assessed parental health and safety behaviours . St and ard measures included parental health , intelligence and literacy . The intervention improved parents ' ability to recognize home dangers , to identify pre caution s to deal with these dangers and result ed in a significant increase in the number of safety pre caution s parents implemented in their homes with all gains being maintained at 3 months post-intervention . Parents ' health behaviours including improved underst and ing of health and symptoms of illness , knowledge of and skills needed to manage life-threatening emergencies , knowledge about visiting the doctor , knowing when to call , what information to provide and what questions to ask , and how to use medicines safely significantly increased . Again , all gains were maintained 3 months post-intervention . The intervention was effective regardless of parental health , literacy skills , and IQ . This form of home-based intervention promotes a healthy and safe environment which is a prerequisite to continuing parental custody BACKGROUND Public health nurses ( PHNs ) often can not receive in-service education due to limitations of time and space . Learning through the Internet has been a widely used technique in many professional and clinical nursing fields . The learner 's attitude is the most important indicator that promotes learning . OBJECTIVES The purpose of this study was to investigate PHNs ' attitude toward web-based learning and its determinants . DESIGN This study conducted a cross-sectional research design . SETTING S 369 health centers in Taiwan . PARTICIPANTS The population involved this study was 2398 PHNs , and we used r and om sampling from this population . Finally , 329 PHNs completed the question naire , with a response rate of 84.0 % . METHODS Data were collected by mailing the question naire . RESULTS Most PHNs revealed a positive attitude toward web-based learning ( mean+/-SD=55.02+/-6.39 ) . PHNs who worked at village health centers , a service population less than 10,000 , PHNs who had access to computer facility and on-line hardware in health centers and with better computer competence revealed more positive attitudes ( p<0.01 ) . CONCLUSIONS Web-based learning is an important new way of in-service education ; however , its success and hindering factors require further investigation . Individual computer competence is the main target for improvement , and educators should also consider how to establish a user-friendly learning environment on the Internet CONTEXT Although the ability to work with numbers is important to the practice of medicine , little is known about physician numeracy ( basic skill with numbers ) . OBJECTIVE To test medical students ' numeracy and how it relates to the ability to interpret risk-reduction information . DESIGN R and omized , cross-sectional survey . SAMPLE 62 first-year medical students at the University of North Carolina at Chapel Hill medical school who attended a risk-communication seminar and had usable survey data ( 46 % of the 134 students who received the survey ) . INTERVENTION Students were given information about the baseline risk for developing a hypothetical disease and were r and omly assigned to one of four risk-reduction presentations-relative risk reduction , absolute risk reduction , number needed to treat ( NNT ) , or a combination of these three formats-about how two drugs would reduce this risk . OUTCOME MEASURES Number of correct answers to three numeracy questions ( stating that 500 heads would be expected in 1000 coin flips ; converting " 1 % of 1000 " to 10 ; and converting " 1 in 1,000 " to 0.1 % ) . Correct data interpretation was judged with two tasks : a comparative task ( i.e. , state which drug provides greater benefit ) and a quantitative task ( i.e. , calculate how much one of the drugs reduces disease risk ) . RESULTS 77 % of students answered all three numeracy questions correctly ; 18 % answered two correctly ; and 5 % answered one or none correctly . While 90 % correctly stated which drug worked better , only 61 % accurately interpreted the quantitative data . The ability to interpret data varied with numeracy : 71 % of students who answered all three numeracy questions correctly also accurately interpreted the quantitative data , compared with 36 % who answered two questions correctly and 0 % who answered one or no questions correctly ( P < 0.01 ) . Correct quantitative interpretation was lower with the NNT format than with the other three formats ( 25 % vs. 75 % ; P = 0.01 ) . CONCLUSIONS Almost one quarter of first-year medical students in our study had trouble performing basic numerical tasks . Those who had trouble also seemed to have difficulty interpreting medical data . This difficulty seemed to be exacerbated by presenting data in the NNT format OBJECTIVE To determine whether changes in family poverty between pregnancy , early childhood , and adolescence predict child cognitive development at 14 years of age . STUDY DESIGN We conducted a population -based prospect i ve birth cohort study of 7223 mothers who gave birth to a live singleton baby , observed to 14 years of age . Family income was measured on 4 occasions from pregnancy to the 14-year follow-up . Child cognitive development was measured at the 14-year follow-up using the Raven 's St and ard Progressive Matrices and Wide Range Achievement Test . RESULTS Poverty experienced at any stage of the child 's development is associated with reduced cognitive outcomes . Exposure to poverty for a longer duration ( birth to 14 years ) is more detrimental to cognitive outcomes than experiencing poverty at only 1 period . For each additional exposure to poverty , the Raven 's St and ard Progressive Matrices scores declined by 2.19 units and the Wide Range Achievement Test scores declined by 1.74 units . CONCLUSION Children experiencing family poverty at any developmental stage in their early life course have reduced levels of cognitive development , with the frequency that poverty is experienced predicting the extent of reduced cognitive scores BACKGROUND Medications can improve the functioning and health-related quality of life of patients with chronic heart failure ( CHF ) and reduce morbidity , mortality , and costs of treatment . However , patients may not adhere to therapy . Patients with complex medication regimens and low health literacy are at risk for nonadherence . OBJECTIVE The primary goal of this project is to develop and assess a multilevel pharmacy-based program to improve patient medication adherence and health outcomes for elderly CHF patients with low health literacy . METHODS In this 4-year , controlled trial , patients aged 50 years with a diagnosis of CHF who are being treated at Wishard Health Services ( Indianapolis , Indiana ) are r and omly assigned to pharmacist intervention or usual care . Intervention patients receive 9 months of pharmacist support and 3 months of postintervention follow-up . The intervention involves a pharmacist providing verbal and written education , icon-based labeling of medication containers , and therapeutic monitoring . The pharmacist identifies patients ' barriers to appropriate drug use , coaches them on overcoming these barriers , and coordinates medication use issues with their primary care providers . Daily up date s of relevant monitoring data are delivered via an electronic medical record system and stored in a personal computer system design ed to support pharmacist monitoring and facilitate documentation of interventions . To measure medication adherence objective ly , electronic monitoring lids are used on all CHF medications for patients in both study groups . Other assessment s include self-reported medication adherence , results of echocardiography ( eg , ejection fraction ) , brain natriuretic peptide concentrations , and health-related quality of life . Health services utilization , refill adherence , and cost data derive from electronic medical records . After completion of this study , the data can be used to assess the effectiveness and cost-effectiveness of our intervention . RESULTS One hundred twenty-two patients have been assigned to receive the intervention and 192 to receive usual care . CONCLUSIONS Our study aims to improve patients ' knowledge and self-management of their medication and to improve medication monitoring in a multilevel pharmacy-based intervention . By doing so , we intend that the intervention will improve the health outcomes of elderly patients with CHF This paper reports the initial results of a pilot study to evaluate the acceptability and effectiveness of a program to enhance health literacy in low-income HIV-infected Latino men and women receiving antiretroviral therapy . Participants rated the program highly on measures of satisfaction , providing evidence of its acceptability . The effectiveness of the program was assessed in comparisons of the intervention ( n = 41 ) and st and ard care only ( n = 40 ) groups at baseline and 6-week intervals . Program participants showed significant improvement over comparison group participants on measures of HIV/AIDS and treatment-related knowledge and recognition and underst and ing of HIV terms . Although there were no significant changes in adherence mastery and behaviors during the 6-week follow up period , there were significant changes in program participants ' knowledge about medication adherence . Future steps to examine the sustainability of the program in the medical management of patients are planned in addition to determining its long-range relative impact Objective : The purpose of the present study was to evaluate the effectiveness of a group psychosocial intervention for children ( aged 12–18 ) of a parent with mental illness ( copmi ) . Method : A treatment and waitlist-control design study with pre- and post-treatment , and 8 week follow up , was carried out . The treatment ( n = 27 ) and control ( n=17 ) groups were compared on three groups of dependent variables : intervention targets ( mental health literacy , connectedness , coping strategies ) , adjustment ( depression , life satisfaction , prosocial behaviour , emotional/behavioural difficulties ) , and caregiving experiences . Results : Group comparisons failed to show statistically significant intervention effects , but reliable clinical change analyses suggested that compared to the control group , more intervention participants had clinical ly significant improvements in mental health literacy , depression , and life satisfaction . These treatment gains were maintained 8 weeks after treatment . Participant satisfaction data supported these treatment gains . Conclusions : Given study limitations and the modest support for intervention effectiveness it is important that this and other similar interventions should continue to be revised and undergo rigorous evaluation In this prospect i ve study , various types and etiology of hearing loss among children attending public schools for the deaf were examined . One hundred students from two schools below the age of 15 years were enrolled in the study . Question naire was sent to all parents . Multiple modalities of investigations of hearing impairment in the children were performed . Out of the 100 students 78 ( 78 % ) had sensorineural hearing loss ( SNHL ) which was congenital in origin while in ( 22 % ) SNHL was acquired as a result of infancy or childhood infection . Forty one cases ( 41 % ) were born as a result of consanguineous marriages . Thirty two cases ( 32 % ) had a family history of deafness . Ninety ( 90 % ) of the students were found to have moderate to severe SNHL . The majority of these children were found to have no hearing aids and some of them were using non-functional hearing aids . Preventive methods through education of the public remain m and atory to minimize the incidence of SNHL . We recommend continuous monitoring and evaluation in association with appropriate care and rehabilitation for these children in order to achieve an acceptable level of speech and literacy OBJECTIVE To study whether paramedical workers from rural primary health centers in India are able to administer oral misoprostol and actively manage the third stage of labor to prevent postpartum hemorrhage ( PPH ) . METHOD Cluster r and omization was used to enroll 1200 women at 30 peripheral health centers from 5 states in India , 600 forming the study 's intervention group ( active management of the third stage of labor with 600 mug of oral misoprostol ) and 600 forming the comparison group ( in which the current government guidelines for the prevention of PPH were followed ) . The primary outcome was blood loss after delivery , which was measured using a calibrated blood collection drape . RESULTS Age , literacy level , occupation , and gravidity were similar in the 2 groups . More than 70 % of women in both groups had moderate anemia ( hemoglobin level < 10 g/dL ) . Paramedical workers followed instructions in almost all deliveries in the intervention group ( 99 % ) . There was a significant reduction in duration of the third stage of labor ( 7.9 + /- 4.2 min vs. 10.9 + /- 4.3 min ; p < .001 ) and median blood loss after delivery ( 100 mL vs. 200 mL ; p < .001 ) in the intervention group . Overall , a low incidence of PPH was observed ( < 1 % ) in both groups . A greater number of women had moderate to severe shivering ( 12.7 % vs. 0.5 % ) and a temperature higher than 38 degrees C ( 9.7 % vs. 4.3 % ) in the intervention group , which was statistically significant . CONCLUSION Simple interventions can be easily implemented in rural health care setting s to reduce the blood loss during labor . This finding has significant implication s for developing countries , in which the prevalence of anemia is high BACKGROUND Effective risk communication in transfusion medicine is important for health-care consumers , but underst and ing the numerical magnitude of risks can be difficult . The objective of this study was to determine the effect of a visual risk communication tool on the knowledge and perception of transfusion risk . STUDY DESIGN AND METHODS Laypeople were r and omly assigned to receive transfusion risk information with either a written or a visual presentation format for communicating and comparing the probabilities of transfusion risks relative to other hazards . Knowledge of transfusion risk was ascertained with a multiple-choice quiz and risk perception was ascertained by psychometric scaling and principal components analysis . RESULTS Two-hundred subjects were recruited and r and omly assigned . Risk communication with both written and visual presentation formats increased knowledge of transfusion risk and decreased the perceived dread and severity of transfusion risk . Neither format changed the perceived knowledge and control of transfusion risk , nor the perceived benefit of transfusion . No differences in knowledge or risk perception outcomes were detected between the groups r and omly assigned to written or visual presentation formats . CONCLUSION Risk communication that incorporates risk comparisons in either written or visual presentation formats can improve knowledge and reduce the perception of transfusion risk in laypeople BACKGROUND Daily fruit and vegetable consumption in black men is low and has remained relatively unchanged during the past 20 years . OBJECTIVE To examine awareness of fruit and vegetable recommendations promoted by federal agencies and correlates of fruit and vegetable consumption among an urban and mostly immigrant population of adult black men . DESIGN A cross-sectional study analyzing baseline data ( n=490 ) from a r and omized controlled trial . SETTING A large health care worker 's union . MAIN OUTCOME MEASURES Knowledge , perceived benefits , stage of readiness , perceived barriers , and daily servings of fruit and vegetable intake . STATISTICAL ANALYSES PERFORMED One-way analysis of variance and t tests were used to compare fruit and vegetable intake across main study variables . Regression analysis was used to identify independent predictors of fruit and vegetable intake . RESULTS Fruit and vegetable intake was low ( mean was three servings/day ) . Ninety-four percent were not aware that men should consume at least nine servings of fruits and vegetables daily and 59.8 % were not aware that eating a colorful variety is important . In contrast , over half ( 54.7 % ) were aware that a single serving is equal to about a h and ful ; 94.1 % correctly reported fruit and vegetables as an important source of fiber ; 79.6 % correctly reported vitamin pills were not a substitute for eating fruits and vegetables ; and 94.5 % recognized that there are health benefits to eating fruits and vegetables , although identification of specific benefits was minimal . In regression analysis , a greater level of fruit and vegetable consumption was significantly associated with greater knowledge of fruit and vegetable recommendations , lower perceived barriers , and a more advanced stage of change ( action vs contemplation/preparation ) . Perceived health benefits were not associated with fruit and vegetable consumption . CONCLUSIONS There is a lack of awareness of the current fruit and vegetable recommendations . In addition , men reported fruit and vegetable intakes that were far below national recommendations . Greater efforts are needed to help urban and primarily immigrant black men realize the importance of and recommendations for fruit and vegetable consumption OBJECTIVE . To assess whether improvements in cognitive and behavioral development seen in preschool educational programs persist , we compared those in a multisite r and omized trial of such a program over the first 3 years of life ( INT ) to those with follow-up only ( FUO ) at 18 months of age . METHODS . This was a prospect i ve follow-up of the Infant Health and Development Program at 8 sites heterogeneous for sociodemographic characteristics . Originally 985 children were r and omized to the INT ( n = 377 ) or FUO ( n = 608 ) groups within 2 birth weight strata : heavier low birth weight ( HLBW ; 2001–2499 g ) and lighter low birth weight ( LLBW ; ≤2000 g ) . Primary outcome measures were the Peabody Picture Vocabulary Test ( PPVT-III ) , reading and mathematics subscales of the Woodcock-Johnson Tests of Achievement , youth self-report on the Total Behavior Problem Index , and high-risk behaviors on the Youth Risk Behavior Surveillance System ( YRBSS ) . Secondary outcomes included Weschler full-scale IQ , caregiver report on the Total Behavior Problem Index , and caregiver and youth self-reported physical health using the Medical Outcome Study measure . Assessors were masked as to study status . RESULTS . We assessed 636 youths at 18 years ( 64.6 % of the 985 , 72 % of whom had not died or refused at prior assessment s ) . After adjusting for cohort attrition , differences favoring the INT group were seen on the Woodcock-Johnson Tests of Achievement in math ( 5.1 points ) , YRBSS ( −0.7 points ) , and the PPVT-III ( 3.8 points ) in the HLBW youth . In the LLBW youth , the Woodcock-Johnson Tests of Achievement in reading was higher in the FUO than INT group ( 4.2 ) . CONCLUSIONS . The findings in the HLBW INT group provide support for preschool education to make long-term changes in a diverse group of children who are at developmental risk . The lack of observable benefit in the LLBW group raises questions about the biological and educational factors that foster or inhibit sustained effects of early educational intervention OBJECTIVE This study compared the efficacy of a media literacy program and a self-esteem program design ed to reduce general and specific risk factors for eating disorders . METHOD Four classes of 86 grade 8 students ( 53 boys and 33 girls ) , mean age of 13 years , were r and omly assigned to either a control condition or one of the two intervention conditions . Assessment of general and specific risk factors was carried out at baseline , postintervention and 3-month follow-up . RESULTS At postintervention the media literacy group had lower mean scores on weight concern than the control group ( p = 0.007 ) but the self-esteem group did not . There were some differences on self-esteem measures at the 3-month follow-up . DISCUSSION Media literacy programs combined with an interactive , student-centered framework may potentially be a safe and effective way of reducing risk factors for eating disorders . The impact of teaching style needs to be further evaluated in prevention research AIMS To investigate whether leisure time physical activity ( LTPA ) characteristics differ between individuals with previously undiagnosed ( screen-detected ) and those with previously diagnosed ( known ) type 2 diabetes . METHODS A population -based r and om sample of 1364 ( participation rate 61 % ) men and 1461 ( 65 % ) women aged 45 - 74 years participated in a cross-sectional health examination including an oral glucose tolerance test and physical activity assessment by a self-administered question naire . RESULTS Women with screen-detected type 2 diabetes ( n=110 ) were physically less active than those with known type 2 diabetes ( n=68 ) with differences in the duration of physical activity sessions ( multivariate-adjusted P=0.041 ) and the number of moderate to high intensity exercise sessions per week ( multivariate-adjusted P=0.007 ) . In men no differences in LTPA were observed between individuals with screen-detected ( n=126 ) and with known type 2 diabetes ( n=109 ) . CONCLUSIONS This study supplies indirect evidence that in women , but not in men , with diagnosed type 2 diabetes exercise counselling or other treatment related factors produces the desired increase in LTPA BACKGROUND The ORACLE II trial compared the use of erythromycin and /or amoxicillin-clavulanate ( co-amoxiclav ) with that of placebo for women in spontaneous preterm labour and intact membranes , without overt signs of clinical infection , by use of a factorial r and omised design . The aim of the present study --the ORACLE Children Study II -- was to determine the long-term effects on children after exposure to antibiotics in this clinical situation . METHODS We assessed children at age 7 years born to the 4221 women who had completed the ORACLE II study and who were eligible for follow-up with a structured parental question naire to assess the child 's health status . Functional impairment was defined as the presence of any level of functional impairment ( severe , moderate , or mild ) derived from the mark III Multi-Attribute Health Status classification system . Educational outcomes were assessed with national curriculum test results for children resident in Engl and . FINDINGS Outcome was determined for 3196 ( 71 % ) eligible children . Overall , a greater proportion of children whose mothers had been prescribed erythromycin , with or without co-amoxiclav , had any functional impairment than did those whose mothers had received no erythromycin ( 658 [ 42.3 % ] of 1554 children vs 574 [ 38.3 % ] of 1498 ; odds ratio 1.18 , 95 % CI 1.02 - 1.37 ) . Co-amoxiclav ( with or without erythromycin ) had no effect on the proportion of children with any functional impairment , compared with receipt of no co-amoxiclav ( 624 [ 40.7 % ] of 1523 vs 608 [ 40.0 % ] of 1520 ; 1.03 , 0.89 - 1.19 ) . No effects were seen with either antibiotic on the number of deaths , other medical conditions , behavioural patterns , or educational attainment . However , more children whose mothers had received erythromycin or co-amoxiclav developed cerebral palsy than did those born to mothers who received no erythromycin or no co-amoxiclav , respectively ( erythromycin : 53 [ 3.3 % ] of 1611 vs 27 [ 1.7 % ] of 1562 , 1.93 , 1.21 - 3.09 ; co-amoxiclav : 50 [ 3.2 % ] of 1587 vs 30 [ 1.9 % ] of 1586 , 1.69 , 1.07 - 2.67 ) . The number needed to harm with erythromycin was 64 ( 95 % CI 37 - 209 ) and with co-amoxiclav 79 ( 42 - 591 ) . INTERPRETATION The prescription of erythromycin for women in spontaneous preterm labour with intact membranes was associated with an increase in functional impairment among their children at 7 years of age . The risk of cerebral palsy was increased by either antibiotic , although the overall risk of this condition was low . FUNDING UK Medical Research Council The current study explored possible sources of demographic effects through analyses of errors from modified formats of the Benton Visual Retention Test ( BVRT ) completed by African American elders . Results indicate that : ( 1 ) reading level was a stronger predictor of BVRT performance than years of education ; ( 2 ) on the single-item matching format of the task , individuals with lower reading levels disproportionately produced errors on items that differed in geometric , rather than spatial features ; and ( 3 ) on a multiple-choice matching format , individuals with lower reading levels committed more errors on items where the target was located in the lower half of a 2 x 2 matrix Background Low health literacy and low cognitive abilities both predict mortality , but no study has jointly examined these relationships . Methods We conducted a prospect i ve cohort study of 3,260 community-dwelling adults age 65 and older . Participants were interviewed in 1997 and administered the Short Test of Functional Health Literacy in Adults and the Mini Mental Status Examination . Mortality was determined using the National Death Index through 2003 . Measurements and Main Results In multivariate models with only literacy ( not cognition ) , the adjusted hazard ratio was 1.50 ( 95 % confidence of interval [ CI ] 1.24–1.81 ) for inadequate versus adequate literacy . In multivariate models without literacy , delayed recall of 3 items and the ability to serial subtract numbers were associated with higher mortality ( e.g. , adjusted hazard ratios [ AHR ] 1.74 [ 95 % CI 1.30–2.34 ] for recall of zero versus 3 items , and 1.32 [ 95 % CI 1.09–1.60 ] for 0–2 vs 5 correct subtractions ) . In multivariate analysis with both literacy and cognition , the AHRs for the cognition items were similar , but the AHR for inadequate literacy decreased to 1.27 ( 95 % CI 1.03 – 1.57 ) . Conclusions Both health literacy and cognitive abilities independently predict mortality . Interventions to improve patient knowledge and self-management skills should consider both the reading level and cognitive dem and s of the material OBJECTIVES Numeracy , the ability to process basic mathematical concepts , may affect responses to graphical displays of health risk information . Displays of probabilistic risk information using grouped dots are easier to underst and than displays using dispersed dots . However , dispersed dots may better convey the r and omness with which health threats occur , so increasing perceived susceptibility . We hypothesized that low numeracy participants would better underst and risks presented using grouped dot displays , while high numeracy participants would have good underst and ing , regardless of display type . Moreover , we predicted that dispersed dot displays , in contrast to grouped dot displays , would increase risk perceptions and worry only for highly numerate individuals . DESIGN AND METHOD One hundred and forty smokers read vignettes asking them to imagine being at risk of Crohn 's disease , in a 2(display type : dispersed/grouped dots ) x 3(risk magnitude : 3%/6%/50 % ) x 2(numeracy : high/low ) design . They completed measures of risk comprehension , perceived susceptibility and worry . RESULTS More numerate participants had better objective risk comprehension , but this effect was not moderated by display type . There was marginally significant support for the predicted numeracy x display type interaction for worry about Crohn 's disease , but not for perceived susceptibility to the condition . CONCLUSIONS Dispersed dot displays somewhat increase worry in highly numerate individuals , but only numeracy influenced objective risk comprehension . The most effective display type for communicating risk information will depend on the numeracy of the population and the goal ( s ) of the communication Nonadherence to medical treatment among heart failure patients is high and results in frequent exacerbations and premature death . This treatment-only pilot study examined whether a year-long group-based self-management intervention is feasible and improves self-management skills in patients with mild-to-moderate heart failure ( ejection fraction < or = 40 % and New York Heart Association functional class I , II , or III ) . A total of 31 of 100 recruited patients ( 31 % ) agreed to participate . Twenty-six ( 84 % ) completed the year-long self-management program . Compared with baseline , the intervention was associated with an increase in overall self-efficacy in practicing self-management skills ( p<0.001 ) and in four of five specific self-management skills . Patients and their group leaders also reported an increase in actual use of self-management skills ( p<0.001 ) and in several psychosocial outcomes . The success of this pilot study suggests the need for a r and omized clinical trial to test the efficacy of group-based self-management training on medical outcomes The marketing of foods to children has been criticised by parents and academics alike and the control of such advertising is being considered by politicians . Much of the current research focuses on TV advertising . This study aim ed to investigate the effects of exposure to printed advertisements for healthy , less healthy and non-food products on children 's mood , hunger , food choice and product recall . Accordingly , 309 children ( mean age 9.7 years ) received booklets in a quasi-r and om order . Each booklet contained one of the three types of adverts , ratings of current self-perception and a food choice measure . The booklets were presented as a school-based media literacy exercise . Body weight , height and body satisfaction were assessed 1 week later . The three groups did not differ in the effect on current state or end of session food choice . However , children recalled more of the less healthy food products , even when accounting for recent exposure . Greater product recall of less healthy foods is relevant to future consumption but has a number of possible interpretations . The further exploration of non-TV food marketing is warranted at a time when marketing through these channels is increasing , not least as a result of greater TV advertising regulations BACKGROUND The ORACLE I trial compared the use of erythromycin and /or amoxicillin-clavulanate ( co-amoxiclav ) with that of placebo for women with preterm rupture of the membranes without overt signs of clinical infection , by use of a factorial r and omised design . The aim of the present study --the ORACLE Children Study I -- was to determine the long-term effects on children of these interventions . METHODS We assessed children at age 7 years born to the 4148 women who had completed the ORACLE I trial and who were eligible for follow-up with a structured parental question naire to assess the child 's health status . Functional impairment was defined as the presence of any level of functional impairment ( severe , moderate , or mild ) derived from the mark III Multi-Attribute Health Status classification system . Educational outcomes were assessed with national curriculum test results for children resident in Engl and . FINDINGS Outcome was determined for 3298 ( 75 % ) eligible children . There was no difference in the proportion of children with any functional impairment after prescription of erythromycin , with or without co-amoxiclav , compared with those born to mothers who received no erythromycin ( 594 [ 38.3 % ] of 1551 children vs 655 [ 40.4 % ] of 1620 ; odds ratio 0.91 , 95 % CI 0.79 - 1.05 ) or after prescription of co-amoxiclav , with or without erythromycin , compared with those born to mothers who received no co-amoxiclav ( 645 [ 40.6 % ] of 1587 vs 604 [ 38.1 % ] of 1584 ; 1.11 , 0.96 - 1.28 ) . Neither antibiotic had a significant effect on the overall level of behavioural difficulties experienced , on specific medical conditions , or on the proportions of children achieving each level in reading , writing , or mathematics at key stage one . INTERPRETATION The prescription of antibiotics for women with preterm rupture of the membranes seems to have little effect on the health of children at 7 years of age . FUNDING UK Medical Research Council Background Despite evidence of inadequate physical examination skills among medical students , teaching these skills has declined . One method of enhancing inspection skills is teaching “ visual literacy , ” the ability to reason physiology and pathophysiology from careful and unbiased observation . Objective To improve students ’ visual acumen through structured observation of artworks , underst and ing of fine arts concepts and applying these skills to patient care . Design Prospect i ve , partially r and omized pre- vs. post-course evaluation using mixed- methods data analysis . Participants Twenty-four pre- clinical student participants were compared to 34 classmates at a similar stage of training . InterventionTraining the Eye : Improving the Art of Physical Diagnosis consists of eight paired sessions of art observation exercises with didactics that integrate fine arts concepts with physical diagnosis topics and an elective life drawing session . Measurements The frequency of accurate observations on a 1-h visual skills examination was used to evaluate pre- vs. post-course descriptions of patient photographs and art imagery . Content analysis was used to identify thematic categories . All assessment s were blinded to study group and pre- vs. post-course evaluation . Results Following the course , class participants increased their total mean number of observations compared to controls ( 5.41 ± 0.63 vs. 0.36 ± 0.53 , p < 0.0001 ) and had increased sophistication in their descriptions of artistic and clinical imagery . A ‘ dose-response ’ was found for those who attended eight or more sessions , compared to participants who attended seven or fewer sessions ( 6.31 + 0.81 and 2.76 + 1.2 , respectively , p = 0.03 ) . Conclusions This interdisciplinary course improved participants ’ capacity to make accurate observations of art and physical findings Background Public health research characterising the course of life through the middle age in developing societies is scarce . The aim of this study is to explore patterns of adult ( 15–64 years ) mortality in an Ethiopian population over time , by gender , urban or rural lifestyle , causes of death and in relation to household economic status and decision-making . Methods The study was conducted in Butajira Demographic Surveillance Site ( DSS ) in south- central Ethiopia among adults 15–64 years old . Cohort analysis of surveillance data was conducted for the years 1987–2004 complemented by a prospect i ve case-referent ( case control ) study over two years . Rate ratios were computed to assess the relationships between mortality and background variables using a Poisson regression model . In the case-referent component , odds ratios ( 95 % confidence intervals ) were used to assess the effect of certain risk factors that were not included in the surveillance system . Results A total of 367 940 person years were observed in a period of 18 years , in which 2 860 deaths occurred . One hundred sixty two cases and 486 matched for age , sex and place of residence controls were included in the case referent ( case control ) study . Only a modest downward trend in adult mortality was seen over the 18 year period . Rural lifestyle carried a significant survival disadvantage [ mortality rate ratio 1.62 ( 95 % CI 1.44 to 1.82 ) , adjusted for gender , period and age group ] , while the overall effects of gender were negligible . Communicable disease mortality was appreciably higher in rural areas [ rate ratio 2.05 ( 95 % CI 1.73 to 2.44 ) , adjusted for gender , age group and period ] . Higher mortality was associated with a lack of literacy in a household , poor economic status and lack of women 's decision making . Conclusion A complex pattern of adult mortality prevails , still influenced by war , famine and communicable diseases . Individual factors such as a lack of education , low economic status and social disadvantage all contribute to increased risks of mortality The effects of early supplementary feeding on cognition are investigated using data collected during two periods in four Guatemalan villages . The first was the Institute of Nutrition of Central America and Panama ( INCAP ) longitudinal study from 1969 to 1977 and the second was a cross-sectional follow-up of former participants carried out in 1988 - 1989 . The principal objective of these studies was to assess the differential effect of two dietary supplements , Atole containing 163 kcal/682 kJ and 11.5 g protein per cup or 180 mL and Fresco containing 59 kcal/247 kJ and 0 g protein per cup , that were given to mothers , infants and young children . Performance was assessed on a battery of psychoeducational and information processing tests that were administered during adolescence . Consistent differences between groups were observed on psychoeducational tests . Subjects receiving Atole scored significantly higher on tests of knowledge , numeracy , reading and vocabulary than those given Fresco . Atole ingestion also was associated with faster reaction time in information processing tasks . In addition , there were significant interactions between type of dietary supplement and socioeconomic status ( SES ) of subjects . In Atole villages , there were no differences in performance between subjects in the lowest and highest SES categories . On the other h and , performance in Fresco villages was best in the highest compared with the lowest SES group . After close scrutiny of alternative hypotheses , it is concluded that dietary changes produced by supplementation provide the strongest explanation for the test performance differences observed in the follow-up between subjects exposed to Atole and those exposed to Fresco supplementation BACKGROUND The effect of screening with prostate-specific-antigen ( PSA ) testing and digital rectal examination on the rate of death from prostate cancer is unknown . This is the first report from the Prostate , Lung , Colorectal , and Ovarian ( PLCO ) Cancer Screening Trial on prostate-cancer mortality . METHODS From 1993 through 2001 , we r and omly assigned 76,693 men at 10 U.S. study centers to receive either annual screening ( 38,343 subjects ) or usual care as the control ( 38,350 subjects ) . Men in the screening group were offered annual PSA testing for 6 years and digital rectal examination for 4 years . The subjects and health care providers received the results and decided on the type of follow-up evaluation . Usual care sometimes included screening , as some organizations have recommended . The numbers of all cancers and deaths and causes of death were ascertained . RESULTS In the screening group , rates of compliance were 85 % for PSA testing and 86 % for digital rectal examination . Rates of screening in the control group increased from 40 % in the first year to 52 % in the sixth year for PSA testing and ranged from 41 to 46 % for digital rectal examination . After 7 years of follow-up , the incidence of prostate cancer per 10,000 person-years was 116 ( 2820 cancers ) in the screening group and 95 ( 2322 cancers ) in the control group ( rate ratio , 1.22 ; 95 % confidence interval [ CI ] , 1.16 to 1.29 ) . The incidence of death per 10,000 person-years was 2.0 ( 50 deaths ) in the screening group and 1.7 ( 44 deaths ) in the control group ( rate ratio , 1.13 ; 95 % CI , 0.75 to 1.70 ) . The data at 10 years were 67 % complete and consistent with these overall findings . CONCLUSIONS After 7 to 10 years of follow-up , the rate of death from prostate cancer was very low and did not differ significantly between the two study groups . ( Clinical Trials.gov number , NCT00002540 . Background Health risk appraisal is a promising method for health promotion and prevention in older persons . The Health Risk Appraisal for the Elderly ( HRA-E ) developed in the U.S. has unique features but has not been tested outside the United States . Methods Based on the original HRA-E , we developed a scientifically up date d and regionally adapted multilingual Health Risk Appraisal for Older Persons ( HRA-O ) instrument consisting of a self-administered question naire and software-generated feed-back reports . We evaluated the practicability and performance of the question naire in non-disabled community-dwelling older persons in London ( U.K. ) ( N = 1090 ) , Hamburg ( Germany ) ( N = 804 ) , and Solothurn ( Switzerl and ) ( N = 748 ) in a sub- sample of an international r and omised controlled study . Results Over eighty percent of invited older persons returned the self-administered HRA-O question naire . Fair or poor self-perceived health status and older age were correlated with higher rates of non-return of the question naire . Older participants and those with lower educational levels reported more difficulty in completing the HRA-O question naire as compared to younger and higher educated persons . However , even among older participants and those with low educational level , more than 80 % rated the question naire as easy to complete . Prevalence rates of risks for functional decline or problems were between 2 % and 91 % for the 19 HRA-O domains . Participants ' intention to change health behaviour suggested that for some risk factors participants were in a pre-contemplation phase , having no short- or medium-term plans for change . Many participants perceived their health behaviour or preventative care uptake as optimal , despite indications of deficits according to the HRA-O based evaluation . Conclusion The HRA-O question naire was highly accepted by a broad range of community-dwelling non-disabled persons . It identified a high number of risks and problems , and provided information on participants ' intention to change health behaviour If health providers are aware of their patients ' literacy skills , they can more appropriately tailor their communication with patients . Few providers , however , assess patient 's literacy skills for fear of offending patients , but no research has ever determined if patients object to such assessment s. Our objectives were to determine the percentage of patients seen for routine health care that would agree to undergo literacy assessment and if satisfaction of patients differs in practice s that perform literacy assessment s versus practice s that do not . We r and omized 20 private and public medical practice s to an intervention group that implemented literacy assessment s with the Newest Vital Sign and a control group that did not . For intervention practice s , we noted the percentage of patients agreeing to undergo the assessment . For both intervention and control practice s , we assessed patient satisfaction . Of 289 patients asked to undergo literacy assessment in the intervention practice s , 284 ( 98.3 % ) agreed to do so , including 125 ( 46.1 % ) with low or possibly low literacy skills . There was no difference in satisfaction between the intervention group and the control group . We conclude that patients are willing to undergo literacy assessment s during routine office visits and performing such assessment s does not decrease patient satisfaction Background The Mental Health First Aid training course was favorably evaluated in an uncontrolled trial in 2002 showing improvements in participants ' mental health literacy , including knowledge , stigmatizing attitudes , confidence and help provided to others . This article reports the first r and omized controlled trial of this course . Methods Data are reported on 301 participants r and omized to either participate immediately in a course or to be wait-listed for 5 months before undertaking the training . The participants were employees in two large government departments in Canberra , Australia , where the courses were conducted during participants ' work time . Data were analyzed according to an intention-to-treat approach . Results The trial found a number of benefits from this training course , including greater confidence in providing help to others , greater likelihood of advising people to seek professional help , improved concordance with health professionals about treatments , and decreased stigmatizing attitudes . An additional unexpected but exciting finding was an improvement in the mental health of the participants themselves . Conclusions The Mental Health First Aid training has shown itself to be not only an effective way to improve participants ' mental health literacy but also to improve their own mental health . It is a course that has high applicability across the community OBJECTIVE To determine the effectiveness of a pictorial ' mind map ' together with the Arthritis Research Campaign ( ARC ) booklet for imparting knowledge to participants with rheumatoid arthritis ( RA ) . Also , we wished to relate this to their reading ability . METHODS We studied 363 participants with RA . Reading ability was assessed using the REALM , and knowledge was assessed using the Knowledge Scale Question naire ( KSQ ) . Information on educational attainment , disease state and levels of anxiety and depression was also collected . Participants were r and omly assigned to receive either the ARC booklet alone or the booklet and the mind map together . RESULTS A significant minority ( 15 % ) of participants were functionally illiterate . There was a statistically significant increase in knowledge across both groups from baseline to re assessment after they were given the literature , but there was no difference in attainment between the groups . The more literate participants gained more knowledge regardless of the information they were given . They were also significantly less anxious and less depressed . CONCLUSIONS The ARC booklet with or without the mind map was associated with a significant increase in knowledge . Poor readers had poor educational attainment and poor knowledge acquisition . The information on the mind map was not more accessible to them . Different educational strategies will be necessary to educate these patients Background Tomorrow 's physicians must learn to access , retrieve , integrate and apply current information into ambulatory patient encounters , yet few medical schools teach ' real time ' information management . Methods We compared two groups of clerkship students ' information management skills using a st and ardized patient case . The intervention group participated in case-based discussion s including exercises that required them to manage new information . The control group completed the same case discussion s without information management exercises . Results After five weeks , there was no significant difference between the control and intervention groups ' scores on the st and ardized patient case . However , third rotation students significantly outperformed first rotation students . Conclusion Case-based exercises to teach information management failed to improve students ' performance on a st and ardized patient case . Increased number of clinical rotations was associated with improved performance BACKGROUND A consulting method known as ' shared decision making ' ( SDM ) has been described and operationalized in terms of several ' competences ' . One of these competences concerns the discussion of the risks and benefits of treatment or care options-'risk communication ' . Few data exist on clinicians ' ability to acquire skills and implement the competences of SDM or risk communication in consultations with patients . OBJECTIVE The aims of this study were to evaluate the effects of skill development workshops for SDM and the use of risk communication aids on the process of consultations . METHODS A cluster r and omized trial with crossover was carried out with the participation of 20 recently qualified GPs in urban and rural general practice s in Gwent , South Wales . A total of 747 patients with known atrial fibrillation , prostatism , menorrhagia or menopausal symptoms were invited to a consultation to review their condition or treatments . Half the consultations were r and omly selected for audio-taping , of which 352 patients attended and were audio-taped successfully . After baseline , participating doctors were r and omized to receive training in ( i ) SDM skills or ( ii ) the use of simple risk communication aids , using simulated patients . The alternative training was then provided for the final study phase . Patients were allocated r and omly to a consultation during baseline or intervention 1 ( SDM or risk communication aids ) or intervention 2 phases . A r and omly selected half of the consultations were audio-taped from each phase . Raters ( independent , trained and blinded to study phase ) assessed the audio-tapes using a vali date d scale to assess levels of patient involvement ( OPTION : observing patient involvement ) , and to analyse the nature of risk information discussed . Clinicians completed question naires after each consultation , assessing perceived clinician-patient agreement and level of patient involvement in decisions . Multilevel modelling was carried out with the OPTION score as the dependent variable , and rater , consultation and clinician levels of data , st and ardized by rater within clinician . RESULTS Following each of the interventions , the clinicians significantly increased their involvement of patients in decision making ( OPTION score increased by 10.6 following risk communication training [ 95 % confidence interval ( CI ) 7.9 -13.3 ; P < 0.001 ] and by 12.9 after SDM skill development ( 95 % CI 10 -15.8 , P < 0.001 ) , a moderate effect size . The level of involvement achieved by the risk communication aids was significantly increased by the subsequent introduction of the skill development workshops ( 7.7 increase in OPTION score , 95 % CI 3.4 - 12 ; P < 0.001 ) . The alternative sequence ( skills followed by risk communication aids ) did not achieve this effect . The use of most risk information formats increased after the provision of specific risk communication aids ( P < 0.001 ) . Clinicians using the risk communication tools perceived significantly higher patient and clinician agreement on treatment ( P < 0.001 ) , patient satisfaction with information ( P < 0.01 ) , clinician satisfaction with decision ( P < 0.01 ) and general overall satisfaction with the consultation ( P < 0.001 ) than those who were exposed to SDM skill development workshops . CONCLUSIONS These clinicians were able to acquire the skills to implement SDM competences and to use risk communication aids . Each intervention provided independent effects . Further progress towards greater patient involvement in health care decision making is possible , and skill development in this area should be incorporated into postgraduate professional development programmes OBJECTIVES Telemedicine applications carry the potential to enhance the quality of life of patients , but studies evaluating telemedicine applications are still scarce . The evidence regarding the effectiveness of telemedicine is limited and not yet conclusive . This study investigated whether telemedicine could be beneficial to the quality of life of cancer patients . DESIGN AND MEASUREMENTS Between 1999 and 2002 , we conducted a prospect i ve controlled trial evaluating the effects of a telemedicine application on the quality of life of patients with cancer involving the head and neck , using quality of life question naires that covered 22 quality of life parameters . All patients had undergone surgery for head and neck cancer at the Erasmus MC , a tertiary university hospital in The Netherl and s. Patients in the intervention group were given access to an electronic health information support system for a period of six weeks , starting at discharge from the hospital . RESULTS In total , we included 145 patients in the control group and 39 in the intervention group . At 6 weeks , the end of the intervention , the intervention group had significantly improved QoL in 5 of the 22 studied parameters . Only one of these five quality of life parameters remained significantly different at 12 weeks . CONCLUSIONS This study adds to the sparse evidence that telemedicine may be beneficial for the quality of life of cancer patients Background Low back pain remains a costly quality -of-life-related health problem . Microdiscectomy is often the surgical procedure of choice for a symptomatic , single-level , lumbar disc herniation in younger and middle-aged adults . The question of whether a post-microdiscectomy exercise program enhances function , quality of life , and disability status has not been systematic ally explored . Thus , the overall purpose of this study is to assess immediate and long-term outcomes of an exercise program , developed at University of Southern California ( USC ) , targeting the trunk and lower extremities ( USC Spine Exercise Program ) for persons who have undergone a single-level microdiscectomy for the first time . Methods / design One hundred individuals between the ages of 18 and 60 who consent to undergo lumbar microdiscectomy will be recruited to participate in this study . Subjects will be r and omly assigned to one of two groups : 1 ) one session of back care education , or 2 ) a back care education session followed by the 12-week USC Spine Exercise Program . The outcome examiners ( evaluators ) , as well as the data managers , will be blinded to group allocation . Education will consist of a one-hour " one-on-one " session with the intervention therapist , guided by an educational booklet specifically design ed for post-microdiscectomy care . This session will occur four to six weeks after surgery . The USC Spine Exercise Program consists of two parts : back extensor strength and endurance , and mat and upright therapeutic exercises . This exercise program is goal -oriented , performance-based , and periodized . It will begin two to three days after the education session , and will occur three times a week for 12 weeks . Primary outcome measures include the Oswestry Disability Question naire , Rol and -Morris Disability Question naire , SF-36 ® quality of life assessment , Subjective Quality of Life Scale , 50-foot Walk , Repeated Sit-to-St and , and a modified Sorensen test . The outcome measures in the study will be assessed before and after the 12-week post-surgical intervention program . Long-term follow up assessment s will occur every six months beginning one year after surgery and ending five years after surgery . Immediate and long-term effects will be assessed using repeated measures multivariate analysis of variance ( MANOVA ) . If significant interactions are found , one-way ANOVAs will be performed followed by post-hoc testing to determine statistically significant pairwise comparisons . Discussion We have presented the rationale and design for a r and omized controlled trial evaluating the effectiveness of a treatment regimen for people who have undergone a single-level lumbar microdiscectomy Context Educational material s aim ed at improving people 's ability to underst and information about risk are scarce . Contribution In 2 trials , adults with high or low socioeconomic status ( SES ) were r and omly assigned to receive a primer about underst and ing risk or a general health booklet . In both SES groups , adults receiving the primer more often passed a medical data interpretation test than did those receiving the general health booklet . They also expressed greater interest in medical statistics but not greater confidence in interpreting statistics , and most rated the primer helpful or very helpful . Caution s The authors did not examine whether improved data interpretation skills affected decision-making . The Editors People face a bewildering array of medical decisions ( for example , should I be tested for BRCA1 ? Should I be screened for prostate cancer ? Should I have lumpectomy and radiation to treat my breast cancer ? ) . If people are to make informed decisions , they need to underst and risk : What is my chance of staying healthy if I undergo this intervention ? What is my chance of staying healthy if I forgo it ? What is the chance of harm ? Underst and ing risk data entails a set of skills . First , people must be able to work with probabilities and changes in probabilities , the typical measures used to communicate risk information . Next , they need to have a framework on which to organize data . In essence , this means having a sense of what additional information is needed to give meaning to a statement about probability ( conversely , how to know when such additional information is lacking ) . For example , putting a particular risk in context ( your chance of breast cancer is 1 in 8) entails knowing what outcome is being considered ( diagnosis vs. death ) , being clear about the time period ( 5 years vs. lifetime ) , and having some perspective on the magnitude of the probability ( How does the risk for a particular condition compare with other important health risks ? ) . Third , people need to be able to make some basic assessment about the quality of the evidence to know whether they can believe the numbers that they are given . Anecdotal experience and a growing body of literature document the trouble many people have in making sense of risk information ( 14 ) , which is now ubiquitous in health messages . This is not surprising : Much more effort goes into disseminating health information ( for example , drug advertisements , media reports , and decision-making aids ) than into preparing the target audiences to underst and it . To address this gap , we developed a primer to help people develop the basic skills needed to make sense of the medical risk data that surround them . In this paper , we report on 2 r and omized trials that tested the primer . We sought to learn how people would respond to the primer : Would they read it ? Would they value this knowledge ? Most important , would the primer improve patients ' abilities to interpret medical data ? Methods Design Overview To test the effect of the primer on how well people underst and risk , we conducted 2 r and omized trials in distinct population s : people with high and low socioeconomic status ( SES ) . Figure 1 shows an overview of the study design . The Committee for the Protection of Human Subjects at Dartmouth College approved this project , and the survey cover letter was considered to be informed consent ( signed consent was waived ) . Figure 1 . Overview of 2 r and omized trials in distinct population s. SES = socioeconomic status ; VA = Veterans Affairs . Setting and Participants We calculated our sample size under the most conservative conditionswhen the pooled proportion of passing scores was 50 % . We asserted that a 20-percentage point absolute difference in the proportion passing the test in the primer group versus the control group would be clinical ly important . In calculating the sample size requirements , we therefore assumed that the proportion passing would be 50 % in the control group and 70 % in the primer group . When a power of 0.8 and a 2-sided P value of 0.05 were used , 100 patients were required for each study group . Assuming that 10 % of participants would be lost to follow-up , we planned to enroll 110 patients per group in each trial . High Socioeconomic Status Trial To study the effect of the primer in a highly educated and affluent group , we recruited alumni from Dartmouth 's Community Medical School . This 9-lecture series on various health and medical topics is taught by Dartmouth faculty and guests ; is held annually in Hanover , New Hampshire , and Manchester , New Hampshire ; and has a $ 25 registration fee ( 5 ) . For this study , the program organizers mailed recruitment letters to 1138 alumni . A total of 334 people who responded to the letter were eligible ( that is , they met the age criterion of 35 to 79 years , spoke English , and had attended the Community Medical School in the past ) and were subsequently r and omly assigned . Ninety-six percent ( n= 322 ) returned a completed survey ( completion rates were not significantly different between the primer and control groups [ 95 % vs. 98 % , respectively ] ) ( P= 0.192 ) . Low Socioeconomic Status Trial To study the effect of the primer in a sample with lower income and less formal education , we recruited veterans and their families at the White River Junction Veterans Affairs ( VA ) Medical Center , White River Junction , Vermont , by posting study advertisements in waiting areas of the outpatient clinic . A total of 221 people who responded to the advertisement were eligible ( that is , they met the age criteria of 35 to 79 years , spoke English , and were a veteran or the family member of a veteran who was enrolled in a VA clinic ) and were subsequently r and omly assigned . Ninety percent ( n= 200 ) returned completed surveys ( completion rates were significantly lower in the primer group than in the control group [ 85 % vs. 96 % , respectively ] ) ( P= 0.005 ) . R and omization and Interventions The letter and the advertisement asked people to participate in a research study to learn how to better give people health information . We did not mention our interest in enhancing quantitative skills . People who responded to the recruitment letter ( high SES group ) or to the advertisement ( low SES group ) were first interviewed to confirm eligibility . We only accepted 1 participant per household . Within each trial , we assigned participants on an individual basis to receive either the primer or control booklet . A list of r and om numbers ( created by using a r and om-number generator ) was given to a research assistant and was used to determine assignments ( r and omization was not stratified or blocked within each trial ) . The research assistant had access to participants ' characteristics . The investigators did not have access to the assignment list , and the deidentified code was only revealed after recruitment and completion of data collection . The appropriate booklet and a survey were mailed or given in person to participants . The survey included the major outcomes that will be described in the next section . To make the survey seem relevant to the control group , it also included additional questions about facts presented in the health booklet ( we did not analyze responses to these questions ) . All participants were asked to read the booklet and return the completed survey within 2 weeks using the self-addressed stamped envelope included with the survey . Reminder letters were sent to nonresponders . Participants who returned surveys were given their choice of a $ 25 gift certificate to a local bakery , restaurant , bookstore , or large retail store . We recruited participants from October 2004 through August 2005 . Primer Group The participants in the primer group received the booklet entitled Know Your Chances : Underst and ing Health Statistics . The goal of the primer is to teach people how to underst and risk messages and health statistics . The first part of the primer teaches people how to underst and disease risk by using the example of colon cancer . The second part focuses on how to underst and the benefits and harms of interventions by using a Zocor direct-to-consumer advertisement for secondary heart disease prevention . Figure 2 shows the summary of main concepts that were taught , which is excerpted from the booklet . The contents of the primer and many of the examples have been developed and revised over years of teaching and through focus groups with people across a diverse socioeconomic spectrum . Figure 2 . Key concepts taught in the primer , excerpted from the final pages . Because many people are intimi date d by numbers and statistics , we worked hard to make the primer inviting and nonthreatening by liberal use of cartoons and figures ; by working through examples , separating the most technical material into optional learn more boxes ; and by providing readers with quizzes ( with answers ) to assess their mastery of the material as they read the primer . Figure 3 shows sample pages from the primer . Most of the primer is written at the eighth- grade or lower reading level ( 6 ) and is a color document approximately 80 pages in length . Figure 3 . Excerpts of primer . Control Group The control group received a 70-page booklet entitled The Pocket Guide for Good Health for Adults , which is published by the U.S. Department of Health and Human Services Agency for Health Care Research and Quality ( 7 ) . We chose this booklet because the length is similar to that of the primer , it is written at a similar reading level ( eighth grade or lower ) ( 6 ) , and it contains general information about risk and reducing risk by following recommended prevention or screening activities . However , it does not include training on how to interpret quantitative information . Measurement and Outcomes All outcome measures were assessed in the survey . Primary Outcome The primary outcome was a measure of participants ' abilities to interpret medical statistics . To measure this outcome , we developed the 18-item data interpretation test during the same time Background Reading skills are important for accessing health information , using health care services , managing one 's health and achieving desirable health outcomes . Our objective was to assess the diagnostic accuracy of the Single Item Literacy Screener ( SILS ) to identify limited reading ability , one component of health literacy , as measured by the S-TOFHLA . Methods Cross-sectional interview with 999 adults with diabetes residing in Vermont and bordering states . Participants were r and omly recruited from Primary Care practice s in the Vermont Diabetes Information System June 2003 – December 2004 . The main outcome was limited reading ability . The primary predictor was the SILS . Results Of the 999 persons screened , 169 ( 17 % ) had limited reading ability . The sensitivity of the SILS in detecting limited reading ability was 54 % [ 95 % CI : 47 % , 61 % ] and the specificity was 83 % [ 95 % CI : 81 % , 86 % ] with an area under the Receiver Operating Characteristics Curve ( ROC ) of 0.73 [ 95 % CI : 0.69 , 0.78 ] . Seven hundred seventy ( 77 % ) screened negative on the SILS and 692 of these subjects had adequate reading skills ( negative predictive value = 0.90 [ 95 % CI : 0.88 , 0.92 ] ) . Of the 229 who scored positive on the SILS , 92 had limited reading ability ( positive predictive value = 0.4 [ 95 % CI : 0.34 , 0.47 ] ) . Conclusion The SILS is a simple instrument design ed to identify patients with limited reading ability who need help reading health-related material s. The SILS performs moderately well at ruling out limited reading ability in adults and allows providers to target additional assessment of health literacy skills to those most in need . Further study of the use of the SILS in clinical setting s and with more diverse population s is warranted The insertion/deletion ( I/D ) polymorphism of the angiotensin I converting enzyme ( ACE ) gene is believed to influence risk of cerebrovascular disease . However , associations with cognitive outcomes remain controversial . As far as we are aware , all studies to date have been carried out in white American or European population s. African-Caribbean population s have high prevalence rates of hypertension , diabetes and cerebrovascular disease but risk factors for cognitive outcomes remain under- research ed . In a UK community sample of 148 African-Caribbean people aged 55 - 75 years , we investigated the association between ACE genotype and cognitive decline over 3 years using a battery of repeated tests . No direct association was found between ACE genotype and decline . However , the association between increased age and cognitive decline was significantly stronger in people with the ACE DD genotype ( odds ratio 3.6 per 5-year increase , 95 % CI : 1.9 - 6.7 ) compared to those with ID/II genotype ( odds ratio 0.7 , 95 % CI 0.4 - 1.2 ) . This interaction was particularly strong for decline in verbal memory and was not apparently mediated by vascular risk factors measured at baseline Background Limited literacy is common among patients with chronic conditions and is associated with poor health outcomes . We sought to determine the association between literacy and blood pressure in primary care patients with hypertension and to determine if this relationship was consistent across distinct systems of healthcare delivery . Methods We conducted a cross-sectional study of 1224 patients with hypertension utilizing baseline data from two separate , but similar r and omized controlled trials . Patients were enrolled from primary care clinics in the Veterans Affairs healthcare system ( VAHS ) and a university healthcare system ( UHS ) in Durham , North Carolina . We compared the association between literacy and the primary outcome systolic blood pressure ( SBP ) and secondary outcomes of diastolic blood pressure ( DBP ) and blood pressure ( BP ) control across the two different healthcare systems . Results Patients who read below a 9th grade level comprised 38.4 % of patients in the VAHS and 27.5 % of the patients in the UHS . There was a significant interaction between literacy and healthcare system for SBP . In adjusted analyses , SBP for patients with limited literacy was 1.2 mmHg lower than patients with adequate literacy in the VAHS ( 95 % CI , -4.8 to 2.3 ) , but 6.1 mmHg higher than patients with adequate literacy in the UHS ( 95 % CI , 2.1 to 10.1 ) ; ( p = 0.003 for test of interaction ) . This literacy by healthcare system interaction was not statistically significant for DBP or BP control . Conclusion The relationship between patient literacy and systolic blood pressure varied significantly across different models of healthcare delivery . The attributes of the healthcare delivery system may influence the relationship between literacy and health outcomes Abstract Objective To evaluate the efficacy of two internet interventions for community-dwelling individuals with symptoms of depression — a psychoeducation website offering information about depression and an interactive website offering cognitive behaviour therapy . Design R and omised controlled trial . Setting Internet users in the community , in Canberra , Australia . Participants 525 individuals with increased depressive symptoms recruited by survey and r and omly allocated to a website offering information about depression ( n = 166 ) or a cognitive behaviour therapy website ( n = 182 ) , or a control intervention using an attention placebo ( n = 178 ) . Main outcome measures Change in depression , dysfunctional thoughts ; knowledge of medical , psychological , and lifestyle treatments ; and knowledge of cognitive behaviour therapy . Results Intention to treat analyses indicated that information about depression and interventions that used cognitive behaviour therapy and were delivered via the internet were more effective than a credible control intervention in reducing symptoms of depression in a community sample . For the intervention that delivered cognitive behaviour therapy the reduction in score on the depression scale of the Center for Epidemiologic Studies was 3.2 ( 95 % confidence interval 0.9 to 5.4 ) . For the “ depression literacy ” site ( BluePages ) , the reduction was 3.0 ( 95 % confidence interval 0.6 to 5.2 ) . Cognitive behaviour therapy ( MoodGYM ) reduced dysfunctional thinking and increased knowledge of cognitive behaviour therapy . Depression literacy ( BluePages ) significantly improved participants ' underst and ing of effective evidence based treatments for depression ( P < 0.05 ) . Conclusions Both cognitive behaviour therapy and psychoeducation delivered via the internet are effective in reducing symptoms of depression OBJECTIVE Despite the importance of self-management support ( SMS ) , few studies have compared SMS interventions , involved diverse population s , or entailed implementation in safety net setting s. We examined the effects of two SMS strategies across outcomes corresponding to the Chronic Care Model . RESEARCH DESIGN AND METHODS A total of 339 out patients with poorly controlled diabetes from county-run clinics were enrolled in a three-arm trial . Participants , more than half of whom spoke limited English , were uninsured , and /or had less than a high school education , were r and omly assigned to usual care , interactive weekly automated telephone self-management support with nurse follow-up ( ATSM ) , or monthly group medical visits with physician and health educator facilitation ( GMV ) . We measured 1-year changes in structure ( Patient Assessment of Chronic Illness Care [ PACIC ] ) , communication processes ( Interpersonal Processes of Care [ IPC ] ) , and outcomes ( behavioral , functional , and metabolic ) . RESULTS Compared with the usual care group , the ATSM and GMV groups showed improvements in PACIC , with effect sizes of 0.48 and 0.50 , respectively ( P < 0.01 ) . Only the ATSM group showed improvements in IPC ( effect sizes 0.40 vs. usual care and 0.25 vs. GMV , P < 0.05 ) . Both SMS arms showed improvements in self-management behavior versus the usual care arm ( P < 0.05 ) , with gains being greater for the ATSM group than for the GMV group ( effect size 0.27 , P = 0.02 ) . The ATSM group had fewer bed days per month than the usual care group ( −1.7 days , P = 0.05 ) and the GMV group ( −2.3 days , P < 0.01 ) and less interference with daily activities than the usual care group ( odds ratio 0.37 , P = 0.02 ) . We observed no differences in A1C change . CONCLUSIONS Patient-centered SMS improves certain aspects of diabetes care and positively influences self-management behavior . ATSM seems to be a more effective communication vehicle than GMV in improving behavior and quality of life A multidisciplinary intervention to reduce protein-energy malnutrition among children in rural areas was piloted in 3 provinces of the Islamic Republic of Iran . Based on an initial situation analysis , a range of interventions were implemented through local nongovernmental organizations , including nutrition , health and literacy education for mothers , improved growth monitoring and fostering rural cooperatives and income generation schemes . Malnutrition before and after the intervention ( in 1996 and 1999 ) was assessed using anthropometric measurements of r and om sample s of children aged 6 - 35 months in control and intervention areas . Three years into the intervention , all indicators of malnutrition had consistently decreased in all intervention areas and the prevalence of underweight and stunting was significantly lower . Control areas showed a mixed pattern of small increases and decreases in malnutrition indicators UNLABELLED This study examines the change in health-related quality of life ( HRQoL ) among ( > or = 60 years ) elderly persons as a result of health education intervention . A community-based intervention study was performed in eight r and omly selected villages ( INTERVENTION n = 4 ; CONTROL n = 4 ) in rural Bangladesh . A total of 1135 elderly persons was selected for this study . The analyses include 839 participants ( INTERVENTION n = 425 ; CONTROL n = 414 ) who participated in both baseline and post-intervention surveys . Participants in the intervention area were further stratified into compliant ( n = 315 ) and non-compliant ( n = 110 ) groups based on the reported compliance to the intervention activities . The intervention includes , for example , physical activity , advice on healthy food intake and other aspects of management . To create an enabling environment , social awareness was provided by means of information about the contribution of and challenges faced by elderly persons at home and the community , including information about elderly persons ' health and health care . The intervention activities were provided to the elderly persons , caregivers , household members and community people for 15 months . The HRQoL was assessed using a multi-dimensional generic instrument design ed for elderly persons . Multivariate analyses revealed that in the non-compliant group the probabilities of increased scores were less likely in overall HRQoL ( OR 0.52 , 95 % CI 0.32 - 0.82 ) . Among the CONTROL group , increased scores were less likely in the physical ( OR 73 , 95 % CI 0.54 - 0.99 ) , social ( OR 0.37 , 95 % CI 0.27 - 0.50 ) , spiritual ( OR 0.60 , 95 % CI 0.34 - 0.94 ) , environment ( OR 0.36 , 95 % CI 0.26 - 0.49 ) dimensions and overall HRQoL ( OR 0.44 , 95 % CI 0.32 - 0.59 ) ( adjusted for age , sex , literacy , marital status and economic status ) . This study concludes that provision of community-based health education intervention might be a potential public health initiative to enhance the HRQoL in old age BACKGROUND A range of adverse birth outcomes is associated with heavy prenatal alcohol exposure . AIM To examine the effects of moderate levels of alcohol consumption during pregnancy on children 's intellectual ability , learning and attention at 14 years of age . STUDY DESIGN AND SUBJECTS The Mater-University of Queensl and Study of Pregnancy involves a prospect i ve birth cohort of 7223 singletons whose mothers were enrolled at the first antenatal visit . At 14 years , 5139 mothers and adolescents completed attentional and learning question naires , and 3731 adolescents completed psychometric assessment s. OUTCOME MEASURES For adolescents , the Wide Range Achievement Test -- Revised ( WRAT-R ) and Raven 's St and ard Progressive Matrices Test ( Raven 's ) were administered . Mothers completed the Child Behaviour Checklist ( CBCL ) and adolescents completed the Youth Self Report ( YSR ) . Learning was assessed by a series of questions in the mother and adolescent question naires . Maternal measures included the quantity and frequency of alcohol consumption , and the extent of binge drinking . RESULTS For consumption of < 1 glass/day in early or late pregnancy , there was no association with any attention , learning or cognitive outcomes . The strongest estimates of effect were found among those consuming > or = 1 glasses/day . Exposure in late pregnancy was associated with increased prevalence of overall learning difficulty in the unadjusted , although not the adjusted analysis . Binge drinking was associated with a higher prevalence of Raven 's score < 85 ( 1 st and ard deviation ) . CONCLUSIONS Although a number of study limitations need to be considered , the results suggest that consumption at the level of < 1 drink/day does not lead to adverse outcomes in relation to attention , learning and cognitive abilities , as measured in the current research OBJECTIVE To identify changes in mental health literacy in regard to depression between 1998 and 2004 . DESIGN AND SETTING Face-to-face interviews with a r and om and representative sample of the South Australian population in 2004 , compared with a similarly conducted survey in 1998 that used the same vignette , questions and methodology . PARTICIPANTS 3015 r and omly selected participants , aged 15 years and over . MAIN OUTCOME MEASURES Responses to both open-ended and direct questions about symptoms and treatment options for depression . RESULTS The 3015 interviews conducted represented a response rate of 65.9 % . Compared with 1998 , in 2004 there was a significant increase in the proportion of people recognising depression in the vignette , acknowledging personal experience of depression , and perceiving professional assistance to be more helpful and less harmful . However , although more people nominated psychiatrists or psychologists as therapists of choice , the difference between 1998 and 2004 was not significant . CONCLUSIONS There has been a significant increase in mental health literacy , at least as regards depression , in the South Australian community between 1998 and 2004 . The lack of significant change in psychiatrists and /or psychologists being perceived as therapists of choice is of concern and suggests that community education about their expertise may be appropriate Background Early detection and treatment of mental disorders in adolescents and young adults can lead to better health outcomes . Mental health literacy is a key to early recognition and help seeking . Whilst a number of population health initiatives have attempted to improve mental health literacy , none to date have specifically targeted young people nor have they applied the rigorous st and ards of population health models now accepted as best practice in other health areas . This paper describes the outcomes from the application of a health promotion model to the development , implementation and evaluation of a community awareness campaign design ed to improve mental health literacy and early help seeking amongst young people . Method The Compass Strategy was implemented in the western metropolitan Melbourne and Barwon regions of Victoria , Australia . The Precede-Proceed Model guided the population assessment , campaign strategy development and evaluation . The campaign included the use of multimedia , a website , and an information telephone service . Multiple levels of evaluation were conducted . This included a cross-sectional telephone survey of mental health literacy undertaken before and after 14 months of the campaign using a quasi-experimental design . R and omly selected independent sample s of 600 young people aged 12–25 years from the experimental region and another 600 from a comparison region were interviewed at each time point . A series of binary logistic regression analyses were used to measure the association between a range of campaign outcome variables and the predictor variables of region and time . Results The program was judged to have an impact on the following variables , as indicated by significant region-by-time interaction effects ( p < 0.05 ) : awareness of mental health campaigns , self-identified depression , help for depression sought in the previous year , correct estimate of prevalence of mental health problems , increased awareness of suicide risk , and a reduction in perceived barriers to help seeking . These effects may be underestimated because media distribution error result ed in a small amount of print material " leaking " into the comparison region . Conclusion We believe this is the first study to apply the rigorous st and ards of a health promotion model including the use of a control region to a mental health population intervention . The program achieved many of its aims despite the relatively short duration and moderate intensity of the campaign OBJECTIVES To determine the prevalence of stunting , wasting and overweight and their determinants in 3-year-old children in the Central Region of Limpopo Province , South Africa . DESIGN Prospect i ve cohort study . SETTING Rural villages in the Central Region of the Limpopo Province , South Africa . SUBJECTS One hundred and sixty-two children who were followed from birth were included in the study . Anthropometric measurements and sociodemographic characteristics of the children were recorded . RESULTS Height-for-age Z-scores were low , with a high prevalence of stunting ( 48 % ) . The children also exhibited a high prevalence of overweight ( 22 % ) and obesity ( 24 % ) . Thirty-one ( 19 % ) children were both stunted and overweight . Gaining more weight within the first year of life increased the risk of being overweight at 3 years by 2.39 times ( 95 % confidence interval ( CI ) 1.96 - 4.18 ) while having a greater length at 1 year was protective against stunting ( odds ratio ( OR ) 0.41 ; 95 % CI 0.17 - 0.97 ) . Having a mother as a student increased the risk for stunting at 3 years by 18.21 times ( 95 % CI 9.46 - 34.74 ) while having a working mother increased the risk for overweight by 17.87 times ( 95 % CI 8.24 - 38.78 ) . All these factors also appeared as risks or as being protective in children who were both overweight and stunted , as did living in a household having nine or more persons ( OR 5.72 ; 95 % CI 2.7 - 12.10 ) . CONCLUSION The results of this study highlight the importance of evaluating anthropometric status in terms of both stunting and overweight . Furthermore , it is important to realise the importance of normal length and weight being attained at 1 year of age , since these in turn predict nutritional status at 3 years of age OBJECTIVE This study describes maternal depression associated with newborn genetic screening for type 1 diabetes after risk notification . RESEARCH DESIGN AND METHODS Mothers of at-risk infants ( n = 192 ) , identified through newborn genetic screening as part of the Prospect i ve Assessment of Newborns for Diabetes Autoimmunity study , were administered a structured telephone interview assessing maternal depressive symptoms 1 and 3.5 months after risk notification . Statistical analyses were conducted to examine predictors and correlates of maternal depressive symptoms . RESULTS For the total sample , maternal depressive symptoms in response to infant risk status were not elevated at 1 and 3.5 months after risk notification . However , at the first interview , mothers from ethnic minority background s ( P < 0.002 ) , with limited education ( P < 0.001 ) , and with postpartum depression symptomatology ( P < 0.001 ) reported significantly more depressive symptoms in response to risk notification ( r2 = 0.354 ) . At the second interview , postpartum depression symptomatology remained a powerful predictor of depressive symptoms in response to risk notification ( P < 0.001 ) . In addition , certain coping styles ( wishful thinking , self-blame , and seeking social support ) were associated with increased depressive symptoms . A history of major depression was a correlate of both postpartum depressive symptomatology ( r = 0.26 ) and maternal depressive response to risk notification ( r = 0.21 ) . CONCLUSIONS For the most part , mothers of infants genetically at risk for type 1 diabetes do not appear to evidence elevated depressive symptoms . This suggests that most mothers are resilient when notified of infant risk . However , certain maternal characteristics such as ethnic minority status , less than a high school education , postpartum depression symptomatology , a history of major depression , and certain coping strategies ( wishful thinking , self-blame , and seeking social support ) appear to be associated with a more difficult maternal response to the news of an infant 's increased genetic risk for type 1 diabetes Background Inconsistent findings reported in the literature contribute to the lack of complete underst and ing of the association of literacy with health outcomes . We evaluated the association between literacy , physiologic control and diabetes complications among adults with diabetes . Methods A cross-sectional study of 1,002 English speaking adults with diabetes , r and omly selected from the Vermont Diabetes Information System , a cluster-r and omized trial of a diabetes decision support system in a region-wide sample of primary care practice s was conducted between July 2003 and March 2005 . Literacy was assessed by the Short-Test of Functional Health Literacy in Adults . Outcome measures included glycated hemoglobin , low density lipoprotein , blood pressure and self-reported complications . Results After adjusting for sociodemographic characteristics , duration of diabetes , diabetes education , depression , alcohol use , and medication use we did not find a significant association between literacy and glycemic control ( beta coefficent,+ 0.001 ; 95 % confidence interval [ CI ] , -0.01 to + 0.01 ; P = .88 ) , systolic blood pressure ( beta coefficent , + 0.08 ; 95 % CI , -0.10 to + 0.26 ; P = .39 ) , diastolic blood pressure ( beta coefficent , -0.03 ; 95 % CI , -0.12 to + 0.07 , P = .59 ) , or low density lipoprotein ( beta coefficent , + 0.04 ; 95 % CI , -0.27 to + 0.36 , P = .77 . We found no association between literacy and report of diabetes complications . Conclusion These findings suggest that literacy , as measured by the S-TOFHLA , is not associated with glycated hemoglobin , blood pressure , lipid levels or self-reported diabetes complications in a cross-sectional study of older adults with diabetes under relatively good glycemic control . Additional studies to examine the optimal measurement of health literacy and its relationship to health outcomes over time are needed PURPOSE To determine the prevalence of refractive errors and to investigate factors associated with refractive error in adults 30 years of age and older in Bangladesh . DESIGN Cross-sectional study . PARTICIPANTS A nationally representative sample of 12 782 adults 30 years of age and older . METHODS The sample of subjects was selected based on multistage , cluster r and om sampling with probability-proportional-to-size procedures . The examination protocol consisted of an interview that included measures of literacy , education , occupation , and refractive correction . Visual acuity testing ( logarithm of the minimum angle of resolution [ logMAR ] ) , automated refraction , and optic disc examination were performed for all subjects . Subjects with < 6/12 ( 0.3 logMAR ) acuity in either eye were grade d additionally for cataract and underwent a dilated fundal examination . Subjects for whom no refractive error was recorded ( 312 subjects ; 2.7 % ) or who had undergone cataract surgery ( 123 subjects ; 1.1 % ) were excluded from the analysis . MAIN OUTCOME MEASURES Refractive error and socioeconomic variables ( literacy , education , occupation ) . RESULTS Eleven thous and six hundred twenty-four subjects were examined ( 90.9 % response rate ; mean age+/-st and ard deviation , 44+/-12.6 years ) . Five thous and four hundred eighty-nine subjects ( 49.1 % ) were men and 5700 subjects ( 50.9 % ) were women . Mean spherical equivalent was -0.19 diopters ( D ; + /-1.50 D ) . Six thous and four hundred twelve subjects ( 57.3 % ) were emmetropic , 2469 ( 22.1 % ) were myopic ( < -0.5 D ) , and 2308 ( 20.6 % ) were hypermetropic ( > + 0.5 D ) . Two hundred six subjects ( 1.8 % ) were highly myopic ( < -5 D ) . Myopia was more common in men ( 26.3 % ) than in women ( 21.0 % ) , whereas hyperopia was more common in women ( 27.4 % ) than in men ( 15.8 % ) . Overall , myopia increased with age ( 17.5 % of those aged 30 - 39 years were myopic , compared with 65.5 % of those age 70 years and older ) . A sub analysis of subjects without cataract showed increasing hyperopia with age and an association between myopia and higher education . Myopia was more common among the employed than in unemployed subjects . Astigmatism ( > 0.5 D ) , present in 3625 subjects ( 32.4 % ) , was more common among women , illiterate subjects , and unschooled subjects . Against-the-rule astigmatism was more common ( 58.7 % ) than oblique astigmatism ( 29.3 % ) , which was more common than with-the-rule ( WTR ) astigmatism ( 12.1 % ) . Against-the-rule astigmatism and oblique astigmatism increased with age , unlike WTR astigmatism . Of 830 ( 7.5 % ) subjects , women were more commonly anisometropic ( > 1.0 D ) . Anisometropia increased with age . CONCLUSIONS Refractive error data are described for a country and region that previously have lacked population -based data . Prevalence and factors associated with refractive error are presented , with a detailed comparison with other population -based surveys regionally and internationally BACKGROUND This study compares the efficacy of two school-based intervention programmes ( Phonology with Reading ( P + R ) and Oral Language ( OL ) ) for children with poor oral language at school entry . METHODS Following screening of 960 children , 152 children ( mean age 4;09 ) were selected from 19 schools on the basis of poor vocabulary and verbal reasoning skills and r and omly allocated to either the P + R programme or the OL programme . Both groups of children received 20 weeks of daily intervention alternating between small group and individual sessions , delivered by trained teaching assistants . Children in the P + R group received training in letter-sound knowledge , phonological awareness and book level reading skills . Children in the OL group received instruction in vocabulary , comprehension , inference generation and narrative skills . The children 's progress was monitored at four time points : pre- , mid- and post-intervention , and after a 5-month delay , using measures of literacy , language and phonological awareness . RESULTS The data are clustered ( children within schools ) and robust confidence intervals are reported . At the end of the 20-week intervention programme , children in the P + R group showed an advantage over the OL group on literacy and phonological measures , while children in the OL group showed an advantage over the P + R group on measures of vocabulary and grammatical skills . These gains were maintained over a 5-month period . CONCLUSIONS Intervention programmes design ed to develop oral language skills can be delivered successfully by trained teaching assistants to children at school entry . Training using P + R fostered decoding ability whereas the OL programme improved vocabulary and grammatical skills that are foundations for reading comprehension . However , at the end of the intervention , more than 50 % of at-risk children remain in need of literacy support Background Mental ill health is a common condition in the general population , yet only about half of those with a mental disorder have treatment contact . Personal experience may affect attitudes , which in turn influence the help-seeking process . This study investigated differences in mental health literacy and attitudes among mentally healthy persons and in persons with symptoms of mental illness with and without treatment contact . Method A postal screening question naire was sent to a r and om sample of the general population aged 20–64 in the county of Skaraborg , Sweden in order to ascertain mental health status and history of treatment contact ; 3538 responded ( 49 % ) . Face-to-face interviews were carried out in r and om sub sample s of mentally healthy persons ( n = 128 ) and in mentally ill persons with ( n = 125 ) and without ( n = 105 ) mental health care contact . Mental health literacy and attitudes to treatment were assessed using questions based on a vignette depicting a person with depression . Past month mental disorder was diagnosed according to the Schedule for Clinical Assessment in Neuropsychiatry ( SCAN ) . Results Two thirds failed to recognize depression in a vignette ; recognition was equally poor in mentally healthy persons and in persons with symptoms of mental illness with and without treatment contact . In response to an open-ended question concerning appropriate interventions , one third suggested counselling and only one percent proposed antidepressant treatment . Again , proportions were similar in all groups . Persons with a history of mental health contact more often suggested that a GP would provide the best form of help . When presented with a list of possible interventions , those with a history of mental health contact were more positive to medical interventions such as antidepressants , hypnotics , and inpatient psychiatric treatment . When asked about the prognosis for the condition described in the vignette , persons with treatment contact were less likely to believe in full recovery without intervention ; mentally ill without treatment contact were more optimistic . Conclusion Mental health literacy , specially concerning attitudes towards interventions is associated with personal history of mental health care PURPOSE Patients with gliomas often experience cognitive deficits , including problems with attention and memory . This r and omized , controlled trial evaluated the effects of a multifaceted cognitive rehabilitation program ( CRP ) on cognitive functioning and selected quality -of-life domains in patients with gliomas . PATIENTS AND METHODS One hundred forty adult patients with low- grade and anaplastic gliomas , favorable prognostic factors , and both subjective cognitive symptoms and objective cognitive deficits were recruited from 11 hospitals in the Netherl and s. Patients were r and omly assigned to an intervention group or to a waiting-list control group . The intervention incorporated both computer-based attention retraining and compensatory skills training of attention , memory , and executive functioning . Participants completed a battery of neuropsychological ( NP ) tests and self-report question naires on cognitive functioning , fatigue , mental health-related quality of life , and community integration at baseline , after completion of the CRP , and at 6-month follow-up . RESULTS At the immediate post-treatment evaluation , statistically significant intervention effects were observed for measures of subjective cognitive functioning and its perceived burden but not for the objective NP outcomes or for any of the other self-report measures . At the 6-month follow-up , the CRP group performed significantly better than the control group on NP tests of attention and verbal memory and reported less mental fatigue . Group differences in other subjective outcomes were not significant at 6 months . CONCLUSION The CRP has a salutary effect on short-term cognitive complaints and on longer-term cognitive performance and mental fatigue . Additional research is needed to identify which elements of the intervention are most effective The development of addition and subtraction accuracy was assessed in first grade rs with cerebral palsy ( CP ) in both mainstream ( 16 ) and special education ( 41 ) and a control group of first grade rs in mainstream education ( 16 ) . The control group out-performed the CP groups in addition and subtraction accuracy and this difference could not be fully explained by differences in intelligence . Both CP groups showed evidence of working memory deficits . The three groups exhibited different developmental patterns in the area of early numeracy skills . Children with CP in special education were found to receive less arithmetic instruction and instruction time was positively related to arithmetic accuracy . Structural equation modeling revealed that the effect of CP on arithmetic accuracy is mediated by intelligence , working memory , early numeracy , and instruction time In this study , we show that invisible flicker adaptation reduces the perceived duration of a subsequently viewed stimulus in control subjects , but not in dyslexics . Dyslexics , like controls , show apparent duration compression after 20Hz flicker and show normal shifts in apparent temporal frequency after adaptation . However a subgroup of the test group , scoring low on both a test of phonological skill ( spoonerisms ) and a test of literacy ( NART ) , show an apparent temporal expansion after 5Hz flicker adaptation , a finding not previously seen in controls . Recent studies have linked genes conferring susceptibility to a cluster of language and sensory deficits to anomalous neural migration , providing a tentative biological basis for dyslexia . However it has proved difficult to establish a clear link between sensory deficits and impaired reading . The results presented here point to an abnormal adaptation response within the early precortical stages of the magnocellular pathway , occurring in t and em with a deficit in word-level cognitive processing , providing psychophysical evidence for anomalous cortico-thalamic circuits in dyslexia Background In the US , an unacceptably high percentage of pregnant women do not undergo prenatal HIV testing . Previous studies have found increased uptake of prenatal HIV testing with abbreviated pre-test counseling , however little is known about patient decision making , testing satisfaction and knowledge in this setting . Methodology / Findings A r and omized-controlled , non-inferiority trial was conducted from October 2006 through February 2008 at San Francisco General Hospital ( SFGH ) , the public teaching hospital of the City and County of San Francisco . A total of 278 English- and Spanish-speaking pregnant women were r and omized to receive either abbreviated or st and ard nurse-performed HIV test counseling at the initial prenatal visit . Patient decision making experience was compared between abbreviated versus st and ard HIV counseling strategies among a sample of low-income , urban , ethnically diverse prenatal patients . The primary outcome was the decisional conflict score ( DCS ) using O'Connor low-literacy scale and secondary outcomes included satisfaction with test decision , basic HIV knowledge and HIV testing uptake . We conducted an intention-to-treat analysis of 278 women – 134 ( 48.2 % ) in the abbreviated arm ( AA ) and 144 ( 51.8 % ) in the st and ard arm ( SA ) . There was no significant difference in the proportion of women with low decisional conflict ( 71.6 % in AA vs. 76.4 % in SA , p = .37 ) , and the observed mean difference between the groups of 3.88 ( 95 % CI : −0.65 , 8.41 ) did not exceed the non-inferiority margin . HIV testing uptake was very high ( 97 . 8 % ) and did not differ significantly between the 2 groups ( 99.3 % in AA vs. 96.5 % in SA , p = .12 ) . Likewise , there was no difference in satisfaction with testing decision ( 97.8 % in AA vs. 99.3 % in SA , p = .36 ) . However , women in AA had significantly lower mean HIV knowledge scores ( 78.4 % ) compared to women in SA ( 83.7 % , p<0.01 ) . Conclusions / Significance This study suggests that streamlining the pre-test counseling process , while associated with slightly lower knowledge , does not compromise patient decision making or satisfaction regarding HIV testing . Trial Registration Clinical Trials.gov OBJECTIVES To examine the extent to which numeracy predicts consumer-directed health plan ( CDHP ) comprehension and health plan choice . Also , to test whether comprehension can be improved using different presentation approaches . STUDY DESIGN We conducted an experimental laboratory study in which 303 adults viewed information about a hypothetical CDHP and a hypothetical preferred provider organization ( PPO ) presented in several different ways . Participants were r and omized to view plan comparisons in a side-by-side or a common/unique format , and whether or not to view a framework . METHODS Participants completed a survey that included comprehension items , numeracy and literacy assessment s , and sociodemographics . Multivariate regression models were developed to examine the independent effects of numeracy and presentation approach on CDHP comprehension and choice . Interactions between numeracy and presentation approaches were tested . RESULTS Although less numerate consumers understood less about CDHPs , they were substantially more likely to select the CDHP . Providing an overarching framework to highlight the differences between the CDHP and PPO boosted comprehension on items related to the framework message . However , it reduced comprehension on items that were not related to the framework , particularly among the less numerate . Participants reported that the common/unique presentation of comparative information was easier to underst and , yet there was a trend toward less comprehension using that presentation approach . CONCLUSIONS This study highlights the difficulty many consumers have in underst and ing comparative plan information and in making informed healthcare choices . Findings also indicate that some presentation strategies may help the less skilled underst and choices better Background Diabetes is a leading cause of death and disability in the US and is twice as common among Hispanic Americans as non-Hispanics . The societal costs of diabetes provide an impetus for developing tools that can improve patient care and delay or prevent diabetes complications . Methods We implemented a feasibility study of a Computerized Adaptive Test ( CAT ) to measure diabetes impact using a sample of 103 English- and 97 Spanish-speaking patients ( mean age = 56.5 , 66.5 % female ) in a community medical center with a high proportion of minority patients ( 28 % African-American ) . The 37 items of the Diabetes Impact Survey were translated using forward – backward translation and cognitive debriefing . Participants were r and omized to receive either the full-length tool or the Diabetes-CAT first , in the patient 's native language . Results The number of items and the amount of time to complete the survey for the CAT was reduced to one-sixth the amount for the full-length tool in both language s , across disease severity . Confirmatory Factor Analysis confirmed that the Diabetes Impact Survey is unidimensional . The Diabetes-CAT demonstrated acceptable internal consistency reliability , construct validity , and discriminant validity in the overall sample , although subgroup analyses suggested that the English sample data evidence d higher levels of reliability and validity than the Spanish sample and issues with discriminant validity in the Spanish sample . Differential Item Function analysis revealed differences in responses tendencies by language group in 3 of the 37 items . Participant interviews suggested that the Spanish-speaking patients generally preferred the paper survey to the computer-assisted tool , and were twice as likely to experience difficulties underst and ing the items . Conclusions While the Diabetes-CAT demonstrated clear advantages in reducing respondent burden as compared to the full-length tool , simplifying the item bank will be necessary for enhancing the feasibility of the Diabetes-CAT for use with low literacy patients Abstract BACKGROUND : Patients ’ ability to manage medications is critical to chronic disease control . Also known as medication management capacity ( MMC ) , it includes the ability to correctly identify medications and describe how they should be taken . OBJECTIVE : To evaluate the effects of low literacy , medication regimen complexity , and sociodemographic characteristics on MMC . DESIGN : Cross-sectional analysis of enrollment data from participants in a r and omized trial . PARTICIPANTS : Patients with coronary heart disease in an inner-city clinic . MEASUREMENTS : Medication management capacity was measured with the Drug Regimen Unassisted Grading Scale ( DRUGS ) , which scores subjects ’ ability to identify , open , describe the dose , and describe the timing of their medications . DRUGS overall and component scores were compared by literacy . Mini Mental State Exam score , regimen complexity ( number of prescription medications ) , and sociodemographic characteristics . RESULTS : Most of the 152 participants were elderly ( mean age 65.4 years ) , women ( 54.6 % ) , and African American ( 94.1 % ) . Approximately half ( 50.7 % ) had inadequate literacy skills , and 28.9 % had marginal skills . In univariate analysis , MMC was significantly associated with literacy ( P<.001 ) , and this effect was driven by the ability to identify medications . In multivariable models , patients with inadequate literacy skills had 10 to 18 times the odds of being unable to identify all of their medications , compared with those with adequate literacy skills ( P<.05 ) . CONCLUSIONS : Adults with inadequate literacy skills have less ability to identify their medications . Techniques are needed to better educate low-literacy patients about their medications , as a potential strategy to enhance adherence BACKGROUND Professional organizations recommend that physicians discuss prostate cancer with patients to make individual screening decisions . However , few studies have tested strategies to encourage such discussion s , particularly among high-risk population s. We examined the effects of two low-literacy interventions on the frequency of prostate cancer discussion and screening . DESIGN R and omized , blinded , controlled trial with concealed allocation . SETTING / PARTICIPANTS Inner-city primary care clinic , serving a predominately African-American population . Participants were men aged 45 - 70 with no history of prostate cancer , presenting for a regular appointment . INTERVENTIONS While waiting to see their physician , patients received a patient education h and out on prostate cancer screening ( PtEd ) , a h and out simply encouraging patients to talk to their doctor about prostate cancer ( Cue ) , or a control h and out . The interventions did not advocate for or against screening . MEASURES Patient-reported discussion of prostate cancer with the physician and chart review s determine prostate-specific antigen ( PSA ) test orders and performance of digital rectal examination ( DRE ) . Adjusted odds ratios ( aOR ) and 95 % confidence intervals ( CI ) were computed . Data were collected in 2003 , and analyses were completed in 2006 . RESULTS Most of the 250 subjects ( 90.4 % ) were African American and 78.8 % read below the ninth grade level . Overall , 48.4 % reported discussing prostate cancer during the appointment . Compared to the control group ( 37.3 % ) , discussion s were significantly more common in the Cue group ( 58.0 % , aOR=2.39 [ 1.26 - 4.52 ] ) , as well as in the PtEd group ( 50.0 % , aOR=1.92 [ 1.01 - 3.65 ] ) . When prostate cancer was discussed , patients in the intervention groups more commonly initiated the conversation ( 47.6 % PtEd and 40.0 % Cue , vs 9.7 % control , p<0.01 for each comparison to control ) . Compared to the control group ( 2.4 % ) , PSA test orders increased in the PtEd group ( 14.1 % , aOR=7.62 [ 1.62 - 35.83 ] ) and in the Cue group ( 12.3 % , aOR=5.86 [ 1.24 - 27.81 ] ) . Documentation of DRE did not change significantly ( 4.7 % PtEd , 6.2 % Cue , and 6.0 % control ) . CONCLUSIONS Two simple low-literacy interventions significantly increased discussion of prostate cancer and PSA test orders but not performance of DRE . Both interventions were effective in empowering low-literacy patients to initiate conversations about prostate cancer with their physician BACKGROUND Research ers have pointed out several factors that correlated with or influenced autonomy in older people . However , these studies covered only a range of socio-demographic or physical factors , while factors from psychosociological and spiritual domains remain ignored . Also , there is lack of quantitative research and publications in this area . OBJECTIVES To explore factors related to autonomy among elders in a senior citizen home . DESIGN A cross-sectional design utilizing a correlational approach was adopted . PARTICIPANTS A stratified r and om sample of 121 subjects older than 64 years was recruited at a senior citizen home . METHODS Question naires and interviews were used to collect data . The structured question naire consisted of five parts , each gauging socio-demographic information , life attitudes , frequency and satisfaction of social support , and autonomy . Descriptive and stepwise multiple linear regression analysis were used to analyze the data . FINDINGS Subjects had a high autonomy score ( mean = 3.63 ) , with the greatest score in independence ( mean = 4.39 ) , followed by individuality ( mean = 3.74 ) and freedom ( mean = 3.22 ) . Multiple regression analysis showed that satisfaction of social support ( beta = .57 ) , functional ability ( beta = .25 ) , life attitudes ( beta = .20 ) , and level of education ( beta = .14 ) significantly affected autonomy in these elderly subjects and explained 64.2 % of the total variance of autonomy in this population . CONCLUSIONS Findings from this study indicate that perceived autonomy is influenced by social support , functional ability , life attitude , and literacy among institutionalized elders Abstract OBJECTIVE : Adherence to complex antiretroviral therapy ( ART ) is critical for HIV treatment but difficult to achieve . The development of interventions to improve adherence requires detailed information regarding barriers to adherence . However , short follow-up and inadequate adherence measures have hampered such determinations . We sought to assess predictors of long-term ( up to 1 year ) adherence to newly initiated combination ART using an accurate , objective adherence measure . DESIGN : A prospect i ve cohort study of 140 HIV-infected patients at a county hospital HIV clinic during the year following initiation of a new highly active ART regimen . MEASURES AND MAIN RESULTS : We measured adherence every 4 weeks , computing a composite score from electronic medication bottle caps , pill count and self-report . We evaluated patient demographic , biomedical , and psychosocial characteristics , features of the regimen , and relationship with one ’s HIV provider as predictors of adherence over 48 weeks . On average , subjects took 71 % of prescribed doses with over 95 % of patients achieving suboptimal ( < 95 % ) adherence . In multivariate analyses , African-American ethnicity , lower income and education , alcohol use , higher dose frequency , and fewer adherence aids ( e.g. , pillboxes , timers ) were independently associated with worse adherence . After adjusting for demographic and clinical factors , those actively using drugs took 59 % of doses versus 72 % for nonusers , and those drinking alcohol took 66 % of doses versus 74 % for nondrinkers . Patients with more antiretroviral doses per day adhered less well . Participants using no adherence aids took 68 % of doses versus 76 % for those in the upper quartile of number of adherence aids used . CONCLUSIONS : Nearly all patients ’ adherence levels were suboptimal , demonstrating the critical need for programs to assist patients with medication taking . Interventions that assess and treat substance abuse and incorporate adherence aids may be particularly helpful and warrant further study OBJECTIVE To compare a simple meal plan emphasizing healthy food choices with a traditional exchange-based meal plan in reducing HbA(1c ) levels in urban African Americans with type 2 diabetes . RESEARCH DESIGN AND METHODS A total of 648 patients with type 2 diabetes were r and omized to receive instruction in either a healthy food choices meal plan ( HFC ) or an exchange-based meal plan ( EXCH ) to compare the impact on glycemic control , weight loss , serum lipids , and blood pressure at 6 months of follow-up . Dietary practice s were assessed with food frequency question naires . RESULTS At presentation , the HFC and EXCH groups were comparable in age ( 52 years ) , sex ( 65 % women ) , weight ( 94 kg ) , BMI ( 33.5 ) , duration of diabetes ( 4.8 years ) , fasting plasma glucose ( 10.5 mmol/l ) , and HbA(1c ) ( 9.4 % ) . Improvements in glycemic control over 6 months were significant ( P < 0.0001 ) but similar in both groups : HbA(1c ) decreased from 9.7 to 7.8 % with the HFC and from 9.6 to 7.7 % with the EXCH . Improvements in HDL cholesterol and triglycerides were comparable in both groups , whereas other lipids and blood pressure were not altered . The HFC and EXCH groups exhibited similar improvement in dietary practice s with respect to intake of fats and sugar sweetened foods . Among obese patients , average weight change , the percentage of patients losing weight , and the distribution of weight lost were comparable with the two approaches . CONCLUSIONS Medical nutrition therapy is effective in urban African Americans with type 2 diabetes . Either a meal plan emphasizing guidelines for healthy food choices or a low literacy exchange method is equally effective as a meal planning approach . Because the HFC meal plan may be easier to teach and easier for patients to underst and , it may be preferable for low-literacy patient population Patients are increasingly being exposed to quantitative information about risks for disease and benefits of treatment . Many authors [ 1 - 6 ] believe that the use of such information is an important component of informed decision making ; others cl aim that only patients given such information can make truly informed choices . This position is reflected in the recent decision of the National Institutes of Health Consensus Panel not to make a recommendation about screening mammography for women aged 40 to 49 years but to advocate that these women make their own decisions about screening on the basis of their personal evaluation of risks and benefits [ 7 ] . This strategy , however , is based on the assumption that patients underst and quantitative information . Research in this area has largely focused on how simple changes in the format of numerical information can influence choices , a concept referred to as framing [ 8 - 20 ] . But just as it is premature to worry about wording before knowing whether patients can read , it may be premature to worry about framing before knowing whether patients can underst and and manipulate numbers . In fact , evidence suggests that many persons do not work well with numbers [ 21 , 22 ] . It is likely that quantitative information is only meaningful to the extent that patients have some facility with basic probability and numerical concepts , a construct called numeracy . To learn more about the role of numeracy in communicating information about risk , we studied women 's comprehension of messages about mammography . Our goal was to underst and how numeracy affects women 's ability to gauge the benefit of mammography after receiving quantitative information . We provided women with typical risk reduction expressions about mammography , framed in relative and absolute terms , to study how well they could make use of such information . We hypothesized that the ability to use quantitative risk information would be related to the level of numeracy . Methods Study Design and Sample In December 1995 , we drew a simple r and om sample of 500 women from a registry of female veterans maintained at the Department of Veterans Affairs Medical Center , White River Junction , Vermont . These women were mailed one of four question naires , which differed only in how the same information on average risk reduction with mammography was presented . Reminder letters were sent to nonrespondents after 2 weeks , and new copies of the question naire were mailed after 4 weeks . The study was closed in February 1996 . Because of errors in the registry , 26 entries in our sample were not usable ( 10 of the listed persons were deceased , and 16 either were not female veterans or were listed twice ) . Thus , our possible respondent pool totaled 474 , of which 302 ( 64 % ) returned the question naire . The returned surveys sometimes contained unanswered questions . Such blanks may represent information about the respondent 's abilities , or they may be a marker of an unmotivated respondent or one who has become fatigued from the survey burden . To remove those who were unmotivated or fatigued , we required completion of four of the five questions on the last page of the survey for inclusion in the analyses . Only 15 women did not meet this criterion . Thus , our final sample comprised 287 women , for a 61 % completion rate . Unanswered numeracy questions were considered wrong answers . Restricting the sample to women who answered these questions yielded results similar to those seen with the entire sample . Question naire Design Assessment of Numeracy Numeracy was assessed with three questions and was scored as the total number of correct responses . The first question assessed basic familiarity with probability : Imagine that we flip a fair coin 1,000 times . What is your best guess about how many times the coin would come up heads in 1,000 flips ? _ _ _ _ times out of 1,000 . The second question asked respondents to convert a percentage ( 1 % ) to a proportion ( 10 in 1000 ) : In the BIG BUCKS LOTTERY , the chance of winning a $ 10 prize is 1 % . What is your best guess about how many people would win a $ 10 prize if 1000 people each buy a single ticket to BIG BUCKS?____person(s ) out of 1,000 . The third question reversed this task , asking the respondent to convert a proportion ( 1 in 1000 ) to a percentage ( 0.1 % ) : In ACME PUBLISHING SWEEPSAKES , the chance of winning a car is 1 in 1,000 . What percent of tickets to ACME PUBLISHING SWEEPSAKES win a car?____% . Presentation of Risk Reduction Data We r and omly assigned each of the 500 women to receive one of four question naires ; the question naires differed only in how the information on risk reduction was framed ( Figure 1 ) . Risk reduction data were framed as a 33 % relative risk reduction , a 33 % relative risk reduction together with the baseline risk for death from breast cancer in the next 10 years , a 4 in 1000 absolute risk reduction , or a 4 in 1000 absolute risk reduction together with the baseline risk for death from breast cancer in the next 10 years . Figure 1 . Overview of the task presented to a woman completing the survey and our measures of her ability to accurately apply risk reduction information . Assessment of Perceived Benefit To assess their perceived risk for death from breast cancer with and without mammography ( Figure 1 ) , women were asked to do the following : Imagine 1,000 women exactly like you . Of these women , what is your best guess about how many will die from breast cancer during the next 10 years if they are not screened every year for breast cancer by mammogram _ _ _ _ _ out of 1000 they are screened every year for breast cancer by mammogram _ _ _ _ _ out of 1000 Calculation of Accuracy To see how accurately respondents applied the risk reduction data that they were given , we compared their perceived risk for death from breast cancer with mammography with their perceived risk for death without mammography ( Figure 1 ) . Accuracy was judged by the ability to adjust perceived risk in accordance with the risk reduction data presented . Accuracy was judged solely by the change between perceived risk with mammography and perceived risk without mammography , which we calculated from the responses to these two questions . Thus , women could grossly overestimate their risk while still accurately applying the risk reduction information . In fact , many women did overestimate their perceived risk without mammography , as observed in previous work [ 23 ] . For the two groups presented with the absolute risk reduction , we subtracted each woman 's perceived risk with mammography from her perceived risk without mammography . For example , a woman who perceived her risk to be 100 out of 1000 without mammography and 96 out of 1000 with mammography indicated an absolute risk reduction of 4 out of 1000 . Because the women in these groups were told that mammography decreases the risk for death from breast cancer by 4 in 1000 , only women whose responses indicated an absolute risk reduction of 4 in 1000 were judged to be accurate . For the two groups presented with the relative risk reduction , we determined the percentage reduction between the perceived risk without mammography and the perceived risk with mammography . For example , a woman with a perceived risk of 100 out of 1000 without mammography and 67 out of 1000 with mammography indicated a 33 % risk reduction . The women in these groups were told that mammography decreases the risk for death from breast cancer by 33 % . To allow for rounding off , women whose responses indicated a relative risk reduction between 30 % and 40 % were judged to be accurate . Statistical Analysis For the assessment of both numeracy and accuracy , the percentage of the sample that had correct answers for each measure was calculated as the number of respondents with correct responses divided by the total number of respondents ( n = 287 ) . Chi-square tests and Kruskal-Wallis tests were used to compare participant characteristics across the four groups . All comparisons were two-sided and were considered statistically significant at a P value of less than 0.05 . We used multiple logistic regression to assess the relation between accuracy in applying the risk reduction information ( dependent variable ) and numeracy ( independent variable ) after adjusting for age , income , education , and the framing of the information provided . Role of the Funding Sponsor This research was funded by the Department of Veterans Affairs Fellowship Program in Ambulatory Care and the Department of Defense 's Breast Cancer Research Program . Neither department had any role in the gathering , analysis , or interpretation of the data or in deciding whether to su bmi t the report for publication . Results Study Sample Overall , the study sample consisted of older female veterans , almost all of whom had at least a high school education . Most reported having annual household incomes of less than $ 25 000 , and fewer than one fourth were currently employed ( Table 1 ) . Most reported having had at least one mammogram , and 9 % had a history of breast cancer . No significant differences were seen in any characteristic across the four groups . Table 1 . Characteristics of the Study Sample * Assessment of Numeracy Almost half of the women ( 46 % ) answered the coin-flip question ( which asked how many times a coin would come up heads in 1000 flips ) incorrectly , raising questions about basic underst and ing of probability . Incorrect answers ranged from 0 to 800 and were largely underestimates ( one third of the sample thought that 1000 flips of a fair coin would result in < 300 heads ) . The most common incorrect answers were 25 , 50 , and 250 . Women also had trouble converting between percentages and probability expressions . The difficulty was greater for the conversion of 1 in 1000 to 0.1 % than for the conversion of 1 % to 10 in 1000 . Although 46 % of 287 respondents were unable to convert 1 % to 10 in 1000 , 80 % were unable to convert 1 in 1000 to 0.1 % . The total number of correct responses to these three simple tasks were as OBJECTIVE To explore the contribution of biologic risk factors versus socio-demographic and environmental risk factors in cognitive development of children with birth weight less than 2000 g , at the age of 12 years . DESIGN Prospect i ve cohort study . SETTING Infants discharged from a NICU of a referral hospital , with birth weight less than 2000 g between 1987 - 89 and followed up in the High Risk Clinic . METHODS The children were assessed at the age of 12 years , with the Weschler 's Intelligence Scale for IQ and by Wide Range Achievement Test for mathematics skills . Mother 's education , father 's education , socio-economic status , family structure , spaciousness of the house , the locality in which the child lived and the type of school the child attended , were all recorded . A stimulation score was determined at 6 and 12 months and 3 years . Family environment score was used at 12 years . RESULTS The cohort consisted of 180 children , with 90 controls . The mean IQ of the study group was 89.5 + - 16.9 , which was significantly lower than that of controls ( 97.2 + - 14.1 ) ( P < 0.05 ) . The mathematical skills of the study group were significantly poorer ( P < 0.05 ) than that of controls . A multiple linear regression analysis was done using IQ as the dependent variable and all risk factors at birth , stimulation scores and socio-environmental factors as independent variables . Mothers education was the most important factor contributing to the total IQ , a variance of 25.2 % of the total variance 44.2 PERCENT . Fathers education emerged as an important factor for mathematics skills . School was the next important factor for IQ as well as academics . Controlling for all other background factors , birth weight was the only biologic factor of significance , and this had a very small contribution . CONCLUSION Parental education and the type of school attended by the child were the most important factors influencing cognitive development . The only biologic factor of importance was birth weight , but this too had a very small contribution The purpose of this study was to test the effect of a motivational message on the intention of laypersons to learn cardiopulmonary resuscitation ( CPR ) and automated external defibrillator ( AED ) use . A pretest-posttest , double-blind , r and omized design was used with 220 community-dwelling adults . Participants were r and omly assigned to the treatment group reading the CPR and AED pamphlet emphasizing learning CPR and AED use to save someone they love and the 3-minute window for response time ; or to the comparison group reading the identical pamphlet without the 2 motivational statements . Intention to learn CPR and AED use and to look for AEDs in public areas was measured before and after reading the respective pamphlet . No significant difference emerged between the groups for the number of participants planning to learn CPR and AED use . A significant number of participants in both groups increased intention to learn CPR and AED use . Significantly more treatment participants than comparison participants planned to routinely look for AEDs in public areas after reading the pamphlet , however . Teaching critical facts such as the low survival rate for out-of-hospital cardiac arrest might encourage laypersons to learn CPR and AED use . Routinely teaching family members of people at risk for a cardiac arrest about the short window of time in which CPR and AED use must begin and encouraging them to learn about CPR and AEDs to save someone they love may encourage family members to identify the location of AEDs in public places OBJECTIVE Personality characteristics are assumed to underlie health behaviors and , thus , a variety of health outcomes . Our aim was to examine prospect ively whether personality traits predict short- and long-term weight loss after laparoscopic adjustable gastric b and ing . RESEARCH METHODS AND PROCEDURES Of patients undergoing laparoscopic adjustable gastric b and ing , 168 ( 143 women , 25 men , 18 to 58 years old , mean 37 years , preoperative BMI 45.9 + /- 5.6 kg/m(2 ) ) completed the Dutch Personality Question naire on average 1.5 years before the operation . The relationship between preoperative personality and short- and long-term postoperative weight loss was determined using multilevel regression analysis . RESULTS The average weight loss of patients progressively increased to 10 BMI points until 18 months after surgery and stabilized thereafter . A lower baseline BMI , being a man , and a higher educational level were associated with a lower weight loss . None of the personality variables was associated with weight outcome at short-term follow-up . Six of seven personality variables did not predict long-term weight outcome . Egoism was associated with less weight loss in the long-term postoperative period . The effect sizes of the significant predictions were small . DISCUSSION None of the personality variables predicted short-term weight outcome , and only one variable showed a small and unexpected association with long-term weight outcome that needs confirmation . This suggests that personality assessment as intake psychological screening is of little use for the prediction of a poor or successful weight outcome after bariatric surgery We report on a prospect i ve longitudinal research programme exploring the connection between language acquisition deficits and dyslexia . The language development profile of children at-risk for dyslexia is compared to that of age-matched controls as well as of children who have been diagnosed with specific language impairment ( SLI ) . The experiments described concern the perception and production of grammatical morphology , categorical perception of speech sounds , phonological processing ( non-word repetition ) , mispronunciation detection , and rhyme detection . The results of each of these indicate that the at-risk children as a group underperform in comparison to the controls , and that , in most cases , they approach the SLI group . It can be concluded that dyslexia most likely has precursors in language development , also in domains other than those traditionally considered conditional for the acquisition of literacy skills . The dyslexia-SLI connection awaits further , particularly qualitative , analyses Purpose We sought to describe the prevalence and patterns of use of personal digital assistants ( PDAs ) among active nurse practitioners ( NPs ) . Data sources A descriptive correlational survey was conducted among NPs in the United States ( N= 126 ) . Participants were r and omly selected from members of the American Academy of Nurse Practitioners who had listed a practice site on their application . Conclusions Sixty-four percent of participants used PDAs . A drug reference was reported to be the most useful and frequently installed application . A large majority of PDA users believed that PDA use supported clinical decision making ( 91 % ) , promoted patient safety ( 89 % ) , and increased productivity ( 75 % ) . Sixty-two percent predicted that PDA use would change their practice within the next 5 years . Implication s for practice As innovative PDA applications with potential to improve patient outcomes become increasingly available , h and held computer skills will be a fundamental practice competency . To prevent errors in clinical decision making with quick access to PDA reference material s , NPs must critically evaluate the legitimacy and worth of PDA software programs . There is a critical need to evaluate the effectiveness of PDA use in clinical setting s and develop an evidence base to guide use of the PDA in solving clinical problems CONTEXT Increased fruit and vegetable intake can reduce cancer risk . Information from this study contributes to research exploring health disparities in high-risk dietary behavior . PURPOSE Changes in fruit and vegetable behavior were evaluated to assess the effects of a low-intensity , physician-endorsed dietary intervention in a rural population . METHODS The study was a r and omized trial of 754 patients from 3 physician practice s in rural Virginia . Low-literacy nutrition education material s and personalized dietary feedback were administered by mail and telephone . Mixed model analysis of variance was used to determine the effect of the intervention on fruit and vegetable intake behavior , knowledge , intentions , and self-efficacy at 1 , 6 , and 12 months . FINDINGS The intervention effect was moderated by age , race , sex , and education . Intake at 1 and 6 months was increased for older and younger participants and those with some college , and further maintained at 12 months by those who did not complete high school . African Americans in the intervention group displayed significantly greater intentions to increase fruit/vegetable intake than whites/others . Knowledge of fruit/vegetable recommendations significantly increased in the intervention group at 12 months , particularly for men . CONCLUSIONS For the rural population , a low-intensity physician-endorsed self-help dietary intervention was successful in initiating fruit and vegetable dietary changes at 1 and 6 months post-intervention , and increasing intentions to change in African Americans . The relationship of the moderating effects of age , race , sex and education need to be further explored in relation to dietary intervention and dietary behavior change for the rural population OBJECTIVE To examine concurrent physical , educational , behavioural , social and family factors associated with cigarette smoking in adolescents at 14 years . METHODOLOGY This study reports cross-sectional data on 14-year-old adolescents and their mothers , drawn from a prospect i ve cohort study commencing at the time of the first antenatal visit . At 14 years , 5247 adolescents completed question naires on current cigarette smoking . Adolescents and mothers completed health , psychological , school and social question naires relating to the youth . A total of 3864 adolescents were assessed physically , and undertook the Wide Range Achievement Test ( WRAT ) and Ravens Progressive Matrices Test . RESULTS Cigarette smoking at 14 years was associated with externalizing and internalizing behaviour problems , school suspension , contact with children 's services and alcohol/illicit drug use . Apart from internalizing behaviour problems , these problems were more prevalent in boys . Poor school performance on maternal/adolescent reports was associated with increased smoking quantity for both genders , though WRAT scores were only decreased in male smokers . The Ravens Progressive Matrices Test scores were lower for boys with greater smoking quantity . The trend was less marked in girls . Body mass index and exercise frequency were not associated with cigarette smoking at 14 years , though girls who smoked had a higher reported prevalence of asthma . Parental smoking , marital conflict , maternal depression , lower income , and mothers aged in their teens and with a lower level of education at the time of this pregnancy were also positively associated with adolescent tobacco use . CONCLUSION Findings of this study indicate that cigarette smoking , at this critical time of smoking initiation , is associated with a broad spectrum of personal and social disadvantage that needs to be considered in intervention strategies CONTEXT As the availability of and dem and for genetic testing for hereditary cancers increases in primary care and other clinical setting s , alternative or adjunct educational methods to traditional genetic counseling will be needed . OBJECTIVE To compare the effectiveness of a computer-based decision aid with st and ard genetic counseling for educating women about BRCA1 and BRCA2 genetic testing . DESIGN R and omized controlled trial conducted from May 2000 to September 2002 . SETTING AND PARTICIPANTS Outpatient clinics offering cancer genetic counseling at 6 US medical centers enrolled 211 women with personal or family histories of breast cancer . INTERVENTIONS St and ard one-on-one genetic counseling ( n = 105 ) or education by a computer program followed by genetic counseling ( n = 106 ) . MAIN OUTCOME MEASURES Participants ' knowledge , risk perception , intention to undergo genetic testing , decisional conflict , satisfaction with decision , anxiety , and satisfaction with the intervention . Counselor group measures were administered at baseline and after counseling . Computer group measures were administered at baseline , after computer use , and after counseling . Testing decisions were assessed at 1 and 6 months . Outcomes were analyzed by high vs low risk of carrying a BRCA1 or BRCA2 mutation . RESULTS Both groups had comparable demographics , prior computer experience , medical literacy , and baseline knowledge of breast cancer and genetic testing , and both counseling and computer use were rated highly . Knowledge scores increased in both groups ( P<.001 ) regardless of risk status , and change in knowledge was greater in the computer group compared with the counselor group ( P = .03 ) among women at low risk of carrying a mutation . Perception of absolute risk of breast cancer decreased significantly after either intervention among all participants . Intention to undergo testing decreased significantly after either intervention among low-risk but not high-risk women . The counselor group had lower mean scores on a decisional conflict scale ( P = .04 ) and , in low-risk women , higher mean scores on a satisfaction-with-decision scale ( P = .001 ) . Mean state anxiety scores were reduced by counseling but were within normal ranges for both groups at baseline and after either intervention , regardless of risk status . CONCLUSIONS An interactive computer program was more effective than st and ard genetic counseling for increasing knowledge of breast cancer and genetic testing among women at low risk of carrying a BRCA1 or BRCA2 mutation . However , genetic counseling was more effective than the computer at reducing women 's anxiety and facilitating more accurate risk perceptions . These results suggest that this computer program has the potential to st and alone as an educational intervention for low-risk women but should be used as a supplement to genetic counseling for those at high risk Healthy control participants ( 46 women , M age = 44.3 yr . , SD = 7.6 ; 29 men ) were recruited to undergo a comprehensive neuropsychological battery and serve as a comparison group in a study of cognitive functioning in patients with Lyme disease . Participants were selected using Mitofsky-Waksberg r and om digit dialing . The Buschke 12-word , six-trial Selective Reminding Test was administered as part of the neuropsychological battery and normative data are presented stratified by age and sex . Performance on alternate forms of this measure were examined . Mean education , intelligence quotient , and Wide Range Achievement Test-3 Reading scores are reported OBJECTIVE The authors present data from a pilot research program initiated to develop , refine , and test the outcomes of Brief Problem-Solving Therapy in Home Care ( PST-HC ) that targets the needs of older adults identified with severe depressive symptoms in an acute home care setting . METHODS A pilot r and omized clinical trial compared the impact of PST-HC to usual care ( UC ) in a sample of older medically ill home care patients identified with severe depressive symptoms . Forty patients were r and omly assigned to either six weekly sessions of PST-HC in their home or st and ard home care services . Depression , quality of life , and problem-solving ability were measured at baseline , posttreatment , three-month follow-up , and six-month follow-up by blinded evaluators . RESULTS All 40 patients provided follow-up data . No differences between the two groups were found on any demographic variables . Outcome data suggested significant improvements in depression scores over time after PST-HC , relative to UC . PST-HC patients reported higher quality of life and problem-solving ability scores relative to UC . CONCLUSION Results suggest that PST-HC is well tolerated and holds promise for reducing persistent depressive symptoms . The authors discuss limitations in terms of the " real-world " applicability of this psychosocial treatment for late-life depression Children with developmental dyslexia struggle to learn to read and spell despite adequate intelligence and educational opportunity . Several lines of research are attempting to establish the neurobiological basis of dyslexia , and low-level sensory and motor deficits have been found in dyslexic population s ; furthermore , behavioural and imaging data point to cerebellar dysfunction in dyslexia . To investigate this , normal readers ( n=19 ) and children with developmental dyslexia ( n=16 ) were asked to perform various cognitive , literacy , and balancing tasks . Children balanced on the left or right foot , with eyes open or closed , for a period of 10 s during which their movements were recorded with a motion-tracking system . Dyslexic children were less stable than the control children in both eyes-open conditions ( left foot P=0.02 , right foot P=0.012 ) . While there were no group differences during the eyes-closed conditions , the dyslexic children dropped a foot to correct balance significantly more often than control children ( P<0.05 ) . Incidence analysis showed that 50 % of the dyslexic group fell into the ‘ impaired ’ category on the eyes-open balancing tasks ; when the mean balancing scores and the foot drops were considered , only three of our dyslexic children showed no evidence of balancing difficulties . There were strong correlations between reading and spelling scores and the mean eyes-open balancing score ( r=0.52 and 0.44 , respectively ) . Thus , while not all children with developmental dyslexia show impaired balancing skills , low-level motor dysfunction may be associated with impaired literacy development . This could be due to several factors , including the involvement of the cerebellum , the magnocellular system , or more general developmental immaturity Health inequity is an emerging issue all over the world . Some population s living in specific geographic areas may have less access to basic health facilities . Therefore , a sample survey of households was carried out to study access of different population groups to reproductive and child health . Cluster sampling technique was used to select 30 clusters ( 18 urban , 9 slum , and 3 rural ) from Ch and igarh Union Territory in India . From each of these clusters , 40 households were selected r and omly . Data were collected using a st and ard question naire developed by UNICEF from April to June 2006 by graduate male and female field workers who were specially recruited and trained for this purpose . A total of 5383 individuals were studied in 1200 sample households with proportionate representation from urban ( 56 % ) , slum ( 33 % ) , and rural ( 11 % ) areas . Literacy rate was higher ( 94.3 % ) in urban than the rural ( 80.6 % ) and slum ( 65.3 % ) areas . About 68 % of the deliveries were at home and not assisted by a skilled birth attendant ( nurse , midwife , or doctor ) in the slums , compared to 21 % and 7 % in rural and urban areas ( p < 0.001 ) , respectively . Fully immunized children at the age of 2 years were 30 % in slums as compared to 74 % and 62.5 % in urban and rural areas ( p < 0.001 ) , respectively . Hib vaccination , which is to be bought at a considerable cost , was nil in slum areas compared to 79 % in urban and 45 % in rural area . Contraceptive prevalence was significantly more in urban ( 73 % ) and rural areas ( 75 % ) compared to the slum areas ( 53.4 % ) ( p < 0.05 ) . It was concluded that reproductive and child health service coverage has large differences in various population groups . Special interventions should be undertaken on a priority basis to bridge the gaps so as to achieve millennium development goals in all population groups Design : Mailed survey to a stratified r and om sample of all medical practice s in Massachusetts in 2005 , with one physician per practice r and omly selected for survey . Measurements : EHR adoption rates . Results : The response rate was 71 % ( 1345/1884 ) . Overall , while 45 % of physicians were using an EHR , EHRs were present in only 23 % of practice s. In multivariate analysis , practice size was strongly correlated with EHR adoption ; 52 % of practice s with 7 or more physicians had an EHR , as compared with 14 % of solo practice s ( adjusted odds ratio , 3.66 ; 95 % confidence interval , 2.28–5.87 ) . Hospital-based practice s ( adjusted odds ratio , 2.44 ; 95 % confidence interval , 1.53–3.91 ) and practice s that teach medical students or residents ( adjusted odds ratio , 2.30 ; 95 % confidence interval , 1.60–3.31 ) were more likely to have an EHR . The most frequently cited barriers to adoption were start-up financial costs ( 84 % ) , ongoing financial costs ( 82 % ) , and loss of productivity ( 81 % ) . Conclusions : While almost half of physicians in Massachusetts are using an EHR , fewer than one in four practice s in Massachusetts have adopted EHRs . Adoption rates are lower in smaller practice s , those not affiliated with hospitals , and those that do not teach medical students or residents . Interventions to exp and EHR use must address both financial and non-financial barriers , especially among smaller practice s. J Am Med Inform Assoc . 2007;14:110–117 . DOI 10.1197/jamia . M2187 . by gest on Sptem er 5 , 2016 PURPOSE To explore social functioning and psychological well-being in a population -based cohort of epilepsy patients compared to matched controls . METHODS A r and om sample of patients with epilepsy ( N = 347 ) and a healthy control group ( N = 430 ) matched for age , gender and domicile were identified through National Registry of Social Insurance Institution in Finl and . The data were collected by postal question naire assessing various factors related to social and psychological well-being and were analyzed by using linear regression analysis to compare the study and control groups . RESULTS The age at onset of epilepsy was significantly associated with the level of further education and the level of seizure control with the employment status . The patients with epilepsy and lower level of basic education had also significantly lower level of further education , employment , and fewer social relations . Some differences in psychological well-being were also seen in those with matriculation examination when compared to matched controls . CONCLUSIONS In young adults with well-controlled epilepsy and successful basic education , social functioning is comparable with healthy peers . The importance of all social and educational support during the time of basic education may be crucial to favorable intellectual , functional , and social development later in life . Both professional and informal support is needed in adjunct to conventional treament of epilepsy , which is emphasized BACKGROUND While limited literacy is common and its prevalence increases with age , no prospect i ve study has assessed whether limited literacy is associated with mortality in older adults . OBJECTIVE To assess the association of limited literacy with mortality . DESIGN AND SETTING Five-year prospect i ve study from 1999 to 2004 of community-dwelling elders from Memphis , TN , and Pittsburgh , PA , who were from the Health , Aging , and Body Composition study . Subjects ' literacy was assessed with the Rapid Estimate of Adult Literacy in Medicine . Scores were categorized into limited ( 0 to 8th grade reading level ) or adequate literacy ( > or = 9th grade reading level ) . PARTICIPANTS Two thous and five hundred and twelve black and white elders without baseline functional difficulties or dementia . MEASUREMENTS Time to death . RESULTS Participants ' mean age was 75.6 years , 48 % were male , 38 % were black , and 24 % had limited literacy ; the median follow-up time was 4.2 years . Compared with those with adequate literacy , those with limited literacy had a higher risk of death ( 19.7 % vs 10.6 % ) with a hazard ratio ( HR ) of 2.03 ( 95 % confidence intervals [ CI ] , 1.62 to 2.55 ) . After adjusting for demographics and socioeconomic status , co-morbid conditions , self-rated health status , health-related behaviors , health care access measures , and psychosocial status , limited literacy remained independently associated with mortality ( HR 1.75 ; 95 % CI , 1.27 to 2.41 ) . CONCLUSIONS Limited literacy is independently associated with a nearly 2-fold increase in mortality in the elderly . Given the growth of the aging population and the prevalence of chronic diseases , the mechanisms by which limited literacy is associated with mortality in the elderly warrant further investigation BACKGROUND Individuals with low levels of health literacy have less health knowledge , worse self-management of chronic disease , lower use of preventive services , and worse health in cross-sectional studies . We sought to determine whether low health literacy levels independently predict overall and cause-specific mortality . METHODS We design ed a prospect i ve cohort study of 3260 Medicare managed-care enrollees in 4 US metropolitan areas who were interviewed in 1997 to determine their demographic characteristics , chronic conditions , self-reported physical and mental health , and health behaviors . Participants also completed the shortened version of the Test of Functional Health Literacy in Adults . Main outcome measures included all-cause and cause-specific ( cardiovascular , cancer , and other ) mortality using data from the National Death Index through 2003 . RESULTS The crude mortality rates for participants with adequate ( n = 2094 ) , marginal ( n = 366 ) , and inadequate ( n = 800 ) health literacy were 18.9 % , 28.7 % , and 39.4 % , respectively ( P < .001 ) . After adjusting for demographics , socioeconomic status , and baseline health , the hazard ratios for all-cause mortality were 1.52 ( 95 % confidence interval , 1.26 - 1.83 ) and 1.13 ( 95 % confidence interval , 0.90 - 1.41 ) for participants with inadequate and marginal health literacy , respectively , compared with participants with adequate health literacy . In contrast , years of school completed was only weakly associated with mortality in bivariate analyses and was not significant in multivariate models . Participants with inadequate health literacy had higher risk-adjusted rates of cardiovascular death but not of death due to cancer . CONCLUSIONS Inadequate health literacy , as measured by reading fluency , independently predicts all-cause mortality and cardiovascular death among community-dwelling elderly persons . Reading fluency is a more powerful variable than education for examining the association between socioeconomic status and health OBJECTIVE The primary objective of the current study was to examine the efficacy of single media literacy lessons in reducing media internalization in young adolescents . METHOD Eleven classes of 237 students ( 100 girls and 137 boys ; mean age = 13.79 years , SD = .42 ) r and omly received 1 of 6 lessons . Eating disorder risk factors were assessed at baseline , and the Sociocultural Attitudes Towards Appearance Question naire-3 ( SATAQ-3 ) was used to assess media internalization postintervention . RESULTS At postintervention , boys had significantly lower SATAQ-3 scores on 4 of the 5 subscales ( effect sizes = .42-.71 ) , whereas girls had significantly lower scores on 1 subscale ( effect size = .54 ) . Higher baseline levels of dietary restraint , magazines bought/read , and perceived sociocultural pressure predicted smaller reductions in boys ' scores , whereas depression predicted smaller reductions in girls ' scores . CONCLUSION The current study provides support that boys be included in eating disorder prevention programs and that media literacy may represent a promising prevention approach OBJECTIVES To assess the reproducibility and validity a 127-item , habitual intake , food-frequency question naire ( FFQ ) , developed for low-income and low-literacy Brazilian workers , by comparison with a 24-hour dietary recall ( 24-HDR ) . DESIGN The FFQ and 24-HDR were interviewer-administered at the local workplace to each subject twice , with a period of 6 months between estimates ; and four 24-HDRs were conducted during the 4-month period between the two FFQs ( FFQ1 and FFQ2 ) . Reproducibility was tested by comparing mean nutrient intakes from the two FFQs . Validity was determined by comparing the mean nutrient intakes from the FFQs with the corresponding averages of the six 24-HDRs ( reference method ) . SETTING Goiânia City , in Central West Brazil . SUBJECTS The study was based on 104 ( 62 women and 42 men ) subjects , aged 18 to 60 years , who were r and omly selected . RESULTS Dietary intake from the FFQ was higher than from the 24-HDR . Reproducibility was assessed by Pearson correlation coefficients for nutrients from FFQ1 and FFQ2 , and ranged from 0.23 for retinol to 0.69 for total energy ( mean 0.52 ) . Intra-class coefficients for nutrients averaged by the 24-HDRs ranged from 0.29 for vitamin C to 0.76 for total energy ; retinol was not significant . In the validation study , correlation between the FFQ and the 24-HDR ranged between 0.21 for vitamin C and 0.70 for total energy ( mean 0.50 ) . Adjusting for total energy lowered the coefficients , except for calcium , retinol and vitamin C. Coefficients increased with attenuation , ranging from 0.35 for carbohydrate to 0.65 for calcium . CONCLUSIONS Results indicate that this question naire had satisfactory reproducibility and reasonable validity Background Electronic health re sources are helpful only when people are able to use them , yet there remain few tools available to assess consumers ’ capacity for engaging in eHealth . Over 40 % of US and Canadian adults have low basic literacy levels , suggesting that eHealth re sources are likely to be inaccessible to large segments of the population . Using information technology for health requires eHealth literacy — the ability to read , use computers , search for information , underst and health information , and put it into context . The eHealth Literacy Scale ( eHEALS ) was design ed ( 1 ) to assess consumers ’ perceived skills at using information technology for health and ( 2 ) to aid in determining the fit between eHealth programs and consumers . Objectives The eHEALS is an 8-item measure of eHealth literacy developed to measure consumers ’ combined knowledge , comfort , and perceived skills at finding , evaluating , and applying electronic health information to health problems . The objective of the study was to psychometrically evaluate the properties of the eHEALS within a population context . A youth population was chosen as the focus for the initial development primarily because they have high levels of eHealth use and familiarity with information technology tools . Methods Data were collected at baseline , post-intervention , and 3- and 6-month follow-up using control group data as part of a single session , r and omized intervention trial evaluating Web-based eHealth programs . Scale reliability was tested using item analysis for internal consistency ( coefficient alpha ) and test-retest reliability estimates . Principal components factor analysis was used to determine the theoretical fit of the measures with the data . Results A total of 664 participants ( 370 boys ; 294 girls ) aged 13 to 21 ( mean = 14.95 ; SD = 1.24 ) completed the eHEALS at four time points over 6 months . Item analysis was performed on the 8-item scale at baseline , producing a tight fitting scale with α = .88 . Item-scale correlations ranged from r = .51 to .76 . Test-retest reliability showed modest stability over time from baseline to 6-month follow-up ( r = .68 to .40 ) . Principal components analysis produced a single factor solution ( 56 % of variance ) . Factor loadings ranged from .60 to .84 among the 8 items . Conclusions The eHEALS reliably and consistently captures the eHealth literacy concept in repeated administrations , showing promise as tool for assessing consumer comfort and skill in using information technology for health . Within a clinical environment , the eHEALS has the potential to serve as a means of identifying those who may or may not benefit from referrals to an eHealth intervention or re source . Further research needs to examine the applicability of the eHEALS to other population s and setting s while exploring the relationship between eHealth literacy and health care outcomes Rapid advances in information technology and media have made distance learning on the Internet possible . This new model of learning allows greater efficiency and flexibility in knowledge acquisition . Since basic computer competence is a prerequisite for this new learning model , this study was conducted to examine the basic computer competence of public health nurses in Taiwan and explore factors influencing computer competence . A national cross-sectional r and omized study was conducted with 329 public health nurses . A question naire was used to collect data and was delivered by mail . Results indicate that basic computer competence of public health nurses in Taiwan is still needs to be improved ( mean = 57.57 + - 2.83 , total score range from 26 - 130 ) . Among the five most frequently used software programs , nurses were most knowledgeable about Word and least knowledgeable about PowerPoint . Stepwise multiple regression analysis revealed eight variables ( weekly number of hours spent online at home , weekly amount of time spent online at work , weekly frequency of computer use at work , previous computer training , computer at workplace and Internet access , job position , education level , and age ) that significantly influenced computer competence , which accounted for 39.0 % of the variance . In conclusion , greater computer competence , broader educational programs regarding computer technology , and a greater emphasis on computers at work are necessary to increase the usefulness of distance learning via the Internet in Taiwan . Building a user-friendly environment is important in developing this new media model of learning for the future Family history is one the greatest risk factors for disease and one of the most important informational tools in medical genetics for the purpose of diagnosis , risk assessment , prevention and treatment . However , research is needed on the comparability of different methods of cancer family history assessment and the influence of psychosocial factors in family history reports . The purpose of this study was to determine if individuals had discrepancies between written and interview reports of cancer family history and the role of psychosocial factors in these discrepancies . Oncology patients ( n=104 ) were administered a survey to assess psychosocial factors ( i.e. , information-seeking , worry , perceived risk , and health literacy ) and were asked to provide family history in a written and an interview form . R and omization determined which form individuals received first . No differences in the amount of missing data or the amount of unspecified data were noted between the written and interview method . Psychosocial factors did not differentiate between those who had discrepancies in family history reports and those who did not have discrepancies in family history reports ; although there was a trend for those with lower literacy and those who were blunters to be more discrepant on type of cancer diagnosis . In sum , this preliminary study indicates that written and interview methods of family history assessment for first degree relatives may be used interchangeably . The ability to use written methods will facilitate collection of basic family history information in the oncology clinic This study examined associations between televised news regarding risk for future terrorism and youth outcomes and investigated the effects of training mothers in an empirically based approach to addressing such news with children . This approach -- Coping and Media Literacy (CML)--emphasized modeling , media literacy , and contingent reinforcement and was compared via r and omized design to Discussion as Usual ( DAU ) . Ninety community youth ( aged 7 - 13 years ) and their mothers viewed a televised news clip about the risk of future terrorism , and threat perceptions and state anxiety were assessed preclip , postclip , and post discussion . Children responded to the clip with elevated threat perceptions and anxiety . Children of CML-trained mothers exhibited lower threat perceptions than DAU youth at postclip and at post discussion . Additionally , CML-trained mothers exhibited lower threat perceptions and state anxiety at postclip and post discussion than did DAU mothers . Moreover , older youth responded to the clip with greater societal threat perception than did younger youth . Findings document associations between terrorism-related news , threat perceptions , and anxiety and support the utility of providing parents with strategies for addressing news with children . Implication s and research suggestions are discussed OBJECTIVE To investigate the cognitive performance and educational attainment at school-age of children with bronchopulmonary dysplasia ( BPD ) , compared with a preterm control group of children . METHODS Seventy preterm infants with BPD and 61 birth weight matched controls were prospect ively followed-up to school-age . The Weschler Intelligence Scale for Children - III ( WISC ) , the Wide Range Achievement Test ( WRAT ) and the Developmental Test of Visual Motor Integration ( VMI ) were administered . The results were compared between the two groups and multiple regression analyses were performed to determine the effect of confounding variables . RESULTS The children in the BPD group performed less well on the Full Scale IQ ( mean 86.7 vs 93.5 ; 95 % CI , 1.9 - 11.7 ) , Verbal IQ ( mean 87.1 vs 94.1 ; 95 % CI , 2.0 - 12.0 ) and the Performance IQ ( mean 88.6 vs 95.2 ; 95 % CI , 2.0 - 11.2 ) of the WISC , the reading component of the WRAT ( mean 93.8 vs 98.9 ; 95 % CI , 0.3 - 9.8 ) and the VMI ( mean 88.9 vs 93.3 ; 95 % , CI 1.1 - 7.8 ) . Despite controlling for social and biological variables , statistical differences persisted for Full Scale and Verbal IQ and reading . A Verbal IQ > 1 SD below the mean was found in 41 % of BPD children compared to 21 % of controls , while on the reading component of the WRAT a greater proportion of BPD children also had scores>1 SD below the mean . CONCLUSION Impaired psychoeducational performance was found in preterm children with BPD compared to controls , especially in the areas of language abilities and reading skills . This supports a greater need for special educational services and counseling for parents for these children In a r and omized trial of different data collection methods , we challenged the untested assumption that reliable data can not be obtained from lower-income and /or minority patients by self-administered question naires . We tested three methods of data collection among a sample of lower-income and minority patients ( n = 697 ) in Indianapolis at a site for the Type II Diabetes Patient Outcomes Research Team . The study included a question naire literacy screening instrument to assess patients ' functional literacy . Based on their functional literacy , patients were r and omized to one of three methods of data collection : mail-out/mail-back , h and -out/assisted , or the in-home interview . We constructed a tiered system for reassigning nonresponders to alternative methods of data collection , using the in-home interview as the fall-back strategy . We compared the response rates , item completion rates , and internal consistency reliabilities of self-reported health status measures between patients with and without literacy limitations and across the three methods of data collection . Patients with and without literacy limitations , across methods of data collection , provided high- quality data , as evidence d by high item completion rates ( > 84 % ) and high reliability assessment s ( internal consistency reliability coefficients > .80 ) for each health status measure . As part of the tiered study design , nonresponders r and omized to either the mail-out/mail-back or the h and -out/assisted method were interviewed . These patients were significantly older , had significantly lower education and income levels , and had significantly poorer self-reported visual function as compared with those who responded to the originally assigned method . We conclude that expensive , labor-intensive data collection methods , such as in-home interviews , are not necessary for many low-income , minority patients to generate high- quality , reliable health status data . Using appropriate screening instruments , those patient subgroups needing special help can be screening instruments , those patient subgroups needing special help can be identified and targeted for more expensive data collection methods . This tiered approach has policy implication s for the cost , feasibility , and quality of data collection in health outcomes research BACKGROUND Spousal violence has wide-ranging effects on the physical , reproductive , sexual and psychological health of women . There are few longitudinal studies that describe this association in developing countries . AIM To test the hypothesis that spousal violence is an independent risk factor for a broad range of adverse health outcomes in women . SETTING AND DESIGN A population -based cohort study of women living in the catchment area of a primary health center in north Goa . Two thous and four hundred and ninety-four of 3000 r and omly selected women were recruited of whom 1750 married women were included for this paper . MATERIAL S AND METHODS Each participant was assessed at baseline with a structured interview for the assessment of exposure to spousal violence ( verbal , physical , sexual ) over two time periods ( lifetime ; recent in the past three months ) . The interview collected data on gynecological complaints and the Revised Clinical Interview Schedule was used for the diagnosis of depressive disorder . Laboratory tests for anemia and sexually transmitted infections ( STI ) were carried out . Longitudinal data was collected after six and 12 months on these outcomes . In addition , baseline measures for nutritional status and menstrual health were also obtained . STATISTICAL ANALYSIS Univariate analyses were carried out on the cross-sectional and longitudinal data to assess the association between each type of spousal violence and each health outcome . Multivariate analyses adjusted for age , literacy , household per capita income . Logistic regression was used for all analyses in Stata ( Version 10 ) . RESULTS Lifetime spousal violence was reported by 290 ( 16.6 % , 95%CI=14.9 - 18.4 ) women ; recent violence was reported by 230 ( 13.0 % , 95%CI=11.6 - 14.8 ) . The cross-sectional data showed an association between violence and a range of self-reported gynecological complaints , low Body Mass Index , depressive disorder and attempted suicide . The longitudinal analyses confirmed these associations only for STI and attempted suicide . CONCLUSION Spousal violence is specifically associated as an independent risk factor for two adverse women 's health outcomes , viz . , STI and attempted suicide . Public health and clinical programs targeting these outcomes must specifically address spousal violence OBJECTIVES To assess insecticide-treated nets ( ITNs ) use , other malaria prevention measures , knowledge of malaria and diffusion of information about ITNs by the National Malaria Control Programme ( NMCP ) in Mali . DESIGN A descriptive cross-sectional study . SETTING Four villages in Mopti region , Mali that had participated in the Mopti Regional Malaria Control Program ( MRMCP ) ITN Education Programme five years prior . PARTICIPANTS Three hundred thirty nine r and omly-selected households . Within each household , mothers of children one to nine years of age were interviewed regarding knowledge of malaria and prevention practice s. RESULTS Overall , 11 % of households used ITNs , with 97 % of these in two villages . Ninety eight percent of households used bednets , 22 % used insecticide sprays and 39 % used mosquito coils . Significant predictors of ITNs use were : head of household literacy , larger family size , Bambara ethnicity , hearing about the NMCP and hearing about ITNs from health agents . Reasons why ITNs were not used included not knowing anything about ITNs , cost and not having net impregnation services readily available in the village . Levels of knowledge concerning malaria disease , transmission and prevention varied amongst the four villages . ITN households had significantly higher levels of knowledge about malaria and its prevention . CONCLUSION Five years after the implementation of the MRMCP , ITNs use was low and diffusion of malaria prevention information was unequal among villages . Future efforts in improving the programme must recognise these differences in knowledge and ITNs utilisation and make village-specific changes that are acceptable for each village OBJECTIVE To explore how rheumatoid arthritis ( RA ) antirheumatic drug-specific knowledge and numeric literacy , patient trust in physician , and demographic and disease-related factors relate to the confidence of patient decision-making related to disease modifying antirheumatic drugs ( DMARD ) . METHODS Data were analyzed from 628 r and omly selected patients with RA receiving care in community rheumatology practice s , who responded to a multicenter , cross-sectional mail survey . We used multiple regression models to predict patient confidence in DMARD decision-making related to their most recently initiated DMARD . RESULTS Significant positive correlation was found between confidence in DMARD decision and trust in physician , DMARD-specific knowledge , and disease duration , but not risk-related numeric literacy , sex , or education . Negative correlations were found with disease severity and current bother with DMARD side effects . A multiple linear regression model of confidence in DMARD decision had an overall R = 0.788 , R2 = 0.620 ( p < 0.001 ) . The 4 dependent variables contributing significantly to the model were female sex , Medicaid insurance status , satisfaction with RA disease control , and trust in physician , with st and ardized beta = 0.077 , -0.089 , 0.147 , and 0.687 , respectively . CONCLUSION In this sample of community patients with RA , the patient trust in physician had substantially greater effect on confidence in DMARD decision than DMARD-specific knowledge , disease-related factors , or demographic characteristics BACKGROUND Insufficient knowledge about mental illness and its treatment has been shown to constitute a major barrier to its adequate care for mental illness in the lay public ( LP ) . We therefore examined Japanese cancer patients ' ( CP ) ability to recognize depression and their preferences of its treatments . PARTICIPANTS AND METHOD One hundred lung CP and 300 LP were selected at r and om to participate in the study . Structured interviews using a vignette of a person with both cancer and depression were conducted with CP , and those using a vignette of a person with depression were carried out with LP , respectively . RESULTS Only 11 % of CP recognized the presence of depression in the vignette , while 25 % of LP did ( p<0.001 ) . There were few significant differences in the preference for st and ard psychiatric treatments between CP and LP : st and ard treatments such as antidepressants ( CP : 39 % , LP : 36 % ) were less often rated as helpful , whereas non-st and ard treatments such as physical activity ( CP : 85 % , LP : 66 % ) were most often rated as helpful . CONCLUSIONS The results indicated that cancer patients ' knowledge about mental illness and its treatment were insufficient . Psychological education may reduce patient-related barriers to seek and to utilize optimal mental health care in cancer patients CONTEXT Adult survivors of childhood cancer are at risk for medical and psychosocial sequelae that may adversely affect their health status . OBJECTIVES To compare the health status of adult survivors of childhood cancer and siblings and to identify factors associated with adverse outcomes . DESIGN , SETTING , AND PARTICIPANTS Health status was assessed in 9535 adult participants of the Childhood Cancer Survivor Study , a cohort of long-term survivors of childhood cancer who were diagnosed between 1970 and 1986 . A r and omly selected cohort of the survivors ' siblings ( n = 2916 ) served as a comparison group . MAIN OUTCOME MEASURES Six health status domains were assessed : general health , mental health , functional status , activity limitations , cancer-related pain , and cancer-related anxiety/fears . The first 4 domains were assessed in the control group . RESULTS Survivors were significantly more likely to report adverse general health ( odds ratio [ OR ] , 2.5 ; 95 % confidence interval [ CI ] , 2.1 - 3.0 ; P<.001 ) , mental health ( OR , 1.8 ; 95 % CI , 1.6 - 2.1 ; P<.001 ) , activity limitations ( OR , 2.7 ; 95 % CI , 2.3 - 3.3 ; P<.001 ) , and functional impairment ( OR , 5.2 ; 95 % CI , 4.1 - 6.6 ; P<.001 ) , compared with siblings . Forty-four percent of survivors reported at least 1 adversely affected health status domain . Sociodemographic factors associated with reporting at least 1 adverse health status domain included being female ( OR , 1.4 ; 95 % CI , 1.3 - 1.6 ; P<.001 ) , lower level of educational attainment ( OR , 2.0 ; 95 % CI , 1.8 - 2.2 ; P<.001 ) , and annual income less than 20 000 dollars ( OR , 1.8 ; 95 % CI , 1.6 - 2.1 ; P<.001 ) . Relative to those survivors with childhood leukemia , an increased risk was observed for at least 1 adverse health status domain among those with bone tumors ( OR , 2.1 ; 95 % CI , 1.8 - 2.5 ; P<.001 ) , central nervous system tumors ( OR , 1.7 ; 95 % CI , 1.5 - 2.0 ; P<.001 ) , and sarcomas ( OR , 1.2 ; 95 % CI , 1.1 - 1.5 ; P = .01 ) . CONCLUSION Clinicians caring for adult survivors of childhood cancer should be aware of the substantial risk for adverse health status , especially among females , those with low educational attainment , and those with low household incomes Aims : To examine the prevalence of cognitive impairment in a Spanish elderly population and to analyse its association with some social and medical factors . Methods : We r and omly selected a representative sample ( n = 600 ) of people over 65 from Narón Council ( A Coruña ) . Socio-demographic and biomedical data were collected and cognitive status was assessed using the Mini-Mental State Examination ( MMSE ) . Results : We determined variations in the prevalence from 35.2 % , when age or level of education distribution was not applied , to 22.2 % when they were applied . Women showed a higher probability of cognitive impairment than men . Negative correlation was observed between the age of the subject and the MMSE score ( Spearman correlation ρ = –0.45 , p < 0.001 ) , with the possibility of developing cognitive impairment increasing each year . For our sample , cognitive impairment was associated with an increase of morbidity and mortality in the elderly population . This association was found with the presence of dementia , heart failure , anaemia , stroke and auditory deficits . Conclusions : Knowledge of the real prevalence rates , together with the establishment of adequate preventive and intervention measures , can be factors that may diminish the socio-sanitary impact of cognitive impairment Adaptive interactive computer-based education programs which can be personalized to patients ' needs and skills might be more suitable for patients ' training as compared to conventional ones . We tested whether there are differences between an adaptive and a conventional version of a computer-based hypoglycaemia education program concerning successful training and user friendliness . One hundred and twenty r and omized diabetic patients were enrolled in this study . The two different programs were compared by using the following criteria : ( 1 ) the number of actions needed to get out of or prevent hypoglycaemia , ( 2 ) the need for external help , ( 3 ) the average time needed for completing one task and ( 4 ) user friendliness as determined by a question naire . Patients using the adaptive computer-based hypoglycaemia education program needed less actions to get out of or prevent hypoglycaemia , less external help and less time to finish tasks . Furthermore , the user friendliness of the adaptive computer program received a significantly better rating by the patients . The adaptive computer-based hypoglycaemia education program shows significantly better results as compared to a conventional one . Therefore , using adaptive computer-based programs might be helpful for education of patients BACKGROUND Little is known about the efficacy of educational interventions for reducing the stigma associated with depression . AIMS To investigate the effects on stigma of two internet depression sites . METHOD A sample of 525 individuals with elevated scores on a depression assessment scale were r and omly allocated to a depression information website ( BluePages ) , a cognitive-behavioural skills training website ( MoodGYM ) or an attention control condition . Personal stigma ( personal stigmatising attitudes to depression ) and perceived stigma ( perception of what most other people believe ) were assessed before and after the intervention . RESULTS Relative to the control , the internet sites significantly reduced personal stigma , although the effects were small . BluePages had no effect on perceived stigma and MoodGYM was associated with an increase in perceived stigma relative to the control . Changes in stigma were not mediated by changes in depression , depression literacy or cognitive-behavioural therapy literacy . CONCLUSIONS The internet warrants further investigation as a means of delivering stigma reduction programmes for depression PURPOSE This study examined the impact of teacher use of a print referencing style during classroom-based storybook reading sessions conducted over an academic year . Impacts on preschoolers ' early literacy development were examined , focusing specifically on the domain of print knowledge . METHOD This r and omized , controlled trial examined the effects of a print referencing style on 106 preschool children attending 23 classrooms serving disadvantaged preschoolers . Following r and om assignment , teachers in 14 classrooms used a print referencing style during 120 large-group storybook reading sessions during a 30-week period . Teachers in 9 comparison classrooms read at the same frequency and with the same storybooks but used their normal style of reading . RESULTS Children whose teachers used a print referencing style showed larger gains on 3 st and ardized measures of print knowledge : print concept knowledge , alphabet knowledge , and name writing , with medium-sized effects . CLINICAL IMPLICATION S The convergence of the present findings with those of previous efficacy studies indicates that print referencing intervention can be used confidently as an approach for facilitating print knowledge in preschool-age children . Speech- language pathologists can serve an important role in supporting preschool educators as they use this evidence -based technique with pupils in their classrooms Duchenne and Becker muscular dystrophy are allelic X-linked disorders causing progressive muscle weakness in males . Duchenne muscular dystrophy is caused by absence of dystrophin in muscle and brain ; boys with Duchenne muscular dystrophy have a static cognitive impairment with mean Full Scale IQ approximately 1 st and ard deviation below the mean . Less is known of the cognitive profile of males with Becker muscular dystrophy , which is associated with variable alterations in the amount or size of the dystrophin protein . The aim of this study was to describe the cognitive and psychological profile of males with Becker muscular dystrophy . This was a prospect i ve cohort study . Clinical data collected included age at diagnosis and assessment , socioeconomic status , serum creatine kinase level , and site of gene deletion/mutation ( by exon number ) . The following psychological tests were used to assess general intellectual functioning , academic achievement , incidence and nature of behavioral problems : The Wechsler Intelligence Scales , The Wide Range Achievement Test — Revised , The Developmental Test of Visual-Motor Integration , The Child Behavior Checklist , and The Conner 's Parent Rating Scale . Twenty-four males were enrolled . The Wechsler Full Scale IQ was normally distributed with a mean of 95.6 ( SD 23.3 ) , which did not differ significantly from the population mean . The frequency of learning difficulties for reading was 21 % , for spelling was 32 % , and for arithmetic was 26 % , significantly higher than the frequency in the general population . The frequency of total behavioral problems in the clinical range was 67 % , and the frequency of autism was 8.3 % . Patients with Becker muscular dystrophy demonstrate a less homogeneous cognitive phenotype than that seen in Duchenne muscular dystrophy . Males with Becker muscular dystrophy have a high incidence of learning difficulties . Autism and behavioral and attention problems are also more common in Becker muscular dystrophy than in the general population PURPOSE The purpose of this study was to investigate predictors of high physical function in people with fibromyalgia ( FM ) . DESIGN Cross-sectional descriptive , correlational study of 2,580 persons with FM who responded to an online survey during fall 2005 . METHODS The survey indicated self-reported physical activity levels , functional abilities , symptoms , health care costs , employment status , work productivity , self management strategies . It had adequate validity and reliability . A significant binary logistic regression model of predictors of physical function ( individual factors , symptoms , self management strategies ) was vali date d using backwards logistic regression . FINDINGS Significant explanatory variables of high physical function were : men , greater education , younger age , lower intensity fatigue , spasticity , and balance problems , not using prescription pain medications , using aerobic or strength training exercise , and not using relaxation methods . CONCLUSIONS People with FM suffer from multiple symptoms and use many modalities to control symptoms to remain functional . Given knowledge of predictors of physical function in FM , health care providers might be able to develop strategies to promote better functioning . Prospect i ve trials are needed to track the natural course of study variables , measuring their effect on function , and to test effects of interventions to maximize function BACKGROUND AND OBJECTIVES The Chronic Renal Insufficiency Cohort ( CRIC ) Study was established to examine risk factors for the progression of chronic kidney disease ( CKD ) and cardiovascular disease ( CVD ) in patients with CKD . We examined baseline demographic and clinical characteristics . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Seven clinical centers recruited adults who were aged 21 to 74 yr and had CKD using age-based estimated GFR ( eGFR ) inclusion criteria . At baseline , blood and urine specimens were collected and information regarding health behaviors , diet , quality of life , and functional status was obtained . GFR was measured using radiolabeled iothalamate in one third of participants . RESULTS A total of 3612 participants were enrolled with mean age + /- SD of 58.2 + /- 11.0 yr ; 46 % were women , and 47 % had diabetes . Overall , 45 % were non-Hispanic white , 46 % were non-Hispanic black , and 5 % were Hispanic . Eighty-six percent reported hypertension , 22 % coronary disease , and 10 % heart failure . Mean body mass index was 32.1 + /- 7.9 kg/m(2 ) , and 47 % had a BP > 130/80 mmHg . Mean eGFR was 43.4 + /- 13.5 ml/min per 1.73 m(2 ) , and median ( interquartile range ) protein excretion was 0.17 g/24 h ( 0.07 to 0.81 g/24 h ) . Lower eGFR was associated with older age , lower socioeconomic and educational level , cigarette smoking , self-reported CVD , peripheral arterial disease , and elevated BP . CONCLUSIONS Lower level of eGFR was associated with a greater burden of CVD as well as lower socioeconomic and educational status . Long-term follow-up of participants will provide critical insights into the epidemiology of CKD and its relationship to adverse outcomes INTRODUCTION H and held computers ( PDAs ) uploaded with clinical decision support software ( CDSS ) have the potential to facilitate the adoption of evidence -based medicine ( EBM ) at the point-of-care among undergraduate medical students . Further evaluation of the usefulness and acceptability of these tools is required . METHODS All 169 Year 4 undergraduate medical students at the University of Hong Kong completed a post-r and omised controlled trial survey . Primary outcome measures were CDSS/PDA usefulness , satisfaction , functionality and utilisation . Focus groups were also conducted to derive complementary qualitative data on the students ' attitudes towards using such new technology . RESULTS Overall , the students found the CDSS/PDA useful ( mean score = 3.90 out of 6 , 95 % confidence interval ( CI ) = 3.78 , 4.03 ) . They were less satisfied with the functional features of the CDSS ( mean score = 3.45 , 95 % CI = 3.32 , 3.59 ) and the PDA ( mean score = 3.51 95 % CI = 3.40 , 3.62 ) . Utilisation was low , with the average frequency of use less than once per week . Although students reported a need for information in patient care at least once daily , they infrequently used the CDSS in a clinical setting ( 20.4 + /- 10.4 % of the time ) , with an average information retrieval success rate of 37.6 + /- 22.1 % requiring 63.7 + /- 86.1 seconds . Multivariable regression shows that higher perceived CDSS/PDA usefulness was associated with more supportive faculty attitudes , greater knowledge of EBM , better computer literacy skills and increased use in a clinical setting . Greater satisfaction with the CDSS/PDA was associated with increased use in a clinical setting and higher successful search rates . Qualitative results were consistent with these quantitative findings and yielded additional information on students ' underlying feelings that may explain the observations . CONCLUSIONS While PDAs uploaded with the CDSS are able to provide students with better access to high quality information , improvements in faculty attitudes , students ' knowledge of EBM and computer literacy skills , and having the CDSS specially design ed for undergraduate use are essential to increasing student adoption of such point-of-care tools BACKGROUND This study evaluated the effectiveness of an intervention for reading-delayed children in Year-1 classes . METHODS A sample ( N = 77 ) of children drawn from 14 schools representing those with the weakest reading skills were r and omly allocated to one of two groups . A 20-week intervention group received the intervention for two consecutive 10-week periods , while a 10-week intervention group only received the intervention for the second 10 weeks of the study . The programme was delivered in daily 20-minute sessions that alternated between small group ( N = 3 ) and individual teaching . The programme combined phoneme awareness training , word and text reading , and phonological linkage exercises . RESULTS The children receiving the intervention during the first 10-week period made significantly more progress on measures of letter knowledge , single word reading , and phoneme awareness than children not receiving the intervention . However , the children who only received the intervention during the second 10-week period made rapid progress and appeared to catch up with the children who had been given the more prolonged intervention . Failure to respond to the intervention was predicted by poor initial literacy skills and being in receipt of free school meals . CONCLUSION A reading intervention programme delivered on a daily basis by trained teaching assistants is an effective intervention for children who show reading delays at the end of their first year in school . However , around one-quarter of the children did not respond to this intervention and these children would appear to need more intensive or more prolonged help to improve their reading skills BACKGROUND Illiteracy is prevalent among current elderly Chinese . There are few brief cognitive tests in Chinese design ed to screen those possibly demented for more detailed evaluation in a clinical setting . OBJECTIVES The present study adapted the Mini-Mental State Examination ( MMSE ) for screening dementia among illiterate or less educated elderly Chinese . METHODS Literacy-dependent items of the MMSE were modified or substituted by equivalent items that are not literacy-dependment . Some items were modified to provide socio-cultural compatibility . After developing it , the Chinese adapted MMSE ( CAMSE ) was administered to 370 elderly out patients from Xijing hospitals located in Xi'an , China , 93 of whom were found to be demented and 277 non-demented . Sensitivities and specificities for detecting dementia were evaluated by adjusting for different CAMSE cut-off points . The optimal cut-off points of 22 for literates and 20 for illiterates yielded a sensitivity of 83.87 % and a specificity of 84.48 % . Corresponding positive predictive value ( PPV ) was 0.65 , and negative predictive value ( NPV ) was 0.94 . The impact of literacy on CAMSE and individual test items was also evaluated . Illiterate subjects got a higher CAMSE total score than literate subjects ( p < 0.05 ) . Only one out of 12 test items , serial sevens , was negatively influenced by illiteracy ( p < 0.01 ) . After an interval of 4 - 6 weeks , 32 r and omly selected subjects were retested with CAMSE . The test-retest reliability for total scores was 0.75 ( p < 0.01 ) . CONCLUSIONS Results suggest that in the socio-cultural context for Chinese , irrespective of their literacy skills , CAMSE proved feasible for use in clinical setting s for dementia screening A nutrition intervention focused on low-fat eating pattern changes was conducted among low-literacy participants in a Twin Cities Metropolitan area Exp and ed Food and Nutrition Education Program ( EFNEP ) . A total of 134 EFNEP participants who participated in the intervention were compared to 70 comparison participants who received EFNEP nutrition education material s. Associations between changes in outcome variables specific to the intervention were evaluated using mixed-model regression analyses . The principal effects seen for this program were related to changes in eating pattern scales . More modest effects were seen in scales related to attitudes of low-fat eating , and although changes in dietary fat intake as measured by 24-hour dietary interviews suggested a positive intervention effect , this did not approach statistical significance BACKGROUND Studies have shown that South Asians are highly susceptible to cardiovascular diseases ( CVDs ) . There is very little information available about the prevalence of risk factors for CVD in the physician population , a group that might be expected to be more aware of cardiovascular risk and health status . AIM To evaluate the prevalence of cardiovascular risk factors - including metabolic , dietary and behavioural - among the physician population in southern India . METHODS Approximately 4000 physicians of differing specialties from eight southern districts in Tamilnadu , India , in and around the city of Madurai were listed . Of these , 1600 were r and omly selected to participate in a cross-sectional survey , of which 1514 physicians agreed to participate . The survey included demographic question naires , objective measurements of blood pressure , fasting blood sugar , fasting lipids and waist circumference , and question naires about their dietary and behavioural habits . RESULTS Complete data were available for 1433 physicians . Using a blood pressure cut-off value of 130/85 mmHg or higher , the study recorded a prevalence of 41 % among men and 23 % among women . On applying the International Diabetes Federation criteria for the metabolic syndrome for the South Asian population , the present study identified 49 % of female physicians and 41 % of male physicians as having the metabolic syndrome . Only 17 % were physically active . Less than one-half of them consumed vegetables . Nearly 31 % of male physicians were smokers . CONCLUSION Analysis of these data suggests that the risk for CVD and stroke is at epidemic proportions in a cohort of well-educated physicians who are in the highest quintile of income A national survey was conducted to determine the information technology skills nurse administrators consider critical for new nurses entering the work force . The sample consisted of 2,000 r and omly selected members of the American Organization of Nurse Executives . Seven hundred fifty-two usable question naires were returned , for a response rate of 38 % . The question naire used a 5-point Likert scale and consisted of 17 items that assessed various technology skills and demographic information . The question naire was developed and pilot tested with content experts to establish content validity . Descriptive analysis of the data revealed that using e-mail effectively , operating basic Windows applications , and search ing data bases were critical information technology skills . The most critical information technology skill involved knowing nursing-specific software , such as bedside charting and computer-activated medication dispensers . To effectively prepare nursing students with technology skills needed at the time of entry into practice , nursing faculty need to incorporate information technology skills into undergraduate nursing curricula OBJECTIVES To evaluate the effects of using an audiovisual animation ( i.e. , digital video ) displayed on a personal digital assistant ( PDA ) for patient education in a clinical setting . METHODS Quasi-experimental study of a prospect i ve technology intervention conducted in an outpatient infectious diseases clinic at an academic medical center . Subjects responded to questions immediately before , immediately after , and 4 - 6 weeks after watching a digital video on a PDA . Outcome measures include participant knowledge of disease , knowledge of medications , and knowledge of adherence behaviors ; attitudes toward the video and PDA ; self-reported adherence ; and practicality of the intervention . RESULTS Fifty-one English-speaking adults who were initiating or taking medications for the treatment of HIV/AIDS participated in the study . At visit one , statistically significant improvements in knowledge of disease ( p<0.005 ; paired t-test ) , knowledge of medications ( p<0.005 ; paired t-test ) , and knowledge of adherence behaviors ( p<0.05 ; ANOVA ) were measured after participants watched the PDA-based video . At visit two ( 4 - 6 weeks later ) , statistically significant improvements in self-reported adherence to the medication regimens ( p<0.005 ; paired t-test ) were reported . Participants liked the PDA-based video and indicated that it was an appropriate medium for learning , regardless of their baseline literacy skills . The video education process was estimated to take 25 min of participant time and was viewed in both private and semi-private locations . CONCLUSIONS Technology-assisted education using a digital video delivered via PDA is a convenient and potentially powerful way to deliver health messages . The intervention was implemented efficiently with participants of a variety of ages and educational levels , and in a range of locations within clinical environments . Additional study of this methodology is warranted UNLABELLED Adolescents with language -based learning disabilities ( LBLD ) often interpret idioms literally . When idioms are provided in an enriched context , comprehension is compromised further because of the LBLD student 's inability to assign multiple meanings to words , assemble and integrate information , and go beyond a local referent to derive a global , coherent meaning . This study tested the effects of context and familiarity on comprehension of 24 idioms in 22 adolescents with LBLD . The students completed the Idiom Comprehension Test ( ICT ) [ Language , Speech , and Hearing Services in Schools 30 ( 1999 ) 141 ; LSHSS 34 ( 2003 ) 69 ] in one of two conditions : in a story or during a verification task . Within each condition were three familiarity levels : high , moderate , and low . The LBLD adolescents ' data were then compared to previously collected data from 21 age- , gender- , and reading ability-matched typically developing ( TD ) peers . The relations between reading and language literacy and idiom comprehension were also examined in the LBLD adolescents . Results showed that : ( a ) the LBLD adolescents generally performed poorly relative to their TD counterparts ; however , the groups performed comparably on the high and moderate familiarity idioms in the verification condition ; ( b ) the LBLD adolescents performed significantly better in the verification condition than in the story condition ; and ( c ) reading ability was associated with comprehension of the low familiarity idioms in the story condition only . Findings are discussed relative to implication s for speech- language pathologists ( SLPs ) and educators working with adolescents with LBLD . LEARNING OUTCOMES As a result of this activity , the participant will be able to ( 1 ) describe the importance of metalinguistic maturity for comprehension of idioms and other figures of speech ; ( 2 ) underst and the roles of context and familiarity when assessing idiom comprehension in adolescents with LBLD ; and ( 3 ) critically evaluate assessment s of idiom comprehension and determine their appropriateness for use with adolescents with LBLD A population -based study was conducted to investigate about AIDS knowledge and attitudes among the general public in Tehran , Iran . Using a short question naire a r and om sample of 1172 individuals aged between 15 and 65 years were interviewed . The mean age of the respondents was 34.8 ( S.D. = 12.9 ) years , 52 % were male and mostly married ( 70 % ) , and had received secondary education or above ( 84 % ) . The findings indicated that the respondents had a fairly good to excellent knowledge about AIDS . The correct answers ranged from 53 % to about 99 % . Also the results showed that the majority of the respondents were strongly agree or agree with the statement that people with AIDS should have social right to study or work ( 84 % ) or with the statement that AIDS is a public health problem ( 98.7 % ) . The majority of the respondents ( 87 % ) said that the mass media including radio , television and newspapers were the main source of their information about HIV/AIDS . The findings from this study indicate that although misconception exist among Iranian about AIDS , in general they have fairly good knowledge and have positive attitudes towards AIDS and people with AIDS . Such findings suggest that prevention programs should be encouraged and these might have the potential role to limit the emergence of Iran 's HIV/AIDS epidemic CONTEXT Low literacy is an important barrier for patients with diabetes , but interventions to address low literacy have not been well examined . OBJECTIVE To examine the role of literacy on the effectiveness of a comprehensive disease management program for patients with diabetes . DESIGN , SETTING , AND PARTICIPANTS Analysis of the influence of literacy on glycemic control and systolic blood pressure using data from a r and omized controlled trial ( conducted from February 2001 through April 2003 ) of a comprehensive diabetes management program . Participants were 217 patients aged 18 years or older with type 2 diabetes and poor glycemic control ( glycosylated hemoglobin [ HbA1c ] levels > or = 8.0 % ) and presenting to a US academic general internal medicine practice . INTERVENTIONS All communication to patients was individualized and delivered to enhance comprehension among patients with low literacy . Intervention patients received intensive disease management from a multidisciplinary team . Control patients received an initial management session and continued with usual care . MAIN OUTCOME MEASURES Achievement of goal HbA1c levels and systolic blood pressure at 12-month follow-up for control and intervention patients stratified by literacy status . RESULTS Complete 12-month data were available for 193 patients ( 89 % ) . Among patients with low literacy , intervention patients were more likely than control patients to achieve goal HbA1c levels ( < or = 7.0 % ) ( 42 % vs 15 % , respectively ; adjusted odds ratio [ OR ] , 4.6 ; 95 % confidence interval [ CI ] , 1.3 to 17.2 ; P = .02 ) . Patients with higher literacy had similar odds of achieving goal HbA1c levels regardless of intervention status ( 24 % vs 23 % ; adjusted OR , 1.0 ; 95 % CI , 0.4 to 2.5 ; P = .98 ) . Improvements in systolic blood pressure were similar by literacy status . CONCLUSIONS Literacy may be an important factor for predicting who will benefit from an intervention for diabetes management . A diabetes disease management program that addresses literacy may be particularly beneficial for patients with low literacy , and increasing access to such a program could help reduce health disparities The goal of this study was to learn more about clinicians ' experiences with , and perceptions of the utility , validity , and feasibility of st and ardized outcome measures in practice . Fifty r and omly selected clinicians from multiple disciplines and multiple service agencies in a large children 's public mental health service system were interviewed individually ( n=30 ) or in focus groups ( n=20 ) using semistructured interviews . There was great variability across clinicians in attitudes about empirical methods of treatment evaluation . There was consensus regarding feasibility challenges of administering st and ardized measures , including time burden and literacy barriers . Although all participants had received scored assessment profiles for their clients , the vast majority reported that they did not use the scores in treatment planning or monitoring . Their suggestions for improved clinical utility of outcome measurement are included . With increased attention and re sources devoted to performance outcome assessment , it is concerning that most clinicians perceive little clinical utility of outcome measurement Objective : To assess the public 's knowledge about depression , attitudes toward treatments for depression , perceived causal factors for depression , and reported prognoses of depression , overall and by sex . Methods : We conducted a cross-sectional telephone survey in Alberta between February and June 2006 . We used a r and om phone number selection procedure to identify a sample of adults in the community ( n = 3047 ) . Participants were presented with a vignette describing an individual with depression and then asked questions to assess recognition of depression , attitudes toward mental health treatments , possible causal factors for depression , and prognosis of depression . Results : The response rate was 75.2 % . Among the final participants , 75.6 % could correctly recognize depression described in a case vignette . General practitioners or family doctors were considered as being the best help for depression . Of the participants , 35 % were in complete agreement with health professionals about appropriate interventions for depression , 28 % believed in dealing with depression alone , and 43 % thought that “ weakness of character ” was a likely cause of depression . Men had poorer mental health literacy than women and were more likely to endorse the use of alcohol to cope . Conclusions : Mental health promotion and education efforts are needed to improve the general public 's mental health literacy and to clarify misunderst and ing about depression . Men need to be a particular target of these efforts We used a r and omized trial to compare two polio vaccine pamphlets written on a sixth grade level -- the vaccine information statement prepared by the Centers for Disease Control ( CDC ) and an easy-to-read pamphlet we developed (LSU)--for reading ability , comprehension and preference among 610 parents with a broad range of demographic characteristics . Parents at all reading levels and incomes preferred LSU ( 76 % vs. 21 % , P < 0.001 ) . Although readers of LSU achieved significantly higher comprehension ( 65 % vs. 60 % , P < 0.05 ) this difference may not be clinical ly significant . The information items presented with instructional graphics were the only items on which differences in comprehension levels achieved both clinical and statistical significance . Comprehension was lowest for the CDC m and ated information on risks and the National Injury Compensation . Our findings demonstrate that simplifying written immunization material and making it more suitable will increase appeal , but such modification may not raise comprehension to an acceptable level without use of instructional graphics . Health education material s intended for general parent population s , which are written on a sixth grade reading level , may not adequately educate parents or prepare them for a discussion with their physicians Abstract BACKGROUND : Health literacy has been linked to health status in a variety of chronic diseases . However , evidence for a relationship between health literacy and mental health outcomes is sparse . OBJECTIVE : We hypothesized that low literacy would be associated with higher addiction severity , higher levels of depressive symptoms , and worse mental health functioning compared with those with higher literacy in adults with alcohol and drug dependence . METHODS : The association of literacy with multiple mental health outcomes was assessed using multivariable analyses . Measurement instruments included the Rapid Estimate of Adult Literacy in Medicine ( REALM ) , the Center for Epidemiologic Studies -Depression ( CES-D ) scale , the Mental Component Summary scale of the Short Form Health Survey , and the Addiction Severity Index for drug and alcohol addiction . Subjects included 380 adults recruited during detoxification treatment and followed prospect ively at 6-month intervals for 2 years . Based on the REALM , subjects were classified as having either low ( ≤8th grade ) or higher ( ≥9th grade ) literacy levels . RESULTS : In longitudinal analyses , low literacy was associated with more depressive symptoms . The adjusted mean difference in CES-D scores between low and high literacy levels was 4 ( P < .01 ) . Literacy was not significantly associated with mental health-related quality of life or addiction severity . CONCLUSIONS : In people with alcohol and drug dependence , low literacy is associated with worse depressive symptoms . The mechanisms underlying the relationship between literacy and mental health outcomes should be explored to inform future intervention efforts OBJECTIVE To assess knowledge of dietary and behaviour-related determinants of non-communicable disease ( NCD ) of urban Senegalese women . DESIGN A cross-sectional , population study using an interviewer-administered knowledge question naire , developed and vali date d for this study . The question naire consisted of 24 items with six scores measuring knowledge of : ( 1 ) diet- and behaviour-related causes of NCD ; ( 2 ) diet quality -NCD relationship ; ( 3 ) fruit and vegetable link with NCD ; ( 4 ) health consequences of obesity ; ( 5 ) causes of cardiovascular disease ( CVD ) ; and ( 6 ) causes of certain cancers . SUBJECTS A r and om sample of 301 women aged 20 - 50 years . RESULTS The knowledge scores developed suggest that the health consequences of obesity ( mean score of 65.4 % ) were best understood followed by causes of CVD ( mean score of 60.6 % ) , because obesity , smoking , high blood cholesterol and dietary fat were well recognised as risk factors for CVD . Subjects scored least for their knowledge of the protective effect of fruit and vegetables ( mean score of 19.9 % ) . Knowledge of causes of certain cancers ( mean score of 36.1 % ) was also low . Women who worked outside the home had better knowledge for two scores but otherwise no relationship was found between knowledge and literacy , formal education or body mass index . CONCLUSIONS Findings suggest reasonable overall knowledge concerning diet and behaviour with NCD , especially given the relatively new context of the obesity epidemic in Senegal . However , there was poor knowledge of the benefit of eating fruit and vegetables and other preventable causes of certain cancers . Education targeting the benefits of vegetables and fruit may have the greatest impact on NCD prevention OBJECTIVE Patients with low health literacy have difficulty underst and ing prescription drug labels and other medication instructions . This article describes the development , implementation , and preliminary evaluation of an illustrated medication schedule ( a " pill card " ) that depicts a patient 's daily medication regimen using pill images and icons . METHODS Participants in a r and omized controlled trial who were assigned to receive the pill card intervention described their use of the card and its perceived effectiveness . Responses were analyzed by level of patient literacy and other characteristics . RESULTS Among the 209 respondents , 173 ( 83 % ) reported using the pill card when they initially received it , though use declined to 60 % approximately 3 months later . Patients with inadequate or marginal literacy skills , less than high school education , or cognitive impairment were most likely to refer to the card on a regular basis initially and at 3 months ( p<0.05 ) . Most pill card users ( 92 % ) rated the tool as very easy to underst and , and 94 % found it helpful for remembering important medication information , such as the name , purpose , or time of administration . CONCLUSION Nearly all patients considered an illustrated medication schedule to be a useful and easily understood tool to assist with medication management . Patients with limited literacy skills , educational attainment , or cognitive function referred to the aid with greater frequency . PRACTICE IMPLICATION S Picture-based instructions promote better underst and ing of prescription medications , particularly among patients with limited literacy skills or cognitive impairment , and should be used more widely in practice Context It is important to establish the predictive validity of medical school grade s. The strength of predictive validity and the ability to identify at-risk students in medical schools depends upon assessment systems such as number grade s , pass/fail ( P/F ) or honours/pass/fail ( H/P/F ) systems . Objective This study was design ed to examine the predictive validity of number grade s in medical school , and to determine whether any important information is lost in a shift from number to P/F and H/P/F grading systems . Subjects The participants in this prospect i ve , longitudinal study were 6656 medical students who studied at Jefferson Medical College over 3 decades . They were grouped into 10 deciles based on their number grade s in Year 1 of medical school . Methods Participants were compared on academic accomplishments in Years 2 and 3 of medical school , medical school class rank , delayed graduation and attrition , performance on medical licensing examinations and clinical competence ratings in the first postgraduate year . Results Results supported the short- and longterm predictive validity of the number grade s. Ratings of clinical competence beyond medical school were predicted by number grade s in medical school . We demonstrated that small differences in number grade s are statistically meaningful , and that important information for identifying students in need of remedial education is lost when students who narrowly meet faculty 's expectations are included with the rest of the class in a broad ' pass ' category . Conclusions The findings refute the argument that knowledge of sciences basic to medicine is not critical to subsequent performance in medical school and beyond if an appropriate evaluation system is used . Furthermore , the results of this study raise questions about ab and oning number grade s in favour of a pass/fail system . Consideration of these findings in policy decisions regarding assessment systems of medical students is recommended BACKGROUND Widespread , appropriate use of clinical decision rules would result in many benefits for health care . While it is known that clinicians report using these rules , little is known about how the rules are actually used in everyday practice . OBJECTIVES To conduct a survey of emergency physicians to examine whether they use the Ottawa Ankle Rules ( OAR ) consistently , exclusively , and accurately . METHODS A postal survey was administered to 399 emergency physicians r and omly selected from the membership list of the Canadian Association of Emergency Physicians using Dillman 's tailored design method for postal surveys . Results were analyzed via frequency distributions and linear regression . RESULTS Response rate was 69.7 % ( 262 of 376 eligible respondents ) , of whom 99.2 % were familiar with the OAR . Most physicians ( 89.6 % ) reported using the OAR always or most of the time in appropriate circumstances , while only 42.2 % reported basing their decisions to order radiography primarily on the rule . Physicians reported considering non-rule factors that are not related to the presence of a fracture ( e.g. , swelling : 54 % ) , and factors that add no more predictive value over and above the rule ( e.g. , age > 55 years : 55.2 % ) . While 82.4 % reported not having review ed the rule for months or years , only 30.9 % of the respondents were able to correctly remember the components of the rule . Errors in remembering rule components were more common among part-time ( beta = 0.18 , p = 0.009 ) and older ( beta = 0.18 , p = 0.04 ) physicians , and those who do not apply the rule consistently ( beta = 0.14 , p = 0.04 ) . CONCLUSIONS Most physicians report using and applying the OAR consistently , but most report that the rule is not the primary determinant of their decisions . Most apply this rule without referring to memory aids , yet their memory for this simple rule is imperfect . Future work should study how different memory aid strategies might improve the accuracy of rule application and reduce the use of nonpredictive cues The epidemiology on “ cognitive impairment no dementia ” ( CIND ) and its natural history are of great importance for underst and ing the transition from normal aging to dementia . Epidemiologic studies of CIND , however , are limited in China . The goal of our study was to determine the prevalence and distribution of CIND in the aged population and analyze socio-demographic factors . To accomplish this , we performed cluster r and om sampling of 6192 people aged over 65 years in Taiyuan , a metropolitan city located in northern China . Socio-demographic factors were surveyed by self-administered question naires . Neuropsychologic testing consisting of the Mini-Mental State Examination , Boston Naming Test , Trail Making Tests A and B , Block Design , Rey Auditory Verbal Learning Test , Visual Reproduction , Logical Memory , letter and category fluency , the National Adult Reading Test , the Geriatric Depression Scale , and the “ state ” section of the State-Trait Anxiety Inventory was also obtained . Pearson χ2 statistics and odds ratio with 95 % confidence intervals were used to identify the relationship between CIND and socio-demographic factors . Logistic regression modeling was undertaken to identify potential risk factors . Results showed that an overall prevalence of CIND was 9.70 % ( 95 % confidence intervals : 9.62%-9.77 % ) . Univariate analyses showed that the prevalence of CIND differed significantly according to age , sex , education level , monthly household income , and marital status ( P<0.01 ) , but not by occupational achievement ( P>0.05 ) . In a multiple logistic regression analysis , age , sex , marital status , educational level , and occupation were significantly associated with increased risk for CIND ( P<0.01 ) . This study confirms the high prevalence of CIND among the elderly population of China , similar to previous epidemiologic studies in other countries . Nearly all socio-demographic characteristics are associated with CIND . The putative risk factors identified merit further study This study was intended to evaluate the mental health literacy vis-à-vis depression among inhabitants of Penang state in North Malaysia . Using a clustered r and om sampling method , 1,855 respondents were approached to participate in the survey . A total of 1,149 respondents actually participated , for a 61.9 % response rate . Face to face interviews were then conducted using a pre-vali date d 21-item question naire . The mean age of the respondents was 30 years ( SD ±11.5 ) . The majority ( n = 884 ; 76.9 % ) could recognize three or more symptoms of depression . Chinese and /or female respondents performed the best in this domain . Respondents with a personal experience of depression displayed a significantly better knowledge of symptoms of and therapies for depression than those who did not ( t = −35.745 , P = < 0.001 ) . Overall , a moderate knowledge level of the symptoms of depression and a cursory knowledge towards therapy were observed among the general population in Penang . Notably , respondents were generally inclined towards the use of alternative medicine . The study suggests that strong beliefs in alternative and traditional medicines could undermine the respondents ’ willingness and ability to seek evidence -based mental health care AIM To assess readability of information provided for patients with Type 2 diabetes on drug treatment for their condition . METHODS A r and om sample of patient information on drug treatments published on the website of the main UK Diabetes charity was assessed for readability using two accepted measures and compared with articles from three national newspapers published the same day , in the setting of a hospital-based diabetes centre . The main outcome measures were Flesch-Reading Ease and Flesch-Kincaid Grade Level scores available within Microsoft Office 2000 . RESULTS Information provided for patients and medically related articles from two of three newspapers had suboptimal readability , requiring literacy skills well above the UK average . CONCLUSIONS Information for patients with diabetes may be of limited value for 20 % of the UK adult population who have problems with literacy BACKGROUND Cannabis use is common in patients with bipolar disorder , however little is known about cannabis as a risk factor for mania . In order to investigate the association between exposure to cannabis and subsequent development of manic symptoms whilst controlling for psychotic symptoms , a longitudinal population -based study was carried out . METHODS 4815 individuals aged 18 to 64 years were interviewed using the Composite International Diagnostic Interview at baseline , 1 year follow up and 3 year follow up , including assessment of substance use , manic symptoms and psychotic symptoms . RESULTS Use of cannabis at baseline increased the risk for manic symptoms during follow-up ( adjusted OR 2.70 , 95 % CI : 1.54 , 4.75 ) , adjusted for age , sex , educational level , ethnicity , single marital status , neuroticism , use of other drugs , use of alcohol , depressive symptoms and manic symptoms at baseline . The association between cannabis use and mania was independent of the prevalence and the incidence of psychotic symptoms . There was no evidence for reverse causality , as manic symptoms at baseline did not predict the onset of cannabis use during follow-up ( OR = 0.35 , 95 % CI : 0.03 , 3.49 ) . LIMITATIONS As 3 years is a relative short period of follow-up , long-term effects of cannabis use on mania outcomes could not be detected . CONCLUSION The results suggest that cannabis use may affect population expression of manic symptoms ( and subsequent risk to develop bipolar disorder [ Regeer , E.J. , Krabbendam , L. , R , DE Graaf , Ten Have , M. , Nolen , W.A. , Van Os , J. , 2006 . A prospect i ve study of the transition rates of subthreshold (hypo)mania and depression in the general population . Psychol Med , 1 - 9 . ] ) . These findings may not be due to the emergence of psychotic symptoms or the effects of self-medication Patients may bring unreliable information to the physician , complicating the physician – patient relationship , or outside information seeking may complement physician information provision , reinforcing patients ' responsibility for their health . The current descriptive evidence base is weak and focuses primarily on the Internet 's effects on physician – patient relations . This study describes how cancer patients bring information to their physicians from a range of sources and are referred by physicians to these sources ; the study also examines explanations for these behaviors . Patients with breast , prostate , and colon cancer diagnosed in 2005 ( N = 1,594 ) were r and omly drawn from the Pennsylvania Cancer Registry ; participants returned mail surveys in Fall 2006 ( response rate = 64 % ) . There is evidence that both bringing information to physicians and being referred to other sources reflects patients ' engagement with health information , preference for control in medical decision making , and seeking and scanning for cancer-related information . There is also evidence that patients who bring information from a source are referred back to that source OBJECTIVE Australian women conceiving with ART are at fourfold risk of admission to early parenting treatment programs compared with those conceiving spontaneously . This study aim ed to identify prevalence and determinants of antenatal mood disturbance and other risks for early parenting difficulties after assisted conception . DESIGN A prospect i ve longitudinal investigation from conception to 18 months postpartum using telephone interviews and self-report question naires . SETTING Melbourne IVF and Royal Women 's Hospital Reproductive Services , Victoria , Australia . PATIENT(S ) A consecutive cohort of English-speaking women with ultrasound-confirmed ART-conceived pregnancies . MAIN OUTCOME MEASURE(S ) St and ardized psychometric measures of mood , quality of marital relationship , mother-to-fetus emotional attachment , and personality . INTERVENTION(S ) None . RESULT ( S ) Of the 288 women with confirmed pregnancies , 239 were contactable , and 183 ( 77 % ) were recruited , 95 % of whom completed both early and late pregnancy assessment s. Participants were socioeconomically advantaged , had very good pregnancy health , exceptional marital relationships , normal personality styles , and intense affectionate attachment to the fetus . Very few ( < 5 % ) had clinical ly significant mood disturbance in late pregnancy . CONCLUSION ( S ) There were low rates of antenatal mood disturbance and other risk factors for postpartum depression . Pregnancy and motherhood might be idealized after ART conception , and preparation for the realities of infant care might then be insufficient UNLABELLED The mouth is regarded as a mirror and the gateway to health . Integration is required between the dental practitioner and the patient , if good dental health is to be attained . Various treatment modalities of late frequently require appointments , which are more than one in number for completion of the entire treatment program . This study was taken up to determine the impact of reported dental attendance patterns of patients on the oral health and treatment quality in teaching hospitals and also on the quality of life in rural areas . AIMS AND OBJECTIVES 1 . To assess the reasons for irregular dental care in the patients attending the clinics in teaching hospitals . 