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600 | 9,677,209 | CONCLUSIONS There is no evidence that albumin administration reduces mortality in critically ill patients with hypovolaemia , burns , or hypoalbuminaemia and a strong suggestion that it may increase mortality . | OBJECTIVE To quantify effect on mortality of administering human albumin or plasma protein fraction during management of critically ill patients . | To assess the effects of crystalloid and colloid resuscitation on hemodynamic response and on lung water following thermal injury , 79 patients were assigned r and omly to receive lactated Ringer 's solution or 2.5 % albumin-lactated Ringer 's solution . Crystalloid-treated patients required more fluid for successful resuscitation than did those receiving colloid solutions ( 3.81 vs. 2.98 ml/kg body weight/% body surface burn , p < 0.01 ) . In study phase 1 ( 29 patients ) , cardiac index and myocardial contractility ( ejection fraction ' and mean rate of internal fiber shortening , Vcf ) were determined by echocardiography during the first 48 hours postburn . Cardiac index was lower in the 12-to 24-hour postburn interval in the crystalloid group , but this difference between treatment groups had disappeared by 48 hours postburn . Ejection fractions were normal throughout the entire study , while Vcf was supranormal ( p < 0.01 vs. normals ) and equal in the two resuscitation groups . In study phase 2 ( SO patients ) , extravascular lung water and cardiac index were measured by a st and ard rebreathing technique at least daily for the first postburn week . Lung water remained unchanged in the crystalloid-treated patients ( p > 0.10 ) , but progressively increased in the colloid-treated patients over the seven day study ( p < 0.0001 ) . The measured lung water in each treatment group was significantly different from one another ( p < 0.001 ) . Cardiac index increased progressively and identically in both treatment groups over the study period ( p < 0.01 ) . These data refute the existence of myocardial depression during postburn resuscitation and document hypercontractile left ventricular performance . The addition of colloid to crystalloid resuscitation fluids produces no long lasting benefit on total body blood flow , and promotes accumulation of lung water when edema fluid is being reabsorbed from the burn wound In a prospect i ve r and omized trial of 16 patients undergoing abdominal vascular reconstructive procedures , changes in plasma volume , serum oncotic pressure ( pis ) , serum albumin and total protein concentration , alveolar to arterial oxygen tension differences ( AaDO2 , FIO2 = 1.0 ) , creatinine clearance , body weight , and fluid and sodium intake were examined . By r and om assignment patients received either an albumin- or a sodium-rich intraoperative fluid regimen . Pulmonary arteriovenous admixture was significantly less in the albumin group ( n = 7 ) than in the electrolyte group ( n = 9 ) on the first postoperative day . The change in AaDO2 correlated positively with the total sodium intake in the electrolyte group . Despite the larger fluid load and significantly greater gain of body weight , patients in the electrolyte group had a postoperative plasma volume significantly lower than the preoperative value . Postoperative values of albumin concentration , circulating albumin mass and pis were significantly greater in the albumin group in comparison to the electrolyte group . Creatinine clearance values were not different between the two groups . The change in pis correlated significantly with sodium intake and circulating albumin mass . Pulmonary shunting and expansion of the extracellular fluid volume may be minimized without adverse effects on renal function by administration of fluids rich in albumin in preference to sodium OBJECTIVE To determine whether replacement of human albumin will improve a patient 's prognosis . DESIGN A r and omized , double-blind , controlled study in which 25 g of human albumin vs. placebo was administered intravenously daily . SETTING A university-affiliated hospital . PATIENTS Thirty-six patients with hypoalbuminemia ( serum albumin of < 2.5 g/dL ) , receiving total parenteral nutrition . None of the patients had known cancer , cirrhosis , or nephrotic syndrome . INTERVENTIONS Each patient received at least 6 days of therapy ( 6 to 24 days of albumin ; 7 to 32 days of placebo ) . Four subjects were excluded from the study since they received therapy for < 6 days . One patient was excluded from the study after nephrotic syndrome was identified . Albumin metabolic rates for those patients receiving albumin were estimated using the formula : Metabolism of albumin = 25 g/day + ( albumin 1 - albumin 2)(Vd)/days , where albumin 1 and 2 are the serum albumin concentrations ( g/L ) at the beginning and end of the serum sampling intervals , respectively ; Vd is the volume of distribution ( L ) ; and days relates to the number of days of the sampling interval . MEASUREMENTS AND MAIN RESULTS Sixteen patients received albumin ; 15 patients received placebo . One patient receiving placebo and two patients receiving albumin died within 30 days . One patient who received placebo and three patients who received albumin developed sepsis or bacteremia ; four patients who received placebo and seven patients who received albumin developed pneumonia during the study ( NS ) . The serum albumin increased in all patients receiving intravenous albumin , but one patient received intravenous albumin for only 6 days . The mean serum albumin concentration increased by 1.42 g/dL in the albumin patients , and increased by 0.29 in the placebo patients ( p < .0001 by unpaired t-test ) . Mean initial albumin metabolism was 17.4 g/day ( 0.3 g/kg/day ) . At the end of therapy , albumin metabolism was 20.5 g/day ( 0.36 g/kg/day ) ( paired t-test , p = .4 , NS ) . CONCLUSIONS a ) The administration of intravenous albumin to hypoalbuminemic patients receiving total parenteral nutrition does not improve morbidity or mortality . b ) Albumin metabolic rates , initially related to the catabolic state , are high ; later , these rates are high related to filling of the albumin space and gluconeogenesis . c ) On the basis of the high albumin catabolic rates at the end of the infusion , doses of albumin of < 25 g/day might be sufficient to replace albumin stores The effects of concurrent administration of albumin with total parenteral nutrition were studied in 12 premature newborns ( birth weight 1.26 + /- 0.1 kg [ mean + /- SEM ] and gestational age 30 + /- 0.8 weeks [ mean + /- SEM ] ) compared with a control group of 12 premature newborns ( birth weight 1.17 + /- 0.2 kg and gestational age 29 + /- 0.1 weeks ) who received total parenteral nutrition . All newborns had a plasma albumin level below 3 g/dL and were in cardiorespiratory distress requiring assisted ventilation . Albumin supplementation of total parenteral nutrition result ed in a sustained increase in serum albumin concentration as well as increased mean arterial blood pressures in the study group . Slow albumin infusion had no observed effect on the severity of respiratory distress . Study group infants regained birth weight earlier than control group infants . These data suggest that the concurrent administration of albumin may be clinical ly beneficial in critically ill newborn infants Patients with colorectal cancer undergoing elective surgery with resection of the tumour and primary anastomosis were r and omly allocated into two groups . 29 patients received a total of 60 - 75 g of albumin postoperatively , 30 patients received no albumin and served as controls . The two groups were comparable with respect to age and sex of the patients and stage of growth of the tumour . The patients who received albumin had a significantly lower preoperative serum albumin concentration . On day 4 after the operation the serum albumin concentrations of the control patients and the patients who received albumin were 20 % and 5 % lower , respectively , than the preoperative value . Eight patients of the albumin group and 5 of the control group developed postoperative complications . There was no significant difference in the postoperative clinical course between the two groups . Preoperative serum albumin levels did not differ between patients who developed postoperative complications and those who had an uneventful postoperative course whether or not they received albumin postoperatively . The present study does not confirm earlier results indicating that serum albumin alone is of prognostic value for the postoperative course following colorectal surgery . Furthermore , the postoperative course is not improved by addition of albumin postoperatively and hence albumin should be given in this situation only when its specific oncotic effect is required Colloid osmotic pressure ( COP ) was followed postoperatively in 55 r and omized patients . After minor operations and short-term infusion therapy only small changes of the COP could be observed and it was concluded that after such operation COP measurement is unnecessary . After major surgical interventions , however , COP measurement gave valuable hints . It was shown that even in the case of moderate blood loss replaced by crystalloids an abnormally low COP did not occur . The same applied also to preoperative hemodilution . It was unnecessary to substitute the withdrawn blood with a colloid solution . In addition , COP measurement helped to avoid expensive albumin administrations and indicated colloid overload in cases of pulmonary edema Albumin replacement to correct hypoalbuminemia in critically ill patients has been controversial . This study was a prospect i ve , r and omized trial of 25 % albumin administration in 40 hypoalbuminemic ( serum albumin , less than 25 g/L [ 2.5 g/dL ] ) , critically ill patients . The treatment group ( 18 patients ) received 25 % albumin supplementation to achieve and maintain serum albumin levels of 25 g/L ( 2.5 g/dL ) or greater , while the nontreatment group ( 22 patients ) received no concentrated albumin . There was no clinical benefit from albumin therapy when assessing mortality ( 39 % vs 27 % , treatment vs control ) or major complication rate ( 89 % vs 77 % of patients ) . There were also no significant differences in length of hospital stay , intensive care unit stay , ventilator dependence , or tolerance of enteral feeding , despite significant elevations of albumin in the treatment group . The costly use of exogenous albumin as treatment for hypoalbuminemia in this patient population does not appear to be justified The effect of decreased colloid oncotic pressure , as seen in hypoalbuminemia and hypoproteinemia , upon intestinal function has been well delineated in the surgical literature . Patients undergoing abdominal aortic aneurysm resection or aortoiliac or aortofemoral bypass grafts are almost uniformly hypoalbuminemic postoperatively ; with these two facts in mind , a prospect i ve , r and omized clinical study was undertaken to identify the role of serum albumin concentration on the length of postoperative ileus in this population . The main hypothesis was that patients whose albumin levels dropped below 3.5 gm/dL would have a more prolonged postoperative hospital course as a result of delay in return of bowel function when compared with those patients in whom the low albumin levels were exogenously acutely replenished to > 3.5 gm/dL. Albumin was replaced to a level greater-than or equal to 3.5 g/dL in one group of 37 patients ( AR ) , with a control group of 32 patients ( NR ) not receiving any albumin . Return of bowel function was measured by the postoperative day that flatus was documented , as well as the postoperative day oral intake was resumed . Mean values were determined for each group , and t tests did not reveal a significant difference in postoperative day of flatus ( AR mean = 4.06 days , NR mean = 4.16 days ) or postoperative day of oral intake ( AR mean = 4.0 , NR mean = 3.75 ) . Additional comparisons between the groups involving the number of postoperative days until a regular diet was begun ( AR mean = 6.06 , NR mean = 5.48 ) and length of postoperative hospital stay ( AR mean = 9.16 , NR mean = 8.43 ) failed to reveal significant differences . ( ABSTRACT TRUNCATED AT 250 WORDS The effects on fluid balance , pulmonary tunctions and economics were evaluated in a r and omized comparison of one colloid free and three colloid containing fluid regimens , for 48 hours during and after coronary artery‐bypass ( CAB ) surgery Cardiac output and pulmonary wedge pressure ( PWP ) were used to evaluate the end point of fluid resuscitation in 20 patients suffering from multiple trauma and shock . Eleven patients received crystalloid resuscitation and nine patients received colloid resuscitation . Fifteen of 20 patients had an adequate cardiac output at the termination of resuscitation , but but only six of these patients had a PWP above 10 mm Hg . There was no significant correlation between left ventricular stroke work index and PWP in these patients , either at the completion of resuscitation or during the following three days . Five patients did not achieve adequate cardiac output and four of these patients died , suggesting that cardiac output was the most important criterion for adequate resuscitation . If the goal of fluid resuscitation is to achieve an adequate cardiac output , then PWP was not a reliable guide . Furthermore , using both cardiac output and PWP as a guide to fluid resuscitation of our patients , we found that the type of fluid ( crystalloid or colloid ) for resuscitation did not influence the course of respiratory distress in these patients up to three days following resuscitation Hemodynamic , pulmonary , and renal variables were measured in 24 patients scheduled for major abdominal aortic operations . Control values were obtained before preoperative medications were given . All patients received 5 % dextrose in Lactated Ringer 's solution intraoperatively . Postoperatively , group 1 patients received 5 % dextrose in water plus albumin , group 2 received 5 % dextrose in 0.45 sodium chloride solution , and group 3 received 5 % dextrose in lactated Ringer 's solution . There were significant increases in Qs/Qt and AaDO2 , 48 hours after operation in group 3 . Oxygen consumption and cardiac output increased in all groups 24 hours after operation . Twenty-four hours later , these two variables returned to control values in group 1 but continued to rise in the other two groups . Significant diuresis occurred in group 1 , 48 hours postoperatively , whereas the other two groups continued to retain water . Use of albumin and 5 % dextrose in water in the postoperative period seemed to produce less deviations from control values of most measured variables , than the other two groups A prospect i ve , r and omized trial was performed to determine whether maintaining serum albumin levels in burned pediatric patients had any effect on morbidity and mortality . Patients < 19 years of age with burns > 20 % total body surface area were r and omized to receive supplemental albumin to maintain levels 2.5 to 3.5 g/dL ( " High Albumin " ) or were given albumin only if levels dropped < 1.5 g/dL ( " Low Albumin " ) after completing burn shock resuscitation . The 36 patients in the Low Albumin group were well matched for age , burn size , depth of injury , and inhalation injury when compared with the High Albumin group ( 34 patients ) . As expected , serum albumin levels were significantly lower in the Low Albumin group when compared with the High Albumin group . No differences between groups were noted for resuscitation needs , maintenance fluid requirements , urine output , tube feedings received , days of antibiotic treatment , or ventilatory requirements . No differences in hematology , electrolytes , or nutritional laboratories were found . Finally , length of stay , complication rate , and mortality were not affected by albumin treatment . Albumin supplementation to maintain normal serum levels does not seem to be warranted in previously healthy children who suffer severe burns and who receive adequate nutrition The accuracy of the STAT-CNT ® hematocrit ( hct ) was compared to Coulter and centrifuge methods in this study of the interrelationship between non-red cell blood constituents and accuracy of conductivity-based hct measurements . In the first part of the study , blood sample s from 31 patients undergoing elective cardiac procedures were analyzed at three times : before induction of anesthesia ( Time 1 ) , during the rewarming period of cardiopulmonary bypass ( CPB ) ( Time 2 ) , and after transfusion of all cell-saver blood available after termination of CPB ( Time 3 ) . Laboratory evaluation included hct using the Stat-Crit , Coulter , and centrifuge methods , and sodium ( Na ) , potassium ( K ) , chloride ( Cl ) , white blood cell count , total protein ( TP ) , and albumin . In the second part of the study , patients were r and omized to receive either 5 % albumin ( n = 14 ) or isotonic crystalloid ( n = 14 ) after termination of CPB to determine the effect of protein colloid replacement on conductivity-based hct measurements . Blood sample s were obtained before and after fluid volume replacement for multivariate analysis . Correlation of Coulter hct ( absolute ) with microhematocrit by centrifuge at all times ( n = 93 ) was 0.95 ( R2 ) with a bias and precision of −0.26 ± 1.7 % . Blood variables having the most significant effect on the Coulter-Stat-Crit difference ( bias ) were protein , C1 , and Na . Single regression analysis indicated that a 1-g/dL decrease in TP result ed in an absolute decrease in the hct reading by 1 hct% units . A 10-mmol/L change in either C1 or Na concentration result ed in a change in Stat-Crit accuracy of 3.5 % and 2.5 % , respectively . The difference between Coulter and Stat-Crit hct was significantly less when albumin was used as a part of fluid volume replacement compared to crystalloid ( P = 0.0006 ) . Therefore , as protein decreases from isotonic hemodilution , Stat-Crit accuracy worsens ; and , as hypoalbuminemia is corrected using 5 % albumin solution , accuracy improves . This study confirms that the Stat-Crit can provide accurate information about patients ' hct when plasma constituents are changing , as long as measurements are adjusted for changes in TP , Cl , and Na We assessed the effect of albumin infusion on weight loss and ventilation requirement in sick premature infants . Thirty infants , median gestational age 29 weeks , were entered into a r and omised controlled trial , at a median of 2 days of age . The infants , all with an albumin level < -30 g/l , received either 5 ml/kg of 20 % albumin or 5 ml/kg of their maintenance fluids ( placebo ) , both given as part of the total daily fluid requirement . The response to the infusion was assessed by comparing two periods ; 12 h immediately prior to the infusion and 12–24hh after the infusion . Albumin infusion was associated with a significant increase in albumin level and a significant reduction in weight , but in the placebo group there was a significant increase in weight . There were , however , no significant changes in the peak inspiratory pressure in response to either infusion . There was only a modest reduction ( < 15 % ) in the inspired oxygen concentration , which occurred in both groups , but reached statistical significance only following the albumin infusion . We conclude that our results suggest that albumin infusion in “ hypoalbuminaemic ” sick preterm infants is unlikely to alter their respiratory status Because several studies have shown a significant inverse correlation between depressed serum concentrations of albumin and hospital morbidity , a study with central total parenteral nutrition ( TPN ) with normal serum albumin ( NSA ) in hypoalbuminemic patients was conducted . Sixty-one patients who required central TPN were r and omized into one of two groups : group 1 ( n = 31 ) received TPN plus NSA ( 25 to 37.5 g/day ) until their measured serum albumin was greater than 3 g/dl , and group 2 ( n = 30 ) , who received TPN alone . All patients were followed for hospital complications until discharge or death . The groups were well matched for age , sex , major diagnoses , initial serum albumin concentrations , hospital complications before TPN , and number of operative procedures . Both groups received comparable doses of energy ( 37.2 + /- 89 vs. 3.30 + /- 6.2 kcal/kg.day ) and protein ( 1.6 + /- 0.4 vs. 1.6 + /- 0.3 g/kg.day ) . After initiation of TPN , there were significantly more hospital complications in group 2 ( 1 = 1.1 + /- 1.4 , n = 33 ; 2 = 2.6 + /- 3.0 , n = 80 , p less than .01 ) . When complications in the patient groups were stratified , significantly more patients in group 2 developed pneumonia ( 18 vs. 9 , p less than .05 ) and septicemia ( 11 vs. 2 , p less than .05 ) . Increasing serum albumin concentrations with NSA in hypoalbuminemic patients receiving central TPN appears to be associated with a reduction in hospital morbidity Summary : Interleukin-2 (IL-2)-based therapy induces a vascular leak syndrome ( VLS ) , manifested by hypotension , tachycardia , and oliguria , as is also seen with septic shock . The optimal method for trating such VLS is not known . A prospect i ve r and omized to receive crystalloid ( 0.9 % normal saline ) or colloid ( 5 % human serum albumin ) fluid boluses to maintain acceptable vital sugns and urine output . Patients refractory to fluid boluses were givern dopamine for oliguria and /or phenlylephrine for hypotension . Of 107 patients who completed one cycle of therapy on sltudy , 76 completed a full tratment course ( two cycles ) on study . The total number of saline and albumin fluid boluses given were 9.5 ± 0.9 versus 7.7 ± 0.7 ( p = 0.36 , n = 107 ) for the first cycle and 19.2 ± 1.8 versus 16.1 ± 1.6 ( p = 0.33 , n - 76 ) for a complete course , respectively . Although patients receiving saline boluses had significantlyn more oliguria during a course of therapy , weight gain , number of IL-2 doses , tachycarcia , hypotension , vasopressor use , hospital stay , and clinical response rates did not significantly differ between arms . Changes in hematocrit , hemoglobin , protein , albumin , blood urea nitrogen ( BUN ) , and creatinine were analyzed , and patients receiving crystalloid showed greater decrases in albumin ( p < 0.0001 ) and total protein ( p < 0.05 ) as expected . A 40-fold greater cost associated with albumin suggested that crystalloid resuscitation be used to treat the VLS associated with IL-2 therapy One possible cause of pulmonary failure after trauma is the type of asanguinous fluid used for resuscitation , i.e. , crystalloid or colloid . To investigate this issue , patients having a laparotomy for trauma r and omly received either Ringer 's lactate ( RLS ) alone or Ringer 's lactate with albumin ( ALB ) . Both groups received washed red cells . Test fluids and red cells were given before and during operation to restore vital signs and hematocrit to normal . Pulmonary function tests were performed for 5 days after operation . One hundred and forty-one cases were studied ( 84 RLS , 57 ALB ) . The volume of asanguinous resuscitation fluid infused was 5.37 + /- 3.38 liters ( -x + /- SD ) for RLS and 5.87 + /- 3.05 liters for ALB . ALB cases received 213 + /- 130 gm of albumin . Red cell transfusions were 1.5 + /- 2.9 units for RLS and 2.0 + /- 3.1 for ALB . Six patients died ( three RLS , there ALB ) . Three RLS and six ALB patients received intermittent m and atory ventilation or continous positive air pressure after operation . Pulmonary function results were not significantly different between the two groups for any parameter on any day after operation . Results of a r and omized trial in human subjects of resuscitation with crystalloid and colloid solutions for acute trauma requiring laparotomy did not reveal significant differences in ( 1 ) survival rate , ( 2 ) incidence of pulmonary failure , or ( 3 ) postoperative pulmonary function This prospect i ve r and omized study deals with the changes in magnitude and distribution of the extracellular fluid volume ( ECV ) and the relation between such changes and the plasma colloid osmotic pressure ( COPP ) in patients having abdominal aortic surgery . Two groups of thirteen patients each received whole blood to replace the blood loss . One group ( ALB ) had additionally 80 g albumin administered on the day of operation and 20 g the following 3 days , the other group ( NON-ALB ) did not receive extra albumin . In the ALB group ECV decreased from 9.3 + /- 1.71 (= 147 ml/kg ) to 8.4 + /- 2.01 ( NS ) on the first postoperative day ( p.o.d . ) and to 9.2 + /- 2.5 1 ( NS ) on the fourth p.o.d . In the NON-ALB group the preoperative ECV of 8.1 + /- 1.11 (= 125 ml/kg ) was unchanged on the first p.o.d . and 8.4 + /- 1.41 ( NS ) on the fourth p.o.d . The differences between the groups were non-significant . The post-operative changes observed in ECV were not related to COPP in the range 33 mmHg to 21 mmHg . The ratio between plasma volume ( PV ) and ECV was 0.35 + /- 0.06 preoperatively in both groups . Postoperative changes were non-significant and no correlation between COPP and PV/ECV could be found . In the present study the distribution of ECV between plasma and interstitium was found to be independent of COPP in the interval 33 - 21 mmHg . Furthermore , no obligatory contraction or expansion of ECV occurred after major elective surgery Objective To determine the efficacy of supplemental 25 % albumin in reducing morbidity and mortality rates in the surgical intensive care unit ( ICU ) . Design Prospect i ve , r and omized , unblinded clinical study . Setting Surgical ICU in a community hospital . Patients Two hundred nineteen patients with admission circulating albumin concentrations of < 3.0 g/dL ( < 30 g/L ) . The groups were well matched regarding age , sex , Acute Physiology and Chronic Health Evaluation II scores and initial circulating albumin concentrations . Interventions The treatment group ( n = 116 ) received 37.5 g/day of albumin until the circulating albumin concentration increased to > 3.0 g/dL ( > 30 g/L ) . The control group ( n = 103 ) received no supplemental albumin . Both groups received st and ard nutritional support . Measurements and Main Results The complication rate was 44 % in the albumin group vs. 36.9 % in the controls ( p = .29 ) . The albumin patients had a mortality rate of 10.3 % vs. 5.8 % in the control group ( p = .22 ) . There were no significant differences between the groups in the number of days spent receiving mechanical ventilation or in the tolerance to tube feedings . Conclusions Routine supplemental administration of 25 % albumin is expensive and offers no apparent outcome advantage and should be ab and oned in the treatment of patients in the surgical ICU . ( Crit Care Med 1994 ; 22:613–619 The effect of postoperative fluid management on pulmonary extravascular thermal volume ( ETV1 ) as in index of pulmonary extravascular water after coronary artery bypass grafting was compared , using the thermal-dye technique , among five patients who received 5 % albumin ( group A ) , five patients who received 6 % hydroxyethyl starch ( group H ) , and five who received lactated Ringer 's solution ( group C ) . lntraoperatively , all patients received lactated Ringer 's solution intravenously , and the cardiopulmonary bypass ( CPB ) circuit prime included 5 % albumin . No statistically significant changes in ETV1 occurred postoperatively in any group , nor did ETV1 differ significantly between groups . After CPB , colloid osmotic pressure ( COP ) significantly decreased and pulmonary artery wedge pressure ( WP ) and the WP-COP gradient significantly increased in each group , implying an increase in transcapillary fluid flux . Cardiac index . changed variably . Pulmonary shunt fraction ( Qsp/Qt ) did not change in groups A and C but decreased during CPB in group H ( from 0.22 ± 0.03 to 0.16 ± 0.11 ) . Postoperatively , patients in the three groups received similar volumes of fluids and had similar perioperative weight gains . By the next morning ( AM1 ) , COP increased in all groups , returning to levels noted before CPB in group C , and exceeding these levels in groups A and H. Wedge pressure was similar in all three groups on AM1 . PaO2 decreased significantly , and alveolar-arterial oxygen partial pressure difference increased significantly in all groups on AM1 . In Group H , Qsp/Qt returned to levels observed before CPB by AM1 ( 0.27 ± 0.09 ) . We conclude that in patients without postoperative increases in WP , ETV1 changes minimally during CPB and is not influenced by the type of fluid administered as the primary volume replacement in the postoperative period A prior prospect i ve r and om study showed that supplemental albumin led to a significant ( P ⩽ 0.05 ) fall in immunoglobulin ( Ig ) content of IgG , IgM , and IgA ; no measurement was made on the immune response to a known antigen . Therefore , the immune response to tetanus toxoid , measured by antibody precipitation , was studied in 43 nonalbumin patients and 22 albumin patients from whom frozen sera were available . The 65 patients received an average of 16 units blood during resuscitation and 0.5 ml tetanus toxoid . Using single radial immunodiffusion technique , duplicate double-blind measurements of precipitants formed by the patients tetanus toxoid antibody and purified tetanus toxoid ( TTA ) incorporated in 1 % agarose gel were made . TTA levels in the 22 albumin patients were compared with all nonalbumin patients and with two subgroups of 22 patients —one r and omly chosen ; the other matched for number of transfusions . TTA was also correlated with time after injury . TTA was significantly less in albumin patients ( 215 ± 100 units ) than in the nonalbumin patients ( 387 ± 233 units ) and both subgroups of nonalbumin patients . TTA correlated directly with time after injury in the nonalbumin patients ( slope = −0.4 ) . Albumin resuscitation for shock results not only in a fall in Ig content but also a reduction in the immune response to tetanus toxoid The effects of supplemental albumin infusion on serum protein homeostasis were studied in 94 seriously injured patients who received an average of 14.4 transfusion , 9.2 L electrolyte solution , and 829 ml fresh frozen plasma before and during operation . Based on r and omization , 46 patients received an average of 31 gm albumin during operation followed by 150 gm/day for 5 days ; 48 patients received no albumin . Supplemental albumin caused a significant ( p = less than 0.05 ) increase in total serum protein and albumin concentrations . In contrast , supplemental albumin caused a significant decrease in alpha 1 globulin , alpha 2 globulin , beta globulin , gamma globulin , and fibrinogen levels . The prothrombin time used as index of prothrombin concentration was significantly prolonged in albumin patients . These changes , not previously documented , need further evaluation to determine clinical significance AIM To compare the efficacy of a colloid ( 5 % albumin ) and a crystalloid ( isotonic saline ) solution for treating hypotension in mechanically ventilated preterm infants . METHODS Sixty three preterm infants weighing 540 to 1950 g at birth and with gestational ages of 23 to 34 weeks , who developed hypotension ( mean arterial pressure < 25 , 30 , and 35 mm Hg for infants with birthweight < 1 , 1 - 1.49 , and 1.5 - 1.99 kg , respectively ) within the first 2 hours of life , were r and omly allocated to receive intravenous infusions at 10 ml/kg of either 5 % albumin ( group 1 , n=32 ) or isotonic ( 0.9 % ) saline ( group 2 , n=31 ) . Inotropic support with dopamine infusion was given if the infants remained hypotensive after a total of three infusions ( 30 ml/kg ) . Subsequent extra doses of volume exp and er in the form of 5 % albumin was given , depending on the infant ’s blood pressure . RESULTS There was no difference in the volume of the test solutions required between the two groups . Outcome , as assessed by the number of infants requiring inotropic support and death or chronic lung disease , did not differ between the groups . After inotropic support , however , group 1 required significantly more volume exp and er to maintain normal blood pressure ( median : 27.5 ml/kgvs 10 ml/kg ; P=0.0187 ) and had a higher mean ( SEM ) percentage weight gain within the first 48 hours of life ( at 24 hours : 6.3(1.3)% vs 3.3(0.8)% ; P=0.049 ; at 48 hours : 5.9(1.9)%vs 0.9(1.7)% ; P=0.045 ) . The difference in weight gain was significant at 48 hours even when only those infants not requiring inotropic support or extra 5 % albumin were compared ( group 1 : 1.5(1.5)% , group 2 : -4.2(1.1)% ; P = 0.027 ) . CONCLUSIONS Isotonic saline is as effective as 5 % albumin for treating hypotension in preterm infants , and it has the additional advantage of causing less fluid retention in the first 48 hours Coagulation and need for postoperative blood and plasma therapy were studied in 94 injured patients requiring massive transfusions ( average = 14.4 ) ; 46 patients , by r and om selection , received supplemental albumin . Albumin therapy increased total protein concentration ( 6.4 vs 5.8 g/dL ) , serum albumin level ( 4.2 vs 2.9 g/dL ) , and plasma volume ( 3,895 vs 3,579 mL ) but not RBC volume ( 1,520 vs 1,530 mL ) . During the initial five postoperative days , patients receiving albumin required more transfusions ( 7.1 vs 3.8 ) and plasma ( 455 vs 317 mL ) . This increased need for blood and plasma correlated with a significant decrease in fibrinogen ( 238 vs 405 mg/dL ) and prolongation of the prothrombin time ( 2.6 vs 1.4 seconds ) . The partial thromboplastin time was prolonged and the platelet concentration was decreased in albumin-treated patients , but not significantly . Deficiencies in specific coagulation factors have not yet been identified but are being studied . Impaired coagulation is another potential hazard of supplemental albumin therapy , which is probably contraindicated in injured patients The effects of intraoperative changes in plasma colloid osmotic pressure ( COP ) on the formation of intestinal edema were studied in patients during modified Whipple 's operation ( hemipancreato-duodenectomy ) . Eighteen patients ( ASA physical status I or II ) were r and omly assigned to one of three groups . They received either lactated Ringer 's ( RL group , n = 6 ) , 10 % hydroxyethyl starch ( HES group , n = 6 ) , or 20 % human albumin ( HA group , n = 6 ) as a volume replacement solution , which was given to maintain central venous pressure ( CVP ) at the preoperative level . Jejunal specimens were obtained after the first transsection of the jejunum and prior to the jejuno-jejunostomy . Their water fraction ( g H2O/g tissue dry weight ) was measured gravimetrically . COP was determined prior to induction of anesthesia and upon removal of the second jejunal sample . In the RL group , 3,850 + /- 584 ml ( data are means + /- SEM ) of volume replacement solution were infused from induction of anesthesia to removal of the second jejunal sample . In the HES group , 1,358 + /- 45 ml were infused , and in the HA group , 463 + /- 49 ml were infused . During this time , COP decreased from 20.3 + /- 0.5 mmHg to 14.1 + /- 0.6 mmHg in the RL group , remained at 22.0 + /- 0.9 mmHg in the HES group , and increased from 20.7 + /- 0.9 mmHg to 28.1 + /- 0.9 mmHg in the HA group . ( ABSTRACT TRUNCATED AT 250 WORDS We have reevaluated and clinical ly tested the current concepts of shock and resuscitation on a logical , physiological , and physical basis . We have considered the currently accepted resuscitation paradigm which is based upon the thesis that early rapid resuscitation of “ lost ” fluid volume is m and atory and that adequacy of resuscitation can be evaluated by central venous pressure , PAP , PAWP , pulse rate , blood pressure , and /or urine volume . Such methods also accept as natural concomitants that capillary beds are “ damaged by injury ” ; that they “ leak ” salt , fluid , and albumin ; and that these are expected occurrences which are injury-related . We have also examined and clinical ly evaluated the thesis that MAP is a primary reflector of the relationships between volume and the size of the currently available functional vascular space . ( Currently available functional vascular space is mediated through the baroreceptor ( stretch receptor)/neuroendocrine mechanisms . ) Under this hypothesis , fluid resuscitation comprises infusion of a volume per unit time given so as to replete currently measurable fluid losses and to normalize and /or sustain MAP and the normal osmolar and oncotic relationships at the capillary/tissue interface while holding hydrostatic pressure at normal . Using burn injury as a model , we compared statistically homogeneous , r and omly selected groups of burn patients who were resuscitated using a hypotonic fluid ( 130 mOsm/liter ) alone ( group R : 7 patients ) , hypertonic fluid ( 240 mOsm/liter ) alone ( group R : 5 patients ) , or the hypertonic fluid containing albumin ( 12.5 g/liter ) ( group A : 7 patients ) . The results indicate that significantly smaller volumes of fluid were needed to resuscitate the patients in group A with a significantly more rapid normalization of physical , physiological , psychological , and biochemical parameters . We conclude that the physically and physiologically appropriate method of resuscitation , demonstrated in burn injury , comprises the use of a fluid given at a rate : ( 1 ) to maintain mean arterial and hydrostatic pressures within normal range ; ( 2 ) that delivers a volume per unit time which does not exceed the capacity of the currently available functional vascular space ; ( 3 ) that replaces concurrent measurable fluid losses ; ( 4 ) that is hypertonic ( to normalize capillary/tissue osmotic gradients ) ; and ( 5 ) that contains colloid ( to normalize capillary/tissue oncotic gradients ) . We further conclude that salt , fluid , and colloid loss into the interstitium during resuscitation frequently is due to the rate delivered and /or the physical nature of the fluid used and not to capillary bed damage outside the zone of injury The effects of i.v . infusion of 5 % albumin and balanced salt solutions were investigated in a prospect i ve study on 18 patients subjected to reconstruction of the abdominal aorta . The same schedules for blood replacement and intraoperative fluid therapy were followed for all patients . Postoperatively , the amounts of fluid administered were adjusted with the aim of keeping the mean pulmonary arterial occlusion pressure ( MPAOP ) close to the preoperative level . Immediately after operation , there was a decrease in cardiac filling pressures , indicating a blood volume deficit , in both groups . Less fluid was needed for adequate haemodynamic restitution in the albumin group . Postoperatively , the mean plasma oncotic pressure ( POP ) in the albumin-treated patients remained steady at 2.4 - 2.5 kPa ( 86 - 88 % of preoperative value ) . In the control group , POP fell to a mean minimum of 1.8 kPa ( 64 % of preoperative value ) 8 h after operation . The difference between POP and MPAOP decreased significantly in both groups , but the difference between the groups was not significant at any time . There was no significant correlation between venous admixture , on the one h and , and POP , MPAOP , POP-MPAOP difference , total sodium intake or net supply of non-colloid fluids , on the other . No clinical ly important differences in haemodynamic or lung function variables were found between the groups Twenty-six consecutive patients in hypovolemic shock were r and omized to fluid challenge with 5 % albumin ( A ) , 6 % hetastarch ( H ) , or 0.9 % saline ( S ) solutions . Fluid challenge consisted of 250 ml of test fluid every 15 min until the pulmonary artery wedge pressure ( WP ) reached 15 mm Hg . Thereafter , WP was maintained at 15 mm Hg for an additional 24 h with infusions of the same test fluid . Vital signs , hemodynamic and respiratory variables , as well as arterial lactate and colloid osmotic pressure ( COP ) were monitored according to protocol . Chest x-rays were performed by st and ardized technique before fluid challenge and at 12 and 24 h of maintenance fluid therapy and were evaluated for evidence of pulmonary edema . Cardiac function and hemodynamic stability were restored by fluid challenge with A , H , and S. Two to 4 times the volume of S as A or H was required to achieve similar hemodynamic endpoints . COP was increased by fluid challenge with A or H but was markedly reduced by fluid challenge with S and throughout the 24-h maintenance period . Fluid challenge result ed in reductions in COP-WP gradient of 62 % in the A , 43 % in the H , and 125 % in the S groups . Resuscitation with S result ed in a significantly higher incidence of pulmonary edema ( 87.5 % ) than did resuscitation with A ( 22 % ) or H ( 22 % ) . Urine output was not different among the groups at any time during the study . We conclude that 6 % H performs as well as 5 % A as a resuscitative fluid and that resuscitation with either of these colloids is associated with a lower incidence of pulmonary edema than is resuscitation with 0.9 % The influence of four different kinds of intravascular volume replacement on platelet function was investigated in 60 patients undergoing elective aortocoronary bypass grafting using cardiopulmonary bypass ( CPB ) . In a r and omized sequence , high-molecular weight hydroxyethyl starch solution ( HMW-HES , mean molecular weight [ Mw ] 450,000 d ) , low-molecular weight HES ( LMW-HES , Mw 200,000 d ) , 3.5 % gelatin or 5 % albumin were infused preoperatively to double reduced filling pressure ( pulmonary capillary wedge pressure [ PCWP ] < 5 mm Hg ) . Fifteen untreated patients served as a control . Platelet function was assessed by aggregometry using turbidometric technique ( inductors : ADP , epinephrine , collagen ) . Maximum aggregation , maximum gradient of aggregation , and platelet volume were measured before , during , and after CPB until the first postoperative day . HMW-HES 840 + /- 90 mL , LMW 850 + /- 100 mL , gelatin 950 + /- 110 mL , and albumin 810 + /- 100 mL were given preoperatively . Maximum platelet aggregation ( ranging from -23 % to -44 % relative from baseline value ) and maximum gradient of platelet aggregation ( ranging from -26 % to -45 % relative from baseline values ) were reduced only in the HMW-HES patients . After CPB , aggregometry also was impaired most markedly in these patients . The other volume groups showed less reduction in platelet aggregation and were similar to the untreated control . On the first postoperative day , aggregation variables had returned almost to baseline in all patients . Platelet volume was the same among the groups within the investigation period . Postbypass blood loss was highest in the HMW-HES group ( 890 + /- 180 mL ) . There was significant ( P < 0.04 ) correlation in this group between blood loss and change in platelet aggregation . ( ABSTRACT TRUNCATED AT 250 WORDS Albumin , when added to a st and ard resuscitation regimen , is purported to enhance plasma volume , improve pulmonary function by its oncotic effect , and prevent renal failure by augmenting salt and water excreation . These factors were evaluated in a prospect i ve r and omized manner in 52 injured |
601 | 28,558,000 | Importantly , all three groups were similar at pre-training for a variety of individual variables purported to moderate transfer of training to fluid intelligence , including personality traits , motivation to train , and expectations of cognitive improvement from training . | Training of working memory as a method of increasing working memory capacity and fluid intelligence has received much attention in recent years .