2 . To assess the satisfaction of the patient as regards the treatment rendered in the teaching institutes . 3 . To correlate the gender of the patient with the regularity in the recall attendance . MATERIAL S AND METHODS A hospital-based cross-sectional study was conducted using a systematic r and om sampling method and every alternate subject was selected from the patients attending the OPD of Department of Periodontics and Community Dentistry . The data was collected using the interview method with the help of a structured , pretested question naire . RESULTS AND CONCLUSION Out of 288 patients , 94 failed to attend the recall appointments . In these 94 patients , various reasons for not attending recall were assessed and lack of time was found to be the most common reason for non-attendance . Relationship between age and reasons for not reporting was found to be significant ( P < 0.01 ) . Patient satisfaction survey showed that 51.54 % of the patients were satisfied with the dental treatment rendered . The present study also showed that males are more prompt in attending recall appointments as compared to females . A positive and significant correlation between literacy and patient reporting status was found ( P < 0.01 ) STUDY OBJECTIVE Health literacy influences a patient 's ability to read and underst and labels on medicine containers , appointment slips , informed-consent documents and medical instructions -- all of which are considered basic health documents that a patient encounters in healthcare setting s. Previous research suggests Spanish-speaking patients have low levels of health literacy . This study compares the functional health literacy ( FHL ) of Spanish- and English-speaking adult patients in a suburban emergency department ( ED ) . METHODS Through a prospect i ve , matched cohort design , Spanish-speaking adult patients and pediatric guardians presenting to the ED were matched with English-speaking patients by age , gender and treatment area . Demographic information , including total years of school completed and self-assessed reading ability , was collected . The Test of Functional Health Literacy in Adults ( TOFHLA ) was administered in the subject 's primary language . A score of < 60 indicated inadequate FHL , 60 - 74 marginally adequate FHL , and > 74 adequate literacy . RESULTS Eighty-six matched pairs were enrolled . The median age was 30.5 years , and 56 % were male . Spanish speakers averaged a TOFHLA score of 59.72 , and English speakers 90.78 . Only 7 % of English speakers had less-than-adequate FHL compared to 74 % of Spanish speakers . The average years of school completed were 10.59 ( 7.95 Spanish ; 13.19 English ) , and 55 % of English speakers reported " excellent " reading ability compared to 13 % of Spanish speakers . Last grade completed ( p=0.004 ) and self-assessed reading ability ( p=0.0007 ) are predictors of TOFHLA scores . Those subjects who completed less than the eighth grade had inadequate FHL . CONCLUSIONS The majority of Spanish-speaking subjects have less-than-adequate FHL . Self-reported reading ability and years of school completed appear to predict FHL and may be clinical ly useful . Due to the disproportionately low level of health literacy among Spanish-speaking patients demonstrated in this and previous studies , future efforts should focus on developing programs that improve health literacy by providing this population with oral translations and pictorial and video instructions OBJECTIVES To determine the prevalence of illiteracy in a cohort of rheumatoid arthritis ( RA ) patients and the impact of illiteracy on disease severity and function . METHODS We performed a prospect i ve cross-sectional study with case record review of 127 consecutive patients with RA attending one centre . All patients completed the Rapid Estimate of Adult Literacy in Medicine ( REALM ) screening test . This 66-word recognition test provides an estimate of reading level in less than 3 min . Demographic data were collected by interview and case record review . Function was assessed with the Health Assessment Question naire ( HAQ ) and depression with the Hospital Anxiety and Depression ( HAD ) scale , both sent prior to clinic attendance . Social deprivation was assessed with the Carstairs index . RESULTS Four patients refused to participate . Of these , three stated they were unable to read . Ninety-seven women and 26 men agreed to be interviewed . All but two were Caucasian . Median age was 56 yr ( range 19 - 77 yr ) and median disease duration was 10 yr ( range 1 - 60 yr ) . Median number of previous disease-modifying anti-rheumatic drugs ( DMARDs ) was two . Eighteen ( 15 % ) patients were functionally illiterate , with a REALM score of less than 60 . Sex , age , disease duration and numbers of joint replacements and previous DMARDs were not influenced by illiteracy . Illiteracy led to more anxiety ( P=0.011 ) , but did not affect HAQ score ( P>0.5 ) . Illiteracy was more common in the deprived ( P=0.0064 ) . Illiterate patients had three times more hospital visits compared with age- and sex-matched RA controls over the previous 12 months . CONCLUSIONS One in six of our patient population are illiterate and would struggle to cope with patient education material s and prescription labels . These patients had significantly more hospital visits but equal function , suggesting that additional re sources be directed towards these individuals . The REALM test is quick and easy to administer and allows us to identify patients who may require more appropriate literature This study explores associations of IQ at age 14 with adult symptoms of suicidal thoughts and attempts at age 21 . Analysis was based on the Mater University Study of Pregnancy and its outcomes , an Australian prospect i ve birth cohort study started in Brisbane Australia in 1981 . We assessed associations with suicide thoughts , plans , and attempts . We used two measures of IQ : the Raven 's St and ard Progressive Matrices and the Wide Range Achievement Test . In multivariable analyses , there was an inverse association between Raven 's IQ and suicide thoughts , plans , and attempts , but no strong evidence of an association between the WRAT3 and the three suicidal items . Specific aspects of intelligence may be associated with suicidal thoughts , plans , and attempts Abstract BACKGROUND : Low literacy influences cervical cancer screening knowledge , and is a possible contributor to racial disparities in cervical cancer . OBJECTIVE : To examine the hypothesis that literacy predicts patient adherence to follow-up recommendations after an abnormal Pap smear . DESIGN : A prospect i ve , continuity clinic-based study . PARTICIPANTS : From a sample of 538 women undergoing literacy testing at the time of Pap smear screening , we studied 68 women with abnormal Pap smear diagnoses . MEASUREMENTS : Literacy was assessed using the Rapid Evaluation of Adult Literacy in Medicine ( REALM ) . We also measured other proxies for literacy , including educational attainment and physician estimates of patients ’ literacy level . Outcome measures included on-time and 1-year follow-up and duration of time to follow-up after an abnormal Pap smear . RESULTS : Only one-third of the cohort adhered to follow-up recommendations . At 1 year , 25 % of the women had not returned at all . Patients with inadequate literacy ( as assessed by the REALM ) were less likely to follow up within 1 year , although this result was not statistically significant ( adjusted odds ratio [ OR ] = 3.8 , 95 % confidence interval [ CI ] : 0.8 to 17.4 ) . Patients subjectively assessed by their physician to have low literacy skills were significantly less likely to follow up within 1 year ( adjusted OR=14 , 95 % CI : 3 to 65 ) . Less than high school education ( hazard ratio (HR)=2.3 ; 95 % CI : 1.2 , 4.6 ) and low physician-estimated literacy level ( HR=3.4 , 95 % CI : 1.4 , 8.2 ) , but not objective literacy level , were significant predictors of duration of time to follow-up , adjusting for recommended days to follow-up and other factors . CONCLUSIONS : Among women with an abnormal Pap smear , those perceived by their physician to have low literacy were significantly more likely to fail to present for follow-up OBJECTIVES This study was undertaken to test the effectiveness of the Stanford Nutrition Action Program , an experimental trial to reduce dietary fat intake among low-literacy , low-income adults . METHODS Twenty-four paired adult education classes ( 351 participants , 85 % women , mean age = 31 years ) were r and omly assigned to receive a newly developed dietary fat curriculum ( the Stanford Nutrition Action Program ) or an existing general nutrition curriculum . Food frequency and nutrition-related data , body mass index , and capillary blood cholesterol were collected at baseline and at two postintervention follow-ups . RESULTS The Stanford Nutrition Action Program classes showed significantly greater net improvements in nutrition knowledge ( + 7.7 ) , attitudes ( /0.2 ) , and self-efficacy ( -0.2 ) than the general nutrition classes ; they also showed significantly greater reductions in the percentage of calories from total ( -2.3 % ) and saturated ( -0.9 % ) fat . There were no significant differences in body mass index or blood cholesterol . All positive intervention effects were maintained for 3 months postintervention . CONCLUSIONS The Stanford Nutrition Action Program curriculum , tailored to the cultural , economic , and learning needs of low-literacy , low-income adults , was significantly more effective in achieving fat-related nutritional changes than the general nutrition curriculum OBJECTIVE To determine if health literacy is associated with patient underst and ing of prenatal screening tests for fetal aneuploidy and neural tube defects . METHODS We performed a prospect i ve observational study on a cohort of English-speaking patients receiving prenatal care in two resident-staffed ambulatory clinics . Health literacy was measured using the Rapid Estimate of Adult Literacy in Medicine-7 . Underst and ing of the prenatal screening tests was assessed using a modified Maternal Serum Screening Knowledge Question naire . RESULTS Over an 8-month period , 125 patients were approached , and 101 ( 81 % ) consented to the study . Thirty-eight ( 38 % ) women demonstrated low health literacy . Patients with low health literacy were more likely to demonstrate inadequate underst and ing when compared to those with adequate health literacy ( 97 % versus 11 % , respectively ; P < 0.01 ) . Similarly , patients with < 12th grade education were more likely to have inadequate underst and ing when compared to patients with > 12th grade education ( 53 % versus 30 % , respectively ; P = 0.02 ) . Health literacy is a more sensitive and specific predictor of inadequate underst and ing than education ( sensitivity 84 % versus 70 % , respectively , P < 0.05 ; specificity 98 % versus 47 % , respectively , P < 0.05 ) . CONCLUSION Patients with low health literacy are more likely to demonstrate inadequate underst and ing of these prenatal screening tests than women with adequate health literacy Study objective : To ( 1 ) describe the setting and design of the Good Ageing in Lahti Region ( GOAL ) programme ; ( 2 ) by using the baseline results of the GOAL cohort study , to examine whether living in urban , semi-urban , or rural communities is related to risk factors for chronic diseases and functional disability in ageing individuals . Design : The baseline data of a cohort study of ageing individuals living in three community types ( urban , semi-urban , rural ) . Data were collected by two question naires and laboratory assessment s. Setting : Fourteen municipalities in the Lahti region ( Päijät-Häme County ) in Finl and . Participants : A regionally and locally stratified r and om sample of men and women born in 1946—50 , 1936—40 , and 1926—30 . A total of 4,272 were invited and 2,815 ( 66 % ) participated . Main results : Elevated serum cholesterol , obesity , disability , sedentary lifestyle ( < 2 times/week walking ) , and high fat intake were more prevalent in rural vs. urban and semi-urban communities . After adjustment for sex , age , education , obesity , diet , physical activity , smoking , and alcohol use , rural communities remained the only community type with increased ( p<0.05 ) probability for high BMI ( OR 1.33 ) and high waist circumference ( OR 1.43 ) . Conclusions : The unfavourable health and lifestyle profile , together with an old population , makes health promotion for elderly citizens a special challenge for rural communities such as those in Päijät-Häme County , Finl and . Most , if not all , of the differences in health between the three community types were explained by educational background , physical activity , and smoking It has previously been demonstrated that patients with heart failure ( HF ) in an urban public hospital had significant gaps in knowledge regarding dietary sodium restriction . The objective of this study was to determine what risk factors were associated with such gaps in knowledge and to determine if these gaps in knowledge would increase the risk for HF readmission . A st and ardized test of sodium knowledge ( scored 0 to 10 ) was administered prospect ively to 97 hospitalized patients with HF < 48 hours before discharge . The incidence of 90-day hospital readmission for HF was compared between subjects with low dietary sodium knowledge ( score 0 to 3 ) and the remainder of the cohort ( score 4 to 10 ) in univariate and multivariate analyses . Another 48 patients with HF were prospect ively recruited , and the dietary sodium knowledge test and a survey of psychosocial and other parameters , including the Test of Functional Health Literacy in Adults , a vali date d measure of health literacy , were administered . The 90-day readmission rate for HF was 3 times higher in those with low sodium knowledge than in the remainder of the cohort ( 28 % vs 9 % , p = 0.02 ) . This association persisted in multivariate models adjusting for potential confounders . Low health literacy , but not other psychosocial parameters , was associated with low dietary sodium knowledge . In conclusion , low dietary sodium knowledge was an independent risk factor for 90-day HF hospital readmission in the urban setting . Deficiency in dietary sodium knowledge is one pathway through which low health literacy leads to adverse outcomes in patients with HF Abstract BACKGROUND : Individuals with limited literacy and those with depression share many characteristics , including low self-esteem , feelings of worthlessness , and shame . OBJECTIVE : To determine whether literacy education , provided along with st and ard depression treatment to adults with depression and limited literacy , would result in greater improvement in depression than would st and ard depression treatment alone . DESIGN : R and omized clinical trial with patients assigned either to an intervention group that received st and ard depression treatment plus literacy education , or a control group that received only st and ard depression treatment . PARTICIPANTS : Seventy adult patients of a community health center who tested positive for depression using the 9- question Patient Health Question naire ( PHQ-9 ) and had limited literacy based on the Rapid Estimate of Adult Literacy in Medicine ( REALM ) . MEASUREMENTS : Depression severity was assessed with PHQ-9 scores at baseline and at 3 follow-up evaluations that took place up to 1 year after study enrollment . Changes in PHQ-9 scores between baseline and follow-up evaluations were compared between the intervention and control groups . RESULTS : The median PHQ-9 scores were similar in both the intervention and control groups at baseline ( 12.5 and 14 , respectively ) . Nine- question Patient Health Question naire scores improved in both groups , but the improvement was significantly larger in the intervention group . The final follow-up PHQ-9 scores declined to 6 in the intervention group but only to 10 in the control group . CONCLUSIONS : There may be benefit to assessing the literacy skills of patients who are depressed , and recommending that patients with both depression and limited literacy consider enrolling in adult education classes as an adjuvant treatment for depression BACKGROUND Low levels of literacy and high levels of behaviour problems in middle childhood often co-occur . These persistent difficulties pose a risk to academic and social development , leading to social exclusion in adulthood . Although parent-training programmes have been shown to be effective in enabling parents to support their children 's development , very few parent interventions offer a combination of behavioural and literacy training . AIMS This paper ( 1 ) reports on a prevention programme which aim ed to tackle behaviour and literacy problems in children at the beginning of school , and ( 2 ) presents the effects of the intervention on children 's literacy . SAMPLE One hundred and four 5- and 6-year-old children selected from eight schools in an inner city disadvantaged community in London participated in the intervention . METHODS This is a r and omized control trial with pre- and post- measurements design ed to evaluate the effectiveness of an intervention . The behavioural intervention consisted of the ' Incredible Years ' group parenting programme combined with a new programme design ed to train parents to support their children 's reading at home . RESULTS Analyses demonstrated a significant effect of the intervention on children 's word reading and writing skills , as well as parents ' use of reading strategies with their children . CONCLUSION A structured multicomponent preventive package delivered with attention to fidelity can enable parents to support their children 's reading at home and increase their literacy skills . Together with the improvement in child behaviour , these changes could improve the life chances of children in disadvantaged communities PURPOSE The purpose of this study was to determine the feasibility of a 2-day in-service education program for ( a ) promoting the use of two emergent literacy strategies by early childhood educators and ( b ) increasing children 's responses to these strategies . METHOD Sixteen early childhood educators were r and omly assigned to an experimental and a control group . The experimental in-service program sought to increase educators ' use of abstract utterances and print references . Educators were videotaped with small groups of preschoolers during storybook reading and a post-story craft activity . Pretest and posttest videotapes were coded to yield rates of abstract language , verbal print references , and children 's responses . RESULTS In comparison to the control group , educators in the experimental program used more abstract utterances that elicited talk about emotions and children 's past experiences during storybook reading . They also used significantly more print references during a post-story craft activity . In addition , children in the experimental group responded more often with appropriate responses to abstract utterances and print references in comparison to children in the control group . CONCLUSION A 2-day in-service education program result ed in short-term behavioral changes in educators ' use of abstract language and print references . Suggestions for improving instruction include providing opportunities for classroom practice with feedback , modeling the use of strategies in classroom routines , and long-term mentoring of educators to promote retention of gains Objective : To examine the relation between household water and sanitation , and the risk of stunting and reversal of stunting in Khartoum and Crezira regions Sudan . Design : Prospect i ve cohort study . Setting : A total of 25 483 children aged 6–72 months from rural Sudan enrolled in an 18-month field trial in 1988 to study the effect of vitamin A supplementation on child health and survival . Results : The mean height-for-age z-scores at baseline and the end of study were −1.66 and −1.55 , respectively , for the group with water and sanitation facilities , and −2.03 and −1.94 for the group without water and sanitation , after adjustment for age , region , gender , mother 's literacy , intervention group ( vitamin A vs placebo ) , family wealth , breastfeeding and cleanliness . Among children of normal height-for-age at baseline , the risk of stunting ( < −2 height-for-age z-score ) was lowest in the group that came from homes that had both water and sanitation compared to children from homes without these facilities ( multivariate RR=0.79 , 95 % CI 0.69–0.90 ) . Among children stunted at baseline , those coming from homes with water and sanitation had a 17 % greater chance of reversing stunting than those coming from homes without either facility ( adjusted RR=1.17 , 95 % CI 0.99–1.38 ) . We did not detect a synergistic association between access to water and sanitation . Conclusions : Water and sanitation are independently associated with improved growth of children . Sponsorship : None The effect of the readability level of patient drug information material s on patient comprehension of and attitude toward the information was studied . The reading level of 108 out patients at a Veterans Administration hospital who could read English , read type of normal size , and who were not receiving warfarin sodium was measured . Patients then were given , on a r and om basis , a warfarin drug monograph written on either the 5th- or 10th- grade level . To test comprehension , all subjects took a true-false test of recall written at the 5th- grade level . A significant relationship was found between comprehension and reading ability ( p less than 0.001 ) . Patients receiving the 5th- grade level monograph exhibited significantly better comprehension than those receiving the 10th- grade level material ( p less than 0.001 ) . As compared with those getting 10th- grade material , the group receiving the 5th- grade material had a more favorable perception of the level of difficulty , underst and ability , and clarity of the material . The study indicates that comprehension of written patient drug information can be improved by adjusting the readability of informational material s to the reading level of the patients The study 's purpose was to examine retention factors in a computer intervention with 158 chronically ill rural women . After a 22-week intervention , 18.9 % of the women had dropped out . A Cox regression survival analysis was performed to assess the effects of selected covariates on retention . Reasons for dropping out were tallied and categorized . Major reasons for dropping out were as follows : lack of time , decline in health status , and nonparticipation in study activities . Four covariates predicted survival time : level of computer skills , marital status , work outside the home , and impact of social events on participants ' lives . Retention-enhancing strategies are suggested for implementation Background Observational epidemiological data suggest that habitual consumption in later life of oily fish , rich in n-3 long-chain polyunsaturated fatty acids ( n-3 LCPs ) , is associated with better cognitive function , slower rates of cognitive decline and a lower risk of dementia . In this paper we present data on baseline fish consumption and cognitive function in cognitively healthy older people r and omised onto the Older People And n-3 Long-chain polyunsaturated fatty acid ( OPAL ) study . Methods In total , 867 older people were recruited to join the OPAL study from 20 general practice s in Engl and and Wales . Participants were aged 70–79 years at baseline were free of dementia and diabetes , had a Mini-Mental State Examination score of 24 or greater and did not report daily fish oil supplement consumption . Self-reported habitual fish consumption was assessed at baseline via questions on frequency and type of fish consumption . Cognitive function at baseline was assessed via vali date d cognitive tests assessing memory , executive function , psychomotor speed and attention , including the Californian Verbal Learning Test ( CVLT ) , the primary outcome of the OPAL study . Reported age at leaving full time education was recorded as a measure of educational achievement and psychological health was measured using the GHQ-30 question naire . Results Unadjusted analysis revealed significant positive associations between reported fish consumption and the CVLT scores with a mean increase of approximately 0.24 words remembered for each increase in level of reported fish consumption . These associations were noticeably attenuated on adjustment for age , gender and reported age at leaving full-time education and did not remain significant on further adjustment for GHQ-30 score . Similar associations were also observed between fish consumption and the global cognitive z-score , memory score , executive function score and delay scores in unadjusted analysis with the associations again attenuated on adjustment . Conclusions Baseline data from participants r and omised into the OPAL study provide support for the hypothesis that higher fish consumption is associated with better cognitive function in later life . However , although in the main associations remain after adjusting for education and psychological health , the data do not allow us to rule out the possibility of residual confounding e.g. from socioeconomic status or other health behaviours . Evidence is needed from r and omised clinical trials to clarify the role of n-3 LCPs in cognitive health in later life in the normal older person population Objectives : To estimate the prevalence of two types of mild cognitive impairment (MCI)—amnestic and multiple domain types — among nondemented and nondepressed elderly subjects aged 50 and older . Methods : The study was carried out in Kolkata , the eastern metropolis of India . A cross-sectional community screening was carried out , and 960 subjects were selected by systematic r and om sampling for the assessment of cognitive function with the help of a vali date d cognitive question naire battery administered through house-to-house survey . A case-control study was also undertaken to identify potential risk factors through univariate analysis . Results : Ultimately , full evaluation of cognitive function was possible in 745 of 960 subjects . An overall prevalence of MCI detected based on neuropsychological testing was 14.89 % ( 95 % CI : 12.19 to 17.95 ) . Prevalence of the amnestic type was 6.04 % ( 95 % CI : 4.40 to 8.1 ) and that of the multiple domain type was 8.85 % ( 95 % CI : 6.81 to 11.32 ) . Adjusted for age , education . and gender , the amnestic type was more common among men and the multiple domain type among women with advancement of age . Rates differed considerably with educational attainment . Hypertension and diabetes mellitus were the major risk factors for both types of MCI . Conclusion : In this first community-based study of mild cognitive impairment ( MCI ) from India , prevalence of the amnestic type is comparable with and that of the multiple domain type is less than the prevalence in developed countries . Variations in age , education , and gender specific prevalence of MCI of both types were encountered . The putative risk factors identified merit further study This cross-sectional study was conducted to estimate the prevalence of type 2 diabetes along with its risk factors in urban slum population of Dhaka , Bangladesh . A r and om sample of 1555 slum dwellers of Dhaka city ( age > or = 20 years ) were included in the study . Capillary blood glucose levels , fasting and 2-h after 75 g oral glucose load ( for a selected subjects , n = 476 ) , were measured . Height , weight , waist and hip circumferences , blood pressure and some other important socio-demographic information on age , sex , education , income , and occupation status were collected . The overall prevalence of type 2 diabetes was found to be 8.1 percent , and the prevalence for men and women were 7.7 percent and 8.5 percent respectively . Prevalence of diabetes was found to be lower following 2-h glucose values in the selected population compared to the FBG procedure . Age , sex , literacy and waist to hip ratio for men were found as significant risk factors following both fasting blood glucose and 2-h post glucose values adjusted for a number of confounding variables . Poor to moderate agreement was observed between fasting blood glucose and 2-h glucose ( kappa 0.41 , p < 0.001 ) . The agreement was even poorer between impaired fasting glucose and impaired glucose tolerance . Poor agreement between FBG and 2-h BG may raise concern for the dependability of diagnostic procedures . Higher prevalence of type 2 diabetes in the urban slum may indicate an epidemiological transition due to fast urban migration and possibly urbanization . However , this issue needs further exploration BACKGROUND Almost half of Canadians experience difficulty using print media , according to the 1994 International Adult Literacy Survey . Our objectives were to estimate the prevalence of low-literacy patients in our practice , to determine whether reading grade level is associated with self-perceived health status in primary care , and to evaluate the reading difficulty of commonly used patient education pamphlets . METHODS We surveyed a r and om sample of 229 patients aged 18 to 85 years presenting for scheduled and walk-in care . Main outcome measures were reading ability as estimated by word decoding skill with the vali date d Rapid Estimate of Adult Literacy in Medicine ( REALM ) and self-perceived health status using COOP/WONCA functional health measures . We assessed the reading difficulty of 120 commonly used patient education pamphlets using the Simple Measure of Gobbledygook ( SMOG ) formula . RESULTS The prevalence of low-literate patients was 9 % . Poor reading ability in English was most likely among patients under 45 years of age not having completed high school , and among those whose maternal language was neither English nor French ( immigrants ) . REALM scores and self-perceived health were weakly correlated but not significant statistically . The mean reading grade level of pamphlets was grade 11.5 ( SD : 1.5 ) . Seventy-eight percent of pamphlets required at least a high school reading level . CONCLUSION Literacy levels were higher than expected in our patient population ; this finding may be due to the rapid assessment tool used , which may have underestimated the difficulty of using print media . Clearly , the vast majority of commonly used patient education material s would not meet the needs of low-literate patients , who may be more likely to experience poorer health . Providers need to be sensitive to the reading limitations of patients and patient education material s should be written at a lower reading level In Germany , high quality health care is offered to just about all socio-economic groups . The question is rarely asked , though , if there are social differences in the utilisation and quality of health care among those with similar needs . These differences are analysed by looking at a group of persons with type 2 diabetes mellitus . Another group of persons without diabetes is included as well . The data are taken from the KORA-A Study in Augsburg , southern Germany . KORA-A is a case-control study based on patients with type 2 diabetes from the MONICA surveys S2 ( 1989/90 ) , S3 ( 1994/95 ) and the Myocardial Infa rct ion Registry , and controls , matched by age and sex to the cases . In 1997/98 , these persons were contacted for the KORA-A study . The data set includes data from 378 type 2 diabetic patients . The group without diabetes comprises 438 persons . The results indicate that the prevalence of " pain while walking " increases with decreasing educational level , and that this association is stronger for persons with type 2 diabetes ( OR 3.53 ; 95 % CI 1.32 - 9.44 ) than for persons without diabetes ( OR 2.02 ; 95 % CI 0.97 - 4.23 ) . The prevalence of intermittent claudication can serve as an indirect assessment of the quality of health care received by diabetic persons . It is concluded that health care should be improved especially for those persons with type 2 diabetes who belong to the group with low socioeconomic status OVERVIEW : Evidence -based practice is a systematic approach to problem solving for health care providers , including RNs , characterized by the use of the best evidence currently available for clinical decision making , in order to provide the most consistent and best possible care to patients . Are RNs in the United States prepared to engage in this process ? This study examines nurses ’ perceptions of their access to tools with which to obtain evidence and whether they have the skills to do so . Using a stratified r and om sample of 3,000 RNs across the United States , 1,097 nurses ( 37 % ) responded to the 93-item question naire . Seven hundred sixty respondents ( 77 % of those who were employed at the time of the survey ) worked in clinical setting s and are the focus of this article . Although these nurses acknowledge that they frequently need information for practice , they feel much more confident asking colleagues or peers and search ing the Internet and World Wide Web than they do using bibliographic data bases such as PubMed or CINAHL to find specific information . They do n’t underst and or value research and have received little or no training in the use of tools that would help them find evidence on which to base their practice . Implication s for nursing and nursing education are discussed INTRODUCTION The purpose of this study was to assess parental response to a clinic-based literacy program at a health maintenance organization . It was hypothesized that participation would be associated with increased literacy orientation by children . METHOD This r and omized community trial took place at a Midwestern health maintenance organization . Six clinics were paired and r and omly assigned to participate or not participate in Project Read . The main outcome variable was literacy orientation ( book use ) . The target population was parents of children younger than 12 months ( N = 165 ) . After 6 months of participation , parents were surveyed by telephone . RESULTS Seventy-five percent and 77 % of the treatment and control groups , respectively , had positive literacy orientation ; this difference was not significant . Persons receiving a videotape were more likely to have a positive literacy orientation ( 82.9 % vs 69.2 % ; P < .05 ) . The multivariate regression analyses also showed that receiving the free videotape was a significant intervention exposure . DISCUSSION The members of the population in this study are reading to their children . Parents who receive a videotape on the importance of reading are likely to read more to their children This cross-sectional study aim ed at determining the clinical and structural brain magnetic resonance imaging correlates of mild cognitive impairment ( MCI ) . The data presented here are from the first wave of the longitudinal Personality and Total Health through Life 60 + project . 2,551 community-dwelling individuals in the age range of 60–64 years were recruited r and omly through the electoral roll . They were screened using Mini-Mental State Examination and a short cognitive battery . Those who screened positive underwent detailed medical and neuropsychological assessment s. Of the 224 subjects who screened positive , 117 underwent a detailed assessment . Twenty-nine subjects fulfilled the Mayo Clinic criteria for MCI . Magnetic resonance imaging scans were analyzed for 26 subjects with MCI as well as normal controls . Subjects were clinical ly evaluated for depressive symptoms and major and minor depression syndromes . Logistic regression analysis was performed predicting MCI from anterior and mid-ventricular brain ratios , cortical atrophy measures , hippocampal volumes , volumes of amygdala and white matter hyperintensities after adjusting for age , gender , years of education , depression and physical disability . None of the neuroanatomical substrates appeared as predictors of MCI . The only predictors were higher depression scores and fewer years of education . Structural neuroimaging may not have an added advantage in the detection of MCI in middle-aged community-dwelling subjects . It may be that this age group is too young for such brain changes to be identified OBJECTIVES The objectives of this study were ( 1 ) to ascertain the level of agreement between the Charlson Comorbidity Index ( CCI ) based on self-report vs. administrative records , and factors affecting agreement and ( 2 ) to compare the predictive validity of the two indices in a sample of older emergency department ( ED ) patients . STUDY DESIGN AND SETTING The study was a secondary analysis of data from a r and omized trial of an ED-based intervention . The self-report and administrative CCI were compared using the intraclass correlation coefficient ( ICC ) . Factors examined for effect on agreement included health service utilization , age , and sex . The predictive validity of the indices was compared using subsequent health services utilization and functional decline as outcomes . Participants ( n=520 ) were recruited at four university-affiliated Montreal hospitals . Eligibility criteria included 65 years of age or older , able to speak English or French , and discharged to the community . RESULTS Agreement between the two sources was poor to fair ( overall weighted ICC 0.43 [ 95 % confidence interval [ CI ] : 0.40 , 0.47 ] ) . The predictive validity was similar for the two indices ( area under the receiver-operating characteristic curve 0.51 - 0.66 , depending on the outcomes ) . CONCLUSION Agreement between self-report and administrative comorbidity data is only poor to fair but both have comparable predictive validity The purpose of this study was to develop and pilot-test an interactive CD-ROM aim ed at the prevention of sexually transmitted infections ( STIs ) in female adolescents . The CD-ROM includes prevention information , models skills for negotiating abstinence and consistent condom use , teaches media literacy , and allows the user to choose a culturally appropriate host to guide them through the CD-ROM . Forty-seven female adolescents attending a health department clinic were r and omized to receive the CD-ROM plus an educator-led didactic session versus the didactic session alone . The CD-ROM was highly acceptable and feasible for use among female adolescents in the clinic setting . Hispanic and African American adolescents were more likely to choose hosts of the same race/ethnicity to guide them through the CD-ROM . HIV/STI knowledge increased significantly and nearly all adolescents intended to use condoms at next intercourse after viewing the CD-ROM . However , there were no significant differences measured between CD-ROM and comparison groups BACKGROUND Stigma is still a strong barrier to provision and utilisation of mental health services and every effort should be made to reduce it . Since there have been contradicting reports about the level of stigma in Africa and developing nations , more studies are needed to assist stakeholders to address the challenges . AIMS AND OBJECTIVES The study strives to determine the level of stigma ( stereotypes , prejudices and discriminating behaviours ) among residents of a traditional Nigerian town of Osogbo to psychiatric patients . It also attempts to proffer ways of further reducing stigma , if any , in the studied population . METHOD During a three-month period , a semi-structured interview schedule was administered to a stratified r and om sample of all consenting eligible adults in the study area . FINDINGS It was found that a significant proportion of the 84 respondents had less stigmatising attitude towards people with psychiatric illness . Respondents ' age , levels of education and belief in causation of mental illness were found to be significantly associated with their responses as regards stigma . CONCLUSION In spite of the limitations of sample size and the relatively high level of education of the respondents ( as compared with the national literacy rate ) , the study showed that public stigma towards psychiatric patients in Osogbo is generally low . While this finding is in keeping with some earlier reports , it was suggested that future studies should employ larger sample size and wider geographical coverage in order to put to rest the conflicting opinions about the level of stigma towards psychiatric patients among Nigerians and Africans as compared to western countries Purpose : To evaluate the responses to requests for eye donation from relatives of postmortem cases in a tertiary care hospital in India . Methods : In a prospect i ve study , the cases brought for postmortem to the Forensic Medicine Department were screened as potential donors by our team . The next of kin of potential donors were approached and counseled in a systematic manner following a st and ard interview pattern . Responses were noted in a pre design ed performa . The religion , level of literacy , socioeconomic status , relationship with the deceased , prior knowledge of eye donation , willingness for eye donation , and reasons for not donating eyes of the deceased were recorded . Results : One hundred fifty-nine potential donors were identified from a total of 721 postmortem cases . There were 119 ( 74.8 % ) men and 40 ( 25.2 % ) women . None of the deceased had previously pledged their eyes for eye donation . Eighty-eight ( 55.4 % ) next of kin were already aware of the concept of eye donation , but 71 ( 44.7 % ) families had not heard of it before . Willingness for eye donation was seen in 66 ( 41.5 % ) , whereas 93 ( 58.5 % ) families refused eye donation . Of those already aware of eye donation , 39 ( 44.3 % ) gave consent for donation . Prior knowledge of eye donation had no influence on willingness for eye donation ( P = 0.424 ) . Similarly , literacy ( P = 0.338 ) and socioeconomic status as estimated by a composite socioeconomic scale based on literacy and family income did not have any influence on willingness for eye donation ( P = 0.338 ) . Major reasons for not donating eyes included refusal to discuss the issue and dissuasion by distant relatives , legal problems , and religious beliefs . Conclusions : In our experience , literacy , socioeconomic status , and prior knowledge of eye donation of next kin had no correlation with donor corneal tissue procurement . Active counseling by a motivated team can be effective even in families with no prior knowledge and low socioeconomic status OBJECTIVES We determined risks of short-term ( 2-year ) hip fracture in a nationally representative , prospect i ve cohort of community-dwelling elderly people 70 years or older . METHODS We used self-report data from 2 waves of the Asset and Health Dynamics Survey ( n = 5630 ) . Sample -weighted logistic regression analyses were conducted to determine risk of hip fracture in relation to several demographic , cognitive , physical , and socioeconomic indicators . RESULTS During the 2-year study period , 102 participants reported a new hip fracture . Several indicators of physical functioning and cognitive status , including incorrect delayed word recall and inability to lift 10 lbs ( 4.5 kg ) , were significantly associated with hip fracture risk . In the final model , mobile home residents , individuals without Medicare part B insurance , and those without a high-school diploma were at more than a 2-fold risk of hip fracture . Educational level , physical functioning , and insurance status were the top 3 contributors to hip fracture risk . CONCLUSIONS In addition to functional status measures , health insurance status , educational level , and type of residence appear to be independent predictors of hip fracture Developmental dyslexia is diagnosed when children fail to acquire literacy skills despite adequate education and intellectual ability . There is evidence of impaired implicit learning in dyslexia , and it is possible that poor implicit learning in dyslexic children affects their acquisition of complex skills such as reading . To assess whether children with dyslexia show evidence of poor implicit motor learning , 45 dyslexic children completed a serial reaction time task ( SRTT ) . Age-matched controls ( n= 44 ) and nondyslexic poor readers ( " garden-variety " poor readers , n= 20 ) were used as comparison groups . The inclusion of the garden-variety poor-reader group allows us to address the specificity of implicit learning deficits to dyslexics , as opposed to poor readers who do not have a discrepancy between their intellectual and literacy skills . There were no significant differences between the three groups in performance accuracy . However , whereas the controls and garden-variety poor readers showed good implicit learning ( measured by a significant reduction in response times from a block of r and om to a block of sequenced trials ) , the dyslexic group did not . These data suggest that implicit motor learning deficits may underlie the laborious learning seen in developmental dyslexia . Because garden-variety poor readers were as able as control children to use the sequence cues to achieve better task performance , there may be differences in how garden-variety poor readers and dyslexic children acquire knowledge . This has important implication s for remediation programs that are specific to children with dyslexia and for distinguishing among varieties of poor readers The study was undertaken in southeastern Nigeria to investigate whether the people 's level of education and what they know about malaria affects how they seek treatment and prevention for the disease . Pre-tested question naires were used to collect data from r and omly selected householders and analysed using logistic regression . Higher levels of education were associated with improved knowledge and practice about the appropriate strategies for the prevention and treatment of malaria . The results thus indicate that education can have a positive impact on the malaria burden and medium/long-term improvement of overall literacy rates . As well as this , short-term health education campaigns about the causes , manifestations and control of malaria will have a positive impact on its control The aim of this study was to determine if preterm birth is associated with socioeconomic status ( SES ) , psychological functioning , and health-related quality of life ( HRQoL ) in adulthood . We used prospect i ve follow-up of 192 adult offspring of mothers who took part in a r and omized controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome ( 66 born at term [ 33 males , 33 females ] 126 born preterm [ 66 males , 60 females ] ) . Cognitive functioning was assessed using the Wechsler Abbreviated Scale of Intelligence . Working memory and attention was assessed using the Benton Visual Retention Test , the Paced Auditory Serial Addition Test , and the Brown Attention Deficit Disorder Scale . Psychiatric morbidity was assessed using the Beck Depression Inventory II , the State-Trait Anxiety Inventory , and the Schizotypy Traits Question naire . H and edness was assessed using the Edinburgh H and edness Inventory . HRQoL was assessed using the Short Form-36 Health Survey . Moderately preterm birth ( median gestation 34wks , mean birthweight 1946 g [ SD 463 g ] ) was not related to later marital status , educational attainment , SES , cognitive functioning , working memory , attention , or symptoms of anxiety or schizotypy at 31 years of age . Preterm birth was associated with fewer symptoms of depression and higher levels of satisfaction in three of the eight HRQoL domains measured ( bodily pain , general health perception , and social functioning ) . Adults who were born moderately preterm have SES , psychological functioning , and HRQoL consistent with those who were born at term . This good long-term outcome can not be extrapolated to those with early childhood disability or very low birthweights Research ers used a quasi-experiment ( N = 723 ) conducted in the field and using both pretests and posttests to carry out a theory-based evaluation of the effectiveness of a media literacy curriculum implemented in Washington state . Results showed that reflective thinking concerning media message about tobacco increased for all media literacy participants , whether or not they had used tobacco previously . Changes in reflective thinking affected a range of decision-making indicators . Lesson participants who had not used tobacco demonstrated greater change at earlier stages of decision making in ways that suggested a greater underst and ing of the persuasive techniques used by tobacco manufacturers , on indicators such as perceived realism , desirability , and similarity . Lesson participants who had tried tobacco demonstrated greater change at later stages of decision making on indicators such as perceived peer norms for tobacco use , identification with tobacco-related portrayals , and expectancies for tobacco use . All participants also showed increases in their ability and motivations to resist smoking-related influences . Overall , the results suggest that media literacy has important and somewhat different effects on those who have and those who have not experimented with tobacco use . The results also show the importance of measuring cognitive and affective indicators of decision making that may change gradually as participants gain experience putting lessons learned into action Malaria is a major public health problem in tribal villages of India , where 8 % of the country 's population lives . Literacy level among tribal population is very low . This study aims to examine the relation between education status and knowledge about malaria among Indian tribal communities . 125 r and omly selected tribal respondents from one tribal village each of 17 states were administered a close ended question naire by trained interviewers to assess their knowledge about various aspects of malaria . Effect of educational status on the level of knowledge was analyzed using chi square test . Stratified analysis was performed using Mantel Haenszel chi square test to eliminate gender bias . 2125 respondents ' , r and omly selected from 17 tribal villages in as many states , findings were analyzed . Fifty seven percent male and 72 % female respondents were illiterate . Only 2 % respondents had college level education . Educated females were more knowledgeable than their male counterparts . Mantel Haenszel chi square analysis showed that educated respondents were more knowledgeable than the illiterates , after adjusting for sex of respondents . However , there was gross lack of knowledge regarding diagnosis and treatment of malaria and use of insecticides irrespective of gender and educational status . Improvement in literacy status of tribal population will help in increasing awareness about malaria . Opportunities for disseminating information about various aspects of malaria should be utilized during treatment of malaria cases by health workers In this article , the authors aim to make accessible the careful application of a method called instrumental variables ( IV ) . Under the right analytic conditions , IV is one promising strategy for answering questions about the causal nature of associations and , in so doing , can advance developmental theory . The authors build on prior work combining the analytic approach of IV with the strengths of r and om assignment design , whether the experiment is conducted in the lab setting or in the " real world . " The approach is detailed through an empirical example about the effects of maternal education on children 's cognitive and school outcomes . With IV techniques , the authors address whether maternal education is causally related to children 's cognitive development or whether the observed associations reflect some other characteristic related to parenting , income , or personality . The IV estimates show that maternal education has a positive effect on the cognitive test scores of children entering school . The authors conclude by discussing opportunities for applying these same techniques to address other questions of critical relevance to developmental science Context Patients sometimes have difficulty following complicated treatment regimens . Contribution In this trial , 314 low-income patients with congestive heart failure were r and omly assigned to a pharmacist intervention or usual care . The pharmacist assessed patient knowledge and provided instructions about medication use . During the 9-month intervention , patients in the intervention group had greater medication adherence than patients in the usual care group ( 79 % vs. 68 % ) . These differences dissipated within 3 months of stopping the intervention . Patients in the intervention group also had fewer exacerbations result ing in emergency department visits or hospitalizations than patients in the usual care group . Implication Ongoing educational intervention by a pharmacist can improve medication adherence and outcomes in patients with heart failure . The Editors In the United States , 5 million people have heart failure , with total health care costs exceeding $ 29 billion ( 1 ) . These costs are largely derived from expensive exacerbations that require emergency visits and hospitalizations ( 1 , 2 ) . Regularly administered cardiovascular medications may preserve cardiac function , improve quality of life , and reduce risk for costly exacerbations . However , patients sometimes do not adhere to prescribed instructions and have poor outcomes ( 35 ) . Research ers have estimated that approximately 50 % of patients with chronic illnesses do not take their medications as prescribed ( 6 ) . Reasons for nonadherence include lack of patient knowledge , skills , and support to appropriately self-manage complicated medication regimens ( 7 , 8) . Although chronic disease management programs abound , few studies have rigorously tested interventions aim ed at improving patient adherence to prescribed medications and their effect on health outcomes ( 9 , 10 ) . We conducted a r and omized clinical trial to assess the effect of a pharmacist intervention on patients who are socioeconomically disadvantaged and medically vulnerable . We hypothesized that the intervention would improve adherence to heart failure medications , reduce exacerbations requiring emergency department visits or hospitalization , improve disease-specific quality of life , increase patient satisfaction , and reduce health care costs . Methods Design Overview The methods for our r and omized trial are described elsewhere ( 1113 ) . We recruited patients from the general medicine and cardiology practice s of Wishard Health Services , Indianapolis , Indiana , which serves socioeconomically disadvantaged and medically vulnerable patients . The study was conducted from February 2001 to June 2004 . Patients took part in the study for 12 months and received 9 months of active intervention by the pharmacist or usual care followed by 3 months of postintervention assessment . Patients in the usual care and intervention groups visited the same pharmacy location , but the intervention pharmacist was instructed to have no contact with patients in the usual care group . The institutional review boards of Indiana UniversityPurdue University and the University of North Carolina at Chapel Hill approved this study . Setting and Patients Indiana University Medical Group , Indianapolis , is an academic primary care group practice composed of primary and specialty care clinics affiliated with Wishard Health Services . Faculty physicians , residents , and nurse practitioners provide care to 13000 adults ( mean age , 57 years [ SD , 15 ] ; 60 % women ; 50 % African American ) . Annually , these patients make approximately 50000 visits to practice s , 72000 visits to emergency departments , and 135000 visits to pharmacies and have 16000 hospitalizations . We recruited patients from 4 identical general medicine practice s , 1 cardiology practice , and Wishard Memorial Hospital . Practice s met in half-day sessions per week that were attended by 2 or 3 faculty members and 3 to 5 residents or fellows from each practice . Faculty physicians practice d 1 to 5 half-days per week , whereas fellows practice d 1 to 2 half-days per week and residents attended the practice 1 half-day per week . Out patients of Wishard Health Services fill their prescriptions at central or de central ized outpatient pharmacies located at the ambulatory care center or at 1 of several satellite pharmacies stationed at neighborhood clinics . Fully stocked de central ized pharmacies serviced all study patients . From February 2001 to January 2003 , the study pharmacy was located in a building adjacent to the ambulatory care center . From February 2003 to June 2004 , the study pharmacy was moved to a space adjacent to the general medicine practice s in the ambulatory care center . Two pharmacists and 1 technician were stationed at the pharmacy . The study pharmacist was instructed to service patients in the intervention group only , and a second pharmacist serviced patients in the usual care group and filled prescriptions to be delivered to patients at outlying clinics . The technician filled prescriptions and read electronic adherence monitors . Weekly lists of eligible patients were created by using the Regenstrief Medical Record System ( Regenstrief Institute , Indianapolis , Indiana ) ( 14 , 15 ) . We invited clinical ly stable patients from general internal medicine practice s , a cardiology clinic , and Wishard Memorial Hospital ( at discharge ) to participate in the study . Of 3034 patients with a diagnosis of heart failure , 1512 met criteria for enrollment . Patients were eligible if they were 50 years of age or older ; planned to receive all of their care , including prescribed medications , at Wishard Health Services ; had a diagnosis of heart failure confirmed by their primary care physician ; regularly used at least 1 cardiovascular medication for heart failure ( angiotensin-converting enzyme [ ACE ] inhibitor or angiotensin-receptor blocker , -adrenergic antagonist , diuretic , digoxin , or aldosterone antagonist ) ; were not using or were not planning to use a medication container adherence aid ( for example , a pill box ) ; had access to a working telephone ; and could hear within the range of normal conversation . We excluded patients with dementia . Patients received their prescription medications through state and local assistance plans at no cost . Thus , cost of medicines was not a deterrent to adherence . R and omization A trained interviewer conducted a baseline interview at enrollment . Interviewers were blinded to patients ' study status and played no role in the delivery of the intervention . Interviewers contacted a central ized data manager at the end of each interview to determine the patient 's study assignment , which was otherwise concealed . We r and omly assigned patients , without blocking or stratification , to receive the pharmacy intervention or usual care by using a univariate discrete distribution from the IMSL Fortran Library 's subroutine RNGDA pseudor and om number generator ( Absoft Corp. , Rochester Hills , Michigan ) ( 16 ) . We r and omly assigned more patients to the usual care group so that this group could also be a prospect i ve cohort for study ing risk factors associated with the clinical deterioration of heart failure . Of the 314 patients included in the study , 229 were recruited from the general internal medicine practice s , 15 from the cardiology clinic , and 70 on discharge from the Wishard Memorial Hospital . The numbers of patients assigned to the intervention and usual care groups did not differ by recruitment site ( P= 0.83 ) . Intervention A pharmacist delivered the intervention by using a protocol ( Appendix Table 1 ) that included a baseline medication history of all prescription and over-the-counter drugs and dietary supplements taken by patients , which patients brought with them to the baseline interview , and the results of an assessment of patient medication knowledge and skills ( 7 , 8) . The pharmacist dispensed enough of the patient 's medications to last approximately 2 months . Appendix Table 1 . Pharmacist 's Intervention Protocol * When medications were dispensed , the pharmacist provided patient-centered verbal instructions and written material s about the medications ( 11 , 13 , 17 ) by using a schema for instruction that has been tested ( 18 , 19 ) . We assigned each medication category an icon ( for example , the icon for ACE inhibitors was a red ace of hearts ) . The same icon appeared on the container label and lid and on the written patient instructions . Written instructions were aim ed at patients with low health literacy and contained an easy-to-follow timeline to remind patients when to take their medications ( 13 ) . The pharmacist monitored patients ' medication use , health care encounters , body weight , and other relevant data by using a study data base ( 20 , 21 ) . Information about patients was communicated as needed to clinic nurses and primary care physicians by face-to-face visits , telephone , paging ( physician only ) , and e-mail ( physician only ) . Technicians supported the pharmacist 's dispensing efforts within the pharmacy throughout the study . We incorporated costs therein into the economic analysis . Pharmacists serviced patients in the usual care group who were not associated with the intervention or the study . An interdisciplinary team of investigators that included pharmacists with advanced training in patient education and cardiovascular pharmacotherapy , a geriatrician , a cardiologist with expertise in heart failure , a behavioral scientist , and a cognitive psychologist trained the intervention pharmacist . The intervention pharmacist also studied guidelines for treating heart failure ( 22 ) , key concepts in the pharmaceutical care of older adults , communication techniques , and the pharmacotherapy of the cardiovascular drugs for heart failure . All pharmacists at Wishard Health Services were aware of the study and were instructed on how to h and le and redirect intervention patients who inadvertently arrived at their pharmacy . Usual Care Patients in the usual care group were aware of the purpose of the study , and their primary care We investigated whether printed or videotaped information is more effective in enhancing colon cancer knowledge . Subjects ( n = 1100 ) were r and omized into three groups : to receive a booklet , view a videotape , or receive no intervention . Subjects receiving the intervention showed increased knowledge compared with control subjects ( booklet = 23 % and videotape = 26 % vs no intervention = 3 % ) . Findings suggest that personalized educational material s are effective in enhancing colon cancer knowledge BACKGROUND Recent research has shown that phonological awareness therapy can improve speech production in children with expressive phonological disorders . This approach may be appealing to clinicians as the therapy may also benefit the children 's general phonological abilities and lead to gains in their literacy skills . AIMS To examine the effectiveness of phonological awareness therapy under conditions more similar to those prevailing in many speech and language therapy clinics . Children were treated in small groups and less intensive therapy was offered than in previous studies . METHODS & PROCEDURES Twenty children were r and omly assigned to treated and untreated groups . A pre-/post-test design was used to monitor their progress in phonological awareness , literacy and speech production . Children were treated in groups of three . They received 12 hours of therapy . OUTCOMES & RESULTS Comparisons of the groups showed that the treated group made significantly greater gains in phonological awareness . However , differences between the groups in the measures of literacy and speech production were smaller and non-significant . Considerable variation was detected in the response of individual children to the therapy . CONCLUSIONS The results show the effectiveness of phonological awareness therapy in benefiting children 's general phonological skills . However , the comparison of these and previous findings suggest that children may require more therapy than is often available if literacy and speech production are also to benefit . Further research is required to confirm the duration and intensity of therapy required . Until such information is available , clinicians might want to take a cautious approach and combine therapies that target phonological awareness with more traditional approaches , that target speech production more directly AIM To examine the incidence of educational and therapeutic re source dependency in a group of very preterm children at 8 years of age . METHODS All children with a gestational age less than 30 weeks , who survived to discharge from the neonatal intensive care unit at Royal Prince Alfred Hospital , between 1987 and 1994 , were prospect ively enrolled in developmental follow-up . At 8 years of age , information regarding re source dependency was obtained from parents and teachers using interviews and question naires . St and ardized psychometric measures of cognition and academic achievement were administered . RESULTS Information was obtained for 365 ( 73.3 % ) of surviving 8-year-old children ; 65 ( 17.8 % ) had a neurosensory disability and 24 ( 36.9 % ) children in this group were in full-time special education . In those without neurosensory disability ( n=300 ) , seven ( 2.3 % ) children were already in full-time special education for an intellectual deficit . Among children in mainstream education , 154/293 ( 52.5 % ) had received or were still receiving additional assistance in some form ( part-time special education , grade retention , therapeutic intervention or private tutoring ) . Difficulty in literacy was the most commonly reported problem . Re source dependency was not related to gestation nor predicted by intelligence in children without neurosensory disability , but was related to maternal education . Children who had had or were continuing to receive part-time assistance showed delays in academic skills at assessment . CONCLUSIONS A high level of on-going re source dependency exists in this group in an attempt to maintain grade appropriate achievement . Re source dependency is not related to gestation in neurologically normal children . General cognitive measures of intelligence do not predict these problems in the majority of children Background : Flexibility is important in choosing methods and modes of question naire administration , to accommo date the needs of patients with diverse linguistic , cultural , educational , and functional skills . Objective : To investigate the extent to which 2 different modes ( interview- vs. self-administration ) yielded comparable estimates of health-related quality of life ( HRQL ) as measured by the Functional Assessment of Cancer Therapy-General ( FACT-G ) . Participants : English- ( n = 739 ) and Spanish-speaking ( n = 456 ) ambulatory cancer patients . Research Design : Patients were r and omly assigned to interview- or self-administration of question naires , stratified by site , language , and race/ethnicity . A 3-phase analytic strategy was implemented : ( 1 ) confirmatory factor analysis to confirm unidimensionality of each FACT-G subscale ; ( 2 ) 2 techniques to evaluate differential item functioning across modes ; and ( 3 ) multivariable regression to compare mean HRQL scores across modes . Results : Confirmatory factor analysis model fit indices provided good support for unidimensionality across all 4 language /mode groups . Three of 27 items demonstrated statistically significant mode differential item functioning in each language . There were no statistically significant or minimally important mode effects on mean HRQL outcomes , with or without adjusting for other factors . Conclusions : Among both English- and Spanish-speaking ambulatory cancer patients , the FACT-G can be administered by either interview- or self-administration , without concern for significant mode effects on the data . Results may not be generalizable to patients with greater disease severity or those with low literacy OBJECTIVE To evaluate whether plasma levels of free fatty acids ( FFAs ) are independently associated with incidence of type 2 diabetes . RESEARCH DESIGN AND METHODS A case-cohort design was used to r and omly select 580 incident cases of diabetes and 566 noncases from 10,275 African-American and white men and women in the Atherosclerosis Risk in Communities study , aged 45 - 64 years and without prevalent diabetes at the baseline exam . Incident diabetes was ascertained at three exams over 9 years of follow-up . FFA levels were measured in plasma sample s collected at the baseline exam . RESULTS At baseline , FFA level was inversely associated with height and positively associated with female sex , BMI , waist circumference , waist-to-hip ratio , heart rate , plasma triglycerides , and an inflammation score quantifying levels of six systemic inflammation markers . Relative risks for incident diabetes ( fourth vs. first quartile of FFAs ) were increased in a basic model adjusted for age , sex , race , and center ( hazard ratio 1.68 , 95 % CI 1.20 - 2.34 ) and in a model further adjusted for baseline fasting glucose , insulin , BMI , waist circumference , triglycerides , and the inflammation score ( 1.63 , 1.04 - 2.57 ) . Relative risks associated with a greater FFA level were lowest among those of normal weight and highest among the obese , but a formal test of interaction between FFAs and BMI was not statistically significant . CONCLUSIONS Individuals with higher fasting levels of plasma FFAs were at modestly higher risk of type 2 diabetes in this cohort of middle-aged adults Objectives : To measure the prevalence of limited functional health literacy in the UK , and examine associations with health behaviours and self-rated health . Design : Psychometric testing using a British version of the Test of Functional Health Literacy in Adults ( TOFHLA ) in a population sample of adults . Setting : UK-wide interview survey ( excluding Northern Irel and and the Scottish Isles ) . Participants : 759 adults ( 439 women , 320 men ) aged 18–90 years ( mean age _ 47.6 years ) selected using r and om location sampling . Main outcome measures : Functional health literacy , self-rated health , fruit and vegetable consumption , physical exercise and smoking . Results : We found that 11.4 % of participants had either marginal or inadequate health literacy . Multivariable logistic regression analysis indicated that the risk of having limitations in health literacy increased with age ( adjusted odds ratio 1.04 ; 95 % confidence interval 1.02 to 1.06 ) , being male ( odds ratio _ 2.04 ; 95 % confidence interval 1.16 to 3.55 ) , low educational attainment ( odds ratio _ 7.46 ; 95 % confidence interval 3.35 to 16.58 ) and low income ( odds ratio _ 5.94 ; 95 % confidence interval 1.87 to 18.89 ) . In a second multivariable logistic regression analysis , every point higher on the health literacy scale increased the likelihood of eating at least five portions of fruit and vegetables a day ( odds ratio _ 1.02 ; 95 % confidence interval 1.003 to 1.03 ) , being a non-smoker ( odds ratio _ 1.02 ; 95 % confidence interval 1.0003 to 1.03 ) and having good self-rated health ( odds ratio _ 1.02 ; 95 % confidence interval 1.01 to 1.04 ) , independently of age , education , gender , ethnicity and income . Conclusions : The results encourage efforts to monitor health literacy in the British population and examine associations with engagement with preventative health behaviours Abstract BACKGROUND : The Centers for Disease Control and Prevention has proposed increasing the proportion of people who learn their HIV serostatus . The health care setting represents a logical site to accomplish this goal . However , little is known about factors that determine acceptability of HIV testing in health care setting s , particularly patients ’ health literacy . OBJECTIVE : To evaluate the association between patients ’ health literacy and acceptance of HIV testing among individuals at an urgent care center ( UCC ) . METHODS : As part of a prospect i ve study that sought to increase HIV testing at a UCC located in an inner-city hospital serving an indigent population , we surveyed patients who had been offered an HIV test by their providers and had accepted or refused testing . Pretest counseling was provided using a low-literacy brochure given to patients upon registration into the clinic . We measured health literacy level using the Rapid Estimate of Adult Literacy in Medicine ( REALM ) scale . RESULTS : Three hundred seventy-two patients were enrolled in the study . In univariate analysis , no statistically significant difference between HIV test acceptors or refusers was found for gender , race/ethnicity , marital status , income , type of health insurance , educational level , or type of test offered . Acceptors were more likely to have a low literacy level ( odds ratio [ OR ] , 1.763 ; 95 % confidence interval [ CI ] , 1.084 to 2.866 ) and be less than 40 years old ( OR , 1.639 ; 95 % CI , 1.085 to 2.475 ) . In multivariate analysis , low health literacy was shown to be a predictor of HIV test acceptance controlling for age and education ( OR , 2.017 ; 95 % CI , 1.190 to 3.418 ) . CONCLUSIONS : Low health literacy was shown to be a predictor of HIV test acceptance . Patients presenting to a UCC with poorer health literacy appear more willing to comply with health care providers ’ recommendations to undergo HIV testing than those with adequate health literacy when an “ opt-out ” strategy combined with a low-literacy brochure is used OBJECTIVE To compare responses to print versions of the Consumer Assessment of Healthcare Providers and Systems 2.0 survey ( CAHPS ) to those for an illustration enhanced format and a telephone based interactive voice response format . METHODS First , 2015 adult patients awaiting primary care visits completed : demographic information , Test of Functional Health Literacy ( S-TOFHLA ) , CAHPS in one of three formats : print , illustrated , or interactive voice . A second sample of 4800 active patients was r and omized to receive alternative formats . RESULTS Response rates for the illustrated ( 31.3 % ) and print ( 30.4 % ) formats were significantly higher than for the interactive voice format ( 18.1 % ) . The results of the illustrated format were comparable to the traditional text version , but required about 2 min more to complete by both low and high literacy groups . There were almost no invalid responses for the interactive voice format , but the format was associated with lower CAHPS satisfaction scores . CONCLUSION Despite extensive efforts to produce formats tailored to individuals with limited literacy , surprisingly we found no consistent advantages to either alternative format . In fact , the interactive voice format yielded lower satisfaction scores and lower response rates . PRACTICE IMPLICATION S Practitioners need to ensure the health instruments they use are aligned with literacy skills and delivery preferences of their consumers . The lack of benefit of the illustrated form does not support investment of re sources in these formats to measure satisfaction . The interactive voice response deserves more study --do lower scores register limited access to or use of telephones , irritation or true signal A r and omized experiment was conducted to test the effectiveness of Even Start , a federally supported family literacy program providing early childhood education , adult education , parenting education , and joint parent-child literacy activities to children and parents from low-literate families . The evaluation of 18 Even Start projects followed 463 families for 2 years and found no statistically significant or educationally important impacts on Even Start families when they were compared with control families on child literacy outcomes , parent literacy outcomes , or parent-child interactions . The study concludes that Even Start projects were able to properly implement family literacy programs , and the observed lack of effectiveness is attributed to a combination of 2 factors : ( a ) a lack of full participation on the part of families and ( b ) instructional services that may be ineffective because of the curriculum content or the instructional approach The aim of the study was to determine the clinical and perceived effectiveness of the Sunflower therapy in the treatment of childhood dyslexia . The Sunflower therapy includes applied kinesiology , physical manipulation , massage , homeopathy , herbal remedies and neuro-linguistic programming . A multi-centred , r and omised controlled trial was undertaken with 70 dyslexic children aged 6 - 13 years . The research study aim ed to test the research hypothesis that dyslexic children ' feel better ' and ' perform better ' as a result of treatment by the Sunflower therapy . Children in the treatment group and the control group were assessed using a battery of st and ardised cognitive , Literacy and self-esteem tests before and after the intervention . Parents of children in the treatment group gave feedback on their experience of the Sunflower therapy . Test scores were compared using the Mann Whitney , and Wilcoxon statistical tests . While both groups of children improved in some of their test scores over time , there were no statistically significant improvements in cognitive or Literacy test performance associated with the treatment . However , there were statistically significant improvements in academic self-esteem , and reading self-esteem , for the treatment group . The majority of parents ( 57.13 % ) felt that the Sunflower therapy was effective in the treatment of learning difficulties . Further research is required to verify these findings , and should include a control group receiving a dummy treatment to exclude placebo effects Background The recent public health risks arising from bioterrorist threats and outbreaks of infectious diseases like SARS ( Severe Acute Respiratory Syndrome ) highlight the challenges of effectively communicating accurate health information to an alarmed public . Objective To evaluate use of the Internet in accessing information related to the anthrax scare in the United States in late 2001 , and to strategize about the most effective use of this technology as a communication vehicle during times of public health crises . Methods A paper-based survey to assess how individuals obtained health information relating to bioterrorism and anthrax during late 2001.We surveyed 500 r and omly selected patients from two ambulatory primary care clinics affiliated with the Brigham and Women 's Hospital in Boston , Massachusetts . Results The response rate was 42 % . While traditional media provided the primary source of information on anthrax and bioterrorism , 21 % ( 95 % CI , 15 % - 27 % ) of respondents reported search ing the Internet for this information during late 2001 . Respondents reported trusting information from physicians the most , and information from health websites slightly more than information from any traditional media source . Over half of those search ing the Internet reported changing their behavior as a result of information found online . Conclusions Many people already look to the Internet for information during a public health crisis , and information found online can positively influence behavioral responses to such crises . However , the potential of the Internet to convey accurate health information and advice has not yet been realized . In order to enhance the effectiveness of public-health communication , physician practice s could use this technology to pro-actively e-mail their patients vali date d information . Still , unless Internet access becomes more broadly available , its benefits will not accrue to disadvantaged population A quasi-experimental , statewide intervention targeting preschool teachers ' enhancement of children 's language and early literacy was evaluated . Across 2 years and 20 Head Start sites , 750 teachers participated ( 500 target , 250 control ) , with 370 classrooms r and omly selected to conduct pre- and posttest assessment s ( 10 r and omly selected children per class ) . The inability to r and omize children to classrooms was addressed by examining children 's performance for teachers who were control teachers in Year 1 and target teachers in Year 2 . We also compared teachers with 2 years of training with teachers with 1 year of training and with control teachers . Greater gains were found for children in target classrooms than for those in control classrooms for all skills , but particularly for language skills , in Year 2 , and this varied by program site . The presence of a research -based early literacy curriculum , higher levels of teacher education , and full-day versus half-day programs were significant moderators of intervention effectiveness . The challenges of implementing a statewide initiative across programs that varied in their readiness to implement a cognitively rich experience for preschool children are discussed This study compares the effects of computer-based and instructor-led training on long-term care staff with a high school education or less on fire safety knowledge , attitudes , and practice s. Findings show that both methods of instruction were effective in increasing staff tests scores from pre- to posttest . Scores of both groups were lower at follow-up three months later but continued to be higher than at pretest . Staff with a high school education increased scores more than those without a high school diploma The effect of the degree of illiteracy ( complete or incomplete ) on phonological skills , verbal and visual memory and visuospatial skills is examined in 97 normal Brazilian adults who considered themselves illiterate , and 41 Brazilian school children aged 7 to 8 years , either nonreaders or beginning readers . Similar literacy effects were observed in children and in adults . Tasks involving phonological awareness and visual recognition memory of nonsense figures distinguish the best nonreaders and beginning readers . Children performed better than adults at oral repetition of short items and figure recall , and adults better than children at semantic verbal fluency , digit span , and word list recall . A principal component analysis of the correlations between tasks showed that phonological awareness/reading , phonological memory/oral repetition , and semantic verbal memory/fluency tasks , generated different components . The respective role of culturally based preschool activities and literacy on the cognitive functions that are explored in this study is discussed This study determined the prevalence of overweight , overall and central obesity in female adolescents and women and their possible association with marital status , occupation , literacy , parity , daily meal and snack consumption . The study was a cross-sectional , r and om survey of households . Rural and urban areas of Islamshahr district in Iran were selected and 1003 female adolescents and women aged 10 - 65 years were studied . The frequency of overweight and obesity were similar in rural and urban areas . On the basis of body mass index ( BMI ) , more than 19 % of adolescents were overweight or at risk of it and 66.8 % of adult females were overweight or obese . Frequency of central obesity [ waist to hip ratio ( WHR ) > or = 0.85]was 35.7 % in all females . The mean BMI was significantly higher in married women and in women with less than 8 years of formal education . The mean WHR was significantly higher in women with less than 8 years of education or with more than 6 parity female adults . In addition , the mean BMI s and WHRs were significantly higher in women without any daily snack consumption . Overweight and obesity was very common in adult females of Islam shahr thus prevention of overweight and obesity through a healthy diet and increased physical activity should now be an important priority area OBJECTIVE To assess the intelligence , visuo-motor perception , motor competence and school performance of children with birth weight less than 2000 grams , at the age of 12 years . DESIGN Prospect i ve cohort study . SETTING Infants discharged from a Neonatal Special Care Unit of a referral hospital with birth weight less than 2000 g between 1987 - 89 and followed up in the High Risk Clinic . METHODS The children were assessed by the Weschler 's Intelligence Scale , Bender Gestalt test for visuo-motor perception , Wide Range Achievement Test for specific learning disability , Draw-a-Person screening test for emotional problems and Movement Assessment Battery for motor competence . Academic achievement was also scrutinised . RESULTS One hundred and eighty children weighing less than 2000 grams at birth and ninety control children were assessed . The mean IQ of the study group was normal ( 89.5 + /- 16.9 ) , though significantly lower than that of controls ( 97.2 + /- 14.1 ; p<0.05 ) . Pre term SGA children had the lowest mean IQ ( 85.4 + /- 17.7 ) . In the 78 VLBW children , there were 12 ( 15.4 % ) mentally retarded children as compared to only 3 ( 3.3 % ) amongst controls ( p<0.001 ) . There were only 3 ( 3.8 % ) ' bright ' children among the VLBW group , as compared to 20 ( 22.2 % ) in the control group ( p<0.001 ) . Visuo-motor perception and motor competence of the study group was poor , and they had writing and mathematics learning disability , especially the preterm SGA and VLBW group . Academic achievement was poor and the incidence of borderline intelligence was 24.4 % , which has increased from 13.4 % at 6 years . CONCLUSIONS The intelligence and academic performance of the children weighing less than 2000 grams is significantly lower than that of controls , though within normal limits . They also have poor visuo-motor perception , motor incompetence , reading and mathematics learning disability . The preterm SGA and VLBW children had the poorest cognitive abilities PURPOSE Appropriate patient treatment necessitates patient literacy due to the increasing use of written screening tools in medicine . We evaluated the frequency , predictors and impact of poor underst and ing of the American Urological Association symptom index on patient care . MATERIAL S AND METHODS This prospect i ve cohort study included 300 male patients older than 40 years who completed the American Urological Association symptom index twice , as self-administered and then as interviewer administered . These 2 responses were compared by calculating correlation coefficients and weighted kappa statistics to assess patient underst and ing of the American Urological Association symptom index . Multivariate logistic regression analyses examined the association between patient characteristics and poor underst and ing of the symptom index , defined as underst and ing fewer than 4 questions , by calculating the OR and corresponding 95 % CI . RESULTS Of the 7 symptom index questions 16 % of patients understood all , 38 % understood more than half , 18 % understood fewer than half and 28 % understood none . The agreement between self-administered and interviewer administered responses decreased with decreasing education level . Compared to patients with at least some college education those with fewer than 9 years of education were more likely to have a poor underst and ing of the American Urological Association symptom index ( OR 102.16 , 95 % CI 23.93 - 436.10 ) , result ing in a 2-fold increase in the risk of symptom misclassification ( p trend < 0.01 ) . After controlling for education associations for age , income , employment and race were not significantly different from null . CONCLUSIONS A significant number of patients with lower education and literacy levels incorrectly self-administer the American Urological Association symptom index , result ing in the misclassification of their symptoms , which may severely limit their access to appropriate care Background : In nonindustrialized nations , illiteracy is independently associated with poor health . The objective of this research was to determine whether such a relation exists in the United States . Methods : One hundred ninety-three persons were r and omly selected from a group of adult students enrolled in a publicly funded literacy training program . Subjects ’ health status was measured with the Sickness Impact Profile ( SIP ) , a behaviorally based measure of sickness-related dysfunction . Subjects ’ literacy skills were also measured . Multivariate statistical techniques were then used to evaluate the relation between health status and literacy level and to adjust for confounding sociodemographic factors . Results : The physical health ( measured by the SIP ) of subjects with extremely low reading levels was poor compared with that of subjects with higher reading levels . The relation between reading level and physical health was statistically significant ( P < 0.002 ) , even after adjusting for confounding sociodemographic variables . Psychosocial health ( measured by the SIP ) was poor across all levels of reading skills and was comparable with the psychosocial health of population s with severe psychosocial disability . The relation between reading level and psychosocial health was statistically significant ( P < 0.02 ) after adjusting for confounding variables . Conclusions : In the United States , illiteracy and poor health status are independently associated This prospect i ve , longitudinal study examined factors affecting intelligence and school readiness in children 4 - 5 years of age with prenatal cocaine/opiate exposure . Intelligence and school readiness scores were not significantly different for the drug-exposed group ( N=104 ) than for unexposed , demographically matched controls ( N=35 ) , although both groups scored slightly below average . Caregivers of drug-exposed children scored significantly lower in intelligence and reading achievement than caregivers of controls ; both were below average . Caregiver reading scores accounted for the largest variance in both child intelligence and school readiness ; for school readiness , birth weight also contributed but was less important in the model . Neither prenatal drug exposure nor continuing caregiver drug use was significant in the regression analyses . The relationship between child scores and caregiver reading achievement is consistent with studies showing the importance of a stimulating , supportive home environment , and suggests interventions to foster caregiver literacy skills and facilitate caregiver-child cognitive interactions such as reading to the child Background Although patient participation in the medical encounter confers significant benefits , many patients are reluctant to ask questions of their physicians . Patients ’ literacy level may affect their level of participation and question -asking behaviors . Objective To examine the effect of literacy on the number and types of questions asked by patients during primary care office visits . Design Convenience sample recruited between April and November 2004 . Physician – patient visits were audiotaped , and patient questions from complete encounters ( N = 57 ) were coded using an adaptation of the Roter Interaction Analysis System . Patients Participants were predominantly middle-aged ( mean age = 56.7 years ) , female ( 75.4 % ) , and African American ( 94.7 % ) . Low literacy skills ( ≤6th grade reading level ) were present in 38.6 % . Measurements We hypothesized prospect ively that low-literacy patients would ask fewer total questions and fewer questions about key aspects of their medical care . Results Low-literacy adults asked significantly fewer questions about medical care issues ( median = 4 vs 6 among patients with higher literacy levels , p = .014 ) . They also tended to ask fewer questions overall ( median = 7 vs 10 , p = .070 ) . Low-literacy patients were more likely to ask the physician to repeat something ( p = .013 ) , indicating an initial lack of underst and ing . They were less likely to use medical terminology , refer to medications by name , request additional services , or seek new information . Question -asking behavior was not significantly related to patient gender , age , years of education , or physician – patient gender concordance . Conclusions Literacy level appears to be an important determinant of patients ’ participation in the medical encounter . Low-literacy patients ask fewer questions about their medical care , and this may affect their ability to learn about their medical conditions and treatments Previous studies on individual differences in mathematical abilities have shown that working memory contributes to early arithmetic performance . In this study , we extended the investigation to algebraic word problem solving . A total of 151 10-year-olds were administered algebraic word problems and measures of working memory , intelligence quotient ( IQ ) , and reading ability . Regression results were consistent with findings from the arithmetic literature showing that a literacy composite measure provided greater contribution than did executive function capacity . However , a series of path analyses showed that the overall contribution of executive function was comparable to that of literacy ; the effect of executive function was mediated by that of literacy . Both the phonological loop and the visual spatial sketchpad failed to contribute directly ; they contributed only indirectly by way of literacy and performance IQ , respectively The WRAT-3 Reading subtest ( WRS ) may be inappropriate in diseases having disproportionate impact on population s with educational disadvantages ( i.e. , HIV/AIDS ) . To underst and how low literate individuals would perform on an IQ test requiring minimal education , the General Ability Measure for Adults ( GAMA ) was studied . HIV+ participants completed WRS , GAMA , and neuropsychological tests . Participants with low WRS ( < 80 SS ) but higher GAMA ( ≥80 SS ) had significantly better overall neuropsychological functioning than those with < 80 SS on both tests . The GAMA may be a useful test when disparities in educational quality render reading-based measures of IQ a poor surrogate of premorbid function PURPOSE Colorectal cancer screening is the most underused cancer screening tool in the United States . The purpose of this study was to test whether a health care provider-directed intervention increased colorectal cancer screening rates . PATIENTS AND METHODS The study was a r and omized controlled trial conducted at two clinic firms at a Veterans Affairs Medical Center . The records of 5,711 patients were review ed ; 1,978 patients were eligible . Eligible patients were men aged 50 years and older who had no personal or family history of colorectal cancer or polyps , had not received colorectal cancer screening , and had at least one visit to the clinic during the study period . Health care providers in the intervention firm attended a workshop on colorectal cancer screening . Every 4 to 6 months , they attended quality improvement workshops where they received group screening rates , individualized confidential feedback , and training on improving communication with patients with limited literacy skills . Medical records were review ed for colorectal cancer screening recommendations and completion . Literacy level was assessed in a subset of patients . RESULTS Colorectal cancer screening was recommended for 76.0 % of patients in the intervention firm and for 69.4 % of controls ( P = .02 ) . Screening tests were completed by 41.3 % of patients in the intervention group versus 32.4 % of controls ( P = .003 ) . Among patients with health literacy skills less than ninth grade , screening was completed by 55.7 % of patients in the intervention group versus 30 % of controls ( P < .01 ) . CONCLUSION A provider-directed intervention with feedback on individual and firm-specific screening rates significantly increased both recommendations and colorectal cancer screening completion rates among veterans OBJECTIVE To examine why older age groups have worse functional health literacy . METHODS Home interviews were conducted with community-dwelling elderly persons ( n = 2,774 ) to determine demographics , years of school completed , newspaper reading frequency , chronic diseases , and health status . Participants completed the Short Test of Functional Health Literacy in Adults ( S-TOFHLA , range 0 - 100 ) and the Mini Mental State Examination ( MMSE ) . RESULTS Mean S-TOFHLA scores declined 1.4 points ( 95 % CI 1.3 - 1.5 ) for every year increase in age ( p < .001 ) . After adjusting for sex , race , ethnicity , and education , the S-TOFHLA score declined 1.3 points ( 95 % CI 1.2 - 1.4 ) for every year increase in age . Even after adjustment for performance on the MMSE , the S-TOFHLA score declined 0.9 points ( 95 % CI 0.8 - 1.0 ) for every year increase in age ( p < .001 ) . Differences in newspaper reading frequency , visual acuity , chronic medical conditions , and health status , did not explain the lower literacy of older participants . DISCUSSION Functional health literacy was markedly lower among older age groups even after adjusting for differences in MMSE performance , newspaper reading frequency , health status , and visual acuity . Future studies should prospect ively examine whether functional literacy declines with age and whether this is explained by declines in cognitive function Limited health literacy , common in patients with diabetes , has been associated with worse diabetes outcomes ( 1–4 ) . While patients with limited health literacy have worse diabetes knowledge ( 2–5 ) , knowledge does not necessarily predict outcomes ( 6–8 ) . Because diabetes requires extensive self-care , differences in self-management behaviors may be a key contributor to the disparity in outcomes . In fact , low health literacy has been associated with poor self-care in other chronic illnesses ( 9,10 ) . However , no study has examined the relationship between health literacy and self-management behaviors in patients with diabetes . In addition , studies have not assessed whether diabetes education , which is widely recommended , is effective in improving self-management behaviors in patients with limited health literacy . The objectives of our study were to examine the association of health literacy with self-management behaviors in patients with diabetes and to determine whether diabetes education improves self-management behaviors in patients with limited compared with adequate health literacy . Underst and ing the relationship between health literacy and self-management behaviors should enhance efforts to improve diabetes outcomes . We conducted a prospect i ve observational study of patients enrolled in diabetes education classes at the Hospital of the University of Pennsylvania . The classes consist of an individual meeting with a diabetes educator and three weekly 3-h group classes and are recognized by the American Diabetes Association ( 11 ) . All patients ≥18 years of age present for a regularly scheduled diabetes class were recruited . This study design ed and piloted an interactive measure to assess learning preferences of Latinos in the United States with diabetes and limited literacy . The measure utilized interactive learning activities to represent four learning styles : visual ( seeing ) , kinesthetic ( doing ) , affective ( feeling/sensing ) , and cognitive ( thinking ) , targeting four diabetes self-management behaviors : choosing healthy foods ; underst and ing portion sizes ; distinguishing foods to eat often/sometimes/rarely ; and limiting fat . Quantitative data were collected using the Spanish Short Test of Functional Health Literacy in Adults ( S-TOFHLA ) . Individual , structured cognitive interview questions asked participants to identify learning activities that most reflected their own experience with diabetes . Participant observations provided additional qualitative data . Ten Spanish-speaking adults with type 2 diabetes and limited literacy participated in two r and omly selected target behaviors and identified easiest and most difficult to underst and learning activities . S-TOFHLA scores ranged from 0 to 21 points ( mean 7.0 ) and identified eight participants with inadequate and two with marginal health literacy . Easiest to underst and tasks were kinesthetic , most difficult to underst and tasks were cognitive . This is one of the first known studies of its kind and offers insight for measuring learning styles of Latinos with diabetes and low health literacy Research suggests that much of the available health education literature requires a level of reading ability that makes it inaccessible to a large proportion of the population in greatest need of health information . The present study tested the value of illustrations and a narrative text style as means of improving the readability of a brochure design ed to provide information on cervical cancer and condyloma . Two versions of the brochure were design ed , one that had only text presented as simple sentences in bullet-type format ( SMOG reading level score of 7.7 ) , and a second version that had somewhat more difficult text formatted in a narrative style ( SMOG grade level score of 8.4 ) together with drawings design ed to complement the text . A r and omized study design was used to test for comprehension , perceived ease of underst and ing , and overall rating of the two brochures . Women selected from one private and three public health primary -care clinics were r and omly assigned to read one of the two brochures . The brochure with illustrations and narrative text was given a significantly higher overall rating than the one with bullet-type text and no illustrations , while no difference was found in perceived ease of reading . Among poor readers , comprehension was significantly greater for women who read the brochure with illustrations and narrative text , with no difference in comprehension of the two brochures for better readers . The results suggest that the use of aids such as illustrations and text style can make health education literature more accessible to high-risk population s , while remaining interesting enough to appeal to individuals at all levels of reading ability Only limited pedagogical use has been made of information and communications technology ( ICT ) in nursing education in Norway . In this study the use of ICT was linked to assignments in the first year undergraduate nursing program and included four on-line discussion s. There is evidence to suggest that on-line discussion s can enhance the learning environment . The students ' experiences of the on-line discussion s are compared to those of the students participating in traditional group discussion s. The results show little difference between the two groups ' opinions of the discussion s ' fruitfulness and the ease in which they expressed their feelings , thoughts and ideas . However , there is a marked difference between the two groups regarding their experience of how the discussion s affected the amount of contact between group members outside the discussion s. Possible reasons for these findings are discussed Introduction : There have been few comprehensive evaluations of smoking reduction , especially in health care delivery systems , and little is known about its cost , maintenance of reduced smoking , or robustness across patient subgroups . Methods : A generally representative sample of 320 adult smokers from an HMO scheduled for outpatient surgery or a diagnostic procedure was r and omized to enhanced usual care or a theory-based smoking reduction intervention that combined telephone counseling and tailored newsletters . Outcomes included cigarettes smoked , carbon monoxide levels , and costs . Results : Both intervention and control conditions continued to improve from 3- to 12-month assessment s. Between-condition differences using intent-to-treat analyses on both self-report and carbon monoxide measures were nonsignificant by the 12-month follow-up ( 25 % vs. 19 % achieved 50 % or greater reductions in cigarettes smoked ) . The intervention was implemented consistently despite logistical constraints and was generally robust across patient characteristics ( eg , education , ethnicity , health literacy , dependence ) . Conclusions : In the absence of nicotine replacement therapy , the long-term effects of this smoking reduction intervention seem modest and nonsignificant . Future research is indicated to enhance intervention effects and conduct more comprehensive economic analyses of program variations OBJECTIVE Assess the pattern of relationships between personal- background characteristics and dimensions of quality of life ( QOL ) in diabetic patients . DESIGN Cross-sectional descriptive study . SAMPLE 117 adults with type 2 diabetes ( 100 female , 17 male ) r and omly selected from out patients referred to Sina hospital ( Tabriz , Iran ) . METHODS Participants answered a three-part question naire including ( 1 ) sociodemographic and medical ( diabetes-related ) personal- background characteristics ; ( 2 ) general health-related QOL instrument based on Swedish Health-Related QOL ; ( 3 ) disease-specific instrument for diabetic patients . Nine QOL dimensions were covered : physical function , pain , daily activities , feelings , sleep , relationships with relatives , overall health , problems with diabetes , satisfaction with diabetes treatment methods . Data were analyzed with inferential statistics , correlation , and multi-stage stepwise regression . RESULTS Personal background characteristics ( age , presence of medically educated people in family , whether patient was family breadwinner , unemployment , complications of diabetes ) accounted for 27 % of variance in the physical function dimension of QOL dimension . Other QOL dimensions ( daily activities , overall health , sleep , satisfaction with diabetes treatment . ) were also related to personal background characteristics . CONCLUSIONS Diabetic patients face great challenges in many dimensions of QOL . Nursing instructors and nursing educators in educational centers for diabetics can use the findings of this research to assess their patients more effectively The New York WORKS demonstration project was design ed to improve employment outcomes for persons with psychiatric disabilities receiving Supplemental Security Income ( SSI ) disability payments . This article shows how the individual characteristics of participants were related to outcomes at each stage of the multistage recruitment process used in the project and how those characteristics contributed to enrollment . The findings are important to program administrators who are interested in ensuring that SSI recipients receive equal access to employment-related services and who want to improve recruitment strategies for future demonstration projects . The New York WORKS recruitment process used administrative records from the Social Security Administration ( SSA ) to identify the population of over 68,000 SSI recipients with a diagnosis of a psychiatric disability in Erie County and New York City . Staff involved in the project documented the results of each stage of the recruitment process . The New York WORKS project included four stages : ( 1 ) the provision of information ( sending a letter and information packet ) ; ( 2 ) demonstrated awareness of the project ( response to a letter containing an overview of the project ) ; ( 3 ) expression of interest ( indication of interest in the project , using a postmarked form returned to New York WORKS project staff ) ; and ( 4 ) participation ( actual enrollment in the program ) . The project staff members were also able to identify data from administrative records that described the characteristics of the population , including age , sex , type of psychiatric diagnosis , the number of months that the person collected benefits before the recruitment process , employment experience before the recruitment process , and annual earnings in the year before the recruitment process . The data on outcomes at each stage of the recruitment process and the characteristics of SSI recipients were analyzed using an empirical method recently suggested by Heckman and Smith . The analysis identified the relationship between the characteristics of SSI recipients and the outcomes at each stage of the recruitment process and demonstrated how those characteristics contributed to the overall likelihood of enrollment . Demographic characteristics , information about diagnosis , and characteristics related to work history had different effects on outcomes at different stages of the recruitment process . For example , younger SSI recipients were less likely to reply to the information letter but more likely to express an interest in the project and more likely to enroll , given that interest . This result suggests that there may be an information barrier for the younger group of SSI recipients during the early recruitment stages . There were also interesting differences by psychiatric diagnosis and by recent employment experience at each stage of the process . Most notably , persons with anxiety disorders were less likely to express an interest in the project and less likely to enroll in the project if they expressed an interest . This finding suggests that project administrators may need to examine more effective methods to accommo date persons with an anxiety disorder at the enrollment stage of the recruitment process . Persons with relatively low earnings in the year before the project were more likely to respond , to express interest in the project , and to enroll than were those with no earnings and those with relatively high earnings . This finding suggests that the recruitment strategy used by the New York WORKS project is more effective at enrolling a subset of the population that has some demonstrated work capacity and that , of those with a demonstrated work capacity , New York WORKS is enrolling those who are likely to have the most to gain from the project . This finding has implication s for the development of sample design s for other demonstration projects , in particular the SSA-proposed mental health treatment study . A number of strategies may lead to improvements in future evaluations of participation in SSA projects and programs . For example , the New York WORKS data did not contain information for all SSI recipients on race , education , or literacy . These factors have been shown to be important in the Job Training Partnership Act literature and are likely to play a role in participation . The inclusion of these data in future evaluations may provide important information on participation in SSA projects . Another useful strategy for future evaluations includes the identification of r and om sample s of those who choose not to enroll at different stages in the process and the collection of information on the reason for the decision . These additional data may help project administrators to gain a clearer description of the reasons for differences in outcome that occur at each stage of the process , assess the overall performance of the recruitment process , and improve the recruitment processes used in future projects BACKGROUND Medication adherence by older adults who are discharged from the emergency department ( ED ) is an essential attribute of effective treatment . Research ers have demonstrated that delivery of well-structured instructions increases the knowledge of discharge regimens and increases adherence among ED population s. OBJECTIVES This study compared the level of medication knowledge of elderly ED patients receiving instruction by one of two teaching methods : the usual preprinted discharge instructions with h and written medication information and individualized computer-generated discharge instructions design ed within a geragogy framework . METHOD The geragogy intervention included large-print , easily readable , specific information ordered within the elderly memory schema . This schema consists of purpose , administration , and emergency information in that order . The Knowledge of Medication Subtest by Horn and Swain ( 1977 ) was administered by telephone 48 to 72 hours after discharge . Sixty patients ( 38 women , 22 men ) with a mean age of 76 years were r and omly assigned to groups and completed the study at three rural ED sites . RESULTS Subjects in the geragogy-based intervention group demonstrated significantly more knowledge of medications than did subjects experiencing the usual discharge teaching method ( t = 2.19 , p = .016 ) . CONCLUSIONS These findings suggest that a medication teaching intervention geared to the special needs of the elderly can be effective in increasing medication knowledge Introduction This study aim ed to investigate the effects of educational intervention on nurses ’ knowledge , attitudes , and behavioral intentions regarding supplying artificial nutrition and hydration ( ANH ) to terminal cancer patients . Material s and methods A quasi-experimental design was adopted . A structured question naire evaluated the effects of educational intervention . From April to June 2005 , 88 nurses were enrolled in the gastroenterology , general surgery , and intensive care unit of Taipei Veterans General Hospital in Taiwan . The nurses were r and omly assigned into experimental and control groups in equal numbers ( 44 nurses in each group ) . After the experimental and control groups completed the pretest , the experimental group participated in a 50-min lecture . Both groups received a post-test 2 weeks after the lecture . Results This study showed that prior to educational intervention , nurses have possessed experiences of ANH use in routine caring for terminal cancer patients . However , due to the lack of knowledge about supplying ANH to terminal cancer patients , the nurses trended toward the negative behavioral intention , although they realized the burdens of ANH in these patients . After educational intervention , mean scores of knowledge , attitudes and behavioral intentions of the experimental group increased significantly ( z = −5.255 , p < 0.001 ; t = −5.191 , p < 0.001 ; z = −3.274 , p ≦ 0.001 ) . Mean score changes of knowledge and attitude between these two groups reached significant differences ( t = −7.306 , p < 0.001 ; t = −4.165 , p < 0.001 ) , but no significant difference was observed in the mean score change of behavioral intention ( z = −1.943 , p > 0.05 ) . Conclusion The educational intervention remarkably improved nurses ’ knowledge and attitudes regarding supplying terminal cancer patients with ANH . As for the changes in the behavioral intentions , it requires long-term moral and ethical training and communication . The results of this research emphasized the importance of educational interventions , which should be considered seriously in future reference nursing education program OBJECTIVE To evaluate an entertainment-based patient decision aid for prostate cancer screening among patients with low or high health literacy . METHODS Male primary care patients from two clinical sites , one characterized as serving patients with low health literacy ( n=149 ) and the second as serving patients with high health literacy ( n=301 ) , were r and omized to receive an entertainment-based decision aid for prostate cancer screening or an audiobooklet-control aid with the same learner content but without the entertainment features . Postintervention and 2-week follow-up assessment s were conducted . RESULTS Patients at the low-literacy site were more engaged with the entertainment-based aid than patients at the high-literacy site . Overall , knowledge improved for all patients . Among patients at the low-literacy site , the entertainment-based aid was associated with lower decisional conflict and greater self-advocacy ( i.e. , mastering and obtaining information about screening ) when compared to patients given the audiobooklet . No differences between the aids were observed for patients at the high-literacy site . CONCLUSION Entertainment education may be an effective strategy for promoting informed decision making about prostate cancer screening among patients with lower health literacy . PRACTICE IMPLICATION S As barriers to implementing computer-based patient decision support programs decrease , alternative models for delivering these programs should be explored BACKGROUND Abortion is a public health concern because of its impact on maternal morbidity and mortality . Each year , about 79 million unintended pregnancies , excluding miscarriage , occur worldwide . More than half of these unintended pregnancies end in abortion . The purpose of this study was to determine the ever-event incidence of abortion ( spontaneous and induced ) and some related factors in a population -based sample of reproductive age women . METHODS From July 2003 through January 2004 , 2470 women were included in the study through multistage r and om sampling and were interviewed . Data were collected using a checklist with questions about demographics and specific items regarding abortion history . Information about age , literacy , gravidity , marriage age , abortion , type of abortion , family history of abortion , history of family marriage , smoking , drug use , alcohol use , coffee intake , and incidence of abortion during the previous year were recorded . Statistical analysis included Student 's t-test , Chi-square , ANOVA , and logistic regression using SPSS software . RESULTS Out of the 2,470 women in the study , 775 ( 45.7 % ) , had at least one abortion in their lives . Of the women who had an abortion , 20.6 % reported induced abortion and 74.2 % reported spontaneous abortion . Forty-one point four percent of women aged 45 years and older had at least one abortion in their lifetime . Fifty-one ( 2.1 % ) women had a history of abortion during the previous year ; the largest proportion was 5.4 % for the age group 15 - 24 years . The most common method of induced abortion in the previous year was dilatation and curettage ( 42 to 67 % ) . In multivariate analysis , household number , coffee consumption , gravidity , smoking , and history of abortion in the family were the most important factors related to abortion in the different age groups of women . CONCLUSION This study shows that the occurrence of at least one abortion in the life of women in our setting is high and varies by age group . There is a need for exp and ed comprehensive sexual and reproductive health services , and more education and accessibility of contraception methods BACKGROUND AND OBJECTIVES This study 's objective was to evaluate the association between health literacy and human immunodeficiency virus/acquired immunodeficiency syndrome ( HIV/AIDS ) knowledge among patients seen at an inner-city , public hospital urgent care center ( UCC ) . METHODS We used a prospect i ve survey of patients offered an HIV test by their providers during a UCC visit . We measured patients ' health literacy level using the Rapid Estimate of Adult Literacy in Medicine ( REALM ) scale and assessed their HIV/AIDS knowledge using a 22-item question naire . RESULTS A total of 372 patients were enrolled . Among participants in this relatively young sample ( 55 % were under the age of 40 ) , 92 ( 25 % ) had a REALM score at or below a sixth- grade level , and 122 ( 33 % ) did not have a high school diploma . Patients ' mean HIV/AIDS knowledge scores differed significantly between patients with inadequate health literacy and those with marginal or adequate health literacy . In multivariate analyses , patients ' REALM scores were positively associated with patients ' HIV/AIDS knowledge even after adjusting for income , education , and risk perception . CONCLUSIONS These findings demonstrate that HIV/AIDS knowledge is strongly associated with patients ' health literacy in this inner-city population . These findings reiterate the need to target HIV prevention strategies toward population s with inadequate health literacy levels and to dispel misconceptions regarding HIV/AIDS that directly influence risk-taking behaviors and health care utilization Research suggests that music is beneficial in teaching both social and academic skills to young children . The purpose of this study was to examine the effects of a music therapy program design ed to teach reading skills versus the " Between the Lions " television program on the early literacy behaviors of Kindergarten children from a low socioeconomic background . Subjects ( n = 86 ) were children , aged 5 - 7 years , enrolled in one of four different Kindergarten classes at a public elementary school in Northwest Florida . Each class was assigned one of four treatment conditions : Music/Video ( sequential presentation of each condition ) , Music-Only , Video-Only , and no contact Control group . Growth in early literacy skills was measured using the Dynamic Indicators of Basic Early Literacy Skills ( DIBELS ) and 3 subtests of the Test of Early reading Ability-3rd edition ( TERA-3 ) . Teachers ' perceptions of classroom literacy behaviors were measured using a pre and post study survey . This study also compared on- and off-task behavior of students during video versus music conditions . Results of the 7 subtests measuring early literacy were varied . The Music/Video and Music-Only groups achieved the highest increases in mean scores from pre to posttest on 4 of the 7 subtests . Students in the Video-Only group scored significantly better on the phonemic segmentation portion of the DIBELS than peers in the Music/Video condition . Furthermore , strong correlations were found between the Letter Naming , Initial Sounds Fluency tests , and total raw score of the TERA-3 tests for both pre and posttesting . Additionally , graphic analysis of mean off-task behavior per session indicated that students were more off-task during both video conditions ( video alone and video portion of Music/Video condition ) than during the music conditions . Off-task behavior was consistently lower during music sessions for the duration of the study . This study confirmed that music increases the on-task behavior of students . Additionally , the combination of music and video enrichment showed gains in 4 of the 8 tests used to measure students ' progress . This pattern supports the need for further investigation regarding benefits of enrichment programs specifically design ed to enhance curricula for students from low socioeconomic background s , particularly programs that incorporate music activities A video colposcopy allows the real-time images viewed by the doctor performing the examination to be viewed by patients on a television monitor during the consultation . Eighty-one women ( requiring either laser treatment or a normal recheck ) were r and omly assigned to either the video intervention group or the control group . A significant decrease in state anxiety was observed from one visit to the next in all patients ( P = 0.000 ) . This decrease in anxiety was significantly greater in the laser patients in the video colposcopy condition than patients in the control group for both groups of patients . Patients in the experimental groups also reported less pain than patients in the control conditions ( P < 0.05 ) . This benefit associated with video colposcopy was not observed on the second ( treatment ) visit . In conclusion , video colposcopy is a useful and time-efficient method that reduces patient anxiety and pain during examination visits , but not necessarily during visits where laser treatment is required Sixty-one noncredible patients ( as documented by psychometric and behavioral criteria ) scored significantly below 25 controls and 88 credible clinic patients with no motive to feign on most RAVLT scores , including added indices of implicit and " automatic " memory . A combination of true recognition ( i.e. , recognition minus false positives ) + implicit memory score ( i.e. , the number of word stems completed with RAVLT items ) + " automatic " memory score ( i.e. , the number of correct temporal order judgments ) < or = 22 was associated with 75.7 % sensitivity with specificity at 91.5 % . However , sensitivity was nearly as high when scores available from the st and ard RAVLT administration alone ( i.e. , no word stem or temporal order trials ) were combined . Specifically , a cut-off of < or = 12 for true recognition ( recognition minus false positives ) + primacy recognition ( i.e. , number of words recognized from the first third of the test ) was associated with 73.8 % sensitivity at 90 % specificity . These results indicate that combined indices of recognition memory from the RAVLT are effective in identifying noncredible memory performance in " real world " sample s and are modestly superior to the 67.2 % sensitivity obtained with the st and ard recognition score BACKGROUND Prevalence of hypertension is greater in older adults , and increased intake of fruits , vegetables , and dairy-good sources of potassium , calcium , and magnesium-can reduce blood pressure . This study examined the hypertension-related dietary patterns of older adults . METHODS A cohort of 180 Pennsylvania adults ( aged > /=65 ) , 90 with hypertension , were r and omly selected from the Geisinger Rural Aging Study ( GRAS ) . Data were collected by trained interviewers at a home visit . Dietary assessment used five 24-h recalls . We compared the characteristics and dietary intake of people with hypertension to those without hypertension and compared their intakes to current recommendations . RESULTS Mean intakes of all participants were less than two thirds of the DRI for calcium and magnesium and fell far short of the 3,500 mg of potassium recommended for prevention and treatment of hypertension . Participants with hypertension consumed less sodium than controls . Both groups ate fewer fruits and vegetables than recommended but reached the dairy recommendation . Calcium intake was mainly from high-fat dairy products , beans were the top source of potassium and magnesium . CONCLUSIONS Older adults with hypertension should be guided to choose more low-fat dairy products and other low-fat calcium sources and to increase intakes of beans , dark green leafy vegetables , and other potassium and magnesium sources To date , efforts to initiate future graduates and nurses currently in practice into the world of information and communication technologies ( ICTs ) have been provided by relatively few nurse educators . In the past decade , nursing informatics leaders have developed a profile of informatics competencies for nurses , novice to expert – for example , the National Nursing Informatics Project ( Hebert 2000 ) – and have demonstrated actual ( Kaminski 2006 ) and possible informatics integration into curricula ( Nagle 2001 ) . Findings from recent studies ( Infoway 2007 ; Nagle and Clarke 2004 ) suggest that a minority of Canadian schools of nursing have tackled the challenge of integrating informatics throughout their nursing curricula . When asked to respond to a recent survey ( Infoway 2007 ) , some schools decided not to participate because there were no faculty members with appropriate expertise in the area , while other schools did not regard informatics as relevant content for their program . Nevertheless , over the years , several schools of nursing have had the foresight to create a single informatics course – usually an elective – at the undergraduate or graduate level . I have held discussion s with several deans and directors of schools of nursing over the past two years , and most of them recognize that this is a content area to be reckoned with sooner rather than later . No graduate nursing program has , as yet , created an informatics specialty option , but stay tuned . An Academic/Learning Advisory Group was recently created as a key component of Infoway ’s user engagement strategy . Since many of the core informatics concepts can be addressed interprofessionally , this group includes academics , students and practitioners from health informatics , nursing , medicine and pharmacy . The m and ate of this advisory group is to provide input to the development of strategies and tactics to support ( a ) continuous professional development for clinicians in practice in the use of electronic health record solutions ( EHRs ) and ( b ) the integration of informatics Everything I Know About Informatics , I Did n’t Learn in Nursing School Lynn M. Nagle Electronic Healthcare Vol . 6 No. 4 Online Exclusive 2008 2 content into the core curricula of the health disciplines . The advisory group members bring knowledge from the academic and healthcare delivery arenas and expertise in informatics , e-learning and knowledge translation . The group has been working on the development of a conceptual framework that will be used to underpin the direction of subsequent work . Infoway ’s future efforts will include the capture of success stories and exemplars of successful EHR training and informatics integration in work environments and basic training programs . To date , an environmental scan has been undertaken in the hope of obtaining representative sample s of schools of nursing , medicine and pharmacy . Additionally , recent graduates were asked to participate in a survey of perceived readiness for the workplace in relation to the use of ICTs . Unfortunately , the response rates to both surveys were insufficient to yield any meaningful conclusions . Unless there has been a dramatic upturn in the integration of informatics among schools of nursing , one might assume that the findings from the 2003 Canadian Nursing Informatics Association ( Nagle and Clarke 2004 ) study of 79 schools of nursing are likely still a reflection of the status quo . That study showed that less than 40 % of the schools had addressed or integrated informatics content . I suspect that there is still much work to be done . So where to begin ? Within healthcare organizations , there are now many experiences in the field with successful and failed implementations . What is well known is the importance of user engagement from the outset of any EHR initiative . What is yet unknown is the effectiveness of the various models and strategies being used within healthcare organizations to get practitioners engaged , educated and trained in the use of EHR applications . Based upon personal experience and discussion with many colleagues across Canada , educators in healthcare organizations need • multiple and flexible methods and tools for delivery , • knowledge of adult learning principles and • credibility among their peers . “ Expert user ” does not equate to “ educator . ” Clinician users want • sustained support post-implementation , • engaged leadership and • extended opportunities to develop a comfort level with applications . These are simple concepts , touted by many as key success factors , but they are not always evident . Among the many challenges within healthcare organizations is not only skillful integration of ICTs with existing practice s , but also sufficient time to educate and train an already overtaxed workforce . Implementation ultimately comes down to the perceived value of the EHR tools to support clinical care delivery effectively – no value , no buy-in , no commitment to learn and use . Canadian schools of nursing are of the highest calibre in the world ; faculty are renowned worldwide for their programs of research and publications . Many are even conducting leading-edge research in the informatics realm . Whether recognized or not , in today ’s Everything I Know About Informatics , I Did n’t Learn in Nursing School Lynn M. Nagle Electronic Healthcare Vol . 6 No. 4 Online Exclusive 2008 3 world , informatics is simply a part of every faculty member ’s tool kit . Therefore , it should not be offered or developed as a separate course . Rather , it should be integrated with approaches to the theoretical and practical teachings in every course . A student nurse recently lamented to me that his class was told they could not use electronic textbooks because of faculty discomfort with the medium . Today ’s students want their texts available on a h and held device ; they want to use technology in their learning and practice . Educators need to encourage the integration of technology , underst and the use and potential of EHRs and become champions in their own right . Otherwise , I fear we run the risk of discouraging the prospect i ve technology-savvy student from pursuing a career in nursing . Hopefully , unlike my generation , nursing students and graduates of the future will know enough about informatics to position themselves in the emerging clinical world of ICTs . While writing this article , I reflected upon the related contributions of the late Dr. Pat Griffin to this work . As executive director of the Canadian Association of Schools of Nursing ( CASN ) and a member of the Infoway Nursing Advisory Group , Pat brought thoughtful insights and her commitment to our discussion s about engaging nurse educators in the informatics agenda . She was a self-procl aim ed “ nontechy , ” telephoning me in recent months to confess abashedly that she had misplaced my e-mail address – “ it would have to be you , of all people ! ” Nonetheless , she recognized the importance of addressing the delivery of informatics knowledge and skills to nurses . In fact , the week prior to her death , she participated in her usual whole-hearted way in an all-day meeting of the advisory group and was planning for my participation in the CASN board meeting the following week . In her memory , I encourage all educators of nurses to boldly embrace this challenge ! About the Author Lynn M. Nagle , RN , PhD , is a senior nursing advisor with Canada Health In recent years , social work has moved in parallel with medicine and the health sciences to use evidence -based criteria to determine the actions of practitioners ( Institute of Medicine , 2001 ; Parker-Oliver & Demiris , 2006 ) . Consequently , social workers employed in health and mental health setting s are compelled to use evidence -based practice s in their work . For many practitioners , evidence -based practice means the application of empirically based service models and a trend toward interventions demonstrated to be effective in changing behavior and ameliorating clients ' problems . However , social workers , including those in medical and mental health services , are often not involved in the research that informs these practice s , and their ability to shape promoted practice s is virtually nonexistent . Health and mental health social workers increasingly view evidence -based practice as prescriptive , with research ers in centers of scholarship developing research for practitioners . This situation has exacerbated the rift between research ers and social workers who are expected to carry out empirically supported practice s , although they are not involved in the production of research or even in the synthesis of evidence that supports particular practice s and rejects others . People with research expertise and the re sources to conduct empirical inquiry are generally located in academic institutions and do not necessarily call on practitioners themselves to critically examine evidence -based practice models . When these prescribed practice s move from the rarified conditions under which r and omized controlled trials are conducted into agency setting s , they confront real-world organizational realities , Real-world " intrusions " may limit fidelity to the model produced by this " gold st and ard " of research . As a result , technology transfer , or reliability for replication of evidence -based practice s , may be compromised . Perhaps most disheartening is how this situation encourages passivity among people in the field to engage in research or remain fluent with current research . Continuing knowledge development is a shared responsibility at all levels of the social work profession ( Lewis , 2003 ) , and current education and practice structures are not encouraging practitioners to be partners in this process . We assert that people closest to direct services are best positioned to point out practice realities that distort programs . Although practice s may be supported by high-level empirical evidence , they may not prove effective or even feasible under real-world conditions . Originally , evidence -based practice was proposed for physicians to make use of the convergence of an explosion of information and technology , so that clinicians could use the growing body of research available through online data bases . Ultimately , other health professionals were supposed to formulate clinical questions , critically assess empirical studies , and decide on the best approaches to bring to a dialogue with clients . The clients were meant to be active partners in decision making about their own care . The institution of the Cochrane Collaboration ( http://www : cochrane.org./index.htm ) and the Campbell Collaboration ( http://www . campbellcollaboration.org/ ) formalized this process , and both apply rigorous , transparent st and ards to their review s of research studies . Although they are meant to serve policymakers , health workers , and people who use services , the extent to which medical social workers consult their readily available Web sites is unclear . Unlike nursing , speech therapy or rehabilitation therapy , or other health professions that have produced a burgeoning literature on information literacy skills as a central concern for educators ( Jacobs , Rosenfeld , & Haber , 2003 ; Nail-Chiwetalu & Bernstein Ratner , 2007 ) , the social work literature is for the most part silent in this area . With the exception of two recent texts that promote a bottom-up approach to evidence -based practice ( Courneyer , 2004 ; Gibbs , 2003 ) and Gary Holden 's remarkable informatics Web site for social workers ( http://www : nyu . OBJECTIVE To evaluate the efficacy of an educational program for patients with rheumatoid arthritis in relation to their knowledge about the disease and to their psychosocial and physical health status . MATERIAL S AND METHODS The study included patients with rheumatoid arthritis classified according to the American College of Rheumatology criteria without any previous participation in disease-specific educational programs . The patients were r and omly assigned to an educational program intervention or a waiting list . The intervention was a 6-week educational program consisting of weekly sessions lasting 1 hour each . Evaluations by a blind assessor were made prior to intervention and after 45 , 90 and 180 days . The main outcome variables were the Patient Knowledge Question naire and the Short-form Health Survey ( SF-36 ) quality of life question naire . Secondary outcome variables were the Health Assessment Question naire , Visual Analogue Pain Scale , Beck Depression Inventory and State-Trait Anxiety Inventory . RESULTS Patients in the intervention group ( n=28 ) had significant improvement in disease-specific knowledge compared to patients in control group ( n=30 ) . There was no significant difference between the groups in terms of pain , depression , anxiety or functional capacity , but the " general health perception " subscale of SF-36 showed a significant improvement in the intervention group ( p=0.041 ) . There was a positive correlation between improvement of disease-specific knowledge and schooling . CONCLUSION Patients who attended the educational program had significant improvement in disease-specific knowledge and general health perception . No harmful effects on their psychosocial status were noticed . The acquisition of knowledge was also found to be proportional to schooling BACKGROUND Studies of the prison population suggest that the numbers of prisoners with language and communication disorders is higher than that of the overall population . However , the prison population is heterogeneous and it is important to focus on specific areas of the population . This study focuses on juvenile offenders . AIMS The study aim ed to screen language and communication skills in half the population of an establishment for juvenile offenders aged 15 - 17 years . METHODS & PROCEDURES A total of 58 participants were selected at r and om and screened on the oral subtests of the Test of Adolescent and Adult Language , 3rd Edn ( TOAL-3 ) , the British Picture Vocabulary Scale ( BPVS-II ) and the Test for Reception of Grammar : Version 2 ( TROG-2 ) . Literacy and numeracy information was also obtained . OUTCOMES & RESULTS The mean age of the group was 17 years ; 19 were looked-after children ; and 90 % had ceased to attend school before age 16 . On the TOAL-3 subtests , 66 - 90 % of juvenile offenders in the sample had below average language skills , with 46 - 67 % of these being in the poor or very poor group . None of the participants reached their age equivalence on the BPVS , but most of them reached the 12-year and above threshold on the TROG . A total of 62 % of the sample had not achieved Level 1 in literacy . The findings suggest that these young people may not have the necessary skills to cope with verbally mediated interventions aim ed at reducing re-offending . CONCLUSIONS The results suggest that speech and language therapy assessment should be available to juvenile offenders with speech and language therapy intervention available to those found to have language and communication difficulties . There are also implication s for speech and language therapy provision to young people who are not engaged within the education system . The TOAL-3 appears to be a useful screening instrument for this population , but a number of issues around the suitability of assessment s for this population are discussed The objective of this prospect i ve study was to determine the impact of early literacy anticipatory guidance ( AG ) with provision of books on language development in 3-year-olds in an early literacy program at a University-affiliated inner-city pediatric clinic . The Peabody Picture Vocabulary Test ( PPVT-III ) and the Expressive One Word Picture Vocabulary Test ( EOWPVT-R ) were administered to 33 - 39-month-old children exposed to an early literacy program , which included AG and provision of an age-appropriate book at each well-child visit starting at 2 months old . Children with developmental delays were excluded . Parental surveys on literacy and demographic data were obtained . Univariate and multivariate analyses were performed . Sixty-four children were evaluated ; 88 % African American , 89 % Medicaid recipients . Fifty-eight percent of families reported familycentered literacy orientation . The PPVT-III scores directly correlated with the number of AG visits with book given x number of books purchased ( r2 = 0.025 , p = 0.0006 ) . Higher scores in EOWPVT-R were predicted by race and the number of visits with books given x number of books purchased ( r2 = 0.182 , p = 0.0009 ) . All families reported reading together , half reporting positive familycentered literacy . Given the same number of books purchased for each child , the outcome scores were higher the greater the number of clinic visits wherein AG included early literacy and provision of books The aim of the study was to compare and evaluate a multidisciplinary educational programme with traditional follow-up visits to a physician after breast cancer surgery in terms of well-being , aspects of self-care and coping ability 1 year after diagnosis . A reduction in the intensity of follow-up after breast cancer surgery is recommended . New follow-up models are being debated and could be of interest . The study design was non-r and omised and comparative . Ninety-six consecutively selected women with newly diagnosed breast cancer , classified as stage I or stage II , participated in either a multidisciplinary educational programme ( n=50 ) , or traditional follow-up by a physician ( n=46 ) . Three question naires were used : Functional Assessment of Cancer Therapy-General ( FACT-G ) , a study specific question naire regarding self-care aspects ( SCA ) and Sense of Coherence ( SOC ) . With the exception of physical well-being at baseline there was no significant difference between the groups . The women in the multidisciplinary educational programme increased their physical and functional well-being ( P<0.01 ) . The women in traditional follow-up by a physician increased their functional well-being while social/family well-being ( P<0.01 ) decreased over time . There was a statistically significant difference in SOC ( P<0.001 ) in the traditional follow-up by a physician between baseline ( mean=74.4 , SD=12.4 ) and the 1-year follow up ( mean=67.7 , SD=11.4 ) . Thus , women in the traditional follow-up by a physician scored lower in the area of SOC 1 year after diagnosis . A multidisciplinary educational programme may be an alternative to traditional follow-up by a physician after breast cancer surgery , but more research is needed about the financial benefits and effectiveness of such a programme BACKGROUND Many people who are depressed do not receive any professional help and their beliefs about the helpfulness of treatment do not always correspond with those of health professionals . To facilitate choices about treatment , the present study examined the effects of providing depressed people in the community with evidence on whether various treatment options work . METHOD A r and omized controlled trial was carried out with 1094 persons selected at r and om from the community who screened positive for depressive symptoms and agreed to participate . Participants were mailed either an evidence -based consumer guide to treatments for depression or , as a control , a general brochure on depression . Outcomes were the rated usefulness of the information provided , changes in attitudes to depression treatments , actions taken to reduce depression , and changes in depressive symptoms , anxiety symptoms and disability . RESULTS Participants rated the evidence -based consumer guide as more useful than the control brochure . Attitudes to some treatments changed . Improvements in symptoms and disability did not differ significantly between interventions . CONCLUSION Providing people who are depressed with evidence on which treatments work produces some changes in attitudes and behaviour . However , this intervention may need to be enhanced if it is to produce symptom change The preliminary results of this study suggested that children with developmental dyscalculia benefit from a numeracy intervention program that focuses on basic numerical knowledge and conceptual knowledge . All children in the experimental group showed considerable and partly significant performance increases on all calculation components . Six children with developmental dyscalculia were trained individually and in small-group setting s for a relatively short duration ( one school semester ) . We argue that the positive intervention effects to a large extent are attributable to the explicit teaching of numerical domains that often have been found to be neglected in school mathematics Two r and omized field experiments tested a social-psychological intervention design ed to improve minority student performance and increase our underst and ing of how psychological threat mediates performance in chronically evaluative real-world environments . We expected that the risk of confirming a negative stereotype aim ed at one 's group could undermine academic performance in minority students by elevating their level of psychological threat . We tested whether such psychological threat could be lessened by having students reaffirm their sense of personal adequacy or “ self-integrity . ” The intervention , a brief in-class writing assignment , significantly improved the grade s of African American students and reduced the racial achievement gap by 40 % . These results suggest that the racial achievement gap , a major social concern in the United States , could be ameliorated by the use of timely and targeted social-psychological interventions OBJECTIVE Patients are commonly presented with complex documents that they have difficulty underst and ing . The objective of this study was to design and evaluate an animated computer agent to explain research consent forms to potential research participants . METHODS Subjects were invited to participate in a simulated consent process for a study involving a genetic repository . Explanation of the research consent form by the computer agent was compared to explanation by a human and a self- study condition in a r and omized trial . Responses were compared according to level of health literacy . RESULTS Participants were most satisfied with the consent process and most likely to sign the consent form when it was explained by the computer agent , regardless of health literacy level . Participants with adequate health literacy demonstrated the highest level of comprehension with the computer agent-based explanation compared to the other two conditions . However , participants with limited health literacy showed poor comprehension levels in all three conditions . Participants with limited health literacy reported several reasons , such as lack of time constraints , ability to re-ask questions , and lack of bias , for preferring the computer agent-based explanation over a human-based one . CONCLUSION Animated computer agents can perform as well as or better than humans in the administration of informed consent . PRACTICE IMPLICATION S Animated computer agents represent a viable method for explaining health documents to patients Poor literacy is associated with poor health status , but whether illiteracy is also linked to higher medical care costs is unclear . We characterized the literacy skills of 402 r and omly selected adult Medicaid enrollees to determine if there was an association between literacy skills and health care costs . Each subject 's literacy skills were measured with a bilingual ( English/ Spanish ) reading- assessment instrument . We also review ed each subject 's health care costs over the same one-year period . The mean reading level of this Medicaid population was at grade 5.6 . Mean annual health care costs were $ 4,574 per person . There was no significant relationship between literacy and health care costs . While there are compelling reasons to improve poor reading skills among Medicaid enrollees , illiteracy in this population does not appear to contribute to the high cost of providing government-sponsored care OBJECTIVE To evaluate the efficacy of a pictogram-based health literacy intervention to decrease liquid medication administration errors by caregivers of young children . DESIGN R and omized controlled trial . SETTING Urban public hospital pediatric emergency department . PARTICIPANTS Parents and caregivers ( N = 245 ) of children aged 30 days to 8 years who were prescribed liquid medications ( daily dose or " as needed " ) . INTERVENTION Medication counseling using plain language , pictogram-based medication instruction sheets . Control subjects received st and ard medication counseling . OUTCOME MEASURES Medication knowledge and practice , dosing accuracy , and adherence . RESULTS Of 245 r and omized caregivers , 227 underwent follow-up assessment s ( intervention group , 113 ; control group , 114 ) . Of these , 99 were prescribed a daily dose medication , and 158 were prescribed medication taken as needed . Intervention caregivers had fewer errors in observed dosing accuracy ( > 20 % deviation from prescribed dose ) compared with caregivers who received routine counseling ( daily dose : 5.4 % vs 47.8 % ; absolute risk reduction [ ARR ] , 42.4 % [ 95 % confidence interval , 24.0%-57.0 % ] ; number needed to treat [ NNT ] , 2 [ 2 - 4 ] ; as needed : 15.6 % vs 40.0 % ; ARR , 24.4 % ( 8.7%-38.8 % ) ; NNT , 4 [ 3 - 12 ] ) . Of intervention caregivers , 9.3 % were nonadherent ( ie , did not give within 20 % of the total prescribed doses ) compared with 38.0 % of controls ( ARR , 28.7 % [ 11.4%-43.7 % ] ; NNT , 3 [ 2 - 9 ] ) . Improvements were also seen for knowledge of appropriate preparation for both medication types , as well as knowledge of frequency for those prescribed daily dose medications . CONCLUSION A plain language , pictogram-based intervention used as part of medication counseling result ed in decreased medication dosing errors and improved adherence among multiethnic , low socioeconomic status caregivers whose children were treated at an urban pediatric emergency department . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00537433 Background / aim : Himalaya Eye Hospital ( HEH ) , established in 1993 , is rendering eye care services in the G and aki and Dhaulagiri zones . The hospital has extensive community outreach activities along with services for out patients , emergencies , and subspecialties such as vitreoretinal , paediatric , and low vision . The operation theatre is well equipped to match the surgical needs including phaco surgery for cataract . The hospital has performed more than 14 000 cataract surgeries and 250 000 treatment services during this period . The aim of this study was to estimate the prevalence of blindness , visual impairment , and cataract surgical coverage among the older adult population of three districts of G and aki Zone , where 80 % of the hospital ’s service recipients reside . Methods : People aged 45 years and older were enrolled in the study using a stratified cluster design . Subjects in 25 r and omly selected clusters from the listed 806 were recruited through door to door visits . Each recruited subject had visual acuity ( VA ) and clinical examination conducted by an ophthalmologist . The survey was preceded by pre-pilot and pilot studies to refine the operational method . To assess quality assurance the interobserver variation in VA measurement was also carried out in five different clusters . Results : Out of 5863 selected subjects 85.3 % were examined . Blindness defined as presenting VA < 6/60 in both eyes was found in 2.6 % ( 95 % confidence interval ( CI ) : 2.2 to 3.9 ) , whereas 16.8 % individuals examined had vision < 6/19 in one or both eyes . Cataract was the principal cause of blindness in 60.5 % , and refractive error was the dominant cause of vision impairment ( < 6/19 ) 83.3 % . Cataract surgical coverage was 59.5 % among the cataract blind and associated with younger age , literacy , and male sex . Conclusion : The finding suggests a positive impact of the HEH programme on the prevalence of blindness and cataract surgical services in the survey area . Strategies to further improve access and utilisation of facilities and increase cataract surgical coverage need to be developed OBJECTIVE To improve the treatment of risk factors of cardiovascular disease ( CVD ) for older patients with diabetes after a cardiac event by using a low-literacy reminder card describing these risk factors in community setting s. STUDY DESIGN A multicenter , r and omized , interventional study . METHODS Patients aged 55 years or older with diabetes hospitalized with an acute myocardial infa rct ion , congestive heart failure exacerbation , or unstable angina were eligible to enter the study . Control and experimental patients were recruited from 4 sites and were enrolled in the study before discharge from the hospital . Experimental subjects received education and a reminder card describing risk factors of CVD . They were instructed to discuss the risk factors described on the reminder card with their primary care physician on their first appointment after discharge . Control subjects did not receive any intervention but were given consent to be able to review their charts . RESULTS One hundred sixty patients completed the study , 82 in the control group and 78 in the experimental group . At the end of the study there was no difference in blood pressure control , lipid levels , and glycosylated hemoglobin levels between the control and experimental patients . Aspirin use and ACE inhibitor use were found to be significantly higher in the control group ( P = .001 and .03 , respectively ) . CONCLUSIONS Reminder cards given to patients to discuss with their primary care providers in community setting s did not improve process measures of CVD risk in patients with documented CVD and diabetes . Other approaches will be needed to improve the treatment of risk factors in these high-risk patients OBJECTIVE To examine the effectiveness and cognitive effects of aripiprazole ( APZ ) in children with a primary diagnosis of attention-deficit/hyperactivity disorder ( ADHD ) . METHODS Youths , ages 8 - 12 years , with a diagnosis of ADHD combined-type or ADHD predominately inattentive-type were enrolled into a 6-week , open-label pilot trial . Outcome measures included the ADHD Rating Scale-IV ( ARS-IV ) , Clinical Global Impressions Scale ( CGI ) , and Children 's Global Assessment Scale ( CGAS ) . The Conners ' Continuous Performance Test II , Reading and Math Fluency subscales of the Woodcock-Johnson III Tests of Achievement , and the Stroop Color and Word Test were administered at baseline and end of study . RESULTS Fourteen ( 9 males and 5 females ) youths were diagnosed with ADHD-combined type , while 9 ( 5 males and 4 females ) were diagnosed with ADHD-inattentive type . At a mean dose of 6.7 mg/day , end of study results showed overall significant improvement from baseline on ADHD and functional outcome measures . No significant differences in baseline performance at end of study were found on the cognitive measures . The most frequently reported adverse events were sedation ( n = 18 ; 78.3 % ) and headache ( n = 11 ; 47.8 % ) . CONCLUSIONS Although this was a brief pilot study with a small sample size , in this cohort , APZ led to clinical benefit in reducing ADHD symptoms and improving overall functioning . Of note , cognitive functioning did not appear to be negatively impacted by APZ treatment Objective : We developed a pharmacist-based patient education intervention to improve older adults ' adherence to chronic heart failure ( CHF ) medications , which included written patient-centered instructions . The study evaluated these instructions by examining whether patients preferred them to st and ard pharmacy instructions . Method : Elders diagnosed with CHF participated in the r and omized controlled trial ( 83 in the intervention ; 153 in usual care control group ) . Instruction preferences were collected after 6 months of participation . Results : Patient-centered instructions were preferred for learning about adherence information ( e.g. , schedule ) and st and ard instructions for learning about drug interactions . Preference for the patient-centered instructions was greater for intervention versus control participants and for participants with lower health literacy . Literacy no longer predicted preferences with patients ' cognitive abilities controlled , suggesting literacy reflected more fundamental cognitive mechanisms . Discussion : The finding that preferences varied with patients ' experience using the instructions and cognitive abilities suggests instructions should accommo date diverse patient needs and abilities Purpose : Peristat is a virtual perimetry system that allows self-testing on any st and ard computer monitor via Internet connection . The sensitivity and specificity of Peristat to detect visual-field defects were compared to st and ard Humphrey Visual Field Analyzer data . Material s and methods : In this prospect i ve , comparative observational case series , 58 eyes of 33 patients were examined . Semiquantitative analyses compared Peristat and Humphrey Visual-Field scores . The study evaluated patients with an established glaucoma diagnosis , as well as glaucoma suspects who had undergone comprehensive ophthalmologic examinations including prior office perimetry evaluation ( Humphrey Field Analyzer ) . Inclusion criteria were ( 1 ) diagnosis or suspicion of glaucoma , ( 2 ) BCVA better than 20/200 , ( 3 ) reliable performance on prior st and ardized office perimetry , and ( 4 ) CDR greater than 0.5 . Computer literacy was not required , and more than 40 % of the patients tested were computer illiterate , with no previous computer or Internet experience . A total of 58 eyes of 33 patients were tested with the Humphrey and the Peristat systems : 10 eyes of 5 patients without documented glaucomatous field loss and 48 eyes of 23 patients with mild-to-severe scotomas by st and ard 24 - 2 office perimetry . A st and ard computer setup was used with a 17 " monitor , and the Peristat system was enabled through a remote connection with a server . Results : In vitro All patients completed the Peristat test without difficulty . Testing time varied between 2 and 5 min , tending to be longer with more severe visual-field defects . Test results were review ed , in a masked fashion , by two glaucoma specialists and one general ophthalmologist . The Peristat demonstrated a high degree of correlation with the Humphrey system . Among the three review ers , sensitivity ranged from 80 % to 83 % . In a second sub analysis in which cases with mild defects were excluded , the Peristat 's sensitivity increased to 84%-86 % while specificity remained between 94 % and 97 % for all three review ers . Patients performed the Peristat test with similar facility to their Humphrey test . Fixation losses and test reliability were comparable for both tests . Conclusions : Peristat is a reliable self-test perimetry system that demonstrates high clinical utility for the detection of visual-field defects from glaucoma . Peristat could be a valuable public health tool for cost-effective screening of glaucoma BACKGROUND There are over two billion telephones in use worldwide . Yet , for millions of Americans with intellectual disabilities ( ID ) , access to the benefits of cellphone technology is limited because of deficits in literacy , numerical comprehension , the proliferation of features and shrinking size of cellphone hardware and user interfaces . Developments in smart phone technology and PDA-based cellphones provide an opportunity to make the social and safety benefits of cellphones more independently accessible to this population . METHOD This project involved employment of universal design and other specialised software development methods to create a multimedia cellphone interface prototype which was compared with a typical mainstream cellphone in a usability evaluation for individuals with ID . Participants completed a structured set of incoming/outgoing phone tasks using both the experimental and control conditions . Usability measurements included the amount of assistance needed and errors made in completing the cellphone use sequence . RESULTS A total of 22 individuals with ID participated in the research by engaging in a series of incoming and outgoing cellphone calls using both the multimedia cellphone prototype system and a mainstream Nokia 6360 cellphone . Test subjects required significantly less help ( P = 0.001 ) and made significantly fewer errors ( P < 0.001 ) when completing eight calls using the specialised multimedia phone system as compared with the mainstream phone . CONCLUSIONS The statistical evidence of both usability results provide promising evidence of the feasibility of implementing universal design and other specialised software development method ologies for increasing independent access to the benefits of cellphone technologies for students and adults with ID . Issues related to design ing cognitively accessible interfaces , study limitations and future directions are discussed BACKGROUND Social isolation is associated with poorer health , and is seen by the World Health Organisation ( WHO ) as one of the major issues facing the industrialised world . AIM To explore the significance of social isolation in the older population for GPs and for service commissioners . DESIGN OF STUDY Secondary analysis of baseline data from a r and omised controlled trial of health risk appraisal . SETTING A total of 2641 community-dwelling , non-disabled people aged 65 years and over in suburban London . METHOD Demographic details , social network and risk for social isolation based on the 6-item Lubben Social Network Scale , measures of depressed mood , memory problems , numbers of chronic conditions , medication use , functional ability , self-reported use of medical services . RESULTS More than 15 % of the older age group were at risk of social isolation , and this risk increased with advancing age . In bivariate analyses risk of social isolation was associated with older age , education up to 16 years only , depressed mood and impaired memory , perceived fair or poor health , perceived difficulty with both basic and instrumental activities of daily living , diminishing functional ability , and fear of falling . Despite poorer health status , those at risk of social isolation did not appear to make greater use of medical services , nor were they at greater risk of hospital admission . Half of those who scored as at risk of social isolation lived with others . Multivariate analysis showed significant independent associations between risk of social isolation and depressed mood and living alone , and weak associations with male sex , impaired memory and perceived poor health . CONCLUSION The risk of social isolation is elevated in older men , older persons who live alone , persons with mood or cognitive problems , but is not associated with greater use of services . These findings would not support population screening for individuals at risk of social isolation with a view to averting service use by timely intervention . Awareness of social isolation should trigger further assessment , and consideration of interventions to alleviate social isolation , treat depression or ameliorate cognitive impairment BACKGROUND Evidence suggests that Deaf people may have a greater prevalence of depressive symptoms . However , it is unclear whether commonly used written screening instruments are accurate with this population because of their unique cultural and linguistic factors . SETTING Deaf persons ( n = 71 ) residing in southeastern Michigan . METHODS Subjects completed the Zung Self-Rated Depression Scale in both the written ( ZSDS-W ) and American Sign Language ( ZSDS-S ) formats and the Hamilton Depression Scale ( HAM-D ) in American Sign Language in counterbalanced order , followed by a Test Of Reading Comprehension ( TORC ) . They also provided extensive data on demographic , hearing loss , language use , social and health care use variables . RESULTS Mean subject age was 52 years , 63 % of subjects were women , 95 % were Caucasian , and 47 % were married ( 87 % to another deaf/hard of hearing person ) . Thirty percent had a college degree and 20 % had less than a 10th grade education . The ZSDS-W and ZSDS-S scores were highly correlated ( r = + 0.79 ) , although the mean ZSDS-W score was 2.8 points higher ( P = .001 ) . The ZSDS-S correlated more highly ( r = 0.80 ) with the HAM-D than the ZSDS-W ( r = 0.71 ) . There was a significant interaction effect ( P < .001 ) such that the ZSDS-W and HAM-D were significantly associated among higher literacy subjects ( beta = 0.80 , P < .001 ) but not lower literacy subjects ( beta = 0.20 , P = .183 ) . There were no other significant associations between depression scores and numerous demographic , educational , hearing loss , social or language variables . CONCLUSIONS Compared with the conventional ZSDS-W , the ZSDS-S more accurately assesses depression severity among deaf persons with lower English literacy . However , given the greater sensitivity of the ZSDS-W and the practical barriers to ZSDS-S in physician practice s , further research should determine which modality is best for routine depression screening The aim of this study was to follow-up prospect ively a cohort of preschool children originally recruited from successive referrals to speech and language therapy community clinics and to investigate their linguistic , literacy , and social outcomes at 7 to 10 years of age . Three hundred and fifty children aged 84 to 113 months ( mean age 99.9mo [ SD 5.4mo ] ) were singletons from monolingual background s where there was concern about their speech and language development . Children who had severe learning difficulties , autism , oromotor deficits , dysfluency , or dysphonia were excluded . Altogether 196 ( 56 % ) , 134 males and 62 females , were seen at follow-up . A control group of children who had never been referred for speech and language therapy , 57 % of whom were males , was also recruited ( n=94 ; mean age 104.4mo [ SD 6.8mo ] ) . All children were assessed on st and ardized measures of speech , language , and literacy . Teachers and parents completed question naires on educational and social outcomes . In total , 139 children in the cohort were within the normal range on st and ardized language assessment s. About 30 % of the original cohort of children continue to struggle with language , literacy , and social difficulties . The study demonstrates the long-term nature of language impairment and reinforces the need for awareness among professionals in child development and education of the ongoing needs of this population of children BACKGROUND The identification of early markers of dementia is of increasing clinical importance . Recently , impaired mitochondrial function has emerged as a potential marker for age-related diseases and the maintenance of mtDNA copy number is essential for the preservation of mitochondrial function . We investigated the association between mtDNA copy number and cognitive function in elderly women . METHODS A total of 107 apparently healthy elderly women were included . Cognitive abilities were assessed using the Mini-Mental State Examination ( MMSE ) . We measured mtDNA copy number in peripheral leukocytes using real-time polymerase chain reaction ( PCR ) methods . Additionally , cardiometabolic risk factors and physical function were measured . RESULTS MMSE scores were negatively correlated with the homeostasis model of insulin resistance ( HOMA-IR ) scores and positively correlated with gait speed as well as mtDNA copy number . After adjusting for age and level of education , the mean values of MMSE scores gradually increased with mtDNA copy number when divided into quartiles . Using step-wise multiple regression analysis , gait speed , mtDNA copy number , and age were determined to be the strongest predictors of MMSE score . CONCLUSIONS These data suggest that reduced mtDNA content may be a possible early marker of dementia , and this finding warrants further study in large , prospect i ve investigations Increasingly , children with Down syndrome receive literacy instruction based on a phonological awareness philosophy with the expectation of acquiring functional reading skills . Previous research demonstrates that a phonological awareness based reading programme delivers excellent results in terms of literacy acquisition and improvements in speech production for children with speech and language delays . Unfortunately , little research exists to support the effectiveness of this approach for children with Down syndrome . The current research study examined using a phonological awareness based intervention programme with three children with Down syndrome ( aged 7;2 , 8;4 , and 8;10 ) . A multiple baseline across behaviours design was selected . The intervention programme focused on the key skills of alliteration detection , phoneme isolation , spelling of orthographically regular words and rhyme detection . Two tasks ( comprehension of passive structures and spatial structures ) were selected as control behaviours . Phoneme segmentation and speech intelligibility were selected to investigate generalisation of intervention targets to other related skill areas . The results indicated that the participants improved the phonological awareness skills targeted in the intervention programme . Unfortunately , no generalisation to other areas of phonological awareness was noted . In summary , the results indicate that children with Down syndrome can benefit from a phonological awareness based approach to literacy BACKGROUND AND OBJECTIVES The influence of literacy on health and health care is an important area of investigation . Studies with a literacy focus are most valuable when literacy is assessed with psychometrically sound instruments . METHODS This study used a prospect i ve cohort sample of 1,610 primary care patients . Patients provided sociodemographics and took the Rapid Estimate of Adult Literacy in Medicine ( REALM ) , a 66-item word pronunciation literacy test . RESULTS The sample was 65 % African American ; 66 % were men ; 51 % had a high school education or less . REALM scores were significantly related to education , age , and race but not gender . When stratified by education , differences between African Americans and Caucasians remained significant . Using 19 different strategies to shorten the 66-item instrument , reliability coefficients above.80 were maintained . CONCLUSIONS The REALM is a robust assessment of health literacy . However , the discordance in scores between African Americans and Caucasians with similar educational attainment needs to be further addressed . A much shorter instrument would still have internally consistent scores and potentially be more useful in clinical setting OBJECTIVE To evaluate program and health care costs of a lifestyle intervention in a high-risk obese population . DESIGN Twelve-month r and omized controlled trial comparing lifestyle case management to usual care . SUBJECTS/ SETTING Health plan members ( n=147 ) with obesity ( body mass index > /=27 ) and type 2 diabetes . INTERVENTION Lifestyle case management entailed individual and group education , support , and referrals by registered dietitians . Those in the usual-care group received educational material . MAIN OUTCOME MEASURES Medical and pharmaceutical health care costs reimbursed by the participant 's primary insurance company . STATISTICAL ANALYSIS Total costs were modeled using the four-equation model using previous year cost as a predictor . RESULTS Net cost of the intervention was $ 328 per person per year . After incorporating program costs , mean health plan costs were $ 3,586 ( 95 % confidence interval [ CI ] : -$8,036 , -$25 , P<0.05 ) lower in case management compared to usual care . The difference was driven by group differences in medical ( -$3,316 , 95 % CI : -$7,829 to -$320 , P<0.05 ) but not pharmaceutical costs ( -$239 , 95 % CI : -$870 to $ 280 , not statistically significant ) , with fewer inpatient admissions and costs among case management compared with usual care ( admission prevalence : 2.8 % vs 22.5 % respectively , P<0.001 ) . CONCLUSION Addition of a modest-cost , registered dietitian-led lifestyle case-management intervention to usual medical care did not increase health care costs and suggested modest cost savings among obese patients with type 2 diabetes . Larger trials are needed to determine whether these results can be replicated in a broader population . The findings can be judiciously applied to support that the addition of a registered dietitian-led lifestyle case-management program to medical care does not increase health care costs OBJECTIVE To determine whether the prevalence of depression , its associated quality of life , treatment and mental health literacy about depression varied according to accessibility to health services . DESIGN Face-to-face interviews with a r and om and representative sample of the South Australian population ( aged > or= 15 years ) were conducted between March and June 2004 , with the respondents stratified using the Accessibility and Remoteness Index of Australia into categories of ' highly accessible ' , ' accessible ' , and ' moderately accessible and remote ' . RESULTS From 4700 households selected , 3015 participants were interviewed ( 65.9 % response rate ) . The prevalence of major depression and other depressions was not significantly different between each of the categories , although there was a trend for those from moderately accessible and remote areas to be less depressed overall . A significantly lower proportion of respondents from moderately accessible and remote locations reported that they had family or close friends who had suffered from symptoms consistent with depression , or that they had ever had treatment for those symptoms . However , there was no significant difference between the groups in those who had ever had or who were currently taking antidepressant medication . For those who were depressed , a significantly higher proportion from the accessible , and moderately accessible and remote regions had seen a community or district health service , social worker or other counsellor as compared with those from the highly accessible area . CONCLUSIONS These findings indicate that depression is no more prevalent in less accessible regions of South Australia , and that when it is present , its treatment , in terms of antidepressants , which can be considered as a proxy marker for the overall management of depression , is similar to treatment in more accessible areas BACKGROUND In this study , we compared the educational value of a multimedia module about aortic valve replacement as a preparation for the operating room with a print medium of identical content . METHODS One hundred twenty-six students were r and omly assigned in a prospect i ve study to either use the multimedia course ( n = 69 ) or a print version ( n = 57 ) . A 20-item multiple-choice test was performed before and after learning with the respective medium . Both groups participated in an operation during which they were evaluated with 28 st and ardized tasks and questions . Individual motivation , computer literacy , and didactic quality of both media were assessed with psychometric tests . RESULTS There were no significant differences in the multiple-choice pretest ( multimedia , 30.6 % + /- 12.4 % versus print , 27.9 % + /- 11.4 % ) and posttest responses ( multimedia , 76.7 % + /- 13.3 % versus print , 76.9 % + /- 11.1 ) . Mean percentage of correct answers during the operation was 82.9 % + /- 10 % in the online group and 64.7 % + /- 12 % in the print group ( p < 0.0001 ) . The multimedia group needed significantly ( p < 0.001 ) less study time ( 105 + /- 24 minutes ) when compared with the text group ( 122 + /- 30 minutes ) . There were no statistically significant differences in motivation , computer literacy , and didactic quality of either medium . CONCLUSIONS Regarding factual knowledge , there is no difference between multimedia-driven learning and a print medium . During heart operations , when underst and ing of complex temporal and spatial events is essential , students ' performance is significantly improved by multimedia-enhanced teaching . The latter further proved to be more efficient in terms of study time PURPOSE To investigate the prevalence of specific reading disability in children with functional amblyopia and to explore the relationship between the two . METHODS In this prospect i ve study , 20 consecutive children , aged 6 to 15 years ( mean 8 + /-1.99 years ) , and diagnosed with amblyopia underwent a vision and reading assessment . The orthoptic examination included the assessment of participants ' visual acuity , ocular motility and binocular functions . Specific reading disability was diagnosed using the Wide Range Achievement Test ( WRAT III Reading Subtest ) . Intelligence , phonological awareness , rapid automatized naming ( RAN ) , and the ability to read pseudo or nonsense words was also assessed using various psycho-linguistic reading tests . RESULTS The prevalence of specific reading disability in this small series of amblyopic children was found to be 5 % ( n=1/20 ) . This was even less than that reported in the local Victoria general population ( 16 % ) . The type of amblyopia appeared related to phonological awareness ( p=0.018 ) and decoding words ( p=0.024 ) , those with anisometropic amblyopia performing significantly better on these tasks than the strabismic amblyopes . The presence of binocular vision functions was also related to decoding words ; those with binocular single vision performed better than those with suppression and lacking single binocular vision ( p=0.007 ) . Generally , amblyopic children also showed a lower RAN score when compared to phonological awareness score . There was no statistically significant difference for the severity of amblyopia ( p=>0.05 ) . CONCLUSIONS In this very small pilot series , reading disorders were relatively rare in children with amblyopia . However , strabismic amblyopia and presence of suppression may have an adverse effect on phonological skills . In addition , amblyopia may be associated with a deficit in RAN . Further research is needed and planned to gain a better underst and ing about the relationship between amblyopia and reading ability A r and om , population -based sample of 431 women aged 18–74 in King County , Washington , USA , completed a survey module on Internet use and access . Level of mental health , level of general health perceptions , older age , and higher income predicted women 's health-related Internet use . Participants without access reported various barriers to obtaining access ; perceived lack of usefulness of the Internet as an information source and unfamiliarity with using this technology appear equally important reasons as financial cost for not adopting the Internet . Internet use motivators are complex ; these findings have relevance to the design of Internet-based interventions OBJECTIVES To test the hypothesis that an inverse association exists between socio-economic position and all-cause mortality in a developing country in Latin America . STUDY DESIGN Prospect i ve cohort study carried out in Chile using data from a simple r and om sample of 920 apparently healthy subjects ( weighted population 11,600 aged 30 - 89 years ) followed for 8 years . METHODS Education level ( 0 - 8 years , 9 - 12 years and > or = 13 years ) and income quartiles were established at the outset of the study , along with behavioural and biological risk factors for chronic diseases : smoking , alcohol use , obesity , diabetes , hypertension , lipids and family history of death by cardiovascular disease . Relative risks of all-cause mortality were estimated using age-adjusted Cox regression models . RESULTS During the follow-up period , 46 deaths were observed . Adjusting for age , gender , and behavioural and biological risk factors , the mortality risk for increasing categories of education after controlling for income was 1.0 , 0.76 and 0.33 ( P for trend<0.01 ) . In contrast , the relative risk for increasing levels of income after controlling for education was 1.0 , 0.98 , 1.33 and 1.17 ( P for trend=0.07 ) . CONCLUSION While education level had a protective effect on mortality risk of Chilean adults , income had a slightly unfavourable effect on survival . This finding is described as suggestive of a ' pauper-rich paradox ' , since the higher income quantiles in this study correspond with the lower income levels in most developed countries . Nevertheless , due to the small number of deaths , additional research is required to assess the validity of these findings A r and omised controlled trial was design ed to test an Internet-based interactive application as a st and -alone support for the development of self- assessment skills among second-year dental students at the Faculty of Dentistry , University of Malmö , Sweden . Fifty-two students were r and omised into an experimental ( n = 26 ) and a control group ( n = 26 ) . Both groups went through four identical learning cases in elementary clinical Periodontology during a period of 1 month . The experimental group received the cases with the interactive software , while the control group received them through a static web page . After the end of the learning phase , both groups were assessed blindly by two assessors during the interactive examination methodology . There was a moderate agreement between the two assessors , but both failed to find any significant differences between the two groups with regard to self- assessment skills and overall performance of the students . Students positively received the Internet support , but several attitude differences were observed between the two groups during the study . Time on task and competence with computers were positively correlated to assessment results for both groups . On the basis of these findings , it remains unclear if computer-based applications with automated feedback can constitute an effective remedial support for the improvement of self- assessment skills of students . In addition , for such applications to be successfully accepted , two factors are critical : students must have a clear perception of the benefits deriving from the use of the software and the use of the software should be integrated in the curriculum , replacing some of the existing workload Changes after 2 years in a Head Start Family Service Center Demonstration Project were assessed through pre-implementation and postimplementation interviews with 80 parents of Head Start children to evaluate changes during the project noted for the children 's parents . Compared with parents in regular Head Start , parents in the supplementary Family Service Center project reported more contact with staff , increased their functional literacy scores , and increased their family incomes . The percentage of these parents with high depression scores decreased . These changes encourage implementation of more intensive social services within Head Start programs as a means of effectively assisting Head Start parents OBJECTIVE Test the efficacy of educational interventions to reduce literacy barriers and enhance health outcomes among patients with inflammatory arthritis . METHODS The intervention consisted of plain language information material s and /or two individualized sessions with an arthritis educator . R and omization was stratified by education level . Principal outcomes included adherence to treatments , self-efficacy , satisfaction with care , and appointment keeping . Secondary outcomes included health status and mental health . Data were collected at baseline , six , and twelve months post . RESULTS Of the 127 patients , half had education beyond high school and three quarters had disease duration greater than five years . There were no differences in the primary outcome measures between the groups . In mixed models controlling for baseline score and demographic factors , the intervention group showed improvement in mental health score at six and twelve months ( 3.0 and 3.7 points , respectively ) , while the control group showed diminished scores ( -4.5 and -2.6 points , respectively ) ( p=0.03 and 0.01 ) . CONCLUSION While the intervention appears to have had no effect on primary outcomes , further studies with continued attention to literacy are warranted . Study site and disease duration must be considered as participants in this study had higher than average health literacy and had established diagnoses for years prior to this study . PRACTICE IMPLICATION S The study offers insight into an application of many of the protocol s currently recommended to ameliorate effects of limited literacy Purpose : To investigate the prevalence and risk factors for lens opacity ( LO ) amongst a nationally representative sample of the adult population of Pakistan . Methods : This national study of blindness and visual impairment ( adults ≥30 years ) used multistage , stratified , cluster r and om sampling . Grading of LO was conducted using the Mehra/Minassian classification system . LO , partly or wholly obscuring the red reflex , or previous cataract surgery were indicators of opacity . Results : 16,402 ( 94.7 % ) adults were included in this analysis ( study conducted 2002–2003 ) . A total of 4,096 ( st and ardized prevalence 20.9 % , 95%CI : 20.3 , 21.5 % ) adults were found to have LO . The highest prevalence of LO was found in Punjab province ( 22.2 % ) , the lowest in Balochistan Province ( 18.0 % ) . Significant positive associations were increasing age ( multivariable odds ratio ( OR ) 3.2 : 95%CI : 3.1 , 3.4 ) , hypertension ( OR 1.2 , 95%CI : 1.1 , 1.3 ) , history of diabetes ( OR 2.6 : 95%CI 2.0 , 3.2 ) and smoking ( OR 1.3 : 95%CI : 1.1 , 1.5 ) . Higher body mass index ( BMI ) ( OR 0.8 : 95%CI 0.7 , 0.9 , heavy vs. normal BMI ) and attendance to school ( OR 0.6 : 95%CI : 0.5 , 0.8 ) were associated with lower risk of LO . Individuals in districts classified as hot were at significantly increased risk ( OR 1.3 : 95%CI : 1.1 , 1.5 ) , and those in wet districts ( > 600 mm annual rainfall ) had lower odds than individuals living in dry districts ( OR 0.7 : 95%CI : 0.6 , 0.8 ) . Conclusions : Almost a fifth of the adult population had LO . Significant positive associations were age , smoking status , hypertension , diabetes , and increased deprivation level . Protective factors included high BMI and educational achievement . The climatic associations offer novel hypothesis for further research into cataractogenesis Background : The relationship between patient adherence and treatment outcomes has been documented across chronic health conditions , but the evidence base for effective adherence interventions in human immunodeficiency virus ( HIV ) and acquired immune deficiency syndrome ( AIDS ) requires more rigorous research and reporting . Objectives : The aims of this study were to determine whether a tailored , nurse-delivered adherence intervention program-Client Adherence Profiling and Intervention Tailoring (CAP-IT)-improved adherence to HIV medications , compared with st and ard care , and to identify the relationship among adherence measures . Methods : A r and omized controlled trial ( RCT ) with repeated measures was used to test the efficacy of CAP-IT over a 6-month period . A convenience sample of 240 participants was recruited from a freest and ing public HIV/AIDS clinic in Houston , TX , that provides medical , psychological , and pharmaceutical services for over 5,000 clients . Study instruments and measures included demographics ; chart audit to capture CD4 count , viral load , and prescribed medications ; health literacy ; and five measures of adherence ( AIDS Clinical Trial Group-Revised Reasons for Missing Medications , Morisky Self-Report of Medication Non-Adherence , Pill Count , Medication Event Monitoring System [ MEMS ] caps , and Pharmacy Refill ) . Results : A logistic regression using generalized estimating equations method showed no significant differences over time on the five medication-adherence measures between the experimental and control groups . Little correlation was documented among the five different adherence measures , and there was minimal correlation with clinical markers . Discussion : It is unclear why the tailored adherence intervention was not efficacious in improving medication adherence . The findings suggest that these measures of medication adherence did not perform as expected and that , perhaps , they are not adequate measures of adherence . Effective and efficient adherence interventions are needed to address the barriers to medication adherence in HIV/AIDS BACKGROUND : The factors influencing medication adherence have not been fully eluci date d. Inadequate health literacy skills may impair comprehension of medical care instructions , and thereby reduce medication adherence . OBJECTIVES : To examine the relationship between health literacy and medication refill adherence among Medicare managed care enrollees with cardiovascular-related conditions . RESEARCH DESIGN : Prospect i ve cohort study .SUBJECTS : New Medicare enrollees from 4 managed care plans who completed an in-person survey and were identified through administrative data as having coronary heart disease , hypertension , diabetes mellitus , and /or hyperlipidemia ( n=1,549 ) . MEASURES : Health literacy was determined using the short form of the Test of Functional Health Literacy in Adults ( S-TOFHLA ) . Prospect i ve administrative data were used to calculate the cumulative medication gap ( CMG ) , a valid measure of medication refill adherence , over a 1-year period . Low adherence was defined as CMG ≥ 20 % . RESULTS : Overall , 40 % of the enrollees had low refill adherence . Bivariate analyses indicated that health literacy , race/ethnicity , education , and regimen complexity were each related to medication refill adherence ( P<.05 ) . In unadjusted analysis , those with inadequate health literacy skills had increased odds ( odds ratio [OR]=1.37 , 95 % confidence interval [ CI ] : 1.08 to 1.74 ) of low refill adherence compared with those with adequate health literacy skills . However , the OR for inadequate health literacy and low refill adherence was not statistically significant in multivariate analyses ( OR=1.23 , 95 % CI : 0.92 to 1.64 ) . CONCLUSIONS : The present study suggests , but did not conclusively demonstrate , that low health literacy predicts poor refill adherence . Given the prevalence of both conditions , future research should continue to examine this important potential association & NA ; It is manifest that the rapid growth of Internet use and improvement of information technology have changed our lifestyles . In recent years , Internet use in Taiwan has increased dramatically , from 3 million users in 1998 to approximately 8.6 million by the end of 2002 . The statistics imply that not only health care professionals but also laypersons rely on the Internet for health information . The purpose of this study was to explore Taiwan consumers ' preferences and information needs , and the problems they encountered when getting information from medical websites . Using simple r and om sampling and systematic r and om sampling , a survey was conducted in Taipei from August 26 , 2002 to October 30 , 2002 . Using simple r and om sampling and systematic r and om sampling , 28 boroughs ( Li ) were selected ; the total sample number was 1043 . Over one-quarter ( 26.8 % ) of the respondents reported having never accessed the Internet , while 763 ( 73.2 % ) reported having accessed the Internet . Of the Internet users , only 396 ( 51.9 % ) had accessed health-related websites , and 367 ( 48.1 % ) reported having never accessed health-related websites . The most popular topics were disease information ( 46.5 % ) , followed by diet consultation ( 34.8 % ) , medical news ( 28.5 % ) , and cosmetology ( 28.5 % ) . The results of the survey show that a large percentage of people in Taiwan have never made good use of health information available on the websites . The reasons for not using the websites included a lack of time or Internet access skills , no motivation , dissatisfaction with the information , unreliable information be provided , and inability to locate the information needed . The author recommends to enhance health information access skills , underst and the needs and preferences of consumers , promote the quality of medical websites , and improve the functions of medical websites We tested the hypothesis that the risk or discomfort associated with a clinical trial influence patients ' decisions to participate . Simultaneously , we evaluated factors likely to influence patients ' decisions such as underst and ing of the risk and discomfort associated with the study , patient age , educational level , and psychological status . With IRB approval , participants , who believed they were being asked to participate in a real trial , were presented one of three sham protocol s : no risk or pain ( Control , n = 48 ) , pain but no risk ( Pain , n = 51 ) , or risk but no pain ( Risk , n = 51 ) . Patients were debriefed at the end of the interview . Our major outcome measures were ( a ) underst and ing risk or pain associated with the proposed studies , ( b ) the extent to which patients felt pressured to participate , and ( c ) willingness to participate . Whereas underst and ing was similar in all groups ( Control , 68 % ; Pain , 67 % ; and Risk , 72 % ) , willingness to participate differed significantly ( Control , 64 % ; Pain , 35 % ; Risk , 26 % ; P < 0.001 ) . Patients who understood the level of risk or pain associated with the protocol s were twice as likely to participate than those who did not ( 49 % versus 24 % ; P = 0.003 ) . Nine percent agreed to participate in the risky or painful protocol s without underst and ing the risks involved . Patients who felt pressured did not agree to participate . Thus , the consent process protected patients , although for unexpected reasons . Underst and ing was poor , but patients who did not underst and the risks or pain involved or who felt pressured rarely consented . Consequently , relatively few patients unknowingly agreed to participate in risky or painful studies BACKGROUND Educational underachievement is a major morbidity associated with very preterm ( VPT ) birth . However , few studies have examined early school outcomes with most employing global , clinic based measures . OBJECTIVE To examine the early school achievement in a cohort of children born VPT and studied to age 6 years . METHODS A regional cohort of 102 VPT children ( < /=33 weeks GA ) were followed prospect ively alongside a comparison group of 108 full term ( FT ) children born during the same period ( 1998 - 2000 ) . At 6 years corrected age , all children underwent a comprehensive neurodevelopmental evaluation that included the Woodcock-Johnson Tests of Achievement ( WJ-III ) , teacher report and national numeracy and literacy test results . Rates of specific learning disabilities ( LD ) were also examined . RESULTS VPT children performed less well than FT children on WJ-III subtests ( ps<.05 ) , national tests ( ps<.01 ) , and in all curricular areas rated by teachers ( ps<.01 ) except expressive language . Even VPT children without severe neurodevelopmental impairment scored lower on the WJ-III math , national tests ( ps<.05 ) and were 2 - 3 times more likely to show delays ( ps<.02 ) in math ( 43 % vs. 19 % ) , written language ( 36 % vs. 22 % ) , language comprehension ( 26 % vs. 14 % ) , h and writing ( 36 % vs. 17 % ) , spelling ( 38 % vs. 30 % ) and physical education ( 33 % vs. 11 % ) . They were also twice as likely as FT children to have math LD ( 47 % vs. 21 % ) . CONCLUSIONS By age 6 , a substantial proportion of VPT children are lagging behind their FT peers across multiple curriculum areas , with difficulties being most prominent in math . Findings highlight the need for early identification and educational supports to help maximise VPT children 's learning opportunities during the transition to school Objectives Previous studies have shown that a single question may identify individuals with inadequate health literacy . We evaluated and compared the performance of 3 health literacy screening questions for detecting patients with inadequate or marginal health literacy in a large VA population . Methods We conducted in-person interviews among a r and om sample of patients from 4 VA medical centers that included 3 health literacy screening questions and 2 vali date d health literacy measures . Patients were classified as having inadequate , marginal , or adequate health literacy based on the Short Test of Functional Health Literacy in Adults ( S-TOFHLA ) and the Rapid Estimate of Adult Literacy in Medicine ( REALM ) . We evaluated the ability of each of 3 questions to detect : 1 ) inadequate and the combination of “ inadequate or marginal ” health literacy based on the S-TOFHLA and 2 ) inadequate and the combination of “ inadequate or marginal ” health literacy based on the REALM . Measurements and Main Results Of 4,384 patients , 1,796 ( 41 % ) completed interviews . The prevalences of inadequate health literacy were 6.8 % and 4.2 % , based on the S-TOHFLA and REALM , respectively . Comparable prevalences for marginal health literacy were 7.4 % and 17 % , respectively . For detecting inadequate health literacy , “ How confident are you filling out medical forms by yourself ? ” had the largest area under the Receiver Operating Characteristic Curve ( AUROC ) of 0.74 ( 95 % CI : 0.69–0.79 ) and 0.84 ( 95 % CI : 0.79–0.89 ) based on the S-TOFHLA and REALM , respectively . AUROCs were lower for detecting “ inadequate or marginal ” health literacy than for detecting inadequate health literacy for each of the 3 questions . Conclusion A single question may be useful for detecting patients with inadequate health literacy in a VA population Recent advances concerning emerging/beginning reading skills , positive behavioral support ( PBS ) , and three-tiered schoolwide prevention models combined with federal m and ates ( i.e. , IDEA and No Child Left Behind ) have stimulated interest in providing early and intensive instructional intervention services to children at risk for reading and behavior problems . New measures for identifying students as early as kindergarten who are not acquiring early basic literacy skills make this possible . However , questions regarding exactly how to formulate , deliver , sustain , and manage secondary -level interventions remain to be addressed . This paper describes first-year , first- grade findings for students participating in secondary -level interventions ( i.e. , small-group reading instruction ) in a r and omized trial of the efficacy of secondary and tertiary reading and behavior interventions under way at the Center for Early Intervention in Reading and Behavior , University of Kansas . The formulation of the experimental secondary -level intervention was guided by evidence supporting the efficacy of ( a ) small groups of 3 to 6 participating students and low student — teacher ratio combined with ( b ) explicit , phonics-based instruction . Selected curricula were Reading Mastery , Proactive Reading , Programmed Reading , and Read Well , use of which varied by choice across experimental-group schools . PBS was an additional intervention context in experimental schools . Comparison schools and first- grade teachers did not employ the three-tiered model , early screening , or PBS ; most students were taught using conventional whole-group instruction , little or no individualization , and curricula with weak scientific evidence . Initial results indicate significantly larger growth for experimental secondary -level at-risk students than for comparisons . Experimental-group first grade rs not showing growth were those identified with disabilities or behavioral risks and English language learners . Implication s are discussed Objective : To review literature on instruments available for assessing the physical and cognitive ability to take medications as prescribed , which serve as a way to rule out reasons for nonadherence . Data Sources : A PubMed search ( 1950–February 2008 ) was conducted to identity relevant articles . Additional references were obtained from cross-referencing the bibliographies of selected articles . Only journals containing English- language articles were selected for review . Study Selection and Data Extraction : Articles that described a simulated assessment of medication management were obtained , irrespective of whether the assessment also contained data about medication adherence or was focused on older adults . Data Synthesis : Fifteen instruments were identified . Six instruments required 5 minutes or less to administer . 