This burgeoning field remains highly controversial with empirically-backed disagreements at all levels of evidence , including individual studies , systematic review s , and even meta-analyses .
The current study investigated the effect of a r and omized six week online working memory intervention on untrained cognitive abilities in a community-recruited sample of healthy young adults , in relation to both a processing speed training active control condition , as well as a no-contact control condition . | Studies of the effects of physical fitness on cognition suggest that exercise can improve cognitive abilities in healthy older adults , as well as delay the onset of age-related cognitive decline . The mechanisms for the positive benefit of exercise and how these effects interact with other variables known to influence cognitive function ( e.g. , involvement in cognitive activities ) are less well understood . The current study examined the associations between the physical fitness , cerebrovascular blood flow regulation and involvement in cognitive activities with neuropsychological function in healthy post-menopausal women . Methods : Forty-two healthy women between the ages of 55 and 90 were recruited . Physical fitness ( V˙O2 max ) , cerebrovascular reserve ( cerebral blood flow during rest and response to an increase in end-tidal ( i.e. , arterial ) PCO2 ) , and cognitive activity ( self-reported number and hours of involvement in cognitive activities ) were assessed . The association of these variables with neuropsychological performance was examined through linear regression . Results : Physical fitness , cerebrovascular reserve and total number of cognitive activities ( but not total hours ) were independent predictors of cognitive function , particularly measures of overall cognitive performance , attention and executive function . In addition , prediction of neuropsychological performance was better with multiple variables than each alone . Conclusions : Cognitive function in older adults is associated with multiple factors , including physical fitness , cerebrovascular health and cognitive stimulation . Interestingly , cognitive stimulation effects appear related more to the diversity of activities , rather than the duration of activity . Further examination of these relationships is ongoing in a prospect i ve cohort study Although within-person comparisons allow direct assessment s of change , some of the observed change may reflect effects associated with prior test experience rather than the processes of primary interest . One method that might allow retest effects to be distinguished from other influences of change involves comparing the pattern of results in a longitudinal study with those in a study with a very short retest interval . Three short-term retest studies with moderately large sample s of adults are used to provide this type of reference information about the magnitude of change , test-retest correlations , reliabilities of change , and correlations of the change in different cognitive variables with each other , and with other types of variables Abstract This study tested the common assumption that , to be most effective , working memory ( WM ) training should be adaptive ( i.e. , task difficulty is adjusted to individual performance ) . Indirect evidence for this assumption stems from studies comparing adaptive training to a condition in which tasks are practice d on the easiest level of difficulty only [ cf . Klingberg ( Trends Cogn Sci 14:317–324 , 2010 ) ] , thereby , however , confounding adaptivity and exposure to varying task difficulty . For a more direct test of this hypothesis , we r and omly assigned 130 young adults to one of the three WM training procedures ( adaptive , r and omized , or self-selected change in training task difficulty ) or to an active control group . Despite large performance increases in the trained WM tasks , we observed neither transfer to untrained structurally dissimilar WM tasks nor far transfer to reasoning . Surprisingly , neither training nor transfer effects were modulated by training procedure , indicating that exposure to varying levels of task difficulty is sufficient for inducing training gains Background A variety of studies have demonstrated gains in cognitive ability following cognitive training interventions . However , other studies have not shown such gains , and questions remain regarding the efficacy of specific cognitive training interventions . Cognitive training research often involves programs made up of just one or a few exercises , targeting limited and specific cognitive endpoints . In addition , cognitive training studies typically involve small sample s that may be insufficient for reliable measurement of change . Other studies have utilized training periods that were too short to generate reliable gains in cognitive performance . Methods The present study evaluated an online cognitive training program comprised of 49 exercises targeting a variety of cognitive capacities . The cognitive training program was compared to an active control condition in which participants completed crossword puzzles . All participants were recruited , trained , and tested online ( N = 4,715 fully evaluable participants ) . Participants in both groups were instructed to complete one approximately 15-minute session at least 5 days per week for 10 weeks . Results Participants r and omly assigned to the treatment group improved significantly more on the primary outcome measure , an aggregate measure of neuropsychological performance , than did the active control group ( Cohen ’s d effect size = 0.255 ; 95 % confidence interval = [ 0.198 , 0.312 ] ) . Treatment participants showed greater improvements than controls on speed of processing , short-term memory , working memory , problem solving , and fluid reasoning assessment s. Participants in the treatment group also showed greater improvements on self-reported measures of cognitive functioning , particularly on those items related to concentration compared to the control group ( Cohen ’s d = 0.249 ; 95 % confidence interval = [ 0.191 , 0.306 ] ) . Conclusion Taken together , these results indicate that a varied training program composed of a number of tasks targeted to different cognitive functions can show transfer to a wide range of untrained measures of cognitive performance . Trial Registration Clinical Trials.gov Two experiments were conducted to compare thec ries of the functional organization of spatial working memory within the human prefrontal cortex . In Experiment I , memory set size for locations was parametrically varied , allowing for the assessment of BOLD signal across maintenance requirements . In the sec ond experiment , manipulation of spatial information held in working memory was contrasted with simple maintenance of that information . Both experiment evoked significant activity in a distributed spatia working memory network . Although dorsolateral prefrontal activation increased monotonically with memory set size , this region was differentially engaged in task conditions involving explicit manipulation of in ternal representations . Activation in the superior frontal sulcal region was associated with maintenance of spatial information , increasing with memory se size . In contrast , ventrolateral prefrontal activation was present only at the highest memory set size , possibly due to the differential use of organizational strategies with more complex stimuli . These results sup port cl aims that the dorsolateral prefrontal cortex is involved in the manipulation of internal representa tions and that the superior frontal sulcal region is involved in the maintenance of spatial information but they suggest a complex role for the ventrolatera prefrontal region Affective cognitive control capacity ( e.g. , the ability to regulate emotions or manipulate emotional material in the service of task goals ) is associated with professional and interpersonal success . Impoverished affective control , by contrast , characterizes many neuropsychiatric disorders . Insights from neuroscience indicate that affective cognitive control relies on the same frontoparietal neural circuitry as working memory ( WM ) tasks , which suggests that systematic WM training , performed in an emotional context , has the potential to augment affective control . Here we show , using behavioral and fMRI measures , that 20 d of training on a novel emotional WM protocol successfully enhanced the efficiency of this frontoparietal dem and network . Critically , compared with placebo training , emotional WM training also accrued transfer benefits to a “ gold st and ard ” measure of affective cognitive control – emotion regulation . These emotion regulation gains were associated with greater activity in the targeted frontoparietal dem and network along with other brain regions implicated in affective control , notably the subgenual anterior cingulate cortex . The results have important implication s for the utility of WM training in clinical , prevention , and occupational setting This article provides a Bayes factor approach to multiway analysis of variance ( ANOVA ) that allows research ers to state grade d evidence for effects or invariances as determined by the data . ANOVA is conceptualized as a hierarchical model where levels are clustered within factors . The development is comprehensive in that it includes Bayes factors for fixed and r and om effects and for within-subjects , between-subjects , and mixed design s. Different model construction and comparison strategies are discussed , and an example is provided . We show how Bayes factors may be computed with BayesFactor package in R and with the JASP statistical package |
602 | 16,160,210 | For patients with atrial fibrillation , treatment recommendations from clinical practice guidelines often differ from patient preferences , with substantial heterogeneity in their individual preferences . | Background .
Patient preferences and expert-generated clinical practice guidelines regarding treatment decisions may not be identical .
The authors compared the thresholds for antithrombotic treatment from studies that determined or modeled the treatment preferences of patients with atrial fibrillation with recommendations from clinical practice guidelines . | BACKGROUND Bleeding is the most serious complication of the use of oral anticoagulation in the prevention and treatment of thromoboembolic complications . We studied the frequency of bleeding complications in out patients treated routinely in anticoagulation clinics . METHODS In a prospect i ve cohort from thirty-four Italian anticoagulation clinics , 2745 consecutive patients were studied from the start of their oral anticoagulation ( warfarin in 64 % , acenocourmarol in the rest ) . The target anticoagulation-intensity was low ( international normalised ratio [ INR ] < or = 2.8 ) in 71 % of the patients and high ( > 2.8 ) in the remainder . We recorded demographic details and the main indication for treatment and , every 3 - 4 months , INR and outcome events . Such events included all complications ( bleeding , thrombosis , other ) , although only bleeding events are reported here , and deaths . We divided bleeding into major and minor categories . FINDINGS 43 % of the patients were women . Nearly three-fifths of the patients were aged 60 - 79 ; 8 % were over 80 . The main indication for treatment was venous thrombolism ( 33 % ) , followed by non-ischaemic heart disease ( 17 % ) . Mean follow-up was 267 days . Over 2011 patient-years of follow-up , 153 bleeding complications occurred ( 7.6 per 100 patient-years ) . 5 were fatal ( all cerebral haemorrhages , 0.25 per 100 patient-years ) , 23 were major ( 1.1 ) , and 125 were minor ( 6.2 ) . The rate of events was similar between sexes , coumarin type , size of enrolling centre , and target INR . The rate was higher in older patients : 10.5 per 100 patient-years in those aged 70 or over , 6.0 in those aged under 70 ( relative risk 1.75 , 95 % Cl 1.29 - 2.39 , p < 0.001 ) . The rate was also higher when the indication was peripheral and /or cerebrovascular disease than venous thromboembolism plus other indications ( 12.5 vs 6.0 per 100 patient-years ) ( 1.80 , 1.2 - 2.7 , p < 0.01 ) , and during the first 90 days of treatment compared with later ( 11.0 vs 6.3 , 1.75 , 1.27 - 2.44 , p < 0.001 ) . A fifth of the bleeding events occurred at low anticoagulation intensity ( INR < 2 , rate 7.7 per 100 patient-years of follow-up ) . The rates were 4.8 , 9.5 , 40.5 , and 200 at INRs 2.0 - 2.9 , 3 - 4.4 , 4.5 - 6.9 , and over 7 , respectively ( relative risks for INR > 4.5 , 7.91 , 5.44 - 11.5 , p < 0.0001 ) . INTERPRETATION We saw fewer bleeding events than those recorded in other observational and experimental studies . Oral anticoagulation has become safer in recent years , especially if monitored in anticoagulation clinics . Caution is required in elderly patients and anticoagulation intensity should be closely monitored to reduce periods of overdosing In recent years quality of life instruments have been featured as primary outcomes in many r and omized trials . One of the challenges facing the investigator using such measures is determining the significance of any differences observed , and communicating that significance to clinicians who will be applying the trial results . We have developed an approach to elucidating the significance of changes in score in quality of life instruments by comparing them to global ratings of change . Using this approach we have established a plausible range within which the minimal clinical ly important difference ( MCID ) falls . In three studies in which instruments measuring dyspnea , fatigue , and emotional function in patients with chronic heart and lung disease were applied the MCID was represented by mean change in score of approximately 0.5 per item , when responses were presented on a seven point Likert scale . Furthermore , we have established ranges for changes in question naire scores that correspond to moderate and large changes in the domains of interest . This information will be useful in interpreting question naire scores , both in individuals and in groups of patients participating in controlled trials , and in the planning of new trials Patients who agree and those who refuse clinical trial entry may differ in attitudes towards decision control and the benefits associated with the trial arms . These differences , if they exist , have implication s for the process of obtaining informed consent and for the generalization of the results of a clinical trial . This paper describes the development and initial application of methods design ed to detect such differences . Developmental work involved creating an inventory of instruments design ed to determine patients ' attitudes towards participating in treatment decision making , permitting r and om selection of treatment , and undertaking the risks and benefits associated with the various treatments in a trial . Initial application involved modifying these instruments in terms of an actual chemotherapeutic trial for colonic adenocarcinoma , seeking responses to these measures from 60 non-eligible colorectal cancer patients , then determining whether those who would agree to trial entry differed systematic ally on these measures from those who indicated that they would refuse such a trial . Twenty-five of the respondents reported that , if faced with the actual decision , they would agree to trial entry : 35 would refuse . Refusers dem and ed more participation in decision making ( Chi-square ; P = 0.01 ) and a greater increment in treatment benefit ( t-test ; P = 0.0001 ) . Twenty-two of the 35 refusers reported aversion to r and omization as their primary reason for trial refusal . Since their particular content can be modified , these measures may be applicable to all clinical trials . They could be used to study the reasons patients accept or refuse trial entry and to determine if agreer-refuser attitude differences undermine the generalizability of a trials results CONTEXT Decision aids are tools design ed to help patients participate in the clinical decision-making process . OBJECTIVE To determine whether use of an audiobooklet ( AB ) decision aid explaining the results of a clinical trial affected the decision-making process of study participants . DESIGN R and omized controlled trial conducted from May 1997 to April 1998 . SETTING Fourteen centers that participated in the Stroke Prevention in Atrial Fibrillation ( SPAF ) III trial . PARTICIPANTS A total of 287 patients from the SPAF III aspirin cohort study , in which patients with atrial fibrillation and a relatively low risk of stroke received 325 mg/d of aspirin and were followed up for a mean of 2 years . INTERVENTION At the end of SPAF III , participants were r and omized to be informed of the study results with usual care plus use of an AB ( AB group ) vs usual care alone ( control group ) . The AB included pertinent information to help patients decide whether to continue taking aspirin or switch to warfarin . MAIN OUTCOME MEASURES Patients ' ability to make choices regarding antithrombotic therapy , and 6-month adherence to these decisions . Their knowledge , expectations , decisional conflict ( the amount of uncertainty about the course of action to take ) , and satisfaction with the decision-making process were also measured . RESULTS More patients in the AB group made a choice about antithrombotic therapy than in the control group ( 99 % vs 94 % ; P = .02 ) . Patients in the AB group were more knowledgeable and had more realistic expectations about the risk of stroke and hemorrhage ( in the AB group , 53%-80 % correctly estimated different risks ; in the control group , 16%-28 % gave correct estimates ) . Decisional conflict and satisfaction were similar for the 2 groups . After 6 months , a similar percentage of patients were still taking their initial choice of antithrombotic therapy ( 95 % vs 93 % ; P = .44 ) . CONCLUSIONS For patients with atrial fibrillation who had participated in a major clinical trial , the use of an AB decision aid improved their underst and ing of the benefits and risks associated with different treatment options and helped them make definitive choices about which therapy to take . Further studies are necessary to evaluate the acceptability and impact of decision aids in other clinical setting In early 1983 , all 1,280 faculty and resident physicians at one hospital who were eligible to be vaccinated against hepatitis B were divided r and omly into three groups : Group 1 physicians received general information about the risks and benefits of alternative vaccine decisions ; Group 2 physicians were additionally invited to provide personal information for an individualized decision analysis ( 12.6 percent responded ) ; and Group 3 physicians , who served as controls , were not contacted . In one year 's follow-up , 20 percent of physicians were screened for hepatitis B antibody or vaccinated . More Group 2 physicians whose decision analyses recommended screening or vaccination took these actions ( 39 percent ) than any other group . Group assignment remained significantly associated with vaccine decisions after analyzing results by the " intention to treat " principle , and after adjusting for training status , exposure to blood and blood products , and pre- study intentions about the vaccine . Despite the low overall vaccine acceptance rate , it is concluded that individualized decision analysis can influence the clinical decisions taken by knowledgeable and interested patients BACKGROUND Given the greater uncertainty surrounding probability estimates associated with qualitative ( use of words or phrases ) descriptions , the use of quantitative ( numerical ) information to communicate the risks and benefits of therapies is recommended but the impact of its use in decision aids is unexplored . OBJECTIVE Using stroke prevention in atrial fibrillation as an example , to compare the impact of quantitative vs. qualitative descriptions of probability risk estimates in decision aids on the clinical decision-making process . DESIGN R and omized trial with a 2 x 2 factorial design . SUBJECTS A total of 198 volunteers aged 60 - 80 years . SETTING Outpatient clinics of a university-affiliated , tertiary-care teaching hospital . METHODS Participants were asked to imagine that they had atrial fibrillation , and using a decision aid , were then r and omized to two ways of receiving pertinent risk information regarding the probability of stroke and major bleeding when taking warfarin , aspirin or no therapy : ( 1 ) quantitatively , in which the 2-year probabilities of stroke and major haemorrhage were presented both numerically and graphically with 100 faces ( e.g. 8 of 100 ) , and ( 2 ) qualitatively in which these probabilities were presented with the use of verbal phrases ( e.g. very low , moderate ) . OUTCOME MEASURES Primary : decisional conflict . Secondary : participants ' choices , knowledge and expectations of outcomes using qualitative and quantitative scales . RESULTS Participants review ing quantitative risk information scored better on the informed subscale of the decisional conflict scale ( P < 0.05 ) and , as expected , were better able to estimate numerically their chance of stroke and bleeding when taking warfarin , aspirin or no medication . For the low risk arm , there were no significant differences in treatment choices for the qualitative and quantitative groups . For the moderate risk arm , treatment choices between the two groups were significantly different ( P = 0.01 ) , with those in the quantitative group more likely to make an actual choice and to choose therapies at the extremes of effectiveness ( warfarin and no treatment ) . There were no significant differences between the quantitative and qualitative groups in their ability to rank-order their stroke risk when taking warfarin , aspirin and no treatment , overall knowledge about atrial fibrillation and its treatment , and other dimensions of decisional conflict ( all P-values > 0.05 ) . CONCLUSIONS For participants without the disease in question , this study found that providing sufficient quantitative risk information makes them feel more informed , which sometimes affects their treatment choices . Further studies are necessary to confirm these findings for patients making actual clinical decisions The management of carotid artery stenosis is an art evolving into a science , increasingly informed by clinical trials of medical management versus carotid endarterectomy ( CEA ) . Ideas about optimal management depend on the confluence of patient-specific variables , surgical expertise , and the state of medical knowledge . In this complex and progressing setting , an up-to- date decision support system could help physicians apply the latest evidence to patient care . Carotid ultrasonography ( US ) studies provide an excellent opportunity to aid in the therapy of carotid stenosis . We developed a Carotid US Report Enhancement ( CURE ) to augment carotid US reports with treatment-specific prognostic information and patient-specific portions of the American Heart Association 's 1998 guideline for the management of carotid artery stenosis . In the process of design ing and implementing the CURE software , we encountered and eventually solved a variety of problems . The first problem was that US test was not always precise enough to distinguish between a moderate and mild carotid stenosis . Likewise , the st and ard US reports did not eluci date several technical problems that decreased the reliability of the US result . Third , although 17 of 18 physicians agreed to receive the CURE reports , they requested non-incriminating wording . Fourth , vascular surgeons supervising the US laboratories were reluctant to support the CURE report if they thought it would be construed as prompting self-referral . Finally , information about some comorbid conditions ( e.g. a history of atrial fibrillation ) could not be obtained reliably from the patients . The result of responding to these problems is a decision support program that is increasingly robust , able to detect many of its own limitations , and capable of integrating data from multiple sources . A r and omized controlled trial now in progress will evaluate the clinical impact of the CURE program The Canadian Atrial Fibrillation Anticoagulation Study was a r and omized double-blind placebo-controlled trial to assess the potential of warfarin to reduce systemic thromboembolism and its inherent risk of hemorrhage . As a result of the publication of two other " positive " studies of similar design and objective , this study was stopped early before completion of its planned recruitment of 630 patients . There were 187 patients r and omized to warfarin and 191 to placebo . Permanent discontinuation of study medication occurred in 26 % of warfarin-treated and 23 % of placebo-treated patients . The target range of the international normalized ratio was 2 to 3 . For the warfarin-treated patients , the international normalized ratio was in the target range 43.7 % of the study days , above it 16.6 % of the study days and below it 39.6 % of the study days . Fatal or major bleeding occurred at annual rates of 2.5 % in warfarin-treated and 0.5 % in placebo-treated patients . Minor bleeding occurred in 16 % of patients receiving warfarin and 9 % receiving placebo . The primary outcome event cluster was nonlacunar stroke , non central nervous systemic embolism and fatal or intracranial hemorrhage . Events were included in the primary analysis of efficacy if they occurred within 28 days of permanent discontinuation of the study medication . The annual rates of the primary outcome event cluster were 3.5 % in warfarin-treated and 5.2 % in placebo-treated patients , with a relative risk reduction of 37 % ( 95 % confidence limits , -63.5 % , 75.5 % , p = 0.17 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Abstract Objective : To determine and compare physicians ' and patients ' thresholds for how much reduction in risk of stroke is necessary and how much risk of excess bleeding is acceptable with antithrombotic treatment in people with atrial fibrillation . Design : Prospect i ve observational study . Setting : Tertiary and peripheral referral centres in Nova Scotia , Canada . Participants : 63 physicians who were treating patients with atrial fibrillation and 61 patients at high risk for atrial fibrillation . Main outcome measures : Participants underwent a face to face interview with a probability trade-off tool . Thresholds were determined for the minimum reduction in risk of stroke necessary and the maximum increase in risk of excess bleeding acceptable for treatment with aspirin and warfarin in people with atrial fibrillation . Results : The minimum number of strokes that needed to be prevented in 100 patients over two years for warfarin to be justified was significantly lower for patients than for physicians ( 1.8 ( SD 1.9 ) v 2.5 ( 1.6 ) , P=0.009 ) , whereas for aspirin there was no difference between patients and physicians ( 1.3 ( 1.3 ) v 1.6 ( 1.5 ) , P=0.29 ) . The maximum number of excess bleeds acceptable in 100 patients over two years for use of warfarin and aspirin was significantly higher for patients than for physicians ( warfarin 17.4 ( 7.1 ) v 10.3 ( 6.1 ) ; aspirin 14.7 ( 8.5 ) v 6.7 ( 6.2 ) ; P<0.001 for both comparisons ) . Conclusions : Patients at high risk for atrial fibrillation placed more value on the avoidance of stroke and less value on the avoidance of bleeding than did physicians who treat patients with atrial fibrillation . The views of the individual patient should be considered when decisions are being made about antithrombotic treatment for people with atrial fibrillation . What is already known on this topic Several observational studies have shown an apparent underuse of antithrombotic drugs in patients with atrial fibrillation , despite evidence of efficacy What this study adds There is considerable variability between physicians and patients in their weighing up of the potential outcomes associated with atrial fibrillation and its treatment For anticoagulation treatment to be acceptable patients required less reduction in risk of stroke and were more tolerant of an increase in risk of bleeding than physicians Physicians varied considerably in how much risk of bleeding they thought was acceptable for a given reduction in risk of stroke associated with antithrombotic BACKGROUND Hypertension guidelines from different organizations often specify different treatment thresholds , and none explicitly state how these thresholds were chosen . This study was undertaken to determine the treatment thresholds of family physicians and hypertensive patients for mild , uncomplicated essential hypertension . A subject 's treatment threshold can be determined by eliciting the minimum reduction in cardiovascular risk that he or she feels outweighs the inconvenience , costs and side effects of antihypertensive therapy ( the minimal clinical ly important difference [ MCID ] ) . METHODS The study subjects consisted of a r and om sample of family physicians and a consecutive sample of hypertensive patients without overt cardiovascular disease from Ottawa and Edmonton . To determine participants ' MCIDs , we used a survey employing hypothetical scenarios ( each depicting a different baseline cardiovascular risk ) and a probability trade-off tool . RESULTS Of 94 family physicians and 146 patients approached for the study , 72 and 74 participated respectively . There was marked variability in the MCIDs of both groups . In general , patients were less likely to want antihypertensive therapy than physicians , particularly when baseline cardiovascular risks were low : 49 % v. 64 % ( p = 0.06 ) , 68 % v. 92 % ( p < 0.001 ) and 86 % v. 100 % ( p = 0.001 ) for 5-year cardiovascular risks of 2 % , 5 % and 10 % respectively . Moreover , patients expressed larger MCIDs ( i.e. , wanted greater benefits before accepting therapy ) than physicians . However , a subgroup of patients ( 15 % to 26 % , depending on the scenario ) wanted treatment even if there was no anticipated benefit . Multivariate analysis showed that no sociodemographic factors strongly predicted the MCIDs of either group . INTERPRETATION Guidelines that set treatment thresholds on the basis of physician or expert opinion may not accurately reflect the preferences of hypertensive patients . There is a need for patient decision aids and attention to patient preferences when initiation of antihypertensive therapy is considered for the prevention of cardiovascular disease . Further research is needed to define treatment thresholds for other chronic conditions and in other groups BACKGROUND Nonrheumatic atrial fibrillation increases the risk of stroke , presumably from atrial thromboemboli . There is uncertainty about the efficacy and risks of long-term warfarin therapy to prevent stroke . METHODS We conducted an unblinded , r and omized , controlled trial of long-term , low-dose warfarin therapy ( target prothrombin-time ratio , 1.2 to 1.5 ) in patients with nonrheumatic atrial fibrillation . The control group was not given warfarin but could choose to take aspirin . RESULTS A total of 420 patients entered the trial ( 212 in the warfarin group and 208 in the control group ) and were followed for an average of 2.2 years . Prothrombin times in the warfarin group were in the target range 83 percent of the time . Only 10 percent of the patients assigned to receive warfarin discontinued the drug permanently . There were 2 strokes in the warfarin group ( incidence , 0.41 percent per year ) as compared with 13 strokes in the control group ( incidence , 2.98 percent per year ) , for a reduction of 86 percent in the risk of stroke ( warfarin : control incidence ratio = 0.14 ; 95 percent confidence interval , 0.04 to 0.49 ; P = 0.0022 ) . There were 37 deaths altogether . The death rate was markedly lower in the warfarin group than in the control group : 2.25 percent as compared with 5.97 percent per year , for an incidence ratio of 0.38 ( 95 percent confidence interval , 0.17 to 0.82 ; P = 0.005 ) . There was one fatal hemorrhage in each group . The frequency of bleeding events that led to hospitalization or transfusion was essentially the same in both groups . The warfarin group had a higher rate of minor hemorrhage than the control group ( 38 vs. 21 patients ) . CONCLUSIONS Long-term low-dose warfarin therapy is highly effective in preventing stroke in patients with non-rheumatic atrial fibrillation , and can be quite safe with careful monitoring BACKGROUND Because most strokes cause neurological impairment rather than death , stroke prophylaxis may improve quality of life more than length of life . Thus , an underst and ing of how stroke and stroke prophylaxis affect quality of life is central to clinical decision making for many patients . METHODS We elicited quality -of-life estimates , known as utilities , for 3 degrees of severity of anticipated stroke-mild , moderate , and major- and for stroke prophylaxis with either warfarin sodium or aspirin therapy . We used the time tradeoff and st and ard gamble methods to elicit these utilities from 83 patients who had atrial fibrillation . RESULTS Seventy patients completed the interview successfully . Their utilities for stroke ranged from worse than death ( < 0 ) to as good as current health ( 1.0 ) . The median utilities for mild , moderate , and major stroke were 0.94 , 0.07 , and 0.0 , respectively . Although the median utilities decreased with increasing severity of stroke ( P < .001 ) , there was high interpatient variability within each degree of stroke severity . For example , 7 subjects ( 10 % ) rated a major stroke above 0.5 , while 58 subjects ( 83 % ) rated it as equal to or worse than death . In contrast to the stroke utilities , the median utilities for warfarin and aspirin therapy were high-0.997 and 1.0 , respectively . However , the interpatient variability for warfarin therapy was also important : 11 patients ( 16 % ) with atrial fibrillation rated the utility of warfarin therapy so low that their quality -adjusted life expectancy would be greater with aspirin . CONCLUSION Patients ' utilities for stroke prophylaxis and anticipated stroke vary substantially . Many patients view the quality of life with major stroke as tantamount to or worse than death . These findings highlight the relevance of incorporating patient preferences when choosing stroke prophylaxis Although practice guidelines suggest that postmenopausal women learn about the benefits and nsks and consider their values when deciding about hormone therapy , the optimal decision-support method has not been established . In a r and omized controlled trial , the authors compared the efficacy of a general educational pamphlet with that of a tailored decision aid . The pamphlet briefly summarized benefits , risks , and likely beneficiaries in general terms . The decision aid , delivered via booklet and audiotape , provided : detailed benefits and risks using functional terms and probabilities tailored to clinical risk ; and steps for considering the issue in a woman 's own situation , including a value-clarification exercise . Compared with the pamphlet group , the decision-aid group had statistically significant ( p < 0.05 ) improvements in terms of realistic personal expectations of the benefits and nsks , decisional conflict , and perceived acceptability of the intervention . Levels of general knowledge about the main benefits and nsks were comparable for the two interventions It is concluded that tailored decision aids prepare women for decision making better than do general pamphlets . Key words : decision making ; choice behavior ; informed consent ; decision-support techniques ; woman education ; woman participation ; health education ; consumer satisfaction ; hormone replacement therapy ; menopause . ( Med Decis Making 1998;18:295 - 303 OBJECTIVE To investigate the effect of patients ' preferences in the treatment of atrial fibrillation by using individualized decision analysis in which probability and utility assessment s are combined into a decision tree . DESIGN Observational study based on interviews with patients . SETTING 8 general practice s in Avon , Engl and . PARTICIPANTS 260 r and omly selected patients aged 70 to 85 years with atrial fibrillation . MAIN OUTCOME MEASURES Patients ' treatment preferences regarding anticoagulation treatment ( warfarin sodium ) after individualized decision analysis ; comparison of these preferences with treatment guidelines on the basis of comorbidity and absolute risk and compared with current prescription . RESULTS Of 195 eligible patients , 97 participated in decision making using decision analysis . Among these 97 , the decision analysis indicated that 59 ( 61 % ; 95 % confidence interval , 50%-71 % ) would prefer anticoagulation treatment , considerably fewer than those who would be recommended treatment according to guidelines . There was marked disagreement between the decision analysis and guideline recommendations ( kappa > or = 0.25 ) . Of 38 patients whose decision analysis indicated a preference for anticoagulation , 17 ( 45 % ) were being prescribed warfarin ; on the other h and , 28 ( 47 % ) of 59 patients were not being prescribed warfarin , although the results of their decision analysis suggested they wanted to be . CONCLUSIONS In the context of shared decision making , individualized decision analysis is valuable in a sizable proportion of elderly patients with atrial fibrillation . Taking account of patients ' preferences would lead to fewer prescriptions for warfarin than under published recommendations . Decision analysis as a shared decision-making tool should be evaluated in a r and omized controlled trial Background . Decision analysis ( DA ) and the probability-tradeoff technique ( PTOT ) are patient preference-based methods of determining optimal therapy for individuals . Using aspirin therapy for the primary prevention of stroke and myocardial infa rct ion ( MI ) in elderly persons as an example , the objective of this study was to determine whether group-level treatment thresholds and individual-level treatment recommendations derived using PTOT are identical to those of DA incorporating the patients ' own values . Methods . Persons in a pilot study of the efficacy of aspirin in the prevention of stroke and MI were asked to participate . Participant values and utilities for pertinent health states ( e.g. , minor and major stroke , MI , major bleeding episode ) were determined . Then , in three hypothetical clinical situations in which the chance of stroke or MI was varied , PTOT was used to directly determine treatment thresholds for aspirin therapy ( i.e. , the smallest reduction in MI or stroke risk for which participants would be willing to take aspirin ) . Using DA modeling , with the same probabilities of events as in the PTOT exercise and incorporating participants ' own values , treatment thresholds for the three clinical situations were determined . The thresholds determined by the two approaches were compared . Finally , based on these treatment thresholds , using the best estimates of the efficacy of aspirin to prevent first-time stroke and MI , PTOT and DA treatment recommendations for individual participants were compared . Results . The 42 participants reported that a major stroke was the least desirable health state , followed by MI , minor stroke , and major bleeding . The minimum risk reduction required to take aspirin was greater for MI prevention compared with stroke prevention . For the two clinical situations in which the hypothetical efficacy of aspirin to prevent stroke was varied , treatment thresholds for the PTOT versus DA approaches differed ( p < 0.04 ) , but this difference was not significant ( p = 0.19 ) for the MI-based clinical situation . Using the best estimate of the efficacy of aspirin to prevent first-time stroke and MI , PTOT and DA treatment recommendations whether or not to take aspirin were discordant for 38 % of participants ( 16 of 42 ) ( p < 0.001 ) . Conclusions . Patient preference-based group-level treatment thresholds and individual-level treatment recommendations can differ significantly depending on whether PTOT or DA is used , apparently because the two emphasize different aspects of the decision-making process . DA theory assumes that effective therapeutic decision making should maximize both quality and quantity of life ; with PTOT , the emphasis for effective clinical decision making allows patients to be fully engaged in the process , thus hopefully leading to fully informed decisions that may result in satisfaction and compliance . Key words : decision making ; decision analysis ; patient preferences ; treatment thresholds . ( Med Decis Making 2000;20:394 - 403 Background : There is an increasing move towards clinical decision making that engages the patient , which has led to the development and use of decision aids to support better decisions . The treatment of patients in atrial fibrillation ( AF ) with warfarin to prevent stroke is a decision that is sensitive to patient preferences as shown by a previous decision analysis . Aim : To develop a computerised decision support tool , building upon a previous decision analysis , which would engage individual patient preferences in reaching a shared decision on whether to take warfarin to prevent stroke . Methods : The development process had two main phases : ( 1 ) the development phase which employed focus groups and repeated interviews with GPs/ practice nurses and patients alongside an iterative development of a computerised tool ; ( 2 ) the training and testing phase in which GPs and practice nurses underwent training in the use of the tool , including the use of simulated patients . The tool was then used in a feasibility study in a small number of patients with AF to inform the design of a subsequent r and omised controlled trial . Results : The prototype tool had three components : ( 1 ) derivation of an individual patient 's values for relevant health states using a st and ard gamble ; ( 2 ) presentation/ discussion of a patient 's risks of stroke using the Framingham equation and the benefits /risks of warfarin from a systematic literature review ; and ( 3 ) decision making component incorporating the outcome of a Markov decision analysis model . Older patients could be taken through the decision analysis based computerised tool , and patients and clinicians welcomed information on risks and benefits of treatments . The tool required time and training to use . Patients ' decisions in the feasibility phase did not necessarily coincide with the output of the decision analysis model , but decision conflict appeared to be reduced and both patients and GPs were satisfied with the process . Conclusions : It is feasible to develop a decision analysis based computer software package that is acceptable to elderly patients and clinicians , but it requires time and expertise to use . It is most likely that a tool of this type will best be used by a small number of clinicians who have developed experience of its use and can maintain their skills From November , 1985 , to June , 1988 , 1007 out patients with chronic non-rheumatic atrial fibrillation ( AF ) entered a r and omised trial ; 335 received anticoagulation with warfarin openly , and in a double-blind study 336 received aspirin 75 mg once daily and 336 placebo . Each patient was followed up for 2 years or until termination of the trial . The primary endpoint was a thromboembolic complication ( stroke , transient cerebral ischaemic attack , or embolic complications to the viscera and extremities ) . The secondary endpoint was death . The incidence of thromboembolic complications and vascular mortality were significantly lower in the warfarin group than in the aspirin and placebo groups , which did not differ significantly . 5 patients on warfarin had thromboembolic complications compared with 20 patients on aspirin and 21 on placebo . 21 patients on warfarin were withdrawn because of non-fatal bleeding complications compared with 2 on aspirin and none on placebo . Thus , anticoagulation therapy with warfarin can be recommended to prevent thromboembolic complications in patients with chronic non-rheumatic AF BACKGROUND There is a lack of evidence regarding the value of tools design ed to aid decision making in patients with newly diagnosed hypertension . AIM To evaluate two interventions for assisting newly diagnosed hypertensive patients in the decision whether to start drug therapy for reducing blood pressure . DESIGN OF STUDY Factorial r and omised controlled trial . SETTING Twenty-one general practice s in south-west Engl and , UK . METHOD Adults aged 32 to 80 years with newly diagnosed hypertension were r and omised to receive either : ( a ) computerised utility assessment interview with individualized risk assessment and decision analysis ; or ( b ) information video and leaflet about high blood pressure ; or ( c ) both interventions ; or ( d ) neither intervention . Outcome measures were decisional conflict , knowledge , state anxiety , intentions regarding starting treatment , and actual treatment decision . RESULTS Of 217 patients r and omised , 212 ( 98 % ) were analysed at the primary follow-up ( mean age = 59 years , 49 % female ) . Decision analysis patients had lower decisional conflict than those who did not receive this intervention ( 27.6 versus 38.9 , 95 % confidence interval [ CI ] for adjusted difference = -13.0 to -5.8 , P < 0.001 ) , greater knowledge about hypertension ( 73 % versus 67 % , adjusted 95 % CI = 2 % to 9 % , P = 0.003 ) and no evidence of increased state anxiety ( 34.8 versus 36.8 , adjusted 95 % CI = -5.6 to 0.1 , P = 0.055 ) . Video/leaflet patients had lower decisional conflict than corresponding controls ( 30.3 versus 36.8 , adjusted 95 % CI = -7.4 to -0.6 , P = 0.021 ) , greater knowledge ( 75 % versus 65 % , adjusted 95 % CI = 6 % to 13 % , P < 0.001 ) and no evidence of increased state anxiety ( 35.7 versus 36.1 , adjusted 95 % CI = -3.9 to 1.7 , P = 0.46 ) . There were no differences between either of the interventions and their respective controls in the proportion of patients prescribed antihypertensive medication ( 67 % ) . CONCLUSIONS This trial demonstrates that , among patients facing a real treatment decision , interventions to inform patients about hypertension and to clarify patients ' values concerning outcomes of treatment are effective in reducing decisional conflict and increasing patient knowledge , while not result ing in any increases in state anxiety Whether or not to treat patients with non-rheumatic atrial fibrillation with anticoagulants to prevent embolic stroke is a dilemma for physicians . If r and omized trials , currently underway , demonstrate a beneficial effect , the dilemma will not be solved because not all of the relevant factors can be addressed by trials . We used current knowledge about non-rheumatic atrial fibrillation and a method of obtaining patient-derived weights for avoiding stroke from eight medically trained subjects , to determine the overall benefit of anticoagulants and to see what factors were relevant and what effect each might have in deciding whether to use anticoagulant therapy . Using st and ard assumptions , anticoagulants gave an expected benefit for all subjects . The expected benefit ( expressed in terms of lives per 1000 saved due to anticoagulants ) varied between 5.4 and 46.7 . This benefit remained for all subjects when we did a sensitivity analysis for different rates of stroke prevented by anticoagulants and different rates of intracranial hemorrhage caused by anticoagulants . When we used different baseline rates of stroke and different impacts of major hemorrhagic complications the benefit disappeared for 3 and 4 subjects respectively . We found the factors that were most crucial to the decision will not be included in r and omized trials ; the weight that an individual would place on avoiding embolic stroke vs the risk of intracranial bleeding from anticoagulant therapy ; and the rate of embolic stroke that could be expected for the subject at risk . Factors which will be measured in r and omized trials , will change results less substantially : the increased risk of major hemorrhages ; the proportion of strokes that could be prevented by treatment ; the increase in risk of intracranial hemorrhage . This method of analysis suggests that for most patients anticoagulants are beneficial and that the most important factor in determining this result is the value that subjects put on different outcomes OBJECTIVE To determine the minimal clinical ly important difference ( MCID ) of warfarin therapy for the treatment of nonvalvular atrial fibrillation from the perspective of patients using 2 different elicitation methods . DESIGN All patients completed 2 face-to-face interviews , which were 2 weeks apart . For each interview , they were r and omized to receive 1 of 2 elicitation methods : ping-ponging or starting at the known efficacy . SETTING The practice s of 2 university-affiliated family medicine centers ( 8 physicians each ) , 14 community-based family physicians , and 2 cardiologists . PATIENTS Sixty-four patients with nonvalvular atrial fibrillation who were initiated with warfarin therapy at least 3 months before the study . INTERVENTION During each interview , the patients ' MCIDs were determined by using ( 1 ) a pictorial flip chart to describe atrial fibrillation ; the consequences of a minor stroke , a major stroke , and a major bleeding episode ; the chance of stroke if not taking warfarin ; the chance of a major bleeding episode if taking warfarin ; examples of the inconvenience , minor side effects , and costs of warfarin therapy ; and then ( 2 ) 1 of the 2 elicitation methods to determine their MCIDs ( the smallest reduction in stroke risk at which the patients were willing to take warfarin ) . Patients ' knowledge of their stroke risk , acceptability of the interview process , and factors determining their preferences were also assessed . MAIN RESULTS Given a baseline risk of having a stroke in the next 2 years , if not taking warfarin , of 10 of 100 , the mean MCID was 2.01 of 100 ( 95 % confidence interval , 1.60 - 2.42 ) . Fifty-two percent of the patients would take warfarin for an absolute decrease in stroke risk of 1 % over 2 years . Before eliciting their MCIDs , patients showed poor knowledge of their stroke risk , which improved afterward . The interview process was well accepted by the patients . The MCID using the ping-ponging elicitation method was 1.015 of 100 smaller compared with use of the starting at the known efficacy method ( P = .01 ) . CONCLUSIONS We were able to determine the MCID of warfarin therapy for the prevention of stroke from the perspective of patients with nonvalvular atrial fibrillation . Their MCIDs were much smaller than those that have been implied by some experts and clinicians . The interview process , using the flip chart approach , appeared to improve the patients ' knowledge of their disease and its consequences and treatment . The method used to elicit the patients ' MCIDs can have a clinical ly important effect on patient responses . The method used in our study can be generalized to other conditions and , thus , could be helpful in 3 ways : ( 1 ) from a clinical decision-making perspective , it could facilitate patient-physician communication ; ( 2 ) it could clarify the patient perspective when interpreting the results of previously completed trials ; and ( 3 ) it could be used to derive more clinical ly relevant sample sizes for r and omized treatment trials Warfarin is an established treatment for prevention of ischaemic stroke in patients with atrial fibrillation , but the value of this agent relative to aspirin in unclear . In the first Stroke Prevention in Atrial Fibrillation ( SPAF-I ) study , direct comparison of warfarin with aspirin was limited by the small number of thromboembolic events . SPAF-II aims to address this issue and also to assess the differential effects of the two treatments according to age . We compared warfarin ( prothrombin time ratio 1.3 - 1.8 , international normalised ratio 2.0 - 4.5 ) with aspirin 325 mg daily for prevention of ischaemic stroke and systemic embolism ( primary events ) in two parallel r and omised trials involving 715 patients aged 75 years or less and 385 patients older than 75 ; we sought reductions in the absolute rate of primary events by warfarin compared with aspirin of 2 % per year and 4 % per year , respectively . In the younger patients , warfarin decreased the absolute rate of primary events by 0.7 % per year ( 95 % CI-0.4 to 1.7 ) . The primary event rate per year was 1.3 % with warfarin and 1.9 % with aspirin ( relative risk [ RR ] 0.67 , p = 0.24 ) . The absolute rate of primary events in low-risk younger patients ( without hypertension , recent heart failure , or previous thromboembolism ) on aspirin was 0.5 % per year ( 95 % CI 0.1 to 1.9 ) . Among older patients , warfarin decreased the absolute rate of primary events by 1.2 % per year ( 95 % CI-1.7 to 4.1 ) . The primary event rate per year was 3.6 % with warfarin and 4.8 % with aspirin ( RR 0.73 , p = 0.39 ) . In this older group , the rate of all stroke with residual deficit ( ischaemic or haemorrhagic ) was 4.3 % per year with aspirin and 4.6 % per year with warfarin ( RR 1.1 ) . Warfarin may be more effective than aspirin for prevention of ischaemic stroke in patients with atrial fibrillation , but the absolute reduction in stroke rate by warfarin is small . Younger patients without risk factors had a low rate of stroke when treated with aspirin . In older patients the rate of stroke ( ischaemic and haemorrhagic ) was substantial , irrespective of which agent was given . Patient age and the inherent risk of thromboembolism should be considered in the choice of antithrombotic prophylaxis for patients with atrial fibrillation Abstract Objective : To investigate the impact of patients ' preferences for the treatment of atrial fibrillation , by using individualised decision analysis combining probability and utility assessment s into a decision tree . Design : Observational study based on interviews with patients . Setting : Eight general practice s in Avon . Participants : 260 r and omly selected patients aged 70–85 years with atrial fibrillation . Main outcome measures : Patients ' treatment preferences regarding anticoagulation treatment ( warfarin ) after individualised decision analysis ; comparison of these preferences with treatment guidelines on the basis of comorbidity and absolute risk and compared with current prescription . Results : Of 195 eligible patients , 97 participated in decision making using decision analysis . Among these 97 , the decision analysis indicated that 59 ( 61 % ; 95 % confidence interval 50 % to 71 % ) would prefer anticoagulation treatment — considerably fewer than those who would be recommended treatment according to guidelines . There was marked disagreement between the decision analysis and guideline recommendations ( kappa = 0.25 or less ) . Of 38 patients whose decision analysis indicated a preference for anticoagulation , 17 ( 45 % ) were being prescribed warfarin ; on the other h and , 28 ( 47 % ) of 59 patients were not being prescribed warfarin although the results of their decision analysis suggested they wanted to be . Conclusions : In the context of shared decision making , individualised decision analysis is valuable in a sizeable proportion of elderly patients with atrial fibrillation . Taking account of patients ' preferences would lead to fewer prescriptions for warfarin than under published guideline recommendations . Decision analysis as a shared decision making tool should be evaluated in a r and omised controlled trial Several studies have established the value of anticoagulation for primary prevention of thromboembolic events in patients with non-rheumatic atrial fibrillation ( NRAF ) . However , in patients with a recent transient ischaemic attack ( TIA ) or minor ischaemic stroke the preventive benefit of anticoagulation or aspirin remains unclear . Physicians in 108 centres from 13 countries collaborated to study this question . 1007 NRAF patients with a recent TIA or minor ischaemic stroke were r and omised to open anticoagulation or double-blind treatment with either 300 mg aspirin per day or placebo ( group 1 , 669 ) . Patients with contraindications to anticoagulation were r and omised to receive aspirin or placebo ( group 2,338 ) . The measure of outcome was death from vascular disease , any stroke , myocardial infa rct ion , or systemic embolism . During mean follow-up of 2.3 years , the annual rate of outcome events was 8 % in patients assigned to anticoagulants vs 17 % in placebo-treated patients in group 1 ( hazard ratio [ HR ] 0.53 ; 95 % confidence interval [ CI ] 0.36 - 0.79 ) . The risk of stroke alone was reduced from 12 % to 4 % per year ( HR 0.34 ; 95 % CI 0.20 - 0.57 ) . Among all patients assigned to aspirin ( groups 1 and 2 ) , the annual incidence of outcome events was 15 % , against 19 % in those on placebo ( HR 0.83 ; 95 % CI 0.65 - 1.05 ) . Anticoagulation was significantly more effective than aspirin ( HR 0.60 ; 95 % CI 0.41 - 0.87 ) . The incidence of major bleeding events was low , both on anticoagulation ( 2.8 % per year ) and on aspirin ( 0.9 % per year ) . No intracranial bleeds were identified in patients assigned to anticoagulation . We conclude that anticoagulation is effective in reducing the risk of recurrent vascular events in NRAF patients with a recent TIA or minor ischaemic stroke . In absolute terms : 90 vascular events ( mainly strokes ) are prevented if 1000 patients are treated with anticoagulation for one year . Aspirin is a safe , though less effective , alternative when anticoagulation is contraindicated ; it prevents 40 vascular events each year for every 1000 treated patients BACKGROUND Nonrheumatic atrial fibrillation is common among the elderly and is associated with an increased risk of stroke . We investigated whether anticoagulation with warfarin would reduce this risk . METHODS We conducted a r and omized , double-blind , placebo-controlled study to evaluate low-intensity anticoagulation with warfarin ( prothrombin-time ratio , 1.2 to 1.5 ) in 571 men with chronic nonrheumatic atrial fibrillation ; 525 patients had not previously had a cerebral infa rct ion , whereas 46 patients had previously had such an event . The primary end point was cerebral infa rct ion ; secondary end points were cerebral hemorrhage and death . RESULTS Among the patients with no history of stroke , cerebral infa rct ion occurred in 19 of the 265 patients in the placebo group during an average follow-up of 1.7 years ( 4.3 percent per year ) and in 4 of the 260 patients in the warfarin group during an average follow-up of 1.8 years ( 0.9 percent per year ) . The reduction in risk with warfarin therapy was 0.79 ( 95 percent confidence interval , 0.52 to 0.90 ; P = 0.001 ) . The annual event rate among the 228 patients over 70 years of age was 4.8 percent in the placebo group and 0.9 percent in the warfarin group ( risk reduction , 0.79 ; P = 0.02 ) . The only cerebral hemorrhage occurred in a 73-year-old patient in the warfarin group . Other major hemorrhages , all gastrointestinal , occurred in 10 patients : 4 in the placebo group , for a rate of 0.9 percent per year , and 6 in the warfarin group , for a rate of 1.3 percent per year . There were 37 deaths that were not preceded by a cerebral end point--22 in the placebo group and 15 in the warfarin group ( risk reduction , 0.31 ; P = 0.19 ) . Cerebral infa rct ion was more common among patients with a history of cerebral infa rct ion ( 9.3 percent per year in the placebo group and 6.1 percent per year in the warfarin group ) than among those without such a history . CONCLUSIONS Low-intensity anticoagulation with warfarin prevented cerebral infa rct ion in patients with nonrheumatic atrial fibrillation without producing an excess risk of major hemorrhage . This benefit extended to patients over 70 years of age |
603 | 12,653,810 | No firm conclusions about the effectiveness of prevention interventions in the short- and medium term were possible .
Over the longer term ( > 3 years ) , the Strengthening Families Programme ( SFP ) showed promise as an effective prevention intervention . | OBJECTIVE To identify and summarize rigorous evaluations of psychosocial and educational interventions aim ed at the primary prevention of alcohol misuse by young people aged up to 25 years , especially over the longer term ( > 3 years ) . | A grade five through eight substance abuse prevention program , later incorporated into the Michigan Model for Comprehensive School Health Education , was developed , implemented , and evaluated . Results focus on students who received seven lessons on alcohol in grade six , and eight lessons on tobacco , alcohol , marijuana , and cocaine in grade seven taught by their regular classroom teachers ( after a 6-hour training in the social pressures resistance skills curriculum ) . Students ( N = 442 ) received either two years of the program or none , and completed individually-coded question naires . Repeated measures analysis of variance result ed in significant treatment by occasion interactions on the use of alcohol , cigarettes , marijuana , cocaine , and other drugs , as well as on knowledge . At the end of grade seven , program students ' rates of substance use had increased significantly less and knowledge of alcohol pressures , effects , and skills to resist had increased significantly more than those of comparison students OBJECTIVES This paper presents the 1-year outcomes evaluation of Project Towards No Drug Abuse ( Project TND ) , a large-scale indicated drug abuse prevention program in southern California applied to continuation high school youth , who are at high risk for drug abuse . METHODS The efficacy of nine-lesson health motivation -- social skills -- decision-making curriculum was evaluated in a three-condition experimental design . Twenty-one schools were r and omly assigned by block to one of three conditions -- st and ard care ( control ) , classroom program , and classroom program plus a semester-long school-as-community component . A pretest was followed by a 3-week-long drug abuse prevention program and then a posttest at 14 continuation high schools . The 7 st and ard care schools received only the pretest followed by the posttest ( same time duration ) . Subjects were followed up 1 year later . RESULTS Changes in use of cigarettes , alcohol , marijuana , and hard drugs were assessed in a pretest-1-year follow-up time interval . The follow-up rate was 67 % ( analysis n = 1,074 ) . Indicated preventive effects were found on alcohol and hard drug use . No differences were found across the two program conditions . CONCLUSIONS Project TND is the first program to demonstrate 1-year self-reported behavioral effects on alcohol use and hard drug use among older , high-risk youth by using a school-based , limited-session model This paper presents the findings from a controlled prospect i ve study of the effectiveness of a school-based alcohol education package for 13 year olds . The research had three phases : ( 1 ) baseline survey of alcohol-related knowledge , attitudes and behaviour ; ( 2 ) development and teaching of a short alcohol education package and ( 3 ) follow-up survey . The results indicate that the students who received the alcohol education knew more about alcohol than the controls . In addition , the educational intervention was found to have influenced the self-reported last consumption of alcohol and maximum consumption , with the ' educated ' youngsters generally exhibiting more restrained behaviour . There has been little scientific evidence that past alcohol education has been effective in changing young people 's drinking behaviour . The outcome of this research reinforces some recent studies which suggest the way forward may lie in an educational approach which takes account of social influences on substance use and misuse The entire early adolescent population of the 15 communities that constitute the Kansas City ( Kansas and Missouri ) metropolitan area has participated in a community-based program for prevention of drug abuse since September 1984 . The Kansas City area is the first of two major metropolitan sites being evaluated in the Midwestern Prevention Project , a longitudinal trial for primary prevention of cigarette , alcohol , and marijuana use in adolescents . The project includes mass media programming , a school-based educational program for youths , parent education and organization , community organization , and health policy components that are introduced sequentially into communities during a 6-year period . Effects of the program are determined through annual assessment s of adolescent drug use in schools that are assigned to immediate intervention or delayed intervention control conditions . In the first 2 years of the project , 22,500 sixth- and seventh- grade adolescents received the school-based educational program component , with parental involvement in homework and mass media coverage . Analyses of 42 schools indicate that the prevalence rates of use for all three drugs are significantly lower at 1-year follow-up in the intervention condition relative to the delayed intervention condition , with or without controlling for race , grade , socioeconomic status , and urbanicity ( 17 % vs 24 % for cigarette smoking , 11 % vs 16 % for alcohol use , and 7 % vs 10 % for marijuana use in the last month ) , and the net increase in drug use prevalence among intervention schools is half that of delayed intervention schools OBJECTIVE To examine the effectiveness of a brief , school-based intervention for preventing alcohol use . DESIGN AND SETTING R and omized , control trial assigning inner-city public school students to an intervention program or a comparison program . PARTICIPANTS Sixth , seventh , and eighth grade students in Jacksonville , Fla ( N=104 ) . INTERVENTIONS Students assigned to the intervention program were given a self-instructional module and corresponding audiotape , a health consultation with a physician or nurse , and a follow-up consultation with a trained peer health model . MAIN OUTCOME MEASURES Alcohol consumption during the month after the intervention and students ' assessment s of the interventions were measured . RESULTS Students ' t tests showed participants were more satisfied with physician or nurse consultations than with peer consultations or the self-instructional module and audiotapes ( P=.05 ) . Analysis of covariance tests showed significant main effects for 30-day quantity of alcohol use ( F=5.15 , P=.02 ) , with intervention students reporting less alcohol consumption at follow-up than comparison students , and for 30-day frequency of alcohol use ( F=5.92,P=.01 ) with intervention students again showing less frequent use at follow-up . CONCLUSIONS A multicomponent , school-based intervention using print and audiotape media , brief physician or nurse consultations , and follow-up peer contacts holds promise in altering short-term alcohol use and selected behavioral factors among inner-city youth This study evaluated the substance initiation effects of an intervention combining family and school-based competency-training intervention components . Thirty-six rural schools were r and omly assigned to 1 of 3 conditions : ( a ) the classroom-based Life Skills Training ( LST ) and the Strengthening Families Program : For Parents and Children 10 - 14 , ( b ) LST only , or ( c ) a control condition . Outcomes were examined 1 year after the intervention posttest , using a substance initiation index ( SII ) measuring lifetime use of alcohol , cigarettes , and marijuana and by rates of each individual substance . Planned intervention-control contrasts showed significant effects for both the combined and LST-only interventions on the SII and on marijuana initiation . Relative reduction rates for alcohol initiation were 30.0 % for the combined intervention and 4.1 % for LST only An alcohol misuse prevention curriculum for tenth- grade students was developed , implemented , and evaluated through twelfth grade with 1041 students from four school districts . The curriculum emphasized social pressures resistance training , immediate effects of alcohol , risks of alcohol misuse , and social pressures to misuse alcohol . There were desirable program effects on alcohol misuse prevention knowledge ( p < 0.001 ) , alcohol misuse ( p < 0.02 ) , and refusal skills ( p < 0.09 ) . Gender by occasion differences were found on alcohol use , alcohol misuse , and driving after drinking , with boys ' rates increasing more than those of girls . Exposure to a sixth- grade , as well as the tenth- grade , program did not result in better outcomes . Despite high levels of alcohol use among high school students , a tenth- grade curriculum can result in some desirable effects . Creative approaches are needed , however , especially for boys who tend to use and misuse alcohol at rates that increase more steeply than those of girls Alcohol-related injuries are a leading cause of death in mid and late adolescence . Schools might contribute to the prevention of these injuries by affecting adolescent drinking . Few school programmes , however , have succeeded . In view of this shortcoming , a previously investigated school based health counselling programme for mid adolescents was applied to work in conjunction with a municipal alcohol policy initiative . A pre-test/post-test quasi-experimental study of 118 sixteen year old students was carried out . The development of alcohol consumption was not found to differ significantly between the experimental and control groups . The students ' perceptions of the negative effects of use of alcohol did not increase . The lack of effect of the counselling programme might be related to the low significance initially attributed by the students to alcohol as a health issue . A shift of emphasis in the schools , from normative education , to discussion s of the immediate threats of serious injuries might alter this perception This r and omized controlled trial evaluated the efficacy of a brief intervention design ed to reduce the harmful consequences of heavy drinking among high-risk college students . Students screened for risk while in their senior year of high school ( 188 women and 160 men ) were r and omly assigned to receive an individualized motivational brief intervention in their freshman year of college or to a no-treatment control condition . A normative group selected from the entire screening pool provided a natural history comparison . Follow-up assessment s over a 2-year period showed significant reductions in both drinking rates and harmful consequences , favoring students receiving the intervention . Although high-risk students continued to experience more alcohol problems than the natural history comparison group over the 2-year period , most showed a decline in problems over time , suggesting a developmental maturational effect OBJECTIVE To evaluate the long-term efficacy of a school-based approach to drug abuse prevention . DESIGN R and omized trial involving 56 public schools that received the prevention program with annual provider training workshops and ongoing consultation , the prevention program with videotaped training and no consultation , or " treatment as usual " ( ie , controls ) . Follow-up data were collected 6 years after baseline using school , telephone , and mailed surveys . PARTICIPANTS A total of 3597 predominantly white , 12th- grade students who represented 60.41 % of the initial seventh- grade sample . INTERVENTION Consisted of 15 classes in seventh grade , 10 booster sessions in eighth grade , and five booster sessions in ninth grade , and taught general " life skills " and skills for resisting social influences to use drugs . MEASURES Six tobacco , alcohol , and marijuana use self-report scales were recorded to create nine dichotomous drug use outcome variables and eight polydrug use variables . RESULTS Significant reductions in both drug and polydrug use were found for the two groups that received the prevention program relative to controls . The strongest effects were produced for individuals who received a reasonably complete version of the intervention -- there were up to 44 % fewer drug users and 66 % fewer polydrug ( tobacco , alcohol , and marijuana ) users . CONCLUSIONS Drug abuse prevention programs conducted during junior high school can produce meaningful and durable reductions in tobacco , alcohol , and marijuana use if they ( 1 ) teach a combination of social resistance skills and general life skills , ( 2 ) are properly implemented , and ( 3 ) include at least 2 years of booster sessions This study developed and tested skills- and community-based approaches to prevent substance abuse among Native American youth . After completing pretest measurements , 1,396 third- through fifth- grade Native American students from 27 elementary schools in five states were divided r and omly by school into two intervention arms and one control arm . Following intervention delivery , youths in all arms completed posttest measurements and three annual follow-up measurements . Youths in schools assigned to the intervention arms learned cognitive and behavioral skills for substance abuse prevention . One intervention arm additionally engaged local community residents in efforts to prevent substance use among Native American youth . Outcome assessment batteries measured youths ' reported use of smoked and smokeless tobacco , alcohol , and marijuana . Over the course of the 3.5-year study , increased rates of tobacco , alcohol , and marijuana use were reported by youths across the three arms of the study . Though cigarette use was unaffected by intervention , follow up rates of smokeless tobacco , alcohol , and marijuana use were lower for youths who received skills intervention than for youths in the control arm . Community intervention components appeared to exert no added beneficial influence on youths ' substance use , beyond the impact of skills intervention components alone . Finally , gender differences were apparent across substances , measurements , and study arms , with girls smoking more cigarettes and boys using more smokeless tobacco , alcohol , and marijuana This study assessed the impact of school-based social competence training on skills , social adjustment , and self-reported substance use of 282 sixth and seventh grade rs . Training emphasized broad-based competence promotion in conjunction with domain-specific application to substance abuse prevention . The 20-session program comprised six units : stress management , self-esteem , problem solving , substances and health information , assertiveness , and social networks . Findings indicated positive training effects on Ss ' skills in h and ling interpersonal problems and coping with anxiety . Teacher ratings revealed improvements in Ss ' constructive conflict resolution with peers , impulse control , and popularity . Self-report ratings indicated gains in problem-solving efficacy . Results suggest some preventive impact on self-reported substance use intentions and excessive alcohol use . In general , the program was found to be beneficial for both inner-city and suburban students OBJECTIVE Systematic evaluation of theoretically and empirically based family programs to prevent adolescent alcohol use/misuse is limited . Data presented here are from a longitudinal study evaluating a home-based universal adolescent alcohol use prevention program . The intervention was design ed to enhance protective factors and minimize risk factors identified as influencing adolescent alcohol use . METHOD A r and omized pretest/posttest repeated measures design was used . Adolescents ( N = 428 ; 54 % females , 86 % European American ) and their parents were recruited from three Midwestern school districts . Families were r and omly assigned to either a three-session family intervention or a no-intervention control condition . Pretest data collection and the intervention occurred when the adolescents were in fourth grade , and a booster intervention was given in seventh grade . Posttest data collection was completed each year for 4 years in the classroom for adolescents . RESULTS The intervention was associated with a reduction in alcohol use ( F = 5.16 , 4/421 df , p < .001 ) and misuse ( F = 3.08 , 4/421 df , p < .05 ) for those adolescents in the intervention condition who were not using alcohol prior to the initiation of the program , but not for those who were using alcohol before initiation of the program . CONCLUSIONS The results support the possible effectiveness of the family intervention as a universal prevention program for decreasing initiation of alcohol use and subsequent misuse for the majority of adolescents who do not report prior drinking . However , additional intervention approaches appear necessary for adolescents who have already used alcohol This study reports on the impact of a “ drink driving education program ” taught to grade ten high school students . The program which involves twelve lessons uses strategies based on the Ajzen and Madden theory of planned behavior . Students were trained to use alternatives to drink driving and passenger behaviors . One thous and seven hundred and seventy-four students who had been taught the program in r and omly assigned control and intervention schools were followed up three years later . There had been a major reduction in drink driving behaviors in both intervention and control students . In addition to this cohort change there was a trend toward reduced drink driving in the intervention group and a significant reduction in passenger behavior in this group . Readiness to use alternatives suggested that the major impact of the program was on students who were experimenting with the behavior at the time the program was taught . The program seems to have optimized concurrent social attitude and behavior change The effectiveness of a 20 session cognitive-behavioral approach to substance abuse prevention was tested on seventh grade students ( n = 1,311 ) from 10 suburban New York junior high schools . The prevention strategy attempted to reduce intrapersonal pressure to smoke , drink excessively , or use marijuana by fostering the development of general life skills as well as teaching students tactics for resisting direct interpersonal pressure to use these substances . Additionally , this study was design ed to compare the relative effectiveness of this type of prevention program when implemented by either older peer leaders or regular classroom teachers . Results indicated that the prevention program had a significant impact on cigarette smoking , excessive drinking , and marijuana use when implemented by peer leaders . Furthermore , significant changes were also evident with respect to selected cognitive , attitudinal , and personality predisposing variables in a direction consistent with non-substance use . These results provide further support for the efficacy of a broad-spectrum smoking prevention strategy and tentative support for its applicability to the prevention of other forms of substance abuse This paper describes the third and final evaluation of drug education conducted by the Napa Project . In the present course students were taught decision-making skills , personal goal setting , a motivational model , peer and media influences on behavior , assertiveness training , and information on the consequences of , and alternatives to , alcohol , cigarette , and marijuana use . The evaluation employed an experimental design in which seventh grade classes in two schools were matched and then r and omly assigned to experimental and control conditions . Pre- , post- , and follow-up tests covered drug knowledge ; drug attitudes ; perceived benefits and costs of substance use ; perceived peer attitudes toward , and use of , substances ; and intentions to use , current use and lifetime use of various substances . The posttest and follow-up data were analyzed using hierarchical analyses of covariance controlling for corresponding pretest scores . The course was found to have had no significant effect on girls and only a few effects at follow-up for boys Alcohol is the most frequently used psycho-active substance during adolescence . Adolescents who misuse or overindulge in alcohol are at risk for serious social and psychological consequences . Several preventive approaches can help adolescents deal with peer pressure that contributes to alcohol use experimentation and escalation . One promising approach involves teaching adolescents skills to refuse offers of alcohol and other drugs . Few studies , however , have examined how this approach works ; that is , the connection between the prevention effort , refusal skills , and drinking behavior . This paper investigates the relationships among the intervention , refusal skills , and alcohol misuse in the Alcohol Misuse Prevention Study , a r and omized , pre/post experimental study . Based on data from sixth through tenth grade rs ( average N per grade = approximately 400 ) , regression analyses indicate that refusal skills are significant mediators of the effect of the intervention on alcohol misuse This study examined the effects of a brief , pilot alcohol prevention intervention for 211 disadvantaged 6th grade school children at posttest and 1-year follow-up . Process data indicated that the intervention was successfully implemented and well received by youth and parent/guardian participants . ANCOVA analyses indicated a significant difference on alcohol use frequency for drinking subjects at 1-month posttest , with less frequent use reported by intervention subjects than subjects receiving the minimal control material s , F(1,22 ) = 5.37 , p = .03 . No differences were found between intervention and control subjects on alcohol use measures at 1-year follow-up . Critical issues to be resolved related to the success of future prevention research and practice are discussed This study examined the long-term substance use outcomes of 2 brief interventions design ed for general population families of young adolescents . Thirty-three public schools were r and omly assigned to 3 conditions : the 5-session Preparing for the Drug Free Years Program , the 7-session Iowa Strengthening Families Program , and a minimal contact control condition . The pretest involved 667 6th grade rs and their families . Assessment s included multiple measures of initiation and current use of alcohol , tobacco , and marijuana . Pretest data were collected in the 6th grade and the reported follow-up data were collected in the 10th grade . Significant intervention-control differences in initiation and current use were found for both interventions . It is concluded that brief family skills-training interventions design ed for general population s have the potential to reduce adolescent substance use and thus have important public health implication An alternatives-oriented , school-based drug abuse prevention program , Positive Alternatives for Youth ( PAY ) , was evaluated over a 2-year period . Using a r and om-assignment , pretest-posttest control group design , 135 PAY students and 106 control group students were assessed on several attitudinal and behavioral measures of drug use . During the first year significant differences were detected between PAY and control students . Fewer differences were found in the second year , although a special analysis showed evidence of impact on PAY students rated as more involved in program activities . Reasons for specific results are discussed and implication s are drawn for the alternatives approach and the field of drug abuse prevention Two drug abuse prevention curricula were tested to determine their efficacy in preventing the onset of tobacco , alcohol , and marijuana use among adolescents . The first program focused on prevention through social pressure resistance training . The second featured affective education approaches to prevention . Curricula were tested on seventh grade students . Subjects were pretested just prior to the program and were post-tested at 12 and 24 months . Post-test analyses indicated that the social program delivered to seventh grade subjects was effective in delaying the onset of tobacco , alcohol , and marijuana use . No preventive effect of the affective education program was observed . By the final post-test , classrooms that had received the affective program had significantly more drug use than controls OBJECTIVES Project Northl and is an efficacy trial with the goal of preventing or reducing alcohol use among young adolescents by using a multilevel , communitywide approach . METHODS Conducted in 24 school districts and adjacent communities in northeastern Minnesota since 1991 , the intervention targets the class of 1998 ( sixth- grade students in 1991 ) and has been implemented for 3 school years ( 1991 to 1994 ) . The intervention consists of social-behavioral curricula in schools , peer leadership , parental involvement/education , and communitywide task force activities . Annual surveys of the class of 1998 measure alcohol use , tobacco use , and psychosocial factors . RESULTS At the end of 3 years , students in the intervention school districts report less onset and prevalence of alcohol use than students in the reference districts . The differences were particularly notable among those who were nonusers at baseline . CONCLUSIONS The results of Project Northl and suggest that multilevel , targeted prevention programs for young adolescents are effective in reducing alcohol use This study evaluated the use of a brief motivational interview ( MI ) to reduce alcohol-related consequences and use among adolescents treated in an emergency room ( ER ) following an alcohol-related event . Patients aged 18 to 19 years ( N = 94 ) were r and omly assigned to receive either MI or st and ard care ( SC ) . Assessment and intervention were conducted in the ER during or after the patient 's treatment . Follow-up assessment s showed that patients who received the MI had a significantly lower incidence of drinking and driving , traffic violations , alcohol-related injuries , and alcohol-related problems than patients who received SC . Both conditions showed reduced alcohol consumption . The harm-reduction focus of the MI was evident in that MI reduced negative outcomes related to drinking , beyond what was produced by the precipitating event plus SC alone BACKGROUND Two strategies for preventing the onset of alcohol abuse , and marijuana and cigarette use were tested in junior high schools in Los Angeles and Orange Counties , California . The first strategy taught skills to refuse substance use offers . The second strategy corrected erroneous normative perceptions about prevalence and acceptability of use among peers and established conservative groups norms regarding use . METHODS Four experimental conditions were created by r and omly assigning schools to receive ( a ) neither of the experimental curricula ( placebo comparison ) , ( b ) resistance skill training alone , ( c ) normative education alone , or ( d ) both resistance skill training and normative education . Students were pretested prior to the program and post-tested 1 year following delivery of the program . RESULTS There were main effects of normative education for summary measures of alcohol ( P = 0.0011 ) , marijuana ( P = 0.0096 ) , and cigarette smoking ( P = 0.0311 ) . All individual dichotomous measures of alcohol , marijuana , and tobacco use indicated significant reductions in onset attributable to normative education . There were no significant main effects of resistance skill training . CONCLUSION These results suggest that establishing conservative norms is an effective strategy for preventing substance use This study examined the effects of brief nurse consultations in preventing alcohol use among inner-city youth . Participants included 138 sixth-eighth grade students attending an inner-city public school in Jacksonville , Florida . Subjects were r and omly assigned by computer to either the intervention ( STARS program ) or a control group . Baseline and three-month post-tests were conducted at the target school site . A significant difference was found on heavy alcohol use with intervention subjects showing a reduction and control subjects an increase in heavy drinking ( t = -2.33 , 120df , p = .02 ) . No differences were found between groups on other alcohol use measures . This study 's findings indicate that a series of brief nurse consultations appear to reduce heavy alcohol consumption among urban school youth Two versions of a school-based alcohol prevention programme for 7th grade students were evaluated against a non-treated comparison condition . Both programme versions were based on a social-cognitive theory approach to alcohol prevention , and differed in the level of role-specifications for participating teachers and peer leaders . Twelve schools with 955 students in Bergen , Norway , participated in the study . Four schools were r and omly assigned to each of the three conditions , and the programme was implemented during 10 class periods over 2 months in Spring , 1992 . Pre- and post-test surveys were conducted , assessing alcohol use , as well as cognitive variables related to alcohol use in a specific context ( intentions , attitudes , norms and self-efficacy expectations ) . Results showed that the highly role-specified ( HRS ) version had a higher degree of student involvement than the less role-specified ( LRS ) version , indicating that the HRS programme was more successful in engaging students in alcohol prevention activities . A significant difference in programme effectiveness was found , as measured by an overall programme effect across all dependent variables . This effect was explained by significantly more positive outcomes in the HRS version compared to both the LRS and the non-treated conditions , while the LRS version did not differ significantly from the non-treated condition BACKGROUND The effectiveness of social skills training/social network restructuring in the primary and secondary prevention of drug use was examined in a multiethnic cohort of 296 female adolescents ages 14 to 19 years who were pregnant or parenting and /or at risk for drug use . METHODS Subjects were r and omly assigned to one of two conditions : ( a ) PALS Skills Training or ( b ) a control intervention involving no skills training . PALS Skills Training is a combination of cognitive and behavioral techniques to improve social skills and to restructure the teens ' social network . All students also participated in a 16-week normative education " Facts of Life " course . RESULTS The prevalence of alcohol and any drug use increased significantly over the three assessment periods in the PALS Skills group but not in the No Skills group . Teens in the PALS Skills group who reported no drug use at baseline were 2.9 times as likely to be using marijuana than teens in the No Skills group at 3 months postintervention . PALS Skills Training was no more effective in the secondary prevention of drug use than the control intervention . CONCLUSIONS Social skills training was found to be ineffective as a means of primary prevention among non-drug-using high-risk adolescents and may even be counterproductive as a means of primary prevention of marijuana use in this population . When combined with normative information on drug use prevalence , acceptability , and hazards , social skills training is no more effective as a means of secondary prevention than normative education alone |
604 | 15,660,187 | Conclusion : Despite controversies regarding PBI after breast-conserving surgery , results of phase I – II trials suggest that sole tumor bed irradiation might be an appropriate therapeutic alternative for selected breast cancer patients . | Background : The st and ard technique of postoperative radiotherapy after breast-conserving surgery is percutaneous irradiation of the entire breast to a total dose of 45–50 Gy which is usually followed by a tumor bed boost .