5 required 6–30 minutes , and 4 had no administration time data reported . A possible advantage of 3 of the instruments is that they use a subject 's own medications and may therefore provide a more authentic assessment . Only 2 instruments have been tested by subjects other than the drug developers and only one has been used in 2 different population s , thereby affording soma insight into generalizability . These studies have used a variety of other vali date d surveys/ assessment s to provide an indication of construct validity , including neuropsychological batteries , caregiver reports , prospect i ve outcomes , instrumental activities of daily living , and levels of care . One instrument determined whether Individuals could tell if refills existed , whom to contact , and re sources to obtain medications . Three assessed numeracy literacy . Conclusions : Five instruments that measure medication management capacity should be compared for potential further use , including Beckman 's tasks , due to their brevity and assessment of numeracy literacy ; the Medication Management Ability Assessment , Drug Regimen Unassisted Grading Scale , and Hopkins Medication Schedule because of the evidence supporting their use ; and the Medication Management Instrument for Deficiencies In the Elderly because it includes an assessment of the patient 's knowledge of how to obtain more medications . No brief tool is available for the primary care setting to identify individuals with medication management problems or to guide the type and amount of support required to manage medications Chronically ill rural women must manage complex illness without easy access to health care re sources including support and health information . The Women to Women project is a technology-based program with an overarching aim to assist rural women in the day-to-day management of their illnesses . An important aspect of the Women to Women program is teaching the women how to use the Internet to meet their support and informational needs . The purpose s of this article are to examine changes in 1 ) the level of computer skills , 2 ) degree of comfort in using the computer , and 3 ) knowledge of Internet functions for the participants in the Women to Women computer-based intervention . Results of the initial analysis of data from 63 women ( intervention group n = 29 , control group n = 34 ) indicate that women participating in the intervention reported greater computer skills and computer comfort and greater knowledge of specific aspects of Internet use than women in the control group . These findings were further strengthened considering that intervention and control group differentials were sustained 8 months after the end of the women 's participation in the computer intervention . With the attainment of computer and Internet skills , it is expected that these rural women will have a sustained ability to access quality Internet information that will allow them to better manage and adapt to their chronic illnesses BACKGROUND In the UK , population screening for unmet need has failed to improve the health of older people . Attention is turning to interventions targeted at ' at-risk ' groups . Living alone in later life is seen as a potential health risk , and older people living alone are thought to be an at-risk group worthy of further intervention . AIM To explore the clinical significance of living alone and the epidemiology of lone status as an at-risk category , by investigating associations between lone status and health behaviours , health status , and service use , in non-disabled older people . DESIGN OF STUDY Secondary analysis of baseline data from a r and omised controlled trial of health risk appraisal in older people . SETTING Four group practice s in suburban London . METHOD Sixty per cent of 2641 community-dwelling non-disabled people aged 65 years and over registered at a practice agreed to participate in the study ; 84 % of these returned completed question naires . A third of this group , ( n = 860 , 33.1 % ) lived alone and two-thirds ( n = 1741 , 66.9 % ) lived with someone else . RESULTS Those living alone were more likely to report fair or poor health , poor vision , difficulties in instrumental and basic activities of daily living , worse memory and mood , lower physical activity , poorer diet , worsening function , risk of social isolation , hazardous alcohol use , having no emergency carer , and multiple falls in the previous 12 months . After adjustment for age , sex , income , and educational attainment , living alone remained associated with multiple falls , functional impairment , poor diet , smoking status , risk of social isolation , and three self-reported chronic conditions : arthritis and /or rheumatism , glaucoma , and cataracts . CONCLUSION Clinicians working with independently-living older people living alone should anticipate higher levels of disease and disability in these patients , and higher health and social risks , much of which will be due to older age , lower educational status , and female sex . Living alone itself appears to be associated with higher risks of falling , and constellations of pathologies , including visual loss and joint disorders . Targeted population screening using lone status may be useful in identifying older individuals at high risk of falling This study investigates the effects of parent-child shared book reading and metalinguistic training on the language and literacy skills of 148 kindergartners in Hong Kong . Children were pretested on Chinese character recognition , vocabulary , morphological awareness , and reading interest and then assigned r and omly to 1 of 4 conditions : the dialogic reading with morphology training ( DR + MT ) , dialogic reading ( DR ) , typical reading , or control condition . After a 12-week intervention period , the DR intervention yielded greater gains in vocabulary , and the DR + MT intervention yielded greater improvement in character recognition and morphological awareness . Both interventions enhanced children 's reading interest . Results confirm that different home literacy approaches influence children 's oral and written language skills differently : Shared book reading promotes language development , whereas parents ' explicit metalinguistic training within a shared book reading context better prepares children for learning to read BACKGROUND Obstetrical and neonatal complications and /or an adverse parenting environment are risk factors for language impairment , but little is known about their effects on early word production ( late talking ) . AIMS To determine obstetrical and neonatal risk factors in children with delayed word production ; to assess the influence of the parenting environment on word production ; to determine whether the toddler 's vocabulary competence is related to his/her social competence ; to document the neurodevelopmental outcome at the late preschool age . STUDY DESIGN Prospect i ve follow-up study . Based on word production at 18 months , children were retrospectively classified into consistent or transient late talkers and controls . SUBJECTS Full-term infants , N=30 ( mean GA 40.3+/-1.1 weeks , mean birth weight 3577+/-267 g ) were assessed at 18 and 24 months ; and 5 years and 7 months . METHODS Austrian Communicative Development Inventories ; Bayley Scales of Infant Development ; Griffiths Developmental Scales . OUTCOME MEASURES Peabody Picture Vocabulary Test ; Kaufman Assessment Battery for Children ; Touwen 's neurological examination . RESULTS AND CONCLUSIONS Lower Apgar scores and the need for neonatal intensive care were associated with delayed word production . The parents ' educational and vocational levels were lower in late talkers . Early vocabulary competence correlated with social competence . With regard to the prediction of lexical and cognitive outcomes , late talkers did not differ from controls . Minor neurological dysfunctions ( MND ) were seen in nearly half of the late talkers and indicate the necessity to follow these children into school age , when MND might become more obvious and literacy can be assessed The Healthy Directions – Small Business r and omized , controlled study aim ed to reduce cancer risk among multiethnic workers in small manufacturing businesses by increasing fruit and vegetable consumption , physical activity , and daily multivitamin in take and decreasing consumption of red meat . The intervention incorporated participatory strategies and was built on a social- context ual framework that addressed people with varying cultural background s and literacy levels . In addition , the intervention aim ed to reduce worker exposure to occupational hazards . Process evaluation was conductedusing quantitative and qualitative research methods . Quantitative results showed high levels of worker awareness of and participation in programs . Qualitative findings suggested that management support , worker input , and a history of social interaction between workers and management may have contributed to high participation rates . Future studies need to examine characteristics associated with participation and nonparticipation of both managers and nonmanagers to increase the likelihood of participation and ultimately improve health behavior Utilizing a r and om sample from the general population ( N= 257 ) , we examined the effect of the radon risk ladder on risk perception , as qualified by respondents ' numeracy . The radon risk ladder provides comparative risk information about the radon equivalent of smoking risk . We compared a risk ladder providing smoking risk information with a risk ladder not providing this information . A 2 ( numeracy ; high , low ) x 3 ( risk level ; high , medium , low ) x 2 ( smoking risk comparison : with/without ) between subjects experimental design was used . A significant ( p < 0.045 ) three-way interaction between format , risk level , and numeracy was identified . Participants with low numeracy skills , as well as participants with high numeracy skills , generally distinguished between low , medium , and high risk levels when the risk ladder with comparative smoking risk information was presented . When the risk ladder without the comparative information about the smoking risk was presented , low-numerate individuals differentiated between risk levels to a much lesser extent than high-numerate individuals did . These results provide empirical evidence that the risk ladder can be a useful tool in enabling people to interpret various risk levels . Additionally , these results allow us to conclude that providing comparative information within a risk ladder is particularly helpful to the underst and ing of different risk levels by people with low numeracy skills A community based cross-sectional study was conducted in the villages of Singur block , Hooghly district , West Bengal during September 2000 to February 2001 . The objectives of the study were to find out the magnitude of Reproductive Tract Infections ( RTI ) among reproductive age group women , their knowledge about RTI and utilization of service available locally . Out of an estimated 896 women of reproductive age group in the study area , 186 women were selected by multistage r and om sampling technique . The study revealed that 66.1 % respondents experienced one or more symptoms of RTI in four weeks recall period of this study . There was significant association ( p < 0.01 ) between literacy status and their experiences of reproductive illness . 57 % had knowledge about RTI . This increased gradually with increase of their ages ( p < 0.01 ) ; literacy status ( p < 0.01 ) and their socio-economic condition ( p < 0.05 ) . 27.6 % of RTI patient did not receive any treatment , and majority of those received treatment ( 41.5 % ) sought advice from private practitioners OBJECTIVES To determine previous computer training and current computer confidence of emergency medicine ( EM ) specialists and trainees , and to determine the accessibility of computer and Internet re sources in New Zeal and ED . METHODS A prospect i ve , cross-sectional study of all New Zeal and EM specialists and trainees between July 2005 and October 2005 , using a 47-item postal question naire . Descriptive statistics with 95 % confidence intervals were compiled . Fisher 's exact test was used to compare proportions , with t-test and Mann-Whitney U-test to compare continuous variables . RESULTS A total of 226 EM specialists and trainees were sent question naires . In total , 144 ( 62 specialists and 82 trainees ) out of 224 were analysed ( response rate 64.3 % ) . The majority of respondents ( 136 , 94.4 % ( 95 % CI 89.4 - 97.6 ) ) had access to a computer at home . Almost all respondents ( 143 , 99.3 % ( 95 % CI 96.2 - 100.0 ) ) also had computer access in the ED 24 h/day . The vast majority ( 140 , 97.2 % ( 95 % CI 93.0 - 99.2 ) ) had access to medical educational material s via the Internet in the ED 24 h/day . Most respondents had limited prior computer training . Respondents felt most confident using word processing and e-mail/communications applications , and least confident using statistical and graphics programs . Compared with specialists , trainees were significantly less confident with spreadsheets ( P = 0.002 ) , literature search ing ( P = 0.034 ) , and e-mail/communications ( P = 0.040 ) . CONCLUSIONS Increased access to computer technology has not been parallelled by increased confidence in the use of computers among EM specialists and trainees . Training must address gaps in computer literacy if computer technology is to be used to its full potential BACKGROUND Providing written medicines information is being legislated in an increasing number of countries worldwide , with the patient information leaflet ( PIL ) being the most widely used method for conveying health information . The impact of providing such information on adherence to therapy is reportedly unpredictable . Therapy for human immunodeficiency virus/acquired immune deficiency syndrome ( HIV/AIDS ) and related opportunistic infections usually involves polytherapy and complex regimens , both of which are risk factors for non-adherence . The objective of this study was to assess the impact of medicines information on adherence to chronic co-trimoxazole therapy in low-literate HIV/AIDS patients . METHODS Two different PILs were design ed for co-trimoxazole tablets and were available in both English and isiXhosa . Participants were r and omly allocated to a control group ( receiving no PIL ) , group A ( receiving a " complex PIL " ) and group B ( receiving a " simple PIL " incorporating pictograms ) . At the first interview , demographic data were collected and the time , date and day that the participant would take his/her first tablet of the month 's course was also documented . In a follow-up interview adherence to therapy was assessed using two methods ; self-report and tablet count . RESULTS The medicines information material s incorporating simple text and pictograms result ed in significantly improved adherence to therapy in the short term , whereas a non-significant increase in adherence was associated with the availability of the more complex information . This was shown by both the self-reported assessment as well as the tablet count . CONCLUSION This research suggests that appropriately design ed written material can have a positive impact in improving adherence and , together with verbal consultation , are essential for enabling patients to make appropriate decisions about their medicine taking The health and life expectancy of Americans has dramatically improved during the past several decades , but racial and ethnic minorities have not benefited equally from this progress . Differences in health outcomes between majority and minority population s , commonly referred to as racial or ethnic disparities in health , are the result of several factors operating in complex sociologic , cultural , political , economic , and health care context s. Until recently , curricula addressing racial and ethnic health disparities focused on factors outside the health care system , including socioeconomic disadvantage and lack of health insurance ( 1 ) , but some publications ( 25 ) , culminating in 2002 with the Institute of Medicine report , Unequal Treatment : Confronting Racial and Ethnic Disparities in Health Care , have highlighted the fact that racial and ethnic minoritieseven those with equivalent access to the health care systemreceive lower- quality care than white patients for many medical conditions ( 6 ) . As a result , increased attention is now focused on addressing racial and ethnic disparities in health care ( hereafter referred to as health care disparities ) as a component of addressing racial and ethnic disparities in health ( hereafter referred to as health disparities ) ( 7 , 8) . Emerging consensus among national experts suggests that without new and more effective interventions , health disparities will be difficult to eliminate ( 9 ) , and they may become an even larger problem as racial and ethnic minorities become a larger proportion of the U.S. population ( 10 ) . Key stakeholders need to engage at many levels to eliminate disparities , including at the community and societal levels . However , considering the significance of the physicianpatient relationship in health care delivery , interventions by individual physicians will be an important component of an overall strategy to reduce health care disparities . Several surveys show that many physicians remain unaware of health care disparities nationally and in their own practice s ( 1113 ) . The Institute of Medicine 's report recommends that health professionals receive training to better underst and and address disparities ( 6 ) . However , few curricula on health disparities exist , and there are no well-accepted guidelines on what and how to teach about this complex topic . This report presents the work of the Society of General Internal Medicine Health Disparities Task Force to develop guidelines for medical education on disparities in health and health care . We provide learning objectives , suggested content , methods for teaching , and a set of current re sources . Although they were developed primarily for teaching medical students , residents , and practitioners in primary care , our general recommendations should apply to learners in any specialty . The Task Force has also developed recommendations for system-level and environment-of-care interventions to eliminate health care disparities , which are as important as recommendations for training individual practitioners but are beyond the scope of this report . Methods The Society of General Internal Medicine is an international organization that comprises internal medicine physicians and others who combine patient care with education and research in primary care internal medicine . The Task Force includes volunteers from the Society of General Internal Medicine membership , many of whom teach about ethics , health disparities , and cross-cultural care at their institutions . The Task Force convened a series of meetings from 2002 to 2005 , which included several conference calls , e-mail exchanges , and 4 face-to-face meetings . After the first meeting , Task Force teams completed a needs assessment and literature review . The entire Task Force then contributed to several versions of the recommendations . Subsequent meetings served to refine and tailor iterative versions of both the literature review and recommendations , which informed each other . Final recommendations were developed by a consensus , although various interpretations remain among members of the Task Force in the application of specific principles . Needs Assessment Few studies have formally assessed the need for health disparities training . Recent surveys on cross-cultural care demonstrate that resident physicians ' self-reported preparedness to deliver cross-cultural care lags well behind preparedness in other clinical and technical areas ( 14 , 15 ) . A national study on resident physicians reported that residents were receiving the message that health care disparities are important and that physicians should play a role in eliminating them , but they had not received guidance on how to do so . As a result , they developed coping behaviors rather than skills ( 16 ) . To supplement these studies , the Task Force conducted its own brief needs assessment survey with the assistance of the Institute for Ethics at the American Medical Association . The survey was sent to 60 r and omly selected internal medicine program directors nationwide , 22 of whom responded within the 1-month time frame ( 37 % response rate ) . Most of the 22 respondents ( 86 % ) reported teaching some information about health disparities , and none reported offering a lot of training . However , 77 % agreed that learning about health disparities was associated with better quality of care , and 73 % reported that a resident 's level of interest was not a barrier to teaching : health disparities . Rather , shortages of qualified faculty and lack of st and ardized curricula were often noted as barriers . Adding to the need for concrete guidance in this domain , the Liaison Committee on Medical Education , which sets st and ards for undergraduate medical education , required in 2004 that medical schools document objectives relating to the development of skills in cultural competence , indicate where in the curriculum students are exposed to such material , and demonstrate the extent to which the objectives are being achieved ( 17 ) . The Accreditation Council on Graduate Medical Education , which accredits residency training programs , has also included cultural sensitivity as a skill set in its core competencies for residency training : Programs must teach and monitor residents ' ability to demonstrate sensitivity and responsiveness to patients ' culture , age , gender , and disabilities ( 18 ) . The American Board of Medical Specialties and the Accreditation Council on Graduate Medical Education have created a toolbox of re sources for monitoring professionalism that includes useful material s for assessing residents in these domains ( 19 ) . Because these accreditation requirements have been implemented , new curricula ( 2022 ) and suggested st and ards for training programs ( 2325 ) have begun to emerge , although none are widely accepted yet . Literature Review Task Force members search ed for published curricula focused on health disparities but found very little documentation . We search ed MEDLINE ( 1966 to 2005 ) , EMBASE ( 1980 to 2005 ) , and the Cochrane Library of Systematic Review s ( all years ) and article bibliographies for curricula on health disparities or cross-cultural medical care by using various search terms . For example , by using the Medical Subject Headings and text terms health disparities and curriculum , our search yielded 39 articles . However , none of these reports on curricula explicitly focused on disparities by discussing the multifactorial causes of health disparities ; describing health care disparities as a component of health disparities ; targeting the elimination of health disparities as a professional goal for medicine ; or teaching learners how to help eliminate disparities . In contrast , several cross-cultural care curricula often prominently mentions the existence of health disparities and some root causes of disparities ( 26 ) . Various studies have summarized these curricula and evaluations of their effectiveness . A 1978 survey of medical school curricula concluded that courses on cross-cultural care in U.S. medical schools had substantial deficits ( 27 ) . A comprehensive review of U.S. and British medical school curricula in 1999 showed little apparent improvement ( 28 ) . At that time , only 13 criteria ; 11 were for first- or second-year medical students , 7 were part of core ( required ) curricula , and we only found 1 curriculum that reported any postteaching evaluation of learners . A survey of all U.S. and Canadian medical schools in 2000 concluded that most schools provided inadequate instruction about cultural issues ; separate courses addressing cultural issues were identified in only 8 % of U.S. schools and in no Canadian schools ( 29 ) . Good evidence indicated that cross-cultural care training can improve a professional 's knowledge , attitude , and skill , but there is little documented evidence of an effect on patient adherence and no evaluations of effects on patient health status ( 3032 ) . Recommendations Recommended Goals of a Curriculum The ultimate aim of a curriculum on disparities is that learners develop a professional commitment to eliminating inequities in health care quality and underst and and accept their role in eliminating racial and ethnic health care disparities . The curriculum should accomplish this by meeting 3 core teaching goals : 1 ) to help learners examine and underst and attitudes , such as mistrust , subconscious bias , and stereotyping , that practitioners and patients may bring to the clinical encounter ; 2 ) to impart knowledge of the existence and magnitude of health disparities , including the multifactorial causes of health disparities and the many solutions required to eliminate them ; and 3 ) to provide the learner with the skills required to effectively communicate and negotiate across cultures , language s , and literacy levels , including the use of key tools to improve communication . Attitudes Helping learners acquire knowledge and skills is commonly the primary goal of teaching ; however , teachers may give little explicit attention to the goal of Background . People ’s treatment decisions are often influenced by anecdotal rather than statistical information . This can lead to patients making decisions based on others ’ experiences rather than on evidence -based medicine . Objective . To test whether the use of a quiz or pictograph decreases people ’s reliance on anecdotal information . Design . Two cross-sectional survey studies using hypothetical scenarios . Participants read a scenario describing angina and indicated a preference for either bypass surgery or balloon angioplasty . The cure rate of both treatments was presented using prose , a pictograph , a quiz , or a pictograph and quiz combination . Participants read anecdotes from hypothetical patients who described the outcome of their treatment ; the number of successful anecdotes was either representative or unrepresentative of the cure rates . Setting and Participants . Prospect i ve jurors at the Philadelphia County Courthouse and travelers at the Detroit-Wayne County Metropolitan Airport . Measurements . Proportion of respondents preferring bypass over balloon angioplasty . Results . In study 1 , when statistical information was presented in prose , treatment choices were influenced by anecdotes , with 41 % of participants choosing bypass when the anecdotes were representative and only 20 % choosing it when the anecdotes were unrepresentative ( x2 = 14.40 , P < 0.001 ) . When statistics were reinforced with the pictograph and quiz , anecdotes had no significant influence on treatment decisions ( 38 % choosing bypass when anecdotes were representative v. 44 % when unrepresentative , x2 = 1.08 , P > 0.20 ) . In study 2 , the tradeoff quiz did not reduce the impact of the anecdotes ( 27 % v. 28 % choosing bypass after receiving or not receiving the quiz , x2 < 1 , P > 0.20 ) . However , the pictograph significantly reduced the impact of anecdotes , with 27 % choosing bypass after receiving no pictograph and 40 % choosing bypass after receiving a pictograph ( x2 = 6.44 , P < 0.001 ) . Conclusions . Presenting statistical information using a pictograph can reduce the undue influence of anecdotal reasoning on treatment choices The objective of this study was to examine the extent of underreporting of total energy intake and associated factors in a low-income , low-literacy , predominantly Caribbean Latino community in Lawrence , MA . Two hundred fifteen Latinos participated in a diabetes prevention study , for which eligibility included a > or=30 % risk of developing diabetes in 7.5 years . Dietary self-reported energy intake was assessed using three r and omly selected days of 24-hour diet recalls . Basal metabolic rate ( BMR ) was estimated using the Mifflin-St Jeor equation . Underreporting was determined by computing a ratio of energy intake to BMR , with a ratio of 1.55 expected for sedentary population s. Linear regression analyses were used to identify factors associated with underreporting ( energy intake : BMR ratio ) . The population was predominately women ( 77 % ) , middle-aged ( mean 52+/-11 years ) , obese ( 78 % had a body mass index > or=30 ) ; low-literate ( 62 % < high school education ) , unemployed ( 57 % reported no job ) , married or living with partner ( 52 % ) , and some had a family history of diabetes ( 37 % had siblings with diabetes ) . Reported total daily energy intake was 1,540+/-599 kcal , whereas estimated BMR was 1,495.7+/-245.1 kcal/day . When multiplied by an activity factor ( 1.20 for sedentariness ) , expected energy intake was 1,794+/-294.0 per day , indicating underreporting by an average of 254 kcal/day . Mean energy intake : BMR was 1.03+/-0.37 , and was lower for participants with higher body mass index , siblings with diabetes , sedentary lifestyle , and those who were unemployed . Energy intake underreporting is prevalent in this low-income , low-literacy Caribbean Latino population . Future studies are needed to develop dietary assessment measures that minimize underreporting in this population INTRODUCTION Male drivers between 18 - 24 years are involved in many more motor-vehicle accidents than female drivers in Sweden . Is there also a gender difference in test performance in the Swedish driving-license tests ? Is it a real difference or do any of the items display differential item functioning ( DIF ) with respect to gender or educational background ? METHOD Two r and om sample s of test-takers ' performance on the Swedish theory driving-license test were examined with descriptive and inference statistics . RESULTS Female test-takers performed better than male test-takers on the theory test , which is a real difference since no items displayed DIF with respect to gender . There was no gender difference in the practical test . The gender difference in the theory test could not be fully explained by differences in educational background . CONCLUSIONS Although everyone who passes the driving-license test has fulfilled the goals stated in the curriculum , it is possible that the gender differences in the theory test are consistent over time , and therefore might be one factor that explains why male drivers are over-represented in traffic accidents . IMPACT ON INDUSTRY Gender differences appear persistent over time . Therefore , by improving male test takers ' result on the test may lead to positive effects on the male test takers future driving career PURPOSE Cancer patients who are deficient in literacy skills are particularly vulnerable to experiencing different outcomes due to disparities in care or barriers to care . Outcomes measurement in low literacy patients may provide new insight into problems previously undetected due to the challenges of completing paper- and -pencil forms . DESCRIPTION OF STUDY A multimedia program was developed to provide a quality of life assessment platform that would be acceptable to patients with varying literacy skills and computer experience . One item at a time is presented on the computer touchscreen , accompanied by a recorded reading of the question . Various colors , fonts and graphic images are used to enhance visibility , and a small picture icon appears near each text element allowing patients to replay the sound as many times as they wish . Evaluation questions are presented to assess patient burden and preferences . RESULTS An ethnically diverse group of 126 cancer patients with a range of literacy skills and computer experience reported that the ' talking touchscreen ' ( TT ) was easy to use , and commented on the usefulness of the multimedia approach . CLINICAL IMPLICATION S The TT is a practical , user-friendly data acquisition method that provides greater opportunities to measure self-reported outcomes in patients with a range of literacy skills BACKGROUND The quality of medication use in older adults is a recurring problem of substantial concern . Efforts to both measure and improve the quality of medication use often define quality too narrowly and fall short of addressing the complexity of an older adult 's medication regimen . OBJECTIVES In an effort to more comprehensively define the quality of medication use in older adults , we conducted a prospect i ve cohort study to : ( 1 ) describe the quality of medication use in community-dwelling older adults at baseline , examining differences between whites and blacks ; ( 2 ) examine the effect of race on medication-related problems ; and ( 3 ) assess the change in quality medication use between whites and blacks over time . This paper presents the research design and methods of this longitudinal study . METHODS We interviewed white and black community-dwelling older adults ( aged > or = 60 years ) 3 times over 1 year ( baseline , 6 , and 12 months ) . We over sample d blacks so that we could estimate racial differences in the quality of medication use . We collected information on the quality of medication use , relying on a clinical pharmacist 's assessment of quality and the Assessing Care of Vulnerable Elders quality indicators . We also collected data on demographic characteristics , health literacy , functional status , and participant-reported drug therapy concerns . RESULTS Four hundred thirty-five older adults were assessed for inclusion ; 200 older adults ( 100 white , 100 black ) were enrolled in the study and completed a baseline visit . Of the 200 , 92 % completed the 6-month visit ( n = 183 ) and 88 % completed the 12-month visit ( n = 176 ) . We present baseline demographic characteristics for the 200 older adults enrolled in the study . CONCLUSION This longitudinal study is an initial step toward developing more comprehensive , patient-centered measures and interventions to address the quality of medication use in older adults BACKGROUND Since it is projected that by 2020 seventy percent of the elderly will reside in developing countries , a reliable screening method for dementia and cognitive impairment in general in population s with diverse language s , culture , education and literacy will be needed . We sought to determine if the Clock Test , a screening test for dementia , was suitable for use in a Nigerian population . STUDY DESIGN Cross-sectional survey of 54 men and 12 women from Northern Nigeria . Research ers administered two dementia screening tools : a question naire-based test adapted for use in a Nigerian population and the Clock Test . RESULTS Overall , 53.0 % of the subjects had an abnormal Clock Test whereas 10.6 % of the subjects had an abnormal question naire score . Only 9.1 % of the subjects had abnormal scores on both tests . Subjects with more schooling had a greater probability of having a positive clock concept ( underst and ing that a circle represented a clock ) . Of those with more than 6 years of schooling , 91.0 % had a positive clock concept . Subjects with a negative clock concept were more likely to have an abnormal Clock Test ( 93.3 % ) than a question naire ( 26.6 % ) . CONCLUSIONS The main finding of our study was the discrepancy between the results of the Clock Test and the question naire . Performance on the Clock Test appeared to have been heavily influenced by education level , indicating the test is not universally applicable across cultures . The question naire-based test appears to reduce the effects of illiteracy on assessing dementia in a Nigerian population . Larger studies should be done to control for how education affects the assessment of dementia Background : The Step Study , a Phase IIb HIV vaccine proof of concept study , enrolled approximately 3000 persons in clade B regions . The Atlanta site sought to enroll a diverse population . This prospect i ve cohort study examined key factors associated with participant enrollment . Methods : We obtained participant information ( eg , sociodemographic , medical ) and followed outcomes from 2005 to 2007 . Of the 810 potential “ Step Study ” participants , 340 cases were analyzed . Results : The recruitment strategy generated strong interest among minorities with 37 % eligible after prescreening , yet 25 % of the minorities enrolled . However , the percentage of whites increased from 62 % eligible ( prescreened sample ) to 75 % enrolled . The regression model was significant with educational level being an enrollment predictor ( P = 0.0023 ) . Those with at least a bachelor 's degree were more likely to enroll compared with those with a K-12 education or some college ( odds ratio = 2.424 , 95 % confidence interval = 1.372 to 4.281 , P < 0.01 ) . White race was also a significant factor ( odds ratio = 2.330 ; 95 % confidence interval = 1.241 to 4.375 , P < 0.01 ) . No difference in enrollment was observed among recruitment approaches , Pearson χ2 ( 2 ) ( n = 336 ) = 5.286 , P = 0.07 . Conclusions : The results from this study indicate that women , minorities , and those with lower educational attainment were less likely to enroll in an HIV vaccine efficacy study at our site . The findings highlight an important consideration on the role of health literacy to sustain participation of eligible minorities in HIV vaccine trials OBJECTIVE To evaluate the ability of six graph formats to impart knowledge about treatment risks/ benefits to low and high numeracy individuals . METHODS Participants were r and omized to receive numerical information about the risks and benefits of a hypothetical medical treatment in one of six graph formats . Each described the benefits of taking one of two drugs , as well as the risks of experiencing side effects . Main outcome variables were verbatim ( specific numerical ) and gist ( general impression ) knowledge . Participants were also asked to rate their perceptions of the graphical format and to choose a treatment . RESULTS 2412 participants completed the survey . Viewing a pictograph was associated with adequate levels of both types of knowledge , especially for lower numeracy individuals . Viewing tables was associated with a higher likelihood of having adequate verbatim knowledge vs. other formats ( p<0.001 ) but lower likelihood of having adequate gist knowledge ( p<0.05 ) . All formats were positively received , but pictograph was trusted by both high and low numeracy respondents . Verbatim and gist knowledge were significantly ( p<0.01 ) associated with making a medically superior treatment choice . CONCLUSION Pictographs are the best format for communicating probabilistic information to patients in shared decision making environments , particularly among lower numeracy individuals . PRACTICE IMPLICATION S Providers can consider using pictographs to communicate risk and benefit information to patients of different numeracy levels BACKGROUND Research ers ' underst and ing of the use of emergency departments ( EDs ) and physicians ' offices for the treatment of toothaches is limited . The authors conducted a study to explore their use by low-income and minority adults in comparison with the use of traditional dental services . METHODS Participants included low-income white , African-American and Hispanic adults who had experienced a toothache during the previous 12 months . A stratified r and om sample of 4,200 households in Maryl and participated in a cross-sectional telephone survey . Trained survey staff completed interviews with someone in 272 ( 68.3 percent ) of 398 eligible households . RESULTS Only 8.7 percent of respondents contacted an ED for toothache pain relief , while 20.1 percent contacted physicians . The majority of respondents who contacted an ED ( 80.5 percent ) or a physician ( 82.6 percent ) also contacted a dentist . Contacts with a dentist were reported by 58.6 percent of respondents . The authors conducted tabular analyses using chi(2 ) tests of statistical significance ( P < .05 ) and SUDAAN 's multivariable logistic regression procedure ( Research Triangle Institute , Research Triangle Park , N.C. ) ( P < .05 ) . CONCLUSIONS Respondents experiencing toothache pain ultimately sought definitive resolution of their pain from dentists while visiting EDs and physicians for temporary relief . Access to dentists ' services was particularly problematic for Hispanics and was exacerbated by health literacy issues . CLINICAL IMPLICATION S The elimination of oral health disparities must involve consideration of cultural influences on minority population s , as well as the responsibilities of the dental profession BACKGROUND AND OBJECTIVES A large proportion of US adults struggle with limited literacy skills , which affect their ability to fully function in health care setting s. This study evaluated the readability of English language American Academy of Family Physicians ( AAFP ) patient education material s. METHODS A r and om sample of 171 AAFP patient education material s was selected from a list of 518 health topics available via the Internet . The SMOG grade formula was used to measure readability of the written patient education material s. RESULTS The mean SMOG grade level of AAFP patient education material s was 9.43 + /- 1.31 ( range=6 - 12 ) . This is higher than the average reading skills of US adults . CONCLUSIONS Our results support and extend the findings of other readability studies across many medical specialties , all of which find that patient education material s are written at a difficulty level that is too high . The AAFP and individual family physicians should strive to improve communication with their patients by providing educational material s that are written at an appropriate reading level BACKGROUND Prescription and nonprescription medications constitute a substantial proportion of the health care costs of countries . National drug policies and attitudes toward medication use may play a role in irrational prescribing and consumption of medicines , leading to drug wastage . The limited re sources of developing countries warrant more careful assessment s of current national drug policies . OBJECTIVE This study quantified the amounts and types of medications that are stored in a sample of urban Iranian households and estimated the extent of drug wastage in these families . METHODS A literature search was conducted using MEDLINE and International Pharmaceutical Abstract s for 1966 to 2004 to identify articles on drug utilization and wastage . R and omly selected households in a large city in Iran were visited to determine the amounts and types of medicines stored in these households . A question naire was used to collect information about medication use in these families . RESULTS A total of 512 households were assessed . The mean ( SD ) family size of household respondents was 4.3 ( 1.6 ) members . Mothers were responsible for managing medications in 58.1 % ( 291/501 ) of families . Presence of chronic illness , insurance coverage , higher economic status , literacy among fathers , and siblings without medically related jobs were the variables that showed a significant relationship with the amount of medicines found in the households . The mean ( SD ) numbers of unit doses of medicines and of drug products found in these households were 238.5 ( 198.6 ) and 22.99 ( 20.1 ) , respectively . The most common therapeutic classes of medications kept at home were central nervous system agents , anti-infectives , and gastrointestinal medications . The real and potential medication wastage was estimated to be 38.8 % and 53.8 % , respectively . CONCLUSIONS Medications were stored in large quantities in these urban Iranian households , and a large percentage was being wasted . Drug-use assessment s and a comprehensive evaluation of the current national drug policies are warranted to curtail this problem PURPOSE To assess the efficacy of a pharmacist-led , primary care-based , disease management program to improve cardiovascular risk factors and glycated hemoglobin ( A(1C ) ) levels in vulnerable patients with poorly controlled diabetes . METHODS A r and omized controlled trial of 217 patients with type 2 diabetes and poor glycemic control ( A(1C ) level > or=8.0 % ) was conducted at an academic general medicine practice from February 2001 to April 2003 . Intervention patients received intensive management from clinical pharmacists , as well as from a diabetes care coordinator who provided diabetes education , applied algorithms for managing glucose control and decreasing cardiovascular risk factors , and addressed barriers to care . Control patients received a one-time management session from a pharmacist followed by usual care from their primary care provider . Outcomes were recorded at baseline and at 6 and 12 months . Primary outcomes included blood pressure , A(1C ) level , cholesterol level , and aspirin use . Secondary outcomes included diabetes knowledge , satisfaction , use of clinical services , and adverse events . RESULTS For the 194 patients ( 89 % ) with 12-month data , the intervention group had significantly greater improvement than did the control group for systolic blood pressure ( -9 mm Hg ; 95 % confidence interval [ CI ] : -16 to -3 mm Hg ) and A(1C ) level ( -0.8 % ; 95 % CI : -1.7 % to 0 % ) . Change in total cholesterol level was not significant . At 12 months , aspirin use was 91 % in the intervention group versus 58 % among controls ( P < 0.0001 ) . Intervention patients had greater improvements in diabetes knowledge and satisfaction than did control patients . There were no significant differences in use of clinical services or adverse events . CONCLUSION Our comprehensive disease management program reduced cardiovascular risk factors and A(1C ) levels among vulnerable patients with type 2 diabetes and poor glycemic control OBJECTIVE We sought to identify interest in different modes of self-management support among diabetes patients cared for in public hospitals , and to assess whether demographic or disease-specific factors were associated with patient preferences . We explored the possible role of a perceived communication need in influencing interest in self-management support . METHODS Telephone survey of a r and om sample of 796 English and Spanish-speaking diabetes patients ( response rate 47 % ) recruited from four urban US public hospital systems . In multivariate models , we measured the association of race/ethnicity , primary language , self-reported health literacy , self-efficacy , and diabetes-related factors on patients ' interest in three self-management support strategies ( telephone support , group medical visits , and Internet-based support ) . We explored the extent to which patients believed that better communication with providers would improve their diabetes control , and whether this perception altered the relationship between patient factors and self-management support acceptance . RESULTS Sixty-nine percent of respondents reported interest in telephone support , 55 % in group medical visits , and 42 % in Internet . Compared to Non-Hispanic Whites , Spanish-speaking Hispanics were more interested in telephone support ( OR 3.45 , 95 % CI 1.97 - 6.05 ) and group medical visits ( OR 2.45 , 95 % CI 1.49 - 4.02 ) , but less interested in Internet self-management support ( OR 0.56 , 95 % CI 0.33 - 0.93 ) . African-Americans were more interested than Whites in all three self-management support strategies . Patients with limited self-reported health literacy were more likely to be interested in telephone support than those not reporting literacy deficits . Forty percent reported that their diabetes would be better controlled if they communicated better with their health care provider . This perceived communication benefit was independently associated with interest in self-management support ( p<0.001 ) , but its inclusion in models did not alter the strengths of the main associations between patient characteristics and self-management support preferences . CONCLUSION Many diabetes patients in safety-net setting s report an interest in receiving self-management support , but preferences for modes of delivery of self-management support vary by race/ethnicity , language proficiency , and self-reported health literacy . PRACTICE IMPLICATION S Public health systems should consider offering a range of self-management support services to meet the needs of their diverse patient population s. More broad dissemination and implementation of self-management support may help address the unmet need for better provider communication among diabetes patients in these setting OBJECTIVES A r and omized controlled trial involving a nurse administered patient-tailored intervention is being conducted to improve blood pressure ( BP ) control . METHODS Veterans with hypertension from an outpatient primary care clinic completed a baseline assessment and were r and omly allocated to either a nurse administered intervention or to usual care . In this ongoing study , intervention patients receive the tailored intervention bi-monthly for 2 years via telephone ; the goal of the intervention is to promote adherence with medication and improve health behaviors . Patient factors targeted for intervention include perceived risk of hypertension , memory , literacy , social support , patients ' relationship with their health care provider , side effects of therapy , pill refill , missed appointments , and health behaviors . RESULTS The sample r and omized to the nurse intervention consisted of 294 veterans with hypertension ( average age = 63 years ; 41 % African-American ) . A comparable sample of veterans was assigned to usual care ( n = 294 ) . We have maintained a 97 % retention rate for the first 12 months of the study . The average phone call has lasted 3.7 min ranging from less than 1 to 40 min . At 6-month post-enrollment , individuals receiving the nurse intervention had a greater increase in confidence with following hypertension treatment ( P < 0.007 ) than the usual care group . DISCUSSION The intervention is easily implemented and is design ed to enhance adherence with prescribed hypertension regimen . The study includes both general and patient-tailored information based upon need assessment . The study design ensures internal validity as well as the ability to generalize study findings to the clinic setting BACKGROUND Many existing models of health behavior advance perceived risk for disease as a key motivator of risk-reduction behavior . Thus evaluating context ual factors that may influence assessment of perceived risk is important . We examined ( 1 ) how mode of assessment ( mail , telephone , web-based ) and numeracy affect reported estimates of perceived risk of colon cancer , and ( 2 ) how the amount of missing perceived risk data differs as a function of mode of assessment and numeracy . METHOD Women ( N=457 ; mean age=61.3 years ) with and without Internet access participated . Women without Internet access ( n=233 ) were r and omized into telephone or mail modes of assessment , and women with Internet access ( n=224 ) were r and omized into telephone , mail , or web-based modes of assessment . Numeracy and four different estimates of perceived lifetime risk for colon cancer ( personal percentage , population percentage , comparative , binary ) were assessed . RESULTS No significant differences were found in obtained risk estimates for any of the four risk perception items across the different modes of assessment . Greater numeracy was associated with lower percentage estimates of perceived risk . In general , the telephone mode of assessment yielded less missing data than the mail mode of assessment . CONCLUSION Mode of assessment largely does not matter when it comes to assessing perceived colon cancer risk . However , numeracy does matter and specifically impacts percentage estimates of perceived risk . While web-based , mail , and telephone modes may be used interchangeably when assessing perceived cancer risk ; less missing data may result with telephone data collection Medication knowledge and compliance among the elderly was examined using a color-coded method , which was design ed to tailor the medication regimen to the person 's daily schedule . Data were collected from 80 elderly , predominantly indigent , and individuals of low literacy . Group 1 of the study received verbal teaching only , whereas Group 2 received verbal teaching and a color-coded medication schedule . Knowledge increased significantly among both groups . Compliance to the medication schedule increased in Group 2 , among those subjects whose pretest compliance scores were low . These results suggest that a method that considers the characteristics of the individual can significantly increase knowledge and compliance The United States has the highest rates of teenage pregnancy and birth in the Western industrialized world , and research indicates that television and other mass media are important sources of sexual information for young people . The purpose of this study was to determine if a teen-led , media literacy curriculum focused on sexual portrayals in the media would increase adolescents ' awareness of media myths concerning sex , decrease the allure of sexualized portrayals , and decrease positive expectancies for sexual activity . A posttest-only quasi-experiment with control groups was conducted at 22 school and community sites in Washington state ( N = 532 ) . The intervention , a 5-lesson media literacy curriculum targeted primarily to middle school students , encouraged sexual abstinence because of federal government funding requirements . Adolescents evaluated the program positively , with 85 % rating it as better than other sex education programs . Compared to control-group participants , students were less likely to overestimate sexual activity among teens , more likely to think they could delay sexual activity , less likely to expect social benefits from sexual activity , more aware of myths about sex , and less likely to consider sexual media imagery desirable . The results showed that media literacy has promise as part of a sex education program by providing adolescents with a cognitive framework necessary to underst and and resist the influence of media on their decision making concerning sex OBJECTIVE To determine the effects of phenobarbital and repeated antenatal steroid use on the primary outcome ( intelligence and achievement ) and secondary outcomes ( behavior and head circumference ) at age 7 years . METHODS This study was a secondary analysis of a double-blind clinical trial ( phenobarbital – vitamin K versus placebo ) . Intelligence ( Wechsler Intelligence Scale for Children , third edition ) , achievement ( Wide Range Achievement Test , third edition ) , and behavioral ( Achenbach Teacher 's Report Form and the Child Behavioral Check List ) testing and head circumference measurement were performed on 7-year-old children whose mothers participated in a trial to determine if antenatal phenobarbital and vitamin K prevented severe intracranial hemorrhage . Antenatal steroid therapy in these women was repeated weekly . RESULTS Two hundred ninety-nine of 372 newborns ( 80 % ) whose mothers participated in the trial were followed up at age 7 years . Comparing mean ( ± st and ard deviation [ SD ] ) Wechsler Intelligence Scale for Children scores in the placebo versus treatment groups , there were no differences ( P > .4 ) in Full Scale IQ ( 100.3 ± 14.2 versus 100.6 ± 14.2 ) , Performance IQ ( 100.3 ± 14.6 versus 101.5 ± 15.6 ) , and Verbal IQ ( 100.2 ± 14.9 versus 99.6 ± 13.7 ) . Comparing mean ( ± SD ) Wide Range Achievement Test st and ardized scores in the placebo versus treatment groups , there were no differences ( P > .4 ) in Reading ( 97.3 ± 13.9 versus 98.0 ± 14.9 ) , Spelling ( 95.8 ± 12.7 versus 95.3 ± 13.3 ) , Mathematics ( 95.9 ± 13.8 versus 94.5 ± 14.5 ) , or head circumference measurements ( 20.3 ± 0.6 cm versus 20.4 ± 0.6 , P > .2 ) . Similarly , there were no differences in the mean Achenbach Teacher 's Report Form and Child Behavioral Check List scores between the placebo and treatment groups . CONCLUSION Antenatal phenobarbital and repetitive antenatal corticosteroid therapy was not associated with adverse effects on intelligence , achievement , behavior , or head circumference at age 7 years UNLABELLED Development and pilot testing of a disease management program for low literacy patients with heart failure . BACKGROUND R and omized trials have shown that disease management programs can reduce hospitalizations and improve symptoms for patients with congestive heart failure . We sought to create and pilot test such a program for patients with low literacy skills . METHODS We used focus groups and individual cognitive response interviews ( CRIs ) to develop an educational booklet for low literacy patients with heart failure . We incorporated the booklet into a disease management intervention that also included an initial individualized 1-h educational session and scheduled supportive phone calls that were tapered over 6 weeks . We then conducted a 3-month before-after study on patients with low literacy skills ( < 9th grade literacy level ) in a university internal medicine clinic to test the acceptability and efficacy of our program . Outcomes of interest included heart failure-related knowledge , self-care behavior and heart failure-related symptoms measured on the Minnesota Living with Heart Failure ( MLwHF ) scale . RESULTS Twenty-five patients were enrolled and 23 ( 92 % ) completed 3-month follow-up . Mean age was 60 years ( range 35 - 74 ) , 60 % were men , 60 % were African-American , and 74 % had household income under $ 15,000 per year . The median reading level was fifth grade with 32 % reading at or below the third grade level . Mean knowledge score at baseline was 67 % and did not improve after the intervention . The proportion of patients reporting weighing themselves daily increased from 32 % at baseline to 100 % at 12 weeks . Mean improvement on the MLwHF scale was 9.9 points over the 3-month trial ( 95 % CI : 0.5 , 19.2 ) , which corresponds to an improvement in one class on the New York Heart Association heart failure scale . CONCLUSION A heart failure disease management program design ed specifically for patients with low literacy skills is acceptable and is associated with improvement in self-care behavior and heart failure related symptoms Abstract Background Palmtop computers provide a promising mobile platform to address barriers to computer‐based supports for people with intellectual disabilities . This study evaluated a specially design ed interface to make navigation and features of palmtop computers more accessible to users with intellectual disabilities . Method The specialised cognitively accessible interface was compared with a st and ard Windows CE interface . Participants completed a structured set of navigation/computer use tasks using both the experimental and control conditions . Measurements included the amount of assistance needed and errors made in completing the navigation/computer use tasks . Results Participants ( N = 32 ) made significantly fewer errors ( p<.001 ) and required significantly fewer prompts ( p<.001 ) while using the specialised software interface compared to the mainstream Windows interface . Conclusions The research demonstrates the feasibility of using special software design methods , such as linear program flows , error minimisation and the incorporation of repetition and consistency , to improve access to palmtop computers for individuals with intellectual disabilities . Issues related to design ing cognitively accessible interfaces are discussed Improving Medicaid program effectiveness for underserved population s is hampered by low survey response rates . This study determined how to maximize Medicaid consumer satisfaction survey response rates to the Consumer Assessment of Health Plans Study ( CAHPS ) survey . In a public immunization clinic , 8 focus groups and 15 extended interviews were used to assess consumer-preferred survey design features and incentives . To test hypotheses , we conducted the following trial . Out of 10,733 total participants in a Kansas Medicaid managed care plan , 3,685 eligible for CAHPS were unduplicated by household . After r and omization of the 968 households with valid addresses to one of three groups , a controlled trial was conducted to assess response rates to CAHPS survey formats and incentives . Response rates were 35 % for a st and ard mailing , 44 % for a user-friendly low-literacy mailing , and 64 % for a user-friendly low-literacy mailing with a $ 10 contingent incentive . Both experimental arms significantly improved response compared with the control ; the response rate of the mailing group with the incentive was higher than the response rate of the group receiving that mailing without any incentive ( p<0.0001 ) . Using consumer-based preferences significantly increased response rates to this Medicaid satisfaction survey . Raising CAHPS response rates may increase validity of Medicaid consumer satisfaction information AIMS To investigate health literacy ( i.e. underst and ing medical information ) in North Shore Hospital 's Emergency Medicine Department patients and to assess differences in comprehension between st and ard and simplified head injury advice sheets . METHODS Prospect i ve r and omised controlled trial in a convenience sample of adult Emergency Medicine patients presenting to an urban emergency department ( ED ) in New Zeal and . Consented patients were r and omised to receive either the st and ard head injury advice sheet or a shorter , simplified sheet . Participants were asked 10 questions ( to test comprehension of advice sheets ) , demographic data collected , and a Rapid Estimation of Adult Literacy in Medicine test administered . Data analysis included descriptive statistics with 95 % confidence intervals , Mann Whitney U test , and regression model analysis . RESULTS 200 participants . Mean age 43.4 years , 77.5 % with 12 or more years of schooling , 84.5 % with reading level of high school age or above . No significant differences in demographics , schooling , and reading levels were observed between study groups . The simplified form study group showed significantly higher comprehension scores ( p<0.0001 ) . In the regression analysis , factors associated with higher comprehension scores included : the simplified form , higher literacy level , more years of schooling , and younger age group . CONCLUSIONS Previous studies have highlighted poor literacy levels in ED population s , a factor thought to affect underst and ing of discharge information . In this study population , where most read at high school level or above , the simplified advice sheet was still better understood . Recommendations for improving discharge information are discussed PURPOSE / OBJECTIVES To develop and test an interactive multimedia module prototype design ed to accommo date adults with limited literacy and without computer skills . DESIGN Experimental , r and omized , controlled , pretest , post-test . SETTING Cancer treatment centers in California , Louisiana ( pilot ) . New Hampshire , Pennsylvania , and Texas . SAMPLE Out patients who were at least 18 years old with a minimum fifth- grade reading level ; 86 experimental treatment , 88 control . METHODS Experimental treatment involved use of the interactive multimedia module ; the control group received customary Instruction . FINDINGS As compared to the control group , subjects in the experimental group had significant improvement ( p = 0.0001 ; 257 % gain ) in self-care ability regardless of age , sex race , education , geographic location , reading ability , computer experience , or preferred learning style ; a 6.515 % increase in fatigue content covered and 16.775 % Increase in instructional duration ; and significantly greater benefit from sleep-related activities and a consistent , positive pattern of self-care behavior . CONCLUSIONS The program is instructionally effective , appropriate for a wide and geographically diverse audience , and feasible for use in the ambulatory setting . IMPLICATION S FOR NURSING PRACTICE The interactive multimedia module is an effective , self-directed re source for individualized patient fatigue education OBJECTIVE To determine the compliance with a st and ard breast-conservation therapy ( BCT ) program in a predominantly indigent , minority population of patients with early breast cancer ( stage I and II ) served by a rural state institution in the South ; to compare the clinical outcomes of this group with those reported in clinical trials ; and to examine the socioeconomic factors that may have contributed to the rate of compliance . SUMMARY BACKGROUND DATA Disease-free survival and overall survival in early breast cancer treated by BCT versus modified radical mastectomy are reported to be equivalent in prospect i ve r and omized trials . However , patients enrolled in clinical trials may not be representative of patients living in the various diverse communities that make up the United States . The authors ' hypothesis is that patients enrolled in clinical trials at the national level may not be representative of indigent patients in the rural South and that clinical trial results may not be directly applicable . METHODS A retrospective review of 55 women with early-stage breast cancer treated from 1990 to 1995 was performed . Clinical data , compliance with treatment and clinical follow-up , and recurrence rates were examined . Statistical analysis performed include the Fisher exact test , Kaplan-Meier survival analysis , and log-rank test . RESULTS Full compliance ( defined as completion of the entire course of radiation therapy and clinical follow-up ) with the BCT program was observed in only 36 % of patients . Fifteen of the 35 noncompliant patients did not complete radiation therapy . A significantly higher local failure rate was observed : 8 of these 15 patients ( 53 % ) have had local failure . In contrast , patients who were either in full compliance with the BCT program or were deficient only in that they missed part of their clinical follow-up had local failure rates of 5 % ( 1/20 ) and 10 % ( 2/20 ) , respectively . Age , race , stage of cancer , economic status ( measured by availability of medical insurance ) , distance of patient 's residence from the hospital , and education level were evaluated as potential predictors of compliance . None predicted patient compliance , although a trend toward higher compliance was noted in patients with a higher education level , as determined by literacy testing . CONCLUSIONS Compliance with the BCT protocol at the authors ' institution was worse than reported in clinical trials , and noncompliance translated into a significant increase in the local failure rate . Factors examined suggest that literacy may play a role in predicting compliance . Although BCT should be discussed with all breast cancer patients , the judicious application of clinical trial data to an institution 's local population is warranted A r and omized trial comparing the amount of knowledge orally recalled from four different presentations of the same consent information was conducted in a non-clinic sample of 233 low-income parents who displayed a range of reading comprehension skill . The study simulated recruitment of children into one of two actual studies underway at another location : one involved high risk to participants , the other did not . Use of a non-clinic sample controlled for prior knowledge of the conditions , and avoiding discussion of the information further assured that differences in recalled information could be attributed more confidently to the format itself . The formats included the original written forms , enhanced print ( simpler language , topic headings , pictures ) , narrated videotapes , and self-paced PowerPoint presentations via laptop computer with bulleted print information , pictures , and narration . No format-related differences in recalled information were found in the full sample but for the 124 individuals with reading comprehension scores at or below the 8th grade level , the enhanced print version tended to be more effective than either the original form or the video . Across all formats , more information was recalled about the low-risk study . The findings emphasize the necessity for clinicians and research ers to verify underst and ing of consent information , especially when there is risk of reduced literacy skill . Reliance on video to convey information in preference to well-done print media appeared question able OBJECTIVE To evaluate a cardiovascular nutrition education package design ed for African-American adults with a wide range of literacy skills . DESIGN Comparison of a self-help group and a full-instruction group ; each group received nutrition counseling and clinical monitoring every 4 months . SUBJECTS Three hundred thirty African-American adults , aged 40 to 70 years , with elevated cholesterol level or high blood pressure were r and omly assigned to the self-help or full-instruction group ; 255 completed the 12-month follow-up . INTERVENTIONS Counseling to reduce intake of dietary fat , cholesterol , and sodium was based on Cardiovascular Dietary Education System ( CARDES ) material s , which included food-picture cards , a nutrition guide ( self-help and full-instruction group ) , a video and audiotape series , and 4 classes ( full-instruction group only ) . MAIN OUTCOME MEASURES Changes in lipid levels and blood pressure after 12 months . STATISTICAL ANALYSES PERFORMED Primary analyses consisted of repeated- measures analysis of variance to examine effects of time and r and omization group on outcomes . RESULTS Total cholesterol and low-density lipoprotein cholesterol level decreased by 7 % to 8 % in the self-help and full-instruction groups of men and women ( P < .01 ) . The ratio of total cholesterol to high-density lipoprotein cholesterol ( HDL-C ) decreased in both groups of women and in the men in the full-instruction group ( P < .01 ) . In full-instruction and self-help participants with elevated blood pressure at baseline , systolic blood pressure decreased by 7 to 11 mm Hg and diastolic blood pressure decreased by 4 to 7 mm Hg ( P < .01 ) . Outcomes did not differ by literacy scores but were positively related to the reported initial frequency of using CARDES material s. APPLICATIONS/ CONCLUSIONS These results suggest that periodic nutrition counseling based on CARDES material s used for home study can enhance management of lipid levels and blood pressure in African-American out patients OBJECTIVE Evaluation of novel treatment delivery methods , such as the Internet are notably absent from the adolescent smoking treatment literature . METHODS Adolescent smokers ages 11 - 18 years were r and omized to a clinic-based , brief office intervention ( BOI ; N=69 ) consisting of four individual counseling sessions ; or to Stomp Out Smokes ( SOS ) , an Internet , home-based intervention ( N=70 ) . Adolescents in SOS had access to the SOS site for 24 weeks . RESULTS The 30-day , point-prevalence smoking abstinence rates for BOI and SOS were 12 % versus 6 % at week 24 and 13 % versus 6 % at week 36 , with no significant treatment differences . Among participants who continued to smoke , SOS was associated with a significantly greater reduction in average number of days smoked than BOI ( P=0.006 ) . The BOI was found to be feasible with high session attendance rates . SOS participants accessed the site a mean+/-S.D. of 6.8+/-7.1 days . SOS use dropped to less than one-third of participants by week 3 . CONCLUSION Additional research is needed to tap the potential capabilities of the Internet for adolescent smoking cessation using proactive , personalized , patient-education components . PRACTICE IMPLICATION S Augmenting the SOS type of intervention with more structured , personal and proactive patient-education components delivered in-person or by telephone or electronic mail is recommended ObjectiveS elf-reported height and weight are commonly used to estimate body mass index . The present study aims to identify the characteristics of participants who reported not to know their height or weight and to evaluate the consequence of these missing data on the estimates of the prevalence of body mass index categories . Design and Participants We evaluated 1492 adults , aged 18–92 years , who were selected using r and om digit dialling . During a general interview , participants were asked to report their current height and weight and actual anthropometrical measurements were obtained as part of a subsequent physical examination . We classified as unaware subjects who reported not to know their height or weight . Results In this sample , 185 ( 12.4 % ) subjects reported not to know their height or weight ( 19.6 % of females and 6.3 % of males , p<0.001 ) . Women unaware of their weight or height were older , less educated , overweight or obese , never smoker and more frequently reported no regular physical exercise practice . In men , only ex-smokers were significantly less aware of their weight or height . In women , the prevalence of obesity using measured data was 25.3 % , decreasing to 22.2 % when considering only participants aware of their weight and height . Using self-reported data the obesity prevalence , in females , was 15.0 % . Conclusion A large proportion of adults , mainly women and older persons , reported not to know their weight and height and the exclusion of those participants results in differential errors depending on the actual values . The exclusion of participants unaware of their weight or height is an additional source of bias that decreases the sensitivity in detecting obesity and underestimates the real problem , namely in the older population OBJECTIVES To ascertain the expectations of Nepalese patients regarding aspects of doctor-patient communication and to review a model of patient-centred care for its appropriateness to Nepalese medical communication training . METHODS A cross-sectional survey , using an adapted version of the Patient-Practitioner Orientation Scale ( PPOS ) , was undertaken with a r and om sample of patients attending a general out patients department in rural Nepal . An alternative survey instrument , derived from the PPOS , was also used . RESULTS The following issues were most important to patients : being treated in a friendly and respectful manner ; being fully informed , and being given adequate consultation time . Patients were happy for the doctor to be in charge and did not want to seek information outside the doctor 's advice . They expressed a strong preference for receiving advice about preventative care . Patient responses were significantly more ' doctor-centred ' than those found in comparable studies in the USA . DISCUSSION Patients expressed strong preferences for some aspects of patient-centred communication ( PCC ) , but were not very concerned with sharing power and control . Models of PCC in Nepal require modification to reflect these local preferences . The importance of good communication techniques requires emphasis in clinical training and practice . Methods of disseminating information need to be enhanced in this low-literacy setting AIM AND OBJECTIVES The aim of this two-part paper is to identify the main transferable lessons learned from both the quantitative and qualitative evaluations of the KA24 ( Knowledge Access 24 ) service of online data bases and selected full-text journals for health and social care staff in London and the south-east of Engl and . The objectives of the qualitative evaluation were to assess the enablers and barriers to usage , and to assess the impact of the service on patient care . METHODS Telephone interviews ( n = 65 ) and a question naire survey ( n = 296 ) were conducted with various types of user , in various Trust setting s. Some non-users were also contacted . Selection of interviewees and question naire recipients was not r and om , and aim ed to cover all groups of users representatively . RESULTS Results show that policy goals were being delivered , with indications of changes to clinical practice , and improved clinical governance . Promotion , training and support needs to be extensive , and tailored to needs , but users are not always aware they need training . The sharing of passwords cast doubts on the reliability of some usage data . CONCLUSIONS Digital health library services , delivered at the point of care , are changing the way some clinicians practise . A combination of qualitative and quantitative evaluation methods are needed to assess digital library services We investigated the long-term effects of an information and communication technology ( ICT ) training programme for people with intellectual disabilities ( ID ) . A community-based ICT training programme was design ed to enhance the computer skills of people with ID and prepare them to make use of ICT in their daily life . Of the 100 who had participated in the original ICT training programme , 59 of them and their caregivers agreed to participate in the follow-up interview . A computer skills checklist was used to assess the ICT competence of the participants before training , after training , and at the 6-month follow-up assessment . All caregivers were interviewed at the 6-month follow-up session to explore the use of ICT by people with ID and their needs for further training . Results from repeated measures ANOVA showed that participants maintained at the 6-month follow-up the basic ICT skills that they acquired during training [ F=13.86 , p<0.001 ] . Caregivers reported that participants spent more time in using the computers , but still needed occasional guidance . They also reported a need to advance their ICT skills beyond the basic computer training . We concluded that ICT training for people with ID would help them in maximizing the benefits of information technology via computers Following the Beijing Conference , it is desirable to empower men to play a more active and responsive role in promoting the health of family members and preventing disease . This cross sectional , community-based , ex-post factor , pilot study was design ed to find out if traditional norms affect marital sexuality and also to identify sociodemographic factors associated with sexual networking among men . A total of 416 married men whose wives had delivered a baby in the last 36 months prior to the study were interviewed from r and omly selected clusters in Ibadan , Nigeria . Of this number , the majority 336 ( 80.8 % ) had sex with pregnant wife in the last pregnancy and proportion of married men who had sex in the pregnancy with wives reduced modestly with increasing age of the men . With regards to sexual networking in pregnancy , 207 ( 49.8 % ) men reported having sex with someone else when wife was pregnant . Of this number 95 ( 45.9 % ) had it with steady girl friends , 56 ( 27.0 % ) with new girl friends , 50 ( 24.2 % ) with another wife and 6 ( 2.9 % ) with commercial sex workers . The prevalence for having sex with someone else in this period was lower in men from the higher socio-economic class ( HSEC ) when compared with the lower socio-economic class (LSEC)(chi2 = -9.89 , P < 0.001 ) . The middle socio-economic class also had a lower rate than the lower socio-economic class ( chi2 = 6.28 , P < 0.01 ) . In addition , men with post secondary /University education had significantly lower rates for networking when their wives were pregnant compared with men of lower educational attainment ( P < 0.05 ) . Three hundred and eleven men ( 74.8 % ) reported that they observed some period ofpostpartum abstinence ( PPA ) with recently delivered wife , which ranged from 5 days to 72 months ( Median was 7.5 months ) . The highest PPA rates were seen in men with no formal education , those from lower SEC and in men who embraced traditional religions . Issues that have to be addressed in more detail in the follow up study include underst and ing why men network as traditional proscriptions are generally not adhered to . Determining the relationship between length of postpartum abstinence and sexual networking and implication of this behaviour in the spread of sexually transmitted diseases and fertility control if postpartum abstinence period is significantly reduced or increased . In this regard , qualitative research as well as quantitative research should be carried out so that the entire study is not left within the realm of a quantitative study , which may be inadequate for explaining social and demographic data Background : The ability to use printed material to function in society ( literacy ) and to h and le basic numerical concepts ( numeracy ) may have implication s in patients ’ ability to follow dosing schedules . We examined literacy and numeracy skills among patients on warfarin and explored their association with anticoagulation control . Methods and Results : Patients older than 50 years attending two anticoagulation management units were prospect ively enrolled . We measured literacy , numeracy , and international normalized ratio ( INR ) . During a 3-month follow-up period , we calculated the variability of the INR and the amount of time a patient ’s INR was within his or her therapeutic range , variables associated with bleeding and effectiveness . Among 143 patients , only 75 ( 52.4 % ) were able to read health-related words at the eighth grade level or less . Patients ’ self-reported grade completed was higher than the measured literacy grade level ( & kgr ; = 0.21 ) . While 79.0 % had completed at least eight grade s , only 47.6 % had a score at that grade level . Sixty-nine patients answered none or correctly answered fewer than two of the six numeracy questions ( 48.3 % ) . The INR variability was higher among patients with lower literacy ( P = 0.009 ) and lower numeracy skills ( P = 0.004 ) . The time in range was similar among patients at different literacy levels ( P = 0.9 ) . Patients with lower numeracy level spent more time above their therapeutic range ( P = 0.04 ) and had a trend of less time spent in range ( P = 0.10 ) . Conclusions : Low literacy was prevalent among study patients taking warfarin . Low literacy and numeracy were associated with measures of poor anticoagulation control Background Rates of communicable disease among young children are considerably higher in Israel than in other western countries . Strategies for reducing the disease rates are needed . Purpose The goal of the Jerusalem H and washing Study ( JHS ) was to evaluate a preschool-based hygiene programme aim ed at reducing illness absenteeism . Methods The trial employed cluster r and omization of preschools to intervention or control . The intervention programme was multifaceted , including various educational activities and environmental changes . The control group received the programme at the end of the study . A supplementary home component was tested using the innovative design strategy of an embedded individually-r and omized trial . All-cause absenteeism and illness-related absenteeism was assessed by daily phone calls to the teachers , supplemented with phone calls to the parents to identify the cause of the absence . The primary endpoint was illness-related absenteeism . In an attempt to avoid bias , survey staff were blinded to the study design and the main outcome as well as intervention status . Validity checks were incorporated to assess the accuracy of educator absenteeism reports and were analysed for differences between the study arms . Observation of h and washing behaviour allowed assessment of behavioural change in the intervention group and spontaneous h and washing changes in the control group . Results Cluster r and omization with delayed implementation in the control group was a feasible and efficient strategy . The individually-r and omized embedded sub-trial proved to be an efficient way to test a supplemental intervention component , and is particularly well-suited to programmes run in educational or other group setting s , including workplaces , clinics , and community centres . Limitations The trial design did not permit analysis of the intervention effect on illness . Conclusions The techniques used in this trial made it possible for a rigorous study of a complex community-based health intervention to be carried out successfully . They should prove helpful to future research ers Purpose . To describe the demographics , health-related and preventive-health behaviors , health status , and health care charges of adults who do and do not pray for health . Design . Cross-sectional survey with 1-year follow-up . Setting . A Minnesota health plan . Subjects . A stratified r and om sample of 5107 members age 40 and over with analysis based on 4404 survey respondents ( 86 % ) . Measures . Survey data included health risks , health practice s , use of preventive health services , satisfaction with care , and use of alternative therapies . Health care charges were obtained from administrative data . Results . Overall , 47.2 % of study subjects reported that they pray for health , and 90.3 % of these believed prayer improved their health . After adjustment for demographics , those who pray had significantly less smoking and alcohol use and more preventive care visits , influenza immunizations , vegetable intake , satisfaction with care , and social support and were more likely to have a regular primary care provider . Rates of functional impairment , depressive symptoms , chronic diseases , and total health care charges were not related to prayer . Conclusions . Those who pray had more favorable health-related behaviors , preventive service use , and satisfaction with care . Discussion of prayer could help guide customization of clinical care . Research that examines the effect of prayer on health status should adjust for variables related both to use of prayer and to health status Abstract OBJECTIVE : To study the effects of three approaches to increasing utilization of screening mammography in a public hospital setting in Northwest Louisiana . DESIGN : R and omized intervention study . POPULATION : Four hundred forty-five women aged 40 years and over , predominantly low-income and with low literacy skills , who had not had a mammogram in the preceding year . INTERVENTION : All interventions were chosen to motivate women to get a mammogram . Group 1 received a personal recommendation from one of the investigators . Group 2 received the recommendation plus an easy-to-read National Cancer Institute ( NCI ) brochure . Group 3 received the recommendation , the brochure , and a 12-minute interactive educational and motivational program , including a soap-operastyle video , developed in collaboration with women from the target population . MEASUREMENTS AND MAIN RESULTS : Mammography utilization was determined at 6 months and 2 years after intervention . A significant increase ( p=.05 ) in mammography utilization was observed after the intervention design ed in collaboration with patients ( 29 % ) as compared with recommendation alone ( 21 % ) or recommendation with brochure ( 18 % ) at 6 months . However , at 2 years the difference favoring the custom-made intervention was no longer significant . CONCLUSIONS : At 6 months there was at least a 30 % increase in the mammography utilization rate in the group receiving the intervention design ed in collaboration with patients as compared with those receiving the recommendation alone or recommendation with brochure . Giving patients an easy-to-read NCI brochure and a personal recommendation was no more effective than giving them a recommendation alone , suggesting that simply providing women in a public hospital with a low-literacy-level , culturally appropriate brochure is not sufficient to increase screening mammography rates . In a multivariate analysis , the only significant predictor of mammography use at 6 months was the custom-made intervention OBJECTIVE : To assess the effect of providing structured information about the benefits and harms of mammography in differing frames on women ’s perceptions of screening . DESIGN : R and omized control trial . SETTING : General internal medicine academic practice . PARTICIPANTS : One hundred seventy-nine women aged 35 through 49.INTERVENTION : Women received 1 of 3 5-minute videos about the benefits and harms of screening mammography in women aged 40 to 49 . These videos differed only in the way the probabilities of potential outcomes were framed ( positive , neutral , or negative ) . MEASUREMENTS AND MAIN RESULTS : We measured the change in accurate responses to questions about potential benefits and harms of mammography , and the change in the proportion of participants who perceived that the benefits of mammography were more important than the harms . Before seeing the videos , women ’s knowledge about the benefits and harms of mammography was inaccurate ( 82 % responded incorrectly to all 3 knowledge questions ) . After seeing the videos , the proportion that answered correctly increased by 52 % , 43 % , and 30 % for the 3 knowledge questions , respectively , but there were no differences between video frames . At baseline , most women thought the benefits of mammography outweighed the harms ( 79 % positive frame , 80 % neutral frame , and 85 % negative frame ) . After the videos , these proportions were similar among the 3 groups ( 84 % , 81 % , 83 % , P=.93 ) . CONCLUSIONS : Women improved the accuracy of their responses to questions about the benefits and harms of mammography after seeing the videos , but this change was not affected by the framing of information . Women strongly perceived that the benefits of mammography outweighed the harms , and providing accurate information had no effect on these perceptions , regardless of how it was framed BACKGROUND : Commentators have suggested that patients may underst and quantitative information about treatment benefits better when they are presented as numbers needed to treat ( NNT ) rather than as absolute or relative risk reductions . OBJECTIVE : To determine whether NNT helps patients interpret treatment benefits better than absolute risk reduction ( ARR ) , relative risk reduction ( RRR ) , or a combination of all three of these risk reduction presentations ( COMBO ) . DESIGN : R and omized cross-sectional survey . SETTING : University internal medicine clinic . PATIENTS : Three hundred fifty-seven men and women , ages 50 to 80 , who presented for health care . INTERVENTIONS : Subjects were given written information about the baseline risk of a hypothetical “ disease Y ” and were asked ( 1 ) to compare the benefits of two drug treatments for disease Y , stating which provided more benefit ; and ( 2 ) to calculate the effect of one of those drug treatments on a given baseline risk of disease . Risk information was presented to each subject in one of four r and omly allocated risk formats : NNT , ARR , RRR , or COMBO.MAIN RESULTS : When asked to state which of two treatments provided more benefit , subjects who received the RRR format responded correctly most often ( 60 % correct vs 43 % for COMBO , 42 % for ARR , and 30 % for NNT , P=.001 ) . Most subjects were unable to calculate the effect of drug treatment on the given baseline risk of disease , although subjects receiving the RRR and ARR formats responded correctly more often ( 21 % and 17 % compared to 7 % for COMBO and 6 % for NNT , P=.004 ) . CONCLUSION : Patients are best able to interpret the benefits of treatment when they are presented in an RRR format with a given baseline risk of disease . ARR also is easily interpreted . NNT is often misinterpreted by patients and should not be used alone to communicate risk to patients BACKGROUND Limited data exist to estimate the use of electronic health records ( EHRs ) in ambulatory care practice s in the United States . METHODS We surveyed a stratified r and om sample of 1829 office practice s in Massachusetts in 2005 . The one-page survey measured use of health information technology , plans for EHR adoption and perceived barriers to adoption . RESULTS A total of 847 surveys were returned , for a response rate of 46 % . Overall , 18 % of office practice s reported having an EHR . Primary -care-only and mixed practice s reported similar adoption rates ( 23 % and 25 % , respectively , P = 0.70 ) . The adoption rate in specialty practice s ( 14 % ) was lower compared with both primary -care-only ( P < 0.01 ) and mixed ( P < 0.05 ) practice s. The number of clinicians in the practice strongly correlated with EHR adoption ( P < 0.001 ) , with fewer small practice s adopting EHRs . Among practice s that have EHRs with laboratory and radiology result retrieval capabilities , at least 87 % of practice s report that a majority of their clinicians actively use these functionalities , while 74 % of practice s with electronic decision support report that the majority of clinicians actively use it . Among the practice s without an EHR , 13 % plan to implement one within the next 12 months , 24 % within the next 1 - 2 years , 11 % within the next 3 - 5 years , and 52 % reported having no plans to implement an EHR in the foreseeable future . The most frequently reported barrier to implementation was lack of adequate funding ( 42 % ) . CONCLUSIONS Overall , fewer than 1 in 5 medical practice s in Massachusetts have an EHR . Even among adopters , though , doctor usage of EHR functions varied considerably by functionality and across practice s. Many clinicians are not actively using functionalities that are necessary to improve health care quality and patient safety . Furthermore , among practice s that do not have EHRs , more than half have no plan for adoption . Inadequate funding remains an important barrier to EHR adoption in ambulatory care practice s in the United States Objective : The aim of the present study was to investigate what news stories about mental illness are recalled by Australian youth and whether these are associated with stigma and help-seeking beliefs . Method : A r and om sample of 3746 Australian youth aged 12–25 years were interviewed about mental health literacy in 2006 . As part of the interview , they were asked whether they could recall any news stories about mental health problems during the past 12 months . Stigma was assessed , as well as willingness to seek help for a mental illness described in a vignette . Common news story themes were entered as predictors of stigma components and willingness to seek help in a series of logistic regressions . Results : Only a minority of youth could recall a news story about mental illness . The most common stories recalled were those involving crime or violence ; mental health system failures ; or disclosures of mental illness by prominent individuals . Recall of a disclosure by a prominent individual was associated with beliefs that people with mental illness are sick rather than weak , while recall of a story involving crime or violence was associated with greater reluctance to tell anyone about a mental health problem . There were no types of stories that predicted willingness to seek help . Conclusions : There is some evidence that recall of positive or negative news stories is associated with specific components of stigma . Overall , however , recall of news stories about mental illness added little explanatory power to differences in stigma or help-seeking intentions OBJECTIVES To hypothesize that numeracy may also predict patient misunderst and ing of the American Urological Association symptom score ( AUA-SS ) . Health literacy consists of document and prose literacy , both considered " traditional " literacy . But , health literacy also comprises quantitative literacy or numeracy . We previously reported that document literacy independently predicts misunderst and ing of the AUA-SS . However , the AUA-SS consists of written and numeric information . METHODS Prospect i ve cohort study of male patients who completed a vali date d , 3- question numeracy test once and the AUA-SS twice , which were self-administered and then interviewer-assisted . These 2 responses were compared with assessed patient underst and ing of the AUA-SS . Multivariate logistic regression analyses examined the association between patient characteristics and poor underst and ing of the symptom score , defined as underst and ing fewer than half of the questions , by calculating the odds ratios and corresponding 95 % confidence intervals . RESULTS A total of 571 patients completed the study , with an average age and education level of 58 and 13.5 years , respectively . On the numeracy test , 16 % , 18 % , 35 % , and 31 % correctly answered 3 , 2 , 1 , and 0 questions , respectively . After adjusting for the highest educational level completed , written literacy , and demographics , completely innumerate respondents ( score = 0 points ) were more than 3 times as likely ( odds ratio = 3.55 ; 95 % confidence interval : 1.58 - 7.99 ; P = .002 ) to misrepresent their AUA-SS compared with those who had some numeracy ( 1 - 3 points ) . CONCLUSIONS Regardless of educational or literacy status , a significant number of patients self-report AUA-SS scores that are different from interviewer-assisted scores , which may severely limit their access to appropriate care Abstract The study aim ed to estimate costs of provision and access to highly active antiretroviral therapy ( HAART ) in order to assist in planning and re source allocation regarding scaling up and sustainable access to HAARTin Benin . A prospect i ve study was carried out to collect data on costs of provision of care at the Outpatient Treatment Centre ( OTC ) of the National University hospital in Cotonou , Benin and on costs borne by people living with HIV/AIDS ( PLWHA ) and their families in accessing care . We used an Excel model , a macro costing approach and WHO guidelines for costing health services . Annual costs were subsequently extrapolated from a societal perspective over a 10-year time horizon . Sensitivity analysis was conducted on major cost categories . The study population was mostly of middle age ( median age of 38 , IQR 34–42 ) , married ( 65 % ) , working class ( 60 % ) with low literacy ( 70 % primary education level or less ) . The main drivers of costs of HAART service provision were drugs ( 73 % ) , biological monitoring ( 15 % ) and personnel ( 8 % ) . Annual costs of provision of HAART and household costs borne by PLWHA and families in seeking care amounted to 1160 USD and 111 USD per PLWHA respectively . These household costs are respectively 40 % and 14 % of household health and education related costs and may represent catastrophic health expenditures for patients and families . The provision of drugs and biological monitoring , and household costs in accessing care , remain by far the main barriers to ensuring universal access to HAART The purpose of this study was to assess the effectiveness of a body image dissatisfaction prevention session that provided information on body image and media literacy to college women . Participants were 81 undergraduates who were r and omly assigned to attend either a body image intervention or a control intervention . Participants completed measures at pre- and post-intervention and at 4-week follow-up . The body image group improved significantly more than the control group on body shape concerns , but not on the other outcome variables . Efficacious interventions capable of reaching large numbers of women are necessary to help dispel the “ normative discontent ” prevalent today Our objective of this study is to develop a conceptual framework for the construct of health numeracy based on patient perceptions , using a cross-sectional , qualitative design . Interested participants ( n = 59 ) meeting eligibility criteria ( age 40–74 , English speaking ) were assigned to one of six focus groups stratified by gender and educational level ( low , medium , high ) . Fifty-three percent were male , and 47 % were female . Sixty-one percent were white non-Hispanic , and 39 % were of minority race or ethnicity . Participants were r and omly selected from three primary care sites associated with an academic medical center . Focus group discussion s were held in May 2004 and focused on how numbers are used in the health care setting . Data were presented from clinical trials to further explore how quantitative information is used in health communication and decision making . Focus groups were audio and videotaped ; verbatim transcripts were prepared and analyzed . A framework of health numeracy was developed to reflect the themes that emerged . Three broad conceptual domains for health numeracy were identified : primary numeric skills , applied health numeracy , and interpretive health numeracy . Across domains , results suggested that numeracy contains an emotional component , with both positive and negative affect reflected in patient numeracy statements . We conclude that health numeracy is a multifaceted construct that includes applied and interpretive components and is influenced by patient affect OBJECTIVES The purpose of this study was to assess the caries status of 5-year-olds in a low caries area , and study associations between dental caries and parent-related factors : parents ' education , national origin , oral health behaviours and attitudes . METHODS The material consisted of 523 children and was a stratified r and om sample . Clinical and radiographic examination was performed in 2007 . Enamel and dentine caries were recorded at surface level . Parents filled in question naires regarding socioeconomic status , their own oral health behaviours and attitudes . RESULTS Most participants ( 66 % ) had no caries experience and 16 % had enamel caries only . Dentine caries experience was present in 18 % of the children , and 5 % had dentine caries experience in five or more teeth . Surfaces with enamel caries constituted half of all surfaces with caries experience . In multiple logistic regression , statistically significant risk indicators for the child having dentine caries experience at the age of five were : having one or both parents of non-western origin ( OR = 4.8 ) , both parents ( OR = 3.0 ) or one parent ( OR = 2.1 ) with low education , parental laxness about the child 's tooth brushing ( OR = 2.8 ) , parents ' brushing their own teeth less than twice a day ( OR = 2.2 ) and having parents with frequent sugar intakes ( OR = 1.8 ) . CONCLUSION Caries prevalence in 5-year-olds was strongly associated with parent-related factors signifying that information on parents ' socioeconomic status , dental behaviours and attitudes should be considered when planning dental services for young children . Our results suggest that the real high risk group is non-western children whose parents have low education OBJECTIVE Food label use is associated with better food choices , an essential part of the management of many chronic diseases . Previous studies suggest lack of comprehension of food labels . We studied a multimedia intervention to improve food label comprehension in a sample of low income patients in New York City . METHODS This r and omized study took place at Gouverneur Healthcare Services from 2005 until 2007 . The intervention group ( n=29 ) received a Nutrition Facts Label pocket card and viewed a video explaining card use . The control group ( n=27 ) received written material s. Participants completed a 12-item pre- and post-intervention nutrition food label quiz . Quiz scores were analyzed using repeated measures analysis of variance . RESULTS The intervention group had greater improvement on the quiz than the control group ( p<0.001 ) . There was a three way interaction by time with health literacy and treatment group where the greatest improvement occurred in patients with adequate health literacy in the intervention group ( p<0.05 ) . There was no improvement in patients with limited health literacy . CONCLUSION A multimedia intervention is an effective way to improve short-term food label comprehension in patients with adequate health literacy . Further research is necessary to improve underst and ing of food labels in patients with limited health literacy Objective : ESC ( Electronic Stability Control ) is a crash avoidance technology that reduces the likelihood of collisions involving loss of control . Although past and emerging research indicates that ESC is effective in reducing collision rates and saving lives , and its inclusion in all vehicle platforms is encouraged , drivers may demonstrate behavioral adaptation or an overreliance on ESC that could offset or reduce its overall effectiveness . The main objective of the present study was to determine whether behavioral adaptation to ESC is likely to occur upon the widespread introduction of ESC into the Canadian vehicle fleet . Secondary objectives were to confirm the results of a previous ESC public survey and to generate a baseline measure for the future assessment of planned and ongoing ESC promotional activities in Canada . Methods : Two separate telephone surveys evaluated drivers ' perceptions and awareness of ESC . The first surveyed 500 r and omly selected owners/drivers of passenger vehicles . The second surveyed 1017 owners/drivers of 2006–2008 ESC-equipped passenger vehicles from the provinces of Quebec and British Columbia , Canada . Results : Though ESC drivers were much more likely than drivers of other vehicles to be aware of ESC ( 77 % vs. 39 % ) and that their own vehicle was equipped with it ( 63 % vs. 8 % ) , 23 percent had never heard of it . Ninety percent of drivers who knew that their vehicle was equipped with ESC believed that ESC had made it safer to drive and reported being confident that ESC would work in an emergency . Twenty-three percent of ESC owners who knew their vehicle had ESC reported noticing long-lasting changes in their driving behavior since they began driving the vehicle . Conclusions : Collectively , results suggest that behavioral adaptation to ESC is likely in certain drivers ; however , its proven effectiveness in reducing the likelihood of being involved in a serious crash probably outweighs any potential increases in unsafe driving . To fully benefit from ESC , vehicle manufacturers are encouraged to market ESC-equipped vehicles in a realistic , safe manner . Driver training and safety organizations are also encouraged to provide balanced educational information about ESC to their members Background The pneumococcal vaccine is widely underused . Patient education is one mechanism not widely explored for increasing vaccination rates . Objective To evaluate the effects of a culturally appropriate patient education videotape on pneumococcal vaccination rates among the clinic population of an inner-city public hospital . Methods R and omized , controlled trial comparing ( 1 ) a videotapebrochure group who both viewed the videotape and received a lowliteracy brochure , ( 2 ) a videotape only group , and ( 3 ) a control group . Results Of 2,962 charts review ed , 558 patients were r and omized . The study population was 94 % black , 73 % female , and elderly ( mean age 63.0 years ) and 64 % had less than a high school education . Patients in the videotape-brochure group were 2.5 ( 1.8 , 3.5 95 % CI ) times more likely to discuss the vaccine with their physician ( p < .001 ) and 3.5 ( 1.9 , 6.5 95 % CI ) times more likely to receive the vaccine ( p < .001 ) than the control group . The videotape-brochure group was 1.6 ( 1.2 , 2.1 95 % CI ) times more likely to discuss the vaccine ( p < .001 ) and 2.3 ( 1.4 , 3.8 95 % CI ) times more likely to receive the vaccine ( p = .002 ) than the video only group . Patients in the video only group were 1.6 ( 1.1 , 2.3 95 % CI ) times more likely to discuss the vaccine with their physician than the control group ( p = .041 ) but were not more likely to receive the vaccine . Conclusion A culturally appropriate videotape along with a lowliteracy brochure significantly increased pneumococcal vaccination rates and physician-patient discussion about the vaccine . These significant outcomes were not observed with use of videotape alone and were likely attributable to the effect of the brochure . We recommend that patient education initiatives to increase vaccination rates not focus solely on audiovisual media OBJECTIVE To describe readiness to use clear health communication principles with a pharmacist before and after participating in the Ask Me 3 ( What is my main problem ? , What do I need to do ? , Why is it important for me to do this ? ) program . DESIGN Modified , separate- sample , pretest-posttest study . SETTING Senior centers in Polk County , IA , between March 2006 and February 2007 . PARTICIPANTS 106 community-dwelling well-elderly . INTERVENTION Information on demographic characteristics , regularity of health care and medication use , health literacy level , and a measurement of multidimensional health locus of control were collected from participants , who were then were r and omly allocated to one of three assessment subgroups : ( 1 ) pretest-posttest , ( 2 ) pretest only , and ( 3 ) posttest only during each of 12 Ask Me 3 program educational sessions . MAIN OUTCOME MEASURE Readiness to use the seven principles of clear health communication described in the Ask Me 3 program . RESULTS Participants were predominantly women and white , had a high school education or higher , had a yearly income of $ 25,000 or less , and had a mean age of 75.1 years . A majority reported good to excellent health status and visited their physician two or more times per year . All took medications regularly for a medical problem . A minority had inadequate to marginal health literacy . Before the Ask Me 3 program , a majority reported planning to or actively asking their pharmacist ( 1 ) for help with questions about their medications ( 88.2 % ) , ( 2 ) to explain how to take their medication ( 82.6 % ) , ( 3 ) to describe the main problem for which their medication is being prescribed ( 78.6 % ) , and ( 4 ) to describe what can happen if they do n't take their medication ( 74.3 % ) . Approximately one-half of participants ( 55.2 % ) made a list of health or medication concerns to tell their pharmacist . A minority brought a list of current medications ( 47.8 % ) or brought a friend or family member to help when visiting their pharmacist ( 27.9 % ) . A significantly higher proportion of participants reported planning to or actively bringing a list of current medications when visiting the pharmacist ( P < or = 0.025 ) after participating in the Ask Me 3 program . Increases were not statistically significant for the remaining principles . CONCLUSION The Ask Me 3 program is a practical tool that creates awareness and reinforces principles of clear health communication . The Ask Me 3 program should be evaluated in diverse pharmacy and health care setting s with patients at high risk for poor health communication Mental health literacy is the knowledge and beliefs about mental disorders that aid in their recognition , management , or prevention ; it is also a determinant of help seeking . As such , it is presumed to be important in community suicide prevention programs . In Australia there have been a number of government , professional , and charitable organizations as well as pharmaceutical company suicide prevention initiatives which have been design ed to enhance public and professional knowledge about mental disorders , particularly depression . This naturalistic study conducted between 1998 and 2004 in a r and om and representative population sample examined the changes in mental health literacy and treatment seeking of those with major depression , both with and without suicidal ideation , and those who were neither depressed nor suicidal . Results indicated that there was marked improvement in mental health literacy for all three groups , although there was less change for those most in need of intervention ( i.e. , those with major depression and suicidal ideation ) . Furthermore , there were fewer changes in appropriate treatment seeking in those with major depression and suicidal ideation . These findings are consistent with literature reporting limited problem solving and decision making in those who are suicidal , and indicate that there are limits to broadbased community education programs . More focused suicide prevention initiatives are required , specifically for those who are depressed and suicidal |
10,470 | 27,558,497 | Conclusion The combination of chemotherapy with bevacizumab increased the response rate , progression-free survival and overall survival of patients with mCRC without prior chemotherapy .
The results of progression-free survival ( PFS ) and overall survival ( OS ) were comparatively higher in those subgroups of patients receiving bolus 5-FU or capecitabine-based chemotherapy plus bevacizumab , when compared to patients treated with infusional % -FU plus bevacizumab ( no difference in PFS and OS ) .
Regarding the type of cytotoxic scheme , regimens containing irinotecan and fluoropyrimidine monotherapy showed superior efficacy results when combined to bevacizumab | Background Colorectal cancer ( CRC ) is the fourth most frequently diagnosed cancer and the second leading cause of neoplasm-related death in the United States .
Several studies analyzed the efficacy of bevacizumab combined with different chemotherapy regimens consisting on drugs such as 5-FU , capecitabine , irinotecan and oxaliplatin .
This systematic review aims to evaluate the effectiveness and safety of chemotherapy plus bevacizumab versus chemotherapy alone in patients with previously untreated advanced or metastatic colorectal cancer ( mCRC ) . | PURPOSE Mutations affecting the KRAS gene are established predictive markers of outcome with anti-epithelial growth factor receptor ( EGFR ) antibodies in advanced colorectal cancer ( CRC ) . The relevance of these markers for anti-vascular endothelial growth factor ( VEGF ) therapy is controversial . This analysis was performed to assess the predictive and prognostic impact of KRAS and BRAF gene mutation status in patients receiving capecitabine with bevacizumab ( CG ) or capecitabine without bevacizumab in the phase III AGITG MAX ( Australasian Gastrointestinal Trials Group MAX ) study . PATIENTS AND METHODS Mutation status was determined for 315 ( 66.9 % ) of the original 471 patients . Mutation status was correlated with efficacy outcomes ( response rate , progression-free survival [ PFS ] , and overall survival [ OS ] ) , and a predictive analyses was undertaken . RESULTS Mutations in KRAS and BRAF genes were observed in 28.8 % and 10.6 % of patients , respectively . KRAS gene mutation status ( wild type [ WT ] v mutated [ MT ] ) had no prognostic impact for PFS ( hazard ratio [ HR ] , 0.89 ; CI , 0.69 to 1.14 ) or OS ( HR , 0.97 ; CI , 0.73 to 1.28 ) . BRAF mutation status ( WT v MT ) was not prognostic for PFS ( HR , 0.80 ; CI , 0.54 to 1.18 ) but was prognostic for OS ( HR , 0.49 ; CI , 0.33 to 0.73 ; P = .001 ) . By using the comparison of capecitabine versus capecitabine and bevacizumab ( CB ) and CB plus mitomycin ( CBM ) , KRAS gene mutation status was not predictive of the effectiveness of bevacizumab for PFS or OS ( test for interaction P = .95 and 0.43 , respectively ) . Similarly , BRAF gene mutation status was not predictive of the effectiveness of bevacizumab for PFS or OS ( test for interaction P = .46 and 0.32 , respectively ) . CONCLUSION KRAS gene mutation status was neither prognostic for OS nor predictive of bevacizumab outcome in patients with advanced CRC . BRAF gene mutation status was prognostic for OS but was not predictive of outcome with bevacizumab PURPOSE To report the results of a planned safety analysis from a phase III trial comparing capecitabine plus oxaliplatin ( XELOX ) with bolus fluorouracil/leucovorin ( FU/LV ) as adjuvant therapy for stage III colon cancer . PATIENTS AND METHODS Patients with stage III colon carcinoma were r and omly assigned to receive either XELOX ( intravenous oxaliplatin plus oral capecitabine ; 3-week cycle for eight cycles ) or st and ard intravenous bolus FU/LV administered as the Mayo Clinic ( Mayo ; Rochester , MN ) or Roswell Park ( RP ; Buffalo , NY ) regimen for a similar length of time . A total of 1,886 patients were r and omly assigned . RESULTS The safety population comprised 1,864 patients , of whom 938 received XELOX and 926 received FU/LV . Most treatment-related adverse events ( AEs ) occurred at similar rates in both treatment arms . However , patients receiving XELOX experienced less all- grade diarrhea , alopecia , and more neurosensory toxicity , vomiting , and h and -foot syndrome than those patients receiving FU/LV . Compared with Mayo , XELOX showed fewer grade 3/4 hematologic AE and more grade 3/4 gastrointestinal AE . Compared with RP , XELOX showed less grade 3/4 gastrointestinal AE and more grade 3/4 hematologic AE . As expected grade 3/4 neurosensory toxicity and grade 3 h and -foot syndrome were higher with XELOX . Treatment-related mortality within 28 days from the last study dose was 0.6 % in the XELOX group and 0.6 % in the FU/LV group . CONCLUSION XELOX has a manageable tolerability profile in the adjuvant setting . Efficacy data will be available within the next 24 months Objective : The objective of this phase III trial was to compare chemotherapy combined with bevacizumab versus chemotherapy alone in the treatment of patients with advanced colorectal cancer . Methods : From September 2004 till September 2008 , 222 treatment-naive patients were enrolled and divided into 2 arms : 114 arm A patients were treated with leucovorin , 5-fluorouracil plus irinotecan in combination with bevacizumab , and 108 arm B patients were treated as above without bevacizumab . All patients were stage IV with histologically confirmed adenocarcinoma . Results : The median overall survival of arm A patients was 22.0 months ( 95 % CI : 18.1–25.9 ) and 25.0 months ( CI : 18.1–31.9 ) for arm B patients . There was no statistically significant difference between the 2 arms ( p = 0.1391 ) . No statistically significant difference between the 2 arms regarding the response ratewas observed : partial response , 42 patients ( 36.8 % ) and 38 patients ( 35.2 % ) for arms A and B , respectively . Hematologic toxicity did not differ in the comparison of the 2 arms . Nonhematologic toxicity in arm A involved hypertension in 23 ( 20.2 % ) of the patients and proteinuria in 7 ( 6.1 % ) ; 3 patients experienced hemorrhage and 1 patient intestinal perforation . None of these side effects was observed in arm B patients . Conclusion : No statistically significant difference in median overall survival in patients with advanced colorectal cancer treated with bevacizumab plus a combination therapy ( arm A ) and those treated with the combination only , without bevacizumab ( arm B ) , was observed As professionals , we want to use the best treatments ; as patients , we want to be given them . Knowing whether an intervention works ( or does not work ) is fundamental to clinical decision making . However , clinical decision making involves more than simply taking published results of research directly to the bedside . Physicians need to consider how similar their patients are to those in the published studies , to take the values and preferences of their patients into account , and to consider their own experience with a given test or treatment . Evidence from clinical research is becoming increasingly important in medical- practice decisions as more and better evidence is published . But when is the evidence strong enough to justify changing a practice ? Individual studies that involve only small numbers of patients may have results that are distorted by the r and om play of chance and thus lead to less than optimal decisions . As is clear from other papers in this series , systematic review s identify , critically appraise , and review all the relevant studies on a clinical question and are more likely to give a valid answer . They use explicit methods and quality st and ards to reduce bias . Their results are the closest we can come to reaching the truth given our current state of knowledge . The questions about an intervention that a systematic review should answer are the following : 1 . Does it work ? 2 . If it works , how well does it work in general and compared with placebo , no treatment , or other interventions that are currently in use ? 3 . Is it safe ? 4 . Will it be safe and effective for my patients ? Whereas the critical appraisal and qualitative synthesis provided by review articles can be interpreted directly , the numerical products of quantitative review s can be more difficult to underst and and apply in daily clinical practice . This paper provides guidance on how to interpret the numerical and statistical results of systematic review s , translate these results into more underst and able terms , and apply them directly to individual patients . Many of these principles can also be used to interpret the numerical results of individual clinical studies . They are particularly relevant to systematic review s , however , because such review s contain more information than do primary studies and often exert greater influence than do individual studies . Making Sense of the Numerical Results of Clinical Studies Although the results of clinical studies can be expressed in intuitively meaningful ways , such results do not always easily translate into clinical decision making . For example , results are frequently expressed in terms of risk , which is an expression of the frequency of a given outcome . ( Risks are probabilities , which can vary between 0.0 and 1.0 . A probability of 0.0 means that the event will never happen , and a probability of 1.0 means that it always happens . ) Consider a hypothetical study of the recurrence of migraine headaches in a control group receiving placebo and a treatment group receiving a new antimigraine preparation , drug M ( a secondary prevention trial ) . Suppose that at the end of the trial , migraines recurred in 30 % of the control group ( the risk for recurrence was 0.30 ) but in only 5 % of the drug M group ( risk of 0.05 ) ( Table 1 ) . Table 1 . Numerical Expression of Hypothetical Clinical Trial Results The outcomes of the study are clear enough for the two groups when they are examined separately . But clinicians and patients are more interested in the comparative results , that is , the outcome in one group relative to the outcome in the other group . This overall ( comparative ) result can be expressed in various ways . For example , the relative risk , which is the risk in the treatment group relative to that in the control group , is simply the ratio of the risks in the two groups . In other words , relative risk is the risk in the treatment group divided by that in the control group , 0.05 0.30 , or 0.17 . The comparison can also be expressed as the reduction in relative risk , which is the ratio between the decrease in risk ( in the treatment group ) and the risk in the control group , 0.25 0.30 , or 0.83 ( Table 1 ) . ( The relative risk reduction can also be calculated as 1 relative risk ) . Although the clinical meaning of relative risk ( and relative risk reduction ) is reasonably clear , relative risk has the distinct disadvantage that a given value ( for example , 0.17 ) is the same whether the risk with treatment decreases from 0.80 to 0.14 , from 0.30 to 0.05 , from 0.001 to 0.00017 , and so forth . The clinical implication s of these changes clearly differ from one another enormously and depend on the specific disease and intervention . An important alternate expression of comparative results , therefore , is the absolute risk reduction . Absolute risk reduction is determined by subtracting the risk in one group from the risk in the other ( for example , the risk in the treatment group is subtracted from the risk in the placebo group ) . In the case of our migraine study , the absolute risk reduction would be 0.30 0.05 , which equals 0.25 , or 25 percentage points . In contrast , for a study in which the risk decreased from 0.001 to 0.00017 , the absolute risk reduction would be only 0.00083 , or 0.083 percentage points , which is a trivial change in comparison ( Table 1 ) . This arithmetic emphasizes the difficulty of expressing the results of clinical studies in meaningful ways . Relative risk and relative risk reduction clearly give a quantitative sense of the effects of an intervention in proportional terms but provide no clue about the size of an effect on an absolute scale . In contrast , although it tells less about proportional effects , absolute risk says a great deal about whether an effect is likely to be clinical ly meaningful . Despite this benefit , even absolute risk is problematic because it is a dimensionless , abstract number ; that is , it lacks a direct connection with the clinical situation in which the patient and physician exist . However , another way of expressing clinical research results can provide that clinical link : the number needed to treat ( NNT ) . Number Needed To Treat The NNT for a given therapy is simply the reciprocal of the absolute risk reduction for that treatment [ 1 , 2 ] . In the case of our hypothetical migraine study ( in which risk decreased from 0.30 without treatment with drug M to 0.05 with treatment with drug M , for a relative risk of 0.17 , a relative risk reduction of 0.83 , and an absolute risk reduction of 0.25 ) , the NNT would be 1 0.25 , or 4 . In concrete clinical terms , an NNT of 4 means that you would need to treat four patients with drug M to prevent migraine from recurring in one patient . To emphasize the difference between the concepts embodied in NNT and relative risk , recall the various situations mentioned above , in all of which the relative risk was 0.17 but in which the absolute risk decreased from 0.80 to 0.14 in one case and from 0.001 to 0.00017 in another . Note that the corresponding NNTs in these two other cases are 1.5 and 1204 , respectively : that is , you would need to treat 1.5 and 1204 patients to obtain a therapeutic result in these two situations compared with 4 patients with drug M ( Table 1 ) . The NNT can be calculated easily and kept as a single numerical reminder of the effectiveness ( or , as we will see , the potential for harm ) of a particular therapy . As we suggested , the NNT has the crucial advantage of direct applicability to clinical practice because it shows the effort that is required to achieve a particular therapeutic target . The NNT has the additional advantage that it can be applied to any beneficial outcome or any adverse event ( when it becomes the number needed to harm [ NNH ] ) . The concept of NNT always refers to a comparison group ( in which patients receive placebo , no treatment , or some other treatment ) , a particular treatment outcome , and a defined period of treatment . In other words , the NNT is the number of patients that you will need to treat with drug or treatment A to achieve an improvement in outcome compared with drug or treatment B for a treatment period of C weeks ( or other unit of time ) . To be fully specified , NNT and NNH must always specify the comparator , the therapeutic outcome , and the duration of treatment that is necessary to achieve the outcome . Important Qualities of the Number Needed To Treat The NNT is treatment specific . It describes the difference between treatment and control in achieving a particular clinical outcome . Table 2 shows NNTs from a selection of systematic review s and large r and omized , controlled trials . Table 2 . Numbers Needed To Treat from Systematic Review s and R and omized , Controlled Trials A very small NNT ( that is , one that approaches 1 ) means that a favorable outcome occurs in nearly every patient who receives the treatment and in few patients in a comparison group . Although NNTs close to 1 are theoretically possible , they are almost never found in practice . However , small NNTs do occur in some therapeutic trials , such as those comparing antibiotics with placebo in the eradication of Helicobacter pylori infection or those examining the use of insecticide for head lice ( Table 2 ) . An NNT of 2 or 3 indicates that a treatment is quite effective . In contrast , such prophylactic interventions as adding aspirin to streptokinase to reduce 5-week vascular mortality rates after myocardial infa rct ion may have NNTs as high as 20 to 40 and still be considered clinical ly effective . Limitations of the Number Needed To Treat Although NNTs are powerful instruments for interpreting clinical effects , they also have important limitations . First , an NNT is generally expressed as a single number , which is known as its point estimate . As with all experimental measurements , however , the true value of the NNT can be higher or lower than the point estimate determined through clinical studies . The 95 % CIs of the NNT are useful in this regard because they provide an indication that AIM To investigate the efficacy and safety of cape-citabine plus irinotecan + /- bevacizumab in advanced or metastatic colorectal cancer patients . METHODS Forty six patients with previously untreated , locally-advanced or metastatic colorectal cancer ( mCRC ) were recruited between 2001 - 2006 in a prospect i ve open-label phase II trial , in German community-based outpatient clinics . Patients received a st and ard capecitabine plus irinotecan ( CAPIRI ) or CAPIRI plus bevacizumab ( CAPIRI-BEV ) regimen every 3 wk . Dose reductions were m and atory from the first cycle in cases of > grade 2 toxicity . The treatment choice of bevacizumab was at the discretion of the physician . The primary endpoints were response and toxicity and secondary endpoints included progression-free survival and overall survival . RESULTS In the CAPIRI group vs the CAPRI-Bev group there were more female than male patients ( 47 % vs 24 % ) , and more patients had colon as the primary tumor site ( 58.8 % vs 48.2 % ) with fewer patients having sigmoid colon as primary tumor site ( 5.9 % vs 20.7 % ) . Grade 3/4 toxicity was higher with CAPIRI than CAPIRI-Bev : 82 % vs 58.6 % . Partial response rates were 29.4 % and 34.5 % , and tumor control rates were 70.6 % and 75.9 % , respectively . No complete responses were observed . The median progression-free survival was 11.4 mo and 12.8 mo for CAPIRI and CAPIRI-Bev , respectively . The median overall survival for CAPIRI was 15 mo ( 458 d ) and for CAPIRI-Bev 24 mo ( 733 d ) . These differences were not statistically different . In the CAPIRI-Bev , group , two patients underwent a full secondary tumor resection after treatment , whereas in the CAPIRI group no cases underwent this procedure . CONCLUSION Both regimens were well tolerated and offered effective tumor growth control in this outpatient setting . Severe gastrointestinal toxicities and thromboembolic events were rare and if observed were never fatal BACKGROUND In an ageing population , a greater proportion of geriatric patients will be considered for systemic chemotherapy . Colorectal cancer ( CRC ) is a common malignancy and will be a major health issue in geriatrics . We used the MAX population to investigate whether age affected the improved outcome found in CRC when bevacizumab is added to capecitabine chemotherapy . PATIENTS AND METHODS MAX , a three arm study of Capecitabine ( C ) versus CBevacizumab ( CB ) versus C BMi tomycin C ( CBM ) , found an improvement in progression-free survival ( PFS ) , with addition of B [ + /- mitomycin C ( MMC ) ] to C. This analysis assesses the effect of adding B ( + /- MMC ) to C on PFS , overall survival ( OS ) , response rate ( RR ) , toxicity and dose intensity in geriatric patients ( age ≥ 75 years ) . RESULTS Ninety-nine patients ( 21 % ) were aged 75 - 86 years . Baseline characteristics were well balanced . Eighty-eight per cent commenced C at the lower optional dose of 2000 mg/m(2)/day ; days 1 - 14 , q21 ( 61 % for < 75 years ) and 88 % were Eastern Cooperative Oncology Group 0 - 1 . Co-morbidities were as expected in this population . The addition of B significantly improved PFS in geriatric patients ( C 5.8 months versus CB 8.8 months , Hazard ratio ( HR ) 0.65 and C versus CBM 10.4 months HR 0.38 ) . The interaction test for OS , RR and PFS revealed no impact of age . Dose intensity was maintained > 90 % in all patients . There were no major differences in toxicity patterns between age cohorts . CONCLUSIONS Addition of B to C significantly improved PFS in this geriatric population , with similar benefits to those aged < 75 years . Treatment was well tolerated with no signal of increased toxicity ( including thromboembolism ) when compared with those aged < 75 years PURPOSE The National Surgical Adjuvant Breast and Bowel Project C-08 trial was design ed to investigate the safety and effectiveness of adding bevacizumab to modified infusional fluorouracil , leucovorin , and oxaliplatin ( FOLFOX ) 6 regimen for the adjuvant treatment of patients with stage II or III colon cancer . We present safety information in advance of the planned analysis of efficacy . PATIENTS AND METHODS Among 2,710 r and omly assigned patients , demographic factors were balanced . Patients received modified FOLFOX6 every 2 weeks x 12 or modified FOLFOX6 plus bevacizumab ( 5 mg/kg every 2 weeks x 26 , experimental group ) . RESULTS Overall rates of grade 4 or 5 toxicities were nearly identical in the FOLFOX6 and FOLFOX6 plus bevacizumab arms ( 15.2 % and 15.0 % , respectively ) . Six-month mortality rates were 0.96 % and 0.90 % for the control and experimental groups , respectively . Grade 3 + toxicities that occurred more often in the experimental arm versus control arm included hypertension ( 12 % v 1.8 % , respectively ) , wound complications ( abdominal incisional hernia or infusion port dehiscence/inflammation ; 1.7 % v 0.3 % , respectively ) , pain ( 11.1 % v 6.3 % , respectively ) , and proteinuria ( 2.7 % v 0.8 % , respectively ) . Grade 2 + neuropathy was increased in the experimental arm versus the control arm ( grade 2 , 33 % v 29 % , respectively ; grade 3 , 16 % v 14 % , respectively ; and grade 4 , < 1 % each ) . In the experimental arm versus control arm , significantly less thrombocytopenia ( 1.4 % v 3.4 % , respectively ) and fewer allergic reactions ( 3.1 % v 4.7 % , respectively ) were observed . Advanced age was associated with a significantly greater rate of grade 4 and 5 toxicities regardless of treatment . CONCLUSION Bevacizumab with modified FOLFOX6 is well tolerated in the surgical adjuvant setting in these patients . No significant increase in GI perforation , hemorrhage , arterial or venous thrombotic events , or death with the addition of bevacizumab to modified FOLFOX6 has been observed . Follow-up for potential delayed adverse effects and efficacy is ongoing PURPOSE We performed this phase III study to compare the irinotecan , leucovorin ( LV ) , and fluorouracil ( FU ) regimen ( FOLFIRI ) versus the oxaliplatin , LV , and FU regimen ( FOLFOX4 ) in previously untreated patients with advanced colorectal cancer . PATIENTS AND METHODS A total of 360 chemotherapy-naive patients were r and omly assigned to receive , every 2 weeks , either arm A ( FOLFIRI : irinotecan 180 mg/m(2 ) on day 1 with LV 100 mg/m(2 ) administered as a 2-hour infusion before FU 400 mg/m(2 ) administered as an intravenous bolus injection , and FU 600 mg/m(2 ) as a 22-hour infusion immediately after FU bolus injection on days 1 and 2 [ LV5FU2 ] ) or arm B ( FOLFOX4 : oxaliplatin 85 mg/m(2 ) on day 1 with LV5FU2 regimen ) . RESULTS One hundred sixty-four and 172 patients were assessable in arm A and B , respectively . Overall response rates ( ORR ) were 31 % in arm A ( 95 % CI , 24.6 % to 38.3 % ) and 34 % in arm B ( 95 % CI , 27.2 % to 41.5 % ; P = .60 ) . In both arms A and B , median time to progression ( TTP ; 7 v 7 months , respectively ) , duration of response ( 9 v 10 months , respectively ) , and overall survival ( OS ; 14 v 15 months , respectively ) were similar , without any statistically significant difference . Toxicity was mild in both groups : alopecia and gastrointestinal disturbances were the most common toxicities in arm A ; thrombocytopenia and neurosensorial were the most common toxicities in arm B. Grade 3 to 4 toxicities were uncommon in both arms , and no statistical significant difference was observed . CONCLUSION There is no difference in ORR , TTP , and OS for patients treated with the FOLFIRI or FOLFOX4 regimen . Both therapies seemed effective as first-line treatment in these patients . The difference between these two combination therapies is mainly in the toxicity profile PURPOSE In a previous study of treatment for advanced colorectal cancer , the LV5FU2 regimen , comprising leucovorin ( LV ) plus bolus and infusional fluorouracil ( 5FU ) every 2 weeks , was superior to the st and ard North Central Cancer Treatment Group/Mayo Clinic 5-day bolus 5FU/LV regimen . This phase III study investigated the effect of combining oxaliplatin with LV5FU2 , with progression-free survival as the primary end point . PATIENTS AND METHODS Four hundred twenty previously untreated patients with measurable disease were r and omized to receive a 2-hour infusion of LV ( 200 mg/m(2)/d ) followed by a 5FU bolus ( 400 mg/m(2)/d ) and 22-hour infusion ( 600 mg/m(2)/d ) for 2 consecutive days every 2 weeks , either alone or together with oxaliplatin 85 mg/m(2 ) as a 2-hour infusion on day 1 . RESULTS Patients allocated to oxaliplatin plus LV5FU2 had significantly longer progression-free survival ( median , 9.0 v 6.2 months ; P = .0003 ) and better response rate ( 50.7 % v 22.3 % ; P = .0001 ) when compared with the control arm . The improvement in overall survival did not reach significance ( median , 16.2 v 14.7 months ; P = . 12 ) . LV5FU2 plus oxaliplatin gave higher frequencies of National Cancer Institute common toxicity criteria grade 3/4 neutropenia ( 41 . 7 % v 5.3 % of patients ) , grade 3/4 diarrhea ( 11.9 % v 5.3 % ) , and grade 3 neurosensory toxicity ( 18.2 % v 0 % ) , but this did not result in impairment of quality of life ( QoL ) . Survival without disease progression or deterioration in global health status was longer in patients allocated to oxaliplatin treatment ( P = .004 ) . CONCLUSION The LV5FU2-oxaliplatin combination seems beneficial as first-line therapy in advanced colorectal cancer , demonstrating a prolonged progression-free survival with acceptable tolerability and maintenance of PURPOSE The National Surgical Adjuvant Breast and Bowel Project C-08 trial was design ed to investigate the safety and efficacy of adding bevacizumab to modified FOLFOX6 ( mFOLFOX6 ; ie , infusional/bolus fluorouracil , leucovorin , and oxaliplatin ) for the adjuvant treatment of patients with stages II to III colon cancer . METHODS Patients received mFOLFOX6 every 2 weeks for 26 weeks alone or modified as FOLFOX6 + bevacizumab ( 5 mg/kg every 2 weeks for 52 weeks [ ie , experimental group ] ) . The primary end point was disease-free survival ( DFS ) . RESULTS Among 2,672 analyzed patients , demographic factors were well balanced by treatment . With a median follow-up of 35.6 months , the addition of bevacizumab to mFOLFOX6 did not result in an overall significant increase in DFS ( hazard ratio [ HR ] , 0.89 ; 95 % CI , 0.76 to 1.04 ; P = .15 ) . The point estimates for 3-year DFS for the overall population were 77.4 % and 75.5 % for the experimental and control arms , respectively . For patients with stages II and III diseases , these same estimates were 87.4 % and 84.7 % , respectively , for stage II and 74.2 % and 72.4 % , respectively , for stage III . Exploratory analyses found that the effect of bevacizumab on DFS was different before and after a 15-month l and mark ( time-by-treatment interaction P value < .0001 ) . Bevacizumab had a strong effect before the l and mark ( HR , 0.61 ; 95 % CI , 0.48 to 0.78 ; P < .001 ) but no significant effect after ( HR , 1.22 ; 95 % CI , 0.98 to 1.52 ; P = .076 ) . CONCLUSION Bevacizumab for 1 year with mFOLFOX6 does not significantly prolong DFS in stages II and III colon cancer . However , a significant but transient effect during bevacizumab exposure was observed in the experimental arm . We postulate that this observation reflects a biologic effect during bevacizumab exposure . Given the lack of improvement in DFS , the use of bevacizumab can not be recommended for use in the adjuvant treatment of patients with colon cancer |
10,471 | 20,678,948 | Despite the remarkable success of public health programs that have instituted newborn screening and early introduction of dietary therapy for PKU , there is a growing body of evidence that suggests that neurocognitive , psychosocial , quality of life , growth , nutrition , bone pathology and maternal PKU outcomes are suboptimal . | BACKGROUND The National Institute of Health ( NIH ) published a Consensus Statement on the screening and management of Phenylketonuria ( PKU ) in 2000 .
The panel involved in the development of this consensus statement acknowledged the lack of data regarding the potential for more subtle suboptimal outcomes and the need for further research into treatment options .
In subsequent years , the approval of new treatment options for PKU and outcome data for patients treated from the newborn period by dietary therapy alone have become available .
We hypothesized that a review of the PKU literature since 2000 would provide further evidence related to neurocognitive , psychosocial , and physical outcomes that could serve as a basis for re assessment of the 2000 NIH Consensus Statement . | Summary Background Pre- and postnatal tissue accretion of long-chain polyunsaturated fatty acids ( LCPUFA ) has been related to visual and cognitive development in healthy children in several studies . Children with phenylketonuria ( PKU ) consume diets with very low contents of preformed LCPUFA . We studied prospect ively the LCPUFA status in infants with PKU without or with LCPUFA supplementation during the first year of life . Subjects and methods Infants with PKU were enrolled at diagnosis ( < 4 weeks of age ) and r and omized double blind to phenylalanine-free amino acid supplements without LCPUFA ( n=11 ) or with both arachidonic ( AA , 0.46 wt% ) and docosahexaenoic acids ( DHA , 0.27 wt% ) ( n=10 ) . At enrolment and again at 1 , 2 , 3 , 4 , 6 , 9 and 12 months , plasma phospholipid fatty acids were measured and dietary intakes were calculated from dietary protocol s. Results Unsupplemented patients showed a marked LCPUFA depletion to levels clearly below those observed in healthy breast-fed infants . In contrast , supplemented infants had stable and higher LCPUFA levels than unsupplemented infants , reaching significant differences for AA values at 3 , 4 and 6 months , and for DHA values at 1 , 3 , 4 , 6 , 9 and 12 months . Plasma phospholipid levels correlated closely with estimated dietary intakes of preformed LCPUFA . Conclusion Low LCPUFA intakes with PKU diets induce marked depletion of AA and particularly of DHA in the first year of life . Thus endogenous synthesis of LCPUFA from precursors supplied by diet seems unable to compensate for low LCPUFA intakes . LCPUFA supplementation of PKU diets during the first year of life effectively enhances LCPUFA status to levels comparable to those of healthy breast-fed infants OBJECTIVE The maternal phenylketonuria ( PKU ) syndrome is caused by high blood phenylalanine ( Phe ) levels during pregnancy , leading to a host of birth defects , especially microcephaly and congenital heart disease ( CHD ) . For finding whether the maternal PKU syndrome could be prevented , an international collaborative study was organized to evaluate treatment with a Phe-restricted diet . Blood Phe levels , maternal weight gain , and nutrient intakes during pregnancy were evaluated as to their effect on the rate of microcephaly and CHD in the offspring . METHODS The study was a prospect i ve , longitudinal effort aim ed at lowering blood Phe during pregnancy . Women were enrolled at time of referral for pregnancy . Nutrient intake analysis , which serves as the basis for this report , was available from 251 pregnancies . Subjects were stratified by blood Phe control of < or = 600 micromol/L by 8 weeks gestation or > 600 micromol/L by 8 weeks gestation . Outcome of these pregnancies was correlated to blood Phe levels , weight gain , and nutrient intake . RESULTS The study goal was to attain blood Phe levels of 120 to 360 micromol/L 3 months preconception ; however , this goal was achieved by only a limited number of patients . Therefore , the data presented were based on blood Phe control < or = 600 micromol/L or > 600 micromol/L by 8 weeks of gestation . Blood Phe control of < or = 600 micromol/L by 8 weeks of gestation was attained by 86 ( 34.3 % ) of the 251 women in this study , whereas the other 165 women had blood Phe control > 600 micromol/L by 8 weeks of gestation . Of the 251 offspring , 166 were born with normal head circumference and 85 were born with microcephaly ( < 2 st and ard deviations below normal ) . Women with blood Phe > 600 micromol/L at 8 weeks of gestation included 78 ( 92 % ) of the 85 infants with microcephaly compared with 8 % in the group of women who had blood Phe levels < or = 600 micromol/L. Weight gain during pregnancy was related to the rate of microcephaly . The highest occurrence of microcephaly ( 58 % ) was found in the pregnant women who gained < 70 % of recommended weight gain . Stepwise logistic regression analysis was used to determine factors associated with microcephaly . Significant factors included higher blood Phe levels when off diet , higher average Phe exposure during the pregnancy , low prepregnancy weight , poor weight gain during the pregnancy , and lower intake of protein and higher iron intake during the pregnancy . Infants with CHD were found only in the group of women who had blood Phe levels > 600 micromol/L by 8 weeks of gestation . There was a higher rate of CHD in the offspring who were born to women who consumed < 50 % of the recommended intake of protein in the first trimester . The main source of protein for women with PKU is the medical food ; therefore , when protein intake was low , vitamin and mineral intakes were also inadequate . CONCLUSIONS The data indicate that blood Phe control and how soon it is attained during pregnancy with PKU is important . Normal pregnancy weight gain should be encouraged to reduce microcephaly . Adequate protein and vitamin intakes early in pregnancy may have a protective effect for the prevention of CHD , even if blood Phe is elevated . The rate of microcephaly and CHD may be reduced if nutrient intake is optimal while attempting to control blood Phe levels PURPOSE To prospect ively determine the relationship between serum phenylalanine levels and apparent diffusion coefficient ( ADC ) values in the cerebral white matter of patients with phenylketonuria ( PKU ) . MATERIAL S AND METHODS Institutional review board approval was obtained , and participants provided informed consent . Magnetic resonance ( MR ) imaging , which included T1- and T2-weighted , fluid-attenuated inversion-recovery ( FLAIR ) , and diffusion-weighted examinations , was performed in 21 patients with PKU ( nine male and 12 female patients ; age range , 3 - 44 years ; mean age , 19.4 years ) . ADC values in deep cerebral white matter were calculated for each patient . Serum phenylalanine levels were obtained in all patients within 12 days after MR imaging . Serum phenylalanine levels were measured in 16 patients 1 year before MR imaging . ADC values in cerebral white matter and serum phenylalanine levels were compared . A total of 21 control subjects ( 12 male and nine female patients ; age range , 3 - 33 years ; mean age , 20.6 years ) underwent MR imaging . ADC values in cerebral white matter were compared with serum phenylalanine levels by using the Pearson correlation . RESULTS Abnormal high signal intensity in white matter on T2-weighted and FLAIR MR images was noted in patients with PKU who had serum phenylalanine levels of more than 8.5 mg/dL ( 514.2 micromol/L ) . Diffusion in posterior deep cerebral white matter tended to be restricted in patients when increased serum phenylalanine levels were measured after MR imaging ( r = -0.62 ) . There was a correlation between ADC values in posterior cerebral white matter and serum phenylalanine levels measured 1 year before MR imaging ( r = -0.77 ) . ADCs of control subjects were significantly higher than ADCs of patients with PKU ( P < .005 ) . CONCLUSION Posterior deep white matter in patients with PKU and a serum phenylalanine level of more than 8.5 mg/dL showed high signal intensity in white matter on T2-weighted and FLAIR MR images and revealed decreased ADC . We suggest that to avoid brain-restricted diffusion due to hyperphenylalanemia , patients with PKU should maintain serum phenylalanine levels of less than 8.5 mg/dL ( 514.2 micromol/L ) Summary : Women with phenylketonuria ( PKU ) must follow a strict low-phenylalanine diet during pregnancy in order to protect the fetus from the deleterious effects of high maternal blood phenylalanine . The Re source Mothers Study of Maternal PKU was undertaken to determine whether a home visitation programme was effective in helping women with PKU attain blood phenylalanine control earlier during pregnancy . Re source Mothers were trained to provide social support and practical assistance to women with PKU during pregnancy . Eight metabolic clinics in the United States participated in the study . Women with PKU who were planning pregnancy or already pregnant were enrolled in the study and were treated with a low-phenylalanine diet aim ed at controlling blood phenylalanine to 120–360 µmol/L. They were r and omly assigned to receive the services of a Re source Mother ( RM group ) or to a control group . Fifty women were enrolled , and accounted for 44 pregnancies which result ed in 28 live births , and 6 spontaneous abortions . Ten women are currently pregnant and another 6 have not become pregnant . Fifty-six percent of enrolled women began the diet prior to becoming pregnant . Fifty-three percent of women in the Re source Mother group were in metabolic control by 10 weeks gestation as compared to 39 % in the control group . In addition , women who began diet after pregnancy and had a Re source Mother attained metabolic control earlier ( mean gestational age of 22.4 weeks in the RM group vs 29.8 weeks in the control group ) . There was no difference in birth measurement z-scores of offspring born to women in the RM group compared to controls . All but 4 women rated themselves as feeling worse about the diet at the end of pregnancy than at the beginning , and few women in either group remained on diet after delivery OBJECTIVE To determine the effects of large neutral amino acid ( LNAA ) supplements on brain and plasma phenylalanine ( Phe ) levels and other metabolites in early treated subjects with classical phenylketonuria ( PKU ) , and to investigate the relationship between these metabolites and neuropsychological performance . METHODS This was a prospect i ve , double blind , cross over study consisting of four two-week phases with a 4 week washout period . Sixteen subjects ( 7 males ) , with classical PKU were recruited into the study and completed all 4 phases . Each phase consisted of either the LNAA supplement or placebo , and either the patient 's usual medical product or not . Subjects were instructed to follow their usual Phe restricted diet , maintain energy intake and complete a 3-day food record during each phase . At the end of each phase , brain Phe and other metabolites were measured by proton magnetic resonance spectroscopy ( MRS ) , and plasma amino acids quantified . A detailed neuropsychological assessment was performed on the same day as the MRS and plasma collection . RESULTS There was no correlation between plasma and brain Phe , but few of the plasma Phe readings were over 1200 micromol/L. Plasma Phe decreased with LNAA supplementation when patients were not taking their medical formula . LNAA supplementation had a specific impact on executive functions particularly in verbal generativity and cognitive flexibility . Measures of attention were better on medical product , with or without LNAA supplements . CONCLUSIONS LNAA supplementation was associated with a trend to a lowering of plasma Phe levels . LNAA supplementation had a specific impact on executive functions particularly in verbal generativity and flexibility . For individuals already complying with diet and PKU medical product , additional supplementation with LNAA is of limited value . LNAA supplementation may be of benefit to those unable to comply with PKU medical product by reducing plasma Phe , perhaps by competing with Phe at the level of transport across the gut OBJECTIVE To assess cognitive and behavioral outcome in treated maternal phenylketonuria ( PKU ) offspring . METHODS In this prospect i ve , longitudinal study , 228 children who were born to mothers with treated PKU or untreated mild hyperphenylalaninemia were compared with 70 control subjects at 7 years of age . RESULTS Offspring cognitive outcome negatively correlated with the number of gestational weeks that elapsed until maternal metabolic control was achieved ( r = -0.61 ) . Behavioral outcome was similarly affected . Postnatal measurement of stimulation in the home was also related to offspring IQ . CONCLUSIONS Children who are born to mothers who have PKU and attain metabolic control before or very early in pregnancy seem to begin life with undiminished potential . Delay in attainment of maternal metabolic control is associated with declines in offspring developmental outcome . The postnatal environment also significantly affects outcome . Interventions to improve dietary compliance before and throughout pregnancy as well as interventions to improve the postnatal home environment may reduce the risks associated with maternal PKU The aims of the study were to examine the relationship between long-chain polyunsaturated fatty acid ( LCPUFA ) status at diagnosis of phenylketonuria ( PKU ) and neurodevelopment through the first 12 months of life , and to assess whether any difference exists between infants breastfed and bottlefed in the first days of life on the basis of LCPUFA status . Twenty infants with PKU were prospect ively examined through the first year of life . Plasma fatty acids were measured in infants at diagnosis . Plasma phenylalanine levels were determined monthly . Main outcome measures were the Bayley Mental Developmental Index ( MDI ) and Psychomotor Developmental Index ( PDI ) at 5 and 12 months of age , and the visual function at 12 months , evaluated by P100 wave latencies with visual evoked potentials . A higher PDI score was associated with higher plasma arachidonic acid at diagnosis ( adjusted correlation coefficient of PDI at 5 months , r=0.38 , p=0.05 ) . P100 wave latency at 15 minutes of arc ( 15 ' ) was associated with the early plasma arachidonic acid ( adjusted r=-0.56 , p=0.02 ) and phenylalanine levels at 12 months ( adjusted r=0.22 , p=0.05 ) . No association was found between MDI score and any essential fatty acids . Breastfed infants exhibited higher plasma arachidonic acid ( mean difference , delta , = 3.4 % ; 95 % confidence interval [CI]=1.2 - 5.6 % ) and shorter P100 wave latency at 15 ' ( delta=-21 ms , 95%CI=-30 to -12 ) than bottlefed infants . Within the population of this study , a weak positive association has been found between plasma LCPUFAs at diagnosis ( higher in breastfed infants ) and neurodevelopmental indices through the first year of life Visual evoked potentials ( VEP ) were measured in 36 patients with early-treated phenylketonuria ( PKU ; aged 1 to 11 years ) and good metabolic control before and after supplementation with omega-3 long-chain polyunsaturated fatty acids ( LC-PUFA ) from fish oil . Patients with PKU had significantly longer P100 latencies than 22 age-matched control subjects . After 3 months of LC-PUFA supplementation , VEP latencies improved significantly in PKU patients but did not change in 12 untreated healthy children . The authors conclude that omega-3 LC-PUFA are essential substrates for nervous system function even beyond infancy Phenylketonuria ( PKU ) is a disorder in which the aromatic amino acid Phe can not be converted to Tyr (1)(2 ) . Unfortunately , many PKU patients do not adhere to their low-Phe diet ( off diet ) , which leads to high concentrations of the amino acid in their blood (1)(2 ) . High Phe concentrations interfere with the production of adrenaline ( A ) , noradrenaline ( NA ) , and dopamine ( DA ) (1)(3 ) . Furthermore , Krause et al. ( 4 ) reported an inverse relationship between NA and DA plasma concentrations and Phe because high Phe concentrations decrease the availability of the amino acids Tyr and Trp , the precursors of catecholamines and serotonin [ 5-hydroxytryptamine ( 5HT ) ] , respectively (5)(6)(7 ) . Acetylcholinesterase ( AChE ) is a membrane-bound enzyme with its active side exposed at the external leaflet of the bilayer ( ectoenzyme ) . When the enzyme is inhibited , it can no longer participate in the hydrolysis of acetylcholine ( ACh ) ( 8) , involving parasympathetic , sympathetic , peripheral , and central nervous system function (8)(9)(10 ) . Alterations of the above substances in the cerebrospinal fluid are correlated with AChE activity in the cerebrospinal fluid of patients with mental impairment ( 11 ) . In our previous study ( 12 ) , incubation of high Phe concentrations with human AChE type XIII led to inhibition of the enzyme ( 40–60 % ) . The effect of Phe on AChE of rat diaphragm and rat brain showed a concentration-dependent enzyme inhibition (13)(14 ) . We therefore aim ed to evaluate AChE activities in the erythrocyte membranes from patients with PKU and to correlate the enzyme activities with blood concentrations of the biogenic amines A , NA , DA , and 5HT as well as with the precursors Tyr and A study of 37 individuals with phenylketonuria ( PKU ; 17 females and 20 males , mean age 9y 9mo ( st and ard deviation [ SD ] 5y 3mo ) , range 2y 8mo to 19y 4mo ; and 35 individuals with hyperphenylalaninaemia ( HPA ; 20 females , 15 males , mean age 7y 10mo [ SD 3y 2mo ] , range 2y 8mo to 17y 3mo ) compared with 29 healthy controls ( 14 females and 15 males , mean age 9y 8mo [ SD 4y 9mo ] , range 2y 6mo to 18y 10mo ) was performed . The aim was to assess cognitive function in persons with HPA and to investigate the relation between cognitive function in PKU and the metabolic control of patients . A wide variety of neuropsychological tests was employed . Those with PKU showed lower values in intelligence and in visuo-spatial , fine motor , executive , and attention functions when compared with a control population . Plasma phenylalanine values from the first 6 years of life were negatively associated with intelligence and other cognitive functions . Executive function scores were significantly lower when comparing HPA patients with the control group . It was concluded that individuals with PKU under dietary treatment may present slightly decreased cognitive function scores when compared with control individuals , while those with HPA have scores mostly similar to those of controls , except for executive function tests . Good metabolic control of PKU seems necessary to prevent cognitive function impairments , especially during the first 6 years of life BACKGROUND Phenylketonuria ( PKU ) is an autosomal recessive metabolic disorder characterized by hyperphenylalaninemia in association with neurocognitive and neuromotor impairment . Sapropterin dihydrochloride ( hereafter referred to as sapropterin ) administered orally as dissolved tablets is approved by the US Food and Drug Administration for hyperphenylalaninemia in patients with tetrahydrobiopterin responsive PKU . OBJECTIVES This study compared the relative oral bioavailability of sapropterin when administered as intact and dissolved tablets . It also assessed the effect of food on the oral bioavailability of sapropterin administered as intact tablets . METHODS This was a r and omized , open-label , 3-treatment , 6-sequence , 3-period crossover study in healthy male and female subjects . Subjects were r and omized to receive single oral 10-mg/kg doses of sapropterin administered as dissolved tablets after a fast ; as intact tablets after a fast ; and as intact tablets with a high-calorie , high-fat meal . The 3 dosing periods were separated by a washout period of at least 7 days . In each dosing period , blood sample s were obtained within 40 minutes before and at 0.5 , 1 , 1.5 , 2 , 2.5 , 3 , 3.5 , 4 , 5 , 6 , 8 , 10 , 12 , 18 , and 24 hours after dosing . A follow-up assessment was performed 5 to 7 days after the last dosing period . The relative bioavailability of sapropterin from the 3 dosing regimens was assessed based on C(max ) , AUC(0-t ) , and AUC(0-infinity ) , estimated from calculated plasma tetrahydrobiopterin concentrations using a noncompartmental model . Safety assessment s included physical examinations , clinical laboratory tests , and ECGs at the beginning and end of the study . Vital signs were monitored periodically during each treatment period . RESULTS The study enrolled 32 healthy subjects ( 16 men , 16 women ) with a mean ( SD ) age of 29.2 ( 9.0 ) years , height of 172.7 ( 10.0 ) cm , weight of 73.0 ( 13.9 ) kg , and body mass index ranging from 18 to 30 kg/m(2 ) . Twenty-three were white , 5 African American , 2 Asian/Pacific Isl and er , 1 Hispanic , and 1 Native American . The estimated geometric mean ratio of AUC(0-t ) for intact compared with dissolved tablets under fasting conditions was 141.24 % ( 90 % CI , 122.05 - 163.43 ) , and the geometric mean ratio of AUC(0-t ) for intact tablets under fed compared with fasting conditions was 143.46 % ( 90 % CI , 124.22 - 165.69 ) . Nine subjects ( 28.1 % ) reported a total of 20 treatment-emergent adverse events ( AEs ) . The most frequently reported AEs were gastrointestinal disorders ( 6 subjects [ 18.8 % ] ) and central nervous system disorders ( 4 [ 12.5 % ] ) . Eight AEs considered possibly or probably related to sapropterin were reported by 4 subjects ( 12.5 % ) ; these were of mild severity and gastrointestinal in nature . No severe or serious AEs or discontinuations due to AEs occurred during the study . CONCLUSIONS Administration of sapropterin as intact tablets and with a high-calorie , high-fat meal was associated with increased drug exposure . Oral administration of sapropterin 10 mg/kg as intact tablets with or without food was generally well tolerated Forty-two infants ( 20 males , 22 females ) with classical phenylketonuria ( PKU ) entered a prospect i ve , double-blind , r and omized study to investigate the effects on biochemical and physiological outcomes of a phenylalanine-free infant formula containing a fat blend supplemented with the long-chain polyunsaturated fatty acids ( LC-PUFA ) , docosahexaenoic acid ( DHA , C22:6 n-3 ) , and arachidonic acid ( AA , C20:4 n-6 ) . Between entry and 20 weeks ( entry and 1y ) of age , median DHA levels in erythrocyte membrane phospholipids decreased by 15 % ( 22 % ) in the LC-PUFA supplemented group ( n=21 ) and by 61 % ( 64 % ) in the control group ( p<0.001 ; n=18 ) . A dietary supply of LC-PUFA in infants with PKU prevents the decline in DHA levels associated with a diet supplying minimal sources of LC-PUFA . DHA status in turn , independent of diet , may influence the maturation of the visual system in infants with PKU CONTEXT Untreated maternal phenylketonuria ( PKU ) increases risk for developmental problems in offspring . The extent to which this risk is reduced by maternal dietary therapy at various stages of pregnancy is not known . OBJECTIVE To determine whether dietary treatment during pregnancy of women with PKU affects developmental outcomes of offspring . DESIGN The Maternal PKU Collaborative Study , an ongoing , longitudinal prospect i ve study begun in 1984 . SETTING A total of 78 metabolic clinics and obstetrical offices in the United States , Canada , and Germany . PARTICIPANTS A total of 253 children of women with PKU ( n = 149 ) , with untreated mild hyperphenylalaninemia ( n = 33 ) , or without known metabolic problems ( comparison group ; n = 71 ) were followed up to age 4 years . INTERVENTION Women with PKU were offered a low-phenylalanine diet prior to or during pregnancy with the aim of maintaining metabolic control ( plasma phenylalanine < or = 10 mg/dL [ < or = 605 micromol/L ] ) . Women with mild hyperphenylalaninemia , who had plasma phenylalanine levels of no more than 10 mg/dL ( 605 micromol/L ) on a normal diet , were not treated . MAIN OUTCOME MEASURES Children 's scores on cognitive and behavioral assessment s ( McCarthy Scales of Children 's Abilities , Test of Language Development , Achenbach Child Behavior Checklist , Vinel and Adaptive Behavior Scales , and Home Observation for Measurement of the Environment ) , compared by maternal metabolic status at 0 to 10 weeks ' , 10 to 20 weeks ' , and after 20 weeks ' gestation . RESULTS Scores on the McCarthy General Cognitive Index decreased as weeks to metabolic control increased ( r = -0.58 ; P<.001 ) . Offspring of women who had metabolic control prior to pregnancy had a mean ( SD ) score of 99 ( 13 ) . Forty-seven percent of offspring whose mothers did not have metabolic control by 20 weeks ' gestation had a General Cognitive Index score 2 SDs below the norm . Overall , 30 % of children born to mothers with PKU had social and behavioral problems . CONCLUSIONS Our data suggest that delayed development in offspring of women with PKU is associated with lack of maternal metabolic control prior to or early in pregnancy . Treatment at any time during pregnancy may reduce the severity of delay BACKGROUND Early and strict dietary management of phenylketonuria is the only option to prevent mental retardation . We aim ed to test the efficacy of sapropterin , a synthetic form of tetrahydrobiopterin ( BH4 ) , for reduction of blood phenylalanine concentration . METHODS We enrolled 89 patients with phenylketonuria in a Phase III , multicentre , r and omised , double-blind , placebo-controlled trial . We r and omly assigned 42 patients to receive oral doses of sapropterin ( 10 mg/kg ) and 47 patients to receive placebo , once daily for 6 weeks . The primary endpoint was mean change from baseline in concentration of phenylalanine in blood after 6 weeks . Analysis was on an intention-to-treat basis . The study is registered with Clinical Trials.gov , number NCT00104247 . FINDINGS 88 of 89 enrolled patients received at least one dose of study drug , and 87 attended the week 6 visit . Mean age was 20 ( SD 9.7 ) years . At baseline , mean concentration of phenylalanine in blood was 843 ( 300 ) micromol/L in patients assigned to receive sapropterin , and 888 ( 323 ) micromol/L in controls . After 6 weeks of treatment , patients given sapropterin had a decrease in mean blood phenylalanine of 236 ( 257 ) micromol/L , compared with a 3 ( 240 ) micromol/L increase in the placebo group ( p<0.0001 ) . After 6 weeks , 18/41 ( 44 % ) patients ( 95 % CI 28 - 60 ) in the sapropterin group and 4/47 ( 9 % ) controls ( 95 % CI 2 - 20 ) had a reduction in blood phenylalanine concentration of 30 % or greater from baseline . Blood phenylalanine concentrations fell by about 200 micromol/L after 1 week in the sapropterin group and this reduction persisted for the remaining 5 weeks of the study ( p<0.0001 ) . 11/47 ( 23 % ) patients in the sapropterin group and 8/41 ( 20 % ) in the placebo group experienced adverse events that might have been drug-related ( p=0.80 ) . Upper respiratory tract infections were the most common disorder . INTERPRETATION In some patients with phenylketonuria who are responsive to BH4 , sapropterin treatment to reduce blood phenylalanine could be used as an adjunct to a restrictive low-phenylalanine diet , and might even replace the diet in some instances BACKGROUND As part of a study on the effects of a fat-supplemented phenylalanine (phe)-free protein substitute on the fatty acid status of children with phenylketonuria ( PKU ) , the adequacy of the diets of children aged 1 - 10 years for fat and essential fatty acids ( EFA ) was assessed . METHODS Subjects r and omized in a 1 : 1 ratio to a phe-free protein substitute supplemented with EFA ( test-treatment group ) or a phe-free , fat-free protein substitute ( control group ) for 20 weeks . 3-day semi-weighed records of food intakes collected at the end of the study period . RESULTS Total fat and alpha-linolenic acid ( alpha-LA ) intakes were found to be poor in the control group ( n = 19 ) . Those in the test-treatment group ( n = 24 ) had higher fat and EFA intakes ( P < 0.05 ) , bringing intakes closer to population norms . The youngest children ( < 5 years of age ) in the control group appeared to be especially vulnerable to poor fat intakes because of the restricted diversity of their diets and , regardless of age , alpha-LA intakes by this group were poor compared with the non-PKU population . CONCLUSIONS The quantity and quality of fat in the diets of children with PKU , in particular young children , should be given careful consideration in trying to optimize the ratio of linoleic acid : alpha-LA in their diets and in satisfying the requirements of this group for fat and alpha-LA Objective : The long-chain polyunsaturated fatty acids ( LC-PUFA ) status of children with PKU is often compromised . LC-PUFA , which are important fatty acids in the development of the CNS , can be synthesis ed endogenously from the parent essential fatty acids ( EFA ) provided dietary intakes are adequate . This study was design ed to assess the biochemical effect over a 20-week period of a phe-free protein substitute that has been supplemented with a balanced blend of n-3 and n-6 EFAs on LC-PUFA status of children with PKU . Design , setting and subjects : Fifty three community-living children aged 1–10 years diagnosed with PKU in the newborn period were recruited from seven tertiary centres in the UK and France and r and omised to a fat-free control formula or the EFA-supplemented test-treatment formula in an open , prospect i ve study . Forty four children completed the study ( 20 controls , 24 test-treatments ) . Fatty acid status was assessed at entry and 20-weeks follow-up . Three day dietary diaries were recorded at 20 weeks ' follow-up . The safety , efficacy and palatability of the test-treatment formula were also assessed . Results : The test-treatment group had significantly higher intakes of fat and EFA than the control group . There was a significant between group difference ( P=0.04 ) in increases in median docosahexaenoic acid ( DHA ) concentrations in erythrocyte phospholipids , which increased by 19 % in the test-treatment group and by 0.5 % in the control group over the study period . Growth and phe control were satisfactory in all subjects . Conclusions : Supplementing the diets of children with PKU with a balanced blend of n-6 and n-3 EFA improves DHA status without compromising AA status Diagnosis by newborn screening and the implementation of a phenylalanine-restricted diet have result ed in normal neurological development in approximately 10 000 persons with phenylketonuria ( PKU ) in the United States . While it is accepted that a phenylalanine-restricted diet is necessary in childhood , the recommended concentration of phenylalanine in the blood varies . Clinicians now must make recommendations for adults with PKU who probably tolerate higher levels of phenylalanine than children . This factor , quality of life issues , the expense of the diet , and varying genetic and socio-economic background s , make the choice of dietary recommendations difficult . Molecular analysis of the mutations in PKU has provided insight but has not result ed in clear recommendations for phenylalanine concentration in the blood . Magnetic resonance imaging has provided the recognition that white-matter changes are present in PKU . However , owing to poor correlation of white-matter changes with clinical factors , analysis of white-matter changes has not proved useful . We hypothesize that measurement of brain phenylalanine directly will aid in clinical decision making . Twenty-one subjects with PKU had blood and brain phenylalanine measured simultaneously . Fifteen were r and omly selected , 2 were examined for clinical reasons and 4 exceptional patients were chosen because they had maintained high IQs , despite having high historic blood concentrations and having been off the diet for at least 10 years . The correlation of blood and brain phenylalanine is in general poor . However , the four exceptional patients all had relatively low concentrations of phenylalanine in their brains compared to their blood . We suggest that their good clinical status , despite high historic blood levels , is due to their comparatively low brain levels of phenylalanine . We further suggest that measurement of brain phenylalanine concentration is useful in the management of PKU patients Summary This study aim ed to evaluate the response to and safety of an 8-day course of sapropterin dihydrochloride ( 6R-tetrahydrobiopterin or 6R-BH4 ) 10 mg/kg per day in patients with phenylketonuria ( PKU ) , who have elevated blood phenylalanine ( Phe ) levels , and to identify a suitable cohort of patients who would respond to sapropterin dihydrochloride treatment with a reduction in blood Phe level . Eligible patients were aged ≥ 8 years , had blood Phe levels ≥ 450 μmol/L and were not adhering to a Phe-restricted diet . Suitable patients were identified by a ≥30 % reduction in blood Phe level from baseline to day 8 following sapropterin dihydrochloride treatment . The proportion of patients who met these criteria was calculated for the overall population and by baseline Phe level ( < 600 , 600 to < 900 , 900 to < 1200 and ≥1200 μmol/L ) . In total , 485/490 patients completed the study and 20 % ( 96/485 ) were identified as patients who would respond to sapropterin dihydrochloride . A reduction in Phe level was observed in all subgroups , although response was greater in patients with lower baseline Phe levels . Wide variability in response was seen across all baseline Phe subgroups . The majority of adverse events were mild and all resolved without complications . Sapropterin dihydrochloride was well tolerated and reduced blood Phe levels across all PKU phenotypes tested . Variability in reduction of Phe indicates that the response to sapropterin dihydrochloride can not be predicted by baseline Phe level Blood-brain ratios ( BBR ) of phenylalanine ( Phe ) were determined by quantitative in vivo 1H magnetic resonance spectroscopy ( 1H-MRS ) in 17 adult patients with early-treated phenylketonuria who were r and omly selected from a sample of 75 adults . Measurements were performed in all patients during steady-state conditions . The BBR showed a unimodal distribution with a mean of 4.0 ( range 3.3 to 4.5 ) . Blood-brain ratios were comparable for subgroups of patients with genotypes classified as severe , moderate , or mild and for patients on different types of diets . Brain Phe concentrations showed a strong linear correlation with blood Phe values ( r = 0.93 , P < 0.001 ) . There were no saturation effects for blood Phe values up to 1.8 mmol/L , and a local regression analysis did not confirm increasing BBR for increasing blood Phe values . The intellectual outcome ( Wechsler Adult Intelligence Scale ) was correlated with long-term dietary control ( r = −0.65 , P < 0.05 ) , fluctuation of blood Phe values during treatment ( r = −0.60 , P < 0.05 ) , and concurrent blood and brain Phe concentration . The severity of white matter changes visible on magnetic resonance images ( MRI ) was increased with high blood and brain Phe concentrations but failed to reach statistical significance . No correlation was found between BBR values , intelligence quotient , and MRI grade . Based on the assumption that BBR show intraindividual stability , the current data do not support the hypothesis that blood-brain barrier transport of Phe is a key explanatory factor for outcome variability in the vast majority of “ typical ” patients with phenylketonuria Phenylketonuria ( PKU ) is an inherited metabolic disease characterized by phenylalanine ( Phe ) accumulation , which can lead to neurocognitive and neuromotor impairment . Sapropterin dihydrochloride , an FDA ‐approved synthetic formulation of tetrahydrobiopterin ( 6R‐BH4 , herein referred to as sapropterin ) is effective in reducing plasma Phe concentrations in patients with hyperphenylalaninemia due to tetrahydrobiopterin (BH4)‐responsive PKU , offering potential for improved metabolic control . Eighty patients , ≥8 years old , who had participated in a 6‐week , r and omized , placebo‐controlled study of sapropterin , were enrolled in this 22‐week , multicenter , open‐label extension study comprising a 6‐week forced dose‐titration phase ( 5 , 20 , and 10 mg/kg/day of study drug consecutively for 2 weeks each ) , a 4‐week dose‐ analysis phase ( 10 mg/kg/day ) , and a 12‐week fixed‐dose phase ( patients received doses of 5 , 10 , or 20 mg/kg/day based on their plasma Phe concentrations during the dose titration ) . Dose‐dependent reductions in plasma Phe concentrations were observed in the forced dose‐titration phase . Mean ( SD ) plasma Phe concentration decreased from 844.0 ( 398.0 ) µmol/L ( week 0 ) to 645.2 ( 393.4 ) µmol/L ( week 10 ) ; the mean was maintained at this level during the study 's final 12 weeks ( 652.2 [ 382.5 ] µmol/L at week 22 ) . Sixty‐eight ( 85 % ) patients had at least one adverse event ( AE ) . All AEs , except one , were mild or moderate in severity . Neither the severe AE nor any of the three serious AEs was considered related to sapropterin . No AE led to treatment discontinuation . Sapropterin is effective in reducing plasma Phe concentrations in a dose‐dependent manner and is well tolerated at doses of 5–20 mg/kg/day over 22 weeks in BH4‐responsive patients with PKU . © 2008 Wiley‐Liss , OBJECTIVE To evaluate the ability of sapropterin dihydrochloride ( pharmaceutical preparation of tetrahydrobiopterin ) to increase phenylalanine ( Phe ) tolerance while maintaining adequate blood Phe control in 4- to 12-year-old children with phenylketonuria ( PKU ) . STUDY DESIGN This international , double-blind , r and omized , placebo-controlled study screened for sapropterin response among 90 enrolled subjects in Part 1 . In Part 2 , 46 responsive subjects with PKU were r and omized ( 3:1 ) to sapropterin , 20 mg/kg/d , or placebo for 10 weeks while continuing on a Phe-restricted diet . After 3 weeks , a dietary Phe supplement was added every 2 weeks if Phe control was adequate . RESULTS The mean ( + /-SD ) Phe supplement tolerated by the sapropterin group had increased significantly from the pretreatment amount ( 0 mg/kg/d ) to 20.9 ( + /-15.4 ) mg/kg/d ( P < .001 ) at the last visit at which subjects had adequate blood Phe control ( < 360 micromol/L ) , up to week 10 . Over the 10-week period , the placebo group tolerated only an additional 2.9 ( + /-4.0 ) mg/kg/d Phe supplement ; the mean difference from the sapropterin group ( + /-SE ) was 17.7 + /- 4.5 mg/kg/d ( P < .001 ) . No severe or serious related adverse events were observed . CONCLUSIONS Sapropterin is effective in increasing Phe tolerance while maintaining blood Phe control and has an acceptable safety profile in this population of children with PKU Aim : To study bone mineralization in a group of phenylketonuric patients and to search for a possible relationship between bone mineral density , dietary control , serum minerals and nutrition intake . The response to treatment with low‐dose 1.25‐(OH)2 vitamin D in patients with osteopenia was evaluated . Methods : Twenty‐eight phenylketonuric patients ( age range : 10–33 y ) on dietary treatment were investigated . Bone density at the lumbar spine ( Dual Energy X‐ray Absorptiometry ) , bone formation markers ( osteocalcin and bone alkaline phosphatase ) , serum minerals , index of dietary control and protein , vitamin D and mineral intakes were determined . Results : Of the patients studied , 78.6 % had good dietary compliance ( 462 ± 89 μmol/L ) . Mean protein , vitamin D and mineral intakes met the recommended dietary allowances ( RDAs ) . Nevertheless , 8 patients had calcium intakes lower than 1000 g/d , and a positive correlation between Z‐score and calcium ( r= 0.585 ; p= 0.002 ) or phosphorus intake ( r= 0.546 ; p= 0.005 ) was observed . Osteopenia was detected in 14 patients ( 50 % ) . Moreover , bone alkaline phosphatase in phenylketonuric patients older than 18 y of age was significantly lower than that in controls ( p > 0.0001 ) . No correlation was found between bone mineral density , age , serum minerals , bone formation markers or index of dietary control . Treatment with 0.25 μg/d calcitriol significantly increased bone density in 6 patients Summary : Recent European studies have shown that growth retardation is common in people with phenylketonuria ( PKU ) during the first years of life while they receive a low-phenylalanine ( Phe ) diet . The aims of the present study were to assess the growth of our PKU patients and to search for nutritional and hormonal explanations for the growth delay . Twenty PKU patients aged 8 months to 7 years entered the study . The design was cross-sectional , a longitudinal study having already been performed in our centre . The following data were recorded : weight/height ( W/H ) , height/age ( H/A ) , and weight/age ( W/A ) Z-scores ; fat-free mass ( measured from bioelectrical impedometry ( FFM1 ) , and skinfold thickness ( FFMA ) . Thyroid hormones , insulin-like growth factor I ( IGF1 ) , insulin-like growth factor binding protein ( IGFBP3 ) , selenium , zinc , and Phe blood levels were measured . Dietary intake was also recorded over 4 days . PKU patients were moderately but significantly shorter ( H/A Z-score varied from −2.12 to 1.61 ; mean −0.49 ) and lighter ( W/A Z-score varied from −2.58 to 1.49 ; mean −0.71 ) than the French reference population . Body composition was not different from that of controls matched for age and sex . IGF1 , IGFBP3 , and thyroid hormone levels were within normal range . All children received more than two-thirds of the recommended daily allowances for energy ( 91%±18 % ) and for proteins ( 146%±26 % ) . The mean daily intake of our patients was sufficient in selenium , but markedly deficient in zinc ( 2.4±2.2 mg/day ) . No correlation was found between zinc daily intake or zinc plasma levels and growth retardation . Moreover , no relation was found between the plasma Phe concentrations , protein or caloric intake and the presence of growth retardation . Our results show that growth retardation in PKU patients is not related to hormonal or caloric deficiencies . Further studies are needed to investigate the effect of various nutrient supplementation regimens ( especially zinc ) on the growth of PKU patients The frequency and types of congenital heart disease in offspring from pregnancies in women with hyperphenylalaninemia were examined in the international prospect i ve Maternal Phenylketonuria Collaborative Study . Relationships of congenital heart disease in offspring to the basal blood phenylalanine level in the mother , metabolic control through diet during pregnancy , and phenylalanine hydroxylase mutations in mother and offspring were determined . The 416 offspring from 412 maternal phenylketonuria pregnancies that produced live births and 100 offspring from the 99 control pregnancies were included in this examination . Thirty-four of the 235 offspring ( 14 % ; 95 % CI , 10.2 to 19.6 % ) from pregnancies in phenylketonuric women with a basal phenylalanine level ≥ 900 μM ( 15 mg/dL ) [ normal blood phenylalanine < 120 μM ( 2 mg/dL ) ] and not in metabolic control [ phenylalanine level ≤ 600 μM ( 10 mg/dL ) ] by the eighth gestational week had congenital heart disease compared with one control offspring ( 1 % ) with congenital heart disease . One offspring among the 50 ( 2 % ) from mothers with non-phenylketonuria mild hyperphenylalaninemia also had congenital heart disease . Coa rct ation of the aorta and hypoplastic left heart syndrome were overrepresented compared with expected percentages among those with congenital heart disease in the general population . A basal maternal phenylalanine level > 1800 μM ( 30 mg/dL ) significantly increased the risk for bearing a child with congenital heart disease ( p = 0.003 ) . Phenylalanine hydroxylase mutations in the mothers and offspring did not have an independent relationship to congenital heart disease but were related through the basal maternal phenylalanine levels . The data in this study indicate that a basal maternal phenylalanine level of 900 μM may be a threshold for congenital heart disease , that women with the most severe degree of phenylketonuria are at highest risk for bearing such a child , and that prevention of the congenital heart disease requires initiation of the low phenylalanine diet before conception or early in pregnancy with metabolic control no later than the eighth gestational week Background Classic phenylketonuria ( PKU ) is due to an inborn error of metabolism result ing in an inability to metabolize the amino acid phenylalanine . To avoid mental retardation , affected individuals observe a phenylalanine-restricted diet . When dietary control is poor , deficits in prefrontally mediated cognitive functions have been observed . It has been suggested that these deficits are due to disruptions in the mesocortical dopamine system that projects to the prefrontal cortex . Methods In this study , dopamine system reactivity was examined in individuals with PKU , relative to age-matched controls , using the non-specific DA antagonist haloperidol , in a repeated measures placebo-controlled design . Outcome variables included neuroendocrine , physiological , and cognitive measures . Results Regardless of drug condition , PKU participants differed from control participants in their blood phenylalanine and tyrosine levels , and in their times to complete measures of attention and working memory . Also , relative to placebo , haloperidol influenced several variables irrespective of group status , including serum prolactin secretion , times to complete attention and working memory tasks , and accuracy of working memory performance . An interaction between group and drug condition was observed for the digit span task , where PKU participants exhibited greater relative impairments on haloperidol . When composite indices of impairment were derived , PKU participants demonstrated selective disruption in executive function on haloperidol relative to control subjects . Conclusions Findings are consistent with the presence of frontostriatal dysfunction in PKU but are less consistent with the notion that PFC dopamine function is specifically affected The metabolic disorder phenylketonuria ( PKU ) is treated early by a low-phenylalanine diet . While this prevents global cognitive impairment , some patients still experience cognitive and neurophysiological abnormalities . Neuropsychological testing of early treated , currently off-diet , PKU patients attending an adult PKU clinic showed a reduction in the Perceptual Organization Index ( POI ) , Processing Speed Index ( PSI ) from the Wechsler Adult Intelligence Scale Third Edition ( WAIS-III ) , and Part A of the Trail Making Test for the PKU group relative to controls . Taken together , these results supported a profile of reduced information-processing speed Lifelong treatment of phenylketonuria ( PKU ) includes a phenylalanine ( phe ) restricted diet that provides sufficient phe for growth and maintenance plus phe-free amino acid formula to meet requirements for protein , energy and micronutrients . Phe tolerance ( mg phe/kg body weight/day ) is the amount of phe those with PKU can consume and maintain acceptable blood phe levels ; it requires individual assessment because of varying phenylalanine hydroxylase activity . The objective was to reassess phe tolerance in eight adults with PKU considering phe requirements , blood phe levels , genotype and phe tolerance at 5 years of age . Subjects had not received a personalized assessment of phe tolerance in several years , and five subjects were overweight , body mass index ( BMI ) 25 - 28 . With the guidance of a metabolic dietitian , seven subjects increased phe tolerance ( by 15 - 173 % ) without significantly increasing blood phe concentration . Increased phe tolerance was associated with both improved dietary compliance and inadequate phe intake at the onset of the protocol compared with current requirements . Improved dietary compliance reflected increased consumption of protein equivalents from amino acid formula and increased frequency of formula intake , from 2.2 to 3 times per day . Predictors of higher final phe tolerance following re assessment included being male and having a lower BMI ( R(2)=0.588 ) . This suggests that the rising trend of overweight and obesity may affect assessment of phe tolerance in adults . Therefore , interaction with the metabolic dietitian to reassess phe tolerance in relation to body mass is essential throughout adulthood to insure adequate intake of phe to support protein synthesis and prevent catabolism |
10,472 | 23,188,834 | In conclusion , insufficient evidence exists to recommend NAC for the prevention of CIN in patients undergoing peripheral angiography | Contrast-induced nephropathy ( CIN ) is a leading cause of hospital-acquired acute kidney injury ( AKI ) .
N-acetylcysteine ( NAC ) was proposed as an effective preventative measure .