Since the majority of local recurrencesin selected patients occur close to the former tumor bed , the question arises whether a sole tumor bed irradiation might be a therapeutic alternative to total breast irradiation .
Hintergrund : Der derzeitige St and ard der postoperativen Strahlentherapie des Mammakarzinoms ist die homogene Bestrahlung der Brust bis zu einer Gesamtdosis von 45–50 Gy mit einer Boostbestrahlung des Tumorbetts .
Nachdem jedoch der Großteil der Lokalrezidive bei selektierten Patientinnen i m Bereich der ehemaligen Tumorhöhle auftritt , wird diskutiert , ob die alleinige Bestrahlung des Tumorbetts die Beh and lung der gesamten Restbrust ersetzen kann . | Background and Purpose : The purpose of this sequential intervention study was to determine the rate of local recurrences and the rate of distant metastases in patients with invasive breast cancer who had been treated with breast-conserving surgery and postoperative radiation therapy to the whole breast either with postoperative electron boost in group 1 or with intraoperative electron boost ( IORT ) in group 2 . Patients and Methods : After breast-conserving surgery , 378 women with invasive breast cancer of tumor sizes T1 and T2 received 51–56.1 Gy of postoperative radiation therapy to the whole breast in 1.7-Gy fractions . 188 of those patients additionally received a postoperative electron boost of 12 Gy in group 1 from January 1996 to October 1998 . Consecutively , from October 1998 to March 2001 , 190 patients received intraoperative electron-boost radiotherapy of 9 Gy to the tumor bed in group 2 . The groups were comparable with regard to age , menopausal status , tumor size , grading , and nodal status . All statistical tests were twosided . Results : During a median follow-up period of 55.3 months in group 1 and 25.8 months in group 2 , local recurrences were observed in eight of 188 patients ( 4.3 % ) in group 1 , and no local recurrence was seen in group 2 ( p = 0.082 ) . Distant metastases occurred in 15 of the 188 patients ( 7.9 % ) in group 1 and in two of the 190 patients ( 1.1 % ) in group 2 ( p = 0.09 ) . The 4-year actuarial rates of local recurrence were 4.3 % ( 95 % confidence interval , 1.8–8.2 % ) and 0.0 % ( 95 % confidence interval , 0.0–1.9 % ) and the 4-year actuarial rates of distant metastases were 7.9 % ( 95 % confidence interval , 4.5–12.8 % ) and 1.1 % ( 95 % confidence interval , 0.1–3.8 % ) . Conclusion : Immediate IORT boost yielded excellent local control figures in this prospect i ve investigation and appears to be superior to conventional postoperative boost in a short-term follow-up . Hintergrund und Ziel : Ziel dieser sequentiellen Interventions studie war die Bestimmung der Lokalrezidiv- und Fernmetastasenrate von Patientinnen mit invasivem Mammakarzinom , die mit brusterhaltender Operation und anschließender Bestrahlung der gesamten Brust , aber verschiedenen Boostbestrahlungen therapiert worden waren . Gruppe 1 erhielt eine postoperative Boostbestrahlung und Gruppe 2 eine intraoperative Radiotherapie ( IORT ) in Boostmodalität . Patienten und Method ik : Nach brusterhaltender Operation erhielten 378 Patientinnen mit invasivem Mammakarzinom mit T1- und T2-Tumoren eine postoperative Bestrahlung der gesamten Brust von 51–56.1 Gy in 1.7-Gy-Fraktionen . Von Januar 1996 bis Oktober 1998 bekamen 188 Patientinnen in Gruppe 1 postoperativ zusätzlich eine Elektronenboostbestrahlung von 12 Gy . Von Oktober 1998 bis März 2001 erhielten 190 Patientinnen in Gruppe 2 eine intraoperative Elektronenboostbestrahlung von 9 Gy direkt auf das Tumorbett . Beide Gruppen waren bezüglich Alter , Menopausenstatus , Tumorgröße , Grading und Nodalstatus vergleichbar . Die statistische Analyse erfolgte zweiseitig . Ergebnisse : Nach einer mittleren Nachbeobachtungszeit von 55,3 Monaten in Gruppe 1 und 25,8 Monaten in Gruppe 2 traten bei acht der 188 Patientinnen in Gruppe 1 ( 4,3 % ) Lokalrezidive auf , während es in Gruppe 2 zu keinem Lokalrezidiv kam ( p = 0.082 ) . Fernmetastasen ereigneten sich bei 15 der 188 Patientinnen ( 7,9 % ) in Gruppe 1 und zwei der 190 Patientinnen ( 1,1 % ) in Gruppe 2 ( p = 0.09 ) . Die 4-Jahres-Raten für Lokalrezidive betrugen 4,3 % ( 95%-Konfidenzintervall 1,8–8,2 % ) und 0 % ( 95%- Konfidenzintervall 0–1,9 % ) und die 4-Jahres-Raten für Fernmetastasen 7,9 % ( 95%-Konfidenzintervall 4.5–12,8 % ) und 1,1 % ( 95%-Konfidenzintervall 0,1–3,8%).Schlussfolgerung : Die intraoperative Boostbestrahlung zeigt exzellente Ergebnisse bezüglich der Lokalrezidivrate und scheint der postoperativen Boostbestrahlung in der Kurzzeitnachbeobachtung überlegen zu sein The aim of this trial was to study the value of adding post-operative radiotherapy to lumpectomy in a subgroup of breast cancer patients with favourable patient- , tumour- , and treatment-related prognostic features . 152 women aged over 40 with unifocal breast cancer seen in preoperative mammography were r and omly assigned to lumpectomy alone ( no-XRT group ) or to lumpectomy followed by radiotherapy to the ipsilateral breast ( 50 Gy given within 5 weeks , XRT group ) . All cancers were required to be invasive node-negative , smaller than 2 cm in diameter and well or moderately differentiated , to contain no extensive intraductal component , to be progesterone receptor-positive , DNA diploid , have S-phase fraction ≤7 and be excised with at least 1 cm margin . During a mean follow-up time of 6.7 years , 13 ( 18.1 % ) cancers recurred locally in the no-XRT and 6 ( 7.5 % ) in the XRT group ( P=0.03 ) . There was no difference between the groups in the ultimate breast preservation rate ( 95.0 % vs. 94.4 % in XRT and no-XRT , respectively , P=0.88 ) , distant metastasis-free survival ( P=0.36 ) , or 5-year cancer-specific survival ( 97.1 % in XRT and 98.6 in no-XRT ) . Radiation therapy given after lumpectomy reduces the frequency of ipsilateral breast recurrences even in women with small breast cancer with several favourable clinical and biological features . However , the breast preservation rate may not increase due to more frequent use of salvage mastectomies in patients treated with postoperative radiotherapy . © 2001 Cancer Research Campaign PURPOSE To evaluate perioperative morbidity , toxicity , and cosmetic outcome in patients treated with interstitial brachytherapy to the tumor bed as the sole irradiation modality after breast-conserving surgery . PATIENTS AND METHODS From November 1 , 2000 to January 31 , 2004 , 176 women with early-stage breast cancer became partakers in a protocol of tumor bed irradiation alone using pulsed-dose-rate ( PDR ) or high-dose-rate ( HDR ) interstitial multicatheter implants . Patients became eligible , if their tumor was an infiltrating carcinoma < or = 3 cm in diameter , the surgical margins were clear by at least 2 mm , the axilla was surgically staged node-negative , the tumor was estrogen and /or progesterone receptor-positive , well or moderately differentiated ( G1/2 ) , the tumor did not contain an extensive intraductal component ( EIC ) and the patient 's age was > 35 years . Implants were positioned using a template guide , delivering either 49.8 Gy in 83 consecutive hours ( PDR ) or 32.0 Gy in two daily fractions over 4 days ( HDR ) . Perioperative morbidity , toxicity , and cosmetic outcome were assessed . Interim findings of the first 69 patients , who were treated in this multicenter trial , after a median follow-up of 24 months ( range , 15 - 39 months ) are presented . RESULTS One of the 69 patients ( 1.4 % ) developed a bacterial infection of the implant . No other perioperative complications , for example bleeding or hematoma , were observed . Acute toxicity was low : 2.9 % of the patients ( 2/69 ) experienced mild radiodermatitis . Late toxicity : hypersensation/mild pain 7.2 % ( 5/69 ) , intermittent but tolerable pain 1.4 % ( 1/69 ) , mild dyspigmentation 10.1 % ( 7/69 ) , mild fibrosis 11.6 % ( 8/69 ) , moderate fibrosis 1.4 % ( 1/69 ) , mild telangiectasia ( < 1 cm(2 ) ) 11.6 % ( 8/69 ) , and moderate teleangiectasia ( 1 - 4 cm(2 ) ) 1.4 % ( 1/69 ) . Good to excellent cosmetic results were observed in 92.4 % of the patients evaluated . All patients ( n = 176 ) remained disease-free to the date of evaluation . CONCLUSION This analysis indicates that accelerated partial breast irradiation with iridium-192 interstitial multicatheter PDR/HDR implants is feasible with low perioperative morbidity , low acute and mild late toxicity , and does not significantly affect cosmetic results at a median follow-up of 24 months AIM We believe that conservative treatment of early breast cancer may not require radiotherapy that encompasses the whole breast in all patients . We have developed a novel therapeutic approach that allows targeted intraoperative radiotherapy ( Targit ) to be safely and accurately delivered in a st and ard operating theatre . We are currently recruiting for a r and omized trial testing whether Targit can replace the whole 6 weeks of post-operative radiotherapy after breast conserving surgery . METHODS This paper describes the operative technique . It employs a miniature electron-beam-driven X-ray source called INTRABEAM ( PeC ) that emits soft X-rays ( 50 kV ) from within the breast . The X-rays are emitted from the tip of a 10 cm x 3.2 mm diameter probe , that is enclosed in a spherical applicator ( available in 2.5 - 5 cm diameter sizes ) , which in turn is inserted in the tumour bed and intraoperative radiotherapy is delivered in about 25 min . The prescribed dose is 5 and 20 Gy at 1 cm and 0.2 cm respectively , from the tumour bed . RESULTS The biologically effective dose is 7 - 53 Gy for alpha/beta=10 and 20 - 120 Gy for alpha/beta=1.5 . The quick attenuation of the radiation reduces the damage to normal tissues and allows radiotherapy to be delivered in a st and ard operating theatre . Tungsten impregnated rubber sheets , cut to size , are placed on the chest wall to protect the heart/lungs and over the wound to stop stray radiation . The skin dose is monitored with thermoluminescent detectors ( TLDs ) . After wide local excision of the tumour and good haemostasis , a spherical applicator is inserted in the tumour bed and the target breast tissues are wrapped around it with a purse-string suture . Thus , true conformation of the target around the applicator source is achieved in real time . CONCLUSION As a tumour bed boost , this technique has the potential to reduce local recurrence by avoiding geographical misses and achieving excellent dosimetry . In patients with low risk of local recurrence , it has the potential to replace the full 6 weeks of post-operative radiotherapy with considerable implication s to patients and hospitals BACKGROUND In women 70 years of age or older who have early breast cancer , it is unclear whether lumpectomy plus tamoxifen is as effective as lumpectomy followed by tamoxifen plus radiation therapy . METHODS Between July 1994 and February 1999 , we r and omly assigned 636 women who were 70 years of age or older and who had clinical stage I ( T1N0M0 according to the tumor-node-metastasis classification ) , estrogen-receptor-positive breast carcinoma treated by lumpectomy to receive tamoxifen plus radiation therapy ( 317 women ) or tamoxifen alone ( 319 women ) . Primary end points were the time to local or regional recurrence , the frequency of mastectomy for recurrence , breast-cancer-specific survival , the time to distant metastasis , and overall survival . RESULTS The only significant difference between the two groups was in the rate of local or regional recurrence at five years ( 1 percent in the group given tamoxifen plus irradiation and 4 percent in the group given tamoxifen alone , P<0.001 ) . There were no significant differences between the two groups with regard to the rates of mastectomy for local recurrence , distant metastases , or five-year rates of overall survival ( 87 percent in the group given tamoxifen plus irradiation and 86 percent in the tamoxifen group , P=0.94 ) . Assessment by physicians and patients of cosmetic results and adverse events uniformly rated tamoxifen plus irradiation inferior to tamoxifen alone . CONCLUSIONS Lumpectomy plus adjuvant therapy with tamoxifen alone is a realistic choice for the treatment of women 70 years of age or older who have early , estrogen-receptor-positive breast cancer PURPOSE Recent r and omized trials have suggested that improved local-regional control after radiation therapy significantly increases survival for breast cancer patients with positive axillary nodes treated with adjuvant systemic therapy ( 1 , 2 ) . It has been our policy to use a third radiation field only in patients with 4 or more positive nodes . The purpose of this study was to assess whether there are any clinical or pathologic factors associated with an increased risk of regional nodal failure ( RNF ) in patients with 0 - 3 positive nodes treated with tangential radiotherapy ( RT ) alone with or without systemic therapy . METHODS AND MATERIAL S We retrospectively analyzed the incidence of RNF for 691 patients with clinical Stage I or II invasive breast cancer treated with complete gross excision of the primary tumor and tangential RT alone between 1978 - 87 ; 12 % also received systemic therapy . All had 0 - 3 positive nodes on axillary dissection that had histologic examination of > or = 6 nodes , and all had potential 8-year follow-up . The median number of axillary nodes removed was 11 ( range 6 - 36 ) . RNF was defined as any recurrence in ipsilateral axillary , internal mammary , supraclavicular , or infraclavicular nodes in the absence of recurrence in the breast , with or without simultaneous distant metastasis . Crude rates for first sites of failure within the first 8 years after treatment were calculated . A polychotomous logistic regression was used to identify factors prognostic for RNF and other sites of first failure . RESULTS Within 8 years , RNF was the first site of failure for 27 patients for a crude 8-year rate of 3.9 % . Isolated axillary failure occurred in 8 patients ( 1.2 % ) . Isolated supraclavicular and /or infraclavicular failure occurred in 5 ( 1.3 % ) and 3 ( 0.4 % ) patients , respectively . Isolated internal mammary node failure occurred in 2 patients ( 0.3 % ) . A polychotomous logistic regression model of first site of failure ( local failure , regional nodal , distant/ opposite breast , dead without recurrence , no evidence of disease ) within 8 years found age < 50 years , moderate or marked necrosis , size greater than 1 cm , and presence of an extensive intraductal component ( EIC ) to be significantly correlated with site of first failure , but only the last two were associated with a significantly larger relative risk of RNF versus being no evidence of disease at 8 years . The incidence of RNF was 0.7 % for patients with tumors < or = 1 cm compared to 5.7 % among patients with larger tumors . Among patients with EIC-positive tumors the incidence of RNF was 7.6 % compared to 3.1 % among those whose tumors were EIC-negative . CONCLUSIONS Although the incidence of RNF has been shown to be somewhat higher in patients with tumors measuring greater than 1 cm and those with an EIC , RNF is uncommon among all subsets of patients with negative or 1 - 3 positive lymph nodes treated with conservative surgery , axillary dissection , and only tangential RT fields . Therefore , giving only tangential RT ( without a separate nodal field ) appears generally acceptable for patients with 0 - 3 positive nodes PURPOSE To study the long-term effectiveness of postoperative radiotherapy after sector resection for breast cancer in a r and omized trial in which mammography is a major pathway to diagnosis . PATIENTS AND METHODS Three hundred eighty-one women with a unifocal breast cancer < or = 20 mm in diameter on the preoperative mammogram and without histopathologic signs of axillary metastases were treated by sector resection plus axillary dissection . Of these patients , 184 women were r and omized to receive postoperative radiotherapy to the breast ( XRT group ) , and 197 women received no further treatment ( non-XRT group ) . RESULTS The local recurrence rate was 8.5 % ( 95 % confidence interval [ CI ] , 3.9 % to 13.1 % ) in the XRT group and 24.0 % ( 95 % CI , 17.6 % to 30.4 % ) in the non-XRT group ( P = .0001 ) . Survival free from regional and distant recurrence was 83 . 3 % in the XRT group ( 95 % CI , 77.5 % to 89.1 % ) and 80.0 % in the non-XRT group ( 95 % CI , 73.9 % to 86.1 % ) ( P = .23 ) . Overall survival was 77.5 % in the XRT group ( 95 % CI , 70.9 % to 84.1 % ) and 78 % in the non-XRT group ( 95 % CI , 71.7 % to 84.3 % ) ( P = .99 ) . A subgroup analysis suggested that women older than 55 years of age without comedo or lobular carcinomas had a low risk of local recurrence of 6.1 % ( 95 % CI , 0.1 % to 9.1 % ) in the XRT-group and 11.0 % ( 4.0 % to 18.0 % ) in the non-XRT group ( P = .16 ) . CONCLUSION Sector resection plus radiotherapy result ed in an absolute reduction in local recurrence of 16 % at 10 years compared with surgery alone . Women older than 55 years of age without comedo or lobular carcinomas may have a low risk of local recurrence . Postoperative radiotherapy was not shown to reduce distant recurrences or improve overall survival BACKGROUND AND METHODS Conservative surgery and radiotherapy have become well-established treatments for breast cancer , and many trials in progress are attempting to define the most acceptable type of procedure . Between 1987 and 1989 we r and omly assigned 567 women with small breast cancers ( < 2.5 cm in diameter ) to quadrantectomy followed by radiotherapy or to quadrantectomy without radiotherapy . All patients underwent total axillary dissection . The median follow-up period was 39 months ( range , 28 to 54 ) . RESULTS The incidence of local recurrence was 8.8 percent among the patients treated with quadrantectomy without radiotherapy , as compared with 0.3 percent among those treated with postsurgical radiotherapy ( P = 0.001 ) . However , there was a substantial effect of age : patients more than 55 years old who did not receive radiotherapy had a low rate of local recurrence ( 3.8 percent ) . The four-year overall survival was similar in the two treatment groups . CONCLUSIONS Administering radiotherapy after quadrantectomy reduces the risk of local recurrence in women with small cancers of the breast , but radiotherapy may not be necessary in elderly women We evaluated the tolerance of a single dose of 800 - 1500 cGy , delivered with an electron beam from an IOERT-dedicated linear accelerator to the tumour bed in patients with breast cancer undergoing conservative treatment , instead of the traditional boost . We enrolled 27 patients ( cT1 - 2 , cN0 ) . The first 6 received a dose of 800 cGy , 6 1000 cGy , 10 1200 cGy and 5 1500 cGy . External beam radiation therapy ( EBRT ) with a conventional schedule , 4000 cGy total dose , was performed after wound healing . The median gap between IOERT and EBRT was 8 weeks . Three patients with adverse prognostic factors undergoing chemotherapy , including doxorubicin or taxanes , received EBRT after completion of chemotherapy . One patient with a prosthesis implant had yielding of the surgical scar 8 months after IOERT ( after 4 cycles of doxorubicin and 4 cycles of CMF complicated by frequent mastitis ) . Another patient with a large serum collection in the axilla manifested delayed scar formation . In the others no significant increase in healing time or surgery-related morbidity was observed . Another 4 patients developed mastitis . The cosmetic outcome was good in 26/27 patients . This treatment is well tolerated at all IOERT doses delivered . In the follow-up , to date , there have been no local relapses PURPOSE To evaluate the value of interstitial brachytherapy ( iBT ) alone in the treatment of low-risk breast cancer patients with regard to local control , side effects , and cosmesis . METHODS AND MATERIAL S From November 2000 to January 2004 , 176 patients with low-risk breast cancer were treated with iBT only . Patients were eligible for entering the study if : the tumor size was <3 cm ; resection margins were clear by at least 2 mm ; there were no lymph node metastases or only one micrometastasis ( pNo , pNmi ) ; age was > 35 years ; steroid hormone receptor was positive ; and histologic grade was 1 or 2 . Seventy-five percent of patients received pulsed-dose-rate brachytherapy ( D(ref ) = 50 Gy ) ; 25 % of patients received high-dose-rate brachytherapy ( D(ref ) = 32.0 Gy ) . An interim analysis is presented for all patients after an interim follow-up of 12 months , and for half the patient population with an interim follow-up of 21 months . RESULTS All patients remained disease-free on the date of analysis . A perioperative complication breast infection was recorded for 1/176 ( 0.6 % ) patients . Late toxicity i.e. , hypersensation , hyperpigmentation , fibrosis , or teleangiectasia was observed in 1 - 12 % of all patients . Grade I Fibrosis was registered in 7.6 % ( 13/172 ) and grade II in 7.0 % ( 12/172 ) of evaluable patients . Similarly , grade I teleangiectasia was observed in 4.7 % ( 8/172 ) , grade II in 0.6 % ( 1/172 ) , and grade III also in 0.6 % ( 1/172 ) of evaluable patients . Excellent or good cosmetic results have been observed in 92 - 95 % of patients . CONCLUSIONS Brachytherapy as monotherapy in low-risk breast cancer patients after breast-conserving surgery is an effective , precise treatment modality without perioperative morbidity , low acute , mild late toxicity , and yields good to excellent cosmetic results Breast cancer multifocality was studied in mastectomy specimens by correlated specimen radiography and histologic techniques . The patients chosen for study were comparable to those eligible for breast‐conserving surgical therapy . Two study groups , one with 282 invasive cancers ( T1‐2 ) and the other with 32 intraductal cancers , were selected from a group of 399 consecutive cases by omitting patients who were clearly , or very probably , not c and i date s for breast‐conserving surgical therapy according to current trial criteria . Omitted patients included those with clinical ly and /or radiologically multifocal cancers and patients with tumor extension into the chest wall or skin ( 7 % ) . Also excluded were the socalled diffuse invasive cancers ( 8 % ) , the clinical ly and radiologically occult tumors ( 3 % ) , and the invasive cancers larger than 5 cm ( 3 % ) . Of the 282 invasive cancers , 105 ( 37 % ) showed no tumor foci in the mastectomy specimen around the reference mass . In 56 ( 20 % ) tumor foci were present within 2 cm , and in 121 ( 43 % ) tumor was found more than 2 cm from the reference tumor . In 75 ( 27 % ) the tumor foci beyond 2 cm were histologically noninvasive cancers , and in 46 cases ( 16 % ) they contained invasive cancers as well . A comparison between the group with reference tumors less than 2 cm and the group with reference tumors more than 2 cm in size showed no significant difference between the groups in terms of presence or absence of tumor foci or distance of tumor foci from the reference tumor . If the 264 invasive cancers in this series that were 4 cm or less in diameter had been removed with a margin of 3 to 4 cm , 7 % to 9 % of the patients would have had invasive cancer left in the remaining breast tissue , and 4 % to 9 % would have had foci of noninvasive cancer left in the remaining breast tissue . On the basis of the data on the distribution of tumor at different distances from the reference tumor , the current study estimates the expected rates of local recurrences after breast‐conserving surgical procedures relative to the extensiveness of the excision . The possible impact of postoperative local radiation therapy on the rates of expected local recurrence is discussed Background and Aims : To evaluate the effect of electron and high-dose-rate brachytherapy ( HDR BT ) boost on local tumor control ( LTC ) , side effects and cosmesis after breast-conserving surgery ( BCS ) in a prospect i ve r and omized study . Patients and Methods : 207 women with stage I – II breast cancer who underwent BCS were treated by 50 Gy irradiation to the whole breast and then r and omly assigned to receive either a boost to the tumor bed ( n = 104 ) or no further radiotherapy ( n = 103 ) . Boost treatments consisted of either 16 Gy electron irradiation ( n = 52 ) or 12–14,25 Gy HDR BT ( n = 52 ) . Breast cancer-related events , side effects , and cosmetic results were assessed . Results : At a median follow-up of 5.3 years , the crude rate of local recurrences was 6.7 % ( 7/104 ) with and 15.5 % ( 16/103 ) without boost . The 5-year probability of LTC , relapse-free survival ( RFS ) , and cancer-specific survival ( CSS ) was 92.7 % vs. 84.9 % ( p = 0.049 ) , 76.6 % vs. 66.2 % ( p = 0.044 ) , and 90.4 % vs. 82.1 % ( p = 0.053 ) , respectively . There was no significant difference in LTC between patients treated with electron or HDR BT boost ( 94.2 % vs. 91.4 % ; p = 0.74 ) . On multivariate analysis , patient age < 40 years ( RR : 4.53 ) , positive margin status ( RR : 4.17 ) , and high mitotic activity index ( RR : 3.60 ) were found to be significant risk factors for local recurrence . The incidence of grade 2–3 side effects was higher in the boost arm ( 17.3 % vs. 7.8 % ; p = 0.03 ) . However , the rate of excellent/good cosmetic results was similar for the two arms ( 85.6 % vs 91.3 % ; p = 0.14 ) . Cosmesis was rated as excellent/good in 88.5 % of patients treated with HDR BT and 82.7 % of patients with electron boost ( p = 0.29 ) . Conclusions : Boost dose significantly improves LTC and RFS in patients treated with BCS and radiotherapy . In spite of the higher incidence of late side effects in the boost arm , boost dose is strongly recommended for patients at high risk for local recurrence . Positive or close margin status , high mitotic activity index , and young patient age should be viewed as absolute indications for tumor bed boost . LTC and cosmesis are excellent and similar to patients boosted with either HDR BT or electrons . Hintergrund und Ziel : In einer prospektiv r and omisierten Studie werden die Effekte eines Elektronenboosts und eines High-Dose-Rate-Brachytherapie-(HDR-BT-)Boosts bezüglich lokaler Tumorkontrolle ( LTC ) , Nebenwirkungen und kosmetischer Ergebnisse nach brusterhaltender Operation ( BCS ) evaluiert . Patienten und Method ik : 207 Patientinnen mit Brustkarzinomen i m Stadium I – II wurden einer BCS zugeführt . Postoperativ erfolgte eine perkutane Radiatio der gesamten Brust bis 50 Gy . Daran schloss sich willkürlich entweder eine Boostbestrahlung des Tumorbetts ( n = 104 ) oder keine weitere Radiatio ( n = 103 ) an . Die Boostbestrahlung erfolgte perkutan mit 16 Gy Elektronen ( n = 52 ) oder in Form einer HDR-BT mit 12–14,25 By ( n = 52 ) . Untersucht wurden LTC , Nebenwirkungen und kosmetische Ergebnisse . Ergebnisse : Die mediane Nachbeobachtungszeit betrug 5,3 Jahre . Die Lokalrezidivrate lag mit Boostbestrahlung bei 6,7 % ( 7/104 ) , ohne Boost bei 15,5 % ( 16/103 ) . Die 5-Jahres-Überlebensrate für LTC , für die rezidivfreie Überlebenszeit ( RFS ) und für die krebsspezifische Überlebenszeit ( CSS ) betrugen 92,7 % vs. 84,9 % ( p = 0,049 ) , 76,6 % vs. 66,2 % ( p = 0,044 ) und 90,4 % vs. 82,1 % ( p = 0,053 ) . Bezüglich der LTC best and kein signifikanter Unterschied zwischen Patienten , die mit einem Elektronen- oder HDR-BT-Boost beh and elt wurden ( 94,2 % vs. 91,4 $ ; p = 0,74 ) . Die multivariate Analyse zeigte , dass Faktoren wie Patientenalter > 40 Jahre ( RR : 4,53 ) , positive Resektionsränder ( RR : 4,17 ) und ein hoher Mitoseaktivitätsindex ( RR : 3.60 ) das Risiko eines lokalen Rezidivs signifikant erhöhen . Die Inzidenz von Nebenwirkungen Grad 2–3 war i m Boost-Arm höher ( 17,3 % vs. 7,8 % ; p = 0,03 ) . Allerdings waren die sehr guten kosmetischen Ergebnisse in beiden Armen gleich ( 85,6 % bs . 91,3 % , p = 0,14 ) . Sehr gute kosmetische Ergebnisse wurden bei 88,5 % der Patientinnen mit HDR-BT-Boost und 82,7 % der Patientinnen mit Elektronenboost erreicht ( p = 0,29 ) . Schlussfolgerungen : Die Boost-Dosis verbessert signifikant LTC und RFS bei Patientinnen , die einer BCS und anschließender Radiatio zugeführt wurden . Obwohl eine höhere Inzidenz an Spätnebenwirkungen i m Boost-Arm gefunden wurde , wird eine Boost-Dosis für Patientinnen mit hohem Risiko für die Entwicklung eines Lokalrezidivs empfohlen . Unserer Meinung nach ist bei Faktoren wie positive Schnittränder , schmaler Sicherheitssaum , hoher Mitoseaktivitätsindex und niedriges Patientenalter , die absolute Indikation zur Boost-Bestrahlung des Tumorbetts gegeben . LTC und die kosmetischen Ergebnisse sind sehr gut und unterscheiden sich nicht in Bezug auf Elektronenboost oder HDR-BT-Boost BACKGROUND Several phase III trials have demonstrated equivalent long-term survival between breast conserving surgery plus radiation therapy and mastectomy in patients with early-stage breast cancer but have not provided information on the optimal volume of breast tissue requiring post-lumpectomy radiation therapy . Therefore , we examined the 5-year results of a single institution 's experience with radiation therapy limited to the region of the tumor bed ( i.e. , limited-field radiation therapy ) in selected patients treated with breast-conserving therapy and compared them with results of matched breast-conserving therapy patients who underwent whole-breast radiation therapy . METHODS A total of 199 patients with early-stage breast cancer were treated prospect ively with breast-conserving therapy and limited-field radiation therapy using interstitial brachytherapy . To compare potential differences in local recurrence rates based on the volume of breast tissue irradiated , patients in the limited-field radiation therapy group were matched with 199 patients treated with whole-breast radiation therapy . Match criteria included tumor size , lymph-node status , patient age , margins of excision , estrogen receptor status , and use of adjuvant tamoxifen therapy . Local-regional control and disease-free and overall survival were analyzed using the Kaplan-Meier method , and the statistical significance of differences between treatment groups was calculated using the log-rank test . All statistical tests were two-sided . RESULTS Median follow-up for surviving patients was 65 months ( range = 12 - 115 months ) . Five ipsilateral breast failures ( i.e. , recurrences ) were observed in patients treated with limited-field radiation therapy . The cumulative incidence of local recurrence was 1 % ( 95 % confidence interval [ CI ] = 0 % to 2.8 % ) . On matched-pair analysis , the rate of local recurrence was not statistically significantly different between the patient groups ( 1 % [ 95 % CI = 0 % to 2.4 % ] for the whole-breast radiation therapy patients versus 1 % [ 95 % CI = 0 % to 2.8 % ] for the limited-field radiation therapy patients ; P = .65 ) . CONCLUSIONS Limited-field radiation therapy administered to the region of the tumor bed has comparable 5-year local control rates to whole-breast radiation therapy in selected patients PURPOSE To investigate the incidence of and variables associated with clinical ly evident fat necrosis in women treated on a protocol of high-dose-rate ( HDR ) brachytherapy alone without external-beam whole-breast irradiation for early-stage breast carcinoma . METHODS AND MATERIAL S From 6/1997 until 8/1999 , 30 women diagnosed with Stage I or II breast carcinoma underwent surgical excision and postoperative irradiation via HDR brachytherapy implant as part of a multi-institutional clinical Phase I/II protocol . Patients eligible included those with T1 , T2 , N0 , N1 ( < or = 3 nodes positive ) , M0 tumors of nonlobular histology with negative surgical margins , no extracapsular lymph-node extension , and a negative postexcision mammogram . Brachytherapy catheters were placed at the initial excision , re-excision , or at the time of axillary sampling . Direct visualization , surgical clips , ultrasound , or CT scans assisted in delineating the target volume defined as the excision cavity plus 2-cm margin . High activity (192)Ir ( 3 - 10 Ci ) was used to deliver 340 cGy per fraction , 2 fractions per day , for 5 consecutive days to a total dose of 34 Gy to the target volume . Source position and dwell times were calculated using st and ard volume optimization techniques . Dosimetric analyses were performed with three-dimensional postimplant dose and volume reconstructions . The median follow-up of all patients was 24 months ( range , 12 - 36 months ) . RESULTS Eight patients ( crude incidence of 27 % ) developed clinical ly evident fat necrosis postimplant in the treated breast . Fat necrosis was determined by clinical presentation including pain and swelling in the treated volume , computed tomography , and /or biopsy . All symptomatic patients ( 7 of 8 cases ) were successfully treated with 3 to 12 months of conservative management . Continuous variables that were found to be associated significantly with fat necrosis included the number of source dwell positions ( p = 0.04 ) , and the volume of tissue which received fractional doses of 340 cGy , 510 cGy , and 680 cGy ( p = 0.03 , p = 0.01 , and p = 0.01 , respectively ) . Other continuous variables including patient age , total excised tissue volume , tumor size , number of catheters , number of days the catheters were in place , planar separation , dose homogeneity index ( DHI ) , and uniformity index ( UI ) were not significant . Discrete variables including the presence/absence of DCIS , sentinel versus full axillary nodal assessment , receptor status , presence/absence of diabetes , and the use of chemotherapy or hormone therapy were not found to have a significant association with the risk of fat necrosis . CONCLUSIONS In this study of HDR brachytherapy of the breast tumor excision cavity plus margin , treatment was planned and delivered in accordance with the dosimetric parameters of the protocol result ing in a high degree of target volume dose homogeneity . Nonetheless , at a median follow-up of 24 months , a high rate of clinical ly definable fat necrosis occurred . The overall implant volume as reflected in the number of source dwell positions and the volume of breast tissue receiving fractional doses of 340 , 510 , and 680 cGy were significantly associated with fat necrosis . Future dosimetric optimization algorithms for HDR breast brachytherapy will need to include these factors to minimize the risk of fat necrosis BACKGROUND In 1976 , we initiated a r and omized trial to determine whether lumpectomy with or without radiation therapy was as effective as total mastectomy for the treatment of invasive breast cancer . METHODS A total of 1851 women for whom follow-up data were available and nodal status was known underwent r and omly assigned treatment consisting of total mastectomy , lumpectomy alone , or lumpectomy and breast irradiation . Kaplan-Meier and cumulative-incidence estimates of the outcome were obtained . RESULTS The cumulative incidence of recurrent tumor in the ipsilateral breast was 14.3 percent in the women who underwent lumpectomy and breast irradiation , as compared with 39.2 percent in the women who underwent lumpectomy without irradiation ( P<0.001 ) . No significant differences were observed among the three groups of women with respect to disease-free survival , distant-disease-free survival , or overall survival . The hazard ratio for death among the women who underwent lumpectomy alone , as compared with those who underwent total mastectomy , was 1.05 ( 95 percent confidence interval , 0.90 to 1.23 ; P=0.51 ) . The hazard ratio for death among the women who underwent lumpectomy followed by breast irradiation , as compared with those who underwent total mastectomy , was 0.97 ( 95 percent confidence interval , 0.83 to 1.14 ; P=0.74 ) . Among the lumpectomy-treated women whose surgical specimens had tumor-free margins , the hazard ratio for death among the women who underwent postoperative breast irradiation , as compared with those who did not , was 0.91 ( 95 percent confidence interval , 0.77 to 1.06 ; P=0.23 ) . Radiation therapy was associated with a marginally significant decrease in deaths due to breast cancer . This decrease was partially offset by an increase in deaths from other causes . CONCLUSIONS Lumpectomy followed by breast irradiation continues to be appropriate therapy for women with breast cancer , provided that the margins of resected specimens are free of tumor and an acceptable cosmetic result can be obtained PURPOSE To investigate magnetic resonance imaging ( MRI ) features of radiation-induced plexopathy ( RIP ) and radiation-induced fibrosis frequently associated with RIP . PATIENTS AND METHODS Seven patients with late radiation sequelae in the supraclavicular region were examined with MRI after a median interval of 7 years ( range , 5 - 18 years ) following radiotherapy and 4 - 7 years after the onset of RIP . Four patients had RIP plus severe soft-tissue fibrosis , two RIP without soft-tissue fibrosis ( n = 2/6 ) , and one patient fibrosis without RIP . Patients underwent surgery of breast cancer ( n = 6 ) or chest wall relapse ( n = 1 ) and radiotherapy to the supraclavicular fossa with cobalt with an anterior portal in fractions of 1.7 - 2.6 Gy to 43 - 51.6 Gy in 3 cm depth . All patients were relapse-free at the time of MRI . Fibrosis and RIP were scored clinical ly ( RTOG classification ) . Fibrosis of the supraclavicular and /or axillary region was marked in three and mild in two patients . RIP was mild , marked and severe in two patients each . MRI was performed with a 1.5-T unit including coronal STIR , coronal and transversal T2-weighted , transversal T1-weighted and fat-saturated post-contrast ( gadolinium-DTPA ) spin echo sequences . RESULTS The brachial plexus appeared normal in all patients , but subtle changes of adjoining tissue ( slight , linear signal intensity in T2-weighted images or contrast enhancement surrounding the plexus ) were detected in patients with RIP ( n = 4/6 ) and the patient without RIP ( n = 1 ) . However , alterations of the soft tissue ( marked signal intensity in T2-weighted sequences ) correlated well with the clinical degree of fibrosis and were restricted to areas of marked to severe fibrosis ( n = 3/3 ) . CONCLUSION Reliable MRI signs of RIP could not be identified . The severity of fibrosis closely corresponded to MRI features . The role of MRI in the diagnostic work-up of RIP is , therefore , the exclusion of tumor relapse Local recurrences after breast conserving surgery occur mostly in the quadrant harbouring the primary carcinoma . The main objective of postoperative radiotherapy should be the sterilisation of residual cancer cells in the operative area , while irradiation of the whole breast may be avoided . We have developed a new technique of intra-operative radiotherapy ( IORT ) of a breast quadrant after the removal of the primary carcinoma . A mobile linear accelerator ( linac ) with a robotic arm is utilised delivering electron beams able to produce energies from 3 to 9 MeV. Through a perspex applicator , the radiation is delivered directly to the mammary gl and and to spare the skin from the radiation , the skin margins are stretched out of the radiation field . To protect the thoracic wall , an aluminium-lead disc is placed between the gl and and the pectoralis muscle . Different dose levels were tested from 10 to 21 Gy without important side-effects . We estimated that a single fraction of 21 Gy is equivalent to 60 Gy delivered in 30 fractions at 2 Gy/fraction . Seventeen patients received a dose of IORT of 10 to 15 Gy as an anticipated boost to external radiotherapy , while 86 patients received a dose of 17 - 19 - 21 Gy intra-operatively as their whole treatment . The follow-up time of the 101 patients varied from 1 to 17 months ( mean follow-up time was 8 months ) . The IORT treatment was very well accepted by all of our patients , either due to the rapidity of the radiation course in cases where IORT was given as the whole treatment or to the shortening of the subsequent external radiotherapy in cases where IORT was given as an anticipated boost . We believe that single dose IORT after breast resection for small mammary carcinomas may be an excellent alternative to the traditional postoperative radiotherapy . However , a longer follow-up is needed for a better evaluation of the possible late side-effects In a prospect i ve r and omized clinical trial conducted by the European Organization for Research and Treatment of Cancer ( EORTC ) , mastectomy was compared with breast-conserving therapy in 903 stage I and stage II breast cancer patients entering the study between 1980 and 1986 . The main participating centers were : Guy 's Hospital , London ; The Netherl and s Cancer Institute , Amsterdam ; University Hospital , Leuven ; Radiotherapy Institute , Rotterdam ; Breast Unit , Tijgerberg , S.A. The data were collected in the EORTC Data Center , Brussels . Treatment in the study arm consisted of lumpectomy , axillary clearance , and radiotherapy to the breast ( 50 Gy external irradiation in 5 weeks followed by boost with iridium implant of 25 Gy ) . Important in this study is the large number of TNM stage II patients ( 755 ) . Most patients were stage II because of the size of the tumor ( 2 - 5 cm ) . The patient and tumor characteristics in the study and control groups were well balanced . So far the survival curves and local recurrence rates are not statistically different for the two study arms . Tumor size was found in univariate analysis to be a significant risk factor for local recurrence in the breast-conserving therapy group but not in the mastectomy group . Results of salvage treatment for local recurrence were not better for the breast-conserving therapy group compared with the mastectomy group . Measurements of quality of life and cosmesis show a clear benefit for the breast-conserving therapy group To study the role of radiotherapy and tamoxifen after breast-conserving surgery ( BCS ) in patients with a favourable prognosis , a clinical trial was initiated by the German Breast Cancer Study Group . Between 1991 and 1998 , 361 patients ( pT1pN0M0 , aged 45 - 75 years , receptor positive , grade I-II ) were r and omised to radiotherapy ( yes/no ) and tamoxifen for 2 years ( yes/no ) in a 2x2 factorial design ; the exclusion of seven centres ( 14 patients ) left 347 patients in the analysis . After a median follow-up of 5.9 years , 77 events concerning event-free survival have been observed . Since a strong interactive effect between radiotherapy and tamoxifen has been established , the results are presented in terms of the treatment effects for all four treatment groups separately . Mainly due to the presence of local recurrences , the event rate was about three times higher in the group with BCS only than in the other three groups . No difference could be established between the four treatment groups for distant disease-free survival rates . It is concluded that even in patients with a favourable prognosis , the avoidance of radiotherapy and tamoxifen after BCS increases the rate of local recurrences substantially PURPOSE To define the role of a 10-Gy boost to the primary tumor in the conservative treatment of early infiltrating breast carcinoma treated by limited surgery and radiotherapy . PATIENTS AND METHODS Between 1986 and 1992 , 1,024 women with early breast carcinoma ( < or = 3 cm in diameter ) were treated by local excision , axillary dissection , and conventional 50-Gy irradiation given in 20 fractions over 5 weeks and then r and omly assigned to receive either no further treatment or a boost of 10 Gy by electrons to the tumor bed . The median follow-up time was 3.3 years as of September 1994 . The occurrence of telangiectasia was reported , and the patients were asked to evaluate the cosmetic result . RESULTS At 5 years , 10 patients of 521 who had received the boost ( Kaplan-Meier estimate of local relapse rate , 3.6 % ) and 20 of 503 who had received no further treatment ( Kaplan-Meier estimate of local relapse rate , 4.5 % ) had developed a local recurrence ( P = .044 ) . After adjustment for the main prognostic variables , the relative risk was still significantly lower for the boost group ( 0.3 ; range , 0.12 to 0.95 ) . The boost group had a higher rate of grade 1 and 2 telangiectasia ( 12.4 % v 5.9 % ) , but no difference was seen between the two treatment arms in the self- assessment score for the cosmetic result . CONCLUSION Delivery of a boost of 10 Gy to the tumor bed after 50 Gy to the whole breast following limited surgery significantly reduces the risk of early local recurrence , with no serious deterioration in the cosmetic result . Additional follow-up evaluation will be required to assess the long-term results In this report , the results of the first controlled clinical trial on breast cancer in Germany , begun in 1983 , are presented after a median follow-up of 8 years . Four-year results have been previously published . In pT1 N0 M0 breast cancer , mastectomy as the st and ard treatment was to be compared with tumorectomy plus radiotherapy to the remaining breast tissue . The study design , originally planned as a comprehensive cohort study including r and omised and non-r and omised patients , had to be changed into a prospect i ve observation study due to the low r and omisation rate . 1036 out of 1119 recruited patients were evaluable . After a median follow-up of 97 months , 237 events ( local recurrence , regional recurrence , distant metastases , contralateral breast cancer or death of the patient without previous recurrence ) occurred . With the exception of death without recurrence , the events were evenly distributed among the two treatment groups . The 8-year local recurrence rate of the whole patient population is 8.8 % . Out of all prognostic factors examined , only tumour size and grade had a significant influence on recurrent disease . Event-free survival decreased in cases with ' uncertain ' tumour margins , whereas the width of the margin has no influence on disease recurrence . Based on 151 deaths observed so far , there was no significant difference in overall survival between the two treatment groups . The 8-year results of this study are in accordance with the 4-year results reported previously and with those of other breast-conserving treatment trials . There was no significant difference between the two treatment groups with regard to event-free and overall survival . Incomplete tumorectomy had a negative influence on recurrence Before 1989 , credible information about the treatment of breast cancer was derived mainly from r and omized clinical trials that enrolled women with either metastatic ( stage IV ) ; locally advanced ( stage III ) ; or primary , operable , axillary lymph node-positive ( stage II ) disease . This report provides information from six recent National Surgical Adjuvant Breast and Bowel Project ( NSABP ) trials involving lymph node-negative ( stage I ) patients . Findings from NSABP B-13 demonstrated , through 14 years of follow-up , improvements in disease-free survival ( DFS ) and overall survival from methotrexate and fluorouracil ( MF ) , regardless of age , in women with estrogen receptor (ER)-negative tumors . Results from NSABP B-19 , which was conducted with similar patients , demonstrated , through 8 years , a greater overall DFS and survival advantage with cyclophosphamide and MF ( CMF ) than that observed with MF . Findings from NSABP B-23 , in which patients similar to those in B-13 and B-19 were r and omly assigned to receive CMF plus placebo , CMF plus tamoxifen ( TAM ) , doxorubicin ( Adriamycin ) and cyclophosphamide ( AC ) plus placebo , or AC plus TAM , demonstrated no difference in relapse-free survival ( RFS ) or overall survival among the four groups through 5 years , either for all patients or relative to age . NSABP B-14 , which was carried out in women with ER-positive tumors , compared the outcomes of those who received either placebo or TAM . Through 14 years , superior DFS and overall survival advantages , as well as a reduction in contralateral breast cancer , were observed with TAM . No additional benefit result ed from TAM administration beyond 5 years . Findings from NSABP B-20 , a second study conducted in patients with ER-positive tumors , showed , after 8 years , both a DFS and an overall survival advantage from TAM plus either MF or CMF over that achieved with TAM alone . A recent meta- analysis in women with negative lymph nodes and either ER-negative or ER-positive tumors of less than or equal to 1 cm in size was conducted using patients from five NSABP trials . After 8 years , the RFS in women with ER-negative tumors was greater in the group treated with surgery and chemotherapy than in those who underwent surgery alone . In women with ER-positive tumors , RFS and overall survival advantages were observed from the addition of chemotherapy to TAM when that treatment regimen was compared with TAM alone . In addition , evidence has been presented from NSABP B-21 , a trial evaluating radiation therapy ( XRT ) and /or TAM for the prevention of ipsilateral breast tumor recurrence ( IBTR ) after lumpectomy in women with tumors less than or equal to 1 cm . Findings have shown that XRT is superior to TAM and that XRT + TAM is superior to XRT alone for preventing IBTR . The findings demonstrate that chemotherapy and /or hormonal therapy is effective for the management of women with negative axillary lymph nodes and either ER-negative or ER-positive tumors . Because it also has been proven effective in women with tumors less than or equal to 1 cm , such therapy might also be considered in the treatment of that patient population INTRODUCTION We believe that conservative treatment of early breast cancer may not require radiotherapy that encompasses the whole breast . We present here the clinico-pathological basis for this view , as well as a novel therapeutic approach that allows intra-operative radiotherapy to be safely and accurately delivered to the target tissues in a st and ard operating theatre . THE RATIONALE : Whole-organ analysis of mastectomy specimens reveals that 80 % of occult cancer foci are situated remote from the index quadrant . In contrast , over 90 % of local recurrences after breast conservative therapy occur near the original tumour , even when radiotherapy is not given . Therefore , the remote occult cancer foci may be clinical ly irrelevant and radiotherapy to the index quadrant alone might be sufficient . A NOVEL TECHNIQUE : The Photon Radiosurgery System ( PRS ) is an ingenious portable electron-beam driven device that can typically deliver intra-operative doses of 5 - 20 Gy , respectively , to 1 cm and 0.2 cm from the tumour bed over about 22 min . The pliable breast tissue -- the target -- wraps around the source , providing perfect conformal radiotherapy . Being soft X-rays , the dose attenuates rapidly ( alpha approximately 1/r3 ) , reducing distant damage . RESULTS In our pilot study of 25 patients ( age 30 - 80 years , T = 0.42 - 4.0 cm ) , we replaced the routine post-operative tumour bed boost with targeted intra-operative radiotherapy . There have been no major complications and no patient has developed local recurrence , although the median follow-up time is short , at 24 months . CONCLUSION It is safe and feasible to deliver targeted intraoperative radiotherapy ( Targit ) for early breast cancer . We have begun a r and omised trial -- the first of its kind -- comparing Targit with conventional six-week course of radiotherapy . If proven equivalent in terms of local recurrence and cosmesis , it could eliminate the need for the usual six-week course of post-operative radiotherapy BACKGROUND Although the conservation management of breast cancer has become a routine method of treatment in most centers , there is still considerable controversy surrounding the ultimate minimum treatment required for node-negative breast cancer to achieve adequate local control . PURPOSE Our purpose was to assess the value of breast irradiation in reducing breast relapse following conservation surgery for node-negative breast cancer . We attempted to define low-risk groups of women for breast and distant site relapse ( i.e. , recurrence outside the breast ) who might be spared breast irradiation or adjuvant systemic therapy . METHODS Eight hundred thirty-seven patients were r and omly assigned to receive radiation therapy or no radiation therapy following lumpectomy and axillary dissection for node-negative breast cancer . RESULTS Breast irradiation reduced relapse in the breast from 25.7 % in the controls to 5.5 % in the irradiated patients . There was no difference in survival between the two groups ( median follow-up , 43 months ) . A low-risk group ( less than 5 % chance of relapse in the breast without irradiation ) could not be defined . Tumor size ( greater than 2 cm ) , age ( less than 40 years ) , and poor nuclear grade were important predictors for breast relapse . Age ( less than 50 years ) and poor nuclear grade were important predictors for mortality . The presence of ductal carcinoma in situ did not predict breast relapse . CONCLUSIONS Breast irradiation significantly reduces breast relapse , but it does not influence survival . Important predictors of breast relapse are age , tumor size , and nuclear grade , but not the presence of ductal carcinoma in situ . Age and , in particular , nuclear grade predict survival . IMPLICATION S Further follow-up may define an acceptable low-risk group for breast relapse . Until then , we recommend that all patients receive breast irradiation . Systemic adjuvant therapy should be considered for patients with poor nuclear grade tumors BACKGROUND We hypothesized that wide-field brachytherapy ( BRT ) after margin negative excision would result in complication rates , local recurrence rates , and cosmesis scores equivalent to external beam radiotherapy ( ERT ) . METHODS Patients with T(is,1,2 ) tumors less than or equal to 4 cm , 0 to 3 positive axillary nodes , and negative inked surgical margins were entered prospect ively into BRT phase I/II trial . Patients who met the eligibility criteria for BRT but were treated with ERT during the same time period were retrospectively identified as controls . A blinded panel of healthcare professionals grade d cosmetic outcome . RESULTS Fifty patients with 51 breast cancers received BRT from January 1992 to October 1993 . We identified 94 patients eligible for BRT but concurrently treated with ERT . At a median follow-up of 75 months , the two groups were similar for grade III treatment toxicities , local/regional recurrence rates , and cosmesis scores . CONCLUSIONS For selected breast cancer patients undergoing breast-conserving therapy , BRT is an attractive alternative to ERT Prognostic factors predicting for breast recurrence following breast conserving surgery and radiotherapy have been identified in a prospect i ve r and omised trial comparing two different radiotherapy techniques . The first used megavoltage radiation to encompass the whole breast and regional nodes ( WF group ) . The second used an electron field directed to the tumour bed only ( LF group ) . With a median follow up of 8 years survival in both groups was the same ( 72 % ) . There was an increased rate of breast recurrence in the LF group : 25 % , compared to the WF group : 13 % ( P = 0.00008 ) , expressed in actuarial terms at 8 years . In a multivariate analysis of factors predicting for breast recurrence , once the difference in treatment technique is allowed for , only two factors were found to be significant : histological grade ( P = 0.013 ) and lymphovascular invasion in the histological specimen ( P = 0.037 ) PURPOSE To analyze factors involved in the development of fibrosis in the boost area after breast conservation therapy ( BCT ) in patients treated with continuous low dose rate iridium implants following 50 Gy whole breast irradiation . METHODS AND MATERIAL S Fibrosis was estimated by palpation in 404 patients by four physicians . The median follow-up ( FUP ) duration was 70 months ( range 30 - 133 months ) . Original implant data were used for reconstruction and dose-volume calculations . The total dose of the external whole breast irradiation and iridium implants was expressed in Normalized Total Dose ( NTD ) : the total dose given in fractions of 2 Gy , which is biologically equivalent to the actual dose given according to the linear-quadratic model , using an alpha/beta value of 2 Gy , and 1.5 h for the recovery half-life of sublethal damage repair . To identify predictors of fibrosis we used a proportional odds model in a polychotomous logistic regression analysis . RESULTS Seven independent factors were identified that were related to the severity of fibrosis : age , duration of FUP , clinical T-size , photon beam energy , NTD level , implant volume , and adjuvant chemotherapy . From the proportional odds model , a volume exponent could be estimated ( 0.16 + /- 0.04 ) that enabled us to determine dose-effect relations for different volumes . A 10-fold higher risk of fibrosis was seen when the total dose was above 79 Gy as compared with doses lower than 70 Gy . A fourfold increase in risk of fibrosis was seen for each 100 cm3 increase in irradiated boost volume . The use of adjuvant chemotherapy result ed in a twofold increase in the risk of fibrosis ( dose modifying factor approximately 1.08 ) . The application of Co-60 beams had a similar effect . The relative odds for the other factors were smaller ( 1.4 for each 10 years of older age , and 1.2 for clinical T-size over 20 mm ) . The FUP-period had a nonlinear effect : relative odds 2.2 at 6 years , 3.6 at 7 - 8 years , and 2.8 at 9 - 11 years . The dose rate ( mean 0.57 , range 0.26 - 0.89 Gy/h ) had no influence on the development of fibrosis and there was no correlation between dose rate and irradiated volume . CONCLUSIONS To optimize cosmetic results after BCT , both the total dose and the irradiated volume should be kept as low as possible . Minimum effective dose levels still have to be established . The boost volume can be minimized by more conformal brachytherapy techniques and optimal localization . It may be worthwhile to take adjuvant chemotherapy into account in decisions on boost dose levels |
605 | 23,728,651 | Primary and secondary outcome measures showed no statistically significant difference when considering neurocognitive abilities , function , neuropsychiatric symptoms and global performance .
Rivastigmine is capable of inducing side effects that lead to withdrawal in a significant proportion of patients | BACKGROUND Vascular dementia represents the second most common type of dementia after Alzheimer 's disease .
In older patients , in particular , the combination of vascular dementia and Alzheimer 's disease is common , and is referred to as mixed dementia .
The classification of vascular dementia broadly follows three clinico-pathological processes : multi-infa rct dementia , single strategic infa rct dementia and subcortical dementia .
Not all victims fulfil strict criteria for dementia and may be significantly cognitively impaired without memory loss , when the term vascular cognitive impairment ( VCI ) is more useful .
Currently , no established st and ard treatment for VCI exists .
Reductions in acetylcholine and acetyltransferase activity are common to both Alzheimer 's disease and VCI , raising the possibility that cholinesterase inhibitors - such as rivastigmine - which are beneficial in Alzheimer 's disease , may also be beneficial for VCI .
OBJECTIVES To assess the efficacy of rivastigmine compared with placebo in the treatment of people with vascular cognitive impairment ( VCI ) , vascular dementia or mixed dementia . | Subcortical vascular dementia ( VaD ) is characterized by executive dysfunction and behavioral problems , reflecting deterioration of the frontal lobe . This study aim ed to determine whether rivastigmine , a dual inhibitor of acetylcholinesterase ( AChE ) and butyrylcholinesterase ( BuChE ) , has any effects on the typical symptoms of subcortical VaD. Patients receiving rivastigmine showed a slight improvement in executive functions and in behavior . Side effects in both groups were tolerable and there were no study withdrawals . Moreover , there are no drug interactions with other therapies previously and concomitantly assumed . Improvements in domains that characterize subcortical VaD were observed , indicating that rivastigmine may have provided targeted treatment in areas of the brain that are particularly affected in this patient population BACKGROUND The majority of patients with Alzheimer 's disease ( AD ) or vascular dementia display , in addition to cognitive impairment , various degrees of behavioral disturbances . As the use of cholinesterase inhibitors for the treatment of cognitive impairment in dementia becomes widespread , many of these patients will be treated concomitantly with cholinesterase inhibitors and with anti-psychotic drugs to ameliorate behavioral disturbances . Despite the widespread use of this combination in clinical practice , the safety and tolerability of such combination therapy has not been evaluated in controlled clinical trials . This pilot study examined the effects of addition of risperidone 0.5 - 2 mg/day to patients on rivastigmine 3 - 12 mg/day , and vice versa . METHODS 65 patients suffering from AD , 10 from vascular dementia , and 15 from both were r and omized to open label rivastigmine and risperidone , alone or in combination , for 20 weeks . Adverse events caused by co-administration were assessed . RESULTS No clinical ly relevant adverse interactions were observed . CONCLUSIONS These preliminary results indicate that rivastigmine and risperidone can be safely co-administered . Confirmation of these results in large clinical trials studies is warranted Further to recent data indicating that patients with vascular dementia ( VaD ) show a cholinergic deficit , we aim ed to determine whether rivastigmine , a dual inhibitor of acetylcholinesterase ( AChE ) and butyrylcholinesterase ( BuChE ) , has any effects on the symptoms of VaD. Patients aged 65 - 80 , with a diagnosis of dementia and probable VaD , received rivastigmine 3 - 6 mg/day ( n=8 ) or cardioaspirin ( n=8 ) in an open study for 22 months . At 22 months , patients treated with rivastigmine showed significant improvements in executive function and behavioural symptoms ( both p<0.05 vs. both baseline and control group ) , which were reflected in reduced caregiver stress ( p<0.05 vs. baseline and controls ) . Baseline scores of global response , cognition , word fluency and activities of daily living were maintained in patients receiving rivastigmine , and there was no increase in benzodiazepine or neuroleptic intake . In contrast , the control group showed no improvements in any domain , and significant deterioration in global response and executive function ( both p<0.05 vs. baseline and rivastigmine group ) . Side effects in both groups were tolerable and there were no study withdrawals . Long-term rivastigmine treatment appeared to be safe and effective in this patient population . In particular , improvements in domains particularly relevant to this condition were observed . These benefits may reflect the drug 's dual inhibitory effects on the cholinergic system , and its particular activity in frontal areas of the brain . A large , double-blind study of rivastigmine in patients with VaD would be worthwhile A number of studies have suggested that cerebral changes , particularly deep white matter lesions ( WML ) visualized on magnetic resonance imaging ( MRI ) , may be involved in the genesis of late life depression . This has been confirmed in a prospect i ve study which also found a relationship between the presence of WML and poor 3-year outcome in elderly depressed subjects . Most studies find these lesions to predominate in frontal lobe and basal ganglia , supporting the hypothesis of " fronto-striatal " dysfunction in depression . To investigate whether WML are associated with mood disturbance in dementia , proton density and T2-weighted images were obtained in 80 subjects with dementia ( dementia with Lewy bodies , n = 27 ; Alzheimer 's disease , n = 28 ; vascular dementia , n = 25 ) and 26 age-matched normal controls . Periventricular lesions ( PVL ) , white matter lesions ( WML ) , and basal ganglia hyperintensities ( BG ) were visually rated blind to diagnosis using a semiquantitative scale . Frontal WML were associated with higher depression scores in patients with dementia , implying a common pathophysiology of depression irrespective of diagnosis . Further study of the neurobiological basis of WML is needed . This can best be achieved by serial clinical assessment combined with in vivo and in vitro MRI and neuropathological examination BACKGROUND Vascular risk factors play a role in the development of dementia , including Alzheimer disease ( AD ) . However , little is known about the effect of body mass index and clustering of vascular risk factors on the development of dementia . OBJECTIVE To investigate the relation between midlife body mass index and clustering of vascular risk factors and subsequent dementia and AD . DESIGN AND SETTING Participants of the Cardiovascular Risk Factors , Aging , and Dementia ( CAIDE ) study were derived from r and om , population -based sample s previously studied in a survey carried out in 1972 , 1977 , 1982 , or 1987 . After an average follow-up of 21 years , 1449 individuals ( 73 % ) aged 65 to 79 years participated in the reexamination in 1998 . MAIN OUTCOME MEASURES Dementia and AD . RESULTS Obesity at midlife ( body mass index>30 kg/m2 ) was associated with the risk of dementia and AD even after adjusting for sociodemographic variables ( odds ratio [ OR ] , 2.4 [ 95 % confidence interval ( CI ) , 1.2 - 5.1 ] ) . The association was somewhat modified by further adjusting for midlife blood pressure , total cholesterol level , and smoking ( OR , 2.1 [ 95 % CI , 1.0 - 4.6 ] ) and also for apolipoprotein E genotype and history of vascular disorders ( OR , 1.9 [ 95 % CI , 0.8 - 4.6 ] ) . Midlife obesity , high total cholesterol level , and high systolic blood pressure were all significant risk factors for dementia with ORs of around 2 for each factor , and they increased the risk additively ( OR , 6.2 for the combination ) . CONCLUSIONS Obesity at midlife is associated with an increased risk of dementia and AD later in life . Clustering of vascular risk factors increases the risk in an additive manner . The role of weight reduction for the prevention of dementia needs to be further investigated We evaluated the efficacy and safety of the central ly acting cholinesterase inhibitor , rivastigmine tartrate , for patients with mild to moderately severe Alzheimer 's disease ( AD ) with or without concurrent vascular risk factors ( VRF ) . Patients ( 45 - 90 years of age ) were r and omized to placebo ( n = 235 ) , low-dose rivastigmine ( 1 - 4 mg/day , n = 233 ) , or high-dose rivastigmine ( 6 - 12 mg/day , n = 231 ) for 26 weeks . Efficacy measures included the Alzheimer 's Disease Assessment Scale-Cognitive subscale ( ADAS-Cog ) , the Clinician 's Interview Based Impression of Change ( CIBIC-Plus ) , the Progressive Deterioration Scale ( PDS ) , the Global Deterioration Scale ( GDS ) , and the Mini-Mental State Examination ( MMSE ) . For efficacy and safety analysis , patients were categorized by baseline Modified Hachinski Ischemic Score ( MHIS ) for the determination of VRF ( MHIS > 0 : presence of VRF ; MHIS = 0 : absence of VRF ) . As early as 12 weeks , the mean change from the baseline ADAS-Cog score was significantly different for those patients treated with high-dose rivastigmine compared with placebo controls in both MHIS categories . However , the treatment difference between high-dose rivastigmine and placebo at each time-point was larger for patients with MHIS > 0 . The proportion of responders was significantly greater in the high-dose rivastigmine group for each level of improvement . No differences were noted between treatment groups regarding safety evaluations . Rivastigmine is effective in both categories of patients , and those with VRF experience greater clinical benefit ( cognition , activities of daily living , and disease severity ) Narasimhalu K , Effendy S , Sim CH , Lee JM , Chen I , Hia SB , Xue HL , Corrales MP , Chang HM , Wong MC , Chen CP , Tan EK . A r and omized controlled trial of rivastigmine in patients with cognitive impairment no dementia because of cerebrovascular disease . Acta Neurol Sc and : 2010 : 121 : 217–224 . © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard This article reports the development and psychometric properties of the Alzheimer 's Disease Cooperative Study - Clinical Global Impression of Change ( ADCS-CGIC ) . At present , a number of unvali date d CGIC scales are used in clinical trials , with various methods for making ratings . The ADCS-CGIC was design ed on the basis of a survey of ADCS clinicians and by adapting existing instruments . It includes an organized but unstructured format , with which a clinician can address clinical ly relevant change . The instrument 's reliability and validity were assessed in a prospect i ve trial of Alzheimer 's disease ( AD ) and healthy subjects over a 12-month period . It showed good short-term reliability at 1 and 2 months , with 90 and 94 % of AD subjects , respectively , rated as having changed not at all or only minimally . The ADCS-CGIC 's face validity was demonstrated by untreated . AD subjects rated as having worsened over time at both 6 months ( 56 % rated as having worsened ) and 12 months ( 81 % rated as having worsened ) , whereas only 2 % of control subjects showed minimal worsening . As a measure of predictive validity , ADCS-CGIC ratings at 12 months were significantly associated with change on four severity scales . As with other measures , change ratings were sensitive to dementia severity . Moderately impaired subjects showed greater worsening than other subjects . ADCS-CGIC ratings of greater worsening were made after the informant interview , regardless of whether informants or subjects were interviewed first . The ADCS-CGIC is a valid and reliable instrument for use in clinical trials We developed a set of informant-based items describing performance of activities of daily living ( ADL ) by patients with Alzheimer 's disease ( AD ) to identify which ADL are useful for assessment of patients in clinical trials . Evaluation of ADL is an important outcome measure in AD clinical trials . For clinical trial measurement , ADL should have broad applicability , good test-retest reliability , scaling to cover a range of performance , and sensitive to detect change in disease progression . A total of 45 ADL items developed from literature review and clinical experience were administered to informants of 242 AD patients and 64 elderly controls as part of the multicenter Alzheimer 's Disease Cooperative Study Instrument protocol . Half of the subjects were re-evaluated at 1 and 2 months and all at 6 and 12 months . Controls performed virtually all ADL items optimally at baseline and at 12 months . Among subjects with AD , 27 of the 45 ADL were widely applicable , i.e. , performed at baseline or premorbidly by > 90 % of subjects ; showed good test-retest reliability between baseline and 1 and 2 months ; correlated with MMSE scores of AD patients cross-sectionally ; and showed a decline in performance from baseline to 12 months in at least 20 % of AD patients . ADL could be identified that capture change in functional ability in patients across the entire range of the MMSE . The remaining 18 ADL included several that may be useful for trials that target specific population s , e.g. , women with AD . Because change on specific items depends on baseline MMSE , ADL evaluation should include items relevant to the severity of dementia of patients enrolled in a clinical trial Recent data indicate that patients with vascular dementia ( VaD ) show a cholinergic deficit . Having obtained good results in a previous study comparing rivastigmine , an inhibitor of acetylcholinesterase ( AChE ) and butyrylcholine-sterase ( BuChE ) , vs. aspirin , we aim ed to compare the efficacy and tolerability of rivastigmine vs. aspirin plus nimodipine . Patients with a diagnosis of dementia and probable VaD received rivastigmine 3 - 6 mg/day ( n = 32 ) or aspirin plus nimodipine ( n = 32 ) in an open study for 16 months . Patients treated with rivastigmine showed superior benefits , compared with those receiving aspirin plus nimodipine , in attention , executive function , instrumental activities of daily living , and behavioural and psychotic disturbances . Side-effects in both groups were tolerable and there were no study withdrawals . The benefits observed with rivastigmine may reflect its inhibitory effects on AChE and BuChE , and the drug 's affinity for frontal brain areas |
606 | 25,030,383 | We did not identify any r and omised trials that evaluated the effects of continuous versus intermittent bolus intragastric tube feeding on gastro-oesophageal reflux disease in preterm and low birth weight infants . | BACKGROUND Gastro-oesophageal reflux disease is a particularly common condition in preterm and low birth weight infants .