As data in relation to the use of NAC for the prevention of CIN in peripheral angiography are lacking , a systematic review and meta- analysis were undertaken . | OBJECTIVES Prophylactic acetylcysteine along with hydration seems to be better than hydration alone in preventing the reduction in renal function induced by a contrast dye . BACKGROUND Contrast media can lead to acute renal failure that may occasionally require hemodialysis . METHODS One hundred eighty-three consecutive patients with impairment of renal function , undergoing coronary and /or peripheral angiography and /or angioplasty , were r and omly assigned to receive 0.45 % saline intravenously and acetylcysteine ( 600 mg orally twice daily ; group A , n = 92 ) or 0.45 % saline intravenously alone ( group B , n = 91 ) before and after nonionic , low-osmolality contrast dye administration . RESULTS The baseline serum creatinine concentrations were similar ( 1.5 + /- 0.4 mg/dl in group A vs. 1.5 + /- 0.4 mg/dl in group B ; p = 0.37 ) . An increase of > or = 25 % in the baseline creatinine level 48 h after the procedure occurred in 6 ( 6.5 % ) of 92 patients in group A and in 10 ( 11 % ) of 91 patients in group B ( p = 0.22 ) . In the subgroup with a low ( < 140 ml ) contrast dose , renal function deterioration occurred in 5 ( 8.5 % ) of 60 patients in group B and in 0 of 60 patients in group A ( p = 0.02 ; odds ratio [ OR ] 0.44 , 95 % confidence interval [ CI ] 0.35 to 0.54 ) . In the subgroup with a high contrast dose , no difference was found ( 5/31 vs. 6/32 patients , p = 0.78 ) . By multivariate analysis , the amount of contrast agent , but not the treatment strategy , was a predictor of the occurrence of contrast dye-associated nephrotoxicity ( OR 2.58 , 95 % CI 1.1 to 4.9 ; p = 0.035 ) . CONCLUSIONS In patients with reduced renal function undergoing angiography and /or angioplasty , the amount of contrast agent , but not the administration of prophylactic acetylcysteine , was a predictor of renal function deterioration . Prophylactic acetylcysteine might provide better protection than hydration alone , only when a small volume of contrast agent is used The nephroprotective role of N-acetylcysteine ( NAC ) against contrast-induced nephropathy ( CIN ) in patients undergoing peripheral arterial angiography remains unclear . A total of 40 patients undergoing peripheral arterial angiography were r and omized to receive intravenous ( iv ) hydration only ( group 1 ) or oral NAC in addition to iv hydration ( group 2 ; IS RCT N : 35882618 ) . Primary outcome was reduction in the elevation of urinary retinol binding protein ( RBP ) , albumin — creatinine ratio ( ACR ) , and serum creatinine ( serC ) . Groups 1 and 2 had equivocal percentage reduction in RBP and ACR levels from baseline ( P = .80 and .30 ) . A significant reduction in serC was , however , observed with NAC by third postprocedure day ( P = .04 ) . One patient in the treatment arm developed CIN compared with 3 patients in the control group ( P = .33 ) . Equivocal changes in RBP and ACR levels by both treatments seem to indicate that either is equally effective in affording renal protection Purpose To determine the role of prophylactic N-acetylcysteine in the prevention of contrast-induced nephrotoxicity . Methods One hundred and sixteen patients undergoing noncoronary angiography , with or without pre-existing renal impairment , were r and omly assigned to receive prophylactic oral N-acetylcysteine or no treatment . Serum creatinine ( sCr ) was measured prior to angiography and 48 hr after the procedure . Urine sample s were collected before and after the examination for measurement of malondialdehyde ( MDA ) concentration . Contrast-induced nephrotoxicity ( CIN ) was defined as a rise in serum creatinine of 0.5 mg/dl ( 44 mmol/l ) at 48 hr . Results Complete data were available on 106 patients , 53 of whom had received N-acetylcysteine . There were no significant differences between the two groups in baseline characteristics , type of angiogram , or volume and concentration of contrast used . Three patients ( 2.8 % ) , all of whom had received N-acetylcysteine , developed CIN . In the N-acetylcysteine group , the mean serum creatinine in patients with renal impairment was 151.0 ± 44.2 μmol/l prior to the procedure and 155.6 ± 48.6 μmol/l ( p = 0.49 ) after the procedure . Respective values for those without renal impairment were 79.6 ± 15.1 μmol/l and 81.2 ± 20.0 μmol/l ( p = 0.65 ) . In the group that had not received N-acetylcysteine , the mean serum creatinine levels before and after the procedure were 150.0 ± 58.1 and 141.4 ± 48.0 μmol/l ( p = 0.17 ) in patients with renal impairment and 79.7 ± 14.2 and 81.4 ± 15.4 μmol/l ( p = 0.34 ) in those without renal impairment . In both groups , no significant change in urinary MDA concentration was observed . Conclusion There is no benefit to the prophylactic administration of N-acetylcysteine in patients undergoing peripheral angiography using current contrast media BACKGROUND Radiographic contrast agents can cause a reduction in renal function that may be due to reactive oxygen species . Whether the reduction can be prevented by the administration of antioxidants is unknown . METHODS We prospect ively studied 83 patients with chronic renal insufficiency ( mean [ + /-SD ] serum creatinine concentration , 2.4+/-1.3 mg per deciliter [ 216+/-116 micromol per liter ] ) who were undergoing computed tomography with a nonionic , low-osmolality contrast agent . Patients were r and omly assigned either to receive the antioxidant acetylcysteine ( 600 mg orally twice daily ) and 0.45 percent saline intravenously , before and after administration of the contrast agent , or to receive placebo and saline . RESULTS Ten of the 83 patients ( 12 percent ) had an increase of at least 0.5 mg per deciliter ( 44 micromol per liter ) in the serum creatinine concentration 48 hours after administration of the contrast agent : 1 of the 41 patients in the acetylcysteine group ( 2 percent ) and 9 of the 42 patients in the control group ( 21 percent ; P=0.01 ; relative risk , 0.1 ; 95 percent confidence interval , 0.02 to 0.9 ) . In the acetylcysteine group , the mean serum creatinine concentration decreased significantly ( P<0.001 ) , from 2.5+/-1.3 to 2.1+/-1.3 mg per deciliter ( 220+/-118 to 186+/-112 micromol per liter ) 48 hours after the administration of the contrast medium , whereas in the control group , the mean serum creatinine concentration increased nonsignificantly ( P=0.18 ) , from 2.4+/-1.3 to 2.6+/-1.5 mg per deciliter ( 212+/-114 to 226+/-133 micromol per liter ) ( P<0.001 for the comparison between groups ) . CONCLUSIONS Prophylactic oral administration of the antioxidant acetylcysteine , along with hydration , prevents the reduction in renal function induced by contrast agents in patients with chronic renal insufficiency Despite myriad improvements in the care of hospitalized patients , a decline in renal function remains a common event . Renal function in 4,622 consecutive patients admitted to the medical and surgical services of an urban tertiary care hospital was followed up prospect ively from the time of admission . Some degree of renal insufficiency developed in 7.2 % of patients . Decreased renal perfusion , medications , surgery , and radiographic contrast media were the most common causes of hospital-acquired renal insufficiency ( HARI ) . The overall mortality rate was 19.4 % and was similar among patients for all causes of renal insufficiency , except sepsis . For patients with a greater than 3.0-mg/dL increase in serum creatinine level , the mortality rate was 37.8 % . As shown by previous investigators , age and preexisting renal insufficiency were risk factors for HARI . Women and blacks had less hospital-acquired renal failure . The increasing acuity of hospital admissions has been accompanied by a greater incidence of acute renal insufficiency in patients admitted to hospitals . There is a trend toward better survival in patients with a severe deterioration in renal function AIMS Prophylactic administration of N-acetylcysteine ( NAC ) ( 600 mg orally twice daily ) , along with hydration , prevents contrast agent-associated nephrotoxicity ( CAN ) induced by a low dose of non-ionic , low-osmolality contrast dye . We tested whether a double dose of NAC is more effective to prevent CAN . METHODS AND RESULTS Two-hundred-twenty-four consecutive patients with chronic renal insufficiency ( creatinine level > or = 1.5mg/dl and /or creatinine clearance < 60ml/min ) , referred to our institution for coronary and /or peripheral procedures , were r and omly assigned to receive 0.45 % saline intravenously and NAC at the st and ard dose ( 600 mg orally twice daily ; SD Group ; n=110 ) or at a double dose ( 1200 mg orally twice daily ; DD Group ; n=114 ) before and after a non-ionic , low-osmolality contrast dye administration . Increase of at least 0.5mg/dl of the creatinine concentration 48h after the procedure occurred in 12/109 patients ( 11 % ) in the SD Group and 4/114 patients ( 3.5 % ) in the DD Group ( P=0.038 ; OR=0.29 ; 95 % CI=0.09 - 0.94 ) . In the subgroup with low ( < 140ml , or contrast ratio < = 1 ) contrast dose , no significant difference in renal function deterioration occurred between the 2 groups . In the subgroup with high ( > or = 140ml , or contrast ratio > 1 ) contrast dose , the event was significantly more frequent in the SD Group . Conclusions Double dose of NAC seems to be more effective than the st and ard dose in preventing CAN , especially with high volumes of non-ionic , low-osmolality contrast agent OBJECTIVE ( S ) Apart from proper hydration , only oral N-acetylcysteine ( NAC ) has shown efficacy in reducing radiographic contrast media (RCM)-induced acute renal failure , though its benefit has been challenged . We investigated the effect of intravenous ( i.v . ) NAC on renal function in patients with vascular disease receiving RCM for angiography . METHODS Single-center , r and omized , double-blind , placebo-controlled trial . Based on a previous study , a trial with 44 patients each in placebo and treatment arms would give at least 80 % power to show a statistically significant difference at the 5 % level . Vascular patients undergoing angiography were consented and segregated into those whose serum creatinine ( SC ) level was normal or raised ( men > 1.32 mg/dl ; women > 1.07 mg/dL ) . All patients received 500 mL i.v . normal saline 6 to 12 hours prior to and then after angiography . Groups with normal SC and raised SC were r and omly assigned to either 1 g of NAC with normal saline before and after angiography or nothing ( placebo ) . Main outcome measures were change in SC and creatinine clearance ( CrCl ) as measured 1 , 2 , and 7 days postangiography ( with comparison between active and placebo groups using unpaired t test ) and incidence of acute renal decline ( > 25 % or 0.5 mg/dL rise in SC ) at 48 hours ( with comparison between active and placebo using the Fisher exact test ) . RESULTS Forty-six patients received NAC ( 29 normal SC , 17 raised SC ) , and 48 received placebo ( 27 normal SC , 21 raised SC ) . There was no significant difference in postangiography SC or CrCl at any of the time points measured between NAC and placebo in patients with either normal or raised SC . In the raised SC group , 3 patients from both the NAC and placebo groups suffered acute renal declines . Importantly , at 48 hours , the impaired SC group had a significant reduction in CrCl ( -14 % + /- 41 % vs + 18 % + /- 58 % : P = .0142 ) and a significant rise in SC ( + 7.0 + /- 25 % vs -1.6 % + /- 10 % ; P = .0246 ) when compared with the normal SC group . CONCLUSIONS NAC ( i.v . at 1 g ) precontrast and postcontrast does not confer any benefit in preventing RCM-induced nephropathy in vascular patients . Patients with pre-existing raised SC have an increased risk of renal impairment as defined by a fall in CrCl and a rise in SC post-RCM when compared with patients with normal SC who appear to benefit from hydration Context Contrast-induced nephropathy ( CIN ) can complicate percutaneous coronary intervention ( PCI ) . A better underst and ing of the relationship among contrast volume , patient characteristics , and CIN could help to reduce this complication . Contribution Of 561 patients who underwent primary PCI in the setting of ST-segment elevation myocardial infa rct ion , 20 % developed CIN , and those with CIN were more likely than those without CIN to die in hospital . Higher contrast volume and contrast ratio ( volume administered/volume calculated ) were associated with CIN and in-hospital death . Caution It is unclear whether the worse outcomes were due to the contrast or whether unmeasured aspects of disease severity led to both the need for more contrast and the worse outcomes . The Editors Primary percutaneous coronary intervention ( PCI ) , defined as intervention in the culprit vessel within 12 hours after the onset of chest pain without previous thrombolytic or other clot-dissolving therapy , is the best available strategy for treatment of ST-segment elevation acute myocardial infa rct ion ( STEMI ) ( 1 ) . Patients having primary PCI , however , are at higher risk for contrast-induced nephropathy ( CIN ) , although most of them do not have preprocedural renal dysfunction ( 2 ) . Contrast-induced nephropathy is associated with a marked increase in in-hospital morbidity and mortality rates , which may partially thwart the survival benefit of primary PCI in patients who develop this serious renal complication ( 2 , 3 ) . Effective CIN prevention may further improve the clinical outcome of patients with STEMI who receive primary PCI . Potential preventive strategies include protecting the kidney from contrast- or ischemic-induced injury and limiting the amount of contrast administered . Studies of the antioxidant agent N-acetylcysteine ( 4 ) have yielded promising results for kidney protection . N-acetylcysteine has been shown to be effective in reducing CIN incidence and in improving clinical outcomes after emergency or primary PCI , particularly when administered as a high-dose intravenous bolus or with sodium bicarbonate ( 4 , 5 ) . Conversely , because few previous studies have reported the amount of contrast used , data on the effect of contrast volume limitation during primary PCI are lacking . Moreover , investigators disagree on the relation between the volume of contrast administered during interventional procedures and the risk for CIN . Some studies have reported no relationship , whereas others have suggested an independent correlation ( 614 ) . ST-segment elevation myocardial infa rct ion further complicates the issue . Patients with STEMI who are not undergoing primary PCI may also have acute worsening of renal function with the same prognostic implication s as for CIN ( 15 ) , which suggests that acute kidney injury may result from hemodynamic compromise rather than from CIN per se . In addition , primary PCI success , a major determinant of clinical outcome in patients with STEMI ( 1618 ) , may require larger amounts of contrast . Thus , an optimal procedural result should be carefully weighed against risk for CIN . The association of contrast volume , as an absolute and a weight- and creatinine-adjusted value ( 19 ) ; CIN incidence ; and clinical outcome in the setting of primary PCI remains unknown . As a result , evidence -based recommendations to guide best procedural strategies during primary PCI are still lacking . We sought to prospect ively assess the possible association between contrast volume and CIN incidence and in-hospital clinical outcome in patients with STEMI who undergo primary PCI . Methods Study Population We conducted our prospect i ve observational study at the Centro Cardiologico Monzino , University of Milan , between 1 January 2002 and 30 September 2007 . We enrolled all consecutive patients with STEMI who were undergoing primary PCI . According to our institute protocol , we included patients who presented within 12 hours ( 18 hours for STEMI complicated by cardiogenic shock ) of the onset of symptoms ( characteristic pain lasting for at least 30 minutes , not responsive to nitrates , with electrocardiographic ST-segment elevation of at least 0.2 mV in 2 or more contiguous leads , or left bundle-branch block ) . We excluded patients receiving long-term peritoneal or hemodialysis treatment . We also excluded patients if they had cardiac surgery for emergency coronary revascularization or STEMI-related mechanical complications , died during PCI , or had been treated with an intravenous bolus of N-acetylcysteine before PCI . The Ethics Committee of the Centro Cardiologico Monzino approved the study , and all patients gave written , informed consent . PCI Procedure A 24-hour on-call interventional team performed primary PCI according to st and ard clinical practice by using st and ard guide catheters ( 6 French ) , guide wires , and balloon catheters via the femoral approach . Patients received a 5000-U bolus of heparin , followed by additional boluses during the procedure to maintain an activated clotting time longer than 300 seconds ( between 200 and 250 seconds when abciximab was used ) . Coronary stenting was performed with st and ard technique . Contrast dose was left to the discretion of the interventional cardiologist . All patients received nonionic , low-osmolar contrast agents ( iomeprol or iohexol ) . After contrast exposure , patients received isotonic ( 0.9 % ) saline intravenously at a rate of 1 mL/kg per hour for 12 hours . In patients with a left ventricular ejection fraction ( LVEF ) lower than 40 % or overt heart failure , the hydration rate was reduced to 0.5 mL/kg per hour . Poststenting antithrombotic treatment consisted of aspirin and either clopidogrel or ticlopidine at st and ard dosages . Data Collection We measured serum creatinine concentration in all patients at hospital admission ( before primary PCI ) , every day for the following 3 days , at discharge from the coronary care unit , and at hospital discharge . We estimated creatinine clearance by applying the CockcroftGault formula to the serum creatinine concentration ( 20 ) . We defined preprocedural renal insufficiency as a creatinine clearance less than 1 mL/s ( 60 mL/min ) ( 21 ) . We calculated the maximum contrast dose ( MCD ) for each patient by using the formula proposed by Cigarroa and colleagues ( 19 ) : MCD ( mL ) = ( 5body weight [ kg ] ) divided by serum creatinine ( mg/dL ) . From this contrast limit , we determined the contrast ratio by dividing the administered contrast amount by the calculated MCD . We left the use of -adrenergic blocking agents , angiotensin-converting enzyme inhibitors , platelet glycoprotein IIb/IIIa receptor inhibitors ( abciximab ) , diuretics , intra-aortic balloon pump , or inotropic drug support to the discretion of the interventional and coronary care unit cardiologists , on the basis of the current st and ards of care recommended by published guidelines ( 22 ) . During hospitalization , medications were changed as needed at the discretion of the cardiologist responsible for the patient . The primary end point of the study was the occurrence of CIN , defined as a greater than 25 % increase in creatinine concentration from the baseline value in the 72 hours after primary PCI ( 23 ) . In-hospital mortality rate and other major adverse clinical events were also evaluated as secondary end points . Statistical Analysis On the basis of our previous study ( 2 ) , we calculated a sample size of 550 patients , assuming a 30 % incidence of patients exceeding the MCD and a 10 % incidence of CIN in patients with a contrast ratio less than 1 . This sample size allowed 84 % statistical power to assess a significantly higher ( error of 0.05 ) CIN incidence of 20 % ( odds ratio , 2 ) in the group with a contrast ratio greater than 1 . We present continuous variables as means ( SDs ) ; we compared them by using the t test for independent sample s or one-way analysis of variance , as appropriate . We compared categorical data by using the chi-square test or the Fisher exact test , as appropriate . The P values reported in Table 1 were not adjusted for multiple comparisons . Table 1 . Patient and Procedure Characteristics We explored the relationship between contrast ratio and maximum percentage increase in creatinine concentration after primary PCI by using linear regression analysis . Both variables were log-transformed before analysis . We estimated predicted probabilities of CIN and mortality from the logistic models with the covariates set to the population average values . We assessed the association among contrast volume , contrast ratio , and clinical outcomes ( CIN and in-hospital mortality ) through logistic regression analysis . First , we included only contrast volume or contrast ratio ( model 1 ) . To adjust for potential confounders selected among recognized clinical predictors of the 2 outcomes ( age , body weight , infa rct location , LVEF , time to reperfusion , and baseline creatinine level ) , we developed 2 multivariable logistic regression models : model 2 , which adjusted for the 2 major predictors ( LVEF and creatinine level ) , and model 3 , which adjusted for the 6 considered variables . Because contrast ratio is a calculated variable that includes both body weight and creatinine , we did not include those 2 variables in the models when we tested the association with contrast ratio . Thus , model 2 included LVEF and time to reperfusion , whereas model 3 included age , infa rct ion location , LVEF , and time to reperfusion . Because of the relatively small number of events , we only considered mortality models with 2 or fewer covariates . To assess whether the effect of contrast volume on CIN differed in patients with renal insufficiency , we stratified our sample according to creatinine clearance ( 1 or < 1 mL/s [ 60 or < 60 mL/min ] ) and tested the appropriate interaction terms by using logistic regression , adjusting with model 2 . All tests were 2-sided . We performed all calculations by using SAS , version 9.13 ( SAS Institute , Cary , North Carolina ) . Role of the Funding Source The Centro Cardiologico BACKGROUND Patients with diabetes mellitus ( DM ) are at increased risk of contrast-associated nephropathy irrespective of their baseline creatinine ( Cr ) . We tested the efficacy of N-acetylcysteine ( NAC ) relative to hydration in unselected patients ( irrespective of baseline Cr ) with DM . METHODS We conducted a r and omized open-label study comparing hydration alone ( combined oral and rapid intravenous hydration , n = 69 ) to NAC plus hydration ( similar hydration protocol plus NAC 600 mg BID x 4 doses , n = 68 ) in diabetic patients ( mean age 65 + /- 10 years , 65 % men ) undergoing elective coronary angiography . The primary end point was the mean change in serum Cr measured up to 96 hours postangiography . RESULTS Baseline Cr was 1.14 + /- 0.43 mg/dL ( Cr > or = 1.3 mg/dL in 37 subjects ) . Baseline characteristics including blood urea nitrogen , Cr , and contrast volume were similar between the 2 groups . The mean Cr change in the NAC group was 0.14 + /- 0.47 versus 0.08 + /- 0.11 mg/dL in the hydration only group ( P = NS ) . Contrast-associated nephropathy , defined as a > or = 0.5 mg/dL increase in Cr , was significantly more common in the NAC group , 9.2 % versus 1.4 % , P = .043 . Similar results were found in the subgroup of participants with either an increased baseline serum Cr ( > or = 1.3 mg/dL ) or in those receiving high contrast volumes ( > 100 mL ) . CONCLUSIONS N-Acetylcysteine provides no benefit over an aggressive hydration protocol in patients with DM undergoing coronary angiography INTRODUCTION Intravenous administration of saline and non-ionic isosmolar contrast media significantly reduces the incidence of contrast-induced nephropathy , one of the most common causes of acute renal failure . Results with oral N-acetylcysteine are conflicting . The aim of our study was to evaluate the prophylactic role of N-acetylcysteine in patients with stable chronic renal failure undergoing coronary and /or peripheral angiography and /or angioplasty . METHODS We r and omized 200 elective , consecutive patients ( mean age 74.9 + /- 7.3 years ; 65 % male , 25 % diabetics ) with basal creatinine clearance < or=55 ml/min to receive oral N-acetylcysteine ( 600 mg bid the day before and the day of the procedure plus saline i.v . 0.9 % 1 ml/kg/h 12 - 24 h before and 24 h after the procedure , n = 99 ) or placebo and saline at the same time intervals , n = 101 . The contrast medium was non-ionic isosmolar ( Iodixanol , Visipaque Amersham Health ) . Contrast-induced nephropathy was defined as an increase in serum creatinine > 0.5 mg/dl or > 25 % within 3 days after the procedure . Serum creatinine was measured at baseline , 24 , 48 and 72 h after the procedure . RESULTS Contrast-induced nephropathy was 8/99 ( 8.1 % ) in the N-acetylcysteine group versus 6/101 ( 5.9 % ) in the placebo group , P = 0.6 . No difference was noted in high-risk subgroups such as diabetics ( 4/25 versus 2/25 P = 0.4 ) and those with serum creatinine clearance < 42.3 ml/min ( 5/54 versus 4/48 ; P = 0.9 ) . CONCLUSION In our experience , N-acetylcysteine did not prevent contrast-induced nephropathy in patients receiving isosmolar ( iodixanol ) contrast media and adequate hydration BACKGROUND Contrast nephropathy ( CN ) is a common cause of renal dysfunction after cardiac angiography . Recently , N-acetylcysteine ( NAC ) has been found to reduce the risk of CN after CT imaging with contrast enhancement . The purpose of the current study was to evaluate the efficacy of NAC for the prevention of CN in the setting of cardiac angiography . METHODS Eligible patients were those undergoing cardiac angiography with serum creatinine>1.7 mg/dL. Patients were r and omized to one of two groups : Group 1 , IV hydration and NAC , 1200 mg one hour before angiography , and a second dose 3 hours after ; Group 2 , IV hydration and placebo . CN was defined as an increase of 0.5 mg/dL in serum creatinine . RESULTS Seventy-nine patients completed the study . There were no significant differences between the groups in baseline characteristics , duration of angiography , mean volume of dye infused or mean IV hydration . Contrast nephropathy developed in 24.0 % of subjects , 26.3 % NAC , and 22.0 % placebo ( P = NS ) . Among subjects with diabetes mellitus , there was no significant difference in the rate of CN between the groups ( 42.1 % NAC , 27.8 % placebo ; P = 0.09 ) . The independent predictors of CN risk were diabetes mellitus and preexisting chronic renal insufficiency . CONCLUSIONS NAC was not effective for the prevention of CN after cardiac angiography OBJECTIVES We sought to evaluate the efficacy of the antioxidant acetylcysteine in limiting the nephrotoxicity after coronary procedures . BACKGROUND The increasingly frequent use of contrast-enhanced imaging for diagnosis or intervention in patients with coronary artery disease has generated concern about the avoidance of contrast-induced nephrotoxicity ( CIN ) . Reactive oxygen species have been shown to cause CIN . METHODS We prospect ively studied 121 patients with chronic renal insufficiency ( mean [ + /-SD ] serum creatinine concentration 2.8 + /- 0.8 mg/dl ) who underwent a coronary procedure . Patients were r and omly assigned to receive either acetylcysteine ( 400 mg orally twice daily ) and 0.45 % saline intravenously , before and after injection of the contrast agent , or placebo and 0.45 % saline . Serum creatinine and blood urea nitrogen were measured before , 48 h and 7 days after the coronary procedure . RESULTS Seventeen ( 14 % ) of the 121 patients had an increase in their serum creatinine concentration of at least 0.5 mg/dl at 48 h after administration of the contrast agent : 2 ( 3.3 % ) of the 60 patients in the acetylcysteine group and 15 ( 24.6 % ) of the 61 patients in the control group ( p < 0.001 ) . In the acetylcysteine group , the mean serum creatinine concentration decreased significantly from 2.8 + /- 0.8 to 2.5 + /- 1.0 mg/dl ( p < 0.01 ) at 48 h after injection of the contrast medium , whereas in the control group , the mean serum creatinine concentration increased significantly from 2.8 + /- 0.8 to 3.1 + /- 1.0 mg/dl ( p < 0.01 ) . CONCLUSIONS Prophylactic oral administration of the antioxidant acetylcysteine , along with hydration , reduces the acute renal damage induced by a contrast agent in patients with chronic renal insufficiency undergoing a coronary procedure NAC reduces the risk of postcardiac catheterization nephropathy in patients with chronic renal insufficiency and decreased ejection fraction . Thus , it should be considered as routine prophylaxis in patients with chronic renal insufficiency undergoing cardiac catheterization BACKGROUND Contrast media cause oxidative stress , which has been suggested as one possible mechanism responsible for contrast-induced nephropathy . Statins appear to have pleiotropic effects , including antioxidant properties . We investigated to determine whether simvastatin pretreatment reduces the risk of contrast-induced nephropathy in a high-risk population of patients with renal insufficiency undergoing coronary angiography . METHODS We conducted a prospect i ve , r and omized , double-blind , placebo-controlled , 2-center trial , involving 247 consecutive patients with chronic renal insufficiency ( calculated creatinine clearance < or = 60 mL/min and /or serum creatinine > or = 1.1 mg/dL ) undergoing coronary angiography . Patients were r and omized to simvastatin ( n = 124 ; 160 mg total , 40 mg orally every 12 hours starting the evening before and ending the morning after the procedure ) or placebo ( n = 123 ) . All patients received pre - and postprocedure hydration . The iso-osmolar contrast agent iodixanol was used for coronary angiography in all patients . RESULTS There was no difference between simvastatin and placebo in mean peak increase in serum creatinine measured within 48 hours after coronary angiography , the primary study end point ( 0.002 + /- 0.164 vs 0.017 + /- 0.230 mg/mL respectively , P = .559 ) . The incidence of contrast-induced nephropathy , a secondary end point defined as increase of either > or = 25 % or > or = 0.5 mg/dL in serum creatinine , was 2.5 % in simvastatin-treated patients ( 3/118 ) and 3.4 % in placebo-treated patients ( 4/118 ) , a nonsignificant difference ( P = 1.00 ) . There were also no differences between the 2 groups in length of hospital stay or 1- and 6-month clinical outcomes . CONCLUSIONS Simvastatin pretreatment for short-term at high dose do not prevent renal function deterioration after administration of contrast medium in patients with baseline renal insufficiency undergoing coronary angiography Presently , only hydration and N-acetylcysteine have been shown to be effective in decreasing the incidence of radiographic contrast-induced nephropathy . We investigated the role of N-acetylcysteine and various hydration protocol s in vascular surgery patients undergoing angiography . A single-center , r and omized , placebo-controlled trial was conducted in patients with stable , preexisting renal dysfunction undergoing elective , outpatient angiography . Patients were r and omized to outpatient oral hydration and N-acetylcysteine , inpatient hydration plus N-acetylcysteine , or our st and ard therapy of inpatient intravenous hydration alone . Two of twenty-eight ( 7 % ) patients who received outpatient oral hydration and N-acetylcysteine developed contrast-induced nephropathy , while two of 25 ( 8 % ) who recieved inpatient hydration plus N-acetylcysteine developed contrast-induced nephropathy and two of 25 ( 8 % ) who received st and ard therapy of inpatient intravenous hydration alone developed contrast-induced nephropathy . There was no statistical difference in incidence of contrast-induced nephropathy between the groups . No statistically significant independent risk factors were identified among the patients who developed contrast-induced nephropathy . N-Acetylcysteine did not confer additional benefit to patients treated with inpatient intravenous hydration . Outpatient oral hydration plus N-acetylcysteine was as effective at preventing contrast-induced nephropathy as inpatient therapies and avoided costly hospital admission BACKGROUND Contrast agents used in angiography procedures for patients with cardiovascular disease are known to cause contrast-induced nephropathy ( CIN ) , which may be partially due to the production of nephrotoxic oxygen-free radicals . It is uncertain whether administration of intravenous ( IV ) anti-oxidant , N-acetylcysteine ( NAC ) , can prevent reduction in renal function and whether this is a cost-effective approach . METHODS Sixty-five day-only patients with renal impairment ( mean serum creatinine concentration 0.16+/-0.03 mmol/l ) due to undergo coronary or peripheral angiography and /or stenting were r and omly assigned to IV NAC 300 or 600 mg immediately before and after the procedure or IV fluid alone . RESULTS Of the 60 patients with complete data , none had acute CIN ( increase in serum creatinine concentration > or = 0.044 mmol/l , 48 h after administration of contrast agent ) . Eight patients ( 13 % ) have demonstrated an increase in their serum creatinine concentration > or = 0.044 mmol/l 30 days after administration of contrast agent : 2/19 ( 11 % ) in the control group , 2/21 ( 10 % ) in the 600 mg NAC group and 4/20 ( 20 % ) the 300 mg NAC group ( p = 0.66 ) . The mean volumes of contrast agent used and prehydration given for each of the three groups did not differ significantly ( p > 0.83 ) . There was significant improvement in creatinine clearance within each group from baseline to 30 days ( p < or = 0.03 ) , but no significant difference between the groups at 48 h and 30 days ( p > or = 0.43 ) . Considering the cost of NAC and its administration , we estimate that this would translate to a saving of dollar 26,637 per annum . CONCLUSION For day-stay patients with mild-to-moderate chronic renal impairment undergoing angiography and /or intervention , prehydration alone is less complicated and more cost-effective than a combination of IV NAC ( at doses used ) and hydration |
10,473 | 28,203,287 | Conclusions : Results of this systematic review suggest that some specific immunotherapies such as Reniale , ACHN-IL-2 , Newcastle disease virus ( NDV ) virus-infected autologous tumor cells , ALT and CIK treatment could be beneficiary for the treatment of patients with RCC | Background : Renal cell cancer ( RCC ) is the tenth most common malignancy in adults .
In recent years , several approaches of active and passive immunotherapy have been studied extensively in clinical trials of patients with RCC .
The aim of this systematic review was to assess the clinical efficacy of various approaches of specific immunotherapy in patients with RCC . | Cytokine induced killer ( CIK ) cell-based treatments have shown antitumor activity against renal cell carcinoma ( RCC ) in vitro and in vivo . But the therapeutic options and benefits of various CIK cells were unknown for different stages of RCC . In this r and om clinical trial , the 3-year disease free survival ( DFS ) of operable RCC patients treated with autologous tumor lysate-pulsed dendritic cells co-cultured with cytokine induced killer ( Ag-DC-CIK ) was 96.7 % compared with 57.7 % in the control group . Ag-DC-CIK immunotherapy decreased the risk of post-operative disease progression and relapse ( P = 0.0418 ) . In inoperable RCC patients treated with CIK , the 3-year overall survival ( OS ) and progression-free survival ( PFS ) were significantly longer than the control group ( P = 0.0116 and P = 0.0212 ) . The CD4(+)/CD8(+ ) T cell ratio in peripheral blood increased after the last cell infusion in the CIK treatment group , and especially further increased in the Ag-DC-CIK treatment group ( P = 0.002 ) . No severe toxicity was observed after infusion of CIK cells . Therefore , tumor antigen-sensitized Ag-DC-CIK cells might be more efficient and personalized for the patients with tumor resection , and CIK cells could improve the prognosis for those inoperable patients . According to the stages of RCC patients , different CIK cell-based immunotherapies would help to achieve more beneficial effects BACKGROUND Organ-confined renal-cell carcinoma is associated with tumour progression in up to 50 % of patients after radical nephrectomy . At present , no effective adjuvant treatment is established . We aim ed to investigate the effect of an autologous renal tumour cell vaccine on risk of tumour progression in patients with stage pT2 - 3b pN0 - 3 M0 renal-cell carcinoma . METHODS Between January , 1997 , and September , 1998 , 558 patients with a renal tumour scheduled for radical nephrectomy were enrolled at 55 institutions in Germany . Before surgery , all patients were central ly r and omised to receive autologous renal tumour cell vaccine ( six intradermal applications at 4-week intervals postoperatively ; vaccine group ) or no adjuvant treatment ( control group ) . The primary endpoint of the trial was to reduce the risk of tumour progression , defined as progression or death . All patients were assessed after st and ardised diagnostic investigations at 6-month intervals for a minimum of 4.5 years . FINDINGS By preoperative and postoperative inclusion criteria , 379 patients were assessable for the intention-to-treat analysis . At 5-year and 70-month follow-up , the hazard ratios for tumour progression were 1.58 ( 95 % CI 1.05 - 2.37 ) and 1.59 ( 1.07 - 2.36 ) , respectively , in favour of the vaccine group ( p=0.0204 , log-rank test ) . 5-year and 70-month progression-free survival rates were 77.4 % and 72 % , respectively , in the vaccine group and 67.8 % and 59.3 % , respectively , in the control group . The vaccine was well tolerated , with only 12 adverse events associated with the treatment . INTERPRETATION Adjuvant treatment with autologous renal tumour cell vaccine in patients with renal-cell carcinoma after radical nephrectomy seems to be beneficial and can be considered in patients undergoing radical nephrectomy due to organ-confined renal-cell carcinoma of more than 2.5 cm in diameter Cancer vaccines such as MVA-5T4 ( TroVax ® ) must induce an efficacious immune response to deliver therapeutic benefit . The identification of biomarkers that impact on the clinical and /or immunological efficacy of cancer vaccines is required in order to select patients who are most likely to benefit from this treatment modality . Here , we sought to identify a predictor of treatment benefit for renal cancer patients treated with MVA-5T4 . Statistical modeling was undertaken using data from a phase III trial in which patients requiring first-line treatment for metastatic renal cell carcinoma were r and omized 1:1 to receive MVA-5T4 or placebo alongside sunitinib , IL-2 or IFN-α . Numerous pre-treatment factors associated with inflammatory anemia ( e.g. , CRP , hemoglobin , hematocrit , IL-6 , ferritin , platelets ) demonstrated a significant relationship with tumor burden and patient survival . From these prognostic factors , the pre-treatment mean corpuscular hemoglobin concentration ( MCHC ) was found to be the best predictor of treatment benefit ( P < 0.01 ) for MVA-5T4 treated patients and also correlated positively with tumor shrinkage ( P < 0.001 ) . Furthermore , MCHC levels showed a significant positive association with 5T4 antibody response ( P = 0.01 ) . The latter result was confirmed using an independent data set comprising phase II trials of MVA-5T4 in patients with colorectal , renal and prostate cancers . Retrospective analyses demonstrated that RCC patients who had very large tumor burdens and low MCHC levels received little or no benefit from treatment with MVA-5T4 ; however , patients with smaller tumor burdens and normal MCHC levels received substantial benefit from treatment with MVA-5T4 Objective . To evaluate the efficacy of autologous cytokine-induced killer ( CIK ) cells in patients with renal cell carcinoma ( RCC ) . Methods . 20 patients diagnosed with TNM stage I or II RCC were r and omly divided into two groups , a CIK cell treatment group and a control group . The endpoint was progression-free survival ( PFS ) evaluated by Kaplan-Meier analyses . Results . CD3 + , CD3+/CD8 + , CD3+/CD4 + , and CD3+/CD56 + levels increased after CIK cell culture ( P < 0.01 ) . The median PFS in CIK cell treatment group was significantly longer than that in control group ( PFS , 32.2 months versus 21.6 months ; log-rank , P = 0.032 ) , all patients were alive during the course of followup , and there are no statistically significant differences between two groups in OS ( log-rank , P = 0.214 ) . Grade III or greater adverse events were not observed . Conclusions . CIK cells treatment could prolong survival in patients with RCC after radical nephrectomy and showed acceptable curative effect with potential enhancement of cellular immune function . This trial is registered with Clinical trials.gov NCT01799083 Several forms of immunotherapy are apparently effective in inducing clinical remissions in metastatic renal cancer , but their benefit on survival times have not been demonstrated so far . The present analysis was design ed to assess the effects of concomitant application of renal cancer vaccine and cytokines on DTH skin responses to tumor cell challenge , clinical remissions and patients survival . 40 patients with advanced RCC , all with distant metastases in at least one organ , were entered after nephrectomy into a protocol involving multiple vaccinations with Newcastle disease virus (NDV)-infected autologous irradiated tumor cells , with subsequent repetitive 3 bi-weekly cycles of low dose interleukin-2 ( r-IL-2 ) and interferon-alpha(2b)/rIFN-alpha(2 ) s.c . ( 1.5 million r-IL-2 Cetus units/m(2)/day and 3 million IFN-alpha IU/m(2)/day ) . In a pilot study the coadministration of a supplement of r-IL-2 proved to be important for augmentation of DTH responsiveness upon tumor cell challenge . Patients with aneuploid tumors vaccinated without r-IL-2 apparently developed an anergy to the vaccine throughout vaccination . In the main study , of the 40 evaluable RCC patients , 5 exhibited a complete response ( CR ) , 6 displayed a partial remission ( PR ) , 12 showed stable disease ( SD , median 25 months ) and 17 tumor progression . Survival distribution analysis predicted for all patients with stable disease a median survival of 31 months while CR+PR patients had a median survival > 4 years . 23/40 ( 57.5 % ) patients ( CR , PR and SD ) appear to have a significant survival advantage compared to the patients with progressive disease during the treatment period and to a historic reference group . Further data analysis revealed that the number of metastatic sites was predictive of survival characteristics ( p<0.05 ) . A marked increase during 3 vaccinations of DTH anti-tumor reactivity predicted a survival advantage ( 35 vs 14 months ) , a correlation that was also significant by the Wilcoxon test . While the multi-modality treatment with autologous tumor vaccine and s.c . administration of IL-2 and IFN-alpha appears to be effective in advanced RCC , a r and omized trial ( ASI-IL-2/IFN-alpha vs IL-2/IFN-alpha without ASI ) is now set up to help assess the role of ASI within the combined treatment regimen Active specific immunotherapy ( ASI ) is a strategy that attempts to boost the host 's immune response specifically against its own tumor . The purpose of this study was to investigate the effect of adjuvant ASI in patients with renal carcinoma Background . Treatment with interleukin‐2 ( IL‐2 ) and lymphokine‐activated killer cells ( LAK ) result ed in responses in some patients with advanced renal cell carcinoma ( RCC ) . However , the relative therapeutic benefit of the addition of LAK to IL‐2 was unknown BACKGROUND It remains a challenge to inhibit the local recurrence or distant metastasis of localized or locally advanced renal cell carcinoma ( RCC ) after surgical resection . We investigated the feasibility , safety and efficacy of immunotherapy using autologous tumor lysate (TL)-pulsed dendritic cells ( DCs ) and cytokine-induced killer ( CIK ) cells in patients with localized or locally advanced RCC . METHODS From January 2001 to July 2009 , we collected 137 patients that met the selection criteria and r and omly divided them into three groups . After surgery , immunotherapy with TL-pulsed DCs-CIK cells ( DC-CIK group ) and interferon (IFN)-α ( IFN-α group ) was performed in 46 patients , respectively . The other 45 patients received no postoperative adjuvant therapy ( the control group ) . The changes in the numbers of T lymphocyte subsets , including CD4(+)CD25(high ) regulatory T cells ( Treg ) , were determined before the operation and after immunotherapy . The overall survival was compared among the three groups . RESULTS An increase of the CD4(+)/CD8(+ ) ratio and a decrease of CD4(+)CD25(high ) cells were observed after TL-pulsed DC-CIK cells or IFN-a immunotherapy . All patients tolerated the TL-pulsed DC-CIK cells immunotherapy very well , and side effects in the DC-CIK group were less than in the IFN-α group . The metastasis and recurrence rates were significantly decreased after TL-pulsed DC-CIK cells or IFN-α immunotherapy compared with the control group ( P < 0.01 ) . The Log-rank test showed that the overall survival rates were significantly higher in the DC-CIK group and IFN-α group than that in the control group ( P < 0.01 ) , but there was no difference between the DC-CIK group and IFN-α group ( P > 0.05 ) . CONCLUSION Postoperative immunotherapy with TL-pulsed DC-CIK cells may prevent recurrence/metastasis and increase the overall survival rate after surgery in localized or locally advanced RCC BACKGROUND Treatment of localised renal cell carcinoma consists of partial or radical nephrectomy . A substantial proportion of patients are at risk for recurrence because no effective adjuvant therapy exists . We investigated the use of an autologous , tumour-derived heat-shock protein ( glycoprotein 96)-peptide complex ( HSPPC-96 ; vitespen ) as adjuvant treatment in patients at high risk of recurrence after resection of locally advanced renal cell carcinoma . METHODS In this open-label trial , patients were r and omly assigned to receive either vitespen ( n=409 ) or observation alone ( n=409 ) after nephrectomy . R and omisation was done in a one to one ratio by a computer-generated pseudo-r and om number generator , with a block size of four , and was stratified by performance score , lymph node status , and nuclear grade . Vitespen was given intradermally once a week for 4 weeks , then every 2 weeks until vaccine depletion . The primary endpoint was recurrence-free survival . The final analysis of recurrence-free survival was planned to take place after 214 or more events of disease recurrence or deaths before recurrence had occurred . Analysis was by intention to treat ( ITT ) . This study is registered with Clinical Trials.gov , number NCT00033904 . FINDINGS 48 patients in the vitespen group and 42 in the observation group were excluded from the ITT population because they did not meet post-surgery inclusion criteria ; the ITT population thus consisted of 361 patients in the vitespen group and 367 in the observation group . Final analysis of recurrence-free survival was triggered in November , 2005 . Re- review of all patients in the ITT population by the clinical events committee identified 149 actual recurrences ( 73 in the vitespen group and 76 in the observation group ) , nine deaths before recurrence ( two in the vitespen group and seven in the observation group ) , and 124 patients with baseline metastatic or residual disease ( 61 in the vitespen group and 63 in the observation group ) . Thus , after a median follow-up of 1.9 years ( IQR 0.9 - 2.5 ) in the ITT population , recurrence events were reported in 136 ( 37.7 % ) patients in the vitespen group and 146 ( 39.8 % ) in the observation group ( hazard ratio 0.923 , 95 % CI 0.729 - 1.169 ; p=0.506 ) . After continued follow-up until March , 2007 , there had been 70 deaths in the vitespen group and 72 in the observation group ( p=0.896 ) ; however , overall survival data were not mature , and patients continue to be followed up for survival . In predefined exploratory analyses by AJCC stage , recurrence events in patients with stage I or II disease were reported in 19 ( 15.2 % ) patients in the vitespen group and 31 ( 27.0 % ) in the observation group ( hazard ratio 0.576 , 95 % CI 0.324 - 1.023 ; p=0.056 ) . The most commonly reported adverse events in the vitespen group were injection-site erythema ( n=158 ) and injection-site in duration ( n=153 ) . One serious adverse event-autoimmune thyroiditis of grade 2 severity-was reported in the vitespen group ; no treatment-related grade 3 or 4 adverse events were reported . INTERPRETATION No difference in recurrence-free survival was seen between patients given vitespen and those who received no treatment after nephrectomy for renal cell carcinoma . A possible improvement in recurrence-free survival in patients with early stage disease who received vitespen will require further validation |
10,474 | 22,492,364 | After the inclusion of 9 trials with imputed BP effects , BP effects were attenuated but remained significant .
In short-term trials , vitamin C supplementation reduced SBP and DBP . | BACKGROUND In observational studies , increased vitamin C intake , vitamin C supplementation , and higher blood concentrations of vitamin C are associated with lower blood pressure ( BP ) .
However , evidence for blood pressure-lowering effects of vitamin C in clinical trials is inconsistent .
OBJECTIVE The objective was to conduct a systematic review and meta- analysis of clinical trials that examined the effects of vitamin C supplementation on BP . | The objective of this study was to assess synergistic antioxidant properties of vitamin C and isoflavones . The design was a placebo-controlled crossover trial : 500 mg vitamin C , 5 mg/kg body weight isoflavones , 500 mg vitamin C plus 5 mg/kg body weight isoflavones , or placebo . Total lipid peroxides , plasma vitamin C , and blood pressure were measured . Eight of 10 healthy postmenopausal women completed the study . A multiple analysis of variance was performed and least-squares difference post-hoc test utilized to determine where differences occurred . Significance was defined as P < .05 . There was a significant reduction in total lipid peroxides between baseline and isoflavone treatments ( 3.22+/-0.72 vs 2.47+/-0.82 nmol/mL , P < .05 ) . Mean systolic blood pressure was higher during isoflavone intervention than placebo ( 117+/-14 vs 125+/-15 mm Hg , P= .042 ) . Supplementation with vitamin C and isoflavones did not produce a synergistic antioxidant effect . A slight but significant increase in systolic blood pressure occurred with isoflavone supplementation . A larger study should be conducted to fully explore the potential interactions between these antioxidants Pathological formation of reactive oxygen species within the coronary circulation has been hypothesized to mediate some clinical manifestations of ischemic heart disease ( IHD ) by interfering with physiological regulation of coronary tone . To determine the degree to which coronary tone responds to acute changes in ambient levels of oxidants and antioxidants in vivo in a clinical setting , we measured the effect of an acute oxidative stress ( breathing 100 % oxygen ) on coronary capacitance artery diameter ( quantitative angiography ) and blood flow velocity through the coronary microcirculation ( intracoronary Doppler ultrasonography ) before and after treatment with the antioxidant vitamin C ( 3-g intravenous infusion ) in 12 IHD patients undergoing a clinical coronary interventional procedure . Relative to room air breathing , 100 % oxygen breathing promptly reduced coronary blood flow velocity by 20 % and increased coronary resistance by 23 % , without significantly changing the diameter of capacitance arteries . Vitamin C administration promptly restored coronary flow velocity and resistance to a slightly suprabasal level , and it prevented the reinduction of coronary constriction with rechallenge with 100 % oxygen . This suggests that acute oxidative stress produces prompt and substantial changes in coronary resistance and blood flow in a clinical setting in patients with IHD , and it suggests that these changes are mediated by vitamin C-quenchable substances acting on the coronary microcirculation . This observation may have relevance for clinical practice AIM The influence of oxidative stress ( OS ) and inflammation on up-regulation of blood pressure ( BP ) has been well established . Peripheral polymorphonuclear leukocytes ( PMNLs ) are primed in essential hypertension ( EH ) patients , releasing uncontrolled superoxide anion contributing to OS in these patients . PMNL priming correlates with PMNL intracellular calcium [Ca2+]i . Previous studies have shown that treatment by calcium channel blockers lowers BP , OS and inflammation . In the same time , there are some trials showing down regulation influence of ' ' anti-oxidative ' ' drugs as Vitamin E and C to inflammation and OS . The data of clinical significance of anti-oxidative drugs to BP is controversial . The aim of this paper was to evaluate the benefit of combined treatment by calcium channel blockers ( Lercanidipine ) and antioxidative drugs ( Vitamins C and E ) on BP and on parameters of inflammation and OS . METHODS Sixteen new diagnosed patients with mild to moderate BP were sample d to 2 groups after r and omization by age , sex , and mean arterial pressure ( MAP ) , cholesterol and glucose level . The first group was treated by Lercanidip-ine only , the second group by combination of Lercanidipine and antioxidative drugs both for 6 months . PMNL priming was assessed by the rate of superoxide release from separated , phorbol ester-stimulated PMNLs and by PMNL-CD11b level . Inflammation was reflected by plasma C-reactive protein ( CRP ) and albumin levels , white blood cells ( WBC ) and PMNL counts and by PMNL apoptosis . RESULTS In both groups , BP decreased after 6 months of treatment , and in a more pronounced manner following the combined treatment . In both groups PMNL priming parameters remained unchanged after 6 months of treatment , with transient differences between the two groups during the experimental period . In both groups inflammation parameters remained unchanged after 6 months of treatment , without difference between the two groups , except a pronounced decrease in the percentage of apoptotic PMNLs in the combined treatment group . CONCLUSION Our trial shows a clinical benefit combining calcium channel blockers treatment with antioxidants in BP treatment , although it did not reveal significant influence of complementation of antioxidants to calcium channel blockers on OS and inflammation parameters . Additional clinical and laboratory investigations are needed to clear this issue . Conflicting data are reported on the influence of vitamins E and C on OS and inflammation together with controversy regarding anti-oxidative drugs and their effect on BP BACKGROUND Loss of endothelium-derived nitric oxide ( EDNO ) contributes to the clinical expression of coronary artery disease ( CAD ) . Increased oxidative stress has been linked to impaired endothelial vasomotor function in atherosclerosis , and recent studies demonstrated that short-term ascorbic acid treatment improves endothelial function . METHODS AND RESULTS In a r and omized , double-blind , placebo-controlled study , we examined the effects of single-dose ( 2 g PO ) and long-term ( 500 mg/d ) ascorbic acid treatment on EDNO-dependent flow-mediated dilation of the brachial artery in patients with angiographically established CAD . Flow-mediated dilation was examined by high-resolution vascular ultrasound at baseline , 2 hours after the single dose , and 30 days after long-term treatment in 46 patients with CAD . Flow-mediated dilation improved from 6.6+/-3.5 % to 10.1+/-5.2 % after single-dose treatment , and the effect was sustained after long-term treatment ( 9 . 0+/-3.7 % ) , whereas flow-mediated dilation was 8.6+/-4.7 % at baseline and remained unchanged after single-dose ( 7.8+/-4.4 % ) and long-term ( 7.9+/-4.5 % ) treatment with placebo ( P=0.005 by repeated- measures ANOVA ) . Plasma ascorbic acid concentrations increased from 41.4+/-12 . 9 to 115.9+/-34.2 micromol/L after single-dose treatment and to 95 . 0+/-36.1 micromol/L after long-term treatment ( P<0.001 ) . CONCLUSIONS In patients with CAD , long-term ascorbic acid treatment has a sustained beneficial effect on EDNO action . Because endothelial dysfunction may contribute to the pathogenesis of cardiovascular events , this study indicates that ascorbic acid treatment may benefit patients with CAD Abstract . Rationale : Physiological responses to stress are considered disruptive to health . High-dose ascorbic acid has reduced indices of stress in laboratory animals . Methods : We conducted a r and omized double-blind , placebo-controlled 14-day trial of sustained-release ascorbic acid ( 60 healthy young adults ; 3 × 1000 mg/day Cetebe ) and placebo ( 60 healthy young adults ) for reduction of blood pressure , cortisol , and subjective response to acute psychological stress ( Trier Social Stress Test , TSST , consisting of public speaking and mental arithmetic ) . Six subjects from each group were excluded . Results : Compared to the placebo group , the ascorbic acid group had less systolic blood pressure ( an increase of 23 versus 31 mmHg ) , diastolic blood pressure , and subjective stress responses to the TSST ; and also had faster salivary cortisol recovery ( but not smaller overall cortisol response ) . Cortisol response to 1 µg ACTH , and reported side-effects during the trial did not differ between groups . Plasma ascorbic acid level at the end of the trial but not pre-trial was associated with reduced stress reactivity of systolic blood pressure , diastolic blood pressure , and subjective stress , and with greater salivary cortisol recovery . Conclusions : Treatment with high-dose sustained-release ascorbic acid palliates blood pressure , cortisol , and subjective response to acute psychological stress . These effects are not attributable to modification of adrenal responsiveness Twelve cigarette smoking and 10 nonsmoking healthy human volunteers , 25 to 38 yr of age , performed lung function and treadmill performance tests over two periods of 3 wk duration while taking either ascorbic acid ( 300 mg daily ) or placebo tablets in a cross-over design . The two exercise periods were separated by a one-month inactive phase . Tablets were administered in a r and om , double-blind manner . Plasma vitamin C levels were significantly increased after 3 wk of ascorbic acid supplementation in both smokers and nonsmokers as compared to initial levels in the same subjects . No differences between ascorbic acid and placebo treatments of smokers and nonsmokers were observed for 1-s forced expiratory volume , forced vital capacity , 1-s forced expiratory percent , resting heart rate , resting and postexercise systolic and diastolic blood pressures , treadmill workload , postexercise blood lactic acid , and ventilation measurements . The postexercise systolic blood pressure values of the nonsmokers were lower , although not quite significantly , after the ascorbic acid treatment than after the placebo . The 300-mg ascorbic acid supplement appeared to have little effect on the lung function and physical performance of healthy smoking and nonsmoking males OBJECTIVE To investigate the effect of supplementation with multivitamin and mineral on blood pressure and C-reactive protein ( CRP ) in obese women with increased cardiovascular disease risk as having hypertension , hyperglycemia or hyperlipemia . SUBJECTS AND METHODS 128 obese Chinese women aged 18 - 55 years with increased cardiovascular disease risk participated in a 26-week r and omized , double-blind , placebo-controlled trial . Subjects were r and omized to four groups , and received either one tablet of high-dose multivitamin and mineral supplement ( MMS ) , or one tablet of low-dose MMS ( Low MMS ) , or calcium 162 mg ( Calcium ) or identical placebo ( Placebo ) daily during the study . Diastolic blood pressure ( DBP ) , systolic blood pressure ( SBP ) and serum concentrations of CRP were measured at baseline and end-trial . RESULTS At baseline , the subjects had an average age of 42.0+/-7.1 years and BMI of 30.9+/-2.8 kg/m2 . There were no significant differences between the four groups in baseline characteristics . One hundred and seventeen subjects completed the study . After 26-week supplementation , both SBP and DBP were significantly lower in the MMS group compared to the placebo group ( p < 0.05 ) . There was also a non-significant trend of lower DBP at 26-week in the MMS and calcium groups compared to baseline ( p < 0.08 ) . At 26-week , the MMS group also had significantly lower serum concentrations of CRP compared with that of baseline and the placebo group ( p < 0.05 ) . CONCLUSIONS Our results showed that supplementation with adequate multivitamin and mineral supplement could reduce blood pressure and serum CRP in obese women with increased cardiovascular disease risk Abstract —In a double-blinded r and omized controlled trial , we investigated the long-term effect of vitamin C supplementation on blood pressure . A total of 439 Japanese subjects with atrophic gastritis initially participated in the trial using vitamin C and & bgr;-carotene to prevent gastric cancer . Before and on early termination of & bgr;-carotene supplementation , 134 subjects dropped out of this trial , whereas 120 and 124 subjects took the vitamin C supplement daily at either 50 mg or 500 mg , respectively , for 5 years . Before supplementation , neither systolic nor diastolic blood pressure was significantly related with the serum vitamin C concentration . This relationship was unchanged after adjustment for age , body mass index , and alcohol intake or after stratification by gender . After 5 years , systolic blood pressure significantly increased in groups , regardless of vitamin C dose , compared with baseline . Systolic blood pressure in the high-dose group ( 500 mg daily ) increased from 125.4 to 131.7 mm Hg ( 5.88 mm Hg increase ; 95 % confidence interval [ CI ] , 3.11 to 8.65 ) . This value was similar with that of the low-dose group ( 5.73 mm Hg increase ; 95 % CI , 2.62 to 8.83 ) and of the dropout group ( 4.52 mm Hg increase ; 95 % CI , 1.26 to 7.77 ) . There was no difference in change of diastolic blood pressure among the 3 groups . In conclusion , we observed no reduction in blood pressure with long-term moderate doses ( 500 mg/day ) of vitamin C supplementation in a high-risk population for stomach cancer and stroke Objective To evaluate three methods aim ed at the reconstruction of brachial pressure from non-invasive finger arterial pressure measurements as implemented in the Finometer ™ , ( FMS , Finapres Measurement Systems , Arnhem , Netherl and s ) , the successor to the Finapres ™ ( TNO Biomedical Instrumentation , Amsterdam , Netherl and s ) . Methods Finger arterial pressure ( FinAP ) may differ from intra-brachial pressure ( BAP ) . Pulse shape differences are removed by applying a generalized waveform filter . Pressure level differences are corrected by a generalized level correction equation using filtered systolic and diastolic levels and by level calibration , which uses an additional return-to-flow ( RTF ) systolic pressure measurement on the ipsilateral upper arm for an individual calibration of the reconstructed brachial pressure . ValidationThese methods were vali date d in 37 subjects , aged 41 to 83 years after a cardiac catheterization procedure . Intra-brachial and Finometer pressures were recorded simultaneously . Finometer pressures were compared after application of waveform filtering and level correction ( flcAP ) , and after an additional RTF calibration ( reBAP ) . Results Finger arterial systolic , diastolic and mean pressures for the group differed from BAP by −9.7 ± 13.0 , −11.6 ± 8.0 and −16.3 ± 7.9 mmHg ( mean ± SD ) respectively . Similarly flcAP differed by −1.1 ± 10.7 , −0.2 ± 6.8 and −1.5 ± 6.6 mmHg and reBAP differed by 3.1 ± 7.6 , 4.0 ± 5.6 and 2.7 ± 4.7 mmHg . Conclusion Reconstruction of BAP from FinAP as implemented in the Finometer reduces the pressure differences , with an individual RTF calibration to well within AAMI requirements 1 . Hypertension affects 30 % of adults and low intakes of antioxidants have been associated with increased risk of hypertension and cardiovascular disease . To investigate the effect of short-term high-dose antioxidant supplementation on blood pressure in hypertensive and normotensive out patients , we undertook a r and omized , double-blind , crossover design placebo-controlled study . 2 . Forty subjects were recruited from medical outpatient clinics , of whom 38 completed the study . Twenty-one were attending for treatment of hypertension and 17 were normotensive , attending for minor gastrointestinal complaints . Subjects were r and omly assigned to receive either 8 weeks placebo followed by 2 weeks washout then 8 weeks antioxidants or vice versa . The combination of antioxidants consisted of 200 mg of zinc sulphate , 500 mg of ascorbic acid , 600 mg of alpha-tocopherol ( sodium succinate salt ) and 30 mg of beta-carotene daily . 3 . Systolic blood pressure fell at the end of the antioxidant phase compared with the placebo phase both in subjects receiving anti-hypertensive therapy ( P < 0.01 ) and those who were normotensive ( P = 0.067 ) . Circulating levels of beta-carotene and alpha-tocopherol increased in all subjects during supplementation ( P < 0.01 ) and urine nitrite increased in hypertensive patients ( P < 0.05 ) . 4 . Short-term oral high-dose combination antioxidant therapy reduces blood pressure , possibly via increased availability of nitric oxide . This study may have implication s for the innovative use of antioxidants as an adjunct to anti-hypertensive therapy Abstract —Experimental evidence suggests that acute parenteral administration of high-dose ascorbic acid has beneficial vascular effects in type 2 diabetes . We studied the hemodynamic effects of chronic oral supplementation in this condition . Thirty patients , 45 to 70 years of age , with type 2 diabetes , were r and omly assigned in a double-blind manner to receive 500 mg ascorbic acid daily by mouth or placebo . Patients were studied at baseline and after 4 weeks of assigned treatment . The central aortic augmentation index ( AgIx ) and the time to wave reflection ( Tr ) were derived from radial artery pulse wave analysis data . AgIx and Tr were used as measures of systemic arterial stiffness and aortic stiffness , respectively . Ascorbic acid decreased brachial systolic blood pressure from 142.1±12.6 ( SD ) to 132.3±12.1 mm Hg ( difference [ 95 % CI ] 9.9 [ 4.7 , 15.0];P < 0.01 ) , brachial diastolic pressure from 83.9±4.8 to 79.5±6.0 mm Hg ( 4.4 [ 1.8 , 7.0];P < 0.01 ) , and AgIx from 26.8±5.5 % to 22.5±6.8 % ( 4.3 [ 1.5 , 7.1];P < 0.01 ) . Tr increased from 137.1±12.6 to 143.4±9.2 ms ( −6.3 [ −10.1 , −2.5];P < 0.01 ) . Placebo had no hemodynamic effects , and this difference between treatments was significant ( P < 0.01 for blood pressure and Tr , P = 0.03 for AgIx ) . We have therefore shown that after 1 month , oral ascorbic acid lowered arterial blood pressure and improved arterial stiffness in patients with type 2 diabetes . As strict control of blood pressure reduces cardiovascular risk in diabetes , ascorbic acid supplementation may potentially be a useful and inexpensive adjunctive therapy . Larger and longer studies now need to be performed OBJECTIVE The present study was design ed to assess the effect of magnesium plus zinc , vitamins C plus E , and a combination of these micronutrients on nephropathy indexes in type 2 diabetic patients . RESEARCH DESIGN AND METHODS In a r and omized , double-blind , placebo-controlled clinical trial , 69 type 2 diabetic patients were r and omly divided into four groups , each group receiving one of the following daily supplement for 3 months : group M ( n = 16 ) , 200 mg Mg and 30 mg Zn ; group V ( n = 18 ) , 200 mg vitamin C and 100 IU vitamin E ; group MV ( n = 17 ) , minerals plus vitamins ; and group P ( n = 18 ) , placebo . Urinary albumin excretion and N-acetyl-beta-d-glucosaminidase activity ( NAG ) in urine were determined at the beginning and at the end of the trial . Treatment effects were analyzed by general linear modeling . RESULTS Results indicate that after 3 months of supplementation , levels of urinary albumin excretion decreased in the V and MV groups ( P = 0.034 and P = 0.005 , respectively ) . Urinary NAG activity did not significantly change in any treatment groups . Levels of systolic , diastolic , and mean blood pressure significantly decreased in the MV group ( P = 0.008 , P = 0.017 , and P = 0.009 , respectively ) . Also , combination of vitamin and mineral supplementation had significant effects in decreasing fasting serum glucose ( P = 0.035 ) and malondialdehyde concentrations ( P = 0.004 ) and in increasing HDL cholesterol and apolipoprotein A1 levels ( P = 0.019 ) . There was no significant change in the levels of these parameters in the other three groups . CONCLUSIONS In conclusion , the results of the present study provide evidence for the effects of vitamins C and E and also combination of magnesium , zinc , and vitamins C and E supplementation on improvement of glomerular but not tubular renal function in type 2 diabetic patients Objective —Limited data exist from r and omized trials evaluating , noninvasively , the impact of antioxidant supplementation on vascular structure and function . Methods and Results —This is a sub study of the SU.VI.MAX Study , which is a r and omized , double-blind , placebo-controlled , cardiovascular and cancer primary prevention trial . Eligible participants ( free of symptomatic chronic diseases and apparently healthy ) were r and omly allocated to daily receive either a combination of antioxidants ( 120 mg vitamin C , 30 mg vitamin E , 6 mg beta carotene , 100 μg selenium , and 20 mg zinc ) or placebo and followed-up over an average of 7.2±0.3 years . At the end-trial examination , the carotid ultrasound examination and carotid – femoral pulse-wave velocity ( PWV ) measurement were performed blindly in 1162 subjects aged older than 50 years and living in the Paris area . The percentage of subjects with carotid plaques was higher in the intervention group compared with the placebo group ( 35.2 % versus 29.5 % , P = 0.04 ) . Common carotid intima-media thickness ( mean±SD ) was not different between the 2 groups ( 0.70±0.08 versus 0.70±0.08 mm , P = 0.38 ) . Mean PWV tended to be lower ( indicating less stiff aortic arteries ) in the intervention group but the difference did not reach statistical significance ( P = 0.13 ) . Conclusion —These results suggest no beneficial effects of long-term daily low-dose supplementation of antioxidant vitamins and minerals on carotid atherosclerosis and arterial stiffness OBJECTIVE To compare the effects of short-term dietary supplementation with tomato juice , vitamin E , and vitamin C on susceptibility of LDL to oxidation and circulating levels of C-reactive protein ( C-RP ) and cell adhesion molecules in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS There were 57 patients with well-controlled type 2 diabetes aged < 75 years treated with placebo for 4 weeks and then r and omized to receive tomato juice ( 500 ml/day ) , vitamin E ( 800 U/day ) , vitamin C ( 500 mg/day ) , or continued placebo treatment for 4 weeks . Susceptibility of LDL to oxidation ( lag time ) and plasma concentrations of lycopene , vitamin E , vitamin C , C-RP , vascular cell adhesion molecule 1 , and intercellular adhesion molecule 1 were measured at the beginning of the study , after the placebo phase , and at the end of the study . RESULTS Plasma lycopene levels increased nearly 3-fold ( P = 0.001 ) , and the lag time in isolated LDL oxidation by copper ions increased by 42 % ( P = 0.001 ) in patients during supplementation with tomato juice . The magnitude of this increase in lag time was comparable with the corresponding increase during supplementation with vitamin E ( 54 % ) . Plasma C-RP levels decreased significantly ( -49 % , P = 0.004 ) in patients who received vitamin E. Circulating levels of cell adhesion molecules and plasma glucose did not change significantly during the study . CONCLUSIONS This study indicates that consumption of commercial tomato juice increases plasma lycopene levels and the intrinsic resistance of LDL to oxidation almost as effectively as supplementation with a high dose of vitamin E , which also decreases plasma levels of C-RP , a risk factor for myocardial infa rct ion , in patients with diabetes . These findings may be relevant to strategies aim ed at reducing risk of myocardial infa rct ion in patients with diabetes A total of 3,318 men and women from a region in rural China were r and omized to receive daily either a multiple vitamin/mineral supplement or a placebo . Deaths that occurred in the participants were ascertained and classified according to cause over the 6-year period from 1985 to 1991 . At the end of supplementation , blood pressure readings were taken , and the prevalence of hypertension was determined . There was a slight reduction in overall mortality in the supplement group ( relative risk ( RR ) = 0.93 , 95 percent confidence interval ( CI ) 0.75 - 1.16 ) , with the decreased relative risk most pronounced for cerebrovascular disease deaths ( RR = 0.63 , 95 percent CI 0.37 - 1.07 ) . This benefit was greater for men ( RR = 0.42 , 95 percent CI 0.19 - 0.93 ) than for women ( RR = 0.93 , 95 percent CI 0.44 - 1.98 ) . Among the survivors , the presence of elevations in both systolic and diastolic blood pressures was less common in those who received the supplement ( RR for men = 0.43 , 95 % CI 0.28 - 0.65 ; RR for women = 0.92 , 95 percent CI 0.68 - 1.24 ) . This study indicates that supplementation with a multivitamin/mineral combination may have reduced mortality from cerebrovascular disease and the prevalence of hypertension in this rural population with a micronutrient-poor diet OBJECTIVE Aging is associated with endothelial dysfunction . We studied the acute and longer-term effects of vitamin C compared to a ' Mediterranean-type ' diet on endothelial function in healthy older subjects . METHODS Bilateral venous occlusion plethysmography was used to measure forearm blood flow in subjects aged 57 - 80 years . Responses to cumulative intra-arterial doses of the endothelium-dependent dilator bradykinin ( BK ; n=56 ; 20 , 40 , 80 pmol/min ) and the nitric oxide donor glyceryl trinitrate ( GTN ; n=54 ; 4 , 8 , 16 nmol/min ) , were determined alone and in the presence of vitamin C ( 25 mg/min ) . We then r and omised 54 subjects to a ' healthy ' diet ( n=18 ) , vitamin C ( 1 g/day ; n=18 ) or placebo for 6 weeks and reassessed endothelial and smooth muscle function . RESULTS Acute intra-arterial vitamin C did not alter dilatation to BK or GTN . Similar increases in plasma vitamin C occurred on oral vitamin C ( 83+/-4 to 135+/-8 micromol/l ) and ' healthy ' diet ( 84+/-5 to 135+/-27 micromol/l ; P<0.01 for both ) , with no change seen on placebo . Treatment with a ' healthy ' diet but not oral vitamin C improved endothelium-dependent ( P=0.043 ) and endothelium-independent dilatation ( P=0.011 ) . CONCLUSIONS A ' Mediterranean-type ' diet rich in vitamin C improves vascular function . Neither acute intra-arterial nor sustained administration of oral vitamin C improves vascular function in healthy older subjects The etiology of essential hypertension includes increased oxidative stress . The role of antihypertensive drug amlodipine as an antioxidant and the benefit of addition of vitamin C , an antioxidant to antihypertensive therapy were studied . Forty male patients of essential hypertension were r and omly divided into two groups and treated with 5 mg amlodipine . In addition one group also received 1000 mg vitamin C ( as two 500 mg tablets ) once daily for three months . Although blood pressure decreased in both groups , the systolic blood pressure in patients given vitamin C was less ( 126.4 ± 7.47 ) compared to the other group ( 130.9 ± 7.27 ) . A decrease in malondialdehyde , an increase in erythrocyte sodium-potassium adenosine triphosphatase ( Na+ K+ ATPase ) and an increase in the superoxide dismutase levels were observed in both groups . The increase in SOD was statistically more in the patients given vitamin C in addition to amlodipine ( 0.1717 ± 0.0150 compared to 0.152 ± 0.0219 units/100 ml assay ) . In spite of the known antihypertensive , antioxidant activity , similarity in correcting endothelial dysfunction independently , giving the two drugs together and early introduction of vitamin C perhaps decreases oxidative stress and augments the antioxidant status . This may prevent further vascular damage due to oxidative stress , leading to a better prognosis in essential hypertension patients Free radicals and oxidation are involved in several aspects of blood pressure physiology . We investigated the relationship between blood pressure and antioxidants , including plasma ascorbic acid ( AscA ) , in a 17-week controlled-diet study . Study subjects included 68 men aged 30 to 59 years who had a mean diastolic blood pressure of 73.4 mm Hg and a mean systolic blood pressure of 122.2 mm Hg . One month of vitamin C depletion was followed by 1-month repletion with 117 mg/d , repeated twice . All food and drink were provided in the study . Subjects did not smoke or drink alcohol , all consumed fruits and vegetables , and body weight was maintained . Plasma was assayed periodically for AscA , & agr;-tocopherol , carotenoids , and lipids . Plasma AscA was inversely related to diastolic blood pressure 1 month later ( correlation −0.48 , P < 0.0001 ) . Persons in the bottom fourth of the plasma AscA distribution had > 7 mm Hg higher diastolic blood pressure than did those in the top fourth of the plasma AscA distribution . Multivariate analysis with control for age , body mass index , other plasma antioxidants , and dietary energy , calcium , fiber , sodium , and potassium did not reduce the plasma AscA effect . One fourth of the variance in diastolic blood pressure was accounted for by plasma AscA alone . Plasma AscA was also significantly associated with systolic blood pressure in logistic regression . Vitamin C may be an important component of the effectiveness of fruits and vegetables in the reduction in blood pressure , and tissue AscA levels may be important in the maintenance of low blood pressure . Long-term intervention studies are warranted Oxidative stress has been associated with mechanisms of EH ( essential hypertension ) . The aim of the present study was to test the hypothesis that the antioxidant properties of vitamins C and E are associated with a decrease in BP ( blood pressure ) in patients with EH . A r and omized double-blind placebo-controlled clinical trial was conducted in 110 men with grade 1 EH ( 35 - 60 years of age without obesity , dyslipidaemia and diabetes mellitus , non-smokers , not undergoing vigorous physical exercise , without the use of any medication and /or high consumption of fruit and vegetables ) . Participants were r and omly assigned to receive either vitamins C+E [ vitamin C ( 1 g/day ) plus vitamin E ( 400 international units/day ) ] or placebo for 8 weeks . Measurements included 24 h ambulatory BP and blood analysis of oxidative-stress-related parameters in erythrocytes ( GSH/GSSH ratio , antioxidant enzymes and malondialdehyde ) and plasma [ FRAP ( ferric reducing ability of plasma ) ] , and levels of 8-isoprostane , vitamins C and E were measured at baseline and after treatment . Following administration of vitamins C+E , patients with EH had significantly lower systolic BP , diastolic BP and mean arterial BP and higher erythrocyte and serum antioxidant capacity compared with either placebo-treated patients with EH or the patients with EH at baseline prior to treatment . BP correlated positively with plasma 8-isoprostane levels and negatively with plasma FRAP levels in the vitamins C+E- and placebo-treated groups . In conclusion , the present study supports the view that oxidative stress is involved in the pathogenesis of EH , and that enhancement of antioxidant status by supplementation with vitamins C and E in patients with EH is associated with lower BP . This suggests intervention with antioxidants as an adjunct therapy for hypertension Background Antioxidant supplementations have the potential to alleviate the atherosclerotic damage caused by excessive production of reactive oxygen species ( ROS ) . The present study evaluated the effects of prolonged antioxidant treatment on arterial elasticity , inflammatory and metabolic measures in patients with multiple cardiovascular risk factors . Methods Study participants were r and omly assigned to two groups . Group 1 received oral supplementation with 2 capsules per day of Mid Life Guard , SupHerb , Israel . In each capsule vitamin C ( 500 mg ) vitamin E ( 200 iu ) , co-enzyme Q10 ( 60 mg ) and selenium ( 100 mcg ) , Group 2 received matching placebo(SupHerb ) for 6 months . Patients were evaluated for lipid profile , HbA1C , insulin , C-peptide , hs-CRP , endothelin , aldosterone , plasma renin activity and Homeostasis model assessment -insulin resistance ( HOMA-IR ) . Arterial elasticity was evaluated using pulse wave contour analysis ( HDI CR 2000 , Eagan , Minnesota ) . Results Antioxidant-treated patients exhibited significant increases in large arterial elasticity index ( LAEI ) as well as small arterial elasticity index ( SAEI ) . A significant decline HbA1C and a significant increase in HDL-cholesterol were also observed . In the placebo group , significant changes in LAEI , SAEI or metabolic measures were not observed . Conclusions Antioxidant supplementation significantly increased large and small artery elasticity in patients with multiple cardiovascular risk factors . This beneficial vascular effect was associated with an improvement in glucose and lipid metabolism as well as decrease in blood pressure BACKGROUND There is evidence for increased formation of free radicals in patients with hypertension , raising the possibility that NO is inactivated by free radicals , which impairs coronary endothelial function . Therefore , we tested the hypothesis that the antioxidant vitamin C could improve abnormal endothelial function of coronary arteries in patients with hypertension . METHODS AND RESULTS In 22 hypertensive patients without relevant coronary artery stenoses , endothelium-dependent vascular responses of the left anterior descending coronary artery ( LAD ) to acetylcholine ( 0.01 , 0.1 , and 1.0 micromol/L ) were determined before and immediately after intravenous infusion of 3 g vitamin C ( 17 patients ) or placebo ( 5 patients ) . In a subgroup of 10 patients , papaverine-induced flow-dependent vasodilation ( FDD ) was measured before and after vitamin C ( 5 patients ) or placebo ( 5 patients ) infusion . Segmental responses of the coronary artery luminal area were analyzed with quantitative coronary angiography . Before vitamin C infusion , the mean changes of LAD luminal areas at increasing doses of acetylcholine were -6.1+/-2.2 % , -15.2+/-4.9 % , and -33.9+/-8.1 % ( negative numbers symbolize vasoconstriction ) and during FDD , 5.4+/-1.0 % . The vasoconstrictor response during acetylcholine was reduced and FDD was augmented by vitamin C. After vitamin C infusion , LAD luminal areas changed by -3.2+/-2.3 % , -5.8+/-3.6 % , and -10.2+/-5.6 % ( P<.05 , acetylcholine ) and 17.8+/-2.8 % ( P<.05 , FDD ) . Doppler flow velocity ( during baseline , acetylcholine , and FDD ) was not significantly affected by vitamin C. CONCLUSIONS Vitamin C improves the endothelium-dependent vasomotor capacity of coronary arteries in patients with hypertension and patent coronary arteries . These findings suggest that increased oxidative stress contributes to endothelial dysfunction in hypertensive patients BACKGROUND Obesity is a well-established risk factor for cardiovascular disease , diabetes , hyperlipidemia , hypertension , osteoarthritis , and stroke . Stimulants , such as ephedrine and caffeine and their herbal counterparts , have proved effective in facilitating body weight loss , but their use is controversial due to their undesired effects . Other nutraceuticals have shown moderate success in reducing body weight , whereas several other compounds have demonstrated little or no effect . Therefore , a tolerable and effective nutraceutical that can increase energy expenditure and /or decrease caloric intake is desirable for body weight reduction . OBJECTIVE The primary purpose of this study was to assess the tolerability and effectiveness of a novel , stimulant-free , dietary supplement containing glucomannan , chitosan , fenugreek , Gymnema sylvestre , and vitamin C on body weight and fat loss and change in body composition in obese adults . METHODS In this single-center , prospect i ve , r and omized , double-blind , placebo-controlled study conducted at the University of Guelph ( Guelph , Ontario , Canada ) , obese adults ( aged 20 - 50 years ; body mass index [ BMI ] , ≥30 kg/m(2 ) ) were r and omized to the treatment or placebo group . The treatment group received 6 capsules of a dietary supplement containing a proprietary blend of glucomannan , chitosan , fenugreek , G sylvestre , and vitamin C daily for 6 weeks , and the placebo group received 6 capsules of rice flour daily for 6 weeks . Body weight ; percentage of body fat ; absolute fat mass ; lean body mass ; BMI ; upper abdominal , waist , and hip circumference ; and anthropometric measurements were recorded at baseline and at study end . Patients completed daily dietary intake records on days 1 to 3 and days 40 to 42 . They also completed weekly activity logs throughout the study . RESULTS Twenty-four subjects ( mean [ SD ] age , 37.0 [ 8.2 ] years [ range , 21 - 48years ] ; mean [ SD ] BMI , 35.7 [ 6.2 ] kg/m(2 ) [ range , 28.9 - 50.9 kg/m(2 ) ] ) were assigned to the treatment group ( 8 women , 4 men ) or the placebo group ( 9 women,3 men ) . Two subjects ( 8.3 % ; 1 patient [ 8.3 % ] from each group ) dropped out for personal reasons unrelated to the study . No significant changes in the consumption of total calories ; the percentage of calories ingested as carbohydrates , fat , or protein ; or activity levels were found in either group throughout the study . Compared with the placebo group , the treatment group lost significantly more body weight ( -2.3 kg vs 0.0 kg ; P<0.01 ) , percentage of body fat ( -1.1 % vs 0.2 % ; P<0.05 ) , and absolute fat mass ( -2.0 kg vs 0.2 kg ; P<0.001 ) . The treatment group also experienced a significantly greater reduction in upper abdominal circumference ( -4.5 cm vs -0.7 cm ) , waist circumference ( -4.1 cm vs 0.1 cm ) , and hip circumference ( -2.9 cm vs 0.6 cm ) compared with the placebo group ( P<0.05 for all ) . No significant changes in heart rate or blood pressure were found in either group . Both the treatment and the placebo were well tolerated . CONCLUSION Within the context of this study , the novel combination of glucomannan , chitosan , fenugreek , G sylvestre , and vitamin C results in significant body weight and fat loss in obese adults . Disclosure : Derek E. Woodgate , MSc , is president and owner of NxCare Inc. , which produces the dietary supplement containing glucomannan , chitosan , fenugreek , Gymnema sylvestre , and vitamin C ( trade name Calorie-Care ™ ) BACKGROUND Insulin therapy may influence cardiovascular disease ( CVD ) and lipid metabolism in type 2 diabetes ( T2D ) . Exaggerated postpr and ial lipaemia ( PPL ) is a feature of diabetic dyslipidaemia affecting CVD via enhanced oxidative stress ( OS ) and endothelial dysfunction . We assessed endothelial function and OS during PPL following insulin and vitamin C. Twenty ( 17 M ) T2D patients were studied ( mean Hba1c 8.4 % ) at baseline , following 6 weeks of insulin lispro ( 0.2 Iu kg-1 ) and vitamin C 1-g daily . Eight-h lipid and glucose profiles were measured following a fatty meal . Endothelial function ( flow-mediated vasodilatation : FMD ) and OS were measured at fasting , 4 h and 8 h. MATERIAL S AND METHODS Glucose , body mass index , and total and LDL cholesterol remained unchanged . FMD improved . Placebo group : fasting , 1.1 + /- 1.2 to 4.2 + /- 1.1 % ( P < 0.001 ) ; 4-h , 0.3 + /- 1.2 to 3.1 + /- 0.9 % ( P < 0.01 ) ; 8-h , 0.7 + /- 1.1 to 3.76 + /- 1.1 % ( P < 0.001 ) . Vitamin C group : fasting , 0.9 + /- 1.1 to 6.1 + /- 1.3 % ( P < 0.001 ) ; 4-h , 0.7 + /- 1.5 to 4.9 + /- 2.1 % ( P < 0.001 ) ; 8-h , 0.8 + /- 0.9 to 5.8 + /- 0.6 % ( P < 0.01 ) . Post-pr and ial lipaemia was attenuated : TG area-under-curve ( mmol L-1 8 h-1 ) , 52.6 + /- 11 to 39.1 + /- 12.5 ( placebo group ) , P < 0.02 ; and 56.9 + /- 8 to 40.1 + /- 10.3 ( vitamin C group ) , P < 0.02 . Oxidative stress was reduced , with greater changes in the vitamin C group . CONCLUSION Insulin may thus exert vascular benefits in T2D , by modifying fasting and postpr and ial lipid metabolism result ing in reduced OS and improved EF . Vitamin C therapy may augment the vascular benefits of insulin in T2D through additional effects on OS and EF Numerous observational studies showed associations of antioxidants ( vitamins C and E ) and folate intake with a reduced risk of cardiovascular disease , but r and omized controlled clinical trials have generally not supported this hypothesis . The objective of this study was to investigate the effects of a daily dosage of 1000 mg vitamin C , 800 mg vitamin E , and 10 mg folate on markers of vascular function in 31 young healthy male adults . Cardiovascular values after a 12-week vitamin ( 14 subjects ) or placebo ( 17 subjects ) intervention were compared to baseline values . Cardiovascular parameters ( blood pressure , stroke volume , heart rate , cardiac output , vascular resistance , arterial compliance ) were measured continuously after an overnight fast under controlled circumstances with a Finometer device . Our main finding was a significant decrease ( p = 0.03 ) in systolic blood pressure in the experimental group . No statistically significant changes were observed within other cardiovascular variables of the experimental group , but possible beneficial decreases in diastolic blood pressure and increases in arterial compliance after 12 weeks of vitamin supplementation were indicated . In conclusion , beneficial effects of antioxidants and folate were observed probably because the supplementation was used by young healthy subjects under carefully controlled conditions The aim of this investigation is to study the hypothesis that vitamin C has beneficial effects on some risk factors of cardiovascular diseases . Sixty-seven volunteers participated in this study . Thirty and thirty-seven subjects were assigned r and omly to two groups . The first was given a placebo and the second was given a vitamin C , respectively . Both regimens were followed for six months . The dose of vitamin C was 500 mg/day . Double blind technique was used throughout the study . These data supported part of the beneficial effects of vitamin C on atherosclerosis process , i.e. reduce significantly body fat , systolic blood pressure , and pulse , and increase significantly high density lipoprotein . On the other h and , these data did not show favourable effects on other lipid parameters , i.e. cholesterol , triglyceride , low density lipoprotein , and very low density lipoprotein Type II diabetes is characterized by increased oxidative stress , endothelial dysfunction and hypertension . We investigated whether short-term treatment with oral vitamin C reduces oxidative stress and improves endothelial function and blood pressure in subjects with Type II diabetes . Subjects ( n = 35 ) received vitamin C ( 1.5 g daily in three doses ) or matching placebo for 3 weeks in a r and omized , double-blind , parallel-group design . Plasma concentrations of 8-epi-prostagl and in F(2alpha ) ( 8-epi-PGF(2alpha ) ) , a non-enzymically derived oxidation product of arachidonic acid , were used as a marker of oxidative stress . Endothelial function was assessed by measuring forearm blood flow responses to brachial artery infusion of the endothelium-dependent vasodilator acetylcholine ( with nitroprusside as an endothelium-independent control ) and by the pulse wave responses to systemic albuterol ( endothelium-dependent vasodilator ) and glyceryl trinitrate ( endothelium-independent vasodilator ) . Plasma concentrations of vitamin C increased from 58+/-6 to 122+/-10 micromol/l after vitamin C , but 8-epi-PGF(2alpha ) levels ( baseline , 95+/-4 pg/l ; after treatment , 99+/-5 pg/l ) , blood pressure ( baseline , 141+/-5/80+/-2 mmHg ; after treatment , 141+/-5/81+/-3 mmHg ) and endothelial function , as assessed by the systemic vasodilator response to albuterol and by the forearm blood flow response to acetylcholine , were not significantly different from baseline or placebo . Thus treatment with vitamin C ( 1.5 g daily ) for 3 weeks does not significantly improve oxidative stress , blood pressure or endothelial function in patients with Type II diabetes BACKGROUND Hypertension is considered resistant if blood pressure can not be reduced to < 140/90 mmHg with an appropriate triple-drug regimen , including an oral diuretic , with all agents administered at maximal dosages . This definition has evolved with the development of new therapies and evidence -based data supporting treatment to lower BP goals . OBJECTIVE To assess whether vitamin C and atorvastatin improve endothelial function and blood pressure control in subjects with resistant arterial hypertension and dyslipidemia . METHODS Forty-eight hyperlipidemic subjects with RH ( office systolic BP > 140 mmHg and /or office diastolic BP > 90 mmHg notwithst and ing antihypertensive treatment with three medications in maximal doses ) were r and omized into three groups to receive additional medication for 8 weeks . Group VTC ( n = 17)--mean 24 hour SBP 150.6 + /- 5.2 mmHg , DBP 86.1 + /- 3.3 mmHg , low density lipoprotein 158.1 + /- 24.5 mg/dl -- received vitamin C 500 mg per day ; Group ATR ( n = 15)--mean 24 hour SBP 153.1 + /- 4.8 mmHg , DBP 87.1 + /- 6.7 mmHg , LDL 162.6 + /- 13.6 mg/dl -- received atorvastatin 20 mg/day ; and Group PLA ( n = 16)--mean 24 hour SBP 151.1 + /- 7.4 mmHg , DBP 84.8 + /- 5.9 mmHg , LDL 156.7 + /- 26.1 mg/dl -- received a placebo . High resolution ultrasound was used to calculate brachial artery flow-mediated dilation , and 24 hour ambulatory BP monitoring was performed at study entry and after 8 weeks . RESULTS In the ATR group there were significant reductions of SBP ( deltaSBP1 - 2 : 13.7 + /- 5.6 mmHg , P 0.001 ) , DBP ( deltaDBP1 - 2 : 7.8 + /- 5.7 mmHg , P 0.01 ) , LDL ( deltaLDL1 - 2 : 67.7 + /- 28.3 mg/dl , P < 0.001 ) and improvement of brachial artery FMD ( deltaFMD2 - 1 : 4.2 + /- 2.6 % ) . No significant changes in BP , LDL and FMD were observed in the other two groups . CONCLUSIONS In subjects with RH and dyslipidemia , atorvastatin 20 mg/day compared to vitamin C 500 mg/day may help to achieve better BP control and improve endothelial function in a finite period . A larger trial is needed to assess the drug 's efficacy in this population for longer periods BACKGROUND R and omized trials have largely failed to support an effect of antioxidant vitamins on the risk of cardiovascular disease ( CVD ) . Few trials have examined interactions among antioxidants , and , to our knowledge , no previous trial has examined the individual effect of ascorbic acid ( vitamin C ) on CVD . METHODS The Women 's Antioxidant Cardiovascular Study tested the effects of ascorbic acid ( 500 mg/d ) , vitamin E ( 600 IU every other day ) , and beta carotene ( 50 mg every other day ) on the combined outcome of myocardial infa rct ion , stroke , coronary revascularization , or CVD death among 8171 female health professionals at increased risk in a 2 x 2 x 2 factorial design . Participants were 40 years or older with a history of CVD or 3 or more CVD risk factors and were followed up for a mean duration of 9.4 years , from 1995 - 1996 to 2005 . RESULTS A total of 1450 women experienced 1 or more CVD outcomes . There was no overall effect of ascorbic acid ( relative risk [ RR ] , 1.02 ; 95 % CI , 0.92 - 1.13 [ P = .71 ] ) , vitamin E ( RR , 0.94 ; 95 % CI , 0.85 - 1.04 [ P = .23 ] ) , or beta carotene ( RR , 1.02 ; 95 % CI , 0.92 - 1.13 [ P = .71 ] ) on the primary combined end point or on the individual secondary outcomes of myocardial infa rct ion , stroke , coronary revascularization , or CVD death . A marginally significant reduction in the primary outcome with active vitamin E was observed among the prespecified subgroup of women with prior CVD ( RR , 0.89 ; 95 % CI , 0.79 - 1.00 [ P = .04 ] ; P value for interaction , .07 ) . There were no significant interactions between agents for the primary end point , but those r and omized to both active ascorbic acid and vitamin E experienced fewer strokes ( P value for interaction , .03 ) . CONCLUSION There were no overall effects of ascorbic acid , vitamin E , or beta carotene on cardiovascular events among women at high risk for CVD The object of the study was to test whether high dose ascorbic acid ( AA ) could normalize glomerular hyperfiltration in insulin-dependent diabetes mellitus ( IDDM ) patients . A prospect i ve , double-blind , r and omized , placebo ( tartaric acid , TA ) controlled study design was used , with parallel treatment lasting 4 weeks . Measurements were made before and after treatment , on 24 normoalbuminuric , normotensive male IDDM patients , who were r and omized to ascorbic acid ( n = 12 , age 35 years ( 18 - 39 ) , diabetes duration 12 years ( 2 - 12 ) , BP 128/82 mmHg ( SD 14/6 ) ) , or to placebo ( TA ) ( n = 12 , age 30 years ( 19 - 36 ) , diabetes duration 8 years ( 2 - 17 ) , BP 119/75 mmHg ( SD 9/7 ) . The intervention consisted of 6 enterosoluble tablets of 500 mg AA or 213 mg TA , twice a day , being daily doses of 6 g AA or 2.55 g TA . No significant differences in any of the parameters measured were seen , when comparing results following AA or placebo treatment . The glomerular filtration rate ( GFR , clearance of 125I-iothalamate ) was unchanged while effective renal plasma flow ( ERPF , clearance of 131I-hippuran ) tended to decline in both groups . The GFRs before and after treatment in the AA-treated group were 141 ( SD 15 ) and 134 ( SD 12 ) ml min-1 1.73 m-2 ; NS ( 2p = 0.09 ) . In the TA-treated group they were 142 ( SD 19 ) and 137 ( SD 16 ) ml min-1 1.73 m-2 ; NS ( 2p = 0.20 ) . The ERPFs in the AA group were 584 ( SD 93 ) and 545 ( SD 47 ) ml min-1 1.73 m-2 ; ( 2p = 0.06 ) . In the TA group they were 618 ( SD 108 ) and 574 ( SD 98 ) ml min-1 1.73 m-2 ( 2p = 0.03 ) . The filtration fractions ( FFs ) in the AA group were 0.244 and 0.246 NS . ( ABSTRACT TRUNCATED AT 250 WORDS Abnormalities of autonomic control of the cardiovascular system are seen in chronic heart failure ( CHF ) and confer a poor prognosis . Nitric oxide appears to be important in the regulation of baroreflex control in health and in disease states . The antioxidant vitamin C increases nitric oxide bioavailability in CHF . We evaluated the effects of vitamin C on baroreceptor sensitivity ( BRS ) by sequence analysis in 100 CHF patients and 44 control subjects . Groups of 55 CHF patients and 22 controls were r and omly allocated to receive a single intravenous injection of vitamin C ( 2 g ) or placebo . In addition , 45 CHF patients were r and omly allocated to receive a 4-week course of oral vitamin C ( 4 g/day ) or placebo . An age-related reference range for BRS was developed in 22 healthy controls matched for age and gender to the CHF group . BRS was significantly impaired in the CHF group compared with age-matched older controls and young controls ( 6.9 + /- 3.1 , 12.5 + /- 4.9 and 21.7 + /- 9.1 mmHg/ms respectively ; P < 0.001 between groups ) . Intravenous vitamin C acutely improved BRS in CHF patients by 24 % ( by 1.8 + /- 4.1 mmHg/ms ; P < 0.05 ) , but not in controls . There was no improvement in BRS in CHF patients given chronic oral vitamin C. Thus acute intravenous , but not chronic oral , vitamin C improved BRS in CHF patients . There was no effect of intravenous vitamin C in healthy subjects , suggesting that the mechanism was either by free radical scavenging or due to central effects Hypertension is associated with low plasma ascorbic acid levels and impaired endothelial function . Recent evidence suggests that increased vascular oxidative stress contributes to the pathophysiology of endothelial dysfunction and hypertension . We recently showed that chronic oral ascorbic acid therapy lowers blood pressure in hypertensive patients . We hypothesized that it would also improve endothelial vasomotor function . In a r and omized , double-blind , placebo-controlled study , we examined the effect of acute ( 2 g po ) and chronic ( 500 mg/day for 1 mo ) ascorbic acid treatment on brachial artery flow-mediated dilation in 39 patients with hypertension . Compared with 82 age- and gender-matched normotensive controls , these patients had impaired endothelium-dependent , flow-mediated dilation of the brachial artery [ 8.9 + /- 6.1 vs. 11.2 + /- 5.7 % ( SD ) , P < 0.04 ] . After therapy , plasma ascorbic acid concentrations increased acutely from 50 + /- 12 to 149 + /- 51 micromol/l and were maintained at 99 + /- 33 micromol/l with chronic treatment ( both P < 0.001 ) . As previously reported , chronic ascorbic acid therapy reduced systolic and mean blood pressure in these patients . However , acute or chronic ascorbic acid treatment had no effect on brachial artery endothelium-dependent , flow-mediated dilation or on endothelium-independent , nitroglycerin-mediated dilation . These results demonstrate that conduit vessel endothelial dysfunction secondary to hypertension is not reversed by acute or chronic treatment with oral ascorbic acid . The effects of this treatment on resistance vessel vasomotor function warrant further investigation Background There is growing evidence that oxidative stress contributes to the pathogenesis of hypertension and endothelial dysfunction . Thus , dietary antioxidants may beneficially influence blood pressure ( BP ) and endothelial function by reducing oxidative stress . Objective To determine if vitamin C and polyphenols , alone or in combination , can lower BP , improve endothelial function and reduce oxidative stress in hypertensive individuals . Design A total of 69 treated hypertensive individuals with a mean 24-h ambulatory systolic blood pressure ≥ 125 mmHg participated in a r and omized , double-blind , placebo-controlled , factorial trial . Following a 3-week washout , participants received 500 mg/day vitamin C , 1000 mg/day grape-seed polyphenols , both vitamin C and polyphenols , or neither for 6 weeks . At baseline and post-intervention , 24-h ambulatory BP , ultrasound-assessed endothelium-dependent and -independent vasodilation of the brachial artery , and markers of oxidative damage , ( plasma and urinary F2-isoprostanes , oxidized low-density lipoproteins and plasma tocopherols ) , were measured . Results A significant interaction between grape-seed and vitamin C treatments for effects on BP was observed . Vitamin C alone reduced systolic BP versus placebo ( −1.8 ± 0.8 mmHg , P = 0.03 ) , while polyphenols did not ( −1.3 ± 0.8 mmHg , P = 0.12 ) . However , treatment with the combination of vitamin C and polyphenols increased systolic BP ( 4.8 ± 0.9 mmHg versus placebo ; 6.6 ± 0.8 mmHg versus vitamin C ; 6.1 ± 0.9 mmHg versus polyphenols mmHg , each P < 0.0001 ) and diastolic BP ( 2.7 ± 0.6 mmHg , P < 0.0001 versus placebo ; 1.5 ± 0.6 mmHg , P = 0.016 versus vitamin C ; 3.2 ± 0.7 mmHg , P < 0.0001 versus polyphenols ) . Endothelium-dependent and -independent vasodilation , and markers of oxidative damage were not significantly altered . Conclusion Although the mechanism remains to be eluci date d , these results suggest caution for hypertensive subjects taking supplements containing combinations of vitamin C and polyphenols In patients with intermittent claudication , exercise is associated with a marked increase in oxidative stress , likely responsible for systemic endothelial perturbation . In 31 claudicant patients , we assessed the effect of vitamin C administration on the acute changes induced by maximal and submaximal exercise in endothelium-dependent , flow-mediated dilation ( FMD ) , and in plasma levels of thiobarbituric acid-reactive substances ( TBARS ) and soluble intercellular adhesion molecule-1 ( sICAM-1 ) . In 16 claudicants , maximal exercise reduced FMD ( from 8.5+/-0.9 to 3.7+/-0.8 % , P<0.01 ) , and increased plasma levels of TBARS ( from 1.93+/-0.06 to 2.22+/-0.1 nmol/ml , P<0.02 ) and of sICAM-1 ( from 282+/-17 to 323+/-19 ng/ml , P<0.01 ) . In eight of these patients , r and omized to vitamin C , exercise-induced changes in FMD and biochemistry were abolished . This beneficial effect was not observed in the eight patients r and omized to saline . In 15 patients , who walked until the onset of claudication pain ( submaximal exercise ) , and in ten control subjects , who performed maximal exercise , no changes were observed with exercise . Thus , in claudicants , vitamin C prevents the acute , systemic impairment in endothelial function induced by maximal exercise . This finding provides a rationale for trials investigating antioxidant therapy and cardiovascular risk in patients with intermittent claudication The SUpplementation en VItamines et Minéraux AntioXydants ( SU.VI.MAX ) Study is a r and omized , double-blind , placebo-controlled , primary -prevention trial design ed to test the efficacy of daily supplementation with antioxidant vitamins ( vitamin C , 120 mg ; vitamin E , 30 mg ; and beta-carotene , 6 mg ) and minerals ( selenium , 100 microg ; and zinc , 20 mg ) at nutrition-level doses ( one to three times the daily recommended dietary allowances ) in reducing several major health problems in industrialized countries , especially the main causes of premature death , cancers and cardiovascular diseases . The present report describes the design , implementation , and baseline characteristics of participants in this 8-year cohort study , which started in 1994 in France ; 12,735 eligible subjects ( women aged 35 - 60 , and men aged 45 - 60 ) were included in 1994 and will be followed for 8 years . Participants undergo a yearly visit consisting , every other year , of either biological sampling or clinical examination . They also regularly provide information on health events and dietary intake by filling out computerized question naires using the Minitel Telematic Network . Data on baseline characteristics of the participants suggest that the present sample is close to the national population in terms of geographic density , socioeconomic status , and the distribution of various major risk factors for the diseases under study . The choice of the study population should allow the results of this trial to apply to adult population s of both sexes in France and other industrialized countries OBJECTIVES The purpose of this study was to determine whether lowering homocysteine levels with folic acid , with or without antioxidants , will improve endothelial dysfunction in patients with coronary artery disease ( CAD ) . BACKGROUND Elevated plasma homocysteine levels are a risk factor for atherosclerosis . Homocysteine may promote atherogenesis through endothelial dysfunction and oxidative stress . METHODS In a double-blind , placebo-controlled , r and omized trial , we used vascular ultrasound to assess the effect of folic acid alone or with antioxidants on brachial artery endothelium-dependent flow-mediated dilation ( FMD ) . Seventy-five patients with CAD ( screening homocysteine level > or = 9 micromol/liter ) were r and omized equally to one of three groups : placebo , folic acid alone or folic acid plus antioxidant vitamins C and E. Patients were treated for four months . Plasma folate , homocysteine , FMD and nitroglycerin-mediated dilation were measured before and after four months of treatment . RESULTS Plasma folate , homocysteine and FMD were unchanged in the placebo group . Compared with placebo , folic acid alone increased plasma folate by 475 % ( p < 0.001 ) , reduced plasma homocysteine by 11 % ( p = 0.23 ) and significantly improved FMD from 3.2 + /- 3.6 % to 5.2 + /- 3.9 % ( p = 0.04 ) . The improvement in FMD correlated with the reduction in homocysteine ( r = 0.5 , p = 0.01 ) . Folic acid plus antioxidants increased plasma folate by 438 % ( p < 0.001 ) , reduced plasma homocysteine by 9 % ( p = 0.56 ) and insignificantly improved FMD from 2.6 + /- 2.4 % to 4.0 + /- 3.7 % ( p = 0.45 ) , as compared with placebo . Nitroglycerin-mediated dilation did not change significantly in any group . CONCLUSIONS Folic acid supplementation significantly improved endothelial dysfunction in patients with coronary atherosclerosis . Further clinical trials are required to determine whether folic acid supplementation may reduce cardiovascular events AIMS Elevated levels of urinary albumin excretion rate ( AER ) predict high risk for progressing to end-stage renal disease . In streptozotocin-induced diabetes , supplementation with vitamin C or E reduces albuminuria and glomerular hypertrophy . We tested the hypothesis that supplementation of both vitamin C and E in pharmacological doses lowers AER in Type 2 diabetic patients with persistent micro/macroalbuminuria . METHODS Thirty Type 2 diabetic patients with AER 30 - 300 mg/24 h were included in a double-blind r and omised , cross-over trial . Patients received vitamin C ( 1250 mg ) and vitamin E ( 680 IU ) per day or matching placebo for 4 weeks with a 3-week wash-out period between treatment periods in r and om order . RESULTS Combined treatment with vitamin C and E reduced AER by 19 % ( 95 % CI 6 - 34 % ) ( p = 0.04 ) , geometric mean 197 mg/24 h ( 95 % CI 114 - 341 mg/24 h ) vs. 243 mg/24 h ( 146 - 404 mg/24 h ) . No changes were seen in serum creatinine , haemoglobin A1C or blood pressure . Fasting plasma concentrations of vitamin C and E increased in all patients during active treatment ( mean vitamin C 79.4 micromol/L ( SD 27.8 ) vs. 41.9 micromol/L ( 18.4 ) and vitamin E 47.0 micromol/L ( 19.8 ) vs. 29.5 micromol/L ( 15.3 ) , P < 0.000001 ) . Except for two patients that started additional blood pressure lowering treatment during the run-in period , no changes in medication , food and exercise habits or in the number of smokers occurred during the study . CONCLUSION Short-term treatment with vitamin C and E in pharmacological doses lowers AER in Type 2 diabetic patients with micro/macroalbuminuria . Further long-term , large-scale studies of this albuminuria reducing treatment modality are warranted Background Evidence from observational epidemiologic studies has indicated that antioxidants consumed through the diet or as dietary supplements lower the risk of developing atherosclerotic cardiovascular disease . Evidence suggesting that the major mechanism for the protective effect of antioxidants is mediated through decreased oxidation of lipids , particularly low-density lipoprotein ( LDL ) cholesterol is accumulating . Other evidence , however , suggests that antioxidants may influence traditional modifiable cardiovascular risk factors such as the blood pressure and serum lipids favorably . The purpose of this study was to determine the effect of antioxidant vitamin supplementation on modifiable risk factors for atherosclerotic cardiovascular disease . Design A r and omized , placebo-controlled , clinical trial of antioxidant vitamin supplementation , conducted at a single community-based clinical research center . Methods We assigned 297 retired teachers who were members of the Maryl and Retired Teachers Association r and omly to 2 - 4 months of dietary supplementation with placebo or combined antioxidant vitamin capsules providing 400 IU/day vitamin E , 500 mg/day vitamin C , and 6 mg/day β-carotene . The outcome measures were the blood pressure , fasting serum total cholesterol , high-density lipoprotein cholesterol , LDL cholesterol , and fasting glucose . Results After 2 - 4 months of supplementation the combined antioxidant supplement had had no significant effect on the systolic and diastolic blood pressures , fasting serum lipids ( total cholesterol , high-density lipoprotein cholesterol , and LDL cholesterol ) and fasting glucose , with unadjusted and adjusted analyses . Conclusion Data from this trial suggest that the protective effect from antioxidant vitamin supplementation , if there is one , likely results from mechanisms other than modification of traditionally modifiable cardiovascular risk factors Objectives To determine the effect of oral vitamin C supplements on ambulatory blood pressure and plasma lipids . Design A 6-month double-blind r and omized placebo-controlled cross-over study with a 1-week washout between cross-over periods . Methods Vitamin C 500 mg daily or matching placebo was given to 40 men and women aged between 60 and 80 years for 3 months each in a cross-over fashion . Clinic and 24-h ambulatory blood pressure , plasma ascorbate and lipids were measured at baseline and at the end of each cross-over phase . Results Clinic blood pressure did not change between placebo and vitamin C phases . Daytime ambulatory blood pressure showed a small but significant fall in systolic blood pressure ( 2.0 ± 5.2 mmHg ; 95 % confidence interval 0–3.9 mmHg ) but not in diastolic blood pressure . Regression analysis showed that with increasing baseline daytime blood pressure the fall in blood pressure with vitamin C supplementation increased . Regression analysis of the change in high-density lipoprotein ( HDL ) cholesterol showed a significant effect of sex on the change in HDL cholesterol . In women , but not men , HDL cholesterol increased significantly by 0.08 ± 0.11 mmol/l , P = 0.007 . There was no change in low-density lipoprotein cholesterol between treatment periods . Conclusion In older adults high intakes of ascorbic acid have modest effects on lowering high systolic blood pressure , which could contribute to the reported association between higher vitamin C intake and lower risk of cardiovascular disease and stroke The effect of vitamin C on blood pressure is not well established . This is a r and omized , double-blind control trial . Eligible patients were followed for 8 months . Patients were r and omized to 500 , 1000 , or 2000 mg vitamin C. During each visit , a history including medication change was obtained and st and ardized blood pressure measurements were performed . A 1-week dietary diary was filled out before each visit . Multiple regression analysis and subsequent multiple comparisons were used for data analysis . Fifty-four patients satisfied our criteria and agreed to participate . Thirty-one patients ( mean age , 62 ± 2 years ; 52 % men , 90 % whites ) were r and omized to the three doses of vitamin C. Overall compliance was 48 ± 2 % . Both mean systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) decreased during the vitamin C supplementation phase [ mean SBP dropped by 4.5 ± 1.8 mm Hg ( P < .05 ) and DBP by 2.8 ± 1.2 mm Hg ( P < .05 ) ] . There was no difference between the three vitamin C groups ( P = .48 ) . This effect was significant for only 1 month of supplementation , but the trend persisted . There was no reported intolerance to vitamin C. There was no change in lipid levels after 6 months of treatment . Vitamin C supplementation lowers blood pressure in mildly hypertensive patients . There is no additional benefit for a higher dose than 500 mg daily . The effect of vitamin C is most likely to be only short term BACKGROUND Essential hypertension is characterized by endothelial dysfunction , arterial stiffness , and increased oxidative stress . We evaluated the effect of short-term combined treatment with the antioxidants vitamins C and E on endothelial function , arterial stiffness , and oxidative stress in untreated essential hypertensive patients . METHODS A r and omized , double-blind , placebo-controlled , crossover study design was used to assign 30 male essential hypertensive patients to either vitamin C ( 1 g ) and vitamin E ( 400 IU ) or placebo for 8 weeks . Endothelium-dependent response was assessed as flow-mediated dilation ( FMD ) of the brachial artery . Arterial stiffness was assessed as central pulse wave velocity ( PWV ) and augmentation index ( AIx ) . Plasma markers of oxidative stress and antioxidant status were measured . RESULTS After vitamin supplementation , FMD was significantly improved . Central PWV was significantly reduced , while AIx tended to decrease . Plasma vitamin levels and antioxidant capacity increased significantly . Levels of oxidative stress decreased . Changes in central PWV were related to changes in levels of oxidative stress . CONCLUSIONS Combined treatment with vitamins C and E has beneficial effects on endothelium-dependent vasodilation and arterial stiffness in untreated , essential hypertensive patients . This effect is associated with changes in plasma markers of oxidative stress The effect of magnesium ( Mg ) and ascorbic acid ( AA ) supplementation on metabolic control was assessed in 56 outpatient diabetics . A 90-day run-in period was followed by two 90-day treatment periods , during which Mg ( 600 mg/day ) and AA ( 2 g/day ) were administered in a r and omized double-blind cross-over fashion . A decrease in systolic and diastolic blood pressure ( 132 + /- 3 vs. 138 + /- 4 and 77 + /- 2 vs. 82 + /- 2 mm Hg ; p < 0.05 ) was observed in insulin-dependent diabetes mellitus subjects during Mg supplementation . No beneficial effect of Mg supplementation was observed on glycemic control , lipids or blood pressure in non-insulin-dependent diabetes mellitus ( NIDDM ) subjects . AA supplementation improved glycemic control among NIDDM subjects and both fasting blood glucose ( 9.1 + /- 0.5 vs. 10.1 + /- 0.6 mmol/l ; p < 0.05 ) and HbA1c ( 8.5 + /- 0.3 vs. 9.3 + /- 0.3 % ; p < 0.05 ) improved . Beneficial effects of AA supplementation on cholesterol ( 5.9 + /- 0.2 vs. 6.2 + /- 0.2 mmol/l ; p < 0.05 ) and triglycerides ( 2.2 + /- 0.2 vs. 2.5 + /- 0.2 ; p < 0.05 ) were also observed in NIDDM subjects . The results suggest that high-dose AA supplementation may have a beneficial effect in NIDDM subjects on both glycemic control and blood lipids The important role of ascorbic acid ( AA ) as an anti-oxidant is particularly relevant in diabetes mellitus where plasma concentrations of AA are reduced . This study was conducted to evaluate the effects of treatment with AA or an aldose reductase inhibitor , tolrestat , on AA metabolism and urinary albumin excretion in diabetes . Blood and urine sample s were collected at 0 , 3 , 6 , 9 , and 12 months from 20 diabetic subjects who were r and omized into two groups to receive either oral AA 500 mg twice daily or placebo . Systolic and diastolic blood pressures , HbA1c , plasma lipids , urinary albumin , and total glycosaminoglycan excretion were measured at all time points , and heparan sulphate ( glycosaminoglycan ) was measured at 0 and 12 months . The same parameters , as well as urinary AA excretion , were determined at 0 and 3 months for 16 diabetes subjects receiving 200 mg tolrestat/day . AA treatment increased plasma AA ( ANOVA , F ratio = 12.1 , p = 0.004 ) and reduced albumin excretion rate ( AER ) after 9 months ( ANOVA , F ratio = 3.2 , p = 0.03 ) , but did not change the other parameters measured . Tolrestat lowered plasma AA ( Wilcoxon ’s signed-rank test , p < 0.05 ) , but did not change AER or the other parameters measured . The ability of AA treatment to decrease AER may be related to changes in extracellular matrix or improvement in oxidative defence mechanism . Unlike the rat model of diabetes , inhibition of aldose reductase did not normalize plasma AA or AER in humans . In fact , tolrestat reduced the plasma AA concentration , a phenomenon which may be due to increased utilization of AA . Dietary supplementation of AA in diabetic subjects may have long-term benefits in attenuating the progression of diabetic complications We have investigated the effect on blood pressure of treatment with vitamin C ( an antioxidant and free radical scavenger ) in patients with both systolic and essential hypertension . Following a 2-week run-in phase , two age- and sex-matched groups of untreated hypertensive subjects were r and omised in a double-blind study to receive 6 weeks ' oral treatment with either vitamin C , 250 mg twice daily ( n = 22 ; 8M/14F , mean age 73.7 + /- 4.9 years ) or placebo , one capsule twice daily ( n = 26 ; 10M/16F , mean age 73.8 + /- 5.3 years ) . Blood pressure was measured in the sitting position using a r and om zero sphygmomanometer on three occasions during the run-in phase , and again at 2 , 4 and 6 weeks after commencing treatment . Venous blood sample s for measurement of plasma ascorbic acid ( AA ) and lipid peroxides ( LP ) were measured in all subjects at baseline and at 4 and 6 weeks after the start of vitamin C or placebo treatment . During the study period , significant falls in both systolic ( vitamin C group , mean change -10.3 ( 95 % CI 0.7 - 20.0 ) mm Hg , p = 0.05 ) and diastolic ( vitamin C group , mean change -5.9 ( 95 % CI 0.2 - 11.5 ) mm Hg , p = 0.03 ; placebo group , mean change -4.7 ( 95 % CI 0.3 - 9.1 ) mm Hg , p = 0.05 ) blood pressure occurred . However , no statistical difference between the effects of either treatment on blood pressure was observed . At baseline , AA concentrations were lower in the vitamin C-treated group compared with the placebo group ( 44.6 + /- 2.4 vs. 57.7 + /- 4.2 mumol/l , p < 0.05 ) . ( ABSTRACT TRUNCATED AT 250 WORDS |
10,475 | 14,973,990 | There was no evidence of a statistically significant difference in the effectiveness of stabilisation splint therapy ( SS ) in reducing symptoms in patients with pain dysfunction syndrome compared with other active treatments .
There is weak evidence to suggest that the use of SS for the treatment of PDS may be beneficial for reducing pain severity , at rest and on palpation , when compared to no treatment .
REVIEW ER 'S CONCLUSIONS There is insufficient evidence either for or against the use of stabilisation splint therapy for the treatment of temporom and ibular pain dysfunction syndrome . | BACKGROUND Pain dysfunction syndrome ( PDS ) is the most common temporom and ibular disorder ( TMD ) .
There are many synonyms for this condition including facial arthromylagia , TMJ dysfunction syndrome , myofacial pain dysfunction syndrome , craniom and ibular dysfunction and myofacial pain dysfunction .
The aetiology of PDS is multifactorial and many different therapies have been advocated .
OBJECTIVES To establish the effectiveness of stabilisation splint therapy in reducing symptoms in patients with pain dysfunction syndrome . | The aim of the present study was to compare the effect of transcutaneous electric nerve stimulation ( TENS ) with the flat occlusal splint in the treatment of temporom and ibular joint ( TMJ ) disk displacement without reduction . Thirty-one patients were included and r and omly selected to be treated 6 weeks with either TENS ( 90 Hz , 30 min , three times/day ) or with a flat occlusal splint ( 24 h/day . Those selected for the TENS group had one electrode placed over the painful TMJ and another electrode over the anterior temporal muscle . The splint group used a conventional flat occlusal splint with cuspid guidance . Both treatment groups visited the clinic once a week . Symptoms and signs were registered before and after treatment . The intensity of pain was recorded with a visual analogue scale ( VAS ) and with an electronic pocket-sized recorder ( Pain-Track ) carried 1 week before and also the last week of treatment for continuous registration of pain . Measured with the VAS , half of the patients treated with splints became pain-free or their TMJ pain improved at least 50 % both at rest and with jaw function compared with only 6 % in the TENS-treated group . With regard to strictly chewing pain , the VAS-registered pain improved in two-thirds of the splint group , compared with 50 % of the TENS group . With the Pain-Track device it was found that in most individuals pain was aggrevated at mealtimes . The conclusion was that flat occlusal splints in several respects are better than TENS in the treatment of symptoms associated with TMJ disk displacement without reduction A r and omized clinical trial which included a follow-up of one year was applied to 118 myogenous TMD- patients . The therapies investigated were : physiotherapy of the masticatory system or splint therapy for patients without occlusal interferences , and occlusal adjustment therapy or the combination of splint and occlusal adjustment therapy for patients with pronounced occlusal interferences . Counseling , which yielded a reduction of 27 % of the scored pain intensity , will most likely eliminate any further need for treatment of patients with a low level of myogenous TMD signs and symptoms . Otherwise , physiotherapy might be preferred as a starting option with respect to splint therapy because of 1 . A similar efficacy ; 2 . A shorter treatment duration so that either chronic facial pain is earlier relieved or a patient can undergo a second type of therapy earlier ; and 3 . Lower costs . One third of the patients selected had pronounced occlusal interferences . Using stringent criteria it might be possible to apply occlusal adjustment therapy without involvement of splint therapy yielding a similar therapy efficacy and with advantages of a shorter treatment duration and lower costs . All types of therapy diminished not only facial pain but also pain of neck and shoulder areas In order to evaluate and compare the effects of biofeedback and occlusal splint therapy on m and ibular dysfunction , 30 patients were r and omly divided into two treatment groups . The patients were women aged 20 - -40 years without any obvious organic reasons for their symptoms . There were no significant differences between the two groups before the start of treatment in respect of signs and symptoms of m and ibular dysfunction . One group used full coverage splints at night for 6 weeks . The other group received biofeedback training up to six times , 30 min per session . One month after completion of the therapy the patients were re-examined . Both groups showed a significant reduction in symptoms , both subjectively and clinical ly . No significant differences between the groups were found . The two treatments were thus equally effective in the short-term perspective in patients with signs and symptoms of m and ibular dysfunction Sixty-three patients with an arthrographic diagnosis of disk displacement with reduction were r and omly assigned to three treatment groups : ( I ) onlays to maintain disk repositioning , ( II ) flat occlusal splint , or ( III ) untreated controls . Guidance for construction of the disk-repositioning onlays was established during arthrography to obtain a recaptured disk position relative to the condyle . The onlays were cemented to the teeth and maintained the new intercuspal position anteriorly and inferiorly . The flat occlusal splint was used at night only and was adjusted to maintain a maximal occlusal contact in centric relation and centric occlusion . Clinical examinations were performed before and after 6 months of treatment . The disk-repositioning onlays improved joint function and reduced joint and muscle pain when compared with the flat occlusal splint and with nontreatment . The signs and symptoms in the flat occlusal splint group were no different from those in the control group . It is concluded that disk-repositioning onlays are effective in reducing pain and dysfunction associated with disk displacement with reduction in patients in whom the disk can be maintained in a normal relationship to the condyle with the aid of such onlays . The symptoms , however , returned when the onlays were removed after 6 months ; this raises the question of whether a permanent change in the intercuspal position is necessary for long-term success Forty-five individuals with long-st and ing facial pain or headache of muscular origin were r and omly allocated into three groups . The first group was treated with acupuncture , the second group received an occlusal splint , and the third group served as controls . Both acupuncture and occlusal splint therapy significantly reduced subjective symptoms and clinical signs from the stomatognathic system . No differences between these two groups were found with regard to treatment effects . It is concluded that acupuncture is an alternative method to conventional stomatognathic treatment for individuals with craniom and ibular disorders of muscular origin Twenty-four patients were selected to participate in this study . Twelve patients were r and omly selected to receive occlusal splint therapy and the other 12 to receive a simplified relaxation therapy technique . Observable pain scores , maximum comfortable interincisal distance , and maximum interincisal distances were recorded for each group before and after treatment . The occlusal splint group showed a significant decrease in total mean observable pain scores ( decrease score of 10.5 , t = 3.124 ; P less than 0.1 ) . The relaxation group showed no significant decrease in total mean observable pain scores ( decrease score of 1.8 , t = 0.888 ; P = ns ) . The occlusal splint group showed a significant increase in the mean maximum comfortable opening ( an increase of 12.4 mm , t = 5.085 ; P less than .01 ) . The relaxation group showed no significant increase in the mean maximum comfortable opening ( an increase of 2.3 mm , t = 0.734 ; P = ns ) . The occlusal splint group showed a significant increase in the mean maximum opening ( an increase of 6.0 mm , t = 2.471 ; P less than .05 ) . The relaxation group showed no increase in the mean maximum opening ( decrease of 0.7 mm , t = 0.343 ; P = ns ) . This study suggests that occlusal splint therapy is a more effective treatment for the pain , tenderness , and limited m and ibular opening associated with temporom and ibular disorders than relaxation therapy . In this study , the relaxation technique used had no significant effect on the patients ' pain , tenderness , or limited opening To assess the differential efficacy of two commonly used treatments for temporom and ibular disorders ( TMD ) , intraoral appliances ( IAs ) and biofeedback ( BF ) , separately and in combination , two studies were conducted . The first study directly compared IA treatment , a combination of biofeedback and stress management ( BF/SM ) , and a waiting list control group in a sample of 80 TMD patients . Both treatments were determined to be equally credible to patients , ruling out this potential threat to the validity of the results obtained . The results demonstrated that the IA treatment was more effective than the BF/SM treatment in reducing pain after treatment , but at a 6-month follow-up the IA group significantly relapsed , especially in depression , whereas the BF/SM maintained improvements on both pain and depression and continued to improve . The second study examined the combination of IA and BF/SM in a sample of 30 TMD patients . The results of this study demonstrated that the combined treatment approach was more effective than either of the single treatments alone , particularly in pain reduction , at the 6-month follow-up . These results support the importance of using both dental and psychologic treatments to successfully treat TMD patients if treatment gains are to be maintained Stabilization appliances are commonly used in the treatment of temporom and ibular disorders ( TMD ) , although the treatment effects are not fully understood . This study evaluated the short-term efficacy of a stabilization appliance in patients with TMD of arthrogeneous origin , using a r and omized , controlled , and double-blind design . Sixty patients were assigned to two equally sized groups : a treatment group given a stabilization appliance and a control group given a control appliance . Improvement of overall subjective symptoms was reported in both groups but significantly more often in the treatment group than in the control group ( P = 0.006 ) . Frequency of daily or constant pain showed a significant reduction in the treatment group ( P = 0.02 ) compared with the control group . The results of this short-term evaluation showed that both the stabilization appliance and the control appliance had an effect on temporom and ibular joint ( TMJ ) pain . It is improbable that the difference observed between the groups is due to chance alone From a total of 1344 consecutive patients referred to a TMD clinic , twenty-six patients fulfilled the strict inclusion criteria s of TMD of mainly muscular origin . Half of the patients were assigned to receive treatment with an interocclusal appliance , the treatment being performed by a dentist . The other half was instructed to perform individualized therapeutic jaw exercises , and this treatment was managed by a dental assistant . The treatment result was evaluated after six months . The two treatments had a positive and equal effect upon both signs and symptoms of TMD . A further follow-up by question naire one to four years after the final clinical examination showed a lasting treatment result in most patients . Many patients , however , continued to perform jaw exercises and /or to wear their appliances . This indicates that these two treatments are mostly symptomatic and not causal . The conclusion of the present investigation is that therapeutic jaw exercises , managed by a dentist or a dental assistant , is a cost effective treatment with a prognosis comparable to a treatment with an interocclusal appliance and can thus be recommended as the first therapy of choice in patients with TMD of mainly muscular origin STATEMENT OF PROBLEM Soft and hard stabilizing appliances have been used to treat temporom and ibular disorders . No data exist to suggest whether a hard or soft appliance is beneficial . PURPOSE This study compared soft and hard acrylic resin stabilizing appliances in the reduction of masticatory muscle pain in patients with temporom and ibular disorders . MATERIAL S AND METHODS Twenty-three patients with at least one clinical sign from the list of diagnostic subgroups of temporom and ibular disorders were alternately assigned a hard or soft appliance for temporom and ibular disorder treatment . No other temporom and ibular disorder treatment ( self-care , physical therapy , biofeedback , or muscle or joint injections ) was rendered . Each patient was seen by two dentists at each visit . One dentist initially fabricated the appliance and adjusted the appliance on each visit and an examining dentist examined the patient each visit and recorded signs of temporom and ibular disorders . The appliance material ( soft or hard ) was not disclosed to the examining dentist , only to the dentist who fabricated and adjusted the appliance . Patients were examined and appliances were adjusted every 2 to 3 weeks for a minimum of 10 weeks . Masticatory muscles were palpated and charted on each visit . Data were analyzed and subjected to nonparametric Mann-Whitney test . RESULTS Eighteen of the initial 23 patients , 7 in the hard appliance group and 11 in the soft appliance group finished the study over 10- to 15-week period . Soft and hard appliances performed the same in reduction of masticatory muscle pain . CONCLUSION This study suggests , based on the limited number of participants , that soft and hard stabilizing appliances may be equally useful in reducing masticatory muscle pain in short-term appliance therapy Objective : To examine whether the stabilisation splint is a suitable treatment for pain dysfunction syndrome and to determine the most appropriate pattern of usage . Design : Prospect i ve r and om control clinical trial . Setting : Dental school clinic unit . Subjects : 70 patients diagnosed with pain dysfunction syndrome were treated with a stabilisation splint for 3 months . Group 1 ( 23 patients ) wore the splint 24 hours/day . Group 2 ( 19 patients ) wore the splint only during the day . Group 3 ( 28 patients ) wore the splint only at night . Results : There was no statistically significant advantage to any pattern of splint usage ; all groups showed a marked improvement by subjective and objective assessment . Conclusions : Patients being treated for pain dysfunction syndrome by a stabilisation splint need wear the splint only at BACKGROUND Hypnorelaxation has a potentially beneficial effect in the treatment of masticatory myofascial pain disorders ( MPD ) . However , there are no data regarding the efficacy of hypnorelaxation in the treatment of MPD compared with other accepted modes of treatment ( such as occlusal appliance ) or with the mere effect of time . OBJECTIVE AND SUBJECTS The purpose of the present study was to evaluate the effectiveness of hypnorelaxation in the treatment of MPD compared with the use of occlusal appliance and /or to minimal treatment . The study population consisted of 40 female patients with myofascial pain who were allocated to 1 of 3 possible treatment groups : ( 1 ) hypnorelaxation ( n = 15 ) , ( 2 ) occlusal appliance ( n = 15 ) , and ( 3 ) minimal treatment group ( n = 10 ) . RESULTS Both active treatment modes ( hypnorelaxation and occlusal appliance ) were more effective than minimal treatment regarding alleviating muscular sensitivity to palpation . However , only hypnorelaxation ( but not occlusal appliance ) was significantly more effective than minimal treatment with regard to the patient 's subjective report of pain on the Visual Analog Scale . CONCLUSION Hypnorelaxation is an effective mode of treatment in MPD , especially with regard to some of the subjective pain parameters Thirty subjects seeking treatment for masticatory muscle pain at a university-based TMJ clinic were r and omly assigned to soft-splint , palliative-treatment , and no-treatment groups . After 4 to 11 weeks of treatment , subjects were evaluated for changes from their baseline levels of symptoms , maximum pain-free opening , pain thresholds measured by a pressure algometer , and occlusal contacts . With the use of the multivariate analysis of variance and analysis of covariance , the results suggest that the soft-splint group had statistically significant improvement ( P < .01 ) , the palliative-treatment group had improvement that was not statistically significant , and the no-treatment group had a slight aggravation of symptoms . The soft-splint group had fewer occlusal contact changes assessed with shimstock compared to the palliative-treatment and no-treatment groups . The findings of this study suggest that the soft splint is an effective short-term treatment for reducing the signs and symptoms of masticatory muscle pain in patients , and the soft splint does not cause occlusal changes Twenty patients with m and ibular dysfunction , all women , aged 17 - 41 years , were r and omized for treatment with either a bite plate with a frontal plateau or a full-coverage stabilization splint . The occlusal appliances were used at night for 6 weeks to compare clinical and electromyographic effects ( EMGs ) . Integrated EMGs were recorded bilaterally from the anterior and posterior parts of the temporal muscle and the masseter muscle in the rest position and during gentle and maximal biting before and after treatment without the appliances in situ . Initially recorded EMG activity in the temporal muscle was correlated to signs of dysfunction in the rest position . Compared with previously investigated healthy subjects , the patients had lower EMG activity in the anterior part of the temporal muscle and in the masseter muscle during maximal biting . Use of occlusal appliances at night for 6 weeks did not change the EMG activity in the rest position or during maximal biting . The clinical signs improved , significantly in the splint group . The subjective symptoms improved in both groups , significantly more in the splint group A flat occlusal splint has been extensively used in the treatment of patients with temporom and ibular joint disk displacement without reduction , but no studies with untreated controls have assessed its effect . We r and omly assigned 51 patients with temporom and ibular joint pain and arthrographically verified disk displacement without reduction to be treated with a flat occlusal splint or to serve as untreated control subjects in a 12-month clinical trial . Pain symptoms disappeared in about one third of the patients in each group . Another third of the patients in the control group improved . Sixteen percent of the patients in the control group and 40 % of the patients treated with a flat occlusal splint were worse at the end than at the beginning of the study . Joint pain and muscle tenderness decreased more frequently in the nontreatment controls than in the treatment group . A statistically significant benefit of a flat occlusal splint over nontreatment control subjects could not be identified in this study of patients with painful disk displacement without reduction . The use of a flat occlusal splint in this patient group should therefore be reconsidered BACKGROUND The research literature reaches inconsistent conclusions about the efficacy of oral splints for treating myofascial face pain . This investigation hypothesizes that their effectiveness varies as a function of the presence or absence of widespread pain . METHODS In a r and omized , controlled clinical trial , 63 women with myofascial face pain were assigned to use of either an active , maxillary , flat-plane , hard acrylic splint or a palatal splint that did not interfere with occlusion . Participants also were classified according to the presence or absence of widespread pain throughout the body . After six weeks , groups were compared regarding pain on palpation , self-reported pain and functional outcome . RESULTS Overall , the findings showed a modest tendency for subjects receiving the active vs. the palatal splint to exhibit improvement on self-reported pain and functional outcome . On further division of the sample into subjects with local vs. widespread pain , the general pattern showed that patients with widespread pain who received an active splint did not experience improvement , while patients with local pain who received the active splint did . CONCLUSIONS The presence or absence of widespread pain may help to define the specific circumstances under which oral splints should be prescribed for patients with myofascial face pain . CLINICAL IMPLICATION S Clinicians should screen patients with myofascial face pain for the presence of widespread pain , since this comorbid symptom pattern may be a contraindication for the use of oral splints & NA ; Oral splints are widely used in the treatment of myofascial pain of masticatory muscles , even though their mechanism of action is unknown . The present study evaluated the therapeutic efficacy of splints using a parallel , r and omized , controlled and blind design . Following a sample size estimation , 63 subjects were recruited and assigned to 3 groups : ( 1 ) passive control : full occlusal splint worn only 30 min at each appointment : ( 2 ) active control : palatal splint worn 24 h/day : and ( 3 ) treatment : full occlusal splint worn 24 h/day . On each of 7 visits over 10 weeks , subjects rated on 100 mm visual analogue scales their pain intensity and unpleasantness at rest and after experimental mastication . The effect of pain on the quality of life was also rated on category scales . All pain ratings decreased significantly with time , and quality of life improved for all 3 groups . However , there were no significant differences between groups in any of the variables . These data suggest that the gradual reduction in the intensity and unpleasantness of myofascial pain , as well as the improvement of quality of life during the trial , was non‐specific and not related to the type of treatment Thirty patients with craniom and ibular disorders and headache were r and omly divided into two groups . One received occlusal equilibration ( O group ) and the other ( S group ) routine stomatognathic treatment , including an occlusal splint . The outcome of treatment was evaluated by means of a question naire , visual analogue scales , and clinical examination . In both groups , the patients reported reduction of symptoms , but the clinical dysfunction score used was significantly diminished only in the S group . A combined treatment regimen , including an occlusal splint , was more effective than occlusal adjustment alone , especially with regard to clinical signs of dysfunction The purpose of this study was to compare the effects of acupuncture and stomatognathic treatment on the mobility of the m and ible in r and om sample s of patients with TMJ dysfunction . One group of 25 patients was treated with acupuncture performed by a specialist in physical medicine and rehabilitation and a second similar group received st and ard stomatognathic treatment . All of the patients were evaluated in terms of the Helkimo dysfunction index by a dentist before treatment , within 1 week of treatment , and 3 months after treatment . No significant differences could be detected in painful movement of the m and ible except in retrusive movement , wherein stomatognathic treatment was clearly superior immediately afterward . Acupuncture seems to be a useful early form of therapy in patients with TMJ disorders that are expected to be largely functional and reversible and with evidence of psychophysiologic or neuromuscular disturbances but not of any marked occlusal interference or joint damage . Acupuncture could well be complementary to stomatognathic treatment , either preceding or following it , to achieve full neuromuscular rehabilitation , to ease the treatment ( for example , occlusal splints ) , or to eliminate other possible contributory factors |
10,476 | 12,137,697 | There were not any statistically significant differences between the groups in the mean body weight or occipitofrontal head circumference at three months or at six months corrected age .
REVIEW ER 'S CONCLUSIONS We did not find any evidence of benefit , but did find evidence of adverse effects , of transpyloric feeding in preterm infants .
Feeding via the transpyloric route can not be recommended for preterm infants | BACKGROUND Enteral feeding tubes for preterm infants may be placed in the stomach ( gastric tube feeding ) or in the upper small bowel ( transpyloric tube feeding ) .
There are potential advantages and disadvantages to both routes .
OBJECTIVES In preterm infants who require enteral tube feeding , does feeding via the transpyloric route versus the gastric route improve feeding tolerance , and growth and development , without increasing adverse consequences ? | Forty three infants under 1400 g were fed by a bolus nasogastric , continuous nasogastric , or transpyloric route . There were more complications with transpyloric feeding and no identifiable benefits in the growth rate , oral energy input , or chosen biochemical indices of nutrition . Bolus or continuous nasogastric feeds rather than transpyloric are better routine methods in infants of low birth weight We compared nasojejunal with nasogastric tube feeding in 18 healthy low-birth-weight infants from eight to 15 days of age . NJ-fed infants had significantly more stools and excreted significantly more fat and potassium in their stools . Growth and weight gain did not differ between the groups during the study period . Future use of NJ feeding in LBW infants should take into account the possibility of malabsorption associated with this technique There were 53 appropriate for gestational age infants with a birth weight of less than 1,700 gm admitted to the Children 's Hospital in Denver who were r and omly assigned to two groups for gavage or transpyloric ( nasojejunal ) feedings . The two groups were not significantly different in terms of gestational age , birth weight , and morbidity . No significant differences were observed for caloric intake after 4 days of age , growth parameters ( weight , length , and head circumference ) , serum total protein levels , feeding-related complications , duration of intravenous fluid supplementation , and length of hospitalization . The results indicate that intermittent gastric gavage feedings are as efficacious as transpyloric feedings in supplying nutrition to the low birth-weight infant . Because of inherently greater risks , costs , radiation , and requisite personnel expertise , transpyloric feedings can not be recommended as a routine method of feeding for the low birth-weight infant OBJECTIVE A relationship between gastroesophageal reflux ( GER ) and apnea of prematurity ( AOP ) has long been suspected but is difficult to prove because most GER in this age group is nonacidic and thus undetectable by pH monitoring , the current st and ard for GER detection . The new multiple intraluminal impedance ( MII ) technique allows pH-independent reflux detection via changes in impedance caused by a liquid bolus inside the esophagus . We used this technique to investigate whether there is a temporal relationship between GER and AOP and whether GER occurs predominantly before a cardiorespiratory ( CR ) event . METHODS Nineteen infants with AOP ( median gestational age at birth : 30 weeks ; range : 24 - 34 ; age at study : 26 days [ 13 - 93 ] ) underwent 20 6-hour recordings of MII , breathing movements , nasal airflow , electrocardiogram , pulse oximeter saturation , and pulse waveforms . MII signals were analyzed , independent of CR signals , for reflux episodes ( RE ) , defined as a fall in impedance in at least the 2 most distal channels . CR signals were analyzed for CR events , ie , apneas of > /=4-second duration , desaturations to < /=80 % , and falls in heart rate to < /=100/min . A temporal relationship between an RE and a CR event was considered present if both commenced within 20 seconds of each other . RESULTS There were 2039 apneas ( median : 67 ; range : 10 - 346 ) , 188 desaturations ( 6 ; 0 - 25 ) , 44 bradycardias ( 0 ; 0 - 24 ) , and 524 RE ( 25 ; 8 - 62 ) . The frequency of apnea occurring within + /- 20 seconds of an RE was not significantly different from that during reflux-free epochs ( 0.19/min [ 0.00 - 0.85 ] vs 0.25/min [ 0.00 - 1.15 ] ) ; the same was true for desaturations and bradycardias . Also , RE occurred similarly often within 20 seconds before as after an apnea ( 2 ; 0 - 14 vs 1 ; 0 - 17 ) . A minority of apneas ( 3.5 % ) was associated with an RE reaching the pharyngeal level ; of these , significantly more ( 45 vs 26 ; median : 1 ; 0 - 10 vs 1 ; 0 - 7 ) occurred after rather than before an RE . CONCLUSION Both CR events and GER were common in these infants but , with few exceptions , did not seem to be temporally related One hundred successive infants weighing less than 1500 g at birth were allocated alternately to intermittent nasogastric or continuous nasoduodenal feeding regimens . Eighty were appropriate for gestational age , and of these 25 fed successfully by nasogastric tube and 16 tolerated nasoduodenal feeding until 1600 g. No significant differences in either calorie intake or growth rates were identified throughout the seven weeks of the study . Because of the increased complexity and radiological exposure involved with feeding transpylorically , nasogastric feeding may be preferred as a method of feeding the low birthweight infant Continuous nasojejunal and intermittent nasogastric feedings were compared in a controlled prospect i ve study in 21 low-birth-weight infants . The groups were comparable in regard to period of gestation , birth weight , head circumference , and clinical findings . Cumulative weight gain , caloric and fluid intake , percent weight lost , blood chemistry values , and complications were used in evaluating the two groups . Upon completion of the 21-day study , N/J infants were found to have had statistically better weight gain , caloric intake , and fluid intake ( p = 0.05 - 0.001 ) during the early part of the study . Weight loss was less in the N/J group ( p less than 0.01 ) . Neither group had abnormalities of blood chemistry or significant complications . It is concluded that N/J feeding in the low-birth-weight neonate is a safe , effective means of early nutritional intake , with advantages most pronounced during the first two weeks of life |
10,477 | 14,571,290 | This meta- analysis demonstrates that amantadine and rimantadine are superior to placebo in the prevention of influenza A illness .
Both antiviral agents have an increased number of adverse events compared with placebo ; however , the use of amantadine is associated with significantly higher numbers of central nervous system events and treatment withdrawals compared with rimantadine . | PURPOSE To evaluate the efficacy and safety of amantadine and rimantadine , the first generation antivirals , for the prophylaxis of influenza virus . | Because the clinics in a multiclinic r and omized clinical trial represent neither fixed stratification effects nor r and om classificatory effects , the appropriate analysis of data from such a trial has been the subject of controversy and debate . The following are some of the elements of controversy that are discussed and for which some bases for resolution are proposed . Is it ever valid to ignore the effects of clinics in the analysis ? Is it ever valid to drop clinics from the analysis ? Is a multiclinic clinical trial similar in structure or not to a single-clinic clinical trial in which patients have been stratified on a classificatory factor ? Assuming that clinics will be taken account of in the analysis , should it be the weighted or the unweighted average of within-clinic treatment differences that is to be taken as the best estimate of the overall difference between the treatments ? How should the data be analyzed if there is evidence of treatment-by-clinic interaction The efficacy and safety of prophylactic low dose amantadine hydrochloride was assessed in two double-blind , placebo-controlled , r and omized studies . In a study of 476 subjects aged 18 to 55 years , adverse reactions were not significantly different between the group receiving 100 mg/day amantadine and the placebo group but significantly greater in the group given 200 mg/day ( P less than 0.009 ) . The influenza attack rate in this study was too low to assess efficacy . In an experimental challenge study of influenza A/Beth/1/85 in 78 subjects of similar age the prophylactic administration of 50 mg , 100 mg or 200 mg/day doses of amantadine were more effective than placebo in preventing influenza illness ( P less than 0.02 , 66 , 74 and 82 % protection , respectively ) , and in suppressing viral replication ( P = 0.02 ) . There was no significant difference between amantadine groups in influenza illness or viral shedding . Compared with the placebo group the 100 and 200 mg amantadine groups showed a significant decrease in infection rate ( 100 mg : 40 % protection : P = 0.012 ; 200 mg : 32 % protection : P = 0.045 ) whereas the 50 mg group did not ( 20 % protection : P = 0.187 ) . These results suggest that 100 mg/day of amantadine will reduce toxicity but maintain the prophylactic efficacy seen with 200 mg/day The relative toxicities of amantadine and rimantadine were compared in a double-blind , placebo-controlled study involving healthy adults . In separate studies , drugs were administered at a dosage of 200 mg/day ( 52 volunteers ) or 300 mg/day ( 196 volunteers ) for 4.5 days . Both drugs were well tolerated at the lower dosage . At 300 mg/day amantadine recipients had a greater frequency and severity of central nervous system ( nervousness , lightheadedness , difficulty concentrating ) and sleep ( insomnia , fatigue ) complaints compared with rimantadine or placebo recipients . Amantadine recipients also performed less well on an objective test measuring sustained attention and problem-solving ability . Both amantadine and rimantadine recipients reported adverse gastrointestinal symptoms more often than placebo recipients . Because of better tolerance at higher dosage , rimantadine offers more promise than amantadine for treatment of influenza A virus infections In a double-blind , placebo-controlled study , the comparative toxicities and blood concentrations of amantadine hydrochloride and rimantadine hydrochloride were determined . Healthy , working adults ingested either 200 ( n = 52 ) or 300 mg ( n = 196 ) per day in divided doses for 4.5 days . Mean plasma drug concentrations at 4 h after the first dose were lower in rimantadine recipients given 100- ( 140 versus 300 ng/ml for rimantadine and amantadine , respectively ; P less than 10(-5 ) ) or 200-mg doses ( 310 versus 633 ng/ml ; P less than 10(-5 ) ) . The plasma drug concentrations after the first dose correlated significantly with total symptom sources for both amantadine and rimantadine , but the plasma levels of toxic and nontoxic subjects overlapped extensively . At 300-mg/day dosage amantadine was associated more often with adverse central nervous system symptoms ( 33 % of amantadine versus 9 % of rimantadine recipients ; P less than 0.001 ) and sleep disturbance ( 39 versus 13 % ; P less than 0.001 ) , but not gastrointestinal symptoms ( 19.5 versus 16.0 % ) . However , no differences between the drugs were noted in symptom frequency or scores in volunteers with similar plasma concentrations . Amantadine and rimantadine differ in their pharmacokinetics but not in their potential for side effects at comparable plasma concentrations In a boarding school for boys , where routine influenza vaccination is carried out annually , 267 boys were given amantadine ( 100 mg daily ) and 269 received no specific treatment during an influenza A ( H1N1 ) outbreak . 3 boys receiving amantadine and 29 boys receiving no medication had laboratory-proven influenza A. There are circumstances when the prophylactic use of amantadine may be justified for the control of influenza A outbreaks in boarding schools and other institutions where high attack-rates are experienced Prophylactic administration of amantadine in doses of 100 mg . twice a day offered statistically significant protection against influenza A2 infection in a double-blind field trial involving 391 medical student volunteers during the influenza A2 Hong Kong epidemic in Helsinki in the winter of 1969 . Serologically verified influenza , as measured by complement fixation and /or haemagglutination inhibition , occurred in 27 out of 192 students in the amantadine group against 57 out of 199 in the placebo group , giving a protection rate of 52 % The usefulness of amantadine in the protection of humans against influenza A ( H1N1 ) virus was evaluated in a double-blind field trial with 555 volunteers in Finl and in the winter of 1978 . Three population s-- patients in a general hospital , adults in a home for the aged , and two groups of military conscripts -- were chosen . Epidemic influenza occurred only in the two groups of conscripts : the incidence of serologically verified influenza was 66 % and 83 % in the groups that received placebo and 43 % and 51 % in the groups that received amantadine , giving protection rates of 36 % ( P = 0.05 ) and 39 % ( P = 0.001 ) . The evaluation of the effect of amantadine on the occurrence of illness was obscured by concomitant adenoviral infections that caused influenza-like symptoms . No clear difference in the occurrences of side effects was observed between the placebo and amantadine-treated groups ; however , a significantly greater number of participants who took 200 mg of amantadine/day ( 16.9 % ) stopped medication during the trial as compared with the placebo groups ( 7.6 % ) ( P < 0.02 ) Abstract Early prophylactic treatment with 1-adamantanamine hydrochloride ( aminoadamantane , amantadine ) of household contacts of index cases of serologically confirmed influenza reduced the incidence of clinical influenza from 14.1 % to 3.6 % . Such treatment also produced a statistically significant reduction in the serological evidence of infection from 39.1 % in the placebo group to 14.6 % in the aminoadamantane-treated group . The incidence of sub clinical ( asymptomatic ) infections in the contacts of serologically confirmed index cases was reduced from 24.6 % in the placebo group to 14.6 % in the aminoadamantane-treated group Amantadine hydrochloride , a chemotherapeutic anti‐influenza compound , was tested for prophylactic and curative effects in double‐blind trials on 794 and 55 prisoner volunteers during an Asian influenza epidemic . Oral 200 mg . doses were given for 10 to 14 days . In the prophylactic trial , 5 of 439 ( 1.1 per cent ) drug‐treated subjects became ill in contrast to 15 of 355 ( 4.2 per cent ) placebo subjects , indicating significant protection . Among unselected drug‐treated subjects , fourfold or greater titer rises occurred in 30 per cent fewer subjects than in the placebo group ( p < 0.05 ) . Subjects with initial titers of 40 or less showed a 43 per cent titer rise difference ( p < 0.02 ) . Measured by the rises of mean titers , amantadine exerted a 52 per cent protection ( p < 0.05 ) . Reduced antibody titer rises accompanying therapeutic drug administration were not significant Abstract Objectives : To determine the extent to which publication is influenced by study outcome . Design : A cohort of studies su bmi tted to a hospital ethics committee over 10 years were examined retrospectively by review ing the protocol s and by question naire . The primary method of analysis was Cox 's proportional hazards model . Setting : University hospital , Sydney , Australia . Studies : 748 eligible studies su bmi tted to Royal Prince Alfred Hospital Ethics Committee between 1979 and 1988 . Main outcome measures : Time to publication . Results : Response to the question naire was received for 520 ( 70 % ) of the eligible studies . Of the 218 studies analysed with tests of significance , those with positive results ( P<0.05 ) were much more likely to be published than those with negative results ( P0.10 ) ( hazard ratio 2.32 ( 95 % confidence interval 1.47 to 3.66 ) , P=0.0003 ) , with a significantly shorter time to publication ( median 4.8 v 8.0 years ) . This finding was even stronger for the group of 130 clinical trials ( hazard ratio 3.13 ( 1.76 to 5.58 ) , P=0.0001 ) , with median times to publication of 4.7 and 8.0 years respectively . These results were not material ly changed after adjusting for other significant predictors of publication . Studies with indefinite conclusions ( 0.05 P<0.10 ) tended to have an even lower publication rate and longer time to publication than studies with negative results ( hazard ratio 0.39 ( 0.13 to 1.12 ) , P=0.08 ) . For the 103 studies in which outcome was rated qualitatively , there was no clear cut evidence of publication bias , although the number of studies in this group was not large . Conclusions : This study confirms the evidence of publication bias found in other studies and identifies delay in publication as an additional important factor . The study results support the need for prospect i ve registration of trials to avoid publication bias and also support restricting the selection of trials to those started before a common date in undertaking systematic review s. Key messages This retrospective cohort study of clinical research projects confirms the findings of publication bias found in previous studies Delay in the publication of studies with negative results has been identified as an additional important factor in publication bias With the recognised importance of evidence based medicine , these results have important implication s for the selection of studies included in systematic review s Prospect i ve registration of clinical research projects will avoid many of the problems associated with publication bias However , it is also important to restrict inclusion in systematic review s to studies started before a certain date to allow for the delay in completing studies with negative A placebo-controlled , double-blind study to evaluate the safety and prophylactic efficacy of a low dose ( 100 mg ) of rimantadine hydrochloride against naturally occurring influenza in adults was conducted at two sites . After the onset of the influenza season , volunteers ( ages , 18 to 55 years ) were assigned r and omly to receive rimantadine or placebo daily . Subjects were monitored for adverse effects and evidence of influenza virus infection weekly for six weeks . Only 10 ( 8.7 % ) of 114 rimantadine recipients and 5 ( 4.4 % ) of 114 placebo control recipients reported one or more mild to moderate adverse symptoms , most of which were related to the gastrointestinal or central nervous system . Compared with placebo , low-dose rimantadine was highly effective in the prevention of influenza A virus infection ( 20 of 110 versus 7 of 112 participants ; P less than 0.01 ) and influenza illness ( 7 of 110 versus 1 of 112 participants ; P = 0.04 ) . Influenza A/Leningrad/87-like ( H3N2 ) virus was recovered from the nasopharynxes of only five placebo recipients . These findings indicate that low-dose rimantadine is well tolerated and highly effective for the prevention of influenza A illness in healthy adults Prospect i ve virologic surveillance has defined two influenza epidemics representing the fifth and sixth outbreaks attributed to H3N2 viruses since the prototype , A/Hong Kong/68 ( ( H3N2 ) , emerged in 1968 . The 1975 epidemic was caused by influenza A/Port Chalmers and yielded an estimated attack rate of 9 per cent ; the second , attributed to influenza A/Victoria , produced an explosive outbreak , with an estimated attack rate of 18 per cent in 1976 . The highest morbidity occurred in preschool children , with an estimated attack rate of over 30 per cent . During the early stages of both epidemics there was a predominance of cases among school-aged children , and school absenteeism peaked earlier than other nonvirologic indexes . These observations support the concept of rapid dissemination of influenza among schoolchildren and suggest that control of epidemic influenza might be facilitated by prophylaxis for that age group and other accessible , healthy population Four hundred fifty volunteers participated in a placebo-controlled , double-blind , r and omized trial of the prophylactic effects of rimantadine and amantadine during an outbreak of influenza A. The subjects received drugs orally at a dose of 100 mg twice a day for six weeks . Influenza-like illness occurred in 41 per cent of the subjects receiving placebo but in only 14 per cent of those receiving rimantadine and 9 per cent of these receiving amantadine ( P less than 0.001 for either drug vs. placebo ) . Laboratory-documented influenza occurred in 21 per cent of placebo recipients , 3 per cent of rimantadine recipients , and 2 per cent of amantadine recipients ( P less than 0.001 ) . These findings represent efficacy rates of 85 per cent for rimantadine and 91 per cent for amantadine , as compared with placebo . More recipients of amantadine ( 13 per cent ) than recipients of rimantadine ( 6 per cent ; P less than 0.05 ) or placebo ( 4 per cent ; P less than 0.01 ) withdrew from the study because of central -nervous-system side effects . On the basis of this study , rimantadine appears to be the drug of choice for the prophylaxis of influenza The effectiveness of amantadine hydrochloride as a prophylactic against influenza was studied during an epidemic caused by viruses related to influenza A2/Hong Kong/1968 variants in Leningrad , USSR , early in 1969 . In all , 8169 subjects , assigned to amantadine-dosed , placebo-dosed , internal control and external control groups , were assessed . The index of effectiveness of the prophylactic medication , based on clinical diagnosis , in subjects who took amantadine regularly was 1.95 . When the clinical diagnoses were confirmed serologically the index of effectiveness for the amantadine compared with the placebo group increased to 2.7 . A comparison of the medicated group with the non-medicated , non-isolated internal control group showed an index of effectiveness of 5.34 . A daily dose of 100 mg of amantadine was associated with an increase of 1.14 % in complaints of sleep disturbances but these had no effect on the working capacity of subjects We tested the effectiveness of amantadine hydrochloride in prevention of illness and infection caused by Russian ( h1n1 ) influenza . The trial lasted seven weeks and was double-blind and placebo controlled . The dosage used was 200 mg daily . Efficacy in prevention of serologically confirmed clinical influenza was 70.7 % . Efficacy in prevention of infection , symptomatic or asymptomatic , was 39.4 % . Side effects seen were all mild , began within two days of the start of the trial , and terminated rapidly on cessation of prophylaxis . The withdrawal rate attributable to use of amantadine was 6.2 % . Those who continued to receive prophylaxis for the remainder of the trial did not exhibit excess side effects . It is concluded that amantadine is safe and effective in prophylaxis of H1N1 strains , as has been shown previously for other subtypes of A influenza |
10,478 | 29,039,160 | There was a reduction in the use of antibiotics in vaccinated children ( 2 trials , 1223 children ; RR 0.70 , 95 % CI 0.59 to 0.83 ; RD -0.11 , 95 % CI -0.16 to -0.06 ; moderate- quality evidence ) .We were unable to demonstrate whether there was any difference in the utilisation of health care .
Influenza vaccine results in a small reduction in AOM .
The benefits may not justify the use of influenza vaccine without taking into account the vaccine efficacy in reducing influenza and safety data . | BACKGROUND Acute otitis media ( AOM ) is one of the most common infectious diseases in children .
It has been reported that 64 % of infants have an episode of AOM by the age of six months and 86 % by one year .
Although most cases of AOM are due to bacterial infection , it is commonly triggered by a viral infection .
In most children AOM is self limiting , but it does carry a risk of complications .
Since antibiotic treatment increases the risk of antibiotic resistance , influenza vaccines might be an effective way of reducing this risk by preventing the development of AOM .