These infants are also more likely to have excessive regurgitation , as they do not have a fully developed antireflux mechanism .
Preterm and low birth weight infants who are unable to suck oral feeds are required to be fed via an intragastric tube for varying lengths of time .
Intragastric tube feeding can be delivered by the intermittent bolus or continuous feeding method .
Use of continuous or intermittent bolus intragastric feeding may have a positive or negative effect on the incidence or severity of gastro-oesophageal reflux disease .
OBJECTIVES To determine whether continuous or intermittent bolus intragastric tube feeding reduces the number of episodes and the duration of gastro-oesophageal reflux disease ( GORD ) in preterm and low birth weight infants .
We intended to perform subgroup analyses for gestational age ; birth weight ; age in days from birth at full enteral feeding via intragastric tube ( breast vs bottle ) ; frequency of intermittent bolus feed ; and type of medication for treatment of GORD ( only if medication prescribed and given similarly to both intervention groups ) . | BACKGROUND & AIMS Nasogastric feeding may result in gastro-oesophageal reflux and , therefore , increase the risk of aspiration . This may be greater when feeds are administered via a bolus than by infusion . We aim ed to measure gastric emptying time and quantify gastro-oesophageal reflux in healthy volunteers given a liquid feed via an oral bolus ( OB ) , a nasogastric tube bolus ( TB ) and a nasogastric tube drip ( TD ) . METHODS Twelve male volunteers participated in three separate studies ( OB , TB and TD ) in r and om order , each 3 days apart . The feed consisted of 220 ml Ensure Plus ( 1.5 kcal/ml ) , labelled with 12 MBq (99m)Tc DTPA . The OB and TB were given over 5 min and the infusion rate for the TD was 55 ml/h . Gastric emptying time was measured using gamma scintigraphy . Gastro-oesophageal reflux was observed continuously until the stomach was empty , using a multichannel intraluminal impedance catheter . RESULTS Mean ( 95 % CI ) T(50 ) gastric emptying times for the OB and TB studies were 41.3 ( 36.5 - 46.2 ) min and 36.2 ( 30.6 - 41.8 ) min respectively ( p=0.19 ) . The stomach emptied at a rate equal to the infusion rate in the TD studies . Median ( IQR ) number of reflux episodes for the OB , TB and TD studies were 4.5 ( 2.0 - 6.0 ) , 3.0 ( 2.0 - 4.75 ) and 2.0 ( 0.25 - 6.25 ) respectively . Median ( IQR ) total duration of reflux for the OB , TB and TD studies were 38 ( 20 - 242 ) , 49 ( 17 - 71 ) and 36 ( 1 - 125 ) s respectively ( p = NS ) . CONCLUSIONS The lack of difference in gastro-oesophageal reflux between bolus and continuous feeding indicates that in healthy volunteers both methods are equally safe with respect to the risk of aspiration BACKGROUND Nearly 90 - 95 % of children with drool have physiologic gastroesophageal reflux ( GER ) that usually resolves by 12 - 15 months of age ; however , 5 - 10 % of children with drool have pathologic GER . Of these children , most recover clinical ly by 18 months of age without therapy , yet 10 % develop chronic , recurrent gastroesophageal reflux disease ( GERD ) with sequelae . The respiratory symptoms associated with GER consist mainly of bronchial asthma and laryngospasm , but often include a persistent cough of unknown aetiology , obstructive apnoea , and an obstructive respiratory syndrome confined to the nasopharynx . Gastric acid reflux , enters the adenoids , causes oedema of the tubal orifices , and later leads to relapsing diseases of the middle ear in children . AIM AND SCOPE To evaluate the incidence of otologic manifestations in children with GER and the efficacy of treatment , comparing two different groups of children ( i.e. , treated versus untreated ) . SUBJECTS AND METHODS From January 2005 to November 2006 , audiologic screening of newborns and suckling children ( 0 - 24 months of age ) at risk for auditory illnesses was held at the University Department of Otolaryngology in Catania . Seventy-three children ( average age , 13 months ) were selected after failing acoustic otoemissions for chronic bilateral catarrhal pathology involving the middle ear ( tympanometry type B ) and were positive for at least one of the different signs of GER at the time of history-taking . The children were r and omised and subdivided into two groups : ( 1 ) a group of 40 children ( 27 females and 13 males ; average age , 12 months ) who received treatment ; and ( 2 ) a group of 29 children ( 16 males and 13 females ; average age , 14 months ) who did not receive treatment . Four children were lost to follow-up after completing the study . All children enrolled in the study underwent a rhinopharynxlaryngeal fibroscopy with flexible optics , a gastric ultrasound scan after clinical observation , and a multi-channel pH-metry for 18 - 24h . RESULTS Findings obtained by rhinopharynxlaryngeal fibroscopy showed that 82 % of cases had diffuse hyperaemia involving the entire rhinopharyngeal mucosa and 13 % of the cases had arytenoidal hyperaemia . Resolution and improvement of the reflux occurred in 52.5 and 40 % of the cases in the treated group , respectively , versus complete resolution and an improvement in symptoms of 45 and 30 % of cases , respectively , in the control group . CONCLUSIONS The hypothesis of a correlation between reflux and chronic middle otitis of the serous-mucous type was confirmed in the present study . Adopting a preventive treatment strategy may be useful in reducing the possibility of ear involvement We compared two feeding regimens , continuous intragastric feedings and intermittent oral feeding , in nine infants with protracted diarrhea and malnutrition and two infants with surgically created short bowel . Continuous nasogastric feeding caused significant increases in enteral balance of the major nutrients , whereas intermittent feedings result ed in negative or only slightly positive enteral balance . The improvements in enteral balance from intermittent to continuous feeding in infants with diarrhea were as follows : Fat from 13 + /- 0.8 to 22 + /- 2.0 gm/24 hours ; nitrogen from 0.63 + /- 0.2 to 1.7 + /- 0.2 gm/24 hours ; calcium from -63 + /- 20 to 145 + /- 4 mg/24 hours ; zinc from -0.57 + /- 0.2 to 1.3 + /- 0.2 mg/24 hours ; and copper from -0.09 + /- 0.03 to 0.21 + /- 0.02 mg/24 hours . There was also a significant increase in body weight during the continuous feeding ( 168 + /- 16 gm/72 hours ) as compared to the intermittent feeding ( -171 + /- 26 gm/72 hours ) . Similar improvements in enteral balance were seen in the two infants with short bowel . These findings document that improved enteral balance can be achieved with continuous feeding in infants with bowel disease Nutritional benefits and feeding-related complications were prospect ively compared in 53 preterm very-low-birth-weight infants receiving isoenergetic feeding by either the continuous nasogastric ( n = 30 ) or intermittent nasogastric ( n = 23 ) route . Stepwise regression techniques were used to develop models relating feeding-associated factors . Feeding method significantly affected weight gain in infants 1000 to 1249 g birth weight with continuous nasogastric feeding associated with an additional weight gain of 3.6 to 6.1 g/kg/d . No effects of feeding method on changes in occipitofrontal circumference , triceps skin-fold thickness , bilirubin values , or total protein values were demonstrable . There were few major differences between feeding groups on measures of feeding complications . Continuous nasogastric feeding was fairly well tolerated and result ed in improved weight gain when compared with intermittent nasogastric feeding in preterm infants 1000 to 1249 g birth weight OBJECTIVE To compare the effects of continuous versus intermittent feeding on gastrointestinal tolerance and growth in very low birth weight ( VLBW ) infants . STUDY DESIGN In a r and omized , controlled trial conducted at 3 neonatal units , 70 premature infants with a gestational age 24 to 29 weeks and birth weight < 1200 g were assigned to 1 of 3 feeding methods : continuous nasogastric feeding , intermittent nasogastric feeding , or intermittent orogastric feeding . Feeding was initiated within 30 hours of birth . Daily enteral and parenteral volumes , caloric and protein intakes , growth , enteral intolerance , and clinical complications were recorded . Cox regression analysis was used to determine primary outcome , the time to achieve full enteral feeding . RESULTS The continuously fed infants achieved full enteral feeding significantly faster than the intermittently fed infants ( hazard ratio [ HR ] = 1.86 ; 95 % confidence interval [ CI ] = 1.07 to 3.22 ) . In stratified analysis according to birth weight , the improvement was even more pronounced in the smallest infants , those with birth weight < or = 850 g ( adjusted HR = 4.13 ; 95 % CI = 1.48 to 11.53 ) . Growth rate was significantly faster in the continuously fed infants ( P = .002 ) . CONCLUSION In VLBW infants , continuous feeding seems to be better than intermittent feeding with regard to gastrointestinal tolerance and growth Purpose : The aim of our study was to evaluate the relationship between gastric emptying and gastroesophageal reflux ( GER ) in infants and children . Methods and Material s : One hundred eight patients ( pts ) between 3 months and 5 years of age ( 77 boys , 31 girls ) with clinical suspicion of GER disease were included in the study . Patients were divided into 2 groups according to the age range : group A , 0–2 years ( 57 pts ) , and group B , 2–5 ( 51 pts ) years . Each group was divided into 2 subgroups according to the scintigraphic study as GER-positive and -negative . Cow 's milk with Tc-99 m sulfur colloid as radiotracer was used . Gastric emptying was expressed as the half emptying time ( T1/2 ) . The detection of activity in the esophagus at any time during scintigraphy was considered an indicator of GER episodes . Reflux episodes were grade d as grade 1 if activity was detected on one or 2 frames and grade 2 if activity was detected on more than 2 frames . Results : Forty of the 108 patients ( 37 % ) had GER findings on scintigraphy . The comparison of gastric emptying time between positive GER scintigraphy and negative GER scintigraphy groups was not statistically significant in any age group . No association was found between age and rate of gastric emptying time . Although the comparison of T1/2 between grade 1 patients and the GER-negative group was not statistically significant , grade 2 patients showed significant differences and had prolonged gastric emptying times . Mild statistical correlation between the number of reflux episodes and gastric emptying half time was found . Conclusions : As a conclusion , the relation between gastroesophageal reflux and delayed gastric emptying can not be ignored . Our results support delayed gastric emptying to be a pathogenetic factor in gastroesophageal reflux in infants and children The increased survival of sick and preterm neonates may be associated with long‐term problems which must be recognised and managed if outcome is to be optimised . In a prospect i ve study of 35 neonates ( median gestational age at birth 34 weeks ) admitted to a neonatal intensive care unit over a 3‐month period , we have documented a high incidence ( 14 of 35 ) of immature or abnormal feeding patterns when infants were assessed at 36 to 40 weeks postmenstrual age . Neonates with prolonged respiratory support and delayed enteral and oral feeding were most affected . Compared with neonates who have normal initial feeding assessment s , neonates with disorganised or dysfunctional feeding were six times more likely to vomit and three times more likely to cough when offered solid food at 6 months of age . At 12 months of age significant differences were also found in tolerating lumpy food and enjoying mealtimes . We hypothesise that these feeding problems contribute to failure to thrive and psychosocial distress after discharge from the neonatal unit and propose potential neonatal measures to reduce their incidence The National Institute of Child Health and Human Development conducts and supports research on all stages of human development from preconception to adulthood in order to better underst and the health of children , youths , adults , families , and communities . Health and human development information is made easily available on the site with a simple A to Z list , along with clinical trials and health education campaign information . Links to clinical trials , news releases , publications , and related web sites are also available , as well as information on research being conducted at present and supported by the National Institute of Child Health and Human Development OBJECTIVE To assess the efficacy of omeprazole in treating irritable infants with gastroesophageal reflux and /or esophagitis . STUDY DESIGN Irritable infants ( n=30 ) 3 to 12 months of age met the entry criteria of esophageal acid exposure > 5 % ( n=22 ) and /or abnormal esophageal histology ( n=15 ) . They completed a 4-week , r and omized , double-blind , placebo-controlled crossover trial of omeprazole . Cry/fuss diary ( minutes/24 hours ) and a visual analogue scale of infant irritability as judged by parental impression were obtained at baseline and the end of each 2-week treatment period . RESULTS The reflux index fell significantly during omeprazole treatment compared with placebo ( -8.9%+/-5.6 % , -1.9%+/-2.0 % , P<.001 ) . Cry/fuss time decreased from baseline ( 267+/-119 ) , regardless of treatment sequence ( period 1 , 203+/-99 , P<.04 ; period 2 , 188+/-121 , P<.008 ) . Visual analogue score decreased from baseline to period 2 ( 6.8+/-1.6 , 4.8+/-2.9 , P=.008 ) . There was no significant difference for both outcome measures while taking either omeprazole or placebo . CONCLUSIONS Compared with placebo , omeprazole significantly reduced esophageal acid exposure but not irritability . Irritability improved with time , regardless of treatment OBJECTIVE The objective was to test the hypothesis that continuous enteral feeding impairs gallbladder emptying in infants . STUDY DESIGN A prospect i ve crossover study was performed in 15 infants : ( 1 ) bolus enteral feeds were given in phase A , ( 2 ) a continuous milk feed was given for 3 days in phase B , and ( 3 ) bolus feeds were resumed in phase C. The gallbladder was studied with ultrasonography in phase A , on days 1 and 3 of phase B , and at the start and on days 2 and 4 of phase C. RESULTS Baseline volume was 116.1 mm(3 ) ( range , 48.1 to 374.8 mm(3 ) ) in phase A and 293.3 mm(3 ) ( range , 109.4 to 1134.9 mm(3 ) ) ( P < .001 ) after 3 days of phase B ; it returned to the phase A value after 4 days of phase C. The contraction index was 65.2 % ( range , 40.6 % to 78.2 % ) in phase A and 1.7 % ( range , 0 % to 8.4 % ) ( P < .001 ) after 3 days of phase B. It returned to its phase A value immediately after bolus enteral feeds were resumed in phase C. CONCLUSIONS Continuous enteral feeding leads to an enlarged , noncontractile gallbladder in infants . Emptying is observed immediately after bolus feeds are resumed , and volume returns to baseline after 4 days . The mode of feeding has important bearings on the motility of the extrahepatic biliary tree BACKGROUND / AIMS Aspiration pneumonia is one of the most serious complications of gastrostomy tube feeding , with a reported incidence of 10%-20 % in nursing home patients . The aims of this prospect i ve study were to examine lower esophageal sphincter ( LES ) pressure before and after placement of gastrostomy tubes and to examine the effects of rapid intragastric bolus and slow , continuous feeding on LES pressure . METHODS Ten subjects were enrolled in the study . Basal LES pressure was measured before and after placement of gastrostomy tubes . Thereafter , LES pressure was measured for 15 minutes during rapid intragastric infusion of 250 mL of an enteral feeding formula and 100 mL water and continuous infusion of the enteral feeding formula at 80 mL/h . Scintigrams evaluating gastroesophageal reflux were obtained during each method of feeding . RESULTS Placement of gastrostomy tubes had no effect on basal LES pressure . Rapid intragastric bolus infusion led to a reduction in LES pressure to incompetent levels at 2.1 + /- 2.0 mm Hg ( P < 0.001 ) . Free gastroesophageal reflux to the sternal notch was shown by scintigraphy . Slow , continuous gastrostomy feedings did not alter LES pressure ( P > 0.05 ) or show free gastroesophageal reflux by scintigraphy . CONCLUSIONS Gastroesophageal reflux and aspiration in patients fed via the gastrostomy tube may be caused by LES relaxation secondary to gastric distention caused by distention of the stomach |
607 | 19,370,591 | For women who had epidural analgesia there were no differences between those r and omised to upright versus recumbent positions for any of the outcomes examined in the review .
There is evidence that walking and upright positions in the first stage of labour reduce the length of labour and do not seem to be associated with increased intervention or negative effects on mothers ' and babies ' wellbeing . | BACKGROUND It is more common for women in the developed world , and those in low-income countries giving birth in health facilities , to labour in bed .
There is no evidence that this is associated with any advantage for women or babies , although it may be more convenient for staff .
Observational studies have suggested that if women lie on their backs during labour this may have adverse effects on uterine contractions and impede progress in labour .
OBJECTIVES The purpose of the review is to assess the effects of encouraging women to assume different upright positions ( including walking , sitting , st and ing and kneeling ) versus recumbent positions ( supine , semi-recumbent and lateral ) for women in the first stage of labour on length of labour , type of delivery and other important outcomes for mothers and babies . | The purpose of this study was to determine whether women in labor report less pain when they are in a vertical ( sitting or st and ing ) position than in a horizontal ( side-lying or supine ) position . Pain scores were obtained from 60 women in early labor ( dilation 2 - 5 cm ) who alternated between the two positions . The results show that about 35 % of women feel less front pain and 50 % feel less back pain when they are in a vertical position than in a horizontal position . The decrease in continuous back pain ( 83 % ) was particularly impressive , but the front and back pains associated with contractions were significantly diminished as well . These results , taken together with those of earlier studies , indicate that many women in early labor have less pain and are generally more comfortable in a vertical than in a horizontal position . Since early labor comprises a substantial proportion of the entire process of labor and delivery , any simple procedure which alleviates pain without danger to mother or child , such as shifting from a horizontal to a vertical position , should be promoted and employed There has been a relatively recent interest in alternative birthing techniques , including increased maternal mobility during labor . This literature review was pursued to evaluate the effect of upright maternal posture and ambulation on the first stage of labor . Although previous review s frequently assume that maternal ambulation speeds labor progress , the data presented in this review are not conclusive as to whether the upright maternal posture or ambulation during the first stage of labor shortens labor length or improves fetal outcome . However , it is clear that ambulation in labor is not harmful either to the mother or fetus . In addition , many investigators have reported that mobility in labor results in greater maternal comfort and ability to tolerate labor and decreased use of anesthesia and analgesia . Thus , acceptance of mobility in labor by patients and staff is generally reported . This information can serve as a guide to clinical management . However , there is a need for further analysis of the effect of maternal ambulation during labor , and specific suggestions for research are presented The cl aim that an upright maternal posture during labour improves the efficiency of the uterus to the benefit of both mother and fetus has been investigated in a r and omised prospect i ve study . 40 patients undergoing induction of labour were allocated to a recumbent group or an upright group . No differences were found between the groups in the length of labour , mode of delivery , requirements of oxytocic and analgesic drugs , or fetal and neonatal condition . Our data do not support calls to change conventional intrapartum nursing attitudes OBJECTIVE Our purpose was to test the hypothesis that the supine versus the lateral position is associated with a greater decrement in cardiac output after epidural analgesia in labor . STUDY DESIGN Twenty-one normal term subjects were r and omized to the left lateral or supine position in early labor . Cardiac output measured by the acetylene rebreathing method , stroke volume , heart rate , mean arterial pressure , and systemic vascular resistance were obtained at 5-minute intervals , beginning before a 500 ml intravenous fluid bolus ( baseline ) and ending 45 minutes after epidural injection . RESULTS Mean baseline supine versus lateral group differences were significant for 21 % lower cardiac output , 21 % lower stroke volume , 19 % higher mean arterial pressure , 50 % higher systemic vascular resistance , and equivalent heart rate . In the supine group fluid bolus result ed in significantly increased cardiac output and stroke volume , decreased mean arterial pressure and systemic vascular resistance , and unchanged heart rate . In the supine group cardiac output and stroke volume decreased significantly after epidural injection . The lateral position group exhibited no hemodynamic alterations after fluid bolus or epidural . CONCLUSIONS In contrast to the lateral position , the supine position is associated with a significant postepidural decrement in cardiac output , not identified by a change in heart rate . This likely reflects an inability to maintain stable preload volume in the supine position Telemetry and conventional cardiotocography were compared by monitoring the labor of 60 patients with an uneventful pregnancy and delivery in the 38th-42nd week of pregnancy . 31 patients were monitored by telemetry and 29 by cardiotocography . The patients were matched for age ( + /- 5 years ) , duration of pregnancy ( + /- 7 days ) and parity ( I or II ) . The husb and attended labor and delivery in 42 % of the cases in the telemetry group and in 59 % of the cases in the control group . Induction of labor by amniotomy was performed in 32 % of the cases in the telemetry group and in 24 % of the cases in the cardiotocography group . The patients monitored subjective pain every half hour during the opening phase . The telemetric patients were encouraged to sit or walk during the first stage . No maternal or fetal complications occurred . All infants were born in good condition with APGAR scores greater than or equal to 7 recorded at one and five minutes . There were 4 operative deliveries in the telemetry group and 5 in the control group . Indications for these were maternal or uterine exhaustion with the exception of two control patients where fetal asphyxia was suspected . The duration of the first stage of labor did not differ significantly between the telemetry and the cardiotocography groups . The telemetric patients received less analgesics than the controls but this difference was not significant . In spite of less analgesia in the telemetry group , the secondparas of the telemetry group experienced significantly less ( p less than 0.01 ) labor pain than the controls . In addition , the secondparas of the telemetry group considered the present labor less painful than the previous one significantly more often than the controls . Among the primiparous patients there was no difference in the amount of pain experienced by the patients Our purpose was to study the feasibility and results of encouraging ambulation during the first stage of labor in routine obstetric practice . Six-hundred and thirty low risk mothers with intact membranes were r and omized into an ambulant and a control group . The results in the ambulant group were not better than in the control group . Our study suggests that , in principle ambulation may be beneficial , but that the concomitant changes in practice should be different from those in our study A prospect i ve study of 300 consecutive deliveries has been made to assess the benefits and acceptability of ambulation during spontaneous labour . Ambulation during the first stage occurred in 48 patients with 55 non‐ambulant patients acting as controls . No difference in the length of first or second stage , incidence of fetal distress or mode of delivery was observed . In spite of the lack of apparent advantage to the fetal condition , ambulation was acceptable to both patients and nursing staff and should not be discouraged The purpose of this study was to determine if women who assumed upright positions during the phase of maximum slope would have a shorter phase of maximum slope in their labor and experience more comfort than women who assumed recumbent positions . Forty laboring women were r and omly assigned to either an upright or recumbent position group . Subjects assumed the positions of their assigned group during the phase of maximum slope in their labor ( cervical dilatation from 4 cm to 9 cm ) . Every hour during the phase of maximum slope , each subject was examined vaginally to determine her cervical dilatation and assessed for her level of comfort using the Maternal Comfort Assessment Tool . Women in the upright position group had a significantly shorter phase of maximum slope in labor , but did not significantly differ in comfort level from women in the recumbent group . Newborn Apgar scores were not significantly different between the two groups . Nurses need to be aware that the upright labor positions have the distinct advantages of facilitating efficient uterine contractions and reducing the duration of the phase of maximum slope in labor , with no increase in the discomfort experienced or adverse effect on newborn well-being Background Ambulatory epidural analgesia ( AEA ) is a popular choice for labor analgesia because ambulation reportedly increases maternal comfort , increases the intensity of uterine contractions , avoids inferior vena cava compression , facilitates fetal head descent , and relaxes the pelvic musculature , all of which can shorten labor . However , the preponderance of evidence suggests that ambulation during labor is not associated with these benefits . The purpose of this study is to determine whether ambulation with AEA decreases labor duration from the time of epidural insertion to complete cervical dilatation . Methods In this prospect i ve , r and omized study , 160 nulliparous women with AEA were r and omly assigned to one of two groups : AEA with ambulation and AEA without ambulation . AEA blocks were initiated with 15–20 ml ropivacaine ( 0.07 % ) plus 100 & mgr;g fentanyl , followed by a continuous infusion of 0.07 % ropivacaine plus 2 & mgr;g/ml fentanyl at 15–20 ml/h . Maternal measured variables included ambulation time , time from epidural insertion to complete dilatation , stage II duration , pain Visual Analogue Scale scores , and mode of delivery . APGAR scores were recorded at 1 and 5 min . Results are expressed as mean ± SD or median and analyzed using the t test , chi-square , or the Mann – Whitney test at P ≤ 0.05 . Results The ambulatory group walked 25.0 ± 23.3 min , sat upright 40.3 ± 29.7 min , or both . Time from epidural insertion to complete dilatation was 240.9 ± 146.1 min in the ambulatory group and 211.9 ± 133.9 min in the nonambulatory group ( P = 0.206 ) . Conclusion Ambulatory epidural analgesia with walking or sitting does not shorten labor duration from the time of epidural insertion to complete cervical dilatation Background The authors recently showed that “ mobile ” epidural analgesia , using low-dose local anesthetic-opioid mixtures , reduces the impact of epidural analgesia on instrumental vaginal delivery , relative to a traditional technique . The main prespecified assessment of pain relief efficacy , women 's postpartum estimates of labor pain after epidural insertion , did not differ . The detailed analgesic efficacy and the anesthetic characteristics of the techniques are reported here . Methods A total of 1,054 nulliparous women were r and omized , in labor , to receive boluses of 10 ml 0.25 % bupivacaine ( traditional ) , combined spinal-epidural ( CSE ) analgesia , or low-dose infusion ( LDI ) , the latter groups utilizing 0.1 % bupivacaine with 2 & mgr;g/ml fentanyl . Visual analog scale pain assessment s were collected throughout labor and delivery and 24 h later . Details of the conduct of epidural analgesia , drug utilization , and requirement for anesthesiologist reattendance were recorded . Results A total of 353 women were r and omized to receive traditional epidural analgesia , 351 received CSE , and 350 received LDI . CSE was associated with a more rapid onset of analgesia , lower median visual analog scale pain scores than traditional in the first hour after epidural insertion , and a significant reduction in bupivacaine dose given during labor . Pain scores reported by women receiving LDI were similar to those in the traditional group throughout labor and delivery . Anesthesiologist reattendance was low but greater with each mobile technique . Conclusions Relative to traditional epidural analgesia , LDI is at least as effective and CSE provided better pain relief in the early stages after insertion . The proven efficacy of mobile epidurals and their beneficial impact on delivery mode make them the preferred techniques for epidural pain relief in labor Published reports imply that intrapartum ambulation may improve labor . This suggests the possible efficacy of ambulation in labors requiring augmentation , provided that adequate monitoring surveillance is maintained . Fourteen patients who failed to progress in active-phase labor , and who required augmentation for " inadequate " contractions were r and omized into ambulation ( eight ) and oxytocin ( six ) groups . Internal fetal monitoring was used in all patients for 30 minute baseline and 2 hour study periods , with two-channel telemetry used in ambulating patients . Oxytocin was administered by infusion pump . Study parameters included changes in cervical dilation and station , contraction frequency , intensity and baseline tonus , and uterine activity . Labor progress was slightly but not significantly better in the ambulatory group . A mean increase in uterine activity units ( UAU ) in the ambulatory group was immediate to ranges not reached in the oxytocin group for 2 hours . Increase in Montevideo units was slightly greater in the ambulatory group during the first hour , but was exceeded by the oxytocin group during the second hour . These initial observations seem to indicate that , in terms of labor progress and initial effects on uterine activity , ambulation is as effective as oxytocin for the enhancement of labor and warrants further investigation Ambulation during labor is becoming more popular , although its impact on the progress of labor and on pain intensity remains unclear . We wondered whether prolonged ambulation with epidural analgesia had a possible effect on duration of labor and pain . In this prospect i ve , r and omized trial , 61 parturients with uncomplicated term pregnancies were allocated to be recumbent ( n = 31 ) or to ambulate ( n = 30 ) . Epidural analgesia was provided with intermittent administrations of 0.08 % bupivacaine-epinephrine plus 1 & mgr;g/mL of sufentanil . Of the 30 women assigned to the ambulatory group , 25 actually walked . Their ambulating time was 64 ± 34 min ( mean ± sd ) , i.e. , 29 % ± 16 % of the first stage . There were no differences between the two groups in the length of labor and in pain visual analog scale scores . However , the ambulatory group received smaller doses of bupivacaine ( 6.4 ± 2.2 mg/h versus 8.4 ± 3.6 mg/h ; P = 0.01 ) and of oxytocin ( 6.0 ± 3.7 mUI/min versus 10.2 ± 8.8 mUI/min ; P < 0.05 ) . A greater ability to void was also found in the ambulatory group ( P < 0.01 ) . Although the duration of labor and pain relief was unchanged , these findings support that ambulation during labor may be advantageous OBJECTIVES Ambulatory epidural analgesia has become a common option for women in labor in France . We tested the hypothesis that a method of epidural analgesia that allowed women to walk had specific advantages regarding mode of delivery , consumption of local anesthetic , oxytocin requirement , and labor duration . METHODS Two hundred and twenty-one women with uncomplicated pregnancies who presented in spontaneous labor between 36 and 42 weeks of gestation or who were scheduled for induced labor were r and omly divided into two groups , ambulatory and non-ambulatory . All were given intermittent epidural injections of 0.1 % ropivacaine with 0.6 microg/ml sufentanil for analgesia during labor ( P<0.05 was considered significant ) . None of the women had previous cesarean delivery . RESULTS There were no significant differences between the two groups in mode of delivery , consumption of local anesthetic , or oxytocin requirement . However , a significant difference was noted in labor duration ( 173.4+/-109.9 min vs. 236.4+/-130.6 min ; P=0.001 ) . CONCLUSIONS Walking with ambulatory labor analgesia shortens labor duration but has no other effect on the progress and outcome of labor Summary . Conventional and telemetric monitoring of labour were compared in a r and omized study of 200 patients to assess the effect on the pattern of labour , outcome and attitude of the patients . All the telemetry patients had the option of mobility , but only 45 % elected to get out of bed , and then often only for short periods . No clear physical benefits accrued from voluntary mobility . Ambulant patients who had spontaneous deliveries had a longer second stage and more of their babies were slow to establish regular respiration . Quantitative subjective assessment s of pain , anxiety and comfort were made . Primigravidae with telemetric monitoring who chose to get out of bed had higher pain scores than primigravidae monitored conventionally , but anxiety scores were highest among primigravidae with telemetry who elected to stay in bed . There was a significant bias towards increased anxiety in the lower social classes . Primigravidae gained more reassurance from monitoring than did multigravidae , but there were no differences result ing from whether or not the recording apparatus was within the patient 's view . Multigravidae who had experienced both forms of monitoring preferred telemetry because they felt less restricted and less anxious We compared ambulation with oxytocin in the treatment of protracted labour with a r and omized , controlled trial of 57 patients . Sixty percent of the women in the ambulant group delivered their babies without oxytocin . In the ambulant group , the mean length of the second stage of labour was shorter and the women themselves held relatively positive views on their experiences . In the oxytocin group , on the other h and , the women experienced stronger contractions before pushing and also suffered from more excessively strong contractions . Our trial included too few women to judge which treatment is better for the infant 's health . Nevertheless , the women 's opinions and the quality of their contractions demonstrate that more attention should be paid to ambulation as a treatment for protracted labour Using continuous cardiotocography , the effect of maternal position on fetal heart rate ( FHR ) was studied during extradural analgesia ( EA ) with either 50 or 100 mg of etidocaine without adrenaline for labour and vaginal delivery . Of 70 healthy parturients , 39 were supine and 40 were in the lateral position . FHR was normal in all patients during the control period before EA , and remained normal during EA in 53 . Transient abnormal patterns occurred in 26 patients , 22 ( 56 % ) in the supine group and four ( 10 % ) in the lateral group , a significant difference ( P less than 0.001 ) . The decrease in arterial pressure ( AP ) did not differ between the groups , but the frequency of abnormal FHR associated with a small or moderate decrease in AP ( 30 % or less ) was greater in the supine ( 51 % ) than in the lateral group ( 3 % ) 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 Summary : This study was conducted at the Lokmanya Tilak Municipal General Hospital , Bombay , India during the year 1990 . The aim was to compare the routinely used supine position versus ambulation in the first stage and squatting position during the second stage of labour . Our study was comprised of 200 patients both primigravidas and multigravidas ; 100 were kept in the supine position throughout labour and 100 were kept ambulatory in the first stage and adopted the squatting position during the second stage . The study showed a shortening of both stages of labour in the squatting group but the incidence of complications was less in the control group . It was concluded that without proper birthing chairs which can give excellent perineal support , the usual supine position is preferable in our setup A r and omised study of 189 deliveries was conducted to compare performance in the conventional dorsal position with that in a birth chair . There was no significant difference in the length of the second stage of labour , the time spent bearing down , or the need for operative delivery . Overall blood-loss was greater among patients delivered in the chair but more of this group had either an intact perineum or only superficial damage . The condition of the neonates in the two delivery groups was similar BACKGROUND The evaluation of the birth position and its effects on maternal and fetal wellbeing has been a topic of perinatal research over the last decades . The aim of our observational study was to determine the effects of a modified and vertical maternal position on fetal oxygen saturation measured by pulse oximetry . METHODS Fetal oxygen saturation was measured by pulse oximetry in 56 labouring women r and omly and successively adopting the supine position in 96.4 % , the sitting position in 25.0 % , the st and ing position in 14.3 % and the prone position in 12.5 % . The statistical analysis addressed the integrated 10 minutes period of SpO2 registration s before versus after adopting the modified position . Furthermore the mean values and the st and ard deviation ( SD ) for the total registration periods of different birth position was calculated . RESULTS While the supine position induced a reduction in oxygen saturation , sitting and prone position were favorable for fetal oxygenation as compared to horizontal position . DISCUSSION These findings implicate a clinical benefit of the modified birth position This study was design ed to evaluate the relationship between the parturient 's position and her abdominal and lumbar ( continuous and contraction ) pain during the first stage of labor . A homogeneous group of 100 parturients was r and omly assigned to alternately assume the horizontal or the vertical position for 15-min periods . Their pain was measured at 2 - 3 , 4 - 5 , 6 - 7 , and 8 - 9 centimeters dilatation . To avoid " carry over " effect , these positions were preceded by a self-elected posture . Thus , the patient adopted ( a ) a self-elected position , ( b ) recumbent ( or erect ) , ( c ) a self-elected position , ( d ) erect ( or recumbent ) , and so on . Pain intensity was measured by the Argentine Pain Question naire 's Present Pain Intensity and the Huskisson 's visual analogue scale . Only the patients with at least one pain evaluation in both positions using both instruments were included in the study . The setting for the study was the obstetric department of a general hospital for people connected with public education ( professors , teachers , or members of school administrative staffs ) . The analysis revealed that a majority of patients felt less abdominal and lumbar pain , either continuous or due to contractions , during recumbency . The effect was more remarkable when dilation exceeded 5 centimeters and less intense during the first half of the first stage of labor BACKGROUND AND METHODS Walking during labor may reduce patients ' discomfort and improve outcomes . We conducted a r and omized trial of walking during active labor to determine whether it altered the duration of labor or other maternal or fetal outcomes . Women with uncomplicated pregnancies between 36 and 41 weeks ' gestation and in active labor were r and omly assigned either to walking or to no walking ( usual care ) . Pedometers were used to quantify walking , and the time spent walking was recorded . RESULTS Of the 536 women assigned to the walking group , 380 actually walked . Their mean ( + /-SD ) walking time was 56+/-46 minutes . There were no significant differences between the women assigned to the walking group and the 531 women assigned to the usual-care group in the duration of the first stage of labor ( 6.1 hours in both groups , P=0.83 ) , the need for labor augmentation with oxytocin ( 23 percent vs. 26 percent , P=0.25 ) , and the use of analgesia ( 84 percent vs. 86 percent , P=0.59 ) . Similarly , the percentages of women requiring delivery by forceps ( 4 percent vs. 3 percent , P=0.35 ) and cesarean section ( 4 percent vs. 6 percent , P=0.25 ) were not significantly different . These labor and delivery outcomes were unrelated to walking in both nulliparous and parous women . The infants ' outcomes were also similar in the two study groups . CONCLUSIONS Walking neither enhanced nor impaired active labor and was not harmful to the mothers or their infants |
608 | 29,273,650 | The main benefits of these devices were decreased surgical operation times and increased surgical accuracy .
CONCLUSIONS All medical fields that assessed 3D-printed devices concluded that they were clinical ly effective .
The fields that most rigorously assessed 3D-printed devices were oral and maxillofacial surgery and the musculoskeletal system , both of which concluded that the 3D-printed devices outperformed their conventional comparators .
However , the efficacy and effectiveness of 3D-printed devices remain undetermined for the majority of medical fields . | OBJECTIVE To evaluate the clinical efficacy and effectiveness of using 3D printing to develop medical devices across all medical fields . | This study develops and vali date s a novel patient-specific navigational template for total knee arthroplasty ( TKA ) . A total of 70 patients who underwent TKA were r and omized and divided into conventional method group and navigational template group . In the navigational template group , the patient-specific navigational templates were design ed and used intraoperatively to assist 35 patients with knee arthroplasty . Information on operation time and blood loss was recorded . After surgery , the positions of the prosthesis were evaluated using CT scan and X-rays . Analysis showed significant differences in errors between the two techniques . In addition , mean operation time and mean blood loss were statistically and significantly lower in the navigational template group than in the conventional group . Overall , the navigational template method showed a high degree of accuracy and efficacy BACKGROUND Sagittal split ramus osteotomy ( SSRO ) can be associated with postoperative neurosensory disturbances . This study aim ed to evaluate the effectiveness of computer-assisted SSRO in reducing the incidence and severity of neurosensory alterations , using a surgical guide fabricated by computer-aided design and rapid prototyping ( to guide bone cutting lateral to the inferior alveolar nerve ) . METHODS A prospect i ve double-blind , r and omized controlled , clinical trial of computer-assisted SSRO vs conventional SSRO ( assigned in a split-mouth design ) in eight patients , mean age 23 ( range 18 - 30 ) years , who participated in one session preoperatively and three sessions at 1 week and 1 , 3 and 6 months postoperatively . At each session , subjective oral sensation was scored and quantitative sensory tests were performed . Neurosensory changes were compared between the two sides . RESULTS The results showed that on the computer-assisted SSRO sides , patients had lower postoperative abnormal thresholds for the Semmes-Weinstein monofilaments on lower lip and chin ( p < 0.05 at 3 months ) and for the two-point discrimination on lower lip ( p < 0.05 at 1 week ) and chin ( p < 0.05 at 6 months ) , with fewer abnormal self-reported changes in lower lip sensation ( p < 0.05 at 1 week ) after surgery . CONCLUSIONS These findings imply that computer-assisted SSRO is associated with better levels of neurosensory function after surgery Objective : To investigate the efficacy of 3-D printed bone models as a tool to facilitate initiation of bisphosphonate treatment among individuals who were newly diagnosed with osteoporosis . Design : Fifty eight participants with estimated fracture risk above that at which guidelines recommend pharmacological intervention were r and omised to receive either a st and ard physician interview or an interview augmented by the presentation of 3-D bone models . Main outcome measures : Participants ’ beliefs about osteoporosis and bisphosphonate treatment , initiation of bisphosphonate therapy assessed at two months using self-report and pharmacy dispensing data . Results : Individuals in the 3-D bone model intervention condition were more emotionally affected by osteoporosis immediately after the interview ( p = .04 ) and reported a greater underst and ing of osteoporosis at follow-up ( p = .04 ) , than the control group . While a greater proportion of the intervention group initiated an oral bisphosphonate regimen ( alendronate ) ( 52 % ) in comparison with the control group ( 21 % ) , the overall initiation of medication for osteoporosis , including infusion ( zoledronate ) , did not differ significantly ( intervention group 62 % , control group 45 % , p = .19 ) . Conclusion : The presentation of 3-D bone models during a medical consultation can modify cognitive and emotional representations relevant to treatment initiation among people with osteoporosis and might facilitate commencement of bisphosphonate treatment Purpose Due to the complexity of acetabulum , achieving anatomical contouring intra-operatively is difficult for surgeon . A 3D ( dimensional ) real model can facilitate us both in contouring the plate pre-operatively and in better pre-operative planning . Patient-specific pre-contoured plate in acetabular fracture has been studied by few research ers but r and omized case – control study was lacking . Hence , we conducted a case – control study to evaluate the accuracy of patient-specific pre-contoured plate . Material s and methods Prospect i ve r and omized case control study was conducted . 21 patients were included . 10 patients were distributed in “ case ” group and remaining 11 in “ control ” group . Inclusion criteria : Displaced acetabulum fractures with displacement of ≥3 mm in adults who reported within 3 weeks of injury . Exclusion criteria were : Open fractures , associated Morel-Lavallée lesion and patients with > 3 weeks old fracture . In case group , patient-specific real 3D model of fractured acetabulum was generated using rapid prototyping technology and plates were contoured pre-operatively . Control group was treated using intra-operative contoured plates . Both the groups were compared using parameters : Blood loss , Surgery time , post-operative reduction on X-ray , post-surgical residual displacement and reduction achieved as evaluated by CT scan . Results Reduced blood loss ( 100 ml less in case group ) and surgical time ( 12 min less in case group ) and better post-operative reduction were observed in case than control . In control group , 4 patients even had step of 2–3 mm , which was not seen in case group . All the pre-contoured plates fitted well to the pelvis intra-operatively . Reduction achieved as evaluated by CT was more in “ case ” group with statistically significant outcomes ( p < 0.05 ) . Conclusion Patient-specific pre-contoured plate made using 3D model is a better implant than intra-operatively contoured plate . Real-time 3D pelvis model is an accurate technique for pre-operative planning in acetabular fractures Prototyping technologies for reconstructions consist of obtaining a 3‐dimensional model of the object of interest . Solid models are constructed by the deposition of material s in successive layers . The purpose of this study was to perform a double‐blind , r and omized , prospect i ve study to evaluate the efficacy of prototype use in head and neck surgeries Background Computer-assisted surgery plays an increasingly important role in m and ibular reconstruction , ensuring the best possible masticatory function and aesthetic outcome . Methods Twenty patients were r and omly assigned to computer-assisted or conventional m and ibular reconstruction with vascularized iliac crest bone graft in a prospect i ve study design .Virtual surgical planning was based on preoperative CT- data using specific surgical planning software . A rapid prototyping guide transferred the virtual surgery plan to the operation site . During surgery the transplant ischemic time , reconstruction time , time for shaping the transplant and amount of bone removed were measured . Additionally , the difference in the intercondylar distance before and after surgery was calculated . Results Computer-assisted surgery shortened the time of transplant ischemia ( P < 0.005 ) and defect reconstruction ( P < 0.001 ) compared to conventional surgery . The time to saw and shape the transplant at the donor site was shorter using conventional surgery ( P < 0.005 ) ; therefore , the overall time for surgery did n’t change ( P = 0.527 ) . In the computer-assisted group , the amount of bone harvested equaled the defect size , whereas the transplant size in the conventional group exceeded the defect site by 16.8 ± 5.6 mm ( P < 0.001 ) on average . The intercondylar distance before compared to after surgery was less affected in the computer-assisted than in the conventional group ( P < 0.001 ) . Conclusions The presented study shows that computer-assisted surgery can help reduce the time for m and ibular defect reconstruction and consequently the transplant ischemic time . In the computer-assisted group , the iliac crest donor site defect was downsized and the postoperative condyle position was less altered , reducing possible risks of postoperative complications and donor site morbidity . Trial Registration Abstract The aim of the study was to evaluate the efficacy custom 3D-printed osteo synthesis plates in the treatment of intercondylar humeral fractures . Thirteen patients with distal intercondylar humeral fractures were r and omized to undergo surgery using either conventional plates ( n = 7 ) or 3D-printed plates ( n = 6 ) at our institution from March to October 2014 . Both groups were compared in terms of operative time and elbow function at 6 month follow-up . All patients were followed-up for a mean of 10.6 months ( range : 6–13 months ) . The 3D-printing group had a significantly shorter mean operative time ( 70.6 ± 12.1 min ) than the conventional plates group ( 92.3 ± 17.4 min ) . At the last follow-up period , there was no significant difference between groups in the rate of patients with good or excellent elbow function , although the 3D-printing group saw a slightly higher rate of good or excellent evaluations ( 83.1 % ) compared to the conventional group ( 71.4 % ) . Custom 3D printed osteo synthesis plates are safe and effective for the treatment of intercondylar humeral fractures and significantly reduce operative time To evaluate the effect of 3D printing in treating trimalleolar fractures and its roles in physician-patient communication , thirty patients with trimalleolar fractures were r and omly divided into the 3D printing assisted- design operation group ( Group A ) and the no-3D printing assisted- design group ( Group B ) . In Group A , 3D printing was used by the surgeons to produce a prototype of the actual fracture to guide the surgical treatment . All patients underwent open reduction and internal fixation . A question naire was design ed for doctors and patients to verify the verisimilitude and effectiveness of the 3D-printed prototype . Meanwhile , the operation time and the intraoperative blood loss were compared between the two groups . The fracture prototypes were accurately printed , and the average overall score of the verisimilitude and effectiveness of the 3D-printed prototypes was relatively high . Both the operation time and the intraoperative blood loss in Group A were less than those in Group B ( P < 0.05 ) . Patient satisfaction using the 3D-printed prototype and the communication score were 9.3 ± 0.6 points . A 3D-printed prototype can faithfully reflect the anatomy of the fracture site ; it can effectively help the doctors plan the operation and represent an effective tool for physician-patient communication BACKGROUND The considerable variation in anatomical abnormalities of hip joints associated with different types of developmental dysplasia of hip ( DDH ) makes reconstruction in total hip arthroplasty ( THA ) difficult . It is desirable to create patient-specific design s for THA procedures . In the cases of adult single DDH , an accuracy-improved method has been developed for acetabular cup prosthesis implantation of hip arthroplasty . METHODS From October 2007 to November 2008 , 22 patients with single DDH ( according to the Crowe st and ard , all dysplasia hips were classified as type I ) were scanned with spiral CT pre-operatively . These patients scheduled for THA were r and omly assigned to undergo either conventional THA ( control group , n = 11 ) or navigation template implantation ( NT group , n = 11 ) . In the NT group , three-dimensional ( 3D ) CT pelvis image data were transferred to a computer workstation and 3D models of the hip were reconstructed using the Mimics software . The 3D models were then processed by the Imageware software . In brief , a template that best fitted the location and shape of the acetabular cup was ' reversely ' built from the 3D model , the rotation centre of the pathological hip determined by mirroring that of the healthy site , and a guiding hole in the template was then design ed . The navigational templates were manufactured using a rapid prototyping machine . These navigation templates guide acetabular component placement . RESULTS Based on the predetermined abduction angle 45 ° and anteversion angle 18 ° , after 1 year follow-up , the NT group showed significantly smaller differences ( 1.6 ° ± 0.4 ° , 1.9 ° ± 1.1 ° ) from the predetermined angles than those in the control group ( 5.8 ° ± 2.9 ° , 3.9 ° ± 2.5 ° ) ( P < 0.05 ) . CONCLUSIONS The template design s facilitated accurate placement of acetabular components in dysplasia of acetabulum . The hip 's center of rotation in DDH could be established using computer-aided design , which provides a useful method for the accurate location of prosthesis with a low cost-performance ratio without excessive technical workload on the surgical team 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 PURPOSE This study was conducted to investigate the feasibility and clinical potential of using the 3D printing technology ( 3DPT ) versus typical strategy ( thin-layer CT scan ) for the treatment of complicated proximal humeral fractures ( PHFs ) in old people . METHODS Sixty-six old patients age ranging from 61 to 76 years with persistent complicated PHFs were r and omly assigned to two groups as per the controlled r and omization table ( 34 cases in the test group and 32 cases in the control group ) . In the test group , 3DPT was applied to build the 3D facture model of a patient , according to the data acquired from the thin-layer CT scan and subsequently processed with Mimics software . This helped to confirm the diagnosis , design the individual operation plan , simulate the surgical procedures and perform the surgery as plan . In the control group , only thin-layer CT scan was applied for the design of the operation plan prior to the surgery . Here , parameters including surgery duration , blood loss volume during surgery , the number of fluoroscopy , time to union were statistically analyzed for two groups after the operation . The screw lengths design ed before the surgery and measured during the surgery were compared . RESULTS The 3D PHF model generated using 3DPT was able to provide the visual display and omni-directional observation of the direction and severity of the fracture dislocation , which facilitated preoperative diagnosis , operation planning and design , data measurement , pre selection of internal fixator and surgical outcome simulation . According to the follow-up ranging from 12∼28 months for the 66 patients , the results showed no significant difference in time to union between the two groups ( P>0.05 ) . Apart from that , less surgery duration , less blood loss during surgery , less number of fluoroscopy can be observed compared with the control group ( P<0.05 ) . CONCLUSIONS In this study , 3DPT showed great clinical feasibility of the treatment of complicated PHFs . The 3D-print PHF model had the ability to clearly display the fracture and thus was useful to determine the fracture classification and the magnitude of fracture injury . It benefited surgeons to gain a better underst and ing of complicated PHFs , design a most suitable operation plan prior to surgery and facilitate the doctor-patient communication . This therefore enabled the reduction of intraoperative injury and the optimization of surgical outcomes BACKGROUND Glenoid component malposition for anatomic shoulder replacement may result in complications . The purpose of this study was to define the efficacy of a new surgical method to place the glenoid component . METHODS Thirty-one patients were r and omized for glenoid component placement with use of either novel three-dimensional computed tomographic scan planning software combined with patient-specific instrumentation ( the glenoid positioning system group ) , or conventional computed tomographic scan , preoperative planning , and surgical technique , utilizing instruments provided by the implant manufacturer ( the st and ard surgical group ) . The desired position of the component was determined preoperatively . Postoperatively , a computed tomographic scan was used to define and compare the actual implant location with the preoperative plan . RESULTS In the st and ard surgical group , the average preoperative glenoid retroversion was -11.3 ° ( range , -39 ° to 17 ° ) . In the glenoid positioning system group , the average glenoid retroversion was -14.8 ° ( range , -27 ° to 7 ° ) . When the st and ard surgical group was compared with the glenoid positioning system group , patient-specific instrumentation technology significantly decreased ( p < 0.05 ) the average deviation of implant position for inclination and medial-lateral offset . Overall , the average deviation in version was 6.9 ° in the st and ard surgical group and 4.3 ° in the glenoid positioning system group . The average deviation in inclination was 11.6 ° in the st and ard surgical group and 2.9 ° in the glenoid positioning system group . The greatest benefit of patient-specific instrumentation was observed in patients with retroversion in excess of 16 ° ; the average deviation was 10 ° in the st and ard surgical group and 1.2 ° in the glenoid positioning system group ( p < 0.001 ) . Preoperative planning and patient-specific instrumentation use result ed in a significant improvement in the selection and use of the optimal type of implant and a significant reduction in the frequency of malpositioned glenoid implants . CONCLUSIONS Novel three-dimensional preoperative planning , coupled with patient and implant-specific instrumentation , allows the surgeon to better define the preoperative pathology , select the optimal implant design and location , and then accurately execute the plan at the time of surgery Stereolithographic ( SL ) biomodelling is a new technology that allows three-dimensional ( 3-D ) computed tomography ( CT ) data to be used to manufacture solid plastic replicas of anatomical structures ( biomodels ) . A prospect i ve trial with the objective of assessing the utility of biomodelling in complex surgery has been performed . Forty-five patients with craniofacial , maxillofacial , skull base cervical spinal pathology were selected . 3-D CT or MR scanning was performed and the data of interest were edited and converted into a form acceptable to the rapid prototyping technology SL . The data were used to guide a laser to selectively polymerize photosensitive resin to manufacture biomodels . The biomodels were used by surgeons for patient education , diagnosis and operative planning . An assessment protocol was used to test the hypothesis that ' biomodels in addition to st and ard imaging had greater utility in the surgery performed than the st and ard imaging alone ' . Biomodels significantly improved operative planning ( images 44.09 % , images with biomodel 82.21 % , P < .01 ) and diagnosis ( images 65.63 % , images with biomodel 95.23 % , P < .01 ) . Biomodels were found to improve measurement accuracy significantly ( image measurement error 44.14 % , biomodel measurement error 7.91 % , P < .05 ) . Surgeons estimated that the use of biomodels reduced operating time by a mean of 17.63 % and were cost effective at a mean price of $ 1031 AUS . Patients found the biomodels to be helpful for informed consent ( images 63.53 % , biomodels 88.54 % , P < .001 ) . Biomodelling is an intuitive , user-friendly technology that facilitated diagnosis and operative planning . Biomodels allowed surgeons to rehearse procedures readily and improved communication between colleagues and patients Introduction The method of free-h and pedicle screw placement is generally safe although it carries potential risks . For this reason , several highly accurate computer-assisted systems were developed and are currently on the market . However , these devices have certain disadvantages . We have developed a method of pedicle screw placement in the lumbar and sacral region using a multi-level drill guide template , created with the rapid prototyping technology and have vali date d it in a clinical study . The aim of the study was to manufacture and evaluate the accuracy of a multi-level drill guide template for lumbar and first sacral pedicle screw placement and to compare it with the free-h and technique under fluoroscopy supervision . Material s and methods In 2011 and 2012 , a r and omized clinical trial was performed on 20 patients . 54 screws were implanted in the trial group using templates and 54 in the control group using the fluoroscopy-supervised free-h and technique . Furthermore , applicability for the first sacral level was tested . Preoperative CT-scans were taken and templates were design ed using the selective laser sintering method . Postoperative evaluation and statistical analysis of pedicle violation , displacement , screw length and deviation were performed for both groups . Results The incidence of cortex perforation was significantly reduced in the template group ; likewise , the deviation and displacement level of screws in the sagittal plane . In both groups there was no significantly important difference in deviation and displacement level in the transversal plane as not in pedicle screw length . The results for the first sacral level resembled the main investigated group . Conclusions The method significantly lowers the incidence of cortex perforation and is therefore potentially applicable in clinical practice , especially in some selected cases . The applied method , however , carries a potential for errors during manufacturing and practical usage and therefore still requires further improvements OBJECTIVES To evaluate and compare the outcome of dental implants placed using a flapless protocol and immediate loading with a conventional protocol and loading after 6 weeks . MATERIAL S AND METHODS Fourteen patients with bilateral maxillary edentulous areas were treated using Straumann SLA-implants . Using a r and omized split-mouth design , implants were placed in one side of the maxilla using a stereolithographic surgical guide for flapless surgery and immediately loaded on temporary abutments with a bridge ( test ) . Implants in the other side were placed using the conventional protocol and loaded after 6 weeks of healing ( control ) . Clinical and radiographic evaluation of peri-implant tissues was performed at time of implant surgery , and after 1 week , 6 weeks , 3 , 6 , 12 and 18 months . RESULTS A total of 70 implants were placed ( 36 test and 34 control ) . One implant ( test ) was lost after 3 months , result ing in a survival rate of 97.3 % for the test implants and 100 % for the control implants . Marginal bone levels were not statistically significantly different between the test and control implants but at baseline the marginal bone level was significantly lower compared to the other evaluation periods ( P < 0.05 ) . The mean bone level for test and control implants was 1.95 mm ± 0.70 and 1.93 mm ± 0.42 after 18 months , respectively . There was a significant change in height of the attached mucosa at implants placed with a conventional flap between post-operative and 1 week and between 1 week and 6 weeks . Statistically significant differences were found between the test side and the control side for opinion about speech , function , aesthetics , self-confidence and overall appreciation the first 6 weeks . CONCLUSION Implants can successfully integrate in the posterior maxilla using a flapless approach with immediate loading similar to a conventional protocol . The mucosal tissues around implants placed with a conventional flap changed significantly compared with flapless placed implants Study Design The application of rapid prototyping ( RP ) technique for improving accuracy of pedicle screw placement in congenital scoliosis is described in this study . Objective To compare the accuracy and safety of pedicle screw placement in congenital scoliosis using the RP technique versus the conventional fluoroscopy . Summary of Background Data Mal developed vertebral components in congenital scoliosis leads to prolonged operation time and higher rate of screw misplacement . RP technique can enhance preoperative and perioperative planning . No data are available on the accuracy of pedicle screw fixation using the RP technique . Methods Sixty-two consecutive patients with hemivertebra had undergone posterior-only hemivertebra resection . Pedicle screws were implanted either by the conventional intraoperative fluoroscopy technique ( C-arm group ; n=28 ) or the RP technique ( RP group ; n=34 ) . Accuracy of pedicle screw placement was compared by postoperative computed tomographic scan . Results Seventy of 677 inserted screws were found to be misplaced , showing an overall accuracy of 89.7 % ( 90.8 % in the thoracic spine and 87.4 % in the lumbar spine ) . In the C-arm group , 86.1 % ( 167 of 194 ) and 82.0 % ( 82 of 100 ) of screws were accurately placed in the thoracic and lumbar spine , respectively . While in the RP group , the respective screw placement accuracies were 94.4 % ( 238 of 252 ) and 91.6 % ( 120 of 131 ) . In the C-arm and the RP groups , 94.8 % ( 279 of 294 ) and 97.9 % ( 375 of 383 ) of the screws were within the safety zone , respectively . Compared with the fluoroscopy method , the RP-assisted technique showed a shorter operation time and higher scoliosis correction rate . No neurovascular-related complication was observed with this technique during the study . Conclusion The application of RP technique in congenital scoliosis can reduce the operation time , the risk of screw misplacement and its consequent complications . The use of RP technique in congenital scoliosis is safe and efficacious OBJECTIVES This pilot r and omised controlled clinical trial aim ed to evaluate the feasibility and effectiveness of using a polycaprolactone ( PCL ) scaffold in fresh extraction sockets for ridge preservation . The hypothesis was that the insertion of a 3D bioresorbable PCL scaffold in fresh extraction sockets allowed for normal bone healing and better maintenance of ridge dimensions after 6 months as compared to extraction sockets without the scaffold . MATERIAL AND METHODS Thirteen patients were r and omised to either the test group ( N = 6 ) where a PCL scaffold was inserted in the tooth socket after extraction or the control group ( N = 7 ) where no space filler was used . Alveolar ridge height and width measurements were made at baseline and 6 months post- extraction , for the evaluation of bone resorption . At 6 months , a core of bone was trephined out from the healed ridge for microcomputed tomographic ( micro CT ) and histological analyses , immediately before Stage I dental implant surgery . Stage II dental implant surgery was performed 4 - 6 months later . RESULTS There was less vertical ridge resorption in the test group compared to the control group , and the difference was statistically significant in the mesio-buccal aspect ( P = 0.008 ) . Micro CT and histological observations showed mainly mineralised bone formation in both groups , except for one specimen in the test group . CONCLUSIONS The insertion of a 3D bioresorbable PCL scaffold in fresh extraction sockets allowed for normal bone healing , and there was better maintenance of ridge height after 6 months as compared to extraction sockets without the scaffold AIM To assess the accuracy of guided surgery ( mucosa and bone-supported ) compared to mental navigation or the use of a surgical template , in fully edentulous jaws , in a r and omized controlled study . MATERIAL AND METHODS Fifty-nine patients ( 72 jaws ) , requiring four to six implants ( maxilla or m and ible ) , were consecutively recruited and r and omly assigned to one of the following treatment groups ; guidance via Material ise Universal( ® )/mucosa , Material ise Universal( ® )/bone , Facilitate ™ /mucosa , Facilitate ™ /bone , or mental navigation or a pilot-drill template . The precision was assessed by matching the planning computed tomography ( CT ) with a post-operative cone beam CT . RESULTS A significant lower mean deviation at the entry point ( 1.4 mm , range : 0.3 - 3.7 ) , at the apex ( 1.6 mm , range : 0.2 - 3.7 ) and angular deviation ( 3.0 ° , range : 0.2 - 16 ° ) was observed for the guiding systems when compared to mental navigation ( 2.7 mm , range : 0.3 - 8.3 ; 2.9 mm , range : 0.5 - 7.4 and 9.9 ° , range : 1.5 - 27.8 ) and to the surgical template group ( 3.0 mm , range : 0.6 - 6.6 ; 3.4 mm , range : 0.3 - 7.5 and 8.4 ° , range : 0.6 - 21.3 ° ) . Differences between bone and mucosa support or type of guidance were negligible . Jaw and implant location ( posterior-anterior , left-right ) , however , had a significant influence on the accuracy when guided . CONCLUSION Based on these findings , guided implant placement appears to offer clear accuracy benefits Patient-specific cutting guides ( PSCGs ) are design ed to improve the accuracy of alignment of total knee replacement ( TKR ) . We compared the accuracy of limb alignment and component positioning after TKR performed using PSCGs or conventional instrumentation . A total of 80 patients were r and omised to undergo TKR with either of the different forms of instrumentation , and radiological outcomes and peri-operative factors such as operating time were assessed . No significant difference was observed between the groups in terms of tibiofemoral angle or femoral component alignment . Although the tibial component in the PSCGs group was measurably closer to neutral alignment than in the conventional group , the size of the difference was very small ( 89.8 ° ( sd 1.2 ) vs 90.5 ° ( sd 1.6 ) ; p = 0.030 ) . This new technology slightly shortened the bone-cutting time by a mean of 3.6 minutes ( p < 0.001 ) and the operating time by a mean 5.1 minutes ( p = 0.019 ) , without tangible differences in post-operative blood loss ( p = 0.528 ) or need for blood transfusion ( p = 0.789 ) . This study demonstrated that both PSCGs and conventional instrumentation restore limb alignment and place the components with the similar accuracy . The minimal advantages of PSCGs in terms of consistency of alignment or operative time are unlikely to be clinical ly relevant |
609 | 29,883,514 | AUTHORS ' CONCLUSIONS We found insufficient evidence to determine whether EN is better or worse than PN , or than combined EN and PN for mortality in hospital , at 90 days and at 180 days , and on the number of ventilator-free days and adverse events .
We found fewer deaths at 30 days when studies gave combined EN and PN , and reduced sepsis for EN rather than PN . | BACKGROUND Critically ill people are at increased risk of malnutrition .
Acute and chronic illness , trauma and inflammation induce stress-related catabolism , and drug-induced adverse effects may reduce appetite or increase nausea and vomiting .
In addition , patient management in the intensive care unit ( ICU ) may also interrupt feeding routines .
Methods to deliver nutritional requirements include provision of enteral nutrition ( EN ) , or parenteral nutrition ( PN ) , or a combination of both ( EN and PN ) .
However , each method is problematic .
This review aim ed to determine the route of delivery that optimizes uptake of nutrition .