OBJECTIVES To assess the effectiveness of influenza vaccine in reducing the occurrence of acute otitis media in infants and children . | Background : We investigated the efficacy and safety of 1 versus 2 doses of live attenuated influenza vaccine ( LAIV ) in influenza vaccine – naive children aged 6 to < 36 months . Patients / Methods : Subjects were r and omized to 1 of 4 regimens in year 1 : 2 doses LAIV , 1 dose LAIV , excipient placebo , or saline placebo . In year 2 , LAIV recipients were to receive 1 dose of LAIV and placebo recipients were to receive saline placebo . Because of an unintended treatment allocation error in year 2 , 1 block of subjects who were r and omized to LAIV received saline placebo and 1 block who were r and omized to placebo received LAIV . Results : In year 1 , vaccine efficacy versus placebo among recipients of 2 and 1 doses of LAIV was 73.5 % and 57.7 % , respectively , against antigenically similar strains . In year 2 , absolute efficacy of a single dose of LAIV was 73.6 % and 65.2 % , respectively , in recipients of 2 and 1 doses of LAIV in year 1 . Year 2 efficacy was 57.0 % in subjects who received 2 doses of LAIV in year 1 and placebo in year 2 . Safety and tolerability of LAIV were consistent with previous studies . Reactogenicity was similar between placebo groups . Seroconversion rates were significantly higher in the 2-dose versus the 1-dose LAIV group in year 1 and in both LAIV groups versus placebo in years 1 and 2 . Conclusions : One dose of LAIV provided clinical ly significant protection against influenza in young children previously unvaccinated against influenza ; 2 doses provided additional protection . Protection after 2 doses in year 1 persisted through a second season without revaccination . LAIV excipients were not a major contributor to reactogenicity . These benefits provide support for increased use of LAIV in children ≥2 years of age Objective . To determine the safety of cold-adapted trivalent intranasal influenza virus vaccine ( CAIV ) in children and adolescents . Study design . A r and omized , double blind , placebo-controlled safety trial in healthy children age 12 months to 17 years given CAIV ( FluMist ; MedImmune Vaccines , Inc. ) or placebo ( r and omization , 2:1 ) . Children < 9 years of age received a second dose of CAIV or placebo 28 to 42 days after the first dose . Enrolled children were then followed for 42 days after each vaccination for all medically attended events . Prespecified outcomes included 4 prespecified diagnostic groups and 170 observed individual diagnostic categories . The relative risk and the 2-sided 90 % confidence interval were calculated for each diagnostic group and individual category by clinical setting , dose and age . More than 1500 relative risk analyses were performed . Results . A total of 9689 evaluable children were enrolled in the study . Of the 4 prespecified diagnostic categories ( acute respiratory tract events , systemic bacterial infection , acute gastrointestinal tract events and rare events potentially associated with wild-type influenza ) , none was associated with vaccine . Of the biologically plausible individual diagnostic categories , 3 , acute gastrointestinal events , acute respiratory events and abdominal pain , had different analyses that demonstrated increased and decreased relative risks , making their association with the vaccine unlikely . For reactive airway disease a significant increased relative risk was observed in children 18 to 35 months of age with a relative risk of 4.06 ( 90 % confidence interval , 1.29 to 17.86 ) in this age group . The individual diagnostic categories of upper respiratory infection , musculoskeletal pain , otitis media with effusion and adenitis/adenopathy had at least one analysis that achieved a significant increased risk ratio . All of these events were infrequent . Conclusion . CAIV was generally safe in children and adolescents . The observation of an increased risk of asthma/reactive airway disease in children < 36 months of age is of potential concern . Further studies are planned to evaluate the risk of asthma/reactive airway disease after vaccine BACKGROUND Universal vaccination of children 6 to 59 months of age with trivalent inactivated influenza vaccine has recently been recommended by U.S. advisory bodies . To evaluate alternative vaccine approaches , we compared the safety and efficacy of intranasally administered live attenuated influenza vaccine with those of inactivated vaccine in infants and young children . METHODS Children 6 to 59 months of age , without a recent episode of wheezing illness or severe asthma , were r and omly assigned in a 1:1 ratio to receive either cold-adapted trivalent live attenuated influenza vaccine ( a refrigeration-stable formulation of live attenuated intranasally administered influenza vaccine ) or trivalent inactivated vaccine in a double-blind manner . Influenza-like illness was monitored with cultures throughout the 2004 - 2005 influenza season . RESULTS Safety data were available for 8352 children , and 7852 children completed the study according to the protocol . There were 54.9 % fewer cases of cultured-confirmed influenza in the group that received live attenuated vaccine than in the group that received inactivated vaccine ( 153 vs. 338 cases , P<0.001 ) . The superior efficacy of live attenuated vaccine , as compared with inactivated vaccine , was observed for both antigenically well-matched and drifted viruses . Among previously unvaccinated children , wheezing within 42 days after the administration of dose 1 was more common with live attenuated vaccine than with inactivated vaccine , primarily among children 6 to 11 months of age ; in this age group , 12 more episodes of wheezing were noted within 42 days after receipt of dose 1 among recipients of live attenuated vaccine ( 3.8 % ) than among recipients of inactivated vaccine ( 2.1 % , P=0.076 ) . Rates of hospitalization for any cause during the 180 days after vaccination were higher among the recipients of live attenuated vaccine who were 6 to 11 months of age ( 6.1 % ) than among the recipients of inactivated vaccine in this age group ( 2.6 % , P=0.002 ) . CONCLUSIONS Among young children , live attenuated vaccine had significantly better efficacy than inactivated vaccine . An evaluation of the risks and benefits indicates that live attenuated vaccine should be a highly effective , safe vaccine for children 12 to 59 months of age who do not have a history of asthma or wheezing . ( Clinical Trials.gov number , NCT00128167 [ Clinical Trials.gov ] . ) BACKGROUND Recommendations vary regarding immediate antimicrobial treatment versus watchful waiting for children younger than 2 years of age with acute otitis media . METHODS We r and omly assigned 291 children 6 to 23 months of age , with acute otitis media diagnosed with the use of stringent criteria , to receive amoxicillin-clavulanate or placebo for 10 days . We measured symptomatic response and rates of clinical failure . RESULTS Among the children who received amoxicillin-clavulanate , 35 % had initial resolution of symptoms by day 2 , 61 % by day 4 , and 80 % by day 7 ; among children who received placebo , 28 % had initial resolution of symptoms by day 2 , 54 % by day 4 , and 74 % by day 7 ( P=0.14 for the overall comparison ) . For sustained resolution of symptoms , the corresponding values were 20 % , 41 % , and 67 % with amoxicillin-clavulanate , as compared with 14 % , 36 % , and 53 % with placebo ( P=0.04 for the overall comparison ) . Mean symptom scores over the first 7 days were lower for the children treated with amoxicillin-clavulanate than for those who received placebo ( P=0.02 ) . The rate of clinical failure -- defined as the persistence of signs of acute infection on otoscopic examination -- was also lower among the children treated with amoxicillin-clavulanate than among those who received placebo : 4 % versus 23 % at or before the visit on day 4 or 5 ( P<0.001 ) and 16 % versus 51 % at or before the visit on day 10 to 12 ( P<0.001 ) . Mastoiditis developed in one child who received placebo . Diarrhea and diaper-area dermatitis were more common among children who received amoxicillin-clavulanate . There were no significant changes in either group in the rates of nasopharyngeal colonization with nonsusceptible Streptococcus pneumoniae . CONCLUSIONS Among children 6 to 23 months of age with acute otitis media , treatment with amoxicillin-clavulanate for 10 days tended to reduce the time to resolution of symptoms and reduced the overall symptom burden and the rate of persistent signs of acute infection on otoscopic examination . ( Funded by the National Institute of Allergy and Infectious Diseases ; Clinical Trials.gov number , NCT00377260 . ) Background : Young children have a high incidence of influenza and influenza-related complications . This study compared the efficacy and safety of cold-adapted influenza vaccine , trivalent ( CAIV-T ) with trivalent inactivated influenza vaccine ( TIV ) in young children with a history of recurrent respiratory tract infections ( RTIs ) . Methods : Children 6 to 71 months of age were r and omized to receive 2 doses of CAIV-T ( n = 1101 ) or TIV ( n = 1086 ) , 35 ± 7 days apart before the start of the 2002–2003 influenza season and were followed up for culture-confirmed influenza , effectiveness outcomes , reactogenicity , and adverse events . Results : Overall , 52.7 % ( 95 % confidence interval [ CI ] = 21.6%–72.2 % ) fewer cases of influenza caused by virus strains antigenically similar to vaccine were observed in CAIV-T than in TIV recipients . Greater relative efficacy for CAIV-T was observed for the antigenically similar A/H1N1 ( 100.0 % ; 95 % CI = 42.3%–100.0 % ) and B ( 68.0 % ; 95 % CI = 37.3%–84.8 % ) strains but not for the antigenically similar A/H3N2 strains ( −97.1 % ; 95 % CI = −540.2 % to 31.5 % ) . Relative to TIV , CAIV-T reduced the number of RTI-related healthcare provider visits by 8.9 % ( 90 % CI = 1.5%–15.8 % ) and missed days of school , kindergarten , or day care by 16.2 % ( 90 % CI = 10.4%–21.6 % ) . Rhinitis and rhinorrhea , otitis media , and decreased appetite were the only events that were reported more frequently in CAIV-T subjects . There was no difference between groups in the incidence of wheezing after vaccination . Conclusions : CAIV-T was well tolerated in these children with RTIs and demonstrated superior relative efficacy compared with TIV in preventing influenza illness OBJECTIVE . The goal was to evaluate the safety , tolerability , and efficacy of an investigational , refrigerator-stable formulation of live attenuated influenza vaccine ( cold-adapted influenza vaccine-trivalent ) against culture-confirmed influenza , acute otitis media , and effectiveness outcomes in young children in day care over 2 consecutive influenza seasons . METHODS . Children 6 to < 36 months of age who were attending day care were assigned r and omly in year 1 to receive 2 doses of vaccine or placebo intranasally , 35 ± 7 days apart . In year 2 , subjects received 1 dose of the same treatment as in year 1 . RESULTS . A total of 1616 subjects ( vaccine : 951 subjects ; placebo : 665 subjects ) in year 1 and 1090 subjects ( vaccine : 640 subjects ; placebo : 450 subjects ) in year 2 were able to be evaluated for efficacy . The mean age at first vaccination was 23.4 ± 7.9 months . In year 1 , the overall efficacy of the vaccine against influenza subtypes similar to the vaccine was 85.4 % ; efficacy was 91.8 % against A/H1N1 and 72.6 % against B. In year 2 , the overall efficacy was 88.7 % ; efficacy was 90.0 % against H1N1 , 90.3 % against A/H3N2 , and 81.7 % against B. Efficacy against all episodes of acute otitis media associated with culture-confirmed influenza was 90.6 % in year 1 and 97.0 % in year 2 . Runny nose or nasal discharge after dose 1 in year 1 was the only reactogenicity event that was significantly more frequent with cold-adapted influenza vaccine-trivalent ( 82.3 % ) than placebo ( 75.4 % ) . CONCLUSIONS . Cold-adapted influenza vaccine-trivalent was well tolerated and effective in preventing culture-confirmed influenza illness in children as young as 6 months of age who attended day care Background Influenza attack rates are high in 6- to 35-month-old children ; vaccines containing both lineages of influenza B ( Yamagata and Victoria ) , in addition to the H3N2 and H1N1 antigens , may improve protection rates . Methods In a r and omized double-blind controlled trial , the immunogenicity and reactogenicity of an inactivated quadrivalent influenza vaccine ( QIV ) and a trivalent control vaccine ( TIV ) were assessed . Results Six hundred one children ( QIV , n = 299 ; TIV , n = 302 ) were enrolled at 8 sites in 3 countries . The primary immunogenicity objective was met : the lower limit ( LL ) of the 2-sided 95 % confidence interval ( CI ) for the seroconversion rate in QIV recipients ranged from 66.6 % to 81.3 % , which was ≥40 % against all 4 strains . The immunogenic superiority of the additional B/Victoria strain in the QIV compared to that in the TIV was confirmed : the LL of the 2-sided 95 % CI of the geometric mean titer ratio ( QIV/TIV ) ( 6.28 [ 95 % CI , 5.32–7.41 ] ) was greater than 1.5 , and the LL of the 2-sided 95 % CI for the difference in the seroconversion rate ( QIV – TIV ) ( 64.19 % [ 95 % CI , 57.65%–69.95 % ] ) was greater than 10 % . Injection-site pain and irritability/fussiness were the most commonly reported solicited injection-site and general adverse events , respectively , from days 0 to 6 and were similar in frequency between the groups . Conclusions In children aged 6 to 35 months , a QIV has superior immunogenicity for the added B strain and acceptable immunogenicity for shared strains , with no notable difference in reactogenicity and safety when compared to a TIV To evaluate the efficacy of an intranasal , inactivated , virosomal subunit influenza vaccine for prevention of new episodes of acute otitis media ( AOM ) in children with recurrent AOM , 133 children aged 1 - 5 years were r and omized to receive the vaccine ( n=67 ) or no vaccination ( n=66 ) . During a 6-month period , 24 ( 35.8 % ) vaccine recipients had 32 episodes of AOM ; 42 ( 63.6 % ) control subjects had 64 episodes . The overall efficacy of vaccination in preventing AOM was 43.7 % ( 95 % confidence interval , 18.6 - 61.1 ; P=.002 ) . Children vaccinated before influenza season had a significantly better outcome than did those vaccinated after the onset of influenza season . The cumulative duration of middle ear effusion was significantly less in vaccinated children than in control subjects . Data suggest that the intranasal virosomal influenza vaccine might be considered among the options for the prevention of AOM in children < 5 years old with recurrent AOM Abstract Background . This phase 2/3 , r and omized , placebo-controlled , observer-blinded study assessed the immunogenicity , reactogenicity , and safety of an inactivated , split-virion H5N1 influenza vaccine ( A/Indonesia/5/2005 ) in children aged 6 months through 17 years . Methods . Children received 2 influenza vaccine doses 21 days apart , each containing 1.9 µg of hemagglutinin and AS03B adjuvant ( 5.93 mg of α-tocopherol ) . The r and omization ratio was 8:3 for vaccine to placebo , with equal allocation between 3 age strata ( 6–35 months , 3–8 years , and 9–17 years ) . Immunogenicity against the vaccine strain was assessed 21 days after the first and second vaccine doses for all vaccinees , at day 182 for half , and at day 385 for the remaining half . Reactogenicity after each dose and safety up to 1 year after vaccination were evaluated . Results . Within each age stratum , the lower limit of the 98.3 % confidence interval for the day 42 seroprotection rate was ≥70 % , thus fulfilling the US and European licensure criteria . The immune responses elicited by vaccine persisted well above baseline levels for 1 year . The vaccine was more reactogenic than placebo , but no major safety concerns were identified . Conclusions . AS03B-adjuvanted H5N1 influenza vaccine was immunogenic and showed an acceptable safety profile in all age groups studied . Clinical Trials Registration . NCT01310413 BACKGROUND The efficacy of antimicrobial treatment in children with acute otitis media remains controversial . METHODS In this r and omized , double-blind trial , children 6 to 35 months of age with acute otitis media , diagnosed with the use of strict criteria , received amoxicillin-clavulanate ( 161 children ) or placebo ( 158 children ) for 7 days . The primary outcome was the time to treatment failure from the first dose until the end-of-treatment visit on day 8 . The definition of treatment failure was based on the overall condition of the child ( including adverse events ) and otoscopic signs of acute otitis media . RESULTS Treatment failure occurred in 18.6 % of the children who received amoxicillin-clavulanate , as compared with 44.9 % of the children who received placebo ( P<0.001 ) . The difference between the groups was already apparent at the first scheduled visit ( day 3 ) , at which time 13.7 % of the children who received amoxicillin-clavulanate , as compared with 25.3 % of those who received placebo , had treatment failure . Overall , amoxicillin-clavulanate reduced the progression to treatment failure by 62 % ( hazard ratio , 0.38 ; 95 % confidence interval [ CI ] , 0.25 to 0.59 ; P<0.001 ) and the need for rescue treatment by 81 % ( 6.8 % vs. 33.5 % ; hazard ratio , 0.19 ; 95 % CI , 0.10 to 0.36 ; P<0.001 ) . Analgesic or antipyretic agents were given to 84.2 % and 85.9 % of the children in the amoxicillin-clavulanate and placebo groups , respectively . Adverse events were significantly more common in the amoxicillin-clavulanate group than in the placebo group . A total of 47.8 % of the children in the amoxicillin-clavulanate group had diarrhea , as compared with 26.6 % in the placebo group ( P<0.001 ) ; 8.7 % and 3.2 % of the children in the respective groups had eczema ( P=0.04 ) . CONCLUSIONS Children with acute otitis media benefit from antimicrobial treatment as compared with placebo , although they have more side effects . Future studies should identify patients who may derive the greatest benefit , in order to minimize unnecessary antimicrobial treatment and the development of bacterial resistance . ( Funded by the Foundation for Paediatric Research and others ; Clinical Trials.gov number , NCT00299455 . ) BACKGROUND Current laboratory tests often can not distinguish between bacterial and aseptic meningitis rapidly and accurately . The ability to make a prompt diagnosis has important implication s for the management and outcome of children with meningitis . The observation that leukocytes aggregate in the cerebrospinal fluid ( CSF ) has been previously reported , and it has been advocated as a reliable method to distinguish the causes of meningitis in children . OBJECTIVE To investigate the utility of CSF leukocyte aggregation as a screening test to distinguish between bacterial and aseptic meningitis . METHODS We compared the clinical and laboratory indices of 109 prospect ively enrolled patients with meningitis ( 67 bacterial , 23 viral , 19 undefined etiology ) and evaluated the validity of the CSF leukocyte aggregation test . The predefined leukocyte aggregation scores ( LAS ) were compared among the types of meningitis , and correlations with other markers of inflammation were calculated . RESULTS The median LAS was significantly higher ( P < 0.001 ) in the bacterial ( 32.1 % ; range , 0 to 84.1 % ) than in the viral ( 0 % ; range , 0 to 16.6 % ) or undefined ( 0 % ; range , 0 to 20.7 % ) groups . The optimal sensitivity of the leukocyte aggregation test , 98.5 to 92.5 % , was demonstrated with LAS values of 0 to 3 % . The corresponding specificity was 64.3 to 88.1 % . The peripheral white blood cell ( WBC ) count , serum C-reactive protein , CSF WBC count , blood culture , CSF Gram stain and CSF culture were inferior to the LAS as screening tests when compared individually . The LAS was as effective as CSF protein , TNF-alpha , IL-1-beta , IL-6 and IL-8 to predict bacterial meningitis . In a logistic regression model that included routine laboratory tests , the best predictor of bacterial meningitis was the LAS ( odds ratio , 1.6 to 3.7 ) . Significant correlations were demonstrated between the LAS and CSF protein , CSF WBC count , IL-1-beta , IL-6 and IL-8 . Duration of symptoms before diagnosis , pretreatment with antibiotics , HIV-1 infection status and CSF red blood cell count did not significantly alter the LAS . CONCLUSIONS There is no single test to diagnose the etiology of meningitis in children promptly and accurately . The finding of leukocyte aggregation in CSF might be of value as a sensitive adjunctive screening tool for the timely diagnosis of bacterial meningitis , recognizing that it has low specificity and potential practical limitations A multicenter , double-blind , r and omized , active-control phase III clinical trial was performed to assess the immunogenicity and safety of a trivalent , inactivated split influenza vaccine . Korean children between the ages of 6 months and 18 y were enrolled and r and omized into a study ( study vaccine ) or a control vaccine group ( commercially available trivalent , inactivated split influenza vaccine ) in a 5:1 ratio . Antibody responses were determined using hemagglutination inhibition assay , and post-vaccination immunogenicity was assessed based on seroconversion and seroprotection rates . For safety assessment , solicited local and systemic adverse events up to 28 d after vaccination and unsolicited adverse events up to 6 months after vaccination were evaluated . Immunogenicity was assessed in 337 and 68 children of the study and control groups . In the study vaccine group , seroconversion rates against influenza A/H1N1 , A/H3N2 , and B strains were 62.0 % ( 95 % CI : 56.8–67.2 ) , 53.4 % ( 95 % CI : 48.1–58.7 ) , and 54.9 % ( 95 % CI : 48.1–60.2 ) , respectively . The corresponding seroprotection rates were 95.0 % ( 95 % CI : 92.6–97.3 ) , 93.8 % ( 95 % CI : 91.2–96.4 ) , and 95.3 % ( 95 % CI : 93.0–97.5 ) . The lower 95 % CI limits of the seroconversion and seroprotection rates were over 40 % and 70 % , respectively , against all strains . Seroconversion and seroprotection rates were not significantly different between the study and control vaccine groups . Furthermore , the frequencies of adverse events were not significantly different between the 2 vaccine groups , and no serious vaccination-related adverse events were noted . In conclusion , the study vaccine exhibited substantial immunogenicity and safety in Korean children and is expected to be clinical ly effective BACKGROUND Influenzavirus vaccine is used infrequently in healthy children , even though the rates of influenza in this group are high . We conducted a multicenter , double-blind , placebo-controlled trial of a live attenuated , cold-adapted , trivalent influenzavirus vaccine in children 15 to 71 months old . METHODS Two hundred eighty-eight children were assigned to receive one dose of vaccine or placebo given by intranasal spray , and 1314 were assigned to receive two doses approximately 60 days apart . The strains included in the vaccine were antigenically equivalent to those in the inactivated influenzavirus vaccine in use at the time . The subjects were monitored with viral cultures for influenza during the subsequent influenza season . A case of influenza was defined as an illness associated with the isolation of wild-type influenzavirus from respiratory secretions . RESULTS The intranasal vaccine was accepted and well tolerated . Among children who were initially seronegative , antibody titers increased by a factor of four in 61 to 96 percent , depending on the influenza strain . Culture-positive influenza was significantly less common in the vaccine group ( 14 cases among 1070 subjects ) than the placebo group ( 95 cases among 532 subjects ) . The vaccine efficacy was 93 percent ( 95 percent confidence interval , 88 to 96 percent ) against culture-confirmed influenza . Both the one-dose regimen ( 89 percent efficacy ) and the two-dose regimen ( 94 percent efficacy ) were efficacious , and the vaccine was efficacious against both strains of influenza circulating in 1996 - 1997 , A(H3N2 ) and B. The vaccinated children had significantly fewer febrile illnesses , including 30 percent fewer episodes of febrile otitis media ( 95 percent confidence interval , 18 to 45 percent ; P<0.001 ) . CONCLUSIONS A live attenuated , cold-adapted influenzavirus vaccine was safe , immunogenic , and effective against influenza A(H3N2 ) and B in healthy children Context . The heptavalent pneumococcal conjugate vaccine ( PCV ) is recommended for infants to protect against invasive disease , but its impact on otitis might also have public health importance . Objective . To examine the impact of PCV on the incidence of otitis media , frequent otitis media and tympanostomy tube procedures and to assess whether the effectiveness of the vaccine wanes after age 24 months and varies by race , sex or season . Design , setting and patients .. From 1995 to 1998 , 37 868 children at Kaiser Permanente in Northern California were r and omized to receive PCV or a control vaccine in a double blind trial and were followed through April 1999 . Interventions . Children received a primary series at 2 , 4 and 6 months of age and a booster at 12 to 15 months . Main outcome measures . Visits for otitis , frequent visits for otitis and tympanostomy tube procedures . Otitis was ascertained from diagnosis checklists routinely marked by physicians . Results . Control children averaged 1.8 otitis visits per year . Children given PCV had fewer otitis visits than control children in every age group , sex , race and season examined . Intention-to-treat analysis permitted rejection of the null hypothesis that PCV is ineffective against otitis media ( P < 0.0001 ) . In children who completed the primary series per protocol , PCV reduced otitis visits by 7.8 % [ 95 % confidence interval ( CI ) , 5.4 to 10.2 % ] and antibiotic prescriptions by 5.7 % ( CI 4.2 to 7.2 % ) . Frequent otitis was reduced by amounts that increased with otitis frequency , from a 10 % reduction in the risk of 3 visits to a 26 % reduction in the risk of 10 visits within a 6-month period . Tube placements were reduced by 24 % ( CI 12 to 35 % ) . Conclusion . In children followed up to 3.5 years , PCV provided a moderate amount of protection against ear infections while reducing frequent otitis media and tube procedures by greater amounts Our aim was to evaluate effectiveness of p and emic influenza A/H1N1 vaccine in preventing acute otitis media ( AOM ) and /or otitis media with effusion ( OME ) , in a r and omized , prospect i ve and single-blind study conducted in the children aged of 6–60 months . This study was done between December 1 , 2009 and April 30 , 2010 during the p and emia between June 2009 and May 2010 . On the healthy children , vaccinated against p and emic influenza A/H1N1 and age-matched unvaccinated controls , the rate of AOM , OME , and any otitis media ( OM ) attack ( sum of AOM and OME attacks ) confirmed by otoscopic and tympanometric examination , and their associations with risk factors were looked for . Otoscopic and tympanometric evaluation was done twice within the follow-up period of 4–8 weeks . Totally 46 vaccinated and 46 unvaccinated healthy children were enrolled . No difference in rates of AOM , OME , or OM was found between vaccinated and unvaccinated children . But logistic regression analysis revealed that unvaccinated children had 2.9-folds more risk for OME and OM , but not for AOM . Further , male gender and bottle feeding and /or using pacifier revealed significant relationships with AOM . Conclusion : We conclude that p and emic influenza A/H1N1 vaccine prevented OME rather than AOM attacks in children with 6–60 months of age Background : This study was design ed to evaluate the efficacy and safety of cold-adapted influenza vaccine , trivalent ( CAIV-T ) against culture-confirmed influenza in children 12 to < 36 months of age during 2 consecutive influenza seasons at multiple sites in Asia . Methods : In year 1 , 3174 children 12 to < 36 months of age were r and omized to receive 2 doses of CAIV-T ( n = 1900 ) or placebo ( n = 1274 ) intranasally ≥28 days apart . In year 2 , 2947 subjects were rer and omized to receive 1 dose of CAIV-T or placebo . Results : Mean age at enrollment was 23.5 ± 7.4 months . In year 1 , efficacy of CAIV-T compared with placebo was 72.9 % [ 95 % confidence interval ( CI ) : 62.8–80.5 % ] against antigenically similar influenza subtypes , and 70.1 % ( 95 % CI : 60.9–77.3 % ) against any strain . In year 2 , revaccination with CAIV-T demonstrated significant efficacy against antigenically similar ( 84.3 % ; 95 % CI : 70.1–92.4 % ) and any ( 64.2 % ; 95 % CI : 44.2–77.3 % ) influenza strains . In year 1 , fever , runny nose/nasal congestion , decreased activity and appetite , and use of fever medication were more frequent with CAIV-T after dose 1 . Runny nose/nasal congestion after dose 2 ( year 1 ) and dose 3 ( year 2 ) and use of fever medication after dose 3 ( year 2 ) were the only other events reported significantly more frequently in CAIV-T recipients . Conclusions : CAIV-T was well tolerated and effective in preventing culture-confirmed influenza illness over multiple and complex influenza seasons in young children in Asia Background . Recent studies indicate that influenza can be clinical ly important in otherwise healthy children . However , the interpretation of many studies is limited because of lack of laboratory confirmation of influenza-like illnesses . Therefore it is difficult to conclude whether the socioeconomic impact of influenza justifies vaccinating all children regardless of age or underlying chronic disorders . Methods . We prospect ively collected data from 3771 children younger than 14 years of age presenting to emergency departments or primary care pediatricians with symptoms of respiratory tract infection during the influenza season of 2001 to 2002 . Influenza infections were verified by virus culture or polymerase chain reaction . We additionally r and omized 303 children age 6 months to 5 years to receive either influenza vaccine ( n = 202 ) or no vaccination ( n = 101 ) before the influenza season . The socioeconomic impact of influenza was assessed for both the participating children and their household contacts . Results . Influenza was documented in 352 ( 9.3 % ) of the 3771 children . Compared with influenza-negative children , children with influenza had longer duration s of fever and absenteeism from day care or school ( P < 0.0001 ) . Further the numbers of medical visits , missed work or school days and the need for help at home to care for the sick children were higher among the household contacts of influenza-positive children ( P < 0.0001 ) . Influenza vaccination reduced significantly the direct and indirect influenza-related costs in healthy children and their unvaccinated family members . Conclusions . The findings of this study support a wider use of influenza vaccine in healthy children of all ages to reduce the socioeconomic burden of influenza on the community Live attenuated , cold-adapted ( ca ) monovalent and bivalent influenza A vaccines were evaluated in seronegative infants ( ages 6 - 18 months ) in a double-blind placebo-controlled trial to assess safety and immunogenicity . A total of 182 seronegative subjects received a single intranasal dose ( 10(6.2 ) TCID50 ) of ca A/Kawasaki/9/86 ( H1N1 ) or ca A/Los Angeles/2/87 ( H3N2 ) , both as a bivalent vaccine , or placebo . Respiratory and systemic symptoms did not differ between groups after vaccination . Hemagglutination antibody seroconversions ( > or = 1:8 ) to H3N2 exceeded 90 % . In contrast , seroconversions to A/Kawasaki/9/86 ( H1N1 ) were significantly less frequent in bivalent ca vaccine recipients ( 31 % ) than in monovalent ca H1N1 recipients ( 83 % ) ( P < .002 ) . During a subsequent H3N2 epidemic , nasal washes were cultured for viruses from any subject with respiratory illness . H3N2 infections documented by virus isolation were reduced by 65 % in ca H3N2 recipients compared with placebo or ca HIM recipients ( P = .01 ) BACKGROUND The efficacy of inactivated influenza vaccine in healthy infants and children younger than 24 months has not been confirmed . The aim of the present study was to determine the prophylactic effect of inactivated influenza vaccine against influenza A in healthy children aged 6 - 24 months . METHODS Healthy infants and young children ( 6 - 24 months old ) were immunized by subcutaneous injection of inactivated influenza vaccine before influenza seasons . Age matched children were r and omly assigned as the control . These children were followed up from January to April in each year ( 2000 , 2001 and 2002 ) . The attack rates of influenza A infection was compared and statistically assessed . RESULTS The attack rate of influenza A virus infection in the vaccine group and the control group were 14.8 % ( n = 27 ) vs 12.5 % ( n = 32 ) in 2000 ( P = 0.526 ) ; 2.8 % ( n = 72 ) vs 7.2 % ( n = 69 ) in 2001 ( P = 0.203 ) ; and 3.4 % ( n = 52 ) vs 8.9 % ( n = 56 ) in 2002 ( P = 0.205 ) . The attack rates of influenza A between the two groups were not significantly different . CONCLUSIONS Inactivated influenza vaccine did not reduce the attack rate of influenza A infection in 6 - 24 month old children To evaluate the effectiveness of influenza vaccination in reducing respiratory-related morbidity among children with recurrent respiratory tract infections ( RRTIs ) and their household contacts , 127 children aged 6 months-9 years ( 78 males ; median age , 3.7 years ) with a history of RRTIs ( > /=6 episodes per year if aged > /=3 years ; > /=8 episodes per year if aged <3 years ) were r and omized to receive the intranasal virosomal influenza vaccine ( n=64 with 176 household contacts ) or a control placebo ( n=63 with 173 household contacts ) . During influenza season , the vaccinated children had fewer respiratory infections , febrile respiratory illnesses , prescribed antibiotics and antipyretics , and missed school days than the controls , and similar benefits and a reduction in the loss of parental work were observed among their household contacts . This study shows that the benefits of influenza vaccination extend to children with RRTIs and their family members and encourages to recommend its use in such children Background : Acute otitis media ( AOM ) is a frequent complication of influenza in young children . Influenza vaccination is known to protect against AOM by preventing influenza illness . We sought to determine the efficacy of the live attenuated influenza vaccine ( LAIV ) against influenza-associated AOM compared with placebo and trivalent inactivated influenza vaccine ( TIV ) . LAIV is approved for eligible children aged ≥2 years in the United States and in several other countries . Methods : AOM incidence data from 6 r and omized , double-blind , placebo-controlled trials and 2 r and omized , double-blind , TIV-controlled trials in children 6 to 83 months of age were pooled and analyzed . Results : A total of 290 cases of AOM were identified in 24,046 study subjects . LAIV efficacy against influenza-associated AOM was 85.0 % ( 95 % confidence interval [ CI ] , 78.3%–89.8 % ) compared with placebo and 54.0 % ( 95 % CI , 27.0%–71.7 % ) compared with TIV . Efficacy trended higher in those ≥24 months of age compared with those aged 6 to 23 months . In placebo-controlled trials , among children who acquired influenza despite vaccination , AOM was diagnosed in 10.3 % of LAIV recipients and 16.8 % of placebo recipients , representing a 38.2 % ( 95 % CI , 11.0%–58.2 % ) relative reduction in the development of AOM . In TIV-controlled studies , among subjects with breakthrough influenza illness , the proportions of LAIV and TIV recipients who developed AOM were similar . Conclusions : Children receiving LAIV had a high level of protection against influenza-associated AOM when compared with placebo or TIV . This was most evident in children older than 2 years , for whom LAIV is indicated . LAIV recipients who contracted breakthrough influenza illness despite vaccination developed AOM at a significantly lower rate than did unvaccinated children who developed influenza CONTEXT Acute otitis media ( AOM ) frequently complicates influenza infection . Previous studies have found influenza vaccine effective in reducing the occurrence of AOM in children mainly older than 2 years . OBJECTIVE To evaluate the effectiveness of inactivated influenza vaccine in preventing AOM in children aged 6 to 24 months . DESIGN , SETTING , AND PATIENTS R and omized , double-blind , placebo-controlled trial of 786 children aged 6 to 24 months enrolled at Children 's Hospital of Pittsburgh before the 1999 - 2000 ( 411 children ) and 2000 - 2001 ( 375 children ) respiratory seasons ( defined as December 1 through March 31 of the respective following year ) . Children received influenza vaccine or placebo in a 2:1 ratio . The first cohort was observed for 1 year and the second cohort until the end of the ensuing respiratory season . INTERVENTION Two doses ( 0.25 mL each ) of inactivated trivalent subvirion influenza vaccine or placebo were administered intramuscularly approximately 4 weeks apart . MAIN OUTCOME MEASURES Proportion of children who developed AOM , monthly occurrence rate of AOM , estimated proportion of time with middle ear effusion , and utilization of selected health care and related re sources . RESULTS Of the 66 children in the vaccine group from whom serum sample s were collected , seroconversion against strains in the vaccine formulations developed in 88.6 % to 96.8 % , depending on the specific strain . The efficacy of the vaccine against culture-confirmed influenza was 66 % ( 95 % confidence interval [ CI ] , 34%-82 % ) in 1999 - 2000 and -7 % ( 95 % CI , -247 % to 67 % ) in 2000 - 2001 ; however , influenza attack rates differed between these 2 periods ( in the placebo group , 15.9 % and 3.3 % , respectively ) . Compared with placebo , influenza vaccine did not reduce the proportion of children who had at least 1 episode of AOM during the respiratory season ( in the first cohort : vaccine , 49.2 % vs placebo , 52.2 % ; P = .56 ] ; in the second cohort : vaccine , 55.8 % vs placebo , 48.3 % ; P = .17 ) . The vaccine also did not reduce the monthly rate of AOM ; the estimated proportion of time with middle ear effusion ; or the utilization of selected health care and related re sources . There were also no differences between the vaccine and placebo groups regarding any of these outcomes during peak influenza periods . The vaccines administered to both cohorts of children were well tolerated . CONCLUSION Administration of inactivated trivalent influenza vaccine to children aged 6 to 24 months did not reduce their burden of AOM or their utilization of selected health care and related re sources BACKGROUND Ear infections are a common cause of illness during the first two years of life . New conjugate vaccines may be able to prevent a substantial portion of cases of acute otitis media caused by Streptococcus pneumoniae . METHODS We enrolled 1662 infants in a r and omized , double-blind efficacy trial of a heptavalent pneumococcal polysaccharide conjugate vaccine in which the carrier protein is the nontoxic diphtheria-toxin analogue CRM197 . The children received either the study vaccine or a hepatitis B vaccine as a control at 2 , 4 , 6 , and 12 months of age . The clinical diagnosis of acute otitis media was based on predefined criteria , and the bacteriologic diagnosis was based on a culture of middle-ear fluid obtained by myringotomy . RESULTS Of the children who were enrolled , 95.1 percent completed the trial . With the pneumococcal vaccine , there were more local reactions than with the hepatitis B vaccine but fewer than with the combined whole-cell diphtheria-tetanus-pertussis and Haemophilus influenzae type b vaccine that was administered simultaneously . There were 2596 episodes of acute otitis media during the follow-up period between 6.5 and 24 months of age . The vaccine reduced the number of episodes of acute otitis media from any cause by 6 percent ( 95 percent confidence interval , -4 to 16 percent [ the negative number indicates a possible increase in the number of episodes ] ) , culture-confirmed pneumococcal episodes by 34 percent ( 95 percent confidence interval , 21 to 45 percent ) , and the number of episodes due to the serotypes contained in the vaccine by 57 percent ( 95 percent confidence interval , 44 to 67 percent ) . The number of episodes attributed to serotypes that are cross-reactive with those in the vaccine was reduced by 51 percent , whereas the number of episodes due to all other serotypes increased by 33 percent . CONCLUSIONS The heptavalent pneumococcal polysaccharide-CRM197 conjugate vaccine is safe and efficacious in the prevention of acute otitis media caused by the serotypes included in the vaccine A trivalent inactivated influenza vaccine ( CSL 's TIV , CSL Limited ) was licensed under USA accelerated approval regulations for use in persons≥18 years . We performed a r and omized , observer-blind study to assess the safety and immunogenicity of CSL 's TIV versus an established US-licensed vaccine in a population ≥6 months to < 18 years of age . Subjects were stratified as follows : Cohort A ( ≥6 months to <3 years ) ; Cohort B ( ≥3 years to < 9 years ) ; and Cohort C ( ≥9 years to < 18 years ) . The subject 's age and influenza vaccination history determined the dosing regimen ( one or two vaccinations ) . Subjects received CSL 's TIV ( n=739 ) or the established vaccine ( n=735 ) in the autumn of 2009 . Serum hemagglutination-inhibition titers were determined pre-vaccination and 30 days after the last vaccination . No febrile seizures or other vaccine-related SAEs were reported . After the first vaccination for Cohorts A and B , respectively , the relative risks of fever were 2.73 and 2.32 times higher for CSL 's TIV compared to the established vaccine . Irritability and loss of appetite ( for Cohort A ) and malaise ( for Cohort B ) were also significantly higher for CSL 's TIV compared to the established vaccine . Post-vaccination geometric mean titers ( GMTs ) for CSL 's TIV versus the established vaccine were 385.49 vs. 382.45 for H1N1 ; 669.13 vs. 705.61 for H3N2 ; and 100.65 vs. 93.72 for B. CSL 's TIV demonstrated immunological non-inferiority to the established vaccine in all cohorts RATIONALE Viral infections of the upper respiratory tract may influence the commensal nasopharyngeal bacteria . Changes in the bacterial niche could affect transmission dynamics . Attenuated vaccine viruses can be used to investigate this empirically in humans . OBJECTIVES To study the effects of mild viral upper respiratory infections on nasopharyngeal bacterial colonization using live attenuated influenza vaccine ( LAIV ) as a surrogate . METHODS We used trivalent LAIV to evaluate the effects of viral infection on bacterial carriage and density of Streptococcus pneumoniae , Moraxella catarrhalis , Haemophilus influenzae , and Staphylococcus aureus . A total of 151 healthy children were r and omized 1:1 to receive the vaccine starting either at recruitment ( n = 74 ) or 28 days later ( n = 77 ) in a stepped wedge fashion , allowing comparisons between recipients and nonrecipients as well as whole-group comparisons pre- and postvaccination . Bacterial carriage and density were determined using quantitative polymerase chain reaction assays . MEASUREMENTS AND MAIN RESULTS A total of 151 children were recruited , 77 in the LAIV group and 74 in the control group . LAIV recipients ( n = 63 analyzed ) showed an apparent transient increase in H. influenzae carriage but no further significant differences in carriage prevalence of the four bacterial species compared with controls ( n = 72 analyzed ) . S. pneumoniae density was substantially higher in vaccine recipients ( 16,687 vs. 1935 gene copies per milliliter ) 28 days after the first dose ( P < 0.001 ) . Whole-group multivariable analysis ( prevaccine , after one dose , and after two doses ) also showed increases in density of other species and H. influenzae carriage prevalence . CONCLUSIONS In the absence of any safety signals despite widespread use of the vaccine , these findings suggest that bacterial density , and thus transmission rates among children and to people in other age groups , may rise following attenuated influenza infections without associated clinical disease . LAIV could therefore be used as an experimental tool to eluci date the dynamics of transmission of nasopharyngeal bacteria The authors provide an analysis of data from a two-year ( 1996 - 1998 ) , multicenter ( ten US cities ) , double-blinded , placebo-controlled influenza vaccine trial in children . The vaccine was the trivalent cold-adapted influenza vaccine . Estimates are made of the vaccine efficacy for susceptibility to culture-confirmed influenza ( VE(S ) ) while taking inter-center variability in the risk of infection into account . Our overall estimate of VE(S ) against influenza is 0.92 ( 95 % confidence interval ( CI ) 0.89 - 0.94 ) . In addition , for the second year , although the vaccine contained antigen for A/Wuhan-like ( H3N2 ) , the estimated VE(S ) for epidemic variant A/Sydney-like ( H3N2 ) was 0.89 ( 95 % CI 0.81 - 0.94 ) . Thus , the vaccine showed a high degree of protection against a variant not closely matched to the vaccine antigen . With regard to natural immunity , an influenza A infection in the first year reduces the estimated risk of an influenza A infection in the second year by a factor of 0.88 ( 95 % CI 0.21 - 0.98 ) . When comparing year 1 to year 2 , there is a negative correlation of -0.50 in the center-specific attack rates in the placebo groups . This is consistent with the theory that natural immunity provides overall community protection to children . The authors argue that mass vaccination of 70 % of the children with the cold-adapted influenza vaccine could provide substantial protection to the community at large Twenty-two healthy infants and children received either cold-recombinant , trivalent influenza vaccine or placebo in a three-dose vaccine trial . Most ( 82 % ) who received vaccine were seronegative to all three vaccine strains ( 10(6 ) TCID50/dose each ) : A/Kawasaki/9/86 ( H1N1 ) , A/Los Angeles/2/87 ( H3N2 ) , and B/Yamagata/16/88 . Vaccine was administered intranasally at time 0 and 2 and 4 months later . The vaccine was well tolerated and immunogenic when administered in a multidose regimen . The first dose stimulated antibody to H1 , H3 , and B in 59 % , 94 % , and 35 % of vaccinees , respectively , by hemagglutination inhibition ( HAI ) or ELISA . After two doses of vaccine , 93 % , 93 % , and 80 % had antibody by HAI or ELISA to H1 , H3 , and B , respectively . Most vaccinees ( 67 % ) responded to all three viruses after two doses of vaccine . The third dose contributed little to the vaccine 's immunogenicity . Multidose trivalent influenza vaccine is safe and induces an immune response in most vaccinees after two doses OBJECTIVE To determine if the use of influenza vaccine in children in day care decreases the incidence of otitis media during the influenza season . DESIGN Prospect i ve cohort study . SETTING Eight day-care centers in North Carolina . PARTICIPANTS One hundred eighty-six children aged 6 to 30 months . INTERVENTION Half the participants received trivalent subvirion influenza virus vaccine . MEASUREMENTS Acute otitis media ( AOM ) and serous otitis media ( SOM ) were assessed biweekly from mid-November 1993 to mid-March 1994 by visual and tympanometric examinations performed by " blinded " observers . The winter season was divided into three periods-before , during , and after influenza season-- and the number of children with AOM or SOM during each period was determined . Unadjusted and adjusted odds ratios ( ORs ) were computed , while controlling for race and sex using logistic regression methods . RESULTS Influenza vaccine was protective against AOM ( OR = 0.69 , 95 % CI , 0.49 - 0.98 ) during the influenza season . Although there may have been some protection against SOM ( OR = 0.75 , 95 % CI , 0.54 - 1.02 ) statistical significance was not achieved . Myringotomy tubes were also significantly protective against AOM and SOM during all three time periods , with ORs between 0.34 and 0.52 , but the greatest protection was seen during the influenza period . CONCLUSIONS Influenza vaccination of 6- to 30-month-old children in day care was associated with a decreased incidence of otitis media during the influenza season . Myringotomy tubes protected against AOM and SOM during all 16 weeks monitored Background : Influenza vaccine must be distributed and administered each year during a limited time interval . To our knowledge , no previous studies have simultaneously evaluated the delivery and administration of privately purchased vaccines and influenza vaccines acquired through the Vaccines for Children ( VFC ) program . Methods : A prospect i ve , observational study was conducted in US outpatient pediatric offices , tracking all influenza vaccinations during the season by age group , first or second vaccination , the child 's need for 1 or 2 doses , type of vaccine , and VFC status . Results : A total of 42 and 84 practice s completed the study in 2007 to 2008 and 2008 to 2009 , respectively . In both seasons , initial shipments of VFC influenza vaccine generally arrived 4 to 5 weeks later than non-VFC shipments ; VFC vaccine administration also started 1 month later than administration of privately purchased vaccine . Vaccine administration peaked in early November and late October in years 1 and 2 , respectively , and declined rapidly thereafter . Overall , approximately one-half of all children who required 2 doses of vaccine were estimated to have received 2 doses . In both years , 2-dose compliance rates in the VFC population were 17 % to 19 % lower than those in the non-VFC population , possibly result ing from the VFC population 's shorter time interval for second dose receipt . Conclusions : The VFC program is critical to ensuring financially vulnerable children have access to vaccination . Manufacturers , distributors , and public health officials should deliver VFC influenza vaccine to providers as quickly as possible . Pediatric healthcare providers should increase efforts to vaccinate all population s , especially the VFC population , in later months 1126 children , 2 months to 3 years old , received a single intranasal dose of 10(4 ) , 10(6 ) , or 10(7 ) TCID50 of cold adapted ( ca ) A/Kawasaki/9/86 ( H1N1 ) and A/Beijing/352/89 ( H3N2 ) or placebo , in a double blind , placebo-controlled , safety and immunogenicity trial . No reactogenicity attributable to vaccine was demonstrated . A single bivalent 10(6 ) or 10(7 ) dose produced high rates of seroconversion to H1N1 ( 77 % ) and H3N2 ( 92 % ) in seronegative children > 6 months old ; serologic responses were lower to H1N1 ( P < 0.001 ) and H3N2 ( P = 0.01 ) in younger infants . A single 10(6 ) dose of bivalent ca influenza A vaccine can be immunogenic in children , but response is age dependent Influenza is a major cause of morbidity and mortality , result ing in excess hospitalization and death ( 13 ) . Data from longitudinal studies suggest that children are an important source of community transmission of influenza ( 48 ) . Vaccinating children against influenza not only protects them but can also provide indirect benefit through herd protection ( that is , reducing the risk for influenza in susceptible persons by rendering immunity in others ) ( 916 ) . However , the choice of vaccine that best achieves herd protection remains uncertain ( 17 , 18 ) . Intranasal live attenuated influenza vaccine ( LAIV ) has been reported to provide 55 % greater protection against influenza in children than inactivated influenza vaccine ( IIV ) ( 19 , 20 ) . Vaccinating children with LAIV compared with IIV should provide better community protection because of better direct protection of children and better indirect effects of herd protection . This question is of public health importance , particularly given differences in recommendations on preferential use of LAIV ( 2123 ) . Most comparative influenza vaccine studies assess direct protection only ( 24 ) . Underst and ing the comprehensive benefit of LAIV versus IIV requires evaluation of both direct and indirect effects . This is best addressed through a r and omized , controlled trial ; however , r and om assignment of the children of entire communities to vaccination with LAIV versus IIV is not possible in most setting s. Hutterite colony members live communally and are relatively isolated from cities and towns , and influenza is regularly introduced into these colonies . This offers an opportunity to test the effect of vaccinating children with LAIV versus IIV on community protection in a cluster r and omized trial ( 11 ) . We hypothesized that a 70 % or greater uptake of trivalent LAIV compared with a similar uptake of trivalent IIV among healthy children and adolescents would reduce laboratory-confirmed influenza by 50 % in the LAIV versus IIV group . A 50 % risk reduction was selected on the basis of a previous trial showing a 55 % direct risk reduction in children who received LAIV compared with IIV ( 19 ) . We also hypothesized that this would translate to a reduction in influenza-associated outcomes . Methods Study Colonies Residents of Hutterite colonies within 150 km of design ated cities or towns in Alberta and Saskatchewan , Canada , were enrolled and followed from 22 October 2012 through 20 May 2015 . Each colony was approached annually regarding whether it would enroll for the next influenza season . Colonies were excluded if the children did not receive any routine vaccinations or if local public health policy was to offer influenza immunization to persons beyond high-risk children ( for example , those with cystic fibrosis ) . Hutterite colonies are small communities ( for example , 70 to 120 residents ) with single-family dwellings and communally shared buildings , such as the kitchen , dining hall , and school . Hutterite families shop in nearby towns for supplies and clothing not available in the colony . The children attend school in the colony . Vaccinated Children Healthy Hutterite children aged 36 months to 15 years ( ages when they attend school ; age 15 years is when Hutterite children are considered to have reached maturity ) were eligible to be vaccinated . Exclusion criteria included anaphylactic reaction to a previous LAIV or trivalent influenza vaccine ; known IgE-mediated hypersensitivity to eggs manifested as hives , swelling of the mouth and throat , difficulty breathing , hypotension , or shock ; history of asthma ; medically diagnosed or treated wheezing within 42 days before enrollment ; GuillainBarr syndrome within 8 weeks of a previous influenza vaccine ; anaphylactic reaction to any vaccine component ; pregnancy ; household contact with a severely immunocompromised person who was being cared for in a protective environment ; and use of aspirin or salicylate-containing products within 30 days before enrollment . Other Hutterite Colony Members All other residents of Hutterite colonies were eligible to participate as nonvaccine recipients and could receive an influenza vaccine outside of the trial . Ethics approval was obtained at McMaster University , the University of Calgary , and the University of Saskatchewan . Participants gave written consent . Participants provided consent for children , and assent was also directly sought from children aged 7 to 15 years . Interventions In the LAIV group , healthy children aged 36 months to 15 years received a 0.2-mL dose of intranasal LAIV ( FluMist [ MedImmune ] ) recommended for the 2012 to 2013 ( influenza A/California/7/2009[H1N1]pdm09 , influenza A/Victoria/361/2011[H3N2 ] , and influenza B/Wisconsin/1/2010like viruses ) , 2013 to 2014 ( influenza A/California/7/2009[H1N1]pdm09 , influenza A/Victoria/361/2011[H3N2 ] , and influenza B/Massachusetts/2/2012like viruses ) , or 2014 to 2015 influenza seasons ( influenza A/California/7/2009[H1N1]pdm09 , influenza A/Texas/50/2012[H3N2 ] , and influenza B/Massachusetts/2/2012like viruses ) . In the IIV group , healthy children aged 36 months to 15 years received a 0.5-mL intramuscular injection of IIV ( Vaxigrip [ Sanofi Pasteur ] ) recommended for the 3 influenza seasons . In both LAIV and IIV groups , previously unvaccinated children younger than 9 years at the time of immunization received a second dose of the vaccine 4 weeks after the first dose . Blinding and Allocation A statistician assigned colonies , using a r and om-number generator , within each of 5 geographic regions where participating Hutterite colonies were located to control for regional differences in influenza circulation . Allocation was to 1 of the 2 study groups ( LAIV or IIV ) in a 1:1 ratio . To minimize bias , we gave precedence to achieving a balance of colonies within strata or health regions as opposed to balancing overall cluster numbers between groups . We reduced the possibility of enrollment bias by allocating LAIV or IIV status to colonies after participant enrollment . Colonies were not r and omly assigned again in the second and third year of the trial so that vaccine allocation remained the same over the entire study . In the event of a colony withdrawal , another colony from the same study region that met eligibility criteria was selected as a replacement and allocated to the same group as the colony that had withdrawn . Arrangements for vaccine shipment from the manufacturer to depots were made by an intermediary clinical trials research organization that received the r and omization code from the statistician . To maintain blinding , children allocated to LAIV received a concurrent 0.5-mL saline injection to mimic IIV . Those allocated to IIV received a 0.2-mL dose of intranasal saline . Among children younger than 9 years who had never previously received seasonal influenza vaccine , those allocated to LAIV received a concurrent 0.5-mL intramuscular injection of sterile saline with the first and second dose of intranasal LAIV . Those in the IIV group received concurrent 0.2-mL doses of intranasal saline administered 4 weeks apart . For blinding purpose s , different teams were used to vaccinate children or assess outcomes . Vaccines were prepared by nurses behind a privacy screen in the preparation room in the Hutterite colony . Surveillance staff , who assessed outcomes , were not involved in vaccination and were blinded to allocation status . Investigators , study coordinators , study monitors , and the data and safety monitoring board were all blinded . Follow-up The start date of the surveillance period for influenza was defined as 1 or more cases of laboratory-confirmed influenza in 2 consecutive weeks from public health surveillance regions that occurred at least 2 weeks after completion of study vaccination in a study colony ; the stop date was defined as no cases of laboratory-confirmed influenza for 2 consecutive weeks in colonies within the health region . Participants were assessed twice weekly by using a st and ardized checklist of self- or parent-reported symptoms or signs . If any new symptoms were reported , the participant was contacted directly by research staff , who confirmed the symptoms and obtained flocked nasal swabs if 2 or more of the following symptoms were present : fever ( temperature 38C ) , cough , nasal congestion , sore throat , headache , sinus problems , muscle aches , fatigue , ear ache or infection , or chills . We provided thermometers for study participants . Outcomes The primary outcome was laboratory-confirmed influenza A or B in all participants , the assessment of which began 2 weeks after vaccination to ensure adequate time for development of an immune response . For participants with 2 or more signs and symptoms , influenza was confirmed on the basis of detecting viral RNA in respiratory sample s through duplex real-time reverse transcriptase polymerase chain reaction ( RT-PCR ) . This test targeted the matrix gene for influenza A virus and the nonstructural gene for influenza B virus ( 25 ) . All specimens with positive results on RT-PCR were then tested by using Centers for Disease Control and Prevention primers capable of differentiating wild-type from vaccine strains . We also assessed antimicrobial prescriptions , influenza-like illness ( defined as a temperature 38.0C and cough ) ( 26 ) , medically attended visits for respiratory illness , school- or work-related absenteeism , emergency department visits , hospital admissions , and deaths . Although we had originally planned to capture hospitalizations , we decided before data collection to consider emergency department visits as a separate outcome from hospital admission . Further , we initially planned to analyze outcomes , including physician-diagnosed otitis media , lower respiratory tract infection , and pneumonia , but a reduction in re sources limited our ability to vali date these outcomes . We captured all hospitalizations and deaths and reported the number of events in each study group , but because of low numbers , we did not conduct analyses . Adverse ABSTRACT The highly sensitive gamma interferon ( IFN-γ ) enzyme-linked immunosorbent spot ( ELISPOT ) assay permits the investigation of the role of cell-mediated immunity ( CMI ) in the protection of young children against influenza . Preliminary studies of young children confirmed that the IFN-γ ELISPOT assay was a more sensitive measure of influenza memory immune responses than serum antibody and that among seronegative children aged 6 to < 36 months , an intranasal dose of 107 fluorescent focus units ( FFU ) of a live attenuated influenza virus vaccine ( CAIV-T ) elicited substantial CMI responses . A commercial inactivated influenza virus vaccine elicited CMI responses only in children with some previous exposure to related influenza viruses as determined by detectable antibody levels prevaccination . The role of CMI in actual protection against community-acquired , culture-confirmed clinical influenza by CAIV-T was investigated in a large r and omized , double-blind , placebo-controlled dose-ranging efficacy trial with 2,172 children aged 6 to < 36 months in the Philippines and Thail and . The estimated protection curve indicated that the majority of infants and young children with ≥100 spot-forming cells/106 peripheral blood mononuclear cells were protected against clinical influenza , establishing a possible target level of CMI for future influenza vaccine development . The ELISPOT assay for IFN-γ is a sensitive and reproducible measure of CMI and memory immune responses and contributes to establishing requirements for the future development of vaccines against influenza , especially those used for children BACKGROUND The efficacy of inactivated influenza vaccines is known to be poor in infants and young children . METHODS We studied the effect of the adjuvant MF59 , an oil-in-water emulsion , on the efficacy of trivalent inactivated influenza vaccine ( TIV ) in 4707 healthy children 6 to less than 72 months of age who had not previously been vaccinated against influenza . The children were r and omly assigned to three study groups , each of which received the assigned vaccines in two doses , 28 days apart , during two consecutive influenza seasons . Two of the groups were given age-appropriate doses of TIV either with or without the MF59 adjuvant , and the third group was given control ( noninfluenza ) vaccines to assess their absolute and relative efficacy against influenza-like illness , as confirmed by means of polymerase-chain-reaction ( PCR ) assay . RESULTS Attack rates of influenza-like illness across both influenza seasons were 0.7 % , 2.8 % , and 4.7 % in the adjuvant , nonadjuvant , and control vaccine groups , respectively . The absolute vaccine efficacy rates against all influenza strains ( 94 of 110 cases were due to vaccine-matched H3N2 viruses ) were 86 % ( 95 % confidence interval [ CI ] , 74 to 93 ) for the MF59-adjuvant vaccine ( ATIV ) and 43 % ( 95 % CI , 15 to 61 ) for the vaccine without the adjuvant ( TIV ) ; the relative vaccine efficacy rate for ATIV versus TIV was 75 % ( 95 % CI , 55 to 87 ) . The efficacy rates for ATIV were 79 % ( 95 % CI , 55 to 90 ) in children 6 to less than 36 months of age and 92 % ( 95 % CI , 77 to 97 ) in those 36 to less than 72 months of age , as compared with 40 % ( 95 % CI , -6 to 66 ) and 45 % ( 95 % CI , 6 to 68 ) , respectively , for TIV . Antibody responses were higher with ATIV and remained so through day 181 . The rates of systemic and local reactions to the influenza vaccines with and without the adjuvant were similar in the younger age group ( relative risk , 1.04 ; 95 % CI , 0.98 to 1.09 ) , but systemic events in the older age group were more frequent after administration of ATIV ( 63 % ) than after administration of TIV ( 44 % ) or the control vaccine ( 50 % ) . Serious adverse events were distributed evenly across the three vaccine groups . CONCLUSIONS Influenza vaccine with the MF59 adjuvant is efficacious against PCR-confirmed influenza in infants and young children . ( Funded by Novartis Vaccines and Diagnostics ; Clinical Trials.gov number , NCT00644059 . ) |
10,479 | 30,014,225 | Education was the most common intervention , although most successful studies combined education with another intervention .
Many studies showed improved compliance to metrics , but few were able to show differences in length of stay , readmissions , or mortality .
Conclusions Our review of quality improvement literature in gastroenterology revealed common themes of successful programs : Education was frequently used but often insufficient , the EMR may be underutilized in guiding decision making , and patient-reported outcomes were infrequently assessed . | Background Quality improvement ( QI ) identifies practical methods to improve patient care ; however , it is not always widely known which QI methods are successful .
We sought to create a primer of QI in gastroenterology for the practicing clinician . | Background Heart failure ( HF ) is a chronic condition affecting nearly 5.7 million Americans and is a leading cause of morbidity and mortality . With an aging population , the cost associated with managing HF is expected to more than double from US $ 31 billion in 2012 to US $ 70 billion by 2030 . Readmission rates for HF patients are high—25 % are readmitted at 30 days and nearly 50 % at 6 months . Low medication adherence contributes to poor HF management and higher readmission rates . Remote telehealth monitoring programs aim ed at improved medication management and adherence may improve HF management and reduce readmissions . Objective The primary goal of this r and omized controlled pilot study is to compare the MedSentry remote medication monitoring system versus usual care in older HF adult patients who recently completed a HF telemonitoring program . We hypothesized that remote medication monitoring would be associated with fewer unplanned hospitalizations and emergency department ( ED ) visits , increased medication adherence , and improved health-related quality of life ( HRQoL ) compared to usual care . Methods Participants were r and omized to usual care or use of the remote medication monitoring system for 90 days . Twenty-nine participants were enrolled and the final analytic sample consisted of 25 participants . Participants completed question naires at enrollment and closeout to gather data on medication adherence , health status , and HRQoL. Electronic medical records were review ed for data on baseline classification of heart function and the number of unplanned hospitalizations and ED visits during the study period . Results Use of the medication monitoring system was associated with an 80 % reduction in the risk of all-cause hospitalization and a significant decrease in the number of all-cause hospitalization length of stay in the intervention arm compared to usual care . Objective device data indicated high adherence rates ( 95%-99 % ) among intervention group participants despite finding no significant difference in self-reported adherence between study arms . The intervention group had poorer heart function and HRQoL at baseline , and HRQoL declined significantly in the intervention group compared to controls . Conclusions The MedSentry medication monitoring system is a promising technology that merits continued development and evaluation . The MedSentry medication monitoring system may be useful both as a st and alone system for patients with complex medication regimens or used to complement existing HF telemonitoring interventions . We found significant reductions in risk of all-cause hospitalization and the number of all-cause length of stay in the intervention group compared to controls . Although HRQoL deteriorated significantly in the intervention group , this may have been due to the poorer HF-functioning at baseline in the intervention group compared to controls . Telehealth medication adherence technologies , such as the MedSentry medication monitoring system , are a promising method to improve patient self-management , the quality of patient care , and reduce health care utilization and expenditure for patients with HF and other chronic diseases that require complex medication regimens . Trial Registration Clinical Trials.gov NCT01814696 ; https:// clinical trials.gov/ct2/show/ study /NCT01814696 ( Archived by WebCite ® at http://www.webcitation.org/6giqAVhno Background : In recent years , leading organizations in inflammatory bowel disease ( IBD ) have developed quality measures for the care of adults with Crohn 's disease or ulcerative colitis . We used chart audits to assess the impact of quality improvement educational activities on documented adherence to Physician Quality Reporting System measures for IBD . Methods : Twenty community-based gastroenterologists were recruited to participate in baseline chart audits ( n = 200 ) , a series of 4 accredited educational activities with feedback , and follow-up chart audits ( n = 200 ) . Trained abstract ors review ed r and omly selected charts of adults with moderate or severe Crohn 's disease . The charts were retrospectively abstract ed for physicians ' documented performance of the 2013 Physician Quality Reporting System IBD quality measures . We compared the physicians ' baseline and posteducation rates of documented adherence with 10 of these measures . In a secondary analysis , we compared preeducation with posteducation difference scores of low-performing physicians , those whose baseline documentation rates were in the lowest quartile , and the rest of the cohort . Results : At baseline , documentation of mean provider-level adherence to the 10 quality measures ranged from 3 % to 98 % ( gr and mean = 35.8 % ) . In the overall analysis , baseline and posteducation rates of documented adherence did not differ significantly for any of the measures . However , for 4 measures , preeducation to posteducation difference scores were significantly greater among low performers than physicians in the highest 3 quartiles . Conclusions : The results of this preliminary pragmatic study indicate that quality improvement education affords the potential to improve adherence to Physician Quality Reporting System quality measures for IBD among low-performing gastroenterologists IMPORTANCE It remains unclear whether telemonitoring approaches provide benefits for patients with heart failure ( HF ) after hospitalization . OBJECTIVE To evaluate the effectiveness of a care transition intervention using remote patient monitoring in reducing 180-day all-cause readmissions among a broad population of older adults hospitalized with HF . DESIGN , SETTING , AND PARTICIPANTS We r and omized 1437 patients hospitalized for HF between October 12 , 2011 , and September 30 , 2013 , to the intervention arm ( 715 patients ) or to the usual care arm ( 722 patients ) of the Better Effectiveness After Transition-Heart Failure ( BEAT-HF ) study and observed them for 180 days . The date s of our study analysis were March 30 , 2014 , to October 1 , 2015 . The setting was 6 academic medical centers in California . Participants were hospitalized individuals 50 years or older who received active treatment for decompensated HF . INTERVENTIONS The intervention combined health coaching telephone calls and telemonitoring . Telemonitoring used electronic equipment that collected daily information about blood pressure , heart rate , symptoms , and weight . Central ized registered nurses conducted telemonitoring review s , protocol ized actions , and telephone calls . MAIN OUTCOMES AND MEASURES The primary outcome was readmission for any cause within 180 days after discharge . Secondary outcomes were all-cause readmission within 30 days , all-cause mortality at 30 and 180 days , and quality of life at 30 and 180 days . RESULTS Among 1437 participants , the median age was 73 years . Overall , 46.2 % ( 664 of 1437 ) were female , and 22.0 % ( 316 of 1437 ) were African American . The intervention and usual care groups did not differ significantly in readmissions for any cause 180 days after discharge , which occurred in 50.8 % ( 363 of 715 ) and 49.2 % ( 355 of 722 ) of patients , respectively ( adjusted hazard ratio , 1.03 ; 95 % CI , 0.88 - 1.20 ; P = .74 ) . In secondary analyses , there were no significant differences in 30-day readmission or 180-day mortality , but there was a significant difference in 180-day quality of life between the intervention and usual care groups . No adverse events were reported . CONCLUSIONS AND RELEVANCE Among patients hospitalized for HF , combined health coaching telephone calls and telemonitoring did not reduce 180-day readmissions . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01360203 Objective To test a multidisciplinary approach to reduce heart failure ( HF ) readmissions that tailors the intensity of care transition intervention to the risk of the patient using a suite of electronic medical record (EMR)-enabled programmes . Methods A prospect i ve controlled before and after study of adult in patients admitted with HF and two concurrent control conditions ( acute myocardial infa rct ion ( AMI ) and pneumonia ( PNA ) ) was performed between 1 December 2008 and 1 December 2010 at a large urban public teaching hospital . An EMR-based software platform stratified all patients admitted with HF on a daily basis by their 30-day readmission risk using a published electronic predictive model . Patients at highest risk received an intensive set of evidence -based interventions design ed to reduce readmission using existing re sources . The main outcome measure was readmission for any cause and to any hospital within 30 days of discharge . Results There were 834 HF admissions in the pre-intervention period and 913 in the post-intervention period . The unadjusted readmission rate declined from 26.2 % in the pre-intervention period to 21.2 % in the post-intervention period ( p=0.01 ) , a decline that persisted in adjusted analyses ( adjusted OR (AOR)=0.73 ; 95 % CI 0.58 to 0.93 , p=0.01 ) . In contrast , there was no significant change in the unadjusted and adjusted readmission rates for PNA and AMI over the same period . There were 45 fewer readmissions with 913 patients enrolled and 228 patients receiving intervention , result ing in a number needed to treat ( NNT ) ratio of 20 . Conclusions An EMR-enabled strategy that targeted scarce care transition re sources to high-risk HF patients significantly reduced the risk-adjusted odds of readmission Background High- quality bowel preparation is necessary for colonoscopy . A few studies have been conducted to investigate improvement in bowel preparation quality through patient education . However , the effect of patient education on bowel preparation has not been well studied . Methods A r and omized and prospect i ve study was conducted . All patients received regular instruction for bowel preparation during a pre-colonoscopy visit . Those scheduled for colonoscopy were r and omly assigned to view an educational video instruction ( video group ) on the day before the colonoscopy , or to a non-video ( control ) group . Qualities of bowel preparation using the Ottawa Bowel Preparation Quality scale ( Ottawa score ) were compared between the video and non-video groups . In addition , factors associated with poor bowel preparation were investigated . Result A total of 502 patients were r and omized , 250 to the video group and 252 to the non-video group . The video group exhibited better bowel preparation ( mean Ottawa total score : 3.03 ± 1.9 ) than the non-video group ( 4.21 ± 1.9 ; P < 0.001 ) and had good bowel preparation for colonoscopy ( total Ottawa score < 6 : 91.6 % vs. 78.5 % ; P < 0.001 ) . Multivariate analysis revealed that males ( odds ratio [ OR ] = 1.95 , P = 0.029 ) , diabetes mellitus patients ( OR = 2.79 , P = 0.021 ) , and non-use of visual aids ( OR = 3.09 , P < 0.001 ) were associated with poor bowel preparation . In the comparison of the colonoscopic outcomes between groups , the polyp detection rate was not significantly different between video group and non-video group ( 48/250 , 19.2 % vs. 48/252 , 19.0 % ; P = 0.963 ) , but insertion time was significantly short in video group ( 5.5 ± 3.2 min ) than non-video group ( 6.1 ± 3.7 min ; P = 0.043 ) . Conclusion The addition of an educational video could improve the quality of bowel preparation in comparison with st and ard preparation method .Trial registration Clinical Research Information Service KCT0001836 . The date of registration : March , 08th , 2016 , Retrospectively registered BACKGROUND St and ards for the detection of adenomas during screening colonoscopy are widely used to measure examination quality . No such st and ards exist for sessile serrated adenomas ( SSAs ) . OBJECTIVE To measure both the adenoma detection rate ( ADR ) and SSA detection rate ( SSADR ) during screening colonoscopy before and after quality improvement/financial incentive measures . DESIGN Retrospective determination of baseline ADR/SSADR by the endoscopist , followed by prospect i ve collection of data after informing physicians of baseline detection rates . SETTING Tertiary cancer center with a large cancer screening program . PATIENTS A total of 2833 average-risk colorectal cancer screening patients 50 to 75 years of age undergoing initial colonoscopy . DATA COLLECTION Electronic medical records for indication and demographics , endoscopy report , and pathology report . MAIN OUTCOME MEASUREMENTS Detection rates of adenomas and SSAs by sex . RESULTS The overall ADR in male and female patients was 50.6 % and 36.6 % , respectively . The overall detection rate of advanced adenomas in male and female patients was 12.4 % and 6.5 % , respectively . The overall SSADR in male and female patients was 10.1 % and 7.1 % , respectively . In 108 patients ( 3.8 % of entire group ) , SSAs were the only premalignant lesions found . Detection rates of both types of premalignant polyps improved over time but did not reach statistical significance . LIMITATIONS Single-center experience with limited sample size and small group of endoscopists . CONCLUSION ADRs far in excess of current st and ards are achievable . Cecal withdrawal time is associated with the ADR . Prevalence of SSA rivals that of advanced adenomas and is greater than current medical literature suggests . The combination of monitoring and financial incentives did not result in statistically significant improvement in ADRs Background Low rates of compliance with quality measures for inflammatory bowel disease ( IBD ) have been reported for US gastroenterologists . Aims We assessed the influence of quality improvement ( QI ) education on compliance with physician quality reporting system ( PQRS ) measures for IBD and measures related to National Quality Strategy ( NQS ) priorities . Methods Forty community-based gastroenterologists participated in the QI study ; 20 were assigned to educational intervention and control groups , respectively . At baseline , r and omly selected charts of patients with moderate-to-severe ulcerative colitis were retrospectively review ed for the gastroenterologists ’ performance of 8 PQRS IBD measures and 4 NQS-related measures . The intervention group participated in a series of accredited continuing medical education ( CME ) activities focusing on QI . Follow-up chart review s were conducted 6 months after the CME activities . Independent t tests were conducted to compare between-group differences in baseline-to-follow-up rates of documented compliance with each measure . Results The analysis included 299 baseline charts and 300 follow-up charts . The intervention group had significantly greater magnitudes of improvement than the control group for the following measures : assessment of IBD type , location , and activity ( + 14 % , p = 0.009 ) ; influenza vaccination ( + 13 % , p = 0.025 ) ; pneumococcal vaccination ( + 20 % , p = 0.003 ) ; testing for latent tuberculosis before anti-TNF-α therapy ( + 10 % , p = 0.028 ) ; assessment of hepatitis B virus status before anti-TNF-α therapy ( + 9 % , p = 0.010 ) ; assessment of side effects ( + 17 % , p = 0.048 ) , and counseling patients about cancer risks ( + 13 % , p = 0.013 ) . Conclusions QI-focused CME improves community-based gastroenterologists ’ compliance with IBD quality measures and measures aligned with NQS priorities OBJECTIVES We determined the effect of a targeted education and support intervention on the rate of readmission or death and hospital costs in patients with heart failure ( HF ) . BACKGROUND Disease management programs for patients with HF including medical components may reduce readmissions by 40 % or more , but the value of an intervention focused on education and support is not known . METHODS We conducted a prospect i ve , r and omized trial of a formal education and support intervention on one-year readmission or mortality and costs of care for patients hospitalized with HF . RESULTS Among the 88 patients ( 44 intervention and 44 control ) in the study , 25 patients ( 56.8 % ) in the intervention group and 36 patients ( 81.8 % ) in the control group had at least one readmission or died during one-year follow-up ( relative risk = 0.69 , 95 % confidence interval [ CI ] : 0.52 , 0.92 ; p = 0.01 ) . The intervention was associated with a 39 % decrease in the total number of readmissions ( intervention group : 49 readmissions ; control group : 80 readmissions , p = 0.06 ) . After adjusting for clinical and demographic characteristics , the intervention group had a significantly lower risk of readmission compared with the control group ( hazard ratio = 0.56 , 95 % CI : 0.32 , 0.96 ; p = 0.03 ) and hospital readmission costs of $ 7,515 less per patient . CONCLUSIONS A formal education and support intervention substantially reduced adverse clinical outcomes and costs for patients with HF Background Cirrhosis is a major risk factor associated with the development of hepatocellular carcinoma ( HCC ) . The American Association for the Study of Liver Diseases recommends surveillance for HCC in cirrhosis patients with ultrasound every six months . However , various studies suggest that surveillance rates in actual practice are quite low . Aim The aims of this study were to evaluate the effectiveness of implementing quality improvement ( QI ) measures in increasing the rate of HCC surveillance among patients in a tertiary care facility . Methods Patients with cirrhosis were prospect ively enrolled into a chronic disease management program , which integrates nursing-based protocol s with automatic reminders when patients are due for surveillance . Patients enrolled in this program between March 2010 and April 2011 were compared to a prior cohort in 2008–2009 . The primary endpoint was the receipt of at least one abdominal imaging study performed for the purpose s of surveillance during the study period . Results Of the 355 patients enrolled , 331 ( 93 % ) had imaging performed for HCC surveillance , compared to 119/160 ( 74 % ) patients in the previous cohort ( p < 0.001 ) . Chart review revealed the most common reasons for failure to undergo surveillance were patients ’ lack of insurance and lack of follow-up on studies ordered at outside institutions . Six patients were diagnosed with HCC during the study period , of which three were at early stage . Conclusions Implementation of QI measures incorporating automatic reminders of surveillance status for providers can significantly increase the rate of HCC surveillance among cirrhosis patients BACKGROUND AND AIMS Patients with decompensated cirrhosis ( DC ) have significant morbidity and re source utilization . In a cohort of patients with DC undergoing usual care ( UC ) in 2009 , we demonstrated that quality indicators ( QI ) were met < 50 % of the time . We established a gastroenterology m and atory consultation ( MC ) to improve the care of patients with DC . We sought to evaluate the impact of the MC intervention on adherence to QI , and compared outcomes to UC . METHODS This was a prospect i ve cohort study with historic control examining all admissions in a year for DC at an academic medical center . All admissions were seen by a gastroenterologist encouraged to implement QIs ( MC ) . Scores were calculated for each group per admission as the proportion of QIs met versus QIs for which the patient was eligible . QI scores were examined as a function of group assignment multivariable fractional logit regression . We evaluated the impact of the intervention on compliance with QIs , length of stay ( LOS ) , 30-day readmission , and inpatient death . RESULTS Three hundred three patients were observed in 695 hospitalizations ( 149 patients in 379 admissions [ UC ] ; 154 patients in 316 admissions [ MC ] ) . The QI score was significantly higher in the MC group than the UC group ( 77.0 % vs 46.0 % , P < 0.001 ) , reflecting better management of ascites and documentation of transplant evaluation . The management of variceal bleeding improved also but did not reach statistical significance . CONCLUSION The MC intervention was associated with greater adherence to recommended care but was not powered to detect difference in LOS , readmission , or mortality rates OBJECTIVES : Adenoma detection rate ( ADR ) is a key measure of quality in colonoscopy . Low ADRs are associated with development of interval cancer after “ negative ” colonoscopy . Uncontrolled studies m and ating longer withdrawal time , and other incentives , have not significantly improved ADR . We hypothesized that an endoscopist training program would increase ADRs . METHODS : Our Endoscopic Quality Improvement Program ( EQUIP ) was an educational intervention for staff endoscopists . We measured ADRs for a baseline period , then r and omly assigned half of the 15 endoscopists to undergo EQUIP training . We then examined baseline and post-training study ADRs for all endoscopists ( trained and un-trained ) to evaluate the impact of training . A total of 1,200 procedures were completed in each of the two study phases . RESULTS : Patient characteristics were similar between r and omization groups and between study phases . The overall ADR in baseline phase was 36 % for both groups of endoscopists . In the post-training phase , the group of endoscopists r and omized to EQUIP training had an increase in ADR to 47 % , whereas the ADR for the group of endoscopists who were not trained remained unchanged at 35 % . The effect of training on the endoscopist-specific ADRs was estimated with an odds ratio of 1.73 ( 95 % confidence interval 1.24–2.41 , P=0.0013 ) . CONCLUSIONS : Our results indicate that ADRs can be improved considerably through simple educational efforts . Ultimately , a trial involving a larger number of endoscopists is needed to vali date the utility of our training methods and determine whether improvements in ADRs lead to reduced colorectal cancer BACKGROUND AND STUDY AIMS Low adenoma detection rates ( ADRs ) at colonoscopy are linked to significantly higher interval cancer rates , and vary between colonoscopists . Studies demonstrate that lesion detection is improved by : withdrawal time of ≥ 6 minutes ; use of hyoscine butylbromide ; position change ; and rectal retroflexion . We evaluated the feasibility of implementing the above " bundle " of interventions into colonoscopy practice , and the effect on ADR . MATERIAL S AND METHODS A longitudinal cohort design was used . Implementation combined central training , local promotion , and feedback . The uptake marker was change in hyoscine butylbromide use . Comparisons were between the 3 months before and the 9 months after the implementation phase , globally , by endoscopy unit and by quartile when colonoscopists were ranked according to baseline ADR . Chi-squared or Fisher 's tests were used to evaluate significance . RESULTS 12 units participated . Global and quartile analyses included data from 118 and 68 colonoscopists and 17 508 and 14 193 procedures respectively . A significant increase in hyoscine butylbromide use was observed globally ( 54.4 % vs. 15.8 % , P < 0.001 ) , in all endoscopy units ( P < 0.001 ) and quartiles ( P < 0.001 ) . A significant increase in ADR was observed globally ( 18.1 % vs. 16.0 % , P = 0.002 ) and in the lower two colonoscopist quartiles ( P < 0.001 ) , with a nonsignificant increase in the upper middle quartile and a significant fall to 21.5 % . in the upper quartile . The significant variations in ADR among the upper three quartiles disappeared . CONCLUSION In routine clinical practice , introduction of a simple , inexpensive , evidence -based " bundle " of measures is feasible and is associated with higher global ADR , driven by improvements amongst the poorest performing colonoscopists OBJECTIVES : We recently completed a r and omized controlled trial of an endoscopic quality improvement program ( EQUIP ) that demonstrated an improved adenoma detection rate ( ADR ) through simple educational interventions . The aim of this study ( phase III ) is to examine whether the improvement in ADR in the trained endoscopists remained stable with further follow-up . METHODS : We prospect ively followed up 15 staff endoscopists who had previously been r and omized to a quality improvement intervention . In the current study , we examined an additional 1,200 colonoscopy procedures conducted over a 5-month time period following the original study , referred to as phase III . During this time , all physicians received quarterly ADR and other quality metric feedback , and the previous control group was offered the educational intervention voluntarily . ADRs and adenoma per patient ( APP ) rates were estimated in the endoscopists who were and were not r and omized to EQUIP training and compared with those obtained in phases I and II of the original study . The study was conducted in a tertiary care Academic Medical Center . The study sample comprised 1200 patients undergoing routine colonoscopy . The main outcome measurement was adenoma detection rate . RESULTS : The previously observed increase in ADR in the trained group from 36 % in phase I to 47 % in phase II was maintained into phase III ( 46 % ) . The ADR of the untrained group remained unchanged from phase I ( 36 % ) to phase II ( 35 % ) ; it was increased only marginally in phase III to 39 % , which was still lower than the 46 % ADR in the trained group . The trained group had an increase in APP , from 0.72 in Phase I to 0.87 in Phase II and 0.98 in Phase III . For the previously untrained group , there was no change in APP from phase I ( 0.68 ) to phase II ( 0.68 ) , but there was possibly a small increase ( to 0.74 ) in Phase III . CONCLUSIONS : This study provides evidence that improvements in ADR obtained through the endoscopic quality -training program can persist for at least 5 months after completion of the program . It further suggests that a focus on ADR does not lead to a “ one and done ” phenomenon . The limitations of this study were as follows : single-center setting , and lack of sessile polyp information/st and ardization BACKGROUND Colonoscopy is protective against colorectal cancer , but its quality and protective benefits can vary . Adenoma detection rate ( ADR ) is associated with quality and the degree of protection against colorectal cancer and death . In a previous , single academic center , r and omized , controlled trial , we demonstrated that an endoscopic quality improvement program increased ADR ( EQUIP-1 ) and that those increases were durable ( EQUIP-2 ) . We hypothesized that EQUIP training would increase ADR in a multicenter clinical practice setting . METHODS Nine large clinical practice sites were recruited . After a baseline period ( phase I ) , 5 sites were r and omized to receive supplemental in-person EQUIP training with active feedback . After follow-up ( phase II ) , the changes in ADRs at these sites were compared with the changes at 4 control sites that did not receive training or feedback until after study completion . RESULTS Twenty-two thous and three hundred sixteen colonoscopies were included . There was a statistically significant increase in ADR at the training sites ( odds ratio [ OR ] , 1.28 ; P = .004 ) with a raw ADR of 31 % in phase I and 42 % in phase II after the intervention . However , raw ADRs also increased at the control sites ( from 36 % to 39 % ) . As a result , there was limited evidence of a training effect ( OR , 1.03 ; 95 % confidence interval [ CI ] , 0.84 - 1.25 ; P = .78 ) . CONCLUSIONS ADRs increased at the sites participating in the endoscopic quality improvement program . However it is not clear to what extent the training program is responsible for the changes , because raw ADRs also increased at the control sites but to a lesser extent . ( Clinical Trials Registration number : NCT02325635 . ) Background Quality performance measures for screening colonoscopy vary among endoscopists . The impact of practice setting is unknown . Aims We aim ed to ( 1 ) compare screening colonoscopy performance measures among three different US practice setting s ; ( 2 ) evaluate factors associated with adenoma detection ; and ( 3 ) assess a scorecard intervention on performance metrics . Methods This multi-center prospect i ve study compared patient , endoscopist , and colonoscopy characteristics performed at a tertiary care hospital ( TCH ) , community-based hospital ( CBH ) , and private practice group ( PPG ) . Withdrawal times ( WT ) , cecal intubation , and adenoma detection rates ( ADR ) were compared by site at baseline and 12 weeks following scorecard distribution . Generalized linear mixed models identified factors associated with adenoma detection . Results Twenty-eight endoscopists performed colonoscopies on 1987 asymptomatic , average-risk individuals ≥50 years . Endoscopist and patient characteristics were similar across sites . The PPG screened more men ( TCH : 42.8 % , CBH : 45.0 % , PPG : 54.2 % ; p < 0.0001 ) . Preparation quality varied with good/excellent results in 70.6 , 88.3 , and 92 % of TCH , CBH , and PPG cases , respectively ( p < 0.0001 ) . Male ADRs , cecal intubation , and WT exceeded recommended benchmarks despite variable results at each site ; female ADRs were < 15 % at the PPG which screened the fewest females . Performance remained unchanged following scorecard distribution . Adenoma detection was associated with increasing patient age , male gender , WT , adequate preparation , but not practice setting . Conclusions Each practice performed high- quality screening colonoscopy . Scorecards did not improve performance metrics . Preparation quality varies among practice setting s and can be modified to improve adenoma detection BACKGROUND Gastro-esophageal reflux disease ( GERD ) is common in primary care but is often underdiagnosed and untreated . GERD can also present with atypical symptoms like chronic cough and asthma , and physicians may be unaware of this presentation . We aim ed to implement and evaluate an intervention to improve diagnosis and treatment for GERD and atypical GERD in primary care . METHOD This was a r and omised controlled trial in primary care office practice using a national network of US practice s ( the Medical Quality Improvement Consortium - MQIC ) that share the same electronic medical record ( EMR ) . Thirteen offices with 53 providers were r and omised to the intervention of EMR-based prompts and education , and 14 offices with 66 providers were r and omised to the control group totalling over 67 000 patients and examining outcomes of GERD diagnosis and appropriate treatment . RESULTS Among patients who did not have GERD at baseline , new diagnoses of GERD increased significantly in the intervention group ( 3.1 % ) versus the control group ( 2.3 % ) ( P<0.01 ) . This remained significant after controlling for clustering with an odds of diagnosis of 1.33 ( 95 % CI 1.13 - 1.56 ) for the intervention group . For patients with atypical symptoms , those in the intervention group had both higher odds of being diagnosed with GERD ( OR 2.02 , 95 % CI 1.41 - 2.88 ) and of being treated for GERD ( OR 1.40 , 95 % CI 1.08 - 1.83 ) than those in the control group . CONCLUSIONS GERD diagnosis and treatment in primary care , particularly among patients with atypical symptoms , can be improved through the use of an EMR-based tool incorporating decision support and education . However , significant room for improvement exists in use of appropriate treatment Cirrhotic complications portend high morbidity and mortality and burden the health care system . Established quality measures in management of cirrhotics include screening for esophageal varices ( EV ) , screening for hepatocellular carcinoma ( HCC ) , and hepatitis A and B immunization . A retrospective review was conducted to identify adherence to cirrhosis . Baseline rates were shared with providers . Compliance with quality measures was measured prospect ively at 1-month , 2-month , 1-year , and 3-year follow-up after provision of performance feedback . Baseline HCC rate was 60 % , EV was 68 % , and hepatitis A and B immunization was 51 % and 47 % , respectively . After performance feedback , HCC , EV , and hepatitis A and B vaccination rates improved to rates ranging from 92 % to 100 % and remained statistically significant after 3 years . Provider feedback , a simple intervention , achieved significant improvement in compliance with quality measures for management of cirrhotics . This improvement in adherence to quality measures was sustainable over a 3-year time period BACKGROUND Appropriateness in GI endoscopy is critical to face the rising amount of dem and s. Education of physicians has been advocated to reduce the level of inappropriateness . OBJECTIVE Our purpose was to assess the effectiveness of an educational program in determining a reduction of inappropriate colonoscopies in an open access system . DESIGN Prospect i ve study . SETTING A single endoscopy unit in Italy . PATIENTS A total of 495 consecutive out patients referred to our endoscopy unit by family physicians for diagnostic colonoscopy before the educational course and 522 after its completion , for a total of 1017 patients . MAIN OUTCOME MEASUREMENTS Inappropriate colonoscopy reduction rates , cost savings , and reduction of waiting lists were evaluated . RESULTS With regard to inappropriate colonoscopies , the post-course group rate of inappropriateness was significantly lower than that of the pre-course group ( P < or = .001 ) . The economic savings for 1 year was estimated to be euro19,000 . The reduction of the waiting list was about 15 % of the original value . CONCLUSIONS Education has a high incidence in reducing inappropriate colonoscopies in an open-access system determining reduction of costs and waiting lists BACKGROUND AND STUDY AIM Continuous quality improvement ( CQI ) is recommended by professional societies as part of every colonoscopy program , but little is known with regard to its effectiveness for colonoscopy outcomes . We prospect ively assessed whether the implementation of a CQI program in routine clinical practice influences the quality performance of colonoscopy . METHODS In an open-access endoscopy unit at a secondary care center in Northern Italy , 6-monthly audit cycles were carried out over a 4-year period , to identify reasons for poor colonoscopy outcomes and institute appropriate changes to improve performance . The colonoscopy completion rate and the polyp detection rate as detected by endoscopists were considered to be key measures for improvement . RESULTS The initial crude colonoscopy completion rate was 84.6 % , with a range for individual endoscopists 80.4%-94 % . Four endoscopists had a completion rate lower than 90 % . The overall polyp detection rate was 34 % , with a wide variation among endoscopists ( range 14%-42 % ) . Poor patient tolerance and differences in colonoscopist expertise were the main determinants of lack of completion and variation in polyp detection rate . Changes to sedation practice , greater access to endoscopy sessions for the endoscopists with the lowest performance rates , and other organizational arrangements , were implemented to improve quality performance . The crude completion rates improved consistently , up to 93.1 % , over the study period . This trend was confirmed even when adjusted completion rates were calculated . All endoscopists reached a crude completion rate of 90 % or more and a polyp detection rate of over 20 % . The introduction of CQI did not significantly change the overall incidence of procedure-related complications . CONCLUSIONS The effectiveness of colonoscopy can be improved by implementing a CQI program in routine colonoscopy practice BACKGROUND Surveillance for hepatocellular carcinoma ( HCC ) with 6-monthly ultrasound is a st and ard of care for higher-risk patients with viral hepatitis . Adherence to screening guidelines is an important quality indicator in hepatology , but multiple studies have demonstrated poor HCC surveillance practice s in real-world setting s. AIMS The aim of this project was to audit and then optimise HCC surveillance of viral hepatitis patients , who fulfilled criteria for screening , associated with a large tertiary hospital . METHODS Clinical practice improvement principles were utilised . A baseline audit of 22 consecutive viral hepatitis patients was performed . Major barriers preventing adequate surveillance were identified and three interventions to improve adherence to guidelines were introduced . These included : improved doctor education , system re design and improved patient education . The effects of interventions were measured by serial r and om audits of patients . A final audit occurred over 3 years after the initial baseline audit . RESULTS At baseline , 46 % and 0 % of patients had appropriate surveillance performed during the prior 6 months ( one surveillance cycle ) and 2 years ( four surveillance cycles ) respectively . Three years after initiation of these strategies , a final audit revealed 92 % ( vs 46 % at baseline ) and 64 % ( vs 0 % at baseline ) of patients had appropriate HCC surveillance performed during the preceding 6 months and 2 years intervals respectively ( P < 0.001 in each case ) . CONCLUSIONS Simple and low-cost interventions can considerably improve the clinical effectiveness of HCC screening programmes in real world setting s. Clinical practice improvement principles appear to be a valid methodology for achieving this positive change BACKGROUND & AIMS There has been no prospect i ve , community-based study to track changes in adenoma detection by individual physicians over time and to determine the effectiveness of targeted educational interventions . METHODS We prospect ively collected information on 47,253 screening colonoscopies in average-risk individuals 50 years and older performed by a community-based practice in the Twin Cities of Minnesota . During a period of 3 years , 5 specific interventions were implemented ; each was design ed to improve adenoma detection rates . Controlling for patient-related and procedure-related factors , rates of adenoma detection and 3-year trends for individual physicians were plotted , and intraclass correlation coefficients were calculated . Generalized estimating equations were used to identify factors associated with detection of adenomas and polyps . RESULTS At least 1 polyp and 1 adenoma were found in 36 % and 22 % of examinations , respectively . Adenoma detection rates by endoscopists ranged from 10%-39 % . There was no significant improvement during the study period despite planned , systematic interventions . Factors associated with adenoma detection included age of the patient ( odds ratio [ OR ] , 1.02 ; 95 % confidence interval [ CI ] , 1.02 - 1.02 ) , male sex ( OR , 1.53 ; 95 % CI , 1.34 - 1.74 ) , and adequate preparation quality ( OR , 2.26 ; 95 % CI , 1.64 - 3.12 ) . CONCLUSIONS The detection of adenomas by individual physicians during a 3-year period varied and did not appear to change between individual endoscopists , despite planned , systematic interventions . This indicates that other targeted interventions might be required to improve adenoma detection rates among experienced , community gastroenterologists |
10,480 | 31,129,662 | We did not observe a reduction in the need for ventilatory assistance or in mortality in the automatic titration period .
Conclusions : In patients requiring supplemental oxygen in the hospital , automatic oxygen titration was associated with a reduction in length of both hospital stay and oxygen therapy , as well as a greater percentage of time spent within the saturation target range .
However , it was not associated with a significant difference in the need for mechanical ventilation or in mortality . | Background : Closed-loop oxygen titration devices have been developed to avoid periods of hypoxemia and hyperoxemia , both detrimental to patients hospitalized for respiratory failure and requiring supplemental oxygen .
However , their clinical impact remains unknown .
Objective : To compare the effect of automatic versus manual oxygen titration on clinical outcomes in pediatric and adult patients requiring supplemental oxygen in the hospital . | Background — Oxygen is commonly administered to patients with ST-elevation – myocardial infa rct ion despite previous studies suggesting a possible increase in myocardial injury as a result of coronary vasoconstriction and heightened oxidative stress . Methods and Results — We conducted a multicenter , prospect i ve , r and omized , controlled trial comparing oxygen ( 8 L/min ) with no supplemental oxygen in patients with ST-elevation – myocardial infa rct ion diagnosed on paramedic 12-lead ECG . Of 638 patients r and omized , 441 patients had confirmed ST-elevation – myocardial infa rct ion and underwent primary end-point analysis . The primary end point was myocardial infa rct size as assessed by cardiac enzymes , troponin I , and creatine kinase . Secondary end points included recurrent myocardial infa rct ion , cardiac arrhythmia , and myocardial infa rct size assessed by cardiac magnetic resonance imaging at 6 months . Mean peak troponin was similar in the oxygen and no oxygen groups ( 57.4 versus 48.0 & mgr;g/L ; ratio , 1.20 ; 95 % confidence interval , 0.92–1.56 ; P=0.18 ) . There was a significant increase in mean peak creatine kinase in the oxygen group compared with the no oxygen group ( 1948 versus 1543 U/L ; means ratio , 1.27 ; 95 % confidence interval , 1.04–1.52 ; P=0.01 ) . There was an increase in the rate of recurrent myocardial infa rct ion in the oxygen group compared with the no oxygen group ( 5.5 % versus 0.9 % ; P=0.006 ) and an increase in frequency of cardiac arrhythmia ( 40.4 % versus 31.4 % ; P=0.05 ) . At 6 months , the oxygen group had an increase in myocardial infa rct size on cardiac magnetic resonance ( n=139 ; 20.3 versus 13.1 g ; P=0.04 ) . Conclusion — Supplemental oxygen therapy in patients with ST-elevation – myocardial infa rct ion but without hypoxia may increase early myocardial injury and was associated with larger myocardial infa rct size assessed at 6 months . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01272713 BACKGROUND : One century after the introduction of the oxygen flow meter into clinical practice , we have developed a device , FreeO2 , that automatically titrates the oxygen flow delivered to spontaneously breathing patients , with the aim of maintaining a stable SpO2 . We evaluated this system in healthy subjects during induced hypoxemia . METHODS : Hypoxemia was induced in 10 healthy subjects while breathing a gas mixture of variable FIO2 ( air + nitrogen ) . Each subject performed 3 hypoxemic challenges with the addition , in a r and om order , of either : air with constant flow ( 1.5 L/min ) ; oxygen with constant flow ( 1.5 L/min ) ; or automatic oxygen flow titration . Subjects were blinded to the intervention . Oxygen flow , SpO2 , end-tidal CO2 , respiratory rate , and heart rate were recorded every second . The primary outcome was the time with SpO2 between 92 % and 96 % . RESULTS : The SpO2 target ( 92–96 % ) was achieved a median of 26.0 % , 36.8 % , and 66.5 % ( P < .001 ) of the time with air , constant oxygen , and automated oxygen titration , respectively . Severe oxygen desaturations ( SpO2 < 88 % ) were respectively observed at a median of 33.7 % , 12.7 % , and 0.4 % of the time ( P < .001 ) . Hyperoxia was present a median of 4.1 % , 39.1 % , and 14.5 % of the time ( P < .001 ) . Tachycardia was present with air and with constant oxygen flow , but not while using automated oxygen titration . These results were obtained with a mean and maximal oxygen flow of 1.3 L/min and 7.6 L/min with the automated titration . CONCLUSIONS : In this model of induced hypoxemia , the FreeO2 system that automatically titrates the oxygen flow was more efficient at maintaining the SpO2 target , while ensuring a statistically significant reduction in the rates of severe hypoxemia and hyperoxia , in comparison with air or constant oxygen flow . These beneficial results were obtained with less oxygen , in comparison to a constant oxygen flow In preterm infants receiving supplemental oxygen , manual control of the inspired oxygen fraction is often time-consuming and inappropriate . We developed a system for automatic oxygen control and hypothesized that this system is more effective than routine manual oxygen control in maintaining target arterial oxygen saturation levels . We performed a r and omized controlled crossover clinical trial in 12 preterm infants receiving nasal continuous positive airway pressure and supplemental oxygen . Periods with automatic and routine manual oxygen control were compared with periods of optimal control by a fully dedicated person . The median ( range ) percentage of time with arterial oxygen saturation levels within target range ( 87 - 96 % ) was 81.7 % ( 39.0 - 99.8 ) for routine manual oxygen control , 91.0 % ( 41.4 - 99.3 ) for optimal control , and 90.5 % ( 59.0 - 99.4 ) for automatic control ( ANOVA : p = 0.01 ) . Pairwise post hoc comparisons revealed a statistically significant difference between automatic and routine manual oxygen control ( Dunnett 's test : p = 0.02 ) . The frequency of manual oxygen adjustments was lowest in automatic control ( Friedman 's test : p < 0.001 ) . Automatic oxygen control may optimize oxygen administration to preterm infants receiving nasal continuous positive airway pressure and reduce nursing time spent with oxygen control Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Introduction We developed a device ( FreeO2 ) that automatically adjusts the oxygen flow rates based on patients ’ needs , in order to limit hyperoxia and hypoxemia and to automatically wean them from oxygen . Objective The aim of this study was to evaluate the feasibility of using FreeO2 in patients hospitalized in the respiratory ward for an acute exacerbation of COPD . Methods We conducted a r and omized controlled trial comparing FreeO2 vs manual oxygen titration in the respiratory ward of a university hospital . We measured the perception of appropriateness of oxygen titration and monitoring in both groups by nurses and attending physicians using a Likert scale . We evaluated the time in the target range of oxygen saturation ( SpO2 ) as defined for each patient by the attending physician , the time with severe desaturation ( SpO2 < 85 % ) , and the time with hyperoxia ( SpO2 > 5 % above the target ) . We also recorded length of stay , intensive care unit admissions , and readmission rate . Fifty patients were r and omized ( 25 patients in both groups ; mean age : 72±8 years ; mean forced expiratory volume in 1 second : 1.00±0.49 L ; and mean initial O2 flow 2.0±1.0 L/min ) . Results Nurses and attending physicians felt that oxygen titration and monitoring were equally appropriate with both O2 administration systems . The percentage of time within the SpO2 target was significantly higher with FreeO2 , and the time with severe desaturation and hyperoxia was significantly reduced with FreeO2 . Time from study inclusion to hospital discharge was 5.8±4.4 days with FreeO2 and 8.4±6.0 days with usual oxygen administration ( P=0.051 ) . Conclusion FreeO2 was deemed as an appropriate oxygen administration system by nurses and physicians of a respiratory unit . This system maintained SpO2 at the target level better than did manual titration and reduced periods of desaturation and hyperoxia . Our results also suggest that FreeO2 has the potential to reduce the hospital length of stay BACKGROUND AND OBJECTIVE : In preterm infants receiving supplemental oxygen , routine manual control ( RMC ) of the fraction of inspired oxygen ( FIO2 ) is often difficult and time consuming . We developed a system for closed-loop automatic control ( CLAC ) of the FIO2 and demonstrated its short-term safety and efficacy in a single-center study . The objective of this study was to test the hypothesis that this system is more effective than RMC alone in maintaining arterial oxygen saturation within target levels when evaluated over 24 hours under routine conditions and with different target levels . METHODS : We performed a multicenter , r and omized controlled , crossover clinical trial in 34 preterm infants receiving mechanical ventilation or nasal continuous positive airway pressure and supplemental oxygen . Twenty-four – hour periods with RMC were compared with 24-hour periods of RMC supported by CLAC . RESULTS : The median ( range ) percentage of time with arterial oxygen saturation levels within target range was 61.4 ( 31.5–99.5 ) for RMC and 71.2 ( 44.0–95.4 ) for CLAC ( P < .001 ) . The median ( range ) number of manual FIO2 adjustments was reduced from 77.0 ( 0.0–224.0 ) for RMC to 52.0 ( 10.0–317.0 ) for CLAC ( P = .007 ) . CONCLUSIONS : CLAC may improve oxygen administration to preterm infants receiving mechanical ventilation or nasal continuous positive airway pressure while reducing workload related to RMC Oxygen is commonly administered in hospitals , with poor adherence to treatment recommendations . We conducted a multicentre r and omised controlled study in patients admitted to the emergency department requiring O2 ≥3 L·min−1 . Patients were r and omised to automated closed-loop or manual O2 titration during 3 h. Patients were stratified according to arterial carbon dioxide tension ( PaCO2 ) ( hypoxaemic PaCO2≤45 mmHg ; or hypercapnic PaCO2>45–≤55 mmHg ) and study centre . Arterial oxygen saturation measured by pulse oximetry ( SpO2 ) goals were 92–96 % for hypoxaemic , or 88–92 % for hypercapnic patients . Primary outcome was % time within SpO2 target . Secondary endpoints were hypoxaemia and hyperoxia prevalence , O2 weaning , O2 duration and hospital length of stay . 187 patients were r and omised ( 93 automated , 94 manual ) and baseline characteristics were similar between the groups . Time within the SpO2 target was higher under automated titration ( 81±21 % versus 51±30 % , p<0.001 ) . Time with hypoxaemia ( 3±9 % versus 5±12 % , p=0.04 ) and hyperoxia under O2 ( 4±9 % versus 22±30 % , p<0.001 ) were lower with automated titration . O2 could be weaned at the end of the study in 14.1 % versus 4.3 % patients in the automated and manual titration group , respectively ( p<0.001 ) . O2 duration during the hospital stay was significantly reduced ( 5.6±5.4 versus 7.1±6.3 days , p=0.002 ) . Automated O2 titration in the emergency department improved oxygenation parameters and adherence to guidelines , with potential clinical benefits . Automated oxygen titration is superior to manual administration in terms of time within oxygenation targets BACKGROUND : Arterial oxygen desaturation frequently occurs in patients with COPD during daily activities at home . Oxygen flow is usually set at fixed and low rates for ambulatory patients . We evaluated an innovative closed-loop system ( FreeO2 ) that automatically adjusts the oxygen flow to the patient 's needs in subjects with COPD during walking followed by recovery time , such as during ambulatory conditions . METHODS : Patients with COPD who exhibited oxygen desaturation on exertion were included in the study . Subjects performed endurance shuttle walk tests followed by 10 min of recovery . The tests were conducted in a r and om order and in crossover with the 3 following conditions : subjects breathing ( 1 ) air at 2 L/min , ( 2 ) oxygen at 2 L/min , or ( 3 ) FreeO2 ( variable oxygen flow ) . SpO2 , pulse rate , PETCO2 , breathing frequency , and oxygen flow were continuously recorded during the 3 conditions . The primary outcome was the percentage of time within the SpO2 target of 92–96 % . Secondary outcomes included the endurance shuttle walk test time and distance . RESULTS : Sixteen subjects with COPD were recruited . The percentage of time with SpO2 in the target range ( 92–96 % ) was higher while using the FreeO2 , and time with severe oxygen desaturation ( SpO2 < 88 % ) was lower with FreeO2 in comparison with constant-flow oxygen and air testing conditions ( 0.6 % vs 23.9 % vs 52.2 % , P < .001 ) . In comparison with air , walking distance was increased by 35 % with oxygen ( P = .045 ) and by 63 % with FreeO2 ( P < .001 ) . The walking distance was increased by 17 % with FreeO2 in comparison with constant oxygen , but the difference was not statistically significant ( P = .22 ) . CONCLUSIONS : Automatic titration of oxygen flow during walking to maintain oxygen saturation in a specified range improves oxygenation and may improve exercise tolerance during daily activity , such as walking , in patients with COPD in comparison with room air and fixed oxygen administration . ( Clinical Trials.gov registration : NCT02150434 . We have used continuous ambulatory electrocardiography and concurrent monitoring of arterial oxygen saturation ( SpO2 ) and non-invasive arterial pressure in a pilot study of 29 unse date d patients undergoing percutaneous peripheral vascular angioplasty . Twelve patients ( Group 1 ) received oxygen 41 min-1 by Hudson mask during the procedure , the remaining 17 patients ( Group 2 ) breathing air . Fourteen patients in Group 2 had an SpO2 of 94 % or below during the procedure , compared with two patients in Group 1 . Episodes of silent ischaemia were recorded during the procedure in one patient in Group 1 and five patients in Group 2 . Administration of oxygen significantly reduced the incidence and severity of hypoxaemia , and may be responsible for the reduction in silent ischaemia OBJECTIVE To assess the efficacy of a system for automated fraction of inspired oxygen ( FiO(2 ) ) adjustment in maintaining oxygen saturation ( SpO(2 ) ) within an intended range in preterm infants with spontaneous fluctuations in SpO(2 ) . STUDY DESIGN Sixteen infants ( gestational age , 24.9 + /- 1.4 weeks ; birth weight , 678 + /- 144 g ; age , 33 + /- 15 days ) with frequent hypoxemia episodes underwent two 4-hour periods of FiO(2 ) adjustment by clinical personnel ( routine ) and the automated system ( automated ) . RESULTS Compared with the routine period , the percent time within intended SpO(2 ) range ( 88%-95 % ) increased during the automated period ( 58 % + /- 10 % versus 42 % + /- 9 % ; P < .001 ) , whereas the percent time with SpO(2 ) higher than the intended range and > or=98 % were reduced ( 9 % + /- 10 % versus 31 % + /- 8 % [ P < .001 ] and 3 % + /- 5 % versus 16 % + /- 9 % [ P < .001 ] , respectively ) . Percent time with SpO(2 ) < 88 % increased during the automated period ( 33 % + /- 7 % versus 27 % + /- 9 % ; P = .003 ) because of more frequent episodes , whereas the time with SpO(2 ) < 75 % did not differ . The 4-hour median FiO(2 ) was lower during the automated period ( 29 % + /- 4 % versus 34 % + /- 5 % ; P < .001 ) . CONCLUSION Automated FiO(2 ) adjustment improved maintenance of SpO(2 ) within the intended range and reduced hyperoxemia and FiO(2 ) . These findings should be examined in longer periods with st and ard clinical conditions and , eventually , in the context of r and omized trials powered to detect clinical ly important effects on outcome Purpose Previous observational studies have inconsistently associated early hyperoxia with worse outcomes after cardiac arrest , and have method ological limitations . We tested this association using a high-resolution data base controlling for multiple disease-specific markers of severity of illness and care processes . Methods This was a retrospective analysis of a single-center , prospect i ve registry of consecutive cardiac arrest patients . We included patients who survived and were mechanically ventilated ≥24 h after arrest . Our main exposure was arterial oxygen tension ( PaO2 ) , which we categorized hourly for 24 h as severe hyperoxia ( > 300 mmHg ) , moderate or probable hyperoxia ( 101–299 mmHg ) , normoxia ( 60–100 mmHg ) or hypoxia ( < 60 mmHg ) . We controlled for Utstein-style covariates , markers of disease severity and markers of care responsiveness . We performed unadjusted and multiple logistic regression to test the association between oxygen exposure and survival to discharge , and used ordered logistic regression to test the association of oxygen exposure with neurological outcome and Sequential Organ Failure Assessment ( SOFA ) score at 24 h. Results Of 184 patients , 36 % were exposed to severe hyperoxia and overall mortality was 54 % . Severe hyperoxia , but not moderate or probable hyperoxia , was associated with decreased survival in both unadjusted and adjusted analysis [ adjusted odds ratio ( OR ) for survival 0.83 per hour exposure , P = 0.04 ] . Moderate or probable hyperoxia was not associated with survival but was associated with improved SOFA score 24 h ( OR 0.92 , P < 0.01 ) . ConclusionS evere hyperoxia was independently associated with decreased survival to hospital discharge . Moderate or probable hyperoxia was not associated with decreased survival and was associated with improved organ function at 24 Objective Conduct a cost-effectiveness analysis of FreeO2 technology versus manual oxygen-titration technology for patients with chronic obstructive pulmonary disease ( COPD ) hospitalised for acute exacerbations . Setting Tertiary acute care hospital in Quebec , Canada . Participants 47 patients with COPD hospitalised for acute exacerbations . Intervention An automated oxygen-titration and oxygen-weaning technology . Methods and outcomes The costs for hospitalisation and follow-up for 180 days were calculated using a microcosting approach and included the cost of FreeO2 technology . Incremental cost-effectiveness ratios ( ICERs ) were calculated using bootstrap resampling with 5000 replications . The main effect variable was the percentage of time spent at the target oxygen saturation ( SpO2 ) . The other two effect variables were the time spent in hyperoxia ( target SpO2 + 5 % ) and in severe hypoxaemia ( SpO2 < 85 % ) . The resamplings were based on data from a r and omised controlled trial with 47 patients with COPD hospitalised for acute exacerbations . Results FreeO2 generated savings of 20.7 % of the per-patient costs at 180 days ( ie , −$C2959.71 ) . This decrease is nevertheless not significant at the 95 % threshold ( P=0.13 ) , but the effect variables all improved ( P<0.001 ) . The improvement in the time spent at the target SpO2 was 56.3 % . The ICERs indicate that FreeO2 technology is more cost-effective than manual oxygen titration with a savings of −$C96.91 per percentage point of time spent at the target SpO2 ( 95 % CI −301.26 to 116.96 ) . Conclusion FreeO2 technology could significantly enhance the efficiency of the health system by reducing per-patient costs at 180 days . A study with a larger patient sample needs to be carried out to confirm these preliminary results . Trial registration number NCT01393015 ; Post- results |
10,481 | 23,001,179 | Conclusions The increasing evidence in favor of low-level laser therapy allowed for the development of two new guidelines supporting this modality in the population s listed above .
Evidence for other population s was also generally encouraging over a range of wavelengths and intensities . | Background The aim of this study was to review the available literature and define clinical practice guidelines for the use of laser and other light therapies for the prevention and treatment of oral mucositis . | Abstract Use of the low-energy helium-neon laser ( LEL ) appears to be a simple atraumatic technique for the prevention and treatment of mucositis of various origins . Preliminary findings , and significant results obtained for chemotherapy-induced mucositis in a previous phase III study , prompted a r and omized multicenter double-blind trial to evaluate LEL in the prevention of acute radiation-induced stomatitis . Irradiation by LEL corresponds to local application of a high-photon-density monochromatic light source . Activation of epithelial healing for LEL-treated surfaces , the most commonly recognized effect , has been confirmed by numerous in vitro studies . The mechanism of action at a molecular and enzymatic level is presently being studied . From September 1994 to March 1998 , 30 patients were r and omized . Technical specification : 60 mW ( 25 mW at Reims , 1 patient ) , He-Ne , wavelength 632.8 nm . The trial was open to patients with carcinoma of the oropharynx , hypopharynx and oral cavity , treated by radiotherapy alone ( 65 Gy at a rate of 2 Gy/fraction , 5 fractions per week ) without prior surgery or concomitant chemotherapy . The malignant tumor had to be located outside the tested laser application areas ( 9 points ) : posterior third of the internal surfaces of the cheeks , soft palate and anterior tonsillar pillars . Patients were r and omized to LEL or placebo light treatment , starting on the first day of radiotherapy and before each session . The treatment time ( t ) for each application point was given by the equation : t (s)=energy (J/cm2) × surface (cm2)/Power ( W ) . Objective assessment of the degree of mucositis was recorded weekly by a physician blinded to the type of treatment , using the WHO scale for grading of mucositis and a segmented visual analogue scale for pain evaluation . Protocol feasibility and compliance were excellent . Grade 3 mucositis occured with a frequency of 35.2 % without LEL and of 7.6 % with LEL ( P<0.01 ) . The frequency of " severe pain " ( grade 3 ) was 23.8 % without LEL , falling to 1.9 % with LEL ( P<0.05 ) . Pain relief was significantly reduced throughout the treatment period ( weeks 2–7 ) . LEL therapy is capable of reducing the severity and duration of oral mucositis associated with radiation therapy . In addition , there is a tremendous potential for using LEL in combined treatment protocol s utilizing concomitant chemotherapy and radiotherapy Background . Oral mucositis is a common complication of bone marrow transplantation ( BMT ) conditioning therapy . Sequelae consist of increased risk for infection , moderate to severe pain , compromised oral function , and bleeding . This study investigated helium‐neon laser treatment for prevention of conditioning‐induced oral mucositis in BMT patients . Patterns and severity of mucositis for specific conditioning drug regimens also were analyzed Background Low-energy laser ( LEL ) treatment has been suggested as an effective and safe method to prevent and /or treat oral mucositis induced by chemotherapy and /or radiotherapy ; however , it has not gained wide acceptance so far . Material s and methods We conducted two clinical trials testing the LEL technique : firstly , as a secondary prevention in patients with various solid tumors treated with chemotherapy who all developed severe mucositis after a previous identical chemotherapy and , secondly , as therapeutic intervention ( compared to sham illumination in a r and omized way ) in patients with hematological tumors receiving intensive chemotherapy and having developed low- grade oral mucositis . Results We entered 26 eligible patients in the first study and 36 were r and omized in the second study . The success rate was 81 % ( 95%CI = 61–93 % ) when LEL was given as a preventive treatment . In the second study , in patients with existing lesions , the therapeutic success rate was 83 % ( 95%CI = 59–96 % ) , which was significantly different from the success rate reached in the sham-treated patients ( 11 % ; 95%CI = 1–35 % ) ; the time to development of grade 3 mucositis was also significantly shorter in the sham-treated patients ( p < 0.001 ) . Conclusion Our results strongly support the already available literature , suggesting that LEL is an effective and safe approach to prevent or treat oral mucositis result ing from cancer chemotherapy Abstract Background and Objective : As Light Emitting Diode ( LED ) devices are commercially introduced as an alternative for Low Level Laser ( LLL ) Therapy , the ability of LED in influencing wound healing processes at cellular level was examined . Study Design / Material s and Methods : Cultured fibroblasts were treated in a controlled , r and omized manner , during three consecutive days , either with an infrared LLL or with a LED light source emitting several wavelengths ( 950 nm , 660 nm and 570 nm ) and respective power outputs . Treatment duration varied in relation to varying surface energy densities ( radiant exposures ) . Results : Statistical analysis revealed a higher rate of proliferation ( p ≤ 0.001 ) in all irradiated cultures in comparison with the controls . Green light yielded a significantly higher number of cells , than red ( p ≤ 0.001 ) and infrared LED light ( p ≤ 0.001 ) and than the cultures irradiated with the LLL ( p ≤ 0.001 ) ; the red probe provided a higher increase ( p ≤ 0.001 ) than the infrared LED probe and than the LLL source . Conclusion : LED and LLL irradiation result ed in an increased fibroblast proliferation in vitro . This study therefore postulates possible stimulatory effects on wound healing in vivo at the applied dosimetric parameters We investigated the clinical effects of low-power laser therapy ( LPLT ) on prevention and reduction of severity of conditioning-induced oral mucositis ( OM ) for hematopoietic stem cell transplantation ( HSCT ) . We r and omized 38 patients who underwent autologous ( AT ) or allogeneic ( AL ) HSCT . A diode InGaAlP was used , emitting light at 660 nm , 50 mW , and 4 J/cm2 , measured at the fiberoptic end with 0.196 cm2 of section area . The evaluation of OM was done using the Oral Mucositis Assessment Scale ( OMAS ) and the World Health Organization ( WHO ) scale . In the LPLT group , 94.7 % of patients had an OM grade ( WHO ) lower than or equal to grade 2 , including 63.2 % with grade 0 and 1 , whereas in the controls group , 31.5 % of patients had an OM grade lower than or equal to grade 2 ( P < .001 ) . Remarkably , the hazard ratio ( HR ) for grade s 2 , 3 , and 4 OM was 0.41 ( range , 0.22 - 0.75 ; P = .002 ) and for grade s 3 and 4 it was 0.07 ( range , 0.11 - 0.53 ; P < .001 ) . Using OMAS by the calculation of ulcerous area , 5.3 % of the laser group presented with ulcers of 9.1 cm2 to 18 cm2 , whereas 73.6 % of the control group presented with ulcers from 9.1 cm2 to 18 cm2 ( P = .003 ) . Our results indicate that the use of upfront LPLT in patients who have undergone HSCT is a powerful instrument in reducing the incidence of OM and is now st and ard in our center OBJECTIVE A pilot clinical study was conducted to evaluate the efficacy and feasibility of low-level laser therapy ( LLLT ) in the prevention and treatment of chemotherapy (CT)-induced oral mucositis ( OM ) in young patients . BACKGROUND DATA Besides compromising the patient 's nutrition and well-being , oral mucositis represents a portal of entry into the body for microorganisms present in the mouth , which may lead to sepsis if there is hematological involvement . Oncologic treatment tolerance decreases and systemic complications may arise that interfere with the success of cancer treatment . LLLT appears to be an interesting alternative to other approaches to treating OM , due to its trophic , anti-inflammatory , and analgesic properties . MATERIAL S AND METHODS Patients undergoing chemotherapy ( 22 cycles ) without mucositis were r and omized into a group receiving prophylactic laser-irradiation ( group 1 ) , and a group receiving placebo light treatment ( group 2 ) . Patients who had already presented with mucositis were placed in a group receiving irradiation for therapeutic purpose s ( group 3 , with 10 cycles of CT ) . Serum granulocyte levels were taken and compared to the progression of mucositis . RESULTS In group 1 , most patients ( 73 % ) presented with mucositis of grade 0 ( p = 0.03 when compared with the placebo group ) , and 18 % presented with grade 1 . In group 2 , 27 % had no OM and did not require therapy . In group 3 , the patients had marked pain relief ( as assessed by a visual analogue scale ) , and a decrease in the severity of OM , even when they had severe granulocytopenia . CONCLUSION The ease of use of LLLT , high patient acceptance , and the positive results achieved , make this therapy feasible for the prevention and treatment of OM in young patients Goal of workThe aim of this study was to investigate the mechanisms whereby low-intensity laser therapy may affect the severity of oral mucositis . Material s and methods A hamster cheek pouch model of oral mucositis was used with all animals receiving intraperitoneal 5-fluorouracil followed by surface irritation . Animals were r and omly allocated into three groups and treated with a 35 mW laser , 100 mW laser , or no laser . Clinical severity of mucositis was assessed at four time-points by a blinded examiner . Buccal pouch tissue was harvested from a subgroup of animals in each group at four time-points . This tissue was used for immunohistochemistry for cyclooxygenase-2 ( COX-2 ) , vascular endothelial growth factor ( VEGF ) , and factor VIII ( marker of microvessel density ) and the result ing staining was quantified . Main results Peak severity of mucositis was reduced in the 35 mW laser group as compared to the 100 mW laser and control groups . This reduced peak clinical severity of mucositis in the 35 mW laser group was accompanied by a significantly lower level of COX-2 staining . The 100 mW laser did not have an effect on the severity of clinical mucositis , but was associated with a decrease in VEGF levels at the later time-points , as compared to the other groups . There was no clear relationship of VEGF levels or microvessel density to clinical mucositis severity . Conclusion The tissue response to laser therapy appears to vary by dose . Low-intensity laser therapy appears to reduce the severity of mucositis , at least in part , by reducing COX-2 levels and associated inhibition of the inflammatory response BACKGROUND AND OBJECTIVES Several studies have suggested that low-level laser therapy ( LLLT ) can ameliorate oral mucositis ; however , the mechanisms involved are not well understood . The aim of this study was to investigate the mechanisms of action of LLLT on chemotherapy-induced oral mucositis , as related to effects on collagen expression and inflammation . MATERIAL S AND METHODS A hamster cheek pouch model of oral mucositis was used with all animals receiving intraperitoneal 5-fluorouracil , followed by surface irritation . Animals were r and omly allocated into three groups , and treated with an InGaAIP diode laser at a wavelength of 660 nm and output power of 35 or 100 mW laser , or no laser . Clinical severity of mucositis was assessed at four time-points by a blinded examiner . Buccal pouch tissue was harvested from a subgroup of animals in each group at four time-points . Collagen was qualitatively and quantitatively evaluated after picrosirius staining . The density of the neutrophil infiltrate was also scored . RESULTS Peak clinical severity of mucositis was reduced in the 35 mW laser group as compared to the 100 mW and control groups . The reduced peak clinical severity of mucositis in the 35 mW laser group was accompanied by a decrease in the number of neutrophils and an increase in the proportion of mature collagen as compared to the other two groups . The total quantity of collagen was significantly higher in the control ( no laser ) group at the day 11 time-point , as compared to the 35 mW laser group , consistent with a more prolonged inflammatory response in the control group . CONCLUSION This study supports two mechanisms of action for LLLT in reducing mucositis severity . The increase in collagen organization in response to the 35 mW laser indicates that LLLT promotes wound healing . In addition , LLLT also appears to have an anti-inflammatory effect , as evidence d by the reduction in neutrophil infiltrate The purpose of this prospect i ve study was to determine the effect of the low-level laser in the prevention and treatment of mucositis in head and neck cancer patients . A total of 70 patients with malignant neoplasms in the oral cavity or oropharynx were evaluated . The patients were r and omized into two low-level laser therapy groups : Group 1 ( 660nm/15mW/3.8J/cm(2)/spot size 4mm(2 ) ) or Group 2 ( 660nm/5mW/1.3J/cm(2)/spot size 4mm(2 ) ) starting on the first day of radiotherapy . Oral mucositis was assessed daily and weekly using the NCI and WHO scales . Oral pain was scored daily with a visual analogue scale before laser application . The patients in Group 1 had a mean time of 13.5days ( range 6 - 26days ) to present mucositis grade II , while the patients in Group 2 had a mean time of 9.8days ( range 4 - 14days ) ( both WHO and NCI p=0.005 ) . In addition , Group 2 also presented a higher mucositis grade than Group 1 with significant differences found in weeks 2 ( p=0.019 ) , 3 ( p=0.005 ) and 4 ( p=0.003 ) for WHO scale and weeks 2 ( p=0.009 ) and 4 ( p=0.013 ) for NCI scale . The patients in Group 1 reported lower pain levels ( p=0.004 ) . Low-level laser therapy during radiotherapy was found to be effective in controlling the intensity of mucositis and pain Introduction Oral mucositis ( OM ) is a significant early complication of hematopoietic cell transplantation ( HCT ) . This phase III r and omized double-blind placebo-controlled study was design ed to compare the ability of 2 different low level GaAlAs diode lasers ( 650 nm and 780 nm ) to prevent oral mucositis in HCT patients conditioned with chemotherapy or chemoradiotherapy . Material s and methods Seventy patients were enrolled and r and omized into 1 of 3 treatment groups : 650 nm laser , 780 nm laser or placebo . All active laser treatment patients received daily direct laser treatment to the lower labial mucosa , right and left buccal mucosa , lateral and ventral surfaces of the tongue , and floor of mouth with energy densities of 2 J/cm2 . Study treatment began on the first day of conditioning and continued through day + 2 post HCT . Mucositis and oral pain was measured on days 0 , 4 , 7 , 11 , 14 , 18 , and 21 post HCT . Results The 650 nm wavelength reduced the severity of oral mucositis and pain scores . Low level laser therapy was well-tolerated and no adverse events were noted . Discussion While these results are encouraging , further study is needed to truly establish the efficacy of this mucositis prevention strategy . Future research needs to determine the effects of modification of laser parameters ( e.g. , wavelength , fluence , repetition rate of energy delivery , etc . ) on the effectiveness of LLE laser to prevent OM The Prospect i ve Oral Mucositis Audit was an observational study in 197 patients with multiple myeloma ( MM ) or non-Hodgkin 's lymphoma ( NHL ) undergoing , respectively , high-dose melphalan or BEAM chemotherapy and autologous SCT at 25 European centres . We evaluated the relationship between severe oral mucositis ( SOM ; WHO Oral Toxicity Scale grade 3–4 ) and local and systemic clinical sequelae and medical re source use . SOM occurred in 44 % of patients . The duration of SOM ( mean 5.3 days ) correlated with time to neutrophil engraftment . The following parameters increased gradiently with maximum grade of oral mucositis : duration of pain score ⩾4 , opioid use , dysphagia score ⩾4 , total parenteral nutrition ( TPN ) use , incidence and /or duration of fever and infection , and duration of antibiotic use . SOM increased the duration of TPN use by 2.7 days ( P<0.001 ) , opioids by 4.6 days ( P<0.001 ) , and antibiotics by 2.4 days ( P=0.045 ) . SOM prolonged hospital stay by 2.3 days ( P=0.013 ) in MM patients , but not in NHL patients ( who tended to have a longer hospital stay ) . In conclusion , this analysis of prospect ively collected observational data provides important insight into the scope and impact of SOM in the European transplant setting The aim of this study was to evaluate the safety , tolerability and efficacy of a topical gel containing histamine dihydrochloride ( HDC ) versus a placebo gel in preventing oral mucositis in hematopoietic stem cell transplantation ( HSCT ) patients . A total of 45 patients post-HSCT were enrolled in a prospect i ve longitudinal , placebo-controlled , double-blind study . Patients were evaluated twice weekly for oral mucositis ( OMAS , NCI score ) , oral pain ( VAS ) , oral function and salivary flow rate . Compliance was assessed using a patient diary . Oral mucositis developed in 85 % of the HDC group and 63 % of the placebo group . The mean maximal intensity for NCI score was 1.45±1 in the HDC group and 1.21±1.27 in the placebo group ( P=0.37 ) . The mean duration of oral mucositis was 4.7±3.6 and 2.33±2.23 days in the HDC and placebo groups , respectively ( P=0.06 ) . The same trends were measured with OMAS . Visual analogue scale for oral pain and oral function was not significantly different between the two groups . Histamine dihydrochloride was found to be safe . In the search for topical agents for the prevention of mucositis , we found that HDC neither improves nor worsens oral mucositis in HSCT patients . The balance between the pro- and anti-inflammatory effects of HDC should be investigated further in order to acquire a clinical ly effective topical medication based on its anti-inflammatory properties BACKGROUND This study assessed the use of low-energy laser in the prevention or reduction of the severity of oral mucositis . PROCEDURE A r and omized clinical trial was carried out . Patients from 3 to 18 years of age treated with chemotherapy or hematopoietic stem-cell transplantation between May , 2003 and February , 2005 were eligible . The intervention group received laser application for 5 days following the start of chemotherapy . The grade of oral mucositis was assessed by the WHO per NCI-CTC common toxicity criteria and the assessment s were made on days 1 , 8 and 15 by a trained examiner blind to the intervention . RESULTS Sixty patients were evaluable for analysis ; thirty-nine ( 65 % ) were males , 35 ( 58 % ) patients had a diagnosis of leukemia or lymphoma , and 25 ( 42 % ) had solid tumors . The mean age was 8.7 + /- 4.3 years . Twenty-nine patients were r and omized in the laser group and 31 in the control group . On day 1 , no patients presented with mucositis . On day 8 , of 20 patients ( 36 % ) who developed mucositis , 13 of them were from the laser group and 7 from the control group . On day 15 , of 24 patients ( 41 % ) who developed mucositis , 13 of them were from the laser group and 11 from the control group . There was no significant difference between groups concerning the grade s of mucositis on day 8 ( P = 0.234 ) or on day 15 ( P = 0.208 ) . CONCLUSIONS This study showed no evidence of benefit from the prophylactic use of low-energy laser in children and adolescents with cancer treated with chemotherapy when optimal dental and oral care was provided BACKGROUND DATA AND OBJECTIVE Oral mucositis ( OM ) is one of the worst cytotoxic effects of chemotherapy and radiotherapy in patients undergoing hematopoietic cell transplantation ( HCT ) , and it causes severe morbidity . Laser phototherapy has been considered as an alternative therapy for prevention and treatment of OM . The aim of this study was to describe the incidence and severity of OM in HCT patients subjected to laser phototherapy , and to discuss its effect on the oral mucosa . PATIENTS AND METHODS Information concerning patient age and gender , type of basic disease , conditioning regimen , type of transplant , absence or presence of pain related to the oral cavity , OM grade , and adverse reactions or unusual events were collected from 30 patients undergoing HCT ( allogeneic or autologous ) . These patients were given oral laser phototherapy with a InGaAIP laser ( 660 nm and 40 mW ) daily . The data were tabulated and their frequency expressed as percentages . RESULTS In the analysis of those with OM , it was observed that 33.4 % exhibited grade I , 40 % grade II , 23.3 % grade III , and 3.3 % grade IV disease . On the most critical post-HCT days ( D+5 and D+8 ) , it was observed that 63.3 % of patients had grade I and 33.3 % had grade II disease ; no patients had grade III or IV disease in this period . This severity of OM was similar to that seen in other studies of laser phototherapy and OM . CONCLUSION The low grade s of OM observed in this survey show the beneficial effects of laser phototherapy , but r and omized clinical trials are necessary to confirm these findings Background Oral mucositis ( OM ) is one of the most frequent complications of chemotherapy for which there is no st and ard therapy ; treatment is mostly conservative . This study was conducted to determine whether low-intensity laser therapy ( LLLT ) can reduce the duration of chemotherapy-induced OM . Procedure A placebo-controlled r and omized trial was carried out using LLLT or placebo ( sham treatment ) . Children and adolescents with cancer receiving chemotherapy or hematopoietic stem-cell transplantation between October 2005 and May 2006 were eligible as soon as they developed OM . Patients received intervention for 5 days . The LLLT group was treated with laser GaAlAs , wavelength ( λ ) : 830 nm ( infrared ) , power : 100 mW , dose : 4 J/cm2 , and placebo group underwent sham treatment . The grade of OM was clinical ly assessed by the National Cancer Institute , Common Toxicity Criteria scale . Results Twenty-one patients developed OM and were evaluable for analysis ; 18 ( 86 % ) patients had a diagnosis of leukemia or lymphoma and 3(14 % ) had solid tumors . The mean age was 8.2 ( ±3.1 ) years . Nine patients were r and omized in the laser group and 12 in the placebo-control group . Once OM was diagnosed , the patients had daily OM grading assessment s before laser or sham application and thereafter until complete healing of the lesions . On day 7 after OM diagnosis , 1/9 of patients remained with lesions in laser group and 9/12 of patients in the placebo-control group ( P=0.029 ) . In the laser group , the mean of OM duration was 5.8±2 days and in the placebo group was 8.9±2.4 days ( P=0.004 ) . Conclusions Our study has shown evidence that laser therapy in addition to oral care can decrease the duration of chemotherapy-induced OM . Our results confirm the promising results observed in adult cancer patients and should encourage pediatric oncologists to use laser therapy as first-line option in children with chemotherapy-induced OM AIM To evaluate the clinical effects of laser therapy on the prevention and reduction of oral mucositis in patients who underwent hematopoietic stem cell transplantation ( HSCT ) . PATIENTS AND METHODS From January 2003 to September 2004 , 24 patients received prophylactic laser therapy ( L+ group ) . The applications started from the beginning of the conditioning regimen up to day + 2 . The oral assessment was performed daily until day + 30 . This group was compared with historical controls , namely 25 patients , who did not receive laser therapy ( L- group ) . RESULTS All patients developed some grade of mucositis . However , the L- group presented initial mucositis by 4.36 days , whereas the L+ group presented it in 6.12 days ( P = 0.01 ) . The maximum mucositis occurred between day + 2 and day + 6 with healing by day + 25 in the L- group and between day + 2 and day + 7 with healing by day + 14 for the L+ group ( P = 0.84 ) . Laser therapy also reduced the time of oral pain from 5.64 to 2.45 days ( P = 0.04 ) , and decreased the consumption of morphine ( P = 0.07 ) . CONCLUSION This study suggests that laser therapy can be useful in oral mucositis to HSCT patients and improve the patient 's quality of life . However , controlled r and omized trials should be performed to confirm the real efficacy of laser therapy OBJECTIVE The aim of this study was to assess the clinical effectiveness of phototherapy with noncoherent light in the alleviation of chemotherapy-induced mucositis in patients with metastatic cancer . BACKGROUND DATA Mucositis occurs in more than 40 % of chemotherapy-treated patients , significantly reducing the quality of their lives . Many different interventions have been evaluated to reduce oral mucositis . Recently , good results have been achieved by phototherapy with photoradiation , a technique which has virtually no side effects . Some clinical results seem to indicate that also phototherapy through noncoherent light emissions which can be produced by less expensive light sources such as light-emitting diodes ( LEDs ) may be effective . However , until now , no studies have been available on this subject . METHODS Twelve patients , aged from 34 to 82 , selected on the basis of a diagnosis of chemotherapy-induced oral mucositis , were treated intra-orally through a noncoherent LED emission , wavelength 645 + /- 15 nm , 7.8 mW , fluence 0.99 J/cm(2 ) , three times a day for 1 week . Mucositis was scored daily using the Daily Mucositis Index ( DMI ) , a scale that evaluates the disease evolution through 16 different items . The primary end-point assessed was the time to recovery , from the start of LED treatment , compared to a nonr and omized control group of 12 patients with comparable stomatitis . RESULTS The median healing time , expressed as the DMI decrease , was 1.7 ( range 1 - 2.8 ) and , in seven LED-treated patients , was shorter than in the control group . The healing rate ( measured as the ratio of the DMIs ) increased from 117 % to 164 % . CONCLUSION This pilot study shows that LED treatment is safe and capable of reducing the duration of chemotherapy-induced mucositis . This result needs to be confirmed in an adequate phase III study This study evaluated the efficacy of low-level laser therapy ( LLLT ) and aluminum hydroxide ( AH ) in the prevention of oral mucositis ( OM ) . A prospect i ve , comparative and non-r and omized study was conducted with 25 patients with head and neck cancer subjected to radiotherapy ( RT ) or radiochemotherapy ( RCT ) . Twelve patients received LLLT ( 830 nm , 15 mW , 12 J/cm² ) daily from the 1st day until the end of RT before each sessions during 5 consecutive days , and the other 13 patients received AH 310 mg/5 mL , 4 times/day , also throughout the duration of RT , including weekends . OM was measured using an oral toxicity scale ( OTS ) and pain was measured using the visual analogue scale ( VAS ) . EORTC question naires were administered to the evaluate impact of OM on quality of life . The LLLT group showed lower mean OTS and VAS scores during the course of RT . A significant difference was observed in pain evaluation in the 13th RT session ( p=0.036 ) . In both groups , no interruption of RT was needed . The prophylactic use of both treatments proposed in this study seems to reduce the incidence of severe OM lesions . However , the LLLT was more effective in delaying the appearance of severe OM BACKGROUND DATA AND OBJECTIVE Patients who have received high doses of chemotherapy , either alone or in combination with total body irradiation often cite oral mucositis ( OM ) as the most debilitating side effect . The aim of this study was to investigate the clinical effects of low-level laser therapy ( LLLT ) on the prevention of conditioning-induced OM in hematopoietic stem cell transplantation ( HSCT ) . METHODS We r and omized 42 patients who underwent autologous or allogeneic HSCT . A low-level InGaAlP diode laser was used , emitting light at 660 nm , 40 mW , and 4 J/cm(2 ) . An evaluation of OM was carried out using the World Health Organization scale . RESULTS AND CONCLUSION In the LLLT group , 57.1 % of patients had an OM grade 0 , 9.6 % had grade 1 , and 33.3 % had grade 2 , whereas in the control group , only 4.8 % of patients were free of OM ( grade 0 ) . Our results indicate that the preventive use of LLLT in patients who have undergone HSCT is a powerful instrument in reducing OM incidence OBJECTIVE The aim of this study was to compare the angiogenic effects of laser and light-emitting diode ( LED ) illumination on wounds induced in rats , with varied fluence . BACKGROUND DATA The LED is an alternative light source that accelerates wound healing , and its efficiency concerning the angiogenic effect was compared to low-level laser therapy ( LLLT ) . METHODS The experimental model consisted of a circular wound inflicted on the quadriceps of 120 rats , using a 15-mm-diameter " punch . " Animals were divided r and omly into five groups : two groups of laser , with dosages of 5 and 20 J/cm(2 ) , respectively , two groups of LED , also with dosages of 5 and 20 J/cm(2 ) , and a control group . Six hours after wound infliction , the treated groups received the diverse applications accordingly and were irradiated every 24 h. Angiogenesis was studied through histomorphometry on days 3 , 7 , 14 , and 21 after the wounds were inflicted . RESULTS On days 3 , 7 , and 14 , the proliferation of blood vessels in all irradiated groups was superior in comparison to those of the control group ( p < 0.05 ) . Treatment with fluence of 5 J/cm(2 ) was better than the laser group with 20 J/cm(2 ) on day 21 . CONCLUSION Red LLLT and LED demonstrated expressive results in angiogenesis . Light coherence was shown not to be essential to angiogenesis . However , further studies are needed in order to investigate the photobiomodulatory effects of LED in relation to LLLT in various biological tissues PURPOSE To evaluate the efficiency of Helium-Neon ( He-Ne ) laser in the prevention of oral mucositis induced by high dose chemoradiotherapy before autologous bone marrow transplantation ( BMT ) . METHODS AND MATERIAL S Between 1993 and 1995 , 30 consecutive patients receiving an autologous peripheral stem-cell or bone marrow transplant ( BMT ) after high dose chemoradiotherapy were r and omized to possibly receive prophylactic laser to the oral mucosa after giving informed consent . Chemotherapy consisted of cyclophosphamide , 60 mg/kg intravenously ( I.V. ) on day (d)-5 and d-4 in 27 cases , or melphalan 140 mg/kg I.V. on d-4 in three cases . Total body irradiation ( TBI ) consisted of 12 Gy midplane dose in six fractions ( 4 Gy/day for three days ) . He-Ne laser ( 632.8 nm wavelength , power 60 mW ) applications were performed daily from d-5 to d-1 on five anatomic sites of the oral mucosa . Oral examination was performed daily from d0 to d + 20 . Mucositis was scored according to an oral exam guide with a 16 item scale of which four were assessed by the patients themselves . Mean daily self assessment scores for oral pain , ability to swallow and oral dryness were measured . A daily mucositis index ( DMI ) and a cumulative oral mucositis score ( COMS ) were established . Requirement for narcotics and parenteral nutrition was recorded . RESULTS The COMS was significantly reduced among laser treated ( L+ ) patients ( p = 0.04 ) . The improvement of DMI in L+ patients was also statistically significant ( p < 0.05 ) from d + 2 to d + 7 . Occurrence and duration of grade III oral mucositis were reduced in L+ patients ( p = 0.01 ) . Laser applications reduced oral pain as assessed by patients ( p = 0.05 ) and L+ patients required less morphine ( p = 0.05 ) . Xerostomia and ability to swallow were improved among the L+ patients ( p = 0.005 and p = 0.01 , respectively ) . Requirement for parenteral nutrition was not reduced ( p = NS ) . CONCLUSION Helium-Neon laser treatment was well tolerated , feasible in all cases , and reduced high dose chemoradiotherapy-induced oral mucositis . Optimal laser treatment schedules still needs to be defined This article describes the system for rating the quality of medical evidence developed and used during creation of the Agency for Health Care Policy and Research -sponsored heart failure guideline . Previous approaches to rating evidence were not design ed for use in the setting of clinical practice guidelines . The present system is based on the tenet that flaws in research design are serious to the extent they threaten the validity of the results of studies . A taxonomy of major and minor flaws based on that tenet was developed for r and omized controlled trials and for cohort and medical registry studies . The use of the system is described in the context of two difficult clinical issues considered by the Panel : the role of coronary artery revascularization and the use of metoprolol OBJECTIVE The objective of this study was to evaluate the efficacy of low-level lasers for the prevention and treatment of radiotherapy-induced oral mucositis in oral cancer patients . MATERIAL AND METHODS Twenty-four hospitalized patients with oral cancer , scheduled to undergo radiotherapy at KMC , Manipal , were enrolled in the present study and assigned to laser ( Group I)/control group ( Group II ) . They were treated using He-Ne laser ( lambda = 632.8 nm , output = 10 mW and energy density = 1.8 J/cm(2 ) ) . Patients were subjected to treatment using laser scanner for 8 days and subsequently were treated using laser probe at 6 anatomic sites in the oral cavity for 5 minutes each . The patients were evaluated on each day of treatment for pain severity ( NRS ) , functional impairment ( FIS ) , and oral mucositis ( RTOG ) and were followed until the end of cancer treatment . Statistical analysis was done using SPSS version 10 . RESULTS Laser therapy applied prophylactically during radiotherapy can reduce the severity of oral mucositis , severity of pain , and functional impairment PURPOSE Oral mucositis is a major complication of concurrent chemoradiotherapy ( CRT ) in head- and -neck cancer patients . Low-level laser ( LLL ) therapy is a promising preventive therapy . We aim ed to evaluate the efficacy of LLL therapy to decrease severe oral mucositis and its effect on RT interruptions . METHODS AND MATERIAL S In the present r and omized , double-blind , Phase III study , patients received either gallium-aluminum-arsenide LLL therapy 2.5 J/cm(2 ) or placebo laser , before each radiation fraction . Eligible patients had to have been diagnosed with squamous cell carcinoma or undifferentiated carcinoma of the oral cavity , pharynx , larynx , or metastases to the neck with an unknown primary site . They were treated with adjuvant or definitive CRT , consisting of conventional RT 60 - 70 Gy ( range , 1.8 - 2.0 Gy/d , 5 times/wk ) and concurrent cisplatin . The primary endpoints were the oral mucositis severity in Weeks 2 , 4 , and 6 and the number of RT interruptions because of mucositis . The secondary endpoints included patient-reported pain scores . To detect a decrease in the incidence of Grade 3 or 4 oral mucositis from 80 % to 50 % , we planned to enroll 74 patients . RESULTS A total of 75 patients were included , and 37 patients received preventive LLL therapy . The mean delivered radiation dose was greater in the patients treated with LLL ( 69.4 vs. 67.9 Gy , p = .03 ) . During CRT , the number of patients diagnosed with Grade 3 or 4 oral mucositis treated with LLL vs. placebo was 4 vs. 5 ( Week 2 , p = 1.0 ) , 4 vs. 12 ( Week 4 , p = .08 ) , and 8 vs. 9 ( Week 6 , p = 1.0 ) , respectively . More of the patients treated with placebo had RT interruptions because of mucositis ( 6 vs. 0 , p = .02 ) . No difference was detected between the treatment arms in the incidence of severe pain . CONCLUSIONS LLL therapy was not effective in reducing severe oral mucositis , although a marginal benefit could not be excluded . It reduced RT interruptions in these head- and -neck cancer patients , which might translate into improved CRT efficacy OBJECTIVE The aim of this multidisciplinary study was to evaluate quantitatively and qualitatively the effect of a 660-nm diode laser in the prevention and treatment of human oral mucositis ( OM ) in patients suffering from head and neck cancer who had undergone radiotherapy and chemotherapy . BACKGROUND DATA OM is a severe oral lesion result ing from the toxic effects of treatment for cancer in the head and neck region . Low-level laser therapy is indicated to prevent and treat this oral complication and may be used alone or in association with conventional drug treatment , producing pain relief and wound repair . METHODS This study included 72 patients with head and neck cancer treated at the Cancer Hospital of Mato-Grosso , Brazil , and divided into a control group ( C ; n = 36 ) and a laser group ( L ; n = 36 ) . Laser therapy was performed in combination with radiotherapy and chemotherapy twice a week using a diode laser ( lambda = 660 nm , power = 30 mW , spot size = 2 mm , energy = 2 J per point ) . RESULTS Statistically significant differences were observed between the two groups . Patients in group L usually did not present with OM or pain , but all patients in group C presented with OM ranging from Level I to III associated with pain . This difference was significant from week 1 on , increased until week 4 and remained stable up to week 7 . CONCLUSION Laser therapy was effective in preventing and treating oral effects induced by radiotherapy and chemotherapy , thus improving the patient 's quality of life |
10,482 | 31,807,973 | Specific barriers span individual and structural levels and include challenges to daily adherence , cost , and stigma .
Combining health services and long-acting PrEP formulas may facilitate better PrEP uptake and adherence . | HIV prevalence among cisgender female sex workers ( FSW ) and /or women who use drugs ( WWUD ) is substantially higher compared to similarly aged women . | BACKGROUND Preexposure prophylaxis with antiretroviral agents has been shown to reduce the transmission of human immunodeficiency virus ( HIV ) among men who have sex with men ; however , the efficacy among heterosexuals is uncertain . METHODS We r and omly assigned HIV-seronegative men and women to receive either tenofovir disoproxil fumarate and emtricitabine ( TDF-FTC ) or matching placebo once daily . Monthly study visits were scheduled , and participants received a comprehensive package of prevention services , including HIV testing , counseling on adherence to medication , management of sexually transmitted infections , monitoring for adverse events , and individualized counseling on risk reduction ; bone mineral density testing was performed semiannually in a subgroup of participants . RESULTS A total of 1219 men and women underwent r and omization ( 45.7 % women ) and were followed for 1563 person-years ( median , 1.1 years ; maximum , 3.7 years ) . Because of low retention and logistic limitations , we concluded the study early and followed enrolled participants through an orderly study closure rather than exp and ing enrollment . The TDF-FTC group had higher rates of nausea ( 18.5 % vs. 7.1 % , P<0.001 ) , vomiting ( 11.3 % vs. 7.1 % , P=0.008 ) , and dizziness ( 15.1 % vs. 11.0 % , P=0.03 ) than the placebo group , but the rates of serious adverse events were similar ( P=0.90 ) . Participants who received TDF-FTC , as compared with those who received placebo , had a significant decline in bone mineral density . K65R , M184V , and A62V resistance mutations developed in 1 participant in the TDF-FTC group who had had an unrecognized acute HIV infection at enrollment . In a modified intention-to-treat analysis that included the 33 participants who became infected during the study ( 9 in the TDF-FTC group and 24 in the placebo group ; 1.2 and 3.1 infections per 100 person-years , respectively ) , the efficacy of TDF-FTC was 62.2 % ( 95 % confidence interval , 21.5 to 83.4 ; P=0.03 ) . CONCLUSIONS Daily TDF-FTC prophylaxis prevented HIV infection in sexually active heterosexual adults . The long-term safety of daily TDF-FTC prophylaxis , including the effect on bone mineral density , remains unknown . ( Funded by the Centers for Disease Control and Prevention and the National Institutes of Health ; TDF2 Clinical Trials.gov number , NCT00448669 . ) ABSTRACT Antiretroviral therapy ( ART ) has transformed HIV into a manageable illness . However , high levels of adherence must be maintained . Lack of access to basic re sources ( food , transportation , and housing ) has been consistently associated with suboptimal ART adherence . Moving beyond such direct effects , this study takes a hierarchical re sources approach in which the effects of access to basic re sources on ART adherence are mediated through interpersonal re sources ( social support and care services ) and personal re sources ( self-efficacy ) . Participants were 915 HIV-positive men and women living in Atlanta , GA , recruited from community centers and infectious disease clinics . Participants answered baseline question naires , and provided prospect i ve data on ART adherence . Across a series of nested models , a consistent pattern emerged whereby lack of access to basic re sources had indirect , negative effects on adherence , mediated through both lack of access to social support and services , and through lower treatment self-efficacy . There was also a significant direct effect of lack of access to transportation on adherence . Lack of access to basic re sources negatively impacts ART adherence . Effects for housing instability and food insecurity were fully mediated through social support , access to services , and self-efficacy , highlighting these as important targets for intervention . Targeting service supports could be especially beneficial due to the potential to both promote adherence and to link clients with other services to supplement food , housing , and transportation . Inability to access transportation had a direct negative effect on adherence , suggesting that free or reduced cost transportation could positively impact ART adherence among disadvantaged population BACKGROUND Antiretroviral pre-exposure prophylaxis reduces sexual transmission of HIV . We assessed whether daily oral use of tenofovir disoproxil fumarate ( tenofovir ) , an antiretroviral , can reduce HIV transmission in injecting drug users . METHODS In this r and omised , double-blind , placebo-controlled trial , we enrolled volunteers from 17 drug-treatment clinics in Bangkok , Thail and . Participants were eligible if they were aged 20 - 60 years , were HIV-negative , and reported injecting drugs during the previous year . We r and omly assigned participants ( 1:1 ; blocks of four ) to either tenofovir or placebo using a computer-generated r and omisation sequence . Participants chose either daily directly observed treatment or monthly visits and could switch at monthly visits . Participants received monthly HIV testing and individualised risk-reduction and adherence counselling , blood safety assessment s every 3 months , and were offered condoms and methadone treatment . The primary efficacy endpoint was HIV infection , analysed by modified intention-to-treat analysis . This trial is registered with Clinical Trials.gov , number NCT00119106 . FINDINGS Between June 9 , 2005 , and July 22 , 2010 , we enrolled 2413 participants , assigning 1204 to tenofovir and 1209 to placebo . Two participants had HIV at enrolment and 50 became infected during follow-up : 17 in the tenofovir group ( an incidence of 0·35 per 100 person-years ) and 33 in the placebo group ( 0·68 per 100 person-years ) , indicating a 48·9 % reduction in HIV incidence ( 95 % CI 9·6 - 72·2 ; p=0·01 ) . The occurrence of serious adverse events was much the same between the two groups ( p=0·35 ) . Nausea was more common in participants in the tenofovir group than in the placebo group ( p=0·002 ) . INTERPRETATION In this study , daily oral tenofovir reduced the risk of HIV infection in people who inject drugs . Pre-exposure prophylaxis with tenofovir can now be considered for use as part of an HIV prevention package for people who inject drugs . FUNDING US Centers for Disease Control and Prevention and the Bangkok Metropolitan Administration Objective : To describe participant adherence to daily oral tenofovir in an HIV preexposure prophylaxis ( PrEP ) trial , examine factors associated with adherence , and assess the impact of adherence on the risk of HIV infection . Design : The Bangkok Tenofovir Study was a r and omized , double-blind , placebo-controlled trial conducted among people who inject drugs , 2005–2012 . Methods : Participants chose daily visits or monthly visits . Study nurses observed participants swallow study drug and both initialed a diary . We assessed adherence using the diary . We examined adherence by age group and sex and used logistic regression to evaluate demographics and risk behaviors as predictors of adherence and Cox regression to assess the impact of adherence on the risk of HIV infection . Results : A total of 2413 people enrolled and contributed 9665 person-years of follow-up ( mean 4.0 years , maximum 6.9 years ) . The risk of HIV infection decreased as adherence improved , from 48.9 % overall to 83.5 % for those with at least 97.5 % adherence . In multivariable analysis , men were less adherent than women ( P = 0.006 ) and participants 20–29 years old ( P < 0.001 ) and 30–39 years old ( P = 0.01 ) were less adherent than older participants . Other factors associated with poor adherence included incarceration ( P = 0.02 ) and injecting methamphetamine ( P = 0.04 ) . Conclusion : In this HIV PrEP trial among people who inject drugs , improved adherence to daily tenofovir was associated with a lower risk of HIV infection . This is consistent with trials among MSM and HIV-discordant heterosexual couples and suggests that HIV PrEP can provide a high level of protection from HIV infection BACKGROUND Preexposure prophylaxis with antiretroviral drugs has been effective in the prevention of human immunodeficiency virus ( HIV ) infection in some trials but not in others . METHODS In this r and omized , double-blind , placebo-controlled trial , we assigned 2120 HIV-negative women in Kenya , South Africa , and Tanzania to receive either a combination of tenofovir disoproxil fumarate and emtricitabine ( TDF-FTC ) or placebo once daily . The primary objective was to assess the effectiveness of TDF-FTC in preventing HIV acquisition and to evaluate safety . RESULTS HIV infections occurred in 33 women in the TDF-FTC group ( incidence rate , 4.7 per 100 person-years ) and in 35 in the placebo group ( incidence rate , 5.0 per 100 person-years ) , for an estimated hazard ratio in the TDF-FTC group of 0.94 ( 95 % confidence interval , 0.59 to 1.52 ; P=0.81 ) . The proportions of women with nausea , vomiting , or elevated alanine aminotransferase levels were significantly higher in the TDF-FTC group ( P=0.04 , P<0.001 , and P=0.03 , respectively ) . Rates of drug discontinuation because of hepatic or renal abnormalities were higher in the TDF-FTC group ( 4.7 % ) than in the placebo group ( 3.0 % , P=0.051 ) . Less than 40 % of the HIV-uninfected women in the TDF-FTC group had evidence of recent pill use at visits that were matched to the HIV-infection window for women with seroconversion . The study was stopped early , on April 18 , 2011 , because of lack of efficacy . CONCLUSIONS Prophylaxis with TDF-FTC did not significantly reduce the rate of HIV infection and was associated with increased rates of side effects , as compared with placebo . Despite substantial counseling efforts , drug adherence appeared to be low . ( Supported by the U.S. Agency for International Development and others ; FEM-PrEP Clinical Trials.gov number , NCT00625404 . ) BACKGROUND Antiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 ( HIV-1 ) infection in heterosexual population s. METHODS We conducted a r and omized trial of oral antiretroviral therapy for use as preexposure prophylaxis among HIV-1-serodiscordant heterosexual couples from Kenya and Ug and a. The HIV-1-seronegative partner in each couple was r and omly assigned to one of three study regimens -- once-daily tenofovir ( TDF ) , combination tenofovir-emtricitabine ( TDF-FTC ) , or matching placebo-- and followed monthly for up to 36 months . At enrollment , the HIV-1-seropositive partners were not eligible for antiretroviral therapy , according to national guidelines . All couples received st and ard HIV-1 treatment and prevention services . RESULTS We enrolled 4758 couples , of whom 4747 were followed : 1584 r and omly assigned to TDF , 1579 to TDF-FTC , and 1584 to placebo . For 62 % of the couples followed , the HIV-1-seronegative partner was male . Among HIV-1-seropositive participants , the median CD4 count was 495 cells per cubic millimeter ( interquartile range , 375 to 662 ) . A total of 82 HIV-1 infections occurred in seronegative participants during the study , 17 in the TDF group ( incidence , 0.65 per 100 person-years ) , 13 in the TDF-FTC group ( incidence , 0.50 per 100 person-years ) , and 52 in the placebo group ( incidence , 1.99 per 100 person-years ) , indicating a relative reduction of 67 % in the incidence of HIV-1 with TDF ( 95 % confidence interval [ CI ] , 44 to 81 ; P<0.001 ) and of 75 % with TDF-FTC ( 95 % CI , 55 to 87 ; P<0.001 ) . Protective effects of TDF-FTC and TDF alone against HIV-1 were not significantly different ( P=0.23 ) , and both study medications significantly reduced the HIV-1 incidence among both men and women . The rate of serious adverse events was similar across the study groups . Eight participants receiving active treatment were found to have been infected with HIV-1 at baseline , and among these eight , antiretroviral resistance developed in two during the study . CONCLUSIONS Oral TDF and TDF-FTC both protect against HIV-1 infection in heterosexual men and women . ( Funded by the Bill and Melinda Gates Foundation ; Partners PrEP Clinical Trials.gov number , NCT00557245 . ) Background Operational research is required to design delivery of pre-exposure prophylaxis ( PrEP ) and early antiretroviral treatment ( ART ) . This paper presents the primary analysis of programmatic data , as well as demographic , behavioural , and clinical data , from the TAPS Demonstration Project , which offered both interventions to female sex workers ( FSWs ) at 2 urban clinic sites in South Africa . Methods and findings The TAPS study was conducted between 30 March 2015 and 30 June 2017 , with the enrolment period ending on 31 July 2016 . TAPS was a prospect i ve observational cohort study with 2 groups receiving interventions delivered in existing service setting s : ( 1 ) PrEP as part of combination prevention for HIV-negative FSWs and ( 2 ) early ART for HIV-positive FSWs . The main outcome was programme retention at 12 months of follow-up . Of the 947 FSWs initially seen in clinic , 692 were HIV tested . HIV prevalence was 49 % . Among those returning to clinic after HIV testing and clinical screening , 93 % of the women who were HIV-negative were confirmed as clinical ly eligible for PrEP ( n = 224/241 ) , and 41 % ( n = 110/270 ) of the women who were HIV-positive had CD4 counts within National Department of Health ART initiation guidelines at assessment . Of the remaining women who were HIV-positive , 93 % were eligible for early ART ( n = 148/160 ) . From those eligible , 98 % ( n = 219/224 ) and 94 % ( n = 139/148 ) took up PrEP and early ART , respectively . At baseline , a substantial fraction of women had a steady partner , worked in brothels , and were born in Zimbabwe . Of those enrolled , 22 % on PrEP ( n = 49/219 ) and 60 % on early ART ( n = 83/139 ) were seen at 12 months ; we observed high rates of loss to follow-up : 71 % ( n = 156/219 ) and 30 % ( n = 42/139 ) in the PrEP and early ART groups , respectively . Little change over time was reported in consistent condom use or the number of sexual partners in the last 7 days , with high levels of consistent condom use with clients and low use with steady partners in both study groups . There were no seroconversions on PrEP and 7 virological failures on early ART among women remaining in the study . Reported adherence to PrEP varied over time between 70 % and 85 % , whereas over 90 % of participants reported taking pills daily while on early ART . Data on provider-side costs were also collected and analysed . The total cost of service delivery was approximately US$ 126 for PrEP and US$ 406 for early ART per person-year . The main limitations of this study include the lack of a control group , which was not included due to ethical considerations ; clinical study requirements imposed when PrEP was not approved through the regulatory system , which could have affected uptake ; and the timing of the implementation of a national sex worker HIV programme , which could have also affected uptake and retention . Conclusions PrEP and early ART services can be implemented within FSW routine services in high prevalence , urban setting s. We observed good uptake for both PrEP and early ART ; however , retention rates for PrEP were low . Retention rates for early ART were similar to retention rates for the current st and ard of care . While the cost of the interventions was higher than previously published , there is potential for cost reduction at scale . The TAPS Demonstration Project results provided the basis for the first government PrEP and early ART guidelines and the rollout of the national sex worker HIV programme in South Africa BACKGROUND Results of the r and omised , double-blind , placebo-controlled Bangkok Tenofovir Study ( BTS ) showed that taking tenofovir daily as pre-exposure prophylaxis ( PrEP ) can reduce the risk of HIV infection by 49 % in people who inject drugs . In an extension to the trial , participants were offered 1 year of open-label tenofovir . We aim ed to examine the demographic characteristics , drug use , and risk behaviours associated with participants ' uptake of and adherence to PrEP . METHODS In this observational , open-label extension of the BTS ( NCT00119106 ) , non-pregnant , non-breastfeeding , HIV-negative BTS participants , all of whom were current or previous injecting drug users at the time of enrolment in the BTS , were offered daily oral tenofovir ( 300 mg ) for 1 year at 17 Bangkok Metropolitan Administration drug-treatment clinics . Participant demographics , drug use , and risk behaviours were assessed at baseline and every 3 months using an audio computer-assisted self-interview . HIV testing was done monthly and serum creatinine was assessed every 3 months . We used logistic regression to examine factors associated with the decision to take daily tenofovir as PrEP , the decision to return for at least one PrEP follow-up visit , and greater than 90 % adherence to PrEP . FINDINGS Between Aug 1 , 2013 , and Aug 31 , 2014 , 1348 ( 58 % ) of the 2306 surviving BTS participants returned to the clinics , 33 of whom were excluded because they had HIV ( n=27 ) or grade 2 - 4 creatinine results ( n=6 ) . 798 ( 61 % ) of the 1315 eligible participants chose to start open-label PrEP and were followed up for a median of 335 days ( IQR 0 - 364 ) . 339 ( 42 % ) participants completed 12 months of follow-up ; 220 ( 28 % ) did not return for any follow-up visits . Participants who were 30 years or older ( odds ratio [ OR ] 1·8 , 95 % CI 1·4 - 2·2 ; p<0·0001 ) , injected heroin ( OR 1·5 , 1·1 - 2·1 ; p=0·007 ) , or had been in prison ( OR 1·7 , 1·3 - 2·1 ; p<0·0001 ) during the r and omised trial were more likely to choose PrEP than were those without these characteristics . Participants who reported injecting heroin or being in prison during the 3 months before open-label enrolment were more likely to return for at least one open-label follow-up visit than those who did not report injecting heroin ( OR 3·0 , 95 % CI 1·3 - 7·3 ; p=0·01 ) or being in prison ( OR 2·3 , 1·4 - 3·7 ; p=0·0007 ) . Participants who injected midazolam or were in prison during open-label follow-up were more likely to be greater than 90 % adherent than were those who did not inject midazolam ( OR 2·2 , 95 % CI 1·2 - 4·3 ; p=0·02 ) or were not in prison ( OR 4·7 , 3·1 - 7·2 ; p<0·0001 ) . One participant tested positive for HIV , yielding an HIV incidence of 2·1 ( 95 % CI 0·05 - 11·7 ) per 1000 person-years . No serious adverse events related to tenofovir use were reported . INTERPRETATION More than 60 % of returning , eligible BTS participants started PrEP , which indicates that a substantial proportion of PWID who are knowledgeable about PrEP might be interested in taking it . Participants who had injected heroin or been in prison were more likely to choose to take PrEP , suggesting that participants based their decision to take PrEP , at least in part , on their perceived risk of incident HIV infection . FUNDING US Centers for Disease Control and Prevention and the Bangkok Metropolitan Administration Introduction In the Microbicide Trial Network MTN-003 ( VOICE ) study , a Phase IIB pre-exposure prophylaxis trial of daily oral or vaginal tenofovir ( TFV ) , product adherence was poor based on pharmacokinetic ( PK ) drug detection in a r and om sub sample . Here , we sought to compare behavioural and PK measures of adherence and examined correlates of adherence misreporting . Methods We included participants with PK and behavioural data from VOICE r and om sub sample . Behavioural assessment s included face-to-face interviews ( FTFI ) , audio computer-assisted self-interviewing ( ACASI ) and pharmacy-returned product counts ( PC ) . TFV concentrations < 0.31 ng/mL in plasma ( oral group ) and < 8.5 ng/swab in vaginal group were defined as “ PK non-adherent . ” Logistic regression models were fit to calculate the combined predictive ability of the behavioural measures as summarized by area under the curve ( AUC ) . Baseline characteristics associated with over-reporting daily product use relative to PK measures was assessed using a Generalized Linear Mixed Model . Results In this r and om adherence cohort of VOICE participants assigned to active products , ( N=472 ) , PK non-adherence was 69 % in the oral group ( N=314 ) and 65 % in the vaginal group ( N=158 ) . Behaviourally , ≤10 % of the cohort reported low/none use with any behavioural measure and accuracy was low ( ≤43 % ) . None of the regression models had an AUC > 0.65 for any single or combined behavioural measures . Significant ( p<0.05 ) correlates of over-reporting included being very worried about getting HIV and being unmarried for the oral group ; whereas for the vaginal group , being somewhat worried about HIV was associated with lower risk of over-reporting . Conclusions PK measures indicated similarly low adherence for the oral and vaginal groups . No behavioural measure accurately predicted PK non-adherence . Accurate real-time measures to monitor product adherence are urgently needed . Trial registration : Clinical Trials.gov identifier : Few studies of pre-exposure prophylaxis ( PrEP ) to prevent HIV infection have focused on drug users . Between February to September 2013 , we asked 351 opiate injectors entering detoxification treatment about HIV risk , knowledge about PrEP , and willingness to use a once daily PrEP pill under one of two r and omly assigned effectiveness scenarios—40 % ( low ) or 90 % ( high ) effective in reducing HIV risk . Participants were 70 % male and 87 % non-Hispanic White . Only 7 % had heard of a drug to reduce HIV risk , yet once informed , 47 % would be willing to take such a pill [ 35 % of those in the low effectiveness scenario and 58 % in the high group ( p < 0.001 ) ] . Higher perceived HIV risk was associated with greater willingness to take medication . Increasing knowledge of PrEP and the rate of HIV reduction-effectiveness promised will influence its use among targeted high-risk drug users Research on street-based female sex workers documents a multitude of problems faced by these women , such as substance use , HIV risk , mental health problems , victimization , and homelessness . The presence of problems such as these is understood as a syndemic , or co-occurrence of two or more risk factors that act synergistically to create an excess burden of disease . However , the syndemic framework has not previously incorporated the examination of resilience to underst and what protective factors enable female sex workers to cope with syndemic risk . Using 562 baseline interviews from street-based African-American female sex workers enrolled in a r and omized intervention trial , this study is the first to investigate expressions of resilience among this vulnerable population . Specifically , these analyses examine high levels of resilience , as measured by personal mastery , in order to underst and the contributions of syndemic risk factors and protective factors on the expression of resilience . In bivariate logistic regression models , women with high resilience reported significantly higher odds of high school education , greater access to transportation , and more social support , in addition to lower odds of foster care history , homelessness , substance dependence , severe mental distress , victimization , and HIV risk . In the multivariate model , higher odds of high school education and increased social support , in addition to lower odds of mental distress and HIV risk remained associated with high resilience . The findings suggest specific targets for intervention to assist female sex workers in coping with syndemic risk factors and achieving better health outcomes . These include the prioritizing of education and training opportunities and the enhancement of social support BACKGROUND Strengthening engagement of female sex workers with health services is needed to eliminate HIV . We assessed the efficacy of a targeted combination intervention for female sex workers in Zimbabwe . METHODS We did a cluster-r and omised trial from 2014 to 2016 . Clusters were areas surrounding female sex worker clinics and were enrolled in matched pairs . Sites were r and omly assigned ( 1:1 ) to receive usual care ( free sexual-health services supported by peer educators , including HIV testing on dem and , referral for antiretroviral therapy [ ART ] , and health education ) or an intervention that supported additional regular HIV testing , on-site initiation of ART , pre-exposure prophylaxis , adherence , and intensified community mobilisation . The primary outcome was the proportion of all female sex workers with HIV viral load 1000 copies per mL or greater , assessed through respondent-driven sampling surveys . We used an adapted cluster- summary approach to estimate risk differences . This trial is registered with Pan African Clinical Trials Registry , number PACTR201312000722390 . RESULTS We r and omly assigned 14 clusters to usual care or the intervention ( seven in each group ) . 3612 female sex workers attended clinics in the usual-care clusters and 4619 in the intervention clusters during the study . Half as many were tested ( 1151 vs 2606 ) and diagnosed as being HIV positive ( 546 vs 1052 ) in the usual-care clusters . The proportion of all female sex workers with viral loads of 1000 copies per mL or greater fell in both study groups ( from 421 [ 30 % ] of 1363 to 279 [ 19 % ] of 1443 in the usual-care group and from 399 [ 30 % ] of 1303 to 240 [ 16 % ] of 1439 in the intervention group ) , but with a risk difference at the end of the assessment period of only -2·8 % ( 95 % CI -8·1 to 2·5 , p=0·23 ) . Among HIV-positive women , the proportions with viral loads less than 1000 copies per mL were 590 ( 68 % ) of 869 in the usual-care group and 588 ( 72 % ) of 828 in the intervention group at the end of the assessment period , adjusted risk difference of 5·3 % ( 95 % CI -4·0 to 14·6 , p=0·20 ) . There were no adverse events . INTERPRETATION Our intervention of a dedicated programme for female sex workers led to high levels of HIV diagnosis and treatment . Further research is needed to optimise programme content and intensity for the broader population . FUNDING UN Population Fund ( through Zimbabwe 's Integrated Support Fund funded by UK Department for International Development , Irish Aid , and Swedish International Development Cooperation Agency ) Background HIV pre-exposure prophylaxis ( PrEP ) is highly effective for prevention of HIV acquisition , but requires HIV testing at regular intervals . Female sex workers ( FSWs ) are a priority population for HIV prevention interventions in many setting s , but face barriers to accessing healthcare . Here , we assessed the acceptability of HIV self-testing for regular HIV testing during PrEP implementation among FSWs participating in a r and omized controlled trial of HIV self-testing delivery models . Methods We used data from two HIV self-testing r and omized controlled trials with identical protocol s in Zambia and in Ug and a. From September – October 2016 , participants were r and omized in groups to : ( 1 ) direct delivery of an HIV self-test , ( 2 ) delivery of a coupon , exchangeable for an HIV self-test at nearby health clinics , or ( 3 ) st and ard HIV testing services . Participants completed assessment s at baseline and 4 weeks . Participants reporting their last HIV test was negative were asked about their interest in various PrEP modalities and their HIV testing preferences . We used mixed effects logistic regression models to measure differences in outcomes across r and omization arms at four weeks . Results At 4 weeks , 633 participants in Zambia and 749 participants in Ug and a reported testing negative at their last HIV test . The majority of participants in both studies were “ very interested ” in daily oral PrEP ( 91 % Zambia ; 66 % Ug and a ) and preferred HIV self-testing to st and ard testing services while on PrEP ( 87 % Zambia ; 82 % Ug and a ) . Participants in the HIV self-testing intervention arms more often reported preference for HIV self-testing compared to st and ard testing services to support PrEP in both Zambia ( P = 0.002 ) and Ug and a ( P < 0.001 ) . Conclusion PrEP implementation programs for FSW could consider inclusion of HIV self-testing to reduce the clinic-based HIV testing burden . Trial registration Clinical Trials.gov NCT02827240 and NCT02846402 Objective To describe the frequency of being partnered and having an HIV-negative partner , and whether this differed by gender , among a cohort of persons living with HIV ( PLWH ) who have ever injected drugs ; to describe awareness of HIV pre-exposure prophylaxis ( PrEP ) and perceived partner interest in PrEP . Setting Secondary analyses of an observational cohort study of PLWH who have ever injected drugs in St. Petersburg , Russia . Methods Primary outcomes were 1 ) being partnered and 2 ) being in a serodiscordant partnership . The main independent variable was gender . Multivariable GEE logistic regression models were fit for binary outcomes , adjusted for age , income , education , and recent opioid use . Descriptive analyses were performed for partners ’ HIV status , substance use , sex risk behaviors , and awareness of PrEP for a subset of participants . Results At baseline , 50 % ( 147/296 ) reported being in a partnership , and of those , 35 % were in a serodiscordant partnership . After adjustment , women had significantly higher odds of being partnered compared to men ( aOR = 3.12 ; 95 % CI : 1.77 , 5.51 ) , but there were no significant gender differences in the odds of being in a serodiscordant partnership ( aOR = 0.58 ; 95 % CI : 0.27 , 1.24 ) . Among a sub- sample of participants queried ( n = 56 ) , 25 % were aware of PrEP for prevention of sexual HIV transmission and 14 % for prevention of injection-related transmission . Conclusion Although half of our sample were partnered and one third of these partnerships were serodiscordant , PrEP awareness was low . Substantial opportunities for HIV prevention exist among PLWH who have ever injected drugs in Russia and their HIV-negative partners . Given the high proportion of HIV-negative partners among this ART-naïve sample , efforts to address the associated inherent risks , such as couples-based interventions , are needed to increase condom use , PrEP awareness , or uptake of other HIV-prevention modalities ( e.g. , ART for the HIV-positive partner ) Abstract Introduction In sub‐Saharan Africa , HIV prevalence remains high , especially among key population s. In such situations , combination prevention including clinical , behavioural , structural and biological components , as well as adequate treatment are important . We conducted a demonstration project at the Dispensaire IST , a clinic dedicated to female sex workers ( FSWs ) in Cotonou , on early antiretroviral therapy ( E‐ART , or immediate “ test‐ and ‐treat ” ) and pre‐exposure prophylaxis ( PrEP ) . We present key indicators such as uptake , retention and adherence . Methods In this prospect i ve observational study , we recruited FSWs from October 4th 2014 to December 31st 2015 and followed them until December 31st 2016 . FSWs were provided with daily tenofovir disoproxil fumarate/emtricitabine ( Truvada ® ) for PrEP or received a first‐line antiretroviral regimen as per Benin guidelines . We used generalized estimating equations to assess trends in adherence and sexual behaviour . Results Among FSWs in the catchment area , HIV testing coverage within the study framework was 95.5 % ( 422/442 ) . At baseline , HIV prevalence was 26.3 % ( 111/422 ) . Among eligible FSWs , 95.5 % ( 105/110 ) were recruited for E‐ART and 88.3 % ( 256/290 ) for PrEP . Overall retention at the end of the study was 59.0 % ( 62/105 ) for E‐ART and 47.3 % ( 121/256 ) for PrEP . Mean ( ±SD ) duration of follow‐up was 13.4 ( ±7.9 ) months for E‐ART and 11.8 ( ±7.9 ) months for PrEP . Self‐reported adherence was over 90 % among most E‐ART participants . For PrEP , adherence was lower and the proportion with 100 % adherence decreased over time from 78.4 % to 56.7 % ( p‐trend < 0.0001 ) . During the 250.1 person‐years of follow‐up among PrEP initiators , two seroconversions occurred ( incidence 0.8/100 person‐years ( 95 % confidence interval : 0.3 to 1.9/100 person‐years ) ) . The two seroconverters had stopped using PrEP for at least six months before being found HIV‐infected . In both groups , there was no evidence of reduced condom use . Conclusions This study provides data on key indicators for the integration of E‐ART and PrEP into the HIV prevention combination package already offered to FSWs in Benin . PrEP may be more useful as an individual intervention for adherent FSWs rather than a specific public health intervention . E‐ART was a more successful intervention in terms of retention and adherence and is now offered to all key population s in Benin . Study registration Clinical Trials.gov |
10,483 | 21,606,136 | Although the data were derived from the baseline screening rounds only , the decrease in the sensitivity for high grade cervical intraepithelial neoplasia using a hybrid capture 2 cut-off level between ≥ 2 rlu/co and ≥ 10 rlu/co seemed acceptable given the international recommendations for testing for human papillomavirus DNA in cervical screening , which require 90 % or more sensitivity for cervical intraepithelial neoplasia grade II or higher compared with hybrid capture 2 at ≥ 1 rlu/co .
The data suggest that the hybrid capture 2 cut-off level could be increased in primary screening ; this seems reasonably safe and is significantly less burdensome for women | OBJECTIVE To determine the trade-off between the sensitivity and the specificity for high grade cervical intraepithelial neoplasia at hybrid capture 2 cut-off values above the st and ard ≥ 1 relative light units/cut-off level ( rlu/co ) . | Background In the HPV FOCAL trial , we will establish the efficacy of hr-HPV DNA testing as a st and -alone screening test followed by liquid based cytology ( LBC ) triage of hr-HPV-positive women compared to LBC followed by hr-HPV triage with ≥ CIN3 as the outcome . Methods / Design HPV-FOCAL is a r and omized , controlled , three-armed study over a four year period conducted in British Columbia . It will recruit 33,000 women aged 25 - 65 through the province 's population based cervical cancer screening program . Control arm : LBC at entry and two years , and combined LBC and hr-HPV at four years among those with initial negative results and hr-HPV triage of ASCUS cases ; Two Year Safety Check arm : hr-HPV at entry and LBC at two years in those with initial negative results with LBC triage of hr-HPV positives ; Four Year Intervention Arm : hr-HPV at entry and combined hr-HPV and LBC at four years among those with initial negative results with LBC triage of hr-HPV positive cases Discussion To date , 6150 participants have a completed sample and epidemiologic question naire . Of the 2019 women enrolled in the control arm , 1908 ( 94.5 % ) were cytology negative . Women aged 25 - 29 had the highest rates of HSIL ( 1.4 % ) . In the safety arm 92.2 % of women were hr-HPV negative , with the highest rate of hr-HPV positivity found in 25 - 29 year old women ( 23.5 % ) . Similar results were obtained in the intervention arm HPV FOCAL is the first r and omized trial in North America to examine hr-HPV testing as the primary screen for cervical cancer within a population -based cervical cancer screening program . Trial Registration International St and ard R and omised Controlled Trial Number Register , IS RCT BACKGROUND Although testing for human papillomavirus ( HPV ) has higher sensitivity and lower specificity than cytology alone for detecting cervical intraepithelial neoplasia ( CIN ) , studies comparing conventional and liquid-based cytology have had conflicting results . METHODS In the first phase of a two-phase multicenter r and omized controlled trial , women aged 35 - 60 years in the conventional arm ( n = 16,658 ) were screened using conventional cytology , and women in the experimental arm ( n = 16,706 ) had liquid-based cytology and were tested for high-risk HPV types using the Hybrid Capture 2 assay . Women in the conventional arm were referred to colposcopy with atypical cells of undetermined significance ( ASCUS ) or higher and those in the experimental arm were referred with ASCUS or higher cytology or with a positive ( > or = 1 pg/mL ) HPV test . Sensitivity and positive predictive value ( PPV ) for detection of cervical intraepithelial neoplasia grade 2 or higher ( CIN2 + ) were calculated . RESULTS The screening methods and referral criterion applied in the experimental arm had higher sensitivity than that in the conventional arm ( relative sensitivity = 1.47 ; 95 % confidence interval [ CI ] = 1.03 to 2.09 ) but a lower PPV ( relative PPV = 0.40 ; 95 % CI = 0.23 to 0.66 ) . With HPV testing alone at > or = 1 pg/mL and at > or = 2 pg/mL , the gain in sensitivity compared with the conventional arm remained similar ( relative sensitivity = 1.43 , 95 % CI = 1.00 to 2.04 and relative sensitivity = 1.41 , 95 % CI = 0.98 to 2.01 , respectively ) but PPV progressively improved ( relative PPV = 0.58 , 95 % CI = 0.33 to 0.98 and relative PPV = 0.75 , 95 % CI = 0.45 and 1.27 , respectively ) . Referral based on liquid-based cytology alone did not increase sensitivity compared with conventional cytology ( relative sensitivity = 1.06 ; 95 % CI = 0.72 to 1.55 ) but reduced PPV ( relative PPV = 0.57 ; 95 % CI = 0.39 to 0.82 ) . CONCLUSIONS HPV testing alone was more sensitive than conventional cytology among women 35 - 60 years old . Adding liquid-based cytology improved sensitivity only marginally but increased false-positives . HPV testing using Hybrid Capture 2 with a 2 pg/mL cutoff may be more appropriate than a 1 pg/mL cutoff for primary cervical cancer screening BACKGROUND In the first recruitment phase of a r and omized trial of cervical cancer screening methods ( New Technologies for Cervical Cancer Screening [ NTCC ] study ) , we compared screening with conventional cytology with screening by human papillomavirus ( HPV ) testing in combination with liquid-based cytology . HPV-positive women were directly referred to colposcopy if aged 35 or older ; if younger , they were retested after 1 year . METHODS In the second recruitment phase of NTCC , we r and omly assigned women to conventional cytology ( n = 24,661 ) with referral to colposcopy if cytology indicated atypical squamous cells of undetermined significance or more severe abnormality or to testing for high-risk HPV DNA alone by Hybrid Capture 2 ( n = 24,535 ) with referral to colposcopy if the test was positive at a concentration of HPV DNA 1 pg/mL or greater . For the main endpoint of the study , histologic detection of cervical intraepithelial neoplasia of grade 2 or more ( CIN2 + ) , we calculated and compared sensitivity and positive predictive value ( PPV ) of the two screening methods using HPV DNA cutoffs of 1 pg/mL and 2 pg/mL. All statistical tests were two-sided . RESULTS For women aged 35 - 60 years , the relative sensitivity of HPV testing for detection of CIN2 + at a cutoff of 1 pg/mL vs conventional cytology was 1.92 ( 95 % CI = 1.28 to 2.87 ) and the relative PPV was 0.80 ( 95 % CI = 0.55 to 1.18 ) . At a cutoff of 2 pg/mL HPV DNA , the relative sensitivity was 1.81 ( 95 % CI = 1.20 to 2.72 ) and the relative PPV was 0.99 ( 95 % CI = 0.67 to 1.46 ) . In this age group , there was no evidence of heterogeneity between study phases . Among women aged 25 - 34 years , the relative sensitivity for detection of CIN2 + of HPV testing at a cutoff of 1 pg/mL vs cytology was 3.50 ( 95 % CI = 2.11 to 5.82 ) , statistically significantly larger ( P = .019 ) than that observed in phase 1 at this age ( 1.58 ; 95 % CI = 1.03 to 2.44 ) . CONCLUSIONS For women aged 35 - 60 years , HPV testing with a cutoff of 2 pg/mL achieves a substantial gain in sensitivity over cytology with only a small reduction in PPV . Among women aged 25 - 34 years , the large relative sensitivity of HPV testing compared with conventional cytology and the difference between relative sensitivity during phases 1 and 2 suggests that there is frequent regression of CIN2 + that are detected by direct referral of younger HPV-positive women to colposcopy . Thus , triage test or repeat testing is needed if HPV is to be used for primary testing in this context CONTEXT Non-cytology-based screen- and -treat approaches for cervical cancer prevention have been developed for low-re source setting s , but few have directly addressed efficacy . OBJECTIVE To determine the safety and efficacy of 2 screen- and -treat approaches for cervical cancer prevention that were design ed to be more re source -appropriate than conventional cytology-based screening programs . DESIGN , SETTING , AND PATIENTS R and omized clinical trial of 6555 nonpregnant women , aged 35 to 65 years , recruited through community outreach and conducted between June 2000 and December 2002 at ambulatory women 's health clinics in Khayelitsha , South Africa . INTERVENTIONS All patients were screened using human papillomavirus ( HPV ) DNA testing and visual inspection with acetic acid ( VIA ) . Women were subsequently r and omized to 1 of 3 groups : cryotherapy if she had a positive HPV DNA test result ; cryotherapy if she had a positive VIA test result ; or to delayed evaluation . MAIN OUTCOME MEASURES Biopsy-confirmed high- grade cervical cancer precursor lesions and cancer at 6 and 12 months in the HPV DNA and VIA groups compared with the delayed evaluation ( control ) group ; complications after cryotherapy . RESULTS The prevalence of high- grade cervical intraepithelial neoplasia and cancer ( CIN 2 + ) was significantly lower in the 2 screen- and -treat groups at 6 months after r and omization than in the delayed evaluation group . At 6 months , CIN 2 + was diagnosed in 0.80 % ( 95 % confidence interval [ CI ] , 0.40%-1.20 % ) of the women in the HPV DNA group and 2.23 % ( 95 % CI , 1.57%-2.89 % ) in the VIA group compared with 3.55 % ( 95 % CI , 2.71%-4.39 % ) in the delayed evaluation group ( P<.001 and P = .02 for the HPV DNA and VIA groups , respectively ) . A subset of women underwent a second colposcopy 12 months after enrollment . At 12 months the cumulative detection of CIN 2 + among women in the HPV DNA group was 1.42 % ( 95 % CI , 0.88%-1.97 % ) , 2.91 % ( 95 % CI , 2.12%-3.69 % ) in the VIA group , and 5.41 % ( 95 % CI , 4.32%-6.50 % ) in the delayed evaluation group . Although minor complaints , such as discharge and bleeding , were common after cryotherapy , major complications were rare . CONCLUSION Both screen- and -treat approaches are safe and result in a lower prevalence of high- grade cervical cancer precursor lesions compared with delayed evaluation at both 6 and 12 months . Trial Registration http:// clinical trials.gov Identifier : NCT00233727 OBJECTIVES Primary cervical screening uses cytology to detect cancer precursor lesions [ cervical intraepithelial neoplasia stage 3 or beyond ( CIN3 + ) ] . Human papillomavirus ( HPV ) testing could add sensitivity as an adjunct to cytology or as a first test , reserving cytology for HPV-positive women . This study addresses the questions : Does the combination of cytology and HPV testing achieve a reduction in incident CIN3 + ? ; Is HPV testing cost-effective in primary cervical screening ? ; Is its use associated with adverse psychosocial or psychosexual effects ? ; and How would it perform as an initial screening test followed by cytology for HPV positivity ? DESIGN ARTISTIC was a r and omised trial of cervical cytology versus cervical cytology plus HPV testing , evaluated over two screening rounds , 3 years apart . Round 1 would detect prevalent disease and round 2 a combination of incident and undetected disease from round 1 . SETTING Women undergoing routine cervical screening in the NHS programme in Greater Manchester . PARTICIPANTS In total 24,510 women aged 20 - 64 years were enrolled between July 2001 and September 2003 . INTERVENTIONS HPV testing was performed on the liquid-based cytology ( LBC ) sample obtained at screening . Women were r and omised in a ratio of 3:1 to have the HPV test result revealed and acted upon if persistently positive in cytology-negative cases or concealed . A detailed health economic evaluation and a psychosocial and psychosexual assessment were also performed . MAIN OUTCOME MEASURES The primary outcome was CIN3 + in round 2 . Secondary outcomes included an economic assessment and psychosocial effects . A large HPV genotyping study was also conducted . RESULTS In round 1 there were 313 CIN3 + lesions , representing a prevalence in the revealed and concealed arms of 1.27 % and 1.31 % respectively ( p = 0.81 ) . Round 2 ( 30 - 48 months ) involved 14,230 ( 58.1 % ) of the women screened in round 1 and only 31 CIN3 + were detected ; the CIN3 rate was not significantly different between the revealed and concealed arms . A less restrictive definition of round 2 ( 26 - 54 months ) increased CIN3 + to 45 and CIN3 + incidence in the arms was significantly different ( p = 0.05 ) . There was no difference in CIN3 + between the arms when rounds 1 and 2 were combined . Prevalence of high-risk HPV types was age-dependent . Overall prevalence of HPV16/18 increased with severity of dyskaryosis . Mean costs per woman in round 1 were 72 pounds and 56 pounds for the revealed and concealed arms ( p < 0.001 ) ; an age-adjustment reduced these mean costs to 65 pounds and 52 pounds . Incremental cost-effectiveness ratio for detecting additional CIN3 + by adding HPV testing to LBC screening in round 1 was 38,771 pounds . Age-adjusted mean cost for LBC primary screening with HPV triage was 39 pounds compared with 48 pounds for HPV primary screening with LBC triage . HPV testing did not appear to cause significant psychosocial distress . CONCLUSIONS Routine HPV testing did not add significantly to the effectiveness of LBC in this study . No significant adverse psychosocial effects were detected . It would not be cost-effective to screen with cytology and HPV combined but HPV testing , as either triage or initial test triaged by cytology , would be cheaper than cytology without HPV testing . LBC would not benefit from combination with HPV ; it is highly effective as primary screening but HPV testing has twin advantages of high negative predictive value and automated platforms enabling high throughput . HPV primary screening would require major contraction and reconfiguration of laboratory services . Follow-up continues in ARTISTIC while maintaining concealment for a further 3-year round of screening , which will help in screening protocol development for the post-vaccination era OBJECTIVES The aim of this study was to determine if there were any long-lasting elevated anxiety levels in women attending colposcopy after an abnormal cervical smear . DESIGN Prospect i ve study . SETTING Department of Obstetrics and Gynaecology , Malmö University Hospital , Sweden . POPULATION One hundred consecutive women were invited to participate when referred for colposcopy . METHODS Women in the study group completed the State-Trait Anxiety Inventory , the Montgomery-Asberg Depression Rating Scale-self-rate ( MADRS-S ) and had a psychosocial interview prior to colposcopy at their two follow-up visits . MAIN OUTCOME MEASURES State anxiety levels and depression scores at first visit , 6 months and 2 years . RESULTS At follow up , levels of state anxiety and the depression scores of the women studied had decreased and were comparable to those of Swedish normative data . Two variables from the MADRS-S , ' ability to focus on different activities ' and ' emotional involvement with others and in activities ' were the most prominent for women with moderate to severe depression . At the 2-year visit , 30 % of the women still had a fear of cancer . CONCLUSIONS Referral for colposcopy after an abnormal cervical smear does not seem to result in long-lasting anxiety and depression . However , a subgroup of women , with the initially highest depression scores , still had at 2-year state anxiety levels and depression scores significantly higher than normal . Almost one-third of the women still had a fear of cancer in spite of lower 2-year state anxiety levels AIM Based on data from r and omised controlled trials ( RCT ) on primary cervical screening , it has been reported that the problem of more frequent false-positive tests in Human Papillomavirus ( HPV ) DNA screening compared to cytology could be overcome . However , these reports predominantly operated with a narrow definition of a (false-)positive test . The aim of this paper was to illustrate how the narrow definition affected the measured adverse effects of HPV DNA screening compared with cytology screening . METHODS In the European RCT data , we measured the impact of the narrow definition of a positive screening test on the published relative positive predictive values ( PPV ) , an indicator of the relative frequency of false-positive screening tests . RESULTS Using the trialists ' definitions of positive screening tests , HPV screening combined with cytology triage had relative PPVs of 0.87 ( 95 % confidence interval ( CI ) : 0.60 - 1.26 ) for ≥ CIN3 based on Swedish RCT data , and 0.78 ( 0.52 - 1.16 ) for ≥ CIN2 in the Italian Phase 1 RCT ( 25 - 34 years ) . These PPVs changed to 0.44 ( 0.30 - 0.64 ) and 0.51 ( 0.33 - 0.79 ) , respectively , when all positive HPV or cytology screening tests were accounted for . In the Finnish RCT data , HPV screening using the cut-off point of ≥ 10 pg/ml had a relative PPV of 0.27 ( 0.15 - 0.50 ) for ≥ CIN3 , which changed to 1.84 ( 0.99 - 3.41 ) . CONCLUSION The relative PPV was incorrectly estimated in six out of seven studies . In three of those six studies , the relative PPV changed significantly after inclusion of the previously erroneously excluded false-positive HPV or cytology tests BACKGROUND Certain types of human papillomavirus ( HPV ) are the primary cause of almost all cervical cancers . HPV testing of cervical smears is more sensitive but less specific than cytology for detecting high- grade cervical intraepithelial neoplasia ( CIN2 + ) . HPV testing as a primary screening approach requires efficient management of HPV-positive women with negative or borderline cytology . We aim ed to compare the detection rate and positive predictive values of HPV assay with cytology and to determine the best management strategy for HPV-positive women . METHODS We did a multicentre screening study of 11085 women aged 30 - 60 years . Women with borderline cytology and women positive for high-risk HPV with negative cytology were r and omised to immediate colposcopy or to surveillance by repeat HPV testing , cytology , and colposcopy at 12 months . FINDINGS HPV testing was more sensitive than borderline or worse cytology ( 97.1 % vs 76.6 % , p=0.002 ) but less specific ( 93.3 % vs 95.8 % , p<0.0001 ) for detecting CIN2 + . Of 825 r and omised women , surveillance at 12 months was as effective as immediate colposcopy . In women positive for HPV at baseline , who had surveillance , 73 ( 45 % ) of 164 women with negative cytology and eight ( 35 % ) of 23 women with borderline cytology were HPV negative at 6 - 12 months . No CIN2 + was found in these women , nor in women with an initial negative HPV test with borderline ( n=211 ) or mild ( 32 ) cytology . INTERPRETATION HPV testing could be used for primary screening in women older than 30 years , with cytology used to triage HPV-positive women . HPV-positive women with normal or borderline cytology ( about 6 % of screened women ) could be managed by repeat testing after 12 months . This approach could potentially improve detection rates of CIN2 + without increasing the colposcopy referral rate BACKGROUND Human papillomavirus ( HPV ) testing is known to be more sensitive , but less specific than cytology for detecting cervical intraepithelial neoplasia ( CIN ) . We assessed the efficacy of cervical-cancer screening policies that are based on HPV testing . METHODS Between March , 2004 , and December , 2004 , in two separate recruitment phases , women aged 25 - 60 years were r and omly assigned to conventional cytology or to HPV testing in combination with liquid-based cytology ( first phase ) or alone ( second phase ) . R and omisation was done by computer in two screening centres and by sequential opening of numbered sealed envelopes in the remaining seven centres . During phase one , women who were HPV-positive and aged 35 - 60 years were referred to colposcopy , whereas women aged 25 - 34 years were referred to colposcopy only if cytology was also abnormal or HPV testing was persistently positive . During phase two , women in the HPV group were referred for colposcopy if the HPV test was positive . Two rounds of screening occurred in each phase , and all women had cytology testing only at the second round . The primary endpoint was the detection of grade 2 and 3 CIN , and of invasive cervical cancers during the first and second screening rounds . Analysis was done by intention to screen . This trial is registered , number IS RCT N81678807 . FINDINGS In total for both phases , 47,001 women were r and omly assigned to the cytology group and 47,369 to HPV testing . 33,851 women from the cytology group and 32,998 from the HPV-testing group had a second round of screening . We also retrieved the histological diagnoses from screening done elsewhere . The detection of invasive cervical cancers was similar for the two groups in the first round of screening ( nine in the cytology group vs seven in the HPV group , p=0.62 ) ; no cases were detected in the HPV group during round two , compared with nine in the cytology group ( p=0.004 ) . Overall , in the two rounds of screening , 18 invasive cancers were detected in the cytology group versus seven in the HPV group ( p=0.028 ) . Among women aged 35 - 60 years , at round one the relative detection ( HPV vs cytology ) was 2.00 ( 95 % CI 1.44 - 2.77 ) for CIN2 , 2.08 ( 1.47 - 2.95 ) for CIN3 , and 2.03 ( 1.60 - 2.57 ) for CIN2 and 3 together . At round two the relative detection was 0.54 ( 0.23 - 1.28 ) for CIN2 , 0.48 ( 0.21 - 1.11 ) for CIN3 , and 0.51 ( 0.28 - 0.93 ) for CIN2 and 3 together . Among women aged 25 - 34 years , there was significant heterogeneity between phases in the relative detection of CIN3 . At round one the relative detection was 0.93 ( 0.52 - 1.64 ) in phase one and 3.91 ( 2.02 - 7.57 ) in phase two . At round two the relative detection was 1.34 ( 0.46 - 3.84 ) in phase one and 0.20 ( 0.04 - 0.93 ) in phase two . Pooling both phases , the detection ratio of CIN2 for women aged 25 - 34 years was 4.09 ( 2.24 - 7.48 ) at round one and 0.64 ( 0.23 - 1.27 ) at round two . INTERPRETATION HPV-based screening is more effective than cytology in preventing invasive cervical cancer , by detecting persistent high- grade lesions earlier and providing a longer low-risk period . However , in younger women , HPV screening leads to over-diagnosis of regressive CIN2 . FUNDING European Union , Italian Ministry of Health , Regional Health Administrations of Piemonte , Tuscany , Veneto and Emilia-Romagna , and Public Health Agency of Lazio The impact of screening by visual inspection with acetic acid ( VIA ) , cytology or HPV testing on cervical cancer incidence and mortality is investigated in a cluster r and omized controlled trial in India . We report findings after the screening phase , when 52 clusters , with a total of 142,701 women aged 30 - 59 years in Osmanabad District , India , were r and omized into 4 arms for a single round of screening by trained midwives with either VIA , cytology or HPV testing as well as a control group . All laboratory tests were done locally . Test-positive women underwent investigations ( colposcopy/biopsy ) and treatment in the base hospital . Data on participation , test positivity , positive predictive value and detection rates of cervical neoplasia were analyzed using cluster design methodology . Of the eligible women , 72 - 74 % were screened . Test positivity rates were 14.0 % for VIA , 7.0 % for cytology and 10.3 % for HPV . The detection rate of high- grade lesions was similar in all intervention arms ( 0.7 % for VIA , 1.0 % for cytology and 0.9 % for HPV testing ) ( p = 0.06 , Mann-Whitney test ) . While the detection rate for VIA dropped to 0.5 % with declining test positivity during the course of the study , it remained constant for cytology and HPV testing . Over 85 % of women with high- grade lesions received treatment . Our results show that a high level of participation and good- quality cytology can be achieved in low-re source setting s. VIA is a useful alternative but requires careful monitoring . Detection rates obtained by HPV testing were similar to cytology , despite higher investments BACKGROUND Testing for human papillomavirus ( HPV ) DNA is more sensitive but less specific than cytological analysis . Loss in specificity is most relevant in women younger than 35 years because of increased HPV prevalence . We aim ed to compare conventional screening with an experimental strategy in women aged 25 - 34 years , and investigate the effect of different criteria of referral to define the best methods of HPV screening . METHODS Women were r and omly assigned to the conventional procedure ( st and ard cytology , with referral to colposcopy if cytology showed atypical squamous cells of undetermined significance or more [ ASCUS+ ] ) or an experimental procedure ( liquid-based cytology and testing for high-risk HPV types , with referral to colposcopy with ASCUS+ cytology ) . Women positive for HPV ( cutoff > or = 1 pg/mL ) but with normal cytology were retested after 1 year . The main endpoint was the presence of cervical intraepithelial neoplasia at grade 2 or more ( CIN2 + ) in review ed histology . The main analysis was by intention to screen . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N81678807 . FINDINGS We r and omly assigned 5808 women aged 25 - 34 years to the conventional group and 6002 to the experimental group . The experimental procedure was significantly more sensitive than the conventional procedure ( 55 vs 33 CIN2 + lesions detected ; relative sensitivity 1.61 [ 95 % CI 1.05 - 2.48 ] ) , but had a lower positive predictive value ( PPV ; relative PPV 0.55 [ 0.37 - 0.82 ] ) . HPV testing ( > or = 1 pg/mL ) with cytology triage was also more sensitive than conventional cytology ( relative sensitivity 1.58 [ 1.03 - 2.44 ] , relative PPV 0.78 [ 0.52 - 1.16 ] ) . Relative PPV could be improved , with minimum loss in sensitivity , by use of a 2 pg/mL cutoff for HPV testing . Compared with conventional cytology , liquid-based cytology had a relative sensitivity of 1.32 ( 0.84 - 2.06 ) , relative PPV 0.58 [ 0.38 - 0.89 ] ) . INTERPRETATION HPV testing alone with cytology triage could be a feasible alternative to conventional cytology for screening women younger than 35 years . Follow-up will provide data on possible overdiagnosis and on the feasibility of extended intervals Since infection with oncogenic human papillomavirus ( HPV ) has been considered a necessary cause of cervical cancer , tests for oncogenic HPV types have been proposed as adjuncts or replacements to Pap cytology . We design ed the Canadian Cervical Cancer Screening Trial ( CCCaST ) to compare the relative efficacy of HPV DNA testing and Pap cytology in primary screening for cervical cancer and its high- grade precursors . CCCaST r and omized women aged 30 - 69 years in Montreal ( Quebec ) and in St. John 's ( Newfoundl and ) to 1 of 2 screening groups : focus on Pap ( conventional ) or focus on HPV testing ( Hybrid Capture 2 ) . Women in both arms received both tests , but were r and omized as to their order , the first test being the index test . Women with an abnormal Pap test or a positive HPV test underwent colposcopy and biopsy , as did a r and om sample of women with a negative index test . CCCaST enrolled 9,667 women between October 2002 and October 2004 . At enrolment , 2.8 % had an abnormal Pap test , 6.1 % had a positive HPV test and 1.1 % were abnormal in both tests . ASC-US was the most frequent cytological abnormality , representing 64 % of abnormal Pap results . The frequency of abnormal Pap and HPV results decreased with increasing age and the proportion of HPV-positive results increased with the severity of Pap abnormality . Efficacy analysis will determine if the extra referrals with HPV DNA testing will translate into a relevant increase in high- grade cervical cancer precursor detection . Because of its design , CCCaST will provide sound evidence for formulating cervical cancer screening strategies Cytological cervical screening is rather inefficient because of relatively high proportions of false negative and false positive smears . To evaluate the efficiency of high‐risk human papillomavirus ( hrHPV ) testing , by GP5+/6 + PCR‐enzyme immunoassay ( EIA ) , in conjunction with cytology ( Intervention Group ) to that of the classical cytology ( Control Group ) , we initiated the Population Based Screening Study Amsterdam ( POBASCAM ) . POBASCAM is a population ‐based r and omized controlled trial for implementation of hrHPV testing in cervical screening . The outcome measure is the proportion of histologically confirmed ≥CIN3 lesions in each study arm up to and including the next screening round after 5 years . We present the design , methods and baseline data of POBASCAM . When , in the next 5 years , the follow‐up will be completed , the data obtained will be used in model studies , including a cost‐effectiveness study , to advise the Dutch Ministry of Public Health in deciding whether cervical screening should be based on combined hrHPV and cytology testing instead of cytology alone . Between January 1999 and September 2002 , 44,102 women ( mean age = 42.8 years ; range = 29–61 ) that participated in the regular Dutch screening program were included in our study . In the Intervention Group the distribution of cytology and hrHPV by cytology class was as follows : normal cytology 96.6 % ( 3.6 % hrHPV positive ) ; borderline and mild dyskaryosis ( BMD ) 2.5 % ( 34.6 % hrHPV positive ) ; and moderate dyskaryosis or worse ( > BMD ) 0.8 % ( 88.3 % hrHPV positive ) , i.e. , 0.4 % moderate dyskaryosis ( 82.9 % hrHPV positive ) , 0.3 % severe dyskaryosis ( 92.5 % hrHPV positive ) , 0.1 % carcinoma in situ ( 95.2 % hrHPV positive ) , < 0.1 % suspected for invasive cancer ( hrHPV positive 100.0 % ) . In the Control Group 96.5 % of the women had normal cytology , 2.4 % BMD and 0.8 % > BMD , i.e. , 0.4 % moderate dyskaryosis , 0.3 % severe dyskaryosis , 0.1 % carcinoma in situ , < 0.1 % suspected for invasive cancer . The presence of hrHPV was age‐dependent , decreasing from 12.0 % at 29–33 years to 2.4 % at 59–61 years . Among women with a positive hrHPV test , the prevalence of BMD was age‐dependent ranging from 20.2 % at 29–33 years to 7.8 % at 54–58 years . In contrast , the risk of > BMD of 13.7 % among women with a positive hrHPV test was not age‐dependent . Our study indicates that large‐scale hrHPV testing by GP5+/6 + PCR‐EIA in the setting of population ‐based cervical screening is practically feasible , is accepted by both participating women and general practitioners and yields highly reproducible results . © 2004 Wiley‐Liss , |
10,484 | 24,808,492 | However , whereas the hypothesis of a better and more sustained performance with a breakfast providing > 20 % daily energy intake still needs substantiation , there does appear to be emerging , but still equivocal , evidence that a lower postpr and ial glycemic response is beneficial to cognitive performance | BACKGROUND Most studies that assess the effects of breakfast on subsequent mental abilities compared performance in subjects who had or had not consumed this meal .
However , characteristics of breakfast itself may induce metabolic and hormonal alterations of the gastrointestinal tract and potentially modify cognitive performance .
Moreover , as far as the evidence on the positive effects of having breakfast is becoming more robust , interest may shift to the specific characteristics of an adequate breakfast .
OBJECTIVE The objective was to summarize existing evidence on the role of nutrient composition or energy intake at breakfast on the accomplishment of school-related tasks and cognition . | The macronutrient composition of a breakfast that could facilitate performance after an overnight fast remains unclear . As glucose is the brain 's major energy source , the interest is in investigating meals differing in their blood glucose-raising potential . Findings vary due to unaccounted differences in glucoregulation , arousal and cortisol secretion . We investigated the effects of meals differing in glycaemic index ( GI ) and glycaemic load ( GL ) on cognition and mood in school children . A total of seventy-four school children were matched and r and omly allocated either to the high-GL or low-GL group . Within each GL group , children received high-GI and low-GI breakfasts . Cognitive function ( CF ) and mood were measured 95 - 140 min after breakfast . Blood glucose and salivary cortisol were measured at baseline , before and after the CF tests . Repeated- measures ANOVA was used to identify differences in CF , mood , glucose and cortisol levels between the breakfasts . Low-GI meals predicted feeling more alert and happy , and less nervous and thirsty ( P < 0·05 for each ) ; high-GL meals predicted feeling more confident , and less sluggish , hungry and thirsty ( P < 0·05 for each ) . High-GL ( P < 0·001 ) and high-GI ( P = 0·05 ) meals increased glucose levels 90 min after breakfast , and high-GI meals increased cortisol levels ( P < 0·01 ) . When baseline mood , glucose and cortisol levels were considered , low-GI meals predicted better declarative-verbal memory ( P = 0·03 ) , and high-GI meals better vigilance ( P < 0·03 ) ; observed GI effects were valid across GL groups . GI effects on cognition appear to be domain specific . On balance , it would appear that the low-GI high-GL breakfast may help to improve learning , and of potential value in informing government education policies relating to dietary recommendations and implementation concerning breakfast Background / Objectives : Considering the importance of glucose as a brain substrate , the postpr and ial rate of glucose delivery to the blood could be expected to affect cognitive functions . The purpose was to evaluate to what extent the rate of glucose absorption affected measures of cognitive performance in the postpr and ial period . In addition , cognitive performance was evaluated in relation to individual glucoregulation . Subjects/ Methods : A white wheat bread ( WWB ) enriched with guar gum ( G-WWB ) with the capacity to produce a low but sustained blood glucose net increment was developed . The G-WWB was evaluated in the postpr and ial period after breakfast with respect to effects on cognitive function ( working memory and selective attention ( SA ) ) in 40 healthy adults ( 49–71 years , body mass index 20–29 kg/m2 ) , using a high glycaemic index WWB for comparison in a r and omised crossover design . Results : The G-WWB improved outcome in the cognitive tests ( SA test ) in the later postpr and ial period ( 75–225 min ) in comparison with the WWB ( P<0.01 ) . Subjects with better glucoregulation performed superior in cognitive tests compared with subjects with worse glucoregulation ( P<0.05 ) . Conclusions : Beneficial effects on cognitive performance were observed with the G-WWB in the late postpr and ial period . The positive effect is suggested to emanate from improved insulin sensitivity , possibly in a combination with an enhanced neural energy supply . The results highlight the importance of carbohydrate foods that induces a low but sustained blood glucose profile in enhancing postpr and ial cognitive functions Background / Objectives : The effect of Glycaemic Index ( GI ) and Load ( GL ) of breakfasts on satiety and aspects of cognitive function in children is inconclusive . We aim ed to assess if isocaloric breakfasts differing in GL ( by replacing high-GI carbohydrate foods with dairy protein foods ) acutely alter cognitive function and satiety in 10- to 12-year-old children . Subjects/ Methods : A total of 39 children , aged 11.6±0.7 years with body mass index 18.9±3.0 kg/m2 ( Mean±s.e . ) participated in a r and omised crossover trial of three isocaloric breakfasts ( 1.3 MJ ) : high GL ( HGL : 7 g protein , 9 g fat , 50 g carbohydrate , GL 33 ) ; medium GL ( MGL : 14 g protein , 9 g fat , 45 g carbohydrate , GL 24 ) and low GL ( LGL : 18 g protein , 10 g fat , 38 g carbohydrate , GL 18 ) . Blood glucose was recorded using a continuous glucose monitor . Subjective hunger and cognitive performance were measured before and hourly after consuming the test breakfast via a computer-delivered battery . Ad libitum intake at a buffet lunch meal was measured at 3 h at the end of testing . Results : Incremental area under the glucose curve ( iAUC ) was significantly different with HGL > MGL > LGL ( P<0.001 ) . Glucose concentrations fell below baseline after 83±6 min for HGL , 63±5 min ( MGL ) and 67±5 min (LGL)(P=0.009 ) . Breakfast GL did not significantly alter changes in cognitive function or self-reported satiety throughout testing . Energy intake at lunch was not significantly different between treatments ( HGL 2943±168 kJ ; MGL 2949±166 kJ ; LGL 2993±191 kJ ) . Conclusions : Reducing breakfast GL by replacing carbohydrate with protein does not alter satiety or cognition over 3 h in 10- to 12-year-old children OBJECTIVE . Breakfast-eating frequency declines through adolescence and has been inversely associated with body weight in cross-sectional studies , with few prospect i ve studies on this topic . This study was conducted to examine the association between breakfast frequency and 5-year body weight change in 2216 adolescents . PATIENTS AND METHODS . Project EAT ( Eating Among Teens ) was a 5-year longitudinal study of eating patterns and weight concerns among adolescents . Surveys were completed in 1998–1999 ( time 1 ) and 2003–2004 ( time 2 ) . Multivariable linear regression was used to examine the association between breakfast frequency and change in BMI , with adjustment for age , socioeconomic status , race , physical activity , time 1 BMI and breakfast category , and time 1 dietary and weight-related variables . RESULTS . At time 1 , frequency of breakfast was directly associated with intake of carbohydrate and fiber , socioeconomic status , white race , and physical activity and inversely associated with smoking and alcohol consumption and dieting and weight-control behaviors . In cross-sectional analyses at times 1 and 2 , inverse associations between breakfast frequency and BMI remained largely independent of all of the confounding and dietary factors . Weight-related factors ( concerns , behaviors , and pressures ) explained little of the breakfast- BMI association . In prospect i ve analyses , frequency of breakfast was inversely associated with BMI in a dose-response manner . Further adjustment for confounding and dietary factors did not seem to explain the association , but adjustment for weight-related variables seemed to partly explain this finding . CONCLUSIONS . Although experimental studies are needed to verify whether the association between breakfast and body weight is of a causal nature , our findings support the importance of promoting regular breakfast consumption among adolescents . Future studies should further examine the role of breakfast habits among youth who are particularly concerned about their weight In order to examine the effect of energy intake at breakfast on school performance the same morning , the parents of ten parallel school classes of 10-year-old school children at five different schools were persuaded to alter their child 's breakfast regimen at home over a period of 4 successive days . A total of 195 families were provided with st and ard breakfasts with either low or high energy content . Uneaten food was returned and weighed . Individual children were r and omly assigned to breakfast alternative on any given day . The teachers who carried out the performance assessment s at school were blind to treatment condition . Voluntary physical endurance and the performance of a creativity test were significantly better after a breakfast from which children derived over 20 % of their recommended daily energy intake than after a breakfast from which they obtained less than 10 % of recommended values . The error rate in an addition task was negatively correlated and the rate of working in a number checking task was positively correlated with individual energy intake from the low-energy breakfast . Significantly fewer children reported feeling bad and self-estimates of hunger sensation were lower during the morning at school after the high energy breakfast . Estimates of energy intake at breakfast based on 24-h dietary recall interviews with the children carried out by telephone at their homes showed good correlation with estimates based on returned food ( r = 0.89 ) . Energy intake at breakfast as estimated from returned food had no significant effect on energy intake at school lunch as estimated by dietary recall Rationale . Glucose is the main metabolic fuel of the brain . The rate of glucose delivery from food to the bloodstream depends on the nature of carbohydrates in the diet , which can be summarized as the glycaemic index ( GI ) . Objectives . To assess the benefit of a low versus high GI breakfast on cognitive performances within the following 4 h. Methods . The influence of the GI of the breakfast on verbal memory of young adults was measured throughout the morning in parallel to the assessment of blood glucose levels . The learning abilities of rats performing an operant-conditioning test 3 h after a breakfast-like meal of various GI was also examined . Results . A low GI rather than high GI diet improved memory in humans , especially in the late morning ( 150 and 210 min after breakfast ) . Similarly , rats displayed better learning performance 180 min after they were fed with a low rather than high GI diet . Conclusion . Although performances appeared to be only remotely related to blood glucose , our data provide evidence that a low GI breakfast allows better cognitive performances later in the morning |
10,485 | 24,358,230 | Evidence from both pairwise and network meta-analyses suggests that CT is the most efficacious means to reduce anthropometric outcomes and should be recommended in the prevention and treatment of overweight , and obesity whenever possible | BACKGROUND The aim of this systematic review of r and omized controlled trials was to compare the effects of aerobic training ( AET ) , resistance training ( RT ) , and combined aerobic and resistance training ( CT ) on anthropometric parameters , blood lipids , and cardiorespiratory fitness in overweight and obese subjects . | Recent guidelines on exercise for weight loss and weight maintenance include resistance training as part of the exercise prescription . Yet few studies have compared the effects of similar amounts of aerobic and resistance training on body mass and fat mass in overweight adults . STRRIDE AT/RT , a r and omized trial , compared aerobic training , resistance training , and a combination of the two to determine the optimal mode of exercise for obesity reduction . Participants were 119 sedentary , overweight or obese adults who were r and omized to one of three 8-mo exercise protocol s : 1 ) RT : resistance training , 2 ) AT : aerobic training , and 3 ) AT/RT : aerobic and resistance training ( combination of AT and RT ) . Primary outcomes included total body mass , fat mass , and lean body mass . The AT and AT/RT groups reduced total body mass and fat mass more than RT ( P < 0.05 ) , but they were not different from each other . RT and AT/RT increased lean body mass more than AT ( P < 0.05 ) . While requiring double the time commitment , a program of combined AT and RT did not result in significantly more fat mass or body mass reductions over AT alone . Balancing time commitments against health benefits , it appears that AT is the optimal mode of exercise for reducing fat mass and body mass , while a program including RT is needed for increasing lean mass in middle-aged , overweight/obese individuals The independent effects of exercise and weight loss on markers of inflammation ( MOI ) in obese individuals have not been clearly characterized . The objectives of this study were to : ( i ) identify the independent effects of exercise and weight loss on MOI and ( ii ) determine whether changes in MOI were associated with changes in fat distribution . Subjects were 126 healthy , premenopausal women , BMI 27 - 30 kg/m(2 ) . They were r and omized to one of three groups : diet only , diet + aerobic- , or diet + resistance training until a BMI < 25 kg/m(2 ) was achieved . Fat distribution was measured with computed tomography , and body composition with dual-energy X-ray absorptiometry . Serum concentrations of tumor necrosis factor (TNF)-α , soluble TNF receptor 1 ( sTNF-R1 ) , soluble TNF receptor 2 ( sTNF-R2 ) , C-reactive protein ( CRP ) , and interleukin (IL)-6 were assessed . Results of repeated- measures ANOVA indicated a significant effect of time on MOI , such that MOI decreased with weight loss . Results of mixed-model analysis indicated that adjusting for intra-abdominal adipose tissue ( IAAT ) and total fat mass explained the decreases in TNF-α and sTNF-R1 , whereas only total fat mass explained the decreases in sTNF-R2 , IL-6 , and CRP . In conclusion , weight loss was associated with decreases in MOI . The effect of weight loss appeared to be mediated by changes in total fat mass or IAAT . Addition of exercise did not alter the response , suggesting that weight loss has a more profound impact for reducing MOI in overweight women than exercise The effects of energy restriction ( diet ) in combination with either aerobic ( DA ) or resistance exercise ( DR ) on adipose tissue ( AT ) distribution were evaluated in 24 obese women ( DA , n = 10 ; DR , n = 14 ) . AT distribution was measured by magnetic resonance imaging ( MRI ) . Comparison between groups demonstrated that the relative losses observed for body weight , subcutaneous AT ( SAT ) , and visceral AT ( VAT ) volume were not significantly different ( P > 0.05 ) . A significant reduction in the volume ratio of VAT to SAT was observed for both groups ( P < 0.01 ) . Comparison of arm , abdomen and torso , and lower-body regions revealed that the regional mobilization of SAT was not significantly different between groups ( P > 0.05 ) and that for both groups there was a preferential mobilization of SAT from the abdominal region ( P < 0.05 ) . Within the VAT depot , significant reductions were observed for both intraperitoneal and extraperitoneal AT ( P < 0.01 ) . These findings suggest that the combination of moderate energy restriction and either resistance or aerobic exercise induces significant reductions in VAT and SAT , with a preferential loss of VAT , and are thus effective means of reducing total and upper-body obesity in obese women Objective : To compare the effects of aerobic and resistance exercise on weight , muscle strength , cardiovascular fitness , blood pressure and mood in obese women who were not on an energy-restricted diet . Design : R and omized , prospect i ve , controlled trial . Setting : Department of Physical Medicine and Rehabilitation , University Hospital . Subjects : Sixty obese women were assigned to one of three groups : aerobic exercise ( n=20 ) , resistance exercise ( n=20 ) and control group ( n=20 ) . Interventions : The aerobic exercise group performed both walking and leg cycle exercise with increasing duration and frequency . The resistance exercise group performed progressive weight-resistance exercises for the upper and lower body . Main outcome measures : Before and after a 12-week period , all subjects were evaluated by anthropometric measurement , rating of mood , cardiorespiratory capacity and maximum strength of trained muscles . Results : After a 12-week training period , subjects in the resistance group showed significant improvement in one-repetition maximum test of hip abductors ( 7.95±3.58 kg ) , quadriceps ( 14±7.18 kg ) , biceps ( 3.37± 2.84 kg ) and pectorals ( 8.75±5.09 kg ) compared with those in the control group ( P<0.001 ) . VO2 max increased ( 0.51±0.40 ) and Beck Depression Scale scores decreased ( -5.40±4.27 ) in the aerobic exercise group compared with the control group , significantly ( P<0.001 ) . Only in hip abductor muscle strength was there a significant increase in the resistance exercise group compared with the aerobic exercise group ( P < 0.05 ) . Conclusion : Both aerobic exercise and resistance exercise result ed in improved performance and exercise capacity in obese women . While aerobic exercise appeared to be beneficial with regard to improving depressive symptoms and maximum oxygen consumption , resistance exercise was beneficial in increasing muscle strength Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND Authorities advocate that resistance and aerobic exercise are essential for reducing risk factors for chronic disease and disability in older adults . However , the incremental effects of combined resistance and aerobic exercise compared with either modality alone on risk factors for disease and disability is generally unknown . METHODS Participants were 136 sedentary , abdominally obese older men and women recruited from September 30 , 2002 , through November 15 , 2006 , at Queen 's University . Participants were r and omized to 1 of the following 4 groups for 6 months : resistance exercise , aerobic exercise , resistance and aerobic exercise ( combined exercise ) , or nonexercise control . Primary outcomes were analyzed by an intent-to-treat model and included changes in insulin resistance by hyperinsulinemic-euglycemic clamp and functional limitation using the average change in 4 tests combined ( average z score ) . RESULTS After controlling for age , sex , and baseline value , insulin resistance improved compared with controls in the aerobic exercise and the combined exercise groups but not in the resistance exercise group . Improvement ( mean [ SE ] ) in the combined exercise group was greater than in the resistance exercise group ( 9.2 [ 1.3 ] vs 1.8 [ 1.3 ] mg/mL/microIU per kilogram of skeletal muscle per minute x100 [ P < .001 ] ) but not in the aerobic exercise group ( 9.2 [ 1.3 ] vs 6.5 [ 1.3 ] mg/mL/microIU per kilogram of skeletal muscle per minute x100 [ P = .46 ] ) . Functional limitation improved significantly in all groups compared with the control group . Improvement in the combined exercise group was greater than in the aerobic exercise group ( 0.5 [ 0.1 ] vs -0.0 [ 0.1 ] ; st and ard units , z score [ P = .003 ] ) but not in the resistance exercise group . Improvement in the resistance exercise group was not different from the aerobic exercise group . CONCLUSION The combination of resistance and aerobic exercise was the optimal exercise strategy for simultaneous reduction in insulin resistance and functional limitation in previously sedentary , abdominally obese older adults . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00520858 The purpose of this study was to investigate the effect of combined aerobic and resistance training on abdominal fat . Our participants in the study consisted of thirty obese women . They were separated into three groups : a control group ( n=10 ) , an aerobic training group ( n=10 ) and a combined training group ( n=10 ) . The aerobic training group was composed of 60 - 70 % HRmax ( intensity ) , 60 minutes a day ( duration ) for 6 days a week ( frequency ) . The combined training group was separated into resistance training ( 3 days a week , Mon , We d , Fri ) and the aerobic training ( 3 days a week , Tue , Thu , Sat ) . The levels for abdominal fat volume were measured by determining the subcutaneous fat volume ( SFV ) , visceral fat volume ( VFV ) , and VFV/SFV by CT ( computed tomography ) . The VO(2max ) was significantly ( p<0.05 ) increased in both groups . The subcutaneous fat and visceral fat levels were decreased in the combined training group more than in the aerobics training group . Also , the lean body mass ( LBM ) was significantly increased only in the combined training group . In addition , the total cholesterol , triglyceride and LDL-C were significantly ( p<.05 ) decreased and the HDL-C was significantly ( p<.05 ) increased in both groups . In conclusion , our results observed that combined training decreased abdominal subcutaneous fat and visceral fat more than aerobic training only OBJECTIVE To determine how multiple risk factors for osteoporotic fractures could be modified by high-intensity strength training exercises in postmenopausal women . DESIGN R and omized controlled trial of 1-year duration . SETTING Exercise laboratory at Tufts University , Boston , Mass. POPULATION Forty postmenopausal white women , 50 to 70 years of age , participated in the study ; 39 women completed the study . The subjects were sedentary and estrogen-deplete . INTERVENTIONS High-intensity strength training exercises 2 days per week using five different exercises ( n = 20 ) vs untreated controls ( n = 19 ) . MAIN OUTCOME MEASURES Dual energy x-ray absorptiometry for bone status , one repetition maximum for muscle strength , 24-hour urinary creatinine for muscle mass , and backward t and em walk for dynamic balance . RESULTS Femoral neck bone mineral density and lumbar spine bone mineral density increased by 0.005 + /- 0.039 g/cm2 ( 0.9 % + /- 4.5 % ) ( mean + /- SD ) and 0.009 + /- 0.033 g/cm2 ( 1.0 % + /- 3.6 % ) , respectively , in the strength-trained women and decreased by -0.022 + /- 0.035 g/cm2 ( -2.5 % + /- 3.8 % ) and -0.019 + /- 0.035 g/cm2 ( -1.8 % + /- 3.5 % ) , respectively , in the controls ( P = .02 and .04 ) . Total body bone mineral content was preserved in the strength-trained women ( + 2.0 + /- 68 g ; 0.0 % + /- 3.0 % ) and tended to decrease in the controls ( -33 + 77 g ; -1.2 % + /- 3.4 % , P = .12 ) . Muscle mass , muscle strength , and dynamic balance increased in the strength-trained women and decreased in the controls ( P = .03 to < .001 ) . CONCLUSIONS High-intensity strength training exercises are an effective and feasible means to preserve bone density while improving muscle mass , strength , and balance in postmenopausal women This study examined , through a r and omized controlled trial , the effects of cross-training ( combined resistance and endurance exercise ) on markers of insulin resistance , ( e.g. , dyslipidemia , intra-abdominal obesity , hyperinsulinemia , and hypertension ) , body composition , and performance in hyperinsulinemic individuals . Sedentary adult males characterized as hyperinsulinemic ( fasting insulin > 2 OuU.mL-1 ) , r and omly assigned to two groups ( N = 8 each ) , completed 14 wk of training at 3 d.wk-1 . An endurance-only ( E ) group performed both continuous cycle exercise and walking ( 30 min each at 60 - 70 % heart rate reserve ) . A cross-training ( C ) group performed both endurance and resistance exercise ( 8 exercises , 4 sets/exercise , 8 - 12 repetitions/set ) in a single session . Both E and C groups demonstrated similar increases in VO2max ( 25 % and 27 % ) while only C demonstrated an increase in 1 RM bench press ( 19 % ) and leg press ( 25 % ) . The changes induced by C training were significantly greater than those from E training alone in percent fat ( 6.9 + /- 1.3 vs 1.4 + /- 1.4 ) , insulin concentration ( 8.5 + /- 2.7 vs 3.0 + /- 1.3 uU.mL-1 ) , glucose levels ( 11.1 + /- 2.9 vs 5.9 + /- 2.6 mg.dL-1 ) , HDL-C levels ( 5.1 + /- 1.3 vs 2.9 + /- 1.6 mg.dL-1 ) , triglyceride concentration ( 43.8 + /- 13.6 mg.dL-1 ) , and systolic blood pressure ( 14.6 + /- 5.5 vs 8.3 + /- 6.8 mm Hg ) . Results indicate that the addition of resistance training to an endurance training program will induce significantly greater differences in markers of insulin resistance and body composition in individuals with hyperinsulinemia than endurance training alone Individuals exhibiting “ the metabolic syndrome ” have multiple coronary artery disease risk factors , including insulin resistance , hyperlipidemia , hypertension , and and roid obesity . We performed a r and omized trial to compare the effects of aerobic and resistance training regimens on coronary risk factors . Twenty-six volunteers who exhibited and roid obesity and at least one other risk factor for coronary artery disease were r and omized to aerobic or resistance training groups . Body mass index , waist-to-hip ratio , glucose , insulin , body composition , 24-hr urinary albumin , fibrinogen , blood pressure , and lipid profile were measured at baseline and after 10 weeks of exercise training . Both groups showed a significant reduction in waist-to-hip ratio and the resistance training group also showed a reduction in total body fat . There was no significant change in mean arterial blood pressure in either group . Fasting plasma glucose , insulin , total cholesterol , low-density lipoprotein ( LDL ) cholesterol , and triglycerides were unchanged in both groups . High-density lipoprotein ( HDL ) cholesterol increased ( 13 % ) with aerobic training only . Plasma fibrinogen was increased ( 28 % and 34 % , P < 0.02 ) in both groups and both groups showed a significant decrease ( 34 % and 28 % , P < 0.03 ) in microalbuminuria after their respective training regimen . In conclusion , resistance training was effective in improving body composition of middle-aged obese sedentary males . Only aerobic training was effective in raising HDL cholesterol . More studies are warranted to assess the effects of exercise on plasma fibrinogen and microalbuminuria PURPOSE The purpose of the present study was to investigate the effects of resistance and endurance training on serum adiponectin and insulin resistance index ( SI ) in healthy men . METHODS Twenty-four healthy males ( age , 35 - 48 years ) participated in the study . The subjects were r and omly assigned to one of three groups : endurance training group ( n=8 ) , resistance training group ( n=8 ) and control group ( n=8 ) . Blood sample s were taken in fasting state from all subjects . The experimental groups performed either endurance or resistance training 3 days a week for 12 weeks . The endurance training programme included continuous running at an intensity corresponding to 75 - 85 % of maximal heart rate , while resistance training consisted of four sets of circuit weight training for 11 stations and at an intensity corresponding to 50 - 60 % of one-repetition maximum . The maximum numbers of repetitions in each station was 12 . RESULTS There were significant negative correlations between serum adiponectin and body fat percentage , waist-to-hip ratio , body mass index and the insulin resistance index at baseline , whereas changes in response to training were not significantly correlated . Both endurance and resistance training result ed in a significant decrease in the SI in comparison with the control group . However , serum adiponectin did not change significantly in response to resistance and endurance training . CONCLUSION Endurance and resistance training caused an improvement in insulin resistance in healthy men , but this improvement was not accompanied by increased adiponectin levels OBJECTIVE To evaluate the effects of an intense physical training program on abdominal fat distribution , glycemic control , and insulin sensitivity in patients with NIDDM and to determine whether branched-chain amino acid ( BCAA ) supplements influence these effects . RESEARCH DESIGN AND METHODS Twenty-four patients ( ages 45 ± 2 [ mean ± SE ] years , BMI 30.2 ± 0.9 kg/m2 , HbA1c 7.9 ± 0.3 % ) were r and omly assigned to four groups : training plus BCAA supplement ( n = 6 ) , training plus placebo ( n = 6 ) , sedentary plus BCAA supplement ( n = 6 ) , and sedentary plus placebo ( n = 6 ) . Physical training consisted of a supervised 45-min cycling exercise at 75 % of their oxygen uptake peak ( VO2 peak ) two times per week and an intermittent exercise one time per week for 2 months . RESULTS Patients who exercised increased their VO2 peak by 41 % and their insulin sensitivity by 46 % . Physical training significantly decreased abdominal fat evaluated by magnetic resonance imaging ( umbilicus ) , with a greater loss of visceral adipose tissue ( VAT ) ( 48 % ) in comparison with the loss of subcutaneous adipose tissue ( 18 % ) , but did not significantly affect body weight . The change in visceral abdominal fat was associated with the improvement in insulin sensitivity ( r = 0.84 , P = 0.001 ) . BCAA supplementation had no effect on abdominal fat and glucose metabolism . CONCLUSIONS Physical training result ed in an improvement in insulin sensitivity with concomitant loss of VAT and should be included in the treatment program for patients with NIDDM PURPOSE The purpose of this study was to examine the physiological effects of a weight-loss dietary regimen with or without exercise . METHODS Thirty-five overweight men were matched and r and omly placed into either a control group ( C ; N = 6 ) or one of three dietary groups ; a diet-only group ( D ; N = 8) , a diet group that performed aerobic exercise three times per week ( DE ; N = 11 ) ; and a diet group that performed both aerobic and strength training three times per week ( DES ; N = 10 ) . RESULTS After 12 wk , D , DE , and DES demonstrated a similar and significant ( P < or = 0.05 ) reduction in body mass ( -9.64 , -8.99 , and -9.90 kg , respectively ) with fat mass comprising 69 , 78 , and 97 % of the total loss in body mass , respectively . The diet-only group also demonstrated a significant reduction in fat-free mass . Maximum strength , as determined by 1-RM testing in the bench press and squat exercise was significantly increased for DES in both the bench press ( + 19.6 % ) and squat exercise ( + 32.6 % ) . Absolute peak O2 consumption was significantly elevated in DE ( + 24.8 % ) and DES ( + 15.4 % ) . There were no differences in performance during a 30-s Wingate test for the DE and DES , whereas D demonstrated a significant decline in peak and mean power output . Resting metabolic rate ( RMR ) ( kcal x d(-1 ) ) was not significantly different for any of the groups except for the DE group . There were no significant changes in basal concentrations of serum glucose , BUN , cortisol , testosterone , and high density lipoprotein ( HDL ) cholesterol for any of the groups . Serum total cholesterol and low density lipoprotein ( LDL ) cholesterol were significantly decreased for all dietary groups . Serum triglycerides were significantly reduced for D and DES at week 6 and remained lower at week 12 for D , while triglycerides returned to baseline values for DES . CONCLUSIONS These data indicate that a weight-loss dietary regimen in conjunction with aerobic and resistance exercise prevents the normal decline in fat-free mass and muscular power and augments body composition , maximal strength , and maximum oxygen consumption compared with weight-loss induced by diet alone OBJECTIVE This study had two objectives . First , we examined whether the influence of diet combined with either aerobic ( DA ) ( n = 10 ) or resistance ( DR ) ( n = 10 ) exercise has effects on insulin and glucose levels that are different in obese men . Second , we tried to determine whether the combination of diet and exercise is associated with improvements in insulin and glucose levels that are greater than those associated with diet alone ( DO ) ( n = 9 ) . RESEARCH DESIGN AND METHODS Insulin and glucose levels were measured after an overnight fast and a 75-g oral glucose challenge ( OGTT ) . Visceral adipose tissue ( AT ) , subcutaneous AT , and skeletal muscle were measured by magnetic resonance imaging ( MRI ) before and after treatment ( 16 weeks ) . RESULTS Reductions in weight ( 12.4 + /- 3.8 kg ) and in visceral ( 37 + /- 15.1 % ) and subcutaneous AT ( 24.3 + /- 8.6 % ) were not different between treatments ( P > 0.05 ) . Skeletal muscle was maintained in the DA and DR groups but was reduced ( 7.3 + /- 2.8 % ) in the DO group ( P < 0.05 ) . Independent of treatment , fasting glucose and OGTT glucose did not change ( P > 0.05 ) . However , fasting insulin , OGTT insulin , and the insulin-to-glucose ratio decreased within all treatments ( P < 0.05 ) . Reductions in the OGTT insulin area under the curve were greater ( P < 0.05 ) within the DA ( 52 + /- 12 % ) and DR ( 42 + /- 17 % ) treatments than in the DO ( 20 + /- 15 % ) treatment . Collapsed across group , reductions in visceral AT were related to reductions in fasting and OGTT glucose ( P < 0.05 ) , whereas reductions in abdominal subcutaneous AT correlated with reductions in fasting insulin ( P < 0.05 ) . CONCLUSIONS Weight loss induced by diet and aerobic or resistance exercise has similar positive effects on lowering fasting and OGTT insulin values that are greater than those with diet alone . Because changes in glucose and insulin were related to reductions in visceral and abdominal subcutaneous AT , we conclude that reduction in abdominal obesity consequent to diet and exercise-induced weight loss is important for attaining improvements in plasma insulin levels , observations that strengthen the concept that abdominal obesity has an important role in mediating insulin resistance Increased levels of inflammatory markers , namely , high-sensitive C-reactive protein ( hs-CRP ) , have been associated with several chronic diseases including atherosclerosis , type 2 diabetes and hypertension . Forty-five women and men aged > 64 years participated in the study and were r and omly assigned to two exercise intervention groups and a non-exercising control group . The participants assigned to the exercising groups followed a 16-week exercise protocol based either on aerobic training ( AT ) or strength training ( ST ) followed by a further 16 weeks off-training period . The control group ( C ) remained sedentary throughout the study . Evaluation of body mass , BMI , waist circumference , aerobic endurance , lower-body strength , upper-body strength , triglycerides , total cholesterol , LDL-cholesterol , HDL-cholesterol and hs-CRP were performed at baseline , after 16 weeks ( post-training for the exercise groups ) and at 32 weeks ( follow-up ) . Both , AT and ST groups significantly increased functional fitness at the end of the exercise programs when compared to baseline values . hs-CRP concentrations were maintained throughout the study for the C group , while decreasing 10 % at 16 weeks and 51 % at 32 weeks for the AT group . In the ST group the hs-CRP concentrations decreased by 11 and 39 % at 16 and 32 weeks , respectively . Decreases in hs-CRP concentrations were statistically significant for the AT and ST groups at the 32-week evaluation when compared to baseline . Reduction in hs-CRP concentrations seemed to be associated with strength gains and adiposity loss |
10,486 | 15,699,754 | Even the best antiviral therapy ( pegylated interferon/ribavirin ) is neither easily used nor reasonably effective . | Antiviral therapy for recurrent hepatitis C after liver transplantation is increasingly used . | Recurrent hepatitis C infection is an important cause of progressive fibrosis , cirrhosis , and graft loss following orthotopic liver transplantation . Treatment for posttransplant recurrence of hepatitis C with interferon-based therapy is difficult but results in loss of detectable virus in up to 30 % of patients . However , the durability of viral clearance and the associated histologic response in this setting is unknown . The aim of this study was to determine whether viral loss in response to antiviral therapy is durable and associated with improvement in liver histology . All liver transplant recipients who received interferon-based treatment for recurrent hepatitis C virus ( HCV ) at the University of Florida from 1991 to 2002 were included in this study . Patients who lost detectable HCV after treatment with interferon alone or in combination with ribavirin were followed to assess the durability of viral response and its impact on liver histology . One hundred nineteen transplant recipients were treated with interferon or combination therapy . Twenty-nine ( 20 men , 9 women ; mean age , 54 yrs [ range , 42 - 74 yrs ] ) lost detectable HCV RNA and remained virus negative for at least 6 months after discontinuing therapy ( sustained viral response[SVR ] ) . The mean follow-up after discontinuing therapy was 24.7 months ( range , 6 - 70 mos ) . Our study cohort included one patient with SVR following interferon monotherapy and 28 patients with SVR following combination therapy with interferon plus ribavirin . All patients remained HCV RNA negative ( assessed by polymerase chain reaction or branched-DNA assay ) during follow-up of up to 5 years . Liver histology assessed 2 years after treatment showed less inflammation compared with before treatment in 50 % and showed no change in 38 % . By 3 to 5 years post-treatment ( n = 15 recipients ) , inflammation was reduced in 60 % and remained unchanged in 33 % . Fibrosis stage at 2 years improved by > or = 1 stage in 27 % , remained unchanged in 38 % , and worsened in 35 % despite viral clearance . At 3 to 5 years , the fibrosis stage had improved in 67 % , remained unchanged in 13 % , and worsened in 20 % . Both grade of inflammation and fibrosis stage improved by 3 to 5 years posttreatment compared with baseline histology ( p < 0.05 ) . In conclusion , loss of HCV after treatment of recurrent chronic hepatitis C with interferon and ribavirin is durable , and the durability of the SVR is associated with improvement in hepatic inflammation and regression of fibrosis The aims of this pilot study were to evaluate the safety and efficacy of interferon-alpha 2b for treatment of hepatitis C virus infection in liver transplant recipients , to monitor changes in hepatitis C virus RNA levels with treatment and to determine pretreatment parameters predictive of a complete response . Eighteen patients with documented hepatitis C virus viremia and histological evidence of hepatitis after liver transplantation received 3 million units of alpha interferon three times weekly for at least 4 mo . Pretreatment serum aminotransferase levels were at least 1.5 times the upper limit of normal and no patient had concomitant hepatitis B virus infection . Response to therapy was defined as normalization of both aspartate and alanine aminotransferase at the end of treatment . Five patients ( 28 % ) had a complete response , whereas 13 ( 72 % ) had persistent elevation of one or both aminotransferases ( nonresponders ) . At the end of therapy , hepatitis C virus RNA levels were reduced in both responders and nonresponders ( p = 0.043 and 0.039 , respectively by Wilcoxon signed rank test ) . After cessation of treatment , aminotransferases remained normal in four of five responders but serum hepatitis C virus RNA levels returned to pretreatment levels in responders and nonresponders . There was no significant change in histological score with therapy . Responders were more likely than nonresponders to have low pretreatment hepatitis C virus RNA levels and low serum bilirubin ( p = 0.0004 and 0.0077 , respectively ) . Responders tended to have a prolonged interval between transplantation and initiation of therapy ( p = 0.10 by rank logistic regression analysis ) . Side effects result ed in early cessation of therapy in two patients and dose reduction in six . ( ABSTRACT TRUNCATED AT 250 WORDS Background . Hepatitis C virus ( HCV ) recurrence after orthotopic liver transplantation ( OLT ) is universal . We aim ed to evaluate the efficacy and safety of pegylated interferon ( PEG-IFN ) and ribavirin ( RIB ) in the treatment of post-OLT HCV recurrence . Methods . Thirty-seven patients with recurrent HCV after OLT were screened and began treatment . Nineteen patients have completed therapy . PEG-IFN was started at a dose of 0.5 & mgr;g/kg per week and titrated toward a maximum dose of 1.5 & mgr;g/kg per week . RIB was started at a dose of 400 mg per day and titrated toward a maximum of 1000 mg per day , as tolerated . Therapy continued for 1 year after HCV replication was undetectable by reverse transcriptase-polymerase chain reaction and was discontinued if there was no virologic clearance at 48 weeks . Results . Twelve patients ( 63 % ) completed the combination regimen . Therapy was discontinued in seven ( 37 % ) patients . Seven patients ( 37 % ) had undetectable viral load at the end of treatment . Of those , five patients ( 26 % ) had sustained viral response 6 months after discontinuation of therapy . Five patients ( 26 % ) had no virologic response . Necro-inflammatory score declined from 5.22 to 2.89 ( P = 0.05 ) in nonresponders versus 6.8 to 2.6 ( P < 0.01 ) in responders . Fibrosis stage did not change in either group . Genotype 1-infected patients had a lower likelihood of attaining end of treatment or sustained viral response ( P < 0.05 for both ) . Conclusions . Post-OLT HCV recurrence can be safely treated with PEG-IFN and RIB . Bone marrow toxicity , depression , and rejection are limiting factors that require aggressive management . There was short-term histologic benefit to the use of this regimen , even in those patients without viral clearance BACKGROUND / AIMS After liver transplantation ( LT ) infection of the graft with the hepatitis C virus ( HCV ) is almost universal and chronic hepatitis and cirrhosis develop in a significant proportion of patients . One of the possible strategies to prevent HCV infection recurrence is to eradicate HCV before LT . METHODS We evaluated the efficacy and safety of antiviral therapy to prevent HCV recurrence in 30 HCV-cirrhotic patients awaiting LT . At the time of inclusion 15 patients were Child-Pugh A and 15 Child-Pugh B/C. The infecting genotype was 1b in 25 patients . Treatment with interferon alpha-2b 3 MU/day and ribavirin 800 mg/day was initiated when the expected time for LT was less than 4 months and continued until LT . The median duration of treatment was 12 weeks . RESULTS Nine patients ( 30 % ) achieved a virological response and 21 did not respond to therapy . In nine ( 43 % ) of the 21 non-responders viral load decreased > or = 2 log10 during treatment . A viral load decrease > or = 2 log10 at week 4 of treatment was the strongest predictor of virological response . All nine virological responders have already undergone LT ; six patients remain free of infection after a median follow-up of 46 weeks and HCV infection recurred in three patients after LT . In one of these patients HCV-RNA was still detectable in the explanted liver . Side effects were frequent and dose reduction was necessary in 19 ( 63 % ) of the 30 patients ; no patient died while on therapy . CONCLUSIONS Our data support the utilization of antiviral therapy in HCV-infected patients awaiting LT as one of the strategies to prevent hepatitis C recurrence after transplantation Recurrent hepatitis C virus ( HCV ) infection is an important cause of fibrosis and cirrhosis after liver transplantation ( LT ) , with histological recurrence developing in at least 50 % of patients within the first year . The aim of this study is to assess the safety and efficacy of interferon alfa-2b plus ribavirin in treating histological recurrent HCV after LT . Since 1998 , patients with HCV with significant histological recurrence ( fibrosis > /= 3 and /or histological activity index > /= 5 ) or progressive cholestatic disease after LT were treated with interferon alfa-2b ( 3 million units subcutaneously three times weekly ) plus ribavirin ( 800 to 1,000 mg/d ) for 12 months . Immunosuppression was tapered to cyclosporine/FK506 monotherapy . HCV RNA was assessed at entry , week 24 , end of treatment , and 6 months after therapy . The primary end point was loss of HCV RNA 6 months after therapy , whereas the secondary end point was histological response . Fifty-four patients met criteria for treatment and have completed follow-up . Patients were mainly men ( 71 % men ; mean age , 51 + /- 5 years ) with genotype 1 infection ( 88 % ) and high viral load ( mean HCV RNA , 38 + /- 9 mEq/mL ) . Dose modification was required in 72 % of patients because of cytopenia or side effects . Intent-to-treat analysis showed that serum HCV RNA was undetectable in 19 patients ( 35 % ) week 24 , 21 patients ( 38 % ) week 48 , and 16 patients ( 30 % ) at the 6-month follow-up . Paired liver biopsy results ( before and within 6 months after treatment ) were available for 35 patients . Patients who achieved viral eradication had no significant progression of fibrosis after 1 year of therapy . In summary , combination therapy is a reasonable antiviral option for recurrent HCV infection for established post-LT hepatitis and appears to prevent histological progression of disease if viral eradication is successful BACKGROUND In a r and omized , controlled trial , we sought to determine whether prophylaxis with interferon-alpha for 6 months had an impact on rate , severity , and timing of onset of recurrent hepatitis C virus ( HCV ) hepatitis in liver transplant recipients and to assess whether interferon use was associated with rejection in liver transplant recipients . METHODS Twenty-four consecutive liver transplant recipients with HCV were r and omized after transplantation to receive either interferon-alpha ( 3 million U three times weekly ) for 6 months or no prophylaxis ; median follow-up was 874 days . RESULTS Recurrent HCV hepatitis ( histopathologically proven ) developed in 50 % ( 6 of 12 ) of the interferon-alpha patients versus 42 % ( 5 of 12 ) of the control patients ( P = NS ) . Severity of recurrence ( as assessed by Knodell score on liver biopsies ) also did not differ between the two groups ( mean 4.0 for interferon-alpha patients versus 3.5 for control patients , P = NS ) . Interferon-alpha , however , significantly delayed the timing of occurrence of HCV hepatitis ; recurrent HCV hepatitis developed a median of 408 days after transplant in the interferon-alpha group versus 193 days in the control group ( P=0.05 ) . No difference in graft or patient survival was demonstrated in the two groups . Rejection episodes , treated with corticosteroids , occurred in 50 % ( 6 of 12 ) of patients in the interferon-alpha group versus 42 % ( 5 of 12 ) in the control group ( P = NS ) . Corticosteroid resistant rejection ( requiring OKT3 ) occurred in only one study patient ( in the control group ) . CONCLUSIONS Interferon-alpha in liver transplant recipients for 6 months delayed the occurrence of HCV hepatitis , but did not decrease the incidence nor the severity of HCV hepatitis after transplantation . Interferon-alpha use was not associated with a higher incidence of rejection compared with the control patients BACKGROUND AND AIMS Hepatitis C virus ( HCV ) reinfection after liver transplantation is frequent and leads to chronic hepatitis and cirrhosis . The use of antiviral therapy in this situation remains controversial . This study aim ed to assess the safety and efficacy of interferon alfa-2b plus ribavirin for recurrent hepatitis C following liver transplantation . METHODS Transplant recipients with recurrent chronic hepatitis C were r and omized to receive either no treatment or therapy with interferon alfa-2b ( 3 MU 3 times a week ) plus 1000 - 1200 mg/day ribavirin for 1 year . Patients were followed up for 6 months after the end of treatment . The primary end point was loss of HCV RNA 6 months after the end of treatment . RESULTS Fifty-two patients were r and omized ( treatment , 28 ; placebo , 24 ) . Sixteen patients were withdrawn from the study ; 12 ( 43 % ) were from the treated group ( mainly for anemia [ 7 patients ] ) and 4 ( 17 % ) from the control group . In the treated group , serum HCV RNA was undetectable in 9 patients ( 32 % ) at the end of treatment and 6 ( 21.4 % ) at the end of the follow-up period , whereas no patient in the control group lost HCV RNA at any point ( P = 0.036 at the end of follow-up ) . However , there was no significant histologic improvement . CONCLUSIONS The combination of interferon alfa-2b plus ribavirin induced a sustained virologic response in 21 % of transplant recipients with recurrent hepatitis C. However , 43 % discontinued therapy due to adverse events ( primarily severe anemia ) . Strategies to enable treatment with lower doses of ribavirin need to be explored Interferon-alpha is currently the only available treatment for HCV hepatitis . We assessed the safety and efficacy of 6 month course of interferon therapy in 18 consecutive liver transplant recipients with recurrent HCV hepatitis and report the long-term response with maintenance interferon . Median follow-up after the institution of interferon was 24 months . Complete response was defined as normalization of both aspartate and alanine aminotransferase . Complete response after 6 months of interferon was observed in 28 % ( 5/18 ) ; an additional 33 % ( 6/18 ) of the patients were late responders . Overall , 61 % ( 11/18 ) of the patients had long-term sustained normal response at a median follow-up of 24 months . Long-term sustained response was observed in 73 % ( 8/11 ) of the patients who continued interferon beyond 6 months vs. 43 % ( 3/7 ) in those who received 6 months of interferon . Fatigue , headache and cytopenia were the most commonly observed side-effects occurring in 39 % , 22 % and 28 % of the patients , respectively . Discontinuation of interferon , however , was not required in any of the patients . Rejection was documented in 6 % ( 1/18 ) patients receiving interferon ; this incidence was not higher than rejection episodes occurring > 6 months post-transplant in other recipients transplanted during the same period and who did not receive interferon . Responders had a trend towards later recurrence of HCV hepatitis after transplantation . In conclusion ; maintenance interferon was well tolerated and appeared to improve the long-term outcome in our patients ; however , future studies should evaluate this in a controlled trial BACKGROUND Hepatitis C ( HCV ) universally recurs following orthotopic liver transplantation ( OLT ) , representing an important cause for retransplantation . Although it is often treated with interferon and ribavirin , ribavirin is contraindicated in the presence of renal failure . In this setting of renal failure , pegylated-interferon monotherapy may be useful for recurrent HCV in liver transplant patients . METHODS Between June 2001 and November 2002 , patients with recurrent HCV were screened to determine if they were eligible for treatment . Renal failure was defined as serum creatinine greater than 1.8 mg/dL. HCVRNA and liver biopsies were performed prior to treatment , end of treatment ( EOT ) and 6 months after EOT for those who were HCV-RNA negative at EOT . Patients were followed prospect ively after starting weekly pegylated-interferon alpha 2b 1.0 microg/kg ( Schering-Plough , Kenilworth , NJ , USA ) . RESULTS Among the 45 patients with recurrent HCV screened , 9 were eligible , including 8 men and 1 woman of average age 55 years . Eight patients were intolerant to the treatment requiring discontinuation within the first 3 months . Two patients developed a sustained response to HCV eradication . One patient who completed treatment has normal liver tests but is still viremic . CONCLUSIONS Pegylated-interferon alpha 2b is poorly tolerated in liver transplant recipients with recurrent HCV and chronic renal failure . Larger , prospect i ve studies are required to determine the optimum duration of treatment and the impact of treatment on histology and quality of life Decompensated liver disease associated with chronic hepatitis C virus ( HCV ) infection is the most common indication for liver transplantation . It was shown previously that greater pretransplantation HCV titers are associated with relatively poor patient and graft survival . The tolerability and efficacy of antiviral therapy in patients with decompensated liver disease are not known . We conducted a pilot study to determine the likely tolerability and efficacy of pretransplantation antiviral therapy with interferon alfa-2b , with or without ribavirin . HCV RNA-positive patients at or near the top of their respective waiting lists were r and omly assigned to one of three treatment regimens until the time of liver transplantation : ( 1 ) group A , interferon alfa-2b , 1 x 10(6 ) U/d ; ( 2 ) group B , interferon alfa-2b , 3 x 10(6 ) U three times weekly ; or ( 3 ) group C , interferon alfa-2b , 1 x 10(6 ) U/d , plus ribavirin , 400 mg twice daily . Less than half the patients screened met entry criteria , with thrombocytopenia and leukopenia the most common reasons for exclusion . Fifteen patients were administered antiviral therapy ; three patients in group A and six patients each in groups B and C. Loss of detectable HCV RNA was seen in 33 % of patients , whereas 55 % had a decrease in viral titers on therapy . Twenty-three adverse events occurred , including 20 serious adverse events . Thrombocytopenia was the most common adverse event . Two infectious complications occurred ; one of these had a fatal outcome . We conclude that although pretransplantation antiviral therapy may reduce HCV titers in a minority of patients who meet treatment initiation criteria , adverse events associated with therapy are frequent and often severe in patients with Child 's class B and C cirrhosis Clinical recurrence of hepatitis C after liver transplantation can lead to cirrhosis , liver failure , and death . In patients undergoing liver transplantation for hepatitis C , we assessed the efficacy of interferon alfa‐2b ( IFN ) in preventing recurrent hepatitis . We r and omized 86 patients to either an IFN group ( 3 MU three times a week starting within 2 weeks after transplantation and continued for 1 year ) or a control ( no IFN ) group . Recurrence , the primary end point , was diagnosed on biopsy performed at 1 year or for abnormal biochemistries . HCV RNA levels were measured by branched‐chain DNA ( bcDNA ) assay and arbitrarily defined as low , moderate , or high ( < 10 × 105 , 10‐100 × 105 , or > 100 × 105Eq/mL , respectively ) . Data on 30 IFN patients and 41 no‐IFN patients who survived ≥3 months were review ed . Mean follow‐up was 669 ± 228 days for IFN patients and 594 ± 254 days for no‐IFN patients . IFN patients were less likely to develop recurrent hepatitis ( 8 IFN vs. 22 no‐IFN patients , P= .017 , log rank analysis ) . IFN and 1‐month HCV RNA level were independent predictors of recurrence . IFN reduced the risk of recurrence by a factor of 0.4 ( P= .04 , Cox proportional hazards model ) ; HCV RNA level > 100 × 105 Eq/mL at 1 month after transplantation increased the risk by a factor of 3.1 ( P = .01 ) . Low , moderate , and high viral levels at 1 and 3 months were associated with significantly different rates of recurrence in IFN patients ( P = .05 at 1 month and P = .003 at 3 months ) but not in untreated patients ( P = .28 at 1 month and P = .25 at 3 months ) . In patients with two or more rejections , the risk of recurrence was increased by a factor of 2.17 ( P = .05 ) . On 47 1‐year biopsies ( 24 IFN ; 23 no IFN ) , piecemeal necrosis was more common in untreated patients ( P < .02 ) . One‐ and 2‐year patient survival , respectively , was 96 % and 96 % with IFN and 91.2 % and 87.2 % without ( P = NS ) . Prophylactic IFN reduced the incidence of recurrent hepatitis after transplant . Although IFN was most effective in patients with low HCV RNA levels , we also noted an effect in patients with moderate levels . IFN did not prevent viremia , suggesting that it may work through alternative mechanisms Background and objective : A proportion of liver transplanted patients with recurrent chronic hepatitis have a sustained virological response to combination therapy with interferon plus ribavirin . However , the long term benefit of antiviral therapy with regard to hepatitis C virus ( HCV ) RNA clearance remains unknown in patients with HCV recurrence . This study examined the long term biochemical , virological , and histological outcome in transplanted patients with recurrent chronic hepatitis who had a sustained virological response to antiviral therapy . Patients and methods : Fifty four patients with recurrent hepatitis C were treated with antiviral therapy involving induction by combination therapy ( interferon ( IFN ) plus ribavirin ) for six months and maintenance ribavirin therapy for 12 months . Fourteen patients who had recurrent chronic hepatitis and sustained virological response to antiviral therapy were followed for three years after the end of antiviral therapy . Serum alanine aminotransferases were assessed every three months during the observation period . Serum hepatitis C RNA detected by polymerase chain reaction was evaluated every six months during follow up , and protocol biopsy procedures were performed routinely every year . Semiquantitative histopathological assessment of allograft hepatitis was performed using the Knodell score and HCV was also detected by polymerase chain reaction on frozen graft tissue sample s. Results : At the end of antiviral therapy , the sustained response rate was 26 % . A complete response ( normal serum alanine aminotransferase level and undetectable serum HCV RNA ) was achieved in 13/14 ( 93 % ) patients three years after the end of treatment . A comparison of liver histology findings before and after a mean of three years after antiviral therapy showed a clear improvement in 12/14 ( 86 % ) patients . In 5/14 ( 36 % ) patients , the last biopsy showed normal or near normal histological findings . After three years of follow up , the total Knodell score was 3.2 ( range 1–8 ) versus 8.3 ( range 5–12 ) before treatment ( p=0.001 ) . Graft HCV RNA was detectable before treatment in all 14 patients and was undetectable at the end of follow up in 13/14 ( 93 % ) patients tested . Conclusion : In patients with biochemical and virological responses induced by ribavirin and interferon , a complete response was sustained in 93 % for at least three years after cessation of therapy . This long term response was associated with absence of detectable intrahepatic hepatitis C RNA and marked histological improvement Hepatitis C virus ( HCV ) infection usually recurs after orthotopic liver transplantation ( OLT ) , and most patients develop graft damage . This study compared the efficacy of interferon alfa ( IFN-alpha ) and ribavirin monotherapies in liver transplant recipients with chronic hepatitis C in the graft . Thirty OLT recipients with chronic hepatitis C were r and omized to receive either IFN-alpha ( 3 MU three times a week ) or ribavirin ( up to 1.2 g daily ) for 24 weeks . Virological , biochemical , and histological responses to treatment were assessed . Twenty-eight patients completed the treatment regimen , two ribavirin-treated patients being withdrawn because of severe hemolysis . Normalization of serum aspartate aminotransferase was achieved in 13 of 14 patients receiving ribavirin ( 93 % ) and 6 of 14 patients receiving IFN-alpha ( 43 % ; P=.01 ) . Lobular inflammation was reduced in 9/14 ribavirin-treated ( 64 % ) and 3 of 14 IFN-alpha-treated patients ( 21 % ; P=.05 ) , each of whom had a biochemical response . However , the total histological activity index did not improve in either the interferon ( P=.43 ) or the ribavirin ( P=.96 ) group . Posttreatment viremia levels were significantly reduced in IFN-alpha-treated ( P=.05 ) but not in ribavirin-treated ( P=.88 ) patients . Hemolysis occurred in all ribavirin-treated patients , with serum hemoglobin decreasing to < 10 g/dL in 50 % . Total leukocyte and lymphocyte counts decreased significantly during ribavirin treatment ( P=.02 and P=.004 , respectively ) . We concluded that in patients with chronic hepatitis C after OLT , IFN-alpha retains an antiviral effect whereas ribavirin is superior in achieving normalization of serum aspartate aminotransferase levels and reducing lobular inflammation , but not the total histological activity index . These findings provide a rationale for combination therapy in the post-OLT setting , although patients must be carefully monitored for hemolysis Background . Hepatitis C virus infection persists after liver transplantation and causes recurrent liver injury in the majority of patients . St and ard dose interferon therapy has been largely unsuccessful for hepatitis C in transplant recipients . Methods . Twelve patients , at least 7 months posttransplant , with detectable hepatitis C virus RNA in serum and features of hepatitis C on liver biopsy were r and omized to interferon-&agr;2a , 3 mU daily for 12 months ( n=8 ) or no treatment ( n=4 ) . The tolerability of daily interferon dosing in liver transplant recipients was evaluated and effects on hepatitis C virus RNA level , quasispecies evolution , and liver histology were studied . Results . Treated patients had an improvement in histological activity index at the end of therapy relative to controls ( median reduction of 2 versus median increase of 1.5 ) ( P = 0.04 ) . Four treated patients had a virological response ( all bDNA negative , one qualitative polymerase chain reaction negative ) compared with none of the untreated patients . Only two of six treated patients tested had evidence of quasispecies diversification on therapy . Seven of eight patients in the treatment group required dose reduction for fatigue and /or depression . They tolerated 1.5 mU of interferon-&agr;2a daily . Two treated patients developed graft dysfunction , one of who had histological evidence of rejection and subsequent graft loss . Conclusions . Low daily doses of interferon were tolerated by liver transplant recipients and provided histological benefit without associated quasispecies diversification in most cases . These findings provide a rationale to study low dose daily or pegylated interferon maintenance therapy for the management of hepatitis C posttransplant Ribavirin therapy was initiated at a median of 181 days after liver transplantation in 18 patients with persistent elevation of alanine aminotransferase values and biopsy-proven hepatitis , and continued for 23 months ( 12 - 44 months ) . All patients had a prompt biochemical response , with alanine aminotransferase decreasing by 69 % ; complete normalization occurred in 5 ( 28 % ) . Serum hepatitis C virus RNA levels did not change during therapy . Liver biopsies obtained after 17 months ( 9 - 38 months ) of therapy showed no improvement in necroinflammation . However , worsening of fibrosis occurred in 12 patients ; and cirrhosis developed in 5 patients ( 28 % ) , with 3 patients progressing to graft failure . Biopsies from 27 untreated patients who did not fulfill treatment criteria ( median follow-up , 38 months ) and 4 patients who received 3 months of ribavirin ( 44 months ) showed cirrhosis in 11 and 75 % , respectively . Patient and graft survival rates for treated and untreated patients were similar . Although ribavirin improves alanine aminotransferase , it does not prevent the development or progression of fibrosis in patients with recurrent hepatitis C virus Hepatitis C virus ( HCV ) infection invariably recurs after liver transplantation ( LT ) , and sequels of chronic hepatitis of the graft are a significant cause of morbidity and mortality . In an uncontrolled trial , 31 patients with histologically confirmed hepatitis C after LT received , sequentially , ribavirin ( 10 mg/kg body weight q.d . ) for 12 weeks , followed by ribavirin at the same dose q.d . plus interferon-alpha ( IFN-alpha ) [ 3 million units three times a week ( 3 MU TIW ) ] for another 48 weeks . Based on an intent-to-treat analysis , the percentages of patients with undetectable HCV RNA in their serum were 0 % , 38.7 % and 45.2 % after 12 , 36 and 60 weeks of therapy , respectively . A sustained virological response , as defined by undetectable serum HCV RNA 24 weeks after the end of treatment , was observed in 9/31 patients ( 29 % ) . Sustained responders had a significant improvement of their liver inflammatory activity score ( P=0.025 ) , but not of their liver fibrosis score . The chances of sustained virological response correlated with the length of treatment , but not with the HCV genotype or baseline HCV RNA level . In conclusion , patients with recurrent hepatitis C after LT might benefit from ribavirin/IFN-alpha therapy , provided that the treatment is tolerated for a sufficient duration of time Currently , alpha interferon is the only recognized therapy for chronic viral hepatitis . As a result of its success in several multicenter trials , the agent was approved recently by the FDA for use in the clinical management of patients with chronic hepatitis C. FDA approval for its use in chronic hepatitis B is anticipated . Based upon this experience in nonimmunosuppressed individuals , the efficacy of alpha interferon therapy in patients who are recipients of liver allografts and are receiving chronic immunosuppression was assessed in a preliminary trial of the agent in 30 patients ( 13 with HBV , 11 with HCV , and 6 with hepatitis non A , non B , non C ) . Therapy was initiated at a dose of 3 X 10(6 ) units three times per week and continued for 6 months . Dose reduction in the amount of the alpha interferon administered was determined by a preestablished protocol . Nine percent of those with HCV and 18 % of those with hepatitis non A , non B , non C experienced a full response to alpha interferon therapy . No full responses to alpha interferon therapy . No full responses were seen in those with HBV disease . Partial responses were common in all three groups but were most frequent in those with hepatitis non A , non B , non C and least frequent in those with HCV-related disease . This preliminary experience demonstrates the following : 1 . Viral hepatitis following OLTx can be treated with alpha-2b-interferon . 2 . The complications of alpha-2b-interferon therapy utilized prior to OLTx can be avoided by giving the therapy following successful OLTx . 3 . The high rate of partial responses noted suggests that future studies should utilize either higher doses or longer duration s of therapy or both . 4 . The response rate was greatest for those having non A , non B , non C hepatitis and least for those with HCV hepatitis . 5 . In this small preliminary series , no episodes of liver graft rejection could be ascribed to the use of alpha-2b-interferon in the patients so treated Liver transplant recipients with recurrent hepatitis C virus ( HCV ) infection often have histological hepatitis , and in some patients , graft failure develops . The aim of this nonr and omized study is to determine the efficacy and tolerability of interferon alfa ( IFN alfa ) alone and IFN alfa and ribavirin combination therapy in such patients . Forty transplant recipients with recurrent hepatitis were initiated on therapy with IFN alfa-2b at 3 million units ( MU ) three times weekly for 1 month followed by 5 MU three times weekly for 5 months . Twenty patients were administered IFN alfa-2b , 3 MU three times weekly for 1 month followed by 5 MU three times weekly for 11 months , and ribavirin , 600 mg , twice daily orally for 12 months concurrently . The primary end point was sustained clearance of serum HCV RNA , and secondary end points were serum alanine aminotransferase ( ALT ) level normalization and histological improvement . Thirty patients completed 6 months of IFN-alfa monotherapy and 15 patients completed 12 months of IFN alfa and ribavirin combination therapy . End-of-treatment biochemical responses were similar in the two groups ( IFN alfa , 20 % v combination therapy , 25 % ) ; however , viral clearance was greater in the combination-therapy group ( 40 % v 15 % ; P = .04 ) . Six months after the completion of therapy , only 1 patient ( 2.5 % ) in the IFN-alfa group and 4 patients ( 20 % ) in the combination-therapy group were HCV RNA negative ( P = .03 ) . Serum ALT and HCV RNA levels declined significantly in both groups during therapy . There was no improvement in inflammatory grade , and fibrosis score was worse in both groups . Ten patients ( 25 % ) in the IFN-alfa group and 5 patients ( 20 % ) in the combination-therapy group withdrew because of adverse effects . We conclude that in liver allograft recipients with recurrent hepatitis C , combination therapy with IFN alfa and ribavirin is more efficacious than treatment with IFN alfa alone . However , the efficacy is limited by tolerability The aim of this open trial was to assess the efficacy and the safety of interferon ( IFN ) alfa therapy in liver transplant recipients with chronic active hepatitis caused by hepatitis C virus . In July 1991 , among 447 liver recipients regularly observed at our institution , 46 had developed HCV-related chronic active hepatitis defined by piece meal necrosis . Fourteen of these 46 patients received IFN alfa 3 mIU three times weekly for a planned duration of 6 months and were compared to the 32 untreated patients . Genotyping and quantification of viremia were performed using type-specific amplification and branched DNA assay . Histological follow-up was available in all patients and routinely before and after IFN therapy . Treated and untreated patients did not differ regarding gender , age , length of follow-up , maximum histological score , and genotypes ( 41 of 46 were of type 1b ) . Induction of chronic rejection was observed in 5 of 14 treated patients leading to retransplantation in 3 . In contrast , chronic rejection occurred in 1 of 32 untreated patients ( P < .005 ) during the posttransplantation follow-up . Among the 9 treated patients without rejection , a decrease of transaminases or of HCV RNA levels of more than 50 % were observed in 8 and 4 , respectively ; 2 patients had a complete response , and 1 did not relapse after discontinuation of IFN . Histological improvement occurred in 2 of the treated patients and in none of the untreated patients . IFN therapy in liver transplant recipients has poor antiviral effect and can induce chronic rejection . Its use in this setting should be cautious BACKGROUND / AIMS Interferon ( IFN ) with ribavirin combination therapy ( CT ) was proposed for the treatment of hepatitis C recurring in liver transplants . We assessed the efficacy of two protocol s of CT in transplanted patients with recurrent severe hepatitis C virus ( HCV ) hepatitis . METHODS Fifty-seven patients ( 68 % genotype 1b ) were treated with IFN alfa-2b 3 million units three times weekly and oral ribavirin 800mg/die for 6 or 12 months . Study end-points were the end of treatment ( ETVR ) and the 12-month post-therapy sustained virologic response ( SVR ; negative HCV-RNA ) . RESULTS ETVR was induced in 9/27 ( 33 % ) and in 7/30 patients ( 23 % ) treated , respectively , for 6 and 12 months ( P=0.4 ) ; a SVR was induced in six ( 22 % ) of the former and five ( 17 % ) of the latter ( P=0.4 ) . HCV genotype non-1 patients responded better than genotype 1 ( SVR : 43 % in genotype non-1 versus 12 % in genotype 1 , P : 0.02 ) . In ETV responders the hepatitis activity index improved by > 2 points in biopsies taken after therapy compared to pre-therapy biopsies . Anemia and leukopenia required reduction of therapy in 51 % of the patients . CONCLUSIONS CT is efficacious in controlling HCV disease in about 20 % of transplants with recurrent hepatitis C. Six months of therapy are as efficacious as 12 months |
10,487 | 15,910,014 | Does episiotomy or incision type , or both , influence future sexual function | Does the practice of liberal or routine episiotomy , compared to more selective use of episiotomy , influence maternal postpartum outcomes ?
2 .
Does episiotomy incision type ( i.e. , midline or mediolateral ) , influence maternal postpartum outcomes ?
3 .
Does the repair of the perineal defect ( i.e. , suture type and repair approach ) influence maternal postpartum outcomes ?
4 .
Does episiotomy have a long-term influence on urinary incontinence , fecal incontinence , or pelvic floor defects ?
5 . | OBJECTIVE : To compare the outcomes of the current practice of liberally or routinely employing episiotomy to prevent perineal tears and pelvic floor relaxation ( control group ) to a policy of restricting episiotomy use to specific fetal and maternal indications ( experimental group ) . DESIGN : A r and omized controlled trial ( RCT ) . SETTING : Three university hospitals in Montreal . SUBJECTS : Seven hundred three low-risk women enrolled at 30 to 34 weeks of gestation were r and omized late in labor to the design ated trial arm , by parity , and followed up to 3 months postpartum . MAIN OUTCOME MEASURES : Antepartum and postpartum information on perineal trauma and pain , pelvic floor symptoms ( urinary incontinence ) , and sexual activity was collected through the use of st and ard question naires ; pelvic floor function was measured by electromyographic ( EMG ) perineometry . RESULTS : Restricting episiotomy use in primiparous women was associated with similar sutured perineal trauma to the liberal or routine approach . Multiparous women in the restricted episiotomy group more often gave birth with an intact perineum ( 31 % compared with 19 % , odds ratio ( OR ) = 1.85 , 95 % confidence interval ( CI ) = 1.09 to 3.16 ) . All but one 3rd/4th-degree perineal tear was associated with median episiotomy ( 46 of 47 in primiparous women and 6 of 6 among multiparous women ) . No difference between trial groups was found in postpartum perineal pain , antepartum and 3-month postpartum EMG perineometry , and urinary and pelvic floor symptoms . CONCLUSIONS : We found no evidence that liberal or routine use of episiotomy prevents perineal trauma or pelvic floor relaxation . Virtually all severe perineal trauma was associated with median episiotomy . Restriction of episiotomy use among multiparous women result ed in significantly more intact perineums and less perineal suturing In a prospect i ve clinical investigation of 2,144 deliveries , we eluci date the indications for episiotomy and how different methods of anesthesia affect the frequency of episiotomy and the perineal problems after episiotomy compared with those after spontaneous perineal laceration . We found a significantly higher infection rate ( p less than 0.001 ) and a longer healing period in the episiotomy group . These differences remain even if only primigravida or the indication , imminent perineal laceration , is studied . The results indicate that many women will unnecessarily suffer after an episiotomy . The patient 's subjective problems are significantly increased , both immediately and at the 3-month postoperative follow-up Episiotomy is a very common operation but little is known of its short-term or long-term morbidity . A prospect i ve study was design ed to record postpartum perineal discomfort and to investigate the presence and persistence of dyspareunia following episiotomy in 140 primigravidae . A comparison was made between those whose perineal skin was sutured with a subcuticular polyglycolic acid ( ; Dexon ' ) stitch and those sutured with interrupted black silk stitches . Patients sutured with subcuticular ; Dexon ' had significantly less perineal discomfort on the third , fourth , and fifth postpartum days . Patients who had epidural analgesia in labour had significantly more pain during the first five postpartum days irrespective of the suture material used . The timing of first coitus after delivery did not influence the presence or persistence of dyspareunia . Dyspareunia was commoner and lasted longer in patients sutured with ; Dexon ' and it was also commoner in older primigravidae irrespective of the suture technique BACKGROUND Trauma to the perineum is a serious and frequent problem after childbirth , with about 350000 women each year in the UK needing sutures for perineal injury after spontaneous vaginal delivery , and many millions more worldwide . We compared the continuous technique of perineal repair with the interrupted method , and the more rapidly absorbed polyglactin 910 suture material with the st and ard polyglactin 910 material . METHODS 1542 women who had a spontaneous vaginal delivery with a second-degree perineal tear or episiotomy were r and omly allocated to either the continuous ( n=771 ) or interrupted ( 771 ) suturing method , and to either the more rapidly absorbed polyglactin 910 suture material ( 772 ) or st and ard polyglactin 910 material ( 770 ) . Primary outcomes were pain 10 days after delivery and superficial dyspareunia 3 months postpartum . Analysis was by intention to treat . FINDINGS At day 10 , three women had dropped out of the study . Significantly fewer women reported pain at 10 days with the continuous technique than with the interrupted method ( 204/770 [ 26.5 % ] vs 338/769 [ 44.0 % ] , odds ratio 0.47 , 95 % CI 0.38 - 0.58 , p<0.0001 ) . Occurrence of pain did not differ significantly between groups assigned the more rapidly absorbed material or st and ard material ( 256/769 [ 33.3 % ] vs 286/770 [ 37.1 % ] , 0.84 , 0.68 - 1.04 , p=0.10 ) . Women reported no difference in superficial dyspareunia at 3 months for the continuous vs the interrupted method ( 98/581 [ 16.9 % ] vs 102/593 [ 17.2 % ] , 0.98 , 0.72 - 1.33 , p=0.88 ) or the more rapidly absorbed versus st and ard material ( 105/586 [ 17.9 % ] vs 95/588 [ 16.2 % ] , 1.13 , 0.84 - 1.54 , p=0.42 ) . Suture removal was done less with the more rapidly absorbed material than with st and ard suture material ( 22/769 [ 3 % ] vs 98/770 [ 13 % ] , p<0.0001 ) , and with the continuous versus interrupted method ( 24/770 [ 3 % ] vs 96/769 [ 12 % ] , p<0.0001 ) . INTERPRETATION A simple and widely practicable continuous repair technique can prevent one woman in six from having pain at 10 days . Also , the more rapidly absorbed polyglactin 910 material obviates need for suture removal up to 3 months postpartum for one in ten women sutured Objective To assess the long term implication s of four alternative approaches to postpartum perineal repair . This report presents results of a comparison perineal muscle function between antepartum and postpartum measurements in a cohort of women with different perineal conditions after childbirth . Data were obtained by using prospect i ve electromyographic perineometry measurements to objective ly determine perineal muscle function before and after delivery in 102 women . In addition , 24 nulliparous , non-pregnant women were studied to determine the effect of pregnancy on perineal muscle function . Pregnancy is associated with a decrease in perineal muscle strength and endurance compared with the postpartum state . The degree to which women improved or did not improve perineal muscle function after birth was related to perineal trauma at delivery . After controlling for parity , maternal age , birthweight , smoking status , and antepartum scores , the order of best to worst performance was cesarean birth , intact perineum , first-degree perineal injury , second- or third-degree perineal injury , and episiotomy . Pre- and post-delivery scores were compared for each woman and analyzed according to perineal outcome . Although all other perineal outcome groups increased muscle function by 6 months postpartum , women with an episiotomy had a mean net loss of perineal muscle performance after birth . These observations do not support the use of episiotomy for the purpose of preserving perineal muscle function Background This study was carried out to identify risk factors associated with urinary incontinence in women three months after giving birth . Methods Urinary incontinence before and during pregnancy was assessed at study enrolment early in the third trimester . Incontinence was re-assessed three months postpartum . Logistic regression analysis was used to assess the role of maternal and obstetric factors in causing postpartum urinary incontinence . This prospect i ve cohort study in 949 pregnant women in Quebec , Canada was nested within a r and omised controlled trial of prenatal perineal massage . Results Postpartum urinary incontinence was increased with prepregnancy incontinence ( adjusted odds ratio [ adj0R ] 6.44 , 95 % CI 4.15 , 9.98 ) , incontinence beginning during pregnancy ( adjOR 1.93 , 95 % CI 1.32 , 2.83 ) , and higher prepregnancy body mass index ( adjOR 1.07/unit of BMI , 95 % CI 1.03,1.11 ) . Caesarean section was highly protective ( adjOR 0.27 , 95 % CI 0.14 , 0.50 ) . While there was a trend towards increasing incontinence with forceps delivery ( adjOR 1.73 , 95 % CI 0.96 , 3.13 ) this was not statistically significant . The weight of the baby , episiotomy , the length of the second stage of labour , and epidural analgesia were not predictive of urinary incontinence . Nor was prenatal perineal massage , the r and omised controlled trial intervention . When the analysis was limited to women having their first vaginal birth , the same risk factors were important , with similar adjusted odds ratios . Conclusions Urinary incontinence during pregnancy is extremely common , affecting over half of pregnant women . Urinary incontinence beginning during pregnancy roughly doubles the likelihood of urinary incontinence at 3 months postpartum , regardless whether delivery is vaginal or by Caesarean section Episiotomy is a widely-done intervention in childbirth , regardless of poor scientific evidence of its benefits . This r and omised controlled trial compares selective with routine use of a mediolateral episiotomy for women having first and second deliveries in 8 public maternity units in Argentina . 2606 women participated ; 1555 were nulliparous ( 778 in the selective group and 777 in the routine group ) and 1051 primiparous ( 520 in the selective group and 531 in the routine group ) . The two interventions compared were selective ( limited to specified maternal or fetal indications ) , and routine episiotomy ( following the hospital 's previous policy ) . Episiotomy was done in 30.1 % of deliveries in the selective , and 82.6 % in the routine group . The main outcome measure was severe perineal trauma . Severe perineal trauma was uncommon in both groups but was slightly less frequent in the selective group ( 1.2 % vs 1.5 % ) . Anterior perineal trauma was more common in the selective group but posterior perineal surgical repair , perineal pain , healing complications , and dehiscence were all less frequent in the selective group . Routine episiotomy should be ab and oned and episiotomy rates above 30 % can not be justified One hundred and eighty one primigravid women delivering vaginally in July and August 1982 in the Rotunda Hospital , Dublin , were r and omly allocated to one of two groups . Patients in one group were to undergo episiotomy . Those in the other group were not to undergo episiotomy unless it was considered to be essential . The outcome was compared with that of the clinical practice over the previous six months at the hospital . Of the 92 patients allocated not to undergo episiotomy , seven ( 8 % ) had one done for medical reasons compared with 507 ( 89 % ) in the previous six months . First degree tears occurred in 23 ( 25 % ) and second degree tears in 43 ( 47 % ) . Nineteen ( 21 % ) , however , retained an intact perineum compared with only 35 ( 6 % ) of the women who had delivered in the preceding six months . Assessment s of perineal pain , bruising , swelling , and healing and records of ingestion of analgesics were made for the first four days after delivery , and again at a check up six weeks after delivery , in patients who had had spontaneous vertex deliveries . Forty patients who underwent episiotomy and 37 who sustained a second degree tear formed two comparable groups . There was no difference in outcome between them . Data were also evaluated for 19 women who retained an intact perineum , 22 who sustained a first degree tear , and 11 who underwent episiotomy and epidural anaesthesia ; all 52 of these women had spontaneous vertex deliveries . Despite severe soft tissue injury in two patients those who fared best were those who retained an intact perineum . First degree tears were associated with symptoms similar to those associated with second degree tears . Those who fared worst were women who underwent episiotomy after epidural anaesthesia . The value of routine episiotomy in primigravid patients is question ed , but the final decision can be made only by the accoucheur at the time of imminent delivery The incidence and outcome of third‐degree tears following 16583 vaginal deliveries were prospect ively assessed over a 55year period . Ninety‐three deliveries ( 0.56 per cent ) were complicated by a third‐degree tear and the patients underwent primary repair . Eighty‐one patients were review ed 3 months postpartum at a colorectal clinic . Third‐degree tears were significantly more common in primigravidae and mothers with higher birth‐weight babies . They were significantly associated with the use of forceps and were not prevented by episiotomy . Of the 81 patients review ed , 30 had an abnormal anorectal examination . Six patients ( 7 per cent ) were incontinent of faeces . A further ten ( 12 per cent ) were incontinent of flatus only . The overall incidence of faecal incontinence was 0.04 per cent . An important group of women with significant sub clinical sphincter injury was identified . Obstetric trauma causes significant anorectal dysfunction and patients with third‐degree tears require assessment by a colorectal specialist Summary . Histoacryl‐tissue adhcsive ( B. Braun Melsungen AG W. Germany ) was used in place of skin sutures ( 2/0 chromic catgut , Ethicon Ltd , Edinburgh , Scotl and ) for episiotomy repair in a group of 20 women . This group was compared with two groups of women undergoing first and repeat episiotomy . Variables analysed included pain in the episiotomy site , pain while walking , sitting , sleeping , lying down , breast‐feeding , micturating and defaecating . The Histoacryl group was superior with regard to all the variables . This simple , new method can reduce pain and inconvenience for patients , especially following the first delivery OBJECTIVES The purpose of the study was to evaluate the use of enbucrilate tissue adhesive compared with subcuticular polyglycolic acid sutures in episiotomy wound closure . METHODS In a prospect i ve controlled trial , two groups were studied after undergoing an episiotomy skin wound repair using either enbucrilate tissue adhesive ( n=32 ) or a subcuticular polyglycolic acid suture ( n=30 ) . The variables measured included pain scores during selected activities in the first 5 postnatal days , the time taken to become pain free after childbirth and the time taken to resume pain free sexual intercourse . Suitable patients were invited by the midwives to participate in the trial . If they gave consent to the trial , the gynecologist was contacted . If available , he would perform a repair using enbucrilate tissue adhesive . If he was not available , one of the midwives would perform a repair using subcuticular polyglycolic acid sutures . In this group , 90 % of the women were recruited and sutured by one midwife . RESULTS Patients treated with enbucrilate were found to have significantly less postnatal pain while walking , became pain free in a shorter period ( mean=25 days vs. 18 days ; P<0.01 ) and were able to resume pain-free intercourse sooner ( mean=34 days vs. 52 days ; P<0.001 ) . CONCLUSIONS Tissue adhesives incorporate the qualities of an ideal skin-closure material . The results demonstrate their advantage over the current st and ard suture-based methods of repair in the perineum . The use of adhesives merits further evaluation OBJECTIVE Our purpose was to compare consequences for women of receiving versus not receiving median episiotomy early and 3 months post partum on the outcomes perineal pain , urinary and pelvic floor functioning by electromyography , and sexual functioning and to analyze the relationship between episiotomy and third- and fourth-degree tears . STUDY DESIGN A secondary cohort analysis was performed of participants within a r and omized clinical trial , analyzed by type of perineal trauma and pain , pelvic floor , and sexual consequences of such trauma , while controlling for trial arm . The study was conducted in three university or community hospitals ; 356 primiparous and 341 multiparous women were studied . RESULTS Early and 3-month-postpartum perineal pain was least for women who gave birth with an intact perineum . Spontaneous perineal tears were less painful than episiotomy . Sexual functioning was best for women with an intact perineum or perineal tears . Postpartum urinary and pelvic floor symptoms were similar in all perineal groups . At 3 months post partum those delivered with an intact perineum had the strongest pelvic floor musculature , those with episiotomy the weakest . Among primiparous women third- and fourth-degree tears were associated with median episiotomy ( 46/47 ) . After forceps births were removed and 21 other variables potentially associated within such tears were controlled for , episiotomy was strongly associated with third- and fourth-degree tears ( odds ratio + 22.08 , 95 % confidence interval 2.84 to 171.53 ) . Physicians using episiotomy at high rates also used other procedures , including cesarean section , more frequently . CONCLUSION Perineal and pelvic floor morbidity was greatest among women receiving median episiotomy versus those remaining intact or sustaining spontaneous perineal tears . Median episiotomy was causally related to third- and fourth-degree tears . Those using episiotomy at the highest rates were more likely use other interventions as well . Episiotomy use should be restricted to specified fetal-maternal indications BACKGROUND The indication of the restricted use of episiotomy at tears presumed to be imminent is not clear . METHODS R and omized controlled trial with two perineal management policies . Use of episiotomy : ( a ) . only for fetal indications and ( b ) . in addition at a tear presumed to be imminent . PARTICIPANTS 146 primiparous women with an uncomplicated singleton pregnancy at > 34 weeks of gestation . For the intention-to-treat analysis those 109 women were included who vaginally delivered a live full-term baby between January 1999 and September 2000 : 49 women in group a , 60 in group b. OUTCOME MEASURES Reduction of episiotomies , increase of intact perinea or only minor perineal trauma ( intact perineum and first-degree tears ) , third-degree tears , anterior perineal trauma , perineal pain in the postpartum period , pH of the umbilical artery , Apgar scores , maternal blood loss . RESULTS Episiotomy rates were 41 % in group a and 77 % in group b ( p < 0.001 ) . Women in the restrictive policy group had a greater chance of an intact perineum ( 29 % vs. 10 % ; p = 0.023 ) or only minor perineal trauma ( 39 % vs. 13 % ; p = 0.003 ) and had significant lower pain scores postpartum at different activities . There were no statistically significant differences with regard to third-degree tears , anterior trauma , pre- and postpartum hemoglobin concentrations , Apgar scores and pH of the umbilical artery . CONCLUSIONS Avoiding episiotomy at tears presumed to be imminent increases the rate of intact perinea and the rate of only minor perineal trauma , reduces postpartum perineal pain and does not have any adverse effects on maternal or fetal morbidity OBJECTIVE To evaluate a policy of two stage postpartum perineal repair leaving the skin unsutured . DESIGN A stratified r and omised controlled trial using a 2 x 2 factorial design . SETTING The maternity unit at Ipswich Hospital NHS Trust , a district general hospital , between 1992 and 1994 . SAMPLE 1780 women requiring surgical repair of episiotomy or first or second degree tear following a spontaneous or simple instrumental delivery . METHODS A policy of two-stage perineal repair leaving skin unsutured was compared with a policy of three stage repair including skin closure with interrupted or subcuticular sutures . Both groups were assessed by a research midwife , blind to the allocation , completing question naires at 24 to 48 hours and 10 days postpartum , and by self-completed question naires at three months after birth . MAIN OUTCOME MEASURES 1 . 24 to 48 hours postpartum : perineal pain ; healing ; 2 . 10 days postpartum : perineal pain , healing and removal of sutures ; 3 . three months postpartum : perineal pain , removal of sutures , resuturing , dyspareunia , and failure to resume pain-free intercourse . RESULTS Completed question naires were returned for 99 % of women at both 24 to 48 hours and ten days and by 93 % of women three months postpartum . No differences were detected in perineal pain at 24 to 48 hours ( 62 % vs 64 % ; RR 0.96 , 95 % CI 0.90 - 1.03 ; 2P = 0.3 ) and 10 days ( 25 % vs 28 % ; RR 0.90 , 95 % CI 0.77 - 1.06 ; 2P = 0.2 ) . Significantly fewer women allocated to two-stage repair reported tight stitches at ten days ( 14 % vs 18 % ; RR 0.77 , 95 % CI 0.62 - 0.96 , 2P = 0.02 ) ; similar numbers of repairs were judged to be breaking down ( five compared with seven women ) . At three months postpartum fewer women allocated to the two-stage repair reported perineal pain and more had resumed pain-free intercourse . Amongst women who had resumed intercourse there was a significant difference in dyspareunia ( 15 % vs 19 % ; RR 0.80 , 95 % CI 0.65 - 0.99 ; 2P = 0.04 ) . Significantly fewer women in the two-stage repair group ( 7 % vs 12 % ; RR 0.61 , 95 % CI 0.45 - 0.83 ; 2P = < 0.01 ) reported removal of suture material . Four women in the two-stage repair group had required resuturing , compared with nine allocated to the three-stage repair . CONCLUSIONS Two-stage repair of perineal trauma leaving the skin unsutured appears to reduce pain and dyspareunia three months postpartum . There are no apparent disadvantages , in particular no evidence of an increased risk of breakdown of the repair and resuturing Objective To compare polyglactin 910 sutures with chromic catgut sutures for postpartum perineal repair typic abnormalities in early onset severe growth retardation ( Fisk et al. 1989 ; Nicolaides et al. 1989 ; Sipes et al. 1991 ) . However , since there is an overlap in mean corpuscular volume between triploid and chromosomally normal growth-retarded fetuses ( Nicolaides et al. 1989 ) it is necessary that the diagnosis is confirmed by cytogenetic analysis which usually takes 7 - 10 days . Using flow cytometry and st and ard DNA quantification techniques , which are now widely used in the clinical management of haematological and other neoplasias , it is possible to diagnose fetal triploidy from fetal blood , within l h of sampling Women who had participated in a r and omised controlled trial of policies of restricted ( 10 % ) versus liberal ( 51 % ) episiotomy during spontaneous vaginal delivery were recontacted by postal question naire three years after delivery . Altogether 674 out of 1000 responded , and there was no evidence of a differential response rate between the two trial groups . Similar numbers of women in the two groups reported further deliveries , almost all of which had been vaginal and spontaneous . Fewer women allocated to restrictive use of episiotomy required perineal suturing after subsequent delivery , but this difference was not significant . Pain during sexual intercourse and incontinence of urine were equally reported in the two groups . The similarity in incontinence rates persisted when severity , type of incontinence , and subsequent deliveries were taken into account . Liberal use of episiotomy does not seem to prevent urinary incontinence or increase long term dyspareunia Summary . Glycerol‐impregnated chromic catgut and untreated chromic catgut were compared in a r and omized controlled trial involving 737 consecutive women who required repair of perineal trauma following spontaneous vaginal delivery . Medical staff preference was equally divided between the two material s. More untreated chromic catgut sutures required removal both by 10 days and by 3 months postpartum . Women whose perineal trauma was repaired with glycerol‐impregnated chromic catgut were 10 % more likely to have perineal pain at 10 days and 33 % more likely to suffer from dyspareunia in the 3 months following delivery . The high rates of maternal morbidity associated with glycerol‐impregnated chromic catgut appear to preclude its use for perineal repair Women suffer a significant degree of perineal morbidity in the postpartum period . For some , it can be significant and interfere with daily activities . Although there seems to be no doubt that polyglycolic acid derivatives are superior to non absorbable sutures with regard to wound healing , problems still occur with their use . In this study a relatively new product , Vicryl rapide , was compared with Vicryl OBJECTIVE to assess the effect of suture material s ( an absorbable synthetic suture material versus catgut ) used in perineal repairs undertaken by midwives who had been trained and accredited in repair techniques . DESIGN r and omised controlled trial . SETTING tertiary obstetric hospital in Australia . PARTICIPANTS 391 women with a live singleton birth at > or = 34 weeks gestation , result ing from a spontaneous vaginal delivery and who required perineal repair due to either an episiotomy or first or second degree tear . INTERVENTION eligible women were r and omly allocated for repair with either polyglycolic acid or chromic catgut . MAIN OUTCOME MEASURES perineal pain and dyspareunia up to six months postpartum . FINDINGS of the 194 women allocated to polyglycolic suture 106 ( 55 % ) were primipara compared with 79 ( 40 % ) of the 197 women allocated to catgut . Due to this unexplained imbalance , odds ratios were estimated with and without adjustment for parity . The parity-adjusted odds ratios were little changed ( < 11 % ) from the crude odds ratios . Although there were no statistically significant differences , parity-adjusted odds ratios ( aOR ) suggest that compared with women sutured with catgut , women sutured with polyglycolic were less likely to experience perineal pain at Day 3 postpartum ( aOR=0.70 95 % confidence interval [ 95 % CI ] 0.46 - 1.08 ) but by six months postpartum were somewhat more likely to experience perineal pain ( aOR=1.77 , 95 % CI 0.57 - 5.47 ) , dyspareunia ( aOR=1.21 [ 0.62 - 2.33 ] and require removal of a suture ( aOR=2.61 95 % CI 0.59 - 12.41 ) . CONCLUSIONS the finding of reduced short-term perineal pain in women repaired with polyglycolic compared with catgut is similar to that of a Cochrane Systematic Review . The possibility that polyglycolic is associated with worse longer-term outcomes has not been previously reported but is biologically plausible ( catgut causes a local inflammatory reaction but is rapidly absorbed , while polyglycolic causes little inflammation but absorption takes longer ) . This trial also illustrates the difficulties of undertaking clinical research in a busy delivery ward In a prospect i ve study , pelvic floor muscle strength was investigated pre‐ and post partum in 87 women with uncomplicated pregnancies . Those vaginally delivered were 71 primiparas , while 16 underwent an elective cesarean section . The objective was to evaluate the effect of the delivery procedure on the pelvic floor muscle strength with the aid of vaginal cones . In the group of women with vaginal delivery three subgroups were identified : episiotomy , spontaneous laceration and intact perineum . Pelvic floor muscle strength was weakest in the episiotomy subgroup , the difference in values between this subgroup and each of the other subgroups and the elective cesarean section group being significant . No significant difference was evident between the spontaneous lacerations and intact perineum subgroups Either catgut or polyglycolic acid sutures ( “ Dexon ” ) were r and omly selected for the repair of episiotomies in 100 patients . Significantly less postpartum perineal pain and oedema occurred when polyglycolic acid sutures were used A r and omized controlled trial , which compared glycerol impregnated chromic catgut with untreated chromic catgut used for cell layers in the repairs of perineal trauma of delivery , was performed 3 years after , 516 women conservered a question naire on dyspareunia , and outcome of a eventuel subsequent One thous and women were allocated at r and om to one of two perineal management policies , both intended to minimise trauma during spontaneous vaginal delivery . In one the aim was to restrict episiotomy to fetal indications ; in the other the operation was to be used more liberally to prevent perineal tears . The result ant episiotomy rates were 10 % and 51 % respectively . An intact perineum was more common among those allocated to the restrictive policy . This group experienced more perineal and labial tears , however , and included four of the five cases of severe trauma . There were no significant differences between the two groups either in neonatal state or in maternal pain and urinary symptoms 10 days and three months post partum . Women allocated to the restrictive policy were more likely to have resumed sexual intercourse within a month after delivery . These findings provide little support either for liberal use of episiotomy or for cl aims that reduced use of the operation decreases postpartum morbidity We set out to compare a policy of two-layered postpartum perineal repair leaving the skin unsutured with a policy of three-layered repair , which involved skin closure . Parturients who sustained a second-degree tear or an episiotomy in four Nigerian centers were r and omised to have either a two-layered repair ( 417 women ) or a three-layered repair ( 406 women ) . Fewer women in the two-layered group reported perineal pain at 48 hours ( 57 % vs. 65 % , relative risk [ RR ] 0.87 , 95 % confidence interval [ CI ] 0.78 - 0.97 ) and 14 days postpartum ( 22 % vs. 28 % , RR 0.77 , CI 0.61 - 0.98 ) . The two-layered repair was also associated with reduced risk of suture removal ( 6 % vs. 10 % , RR 0.62 , CI 0.39 - 0.99 ) , and less superficial dyspareunia at 3 months ( 6 % vs. 12 % , RR 0.52 , CI 0.33 - 0.81 ) . The rates of wound healing were similar between the two groups . Leaving the skin unsutured during postpartum perineal repair reduces perineal pain and dyspareunia BACKGROUND Incontinence of stool and flatus are frequent complications of childbirth . We examined the prevalence and possible causes of these adverse outcomes in a large cohort of women . METHODS We studied 949 pregnant women who gave birth in 5 hospitals in 1995/96 in the province of Quebec . These women , participants in a r and omized controlled trial of prenatal perineal massage , completed a self-administered question naire 3 months after giving birth . RESULTS Three months after delivery 29 women ( 3.1 % ) reported incontinence of stool , and 242 ( 25.5 % ) had involuntary escape of flatus . Incontinence of stool was more frequent among women who delivered vaginally and had third- or fourth-degree perineal tears than among those who delivered vaginally and had no anal sphincter tears ( 7.8 % v. 2.9 % ) . Forceps delivery ( adjusted risk ratio [ RR ] 1.45 , 95 % confidence interval [ CI ] 1.01 - 2.08 ) and anal sphincter tears ( adjusted RR 2.09 , 95 % CI 1.40 - 3.13 ) were independent risk factors for incontinence of flatus or stool or both . Anal sphincter injury was strongly and independently associated with first vaginal birth ( RR 39.2 , 95 % CI 5.4 - 282.5 ) , median episiotomy ( adjusted RR 9.6 , 95 % CI 3.2 - 28.5 ) , forceps delivery ( adjusted RR 12.3 , 95 % CI 3.0 - 50.4 ) and vacuum-assisted delivery ( adjusted RR 7.4 , 95 % CI 1.9 - 28.5 ) but not with birth weight ( adjusted RR for nirth weight 4000 g or more : 1.4 , 95 % CI 0.6 - 3.0 ) or length of the second stage of labour ( adjusted RR for second stage 1.5 hours or longer compared with less than 0.5 hours : 1.2 , 95 % CI 0.5 - 2.7 ) . INTERPRETATION Anal incontinence is associated with forceps delivery and anal sphincter laceration . Anal sphincter laceration is strongly predicted by first vaginal birth , median episiotomy , and forceps or vacuum delivery but not by birth weight or length of the second stage of labour Commonly used suture material s and techniques for perineal repair following vaginal delivery were compared in a r and omized controlled trial involving 1574 women . Three comparisons were made using a modified factorial design . In the comparison of teflon‐coated polyglycolic acid ( Dexon plus ) with chromic catgut for repair of the vagina and deep perineal tissues there was no clear difference other than less short‐term analgesia being required in association with polyglycolic acid . Outcome was also similar after skin repair with either polyglycolic acid or chromic catgut or silk , although silk repair required more packets of material and was associated with delay in resuming sexual intercourse ; polyglycolic acid was more likely to need removal than chromic catgut but it appeared to reduce the need for resuturing . There was no clear difference between continuous subcuticular and interrupted transcutaneous sutures for repair of perineal skin OBJECTIVE : To evaluate the effect of mediolateral episiotomy on puerperal pelvic floor strength and dysfunction ( urinary and anal incontinence , genital prolapse ) . METHODS : Five hundred nineteen primiparous women were enrolled 3 months after vaginal delivery . Puerperae were divided in 2 groups : group A ( 254 women ) comprised the women who received mediolateral episiotomy and group B ( 265 women ) the women with intact perineum and first- and second-degree spontaneous perineal lacerations . Each woman was question ed about urogynecological symptoms and examined by digital test , vaginal perineometry , and uroflowmetric stop test score . Data were subjected to Student t test and Fisher exact test to assess , respectively , the difference between the mean values and the proportions within the sub population s. Using a simple logistic regression model to test an estimate of relative risk , we expressed the odds ratios of the variables considered with respect to the control population ( group B ) . RESULTS : No significant difference was found with regard to the incidence of urinary and anal incontinence and genital prolapse , whereas dyspareunia and perineal pain were significantly higher in the episiotomy group ( 7.9 % versus 3.4 % , P = .026 ; 6.7 % versus 2.3 % , P = .014 , respectively ) . Episiotomy was associated with significantly lower values , both in digital test ( 2.2 versus 2.6 ; P < .001 ) and in vaginal manometry ( 12.2 versus 13.8 cm water ; P < .001 ) , but not in uroflowmetric stop test . CONCLUSION : Mediolateral episiotomy does not protect against urinary and anal incontinence and genital prolapse and is associated with a lower pelvic floor muscle strength compared with spontaneous perineal lacerations and with more dyspareunia and perineal pain . LEVEL OF EVIDENCE : Recent , large , r and omized , controlled trials of the effects of episiotomy on perineal damage have confirmed that episiotomy is associated with an increased risk of damage to the perineum . Yet episiotomy remains the most common surgical procedure women undergo . This article examines if clinician experience , rather than scientific evidence , forms the basis for continuing this practice . Perineal outcome data are analyzed for 865 low-risk women who were attended at birth by the staff nurse-midwives or faculty obstetricians at a university-based , tertiary-care hospital . Data were collected under routine , nonexperimental conditions such that the circumstances of the labor and the clinician 's preferences were allowed to determine management decisions regarding the use of episiotomy or other techniques of perineal management . Multivariate findings indicate that in the absence of episiotomy , rates of perineal integrity were highest among clinicians who usually had the lowest rate of episiotomy use . When an episiotomy was done , rates of third- and fourth-degree extensions were highest among clinicians who used episiotomy most frequently . This finding challenges the idea that clinicians who were very experienced with the use of episiotomy would avoid complications such as extensions . Future research should explore the use of nonsurgical techniques such as those employed by midwives to promote perineal integrity . Then interdisciplinary research and evidence -based education regarding these techniques can occur to improve perineal outcomes for all women |
10,488 | 25,731,186 | Results : In the UK , Germany , Switzerl and , South Africa , Japan and Brazil , DCB angioplasty is cost-effective when compared with drug-eluting stents to treat either BMS-ISR or DES-ISR .
Conclusions : DCB angioplasty ought to be the preferred treatment option for patients with BMS-ISR and DES-ISR from the payers ’ point of view | Objectives : The clinical efficacy and safety of drug-coated balloon ( DCB ) angioplasty in patients with coronary in-stent restenosis ( ISR ) has been demonstrated .
The objective of this article is to provide comparative cost efficacy data for DCB angioplasty in various countries based on the original methodology of the Medical Technologies Evaluation Programme ( MTEP ) at the National Institute for Health and Clinical Excellence ( NICE ) in 2010 . | OBJECTIVES The intention of the PEPCAD China ISR ( A Prospect i ve , Multicenter , R and omized Trial of Paclitaxel-Coated versus Paclitaxel-Eluting Stent for the Treatment of Drug-Eluting Stent In-Stent Restenosis ) was to demonstrate the efficacy of paclitaxel-coated balloon ( PCB ) angioplasty in a non-European patient population with coronary drug-eluting stent in-stent restenosis ( DES-ISR ) . BACKGROUND The treatment of DES-ISR is still challenging with no established best strategy . Moreover , there is no study on the effect of PCB in the treatment of ISR in the Chinese population . METHODS PEPCAD China ISR was a 220-patient r and omized ( 1:1 ) , single-blind prospect i ve multicenter trial conducted in China . Patients with coronary DES-ISR received either PCB ( SeQuent Please , B. Braun Melsungen AG , Melsungen , Germany ) or paclitaxel-eluting stent ( Taxus Liberté , Boston Scientific , Natick , Massachusetts ) treatment . The primary endpoint was in-segment late lumen loss at 9 months . RESULTS There were no significant baseline differences between both treatment groups in terms of patient , lesion , or procedural characteristics . At 9 months , in-segment late lumen loss in the PCB group was noninferior to that of the paclitaxel-eluting stent group ( 0.46 ± 0.51 mm vs. 0.55 ± 0.61 mm ; difference : -0.06 mm with 95 % confidence interval : -0.23 to 0.10 ; p for noninferiority = 0.0005 ) . The 9-month rate of binary restenosis and 12-month composite clinical event rates were not significantly different between groups . CONCLUSIONS In a r and omized trial of 220 patients , angioplasty with a PCB was noninferior to paclitaxel-eluting stent implantation when used to treat DES-ISR . On the basis of these , as well as previous r and omized trial data , PCB angioplasty offers an effective treatment for DES-ISR without the necessity of implanting additional metal layers for drug release . ( A Safety and Efficacy Study of Paclitaxel-Eluting Balloon to Paclitaxel-Eluting Stent [ PEPCAD ] ; NCT01622075 ) OBJECTIVES This study sought to define the impact of paclitaxel-coated balloon angioplasty for treatment of drug-eluting stent restenosis compared with uncoated balloon angioplasty alone . BACKGROUND Drug-coated balloon angioplasty is associated with favorable results for treatment of bare-metal stent restenosis . METHODS In this prospect i ve , single-blind , multicenter , r and omized trial , the authors r and omly assigned 110 patients with drug-eluting stent restenoses located in a native coronary artery to paclitaxel-coated balloon angioplasty or uncoated balloon angioplasty . Dual antiplatelet therapy was prescribed for 6 months . Angiographic follow-up was scheduled at 6 months . The primary endpoint was late lumen loss . The secondary clinical endpoint was a composite of cardiac death , myocardial infa rct ion attributed to the target vessel , or target lesion revascularization . RESULTS There was no difference in patient baseline characteristics or procedural results . Angiographic follow-up rate was 91 % . Treatment with paclitaxel-coated balloon was superior to balloon angioplasty alone with a late loss of 0.43 ± 0.61 mm versus 1.03 ± 0.77 mm ( p < 0.001 ) , respectively . Restenosis rate was significantly reduced from 58.1 % to 17.2 % ( p < 0.001 ) , and the composite clinical endpoint was significantly reduced from 50.0 % to 16.7 % ( p < 0.001 ) , respectively . CONCLUSIONS Paclitaxel-coated balloon angioplasty is superior to balloon angioplasty alone for treatment of drug-eluting stent restenosis . ( PEPCAD DES-Treatment of DES-In-Stent Restenosis With SeQuent ® Please Paclitaxel Eluting PTCA Catheter [ PEPCAD-DES ] ; NCT00998439 ) INTRODUCTION The paclitaxel-coated balloon catheter ( DCB ) based on the PACCOCATH ( ® ) technology has yielded angiographic and clinical results superior to drug-eluting stents ( DES ) in situations like in-stent restenosis ( ISR ) and a trend towards superior results in small coronary vessels and side branches of coronary bifurcations . Using the DCB followed by cobalt-chromium stent ( CoCr ) deployment or with a reverse sequence may yield different outcomes in terms of late loss . METHODS 97 patients with de-novo coronary stenosis ( 55.6 ± 10.7 years , 79.4 % male , ≥70 % , length : ≤25 mm , vessel diameter : 2.5 - 4.0 mm ) were r and omly treated with the DCB ( 3 μg/mm² ) followed by a CoCr-stent or stent first and DCB later . Six-month angiographic and one-year clinical follow-up intention-to-treat analyses were performed . RESULTS Angiographic and demographic baseline data was comparable between the two groups . When comparing balloon first versus stent first technique , the primary outcome variables were not statistically different for mean in-segment ( 0.51 ± 0.56 mm vs. 0.36 ± 0.55 mm , p = 0.23 ) and in-stent ( 0.52 ± 0.55 mm vs. 0.46 ± 0.52 mm , p = 0.65 ) late lumen loss . The lesion related 12-month MACE rates were 5/49 ( 10.2 % ) and 2/48 ( 4.2 % ) ( p = 0.44 ) . Lesion related thrombotic events occurred in three patients in balloon first and in one patient in stent first group , two of which were associated with early discontinuation of continuous dual anti-platelet therapy , two with suboptimal PCI , and one each were performed in a thrombotic lesion and a bifurcation type 1.1.0 . CONCLUSION Drug-coated balloon first followed by cobalt chromium stent deployment versus a reverse sequence is not associated with statistically significantly different 6-month angiographic or 12-month clinical outcomes Background — Treatment of in-stent restenosis with paclitaxel-coated balloon catheter as compared with plain balloon angioplasty has shown surprisingly low late lumen loss at 6 months and fewer major adverse cardiac events up to 2 years . We compared the efficacy and safety of a paclitaxel-coated balloon with a paclitaxel-eluting stent as the current st and ard of care . Methods and Results — One hundred thirty-one patients with coronary in-stent restenosis were r and omly assigned to treatment by a paclitaxel-coated balloon ( 3 & mgr;g/mm2 ) or a paclitaxel-eluting stent . The main inclusion criteria encompassed diameter stenosis of ≥70 % and ≤22 mm in length , with a vessel diameter of 2.5 to 3.5 mm . The primary end point was angiographic in-segment late lumen loss . Quantitative coronary angiography revealed no differences in baseline parameters . At 6 months follow-up , in-segment late lumen loss was 0.38±0.61 mm in the drug-eluting stent group versus 0.17±0.42 mm ( P=0.03 ) in the drug-coated balloon group , result ing in a binary restenosis rate of 12 of 59 ( 20 % ) versus 4 of 57 ( 7 % ; P=0.06 ) . At 12 months , the rate of major adverse cardiac events were 22 % and 9 % , respectively ( P=0.08 ) . This difference was primarily due to the need for target lesion revascularization in 4 patients ( 6 % ) in the coated-balloon group , compared with 10 patients ( 15 % ) in the stent group ( P=0.15 ) . Conclusions — Treatment of coronary in-stent restenosis with the paclitaxel-coated balloon was at least as efficacious and as well tolerated as the paclitaxel-eluting stent . For the treatment of in-stent restenosis , inhibition of re-restenosis does not require a second stent implantation Background Treatment of lesions in small coronary arteries by percutaneous transluminal coronary intervention is limited by a high recurrence rate . We assessed the use of a paclitaxel-coated balloon in this indication . Methods One-hundred eighteen patients with stenoses in small coronary vessels were treated by a paclitaxel-coated balloon ( 3 μg/mm2 ) . The main inclusion criteria encompassed diameter stenosis of ≥70 % and ≤22 mm in length with a vessel diameter of 2.25–2.8 mm . Follow-up angiography was performed at scheduled 6-month post-intervention or whenever driven by clinical or electrocardiographic signs of ischemia . The primary endpoint was angiographic in-segment late lumen loss . Results Eighty-two of 118 patients ( 70 % ) with a vessel diameter of 2.35 ± 0.19 mm were treated with the drug-coated balloon only , while 32 patients required additional stent deployment . The mean in-segment late lumen loss was 0.28 ± 0.53 mm . In patients treated with the drug-coated balloon only , the in-segment late lumen loss was 0.16 ± 0.38 mm . At 12 months , the rate of major adverse cardiac events was 15 % which was primarily due to the need for target lesion revascularization in 14 patients ( 12 % ) . In those with additional bare metal stent implantation geographical mismatch between coated-balloon dilatation and stent implantation was significantly associated with the occurrence of restenosis . Conclusion Treatment of coronary stenosis in small coronary vessels with the paclitaxel-coated balloon was well tolerated . It may offer an alternative to the implantation of a drug-eluting stent ( Clinical Trials.gov Identifier : NCT00404144 ) BACKGROUND The best way to manage restenosis in patients who have previously received a drug-eluting stent is unknown . We investigated the efficacy of paclitaxel-eluting balloons ( PEB ) , paclitaxel-eluting stents ( PES ) , and balloon angioplasty in these patients . METHODS In this r and omised , open-label trial , we enrolled patients older than 18 years with restenosis of at least 50 % after implantation of any limus-eluting stent at three centres in Germany between Aug 3 , 2009 , and Oct 27 , 2011 . Patients were r and omly assigned ( 1:1:1 ; stratified according to centre ) to receive PEB , PES , or balloon angioplasty alone by means of sealed , opaque envelopes containing a computer-generated sequence . Patients and investigators were not masked to treatment allocation , but events and angiograms were assessed by individuals who were masked . The primary endpoint was diameter stenosis at follow-up angiography at 6 - 8 months . Primary analysis was done by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00987324 . FINDINGS We enrolled 402 patients , of whom 137 ( 34 % ) were assigned to PEB , 131 ( 33 % ) to PES , and 134 ( 33 % ) to balloon angioplasty . Follow-up angiography at 6 - 8 months was available for 338 ( 84 % ) patients . PEB was non-inferior to PES in terms of diameter stenosis ( 38·0 % [ SD 21·5 ] vs 37·4 % [ 21·8 ] ; difference 0·6 % , one-sided 95 % CI 4·9 % ; p(non-inferiority)=0·007 ; non-inferiority margin of 7 % ) . Findings were consistent in per- protocol analysis ( p(non-inferiority)=0·011 ) . PEB and PES were superior to balloon angioplasty alone ( 54·1 % [ 25·0 ] ; p(superiority)<0·0001 for both comparisons ) . Frequency of death , myocardial infa rct ion , or target lesion thrombosis did not differ between groups . INTERPRETATION By obviating the need for additional stent implantation , PEB could be a useful treatment for patients with restenosis after implantation of a drug-eluting stent . FUNDING Deutsches Herzzentrum OBJECTIVES The aim of this study was to investigate the efficacy of a paclitaxel-eluting balloon ( PEB ) for the treatment of sirolimus-eluting stent ( SES ) restenosis . BACKGROUND Because drug-eluting stents ( DES ) are being used in increasingly complicated setting s , DES restenosis is no longer an uncommon phenomenon , and its optimal treatment is unknown . METHODS This study was a prospect i ve single-blind r and omized trial conducted in 50 patients with SES restenosis . Patients were r and omly assigned to a PEB group ( n = 25 ) or a conventional balloon angioplasty ( BA ) group ( n = 25 ) . The primary end point was late lumen loss at 6-month follow-up . Secondary end points included the rate of binary restenosis ( in-segment analysis ) and major adverse cardiac events ( MACE ) at 6-month follow-up . RESULTS At 6-month angiographic follow-up ( follow-up rate : 94 % ) , in-segment late lumen loss was lower in the PEB group than in the BA group ( 0.18 ± 0.45 mm vs. 0.72 ± 0.55 mm ; p = 0.001 ) . The incidence of recurrent restenosis ( 8.7 % vs. 62.5 % ; p = 0.0001 ) and target lesion revascularization ( 4.3 % vs. 41.7 % ; p = 0.003 ) was also lower in the PEB group than in the BA group . The cumulative MACE-free survival was significantly better in the PEB group than in the BA group ( 96 % vs. 60 % ; p = 0.005 ) . CONCLUSIONS In patients with SES restenosis , PEB provided much better clinical , angiographic outcomes than conventional BA AIMS Paclitaxel drug-eluting balloons ( pDEB ) could be an attractive option to minimise side branch ( SB ) restenosis in bifurcated coronary lesions . We compared angiographic and clinical outcomes with pDEB plus bare metal stent ( BMS ) versus drug-eluting stents ( DES ) in de novo bifurcated lesions . METHODS AND RESULTS This multicentre r and omised trial included 108 patients . Sequential main branch (MB)/SB dilatation with pDEB , with provisional T-stenting with BMS in the MB was performed in the pDEB group , and with everolimus DES in the DES group . The primary endpoint was late lumen loss ( LLL ) at nine months . The secondary endpoint was the incidence of major adverse cardiac events ( MACE : death , myocardial infa rct ion , or target lesion revascularisation ) . In-segment MB LLL was 0.31±0.48 mm in the pDEB group , and 0.16±0.38 mm in the DES group ( p=0.15 ) ; mean difference was 0.15 mm ( upper limit one-sided 95 % CI : 0.27 mm ; p=0.001 ; non-inferiority test ) . LLL in SB was -0.04±0.76 mm in the pDEB group and -0.03±0.51 mm in the DES group ( p=0.983 ) . MACE and TLR were higher in the pDEB group ( 17.3 % vs. 7.1 % ; p=0.105 , and 15.4 % vs. 3.6 % ; p=0.045 ) , due to higher MB restenosis ( 13.5 % vs. 1.8 % ; p=0.027 ) . CONCLUSIONS pDEB bifurcation pretreatment with BMS implantation in MB showed greater LLL ( ns ) and increased incidence of MACE compared to everolimus DES . Both strategies showed similar results in the SB Background Percutaneous coronary intervention with stent implantation is limited by the occurrence of re-stenosis and the risk of stent thromboses . Objective To define the impact of paclitaxel-coated balloon angioplasty plus endothelial progenitor cell capturing ( EPC ) stent implantation in de novo coronary artery disease . This combination may reduce neointimal proliferation within the EPC stent and address the risk of stent thrombosis by facilitating rapid endothelialisation . Methods In this prospect i ve single-blind multicentre r and omised trial , 120 patients with a de novo lesion in a native coronary artery were r and omly assigned to undergo treatment with paclitaxel-coated balloon plus EPC stent or EPC stent alone . Dual antiplatelet therapy was prescribed for 3 months . Angiographic follow-up was scheduled at 6 months . The primary endpoint was in-stent late lumen loss . The secondary clinical endpoint was a composite of death from a cardiac cause , myocardial infa rct ion attributed to the target vessel or target lesion revascularisation . Results There was no difference in patient baseline characteristics or procedural results . The angiographic follow-up rate was 96 % . Treatment with paclitaxel-coated balloon plus EPC stent was superior to EPC stent alone , with an in-stent late loss of 0.34±0.45 mm versus 0.88±0.48 mm ( p<0.001 ) . The re-stenosis rate was reduced from 23.2 % to 5.1 % ( p=0.006 ) and the clinical endpoint was reduced from 17.2 % to 4.8 % ( p=0.039 ) . There was no definite or probable stent thrombosis . Conclusions Paclitaxel-coated balloon plus EPC stent implantation is superior to EPC stent implantation alone for treatment of de novo coronary artery disease . Trial registration NCT00732953 AIMS Percutaneous coronary interventions for bifurcation lesions are often complex and associated with an unsatisfactory result . The aim of this first-in-man , observational study was to investigate the efficacy and safety of a paclitaxel-eluting balloon in these lesions . METHODS AND RESULTS Twenty-eight patients presenting significant coronary bifurcational lesions of the left coronary artery were studied . The main branch ( MB ) and the side branch ( SB ) were dilated with a drug-eluting balloon ( DEB ; SeQuent Please balloon catheter , 3 µg paclitaxel/mm2 balloon surface ) . An open-cell bare-metal stent ( BMS ; Coroflex ) was then deployed in the MB . Only if the SB had a TIMI flow < III and /or a residual stenosis of ≥ 50 % , a BMS was implanted in the SB . The procedure was successful in all patients . At nine months , the late lumen loss ( LLL ) in the MB was 0.38 ± 0.46 mm and 0.21 ± 0.48 mm in the SB result ing in an MLD of 2.2 ± 0.60 mm in the MB and 1.7 ± 0.44 mm in the SB . Three patients had angiographic restenosis and in one a target lesion revascularisation ( TLR ) was performed . Two patients experienced a late stent thrombosis at six and eight months . No patient died . CONCLUSIONS Percutaneous treatment of bifurcation lesions with a drug-eluting balloon result ed in a procedural success of 100 % . Follow-up angiography at nine months showed DES-like results in MB and SB . However , when the DEB was used in combination with a BMS ( MB ) , the possibility of late stent thrombosis can not be ruled out AIMS Coronary lesions in diabetics ( DM ) are associated with a high recurrence following percutaneous coronary intervention ( PCI ) , even after drug-eluting stent ( DES ) deployment . Encouraging clinical data of the drug-eluting balloon catheter ( DEB ) SeQuent Please warrant its investigation in these patients . METHODS AND RESULTS Eighty-four diabetic patients ( 60.8 ± 9.1 years , 76.2 % male ) were r and omised to either the DEB SeQuent Please or the DES Taxus Liberté to compare the 9-month clinical and angiographic outcome of PCI in native coronary arteries . Comparing the DEB vs. the DES the 9-month results ( follow-up DEB 39/45 [ 86.7 % ] , DES 36/39 [ 92.3 % ] ) are statistically not different at the 0.05 level for the primary endpoint of in-segment ( 0.37 ± 0.59 mm vs. 0.35 ± 0.63 mm ) and in-stent ( 0.51 ± 0.61 mm vs. 0.53 ± 0.67 mm ) late lumen loss , overall and cardiac deaths ( 2/45 [ 4.4 % ] and 3/45 [ 6.7 % ] vs. 0 ) , target lesion revascularisation ( 3/45 [ 8.9 % ] vs. 4/39 [ 10.3 % ] ) , the total MACE rate ( 6/45 [ 13.3 % ] vs. 6/39 [ 15.4 % ] ) , and the event free survival after 10.2 ± 3.8 months ( Kaplan-Meier analysis , p<0.80 , log rank test ) . CONCLUSIONS The clinical and angiographic outcome of the combination of the drug-eluting balloon SeQuent Please with a cobalt chromium stent compared to the drug eluting Taxus stent are similar OBJECTIVES This study sought to assess the safety and efficacy of paclitaxel-coated balloon ( PCB ) angioplasty in an international , multicenter , prospect i ve , large-scale registry study . BACKGROUND In small r and omized trials , PCB angioplasty was superior to uncoated balloon angioplasty for treatment of bare-metal stent ( BMS ) and drug-eluting stent ( DES ) restenosis . METHODS Patients treated with SeQuent Please PCBs were included . The primary outcome measure was the clinical ly driven target lesion revascularization ( TLR ) rate at 9 months . RESULTS At 75 centers , 2,095 patients with 2,234 lesions were included . The TLR rate was 5.2 % after 9.4 months . Definite vessel thrombosis occurred in 0.1 % . PCB angioplasty was performed in 1,523 patients ( 72.7 % ) with DES or BMS restenosis and 572 patients ( 27.3 % ) with de novo lesions . The TLR rate was significantly lower in patients with PCB angioplasty for BMS restenosis compared with DES restenosis ( 3.8 % vs. 9.6 % , p < 0.001 ) . The TLR rate did not differ for PCB angioplasty of paclitaxel-eluting stent and non-paclitaxel-eluting sten restenosis ( 8.3 % vs. 10.8 % , p = 0.46 ) . In de novo lesions ( small vessels ) , the TLR rate was low and did not differ between PCB angioplasty with and without additional BMS implantation ( p = 0.31 ) . CONCLUSIONS PCB angioplasty in an all-comers , prospect i ve , multicenter registry was safe and confirmed in a large population the low TLR rates seen in r and omized clinical trials . PCB angioplasty was more effective in BMS restenosis compared with DES restenosis , with no difference regarding the type of DES OBJECTIVES This study presents long-term clinical follow-up , including binary restenosis rate and major adverse cardiovascular events , of the PACCOCATH-ISR ( Treatment of In-Stent Restenosis by Paclitaxel Coated PTCA Balloons ) I and II trial . BACKGROUND The PACCOCATH-ISR trial was a first-in-human study with a drug-coated balloon catheter and the first study for the treatment of coronary ISR with a drug-coated balloon . So , far no long-term follow-up data have been presented . METHODS This study enrolled 108 patients in a r and omized , double-blinded multicenter trial on the efficacy and safety of a paclitaxel-coated balloon ( 3 μg/mm(2 ) balloon surface ; PACCOCATH [ Bayer AG , Germany ] ) compared with an uncoated balloon . The main inclusion criteria were a diameter stenosis of ≥ 70 % and < 30-mm length with a vessel diameter of 2.5 to 3.5 mm . The primary endpoint was angiographic late lumen loss in-segment after 6 months . Combined antiplatelet therapy was continued only for 1 month followed by treatment with aspirin alone . RESULTS During a follow-up of 5.4 ± 1.2 years , the clinical event rate was significantly reduced in patients treated with the drug-coated balloon ( major adverse cardiovascular events : 59.3 % vs. 27.8 % , p = 0.009 ) , which was mainly driven by the reduction of target lesion revascularization from 38.9 % to 9.3 % ( p = 0.004 ) . CONCLUSIONS Treatment of coronary ISR with paclitaxel-coated balloon catheters is safe and persistently reduces repeat revascularization during long-term follow-up . The initial results were sustained over the 5-year period . ( Treatment of In-Stent Restenosis by Paclitaxel Coated PTCA Balloons [ PACCOCATH ISR I ] ; NCT00106587 . Treatment of In-Stent Restenosis by Paclitaxel Coated PTCA Balloons [ PACCOCATH ISR II ] ; NCT00409981 ) OBJECTIVES The aim of this study was to evaluate the efficacy of drug-eluting balloons ( DEB ) compared with paclitaxel-eluting stents ( PES ) for the reduction of restenosis in small vessels . BACKGROUND DEB have been shown to be effective in the treatment of coronary in-stent restenosis , but data are limited regarding their efficacy in de novo disease . METHODS BELLO ( Balloon Elution and Late Loss Optimization ) is a prospect i ve , multicenter trial that r and omized 182 patients with lesions located in small vessels ( reference diameter < 2.8 mm ) to treatment with paclitaxel DEB and provisional bare-metal stenting ( n = 90 ) or PES implantation ( n = 92 ) . The primary endpoint was noninferiority of angiographic in-stent ( in-balloon ) late loss with a delta of 0.25 mm . Secondary endpoints were angiographic restenosis , target lesion revascularization , and major adverse cardiac events ( MACE ; death , myocardial infa rct ion , target vessel revascularization ) at 6 months . RESULTS Baseline characteristics were well matched , except for a smaller vessel size in the DEB group ( 2.15 ± 0.27 mm vs. 2.25 ± 0.24 mm ; p = 0.003 ) . The majority ( 89 % ) of lesions involved vessels with a diameter < 2.5 mm . Bailout stenting was required in 20 % of lesions in the DEB group . The primary endpoint of in-stent ( in-balloon ) late loss was significantly less with DEB compared with PES ( 0.08 ± 0.38 mm vs. 0.29 ± 0.44 mm ; difference -0.21 ; 95 % CI : -0.34 to -0.09 ; p(noninferiority ) < 0.001 ; p(superiority ) = 0.001 ) . At 6 months , DEB and PES were associated with similar rates of angiographic restenosis ( 10 % vs. 14.6 % ; p = 0.35 ) , [ corrected ] target lesion revascularization ( 4.4 % vs. 7.6 % ; p = 0.37 ) , and MACE ( 10 % vs. 16.3 % ; p = 0.21 ) . [ corrected ] . CONCLUSIONS Treatment of small-vessel disease with a paclitaxel DEB was associated with less angiographic late loss and similar rates of restenosis and revascularization as a PES . ( Balloon Elution and Late Loss Optimization [ BELLO ] ; Study NCT01086579 ) Background Percutaneous coronary intervention ( PCI ) of small vessels is limited by an increased risk of restenosis and adverse outcome , even when drug-eluting stents ( DES ) are employed . In recent years , the paclitaxel-coated balloon ( PCB ) has been shown to reduce neointimal proliferation and the need for target lesion revascularization ( TLR ) in an in-stent restenosis setting . The impact of a PCB during PCI of small coronary vessels was evaluated and compared to one of the most widely used DES . Methods In the PICCOLETO r and omised clinical trial , patients with stable or unstable angina undergoing PCI of small coronary vessels ( ≤2.75 mm ) were r and omised to Dior PCB ( 28 patients ) or Taxus DES ( 29 patients ) . The primary study end point was per cent diameter stenosis at 6-month angiographic follow-up ( non-inferiority ) , secondary end points were angiographic binary restenosis and occurrence of major adverse cardiac events ( MACE : death , Q-wave myocardial infa rct ion , TLR ) at 9 month follow-up . Results The two groups were not dissimilar regarding clinical and angiographic characteristics . Study was interrupted after enrolment of two-thirds of patients due to a clear superiority of one study group . The primary end point was not met , because the PCB group showed higher per cent diameter stenosis ( 43.6 % vs 24.3 % , p=0.029 ) ; angiographic restenosis was higher as well ( 32.1 vs 10.3 % , p=0.043 ) , whereas MACE were 35.7 % in the PCB group and 13.8 % in the DES group ( p=0.054 ) . Conclusions Dior PCB failed to show equivalence to Taxus DES regarding angiographic end points during PCI of small coronary arteries . Clinical Trial Registration Number ( EudraCT code ) 2009 - 012268 - 15 BACKGROUND We are presenting an extension of a previously published trial on the efficacy and safety of a paclitaxel-coated balloon in coronary ISR in a larger patient population and after a complete follow-up of 2 years . METHODS Hundred eight patients were enrolled in two separately r and omized , double-blind multicenter trials on efficacy and safety using an identical protocol . Patients were treated by the paclitaxel-coated ( 3 microg/mm(2 ) balloon surface ; Paccocath ) or an uncoated balloon . The main inclusion criteria were a diameter stenosis of > or=70 % and < 30 mm length with a vessel diameter of 2.5 - 3.5 mm . The primary endpoint was angiographic late lumen loss in-segment . Secondary endpoints included binary restenosis rate and major adverse cardiovascular events ( MACE ) . RESULTS Quantitative coronary angiography revealed no differences in baseline parameters . After six months in-segment late lumen loss was 0.81 + /- 0.79 mm in the uncoated balloon group vs. 0.11 + /- 0.45 mm ( P < 0.001 ) in the drug-coated balloon group result ing in a binary restenosis rate of 25/49 vs. 3/47 ( P < 0.001 ) . Until 12 months post procedure 20 patients in the uncoated balloon group compared to two patients in the coated balloon group required target lesion revascularization ( P = 0.001 ) . Between 12 and 24 only two MACE were recorded , a stroke in the uncoated and a target lesion revascularization in the coated balloon group . CONCLUSION Treatment of coronary ISR with paclitaxel-coated balloon catheters persistently reduces repeat restenosis up to 2 years . ( Clinical Trials.gov Identifier : NCT00106587 , NCT00409981 ) |
10,489 | 26,349,905 | Results : Cortisol was the biomarker used most frequently .
Overall , psychosocial stress was associated with CVD risks such as vascular pathology ( hypertension , blood pressure fluctuation , and carotid artery plaque ) as well as metabolic factors such as abnormal blood glucose , dyslipidemia , and elevated cardiac enzymes .
Conclusion : Diverse salivary biomarkers have been useful in stress research , particularly when linked to CVD risks | Background : The use of salivary biomarkers in stress research is increasing , and the precision and accuracy with which research ers are able to measure these biomarkers have dramatically improved .
Chronic psychosocial stress is often linked to the pathogenesis of cardiovascular disease ( CVD ) .
Salivary biomarkers represent a noninvasive biological method of characterizing the stress phenomenon that may help to more fully describe the mechanism by which stress contributes to the pathogenesis and outcomes of CVD .
Objectives : We conducted a systematic review of 40 research articles to identify the salivary biomarkers research ers have most commonly used to help describe the biological impact of chronic psychosocial stress and explore its associations with CVD risk .
We address strengths and weaknesses of specimen collection and measurement . | The salivary enzyme alpha-amylase has been proposed to indicate stress-reactive bodily changes . A previous study by the authors revealed marked increases in salivary alpha-amylase following psychosocial stress , indicating a stress-dependent activation of salivary alpha-amylase . Salivary alpha-amylase has been suggested to reflect catecholaminergic reactivity . Our aim was to assess/evaluate a possible relationship between salivary alpha-amylase and adrenergic parameters , i.e. catecholamines , as well as other stress markers . Using an intra-individual repeated measures design , 30 healthy young men underwent the Trier Social Stress Test ( TSST ) , which consists of a mental arithmetic task and free speech in front of an audience and a control condition in r and omized order . Salivary alpha-amylase and salivary cortisol as well as plasma catecholamines and cardiovascular activity were repeatedly measured before , during , and after both conditions . Significant differences were found between the stress and the rest condition in salivary alpha-amylase , salivary cortisol , plasma catecholamines , and cardiovascular parameters ( heart rate , LF , HF , LF/HF ) . However , general alpha-amylase responses ( area under the curve ) were not associated with general responses in catecholamines and cortisol in the stress condition ( r smaller than 0.25 for all analyses ) . Analysis of cardiovascular parameters indicates a positive relationship between amylase and sympathetic tone ( LF/HF ) during stress . Salivary alpha-amylase is sensitive to psychosocial stress . Since it does not seem to be closely related to other biological stress markers such as catecholamines and cortisol , salivary alpha-amylase may be a useful additional parameter for the measurement of stress This investigation evaluates the moderating influence of social support on the negative effects of stress for family caregivers and vali date s the Perceived Stress Scale as a st and ard of measurement . Seventy-five family caregivers to older adults with heart failure were interviewed in their homes about perceived stress , depressive symptoms , and social support after hospital discharge . The Perceived Stress Scale demonstrated internal consistency . Social support did not moderate the effects of stress on depressive symptoms . Lack of a significant association between salivary cortisol and the Perceived Stress Scale did not support testing of construct validity . Stress levels , however , frequently vary due to caregiving dem and s and additional influencing factors Background Psychosocial stress is a risk factor for coronary heart disease ( CHD ) . The mechanisms are incompletely understood , although dysfunction of the hypothalamic pituitary adrenal ( HPA ) axis might be involved . We examined the association between cortisol responses to laboratory-induced mental stress and the progression of coronary artery calcification ( CAC ) . Methods and Results Participants were 466 healthy men and women ( mean age = 62.7±5.6 yrs ) , without history or objective signs of CHD , drawn from the Whitehall II epidemiological cohort . At the baseline assessment salivary cortisol was measured in response to mental stressors , consisting of a 5-min Stroop task and a 5-min mirror tracing task . CAC was measured at baseline and at 3 years follow up using electron beam computed tomography . CAC progression was defined as an increase > 10 Agatston units between baseline and follow up . 38.2 % of the sample demonstrated CAC progression over the 3 years follow up . There was considerable variation in the cortisol stress response , with approximately 40 % of the sample responding to the stress tasks with an increase in cortisol of at least 1 mmol/l . There was an association between cortisol stress reactivity ( per SD ) and CAC progression ( odds ratio = 1.27 , 95 % CI , 1.02–1.60 ) after adjustments for age , sex , pre-stress cortisol , employment grade , smoking , resting systolic BP , fibrinogen , body mass index , and use of statins . There was no association between systolic blood pressure reactivity and CAC progression ( odds ratio per SD increase = 1.03 , 95 % CI , 0.85–1.24 ) . Other independent predictors of CAC progression included age , male sex , smoking , resting systolic blood pressure , and fibrinogen . Conclusion Results demonstrate an association between heightened cortisol reactivity to stress and CAC progression . These data support the notion that cortisol reactivity , an index of HPA function , is one of the possible mechanisms through which psychosocial stress may influence the risk of CHD Assessment of sympathoadrenal medullary system ( SAM ) activity is only possible to date via measurement of catecholamines in blood plasma or via electrophysiological methods . Both ways of measurement are restricted to endocrinological or psychophysiological laboratories , as both require either immediate freezing of blood sample s or complex recording devices . Efforts have therefore been undertaken to find a method comparable to salivary cortisol measurements , in which noninvasive sample s can be taken at any place and stored at room temperature for sufficient time before later analysis in the laboratory . Salivary alpha-amylase ( sAA ) is a c and i date that may prove useful in this context . We show here that sAA activity is increased by acute psychosocial stress ( Trier Social Stress Test ) and that increases in sAA correlate with increases in norepinephrine . We further report that sAA exhibits a stable circadian pattern that mirrors that of salivary cortisol . In conclusion , the current data show that salivary alpha-amylase may serve as an easy-to-use index for SAM activity . However , some questions remain to be answered ; for example , what impact does salivary flow rate exert on stress-induced sAA activity This investigation was design ed to evaluate the production rates and concentrations of salivary alpha-amylase as a measure of adrenergic activity under several conditions of stress in human subjects . Saliva and blood sample s were simultaneously collected from men at four 15 min intervals both before and after regimens for exercise , a written examination , or a rest period . The regressions of salivary alpha-amylase on plasma norepinephrine ( NE ) concentrations were significant for both exercise ( P < 0.001 ) and examination ( P < 0.01 ) protocol s. Aerobic exercise induced a 3-fold mean increase in alpha-amylase ; both NE and epinephrine ( EP ) increased approximately 5-fold over control levels . Levels of alpha-amylase and NE returned to control levels within 30 - 45 min after exercise , but EP remained elevated by approximately 2-fold during the remaining hour of observation . During the written examination , alpha-amylase and NE , but not EP , concentrations increased in parallel . In further studies the effects of exercise and exposure to heat and cold on the relationship of salivary alpha-amylase to heart rate and body temperature were investigated . Greater intensities of exercise were associated with greater increases in alpha-amylase concentrations . During heat exposure in a sauna ( 66 degrees C for 40 min ) amylase , heart rate and body temperature all increased progressively . However , during exposure to cold ( 4 degrees C for 40 min ) amylase increased rapidly , though heart rate and body temperature remained unchanged . Salivary cortisol concentrations were unchanged during exposure to heat or cold . We conclude that salivary alpha-amylase concentrations are predictive of plasma catecholamine levels , particularly NE , under a variety of stressful conditions , and may be a more direct and simple end point of catecholamine activity than are changes in heart rate Chronic stress can result in frequent or persistent challenges of the hypothalamic-pituitary-adrenal ( HPA ) axis result ing in abnormal cortisol patterns and increased risk for cardiovascular disease ( CVD ) . Police work is an environment replete with stress . The present article describes associations between cortisol , a biomarker of stress , and brachial artery flow mediated dilation ( FMD ) in police officers . A r and om sample stratified on gender ( n=100 , 33 % women ) was generated from officers in a mid-sized urban department . Four salivary cortisol parameters were derived : after awakening , following a st and ardized high protein meal challenge , during the entire day , and after a dexamethasone suppression test . Continuous scan B-Mode ultrasound was used to measure percent change in brachial artery FMD following occlusion and release . Elevated cortisol secretion after awakening was significantly associated with impaired FMD in women , reflected by an inverse trend . Adjustment for age , smoking , and alcohol consumption did not appreciably alter this trend . A similar result was not evident among male officers . Responses of other cortisol challenges to the HPA axis were not associated with FMD . In conclusion , increased cortisol secretion after awakening was independently associated with impaired FMD in female police officers only , indicating a possible link between HPA axis stress response and sub clinical CVD . However , because associations were not found with other cortisol parameters and were not evident in male officers , replication of these findings with a prospect i ve study design may be warranted OBJECTIVE The pathophysiological pathways from stress caused by psychosocial stress to IHD has not been dealt with very extensively . The objective of this study was to analyse the association between cortisol levels and progression in intima media thickness ( IMT ) . METHODS AND RESULTS In 1998 and 2002 , 95 participants went through a clinical investigation including ultrasound of the artery carotis communis . Progression in IMT was analysed in relation to levels of salivary cortisol in 1998 and the average levels of salivary cortisol in 1998/2002 . Further , the significance of conventional coronary risk factors , testosterone and dehydro-epi and rosterone sulphate ( DHEAS ) were evaluated . Among the men , only age and HDL-cholesterol ( negative ) were significantly correlated with progression in IMT . Among the women , awakening cortisol response was significantly correlated with progression in IMT . Testosterone and DHEAS were borderline significantly associated ( negatively ) with progression in IMT in both genders . CONCLUSION Progression in atherosclerosis were determined by different risk factors in women and men . The awakening cortisol response was of great importance to IMT progression in women but not in men OBJECTIVES Previous studies have suggested that abnormal levels of cortisol and testosterone might increase the risk of serious somatic diseases . To test this hypothesis , we conducted a 5-year follow-up study in middle-aged men . METHODS A population -based cohort study conducted in 1995 amongst 141 Swedish men born in 1944 , in whom a clinical examination supplemented by medical history aim ed to disclose the presence of cardiovascular disease ( CVD ) ( myocardial infa rct ion , angina pectoris , stroke ) , type 2 diabetes and hypertension were performed at baseline and at follow-up in the year 2000 . In addition , salivary cortisol levels were measured repeatedly over the day . Serum testosterone concentrations were also determined . Using the baseline data , an algorithm was constructed , which classified the secretion pattern of cortisol and testosterone from each individual as being normal or abnormal . RESULTS By the end of follow-up , men with an abnormal hormone secretion pattern ( n = 73 ) had elevated mean arterial pressure ( P = 0.003 ) , fasting insulin ( P = 0.009 ) and insulin : glucose ratio ( P = 0.005 ) compared with men with a normal secretion pattern ( n = 68 ) . Body mass index , waist circumference , and waist : hip ratio were significantly elevated in both groups . However , the 5-year incidence of CVD , type 2 diabetes , and hypertension were significantly higher ( P < 0.001 ) in men with an abnormal neuroendocrine secretory pattern compared to men with a normal pattern . CONCLUSIONS These data suggest that an abnormal neuroendocrine secretory pattern is prospect ively associated with an increased incidence of cardiovascular-related events and type 2 diabetes Hyperactivity of the hypothalamic-pituitary-adrenal axis ( HPAA ) result ing from fetal programming may play a role in the development of high blood pressure ( BP ) in black people . We assessed the diurnal salivary cortisol profile in children with and without increased BP and evaluated their mother 's HPAA . In a cross-sectional study , 20 Afro-Caribbean children ( mean age 9.6 years ) with higher blood pressures and 20 children with lower blood pressures were chosen from a prospect i ve study of 569 mothers and children in Jamaica . Daytime salivary cortisol profiles were collected in the children and their mothers . The mothers were also assessed for features of the metabolic syndrome . Children with higher BP had higher mean morning salivary cortisol concentrations than those with lower BP ( 7.9 S.D. 1.9 vs. 4.5 S.D. 2.4nmol/l ; p=0.03 ) . Their mothers also had increased morning salivary cortisol concentrations ( 9.9 S.D. 1.8 vs. 5.5 S.D. 2.5nmol/l ; p=0.02 ) , but no changes in fasting glucose , insulin , lipids , BP or adiposity . Maternal and offspring cortisol concentrations correlated significantly ( r=0.465 , p=0.004 ) . Maternal cortisol concentrations were significantly associated with the child 's BP . We conclude that Afro-Caribbean children with higher BP have higher morning salivary cortisol concentrations . The children 's cortisol concentrations correlate significantly with the mother 's cortisol concentrations . These findings suggest that the HPAA may play a role in the development of raised BP in Afro-Caribbean people There is widespread consensus that stress induces dramatic physiological changes , but no agreement on the quantitative parameters that are appropriate to measure these responses . More importantly , the interpretation of various stress measurements , and how individual responses should be evaluated , has not been properly addressed . Even the definition of baseline , against which stress responses must be measured , is not clearly established . The current experiment sought to address these shortcomings by comparing the predictive value of different calculated parameters for psychosocial and physiological measures of stress across individuals . Subjects were 29 male and 59 female healthy undergraduate students with saliva sample s collected over a 3-h interval that included a Trier Social Stress Test . Salivary cortisol and alpha-amylase response were analyzed using the absolute concentration , the percent change in concentration , the area under the curve ( Pruessner et al. , 2003 ) , and the arrival index ( change from arrival to 1h after arrival ) . The arrival index correlated with the subsequent stress response for both cortisol ( r=0.76 , p<0.01 ) and alpha-amylase ( r=0.86 , p<0.01 ) . The arrival index for both cortisol and alpha-amylase was also related to subjective ratings of anxiety following the psychosocial stressor . A subset of individuals with high self-reported anxiety also displayed higher reactivity in response to the psychosocial stressor . Thus , the magnitude of the difference in cortisol and alpha-amylase between arrival and 1h after arrival was a predictor of subsequent stress reactivity . These findings suggest that different psychosocial profiles may be reflected in cortisol and alpha-amylase changes . For this reason : ( 1 ) a recovery period after arrival is essential to establish a baseline , ( 2 ) the difference between arrival and post-recovery period baseline should be included in experimental design s as a predictive variable , and ( 3 ) transformation of individual measures into proportional changes relative to the arrival sample is very likely to obscure important underlying individual differences Major depression is associated with an increased risk for myocardial infa rct ion . Adipokines have been shown to link obesity with metabolic disturbances . Based on this finding the present study was design ed to investigate the effect of antidepressive treatment with either amitriptyline or paroxetine on circulating concentrations of resistin and adiponectin in depressed patients , and to establish , whether these adipokines are associated with the activation of the hypothalamic-pituitary-adrenal (HPA)-system . Thirty-seven depressed in- patients were treated in a double-blind , r and omized protocol with either amitriptyline or paroxetine over a period of five weeks . After six drug free days blood was drawn on day 1 and again 36 days after antidepressive treatment for the measurement of resistin and adiponectin , fasting glucose and insulin concentrations . For quantification of free cortisol levels saliva was obtained daily at 0800 hours during weeks 1 and 5 . While resistin concentrations decreased in patients remitting under amitriptyline and paroxetine ( p<0.03 ) , no changes were observed in non-remitters . At baseline , though not during treatment , circulating resistin concentrations correlated positively with free cortisol levels and with BMI ( p<0.01 ) . Adiponectin levels , however , did not change during treatment and were not associated with free cortisol concentrations but were instead positively related to QUICKI ( p<0.03 ) . In conclusion , the present data revealed resistin but not adiponectin to be related to free cortisol concentrations and to decline in remitters to antidepressive treatment Socioeconomic and psychosocial factors have been found to be associated with systemic inflammation . Although stress is often proposed as a contributor to these associations , no population studies have investigated the links between inflammation and biomarkers of stress . The current study examines associations between daily cortisol profiles and inflammatory markers interleukin-6 ( IL-6 ) , interleukin-10 ( IL-10 ) , and tumor necrosis factor ( TNF-a ) in a population -based sample of 869 adults with repeat measures of cortisol over multiple days . Persons with higher levels of IL-6 had a less pronounced cortisol awakening response , a less steep daily decline , and higher cortisol area under the curve for the day with associations persisting after controls for risk factors and other cytokines . Persons with higher levels of TNF-a had lower cortisol levels upon waking , and flatter daily decline , although associations with decline were attenuated when controlling for inflammatory risk factors . Higher levels of IL-10 were associated with marginally flatter daily cortisol decline ( p<.10 ) . This study is the first to identify associations of basal cortisol activity and inflammatory markers in a population based sample . Findings are consistent with the possibility that HPA axis activity may mediate associations between psychosocial stressors and inflammatory processes . Additional prospect i ve data are necessary to clarify the directionality of associations between cortisol and inflammatory markers CONTEXT Evidence for the association of cortisol with mortality or disease events is mixed , possibly due to a failure to consider diurnal cortisol patterns . OBJECTIVE Our objective was to examine the association of diurnal cortisol patterns throughout the day with cardiovascular and noncardiovascular mortality in a community-dwelling population . DESIGN This was a prospect i ve cohort study among 4047 civil servants , the Whitehall II study , United Kingdom . We measured diurnal cortisol patterns in 2002 - 2004 from six saliva sample s obtained over the course of a normal weekday : at waking , + 30 min , + 2.5 h , + 8 h , + 12 h , and bedtime . Participants were subsequently followed for all-cause and cause-specific mortality until January 2010 . PARTICIPANTS Participants included 4047 men and women aged 61 yr on average at baseline . OUTCOMES We assessed all-cause , cardiovascular , and noncardiovascular death . RESULTS There were 139 deaths , 32 of which were deaths due to cardiovascular disease , during a mean follow-up period of 6.1 yr . Flatter slopes in cortisol decline across the day were associated with increased risk of all-cause mortality ( hazard ratio for 1 sd reduction in slope steepness 1.30 ; 95 % confidence interval ( CI ) = 1.09 - 1.55 ) . This excess mortality risk was mainly driven by an increased risk of cardiovascular deaths ( hazard ratio = 1.87 ; 95 % confidence interval = 1.32 - 2.64 ) . The association with cardiovascular deaths was independent of a wide range of covariates measured at the time of cortisol assessment . There was no association between morning cortisol , the cortisol awakening response , and mortality outcomes . CONCLUSIONS These findings demonstrate , for the first time , the relationship between a flatter slope in cortisol levels across the day and an increased risk of cardiovascular disease mortality in a non clinical population |
10,490 | 27,185,295 | CONCLUSIONS The evidence indicates the potential of apps in improving symptom management through self-management interventions .
The use of apps in mHealth has the potential to improve health outcomes among those living with chronic diseases through enhanced symptom control . | BACKGROUND Long-term conditions and their concomitant management place considerable pressure on patients , communities , and health care systems worldwide .
International clinical guidelines on the majority of long-term conditions recommend the inclusion of self-management programs in routine management .
Self-management programs have been associated with improved health outcomes ; however , the successful and sustainable transfer of research programs into clinical practice has been inconsistent .
Recent developments in mobile technology , such as mobile phone and tablet computer apps , could help in developing a platform for the delivery of self-management interventions that are adaptable , of low cost , and easily accessible .
OBJECTIVE We conducted a systematic review to assess the effectiveness of mobile phone and tablet apps in self-management of key symptoms of long-term conditions . | OBJECTIVE To test whether adding mobile application coaching and patient/provider web portals to community primary care compared with st and ard diabetes management would reduce glycated hemoglobin levels in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS A cluster-r and omized clinical trial , the Mobile Diabetes Intervention Study , r and omly assigned 26 primary care practice s to one of three stepped treatment groups or a control group ( usual care ) . A total of 163 patients were enrolled and included in analysis . The primary outcome was change in glycated hemoglobin levels over a 1-year treatment period . Secondary outcomes were changes in patient-reported diabetes symptoms , diabetes distress , depression , and other clinical ( blood pressure ) and laboratory ( lipid ) values . Maximal treatment was a mobile- and web-based self-management patient coaching system and provider decision support . Patients received automated , real-time educational and behavioral messaging in response to individually analyzed blood glucose values , diabetes medications , and lifestyle behaviors communicated by mobile phone . Providers received quarterly reports summarizing patient ’s glycemic control , diabetes medication management , lifestyle behaviors , and evidence -based treatment options . RESULTS The mean declines in glycated hemoglobin were 1.9 % in the maximal treatment group and 0.7 % in the usual care group , a difference of 1.2 % ( P = 0.001 ) over 12 months . Appreciable differences were not observed between groups for patient-reported diabetes distress , depression , diabetes symptoms , or blood pressure and lipid levels ( all P > 0.05 ) . CONCLUSIONS The combination of behavioral mobile coaching with blood glucose data , lifestyle behaviors , and patient self-management data individually analyzed and presented with evidence -based guidelines to providers substantially reduced glycated hemoglobin levels over 1 year OBJECTIVE To improve quality and efficiency of care for elderly patients with type 2 diabetes , we introduced elderly-friendly strategies to the clinical decision support system (CDSS)-based ubiquitous healthcare ( u-healthcare ) service , which is an individualized health management system using advanced medical information technology . RESEARCH DESIGN AND METHODS We conducted a 6-month r and omized , controlled clinical trial involving 144 patients aged > 60 years . Participants were r and omly assigned to receive routine care ( control , n = 48 ) , to the self-monitored blood glucose ( SMBG , n = 47 ) group , or to the u-healthcare group ( n = 49 ) . The primary end point was the proportion of patients achieving A1C < 7 % without hypoglycemia at 6 months . U-healthcare system refers to an individualized medical service in which medical instructions are given through the patient ’s mobile phone . Patients receive a glucometer with a public switched telephone network-connected cradle that automatically transfers test results to a hospital-based server . Once the data are transferred to the server , an automated system , the CDSS rule engine , generates and sends patient-specific messages by mobile phone . RESULTS After 6 months of follow-up , the mean A1C level was significantly decreased from 7.8 ± 1.3 % to 7.4 ± 1.0 % ( P < 0.001 ) in the u-healthcare group and from 7.9 ± 1.0 % to 7.7 ± 1.0 % ( P = 0.020 ) in the SMBG group , compared with 7.9 ± 0.8 % to 7.8 ± 1.0 % ( P = 0.274 ) in the control group . The proportion of patients with A1C < 7 % without hypoglycemia was 30.6 % in the u-healthcare group , 23.4 % in the SMBG group ( 23.4 % ) , and 14.0 % in the control group ( P < 0.05 ) . CONCLUSIONS The CDSS-based u-healthcare service achieved better glycemic control with less hypoglycemia than SMBG and routine care and may provide effective and safe diabetes management in the elderly diabetic patients Objective To determine whether mobile phone based monitoring improves asthma control compared with st and ard paper based monitoring strategies . Design Multicentre r and omised controlled trial with cost effectiveness analysis . Setting UK primary care . Participants 288 adolescents and adults with poorly controlled asthma ( asthma control question naire ( ACQ ) score ≥1.5 ) from 32 practice s. Intervention Participants were central ly r and omised to twice daily recording and mobile phone based transmission of symptoms , drug use , and peak flow with immediate feedback prompting action according to an agreed plan or paper based monitoring . Main outcome measures Changes in scores on asthma control question naire and self efficacy ( knowledge , attitude , and self efficacy asthma question naire ( KASE-AQ ) ) at six months after r and omisation . Assessment of outcomes was blinded . Analysis was on an intention to treat basis . Results There was no significant difference in the change in asthma control or self efficacy between the two groups ( ACQ : mean change 0.75 in mobile group v 0.73 in paper group , mean difference in change −0.02 ( 95 % confidence interval −0.23 to 0.19 ) ; KASE-AQ score : mean change −4.4 v −2.4 , mean difference 2.0 ( −0.3 to 4.2 ) ) . The numbers of patients who had acute exacerbations , steroid courses , and unscheduled consultations were similar in both groups , with similar healthcare costs . Overall , the mobile phone service was more expensive because of the expenses of telemonitoring . Conclusions Mobile technology does not improve asthma control or increase self efficacy compared with paper based monitoring when both groups received clinical care to guidelines st and ards . The mobile technology was not cost effective . Trial registration Clinical Trials NCT00512837 Numerous diabetes-management systems and programs for improving glycemic control to meet guideline targets have been proposed , using IT technology . But all of them allow only limited-or no-real-time interaction between patients and the system in terms of system response to patient input ; few studies have effectively assessed the systems ' usability and feasibility to determine how well patients underst and and can adopt the technology involved . DialBetics is composed of 4 modules : ( 1 ) data transmission module , ( 2 ) evaluation module , ( 3 ) communication module , and ( 4 ) dietary evaluation module . A 3-month r and omized study was design ed to assess the safety and usability of a remote health- data monitoring system , and especially its impact on modifying patient lifestyles to improve diabetes self-management and , thus , clinical outcomes . Fifty-four type 2 diabetes patients were r and omly divided into 2 groups , 27 in the DialBetics group and 27 in the non-DialBetics control group . HbA1c and fasting blood sugar ( FBS ) values declined significantly in the DialBetics group : HbA1c decreased an average of 0.4 % ( from 7.1 ± 1.0 % to 6.7 ± 0.7 % ) compared with an average increase of 0.1 % in the non-DialBetics group ( from 7.0 ± 0.9 % to 7.1 ± 1.1 % ) ( P = .015 ) ; The DialBetics group FBS decreased an average of 5.5 mg/dl compared with a non-DialBetics group average increase of 16.9 mg/dl ( P = .019 ) . BMI improvement-although not statistically significant because of the small sample size-was greater in the DialBetics group . DialBetics was shown to be a feasible and an effective tool for improving HbA1c by providing patients with real-time support based on their measurements and inputs Objective Cardiac rehabilitation ( CR ) is pivotal in preventing recurring events of myocardial infa rct ion ( MI ) . This study aims to investigate the effect of a smartphone-based home service delivery ( Care Assessment Platform ) of CR ( CAP-CR ) on CR use and health outcomes compared with a traditional , centre-based programme ( TCR ) in post-MI patients . Methods In this unblinded r and omised controlled trial , post-MI patients were r and omised to TCR ( n=60 ; 55.7±10.4 years ) and CAP-CR ( n=60 ; 55.5±9.6 years ) for a 6-week CR and 6-month self-maintenance period . CAP-CR , delivered in participants ’ homes , included health and exercise monitoring , motivational and educational material delivery , and weekly mentoring consultations . CAP-CR uptake , adherence and completion rates were compared with TCR using intention-to-treat analyses . Changes in clinical outcomes ( modifiable lifestyle factors , biomedical risk factors and health-related quality of life ) across baseline , 6 weeks and 6 months were compared within , and between , groups using linear mixed model regression . Results CAP-CR had significantly higher uptake ( 80 % vs 62 % ) , adherence ( 94 % vs 68 % ) and completion ( 80 % vs 47 % ) rates than TCR ( p<0.05 ) . Both groups showed significant improvements in 6-minute walk test from baseline to 6 weeks ( TCR : 537±86–584±99 m ; CAP-CR : 510±77–570±80 m ) , which was maintained at 6 months . CAP-CR showed slight weight reduction ( 89±20–88±21 kg ) and also demonstrated significant improvements in emotional state ( K10 : median ( IQR ) 14.6 ( 13.4–16.0 ) to 12.6 ( 11.5–13.8 ) ) , and quality of life ( EQ5D-Index : median ( IQR ) 0.84 ( 0.8–0.9 ) to 0.92 ( 0.9–1.0 ) ) at 6 weeks . Conclusions This smartphone-based home care CR programme improved post-MI CR uptake , adherence and completion . The home-based CR programme was as effective in improving physiological and psychological health outcomes as traditional CR . CAP-CR is a viable option towards optimising use of CR services . Trial registration number ANZCTR12609000251224 Background Self-management is crucial in the daily management of type 2 diabetes . It has been suggested that mHealth may be an important method for enhancing self-management when delivered in combination with health counseling . Objective The objective of this study was to test whether the use of a mobile phone – based self-management system used for 1 year , with or without telephone health counseling by a diabetes specialist nurse for the first 4 months , could improve glycated hemoglobin A1c ( HbA1c ) level , self-management , and health-related quality of life compared with usual care . Methods We conducted a 3-arm prospect i ve r and omized controlled trial involving 2 intervention groups and 1 control group . Eligible participants were persons with type 2 diabetes with an HbA1c level ≥7.1 % ( ≥54.1 mmol/mol ) and aged ≥18 years . Both intervention groups received the mobile phone – based self-management system Few Touch Application ( FTA ) . The FTA consisted of a blood glucose – measuring system with automatic wireless data transfer , diet manual , physical activity registration , and management of personal goals , all recorded and operated using a diabetes diary app on the mobile phone . In addition , one intervention group received health counseling based on behavior change theory and delivered by a diabetes specialist nurse for the first 4 months after r and omization . All groups received usual care by their general practitioner . The primary outcome was HbA1c level . Secondary outcomes were self-management ( heiQ ) , health-related quality of life ( SF-36 ) , depressive symptoms ( CES-D ) , and lifestyle changes ( dietary habits and physical activity ) . Data were analyzed using univariate methods ( t test , ANOVA ) and multivariate linear and logistic regression . Results A total of 151 participants were r and omized : 51 to the FTA group , 50 to the FTA-health counseling ( FTA-HC ) group , and 50 to the control group . Follow-up data after 1 year were available for 120 participants ( 79 % ) . HbA1c level decreased in all groups , but did not differ between groups after 1 year . The mean change in the heiQ domain skills and technique acquisition was significantly greater in the FTA-HC group after adjusting for age , gender , and education ( P=.04 ) . Other secondary outcomes did not differ between groups after 1 year . In the FTA group , 39 % were substantial users of the app ; 34 % of the FTA-HC group were substantial users . Those aged ≥63 years used the app more than their younger counterparts did ( OR 2.7 ; 95 % CI 1.02 - 7.12 ; P=.045 ) . Conclusions The change in HbA1c level did not differ between groups after the 1-year intervention . Secondary outcomes did not differ between groups except for an increase in the self-management domain of skill and technique acquisition in the FTA-HC group . Older participants used the app more than the younger participants did Background Persistently poor glycemic control in adult type 1 diabetes patients is a common , complex , and serious problem initiating significant damage to the cardiovascular , renal , neural , and visual systems . Currently , there is a plethora of low-cost and free diabetes self-management smartphone applications available in online stores . Objective The aim of this study was to examine the effectiveness of a freely available smartphone application combined with text-message feedback from a certified diabetes educator to improve glycemic control and other diabetes-related outcomes in adult patients with type 1 diabetes in a two-group r and omized controlled trial . Methods Patients were recruited through an online type 1 diabetes support group and letters mailed to adults with type 1 diabetes throughout Australia . In a 6-month intervention , followed by a three-month follow-up , patients ( n=72 ) were r and omized to usual care ( control group ) or usual care and the use of a smartphone application ( Glucose Buddy ) with weekly text-message feedback from a Certified Diabetes Educator ( intervention group ) . All outcome measures were collected at baseline and every three months over the study period . Patients ’ glycosylated hemoglobin levels ( HbA1c ) were measured with a blood test and diabetes-related self-efficacy , self-care activities , and quality of life were measured with online question naires . Results The mean age of patients was 35.20 years ( SD 10.43 ) ( 28 male , 44 female ) , 39 % ( 28/72 ) were male , and patients had been diagnosed with type 1 diabetes for a mean of 18.94 years ( SD 9.66 ) . Of the initial 72 patients , 53 completed the study ( 25 intervention , 28 control group ) . The intervention group significantly improved glycemic control ( HbA1c ) from baseline ( mean 9.08 % , SD 1.18 ) to 9-month follow-up ( mean 7.80 % , SD 0.75 ) , compared to the control group ( baseline : mean 8.47 % , SD 0.86 , follow-up : mean 8.58 % , SD 1.16 ) . No significant change over time was found in either group in relation to self-efficacy , self-care activities , and quality of life . Conclusions In adjunct to usual care , the use of a diabetes-related smartphone application combined with weekly text-message support from a health care professional can significantly improve glycemic control in adults with type 1 diabetes . Trial Registration Australian New Zeal and Clinical Trials Registry : ACTRN12612000132842 ; https://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?ACTRN=12612000132842 ( Archived by WebCite at http://www.webcitation.org/6Kl4jqn5u ) The self-management of asthma can improve clinical outcomes . Recently , mobile telephones have been widely used as an efficient , instant personal communication tool . This study investigated whether a self-care system will achieve better asthma control through a mobile telephone-based interactive programme . This was a prospect i ve , controlled study in outpatient clinics . From 120 consecutive patients with moderate-to-severe persistent asthma , 89 were eventually recruited for the study , with 43 in the mobile telephone group ( with a mobile telephone-based interactive asthma self-care system ) . In the mobile telephone group , mean±sem peak expiratory flow rate significantly increased at 4 ( 378.2±9.3 L·min−1 ; n = 43 ; p = 0.020 ) , 5 ( 378.2±9.2 L·min−1 ; n = 43 ; p = 0.008 ) and 6 months ( 382.7±8.6 L·min−1 ; n = 43 ; p = 0.001 ) compared to the control group . Mean±sem forced expiratory volume in 1 s significantly increased at 6 months ( 65.2±3.2 % predicted ; n = 43 ; p<0.05 ) . Patients in the mobile telephone group had better quality of life after 3 months , as determined using the Short Form-12 ® physical component score , and fewer episodes of exacerbation and unscheduled visits than the control group . Patients in the mobile telephone group significantly increased their mean daily dose of either systemic or inhaled corticosteroids compared with the control group . The mobile telephone-based interactive self-care system provides a convenient and practical self-monitoring and -management of asthma , and improves asthma control Low-income , racial/ethnic minorities are often nonadherent to diabetes medications , have uncontrolled glycemia , and have high rates of diabetes-related morbidity . Cell phones provide a viable modality to support medication adherence , but few cell phone-based interventions have been design ed for low-income persons , a population with more feature phone penetration than smartphone penetration . In an effort to reach the broadest range of patients , we leveraged the voice and text messaging capabilities shared by all cell phones to design the MEssaging for Diabetes intervention . We specifically advanced and adapted an existing tailored text messaging system to include interactive voice response functionality and support the medication adherence barriers of low-income , diverse adults with type 2 diabetes mellitus . We report on the design process and feasibility testing results ( i.e. , technical use patterns and subjective user experiences ) from patients from the target population who used the intervention in one of three user-centered design iterations . The types of challenges encountered in design were related to providing text message content with valued information and support that engages patients . The design process also highlighted the value of obtaining mixed methods data to provide insight into legitimate versus illegitimate missing data , patterns of use , and subjective user experiences . The iterative testing process and results outlined here provide a potential template for other teams seeking to design technology-based self-care support solutions for comparable patient population |
10,491 | 25,202,988 | Overall , there is no evidence that oral zinc increases the healing of arterial or venous leg ulcers . | BACKGROUND Leg ulcers affect up to one percent of people at some time in their life .
Leg ulceration is chronic in nature and ulcers may be present for months or even years without healing .
After healing there is a high risk of recurrence .
Treatments include wound dressings alongside the treatment of underlying medical problems such as poor blood supply , infection and poor nutrition .
OBJECTIVES To assess the effectiveness of oral zinc in healing arterial or venous leg ulcers . | Summary .— The results of a double‐blind trial of zinc sulphate in patients with chronic venous leg ulceration are reported . No significantly increased rate of healing was observed in the zinc‐treated group Abstract The need for zinc in the optimal healing of wounds was demonstrated by the acceleration of healing of granulating wounds caused by excision of pilonidal-sinus tracts in young , healthy airmen who were given zinc sulphate U.S.P. , 220 mg . t.i.d . by mouth during the period of repair . The rate of healing was determined by measurements of the wound volumes and the number of days for complete repair . Ten r and omly selected controls ( mean age 25·0 years and wound volume 32·3 ml . ) were matched against ten who were given the drug ( mean age 24·6 years and wound volume 54·5 ml . ) . The days ±S.E. for healing averaged 80·1±13·7 in the controls and 45·8±2·6 ( The effect of oral zinc on the healing of chronic venous leg ulcers has been investigated in 91 hospitalized patients aged approximately 70 years . The patients were divided into three groups : group A consisted of patients with serum zinc concentrations in the upper normal range ( Zn greater than or equal to 1.0 mg/l ) who received no zinc therapy . Groups B and C consisted of patients with serum zinc concentrations in the lower normal range ( Zn less than 1.0 mg/l ) who received either 3 daily doses of 220 mg zinc sulphate ( group B ) or placebo ( group C ) . In group B , a marked increase in serum zinc concentration occured within one month ( from 0.9 to 1.25 mg/L ) . In group A , serum zinc levels decreased slightly during the observation period of three months ( from 1.1 to 1.0 mg/l ) while a slight rise was seen in group C ( from 0.9 to 1.0 mg/l ) . The healing rate of the ulcers in group A was not superior to that in group C. Zinc substitution in the low zinc group B did not improve healing as compared to placebo-treated low zinc group C. A favourable effect of oral zinc on wound healing in patients with initially low serum zinc concentrations could not be demonstrated . Initial ulcer areas were significantly smaller in patients with higher serum zinc levels than in patients with lower serum zinc levels . Low serum zinc levels appear to be a consequence of insufficient nutrition , an observation which may indicate a correlation between nutritional deficiency and ulcer area . The healing rate did not depend significantly upon age , sex , weight or cause . It was , however , accelerated in the case of larger ulcers The toxicity of oral zinc was investigated in patients hospitalized for chronic leg ulcers . Untoward effects were monitored by reference to clinical tolerance , hematological , hepatic and renal parameters , and serum concentrations of copper and iron . The investigation was conducted by comparing two groups of patients who initially did not differ significantly with regard to ulcer area , hemoglobin , leukocytes , copper , iron and zinc . Both groups had serum zinc concentrations in the lower normal range . One group was treated with 3 daily doses of 220 mg oral zinc sulfate and the other with placebo , and hence , untoward effects of zinc should have become manifest in the zinc-treated group . This was not the case . Therefore , oral zinc appears to be well tolerated clinical ly and does not cause hematological , renal or hepatic toxicity . In view of the increasing interest in and range of indications for zinc , particularly in conditions associated with cellular immunological hyporeactivity , this finding is a prerequisite for the institution of clinical zinc therapy Abstract A hundred and four in patients of various ages with ulcers of the lower limb were included in a controlled trial of oral zinc sulphate . Identical capsules containing 220 mg . of lactose ( placebo ) or zinc sulphate were given three times a day to equal numbers of controls and treated patients . Ulcers healed more quickly in the treatment group . The ulcers of the treatment group healed in 32 on average , as against 77 days for the control group . There was no significant dependence on age or sex . Mild diarrhœa in three patients was the only toxic effect of zinc-sulphate therapy . Oral zinc sulphate would seem to have a place in the treatment of chronic leg ulcers which do not respond to topical treatment . Prolonged or repeated courses should , however , be avoided since not enough is known about the side-effects of systemic zinc salts Abstract In a double-blind trial in twenty-seven patients , the healing of chronic venous leg ulcers was investigated with respect to the serum-zinc level and to the effect of an effervescent preparation of oral zinc sulphate or placebo . Ulcers in patients with a serum-zinc level higher than 110 μg . per 100 ml . initially , or after oral zinc sulphate 200 mg . three times a day , healed significantly faster than did those in patients with a low serum-zinc level . No haematological or biochemical evidence of toxicity was found during 4 months of zinc administration Summary An objective method of determining the healing rate in patients with chronic leg ulcers has been used in forty patients to date . Almost all patients showed improvement on a regimen of cleanliness and external support . The serum zinc levels of twenty-four of the patients ranged from 39 to 219 μg per cent , but there was no correlation between the healing rate and the serum level . The addition of supplemental oral zinc to the therapeutic regime did not acclerate the healing rate in any patient The results of a double‐blind study of zinc sulphate treatment in patients with venous leg ulceration are reported . No significantly increased rate of healing occurred in the zinc treated group . The serum zinc concentration at the onset of treatment did not significantly influence the rate of healing in zinc‐treated patients , but patients with an initial low serum zinc showed a more rapid rate of healing than those with a high zinc level irrespective of treatment . This finding could be accounted for by a defect of distribution of zinc in patients with venous leg ulceration |
10,492 | 26,001,356 | Clinical pharmacy services that focused on specific medical conditions , such as hypertension or diabetes mellitus , revealed a positive impact of pharmacists ’ interventions on patient outcomes .
For other medical conditions , however , the results were inconclusive ( e.g. , dyslipidemia or thromboprophylaxis ) .
Interventions that targeted medication adherence and assessed the impact of clinical pharmacy services in prescription appropriateness also produced inconclusive results because of the variability of methods used to assess both medication adherence and medication appropriateness .
Conclusions Systematic review s that assessed clinical pharmacy services targeting specific conditions were more conclusive given that the intervention was well defined , and the measured outcomes were unequivocal and tangible .
Conversely , the results were inconclusive for interventions with a broader target and with monitoring parameters that were unclearly established or inconsistently assessed across studies . | Background Multiple review s have evaluated the impact of pharmacist-delivered patient care on health-related outcomes .
However , it is unclear which of the pharmacist-delivered interventions in these services are the most effective . | OBJECTIVE : To review the literature on strategies to optimize medication adherence in community-dwelling older adults and to make recommendations for clinical practice . METHODS : A systematic literature search was conducted using the MEDLINE , CINAHL , PsycINFO , International Pharmaceutical Abstract s , and EMBASE data bases for r and omized controlled trials examining strategies to optimize medication adherence in patients aged 65 or older prescribed long-term medication regimens . Additional studies were found by examining the reference lists of systematic review s and selected papers . 34 papers reporting on 33 studies met the eligibility criteria and were included in this review . RESULTS : Improvement in adherence was mixed across the studies examining educational interventions , with only 12 of the 28 studies showing improvement in adherence ; most were delivered by pharmacists . Effect sizes for the statistically significant educational interventions ranged from Cohen 's d = 0.14 to 4.93 . Four of the 5 interventions using memory aids and cues , some in conjunction with newer technologies , improved adherence . Effect sizes for the statistically significant interventions using memory aids and cues ranged from Cohen 's d = 0.26 to 2.72 . CONCLUSION : The evidence from this review does not clearly support one single intervention to optimize medication adherence in older patients . Future studies should explore suggestive strategies , such as tailored interventions involving ongoing contact , and should endeavor to correct method ologic weaknesses found in the literature OBJECTIVE To compare patients ' adherence to therapy , expectations , satisfaction with pharmacy services , and health-related quality of life ( HRQOL ) after the provision of pharmaceutical care with those of patients who received traditional pharmacy care . DESIGN R and omized controlled cluster design . SETTING Sixteen community pharmacies in Alberta , Canada . PATIENTS AND OTHER PARTICIPANTS Ambulatory elderly ( > or = 65 years of age ) patients covered under Alberta Health & Wellness 's senior drug benefit plan and who were concurrently using three or more medications according to pharmacy profiles . INTERVENTION Pharmacies were r and omly assigned to either treatment ( intervention ) or control ( traditional pharmacy care ) groups . Patients at treatment pharmacies were recruited into the study , and pharmacists provided comprehensive pharmaceutical care services . Pharmacists at control pharmacies continued to provide traditional pharmacy care . MAIN OUTCOME MEASURES Study participants ' opinions , adherence to therapy , and scores on the Medical Outcomes Study 36-Item Short Form Health Survey ( SF-36 ) . RESULTS Compared with those of patients receiving traditional care , treatment patients ' expectations that their pharmacist would perform activities congruent with pharmaceutical care changed over the study period . Treatment patients ' satisfaction with the constructs " trust , " " evaluation and goal setting , " and " communicates with doctor " were also positively affected . HRQOL and patient adherence were not significantly affected by pharmaceutical care interventions . CONCLUSION Successful implementation of a pharmaceutical care practice model has the potential to increase patients ' satisfaction with their pharmacists ' activities and may increase patients ' expectations that pharmacists will work on their behalf to assist them with their health care needs . If pharmaceutical care affects patients ' HRQOL , instruments more specific than the SF-36 may be needed to detect the differences RATIONALE , AIMS AND OBJECTIVES DEPICT ( Descriptive Elements of Pharmacist Intervention Characterization Tool ) was created in response to the frequently reported issue of poor intervention description across studies assessing the impact of clinical pharmacy activities . The aim of this study was to create an improved version of DEPICT ( i.e. DEPICT 2 ) to better characterize clinical pharmacy services in order to ensure consistent reporting , therefore enhancing reproducibility of interventions in practice . METHOD A qualitative approach through a thematic content analysis was performed to identify components of pharmacist interventions described in 269 r and omized controlled trials . A preliminary version of DEPICT 2 was applied independently by two authors to a r and om sample of 85 of the 269 RCTs and reliability determined by the prevalence-adjusted bias-adjusted kappa ( PABAK ) or the intraclass correlation coefficient ( ICC ) . The final version of DEPICT 2 was compared against DEPICT 1 . RESULTS The final version of DEPICT 2 comprised 146 items and 11 domains . The inter-rater agreement analysis showed that DEPICT presented good to optimal reproducibility , with a mean PABAK value of 0.87 ( 95 % CI 0.85 - 0.89 ) and a mean ICC value of 0.88 ( 95 % CI 0.62 - 1.14 ) . The mean difference between items checked in the two versions ( DEPICT 2 - DEPICT 1 ) was 10.58 ( 95 % CI 9.55 - 11.61 ) , meaning that approximately 11 more components were identified in the new version of DEPICT . CONCLUSIONS DEPICT 2 is a reliable tool to characterize components of clinical pharmacy services , which should be used to ensure consistent reporting of interventions to allow their reproducibility in practice The objective of this systematic review was to evaluate the impact of pharmacist delivered community-based services to optimise the use of medications for mental illness . Twenty-two controlled ( r and omised and non-r and omised ) studies of pharmacists ' interventions in community and residential aged care setting s identified in international scientific literature were included for review . Papers were assessed for study design , service recipient , country of origin , intervention type , number of participating pharmacists , method ological quality and outcome measurement . Three studies showed that pharmacists ' medication counselling and treatment monitoring can improve adherence to antidepressant medications among those commencing treatment when calculated using an intention-to-treat analysis . Four trials demonstrated that pharmacist conducted medication review s may reduce the number of potentially inappropriate medications prescribed to those at high risk of medication misadventure . The results of this review provide some evidence that pharmacists can contribute to optimising the use of medications for mental illness in the community setting . However , more well design ed studies are needed to assess the impact of pharmacists as members of community mental health teams and as providers of comprehensive medicines information to people with schizophrenia and bipolar OBJECTIVE : To compare medication adherence calculated from four different data sources including a pill count and self-report obtained during a home medication history , as well as calculations based on refill frequency derived from a provincial prescription cl aims data base ( manual and electronic ) . DESIGN : Baseline medication adherence was collected as part of a prospect i ve , r and omized , controlled study . Mean medication adherence results obtained from the four data sources were compared using repeated- measures ANOVA followed by a Tukey 's multiple range test . SETTING : A pharmacy consultation service located at an interdisciplinary wellness center for noninstitutionalized elderly . PATIENTS : 65 years or older , noninstitutionalized , taking one or more prescribed or nonprescribed medications . Clients would either present to the wellness center or be referred by the Provincial Home Care program . RESULTS : When calculated from self-report or manual or electronic prescription cl aims data , mean percent adherence by drug was high and not statistically different ( 95.8 % ± 17.1 % , 107.6 % ± 40.3 % , and 94.6 % ± 24.0 % , respectively ) , whereas the pill count adherence was significantly lower at 74.0 % ± 41.5 % ( p < 0.0001 ) . CONCLUSIONS : An unexpected finding was that the pill count technique used in this study of elderly clients using chronic , repeat medications appeared to underestimate medication adherence . Numerous other limitations of pill count , self-report , and a province-wide prescription cl aims data base in estimating medication adherence are presented . When using medication adherence as a process measure , the research er and practitioner should be aware of the limitations unique to the data source they choose , and interpret data cautiously The objectives of this study were to compare indices of 24-hour blood pressure ( BP ) following a physician-pharmacist collaborative intervention and to describe the associated changes in antihypertensive medications . This was a secondary analysis of a prospect i ve , cluster-r and omized clinical trial conducted in 6 family medicine clinics r and omized to co-managed ( n=3 clinics , 176 patients ) or control ( n=3 clinics , 198 patients ) groups . Mean ambulatory systolic BP ( SBP ) was significantly lower in the co-managed vs the control group : daytime BP 122.8 mm Hg vs 134.4 mm Hg ( P<.001 ) ; nighttime SBP 114.8 mm Hg vs 123.7 mm Hg ( P<.001 ) ; and 24-hour SBP 120.4 mm Hg vs 131.8 mm Hg ( P<.001 ) , respectively . Significantly more drug changes were made in the co-managed than in the control group ( 2.7 vs 1.1 changes per patient , P<.001 ) , and there was greater diuretic use in co-managed patients ( 79.6 % vs 62.6 % , P<.001 ) . Ambulatory BPs were significantly lower for the patients who had a diuretic added during the first month compared with those who never had a diuretic added ( P<.01 ) . Physician-pharmacist co-management significantly improved ambulatory BP compared with the control group . Antihypertensive drug therapy was intensified much more for patients in the co-managed group A consecutive sample of 64 healthy adults ( 33 female and 31 male ) were recruited at the University of Michigan Medical Center , Ann Arbor . Data were available for analysis on 57 subjects . The participants were asked to take a single daily dose of aspirin ranging from 0 to 640 mg . Adherence to the daily aspirin ingestion was measured by self-report and the Medication Event Monitoring System ( MEMS , Aprex Corp , Fremont , Calif ) ; adherence rate for the study population was 35 % . The adherence rates for all dosing errors between self-report and Medication Event Monitoring System were significantly different ( P = .002 ) . There was no significant gender difference in adherence rates . Adherence to regular aspirin ingestion was poor in healthy , paid subjects despite explicit , written and verbal instructions . Patient self-report alone is not a reliable measure of adherence BACKGROUND Nonadherence to cardiovascular medications is a significant public health problem . This r and omized study evaluated the effect on medication adherence of linking hospital and community pharmacists . METHODS Hospitalized patients with coronary artery disease discharged on aspirin , β-blocker , and statin who used a participating pharmacy were r and omized to usual care or intervention . The usual care group received discharge counseling and a letter to the community physician ; the intervention group received enhanced in-hospital counseling , attention to adherence barriers , communication of discharge medications to community pharmacists and physicians , and ongoing assessment of adherence by community pharmacists . The primary end point was self-reported use of aspirin , β-blocker , and statin at 6 months postdischarge ; the secondary end point was a ≥ 75 % proportion of days covered ( PDC ) for β-blocker and statin through 6 months postdischarge . RESULTS Of 143 enrolled patients , 108 ( 76 % ) completed 6-month follow-up , and 115 ( 80 % ) had 6-month refill records . There was no difference between intervention and control groups in self-reported adherence ( 91 % vs 94 % , respectively , P = .50 ) . Using the PDC to determine adherence to β-blockers and statins , there was better adherence in the intervention versus control arm , but the difference was not statistically significant ( 53 % vs 38 % , respectively , P = .11 ) . Adherence to β-blockers was statistically significantly better in intervention versus control ( 71 % vs 49 % , respectively , P = .03 ) . Of 85 patients who self-reported adherence and had refill records , only 42 ( 49 % ) were also adherent by PDC . CONCLUSIONS The trend toward better adherence by refill records with the intervention should encourage further investigation of engaging pharmacists to improve continuity of care This study was conducted to evaluate the effect of automated telephone patient monitoring and counseling on patient adherence to antihypertensive medications and on blood pressure control . A r and omized controlled trial was conducted in 29 greater Boston communities . The study subjects were 267 patients recruited from community sites who were > or= 60 years of age , on antihypertensive medication , with a systolic blood pressure ( SBP ) of > or= 160 mm Hg and /or a diastolic blood pressure ( DBP ) of > or= 90 mm Hg . The study compared subjects who received usual medical care with those who used a computer-controlled telephone system in addition to their usual medical care during a period of 6 months . Weekly , subjects in the telephone group reported self-measured blood pressures , knowledge and adherence to antihypertensive medication regimens , and medication side-effects . This information was sent to their physicians regularly . The main study outcome measures were change in antihypertensive medication adherence , SBP and DBP during 6 months , satisfaction of patient users , perceived utility for physicians , and cost-effectiveness . The mean age of the study population was 76.0 years ; 77 % were women ; 11 % were black . Mean antihypertensive medication adherence improved 17.7 % for telephone system users and 11.7 % for controls ( P = .03 ) . Mean DBP decreased 5.2 mm Hg in users compared to 0.8 mm Hg in controls ( P = .02 ) . Among nonadherent subjects , mean DBP decreased 6.0 mm Hg for telephone users , but increased 2.8 mm Hg for controls ( P = .01 ) . For telephone system users , mean DBP decreased more if their medication adherence improved ( P = .03 ) . The majority of telephone system users were satisfied with the system . Most physicians integrated it into their practice s. The system was cost-effective , especially for nonadherent patient users . Therefore , weekly use of an automated telephone system improved medication adherence and blood pressure control in hypertension patients . This system can be used to monitor patients with hypertension or with other chronic diseases , and is likely to improve health outcomes and reduce health services utilization and costs BACKGROUND The complexity of clinical pharmacy services usually leads to an inconsistent or even poor description of their interventions in scientific reports . To ensure comparability and reproducibility of the evidence , an in-depth description of pharmacist interventions is required . OBJECTIVE To vali date a new tool called DEPICT ( Descriptive Elements of Pharmacist Intervention Characterization Tool ) to characterize clinical pharmacy services . METHODS We developed a 3-phase study . First , to create a theoretical framework , an overview of systematic review s was performed in PubMed between 2000 and 2010 . Then , an in-depth analysis of the included studies was carried out to identify a list of components in order to create the instrument . Finally , 2 independent raters separately applied the tool to a r and om sample of 28 r and omized clinical trials extracted from the systematic review s. Interrater agreement was evaluated using PABAK ( prevalence-adjusted bias-adjusted κ ) coefficient or intraclass correlation coefficient ( ICC ) . RESULTS We included 49 systematic review s in our overview . Analysis of these studies result ed in 58 intervention components , with 57 dichotomous variables and 1 discrete variable . These items result ed in a preliminary version of the instrument . The reliability analysis showed that 8 binary items of this version had a PABAK less than or equal to 0.60 . These items were then excluded or modified , result ing in a final version of the tool , with 54 items organized into 12 domains . DEPICT showed an average PABAK of 0.85 ( 95 % CI 0.81 to 0.88 ) and an ICC of 1.0 . Twenty items presented a PABAK value between 0.61 and 0.80 ( substantial agreement ) and 33 had a value between 0.81 and 1.0 ( almost perfect agreement ) . CONCLUSIONS DEPICT is a reproducible instrument for describing the components of pharmacist interventions performed as part of clinical pharmacy services . It allows retrospective analysis of published studies and can be used as a reference guide to report pharmacist interventions in future studies AIMS The use of medication and information discharge summaries ( MIDS ) has become a st and ard procedure in many hospitals . We have evaluated if these summaries , together with in-patient pharmaceutical counselling backed up with a simple medicine reminder card , may help with the delivery of seamless pharmaceutical care . METHODS Elderly patients prescribed more than four items discharged to their own home received the st and ard discharge policy including a recently introduced MIDS and medicine reminder card . Each patient 's GP was sent a copy on discharge . Pre-discharge a pharmacist counselled study patients about their medicines and compliance . A research pharmacist visited patients in their home approximately 2 - 3 weeks and at 3 months post-discharge to determine their drug knowledge , compliance , home medicine stocks and any healthcare related events . RESULTS Forty-three study and 40 control patients completed both visits . Their mean ( s.d . ) ages were 80.2 ( 5,7 ) and 81.1 ( 5,8 ) years and they were prescribed 7.1 ( 1.8 ) and 7.1 ( 2.3 ) items , respectively . At visit 1 knowledge ( P < 0.01 ) and compliance ( P < 0.001 ) was better in the study group . At visit 2 compliance had improved in the study group ( P < 0.001 ) . Unplanned visits to the GP and readmission to hospital amongst the study group were 19 and 5 , respectively , which were both significantly less ( P < 0.05 ) than 27 and 13 in the control group . At visit 2 for the study group the 24 unplanned GP visits and three re-admissions were significantly ( P < 0.05 ) less than the respective 32 and 15 in the control group . At visit 1 , two study group patients had altered their own medication compared with 10 control patients . At visit 2 these reduced to 0 and 4 , respectively . CONCLUSIONS In-patient pharmaceutical counselling , linked to a medication and information discharge summary and a medicine reminder card , contributed to better drug knowledge and compliance together with reduced unplanned visits to the doctor and re-admissions . A pharmaceutical domiciliary visit consoli date d the improved healthcare outcomes |
10,493 | 26,670,456 | Reaction time and accuracy , foot placement , and in-line lunge movement have been shown to be related to agility performance .
The contribution of strength remains unclear .
Conclusions Agility tests generally offer good reliability , although this may be compromised in younger participants responding to various scenarios .
A human and /or video stimulus seems the most appropriate method to discriminate between st and ard of playing ability .
Small-sided games and video training may offer effective methods of improving agility , although practical issues may hinder the latter | Background Agility is an important characteristic of team sports athletes .
There is a growing interest in the factors that influence agility performance as well as appropriate testing protocol s and training strategies to assess and improve this quality .
Objective The objective of this systematic review was to ( 1 ) evaluate the reliability and validity of agility tests in team sports , ( 2 ) detail factors that may influence agility performance , and ( 3 ) identify the effects of different interventions on agility performance . | Vibration exercise ( VbX ) has been a popular modality to enhancing physical performance , where various training methods and techniques have been employed to improve immediate and long-term sprint performance . However , the use of acute side-alternating VbX on sprint and agility performance remains unclear . Eight female athletes preformed side-alternating vibration exercise ( VbX ) and control ( no VbX ) in a cross over r and omised design that was conducted one week apart . After performing a warm-up , the athletes undertook maximal 5 m sprints and maximal reactive agility sprints ( RAT ) , this was followed by side-alternating VbX ( 26 Hz , 6 mm ) or control ( no VbX ) . Immediately following the intervention , post-sprint tests and RAT were performed . There was a significant treatment effect but there was no time effect ( pre vs. post ) or interaction effect for sprint and RAT ; however , side-alternating VbX did not compromise sprint and agility performance . Key PointsAcute VbX could be beneficial for the acceleration phase ( 1.5 m ) of a short-distance sprint . Acute VbX does not have positive influence on short-distance ( 3 m & 5 m ) sprint performance . Acute VbX does not enhance reactive agility performance Abstract We investigated the relationship between skill qualities and contact injury risk in professional rugby league players . Sixty-six professional rugby league players aged 23 ± 4 years ( mean ± s ) participated in this three-year prospect i ve study . Players underwent assessment s of tackling proficiency , dual-task draw- and -pass proficiency , reactive agility , pattern recall , and pattern prediction . The frailty model was applied to calculate the adjusted risk ratios of injury . When the players ' age and playing position were adjusted in the frailty model , the risk ratios showed that reactive agility was a predictor for the risk of injury . Players with reactive agility decision times of > 80 ms had a lower incidence ( relative risk = 0.68 , 95 % CI 0.47–0.98 , P = 0.04 ) of injuries than players with reactive agility decision times of ≤80 ms . Although there was no relationship between injury and the majority of skill qualities ( P = 0.47–0.93 ) , players with poor reactive agility performances ( specifically longer decision times ) had a lower risk of injury , suggesting that poor perceptual skill is protective against contact injuries in professional rugby league players . These players might inadvertently avoid the heavy collisions that result in injury , or at best result in partial contact that does not result in exposure to the full force of a tackle PURPOSE This study examined the effects of acute caffeine ingestion on agility performance and decision-making accuracy after simulated team-sport exercise . METHODS Using a r and omized , double-blinded , counterbalanced design , 10 moderately trained male team-sport athletes ingested either caffeine ( 6 mg·kg(-1 ) ) or placebo ( dextrose ) 60 min before completing an 80-min ( 4 × 20 min ) simulated team-game , intermittent running protocol . Interspersed between each exercise quarter was a reactive agility test ( RAT ) consisting of five trials where measures of total time ( TT ) , reactive agility ( RA ) time , decision time ( DT ) , movement time ( MT ) , and decision-making accuracy were obtained . RESULTS Although there were no significant differences between trials for TT ( P = 0.54 ) , RA time ( P = 0.84 ) , MT ( P = 0.89 ) , or DT ( P = 0.91 ) , caffeine ingestion result ed in consistently faster TT ( 2.3 % ) , RA time ( 3.9 % ) , MT ( 2.7 % ) , and DT ( 9.3 % ) scores compared with placebo ( significant main effect for condition for RA time , TT , DT , and MT ; P < 0.05 ) . These faster times were supported by qualitative analyses of " almost certain benefit " and large effect size ( ES ) for RA ( quarter 3 ) and " likely " to " very likely benefits " and moderate to large ES for TT ( precircuit and quarters 1 , 2 , and 4 ) and RA time ( precircuit and quarters 1 , 2 and 4 ) . A " likely benefit " and moderate ES was found for MT ( quarters 1 and 3 ) , but the effect of caffeine on DT was largely " unclear , " with small ES and only a " likely " chance of benefit ( quarters 2 and 3 ) . Improved decision-making accuracy ( 3.8 % ) after caffeine ingestion was supported by a " likely benefit " ( quarter 1 ) and large ES ( quarters 1 and 4 ) . CONCLUSION Caffeine ingestion may be beneficial to RA performance when athletes are fresh and fatigued Objective : To quantify the acute effect of whole body vibration ( WBV ) training on arm countermovement vertical jump ( ACMVJ ) , grip strength , and flexibility performance . Methods : Eighteen female elite field hockey players each completed three interventions of WBV , control , and cycling in a balanced r and om manner . WBV was performed on a Galileo machine ( 26 Hz ) with six different exercises being performed . For the control , the same six exercises were performed at 0 Hz , whilst cycling was performed at 50 W. Each intervention was 5 min in duration with ACMVJ , grip strength , and flexibility measurements being conducted pre and post intervention . Results : There was a positive interaction effect ( intervention × pre-post ) of enhanced ACMVJ ( p<0.001 ) and flexibility ( p<0.05 ) parameters following WBV ; however no changes were observed after the control and cycling interventions . There was no interaction effect for grip strength following the three interventions . Conclusions : Acute WBV causes neural potentiation of the stretch reflex loop as shown by the improved ACMVJ and flexibility performance . Additionally , muscle groups less proportionally exposed to vibration do not exhibit physiological changes that potentiate muscular performance OBJECTIVES This study investigated the acute effects of a currently implemented team-sport warm-up and two alternative , high-intensity , short- duration protocol s - 5 repetition maximum leg press and small-sided games . DESIGN Ten male soccer players participated in a r and omised , cross-over study . METHODS Participants performed a team-sport , a leg-press , or a small-sided game warm-up . Subsequent performance tests included counter-movement jump , reactive agility , and 15 × 20 m sprints embedded in an intermittent exercise task . Physiological measures included core temperature , blood lactate concentration , heart rate and rating of perceived exertion . Data were analysed using the effect size statistic with 90 % confidence intervals , and percentage change , to determine magnitude of effects . RESULTS Counter-movement jump height improved following the small-sided game ( 6 % , ES : 0.8±0.8 ) and leg-press warm-up ( 2 % , ES : 0.3±0.5 ) , but not after the team-sport warm-up ( ' unclear ' effect ) . Reactive agility improved after the small-sided game ( 4 % , ES : 0.8±0.7 ) and leg-press warm-ups only ( 5 % , ES : 1.1±0.7 ) , when compared to baseline . Mean 20-m sprint times during the intermittent exercise task improved following the leg-press warm-up , when compared with the small-sided game ( 9 % , ES : 0.9±0.3 ) and team-sport warm-ups ( 7 % , ES : 0.6±0.6 ) . Core temperature was lower following the leg-press warm-up compared to small-sided game ( 1 % , ES : 0.9±0.7 ) and the team-sport WUs ( 2 % , ES : 2.4±0.8 ) . Blood lactate was highest following the small-sided game ( 67 % , ES : 2.7±0.8 ) and team-sport warm-ups ( 66 % , ES : 2.9±0.9 ) . CONCLUSIONS A leg-press and small-sided game warm-up may improve acute team-sport performance tests when compared to a traditional warm-up protocol This study examined the effects of caffeine supplementation ( 6 mg·kg-1 ) on performance of a reactive agility test ( RAT ) in 17 elite , male , youth ( M = 14 y ) soccer players . Using a double-blind , repeated- measures design , players completed 4 days of testing on the RAT after a st and ardized warm-up . On day 1 , anthropometric measurements were taken and players were accommo date d to the RAT . On day 2 , baseline performance was established . Caffeine or placebo conditions were r and omly assigned on day 3 and the condition was reversed on day 4 . Players completed 3 r and omized trials of the RAT on days 2 , 3 , and 4 with at least 1 trial to the players ' dominant and nondominant sides . There were no significant differences among conditions in reaction time ( RT ) to the dominant side , heart rates at any point of measurement , or ratings of perceived exertion ( RPE ) after completion of the warm-up . Caffeine produced faster RT to the nondominant side ( P = .041 ) and higher RPE at the conclusion of the RAT ( P = .013 ) . The effect on the total time ( TT ) to complete the agility test to the nondominant side approached significance ( P = .051 ) . Sprint time and TT to either side did not differ . Caffeine supplementation may provide ergogenic benefit to elite , male , youth soccer players UNLABELLED There is little evidence regarding the benefits of caffeine ingestion on cognitive function and skillful actions during sporting performance , especially in sports that are multifaceted in their physiological , skill , and cognitive dem and s. PURPOSE To examine the influence of caffeine on performance during simulated soccer activity . METHODS Twelve male soccer players completed two 90-min soccer-specific intermittent running trials interspersed with tests of soccer skill ( LSPT ) . The trials were separated by 7 days and adhered to a r and omized crossover design . On each occasion participants ingested 6 mg/kg body mass ( BM ) of caffeine ( CAF ) or a placebo ( PLA ) in a double-blind fashion 60 min before exercise . Movement time , penalties accrued , and total time were recorded for the LSPT . Physiological and performance markers were measured throughout the protocol . Water ( 3 ml/kg BM ) was ingested every 15 min . RESULTS Participants accrued significantly less penalty time in the CAF trial ( 9.7 + /- 6.6 s vs. PLA 11.6 + /- 7.4 s ; p = .02 ) , leading to a significantly lower total time in this trial ( CAF 51.6 + /- 7.7 s vs. PLA 53.9 + /- 8.5 s ; p = .02 ) . This decrease in penalty time was probably attributable to an increased passing accuracy in the CAF trial ( p = .06 ) . Jump height was 2.7 % ( + /- 1.1 % ) higher in the CAF trial ( 57.1 + /- 5.1 cm vs. PLA 55.6 + /- 5.1 cm ; p = .01 ) . CONCLUSIONS Caffeine ingestion before simulated soccer activity improved players ' passing accuracy and jump performance without any detrimental effects on other performance parameters Gabbett , TJ , Sheppard , JM , Pritchard-Peschek , KR , Leveritt , MD , and Aldred , MJ . Influence of closed skill and open skill warm-ups on the performance of speed , change of direction speed , vertical jump , and reactive agility in team sports athletes . J Strength Cond Res 22(5 ) : 1413 - 1415 , 2008-In this study , we evaluated the efficacy of two different dynamic warm-up conditions , one that was inclusive of open skills ( i.e. , reactive movements ) and one that included only preplanned dynamic activities ( i.e. , closed skills ) on the performance of speed , change of direction speed , vertical jump , and reactive agility in team sport athletes . Fourteen ( six male , eight female ) junior ( mean ± SD age , 16.3 ± 0.7 year ) basketball players participated in this study . Testing was conducted on 2 separate days using a within-subjects cross-over study design . Each athlete performed a st and ardized 7-minute warm-up consisting of general dynamic movements and stretching . After the general warm-up , athletes were r and omly allocated into one of two groups that performed a dynamic 15-minute warm-up consisting entirely of open or closed skills . Each of the warm-up conditions consisted of five activities of 3 minute duration . At the completion of the warm-up protocol , players completed assessment s of reactive agility , speed ( 5- , 10- , and 20-m sprints ) , change of direction speed ( T-test ) , and vertical jump . No significant differences ( p > 0.05 ) were detected among warm-up conditions for speed , vertical jump , change of direction speed , and reactive agility performances . The results of this study demonstrate that either open skill or closed skill warm-ups can be used effectively for team sport athletes without compromising performance on open skill and closed skill tasks The purpose of this study was to present a new methodology for the measurement of agility for netball that is considered more ecologically valid than previous agility tests . Specifically , the agility performance of highly-skilled ( n = 12 ) , moderately-skilled ( n = 12 ) and lesser-skilled players ( n = 8) when responding to a life-size , interactive video display of a netball player initiating a pass was compared to a traditional , pre-planned agility movement where no external stimulus was present . The total movement times and decision times of the players were the primary dependent measures of interest . A second purpose of the research was to determine the test-retest reliability of the testing approach . Results revealed significant differences existed between the 2 test conditions demonstrating that they were measuring different types of agility . The highly-skilled group was significantly faster in both the reactive and planned test conditions relative to the lesser-skilled group , while the moderately-skilled group was significantly faster than the lesser-skilled group in the reactive test condition . The decision time component within the reactive test condition revealed that the highly-skilled players made significantly faster decisions than the lesser-skilled players . It is reasoned that it is this decision-making component of reactive agility that contributes to the significant differences between the two test conditions . The testing approach was shown to have good test-retest reliability with an intra-class correlation of r = .83 PURPOSE The purpose of the current study was to assess the reliability of a new protocol that examines different components of agility using commercially available timing gates . METHODS Seventeen physically active males completed four trials of a new protocol , which consisted of a number of 10-m sprints . Sprints were completed in a straight line or with a change of direction after 5 m. The change of direction was either planned or reactive , with participants reacting to a visual light stimulus . RESULTS There was no systematic bias in any of the measures , although r and om variation was reduced in the straight acceleration and planned agility when considering only the final pair of trials , with mean coefficients of variation ( CV ) of 1.6 % ( 95 % CI , 1.2 % to 2.4 % ) and 1.1 % ( 0.8 % to 1.7 % ) , respectively . Reliability of reactive agility remained consistent throughout with mean CVs of approximately 3 % . Analyses revealed a high degree of common variance between acceleration times and both planned ( r2 = .93 ) and reactive ( r2 = .83 ) agility , as well as between the two agility protocol s ( r2 = .87 ) . CONCLUSION Both planned and reactive agility could be measured reliably . Protocol design and use of a light stimulus in the reactive test emphasize physical abilities comparable with other test measures . Therefore , inclusion of a reactive light stimulus does not appear to require any additional perceptual qualities Previous studies have suggested that short-term whole-body vibration ( WBV ) training produces neuromuscular improvement similar to that of power and strength training . However , it is yet to be determined whether short-term WBV exposure produces neurogenic enhancement for power , speed , and agility . The purpose of this study was to investigate the effect short-term WBV training had on vertical jump , sprint , and agility performance in nonelite athletes . Twenty-four sport science students ( 16 men and 8 women ) were r and omly assigned to 2 groups : WBV training or control . Each group included 8 men and 4 women . Countermovement jump ( CMJ ) height , squat jump ( SJ ) height , sprint speed over 5 , 10 , and 20 m , and agility ( 505 , up and back ) were performed by each participant before and after 9 days of either no training ( control ) or WBV training . Perceived discomfort of every participant was recorded after daily WBV exposure and nonexposure . There were no significant differences between WBV and control groups for CMJ , SJ , sprints , and agility . Perceived discomfort differed between the first and subsequent days of WBV training ( p < 0.05 ) ; however , there was no difference between the WBV and control groups . It is concluded that short-term WBV training did not enhance performance in nonelite athletes Abstract The purpose of this study was to determine the effects of training change-of-direction speed and small-sided games on performance in the Planned-AFL agility test and reactive agility . Twenty-five elite-st and ard U-18 Australian Rules football players were r and omly allocated either to a change-of-direction group or a small-sided games group . Players participated in one or two 15-min sessions per week with 11 sessions conducted over a 7-week period during the season . Tests conducted immediately before and after the training period included the Planned-AFL agility test and a video-based reactive agility test specific to Australian Rules football . The reactive agility test variables were total time , decision time and movement response time . The small-sided games group improved total time ( P = 0.008 , effect size = 0.93 ) , which was entirely attributable to a very large reduction in decision time ( P < 0.001 , effect size = 2.32 ) . Small-sided games produced a trivial change in movement response time as well as in the Planned-AFL agility test ( P > 0.05 ) . The change-of-direction training produced small to trivial changes in all of the test variables ( P > 0.05 , effect size = 0–0.2 ) . The results suggest that small-sided games improve agility performance by enhancing the speed of decision-making rather than movement speed . The change-of-direction training was not effective for developing either change-of-direction speed as measured by the Planned-AFL test or reactive agility Does improved decision-making ability reduce the physiological dem and s of game-based activities in field sport athletes ? J Strength Cond Res 22(6 ) : 2027 - 2035 , 2008-This study investigated the effects of video-based perceptual training on pattern recognition and pattern prediction ability in elite field sport athletes and determined whether enhanced perceptual skills influenced the physiological dem and s of game-based activities . Sixteen elite women soccer players ( mean ± SD age , 18.3 ± 2.8 years ) were allocated to either a video-based perceptual training group ( N = 8) or a control group ( N = 8) . The video-based perceptual training group watched video footage of international women 's soccer matches . Twelve training sessions , each 15 minutes in duration , were conducted during a 4-week period . Players performed assessment s of speed ( 5- , 10- , and 20-m sprint ) , repeated-sprint ability ( 6 × 20-m sprints , with active recovery on a 15-second cycle ) , estimated maximal aerobic power ( & OV0312;o2 max , multistage fitness test ) , and a game-specific video-based perceptual test of pattern recognition and pattern prediction before and after the 4 weeks of video-based perceptual training . The on-field assessment s included time-motion analysis completed on all players during a st and ardized 45-minute small-sided training game , and assessment s of passing , shooting , and dribbling decision-making ability . No significant changes were detected in speed , repeated-sprint ability , or estimated & OV0312;o2 max during the training period . However , video-based perceptual training improved decision accuracy and reduced the number of recall errors , indicating improved game awareness and decision-making ability . Importantly , the improvements in pattern recognition and prediction ability transferred to on-field improvements in passing , shooting , and dribbling decision-making skills . No differences were detected between groups for the time spent st and ing , walking , jogging , striding , and sprinting during the small-sided training game . These findings demonstrate that video-based perceptual training can be used effectively to enhance the decision-making ability of field sport athletes ; however , it has no effect on the physiological dem and s of game-based activities UNLABELLED Agility is the player 's capability to perform rapid whole-body movement with change of velocity or direction in response to a stimulus . The aims of this study were as follows : 1 ) to assess the reliability of a reactive visual stimuli agility field test ( RVS-T ) ; and 2 ) to evaluate differences in RVS-T and planned ( PVS-T ) agility performances between female soccer and futsal players . MATERIAL AND METHODS Sixty-six female players belonging to Italian teams of regional level were recruited to the study . The experimental apparatus consisted of four lighted spherical visual stimuli connected to a computer able to r and omly generate three different sequences . Differences between RVS-T and PVS-T performances were calculated to evaluate the decision-making time ( DMT ) of players . RESULTS The intraclass reliability coefficient for RVS-T was 0.80 . Significant ( P<0.05 ) differences emerged only for RVS-T ( futsal , 17.3±0.5 s ; soccer , 18.8±1.1 s ) and DMT ( futsal , 2.6±0.6 s ; soccer , 4.1±1.2 s ) , whereas similar performances between groups result ed for PVS-T ( futsal , 14.7±0.6 s ; soccer , 14.6±0.6 s ) . CONCLUSIONS The RVS-T proved to be a reliable tool to evaluate agility in field conditions . Futsal players showed better RVS-T and DMT performances with respect to soccer counterparts , probably due to the higher velocity of actions and faster decision-making of their sport . The lack of difference in PVS-T performances confirms the importance to evaluate agility capabilities of players in both planned and reactive conditions AIM This study assessed the effects of caffeine on repeated sprint ability ( RSA ) , reactive agility time ( RAT ) , sleep and next day exercise performance . METHODS Ten moderately trained male athletes ( single-blind , r and omized , crossover design ) ingested either caffeine ( 6 mg.kg-1 bm ) or placebo 1 h before exercise . Trials were performed on the same day one week apart . Performance measures included a RAT test ( 10 trials¥10.2 m , separated by 30 s ) , followed by 7 min of active recovery and then a RSA test ( five sets of 6¥20 m sprints with 25 or 60 s of recovery ) . The RSA was then followed by 5 min of active recovery and another RAT . That night , participants wore a wrist sleep actigraph to bed . Next day , participants repeated the RAT and the first set of the RSA tests . RESULTS Significant improvements were demonstrated after caffeine ingestion compared to placebo for the combined total time of each set ( TT ; combined sets 1 , 3 , 5 ; 58.947±1.88 vs. 59.683±2.54 s , respectively ; P=0.05 ) , best sprint time ( BT ; next day performance ; 3.176±0.10 vs. 3.230±0.12 s , respectively , P=0.01 ) , and % decrement ( combined sets 2 , 4 ; 2.866±1.24 vs. 3.801±1.69 s , respectively ; P=0.02 ) . Moderate to strong effect sizes were found for % decrement for set 2 ( Cohen 's d=-0.82 ; 1.312±0.65 vs. 2.110±1.20 s for caffeine and placebo conditions , respectively ) and for sets 2 and 4 combined ( Cohen 's d=-0.63 ; 2.866±1.24 vs. 3.801±1.69 for caffeine and placebo conditions , respectively ) . No significant differences were found for RAT or for sleep measures ( P>0.05 ) . CONCLUSION Caffeine improved RSA , including next day performance , but had little effect on RAT or sleep parameters During the past two decades a considerable amount of research has focused on expert performance in sport ( e.g. , see Ericsson , 1996 ; Starkes & Allard , 1993 ; Tenenbaum , 1999 ) . This body of work indicates that expertise in sport , as in other domains , is based on perceptual and cognitive skill as well as the efficient and effective execution of movement patterns . Experts are differentiated from their novice counterparts on a range of perceptual and cognitive measures ( for a detailed review , see Williams , Davids , & Williams , 1999 ) . For example , experts are better at recalling and recognizing patterns ofplay ( Allard , Graham , & Paarsalu , 1980 ; Williams & Davids , 1995 ) and are more effective than novices at anticipating an opponent 's actions based on advance visual cues ( Salmela & Fiorito , 1979 ; Williams & Burwitz , 1993 ) . However , despite the extensive literature , relatively little is known about how important skills underlying expert performance are developed and even less about whether acquiring perceptual skills can be facilitated through practice and instruction . The key question is : Are there instructional techniques available to facilitate the acquisition of perceptual skill in sport ? or , worded slightly differently , Can perceptual skill be trained ? In two recent review s , Williams and colleagues ( e.g. , Williams & Grant , 1999 ; Williams & Ward , 2003 ) concluded that cognitive interventions , which develop PURPOSE To determine how unanticipated performance of cutting maneuvers in sport affects the external loads applied to the knee joint and the potential risk for ligament injury . METHODS A 50-Hz VICON motion analysis system was used to determine the lower limb kinematics of 11 healthy male subjects during running and cutting tasks performed under preplanned ( PP ) and unanticipated ( UN ) conditions . Subjects performed the UN tasks in response to a light stimulus on a target board . A kinematic model was then used in conjunction with force place data to calculate the three-dimensional loads at the knee joint . RESULTS External flexion/extension moments at the knee joint were similar between PP and UN conditions ; however , the varus/valgus and internal/external rotation moments during the UN cutting tasks were up to twice the magnitude of the moments measured during the PP condition . CONCLUSION Cutting maneuvers performed without adequate planning may increase the risk of noncontact knee ligament injury due to the increased external varus/valgus and internal/external rotation moments applied to the knee . These results are probably due to the small amount of time to make appropriate postural adjustments before performance of the task , such as the position of the foot on the ground relative to the body center of mass . Subsequently , training for the game situation should involve drills that familiarize players with making unanticipated changes of direction . Practice sessions should also incorporate plyometrics and should focus on better interpretation of visual cues to increase the time available to preplan a movement This study investigated the effects of high-dose large neutral amino acid ( LNAA ) supplementation on attenuating fatigue-induced decrements in exercise and motor skill performance in Australian Rules Football ( ARF ) players . Fifteen subelite ARF players participated in 3 testing sessions separated by 7 days . Players completed an initial control trial involving a reactive motor skills test ( RMST ) and a reactive agility test ( RAT ) carried out before and after fatiguing exercise . In the subsequent experimental trials , players ingested a serotonin-depleting or protein control ( PC ) LNAA mixture 3 h before testing , allocated in a double-blind r and omized cross-over design . Blood sample s were taken at presupplementation and pre- and postexercise for analysis of plasma amino acid , insulin , and metabolite concentrations . The effect of the LNAA was established as the difference in the change in the mean RMST and RAT test scores among the depleting , PC , and baseline ( BL ) trials . Mean overall repetition time of the RAT was moderately improved by -5.2 % ± 3.4 % ( mean ± 90 % confidence limits ; effect size -0.45 ± 0.28 ) after ingestion of the serotonin-depleting mixture compared with the BL trial . Serotonin-depleting and PC supplements had a divergent effect on mean repetition time after fatiguing exercise in RMST : depleting serotonin elicited a small improvement ( -3.0 % ± 2.7 % ) in motor skill performance in contrast to a small decrement ( 2.4 % ± 2.7 % ) after ingestion of the PC mixture , when compared to the BL . High-dose serotonin-"depleting " LNAA supplementation given 3 h prior to intermittent high-intensity exercise improved reactive motor skill and agility performance in ARF players Abstract Chaouachi , A , Chtara , M , Hammami , R , Chtara , H , Turki , O , and Castagna , C. Multidirectional sprints and small-sided games training effect on agility and change of direction abilities in youth soccer . J Strength Cond Res 28(11 ) : 3126–3132 , 2014—The aim of this study was to compare the training effects of a small-sided game ( SSG ) and multidirectional sprint intervention on agility and change of direction ( COD ) ability in young male soccer players . Thirty-six soccer players ( age : 14.2 ± 0.9 years ; height : 167.2 ± 5.7 cm ; body mass : 54.1 ± 6.3 kg , body fat : 12.5 ± 2.2 % ) participated in a short-term ( 6 weeks ) r and omized parallel fully controlled training study , with pre-to-post measurements . Players were r and omly assigned to 2 experimental groups : training with preplanned COD drills ( CODG , n = 12 ) or using SSGs ( SSGG , n = 12 ) and to a control group ( CONG , n = 12 ) . Pre- and post-training players completed a test battery involving linear sprinting ( 15- and 30-m sprint ) , COD sprinting ( COD : 15 m , ball : 15 m , 10 - 8 - 8 - 10 m , zigzag : 20 m ) , reactive agility test ( RAT , RAT-ball ) , and vertical and horizontal jumping ( countermovement jump and 5-jump , respectively ) . A significant ( p ⩽ 0.05 ) group × time effect was detected for all variables in CODG and SSGG . Improvements in sprint , agility without ball , COD , and jumping performances , were higher in CODG than in the other groups . The SSGG improved significantly more ( p ⩽ 0.05 ) than other groups in agility tests with the ball . The CONG showed significant improvements ( p ⩽ 0.05 ) on linear sprinting over a distance longer than 10 m and in all the agility and COD tests used in this study . It is concluded that in young male soccer players , agility can be improved either using purpose -built SSG or preplanned COD sprints . However , the use of specifically design ed SSG may provide superior results in match-relevant variables |
10,494 | 30,261,927 | Findings indicated that managers performed a diverse range of leadership behaviours that encompassed change-oriented , relation-oriented and task-oriented behaviours .
The most commonly described behavior was support for the change , which involved demonstrating conceptual and operational commitment to research -based practice s. Conclusions This systematic review adds to the growing body of evidence that indicates that manager-staff dyads are influential in translating research evidence into action .
Findings also reveal that leadership for research use involves change and task-oriented behaviours that influence the environmental milieu and the organisational infrastructure that supports clinical care . | Background Leadership by point-of-care and senior managers is increasingly recognized as critical to the acceptance and use of research evidence in practice .
The purpose of this systematic review was to identify the leadership behaviours of managers that are associated with research use by clinical staff in nursing and allied health professionals . | Background The Stroke Canada Optimization of Rehabilitation by Evidence Implementation Trial ( SCORE-IT ) was a cluster r and omized controlled trial that evaluated two knowledge translation ( KT ) interventions for the promotion of the uptake of best practice recommendations for interventions targeting upper and lower extremity function , postural control , and mobility . Twenty rehabilitation centers across Canada were r and omly assigned to either the facilitated or passive KT intervention . The objective of the current study was to underst and the factors influencing the implementation of the recommended treatments and KT interventions from the perspective of nurses , occupational therapists and physical therapists , and clinical managers following completion of the trial . Methods A qualitative descriptive approach involving focus groups was used . Thematic analysis was used to underst and the factors influencing the implementation of the recommended treatments and KT interventions . The Clinical Practice Guidelines Framework for Improvement guided the analysis . Results Thirty-three participants were interviewed from 11 of the 20 study sites ( 6 sites from the facilitated KT arm and 5 sites from the passive KT arm ) . The following factors influencing the implementation of the recommended treatments and KT interventions emerged : facilitation , agreement with the intervention – practical , familiarity with the recommended treatments , and environmental factors , including time and re sources . Each of these themes includes the sub-themes of facilitator and /or barrier . Improved team communication and interdisciplinary collaboration emerged as an unintended outcome of the trial across both arms in addition to a facilitator to the implementation of the treatment recommendations . Facilitation was identified as a facilitator to implementation of the KT interventions in the passive KT intervention arm despite the lack of formally instituted facilitators in this arm of the trial . Conclusions This is one of the first studies to examine the factors influencing the implementation of stroke recommendations and associated KT interventions within the context of a trial . Findings highlight the important role of self-selected facilitators to implementation efforts . Future research should seek to better underst and the specific characteristics of facilitators that are associated with successful implementation and clinical outcomes , especially within the context of stroke rehabilitation Background Little is known about the impact of implementing nursing-oriented best practice guidelines on the delivery of patient care in either hospital or community setting s. Methods A naturalistic study with a prospect i ve , before and after design documented the implementation of six newly developed nursing best practice guidelines ( asthma , breastfeeding , delirium-dementia-depression ( DDD ) , foot complications in diabetes , smoking cessation and venous leg ulcers ) . Eleven health care organisations were selected for a one-year project . At each site , clinical re source nurses ( CRNs ) worked with managers and a multidisciplinary steering committee to conduct an environmental scan and develop an action plan of activities ( i.e. education sessions , policy review ) . Process and patient outcomes were assessed by chart audit ( n = 681 pre-implementation , 592 post-implementation ) . Outcomes were also assessed for four of six topics by in-hospital/home interviews ( n = 261 pre-implementation , 232 post-implementation ) and follow-up telephone interviews ( n = 152 pre , 121 post ) . Interviews were conducted with 83/95 ( 87 % ) CRN 's , nurses and administrators to describe recommendations selected , strategies used and participants ' perceived facilitators and barriers to guideline implementation . Results While statistically significant improvements in 5 % to 83 % of indicators were observed in each organization , more than 80 % of indicators for breastfeeding , DDD and smoking cessation did not change . Statistically significant improvements were found in > 50 % of indicators for asthma ( 52 % ) , diabetes foot care ( 83 % ) and venous leg ulcers ( 60 % ) . Organizations with > 50 % improvements reported two unique implementation strategies which included h and s-on skill practice sessions for nurses and the development of new patient education material s. Key facilitators for all organizations included education sessions as well as support from champions and managers while key barriers were lack of time , workload pressure and staff resistance . Conclusion Implementation of nursing best practice guidelines can result in improved practice and patient outcomes across diverse setting s yet many indicators remained unchanged . Mobilization of the nursing workforce to actively implement guidelines and to monitor the delivery of their care is important so that patients may learn about and receive recommended healthcare Background Hypertension and diabetes , key risk factors for cardiovascular disease , are significant health problems globally . As cardiovascular disease is one of the leading causes of mortality in Mongolia since 2000 , clinical guidelines on arterial hypertension and diabetes were developed and implemented in 2011 . This paper explores the barriers and enablers influencing the implementation of these guidelines in the primary care setting . Methods A phenomenological qualitative study with semi-structured interviews was conducted to explore the implementation of the diabetes and hypertension guidelines at the primary care level , as well as to gain insight into how practitioners view the usability and practicality of the guidelines . Ten family health centres were r and omly chosen from a list of all the family health centres ( n = 136 ) located in Ulaanbaatar City . In each centre , a focus group discussion with nurses ( n = 20 ) and individual interviews with practice doctors ( n = 10 ) and practice managers ( n = 10 ) were conducted . Data was analysed using a thematic approach utilising the Theoretical Domains Framework . Results The majority of the study participants reported being aware of the guidelines and that they had incorporated them into their daily practice . They also reported having attended guideline training sessions which were focused on practice skill development . The majority of participants expressed satisfaction with the wide range of re sources that had been supplied to them by the Mongolian Government to assist with the implementation of the guidelines . The re sources , supplied from 2011 onwards , included screening devices , equipment for blood tests , medications and educational material s. Other enablers were the participants ’ commitment and passion for guideline implementation and their belief in the simplicity and practicality of the guidelines . Primary care providers reported a number of challenges in implementing the guidelines , including frustration caused by increased workload and long waiting times , time constraints , difficulties with conflicting tasks and low patient health literacy . Conclusions This study provides evidence that comprehensive and rigorous dissemination and implementation strategies increase the likelihood of successful implementation of new guidelines in low re source primary care setting s. It also offers some key lessons that might be carefully considered when other evidence -based clinical guidelines are to be put into effect in low re source setting s and elsewhere Background The case has been made for more and better theory-informed process evaluations within trials in an effort to facilitate insightful underst and ings of how interventions work . In this paper , we provide an explanation of implementation processes from one of the first national implementation research r and omized controlled trials with embedded process evaluation conducted within acute care , and a proposed extension to the Promoting Action on Research Implementation in Health Services ( PARIHS ) framework . Methods The PARIHS framework was prospect ively applied to guide decisions about intervention design , data collection , and analysis processes in a trial focussed on reducing peri-operative fasting times . In order to capture a holistic picture of implementation processes , the same data were collected across 19 participating hospitals irrespective of allocation to intervention . This paper reports on findings from data collected from a purposive sample of 151 staff and patients pre- and post-intervention . Data were analysed using content analysis within , and then across data sets . Results A robust and uncontested evidence base was a necessary , but not sufficient condition for practice change , in that individual staff and patient responses such as caution influenced decision making . The implementation context was challenging , in which individuals and teams were bounded by professional issues , communication challenges , power and a lack of clarity for the authority and responsibility for practice change . Progress was made in sites where processes were aligned with existing initiatives . Additionally , facilitators reported engaging in many intervention implementation activities , some of which result in practice changes , but not significant improvements to outcomes . Conclusions This study provided an opportunity for reflection on the comprehensiveness of the PARIHS framework . Consistent with the underlying tenant of PARIHS , a multi-faceted and dynamic story of implementation was evident . However , the prominent role that individuals played as part of the interaction between evidence and context is not currently explicit within the framework . We propose that successful implementation of evidence into practice is a planned facilitated process involving an interplay between individuals , evidence , and context to promote evidence -informed practice . This proposal will enhance the potential of the PARIHS framework for explanation , and ensure theoretical development both informs and responds to the evidence base for implementation . Trial registration IS RCT N18046709 - Peri-operative Implementation Study Evaluation ( PoISE ) Background In healthcare and allied healthcare setting s , leadership that supports effective implementation of evidence d-based practice s ( EBPs ) is a critical concern . However , there are no empirically vali date d measures to assess implementation leadership . This paper describes the development , factor structure , and initial reliability and convergent and discriminant validity of a very brief measure of implementation leadership : the Implementation Leadership Scale ( ILS ) . Methods Participants were 459 mental health clinicians working in 93 different outpatient mental health programs in Southern California , USA . Initial item development was supported as part of a two United States National Institutes of Health ( NIH ) studies focused on developing implementation leadership training and implementation measure development . Clinician work group/team-level data were r and omly assigned to be utilized for an exploratory factor analysis ( n = 229 ; k = 46 teams ) or for a confirmatory factor analysis ( n = 230 ; k = 47 teams ) . The confirmatory factor analysis controlled for the multilevel , nested data structure . Reliability and validity analyses were then conducted with the full sample . Results The exploratory factor analysis result ed in a 12-item scale with four subscales representing proactive leadership , knowledgeable leadership , supportive leadership , and perseverant leadership . Confirmatory factor analysis supported an a priori higher order factor structure with subscales contributing to a single higher order implementation leadership factor . The scale demonstrated excellent internal consistency reliability as well as convergent and discriminant validity . Conclusions The ILS is a brief and efficient measure of unit level leadership for EBP implementation . The availability of the ILS will allow research ers to assess strategic leadership for implementation in order to advance underst and ing of leadership as a predictor of organizational context for implementation . The ILS also holds promise as a tool for leader and organizational development to improve EBP implementation Background : Many hospitals are unable to consistently implement evidence -based practice s. For example , implementation of the central line bundle ( CLB ) , known to prevent catheter-related bloodstream infections ( CRBSIs ) , is often challenging . This problem is broadly characterized as “ change implementation failure . ” Purpose : The theoretical literature on organizational change has suggested that periodic top-down communications promoting tacit knowledge exchanges across professional subgroups may be effective for enabling learning and change in health care organizations . However , gaps remain in underst and ing the mechanisms by which top-down communications enable practice change at the unit level . Addressing these gaps could help identify evidence -based management strategies for successful practice change at the unit level . Our study sought to address this gap . Methods : A prospect i ve study was conducted in two intensive care units within an academic health center . Both units had low baseline adherence to CLB and higher-than-expected CRBSIs . Periodic top-down quality improvement communications were conducted over a 52-week period to promote CLB implementation in both units . Simultaneously , the study examined ( a ) the content and frequency of communication related to CLB through weekly “ communication logs ” completed by unit physicians , nurses , and managers and ( b ) unit outcomes , that is , CLB adherence rates through weekly chart review s. Findings : Both units experienced substantially improved outcomes , including increased adherence to CLB and statistically significant ( sustained ) declines in both CRBSIs and catheter days ( i.e. , central line use ) . Concurrently , both units indicated a statistically significant increase in “ proactive ” communications — that is , communications intended to reduce infection risk — between physicians and nurses over time . Further analysis revealed that , during the early phase of the study , “ champions ” emerged within each unit to initiate process improvements . Practice Implication s : The study helps identify evidence -based management strategies for successful practice change at the unit level . For example , it underscores the importance of ( a ) screening each unit for change champions and ( b ) enabling champions to emerge from within the unit to foster change implementation BACKGROUND Decreasing the use of continuous electronic fetal monitoring and increasing professional labor support for low-risk pregnancies are recommended by the Society of Obstetricians and Gynecologists of Canada . This study explored factors influencing the successful ( and unsuccessful ) introduction of an evidence -based fetal health surveillance guideline . METHODS This qualitative case study was conducted at two tertiary and one community hospital . Data were collected in 14 clinician focus groups ( 51 nurses ) , followed by 8 interviews with nurse administrators and educators . Analysis of verbatim transcripts and unit records included coding and categorizing data to form profiles that were compared across hospitals . RESULTS Implementation of the guideline recommendations in the hospital setting s was affected by many different factors originating in the practice environment , with the potential adopters , and related to the characteristics of the guideline . The influences of these diverse factors interacted sometimes to magnify or counteract each other 's effect . The physical setting , adopter concerns , and the medicolegal issues surrounding the guideline played critical roles in uptake . In addition , changes preceding the introduction of the recommendations , the institution 's agenda , and nursing and medical leadership influenced the uptake of guideline recommendations . The number and experience of nurses in each setting and availability of equipment also affected guideline acceptance and use . CONCLUSIONS When implementing best practice , it is important to identify organizational barriers to the change that will need managing by the appropriate level of administration in the organization . Careful tailoring of implementation interventions to the barriers originating with the potential adopters is also necessary . Be prepared for unanticipated effects Background : Despite three decades of empirical investigation into research utilization and a renewed emphasis on evidence -based medicine and evidence -based practice in the past decade , underst and ing of factors influencing research uptake in nursing remains limited . There is , however , increased awareness that organizational influences are important . Objectives : To develop and test a theoretical model of organizational influences that predict research utilization by nurses and to assess the influence of varying degrees of context , based on the Promoting Action on Research Implementation in Health Services ( PARIHS ) framework , on research utilization and other variables . Methods : The study sample was drawn from a census of registered nurses working in acute care hospitals in Alberta , Canada , accessed through their professional licensing body ( n = 6,526 nurses ; 52.8 % response rate ) . Three variables that measured PARIHS dimensions of context ( culture , leadership , and evaluation ) were used to sort cases into one of four mutually exclusive data sets that reflected less positive to more positive context . Then , a theoretical model of hospital- and unit-level influences on research utilization was developed and tested , using structural equation modeling , and 300 cases were r and omly selected from each of the four data sets . Results : Model test results were as follows-low context : & khgr;2 = 124.5 , df = 80 , p < . 001 ; partially low : & khgr;2 = 144.2 , p < . 001 , df = 80 ; partially high : & khgr;2 = 157.3 , df = 80 , p < . 001 ; and partially low : & khgr;2 = 146.0 , df = 80 , p < . 001 . Hospital characteristics that positively influenced research utilization by nurses were staff development , opportunity for nurse-to-nurse collaboration , and staffing and support services . Increased emotional exhaustion led to less reported research utilization and higher rates of patient and nurse adverse events . Nurses working in context s with more positive culture , leadership , and evaluation also reported significantly more research utilization , staff development , and lower rates of patient and staff adverse events than did nurses working in less positive context s ( i.e. , those that lacked positive culture , leadership , or evaluation ) . Conclusion : The findings highlight the combined importance of culture , leadership , and evaluation to increase research utilization and improve patient safety . The findings may serve to strengthen the PARIHS framework and to suggest that , although it is not fully developed , the framework is an appropriate guide to implement research into practice SIGNIFICANCE The importance of leadership to influence nurses ' use of clinical guidelines has been well documented . However , little is known about how to develop and evaluate leadership interventions for guideline use . PURPOSE The purpose of this study was to pilot a leadership intervention design ed to influence nurses ' use of guideline recommendations when caring for patients with diabetic foot ulcers in home care nursing . This paper reports on the feasibility of implementing the study protocol , the trial findings related to nursing process outcomes , and leadership behaviors . METHODS A mixed methods pilot study was conducted with a post-only cluster r and omized controlled trial and descriptive qualitative interviews . Four units were r and omized to control or experimental groups . Clinical and management leadership teams participated in a 12-week leadership intervention ( workshop , teleconferences ) . Participants received summarized chart audit data , identified goals for change , and created a team leadership action . Criteria to assess feasibility of the protocol included : design , intervention , measures , and data collection procedures . For the trial , chart audits compared differences in nursing process outcomes . PRIMARY OUTCOME 8-item nursing assessment s score . Secondary outcome : 5-item score of nursing care based on goals for change identified by intervention participants . Qualitative interviews described leadership behaviors that influenced guideline use . RESULTS Conducting this pilot showed some aspects of the study protocol were feasible , while others require further development . Trial findings observed no significant difference in the primary outcome . A significant increase was observed in the 5-item score chosen by intervention participants ( p = 0.02 ) . In the experimental group more relations-oriented leadership behaviors , audit and feedback and reminders were described as leadership strategies . CONCLUSIONS Findings suggest that a leadership intervention has the potential to influence nurses ' use of guideline recommendations , but further work is required to refine the intervention and outcome measures . A taxonomy of leadership behaviors is proposed to inform future research The aim of this study was to investigate staff experiences in implementing guidelines for Kangaroo Mother Care in neonatal care . The study was part of a r and omized controlled trial , the overall goal of which was to assess the impact of external facilitation . A total of eight focus group interviews were held at two intervention and two control units . The establishment of a change team to implement the guideline result ed in activities that impacted staff behaviour , which in turn was perceived to influence patients ' well-being . The guideline and context ual factors , such as leadership and staff colleagues ' attitudes , were of significant importance in that process . The study intervention -- facilitation -- promoted implementation activities and was highly appreciated by the change teams . However , review ing the development of events at one of the control units , the provided facilitation appeared to be no more effective than an improvement-focused organizational culture in which the nurse manager was actively involved in the change process . Overall , learning and behaviour change seemed to be a social phenomenon , something that greatly benefited from people 's interaction with one another |
10,495 | 30,416,528 | Data from the majority of properly controlled clinical trials demonstrate that SLIT is effective not only with short-term use ( first year ) but also with long-term use ( up to the third year of active therapy ) , for treating ARDs in children and adults .
Both continuous and discontinuous schemes of administration showed significant reductions in symptom and medication scores .
Moreover , a SLIT-induced disease-modifying effect has been documented mainly with grass pollen extracts , since improvement is maintained during at least 2 years of follow-up after a 3-year treatment period .
This therapy is also safe , producing only a few mainly local and mild-to-moderate adverse events , and usually self-limited in time . | The objective of the systematic review is to provide complete and up date d information on efficacy and safety of sublingual immunotherapy ( SLIT ) formulations for the treatment of allergic respiratory diseases ( ARDs ) . | BACKGROUND Sublingual immunotherapy with liquid extracts provides an appealing alternative to subcutaneous immunotherapy for the treatment of allergic rhinoconjunctivitis ( ARC ) , but a lack of robust evidence has deterred its use in North America . OBJECTIVE To determine the efficacy and tolerability of st and ardized glycerinated short ragweed sublingual allergen immunotherapy liquid ( RW-SAIL ) extract in subjects with ragweed-related ARC . METHODS This phase 3 , r and omized , placebo-controlled trial was conducted in North America . Subjects ( age range , 18 - 55 years ) with or without asthma were selected based on ARC symptom severity and erythema skin prick reaction to short ragweed . Subjects self-administered the maximum tolerated dose of RW-SAIL ( n = 218 ) or placebo ( n = 211 ) daily beginning approximately 8 to 16 weeks before and through the end of the ragweed pollen season . The primary end point was subject-assessed total combined daily rhinoconjunctivitis symptom and medication scores ( TCS ) . RESULTS During the entire season , there was a 43 % decrease in TCS in subjects treated with RW-SAIL compared with placebo . Similar decreases were observed in TCS between the 2 groups during peak season ( 42 % ) and in daily symptom scores during the entire ( 42 % ) and peak ( 41 % ) seasons . The occurrence of adverse events was similar between the treatment groups ; most were mild in severity . Treatment-related oromucosal local application site reactions occurred early and were transient and self-limited . No anaphylaxis occurred . CONCLUSIONS This is the first successful North American confirmatory phase 3 clinical trial to demonstrate the safety and efficacy of a sublingual st and ardized ragweed allergen immunotherapy liquid extract for the treatment of ARC BACKGROUND The efficacy and safety of the 300-index of reactivity ( IR ) dose of 5-grass-pollen sublingual immunotherapy ( SLIT ) tablets ( Stallergènes , Antony , France ) have been demonstrated for the treatment of hay fever in adults . OBJECTIVE We sought to assess the efficacy and safety of this tablet in children and adolescents with grass pollen-related allergic rhinitis . METHODS In this multinational , r and omized , double-blind , placebo-controlled study , 278 children ( 5 - 17 years of age ) with grass pollen-related rhinoconjunctivitis ( confirmed by means of a positive grass pollen skin prick test response and serum-specific IgE measurement ) received once-daily SLIT tablets or placebo . Treatment was initiated 4 months before the estimated pollen season and continued throughout the season . The primary outcome was the rhinoconjunctivitis total symptom score ( RTSS ) , a sum of 6 individual symptom scores : sneezing , runny nose , itchy nose , nasal congestion , watery eyes , and itchy eyes . Secondary end points included rescue medication intake , individual scores , and safety . RESULTS The intent-to-treat population included 266 children ( mean age , 10.9 + /- 3.22 years ) . The RTSS for the 300-IR group was highly significantly different from that of the placebo group ( P = .001 ) . The 300-IR group showed a mean improvement for the RTSS of 28.0 % over that seen with placebo and a median improvement of 39.3 % . Significant differences between the 300-IR and placebo groups were also observed regarding rescue medication score and proportion of days using rescue medication during the pollen season ( P = .0064 and P = .0146 , respectively ) . Adverse events were generally mild or moderate in intensity and expected . No serious side effects were reported . CONCLUSION Five-grass-pollen SLIT tablets ( 300 IR ) reduce both symptom scores and rescue medication use in children and adolescents with grass pollen-related rhinoconjunctivitis Background : Data supporting a carry‐over effect with sublingual immunotherapy ( SLIT ) are scarce . This r and omized , double‐blind , placebo‐controlled study evaluated the efficacy , carry‐over effect and safety of grass pollen SLIT using co‐seasonal treatment IMPORTANCE The house dust mite ( HDM ) sublingual allergen immunotherapy ( SLIT ) tablet is a potential novel treatment option for HDM allergy-related asthma . OBJECTIVES To evaluate the efficacy and adverse events of the HDM SLIT tablet vs placebo for asthma exacerbations during an inhaled corticosteroid ( ICS ) reduction period . DESIGN , SETTING S , AND PARTICIPANTS Double-blind , r and omized , placebo-controlled trial conducted between August 2011 and April 2013 in 109 European trial sites . The trial included 834 adults with HDM allergy-related asthma not well controlled by ICS or combination products , and with HDM allergy-related rhinitis . Key exclusion criteria were FEV1 less than 70 % of predicted value or hospitalization due to asthma within 3 months before r and omization . Efficacy was assessed during the last 6 months of the trial when ICS was reduced by 50 % for 3 months and then completely withdrawn for 3 months . INTERVENTIONS 1:1:1 r and omization to once-daily treatment with placebo ( n = 277 ) or HDM SLIT tablet ( dosage groups : 6 SQ-HDM [ n = 275 ] or 12 SQ-HDM [ n = 282 ] ) in addition to ICS and the short-acting β2-agonist salbutamol . MAIN OUTCOMES AND MEASURES Primary outcome was time to first moderate or severe asthma exacerbation during the ICS reduction period . Secondary outcomes were deterioration in asthma symptoms , change in allergen-specific immunoglobulin G4 ( IgG4 ) , change in asthma control or asthma quality -of-life question naires , and adverse events . RESULTS Among 834 r and omized patients ( mean age , 33 years [ range , 17 - 83 ] ; women , 48 % ) , 693 completed the study . The 6 SQ-HDM and 12 SQ-HDM doses both significantly reduced the risk of a moderate or severe asthma exacerbation compared with placebo ( hazard ratio [ HR ] : 0.72 [ 95 % CI , 0.52 - 0.99 ] for the 6 SQ-HDM group , P = .045 , and 0.69 [ 95 % CI , 0.50 - 0.96 ] for the 12 SQ-HDM group , P = .03 ) . The absolute risk differences based on the observed data ( full analysis set ) in the active groups vs the placebo group were 0.09 ( 95 % CI , 0.01 - 0.15 ) for the 6 SQ-HDM group and 0.10 ( 95 % CI , 0.02 - 0.16 ) for the 12 SQ-HDM group . There was no significant difference between the 2 active groups . Compared with placebo , there was a reduced risk of an exacerbation with deterioration in asthma symptoms ( HR , 0.72 [ 95 % CI , 0.49 - 1.02 ] for the 6 SQ-HDM group , P = .11 , and 0.64 [ 95 % CI , 0.42 - 0.96 ] for the 12 SQ-HDM group , P = .03 ) and a significant increase in allergen-specific IgG4 . However , there was no significant difference for change in asthma control question naire or asthma quality -of-life question naire for either dose . There were no reports of severe systemic allergic reactions . The most frequent adverse events were mild to moderate oral pruritus ( 13 % for the 6 SQ-HDM group , 20 % for the 12 SQ-HDM group , and 3 % for the placebo group ) , mouth edema , and throat irritation . CONCLUSIONS AND RELEVANCE Among adults with HDM allergy-related asthma not well controlled by ICS , the addition of HDM SLIT to maintenance medications improved time to first moderate or severe asthma exacerbation during ICS reduction , with an estimated absolute reduction at 6 months of 9 to 10 percentage points ; the reduction was primarily due to an effect on moderate exacerbations . Treatment-related adverse events were common at both active doses . Further studies are needed to assess long-term efficacy and safety . TRIAL REGISTRATION clinical trialsregister.eu Identifier : 2010 - 018621 - 19 BACKGROUND The 5-grass pollen sublingual tablet has been approved for the treatment of grass pollen-induced allergic rhinoconjunctivitis in subjects with or without intermittent asthma . OBJECTIVE To provide a comprehensive analysis of the safety profile of the 5-grass tablet on the basis of pooled data from 8 clinical trials . METHODS Subjects ( 5 - 65 years old ) with medically confirmed grass pollen-induced allergic rhinoconjunctivitis were included in the double-blind studies . Those with intermittent asthma not requiring treatment other than inhaled beta-2 agonists could participate . R and omized subjects received a 5-grass or placebo tablet daily 2 or 4 months preseasonally and coseasonally ( 5 single-season studies , over 3 years in a long-term study ) or outside the season ( phase I studies ) . Adverse events were pooled and analyzed descriptively . RESULTS Among 2,512 subjects enrolled , 1,514 received the 5-grass tablet . A total of 1,038 adults and 154 pediatric ( 5 - 17 years old ) subjects were treated with the 300 Index of Reactivity dose ( vs 840 and 158 placebo recipients , respectively ) ; 17 % had intermittent asthma , and 62 % were polysensitized . Adverse reactions ( ADRs ) reported in more than 10 % of actively treated subjects were mild or moderate application-site reactions , for example , oral pruritus 25 % ( placebo 4 % ) and throat irritation 21 % ( placebo 3 % ) . These generally occurred during the first week of treatment and decreased over time . They led to discontinuation in less than 2.5 % of subjects . None of the 3 serious ADRs were reports of anaphylaxis . No notable differences were detected in terms of incidence , nature , and severity of ADRs between adult and pediatric population s , nor between subjects with or without asthma . CONCLUSIONS The pooled analysis in 1,514 subjects from 8 clinical studies demonstrates that the 5-grass pollen sublingual tablet has a similar good safety profile in adult and pediatric patients with or without mild , intermittent asthma Background : The SQ house dust mite ( HDM ) SLIT-tablet ( ALK , Denmark ) addresses the underlying cause of HDM respiratory allergic disease , and a clinical effect has been demonstrated for both HDM allergic rhinitis and allergic asthma . Here , we present pooled safety data from an adult population with HDM respiratory allergy , with particular focus on the impact of asthma on the SQ HDM SLIT-tablet tolerability profile . Methods : Safety data from 2 r and omised double-blind , placebo-controlled clinical trials were included : MT-04 : 834 adults with HDM allergic asthma not well controlled by inhaled corticosteroids and with HDM allergic rhinitis , and MT-06 : 992 adults with moderate-to-severe HDM allergic rhinitis despite the use of allergy pharmacotherapy and with or without asthma . Results : The proportion of subjects experiencing adverse events ( AEs ) was greater in the active treatment group ( 12 SQ-HDM ; 73 % of subjects ) compared to placebo ( 53 % ) . The most common treatment-related AEs were local allergic reactions . No AEs were reported as systemic allergic reactions . Regardless of asthma status , most AEs were mild or moderate ( > 97 % of AEs ) and the frequency of serious AEs was low . Subgroup analysis revealed no statistically significant difference in the risk of experiencing moderate or severe treatment-related AEs for subjects with asthma compared to subjects without asthma ( p = 0.88 ) . In addition , subjects with partly controlled or uncontrolled asthma were no more likely to experience moderate or severe treatment-related AEs than subjects with controlled asthma ( p = 0.42 ) . Conclusion : The SQ HDM SLIT-tablet is well tolerated , and the safety profile was comparable for subjects with HDM respiratory allergic disease irrespective of asthma status BACKGROUND Treatment with SQ house dust mite ( HDM ) sublingual immunotherapy ( SLIT ) tablet is effective for HDM respiratory allergic disease , but data on long-term effects are lacking . OBJECTIVE Post hoc analyses were conducted to determine the long-term effect of SQ HDM SLIT-tablet on nasal , ocular , and cough symptoms 1 year after discontinuation of treatment . METHODS Study participants underwent environmental exposure chamber ( EEC ) challenges at baseline and week 24 in a r and omized , placebo-controlled , double-blind trial ( NCT01644617 ) during which participants received daily 12 SQ-HDM , 6 SQ-HDM , or placebo for 24 weeks . Asthma had to be stable , well controlled , and nonsevere . The mean total asthma symptom score ( TASS ; sum of 3 symptoms : cough , wheeze , and dyspnea ) during baseline and week 24 EEC challenge was analyzed in all participants who completed the trial ( n = 106 ) . Approximately 1 year after trial completion , another EEC challenge was conducted in a subset of participants ( n = 51 ) . Total nasal symptom score ( sum of 4 symptoms ) , total ocular symptom score ( sum of 2 symptoms ) , and cough were assessed . RESULTS Compared with baseline and end-of-treatment values , sustained improvement of all symptoms assessed at the 1-year follow-up EEC challenge was evident in participants treated with 12 SQ-HDM . Results with 6 SQ-HDM were less notable . After 24 weeks of 12 SQ-HDM , TASS during EEC challenge was improved 65 % vs baseline ; at 1-year follow-up , cough was improved 57 % vs baseline . CONCLUSION Persistent improvement of nasal and ocular symptoms was observed up to 1 year after completing 24 weeks of 12 SQ-HDM treatment . Beneficial effects on cough were also observed . TRIAL REGISTRATION clinical trials.gov Identifier NCT01644617 Background : Local application of allergen extracts in specific immunotherapy is accompanied by increased compliance and significantly reduced side effects . However , efficacy of local immunotherapy in children has yet not been sufficiently demonstrated . This study was performed to determine clinical efficacy of high dose sublingual swallow immunotherapy ( SLIT ) by a double‐blind placebo‐controlled study in children with grass pollen allergy using high dose allergen extracts BACKGROUND In North America and Europe , millions of patients experience symptoms of allergic rhinitis with or without conjunctivitis ( AR/C ) on exposure to ragweed pollen . The disease burden can be significant , with most patients relying on symptomatic medications without disease-modifying potential . However , novel sublingual immunomodulatory treatment options may potentially play an important role if efficacy and side effect profiles allow the convenience of self-administration . OBJECTIVES This study evaluated an allergy immunotherapy tablet ( AIT ; SCH 39641/MK-3641 ) for treatment of ragweed-induced AR/C in the first large r and omized , double-blind multinational trial of this therapeutic modality for ragweed allergy . METHODS Adults ( n = 784 ) with short ragweed-induced AR/C were r and omly assigned to approximately 52 weeks of daily self-administered ragweed AIT of 1.5 , 6 , or 12 units of Ambrosia artemisiifolia major allergen 1 ( Amb a 1-U ) or placebo . Subjects could use as-needed allergy rescue medication . Symptoms and medications were recorded daily . The primary efficacy end point was total combined daily symptom/medication score ( TCS ) during peak ragweed season . Safety was monitored through adverse event diaries maintained through study duration . RESULTS During peak ragweed season , ragweed AIT of 1.5 , 6 , and 12 Amb a 1-U reduced TCS by 9 % ( -0.76 ; P = .22 ) , 19 % ( -1.58 ; P = .01 ) , and 24 % ( -2.04 ; P = .002 ) compared with placebo . During the entire season , ragweed AIT of 1.5 , 6 , and 12 Amb a 1-U reduced TCS by 12 % ( -0.88 ; P = .09 ) , 18 % ( -1.28 ; P = .01 ) , and 27 % ( -1.92 ; P < .001 ) compared with placebo . Treatment was well tolerated ; no systemic allergic reactions occurred . CONCLUSIONS In this trial , ragweed AIT of 12 Amb a 1-U was effective and tolerable with a safety profile that permitted daily self-administration of ragweed allergen immunotherapy UNLABELLED SAFETY and efficacy of sublingual ( sublingual-swallow ) immunotherapy ( IT ) with house dust mite extract were evaluated in 30 children ( 6 - 15 2/3 years of age ) over the first 12 months of an ongoing study . The cumulative dose was 570 micrograms Der p I ( five times that administered with subcutaneous therapy ) . SAFETY One patient on active treatment dropped out after 8 weeks because of a subjective feeling of severe weakness , question ably induced by the therapy . Five patients on active therapy and one patient on placebo reported minor local side effects . EFFICACY Pulmonary symptoms were reduced after 12 months in actively treated asthmatics , but this was not consistent with the lack of improvement in bronchial reactivity , skin sensitivity and specific IgG and IgG4 against D.pt . in this group . In patients with rhinitis nasal sensitivity was reduced in the placebo group without concomitant improvement in the nasal symptom score . Specific IgE ( D.pt . and D.f . ) increased significantly more in the active treatment group after 3 and 12 months . We conclude that sublingual IT over 12 months with the fivefold Der p 1 dose of subcutaneous IT was well tolerated , but there was no consistent clinical or immunological benefit compared to placebo A double-blind , placebo-controlled study of immunotherapy was conducted in 31 patients with allergic rhinitis due to Parietaria pollen to evaluate the efficacy and safety of high doses of allergen via the sublingual route . The patients were assessed before and after a 10-month period of treatment by clinical ( symptom-medication scores and specific nasal reactivity ) and immunological ( total IgE , specific IgE , IgG and IgG4 antibodies ) parameters . High doses of Parietaria extract corresponding to a cumulative dose of 105 BU for each patient were administered with negligible side effects . The actively treated patients had significantly lower medication scores than those on placebo ( p < 0.05 ) when the maximum pollen count was recorded , and at the end of the trial they showed a significant decrease in nasal reactivity ( p < 0.02 ) and a significant increase in serum specific IgG4 ( p = 0.02 ) . No differences were detected in any of these parameters in the placebo group . Possible explanations for the mechanisms of sublingual immunotherapy are proposed BACKGROUND House dust extract is used in conventional immunotherapy for house dust-mite ( HDM ) allergic rhinitis in Japan . However , an alternative administration route is desired . The aims of the present double blind , placebo-controlled trial were to evaluate the therapeutic efficacy and safety of sublingual immunotherapy ( SLIT ) with house dust extract in pediatric patients with HDM allergic rhinitis . METHODS The study population comprised 31 subjects ( 21 males and 10 females ) aged from 7 to 15 years old . Twenty patients ( the active group ) received house dust extract and 11 received placebo via sublingual administration . Extract or placebo ( 1 ml ) was administered at 10-fold dilution once weekly for 40 weeks . During the study period , the subjects recorded their daily nasal symptoms and use ( dose and frequency ) of other medications in a nasal allergy diary . RESULTS The symptom scores in the active group began to decrease about 24 weeks after initiation of treatment and significant differences between the active and placebo groups were observed after 30 weeks . The average scores for the last four weeks of the study were significantly lower than those for the first four weeks in the active group but not in the placebo group . The only local adverse effect was a bitter taste reported by one patient . There were no other local or systemic adverse effects associated with SLIT . CONCLUSIONS Our results suggest that SLIT with house dust extract for more than 30 weeks is safe and effective treatment for HDM allergic rhinitis in children BACKGROUND Allergen immunotherapy ( desensitization ) by injection is effective for seasonal allergic rhinitis and has been shown to induce long-term disease remission . The sublingual route also has potential , although definitive evidence from large r and omized controlled trials has been lacking . OBJECTIVE The aim was to confirm the efficacy of a rapidly dissolving grass allergen tablet ( GRAZAX , ALK-Abelló , Hørsholm , Denmark ) compared with placebo in patients with seasonal rhinoconjunctivitis . METHODS A longitudinal , double-blind , placebo-controlled , parallel-group study that included 51 centers from 8 countries . Subjects were r and omized ( 1:1 ) to receive a grass allergen tablet or placebo once daily . A total of 634 subjects with a history of grass pollen-induced rhinoconjunctivitis for at least 2 years and confirmation of IgE sensitivity ( positive skin prick test and serum-specific IgE ) were included in the study . Subjects commenced treatment at least 16 weeks before the grass pollen season , and treatment was continued throughout the entire season . RESULTS The primary efficacy analysis showed a reduction of 30 % in rhinoconjunctivitis symptom score ( P < .0001 ) and a reduction of 38 % in rhinoconjunctivitis medication score ( P < .0001 ) compared with placebo . Side effects mainly comprised mild itching and swelling in the mouth that was in general well tolerated and led to treatment withdrawal in less than 4 % of participants . There were no serious local side effects and no severe systemic adverse events . CONCLUSION Sublingual immunotherapy with grass allergen tablets was effective in grass pollen-induced rhinoconjunctivitis . The tablet was well tolerated with minor local side effects . CLINICAL IMPLICATION S The grass allergen tablet represents a safe alternative to injection immunotherapy suitable for home use BACKGROUND There is a growing consensus on the benefits of sublingual-swallow immunotherapy in the treatment of allergic diseases . METHODS This r and omized , double-blind placebo-controlled study was undertaken to assess the efficacy and safety of sublingual immunotherapy with st and ardized ragweed pollen extract tablets , in patients with an allergic rhinitis . A total of 110 out patients were r and omized ( immunotherapy [ I ] : 55 ; placebo [ P ] : 55 ) , of whom 99 were analyzable for efficacy ( I : 48 ; P : 51 ) and 106 analyzable for safety ( I : 53 ; P : 53 ) . After a 28-day progression phase , the patients received a maintenance treatment during 6.5 months . Efficacy variables included a global assessment of efficacy ( patient/ investigator ) , symptoms and medication scores as well as the frequency of asthma attacks . RESULTS In the active treatment group , 43 patients completed the study , versus 49 on placebo . During the whole period of pollination , the difference favoring immunotherapy was highly significant for the global assessment by the patient ( p = 0.004 ) and by the investigator ( p = 0.005 ) . Adverse reactions were reported more often in the active treatment but mild or moderate , and they abated after dose adjustment . A subgroup analysis of those patients receiving the highest dose of immunotherapy ( 3 tablets 3 times a week ) showed a highly significant response for rhinitis and conjunctivitis total scores by comparison to lower dosages . CONCLUSION This study confirms the efficacy and safety of sublingual immunotherapy and strongly suggests a dose-response relationship BACKGROUND Sublingual immunotherapy ( SLIT ) is accepted as a safe and effective route for the treatment of grass pollen allergy , but clarification of its clinical and biological efficacy requires more study . OBJECTIVE To evaluate the efficacy , safety , and compliance of SLIT with a st and ardized 3-grass pollen extract in patients with grass pollen seasonal allergic rhinoconjunctivitis , with or without mild asthma . METHODS This multicenter , r and omized , double-blind study included 127 patients ( aged 12 - 41 years ; mean age , 24.9 years ) with grass pollen seasonal allergic rhinoconjunctivitis , with or without mild asthma . They received either SLIT with a high-dose , st and ardized , 3-grass pollen extract or placebo for 10 months before and during the grass pollen season . The efficacy evaluation compared weekly clinical scores ( defined as the sum of the symptom score and rescue medication score ) to measure rhinoconjunctivitis and asthma for the first 8 weeks of the pollen season . We also evaluated safety and compliance and measured changes in anti-Dactylis specific IgG4 antibody levels . RESULTS There was a trend in favor of the study group in the mean adjusted clinical score . The groups were not comparable on inclusion ( P = .02 ) : the SLIT group included more subjects with asthma and had a higher mean IgG4 serum level . Additional exploration according to subgroups with and without asthma found that among the patients without asthma , the SLIT group had a significantly better clinical score ( P = .045 ) . Anti-Dactylis specific IgG4 levels increased significantly in the SLIT group . CONCLUSION SLIT with a st and ardized , high-dose , 3-grass pollen extract is safe and significantly improves the clinical score in patients with hay fever and without asthma during the pollen season Thirty-four patients suffering from rhinoconjunctivitis with or without asthma due to grass pollen , were su bmi tted to sublingual immunotherapy according to a double blind placebo controlled experimental plan ; eighteen patients received the active therapy , sixteen the placebo . A rush preseasonal treatment schedule was followed in order to reach the maintenance dose in 15 days with two administrations per day ; the top dose reached was then administered three times a week until the end of the pollen season . The symptoms and drugs related to rhinoconjunctivitis and asthma were recorded by means of diary cards and grass pollen counts were performed during the season . The actively treated group showed a reduction of symptoms of rhinoconjunctivitis and asthma and a lower intake of drugs for the same symptoms ; all these differences result ed to be statistically significant . No patient showed local or systemic side effects of any relevance . According to these results of our study , sublingual rush immunotherapy is clinical ly effective and because of the ease of h and ling , the shortness of the treatment , the absence of relevant side effects and the high compliance of the patient can be considered as an alternative to classic injective immunotherapy in grass pollen allergic patients BACKGROUND Sublingual swallow immunotherapy has been increasingly recognized as a safe and efficacious alternative to parenteral specific immunotherapy . OBJECTIVE To determine the safety and efficacy of sublingual swallow immunotherapy ragweed allergen extract for rhinoconjunctivitis treatment starting just before and continuing through the ragweed pollen season . METHODS This r and omized , double-blind , placebo-controlled study was performed in children and adults with a documented history of allergic rhinoconjunctivitis during ragweed season at 9 Canadian allergy centers . Active treatment was st and ardized extract of ragweed allergen administered as sublingual swallow drops at increasing doses starting shortly before the pollen season and maintenance doses continued daily during the season . Primary efficacy variables were symptom and medication scores , and secondary variables included global evaluation of efficacy and immunologic measurements . RESULTS Eighty-three patients were included in the safety analysis ; 76 patients were included in the intent-to-treat analysis . Nine placebo recipients and 1 treatment recipient withdrew for lack of efficacy ( P = .004 ) . Nine patients in the treatment group withdrew because of adverse events , none serious ( P = .003 ) . Investigator evaluation of efficacy showed that significantly more patients improved and fewer deteriorated in the treatment group vs the placebo group ( P = .047 ) . Ragweed IgE and IgG4 levels increased significantly in treatment recipients vs placebo users ( P < .001 ) . Sneezing and nasal pruritus approached significant improvement in the treatment group vs the placebo group ( P = .09 and .06 , respectively ) . Quebec City experienced low pollen counts . Excluding Quebec City , significant improvement was seen for these 2 symptoms ( P = .04 ) . CONCLUSION Sublingual swallow immunotherapy seems to be safe and efficacious for ragweed rhinoconjunctivitis even when started immediately before the ragweed pollen season Background : Especially in childhood , sublingual immunotherapy ( SLIT ) could offer advantages over subcutaneous therapy . However , limited data on its efficacy is available Allergen immunotherapy ( AIT ) is a guidelines -approved , disease-modifying treatment option for respiratory allergies , including allergic rhinitis ( AR ) induced by pollen . The various AIT regimens employed to date in pollen-induced AR can be classified as continuous ( i.e. year-round ) or discontinuous ( i.e. pre-seasonal alone , co-seasonal alone or pre- and co-seasonal ) . Pre- and co-seasonal regimens are typically used for sublingual allergen immunotherapy ( SLIT ) and have economic and compliance advantages over perennial ( year-round ) regimens . However , these advantages must not come at the expensive of poor efficacy or safety . The results of recent double-blind , placebo-controlled , r and omized clinical trials show that pre- and co-seasonal SLIT is safe and effective in patients with AR induced by grass pollen ( treated with a tablet formulation ) or by birch pollen ( treated with a liquid formulation ) . Progress in SLIT has been made in defining the optimal dose of major allergen , the administration frequency ( daily ) , the duration of pre-seasonal treatment ( four months ) and the number of treatment seasons ( at least three ) . Post-marketing , “ real-life ” trials of pre- and co-seasonal birch or grass pollen SLIT regimens have confirmed the efficacy and safety observed in the clinical trials . In the treatment of pollen-induced AR , pre- and co-seasonal SLIT regimens appear to be at least as effective and safe as perennial SLIT regimens , and are associated with lower costs and good compliance . Good compliance may mean that pre- and co-seasonal SLIT regimens are inherently more effective and safer than perennial SLIT regimens . When considering the pre- and co-seasonal discontinuous regimen in particular , a 300 IR five-grass-pollen formulation is the only SLIT tablet with a clinical development programme having provided evidence of short-term , sustained and post-treatment efficacy The aim of the study was to confirm the safety of an orodispersible grass allergen tablet 75,000 SQ-T ( Grazax , ALK-Abelló A/S , Hørsholm , Denmark ) in children aged 5 - 12 yr . The study was r and omized , double-blinded and placebo-controlled . Sixty children aged 5 - 12 yr suffering from grass pollen-induced rhinoconjunctivitis ( with or without asthma ) from five centres in two countries ( three in Germany and two in Spain ) participated in the study . They were r and omized at the ratio of 3:1 as receiving either Grazax or placebo tablet given sublingually once daily for 28 days outside the grass pollen season . A total of 810 treatment-related adverse events were reported in the Grazax group . The majority of these were local reactions in the mouth or throat and were mostly mild ( 71 % ) to moderate ( 27 % ) in severity and resolved within days . Thirty-five ( 78 % ) subjects treated with Grazax and five ( 33 % ) treated with placebo reported at least one treatment-related adverse event . Oral pruritus , throat irritation , mouth oedema and ear pruritus appeared as the most frequently reported treatment-related adverse events . 62 % ( 28 of 45 ) of the actively treated subjects reported oral pruritus , 36 % ( 16 of 45 ) throat irritation , 31 % ( 14 of 45 ) mouth oedema and 22 % ( 10 of 45 ) ear pruritus . Two actively treated subjects withdrew from the study : one subject due to four adverse events ( moderate eye pruritus , moderate pharyngolaryngeal pain , moderate non-cardiac chest pain and moderate dysphagia ) and one subject due to a serious adverse event ( asthmatic attack ) . The subjects recovered completely from the events . In conclusion , in the present study , Grazax was in general tolerated in a paediatric population and considered suitable for further clinical investigations in children Sublingual immunotherapy has been suggested for the treatment of respiratory allergies . Many controversial studies have been reported on the efficacy of sublingual immunotherapy . The aim of this prospect i ve study was to evaluate whether sublingual immunotherapy was effective according to clinical and laboratory results in pediatric allergies . Thirty-nine allergic , grass pollen sensitive children were admitted into the study . Sublingual immunotherapy was given over a 12-month period to 21 children ( mean age 10.5 + /- 3.3 years ) , 10 of whom had seasonal allergic rhinitis and 11 seasonal allergic asthma . During the same period , 18 children ( mean age 11.1 + /- 2.5 years ) , 10 with seasonal allergic rhinitis and eight with seasonal allergic asthma , received placebo . Symptom scores and drug requirements were recorded and urine sample s were collected to detect urinary levels of leukotrienes ( Uc-LTB4 and Uc-LTE4 ) . In patients who received sublingual immunotherapy , the symptom scores of seasonal allergic rhinitis significantly decreased , but no statistically significant changes were observed in terms of symptoms of seasonal allergic asthma . Uc-LTE4 and Uc-LTB4 levels of seasonal allergic rhinitis , with a geometric mean and 95 % confidence interval ( CI ) , were significantly decreased from 216 ( 103 - 464 ) and 61 ( 22 - 198 ) pmol/mmol creatinine to 78 ( 29 - 159 ) and 35 ( 12 - 118 ) pmol/mmol creatinine , respectively ( p < 0.05 and p < 0.05 ) . On the other h and , Uc-LTE4 and Uc-LTB4 levels for seasonal allergic asthma were 180 ( 92 - 355 ) and 78 ( 44 - 258 ) pmol/mmol creatinine and decreased to 156 ( 72 - 402 ) and 69 ( 32 - 254 ) pmol/mmol creatinine , respectively . These changes were not statistically significant ( p > 0.05 ) . According to our clinical results and urinary levels of leukotrienes , which are mediators showing the severity of allergic inflammation , it can be suggested that sublingual immunotherapy may be useful in the treatment of seasonal allergic rhinitis but not of seasonal allergic asthma Immunotherapy is the only treatment for allergy that has the potential to alter the natural course of the disease . Sublingual immunotherapy for grass pollen-induced rhinoconjunctivitis has been developed to make immunotherapy available to a broader group of allergic patients . Here , a safe dose range and the safety during daily sublingual administration were investigated for a new tablet-based sublingual immunotherapy for grass pollen allergy . Simultaneously , immunological changes were monitored . A r and omized , double-blind , placebo-controlled phase I trial was undertaken , with stepwise dose-escalation during the dose-finding period , and afterwards with daily dosing 8 weeks prior to and 15 weeks during the grass pollen season ( 2500 , 25000 , or 75000 st and ardized quality tablet [ SQ-T ] units , or placebo ) . Fifty-two participants with grass pollen-induced rhinoconjunctivitis and a positive skin prick test and specific IgE to Phleum pratense entered the trial . During the daily-dose treatment periods , 67 % of the participants reported adverse events . The most frequent were itching in the mouth , eyes , or throat , and rhinitis , and most were mild and resolved within 1 day . Two participants withdrew due to adverse events ( sting and blisters in the mouth and itching in the mouth ) . Time- and dose-dependent increases of P pratense-specific IgG , IgA , IgE , and IgE-competing components were found in serum during the first 8 weeks of daily dosing , indicating that the treatment had a significant allergen-specific effect on the immune system . In conclusion , the grass allergen tablet , administered in a dose of 75000 SQ-T once daily , was well tolerated and displayed systemic immunogenicity BACKGROUND Sublingual immunotherapy with grass allergen tablets may be the future treatment for grass pollen allergy because it reduces symptoms and medication use , improves quality of life and is easy to use . Rhinoconjunctivitis and asthma co-exist and we aim ed to find a safe dose range of a self-administered grass allergen tablet ( ALK Abello A/S ) in patients suffering from rhinoconjunctivitis and asthma . METHODS Four doses were investigated in a r and omised , double-blind , placebo-controlled , dose escalation trial . Outside the pollen season 4 groups of 12 patients commenced treatment in a staggered manner , at intervals of 1 week . For 28 days doses of 75000 ( approximately 15microg Phleum pratense protein 5 ) , 150,000 , 300,000 , 500,000 st and ardised quality tablet ( SQ-T ) units or placebo were given once daily as sublingual tablets . RESULTS Fourty three patients were r and omised to receive either active treatment or placebo ( 3:1 ) . Each dose group consisted of 12 patients except the 500000 SQ-T group ( 5 active , 2 placebo ) . No asthma exacerbations were seen and no serious or severe adverse events were reported . The majority of adverse events were local reactions . The number of adverse events was dose related . No patients withdrew from the study . CONCLUSIONS Treatment with grass allergen tablets in doses up to 500000 SQ-T in patients with asthma and rhinoconjunctivitis was safe and well tolerated Sublingual‐swallow immunotherapy ( SLIT ) using high doses of st and ardized allergen extracts has been found to be effective in reducing allergic symptoms and medication needs . A double‐blind , placebo‐controlled study was carried out in a large number of patients to determine whether medication needs can be reduced by SLIT . Some 136 patients with grass‐pollen rhinitis with or without mild asthma were studied . Patients received either placebo or SLIT with a st and ardized grass‐pollen extract administered daily with increasing doses up to 300 IR ( index of reactivity ) from January to the end of July 1994 . During the grass‐pollen season , patients were instructed to use medications as required and to visit their doctors in case of asthma . Symptom‐medications scores were assessed during the pollen season , and serum‐specific IgG4 was measured before and at the end of SLIT . In the SLIT group , drug consumption dropped significantly throughout the pollen season ( P<0.02 ) . Moreover , at the peak of the pollen season , betamethasone consumption was significantly reduced in the SLIT group ( P<0.02 ) . Only one patient in the SLIT group had an asthma attack compared to eight patients in the placebo group ( P<0.02 ) . IgG4 levels increased significantly in the SLIT group ( P<0.001 ) but without correlation with symptoms . Side‐effects were comparable in both groups . This study indicates that SLIT in grass‐pollen rhinitis is well tolerated , improves overall clinical symptoms , and reduces drug consumption and the need for oral corticosteroids BACKGROUND Specific allergen immunotherapy is most often delivered subcutaneously , but sublingual immunotherapy may confer greater benefit in terms of tolerability and safety , accessibility , and improved antigen delivery . OBJECTIVE This r and omized , double-blind , placebo-controlled trial was conducted to identify a safe and effective maintenance dose range of sublingual st and ardized glycerinated short ragweed pollen extract in adults with ragweed-induced rhinoconjunctivitis . METHODS In May 2006 , a total of 115 patients with ragweed-induced rhinoconjunctivitis were r and omly allocated to placebo ( n = 40 ) , medium-dose extract ( 4.8 microg Amb a 1/d ; n = 39 ) , or high-dose extract ( 48 microg Amb a 1/d ; n = 36 ) . In a 1-day ( rush ) dose-escalation regimen , ragweed pollen extract was administered sublingually in incremental doses until maximum tolerable or scheduled dose was reached and then maintained during the ragweed pollen season . Patient diaries were used to monitor nasal and ocular symptoms and medication . The primary endpoint was symptom score . RESULTS Both active treatment groups achieved a 15 % reduction in total rhinoconjunctivitis symptom scores compared with placebo during the entire ragweed pollen season , but the difference was not statistically significant ( P > .10 ) However , in an analysis of covariance correcting for preseasonal symptoms , both mean daily symptom scores ( 0.19 + /- 1.16 vs 1.00 + /- 2.30 ) and medication scores ( 0.0003 + /- 1.64 vs 0.63 + /- 1.06 ) for the entire pollen season were significantly reduced in the high-dose versus placebo groups , respectively ( P < or= .05 ) . Ragweed-specific IgG , IgG(4 ) , and IgA antibodies were increased after treatment in the medium- and high-dose groups and not the placebo group . Frequency of adverse events was similar between the placebo and treatment groups , but oral-mucosal adverse events occurred more often with treatment . CONCLUSION St and ardized glycerinated short ragweed pollen extract administered sublingually at maintenance doses of 4.8 to 48 microg Amb a 1/d was safe and can induce favorable clinical and immunologic changes in ragweed-sensitive subjects . However , additional trials are needed to establish efficacy BACKGROUND The aim of this study was to confirm the clinical efficacy and safety of a preseasonal sublingual immunotherapy ( SLIT ) in a group of allergic patients with seasonal rhinoconjunctivitis with or without mild intermittent or mild persistent asthma . The immunotherapy was administered through the oral mucosa with a monomeric carbamylated allergoid ( allergoid SLIT ) for grass pollens . A secondary endpoint was to evaluate the effect of the allergoid SLIT on nasal reactivity . METHODS AND RESULTS A single-center , r and omized , double-blind , placebo-controlled study was performed . Patients were selected and r and omly allocated to two groups : one group received active treatment ( allergoid SLIT ) for 2 years and the other received placebo . Both groups received the necessary drug treatment throughout the trial . Thirty-three out patients ( 20 men and 13 women , mean age : 30 years ; range : 19 - 43 ) attending our center were enrolled in the study . Symptoms and medications were scored on diary cards during the pollen season . An allergen nasal challenge was performed at baseline and after 2 years of SLIT to evaluate nasal reactivity . Because the clinical scores were non-normally distributed , the Mann-Whitney and the Chi-square tests for intergroup comparisons and the Wilcoxon test for intragroup comparisons were used . The results were evaluated after 1 and 2 years of treatment . Between the first and second years of treatment , no changes in the scores for the placebo group were found , while for the active vaccine group significant decreases were found in rhinorrhea ( p < 0.03 ) , sneezing ( p < 0.03 ) , and conjunctivitis ( p < 0.02 ) . Symptom scores after nasal challenge decreased ( p < 0.03 ) after 2 years ' treatment . Nasal steroid use significantly decreased in the active treatment group during May and June in both the years of treatment ( p < 0.02 ) . Only two mild local adverse events were reported in the active group and none was reported in the placebo group . CONCLUSIONS The results of this study show that the allergoid SLIT is safe and effective in decreasing symptom scores and drug use in rhinitic patients allergic to grass pollen OBJECTIVE The purpose of this r and omized , double-blind , placebo-controlled study was to evaluate the clinical efficacy and tolerance of once-daily sublingual immunotherapy without updosing . Reduction in symptoms and medication use was the primary endpoint . METHODS One hundred five patients with rhinitis and /or asthma due to grass and olive sensitization were r and omized to be treated with placebo or active sublingual immunotherapy with the SLITone grass mix plus olive pollen extract for 6 months before the 2005 pollen season . Patients recorded symptoms and medication intake for 8 weeks during the pollen seasons in 2004 ( n=37 ) and 2005 ( n=85 ) . RESULTS Allergic symptoms were significantly decreased in the active immunotherapy group ( P = .004 ) but not in the placebo group . There were no differences in scores between groups during the 2005 pollen season . Subjective assessment s on a visual analog scale and a quality -of-life question naire indicated an improvement in actively treated patients with significant differences in both symptoms and medication use ( P = .006 ) . The rate of systemic adverse reactions was comparable in the 2 groups . No anaphylactic or severe adverse reactions were reported . Local adverse reactions , which were more common in the active immunotherapy group , were mostly immediate , were limited to the lips and mouth , and did not require treatment . CONCLUSION Once-daily sublingual immunotherapy without updosing was well tolerated . The actively treated patients showed a significant reduction in symptom and medication scores and an improvement in their quality of life although there were no significant differences between the groups probably due to the low allergen season in which the study was evaluated BACKGROUND Seasonal allergic rhinoconjunctivitis affects millions of persons . The efficacy of allergen sublingual immunotherapy ( SLIT ) was demonstrated in previous short-term studies . OBJECTIVES We sought to evaluate the sustained efficacy of 2 dosing regimens of a pre- and coseasonal treatment with 300 IR ( index of reactivity ) 5-grass-pollen SLIT tablets ( Oralair ) compared with placebo assessed by using the average adjusted symptom score ( AAdSS ) at season 3 in adults with grass pollen-induced rhinoconjunctivitis . METHODS Six hundred thirty-three patients were treated for either 2 or 4 months before and then during the grass pollen season with active or placebo treatment for 3 consecutive seasons . The primary outcome was the AAdSS , a symptom score adjusted for rescue medication use , after 3 consecutive treatment seasons . Secondary outcomes were symptoms and rescue medication score , quality -of-life , and safety assessment s. RESULTS The mean AAdSS was reduced by 36.0 % and 34.5 % at season 3 in the 2- and 4-month pre- and coseasonal active treatment groups , respectively , compared with that in the placebo group ( P < .0001 for both ) . Reductions were observed in total symptom scores and ISSs and the medication score , with a marked improvement in quality of life for both active groups compared with the placebo group at season 3 . Most treatment-emergent adverse events were local reactions expected with SLIT , decreasing in number and intensity in each treatment season . CONCLUSIONS Sustained efficacy of 2- and 4-month pre- and coseasonal treatment with the 300 IR tablet over 3 pollen seasons was demonstrated , with reduction in symptoms and rescue medication use . The treatment was well tolerated . Adverse events decreased in number and intensity over the 3 seasons BACKGROUND The efficacy and safety of a 5-grass-pollen sublingual immunotherapy ( SLIT ) tablet ( Stallergènes SA , Antony , France ) have been evaluated in clinical studies during the pollen season . The allergen challenge chamber ( ACC ) has been developed as a pharmacodynamic assessment tool to control the environmental allergens and to avoid all problems associated with unpredictable pollen seasons . OBJECTIVE We sought to evaluate the onset of action and efficacy of 300-IR ( index of reactivity ) SLIT tablets by using an ACC . METHODS Patients with grass pollen-induced rhinoconjunctivitis were r and omized into the active or placebo groups . A st and ardized allergen challenge with grass pollen and symptom evaluation every 15 minutes was performed at baseline , 1 week , and 1 , 2 , and 4 months of treatment . The primary end point was the average rhinoconjunctivitis total symptom score ( ARTSS ) . Allergen-specific basophil activation , T-cell proliferation , and plasmatic IgE and IgG responses were assessed before and after treatment . RESULTS In the intention-to-treat population ( n = 89 ) a significant treatment effect was achieved after the first month ( P = .0042 ) and second month ( P = .0203 ) and was maintained through to the fourth month ( P = .0007 ) . In the active group the ARTSS ( means + /- SDs ) decreased at each challenge : week 1 , 7.40 + /- 2.682 ; month 1 , 5.89 + /- 2.431 ; month 2 , 5.09 + /- 2.088 ; and month 4 , 4.85 + /- 1.999 . An improvement ( vs placebo ) of 29.3 % for the mean ARTSS ( median , 33.3 % ) was observed at end point . Furthermore , the induction of grass pollen allergen-specific IgGs was associated with clinical response . The most frequent adverse reactions were local : oral pruritus , ear pruritus , and throat irritation . CONCLUSIONS In this ACC study the 300-IR 5-grass-pollen SLIT tablets had a significant effect on rhinoconjunctivitis symptoms ( vs placebo ) from the first month of treatment onward BACKGROUND Specific immunotherapy is the only treatment modality that has the potential to alter the natural course of allergic diseases . Sublingual immunotherapy has been developed to facilitate access to this form of treatment and to minimize serious adverse events . OBJECTIVE To investigate the efficacy and safety of sublingual grass allergen tablets in seasonal allergic rhinoconjunctivitis . METHODS A multinational , multicenter , r and omized , placebo-controlled trial conducted during 2002 and 2003 . Fifty-five centers in 8 countries included 855 participants age 18 to 65 years who gave a history of grass pollen-induced allergic rhinoconjunctivitis and had a positive skin prick test and elevated serum allergen-specific IgE to Phleum pratense . Participants were r and omized to 2500 , 25,000 , or 75,000 SQ-T grass allergen tablets ( GRAZAX ; ALK-Abelló , Hørsholm , Denmark ) or placebo for sublingual administration once daily . Mean duration of treatment was 18 weeks . RESULTS Average rhinoconjunctivitis scores during the season showed moderate reductions of symptoms ( 16 % ) and medication use ( 28 % ) for the grass allergen tablet 75,000 SQ-T ( P = .0710 ; P = .0470 ) compared with placebo . Significantly better rhinoconjunctivitis quality of life scores ( P = .006 ) and an increased number of well days ( P = .041 ) were also observed . Efficacy was increased in the subgroup of patients who completed the recommended preseasonal treatment of at least 8 weeks before the grass pollen season ( symptoms , 21 % , P = .0020 ; and medication use , 29 % , P = .0120 ) . No safety concerns were observed . CONCLUSION This study confirms dose-dependent efficacy of the grass allergen tablet . Although further studies are required , the greater tolerability of the tablet may permit immunotherapy to be available to a much broader group of patients with impaired quality of life caused by grass pollen allergy . CLINICAL IMPLICATION S For patients with grass pollen allergy , sublingual immunotherapy is well tolerated and can reduce symptoms and improve quality of life Background : Japanese cedar ( JC ) pollinosis is the most common seasonal allergic rhinitis in Japan . St and ardized JC pollen extract is available for subcutaneous immunotherapy , but this treatment is limited by potentially serious side effects . The aim of this double-blind , r and omized comparative study was to evaluate the efficacy and safety of st and ardized JC pollen extract in a new oral formulation ( CEDARTOLEN ® , Torii Pharmaceutical Co. , Ltd. , Tokyo , Japan ) for sublingual immunotherapy ( SLIT ) for JC pollinosis . Methods : A total of 531 subjects with JC pollinosis were r and omized into 2 groups at a ratio of 1:1 to receive daily sublingual administration of st and ardized JC pollen extract with a maintenance dose of 2,000 Japanese allergy units ( JAU ) or placebo for 2 consecutive pollen seasons . The efficacy was evaluated using the total nasal symptom and medication score ( TNSMS ) as the primary end point . Secondary end points included the total ocular symptom and medication score ( TOSMS ) and scores for individual symptoms and medication . Results : The TNSMS was significantly lower ( p < 0.0001 ) in the SLIT group than in the placebo group in the peak symptom period by 18 and 30 % in the first and second seasons , respectively . All secondary end points were also significantly lower in the SLIT group in both seasons . No systemic anaphylaxis occurred . Conclusions : SLIT with daily administration of st and ardized JC pollen extract was effective for improving nasal and ocular symptoms of JC pollinosis and reducing the use of relief medication . The JC pollen extract was well tolerated with only local adverse events BACKGROUND House dust mite ( HDM ) allergy is associated with persistent allergic rhinitis ( AR ) and allergic asthma . OBJECTIVE To investigate the efficacy and safety of a SQ HDM sublingually administered immunotherapy tablet ( ALK , Hørsholm , Denmark ) in adults and adolescents with HDM respiratory allergic disease and report the AR results . METHODS Six hundred four subjects at least 14 years old with HDM AR and mild to moderate HDM allergic asthma were r and omized 1:1:1:1 to double-blinded daily treatment with 1 , 3 , 6 SQ-HDM or placebo . End-of-treatment rhinoconjunctivitis symptoms and medication score were predefined extrapulmonary end points . A subgroup analysis was conducted post hoc in subjects with a total combined rhinitis score ( TCRS ) > 0 ( ie , with AR symptoms and /or AR medication use during the 4-week baseline period ) . The subgroup was comprised of 498 subjects ( 82 % ) . RESULTS In the subgroup , the absolute difference in end-of-treatment TCRS between 6 SQ-HDM and placebo was -0.78 ( 95 % confidence interval -1.47 to -0.07 , relative difference 28.8 % , P = .0357 ) . Furthermore , a significant difference was found for the total score of the Rhinitis Quality of Life Question naire with St and ardized Activities RQLQ(S ) and for the individual domains : activities , sleep , non-nose and non-eye symptoms , and nasal symptoms . For the TCRS and Rhinitis Quality of Life Question naire score , a dose response was seen , with numerically lower , nonsignificant differences for 1 and 3 SQ-HDM . The predefined analysis for the entire trial population showed no statistically significant difference between the placebo and actively treated groups . No safety concerns were observed . CONCLUSION Efficacy in mild to severe AR of 6 SQ-HDM compared with placebo was demonstrated by statistically significant improvements in TCRS and Rhinitis Quality of Life Question naire score in subjects with AR present at baseline . The treatment was well tolerated . TRIAL REGISTRATION EudraCT , no 2006 - 001795 - 20 ; Clinical Trials.gov , identifier NCT00389363 BACKGROUND To assess the efficacy and safety of sublingual immunotherapy in patients with allergic rhinitis/conjunctivitis , a double blind placebo controlled study was performed . METHODS AND RESULTS Fifty-seven ( 57 ) patients with a well-documented history of seasonal grass pollen allergy were evaluated in a DBPC trial over a period of 10 months ( January to November 1995 ) with a view to investigating the efficacy and safety of sublingual immunotherapy with a grass pollen extract , 9,500 BU/ml . The course of treatment consisted of an incremental phase of approximately 3 weeks followed by a twice weekly maintenance dosage of 9,500 BU . Compared with the placebo group ( 30 patients ) , the group treated with grass pollen extract ( 27 patients ) showed a significant ( p < 0.03 ) lower mean severity of allergic complaints , i.e. sneezing , and itchy nose , a watery runny nose and itching of the eyes during the maximum pollen counts of the season . The use of anti-allergic medication was similar in the two groups . Both groups showed a significant increase in grass-pollen-specific IgG serum levels . However , the increase shown in the patients treated with grass pollen extract occurred earlier in the season and was significantly ( p < 0.002 ) higher than the increase detected in the placebo group . Side effects were limited to a small number of generally mild local reactions . CONCLUSIONS The treatment with sublingually applied grass pollen extract in patients suffering from allergic rhinoconjunctivitis caused by grass pollen was well tolerated and served to reduce the severity of allergic complaints , without reducing the consumption of anti-allergic medication Background The 300IR ( index of reactivity ) 5-grass pollen tablet has favorable short-term and sustained clinical efficacy in patients with grass pollen-induced allergic rhinoconjunctivitis ( ARC ) . Here , we report maintenance of efficacy and safety over 2 years following treatment discontinuation . Methods R and omized , double-blind , placebo-controlled , parallel-group , multicenter Phase 3 trial in patients aged 18–50 years with ARC . During study years 1–3 , patients received a daily sublingual tablet containing either 300IR 5-grass pollen extract or placebo , according to a discontinuous pre- and coseasonal protocol . Study years 4 and 5 were treatment-free . In response to health authorities ’ recommendations , the daily combined score ( DCS ) was assessed in a post-hoc analysis as the efficacy endpoint . Components of the DCS were daily rhinoconjunctivitis total symptom score ( DRTSS ) and daily rescue medication score ( DRMS ) . Results 633 patients with ARC were r and omized to placebo ( n = 219 ) or 300IR 5-grass pollen tablet , beginning 4 months ( 4 M , n = 207 ) or 2 months ( 2 M , n = 207 ) prior to the estimated start of the grass pollen season and continuing until season ’s end . During the first post-treatment year , a statistically significant difference versus placebo in least squares ( LS ) mean DCS was noted in patients previously receiving active treatment ( 300IR ( 2 M ) point estimate : −0.16 , 95 % confidence interval ( CI95 % ) : [ −0.26 , −0.06 ] , p = 0.0019 ; −31.1 % ; 300IR ( 4 M ) point estimate : −0.13 , CI95 % : [ −0.23 , −0.03 ] , p = 0.0103 , −25.3 % ) . During the second post-treatment year , patients in the 300IR ( 4 M ) group , but not the 300IR ( 2 M ) group , showed a statistically significant difference in LS mean DCS versus placebo ( point estimate : −0.11 , CI95 % : [ −0.21 ; 0.00 ] , p = 0.0478 , −28.1 % ) . This significant efficacy seen during the post-treatment years in patients previously treated with 5-grass pollen tablet compared favorably with that during the 3 prior years of active treatment . A statistically significant difference versus placebo was also noted in secondary efficacy measures in both post-treatment years ( except for DRTSS in year 5 ) . In the absence of any active treatment , the safety profile was similar in the active groups versus placebo group during either post-treatment year . Conclusions In adults with grass pollen-associated ARC , 5-grass pollen tablet therapy beginning 4 months before the pollen season and continuing to season ’s end demonstrated efficacy across all variables during active treatment , and this effect was prolonged for up to 2 years post-treatment . Trial registration Clinical Trials.gov identifier : NCT00418379 BACKGROUND Immunotherapy with the SQ-st and ardized grass tablet Grazax is efficacious and well-tolerated in adult patients with rhinoconjunctivitis . Allergic asthma and rhinoconjunctivitis are closely linked , and a strategy combining treatment of the upper and lower airways is recommended . OBJECTIVE To investigate the efficacy of treatment with the grass tablet on grass pollen-induced rhinoconjunctivitis and asthma as well as the immunologic response and the safety profile in children . METHODS A total of 253 children age 5 to 16 years , with grass pollen-induced rhinoconjunctivitis with/without asthma , were r and omized 1:1 to active treatment or placebo . Treatment was initiated 8 to 23 weeks before the start of the grass pollen season 2007 and continued throughout the entire season . Symptomatic medication was provided as relief medication to both groups in a stepwise fashion . Primary endpoints were rhinoconjunctivitis symptom and medication scores . RESULTS The rhinoconjunctivitis symptom and medication scores and the asthma symptom score were all statistically significantly different between the 2 treatment groups . The differences in medians relative to placebo were 24 % , 34 % , and 64 % in favor of active treatment . The immunologic response was similar to that observed in adults . The most common adverse reaction was oral pruritus , reported by 40 subjects ( 32 % ) in the active and 3 ( 2 % ) in the placebo group . Six subjects withdrew because of adverse events . No serious adverse events were assessed as treatment-related . CONCLUSION Immunotherapy with the grass tablet reduced grass pollen-induced rhinoconjunctivitis and asthma symptoms in a pediatric population and introduced an immunomodulatory response , consistent with treatment of the underlying allergic disease . The treatment was well tolerated Sustained efficacy over three pollen seasons of pre‐ and co‐seasonal treatment with 300IR 5‐grass pollen sublingual tablet has been demonstrated in adults with moderate‐severe grass pollen‐associated allergic rhinoconjunctivitis BACKGROUND Sublingual immunotherapy ( SLIT ) tablets could be an important alternative to subcutaneous immunotherapy for house dust mite ( HDM ) allergy in children . OBJECTIVE To characterize the safety , tolerability , and duration of local adverse events ( AEs ) of an HDM SLIT tablet ( MK-8237 ; Merck , ALK Abellò , and Torii ) in North American children 12 to 17 years old with HDM allergic rhinitis with and without conjunctivitis and with or without asthma . METHODS In this phase 1 , multicenter , double-blinded , r and omized trial ( NCT01678807 ) , children received placebo , HDM SLIT tablet 6 st and ardized quality ( SQ ) HDM , or 12 SQ-HDM once daily for 28 days . The primary end point was the proportion of subjects with treatment-emergent AEs receiving active treatment vs placebo . The secondary end point was the proportion of subjects who discontinued owing to AEs . RESULTS In total 195 subjects were r and omized . The 2 HDM SLIT tablet doses were well tolerated . No anaphylactic reactions , systemic allergic reactions , AEs requiring epinephrine , serious AEs , or local swellings in the mouth or throat assessed as severe were reported . The proportion of subjects with treatment-emergent AEs was 54 % with 6 SQ-HDM and 57 % with 12 SQ-HDM ( nonsignificant vs 43 % with placebo ) . Local AEs were the most commonly reported treatment-emergent AEs . On day 1 , the median duration of individual local AEs ranged from 1 to 43 minutes . The proportion of subjects who discontinued owing to AEs was 0 % , 6.2 % , and 6.2 % , and who experienced treatment-related AEs was 25 % , 45 % , and 52 % for the placebo , 6 SQ-HDM , and 12 SQ-HDM groups , respectively . CONCLUSION The 6 and 12 SQ-HDM doses of the HDM SLIT tablet MK-8237 were well tolerated , and local AEs were of short duration . TRIAL REGISTRATION Clinical Trials.gov , identifier NCT01678807 A double‐blind , placebo‐controlled study was carried out in 85 patients with a well‐documented history of perennial asthma caused by house‐dust mites . Patients received either placebo or sublingual immunotherapy ( SLIT ) with a st and ardized Dermatophagoides pteronyssinus (DP)–D. farinae ( DF ) 50/50 extract . After a run‐in period , patients received increasing doses up to 300 IR every day for 4 weeks and then three times a week for the following 24 months . The cumulative dose was about 104 000 IR , equivalent to 4.2 mg Der p 1 and 7.3 mg Der f 1 . Symptom and medication scores and respiratory function were assessed throughout the trial . Serum specific IgE and IgG4 were determined before SLIT ( t0 ) and after 6 ( t1 ) , 11 ( t2 ) , 17 ( t3 ) , and 25 months ( t4 ) of SLIT . Mite exposure was evaluated at t0 , t2 , and t4 by semiquantitative guanine determinations . Patients aged 15 years and older were asked to assess their quality of life ( QoL ) by completing the SF20 ( Short Form Health Status Survey ) plus two items at t0 , t2 , and t4 . Use of inhaled corticosteroids and β2‐agonists was significantly decreased after 25 months of treatment in both groups ( P<0.03 ) . SLIT patients showed significant improvements in respiratory function at t4 ( % predicted FEV1 ( P=0.01 ) , VC ( P=0.002 ) , morning ( P=0.01 ) and evening ( P=0.03 ) PEFR ) , and reduction in daytime asthma score ( P=0.02 ) . In the SLIT group , the post‐treatment PD20 was 1.75 times higher than the baseline value . There was no change in PD20 in the placebo group . Compared to the placebo group , the SLIT group showed a significant increase in specific IgE DP ( P=0.05 ) , IgE DF ( P=0.02 ) , IgG4 DP ( P=0.001 ) , and IgG4 DF ( P=0.001 ) levels after SLIT . QoL scores were similar in both groups at t0 and t2 . At t4 , all scores were better in the SLIT group than in the placebo group , with the differences being most marked for the general perception of health ( P=0.01 ) and physical pain ( P=0.02 ) . Adverse events were similar in the two groups . This study shows that SLIT in house‐dust‐mite‐related asthma has a good safety profile and improves respiratory function , bronchial hyperreactivity , and The safety of allergen immunotherapy ( AIT ) in asthma has not always been sufficiently documented ; accordingly , fear of asthma exacerbations has made physicians somewhat reluctant to prescribe AIT in this context . In a double‐blind , placebo‐controlled , r and omized clinical trial , house dust mite ( HDM ) sublingual AIT was found to be efficacious in moderate , persistent asthma . The trial 's safety results are now reported in detail Immunotherapy in elderly patients is controversial , and there is still no evidence supporting this treatment 's safety and efficacy in this population . This study was performed to evaluate the safety and efficacy of specific sublingual immunotherapy for house dust mite ( HDM ) allergens in patients over 60 years of age with allergic rhinitis and a confirmed allergy to HDM UNLABELLED Sublingual immunotherapy ( SLIT ) has been recognized as a viable alternative to subcutaneous immunotherapy for respiratory allergies both in adults and children , but clinical documentation about safety and efficacy in children is still poor . The purpose of this study was to assess the efficacy and tolerance of SLIT in children who are sensitized to grass pollen . METHODS Children with a clinical history of intermittent rhinoconjunctivitis , with or without mild asthma and positive skin prick tests to grass pollen , were selected to participate in a 2-year double-blind , placebo-controlled study with SLIT , using a grass extract ( ALK-Abellò ) . RESULTS 22 children were analyzed at the end of the study . No relevant side effects occurred in the active group . A statistically significant difference ( p = 0.05 ; Mann-Whitney test ) in favor of the active group ( n = 10 ) could be shown for drug consumption during the second year , as well as a significant improvement as compared to the first year of SLIT ( p = 0.05 ; Wilcoxon test ) . CONCLUSIONS Despite the small number of patients , our data suggest that SLIT with a grass pollen extract is well tolerated in children and is able to significantly reduce drug consumption during the second year of treatment . Studies in larger groups of children sensitized to both grass and tree pollens are needed to definitively assess the role of SLIT in intermittent , seasonal rhinitis and pollen asthma Background Immunotherapy is a recognized treatment for allergic respiratory diseases BACKGROUND Sublingual immunotherapy ( SLIT ) is considered safer and more convenient than subcutaneous therapy and therefore has been proposed as especially suitable for children and in primary care . Most efficacy studies in children lack power to be conclusive , and all have been performed in referral centers . OBJECTIVE To investigate the efficacy of SLIT with grass pollen allergen in children and adolescents with rhinoconjunctivitis in a primary care setting . METHODS Youngsters aged 6 - 18 years with hay fever were enrolled from general practice s and r and omly assigned to receive placebo or grass pollen mix for 2 years . The primary outcome was the mean daily total symptom score ( scale 0 - 15 ) comprising sneezing , itching nose , watery running nose , nasal blockage , and itching eyes during the months May-August of the second treatment year . RESULTS Out of 204 youngsters r and omized , 168 entered the intention-to-treat analysis ( 91 verum , 77 placebo ) . The mean daily total symptom score did not differ between participants allocated to verum and those allocated to placebo ( difference for verum minus placebo : -0.08 , 95%CI , -0.66 - 0.50 ; P = .78 ) . No differences were found for rescue medication-free days , disease-specific quality of life , and overall evaluation of the treatment effect . Local side effects were more frequent in the verum group ( 39 % vs 17 % of participants ; P = .001 ) . CONCLUSION Sublingual immunotherapy with grass pollen in a primary care setting is not effective in children and adolescents . CLINICAL IMPLICATION S Currently , SLIT can not be recommended for general practitioners as a therapeutic modality in youngsters with grass pollen allergy BACKGROUND Sublingual immunotherapy is well tolerated and data suggest its effectiveness for the treatment of allergic rhinitis in adults , but it lacks optimum dose definition . OBJECTIVE To assess the efficacy , safety , and optimal dose of grass pollen tablets for immunotherapy of patients with allergic rhinoconjunctivitis . METHODS In this multinational , r and omized , double-blind , placebo-controlled study , 628 adults with grass pollen rhinoconjunctivitis ( confirmed by positive skin prick test and serum-specific IgE ) received 1 of 3 doses of a st and ardized 5-grass pollen extract , or placebo , administered sublingually using a once-daily tablet formulation . The treatment was initiated 4 months before the estimated pollen season and continued throughout the season . The primary outcome was Rhinoconjunctivitis Total Symptom Score ; secondary outcomes included 6 individual symptom scores , rescue medication use , quality of life , and safety assessment s. RESULTS Both the 300-index of reactivity ( IR ) and 500-IR doses significantly reduced mean Rhinoconjunctivitis Total Symptom Score ( 3.58 + /- 3.0 , P = .0001 ; and 3.74 + /- 3.1 , P = .0006 , respectively ) compared with placebo ( 4.93 + /- 3.2 ) in the intent-to-treat and per- protocol analyses . The 100-IR group ( 4.70 + /- 3.1 ) score was not significantly different from placebo . Analysis of all secondary efficacy variables ( sneezing , runny nose , itchy nose , nasal congestion , watery eyes , itchy eyes , rescue medication usage , and quality of life ) confirmed the efficacy of the 300-IR and 500-IR doses . No serious side effects were reported . CONCLUSION In the first pollen season , the efficacy and safety of sublingual immunotherapy with grass tablets was confirmed . The 300-IR and 500-IR doses both demonstrated significant efficacy compared with placebo . CLINICAL IMPLICATION S The risk-benefit ratio favors the use of 300-IR tablets for clinical practice Background Previous studies suggest that sublingual immunotherapy ( SLIT ) represents a safer alternative to injection immunotherapy but equivalent efficacy is yet to be confirmed BACKGROUND Sublingual immunotherapy ( SLIT ) is a recognized and safe treatment for allergic rhinitis and conjunctivitis . The aim was to evaluate the efficacy and safety of tablets for grass and rye pollen- induced rhinitis and conjunctivitis . METHODS A double-blind , r and omized , placebo-controlled trial was carried out over 9 months . 105 patients received a st and ardized grass/rye mix extract or a placebo using sublingual drops during the build-up phase . Drops were replaced by sublingual tablets during the maintenance phase ( 300 IR/daily ) . RESULTS In patients that received active treatment , a significantly lower total symptom score ( rhinitis and conjunctivitis ) compared to the placebo group was observed ( p = 0.038 ) . The investigators ' assessment revealed a significant improvement in favor of the active treatment group ( p = 0.018 ) . Skin reactivity to grass and rye pollen was significantly reduced in the active treatment group ( p < 0.05 ) . No statistical difference was observed between the two groups for serum-specific IgG4 levels . Side effects were local and mild , and no severe systemic reactions were reported . CONCLUSION This study indicates that tablet-based sublingual immunotherapy was safe and significantly improved grass/rye pollen-induced rhinoconjunctivitis symptoms . It was also associated with a significant inhibition of the immediate skin response The efficacy and safety of five-grass pollen 300IR sublingual immunotherapy ( SLIT ) tablets ( Stallergènes SA , France ) have previously been demonstrated in paediatric patients . This report presents additional data concerning efficacy at pollen peak , efficacy and safety according to age , nasal and ocular symptoms , use of rescue medication , satisfaction with treatment and compliance . Children ( 5 - 11 yr ) and adolescents ( 12 - 17 yr ) with grass pollen-allergic rhinoconjunctivitis were included in a multinational , r and omized , double-blind , placebo-controlled study and received either a 300IR five-grass pollen tablet or placebo daily in a pre- ( 4 months ) and co-seasonal protocol . The severity of six symptoms ( sneezing , rhinorrhoea , nasal congestion , nasal and ocular pruritis , and tearing ) was scored , and rescue medication use was recorded daily during the pollen season . Patient satisfaction was recorded at the season end . A total of 161 children and 117 adolescents were evaluated ( n = 267 ) . 300IR SLIT was effective over the whole season ( p = 0.0010 ) and at the pollen peak ( p = 0.0009 ) . The adjusted mean difference between 300IR and placebo groups was significant for both nasal ( p = 0.0183 ) and ocular ( p < 0.0001 ) symptoms . Rescue medication use was statistically lower in the SLIT group during the pollen season and at the pollen peak ( both p < 0.05 ) . More patients in the SLIT group were satisfied with their treatment compared to placebo ( 83.2 % vs. 68.1 % , p = 0.0030 ) , and compliance was high ( SLIT 93.9 % of patients were compliant , placebo 94.8 % of patients were compliant ) . SLIT was well tolerated by children and adolescents . 300IR five-grass pollen tablets are effective and safe during the pollen season and at the pollen peak in children and adolescents with grass pollen rhinoconjunctivitis Background : Sublingual immunotherapy ( SLIT ) allergy vaccines have an excellent safety profile , but opinions vary on their efficacy , and treatment regimens are often lengthy . This study assessed the effects of the Toll-like receptor 4 agonist monophosphoryl lipid A ( MPL ® ) on safety/tolerability and clinical and immunological efficacy when combined with grass pollen SLIT formulations in treating patients with seasonal allergic rhinitis . This is the first reported study of adjuvanted SLIT . Methods : In this double-blind placebo-controlled phase I/IIa study , 80 grass pollen-sensitive subjects were r and omized into 4 groups of 20 subjects to receive daily treatment for 8 weeks . Sixteen patients per group received SLIT and 4 received placebo . The formulation given to each group varied with respect to grass pollen extract and MPL content . Grass allergen nasal challenge tests ( NCTs ) were performed prior to dosing and in weeks 4 and 10 . Grass pollen-specific immunoglobulin G ( IgG ) and IgE antibodies were measured at baseline and prior to dosing in weeks 2 , 3 , 4 , 5 and 10 . Results : Local and systemic adverse events were generally comparable for patients who received active treatment and placebo . Patients in the 2 groups given SLIT containing the highest amount of MPL experienced the highest proportion of negative NCTs after 10 weeks ( 47 and 44 % , vs. 20 % with placebo ) . These patients also showed earlier median increases in specific IgG and smaller increases in IgE levels than those receiving other formulations . Conclusions : These results suggest that SLIT preparations containing MPL are well tolerated and alter the immunological response to grass antigens after 3 weeks of exposure , with an associated suppression of nasal challenge responses Induction of allergen-specific , tolerogenic , IL-10 and /or TGF-β-producing T-regulatory ( Treg ) cells that express transcription factor FOXP3 is considered as one of the key mechanisms of allergen-specific immunotherapy . However , little is known of the induction of FOXP3 expression in children during sublingual immunotherapy ( SLIT ) . Recently , also , a novel subgroup of T-helper ( Th ) cells , the Th17 cells , secreting predominantly IL-17 ( IL-17A ) , was identified . The expressions of IL-17 or the Th17-regulating cytokines IL-23 and IL-27 during SLIT are currently completely unexplored . This r and omized , placebo-controlled dose-response study was performed to analyze the effects of SLIT on FOXP3 , IL-17 , IL-23 , and IL-27 expressions in peripheral blood mononuclear cells ( P BMC ) of children with allergic rhinitis and their associations with clinical outcome . Thirty children were included : ten received SLIT with a glycerinated mixture of birch , hazel and alder with a cumulative weekly dose of 24,000 SQ-U , 10 with dose 200,000 SQ-U/wk , and ten received placebo . Cytokine and FOXP3 mRNA expressions in allergen- , purified protein derivative-stimulated and non-stimulated P BMC were determined at 0 , 1 and 2 yr of SLIT by real-time RT-PCR ( TaqMan ) . Symptoms and medications were recorded using diary cards . Allergen-induced IL-17 mRNA expression was significantly increased in the study subjects with elevated combined Symptom Medication Score ( SMS ) after 2 yr . There was also a significant positive correlation between the allergen-induced IL-17 and SMS in whole study group ( r = 0.38 , p = 0.039 ) and especially the 200,000 SQ-U dose-treated group ( r = 0.74 , p = 0.027 ) at 2 yr . Allergen-induced FOXP3 mRNA expression was significantly increased in the 200,000 SQ-U dose-treated children after two study years as compared with baseline ( p = 0.016 ) and placebo-treated children ( p = 0.028 ) . The changes in FOXP3 mRNA expression positively correlated with IL-10 and TGF-β mRNAs during SLIT in whole study population . Increased allergen-induced IL-17 responses during SLIT are associated with elevated SMS . Increased tolerogenic , allergen-specific Treg responses are also observed in children during SLIT BACKGROUND Sublingual-swallow immunotherapy was recently recognized in the World Health Organization Position Paper ( Allergen immunotherapy : therapeutic vaccines for allergic diseases ) " as a viable alternative to parenteral injection therapy to treat allergic diseases " in adults . More controlled studies were required to assess the efficacy and safety of this treatment in children . OBJECTIVE This study was carried out to assess the clinical efficacy and safety profile of sublingual-swallow immunotherapy with high-dose allergen in children with allergies . METHODS We used a double-blind placebo-controlled design . Forty-one children with Parietaria -induced rhinoconjunctivitis were r and omized to receive sublingual st and ardized Parietaria judaica extract ( n = 20 ) or placebo ( n = 21 ) for 2 years . The cumulative dose of allergen was 375 times higher than that used in parenteral immunotherapy and the cumulative dose of Par j 1 major allergen was 52.5 mg over 2 years . The main efficacy assessment criteria were symptoms and rescue medication scores recorded on the patients ' diary cards . Secondary criteria were changes in skin and conjunctival specific reactivity as well as blood parameters , analyzed after 1 and 2 years of immunotherapy . The safety of the treatment was assessed by evaluating the frequency and severity of adverse effects . RESULTS A significant reduction in rhinitis symptoms was observed in the active treatment group during the second season ( P = .02 ) , with no difference in medication scores . A significant decrease in skin reactivity ( P = .002 after 2 years of treatment ) and an increase in the threshold dose for conjunctival allergen provocation test ( P = .02 ) were observed in the active treatment group compared with the group receiving placebo . A significant increase in specific IgG(4 ) levels ( P = .02 ) was also observed in the active group . Immunotherapy was well tolerated . CONCLUSION Sublingual-swallow immunotherapy in Parietaria -allergic children provided a clinical benefit and a decreased specific reactivity to the allergen . The safety profile of this treatment , which constitutes an important issue , indicated good tolerance and compliance The aim of this double-blind placebo-controlled study was to evaluate the efficacy and tolerability of short-term birch pollen sublingual immunotherapy . Forty-one patients suffering from allergic rhinoconjunctivitis caused by Betula alba were included . Exclusion criteria were the following : undergoing immunotherapy within the last 2 years , contraindications to immunotherapy , pregnancy and nursing . The treatment schedule comprised a 28-day basic course , followed by a 3-month maintenance treatment . The evaluation of the parameters was performed before treatment and 4 months after the last maintenance dose . Skin prick test and conjunctival provocation test ( CPT ) in a dilution series were carried out to determine the threshold of the reaction . The objective parameters used were the diameter of the skin wheals and the lowest concentration , of the allergen extract to induce the symptoms of itching and reddening of the eyes . The allergic reaction in general was evaluated with the help of a 2-h birch pollen challenge in the Vienna Challenge Chamber ( VCC ) ; nasal flow and resistance was measured by rhinomanometry ; and nasal secretion was quantified by weighing used h and kerchiefs . Bronchial reactions were objectified by spirometry ; subjective symptoms of the eyes , the nose and the bronchial tract were documented by the patients via a visual analog scale . Birch pollen specific IgE and IgG were evaluated by monoclonal antibody enzyme immunoassay before ( T0 ) and after ( T1 ) treatment . For statistics p < 0.05 was applied . At T0 there was no decisive difference in the in vitro and in vivo results between the two groups . After the treatment period ( T1 ) , actively treated patients showed a significantly higher tolerance to the birch pollen CPT ( p < 0.01 ) . The skin reaction was significantly lower than in the placebo group . Furthermore , actively treated patients produced less than half of the nasal secretion of placebo-treated patients during the challenge session . The rhinomanometry analysis during the challenge showed significant differences for verum and placebo in favor of the actively treated patients ( p = 0.033 ) . There was no significant difference in the specific IgE and IgG concentrations . The side effects and compliance during the treatment were comparable in both groups . In conclusion , sublingual immunotherapy is a well tolerated and clinical ly effective method of treatment BACKGROUND Sublingual immunotherapy ( SLIT ) is increasingly being used for the treatment of allergic rhinitis , but there are conflicting study results demonstrating clinical ly relevant efficacy . OBJECTIVE To show clinical efficacy and safety of a new high-dose grass pollen preparation for SLIT . METHODS In a 2-year , double-blind , placebo-controlled trial , 185 subjects with rhinitis or rhinoconjunctivitis , with or without asthma , were treated with a recently developed , high-dose , 6-grass pollen mixture for SLIT once daily . RESULTS The primary end point , a combined symptom-medication score , showed almost no change in the placebo group during a 42-day evaluation period in the grass pollen season from 2003 to 2005 , whereas active treatment was associated with a significant and clinical ly relevant improvement ( full analysis set , P = .01 ; main data set , P = .002 ) . The effect was irrespective of asthma diagnosis . Allergen-specific IgE showed no difference in both groups , and specific IgG4 and IgG1 increased with active treatment in the first and second study years compared with placebo , clearly indicating the immunogenic effect of the active treatment . The SLIT was well tolerated . No serious adverse drug reactions occurred . CONCLUSIONS High-dose , sublingual , specific immunotherapy with an extract of a 6-grass pollen mixture showed a significant and clinical ly relevant improvement in subjects with grass pollen-associated rhinitis or rhinoconjunctivitis , with or without asthma . The treatment with the sublingual solution was well tolerated BACKGROUND The main aim of specific immunotherapy is sustained effect due to changes in the immune system that can be demonstrated only in long-term trials . OBJECTIVE To investigate sustained efficacy and disease modification in a 5-year double-blind , placebo-controlled trial , including 2 years of blinded follow-up after completion of a 3-year period of treatment , with the SQ-st and ardized grass allergy immunotherapy tablet , Grazax ( Phleum pratense 75,000 SQ-T/2,800 BAU,(∗ ) ALK , Denmark ) or placebo . METHODS A r and omized , double-blind , placebo-controlled , multinational , phase III trial included adults with a history of moderate-to-severe grass pollen-induced allergic rhinoconjunctivitis , with or without asthma , inadequately controlled by symptomatic medications . Two hundred thirty-eight participants completed the trial . End points included rhinoconjunctivitis symptom and medication scores , combined scores , asthma symptom and medication scores , quality of life , days with severe symptoms , immunologic end points , and safety parameters . RESULTS The mean rhinoconjunctivitis daily symptom score was reduced by 25 % to 36 % ( P ≤ .004 ) in the grass allergy immunotherapy tablet group compared with the placebo group over the 5 grass pollen seasons covered by the trial . The rhinoconjunctivitis DMS was reduced by 20 % to 45 % ( P ≤ .022 for seasons 1 - 4 ; P = .114 for season 5 ) , and the weighted rhinoconjunctivitis combined score was reduced by 27 % to 41 % ( P ≤ .003 ) in favor of active treatment . The percentage of days with severe symptoms during the peak grass pollen exposure was in all seasons lower in the active group than in the placebo group , with relative differences of 49 % to 63 % ( P ≤ .0001 ) . Efficacy was supported by long-lasting significant effects on the allergen-specific antibody response . No safety issues were identified . CONCLUSION The results confirm disease modification by SQ-st and ardized grass allergy immunotherapy tablet in addition to effective symptomatic treatment of allergic rhinoconjunctivitis Background : Allergic rhinitis ( AR ) impairs quality of life ( QoL ) , sleep and work . The Allergic Rhinitis and its Impact on Asthma ( ARIA ) classification is widely used , but the impact of the different symptoms on QoL is not clear . Objective : To describe characteristics of patients consulting in primary care for AR and to study the impact of AR symptoms and the ARIA classes on QoL. Methods : A multicenter prospect i ve observational cross-sectional study assessed the visual analogue scale ( VAS ) in the management of AR in 990 patients consulting general practitioners for AR . Patients were classified according to the four classes of ARIA . VAS , Rhinoconjunctivitis Quality of Life Question naire ( RQLQ ) and total symptom score ( TSS ) for nasal and non-nasal symptoms were evaluated . VAS and TSS measures were compared with RQLQ . Results : Mild intermittent rhinitis was diagnosed in 20 % of patients , mild persistent rhinitis in 17 % , moderate/severe intermittent rhinitis in 15 % and moderate/severe persistent rhinitis in 48 % . The presence of treatments did not affect VAS levels . Both severity and duration of rhinitis had an impact on QoL and VAS levels . Ocular symptoms ( OR : 2.78 , 95 % CI : 1.965–3.939 ) including eyelid edema ( OR : 2.07 , 95 % CI : 1.274–3.360 ) and asthenia ( OR : 2.73 , 95 % CI : 1.922–3.877 ) had more impact on RQLQ than nasal obstruction ( OR : 1.61 , 95 % CI : 1.078–2.405 ) and nasal pruritus ( OR 1.45 , 95 % CI : 1.028–2.042 ) . Sneezing and rhinorrhea did not impact RQLQ . Conclusions : This study confirmed that ocular symptoms and , to a lesser degree , nasal obstruction and pruritus have a significant impact on BACKGROUND AND OBJECTIVE The orodispersible house dust mite ( HDM ) sublingual immunotherapy (SLIT)-tablet ( ALK , Denmark ) is being developed for the treatment of HDM respiratory allergic disease . The objective of the 2 phase I trials was to investigate tolerability and the acceptable dose range of HDM SLIT-tablet treatment in adults and children with HDM respiratory allergic disease . PATIENTS AND METHODS The trials were r and omized , multiple-dose , dose-escalation , double-blind , placebo-controlled phase I trials including patients with HDM-induced asthma , with or without rhinoconjunctivitis . Both trials were registered in EudraCT ( Trial 1 : 2005 - 002151 - 41 ; Trial 2 : 2007 - 000402 - 67 ) . Trial 1 included 71 adults ( 18 - 63 years ) and trial 2 included 72 children ( 5 - 14 years ) . Both trials included 6 dose groups that were r and omized 3:1 to active treatment or placebo once daily for 28 days . Adverse events ( AEs ) were coded in MedDRA ( version 8.1 or later ) . Immunological variables included specific IgE and IgE-blocking factor . RESULTS No serious AEs were reported . In trial 1 ( maximum dose , 32 development units [ DU ] ) , 1 patient in the 16 DU group discontinued due to AEs . The entire 32 DU group was discontinued as 1 patient had a severe adverse reaction . In trial 2 ( maximum dose , 12 DU ) , no patients discontinued prematurely . The most frequently reported AEs were mild application-site related events . The total number of events was dose-related within each trial . HDM SLIT-tablet treatment induced changes in immunological parameters in a dose-dependent manner . CONCLUSIONS These trials demonstrate that doses up to 12 DU of HDM SLIT-tablet were tolerated in the selected population s , and thus are suitable for further clinical investigations in adults and children with HDM respiratory allergic disease Background : The use of immunotherapy in asthmatic children is still controversial . Sublingual immunotherapy ( SLIT ) may represent an advance , due to the good safety profile , but little is known about its effects on lung function and nonspecific bronchial responsiveness BACKGROUND Preliminary studies have suggested the efficacy of sublingual tablets of house dust mite ( HDM ) extracts in adults with allergic rhinitis . OBJECTIVES We sought to assess the efficacy and safety of 2 doses of HDM sublingual tablets over 1 treatment year and the subsequent immunotherapy-free year . METHODS Adults with HDM-associated allergic rhinitis were r and omized in a double-blind , placebo-controlled study to receive 500 index of reactivity ( IR ) tablets , 300IR tablets , or placebo administered once daily for 1 year and were followed for the subsequent year . The primary efficacy variable was the Average Adjusted Symptom Score over the year 1 primary period ( ie , October 1 to December 31 ) . Symptoms and rescue medication scores , onset of action , patient-reported outcomes , and safety were secondary variables . The same end points were evaluated during the immunotherapy-free year . The primary efficacy end point was analyzed by using analysis of covariance . RESULTS Five hundred nine participants were r and omized , and 427 continued in the immunotherapy-free year . Both the 500IR and 300IR HDM sublingual tablets significantly reduced mean Average Adjusted Symptom Scores compared with placebo by -20.2 % ( P = .0066 ) and -17.9 % ( P = .0150 ) , respectively . Efficacy of both doses was maintained during the treatment-free follow-up phase . The onset of action was at 4 months . Participants ' global evaluation of treatment success was significantly higher in the 500IR and 300IR groups compared with the placebo group ( P = .0206 and P = .0001 , respectively ) . Adverse events were generally application-site reactions . There were no reports of anaphylaxis . CONCLUSIONS Twelve months of treatment with 500IR and 300IR sublingual tablets of HDM allergen extracts was efficacious and well tolerated . Efficacy was maintained during the treatment-free follow-up year BACKGROUND Biomarkers that enable objective evaluation of the clinical effects of immunotherapy for allergic rhinitis have yet to be identified . METHODS This study included 40 patients who were enrolled in a large r and omized , double-blind , placebo-controlled , multicenter study examining the efficacy of sublingual immunotherapy ( SLIT ) using Japanese cedar ( JC ) pollen extract during two consecutive pollen seasons from 2010 to 2012 . Based on changes in total nasal symptom medication score , patients in the SLIT and placebo groups were subdivided into two subgroups : good responders and poor responders . The levels of JC pollen-specific IL-10+Foxp3 + cells and specific Th2 cytokine-producing cells were measured and the association with the efficacy of SLIT was analysed . RESULTS The total nasal symptom medication score was significantly lower in the SLIT group compared with the placebo group . The number of JC pollen-specific Th2 cytokine-producing cells increased during the pollen season in the placebo group and in poor responders in the SLIT group ; however , the increases were inhibited in the good responders in the SLIT group . The number of JC pollen-specific IL-10+Foxp3 + cells increased only in these good responders . CONCLUSIONS Changes in levels of allergen-specific Th2 cytokine-producing cells and IL-10+Foxp3 + cells could be objective biomarkers for SLIT Background : New routes of administering immunotherapy in respiratory allergy are being studied as an alternative to conventional injective immunotherapy . We carried out a study to evaluate the clinical efficacy and effects of sublingual immunotherapy in patients with Parietaria judaica‐induced respiratory allergy For evaluation of the efficacy and the safety of specific sublingual immunotherapy with high allergen dose , 66 children with seasonal asthma , rhinitis , and conjunctivitis due to sensitization to olive pollen were enrolled in a double‐blind , r and omized , placebo‐controlled study between October 1994 and October 1996 in Greece . Thirty‐four patients were r and omly allocated to the active group , and 32 received placebo . Immunotherapy consisted of olive‐allergen extracts ( Stallergenes SA ) administered sublingually pre‐ and coseasonally from January to July for 2 consecutive years . Serial concentrations from 1 to 300 IR were used up to the maintenance dose of 20 drops of 300 IR daily . The cumulative dose for each patient was 300 times higher than in parenteral immunotherapy , and the cumulative dose of the major allergen Ole e 1 was 8.1 mg/2 years . The patients were assessed by clinical parameters ( symptom and medication scores from patients ' daily diaries ) and immunologic measurements ( specific IgE. lgG4 . eosinophil cationic protein [ ECP ] ) were performed . The actively treated patients had a significantly lower score for dyspnea ( P<0.04 during the first season ; P<0.03 during the second season ) . At the poUinic peak during the second year , a lower score of conjunctivitis was recorded ( P<0.05 ) in the actively treated patients . The analysis of intragroup evolution showed that the total score of rhinitis increased significantly during the pollinic peak in the group under placebo , whereas there was no symptomatic peak for the same period in the group under active treatment . However , the difference between the groups was not significant . The medication score did not differ significantly between the groups . Oral steroids were the only variables with a P value near the significance level ( P=0.06 ) in favor of the actively treated group . A significant decrease in skin reactivity was recorded in the active group after 2 years of treatment . No significant variation in specific IgE and IgG4 was detected . A significantly lower level of serum ECP was observed at the pollinic peak in the actively treated patients during the first pollen season ( P=0.01 ) , but this was not confirmed the second year when the ECP levels doubled in both groups without correlation to the clinical findings . Tolerance was excellent with only a few minor side‐effects reported . In conclusion , high‐dose specific sublingual immunotherapy appears to be safe and effective in improving mild seasonal asthma and conjunctivitis linked to olive‐pollen sensitization BACKGROUND In a natural field study , sublingual tablets of house dust mite ( HDM ) allergen extracts ( STG320 ) were efficacious in treating HDM-associated allergic rhinitis . OBJECTIVES We sought to assess the efficacy and safety of 3 doses of STG320 in an environmental exposure chamber . METHODS In this r and omized , double-blind study , adults with HDM-associated allergic rhinitis were given a daily sublingual tablet containing placebo or STG320 at a dose of 500IR , 300IR , or 100IR ( IR , index of reactivity ) for 6 months . Participants recorded their rhinitis symptoms during 4-hour HDM EEC challenges at r and omization and months 1 , 2 , 4 , and 6 . The primary efficacy end point was the change from baseline to end of treatment in the area under the curve of the rhinitis total symptom score ( ChBLAUCRTSS 0 - 4h ) . Differences from the placebo group were analyzed by analysis of covariance . Adverse events ( AEs ) and routine safety parameters were recorded . RESULTS A total of 355 subjects were r and omized to 1 of 4 groups : 500IR ( n = 93 ) , 300IR ( n = 86 ) , 100IR ( n = 89 ) , or placebo ( n = 87 ) . The least squares mean differences from placebo in ChBLAUCRTSS 0 - 4h for the 500IR , 300IR , and 100IR groups indicated a dose-dependent effect , with reductions in symptom scores of 33 % , 29 % , and 20 % , respectively . The most frequent AEs were throat irritation and oral pruritus . There were no reports of anaphylaxis or reports consistent with severe laryngopharyngeal disorders and no use of epinephrine . AEs leading to premature discontinuations were more common in the 500IR group . CONCLUSIONS A dose-dependent effect of sublingual HDM immunotherapy was demonstrated in this environmental exposure chamber study , supporting further development of this treatment OBJECTIVES /HYPOTHESIS To investigate how quickly an allergic rhinitis ( AR ) patients ' symptoms will improve with sublingual immunotherapy ( SLIT ) . STUDY DESIGN Double-blind placebo study . METHODS This is a multicenter , r and omized , double-blind , placebo-controlled study of SLIT used to treat house dust mite-induced AR . A total of 120 AR patients , aged 4 to 60 years , were treated for 6 months and r and omized into two groups : 1 ) SLIT with Dermatophagoides pteronyssinus ( D.p . ) and Dermatophagoides farina ( D.f . ) extract ( n = 60 ) ; and 2 ) matched placebo controls ( n = 60 ) . Symptom , medications received , and a visual analog scale score were recorded during the whole study . Serum-specific IgE and IgG4 to D. p. and D. f. were assessed before and after the treatment . RESULTS Eighty-five patients ( 70.8 % ) completed the study . Twelve patients ( 20 % ) chose to withdraw from the SLIT group , but none because of serious adverse effects . The total symptom and visual analog scores VAS in the SLIT group decreased significantly when compared to the placebo controls ( P < 0.05 ) after week 14 , as well as for the significant ( P < 0.05 ) improvement of all individual AR symptoms in the SLIT group ( e.g. , sneezing , nasal discharge , itching , and nasal obstruction ) after week 22 . There was a significant ( P < 0.05 ) increase of IgG4 to both D.f . and D.p . in the SLIT , but not in the placebo group after treatment . CONCLUSION SLIT with a mixture of D.f . and D.p . extract is an effective and safe treatment for patients with house dust mite-induced AR . Its onset of action can be observed as early as 14 weeks after treatment BACKGROUND Seasonal allergic rhinitis ( SAR ) induced by Japanese cedar pollen is a substantial problem in Japan . Sublingual immuno-therapy ( SLIT ) is safer than conventional antigen-specific immunotherapy , the only treatment modality by which complete cure of the disease can be expected . We investigated the safety and efficacy of SLIT in the treatment of cedar pollinosis patients compared to placebo . METHODS A r and omized , placebo-controlled , double-blind study was conducted in 61 cedar pollinosis patients . Increasing doses of st and ardized Japanese cedar extract or placebo were administered sublingually in intervals ranging from daily to once a week after six weeks . The primary efficacy variable was the mean of the daily total symptom scores ( TSS ) during the pollen dispersing period . Secondary efficacy variables included the QOL scores and related variables . RESULTS Primary efficacy variable scores were significantly lower for some days in the SLIT group than in the placebo group ( P < .01 or P < .05 ) . Secondary efficacy for the QOL score in SLIT group was almost of half of placebo group . There was no significant difference in the overall incidence of side effects between the SLIT group and the placebo group . CONCLUSIONS SLIT was effective and safe in the treatment of cedar pollinosis Background : The efficacy and safety of sublingual immunotherapy ( SLIT ) in patients with chronic rhinitis related to sensitization to house dust mites are still controversial BACKGROUND Sustained and disease-modifying effects of sublingual immunotherapy have never before been confirmed in a large-scale r and omized , double-blind , placebo-controlled trial . OBJECTIVE We sought to investigate sustained efficacy 1 year after a 3-year period of daily treatment with the SQ-st and ardized grass allergy immunotherapy tablet Grazax ( Phleum pratense 75,000 SQ-T/2,800 BAU ; ALK-Abelló , Hørsholm , Denmark ) . METHODS A r and omized , double-blind , placebo-controlled , phase III trial including adults with a history of moderate-to-severe grass pollen induced rhinoconjunctivitis inadequately controlled by symptomatic medications . The analysis set comprised 257 subjects at the follow-up . Efficacy end points were rhinoconjunctivitis symptom and medication scores , quality of life , and percentages of symptom and medication free days . Immunologic end points included grass pollen-specific serum IgG4 and IgE-blocking factor . Safety was assessed based on adverse events . RESULTS Significant improvements in efficacy were consistently shown during 3 years ' treatment . One year after treatment , the active group showed sustained reductions in mean rhinoconjunctivitis symptom scores ( 26 % , P < .001 ) and medication scores ( 29 % , P = .022 ) when compared with placebo . This level was similar to the efficacy observed during the 3-year treatment period . The differences in percentages of symptom- and medication-free days were significant during and 1 year after treatment . The active group also reported sustained and significant improvements in quality of life . Sustained clinical benefit was accompanied by immunologic changes . No safety issues were identified . CONCLUSION Three years of treatment with the SQ-st and ardized grass allergy immunotherapy tablet result ed in consistent clinical improvement and accompanying immunologic changes that were sustained 1 year after treatment , which is indicative of disease modification and associated long-term benefits The effect of sublingual immunotherapy on quality of life ( QoL ) was examined in patients with grass pollen-induced rhinoconjunctivitis . Patients ( n = 855 ) were r and omised to once-daily grass allergen tablets ( 2,500 ; 25,000 ; or 75,000 SQ-T Phleum pratense extract ; GRAZAX ® ) or placebo . Treatment was initiated 8 weeks before the start of the grass pollen season and continued throughout . If symptoms were present , patients received loratadine or placebo rescue medication . There were three major findings : in patients using loratadine , grass allergen tablets provided QOL benefits over placebo ; Rhinoconjunctivitis Quality of Life Question naire ( RQLQ ) score was 17 % ( p = 0.006 ) and 20 % ( p = 0.020 ) greater with 75,000 SQ-T tablet than with placebo at first and second seasonal visit , respectively ; in patients not using loratadine , grass allergen tablets improved QoL more than placebo ; RQLQ score was 21 % greater ( p = 0.021 ) with 75,000 SQ-T tablet at second seasonal visit ; grass tablets ( without loratadine ) had a greater effect on QoL than loratadine alone . RQLQ score was 26 % ( p = 0.014 ) greater with 75,000 SQ-T tablets than loratadine at second seasonal visit . These data show that sublingual immunotherapy with grass allergen tablets improves QOL in allergic rhinoconjunctivitis , reduces symptoms , and that this effect is greater than rescue antihistamine alone BACKGROUND In North America , few studies have evaluated sublingual immunotherapy for allergic rhinitis with or without conjunctivitis ( AR/C ) ; pediatric data are sparse . The authors report findings from the largest published immunotherapy trial yet conducted in adults and children . OBJECTIVE To evaluate grass sublingual immunotherapy tablet ( MK-7243 ) treatment in subjects with AR/C. METHODS North American subjects ( 5 - 65 years old ) with grass allergy were r and omized 1:1 to once-daily MK-7243 ( 2,800 BAU Phleum pratense ) or placebo . The first dose was given at the investigator 's office ; subsequent doses were self-administered at home . The primary end point was total combined score ( TCS ; rhinoconjunctivitis daily symptom score [ DSS ] plus daily medication score [ DMS ] ) over the entire grass pollen season ( GPS ) . Key secondary end points included entire-season DSS , DMS , peak-season TCS , and rhinoconjunctivitis quality -of-life question naire scores . Safety outcomes included adverse events ( AEs ) . RESULTS One thous and five hundred one subjects were r and omized ( 85 % polysensitized , 25 % had asthma ) . MK-7243 yielded improvements vs placebo of 23 % in entire-season TCS ( median difference -0.98 , P < .001 ) , 29 % in peak-season TCS ( median difference -1.33 , P < .001 ) , 20 % in entire-season DSS ( median difference -0.64 , P = .001 ) , 35 % in entire-season DMS ( mean difference -0.48 , P < .001 ) , and 12 % in peak-season rhinoconjunctivitis quality -of-life question naire ( median difference -0.13 , P = .027 ) . Efficacy between children and adults was similar . Most AEs were transient local application-site reactions , with no serious treatment-related AEs or anaphylactic shock . Three subjects ( 1 placebo , 2 MK-7243 ) had moderate systemic allergic reactions . CONCLUSION MK-7243 was effective in polysensitized grass-allergic North American children and adults with AR/C in this large trial , confirming previous research Although several studies have demonstrated the efficacy of subcutaneous immunotherapy in allergic asthma , few have shown the same benefit using sublingual immunotherapy ( SLIT ) in asthmatic patients . This study was conducted to assess the efficacy of house dust mite ( HDM ) SLIT in addition to allergen avoidance and st and ard pharmacologic treatment . A double-blind , placebo-controlled trial was performed in 111 children ( aged 5 - 15 yr ) with HDM-induced mild-to-moderate asthma . After a 4-week baseline phase , patients were r and omly assigned to receive SLIT with tablets of HDM extract ( n = 55 ) or placebo ( n = 56 ) for 18 months . Pharmacologic treatment was adjusted every 3 months following a step-down approach . Asthma symptom scores , reduction in use of inhaled corticosteroids and inhaled beta(2)-agonists , rhinitis symptoms , lung function tests , skin sensitivity to HDM , dust mite-specific immunoglobulin ( Ig ) E and IgG(4 ) , and quality of life ( QoL ) were assessed during the study . After 18 months of treatment , diurnal and nocturnal asthma symptoms scores did not show significant differences between SLIT and placebo groups . Inhaled corticosteroids and inhaled beta(2)-agonists use was reduced in both groups without significant differences between groups . There were no significant differences in lung function ( forced expiratory volume in 1 s and peak flow rate variations ) between groups . Rhinitis symptom score decreased in both groups , with no difference between the two groups . The severity dimension of QoL was significantly improved in the SLIT group ( age 6 - 12 yr ) . SLIT induced a significant reduction of skin sensitivity to HDM ( p < 0.01 ) and a significant increase in HDM-specific IgE and IgG(4 ) antibodies ( p < 0.001 ) in the SLIT group compared with the placebo group . SLIT was well tolerated with mild/moderate local adverse events . No severe systemic reactions were reported . This study indicates that , when mild-moderate asthmatic children are optimally controlled by pharmacologic treatment and HDM avoidance , SLIT does not provide additional benefit , despite a significant reduction in allergic response to HDM . Under such conditions , only a complete , but ethically unfeasible , discontinuation of inhaled corticosteroid would have demonstrated a possible benefit of SLIT Objective This study was design ed to evaluate the efficacy and safety of sublingual immunotherapy ( SLIT ) with house-dust mite ( HDM ) extract in Chinese patients with HDM-induced allergic rhinitis ( AR ) . Methods A r and omized , double-blind , placebo controlled trial was conducted with the out patients of the Eye , Ear , Nose , and Throat Hospital , Fudan University . Forty-eight patients were eligible for r and omization to SLIT with a mixture of Dermatophagoides pteronyssinus and Dermatophagoides farinae extract or placebo for 1 year . The primary outcome measures for efficacy were the total nasal symptom score ( TNSS ) and the individual nasal symptom score . Secondary end points were allergic conjunctivitis scores ( ACS ) and medication scores ( MS ) . Adverse events ( AE ) also were monitored . Results Intragroup analysis demonstrated a significant improvement in the active treatment group for individual nasal symptom score and TNSS ( p < 0.05 ) , although no improvement was observed in the placebo group of congestion , sneezing , and itching ( p > 0.05 ) . Furthermore , the ACS and MS in the active treatment group also statistically decreased ( p < 0.05 ) . In addition , the active treatment had significant effects on relieving nasal symptoms both in adults and children ( p < 0.05 ) , and no statistical difference was observed between these two subgroups ( p > 0.05 ) . AEs that occurred ranged from mild to moderate , and no severe systematic reactions were observed . Conclusion SLIT with a mixture of HDM extract significantly relieved allergy symptoms and reduced the need for antiallergic drugs , which indicated the superiority of active treatment over placebo for patients with HDM-induced AR . However , due to the limited sample size , the findings need to be further confirmed Background This study evaluates the safety and efficacy of specific sublingual immunotherapy ( SLIT ) against grass pollen allergens in patients > 60 years of age with seasonal allergic rhinitis ( SAR ) and /or asthma . This study sought to assess nasal symptoms during the grass pollen season , reduce medication use , and monitor adverse reactions during immunotherapy . Methods Seventy-eight 60- to 70-year-old patients with SAR and a confirmed grass pollen allergy according to skin-prick tests , nasal provocation , and measurement of serum IgE were included in the study . The patients were individually r and omized to the act or placebo groups using a double-blind method . A total of 41 subjects in the SLIT group ( 5 grass pollen mixture ) and 37 subjects in the placebo group were monitored for 3 years . The patients were required to record each use of an antiallergy medication on a diary card . Results Thirty-eight patients completed 3 years ( preseasonal ) of SLIT , and 34 subjects finished the placebo treatment in the same time period . The total nasal symptom score decreased by 64 % in the active group and 7 % in the placebo group a SLIT . This difference was only significant in the active group ( p < 0.05 ) . At the end of therapy , the total medication score of the active group decreased significantly by a maximum of 51 % ( p < 0.05 ) , whereas the total medication score of the placebo group had an insignificant decrease . None of the study participants had systemic adverse reactions during the study period . Conclusions SLIT in elderly patients with a grass pollen allergy generated significant clinical improvement in the active group compared with the placebo group for grass pollen season . This therapy was well tolerated BACKGROUND Seasonal allergic rhinitis is common and troublesome . Sublingual immunotherapy ( SLIT ) has been proposed as an alternative to injection immunotherapy and might offer some advantages if it were effective and practical in a community setting . OBJECTIVES To assess the efficacy and side-effect profile of SLIT in patients with summer hay fever uncontrolled on current st and ard medication . To assess the feasibility of delivering SLIT in a United Kingdom general practice setting . METHODS Double-blind , placebo-controlled study in 186 patients with severe summer hay fever identified from 16 United Kingdom general practice s. After a baseline year to ensure balanced groups , subjects were r and omized , and SLIT was given for 1 or 2 years and compared with placebo . The principal outcome measure was symptoms as recorded on diary cards . Secondary criteria were skin and conjunctival reactivity , allergen-specific IgE and IgG 4 , and the frequency and severity of adverse effects . RESULTS One hundred thirty-six subjects completed the study . After 1 year , no significant differences were found between actively treated subjects and the placebo group . After the second year of therapy , subjects who had received 2 years treatment were 6.8 times more likely to show a reduction in nose running ( P < .001 ) and 2.4 times more likely to have reduced sneezing ( P < .05 ) compared with subjects in the placebo group . Benefits for nasal blockage were found at the peak pollen season and were similar in both actively treated groups . CONCLUSION Sublingual immunotherapy can be given successfully and safely in the community . High-dose SLIT has beneficial effects on nasal symptoms during the peak pollen season in patients with severe seasonal allergic rhinitis . At least 2 years of treatment with SLIT is required to show a benefit Background : Sublingual immunotherapy ( SLIT ) has been demonstrated to be a viable alternative to injection immunotherapy . Administration of high doses of allergens to ensure efficacy has been shown to be well tolerated . The aim of the present study was the first step to address the issue of fast-induction regimens using various induction SLIT regimens in paediatric and adult patients . Methods : Sixty-four patients ( age range 5–46 years ) with grass pollen rhinoconjunctivitis were enrolled in an 8-month double-blind , placebo-controlled trial of SLIT . Sixty-three patients were r and omized to four groups and evaluated at the end of the study . One group received placebo ( n = 16 ) and the other three groups ( n = 47 ) received five grass pollen extracts according to three different induction regimens : regimen 1 starting with 3 IR tablets ( n = 15 ) , regimen 2 starting with 10 IR ( n = 16 ) and regimen 3 starting with 30 IR ( n = 16 ) . The maintenance phase was made with sublingual-swallow drops at the same concentration of 300 IR/ml for all the patients . Adverse events were recorded on diary cards . Results : During induction phase , 25/47 patients in the SLIT groups had adverse reactions in comparison to 2/16 patients in the placebo group ( p < 0.05 ) . The rate of adverse reactions was 33.3 % ( 11.8–61.6 ) ( 95 % CI ) for regimen 1 , 31.3 % ( 11.0–58.7 ) for regimen 2 , 43.8 % ( 19.8–70.1 ) for regimen 3 and 12.5 % ( 1.6–38.3 ) for placebo . Fifty-seven reactions were local reactions involving the oral region ( 54 SLIT , 3 placebo ) and 13 were systemic reactions ( all in the SLIT groups ) . 11/13 reactions were mild ( gastrointestinal disorders , rhinoconjunctivitis ) , 1/13 consisted of moderate asthma and 1/13 consisted of severe abdominal pain . No urticaria , angioedema or life-threatening events were observed . Conclusions : These preliminary data showed that various induction regimens for SLIT are generally well tolerated and could allow a fast build-up phase of SLIT BACKGROUND non-injective routes of immunotherapy in respiratory allergy have being proposed as an alternative to conventional immunotherapy . We carried out a study to evaluate the clinical efficacy and effects sublingual immunotherapy ( SLIT ) in patient with Cupressaceae pollen respiratory allergy . METHODS twenty patients with Cupressaceae pollen ( C. sempervirens ) rhinoconjunctivitis , mild asthma or both were r and omly chosen for sublingual immunotherapy ( 10 patients ) or placebo treatment ( 10 patients ) using a double blind placebo controlled technique . We have used an extract of Cupressus arizonica because of its better stability in solution and its crossreactivity with Cupressus sempervirens . The patients underwent treatment for 12 months ( from april 1999 to april 2000 ) . Symptoms and drug scores as well as nasal provocation tests were recorded . The pollen counts were carried out , during all the same period . RESULTS we found significantly lower symptom scores ( p < 0.05 ) and drug consumption scores ( p < 0.05 ) in the immunotherapy group than in the placebo group , during the pollen season , after the first year of therapy . Besides threshold of allergen reactivity in nasal provocation tests was increased in the active group ( p < 0.01 ) . No untoward reactions have been observed . CONCLUSIONS SLIT with Cupressus arizonica ( pollen extracts ) produced , after one year treatment , a significant improvement of allergic symptoms and a decrease of drug consumption scores and allergen-specific nasal reactivity . SLIT with Cupressus arizonica appeared to be effective and safe in the treatment of Cupressaceae pollen respiratory allergy In a multi-centre , r and omized , double-blind , placebo-controlled clinical trial over 3 years high dose sublingual specific immunotherapy with an extract of a 6-grass-pollen mixture showed a highly significant and clinical ly relevant improvement in patients with grass pollen rhinitis/-conjunctivitis with or without asthma and an increase in allergen specific antibodies ( IgG1 , IgG4 ) indicating immunological efficacy . A difference of 46 % in mean symptom medication score between active and placebo group was seen . The treatment with the sublingual solution was well tolerated . High dose sublingual immunotherapy can therefore be considered as an efficient therapeutic option in the management of IgE-mediated allergic airway diseases BACKGROUND Respiratory allergy due to Alternaria is a relevant clinical problem , and specific immunotherapy may represent a viable treatment option . Sublingual immunotherapy ( SLIT ) is safe and effective , but data for Alternaria are lacking . OBJECTIVE To assess the efficacy of st and ardized SLIT in patients sensitized to Alternaria in a r and omized , prospect i ve , double-blind , placebo-controlled trial . METHODS Patients with rhinitis with or without intermittent asthma and ascertained allergy to Alternaria were enrolled . After a baseline season , SLIT or matched placebo was given for 10 months . Symptoms and rescue medication intake were recorded on diary cards between June and October . Skin prick testing was performed and specific IgE , IgG4 , and precipitin levels were measured at baseline and at the end of the study . RESULTS Twenty-seven patients ( age range , 14 - 42 years ) were r and omized , and 26 completed the study . The baseline characteristics were homogeneous in the 2 groups . After treatment , patients receiving SLIT had a significant improvement in symptoms and a reduction in medication intake vs placebo and vs the run-in season , whereas no change was seen in the placebo group . Skin prick test reactivity significantly decreased only in the SLIT group . No change was seen in specific IgG4 levels in the 2 groups , whereas Alt a 1 specific IgE levels significantly increased in the active group . One patient in the active group reported oral itching and conjunctivitis at the beginning of treatment . CONCLUSION SLIT seems effective and safe and may represent a valuable therapeutic option in respiratory allergy due to Alternaria BACKGROUND Cytokine responses accompanying sublingual immunotherapy ( SLIT ) responder phenotypes have not previously been reported . OBJECTIVE To investigate clinical and cytokine responses of house dust mite ( HDM ) sensitive patients with allergic rhinitis receiving HDM SLIT or placebo for 2 years . METHODS Sixty adults were r and omized to receive SLIT or placebo . Clinical symptoms were measured using the Total 5 Symptom Score ( TSS5 ) and Juniper Rhinitis Quality of Life Question naire . HDM specific IgE , IgG , skin prick tests , and HDM-stimulated release of interleukin ( IL ) 5 and interferon γ ( IFN-γ ) in peripheral blood mononuclear cells was studied at 0 , 6 , 12 , and 24 months and IL-13 , IL-4 , and IL-10 at 0 and 24 months . RESULTS A total of 32 of 39 SLIT and 16 of 21 placebo patients completed the study . There was significant clinical improvement in both the SLIT and placebo groups . Median T5SS decreased from 14.75 to 5.25 in the SLIT group ( P < .001 ) and 12.7 to 6.0 in the placebo group ( P = .003 ) . The median quality -of-life score also decreased in the SLIT group ( P < .001 ) and the placebo group ( P < .001 ) . A subgroup analysis of patients found a 60 % or greater improvement ( on the T5SS and the Juniper Rhinitis Quality of Life Question naire ) in the good responders group and a 30 % to 59 % improvement or no improvement in the intermediate responders group . This subgroup analysis also found more good responders in the SLIT group ( 47 % ) compared with the placebo group ( 25 % ; P = .07 ) . Significant decreases in the IL-5/IFN-γ ( P < .001 ) , IL-13/IFN-γ ( P < .001 ) , and IL-4/IFN-γ ( P = .03 ) ratios were found in the combined good clinical improvement group at 24 months . CONCLUSION A good clinical response ( ≥60 % improvement in both TSS5 and quality of life ) is associated with significant decreases in IL-5 , IL-13 , and IL-4 relative to IFN-γ during 2 years of SLIT therapy for HDMs BACKGROUND The safety and efficacy of high-dose sublingual-swallow immunotherapy ( SLIT ) has been established in pollen rhinoconjunctivitis . This treatment has now been evaluated using an ultra-rush incremental dose regimen with a Juniperus ashei allergen extract in patients allergic to Cupressus sempervirens and Cupressus arizonica . METHODS Patients received either placebo or SLIT . Evaluation of safety was based on the frequency of adverse events during the incremental dose period ( half a day ) and during maintenance therapy ( 4 months ) . Evaluation of efficacy was based on symptom and medication scores at the pollen peak . RESULTS Seventy of the 76 patients included completed the study . There were no drop-outs during the rush procedure . One patient in the active group dropped out during the maintenance therapy due to adverse events : gastric pain and vomiting . There was also 1 drop-out in the placebo group due to pregnancy . Adverse events were infrequent , local and mild . Symptom scores for rhinitis and conjunctivitis were not statistically different between groups , but there was a marked and significant ( p < 0.03 ) decrease of the medication score ( about 50 % ) and nasal steroid consumption ( about 75 % ) in the active treatment group . An increase from baseline of serum IgE and IgG4 J. ashei-specific antibodies was only observed in actively treated patients ( p < 0.04 and p < 0.01 , respectively ) . CONCLUSIONS The tolerability and safety of high-dose ultra-rush SLIT were comparable to those reported in previous SLIT studies . SLIT with J. ashei extract , due to its high Jun a 1 content , significantly reduced nasal steroid consumption in patients allergic to European cypress INTRODUCTION In a double-blind , placebo-controlled trial ( EudraCT identifier : 2006 - 001795 - 20 ) , the st and ardised quality ( SQ ) house dust mite ( HDM ) sublingual immunotherapy (SLIT)-tablet ( ALK , Denmark ) was investigated . METHOD The trial included 604 subjects , ≥14 years , with mild-moderate HDM allergic asthma . Subjects were r and omised 1:1:1:1 to 1 , 3 or 6 SQ-HDM or placebo once daily . The primary endpoint was reduction in inhaled corticosteroid ( ICS ) after one year . ICS reduction , asthma quality of life question naire ( AQLQ ) and asthma control question naire ( ACQ ) score was analysed post hoc in a subgroup with daily ICS use of 400 - 800 μg and ACQ score of 1 - 1.5 , corresponding to partly controlled asthma ( N = 108 ) . RESULTS The trial met its primary endpoint . In the subgroup , the difference between placebo and 6 SQ-HDM in change from baseline in daily ICS use was 327 μg ( p < 0.0001 ) , while it was 0.52 ( p = 0.010 ) for AQLQ . The treatment effect on ICS reduction and AQLQ was increased for the subgroup versus the residual population ( ICS reduction : p < 0.001 ) ; AQLQ : p = 0.044 ) . CONCLUSION In this subgroup , including only patients with partly controlled asthma , the benefit of 1 year of treatment with SQ HDM SLIT-tablet was significantly higher than for the less severe full population , both in terms of increased asthma control and improved quality of life Background : Immunotherapy through local routes is thought to be a valuable therapeutic option for respiratory allergy . We investigated the clinical efficacy and immunologic effects of sublingual immunotherapy ( SLIT ) in asthmatic children with mite‐induced respiratory allergy In a double‐blind placebo‐controlled cross‐over trial , low dose sublingual therapy with house dust mite was effective in relieving symptoms in 72 % of the group of patients with perennial rhinitis due to house dust mite ( P < 0·03 ) . Following active treatment , there was a significant increase in morning peak nasal inspiratory flow rate ( P < 0·01 ) in those who improved ( thirteen out of eighteen ) and resistance to nasal provocation with house dust mite also increased , in some cases up to 1000‐fold ( P < 0·05 ) . Oral therapy is safe and avoids the side effects of desensitizing injections which can be serious . The potential for oral desensitization is great and further studies on this form of treatment are needed Background : Both sublingual allergen‐specific immunotherapy ( SLIT ) and subcutaneous immunotherapy ( SCIT ) have a documented clinical efficacy , but only few comparative studies have been performed Background : A single‐centre , r and omized , double‐blind , placebo‐controlled study . The recommendation to use sublingual-swallow immunotherapy ( SLIT ) in children and adults with allergic rhinitis has been established over the past decade . Recently , ultra-rush titration of SLIT has become more and more common , raising concerns about its safety in children with asthma . Fifty-four children with asthma and adolescents aged 6–14 with documented allergic disease because of tree pollen ( birch and possibly alder and /or hazel ) from 14 study centers in Germany participated in a r and omized , double-blind , and placebo-controlled study . Twenty-seven were r and omized to receive SLIT with st and ardized birch pollen allergen extract and the other 27 to receive placebo . An ultra-rush high-dose SLIT titration regimen reaching the maintenance dose of 300 index of reactivity ( IR ) within 90 min ( 30–90–150–300 IR ) was used . The difference in mean PFR changes during ultra-rush titration between SLIT and placebo was not significant ( p = 0.056 ) . A 95 % probability that SLIT does not decrease PFR during ultra-rush titration was demonstrated . Neither anaphylactic shock nor else serious systemic reactions to the study drug occurred . No serious adverse event assessed by the investigator as related to study drug treatment was reported BACKGROUND Sublingual allergen-specific immunotherapy is a viable alternative to subcutaneous immunotherapy particularly attractive for use in children . OBJECTIVE This study investigated efficacy and safety of high-dose sublingual immunotherapy ( SLIT ) in children allergic to grass pollen in a r and omized , double-blind , placebo-controlled trial . METHODS After a baseline seasonal observation , 207 children aged 4 to 12 years with grass pollen-allergic rhinitis/rhinoconjunctivitis with/without bronchial asthma ( Global Initiative for Asthma I/II ) received either high-dose grass pollen SLIT or placebo daily for 1 pre-/co-seasonal period . The primary end point was the change of the area under the curve of the symptom-medication score ( SMS ) from the baseline season to the first season after start of treatment . Secondary outcomes were well days , responders , immunologic changes , and safety . RESULTS Mean changes in the area under the curve of the SMS from the baseline to the first grass pollen season after the start of treatment were -212.5 for the active group and -97.8 for the placebo group ( P = .0040 ) . Rhinoconjunctivitis SMS ( P = .0020 ) and separated symptom and medication scores were also statistically different between the 2 groups ( P = .0121 and P = .0226 , respectively ) . The number of well days and the percentage of responders were greater in the active group . Changes in allergen-specific IgE and IgG levels indicated a significant immunologic effect . The treatment was well tolerated , and no serious treatment-related events were reported . CONCLUSIONS This study confirmed that this SLIT preparation significantly reduced symptoms and medication use in children with grass pollen-allergic rhinoconjunctivitis . The preparation showed significant effects on allergen-specific antibodies , was well tolerated , and appeared to be a valid therapeutic option in children allergic to grass pollen . This trial was registered at www . clinical trials.gov as NCT00841256 Background The SQ house dust mite ( HDM ) sublingual immunotherapy ( SLIT ) tablet has been approved in 11 European countries and Japan for patients with HDM‐induced respiratory allergic disease . Objective This trial was conducted to confirm the efficacy and safety of the SQ HDM SLIT tablet in Japanese patients with moderate‐to‐severe HDM‐induced allergic rhinitis ( AR ) . Methods The trial was a r and omized , double‐blind , placebo‐controlled trial including 946 Japanese adults and adolescents ( 12‐64 years ) . Subjects were r and omly assigned to daily treatment with the SQ HDM SLIT tablet at a dose of 10,000 Japanese allergy units ( JAU ) or 20,000 JAU or to placebo ( 1:1:1 ) . The primary end point was the total combined rhinitis score ( TCRS ) , which is composed of AR symptom and medication scores during the efficacy evaluation period . Symptom and medication scores of AR and conjunctivitis , rhinitis quality of life , and symptom‐free and symptom‐severe days were evaluated as secondary end points . Results Analysis of the primary end point demonstrated statistically significant reductions in TCRSs of 1.15 ( 22 % , P < .001 ) in the 10,000‐JAU group and 0.99 ( 19 % , P < .001 ) in the 20,000‐JAU group compared with the placebo group . The statistically significant treatment effect was evident from 12 weeks of treatment onward . All secondary end points , except AR medication score , were statistically significant in favor of active treatment compared with placebo . Post hoc analysis of TCRSs in adolescents showed the same efficacy as in adults ( P < .05 ) . The treatment was well tolerated by both adults and adolescents . Conclusion The trial confirmed the efficacy and safety profile of the SQ HDM SLIT tablet in Japanese adult and adolescent patients with moderate‐to‐severe HDM‐induced AR . These data support the robust efficacy and safety profile of previously reported European data BACKGROUND Sublingual immunotherapy ( SLIT ) with a high-dose 6-grass pollen SingleDose preparation was shown to be effective and safe in a 2-year r and omized , double-blind , placebo-controlled trial . OBJECTIVE We evaluated the effect of the third year of SLIT in comparison to the second year . METHODS 46 grass pollen-allergic patients who had received active treatment for 3 consecutive years were included in the safety set . Diary data from 39 subjects were evaluated to calculate symptom and medication scores as well as ' well days ' . RESULTS Symptoms and medication intake further decreased in the third year of SLIT during the grass pollen season in comparison to the previous years and the number of ' well days ' increased accordingly . No serious adverse events occurred during the three years of SLIT . CONCLUSION The third year of SLIT with the high-dose 6-grass pollen preparation results in sustained and even further increased clinical efficacy BACKGROUND Investigations meeting current st and ards are limited for the effect of house dust mite ( HDM ) allergy immunotherapy in asthmatic patients . OBJECTIVE This trial investigated the efficacy and safety of a st and ardized quality ( SQ ; allergen st and ardization method proprietary to the trial sponsor ) HDM SLIT-tablet ( ALK , Hørsholm , Denmark ) in adults and adolescents with HDM respiratory allergic disease . This publication reports the results of the endpoints related to asthma . METHODS Six hundred four subjects 14 years or older with HDM allergic rhinitis and mild-to-moderate asthma were r and omized 1:1:1:1 to double-blind daily treatment with one of 3 active doses ( 1 , 3 , or 6 SQ-HDM ) or placebo . Their use of inhaled corticosteroid ( ICS ) was st and ardized and adjusted at baseline and the end of treatment to the lowest dose providing asthma control . The primary end point was a reduction in ICS dose from the individual subject 's baseline dose after 1 year of treatment . RESULTS The primary analysis revealed a mean difference between 6 SQ-HDM and placebo in the reduction in daily ICS dose of 81 μg ( P = .004 ) . Relative mean and median reductions were 42 % and 50 % for 6 SQ-HDM and 15 % and 25 % for placebo , respectively . No statistically significant differences were observed for the other assessed asthma parameters , reflecting the intended controlled status of the trial subjects . The most common adverse events were local reactions in the mouth . The rate and severity of adverse events were higher for 3 and 6 SQ-HDM than for 1 SQ-HDM and placebo . CONCLUSION Efficacy in mild-to-moderate asthma of 6 SQ-HDM relative to placebo was demonstrated by a moderate statistically significant reduction in the ICS dose required to maintain asthma control . All active doses were well tolerated Background : Japanese cedar pollen represents an important and unique allergen . Sublingual immunotherapy ( SLIT ) has been suggested to be a highly effective route of desensitization against a variety of allergens . However , little information is available about its use in cedar pollen allergy . Methods : A blinded r and omized , placebo-controlled trial employing SLIT for cedar pollinosis was conducted over a period of 6 months . Sixty-seven subjects were enrolled and the symptom scores during the pollen season were evaluated by a symptom diary , measurement of cedar-specific IgE and IgG4 , and determination of Cry j-specific Th2 clones before SLIT and before and after the pollen season . Results : No major adverse effects were observed in either group . The serum-specific IgG4 activity increased significantly after SLIT in the active group . The active group also exhibited significantly lower symptom scores compared to the placebo . The specific Th2 clone sizes were not significantly different between the groups before the pollen season . However , an increase in the clone size was observed after the pollen season in the placebo group , but not in the active group . Conclusion : Use of SLIT for Japanese cedar pollinosis was found to be safe and associated with an increase in cedar-specific IgG4 levels . Such therapy inhibited the increase in Cry j-specific Th2 clone size induced by pollen exposure . Finally , use of SLIT result ed in significant improvement of the clinical symptoms of cedar pollinosis in this patient population . These observations suggest that SLIT may offer another safe approach to the management of cedar pollinosis BACKGROUND The local ( noninjection ) routes of immunotherapy are presently regarded as viable therapeutic options for respiratory allergy , and their mechanisms of action are currently undergoing investigation . OBJECTIVE We evaluated the clinical efficacy of a preseasonal rush sublingual-swallow immunotherapy and its effects on allergic inflammation in patients with seasonal rhinoconjunctivitis caused by Parietaria species . METHODS Thirty patients with Parietaria species-induced rhinoconjunctivitis ( 13 with mild intermittent asthma ) were r and omly assigned sublingual-swallow immunotherapy or placebo in a rush preseasonal course . We assessed the seasonal symptom-drug intake score by diary card and the inflammatory infiltration and the intercellular adhesion molecule 1 expression on nasal epithelium after specific allergenic challenge before and after treatment . RESULTS The investigated immunotherapy was well tolerated , and no side effects were recorded . A significant reduction of the symptom score ( P = .016 ) and drug intake score ( P = . 008 ) after immunotherapy was observed only in the active group . A decrease of the cumulative score was observed also in the placebo group ( P = .046 ) , but the significance was clearly higher ( P = .006 ) in the active group . In the active group a reduction of neutrophils ( P = .001 ) , eosinophils ( P = .01 ) , and intercellular adhesion molecule 1 expression ( P = .04 ) after specific nasal challenge was also detected . CONCLUSION The present results suggest that this sublingual-swallow immunotherapy administered through a rush schedule is clinical ly effective and safe and that it decreases the immune-mediated inflammatory responses to the allergen BACKGROUND The magnitude of effect of sublingual immunotherapy for house dust mite (HDM)-induced allergic rhinitis with or without conjunctivitis is uncertain , partly because there are few well-controlled trials with well-defined doses . OBJECTIVE We sought to determine the dose-related efficacy and onset of action of the HDM sublingual immunotherapy tablet MK-8237 ( Merck/ALK-Abelló ) using the Vienna Challenge Chamber . METHODS In this r and omized , double-blind , single-site trial , adults with HDM-induced allergic rhinitis with or without conjunctivitis and with or without asthma ( n = 124 ) received 12 developmental units ( DU ) of MK-8237 , 6 DU of MK-8237 , or placebo daily for 24 weeks . Subjects underwent 6-hour exposure challenges at screening and weeks 8 , 16 , and 24 . The total nasal symptom score ( TNSS ) during chamber challenge at week 24 was the primary end point . The TNSS was the sum of 4 nasal symptom scores ( maximum = 12 ) . Total ocular symptom scores ( TOSSs ; 2 symptoms ; maximum = 6 ) and total symptom scores ( TSSs ; TSS = TNSS plus TOSS ; maximum = 18 ) were secondary end points . RESULTS Dose- and time-dependent improvements with MK-8237 versus placebo were observed . At week 24 , TNSS improvement relative to placebo was 48.6 % ( 95 % CI , 35.3 % to 60.2 % ) with 12 DU of MK-8237 and 26.6 % ( 95 % CI , 11.2 % to 39.6 % ) with 6 DU of MK-8237 . Statistically significant improvements for TNSSs were also observed at weeks 8 ( 12 DU of MK-8237 ) and 16 ( 6 and 12 DU of MK-8237 ) and for TOSSs and TSSs by both doses at week 24 . MK-8237 was well tolerated . No investigator-assessed anaphylactic allergic reactions or reactions requiring epinephrine were observed . CONCLUSIONS MK-8237 , 12 DU , reduced nasal and ocular symptoms and exceeded World Allergy Organization-established clinical efficacy criteria ( ≥20 % improvement vs placebo ) . The onset of action for 12 DU of MK-8237 was week 8 . MK-8237 , 12 DU , is appropriate for further evaluation to determine the magnitude of effect in an uncontrolled allergen exposure environment Fifty‐eight patients with well‐documented history of seasonal rhinoconjunctivitis caused by grass pollens were allocated r and omly on a double‐blind basis to receive either sublingual therapy with a solution of purified , st and ardized allergen preparation ( Stallergenes ) or a matched placebo for 17 weeks . The assessment of the effect of oral immunotherapy , done with drops of five‐grass allergen extract , was on the clinical symptoms and on the medication score of the authorized rescue treatments . The actively treated patients had significantly ( P<0.05 to P<0.01 ) fewer symptoms of rhinitis ( sneezing and rhinorrhea ) and of conjunctivitis ( redness and tears ) during the pollen season than the placebo group . Consumption of nasal solution of sodium cromoglycate and of betamethasone and dexchlorpheniramine was significantly less in the desensitized group ( P<0.01 ) . Side‐effects were negligible . This study concludes that perlingual immunotherapy with grass pollen extract in grass‐pollen‐sensitive seasonal hay fever and conjunctivitis patients is effective , easy to perform , inexpensive , and safe ABSTRACT Objectives : Treatment with allergy immunotherapy improves allergic rhinoconjunctivitis , but can also improve comorbidities associated with allergic rhinitis such as asthma . Sublingual immunotherapy (SLIT)-tablets are a convenient and efficacious method of allergy immunotherapy . They are self-administered after the first tablet has been provided under medical supervision . Therapy may elicit local reactions or , rarely , systemic allergic reactions . The objective of this report is to inform healthcare practitioners about the safety and tolerability profile of SLIT-tablets and use this information to provide practical guidance that may inform patients regarding potential adverse reactions and how to manage them . Methods : Pooled analyses of safety data from completed r and omized , multicenter , double-blind , placebo-controlled phase 2 and phase 3 US and EU trials of timothy grass , short ragweed , and SQ house dust mite SLIT-tablets were conducted to characterize safety and tolerability . Results : SLIT-tablets are generally well tolerated . No life-threatening events , serious systemic allergic reactions , or events that compromised the airway have been reported . The most common treatment-related adverse events ( AEs ) are oral site reactions , most of which begin on day 1 of treatment , recur for less than 2 weeks , and resolve after approximately 30–60 minutes . Systemic allergic reactions have been managed with conventional pharmacotherapy . Reactions treated with epinephrine are uncommon , but have been reported . Treatment of AEs , treatment discontinuation considerations , and patient FAQs regarding SLIT-tablet safety/tolerability are discussed . Conclusions : This report gives healthcare providers valuable information to educate patients regarding what to expect in terms of SLIT-tablet safety and tolerability . Practical guidance is also provided to ensure proper treatment of any adverse reactions BACKGROUND Immunotherapy for allergic rhinoconjunctivitis ( ARC ) in North America is generally administered subcutaneously , but alternative formulations might be safer and more convenient . Trials of sublingual formulations in North America are needed to confirm European efficacy and safety data . OBJECTIVE We sought to investigate the efficacy and safety of timothy grass allergy immunotherapy tablet ( AIT ) treatment in North American subjects with ARC . METHODS Four hundred thirty-nine adults with grass pollen-induced ARC with or without asthma were r and omized to once-daily 2,800 bioequivalent allergen units of st and ardized grass AIT ( oral lyophilisate , Phleum pratense , 75,000 st and ardized quality tablet , containing approximately 15 μg of Phl p 5 ) or placebo approximately 16 weeks before the 2009 grass pollen season ( GPS ) . The primary end point was the average total combined score of the daily symptom score and the daily medication score during the GPS . Rhinoconjunctivitis Quality of Life Question naire with st and ardized activities ( RQLQ[S ] ) scores , Phl p 5-specific IgG4 levels , and IgE-blocking factor levels were additional end points . Adverse events ( AEs ) were monitored for safety . RESULTS Relative to placebo , grass AIT treatment improved total combined scores by 20 % ( P = .005 ) , daily symptom scores by 18 % ( P = .02 ) , and RQLQ(S ) scores by 17 % ( P = .02 ) . Daily medication scores were improved by 26 % and trended toward significance ( P = .08 ) . Phl p 5-specific IgG4 and IgE-blocking factor levels were higher after grass AIT treatment compared with those after placebo at the end of the GPS ( P < .001 ) . Grass AIT treatment was safe and well tolerated . The majority of AEs were transient mild local reactions with no investigator-diagnosed grass AIT-related serious AEs or reports of anaphylactic shock/respiratory compromise . In the grass AIT group , 1 subject received epinephrine after experiencing a possible grade 1 systemic reaction ( local site reactions , chest discomfort , and rash ) . CONCLUSIONS Timothy grass AIT treatment ( cross-reactive with related Pooideae grasses ) was demonstrated to be effective , generally safe , and well tolerated in North American adults with grass pollen-induced ARC BACKGROUND Sublingual administration of Phleum pratense allergen immunotherapy ( SLIT ) tablets is a clinical ly efficient treatment for grass pollen-induced rhinoconjunctivitis . This immunotherapy downregulates TH2 immune responses , induces tolerogenic pathways , and increases regulatory T cells . However , associated immune response markers of allergen desensitization remain undefined . OBJECTIVE We sought to characterize the kinetics of individual changes in the immunologic response to grass tablet SLIT . METHODS We evaluated the systemic effects of SLIT in a longitudinal analysis of humoral and cellular immune parameters in peripheral blood sample s. RESULTS Grass tablet SLIT administration induced a 2-phase systemic humoral and cellular response . The TH2 response was initially exacerbated and detected as increased allergen-specific IgE ( sIgE ) and IgG4 ( sIgG4 ) levels and an increase in IL-4-producing cells , followed by downregulation of the TH2 response with a shift toward a TH1 cytokine profile . T cells with a regulatory phenotype were also elicited . Statistical correlations between immunologic measurements for each patient throughout therapy indicated that TH2 response downregulation and reduction of the immediate SLIT-induced IgE response were associated with increased allergen-specific IgG4 synthesis early in therapy . TH2 response downregulation by month 4 correlated with increased frequency of CD4(+ ) T cells with a regulatory phenotype by 12 months . CONCLUSION Changes in sIgE levels after therapy were linked to a specific IgG4 response , and production of blocking antibodies correlated with TH2 response downregulation . Reduced IL-4(+ ) cell frequency was linked to an increase in the frequency of CD4(+ ) T cells with a regulatory phenotype . Changes in sIgE levels and reduced IL-4 and blocking antibody levels could thus be used as indicators of a patient 's immune response to therapy BACKGROUND The SQ HDM SLIT-tablet ( ALK ) has been developed for treatment of house dust mite (HDM)-induced respiratory allergic disease . OBJECTIVE This trial investigated the efficacy and safety of the SQ HDM SLIT-tablet in adults with moderate-to-severe HDM-induced allergic rhinitis ( AR ) . METHODS The trial was a r and omized , double-blind , placebo-controlled phase III trial conducted in 12 European countries including 992 adults with moderate-to-severe HDM-induced AR despite treatment with pharmacotherapy . Subjects were r and omized 1:1:1 to 1 year of daily treatment with placebo , 6 SQ-HDM , or 12 SQ-HDM . The primary end point was the total combined rhinitis score ( ie , the sum of rhinitis symptom and medication scores ) during the efficacy assessment period ( approximately the last 8 weeks of the treatment period ) . Key secondary end points were rhinitis symptoms , medication scores , quality of life , and the combined rhinoconjunctivitis score . RESULTS Analysis of the primary end point ( observed data ) demonstrated absolute reductions in total combined rhinitis score of 1.18 ( P = .002 ) and 1.22 ( P = .001 ) compared with placebo for 6 SQ-HDM and 12 SQ-HDM , respectively . The statistically significant treatment effect was evident from 14 weeks of treatment onward . For all key secondary end points , efficacy was confirmed for 12 SQ-HDM , with statistically significant reductions of rhinitis symptoms and medication scores , improved quality of life , and a reduced combined rhinoconjunctivitis score in the efficacy assessment period compared with placebo . The treatment was well tolerated . CONCLUSION The trial confirmed the efficacy and favorable safety profile of both 6 SQ-HDM and 12 SQ-HDM in adults with HDM-induced AR . The treatment effect was present from 14 weeks of treatment onward BACKGROUND The house dust mite ( HDM ) sublingual immunotherapy ( SLIT ) tablet ( MK-8237 ; Merck & Co , Kenilworth , NJ/ALK-Abelló , Hørsholm , Denmark ) has demonstrated beneficial effects on allergic rhinoconjunctivitis and asthma outcomes in European trials . OBJECTIVE This is the first trial to assess the efficacy/safety of HDM SLIT-tablets in North American subjects with HDM-induced allergic rhinitis with or without conjunctivitis ( AR/C ) . METHODS In this double-blind , multicenter trial ( NCT01700192 ) 1482 subjects ( aged ≥12 years ) with HDM-induced AR/C with or without asthma were r and omized to a daily SQ HDM SLIT-tablet ( 12 SQ-HDM dose ) or placebo for up to approximately 52 weeks . A rhinitis daily symptom score ( DSS ; 4 nasal symptoms , maximum score = 12 ) of 6 or greater , or 5 or greater with 1 symptom being severe , on 5 of 7 consecutive days before r and omization was required . The primary end point was the average total combined rhinitis score , which was defined as the rhinitis DSS plus rhinitis daily medication score ( DMS ) , during the last 8 treatment weeks . RESULTS Treatment with 12 SQ-HDM improved the total combined rhinitis score by 17 % ( 95 % CI , 10 % to 25 % ) versus placebo . Improvements versus placebo in the secondary end points of average rhinitis DSS , rhinitis DMS , total combined rhinoconjunctivitis score , and visual analog scale-assessed AR/C symptoms were 16 % , 18 % , 17 % , and 16 % , respectively . All nominal P values were less than .001 versus placebo , except rhinitis DMS ( P = 0.15 ) . No treatment-related adverse events meeting the International Council on Harmonization definition of a serious adverse event were reported ; 1 nonserious treatment-related systemic allergic reaction occurred ( assessed as moderate intensity ) at first administration under medical supervision and was treated with epinephrine . CONCLUSIONS In the first North American trial of use of a SLIT-tablet for HDM allergy , 12 SQ-HDM was well tolerated and improved HDM-induced rhinitis symptoms in adults and adolescents Background : Allergy immunotherapy targets the immunological cause of allergic rhinoconjunctivitis and allergic asthma and has the potential to alter the natural course of allergic disease . Objective : The primary objective was to investigate the effect of the SQ grass sublingual immunotherapy tablet compared with placebo on the risk of developing asthma . Methods : A total of 812 children ( 5‐12 years ) , with a clinical ly relevant history of grass pollen allergic rhinoconjunctivitis and no medical history or signs of asthma , were included in the r and omized , double‐blind , placebo‐controlled trial , comprising 3 years of treatment and 2 years of follow‐up . Results : There was no difference in time to onset of asthma , defined by prespecified asthma criteria relying on documented reversible impairment of lung function ( primary endpoint ) . Treatment with the SQ grass sublingual immunotherapy tablet significantly reduced the risk of experiencing asthma symptoms or using asthma medication at the end of trial ( odds ratio = 0.66 , P < .036 ) , during the 2‐year posttreatment follow‐up , and during the entire 5‐year trial period . Also , grass allergic rhinoconjunctivitis symptoms were 22 % to 30 % reduced ( P < .005 for all 5 years ) . At the end of the trial , the use of allergic rhinoconjunctivitis pharmacotherapy was significantly less ( 27 % relative difference to placebo , P < .001 ) . Total IgE , grass pollen – specific IgE , and skin prick test reactivity to grass pollen were all reduced compared to placebo . Conclusions : Treatment with the SQ grass sublingual immunotherapy tablet reduced the risk of experiencing asthma symptoms and using asthma medication , and had a positive , long‐term clinical effect on rhinoconjunctivitis symptoms and medication use but did not show an effect on the time to onset of asthma . Graphical abstract Figure . No caption available PURPOSE The tree pollen sublingual immunotherapy (SLIT)-tablet ( ALK , Denmark ) is being developed for the treatment of tree pollen induced allergic rhinitis with or without conjunctivitis . The objective of this Phase I trial was to investigate the tolerability and acceptable dose range of the SQ tree SLIT-tablet in adults with allergic rhinoconjunctivitis . METHODS The trial was a r and omized , double-blind , placebo-controlled , dose escalation Phase I trial that included 70 adults ( aged 19 - 61 years ) with birch pollen-induced rhinoconjunctivitis with or without mild to moderate asthma . The trial included 6 different dosage groups that were r and omized 3:1 to active treatment or placebo once daily for 28 days . Adverse events ( AEs ) were coded in the Medical Dictionary for Regulatory Activities by medically qualified personnel . Immunologic assessment s included IgE and IgE-blocking factor . FINDINGS Most ( 96 % ) reported AEs were mild , and only 5 severe events ( 0.2 % ) were reported . The most frequently reported investigational medicinal product-related AEs were oral pruritus , ear pruritus , mouth edema , sensation of foreign body , throat irritation , pharyngolaryngeal pain , dry throat , tongue blistering , eye pruritus , and headache . The trial included doses ranging from 1 to 24 development units ( DU ) , and the mean number of investigational medicinal product-related AEs per participant was highest in the 24 DU group . The 12 and 24 DU doses induced statistically significant changes from baseline compared with placebo in birch specific IgE and IgE-blocking factor . IMPLICATION S The trial found that doses up to 12 DU of the SQ tree SLIT tablet have a tolerability profile suitable for at-home administration . An immunomodulatory effect was found for all doses included in the trial , and doses up to 12 DU were thus chosen for further clinical development of the SQ tree SLIT tablet . EudraCT identifier : 2007 - 003234 - 42 PURPOSE The SQ tree sublingual immunotherapy (SLIT)-tablet containing allergen extracts with the major allergen Bet v 1 from birch pollen is currently being developed for the treatment of tree pollen-induced allergic rhinitis/conjunctivitis with or without asthma . The aim of this Phase II trial was to investigate the dose-related efficacy and safety of the SQ tree SLIT-tablet . METHODS This study was a r and omized , parallel-group , double-blind , placebo-controlled , multi-national trial conducted in Europe . A total of 637 participants were r and omized equally to receive placebo or treatment with the SQ tree SLIT-tablet in doses of 0.5 , 1 , 2 , 4 , 7 , or 12 development units ( DU ) . Treatment was initiated ~16 weeks before onset of the 2013 birch pollen season ( BPS ) and was continued throughout the BPS with a total duration of at least 6 months . During the BPS and tree pollen season ( TPS ) , subjects assessed rhinoconjunctivitis symptoms and medication use on a daily basis in an electronic diary ; weekly assessment s of rhinoconjunctivitis quality of life were also made . FINDINGS Analysis of the average daily symptom score during the BPS and the TPS showed that the difference between active treatment and placebo was statistically significant for the 7 DU group ( BPS , P = 0.02 ; TPS , P = 0.03 ) , with no clear dose-response relationship . All doses of the SQ tree SLIT-tablet induced changes from baseline in birch-specific IgE and IgG4 that were statistically significant compared with placebo at all time points assessed ( P < 0.0001 ) with a clear dose-response relationship for birch specific IgG4 . In general , the SQ tree SLIT-tablet was well tolerated , with the majority of treatment-related adverse events ( ≥95 % ) being mild or moderate in severity . The most frequently reported treatment-related adverse events were generally related to the sublingual administration of the tablet ( ie , they occurred in the oral cavity ) . IMPLICATION S The results from this trial suggest that the SQ tree SLIT-tablet in doses up to 12 DU has a tolerability profile suitable for at-home administration . The immunomodulatory changes indicate a dose-response relationship , but clinical efficacy parameters were inconclusive , probably due to low pollen counts , emphasizing the importance of pollen exposure for the outcome of a pollen allergy immunotherapy trial . EudraCT no : 2012 - 000031 - 59 Abstract Background : There is ample evidence to support the efficacy of sublingual immunotherapy ( SLIT ) on allergic rhinitis , while there is less solid data regarding asthma . We evaluated the effects of a high dose birch SLIT on birch-induced rhinitis and asthma in a controlled study . Methods : This double-blind , placebo-controlled , r and omised , single centre trial on SLIT with birch pollen allergen extract ( Stallergenes , Antony , France ) included 24 patients presenting severe rhinitis and slight to moderate asthma , 14 actively and 10 placebo treated . SLIT was performed by a pre-coseasonal protocol , and was repeated for 2 years . The study plan included a selection visit , a visit at the start of the first and the second treatment cycle , a follow-up visit after 1–3 months from the start of each cycle , and a final visit at the end of each yearly cycle . Results : A significant decrease ( p < 0.05 ) in rhinorrhoea and nasal obstruction occurred in actively treated patients . The median number of days with asthma at visit 3 was 10 ( 0–27 ) in the active ( SLIT ) group and 13 ( 0–29 ) in the placebo group . The median number of days with asthma at visit 6 was 2 ( 0–6 ) in the SLIT group and 7 ( 0–15 ) in the placebo group ( p < 0.05 between groups ) . A stepdown of asthma occurred in 77 % of actively treated vs. none of placebo treated patients ( p = 0.05 ) . No severe adverse events were observed . Conclusions : This pilot study suggests that SLIT with high dose birch extract may be able to step down seasonal pollen-induced asthma after prolonged treatment The efficacy and safety of sublingual immunotherapy in house dust mite – induced asthma have yet to be firmly established . We report the results of a double‐blind , placebo‐controlled , r and omized clinical trial performed in mainl and China A sublingually administered allergy immunotherapy tablet ( AIT ) is under development to treat ragweed ( Ambrosia artemisiifolia)-induced allergic rhinoconjunctivitis ( ARC ) . This study investigates the optimal tolerable dose of once daily ragweed pollen AIT.Subjects 18 - 50 years old with ragweed-induced ARC were enrolled at two U.S. centers in a double-blind , placebo-controlled , dose-escalation study outside ragweed season . Groups ( 12 subjects each ) were to be r and omized 3:1 to 28 days of active treatment ( groups assigned in sequence to 3 , 6 , 12 , 24 , 50 , or 100 units of Ambrosia artemislifolia major allergen 1 [ Amb a 1 U],without dose buildup at any level ) or matching placebo . Recruitment to 50 Amb a 1-U was discontinued because of adverse events ( AEs ) after four AIT subjects were enrolled ; 100 Amb a 1-U was not initiated . Fifty-three subjects were r and omized ( AIT , n = 40 ; placebo , n = 13 ) ; four discontinued , all because of AEs ( AIT , n = 3 ; placebo , n = 1 ) . Treatment-related AEs ( TRAEs ) were more frequent with AIT ( 73 % ) than placebo ( 31 % ) , increasing with dose level . AIT TRAEs were mostly mild ( 94 % ) or moderate(5 % ) . No serious TRAEs or anaphylactic shock occurred . The most common TRAEs with AIT were localized pruritus , nasal irritation , and throat irritation . Median onset for common AIT application site reactions was 24 ≤ hours after first treatment ( median duration , 15 - 50 minutes ) . AIT increased immunoglobulin ( Ig ) significantly more than placebo ( ragweed-specific IgE [ 6 , 12 , and 24 Amb a 1-U ] ; IgG4 [ all doses ] ; p < 0.05 ) . Three subjects in dose groups ≥ 24 Amb a 1-U experienced symptoms suggestive of systemic reaction . Of tested doses , ragweed AIT 24 < Amb a 1-U once-daily was well tolerated in subjects with ragweed-induced ARC . Clinical trial registration URL and registration number : www . clinical trials.gov/ct2/show/NCT01134705 [ corrected ] |
10,496 | 30,496,308 | Some particularities were highlighted for specific muscles .
Except for manual slice by slice segmentation , reliability has rarely been reported .
The results of this systematic review help the choice of appropriate segmentation techniques , according to the purpose of the measurement .
In healthy population s , techniques that greatly simplified the process of manual segmentation yielded greater errors in volume and shape estimations .
Reduction of the number of manually segmented slices was possible with appropriately chosen segmented slices or with DPSO .
Other automatic techniques showed promise , but data were insufficient for their validation . | AIMS The aim of this study was to report the metrological qualities of techniques currently used to quantify skeletal muscle volume and 3D shape in healthy and pathological muscles . | PURPOSE This prospect i ve study examined the association between quadratus lumborum ( QL ) asymmetry and the development of symptomatic pars interarticularis lesions in the lumbar spine of adolescent cricket fast bowlers . METHODS Annual magnetic resonance imaging was used to measure QL volume asymmetry and for identifying pars lesions of the lumbar vertebrae in fast bowlers ( N=51 ) and a control group of swimmers ( N=18 ) . Manual segmentation of axial images spanning the lumbar spine was performed to calculate percent QL asymmetry relative to the bowling- or throwing- ( swimmers ) arm side . Asymmetry above 100 % indicated a larger QL volume on the bowling- ( throwing ) arm side . RESULTS The mean QL asymmetry in bowlers of 110.5 % ( SD=12.1 % ) was significantly different from the 96.6 % ( SD=5.0 % ) asymmetry in swimmers ( t=6.75 , P < or=0.001 ) . In bowlers with symptomatic unilateral L4 pars lesions ( N=11 ) , which all developed opposite the bowling-arm side , the mean 124.3 % ( SD=8.3 % ) QL asymmetry exceeded the 106.7 % ( SD=10.1 % ) asymmetry in bowlers without these one-sided lesions . A logistic regression model ( intercept=-22.1 , P < or=0.001 ; asymmetry coefficient=0.18 , P < or=0.001 ) demonstrated a significant association between increasing QL asymmetry and L4 lesions in bowlers . Receiver operating characteristic curve analysis demonstrated that QL asymmetry was an excellent predictor of L4 lesions in fast bowlers ( area under curve=0.89 , 95 % confidence interval : 0.79 , 0.98 ) . CONCLUSION The strong association between QL asymmetry and the development of symptomatic unilateral L4 pars lesions in adolescent bowlers conceivably reflects a mechanical coupling between the loading milieu generating these injuries and preferential hypertrophy of this paraspinal muscle in response to repetitive activation during fast bowling We present a novel probabilistic shape representation that implicitly includes prior anatomical volume and adjacency information , termed the generalized log-ratio ( GLR ) representation . We demonstrate the usefulness of this representation in the task of thigh muscle segmentation . Analysis of the shapes and sizes of thigh muscles can lead to a better underst and ing of the effects of chronic obstructive pulmonary disease ( COPD ) , which often results in skeletal muscle weakness in lower limbs . However , segmenting these muscles from one another is difficult due to a lack of distinctive features and inter-muscular boundaries that are difficult to detect . We overcome these difficulties by building a shape model in the space of GLR representations . We remove pose variability from the model by employing a presegmentation-based alignment scheme . We also design a rotationally invariant r and om forest boundary detector that learns common appearances of the interface between muscles from training data . We combine the shape model and the boundary detector into a fully automatic globally optimal segmentation technique . Our segmentation technique produces a probabilistic segmentation that can be used to generate uncertainty information , which can be used to aid subsequent analysis . Our experiments on challenging 3D magnetic resonance imaging data sets show that the use of the GLR representation improves the segmentation accuracy , and yields an average Dice similarity coefficient of 0.808 ±0.074 , comparable to other state-of-the-art thigh segmentation techniques Abstract Objective Our aim was to vali date the use of cross-sectional area ( CSA ) measurements at multiple quadriceps muscle levels for estimating the total muscle volume ( TMV ) , and to define the best correlating measurement level . Methods Prospect i ve institutional review board (IRB)-approved study with written informed patient consent . Thighs of thirty-four consecutive patients with ACL-reconstructions ( men , 22 ; women , 12 ) were imaged at 1.5-T using three-dimensional ( 3D ) spoiled dual gradient-echo sequences . CSA was measured at three levels : 15 , 20 , and 25 cm above the knee joint line . TMV was determined using dedicated volumetry software with semiautomatic segmentation . Pearson ’s correlation and regression analysis ( including st and ard error of the estimate , SEE ) was used to compare CSA and TMV . Results The mean ± st and ard deviation ( SD ) for the CSA was 60.6 ± 12.8 cm2 ( range , 35.6–93.4 cm2 ) , 71.1 ± 15.1 cm2 ( range , 42.5–108.9 cm2 ) and 74.2 ± 17.1 cm2 ( range , 40.9–115.9 cm2 ) for CSA-15 , CSA-20 and CSA-25 , respectively . The mean ± SD quadriceps ’ TMV was 1949 ± 533.7 cm3 ( range , 964.0–3283.0 cm3 ) . Pearson correlation coefficient was r = 0.835 ( p < 0.01 ) , r = 0.906 ( p < 0.01 ) , and r = 0.956 ( p < 0.01 ) for CSA-15 , CSA-20 and CSA-25 , respectively . Corresponding SEE , expressed as percentage of the TMV , were 15.2 % , 11.6 % and 8.1 % , respectively . Conclusion The best correlation coefficient between quadriceps CSA and TMV was found for CSA-25 , but its clinical application to estimate the TMV is limited by a relatively large SEE.Key points• Cross-sectional area was used to estimate QFM size in patients with ACL-reconstruction • A high correlation coefficient exists between quadriceps CSA and volume • Best correlation was seen 25 cm above the knee joint line • A relatively large st and ard error of the estimate limits CSA The R and om Walks ( RW ) algorithm is one of the most efficient and easy-to-use probabilistic segmentation methods . By combining contrast terms with prior terms , it provides accurate segmentations of medical images in a fully automated manner . However , one of the main drawbacks of using the RW algorithm is that its parameters have to be h and -tuned . we propose a novel discriminative learning framework that estimates the parameters using a training data set . The main challenge we face is that the training sample s are not fully supervised . Specifically , they provide a hard segmentation of the images , instead of a probabilistic segmentation . We overcome this challenge by treating the optimal probabilistic segmentation that is compatible with the given hard segmentation as a latent variable . This allows us to employ the latent support vector machine formulation for parameter estimation . We show that our approach significantly outperforms the baseline methods on a challenging data set consisting of real clinical 3D MRI volumes of skeletal muscles In an effort to measure strength characteristics of the calf muscles , 18 subjects ( 14 male , 4 female , age = 34.3+/-2.4yrs ) were tested using a specially design ed torque velocity device ( TVD ) . This TVD is a hardware interface with the subject 's lower leg which stabilizes the leg for calf muscle strength measurements . Calf muscle strength measurements consisted of 1 ) isometric force production at ankle angles of 80 , 90 , and 100 degrees of plantar flexion , 2 ) peak torque at six isokinetic angular velocities 0.52 , 1.05 , 2.09 , 3.14 , 4.19 , and 5.24 rad x s(-1 ) , and 3 ) a fatigue test consisting of 30 maximal contractions at 3.14 rad x s(-1 ) . The greatest force production occurred at 80 degrees of ankle plantar flexion ( 148.5 + /- 40.2 Nm ) . Isokinetic force production ranged from 114.1 + /- 24.7 Nm at 0.52 rad x s(-1 ) to 16.8 + /- 6.5 Nm at 5.24 rad x s(-1 ) . A fatigue test consisting of 30 maximal repetitions at 3.14 rad x s(-1 ) result ed in a 61 + /- 15 % decline in force production . To assess reproducibility and day to day variation , measurements at 1.05 and 2.09 rad x s(-1 ) were made during five different trials in a single day and one trial per day for three days , respectively . The within subject coefficient of variation was 2.6 to 6.5 % for reproducibility and 1.9 to 7.4 % for day to day variation . Magnetic resonance imaging ( MRI ) of the lower limb and muscle biopsy specimens from the gastrocnemius ( lateral head ) and soleus muscles were obtained to examine the relationship between strength and morphological characteristics of the calf muscles . Cross-sectional area of the primary plantar flexors ( gastrocnemius and soleus ) was 47.9 + /- 1.3 cm2 while muscle volume was 642 + /- 16 cm3 . Muscle fiber composition of the gastrocnemius and soleus averaged 57 + /- 2 and 85 + /- 3 % type I fibers , respectively . A poor correlation was found between fiber type and maximal isometric force production ( r = 0.38 ; p>0.05 ) . However , calf muscle strength and muscle size was positively correlated ( r = 0.76 ; p < 0.05 ) . These data indicate that using the TVD interface to stabilize the lower leg is a reliable and reproducible procedure for the measurement of calf muscle strength OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity Abstract . The volume of the human tibialis anterior ( TA ) muscle was estimated in vivo by ultrasonography ( ULT ) and by magnetic resonance imaging ( MRI ) in six subjects . In both methods , 11 axial scans were taken along the muscle belly , and the cross-sectional area of the muscle in each scan was digitised . Muscle volume was calculated by treating the muscle as a series of truncated cones . To assess the reproducibility of the ULT method , all subjects were scanned twice . A high test-retest reliability was found ( R2=0.99 ) , with the two ULT measurements being significantly correlated with each other ( P<0.05 ) . The ULT and MRI methods gave similar results [ mean ( SD ) ULT : 133.2 ( 20 ) cm3 ; MRI : 131.8 ( 18 ) cm3 ] . Nevertheless , a systematic bias of 3.33 cm3 and a r and om error of 3.53 cm3 were found when using the ULT method compared with the MRI method , which results in an error of –0.15 % to 5.17 % . We conclude that the ULT method is a reproducible and valid method for the estimation of human muscle volume PURPOSE To evaluate the effect of 6-week self-perceived maximal resistance training on muscle volume utilizing magnetic resonance imaging and maximal , average , and endurance strength of the elbow extensors and to assess the relationship between muscle strength and volume before and after the training . MATERIAL S AND METHODS This was a prospect i ve blinded study . A total of 15 healthy untrained men , aged 22.5+/-3.7 years ( mean+/-SD ) , were engaged in elbow extensor training using isoacceleration dynamometry for 6 weeks with a frequency of five sessions per week ( five sets of 10 maximal voluntary contractions , 1-minute rest period between each set ) . Prior to and after the training , cross-sectional magnetic resonance images of the upper arm were obtained and muscle volumes were calculated using the truncated cone formula . RESULTS Average , maximal , and endurance strength of the upper arm extensors increased significantly by 43 % , 15 % , and 56 % , respectively . The volume of triceps brachii increased in both arms ( P<0.05 ) : right from 456.9+/-113.8 cm3 to 475.8+/-100.9 cm3 and left from 444.3+/-121.9 cm3 to 468.4+/-110.4 cm3 , or 5 % . Maximal and average strength correlated significantly with muscle volume before and after the training . CONCLUSION A specific 6-week resistance training protocol result ed in muscle strength improvement , together with increase in triceps brachii muscle volume , as demonstrated by volumetric imaging Purpose : This study aim ed to identify the best single-slice anatomical muscle cross-sectional area ( CSA ) and muscle thickness ( MT ) on magnetic resonance imaging ( MRI ) to estimate the overall individual muscle volumes ( MVs ) of knee extensors and flexors in patients with knee osteoarthritis ( KOA ) . Methods : Twelve patients ( 24 legs ; 4 men and 8 women ) with KOA underwent a 1.5-Tesla axial MRI scan in the femoral region of interest ( ROI ) , between the lesser trochanter and rectus femoris tendon . Individual MVs were calculated by numerical integration based on individual CSAs analyzed at the ROI . The best slice was determined as follows : coefficient of determination ( R 2 ) between MVs measured and those estimated from the femoral length ( FL ) × CSAs or FL × MTs measured at each 10 % interval level of the ROI . These estimation equations were applied for a cross-validation group ( 24 KOA patients : 12 men and 12 women ) . Results : Estimated individual MVs of knee extensors and flexors , based on the CSAs at the distal 10 % level , significantly correlated with each of the measured individual MVs ( R 2 : 0.79–0.96 , p < 0.05 for all ) . Similarly , estimated individual knee extensor MVs , based on MTs at the mid-slice , significantly correlated with each of the measured individual MVs ( R 2 : 0.77–0.84 , p < 0.05 for all ) . The application of the developed regression equation to the cross-validation group did not exhibit any systematic bias . Conclusion : These simple methods could be applied in prospect i ve research with a larger number of patients with KOA PURPOSE Magnetic resonance imaging ( MRI ) is one of the most widely used noninvasive diagnostic modalities for musculoskeletal evaluation . We conducted a retrospective study to determine whether MRI of the hip joint abductor and external rotator muscles yields reproducible findings in patients after total hip arthroplasty ( THA ) . MATERIAL S AND METHODS MR images were obtained 12 months after THA in 10 patients and were analyzed by two independent , blinded observers . The images were analyzed on workstations with three-dimensional analysis capabilities . The readers evaluated the gluteus medius , gluteus minimus , and obturator externus muscles on the nonoperated side ( NOS ) and the THA side . For each of the three muscles , the readers analyzed the cross-sectional area , cross-sectional signal intensity , intensity in a region of interest ( ROI ) , and volume on both sides . RESULTS Unlike intraobserver variability , interobserver variability showed significant differences between the measurements for some abductor and external rotator muscles , especially for volume ( p<0.001 - 0.02 ) and cross-sectional area ( p<0.001 - 0.05 ) analysis of the gluteus medius and minimus muscles on the THA side but also on the NOS . There were no differences in signal intensity in the ROI ( p=0.29 - 0.83 ) . The coefficients of variation ( CoV ) of all 4 parameters quantified were lower on the NOS ( average , 5.9 % ) than on the THA side ( average , 7.3 % ) . Analysis of the gluteus minimus muscle volume showed both higher intraobserver ( 18.8 % ) and interobserver ( 13.9 % ) variability on the THA side . CONCLUSION MRI is an accurate and reliable test for evaluation of soft tissue structures in patients who have undergone THA . MRI evaluation of abductor muscles yields reproducible results on the THA side and on the NOS . Prosthesis artifacts limit evaluation of the gluteus minimus muscle on the THA side and can not be recommended . Since interobserver variability was always higher than intraobserver variability , follow-up examinations should ideally be performed by the same reader in order to obtain clinical ly meaningful results |
10,497 | 31,003,489 | Significant detrimental effects of food marketing , including enhanced attitudes , preferences and increased consumption of marketed foods were documented for a wide range of marketing techniques , particularly those used in television/movies and product packaging .
Together , these studies contribute strong evidence to support the restriction of food marketing to children . | Exposure to the marketing of unhealthy foods and beverages is a widely acknowledged risk factor for the development of childhood obesity and noncommunicable diseases .
Food marketing involves the use of numerous persuasive techniques to influence children 's food attitudes , preferences and consumption .
This systematic review provides a comprehensive contemporary account of the impact of these marketing techniques on children aged 0 - 18 years and critically evaluates the method ologies used . | Objectives : To investigate the role of product evaluations , nutritional and persuasion knowledge on children ’s food choices conducted because of limited evidence about the role of product evaluations on consumer choices in conjunction with cognitive defences . Design : A r and omised controlled 2 × 2 factorial experiment with an exposure to a food and a control ( toy ) advertisement conducted in a non-laboratory setting at an annual event traditionally visited by families . Subjects : Children aged 7–13 years with biometric/weight data representative of the general Australian population . Measurements : Height and weight ( converted into body mass index z-scores ) measured in addition to children ’s nutritional and persuasion knowledge , product evaluations , age and gender . Results : The factors that undermine children ’s cognitive defences relate to taste , social appeal of foods and low nutritional and persuasion knowledge . An interplay between the above-mentioned factors was also observed , identifying four groups among young consumers , alluding to a complex and at times impulsive nature of children ’s decisions : ( 1 ) knowledgeable children with less positive product evaluations choosing a healthy snack ; ( 2 ) knowledgeable but hedonism-oriented children seeking peer conformity choosing an advertised product ; ( 3 ) knowledgeable children who chose a snack belonging to the same product category ; and ( 4 ) less knowledgeable children with positive product evaluations and low nutritional knowledge choosing snacks from the advertised product category . Obese children were more likely to belong to a cluster of less knowledgeable and hedonism-oriented children . Conclusions : The problem of consumption of less healthy foods is complex and multiple factors need to be considered by health practitioners , social marketers and parents to address the issue of childhood obesity . Nutritional knowledge alone is not sufficient to ensure children make healthier food choices and emphasis should also be placed on persuasion knowledge education , targeting of peer norms , self-efficacy and stricter regulation of advertising aim ed at children OBJECTIVE The present study sought to determine the feasibility of an experimental research design to investigate the effects of exposure to magazine advertising on children 's food choices . DESIGN Children were r and omized to read either a magazine with food advertisements or a magazine with no food advertisements . They then chose two food items from the intervention ' store ' to eat after the session . Data were also collected on attitudes to advertising and snack food preferences . Finally , participants ' parents were provided with a self-completion survey on food choices and other variables ( n 24 ) . SETTING Three vacation care centres in regional New South Wales , Australia . SUBJECTS Children aged 5 - 12 years ( n 47 ) . RESULTS Children in the experimental condition were more likely to choose advertised foods than those in the control group . Interestingly , the majority reported taste and healthiness as the most important factors in snack food choices ; however , when faced with the actual food choice , they predominantly chose unhealthy foods ( eighty-two unhealthy and only twelve healthy items were chosen ) . CONCLUSIONS This was the first study to assess the effects on children of exposure to food advertising within the context of reading a child-targeted magazine . Importantly , even with the small sample size and venue limitations , we found that exposure to magazine advertising influenced food choices . Children 's magazines are an under- research ed and poorly regulated medium , with considerable potential to influence children 's food choices . The present study shows that the methodology is feasible , and future studies could replicate this with larger sample The weight of evidence points to the advertising of food affecting food consumption , especially among children . Such advertising often promotes unhealthy foods . Current policy deliberations focus on developing effective ' protective ' messages to increase advertising literacy and consequent scepticism about advertising targeting children . This study examined whether incorporating a ' protective ' message in an advergame promoting energy-dense snacks would reduce children 's snack intake . A r and omized between-subject design was conducted in the Netherl and s ( N = 215 ) and Spain ( N = 382 ) with an advergame promoting either energy-dense snacks or nonfood products . The results showed that playing an advergame promoting energy-dense snacks increased caloric intake in both countries , irrespective of whether the ' protective ' message was present or not . These results point to the limitations of ' protective ' messages and advertising literacy and provide policy makers with a rationale for extending the current prohibition of food advertising to young children in the terrestrial media to online environments BACKGROUND Food companies often use healthy lifestyle messages in child-directed advertising , raising public health concerns about health halo effects for nutrient-poor food/drinks . OBJECTIVE Examine effects of health messages promoting nutrient-poor foods in child-directed advertising . METHODS R and omized controlled experiment ( N = 138 ) . Children ( 7 - 11 years ) viewed three child-friendly commercials in one of three conditions : ( 1 ) health halo ( unfamiliar nutrient-poor food/drink ads with healthy messages ) ; ( 2 ) nutrient-poor food/drink ads with other messages and ( 3 ) healthy food/drink ads . They rated the commercials and advertised products , provided attitudes about exercise and nutrition and consumed and rated healthy and unhealthy snack foods . RESULTS Children in the health halo condition rated the advertised nutrient-poor products as significantly healthier compared with children in other conditions ( p = .003 ) , but the other commercials did not affect children 's attitudes about other advertised products ( p 's > .50 ) . Child age , gender or TV viewing habits did not significantly predict their ratings ( p 's > .18 ) . There was no evidence that healthy lifestyle messages and /or healthy food commercials improved children 's attitudes about nutrition , exercise or healthy snack consumption . CONCLUSION Promoting healthy lifestyle messages in child-directed commercials for nutrient-poor food/drinks likely benefits br and s by increasing products ' perceived healthfulness , but these ads are unlikely to positively affect children 's attitudes about health and nutrition Background / Objective : Exposure to food advertisements may cue overeating among children , especially among those genetically predisposed to respond to food cues . We aim ed to assess how television food advertisements affect eating in the absence of hunger among children in a r and omized trial . We hypothesized that the fat mass and obesity-associated gene ( FTO ) rs9939609 single-nucleotide polymorphism would modify the effect of food advertisements . Subjects/ Methods : In this r and omized experiment , 200 children aged 9–10 years were served a st and ardized lunch and then shown a 34-min television show embedded with either food or toy advertisements . Children were provided with snack food to consume ad libitum while watching the show and we measured caloric intake . Children were genotyped for rs9939609 and analyses were conducted in the overall sample and stratified by genotype . A formal test for interaction of the food advertisement effect on consumption by rs9939609 was conducted . Results : About 172 unrelated participants were included in this analysis . Children consumed on average 453 ( s.d.=185 ) kcals during lunch and 482 ( s.d.=274 ) kcals during the experimental exposure . Children who viewed food advertisements consumed an average of 48 kcals ( 95 % confidence interval : 10 , 85 ; P=0.01 ) more of a recently advertised food than those who viewed toy advertisements . There was a statistically significant interaction between genotype and food advertisement condition ( P for interaction=0.02 ) , where the difference in consumption of a recently advertised food related to food advertisement exposure increased linearly with each additional FTO risk allele , even after controlling for body mass index percentile . Conclusions : Food advertisement exposure was associated with greater caloric consumption of a recently advertised food , and this effect was modified by an FTO genotype . Future research is needed to underst and the neurological mechanism underlying these associations Background Policies restricting children ’s exposure to unhealthy food marketing have been impeded by the lack of evidence showing a direct link between food advertising exposure and children ’s energy intake and body weight . Food advertising exposure increases children ’s immediate food consumption , but whether this increased intake is compensated for at later eating occasions is not known ; consequently the sustained effect on diets remains unclear . Methods We conducted a within-subject , r and omised , crossover , counterbalanced study across four , six-day holiday camps in New South Wales , Australia between April 2016 and January 2017 . Children ( 7–12 years , n = 160 ) were recruited via local schools , email networks and social media . Two gender- and age-balanced groups were formed for each camp ( n = 20 ) , r and omised to either a multiple- or single- media condition and exposed to food and non-food advertising in an online game and /or a television cartoon . Children ’s food consumption ( kilojoules ) was measured at a snack immediately after exposure and then at lunch later in the day . Linear mixed models were conducted to examine relationships between food advertising exposure and dietary intake , taking into account gender , age and weight status . Results All children in the multiple-media condition ate more at a snack after exposure to food advertising compared with non-food advertising ; this was not compensated for at lunch , leading to additional daily food intake of 194 kJ ( 95 % CI 80–308 , p = 0.001 , d = 0.2 ) . Exposure to multiple-media food advertising compared with a single-media source increased the effect on snack intake by a difference of 182 kJ ( 95 % CI 46–317 , p = 0.009 , d = 0.4 ) . Food advertising had an increased effect among children with heavier weight status in both media groups . Conclusion Online ( ‘ advergame ’ ) advertising combined with TV advertising exerted a stronger influence on children ’s food consumption than TV advertising alone . The lack of compensation at lunch for children ’s increased snack intake after food advertising exposure suggests that unhealthy food advertising exposure contributes to a positive energy-gap , which could cumulatively lead to the development of overweight . Trial registration Australian New Zeal and Clinical Trials Registry , number ACTRN12617001230347 ( Retrospectively registered ) Background The inclusion of toys in food packages is a common marketing practice , and it is suspected of promoting obesogenic behaviours . This study aim ed to determine whether toys packaged with food are indeed increasing the amount of food eaten by children , and if this effect is enhanced by contemporary exposure to TV and /or advertising . Methods A total of 600 children ( balanced according to gender and age groups , 3–6 and 7–10 years old ) were r and omized in three school facilities in Argentina , Brazil and Mexico and exposed to food ( snacks ) alone or food associated with toys in an experimental setting . All of the children received the same meal at lunchtime . The products were packages in which chocolate was associated with toys in an egg-shaped container partially filled by chocolate . The children were asked to eat ad libitum for 20 minutes during the afternoon break . In addition , the children were r and omized into two groups and either shown or not shown a movie cartoon , with three different levels of exposure to commercials in the TV viewing condition ( 1 , 2 or 3 advertisements ) . Results No significant differences emerged between the “ toys ” and “ no toys ” groups even after taking into account exposure to TV , commercials and other confounding factors . Conclusions The inclusion of toys in food packages was not shown per se to lead to an increase in the caloric intake of children Objective To investigate , in a large pan Indian sample of school children , whether gadgets ( toys ) added to food increase food consumption , and if contemporary exposure to TV and /or advertising is a further promoting factor . Methods A total of 1,680 Indian children were first r and omized to food exposure with or without toy and then to a five-level exposure to TV viewing and advertising according to a 2 × 5 full factorial ad libitum eating design study . The sample size was computed to detect a difference of 20 Kcal of caloric intake ( assuming the same st and ard deviation of 20 Kcal in both groups ) between “ food with gadget ” ( Toy ) and “ food alone ” ( No Toy ) groups in each level of the exposure to TV and advertising factor , given an alpha error equal to 0.05 and a power of 0.90 . Results Mean caloric intake both in “ Toy ” and “ No Toy ” group was around 223 Kcal . When considering exposure to TV and advertising , mean values varied negligibly between 222 and 225 Kcal . According to linear models for the effect of gadget and exposure to TV and /or advertising on children ’s intake , no significant adjusted associations were found , neither as main effects nor as interactions . Conclusions Food consumption by children is not influenced by the presence of added toys , even after adjustment for several potential confounding factors . The city where they live and age significantly influences Indian children ’s caloric intake OBJECTIVES To assess pre-adolescent children 's responses to common child-oriented front-of-pack food promotions . METHODS Between-subjects , web-based experiment with four front-of-pack promotion conditions on energy-dense and nutrient-poor ( EDNP ) foods : no promotion [ control ] ; nutrient content cl aims ; sports celebrity endorsements ( male athletes ) and premium offers . Participants were 1302 grade 5 and 6 children ( mean age 11 years ) from Melbourne , Australia . Participants chose their preferred product from a r and omly assigned EDNP food pack and comparable healthier food pack then completed detailed product ratings . Child-oriented pack design s with colourful , cartooned graphics , fonts and promotions were used . RESULTS Compared to the control condition , children were more likely to choose EDNP products featuring nutrient content cl aims ( both genders ) and sports celebrity endorsements ( boys only ) . Perceptions of nutritional content were enhanced by nutrient content cl aims . Effects of promotions on some product ratings ( but not choice ) were negated when children referred to the nutrition information panel . Premium offers did not enhance children 's product ratings or choice . CONCLUSIONS Nutrient content cl aims and sports celebrity endorsements influence pre-adolescent children 's preferences towards EDNP food products displaying them . Policy interventions to reduce the impact of unhealthy food marketing to children should limit the use of these promotions The marketing of foods to children has been criticised by parents and academics alike and the control of such advertising is being considered by politicians . Much of the current research focuses on TV advertising . This study aim ed to investigate the effects of exposure to printed advertisements for healthy , less healthy and non-food products on children 's mood , hunger , food choice and product recall . Accordingly , 309 children ( mean age 9.7 years ) received booklets in a quasi-r and om order . Each booklet contained one of the three types of adverts , ratings of current self-perception and a food choice measure . The booklets were presented as a school-based media literacy exercise . Body weight , height and body satisfaction were assessed 1 week later . The three groups did not differ in the effect on current state or end of session food choice . However , children recalled more of the less healthy food products , even when accounting for recent exposure . Greater product recall of less healthy foods is relevant to future consumption but has a number of possible interpretations . The further exploration of non-TV food marketing is warranted at a time when marketing through these channels is increasing , not least as a result of greater TV advertising regulations OBJECTIVE To evaluate whether advertising for food influences choices made by children , the strength of these influences , and whether they might be easily undone by parental influences . STUDY DESIGN Children between 3 and 8 years of age ( n=75 ) were r and omized to watch a series of programs with embedded commercials . Some children watched a commercial for a relatively healthy food item , the other children watched a commercial for a less healthy item , both from the same fast-food company . Children were also r and omized either to receive parental encouragement to choose the healthy item or to choose whichever item they preferred . RESULTS Results indicated that children were more likely to choose the advertised item , despite parental input . Parental input only slightly moderated this influence . CONCLUSION Although advertising impact on children 's food choices is moderate in size , it appears resilient to parental efforts to intervene . Food advertisements directed at children may have a small but meaningful effect on their healthy food choices BACKGROUND : Preschoolers in the United States are heavily exposed to unhealthy food advertisements . Whether such exposure promotes cued eating has not been documented in this age group . METHODS : R and omized experiment among 60 children , aged 2 to 5 years , recruited in 2015–2016 from New Hampshire and Vermont . Children completed the experiment at a behavioral laboratory . Children were provided with a healthy snack to consume upon arrival then r and omized to view a 14-minute TV program embedded with advertisements for either a food or a department store . Children were provided 2 snack foods to consume ad libitum while viewing the TV program ; 1 of those snacks was the food advertised . Eating in the absence of hunger ( EAH ) was operationalized as the kilocalories of snack foods consumed . t tests were used to compare EAH by advertisement condition ; linear regression models assessed effect modification by the child ’s age , sex , BMI percentile , and parental feeding restriction . RESULTS : Mean age was 4.1 ( SD 0.9 ) years , 55 % of children were male , 80 % were non-Hispanic white , and 20 % were overweight or obese . There were no differences in child or socioeconomic characteristics by advertisement condition . Child BMI was not related to EAH . Mean kilocalories consumed during the EAH phase was greater among children exposed to the food advertisements ( 126.8 , SD : 58.5 ) versus those exposed to the nonfood advertisements ( 97.3 , SD : 52.3 ; P = .04 ) , an effect driven by greater consumption of the advertised food ( P < .01 ) . There was no evidence of effect modification . CONCLUSIONS : Findings suggest that food advertisement exposure may encourage obesogenic-eating behaviors among the very young BACKGROUND Previous studies have focused on the effects of television advertising on the energy intake of children . However , the rapidly changing food-marketing l and scape requires research to measure the effects of nontraditional forms of marketing on the health-related behaviors of children . OBJECTIVES The main aim of this study was to examine the effect of advergames that promote energy-dense snacks or fruit on children 's ad libitum snack and fruit consumption and to examine whether this consumption differed according to br and and product type ( energy-dense snacks and fruit ) . The second aim was to examine whether advergames can stimulate fruit intake . DESIGN We used a r and omized between-subject design with 270 children ( age : 8 - 10 y ) who played an advergame that promoted energy-dense snacks ( n = 69 ) , fruit ( n = 67 ) , or nonfood products ( n = 65 ) or were in the control condition ( n = 69 ) . Subsequently , we measured the free intake of energy-dense snacks and fruit . The children then completed question naire measures , and we weighed and measured them . RESULTS The main finding was that playing an advergame containing food cues increased general energy intake , regardless of the advertised br and or product type ( energy-dense snacks or fruit ) , and this activity particularly increased the intake of energy-dense snack foods . Children who played the fruit version of the advergame did not eat significantly more fruit than did those in the other groups . CONCLUSION The findings suggest that playing advergames that promote food , including either energy-dense snacks or fruit , increases energy intake in children Background Following publication of the PRISMA statement , the UK Centre for Review s and Dissemination ( CRD ) at the University of York in Engl and began to develop an international prospect i ve register of systematic review s with health-related outcomes . The objectives were to reduce unplanned duplication of review s and provide transparency in the review process , with the aim of minimizing reporting bias . Methods An international advisory group was formed and a consultation undertaken to establish the key items necessary for inclusion in the register and to gather views on various aspects of functionality . This article describes the development of the register , now called PROSPERO , and the process of registration . Results PROSPERO offers free registration and free public access to a unique prospect i ve register of systematic review s across all areas of health from all around the world . The dedicated web-based interface is electronically search able and available to all prospect i ve registrants . At the moment , inclusion in PROSPERO is restricted to systematic review s of the effects of interventions and strategies to prevent , diagnose , treat , and monitor health conditions , for which there is a health-related outcome .Ideally , registration should take place before the research ers have started formal screening against inclusion criteria but review s are eligible as long as they have not progressed beyond the point of completing data extraction .The required data set captures the key attributes of review design as well as the administrative details necessary for registration .Su bmi tted registration forms are checked against the scope for inclusion in PROSPERO and for clarity of content before being made publicly available on the register , rejected , or returned to the applicant for clarification . The public records include an audit trail of major changes to planned methods , details of when the review has been completed , and links to result ing publications when provided by the authors . Conclusions There has been international support and an enthusiastic response to the principle of prospect i ve registration of protocol s for systematic review s and to the development of PROSPERO .In October 2011 , PROSPERO contained 200 records of systematic review s being undertaken in 26 countries around the world on a diverse range of interventions BACKGROUND AND OBJECTIVES : Previous studies have focused on the effect of food advertisements on the caloric intake of children . However , the role of individual susceptibility in this effect is unclear . The aim of this study was to examine the role of impulsivity in the effect of advergames that promote energy-dense snacks on children ’s snack intake . METHODS : First , impulsivity scores were assessed with a computer task . Then a r and omized between-subject design was conducted with 261 children aged 7 to 10 years who played an advergame promoting either energy-dense snacks or nonfood products . As an extra manipulation , half of the children in each condition were rewarded for refraining from eating , the other half were not . Children could eat freely while playing the game . Food intake was measured . The children then completed question naire measures , and were weighed and measured . RESULTS : Overall , playing an advergame containing food cues increased general caloric intake . Furthermore , rewarding children to refrain from eating decreased their caloric intake . Finally , rewarding impulsive children to refrain from eating had no influence when they were playing an advergame promoting energy-dense snacks , whereas it did lead to reduced intake among low impulsive children and children who played nonfood advergames . CONCLUSIONS : Playing an advergame promoting energy-dense snacks contributes to increased caloric intake in children . The advergame promoting energy-dense snacks overruled the inhibition task to refrain from eating among impulsive children , making it more difficult for them to refrain from eating . The findings suggest that impulsivity plays an important role in susceptibility to food advertisements This study examined the potential moderating role of attentional bias ( i.e. , gaze duration , number of fixations , latency of initial fixation ) in the effect of advergames promoting energy-dense snacks on children 's snack intake . A r and omized between-subject design was conducted with 92 children who played an advergame that promoted either energy-dense snacks or nonfood products . Eye movements and reaction times to food and nonfood cues were recorded to assess attentional bias during playtime using eye-tracking methods . Children could eat freely after playing the game . The results showed that playing an advergame containing food cues increased total intake . Furthermore , children with a higher gaze duration for the food cues ate more of the advertised snacks . In addition , children with a faster latency of initial fixation to the food cues ate more in total and ate more of the advertised snacks . The number of fixations on the food cues did not increase actual snack intake . Food advertisements are design ed to grab attention , and this study shows that the extent to which a child 's attention is directed to a food cue increases the effect of the advertisement Food advertisements ( ads ) in TV programs influence food choice and have been associated with higher energy intake from snacks in children ; however , their effects at mealtime have not been reported . Therefore , we measured energy intake at a pizza meal consumed by normal weight ( NW ) and overweight/obese ( OW/OB ) children ( aged 9 - 14 years ) while they watched a TV program with or without food ads and following pre-meal consumption of a sweetened beverage with or without calories . NW and OW/OB boys ( experiment 1 , n = 27 ) and girls ( experiment 2 , n = 23 ) were r and omly assigned to consume equally sweetened drinks containing glucose ( 1.0 g/kg body weight ) or sucralose ( control ) . Food intake was measured 30 min later while children watched a program containing food or nonfood ads . Appetite was measured before ( 0 - 30 min ) and after ( 60 min ) the meal . Both boys and girls reduced energy intake at the meal in compensation for energy in the glucose beverage ( p < 0.05 ) . Food ads result ed in further compensation ( 51 % ) in boys but not in girls . Food ads increased energy intake at the meal ( 9 % ; p = 0.03 ) in OW/OB girls only . In conclusion , the effects of TV programs with food ads on mealtime energy intake and response to pre-meal energy consumption in children differ by sex and body mass index |
10,498 | 22,456,657 | There was a negative association between prelabor CD and early breastfeeding .
If breastfeeding is initiated , mode of delivery has no apparent effect on the number of mothers still breastfeeding at 6 mo . | BACKGROUND The rate of exclusive breastfeeding remains low in many countries .
Furthermore , cesarean delivery ( CD ) is increasing and may affect breastfeeding success .
OBJECTIVE The objective was to conduct a systematic review and meta- analysis of observational studies to determine whether CD ( prelabor or in-labor ) is associated with a lower rate of breastfeeding compared with vaginal delivery ( VD ) . | The objective of the study was to increase breastfeeding initiation and duration rates among postcesarean women by implementing a culturally appropriate breastfeeding intervention . This study was a prospect i ve population -based , controlled evaluation of a breastfeeding intervention consisting of 570 Jewish and Muslim postcesarean women who had delivered healthy , term infants at an Israeli hospital . Women in the control group ( n = 264 ) received st and ard hospital care and women in the intervention group ( n = 306 ) received early , culturally sensitive , postcesarean breastfeeding guidance . Surveys regarding breastfeeding duration practice s were conducted at 10 and 16 weeks postpartum . Overall and exclusive 4-month breastfeeding duration rates were significantly higher for the intervention group as compared to the control group for the Jewish women at 10 and 16 weeks postpartum . Since few Muslim women ceased breastfeeding , only exclusive breastfeeding rates were evaluated . At 10 and 16 weeks , significantly more Muslim women in the intervention group were exclusively breastfeeding as compared to the control group , although rates dramatically declined by 16 weeks . Despite the challenges to breastfeeding posed by cesarean delivery , early and appropriate breastfeeding guidance facilitated successful outcomes for both Jewish and Muslim women Objective To assess whether exclusive and prolonged breast feeding reduces the risk of childhood asthma and allergy by age 6.5 years . Design Cluster r and omised trial . Setting 31 Belarussian maternity hospitals and their affiliated polyclinics . Participants A total of 17 046 mother-infant pairs were enrolled , of whom 13 889 ( 81.5 % ) were followed up at age 6.5 years . Intervention Breastfeeding promotion intervention modelled on the WHO/UNICEF baby friendly hospital initiative . Main outcome measures International study of asthma and allergies in childhood ( ISAAC ) question naire and skin prick tests of five inhalant antigens . Results The experimental intervention led to a large increase in exclusive breast feeding at 3 months ( 44.3 % v 6.4 % ; P<0.001 ) and a significantly higher prevalence of any breast feeding at all ages up to and including 12 months . The experimental group had no reduction in risks of allergic symptoms and diagnoses or positive skin prick tests . In fact , after exclusion of six sites ( three experimental and three control ) with suspiciously high rates of positive skin prick tests , risks were significantly increased in the experimental group for four of the five antigens . Conclusions These results do not support a protective effect of prolonged and exclusive breast feeding on asthma or allergy . Trial registration Current Controlled Trials IS RCT N37687716 CONTEXT The evidence that breastfeeding improves cognitive development is based almost entirely on observational studies and is thus prone to confounding by subtle behavioral differences in the breastfeeding mother 's behavior or her interaction with the infant . OBJECTIVE To assess whether prolonged and exclusive breastfeeding improves children 's cognitive ability at age 6.5 years . DESIGN Cluster-r and omized trial , with enrollment from June 17 , 1996 , to December 31 , 1997 , and follow-up from December 21 , 2002 , to April 27 , 2005 . SETTING Thirty-one Belarussian maternity hospitals and their affiliated polyclinics . PARTICIPANTS A total of 17,046 healthy breastfeeding infants were enrolled , of whom 13,889 ( 81.5 % ) were followed up at age 6.5 years . INTERVENTION Breastfeeding promotion intervention modeled on the Baby-Friendly Hospital Initiative by the World Health Organization and UNICEF . MAIN OUTCOME MEASURES Subtest and IQ scores on the Wechsler Abbreviated Scales of Intelligence , and teacher evaluations of academic performance in reading , writing , mathematics , and other subjects . RESULTS The experimental intervention led to a large increase in exclusive breastfeeding at age 3 months ( 43.3 % for the experimental group vs 6.4 % for the control group ; P < .001 ) and a significantly higher prevalence of any breastfeeding at all ages up to and including 12 months . The experimental group had higher means on all of the Wechsler Abbreviated Scales of Intelligence measures , with cluster-adjusted mean differences ( 95 % confidence intervals ) of + 7.5 ( + 0.8 to + 14.3 ) for verbal IQ , + 2.9 ( -3.3 to + 9.1 ) for performance IQ , and + 5.9 ( -1.0 to + 12.8 ) for full-scale IQ . Teachers ' academic ratings were significantly higher in the experimental group for both reading and writing . CONCLUSION These results , based on the largest r and omized trial ever conducted in the area of human lactation , provide strong evidence that prolonged and exclusive breastfeeding improves children 's cognitive development . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N37687716 BACKGROUND Insulin , growth hormone ( GH ) , and growth factors ( insulin-like growth factors [ IGFs ] and their binding proteins [ IGFBPs ] ) are known to influence fetal growth and also the synthesis /secretion of the recently discovered hormones leptin and ghrelin . METHODS In 153 delivering mothers and their offspring at birth , we prospect ively investigated the association between mothers ' and babies ' serum concentrations of ghrelin , leptin , insulin , IGF-1 , and IGFBP-3 and neonatal anthropometric characteristics and the growth of the fetus . We also tried to put babies ' serum glucose and GH measurements in this context . RESULTS Birth weight ( BW ) , birth length , head circumference , and ponderal index ( PI ) were positively associated with cord IGF-1 , IGFBP-3 , and leptin and negatively associated with GH . BW was independently associated with maternal stature and prepartum weight , birth length with maternal stature , PI with maternal insulin and prepartum weight , and head circumference with maternal ghrelin . Compared with preterm infants whose development was appropriate for gestational age ( AGA ) , preterm growth-restricted babies displayed alteration in GH-IGF axis ( increased GH and low IGF-1 and IGFBP-3 concentrations ) , low leptin and glucose concentrations , and increased ghrelin concentrations . In large-for-gestational-age ( LGA ) babies , leptin , IGFBP-3 , insulin , and glucose concentrations were significantly higher in asymmetric LGA newborns than in symmetric LGA and AGA newborns . CONCLUSIONS We found relationships between metabolic factors , fetal growth , and anthropometry . Intrauterine growth restriction involved alteration in the fetal GH-IGF axis , with relatively low leptin and glucose concentrations and increased ghrelin concentrations . Leptin , insulin , and IGFBP-3 delineated subtypes of fetal overgrowth BACKGROUND Documented barriers to the implementation of Step 4 of the Baby Friendly Hospital Initiative , which relates to early initiation of breastfeeding , have not considered the impact of operative intervention in delivery on achievement of the goal . This study was design ed to test the hypothesis that hospital practice s in the immediate postpartum period that are associated with operative intervention in delivery can affect first mother-infant contact and initiation of breastfeeding . METHODS In a prospect i ve , longitudinal study , a sociodemographically representative sample of 203 primiparous women was recruited . Participants were interviewed at 2 days postpartum in metropolitan hospitals in Melbourne , Australia , and medical records were inspected . At 8 months postpartum 81 percent of participants completed a postal question naire . Three mode-of-delivery groups ( spontaneous vaginal delivery , instrumentally assisted vaginal delivery and cesarean section ) and 4 hospital-of-delivery groups ( including one accredited Baby Friendly Hospital ) were compared . RESULTS Two way ANOVA revealed that women who had a cesarean section experienced a significant delay in initiating breastfeeding compared with women giving birth vaginally , with or without instrumental assistance ( p < 0.001 ) . Significant differences in this aspect of care were also observed among hospitals , with the Baby-Friendly hospital performing significantly better than the other three hospitals ( p < 0.001 ) . An effect due to mode of delivery alone was demonstrated that could not be abolished by differences in hospital practice s ( p = 0.231 ) . Nevertheless , shorter elapsed time between birth and initiation of breastfeeding was not significantly associated with continuation of breastfeeding at 8 months postpartum ( p = 0.642 ) . CONCLUSIONS The findings confirmed that cesarean section was a significant barrier to the implementation of Baby Friendly Hospital Initiative Step 4 and that hospital practice s were amenable to changes that enabled its implementation regardless of the mode of delivery Background In Jordan , as in neighboring countries in the Middle East , higher education and higher employment rates in recent years among women have had an impact on traditionally based infant feeding . The objective of this study was to evaluate practice , knowledge and attitude to breastfeeding and to assess factors associated with breastfeeding among women in the north of Jordan . Methods A cross sectional study was carried out between 15 July 2003 and 15 August 2003 . A total of 344 women with children aged between 6 months and 3 years from five different villages in the north of Jordan were r and omly selected and interviewed . Information regarding participants ' demographics , infant feeding in first six months of life , knowledge and attitude towards breastfeeding was collected . Results Full breastfeeding was reported by 58.3 % , mixed feeding was reported by 30.3 % and infant formula feeding was reported by 11.4 % . Almost one third of the full breastfeeding group did so for 6–12 months , and almost two thirds did continue breastfeeding for more than one year . Employed women were more likely not to practice full breastfeeding compared to unemployed women ( odds ratio 3.34 , 95 % CI 1.60 , 6.98 ) , and women who had caesarian delivery were more likely not to practice full breastfeeding compared to those who had vaginal delivery ( odds ratio 2.36 , 95 % CI 1.17 , 4.78 ) . Jordanian women had a positive attitude but work place and short maternity leaves had a negative impact on breastfeeding . Conclusion This study showed that a high proportion of Jordanian women did breastfeed for more than one year . However , working women and those who deliver by caesarean section were less likely to breastfeed . It is speculated that adopting facilitatory measures at hospitals and work place could increase the rate of full breastfeeding BACKGROUND There has been concern about rising rates of caesarean section worldwide . This Article reports the third phase of the WHO global survey , which aim ed to estimate the rate of different methods of delivery and to examine the relation between method of delivery and maternal and perinatal outcomes in selected facilities in Africa and Latin America in 2004 - 05 , and in Asia in 2007 - 08 . METHODS Nine countries participated in the Asia global survey : Cambodia , China , India , Japan , Nepal , Philippines , Sri Lanka , Thail and , and Vietnam . In each country , the capital city and two other regions or provinces were r and omly selected . We studied all women admitted for delivery during 3 months in institutions with 6000 or fewer expected deliveries per year and during 2 months in those with more than 6000 deliveries . We gathered data for institutions to obtain a detailed description of the health facility and its re sources for obstetric care . We obtained data from women 's medical records to summarise obstetric and perinatal events . FINDINGS We obtained data for 109 101 of 112 152 deliveries reported in 122 recruited facilities ( 97 % coverage ) , and analysed 107 950 deliveries . The overall rate of caesarean section was 27.3 % ( n=29 428 ) and of operative vaginal delivery was 3.2 % ( n=3465 ) . Risk of maternal mortality and morbidity index ( at least one of : maternal mortality , admission to intensive care unit [ ICU ] , blood transfusion , hysterectomy , or internal iliac artery ligation ) was increased for operative vaginal delivery ( adjusted odds ratio 2.1 , 95 % CI 1.7 - 2.6 ) and all types of caesarean section ( antepartum without indication 2.7 , 1.4 - 5.5 ; antepartum with indication 10.6 , 9.3 - 12.0 ; intrapartum without indication 14.2 , 9.8 - 20.7 ; intrapartum with indication 14.5 , 13.2 - 16.0 ) . For breech presentation , caesarean section , either antepartum ( 0.2 , 0.1 - 0.3 ) or intrapartum ( 0.3 , 0.2 - 0.4 ) , was associated with improved perinatal outcomes , but also with increased risk of stay in neonatal ICU ( 2.0 , 1.1 - 3.6 ; and 2.1 , 1.2 - 3.7 , respectively ) . INTERPRETATION To improve maternal and perinatal outcomes , caesarean section should be done only when there is a medical indication . FUNDING US Agency for International Development ( USAID ) ; UNDP/UNFPA/WHO/World Bank Special Programme of Research , Development and Research Training in Human Reproduction ( HRP ) , WHO , Switzerl and ; Ministry of Health , Labour and Welfare of Japan ; Ministry of Public Health , China ; and Indian Council of Medical Research Breastfeeding is the recommended feeding for all healthy infants . The aim of our study was to assess the current state of breastfeeding prevalence , duration and behaviour in Bavaria , Germany as a basis for targeting breastfeeding promotion measures . The Bavarian Breastfeeding Study is a prospect i ve cohort study of 3822 mothers who delivered in April 2005 in Bavaria , Germany . Breastfeeding duration and determinants such as socioeconomic status , attitudes towards breastfeeding , birth mode and breastfeeding problems were assessed by question naires 2 - 6 d after birth and 2 , 4 , 6 , and 9 months after birth . The initial breastfeeding rate was 90 % . After 4 months 61 % still breastfed ( any breastfeeding ) . In the multivariate analyses the main influencing factor reducing breastfeeding initiation was the partner 's negative attitude towards breastfeeding ( OR 21.79 ; 95 % CI 13.46 , 35.27 ) . No initial breastfeeding was also associated with lower education , maternal gr and mother 's negative attitude and pre-term birth . Protective factors were primary breastfeeding experience and information on breastfeeding before birth . Breastfeeding duration < 4 months was strongly associated with breastfeeding problems ( OR 7.56 ; 95 % CI 6.21 , 9.19 ) , smoking , lower education , partner 's negative attitude and Caesarean section . Since the attitude of family members is an important influencing factor on breastfeeding rates , breastfeeding promotion should also target the partners of pregnant women and the families of newborn infants . Public health interventions such as more effective support for the management of breastfeeding problems , especially in lower social status families , should be implemented and their effectiveness should be critically evaluated OBJECTIVE Breast-feeding ( BF ) provides the ideal food for the healthy growth and development of infants . The prevalence of BF in Lebanon shows mixed results . The present study was the first large-scale , extensive survey on BF parameters in Lebanon that aim ed to explore demographic , socio-economic and other fundamental issues associated with the initiation and duration of BF by Lebanese mothers . DESIGN The survey was cross-sectional in design and administered over 10 months . SETTING Information on all variables was collected from mothers at health centres . SUBJECTS Two-stage sampling was conducted to select participants . A total of 1,000 participants were r and omly selected . A consent form was provided to each participant . Data were collected from 830 of these . RESULTS Almost all mothers were Lebanese , married and had given birth in a hospital . About a third stated that breast milk was the first food introduced after birth . Although 55.9 % started breast-feeding their newborns within a few hours after birth , and 18.3 % within half an hour , 21.2 % replied that they initiated BF a few days after birth . Only 4.6 % of the mothers replied that they never breast-fed their infant . Timing of initiation of BF was associated with the type of delivery ( vaginal/Caesarean section ) and hospital-related factors ( rooming-in , night feedings and frequency of mother-infant interaction ) . Of the mothers who breast-fed exclusively beyond 6 months , 86.7 % had initiated BF a few hours following delivery , while only 13.3 % had initiated BF a few days later . Compared with the exceptionally high proportion of BF initiation , exclusivity of BF was low , dropping to 52.4 % at 1 month . Exclusivity of BF was also associated with place of residence ( urban/rural ) and negatively associated with educational level of the mother . Duration of BF was inversely associated with the use of pain killers during delivery and maternal education . Rural mothers and those who practised exclusive BF maintained BF for a longer duration . CONCLUSION Initiation rates of BF are very high in Lebanon but rates of exclusive BF are low and duration of BF is short . Future research targeting the factors associated with BF , with particular emphasis on exclusivity , is needed . For the 95.4 % of mothers who initiated BF , an ecological perspective on intervention aim ed at women and their social support system is required to improve duration and exclusivity OBJECTIVE To investigate contact between mothers and their newborn child and study if there are differences between those who requested an elective caesarean section compared to women who had a vaginal birth and those who underwent an elective caesarean section due to obstetrical indication . The psychometric properties of a scale that measure the contact between mother and child were also investigated . DESIGN A prospect i ve cohort study . SETTING D and eryd Hospital , Stockholm , Sweden . SAMPLE 510 primiparas from three groups : women undergoing caesarean section on maternal request ( n=96 ) , women undergoing caesarean section on obstetrical indication ( n=116 ) and women planning a vaginal delivery ( n=198 ) . The later were further divided into subgroups ; women who underwent assisted vaginal delivery ( n=35 ) and women who had an emergency caesarean section ( n=65 ) . METHODS The instrument used was the Alliance Scale . MAIN OUTCOME MEASURE The contact between mother and child in relation to mode of delivery . RESULTS The contact with the child was rated as positive on all occasions : there were no significant differences between the groups . The relation to the partner was rated as positive at all occasions . Mothers with a vaginal delivery experienced breastfeeding less stressful than the mothers with a caesarean delivery . Three and nine months after delivery the mothers with a caesarean delivery on request reported more breastfeeding problems than mothers in the other groups . Mothers with a vaginal delivery rated less sadness at every occasion . CONCLUSION Mode of delivery does not seem to affect how mothers experience their contact towards the newborn child Aims : To investigate the effect of caesarean section on gastrointestinal symptoms , atopic dermatitis , and sensitisation to nutritional allergens in infants . Methods : A total of 865 healthy full term neonates with parental history of allergy participating in the prospect i ve German Infant Nutritional Intervention Program ( GINI ) were exclusively breast fed during the first four months of life and had a one year follow up . Data were obtained by follow up visits at age 1 , 4 , 8 , and 12 months , weekly diaries for the first six months , and measurement of total and specific IgE at birth and 12 months . Results : Infants born by caesarean section ( 147/865 , 17 % ) had a greater risk of diarrhoea ( ORadj 1.46 , 95 % CI 1.022 to 2.10 ) and sensitisation to food allergens , both in adjusted ( ORadj 2.06 , 95 % CI 1.123 to 3.80 ) and stratified analyses ( by cord blood IgE ) . Caesarean delivery was not associated with colicky pain and atopic dermatitis . Conclusion : Caesarean delivery might be a risk factor for diarrhoea and sensitisation in infants with family history of allergy . Further research in this area seems warranted as choosing caesarean section becomes increasingly popular INTRODUCTION The rate of cesarean delivery ( CD ) has significantly increased over the last years , even in low risk pregnancies . Our objective was to compare the neonatal morbidity rate in low risk term infants delivered by vaginal or CD . DESIGN Prospect i ve observational and analytical cohort study . Main outcome measures . Incidence of any neonatal morbidity and respiratory morbidity . Population and methods . Infants < or = 37 weeks born at the Hospital Italiano de Buenos Aires between December 2004 and July 2006 were eligible . Exclusion criteria included : any maternal related disorder , acute or chronic fetal distress , breech presentation in primiparous women , multiple pregnancies , intrauterine growth restriction and newborns with major malformations . RESULTS A total of 2021 infants were included , 1120 born vaginally and 901 by CD . Main indications for CD were failure to progress labor ( 46 % ) and previous CD ( 37 % ) . Only 3 % of CD was performed by maternal request . Any neonatal morbidity rate was 9 % in infants born by CD and 6.6 % in infants born vaginally ( RR 1.36 ; 95%CI 1.01 - 1.8 ) . Respiratory morbidity rate was 5.3 % in infants born by CD and 3.1 % in those born vaginally ( RR 1.7 ; 95%CI 1.1 - 2.6 ) . When stratified by gestational age , respiratory morbidity was higher only for infants < or = 38 weeks ( 7.4 % in CD vs. 2.1 % in vaginal delivery ; RR 3.5 ; 95%CI 1.5 - 8.1 ) . Also , respiratory morbidity was higher in infants born < or = 38 weeks by CD without labor vs. those with labor 10.5 % and 3.9 % , respectively ( RR 1.35 ; 95%CI : 1.07 - 1.70 ) . In a logistic regression analysis , CD and male sex were independently associated with higher respiratory morbidity . There were not significant differences in other morbidities . NICU admission was higher in infants born by CD ( 9.5 % vs. 6.1 % ; RR 1.5 ; 95 % CI : 1.1 - 2.1 ) . Sixty-eight percent of the mothers from the CD group refereed having moderate to severe pain in the puerperium vs. 36 % in the vaginal group ( RR 1.9 ; 95 % CI : 1.7 - 2.1 ) . Exclusive breastfeeding at discharge was significantly lower in infants born by CD ( 90 % vs. 96 % ; RR 0.94 95%CI 0.92 - 0.96 ) . CONCLUSIONS Low risk CD at term was associated with a higher neonatal morbidity , NICU admission and maternal pain in the puerperium . It also reduces exclusive breastfeeding rate at discharge OBJECTIVE To determine the influence of joined mother-child hospital lodging ( JL ) on the frequency of exclusive human lactation ( EHL ) from birth to four months of age . MATERIAL AND METHODS Non-r and omized cohort study performed at the lactation clinic of the " Luis Castelazo Ayala " Hospital of the Mexican Social Security Institute from January 1993 to October 1994 which included 178 healthy mother-child pairs ( MCP ) with term pregnancy . The jointly lodged group ( JL ) consisted of 90 MCP in which mothers received assessment for lactation ; 88 MCP were lodged separately and no assessment was provided . Results were statistically analyzed to determine frequency and variable associations . RESULTS Feeding was recorded as either EHL , powdered milk or both . Groups with or without JL were stratified by form of birth , either labor or Cesarean section . With the Mantel-Haenszel X2 and logarithmic range , differences were significant with p < 0.05 . During the study , global lactation was similar among groups . In the first month , EHL was higher in the JL group , 61 vs 42 % independently of the form of birth ( p < 0.05 ) . The only variable which influenced EHL was JL . CONCLUSIONS Mother-child JL favours EHL during the first month post-partum Objective . The purpose of this study was to investigate first‐time mothers undergoing cesarean section in the absence of medical indication , their reason for the request , self‐estimated health , experience of delivery , and duration of breastfeeding . We also aim ed to study if signs of depression postpartum are more common in this group . Method . In a prospect i ve cohort study 357 healthy primiparas from two different groups , “ cesarean section on maternal request ” ( n = 91 ) and “ controls planning a vaginal delivery ” ( n = 266 ) completed three self‐ assessment question naires in late pregnancy , two days after delivery and 3 months after birth . Symptom scores from the Edinburgh postnatal depression scale at three months after birth were also investigated . Results . Women requesting cesarean section experienced their health ass less good ( p<0.001 ) and were more often planning for one child only ( p<0.001 ) . They more often reported anxiety for lack of support during labor ( p<0.001 ) , for loss of control ( p<0.001 ) , and concern for fetal injury/death ( p<0.001 ) . After planned cesarean section women in this group reported a better birth experience compared to women planning a vaginal birth ( p<0.001 ) . They were breastfeeding to a lesser extent three months after birth ( p<0.001 ) . There were no differences in signs of postpartum depression between the groups three months after birth ( p = 0.878 ) . Conclusion . The knowledge gained from this study may help in underst and ing why some women prefer to give birth with elective cesarean section . It also eluci date s the need for awareness of professional support during vaginal birth A comparative study has been made on two groups of 102 mothers each who delivered children in the postnatal ward of obstetrics and gynaecology department of Calcutta National Medical College before and after the introduction of BFHI ( Baby Friendly Hospital Initiative ) . The study revealed that only 14.3 % of the babies who were delivered normally were given their first breast feed in time , the ideal time of half an hour , while not a single baby delivered by caesarean section were given their breast feed within the stipulated time period of 4 - 6 hours . However , there has been a significant overall reduction in the time gap between the birth and the first breast feed in all types of delivery . BFHI has also made significant reduction of prelacteal feeds and in-between feeds in the newborns especially those delivered normally . The fact that babies of first order and those delivered by caesarean section are lagging behind as far as exclusive breast feeding is concerned has been highlighted in the study The objectives of the study were to increase post-Caesarean breastfeeding rates and decrease timing of post-Caesarean breastfeeding initiation in multicultural population s following a post-Caesarean breastfeeding intervention . The study was a prospect i ve population -based evaluation of a breastfeeding intervention for post-Caesarean women of different cultures at a southern Israeli hospital . The study population consisted of 570 Jewish and Muslim post-Caesarean women who had delivered healthy , term infants . The control group ( n=264 ) received st and ard hospital care and the intervention group ( n=306 ) received early , culturally sensitive , post-Caesarean breast-feeding guidance and education by trained professionals . Timing of post-Caesarean maternal-infant contact and breastfeeding initiation outcomes for the Jewish and Muslim women significantly improved following the intervention OBJECTIVE To investigate the impact of intrapartum analgesia on infant feeding at hospital discharge . DESIGN Retrospective cohort . SETTING Maternity unit of a UK district general hospital . POPULATION A r and om sample of 425 healthy primiparae delivering healthy singleton babies at term in 2000 . METHODS A r and om sample of primiparae delivering term neonates was identified from the birth register . We retrieved and analysed the corresponding joint midwifery/obstetric case notes . MAIN OUTCOME MEASURE Infant feeding method at discharge from hospital . RESULTS Women [ 190/424 ( 45 % ) ] were exclusively bottle feeding their babies at discharge from hospital . No one commenced breastfeeding after hospital discharge . Regression analysis revealed that the main determinants of bottle feeding were as follows : maternal age [ odds ratio ( OR ) 0.90 , 95 % confidence interval [ CI ] 0.85 - 0.95 per year ] ; occupation ( OR 0.63 , 95 % CI 0.40 - 0.99 for each category , unemployed , manual , non-manual ) ; antenatal feeding intentions ( OR 0.12 , 95 % CI 0.080 - 0.19 for each category , bottle feeding , undecided , breastfeeding ) ; caesarean section ( OR 0.25 , 95 % CI 0.13 - 0.47 , caesarean or vaginal delivery ) ; and dose of fentanyl administered intrapartum ( OR 1.004 , 95 % CI 1.000 - 1.008 , 90 % CI 1.001 - 1.007 for each microgram administered , range 8 - 500 mug ) . CONCLUSIONS A dose-response relationship between fentanyl and artificial feeding has not been reported elsewhere . When well-established determinants of infant feeding are accounted for , intrapartum fentanyl may impede establishment of breastfeeding , particularly at higher doses Object To evaluate the effects of psychosocial support during labour , delivery and the immediate postpartum period provided by a female companion ( doula ) BACKGROUND To evaluate the influence of regional techniques of anesthesia and analgesia on breastfeeding rate after cesarean section and vaginal delivery . METHODS STUDY DESIGN prospect i ve , area-based . SETTING Obstetrics and Pediatrics Department at Aosta Valley Regional Hospital . SUBJECTS all the mothers and their newborns during a three-year period ( 1993 - 1995 ) . Maternal wish to breastfeed was the main inclusion criterion . Data recorded : feeding modality at discharge , anesthesia and analgesia modality , maternal/neonatal socio-demographic and clinical data . RESULTS 2725 records were examined , among them 1920 vaginal deliveries and 355 cesarean sections were statistically analyzed . chi 2 analysis showed a significant greater incidence of breastfeeding after cesarean section under regional anesthesia ( spinal or epidural ) versus general anesthesia : 95 % vs 85.5 % , p = 0.002 . Breastfeeding rate was not different after vaginal delivery with epidural analgesia versus delivery without analgesia : 96.5 % vs 97.8 % . Logistic regression confirmed the positive role of regional anesthesia and few other maternal and neonatal variables on breastfeeding rate after cesarean section . CONCLUSIONS Regional anesthesia seems to be advantageous for breastfeeding after cesarean section , probably because of a faster neonatal-maternal bonding if compared with general anesthesia . Epidural analgesia for vaginal delivery does not adversely affects breastfeeding if compared with delivery without analgesia BACKGROUND Operative delivery rates are currently rising in many countries , but the effects of this factor on the initiation and duration of breastfeeding are unclear . The purpose of this study was to evaluate breastfeeding success after instrumental vaginal delivery or cesarean section at full dilatation , and to investigate whether timing of discharge after operative delivery affects breastfeeding rates . METHODS A prospect i ve cohort study was conducted of 393 women with term , singleton , live , cephalic pregnancies who required delivery in theater during the second stage of labor between February 1999 and February 2000 . Postal question naires were mailed to participants at 6 weeks and 1 year . Logistic regression models were used to explore the relationships between infant feeding and mode of delivery , controlling for factors previously correlated with breastfeeding success . RESULTS Rates of exclusive breastfeeding at discharge and 6 weeks postpartum were 70 and 44 percent , respectively . No significant differences occurred when instrumental vaginal delivery was compared with cesarean section , adjusted OR 0.84 ( 95 % CI 0.50 , 1.41 ) and 1.15 ( 95 % CI 0.69 , 1.93 ) respectively . Breastfeeding rates after failed instrumental delivery were similar to those after immediate cesarean section , adjusted OR 0.99 ( 95 % CI 0.72 , 1.38 ) and 1.28 ( 95 % CI 0.91 , 1.78 ) . Women who had a longer in-patient stay after cesarean section were more likely to achieve exclusive breastfeeding at hospital discharge ( 78 % vs 66 % , p = 0.03 ) . CONCLUSIONS Method of operative delivery in the second stage of labor does not appear to influence initiation or duration of exclusive breastfeeding . A longer inpatient stay may help cesarean-delivered women to initiate breastfeeding BACKGROUND Short postpartum hospital stays may leave inadequate time for women to receive assistance with breastfeeding . Women leaving the hospital early may also have household responsibilities that could interfere with breastfeeding . This study examined the relationship between postpartum length of stay and breastfeeding cessation . METHODS This study used data from 10,519 respondents to the California Maternal and Infant Health Assessment ( MIHA ) surveys from 1999 to 2001 . MIHA is an annual statewide stratified r and om sample , population -based study of childbearing women in California . Survival analysis was used to examine the relationship between length of stay and length of time breastfeeding . Women were asked about the number of nights their infant stayed in the hospital at birth , whether they breastfed , and if so , the age of the child when they stopped . Hospital stay was defined in three categories : st and ard ( 2 nights for a vaginal delivery , 4 nights for a cesarean section ) , or shorter or longer than the st and ard stay . RESULTS Approximately 88 percent of women initiated breastfeeding . Unadjusted predictors of breastfeeding cessation included short or long postpartum stay ; young maternal age ; Hispanic , African American , or Asian/Pacific Isl and er race/ethnicity ; being unmarried ; low income or education level ; primiparity ; being born in the 50 United States or the District of Columbia ; smoking during pregnancy ; and low infant birthweight . After adjustment for potential confounders , women with a short stay remained slightly more likely to terminate breastfeeding than women with a st and ard stay ( relative risk , 1.11 , 95 % confidence interval 1.01 , 1.23 ) . CONCLUSION Women who leave the hospital earlier than the st and ard recommended stay are at somewhat increased risk of terminating breastfeeding early Recently , there has been increasing concern about the decline in breast-feeding pattern in developing countries . The objectives of this study were to document the recent breast-feeding trends in Jeddah during the first year of an infant 's life and identify the probable maternal risk factors implicated in breast-feeding cessation . Data were collected from six r and omly selected primary health care centres in Jeddah City . All married women with an infant < /= 12 completed months of age were interviewed , and information on socio-demographic characteristics , breast feeding and contraceptive use were collected . Cox proportional hazard regression model was used to calculate the adjusted odds ratios for the various maternal risk factors related to breast-feeding cessation . A total of 400 women were enrolled in the study . Their mean age at delivery was 28.0 years ( SD = 4.1 years ) . Approximately 40.0 % had never attended school , 43.0 % had at least five children and 13.8 % were smokers . Deliveries by caesarean section were reported by 13.0 % of women and contraceptive use by 44.7 % , among whom oral contraceptives were the commonest method . Around 94.0 % of women ever initially breast fed their infants , and this proportion dropped to 40.0 % by the infant 's 12th month . Women who delivered by caesarean section ( OR = 1.9 [ 95 % CI 1.3 , 2.8]P = 0.001 ) and those who used oral contraceptives ( OR = 1.5 [ 95 % CI 1.1 , 2.2]P = 0.031 ) were at higher risk of stopping breast feeding and lower probability of maintaining breast feeding to the 12th month post partum than those who delivered vaginally and did not use oral contraceptives . Breast-feeding practice seems to decline rapidly during the first year of the infant 's life . Health care professionals should promote breast-feeding practice as early as the antenatal period . They should also take into consideration the impact of caesarean section deliveries and early oral contraceptive use to avoid their negative impact on breast-feeding practice A personal prospect i ve study was made of some perinatal and postnatal problems associated with induction of labour by three different methods in primiparous women with unripe cervices . The methods of induction were : ( A ) amniotomy followed by intravenous oxytocin [ 49 ] , ( B ) amniotomy followed by intravenous prostagl and in E2 [ 39 ] , ( C ) prostagl and in E2 by the extra-amniotic route [ 42 ] . A spontaneous group ( D ) comprising 54 mother -- infant pairs was also studied . Length of gestation was between 37 and 42 wk in all but 2 cases . There was no perinatal mortality , and no infant had hyaline membrane disease . A close association was found between method of delivery and method ( or absence ) or induction . The caesarean section rate was highest in group C and lowest in group D. The spontaneous vaginal delivery rate was lowest in group C and highest in group D. More infants in the three induction groups were admitted to the Special Care Baby Unit ( SCBU ) than in the spontaneous group . No significant associations were found between the severity of the conditions leading to induction and caesarean section rates , low Apgar scores , admissions to SCBU , or the favourability of the cervix before induction . Among those who intended to breast feed fewer infants in the spontaneous group changed from breast to bottle while in hospital and after discharge from hospital than in the combined induction groups . Success in breast-feeding was not significantly associated with method of delivery or whether the infant was admitted to SCBU or not Various clinical practice s have been found to be associated with breast-feeding problems . However , little is known about the effect of pain , obstetrical procedures and analgesia on breast-feeding behaviour . We design ed a retrospective study with a question naire concerning pain , obstetrical procedures and breast-feeding practice s mailed to 164 primiparae in Lapl and . Altogether 99 mothers ( 60 % ) returned completed question naires that could be included in the analysis , which was carried out in two steps . Firstly , all accepted question naires were grouped according to the success or failure to breast-feed fully during the first 12 weeks of life . Secondly , an ad hoc cohort study was performed on the sub- sample of 64 mothers delivered vaginally . As many as 44 % of the 99 mothers reported partial breast feeding or formula feeding during the first 12 weeks . Older age of the mother , use of epidural analgesia and the problem of " not having enough milk " were associated with the failure to breast-feed fully . Caesarean section , other methods of labour analgesia and other breast-feeding problems were not associated with partial breast feeding or formula feeding . In the sub- sample , 67 % of the mothers who had laboured with epidural analgesia and 29 % of the mothers who laboured without epidural analgesia reported partial breast feeding or formula feeding ( P = 0.003 ) . The problem of " not having enough milk " was more often reported by those who had had epidural analgesia . Further studies conducted prospect ively are needed to establish whether a causal relationship exists between epidural analgesia and breast-feeding problems OBJECTIVE To examine the effects of cesarean and forceps or vacuum delivery and parental smoking habits on the initiation and duration of breast‐feeding . METHODS We conducted a prospect i ve , population ‐based birth cohort study in 1997 . Data were collected on breast‐feeding history , household smoking habits , method of delivery , and other demographic , obstetric , behavioral , and potential confounding variables via a st and ardized self‐administered question naire . Multivariable logistic regression was used to examine the association between method of birth ( cesarean versus forceps or vacuum delivery versus normal vaginal birth ) and either not initiating breast‐feeding or doing so for less than 1 month . Among women who breast‐fed for 1 month or more , multivariable survival analysis was employed to study the relationship between method of delivery and breast‐feeding duration . We repeated these analyses to examine the link between parental smoking habits and breast‐feeding initiation and duration . RESULTS A total of 7825 mother‐infant pairs were followed up for 9 months . Cesarean delivery was a risk factor for not initiating breast‐feeding , for breast‐feeding less than 1 month , and remained a significant hazard against breast‐feeding duration . Assisted delivery with forceps or vacuum , although not associated with breast‐feeding initiation , was a significant risk against breast‐feeding duration . Conversely , current parental smoking habits only affected breast‐feeding initiation but were unrelated to breast‐feeding duration . CONCLUSION This study indicates a possible effect of forceps or vacuum delivery on breast‐feeding and of cesarean on long‐term breast‐feeding duration . The findings provide additional evidence in support of the avoidance of unnecessary obstetric interventions Objective . The objective of this study was to evaluate clinical and epidemiological characteristics of the maternal and neonatal immigrant population and to compare it with the Italian population in the Agostino Gemelli Hospital ( Rome ) . Methods . This study was a prospect i ve population -based study . We compared 595 newborns from immigrant mothers with 2413 newborns from Italian mothers . Neonatal characteristics included in this study were sex , gestational age , birth weight , Apgar score , transfer to pathology units , minor pathologies , and type of breastfeeding at discharge . Maternal characteristics included nationality , age , parity , type of delivery , twin birth , and pathology during the pregnancy . Results . Immigrant newborns comprised 20 % of the total births included in the study . No statistically significant differences were found between immigrant and Italian newborns in gestational age , birth weight , or Apgar score . Immigrant newborns were transferred to the Paediatric Infectious Disease Unit more frequently than Italian newborns , had a significantly higher incidence of hyperbilirubinemia and a higher rate of exclusive and prevalent breastfeeding at discharge . Immigrant mothers came predominantly from Eastern Europe , were younger and had caesarean sections less frequently than Italian mothers . Conclusion . No significant differences in biological and clinical characteristics or in medical practice were found between groups , except for a higher frequency of neonatal hyperbilirubinemia and an inclination among immigrant mothers toward breastfeeding BACKGROUND Both the initiation and maintenance of breastfeeding have been reported to be negatively affected by maternal type 1 diabetes ( T1D ) . The aim of this study was to prospect ively examine the breastfeeding patterns among mothers with and without T1D participating in a large international r and omized infant feeding trial ( TRIGR ) . METHODS Families with a member affected by T1D and with a newborn infant were invited into the study . Those who had HLA-conferred genetic susceptibility for T1D tested at birth with gestation > 35 weeks and were healthy were eligible to continue in the trial . Among the 2160 participating children , 1096 were born to women with T1D and 1064 to unaffected women . Information on infant feeding was acquired from the family by frequent prospect i ve dietary interviews . RESULTS Most ( > 90 % ) of the infants of mothers with and without T1D were initially breastfed . Breastfeeding rates declined more steeply among mothers with than without T1D being 50 and 72 % at 6 months , respectively . Mothers with T1D were younger , less educated and delivered earlier and more often by caesarean section than other mothers ( p < 0.01 ) . After adjusting for all these factors associated with the termination of breastfeeding , there was no difference in the duration of breastfeeding among mothers with and without T1D . CONCLUSIONS Maternal diabetes status per se was not associated with shorter breastfeeding . The lower duration of breastfeeding in mothers with T1D is largely explained by their more frequent caesarean sections , earlier delivery and lower age and education At a time when there is much criticism of increasing caesarean section rates , as well as an increased emphasis on involving the patient in decisions regarding her care , we decided to assess the effect of maternal request on the elective caesarean section rate . The study was a prospect i ve patient interview and case note review , set at a District General Hospital in Watford , Hertfordshire over a 1-year period . Eligible patients included all women undergoing elective caesarean section , with the main outcome measure being the number of elective caesarean sections performed without obstetric contraindication to vaginal delivery . Out of 3025 deliveries , 570 ( 18.8 % ) were delivered by caesarean section , 276 ( 9.1 % ) electively and 293 ( 9.7 % ) as an emergency procedure . Of the elective procedures ( 18.2 % of the total number of operations ) , 38 % were performed because of maternal request . We conclude that maternal request is a significant factor in the rise in caesarean section rate The incidence of breastfeeding among women with insulin dependent diabetes mellitus ( IDDM ) has received little attention . During a 17-month period , 19 pregnant women with IDDM attending the prenatal clinic of the Royal Women 's Hospital ( Brisbane ) were recruited into a prospect i ve study to compare their breastfeeding outcomes with a control group of 18 women who were not diabetic ( non-IDDM ) . The incidence of breastfeeding was monitored . At discharge , 63 percent of IDDM and 78 percent of non-IDDM mothers were breastfeeding . At eight weeks , the proportion of each were nearly identical ( 58 percent and 56 percent respectively ) , and at three months of age , 47 percent of IDDM mothers and 33 percent of non-IDDM women continued to breastfeed . We conclude that women with IDDM breastfeed at least as commonly and for as long as women without diabetes , despite the fact that infants of the IDDM women were artificially fed more often and began breastfeeding later than infants in the control group . In addition , the IDDM women were more likely to be delivered by Caesarean section ( p<0.0005 ) , to be delivered earlier ( p<0.0002 ) , and their babies more likely to be admitted to the special care nursery ( p<0.0005 ) CONTEXT Current evidence that breastfeeding is beneficial for infant and child health is based exclusively on observational studies . Potential sources of bias in such studies have led to doubts about the magnitude of these health benefits in industrialized countries . OBJECTIVE To assess the effects of breastfeeding promotion on breastfeeding duration and exclusivity and gastrointestinal and respiratory infection and atopic eczema among infants . DESIGN The Promotion of Breastfeeding Intervention Trial ( PROBIT ) , a cluster-r and omized trial conducted June 1996-December 1997 with a 1-year follow-up . SETTING Thirty-one maternity hospitals and polyclinics in the Republic of Belarus . PARTICIPANTS A total of 17 046 mother-infant pairs consisting of full-term singleton infants weighing at least 2500 g and their healthy mothers who intended to breastfeed , 16491 ( 96.7 % ) of which completed the entire 12 months of follow-up . INTERVENTIONS Sites were r and omly assigned to receive an experimental intervention ( n = 16 ) modeled on the Baby-Friendly Hospital Initiative of the World Health Organization and United Nations Children 's Fund , which emphasizes health care worker assistance with initiating and maintaining breastfeeding and lactation and postnatal breastfeeding support , or a control intervention ( n = 15 ) of continuing usual infant feeding practice s and policies . MAIN OUTCOME MEASURES Duration of any breastfeeding , prevalence of predominant and exclusive breastfeeding at 3 and 6 months of life and occurrence of 1 or more episodes of gastrointestinal tract infection , 2 or more episodes of respiratory tract infection , and atopic eczema during the first 12 months of life , compared between the intervention and control groups . RESULTS Infants from the intervention sites were significantly more likely than control infants to be breastfed to any degree at 12 months ( 19.7 % vs 11.4 % ; adjusted odds ratio [ OR ] , 0.47 ; 95 % confidence interval [ CI ] , 0.32 - 0.69 ) , were more likely to be exclusively breastfed at 3 months ( 43.3 % vs 6.4 % ; P<.001 ) and at 6 months ( 7.9 % vs 0.6 % ; P = .01 ) , and had a significant reduction in the risk of 1 or more gastrointestinal tract infections ( 9.1 % vs 13.2 % ; adjusted OR , 0.60 ; 95 % CI , 0.40 - 0.91 ) and of atopic eczema ( 3.3 % vs 6.3 % ; adjusted OR , 0.54 ; 95 % CI , 0.31 - 0.95 ) , but no significant reduction in respiratory tract infection ( intervention group , 39.2 % ; control group , 39.4 % ; adjusted OR , 0.87 ; 95 % CI , 0.59 - 1.28 ) . CONCLUSIONS Our experimental intervention increased the duration and degree ( exclusivity ) of breastfeeding and decreased the risk of gastrointestinal tract infection and atopic eczema in the first year of life . These results provide a solid scientific underpinning for future interventions to promote breastfeeding We studied the involvement of naturally occurring odours in guiding the baby to the nipple . One breast of each participating mother was washed immediately after delivery . The newborn infant was placed prone between the breasts . Of 30 infants , 22 spontaneously selected the unwashed breast . The washing procedure had no effect on breast temperature . We concluded that the infants responded to olfactory differences between the washed and unwashed breasts OBJECTIVE To study the effects of caesarean section on breastfeeding . METHODS Six hundred and two [ 301 cases was caesarean section ( caesarean section group ) and 301 cases was vaginal delivery ( vaginal delivery group ) ] nulliparas were interviewed face-to-face at antepartum and postpartum in an indication-matched prospect i ve study . RESULTS There was a significantly lower postpartum prolactin ( PRL ) level in the caesarean section group ( 8.48 nmol/L , 95 % CI : 7.80 - 9.21 nmol/L ) compared with vaginal delivery group ( 9.61 nmol/L , 95 % CI : 8.99 - 10.26 nmol/L ) during 6 - 24 hours in the daytime after delivery . The median time of breastfeeding initiation was 12 hours and 2 hours after birth for caesarean section and vaginal delivery groups respectively . Caesarean section was an important hazard for a shorter duration of breastfeeding ( RR = 1.21 ; 95 % CI : 1.10 - 1.33 ) within one year after childbirth . CONCLUSIONS Caesarean section is associated with significantly lower postpartum PRL , which is in line with the longer breastfeeding initiation and lower rate of successful breastfeeding . Necessary measures including promoting the secretion of postpartum PRL such as early contact , early sucking and analgesic method should be taken to improve the successful breastfeeding rate OBJECTIVES ( I ) To determine the barriers to timely initiation of breastfeeding in mothers who Hospital . ( 2 ) . To determine if there is any statistical association between the time of initiation of breastfeeding and certain socio-demographic , obstetric , psychosocial and environmental factors in the mother-baby pairs . METHOD OLOGICAL : A prospect i ve , hospital-based study of 500 consecutive health mother-infant pairs delivered at UPTH ( both vaginally and by Caesarian section ) . Information was obtained using a structured question naire , medical record review and direct observation . Early initiation , i.e. mothers who initiated breastfeeding within 30 minutes of delivery ( in the case of the vaginally delivered ( VD ) mothers ) or within 30 minutes of recovery of post-operative consciousness ( in the case of those delivered by Caesarian section ) were compared with those who initiated breastfeeding after 30 minutes ( Late initiator ) in the VD and C/S groups . The association between time of breastfeeding initiation and factors under consideration were determine using the chi-squared test . RESULTS Approximately 34 % of the VD mother initiated breastfeeding early while no mother with Caesarean section had early initiation of breastfeeding . The mean time of breastfeeding initiation was 3.35 -/+ 2.6 hours in mother who had vaginal delivery , 6.50 + /- 3.4 hours and 5.9 + /- 1.9 hours in those who had Caesarean section with general or spinal anaesthesia respectively . Among those with vaginal delivery , mothers younger than 25 years and of high socioeconomic class were found to practice early breastfeeding initiation . Delay in the time of repair of episiotomy and labour duration less than 12 hours were associated with early breastfeeding initiation . Early contact between baby and mother , help received on the delivery table and the presence of more than one delivery assistant also positively influenced breastfeeding initiation . Similarly , the presence of a breastfeeding-trained delivery assistant enhanced the mother ' practice of early initiation of breastfeeding . Observation of routine labour ward practice s such as cleaning of the newborn and weight/length measurement had negative impact on the practice of early initiation of breastfeeding . Early contact between the mother and her newborn on the delivery table with assistance to initate breastfeeding was the most important predictor of early breastfeeding initiation . Parity , attendance at the antenatal clinic , receipt of breastfeeding information and use of analgesics during labour did not show any statistical association with time of initiation of breastfeeding . CONCLUSION / RECOMMENDATION There was a low prevalence of early initiation of breastfeeding in mothers delivered at the University of Port Harcourt Teaching Hospital . This low prevalence was due to delay in helping the newly delivered mother , especially those with Caesarean delivery . Routine labour ward practice s interfere with the time of breastfeeding initiation . Routine labour ward and delivery table , specific assignment to the staff in the delivery/labour rooms help newly delivered mothers initiate breastfeeding early , and empowering the to request for babies are recommended BACKGROUND Many publications have examined the reasons behind the rising cesarean delivery rate around the world . Women 's responses to the Maternity Experiences Survey of the Canadian Perinatal Surveillance System were examined to explore correlates of having a cesarean section on other experiences surrounding labor , birth , mother-infant contact , and breastfeeding . METHODS A r and omly selected sample of 8,244 estimated eligible women stratified primarily by province and territory was drawn from the May 2006 Canadian Census . Completed responses were obtained from 6,421 women ( 78 % ) . RESULTS Three-quarters of the women ( 73.7 % ) gave birth vaginally and 26.3 percent by cesarean section , including 13.5 percent with a planned cesarean and 12.8 percent with an unplanned cesarean . In addition to more interventions in labor , women who had a cesarean birth after attempting a vaginal birth had less mother-infant contact after birth and less optimal breastfeeding practice s. CONCLUSION Findings from the Maternity Experiences Survey indicated that women who have cesarean births experience more interventions during labor and birth and have less optimal birthing and early parenting outcomes |
10,499 | 18,071,810 | Length of hospital stay is shorter , blood loss and pain are less , and return to usual activities is likely to be faster after LR than after OR , but duration of operation is longer .
Lymph node retrieval , completeness of resection and quality of life do not appear to differ .
No statistically significant differences were observed in rates of anastomotic leakage , abdominal wound breakdown , incisional hernia , wound and urinary tract infections , operative and 30-day mortality , and recurrences , nor in overall and disease-free survival up to three years .
Conclusions LR is associated with a quicker recovery in terms of return to usual activities and length of hospital stay with no evidence of a difference in complications or long-term outcomes in comparison to OR , up to three years postoperatively | Objective To determine the clinical effectiveness of laparoscopic and laparoscopically assisted surgery in comparison with open surgery for the treatment of colorectal cancer .
Background Open resection is the st and ard method for surgical removal of primary colorectal tumours .
However , there is significant morbidity associated with this procedure .
Laparoscopic resection ( LR ) is technically more difficult but may overcome problems associated with open resections ( OR ) . | CONTEXT Laparoscopic-assisted colectomy ( LAC ) has emerged as the preferred minimally invasive surgical strategy for diseases of the colon . The safety and efficacy of LAC for colon cancer are unknown , and the nature and magnitude of any quality -of-life ( QOL ) benefit result ing from LAC for colon cancer is also unknown . OBJECTIVE To compare short-term QOL outcomes after LAC vs open colectomy for colon cancer . DESIGN , SETTING , AND PARTICIPANTS Multicenter , r and omized controlled trial ( Clinical Outcomes of Surgical Therapy [ COST ] ) . Between September 1994 and February 1999 , 37 of 48 centers provided data for the QOL component of the trial for 449 consecutive patients with clinical ly resectable colon cancer . MAIN OUTCOME MEASURES Scores on the Symptoms Distress Scale ( SDS ) , Quality of Life Index , and a single-item global rating scale at 2 days , 2 weeks , and 2 months postoperative ; duration of postoperative in-hospital analgesic use ; and length of stay . RESULTS Of 449 patients , 428 provided QOL data . In an intention-to-treat analysis comparing SDS pain intensity , SDS summary , QOL Index summary , and global rating scale scores at each time point , the only statistically significant difference observed between groups was the global rating scale score for 2 weeks postsurgery . The mean ( median ) global rating scale scores for 2 weeks postsurgery were 76.9 ( 80 ) for LAC vs 74.4 ( 75 ) for open colectomy ( P = .009 ) . While in the hospital , patients assigned to LAC required fewer days of both parenteral analgesics compared with patients assigned to open colectomy ( mean [ median ] , 3.2 [ 3 ] vs 4.0 [ 4 ] days ; P<.001 ) and oral analgesics ( mean [ median ] , 1.9 [ 1 ] vs 2.2 [ 2 ] days ; P = .03 ) . CONCLUSION Only minimal short-term QOL benefits were found with LAC for colon cancer compared with st and ard open colectomy . Until ongoing trials establish that LAC is as effective as open colectomy in preventing recurrence and death from colon cancer , this procedure should not be offered to patients with colon cancer OBJECTIVE The aims of this study were to evaluate the safety and efficacy of laparoscopic abdominoperineal resection compared to conventional approach for surgical treatment of patients with distal rectal cancer presenting with incomplete response after chemoradiation . METHOD Twenty eight patients with distal rectal adenocarcinoma were r and omized to undergo surgical treatment by laparoscopic abdominoperineal resection or conventional approach and evaluated prospect ively . Thirteen underwent laparoscopic abdominoperineal resection and 15 conventional approach . RESULTS There was no significant difference ( p<0,05 ) between the two studied groups regarding : gender , age , body mass index , patients with previous abdominal surgeries , intra and post operative complications , need for blood transfusion , hospital stay after surgery , length of resected segment and pathological staging . Mean operation time was 228 minutes for the laparoscopic abdominoperineal resection versus 284 minutes for the conventional approach ( p=0.04 ) . Mean anesthesia duration was shorter ( p=0.03 ) for laparoscopic abdominoperineal resection when compared to conventional approach : 304 and 362 minutes , respectively . There was no need for conversion to open approach in this series . After a mean follow-up of 47.2 months and with the exclusion of two patients in the conventional abdominoperineal resection who presented with unsuspected synchronic metastasis during surgery , local recurrence was observed in two patients in the conventional group and in none in the laparoscopic group . CONCLUSIONS We conclude that laparoscopic abdominoperineal resection is feasible , similar to conventional approach concerning surgery duration , intra operative morbidity , blood requirements and post operative morbidity . Larger number of cases and an extended follow-up are required to adequate evaluation of oncological results for patients undergoing laparoscopic abdominoperineal resection after chemoradiation for radical treatment of distal rectal cancer Background : A shorter duration of postoperative ileus and earlier oral alimentation of patients may be a clinical ly relevant benefit of laparoscopic compared with conventional colorectal resection . Patients / Methods : A total of 60 patients were r and omised to either laparoscopic ( n=30 ) or conventional ( n=30 ) resection of colorectal tumours . Major endpoints were the postoperative time to the first bowel movement and the time until oral feeding without parenteral alimentation was tolerated . Minor endpoints were the postoperative interval to the first peristalsis and first passage of flatus , the distribution of radio-opaque markers in abdominal radiographs on day 3 and day 5 and the incidence of postoperative vomiting . Results : Age , gender , ASA-classification and type of resection were comparable in thetwo groups . Peristalsis was first noticed 26±9 h after laparoscopic and 38±17 h after conventional colorectal resection ( P<0.01 ) . First flatus occurred 50±19 h after laparoscopic and 79±21 h after conventional surgery ( P<0.01 ) . The incidence of postoperative vomiting was similar in both groups . Three days after surgery radio-opaque markers were found more often in the right colon ( P<0.01 ) and less often in the small intestine ( P<0.05 ) in laparoscopic compared with conventional patients . Five days after laparoscopic surgery , more markers had reached the left colon ( P<0.05 ) . The first bowel movement occurred 70±32 h after laparoscopic and 91±22 h after conventional resection ( P<0.01 ) . Oral feeding without additional parenteral alimentation was tolerated 3.3±0.7 days after laparoscopic and 5.0±1.5 days after conventional surgery ( P<0.01 ) . Conclusion : The shorter duration of postoperative ileus allows earlier restoration of oral feeding after laparoscopic compared with conventional colorectal resection and therefore increases quality of life immediately after resection of colorectal tumours BACKGROUND Minimally invasive , laparoscopically assisted surgery was first considered in 1990 for patients undergoing colectomy for cancer . Concern that this approach would compromise survival by failing to achieve a proper oncologic resection or adequate staging or by altering patterns of recurrence ( based on frequent reports of tumor recurrences within surgical wounds ) prompted a controlled trial evaluation . METHODS We conducted a noninferiority trial at 48 institutions and r and omly assigned 872 patients with adenocarcinoma of the colon to undergo open or laparoscopically assisted colectomy performed by credentialed surgeons . The median follow-up was 4.4 years . The primary end point was the time to tumor recurrence . RESULTS At three years , the rates of recurrence were similar in the two groups--16 percent among patients in the group that underwent laparoscopically assisted surgery and 18 percent among patients in the open-colectomy group ( two-sided P=0.32 ; hazard ratio for recurrence , 0.86 ; 95 percent confidence interval , 0.63 to 1.17 ) . Recurrence rates in surgical wounds were less than 1 percent in both groups ( P=0.50 ) . The overall survival rate at three years was also very similar in the two groups ( 86 percent in the laparoscopic-surgery group and 85 percent in the open-colectomy group ; P=0.51 ; hazard ratio for death in the laparoscopic-surgery group , 0.91 ; 95 percent confidence interval , 0.68 to 1.21 ) , with no significant difference between groups in the time to recurrence or overall survival for patients with any stage of cancer . Perioperative recovery was faster in the laparoscopic-surgery group than in the open-colectomy group , as reflected by a shorter median hospital stay ( five days vs. six days , P<0.001 ) and briefer use of parenteral narcotics ( three days vs. four days , P<0.001 ) and oral analgesics ( one day vs. two days , P=0.02 ) . The rates of intraoperative complications , 30-day postoperative mortality , complications at discharge and 60 days , hospital readmission , and reoperation were very similar between groups . CONCLUSIONS In this multi-institutional study , the rates of recurrent cancer were similar after laparoscopically assisted colectomy and open colectomy , suggesting that the laparoscopic approach is an acceptable alternative to open surgery for colon cancer PURPOSE : Traumatic manipulation of cancer specimens during laparoscopic colectomy may increase exfoliation of malignant cells into the peritoneal cavity , causing an early occurrence of peritoneal carcinomatosis or port-sites recurrence . Because of this concern , the routine use of intraperitoneal chemotherapy after laparoscopic colectomy for cancer was suggested recently . We assessed if laparoscopicvs . conventional surgery increases exfoliated malignant cells in the peritoneal cavity during resection of colorectal cancer . METHODS : In a prospect i ve , r and omized fashion , 38 colorectal cancer patients undergoing an elective , curative operation were assigned to either a conventional or laparoscopic procedure between June 1996 and May 1997 . In either group ( n=19 ) , after the abdominal cavity was entered , saline was instilled into the peritoneal cavity , and the fluid was collected ( Specimen 1 ) . During surgery , all irrigating fluids were collected ( Specimen 2 ) . Both specimens were assessed for malignancy using four techniques : filtration process ( ThinPrep ® ) , smear , cell block , and immunochemistry using Ber-EP4 . The change in the amount of tumor cells in both specimens was compared between surgical groups . A pilot study was performed to vali date the proposed cytologic method . RESULTS : In the pilot study of 20 consecutive patients with colorectal cancer , postresectional peritoneal cytology was positive in six patients , including two Stage II ( T3,N0,M0 ) patients . The pilot study also vali date d that our semiquantitative scoring system can be reliably used to assess the amount of free peritoneal cancer cells . In the main study , 16 right colectomies , 3 extended right colectomies , 17 proctosigmoidectomies , and 1 left colectomy were performed . The T and N stages were T1 ( n=13 ) , T2 ( n=5 ) , T3 ( n=8 ) , T4 ( n=11 ) ; N0 ( n=22 ) , N1 ( n=8 ) , N2 ( n=7 ) . Malignant cells were not detected in any Specimens 1 or , more importantly , in Specimens 2 in either surgical group . CONCLUSION : When performed according to strict oncologic surgical principles , laparoscopic techniques in curative colorectal cancer surgery did not have an increased risk of intraperitoneal cancer cell spillage , compared with conventional techniques . We hope that these results can decrease some of the concerns about tumors cell spillage and seeding during laparoscopy BACKGROUND The safety and short-term benefits of laparoscopic colectomy for cancer remain debatable . The multicentre COLOR ( COlon cancer Laparoscopic or Open Resection ) trial was done to assess the safety and benefit of laparoscopic resection compared with open resection for curative treatment of patients with cancer of the right or left colon . METHODS 627 patients were r and omly assigned to laparoscopic surgery and 621 patients to open surgery . The primary endpoint was cancer-free survival 3 years after surgery . Secondary outcomes were short-term morbidity and mortality , number of positive resection margins , local recurrence , port-site or wound-site recurrence , metastasis , overall survival , and blood loss during surgery . Analysis was by intention to treat . Here , clinical characteristics , operative findings , and postoperative outcome are reported . FINDINGS Patients assigned laparoscopic resection had less blood loss compared with those assigned open resection ( median 100 mL [ range 0 - 2700 ] vs 175 mL [ 0 - 2000 ] , p<0.0001 ) , although laparoscopic surgery lasted 30 min longer than did open surgery ( p<0.0001 ) . Conversion to open surgery was needed for 91 ( 17 % ) patients undergoing the laparoscopic procedure . Radicality of resection as assessed by number of removed lymph nodes and length of resected oral and aboral bowel did not differ between groups . Laparoscopic colectomy was associated with earlier recovery of bowel function ( p<0.0001 ) , need for fewer analgesics , and with a shorter hospital stay ( p<0.0001 ) compared with open colectomy . Morbidity and mortality 28 days after colectomy did not differ between groups . INTERPRETATION Laparoscopic surgery can be used for safe and radical resection of cancer in the right , left , and sigmoid colon A r and omized controlled trial was started in Japan to evaluate whether laparoscopic surgery is the optimal treatment for colorectal cancer . Patients with T3 or deeper carcinoma in the colorectum without transverse and descending colons are pre-operatively r and omized to either open or laparoscopic colorectal resection . Surgeons in 24 specialized institutions will recruit 818 patients . The primary end-point is overall survival . Secondary end-points are relapse-free survival , short-term clinical outcome , adverse events , the proportion of conversion from laparoscopic surgery to open surgery , and the proportion of completion of laparoscopic surgery Laparoscopic surgery is believed to produce an attenuated metabolic stress response and to have a less dampening effect on the immune response than open surgery . To date , the effect has not been studied in a r and omized clinical trial of colorectal cancer Background The Laparoscopic approach has been applied to colorectal surgery for many years ; however , there are only a few reports on laparoscopic low and ultralow anterior resection with construction of coloanal anastomosis . This study compares open versus laparoscopic low and ultralow anterior resections , assesses the feasibility and efficacy of the laparoscopic approach of total mesorectal excision ( TME ) with anal sphincter preservation ( ASP ) , and analyzes the short-term results of patients with low rectal cancer . Methods We analyzed our experience via a prospect i ve , r and omized control trail . From June 2001 to September 2002 , 171 patients with low rectal cancer underwent TME with ASP , 82 by the laparoscopic procedure and 89 by the open technique . The lowest margin of tumors was below peritoneal reflection and 1.5–8 cm above the dentate line ( 1.5–4.9 cm in 104 cases and 5–8 cm in 67 cases ) . The grouping was r and omized . Results Results of operation , postoperative recovery , and short-term oncological follow-up were compared between 82 laparoscopic procedures and 89 controls who underwent open surgery during the same period . In the laparoscopic group , 30 patients in whom low anterior resection was performed had the anastomosis below peritoneal reflection and more than 2 cm above the dentate line , 27 patients in whom ultralow anterior resection was performed had anastomotic height within 2 cm of the dentate line , and 25 patients in whom coloanal anastomosis was performed had the anastomosis at or below the dentate line . In the open group , the numbers were 35 , 27 , and 27 , respectively . There was no statistical difference in operation time , administration of parenteral analgesics , start of food intake , and mortality rate between the two groups . However , blood loss was less , bowel function recovered earlier , and hospitalization time was shorter in the laparoscopic group . Conclusion Totally laparoscopic TME with ASP is feasible , and it is a minimally invasive technique with the benefits of much less blood loss during operation , earlier return of bowel function , and shorter hospitalization BACKGROUND Although laparoscopic resection of colorectal carcinoma improves post-operative recovery , long-term survival and disease control are the determining factors for its application . We aim ed to test the null hypothesis that there was no difference in survival after laparoscopic and open resection for rectosigmoid cancer . METHODS From Sept 21 , 1993 , to Oct 21 , 2002 , 403 patients with rectosigmoid carcinoma were r and omised to receive either laparoscopic assisted ( n=203 ) or conventional open ( n=200 ) resection of the tumour . Survival and disease-free interval were the main endpoints . Patients were last followed-up in March , 2003 . Perioperative data were recorded and direct cost of operation estimated . Data were analysed by intention to treat . FINDINGS The demographic data of the two groups were similar . After curative resection , the probabilities of survival at 5 years of the laparoscopic and open resection groups were 76.1 % ( SE 3.7 % ) and 72.9 % ( 4.0 % ) respectively . The probabilities of being disease free at 5 years were 75.3 % ( 3.7 % ) and 78.3 % ( 3.7 % ) , respectively . The operative time of the laparoscopic group was significantly longer , whereas postoperative recovery was significantly better than for the open resection group , but these benefits were at the expense of higher direct cost . The distal margin , the number of lymph nodes found in the resected specimen , overall morbidity and operative mortality did not differ between groups . INTERPRETATION Laparoscopic resection of rectosigmoid carcinoma does not jeopardise survival and disease control of patients . The justification for adoption of laparoscopic technique would depend on the perceived value of its effectiveness in improving short-term post-operative outcomes BACKGROUND : This study was conducted to determine if laparoscopic colon surgery has changed the incidence of wound complications after colon resection . METHODS : Eighty-three patients were r and omized to undergo either laparoscopic ( LCR ) or open colon resection ( OCR ) for cancer at our institution as part of a multicenter trial . Data were tabulated from review of the prospect i ve data base and physician records . RESULTS : Thirty-seven patients were r and omized to LCR and 46 to OCR . Seven patients in the LCR group were converted to OCR . LCR was performed using a limited midline incision for anastomosis and specimen extraction . Incision length was significantly greater ( p < 0.001 ) in the OCR group ( 19.4 ± 5.6 cm ) compared to the LCR extraction site ( 6.3 ± 1.4 cm ) . Wound infections occurred in 13.5 % of patients after LCR ( 2.7 % trocar , 10.8 % extraction sites ) and in 10.9 % of patients after OCR . Over a mean follow-up period of 30.1 ± 17.8 months , incisional hernias developed in 24.3 % of patients after LCR and 17.4 % after OCR . In the LCR group , extraction sites accounted for 85.7 % of all wound complications . CONCLUSIONS : The extraction site for LCR is associated with a high incidence of complications , comparable to open colectomy . Strategies to alter operative technique should be considered to reduce the incidence of these complications Background : After confirming a favorable outcome of laparoscopic surgery for early colorectal cancer , we conducted a r and omized controlled trial to compare short-term outcomes of laparoscopic and open colectomy for advanced colorectal cancer . Methods : Fifty-nine patients with T2 or T3 colorectal cancer were r and omized to undergo laparoscopic ( n = 29 ) or open ( n = 30 ) colectomy . Median follow-up was 20 months ( range , 6–34 months ) . Results : Operative time was longer ( p < 0.0001 ) and blood loss ( p = 0.0034 ) and postoperative analgesic requirement were less in the laparoscopic group than in the open group . An earlier return of bowel motility and earlier discharge from the hospital ( p = 0.0164 ) were observed after laparoscopic surgery . Serum C-reactive protein levels on postoperative days 1 ( p < 0.0001 ) and 4 ( p = 0.0039 ) were lower in the laparoscopic group than in the open group . Postoperative complications did not differ between the two groups . Conclusion : Laparoscopic surgery for advanced colorectal cancer is feasible , with favorable short-term outcome PURPOSE The aim of this study was to evaluate whether laparoscopic colorectal surgery can modify the risk factors for the occurrence of postoperative morbidity . METHODS A total of 384 consecutive patients with colorectal disease were r and omized to laparoscopic resection ( n = 190 ) or open resection ( n = 194 ) . On admission , demographics , comorbidity , and nutritional status were recorded . Operative variables , patient outcome , and length of stay were also recorded . Postoperative complications were registered by four members of staff not involved in the study . RESULTS The overall morbidity rate was 27.1 percent , with the rate in the laparoscopic group ( 18.7 percent ) being less than that in the open group ( 31.5 percent ; P = 0.003 ) . Patients who underwent laparoscopic resection had a faster recovery of bowel function ( P = 0.0001 ) and a shorter length of stay ( P = 0.0001 ) . In the whole cohort of patients , multivariate analysis identified open surgery ( P = 0.003 ) , duration of surgery ( P = 0.01 ) , and homologous blood transfusion ( P = 0.01 ) as risk factors for postoperative morbidity . In the open group , blood loss ( P = 0.01 ) , homologous blood transfusion ( P = 0.01 ) , duration of surgery ( P = 0.009 ) , weight loss ( P = 0.06 ) , and age ( P = 0.08 ) were related to postoperative morbidity . In the laparoscopic group the only risk factor identified was duration of surgery ( P = 0.005 ) . CONCLUSION In the laparoscopic group , both postoperative morbidity and length of stay were significantly reduced and most risk factors for postoperative morbidity disappeared Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists BACKGROUND Uncontrolled studies using laparoscopic techniques in colorectal surgery have not demonstrated clear advantages to these procedures compared with conventional ones , and surgeons are concerned about unusual early recurrences reported after laparoscopic colorectal cancer surgery . STUDY DESIGN We conducted a prospect i ve , r and omized trial in one surgical department comparing laparoscopic ( LAP ) and conventional ( CON ) techniques in 109 patients undergoing bowel resection for colorectal cancers or polyps . Postoperatively , all patients underwent measurement of pulmonary function tests every 12 hours , and were treated identically on a highly controlled protocol with regard to analgesic administration , feeding , and postoperative care . RESULTS Of the 55 patients assigned to LAP and 54 to the CON group , there were 42 and 38 with cancer , respectively ( the other patients had large adenomas ) . Overall recovery of 80 % of forced expiratory volume in 1 second and forced vital capacity was a median of 3 days for LAP and 6.0 days for CON ( p = 0.01 ) . LAP patients used significantly less morphine than CON patients up to the second day after surgery ( 0.78 + /- 0.32 versus 0.92 + /- 0.34 mg/kg per day , p = 0.02 ) . Flatus returned a median of 3.0 days after LAP versus 4.0 days after CON surgery ( p = 0.006 ) . Tumor margins were clear in all patients . After a median followup of 1.5 years ( LAP ) and 1.7 years ( CON ) , there were no port site recurrences in the LAP group . Seven cancer-related deaths have occurred ( three in the LAP group , four in the CON group ) . CONCLUSIONS Within this prospect i ve , r and omized trial , laparoscopic techniques were as safe as conventional surgical techniques and offered a faster recovery of pulmonary and gastrointestinal function compared with conventional surgery for selected patients undergoing large bowel resection for cancer or polyps . There were no apparent shortterm oncologic disadvantages . Longer followup is needed to fully assess oncologic outcomes Background : Although the pneumoperitoneum decreases venous reflux from the lower extremities , the rate of thromboembolic complcations seems to be lower after laparoscopic than after conventional procedures . Therefore , it has been assumed that laparoscopic surgery better preserves the intravasal fibrinolytic capacity . The aim of this study was to determine the influence of the operative technique on intravasal fibrinolytic capacity in colorectal resection . Methods : R and omized controlled trial conducted in parallel with the multicenter trial LAPKON II comparing the long-term effects of elective laparoscopic ( group I ) and conventional ( group II ) resections for colorectal cancer . Blood sample s were taken from 30 patients preoperatively , at the beginning and end of surgery as well as 2 , 8 , and 24 hr postoperatively . Activities and concentrations of tissue plasminogen activator ( tPA ) , plasminogen activator inhibitor type 1 ( PAI-1 ) , tPA/PAI complex , fibrinogen , and D-dimers were determined in all specimen with ELISA tests . Area under the curve values ( AUC ) were calculated for all parameters . Results : Patient characteristics and indication for surgery were not different between both groups . Preoperative values of fibrinolytic parameters were similar in both groups . Postoperatively , tPA activity decreased significantly in both groups , but AUC values for tPA and PAI-1 activity ( p = 0.23 ; p = 0.68 ) ; concentration of tPA , PAI-1 , and tPA/PAI complex ( p = 0.52 ; p = 0.78 ; p = 0.95 ) ; and concentration of fibrinogen and D-dimers ( p = 0.67 ; p = 0.71 ) did not differ between the groups . Conclusions : An intravasal fibrinolytic " shutdown " occurs not only after conventional but also after laparoscopic colorectal resection . Both operative techniques had similar effects on postoperative intravasal fibrinolytic capacity . Therefore , the lower incidence of thromboembolic complications after laparoscopic colorectal resections does not seem to be caused by a lesser depression of the intravasal fibrinolytic capacity In a prospect i ve r and omised study the influence of the operative technique on postoperative quality of life was evaluated in 60 patients undergoing laparoscopic ( n = 30 ) or conventional ( n = 30 ) resection of colorectal tumors . Quality of life was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Core 30 Question naire ( EORTC-QLQ-C30 ) before surgery as well as 1 week , 4 weeks and 3 months after surgery . Age , sex , sociological parameters , tumor characteristics and type of resection were comparable in both groups . There were no significant differences in preoperative global quality of life , the functional aspects of quality of life and the severity of disease related symptoms . The global quality of life was significantly better in the laparoscopic group compared to the conventional group 1 week and 4 weeks after surgery ( p = 0.05 ) . Physical and emotional function were more impaired 1 week after conventional compared to laparoscopic surgery ( p < 0.05 ) . Pain , dyspnea and loss of appetite were more severe 1 week after conventional than laparoscopic surgery ( each p < 0.05 ) . There were no differences in quality of life in the further postoperative course . Laparoscopic resection of colorectal tumor is related with a better short-term quality of life than conventional resection , but a longer lasting effect of the laparoscopic technique on quality of life could not be detected with the EORTC-QLQ-C30 Abstract Background : Conventional colorectal resections are associated with severe postoperative pain and prolonged fatigue . The laparoscopic approach to colorectal tumors may result in less pain as well as less fatigue , and may improve postoperative recovery after colorectal resections . Methods : Sixty patients were included into a prospect i ve r and omized trial to determine the influence of laparoscopic ( n= 30 ) or conventional ( n= 30 ) resection of colorectal tumors on postoperative pain and fatigue . Major endpoints of the study were dose of morphine sulfate during patient-controlled analgesia ( PCA ) , visual analog scale for pain while coughing ( VASC ) , and visual analogue scale for fatigue ( VASF ) . Efficacy of pain medication was assessed by visual analogue score at rest ( VASR ) . Results : Preoperative age , sex , stage , and localization of tumors were comparable in both groups . The PCA dose of morphine given immediately after surgery until postoperative day 4 was higher in the conventional group ( median , 1.37 mg/kg ; 5–95 percentile 0.71–2.46 mg/kg ) than the laparoscopic group ( 0.78 mg/kg ; 0.24–2.38 mg/kg , p < 0.01 ) . Postoperative VASR was comparable between both groups , but VASC was higher from the first to the seventh postoperative day ( p < 0.01 ) . Postoperative fatigue was higher after conventional than after laparoscopic surgery from the second to the seventh day ( p < 0.05 ) . Conclusions : This study confirms that analgetic requirements are lower and pain is less intense after laparoscopic than after conventional colorectal resection . Patients also experience less fatigue after minimal invasive surgery . Because of these differences , the duration of recovery is shortened , and the postoperative quality of life is improved after laparoscopic colorectal resections PURPOSE : Our aim was to test the hypothesis that laparoscopic‐assisted resection for colorectal cancer has an immunologic advantage over traditional open surgery . METHODS : Sixteen patients with colorectal cancer were r and omized to undergo laparoscopic‐assisted resection or open surgery . Basic patient data were recorded , and serum interleukin‐6 levels , relative proportions of lymphocytes , and human leukocyte antigen‐DR expression on monocytes were determined at specific time intervals . RESULTS : Operating time was longer for laparoscopic‐assisted resection ( P=0.02 ) , but analgesic requirements were less ( P=0.04 ) . All patients exhibited the following : interleukin‐6 levels increased to a maximum at 4 hours and returned to preoperative levels within 48 hours . This response appeared greater for open resection ( mean peak level , 313 vs. 173 pg/ml ; P=0.25 ) . Relative granulocytosis ( P<0.001 ) was seen within 48 hours , which was offset by a decrease in percentage of lymphocytes ( P<0.001 ) . Changes in lymphocyte subfractions were most significant seven days post‐surgery : natural killer cells decreased ( P=0.003 ) ; T cells increased ( P=0.008 ) , with elevation in the CD4/CD8 ratio ( P=0.003 ) . B cells were largely unchanged at all time periods . Human leukocyte antigen‐DR expression on monocytes was significantly less at 48 hours postsurgery ( P<0.001 ) . All changes were reversed within three weeks of surgery . There were no differences when comparing laparoscopic‐assisted resection with open surgery . CONCLUSIONS : Both laparoscopic‐assisted resection and open surgery affect the immune response . It would appear that laparoscopic‐assisted resection does not have an immunologic advantage over open surgery in patients with colorectal cancer BACKGROUND The role of laparoscopic colon resection in the management of colon cancer is unclear . The aims of this study were to compare perioperative results and long-term outcomes in patients r and omized to either open ( O ) or laparoscopically assisted ( LA ) colon resection for colon cancer . METHODS A prospect i ve r and omized trial comparing O to LA colon resection was conducted from January 1993 to November 1995 . Preoperative workup , intraoperative results , complications , length of stay , pathologic findings , and long-term outcomes were compared between the two groups . Statistical analysis was performed with t-test . Follow-up periods ranged from 3.5 to 6.3 years ( mean , 4.9 years ) . RESULTS No port-site or abdominal wall recurrences were noted in any patients . [ table : see text ] CONCLUSIONS These results suggest that laparoscopically assisted colon resection for malignant disease can be performed safely , with morbidity , mortality , and en bloc resections comparable with those of open laparotomy . Long-term ( 5-year ) follow-up assessment shows similar outcomes in both groups of patients , demonstrating definite perioperative advantages with LA surgery and no perioperative or long-term disadvantages PURPOSE Although laparoscopic-assisted colectomy ( LAC ) has evolved as a technical option in the treatment of benign colonic diseases , its role in the treatment of malignancies remains controversial . The purpose of this prospect i ve r and omized trial was to compare perioperative parameters and outcomes between LAC vs. open colectomy ( OC ) in patients with stage I-III colon cancer . PATIENTS AND METHODS Eligible patients with colon cancer who were scheduled for an elective colon resection from January 1995 to February 2001 were r and omized to either the LAC or the OC treatment group . The two groups were compared with regard to operative time , blood loss , complications , pathologic findings and lymph node yield , length of postoperative hospital stay , gastrointestinal function , use of analgesic drugs , recurrence , and survival rates . The median follow-up was 35 months ( range , 3 - 69 months ) . RESULTS A total of 49 patients were enrolled in the study : 20 were r and omized to OC and 29 to LAC , one of whom was lost to follow-up . Thirteen patients in the LAC group had to be converted to OC ( COC ) , and were analyzed in a separate group . The three patient groups were comparable with regard to age , gender distribution , tumor site , lymph node harvest , operative procedure , anastomotic type , perioperative complication , recurrence , and survival rates . Tumor margins were clear in all patients . No incidence of port-site recurrence in the LAC group , or wound recurrence in the OC and COC groups , was found . Three patients died of cancer-related causes , one in each patient group . The LAC patients had significantly shorter hospital stay , faster recovery of gastrointestinal function , and less use of intravenous analgesia . CONCLUSION Short-term outcomes revealed that LAC could be performed safely and has therapeutic results similar to OC for colon cancer . Conversion of LAC to an open procedure was frequent but was not associated with a negative outcome BACKGROUND Laparoscopic-assisted surgery for colorectal cancer has been widely adopted without data from large-scale r and omised trials to support its use . We compared short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer to predict long-term outcomes . METHODS Between July , 1996 , and July , 2002 , we undertook a multicentre , r and omised clinical trial in 794 patients with colorectal cancer from 27 UK centres . Patients were allocated to receive laparoscopic-assisted ( n=526 ) or open surgery ( n=268 ) . Primary short-term endpoints were positivity rates of circumferential and longitudinal resection margins , proportion of Dukes ' C2 tumours , and in-hospital mortality . Analysis was by intention to treat . This trial has been assigned the International St and ard R and omised Controlled Trial Number IS RCT N74883561 . FINDINGS Six patients ( two [ open ] , four [ laparoscopic ] ) had no surgery , and 23 had missing surgical data ( nine , 14 ) . 253 and 484 patients actually received open and laparoscopic-assisted treatment , respectively . 143 ( 29 % ) patients underwent conversion from laparoscopic to open surgery . Proportion of Dukes ' C2 tumours did not differ between treatments ( 18 [ 7 % ] patients , open vs 34 [ 6 % ] , laparoscopic ; difference -0.3 % , 95 % CI -3.9 to 3.4 % , p=0.89 ) , and neither did in-hospital mortality ( 13 [ 5 % ] vs 21 [ 4 % ] ; -0.9 % , -3.9 to 2.2 % , p=0.57 ) . Apart from patients undergoing laparoscopic anterior resection for rectal cancer , rates of positive resection margins were similar between treatment groups . Patients with converted treatment had raised complication rates . INTERPRETATION Laparoscopic-assisted surgery for cancer of the colon is as effective as open surgery in the short term and is likely to produce similar long-term outcomes . However , impaired short-term outcomes after laparoscopic-assisted anterior resection for cancer of the rectum do not yet justify its routine use |
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