OBJECTIVES To compare the effects of enteral versus parenteral methods of nutrition , and the effects of enteral versus a combination of enteral and parenteral methods of nutrition , among critically ill adults , in terms of mortality , number of ICU-free days up to day 28 , and adverse events . | Objective To evaluate the potential clinical , metabolic , and economic advantages of enteral nutrition over total parenteral nutrition . Design Prospect i ve , r and omized clinical trial . Setting Department of surgery in a university hospital . Patients Two hundred and fifty-seven patients with cancer of the stomach ( n = 121 ) , pancreas ( n = 110 ) , or esophagus ( n = 26 ) were r and omized to receive postoperative total parenteral nutrition ( TPN group , n = 131 ) or early enteral nutrition ( EEN group , n = 126 ) . The nutritional goal was 25 kcal/kg/day . The two nutritional formulas were isocaloric and isonitrogenous , and they were continued until oral intake was at least 800 kcal/day . Measurements Morbidity , mortality , length of hospital stay , and treatment costs were evaluated in all patients . In 40 consecutive patients , selected nutritional , immunologic and inflammatory variables were studied . Moreover , intestinal oxygen tension was evaluated by micropolarographic implantable probes . Main Results The nutritional goal was reached in 100/126 ( 79.3 % ) patients in the EEN group and in 128/131 ( 97.7 % ) patients in the TPN group ( p < .001 ) . In the EEN group , hyperglycemia ( serum glucose , > 200 mg/dL ) was observed in 4.7 % of the patients vs. 9.1 % in the TPN group ( p = NS ) . Alteration of serum electrolyte levels was 3.9 % in the EEN group vs. 13.7 % in the TPN group ( p < .01 ) . No significant difference was found in nutritional , immunologic , and inflammatory variables between the two groups . The overall complication rate was similar ( 40.4 % for TPN vs. 35.7 % , for EEN;p = .52 ) . No difference was detected for either infectious or noninfectious complications , length of hospital stay , and mortality . From postoperative day 5 , intestinal oxygen tension recovered faster in the EEN group than in the TPN group ( 43 ± 5 mm Hg vs. 31 ± 4 mm Hg at day 7;p < .001 ) . EEN was four-fold less expensive than TPN ( $ 25 vs. $ 90.60/day , respectively ) . Conclusion EEN represents a rational alternative to TPN in patients who undergo upper gastrointestinal tract surgery for cancer and who clinical ly require postoperative artificial nutrition Objectives : To investigate direct postoperative outcome and plasma amino acid concentrations in a study comparing early enteral nutrition versus early parenteral nutrition after major rectal surgery . Previously , it was shown that a low plasma glutamine concentration represents poor prognosis in ICU patients . Design : A preplanned sub study of a previous prospect i ve , r and omized , open-label , single-centre study , comparing early enteral nutrition versus early parenteral nutrition in patients at high risk of postoperative ileus after surgery for locally advanced or locally recurrent rectal cancer . Early enteral nutrition reduced postoperative ileus , anastomotic leakage , and hospital stay . Setting : Tertiary referral centre for locally advanced and recurrent rectal cancer . Patients : A total of 123 patients with locally advanced or recurrent rectal carcinoma requiring major rectal surgery . Interventions : Patients were r and omized ( ALEA web-based external r and omization ) preoperatively into two groups : early enteral nutrition ( early enteral nutrition , intervention ) by nasojejunal tube ( n = 61 ) or early parenteral nutrition ( early parenteral nutrition , control ) by jugular vein catheter ( n = 62 ) . Eight hours after the surgical procedure artificial nutrition was started in hemodynamically stable patients , stimulating oral intake in both groups . Blood sample s were collected to measure plasma glutamine , citrulline , and arginine concentrations using a vali date d ultra performance liquid chromatography-t and em mass spectrometric method . Measurements and Main Results : Baseline concentrations were comparable for both groups . Directly after rectal surgery , a decrease in plasma amino acids was observed . Plasma glutamine concentrations were higher in the parenteral group than in the enteral group on postoperative day 1 ( p = 0.027 ) and day 5 ( p = 0.008 ) . Arginine concentrations were also significantly increased in the parenteral group at day 1 ( p < 0.001 ) and day 5 ( p = 0.001 ) . Conclusions : Lower plasma glutamine and arginine concentrations were measured in the enteral group , whereas a better clinical outcome was observed . We conclude that plasma amino acids do not provide a causal explanation for the observed beneficial effects of early enteral feeding after major rectal surgery Gut malnutrition in patients with persistent hypermetabolism is hypothesized to be an important factor in postseptic multiple organ failure syndrome ( MOFS ) . The hypothesis was made that enteral nutrition ( EN ) started at the onset of hypermetabolism could reduce the incidence of MOFS . Sixty-six patients with persistent hypermetabolism 4 to 6 days after onset of sepsis were prospect ively r and omized to receive either parenteral nutrition ( PN ) or enteral nutrition ( EN ) at 1.5 gm protein/kg/day and 30 nonprotein calories/kg/day ; the EN and TPN were of the same composition . There was no reduction in either the incidence of MOFS or mortality attributable to the route of nutrition administration . The PN group tended to have better visceral protein support ; the EN group had more gut complications . When analyzed , the type of formula given did have an effect on the nutritional outcome but not on the mortality rate . A formula with a nonprotein-calorie-to-nitrogen ratio of 100:1 was associated with more nitrogen retention , higher levels of visceral proteins , and better gut tolerance . The route of nutrition administration does not seem to affect the incidence of postseptic MOFS or mortality when hypermetabolism is already present and when commercially available nutritional formulas are used . The relationships among the route of nutrition , the type of enteral formula , and the disease process of hypermetabolism and MOFS appear to be complex and require much more investigation before the role of the gut and enteral nutrition can be defined OBJECTIVE To develop a model of established respiratory immunity against Pseudomonas aeruginosa pneumonia and to investigate the effects of route and type of nutrition on this immunity . SUMMARY BACKGROUND DATA Diet influences the ability of gut-associated lymphoid tissue ( GALT ) to maintain mucosal immunity . Complex enteral diets and chow maintain normal GALT population s against established IgA-mediated antiviral respiratory immunity . Both intravenous and intragastric total parenteral nutrition ( TPN ) produce GALT atrophy , but only intragastric TPN preserves established antiviral immunity . The authors hypothesized that both GALT-depleting diets ( intragastric and intravenous TPN ) would impair immunity against bacterial pneumonia . METHODS P. aeruginosa was administered intratracheally to determine the mortality rate at increasing doses , and liposomes containing P. aeruginosa antigens were used to generate effective respiratory immunization . In the final experiment , mice received liposomes containing P. aeruginosa antigens to establish immunity and then were r and omized to chow , complex enteral diets , intragastric TPN , or intravenous TPN . After 5 days of diet , mice received live intratracheal P. aeruginosa , and the death rate was recorded at 24 and 48 hours . RESULTS The LD50 and LD100 were 9 x 10(7 ) and 12 x 10(7 ) , respectively . Immunization reduced the mortality rate from 66 % to 12 % . This immunization was maintained in mice fed chow or a complex enteral diet and was lost in animals receiving intravenous TPN . Intragastric TPN partially preserved this respiratory immunity . CONCLUSIONS Protection against bacterial pneumonia can be induced by prior antigenic immunization . This protection is lost with intravenous TPN , partially preserved with a chemically defined enteral diet , and completely preserved with chow or complex enteral diets . Both route and type of nutrition influence antibacterial respiratory tract immunity Abstract Purpose We assessed the effects of early goal -directed nutrition ( EGDN ) vs. st and ard nutritional care in adult intensive care unit ( ICU ) patients . Methods We r and omised acutely admitted , mechanically ventilated ICU patients expected to stay longer than 3 days in the ICU . In the EGDN group we estimated nutritional requirements by indirect calorimetry and 24-h urinary urea aim ing at covering 100 % of requirements from the first full trial day using enteral and parenteral nutrition . In the st and ard of care group we aim ed at providing 25 kcal/kg/day by enteral nutrition . If this was not met by day 7 , patients were supplemented with parenteral nutrition . The primary outcome was physical component summary ( PCS ) score of SF-36 at 6 months . We performed multiple imputation for data of the non-responders . Results We r and omised 203 patients and included 199 in the intention-to-treat analyses ; baseline variables were reasonably balanced between the two groups . The EGDN group had less negative energy ( p < 0.001 ) and protein ( p < 0.001 ) balances in the ICU as compared to the st and ard of care group . The PCS score at 6 months did not differ between the two groups ( mean difference 0.0 , 95 % CI −5.9 to 5.8 , p = 0.99 ) ; neither did mortality , rates of organ failures , serious adverse reactions or infections in the ICU , length of ICU or hospital stay , or days alive without life support at 90 days . Conclusions EGDN did not appear to affect physical quality of life at 6 months or other important outcomes as compared to st and ard nutrition care in acutely admitted , mechanically ventilated , adult ICU patients . Clinical trials.gov identifier no. NCT01372176 We measured energy expenditure ( MREE ) and nitrogen excretion ( UUN ) in patients with severe head injury r and omized to early parenteral ( TPN , n = 21 ) or jejunal ( ENT , n = 27 ) feeding with identical formulations . The MREE rose to 2400 + /- 531 kcal/day in both groups and remained at 135 % + /- 26 % to 146 % + /- 42 % of predicted energy expenditure over 4 weeks . Nitrogen excretion peaked the second week at 33.4 + /- 10 ( TPN ) and 31.2 + /- 7.5 ( ENT ) g N/day . Both routes were equally effective at meeting nutritional goals ( 1.2 x MREE , 2.5 g protein/kg/day intake , stabilized albumin and transferrin levels ) . Infections were equally frequent : 1.86 episodes/TPN patient versus 1.89 episodes/ENT patient . While patient charges were much greater for TPN , the hospital costs were similar for TPN and ENT support regimens . These findings show that patients with head injuries are hypermetabolic for weeks , that only 27 % are capable of spontaneously eating nutritional requirements by discharge , and that either TPN or ENT support is equally effective when prescribed according to individual measurements of MREE and nitrogen excretion Background Nutrition is one of the fundamentals of care provided to critically ill adults . The volume of enteral nutrition received , however , is often much less than prescribed due to multiple functional and process issues . To deliver the prescribed volume and correct the energy deficit associated with enteral nutrition alone , parenteral nutrition can be used in combination ( termed “ supplemental parenteral nutrition ” ) , but benefits of this method have not been firmly established . A multi-centre , r and omised , clinical trial is currently underway to determine if prescribed energy requirements can be provided to critically ill patients by using a supplemental parenteral nutrition strategy in the critically ill . Methods / design This prospect i ve , multi-centre , r and omised , stratified , parallel-group , controlled , phase II trial aims to determine whether a supplemental parenteral nutrition strategy will reliably and safely increase energy intake when compared to usual care . The study will be conducted for 100 critically ill adults with at least one organ system failure and evidence of insufficient enteral intake from six intensive care units in Australia and New Zeal and . Enrolled patients will be allocated to either a supplemental parenteral nutrition strategy for 7 days post r and omisation or to usual care with enteral nutrition . The primary outcome will be the average energy amount delivered from nutrition therapy over the first 7 days of the study period . Secondary outcomes include protein delivery for 7 days post r and omisation ; total energy and protein delivery , antibiotic use and organ failure rates ( up to 28 days ) ; duration of ventilation , length of intensive care unit and hospital stay . At both intensive care unit and hospital discharge strength and health-related quality of life assessment s will be undertaken . Study participants will be followed up for health-related quality of life , re source utilisation and survival at 90 and 180 days post r and omisation ( unless death occurs first ) . Discussion This trial aims to determine if provision of a supplemental parenteral nutrition strategy to critically ill adults will increase energy intake compared to usual care in Australia and New Zeal and . Trial outcomes will guide development of a subsequent larger r and omised controlled trial . Trial registration NCT01847534 ( First registered 5 February 2013 , last up date d 14 October 2015 Objective To compare the conjoint effect of enteral nutrition ( EN ) and parenteral nutrition ( PN ) with single EN or PN on immune function , nutritional status , complications and clinical outcomes of patients with severe traumatic brain injury ( STBI ) . Methods A prospect i ve r and omized control trial was carried out from January 2009 to May 2012 in Neurological Intensive Care Unit ( NICU ) . Patients of STBI who met the enrolment criteria ( Glasgow Coma Scale score 6~8 ; Nutritional Risk Screening ≥3 ) were r and omly divided into 3 groups and were admi- nistrated EN , PN or EN+PN treatments respectively . The indexes of nutritional status , immune function , complications and clinical outcomes were examined and compared statistically . Results There were 120 patients enrolled in the study , with 40 pationts in each group . In EN+PN group , T lymthocyte subsets CD3+% , CD4+% , ratio of CD3+/CD25 + , ratio of CD4+/CD8 + , the plasma levels of IgA , IgM , and IgG at 20 days after nutritional treatment were significantly increased compared to the baseline(t=4.32 - 30.00 , P<0.01 ) , and they were significantly higher than those of PN group ( t=2.44 - 14.70 ; P<0.05,or P<0.01 ) with exception of CD4+/CD8 + , higher than those of EN group ( t=2.49 - 13.31 , P<0.05 , or P<0.01 ) with exceptions of CD3+/CD25 + , CD4+/CD8 + , IgG and IgM. For the nutritional status , the serum total protein , albumin , prealbumin and hemoglobin were significantly higher in the EN ( t=5.87 - 11.91 ; P<0.01 ) and EN+PN groups ( t=6.12 - 13.12 ; P<0.01 ) than those in PN group after nutrition treatment . The serum prealbumin was higher in EN+PN group than that in EN group ( t=2.08 ; P<0.05 ) . Compared to the PN group , the complication occurrence rates of EN+PN group were significantly lower in stress ulcer ( 22.5 % vs. 47.5 % ; χ2= 8.24 , P<0.01 ) , intracranial infection ( 12.5 % vs 32.5%;χ2= 6.88 , P<0.01 ) and pyemia ( 25.0 % vs. 47.5 % ; χ2= 6.57 , P<0.05 ) . Compared to the EN group , the complication occurrence rates of EN+PN group were significantly lower in aspirated pneumonia ( 27.5 % vs. 50.0 % ; χ2= 6.39 , P<0.05 ) , hypoproteinemia ( 17.5 % vs. 55.0 % ; χ2= 18.26 , P<0.01 ) and diarrhea ( 20.0 % vs. 60.0 % ; χ2= 20.00 , P<0.01 ) . The EN+PN group also had significant less length of stay in NICU ( t=2.51 , 4.82 ; P<0.05 , P<0.01 ) , number of patients receiving assisted mechanical ventilation ( χ2= 6.08 , 12.88 ; P<0.05 , P<0.01 ) and its duration s ( t=3.41 , 9.08 ; P<0.05 , P<0.01 ) , and the death rate ( χ2=7.50 , 16.37 ; P<0.05 , P<0.01 ) than those of EN or PN group . Conclusion Early EN+PN treatment could promote the recovery of the immune function , enhance nutritional status , decrease complications and improve the clinical outcomes in patients with severe traumatic brain injury To investigate the importance of route of nutrient administration on septic complications after blunt and penetrating trauma , 98 patients with an abdominal trauma index of at least 15 were r and omized to either enteral or parenteral feeding within 24 hours of injury . Septic morbidity was defined as pneumonia , intra-abdominal abscess , empyema , line sepsis , or fasciitis with wound dehiscence . Patients were fed formulas with almost identical amounts of fat , carbohydrate , and protein . Two patients died early in the study . The enteral group sustained significantly fewer pneumonias ( 11.8 % versus total parenteral nutrition 31.% , p less than 0.02 ) , intra-abdominal abscess ( 1.9 % versus total parenteral nutrition 13.3 % , p less than 0.04 ) , and line sepsis ( 1.9 % versus total parenteral nutrition 13.3 % , p less than 0.04 ) , and sustained significantly fewer infections per patient ( p less than 0.03 ) , as well as significantly fewer infections per infected patient ( p less than 0.05 ) . Although there were no differences in infection rates in patients with injury severity score less than 20 or abdominal trauma index less than or equal to 24 , there were significantly fewer infections in patients with an injury severity score greater than 20 ( p less than 0.002 ) and abdominal trauma index greater than 24 ( p less than 0.005 ) . Enteral feeding produced significantly fewer infections in the penetrating group ( p less than 0.05 ) and barely missed the statistical significance in the blunt-injured patients ( p = 0.08 ) . In the sub population of patients requiring more than 20 units of blood , sustaining an abdominal trauma index greater than 40 or requiring reoperation within 72 hours , there were significantly fewer infections per patient ( p = 0.03 ) and significantly fewer infections per infected patient ( p less than 0.01 ) . There is a significantly lower incidence of septic morbidity in patients fed enterally after blunt and penetrating trauma , with most of the significant changes occurring in the more severely injured patients . The authors recommend that the surgeon obtain enteral access at the time of initial celiotomy to assure an opportunity for enteral delivery of nutrients , particularly in the most severely injured patients IMPORTANCE Monitoring of residual gastric volume is recommended to prevent ventilator-associated pneumonia ( VAP ) in patients receiving early enteral nutrition . However , studies have challenged the reliability and effectiveness of this measure . OBJECTIVE To test the hypothesis that the risk of VAP is not increased when residual gastric volume is not monitored compared with routine residual gastric volume monitoring in patients receiving invasive mechanical ventilation and early enteral nutrition . DESIGN , SETTING , AND PATIENTS R and omized , noninferiority , open-label , multicenter trial conducted from May 2010 through March 2011 in adults requiring invasive mechanical ventilation for more than 2 days and given enteral nutrition within 36 hours after intubation at 9 French intensive care units ( ICUs ) ; 452 patients were r and omized and 449 included in the intention-to-treat analysis ( 3 withdrew initial consent ) . INTERVENTION Absence of residual gastric volume monitoring . Intolerance to enteral nutrition was based only on regurgitation and vomiting in the intervention group and based on residual gastric volume greater than 250 mL at any of the 6 hourly measurements and regurgitation or vomiting in the control group . MAIN OUTCOME MEASURES Proportion of patients with at least 1 VAP episode within 90 days after r and omization , as assessed by an adjudication committee blinded to patient group . The prestated noninferiority margin was 10 % . RESULTS In the intention-to-treat population , VAP occurred in 38 of 227 patients ( 16.7 % ) in the intervention group and in 35 of 222 patients ( 15.8 % ) in the control group ( difference , 0.9 % ; 90 % CI , -4.8 % to 6.7 % ) . There were no significant between-group differences in other ICU-acquired infections , mechanical ventilation duration , ICU stay length , or mortality rates . The proportion of patients receiving 100 % of their calorie goal was higher in the intervention group ( odds ratio , 1.77 ; 90 % CI , 1.25 - 2.51 ; P = .008 ) . Similar results were obtained in the per- protocol population . CONCLUSION AND RELEVANCE Among adults requiring mechanical ventilation and receiving early enteral nutrition , the absence of gastric volume monitoring was not inferior to routine residual gastric volume monitoring in terms of development of VAP . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01137487 Reprioritization of hepatic protein synthesis , a process involving accelerated production of acute-phase proteins at the expense of constitutive proteins , accompanies major trauma . The impact of isocaloric , isonitrogenous total enteral nutrition ( TEN ) versus total parenteral nutrition ( TPN ) on hepatic reprioritization was investigated in a prospect i ve , r and omized trial . Of the 59 patients with an abdominal trauma index ( ATI ) greater than 15 but not more than 40 , 45 evaluable patients were followed . Results from 36 ( 18 TEN , 18 TPN ) evaluable patients revealed that mean serum levels of acute-phase proteins increased , whereas mean serum levels increased to a greater extent in the TPN group . The maximal increase from baseline for the acute-phase response in both groups occurred at postinjury day 5 and was significantly higher for alpha 1-antitrypsin ( alpha 1AT , p = 0.03 ) and orosomucoid ( p = 0.02 ) in the TPN group . Nonacute-phase proteins reached a nadir at day 10 in the TPN group and increased in the TEN group ; significant differences between TEN and TPN groups appeared for albumin ( p = 0.004 ) and retinol-binding protein ( RBP , p = 0.03 ) ; alpha 2-macroglobulin ( alpha 2 M ) approached significance at day 10 ( p = 0.07 ) . When change from baseline values was compared , day 10 increases in alpha 2 M were significantly higher ( p = 0.04 ) in the TEN group . These data suggest that postinjury TEN attenuates reprioritization of hepatic protein synthesis in patients sustaining major trauma Although enteral nutrition is considered more ' physiologic ' than parenteral nutrition , there is greater published experience with parenteral nutrition in trauma patients . To compare the efficacy of these two techniques , we prospect ively r and omized multiple trauma patients during their admission laparotomy to receive either central venous parenteral nutritional ( TPN : n = 23 ) or enteral nutrition by jejunostomy ( Jej : n = 23 ) . Nutritional support began on the first postoperative day ; the study period continued a maximum of 14 days . There were no significant differences between the two groups in age , sex , injury severity , estimated caloric needs ( 3,322 TPN ; 3,114 Jej ) , hours to achieve full prescription ( 77 PTN ; 79 Jej ) , or the number of days on nutritional support ( 22 TPN ; 25 Jej ) . Average daily caloric intakes , nitrogen balance results , and complication rates were also comparable . These results suggest that early postoperative jejunostomy feeding is a safe and efficacious choice for multiple trauma patients undergoing laparotomy Objective : To evaluate the effects of early enteral nutrition on the gastrointestinal motility and intestinal mucosal barrier of patients with burn-induced invasive fungal infection . Methods : A total of 120 patients with burn-induced invasive fungal infection were r and omly divided into an early enteral nutrition ( EN ) group and a parenteral nutrition ( PN ) group ( n=60 ) . The patients were given nutritional support intervention for 14 days , and the expression levels of serum transferrin , albumin , total protein , endotoxin , D-lactic acid and inflammatory cytokines were detected on the 1st , 7th and 14th days respectively . Results : As the treatment progressed , the levels of serum transferrin , albumin and total protein of the EN group were significantly higher than those of the PN group ( P<0.05 ) , while the levels of serum endotoxin and D-lactic acid of the form group were significantly lower ( P<0.05 ) . After treatment , the expression levels of IL-6 and TNF-α were decreased in the EN group , which were significantly different from those of the PN group ( P<0.05 ) . During treatment , the incidence rates of complications such as abdominal distension , diarrhea , sepsis , nausea , vomiting and gastric retention were similar . The mean healing time of wound surface was 9.34±0.78 days in the EN group and 12.46±2.19 days in the PN group , i.e. such time of the former was significantly shorter than that of the latter ( P<0.05 ) . Conclusion : Treating patients having burn-induced invasive fungal infection by early enteral nutrition support with arginine can safely alleviate malnutrition and stress reaction , strengthen cellular immune function and promote wound healing , thereby facilitating the recovery of gastrointestinal motility and the function of intestinal mucosal barrier Objectives We compared early parenteral nutrition ( PN ) and early enteral immunonutrition ( iEN ) in critically ill patients , distinguishing those with and without severe sepsis or septic shock ( SS ) on admission to intensive care units ( ICUs ) . Design and setting Multicenter , r and omized , unblinded clinical trial in 33 Italian general ICUs . Patients and participants The study included 326 patients , 287 of whom did not have SS on ICU admission . Eligibility criteria excluded the two tails in the spectrum of critical conditions , i.e. , patients either too well or too ill . Of the patients recruited 160 were r and omized to iEN ( 142 without SS ) and 166 to PN ( 145 without SS ) . Interventions Patients were r and omized to two arms : early iEN or early PN . Measurements and results Primary endpoint was 28-day mortality for all patients and the occurrence of SS during ICU stay for patients admitted without such condition . While 28-day mortality did not differ between iEN and PN ( 15.6 % vs. 15.1 % ) , patients without SS who received iEN had fewer episodes of severe sepsis or septic shock ( 4.9 % vs. 13.1 % ) . ICU length of stay was 4 days shorter in patients given iEN . Conclusions Compared to parenteral nutrition iEN appears to be beneficial in critical patients without severe sepsis or septic shock . Parenteral nutrition in these patients should be ab and oned , at least when enteral nutrition can be administered , even at an initial low caloric content BACKGROUND Enteral nutrition ( EN ) is recommended for patients in the intensive-care unit ( ICU ) , but it does not consistently achieve nutritional goals . We assessed whether delivery of 100 % of the energy target from days 4 to 8 in the ICU with EN plus supplemental parenteral nutrition ( SPN ) could optimise clinical outcome . METHODS This r and omised controlled trial was undertaken in two centres in Switzerl and . We enrolled patients on day 3 of admission to the ICU who had received less than 60 % of their energy target from EN , were expected to stay for longer than 5 days , and to survive for longer than 7 days . We calculated energy targets with indirect calorimetry on day 3 , or if not possible , set targets as 25 and 30 kcal per kg of ideal bodyweight a day for women and men , respectively . Patients were r and omly assigned ( 1:1 ) by a computer-generated r and omisation sequence to receive EN or SPN . The primary outcome was occurrence of nosocomial infection after cessation of intervention ( day 8) , measured until end of follow-up ( day 28 ) , analysed by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00802503 . FINDINGS We r and omly assigned 153 patients to SPN and 152 to EN . 30 patients discontinued before the study end . Mean energy delivery between day 4 and 8 was 28 kcal/kg per day ( SD 5 ) for the SPN group ( 103 % [ SD 18 % ] of energy target ) , compared with 20 kcal/kg per day ( 7 ) for the EN group ( 77 % [ 27 % ] ) . Between days 9 and 28 , 41 ( 27 % ) of 153 patients in the SPN group had a nosocomial infection compared with 58 ( 38 % ) of 152 patients in the EN group ( hazard ratio 0·65 , 95 % CI 0·43 - 0·97 ; p=0·0338 ) , and the SPN group had a lower mean number of nosocomial infections per patient ( -0·42 [ -0·79 to -0·05 ] ; p=0·0248 ) . INTERPRETATION Individually optimised energy supplementation with SPN starting 4 days after ICU admission could reduce nosocomial infections and should be considered as a strategy to improve clinical outcome in patients in the ICU for whom EN is insufficient . FUNDING Foundation Nutrition 2000Plus , ICU Quality Funds , Baxter , and Fresenius Kabi Background Nutrition guidelines recommendations differ on the use of parenteral nutrition ( PN ) , and existing clinical trial data are inconclusive . Our recent observational data show that amounts of energy/protein received early in the intensive care unit ( ICU ) affect patient mortality , particularly for inadequate nutrition intake in patients with body mass indices ( BMI s ) of < 25 or > 35 . Thus , we hypothesized increased nutrition delivery via supplemental PN ( SPN ) + enteral nutrition ( EN ) to underweight and obese ICU patients would improve 60-day survival and quality of life ( QoL ) versus usual care ( EN alone ) . Methods In this multicenter , r and omized , controlled pilot trial completed in 11 centers across four countries , adult ICU patients with acute respiratory failure expected to require mechanical ventilation for > 72 hours and with a BMI of < 25 or ≥35 were r and omized to receive EN alone or SPN + EN to reach 100 % of their prescribed nutrition goal for 7 days after r and omization . The primary aim of this pilot trial was to achieve a 30 % improvement in nutrition delivery . Results In total , 125 patients were enrolled . Over the first 7 post-r and omization ICU days , patients in the SPN + EN arm had a 26 % increase in delivered calories and protein , whereas patients in the EN-alone arm had a 22 % increase ( both p < 0.001 ) . Surgical ICU patients received poorer EN nutrition delivery and had a significantly greater increase in calorie and protein delivery when receiving SPN versus medical ICU patients . SPN proved feasible to deliver with our prescribed protocol . In this pilot trial , no significant outcome differences were observed between groups , including no difference in infection risk . Potential , although statistically insignificant , trends of reduced hospital mortality and improved discharge functional outcomes and QoL outcomes in the SPN + EN group versus the EN-alone group were observed . Conclusions Provision of SPN + EN significantly increased calorie/protein delivery over the first week of ICU residence versus EN alone . This was achieved with no increased infection risk . Given feasibility and consistent encouraging trends in hospital mortality , QoL , and functional endpoints , a full-scale trial of SPN powered to assess these clinical outcome endpoints in high-nutritional-risk ICU patients is indicated — potentially focusing on the more poorly EN-fed surgical ICU setting .Trial registration Objective : To determine whether nutrient intake by early enteral nutrition with parenteral nutrition improves levels of retinol-binding protein and prealbumin ( primary endpoint ) and reduce morbidity and mortality ( secondary endpoint ) in ICU patients . Design : Prospect i ve , double-blind , and r and omized , placebo-controlled study . Setting : Two intensive care units in a tertiary institution . Patients and participants : 120 patients in two groups of 60.¶ Interventions : Patients received either enteral plus parenteral nutrition ( treatment group ) or enteral nutrition plus placebo ( placebo group ) for 4–7 days after initiation of nutritional support . Measurements and results : Retinol-binding protein ( P = 0.0496 ) and prealbumin ( P = 0.0369 ) increased significantly in the treatment group from day 0 to day 7 . There was no reduction in morbidity in ICU . There was no difference in OMEGA score ( 263 vs. 244 ) and length of stay in the ICU ( 16.9 vs. 17.3 ) , but a reduction in length of stay at hospital ( 31.2 ± 18.5 vs. 33.7 ± 27.7 , P = 0.0022 ) . Mortality on day 90 ( 17 vs. 18 ) and after 2 years ( 24 vs. 24 ) was identical . Conclusions : Although it enhances nutrient intake and corrects nutritional parameters such as RBP and prealbumin more rapidly , within 1 week , supplemental parenteral nutrition has no clinical ly relevant effect on outcome in ICU patients at the early phase of nutritional support This prospect i ve r and omized controlled clinical trial compares the effects of early parenteral nutrition and traditional delayed enteral nutrition upon the outcome of head-injured patients . Thirty-eight head-injured patients were r and omly assigned to receive total parenteral nutrition ( TPN ) or st and ard enteral nutrition ( SEN ) . Clinical and nutritional data were collected on all patients until death or for 18 days of hospitalization . Survival and functional recovery were monitored in survivors for 1 year . Of the 38 patients , 18 were r and omized to the SEN group and 20 to the TPN group . Demographically , the two groups of patients were similar on admission . There was no significant difference in the severity of head injury between the two groups as measured by the Glasgow Coma Scale ( p = 0.52 ) . The outcome for the two groups was quite different , with eight of the 18 SEN patients dying within 18 days of injury , whereas no patient in the TPN group died within this period ( p less than 0.0001 ) . The basis for the improved survival in the TPN patients appears to be improved nutrition . The TPN patients had a more positive nitrogen balance ( p less than 0.06 ) , and a higher serum albumin level and total lymphocyte count . More adequate nutritional status may have improved the patients ' immunocompetence , result ing in decreased susceptibility to sepsis . The data from this study strongly support the favorable effect of early TPN on survival from head injury The use of total parenteral nutrition ( TPN ) , in the critically ill , may be associated with the translocation of bacteria and their products from the lumen of the gastrointestinal tract ( GIT ) to the systemic circulation . We report a study comparing the effects of TPN and enteral nutrition ( EN ) on GIT function . Twenty-four critically ill patients were r and omly allocated to receive TPN or EN . GIT absorption was measured by urinary recovery of D-xylose and 3-O-methyl-D-glucose ( 3O MG ) after enteral administration . The ratio between urinary recovery of lactulose and L-rhamnose ( L/R ) was used to measure GIT mucosal permeability . Results are expressed as the percentage of enterally administered saccharide recovered . Measurements were performed at entry to the study and on every subsequent third day . Baseline recovery of D-xylose ( 5.95 + /- 1.61 % , EN ; 6.56 + /- 3.38 % , TPN ) and 3O MG ( 12.35 + /- 4.06 % , EN ; 7.96 + /- 4.19 % , TPN ) was significantly lower than for the controls ( 35.03 + /- 1.40 % for D-xylose , p < 0.05 compared to both study groups ; 49.20 + /- 1.98 % for 3O MG , p < 0.05 compared to both study groups ) . Baseline L/R ratio was increased ( 0.292 + /- 0.072 % , EN ; 0.463 + /- 0.118 % , TPN ) compared with the controls ( 0.038 + /- 0.006 % , p < 0.05 compared to both study groups ) . In the EN group , the L/R ratio displayed a progressive , significant fall . In the TPN group , no significant change in the L/R ratio occurred . This study demonstrates that GIT dysfunction is evident in critically ill patients and suggests that loss of GIT mucosal integrity is reversed by the institution of EN Background For critically ill patients treated in intensive care units ( ICU ) , two feeding strategies are currently being advocated , one by American/Canadian and the other by European expert guidelines . These guidelines differ particularly in the timing of initiating parenteral nutrition ( PN ) in patients for whom enteral nutrition ( EN ) does not reach caloric targets . Methods / Design The EPaNIC trial is an investigator-initiated , non-commercial , multi-center , r and omized , controlled , clinical trial with a parallel group design . This study compares early ( European guideline ) versus late ( American/Canadian guideline ) initiation of PN when EN fails to reach a caloric target . In the early PN group , PN is initiated within 24 - 48 hours after ICU admission to complete early enteral nutrition ( EN ) up to a calculated nutritional target . In the late PN group , PN completing EN is initiated when the target is not reached on day 8 . In both groups , the same early EN protocol is applied . The study is design ed to compare clinical outcome ( morbidity and mortality ) in the 2 study arms as well as to address several mechanistical questions . We here describe the EPaNIC study protocol and the statistical analysis plan for the primary report of the clinical results . Discussion The study has been initiated as planned on august 01 2007 . One interim analysis advised continuation of the trial . The study will be completed in February 2011.Trial Registration Clinical Trials ( NCT ) : BACKGROUND & AIMS Enteral nutrition ( EN ) is the preferred method of nutrition support in hospitalized patients but only 50 - 90 % of the required calories are actually delivered . In order to identify where our nutrition support team ( NST ) should focus its activity , we prospect ively evaluated the level of coverage of energy and protein needs during the first 5 days of EN in intensive care unit ( ICU ) and non-ICU patients and the relationship of energy and protein coverage with serum albumin , transthryretin , insulin-like growth factor-1 ( IGF-1 ) and C-reactive protein ( CRP ) . METHODS Subjects ( n=183 ) who required nutrition support and received EN were prospect ively recruited . Calorie prescription was 20 and 25 , 25 and 30 kcal/kg BW for women and men 60 years and < 60 years , respectively . Protein needs were estimated as 1.2 g protein/kg BW . Logistic regression analysis was used to estimate odds ratios ( OR ) for energy and protein delivery 66.6 % and < 66.6 % and albumin , transthryretin , IGF-1 ( low vs. normal ) and CRP ( high vs. normal ) in ventilated vs. non-ventilated patients . RESULTS Significantly more mechanically ventilated than non-ventilated patients received < 66.6 % of energy ( 71 % vs. 48 % ) and protein ( 96 % vs. 65 % ) . The ventilated patients were more likely to be energy ( OR 2.1 , CI 1.1 - 4.0 ) and protein ( OR 15.7 , CI 4.9 - 50.8 ) underfed than non-ventilated patients . There was a significant association on day 5 between low protein delivery and low albumin ( OR 2.9 , CI 1.3 - 6.5 ) , low transthyretin ( OR 3.0 , CI 1.4 - 6.5 ) , low IGF-1 ( OR 2.8 , CI 1.2 - 6.7 ) and high CRP ( OR 3.5 , CI 1.6 - 7.8 ) . CONCLUSIONS The energy and protein needs of hospitalized patients are not met during the first 5 days of EN . Ventilated patients are more likely to be energy and protein underfed than non-ventilated patients and to have low plasma protein level . These findings support our decision to intensify EN monitoring by our NST in ventilated patients to optimize their nutritional coverage Fifty-one brain-injured patients with peak 24-hour admission Glasgow Coma Scale ( GCS ) scores of 4 to 10 were prospect ively r and omly assigned to receive total parenteral ( TPN ) or enteral ( EN ) nutrition . Patients were studied from hospital admission to 18 days postinjury . Outcome was assessed by the Glasgow Outcome Scale at 3 months , 6 months , and 1 year postinjury . The TPN group received a significantly higher cumulative mean intake of protein than the EN group ( mean + /- st and ard error of the mean : 1.35 + /- 0.12 vs. 0.91 + /- 0.9 gm/kg/day ; p = 0.004 ) . Mean cumulative caloric balance was also significantly higher in the TPN than in the EN group ( 75.6 % + /- 5.13 % vs. 59 % + /- 4.26 % ; p = 0.02 ) . Nitrogen balance was significantly more negative in the EN group during the 1st week postinjury ( p = 0.002 ) . The incidence of pneumonia , urinary tract infections , septic shock , and infections was not significantly different between groups . Classic nutritional assessment parameters such as anergy screens , total lymphocyte counts , and albumin levels were not significantly different between groups . The 11 patients in the EN group who did not tolerate tube feedings for 1 week postinjury had a significantly higher incidence of septic shock ( p = 0.008 ) . The change over time in GCS scores between groups was significantly different , with the TPN group showing a mean four-point increase in GCS score compared with a three-point increase in the EN group ( p = 0.02 ) . At 3 months the TPN group had a significantly higher percentage of favorable outcomes ( 43.5 % vs. 17.9 % , respectively ; p = 0.05 ) . At 6 months , 43.5 % of the TPN group had a favorable outcome while 32.1 % of the EN group had a favorable outcome ( p = 0.29 ) . By 1 year , 47.8 % of the TPN group and 32.1 % of the EN group had a favorable outcome ( p = 0.20 ) . In conclusion , more calories and protein usually can be administered to acute brain injury patients via the TPN route than by EN feedings via nasogastric or nasoduodenal routes . Traditional parameters for nutritional assessment are not useful in study ing the efficacy of nutritional support during the first 2 weeks after head injury . Neurological recovery from head injury occurs more rapidly in patients with better early nutritional support This study assessed the feasibility and effectiveness of jejunal feeding ( JF ) after surgery due to secondary peritonitis or failed conservative therapy of severe pancreatitis . Of 60 patients , 30 were r and omly assigned to receive postoperative JF and the remaining 30 constituted the control group . Acute Physiology and Chronic Health Evaluation II , nutritional intake , systemic inflammatory response syndrome , and outcomes were measured . Patients in JF group received the daily mean of 1294.6 ( 362.6 ) kcal including 830.6 ( 372.7.0 ) kcal enterally , versus 472.8 ( 155.8 ) kcal daily in the control group ( P < 0.0001 ) . There were fewer complications in the JF patients , with no significant difference ; length of stay in the intensive care unit and in the hospital did not differ . The frequency of systemic inflammatory response syndrome was similar in both groups , but outcomes differed . The first surgical intervention result ed in 3.3 % of relaparotomies in JF patients , caused by unresolved peritonitis , versus 26.7 % in the control subjects ( P = 0.03 ) . Recovery of bowel transit took significantly less time in the JF patients ( mean : 54.6 h versus 76.8 h in control subjects , P = 0.01 ) . JF result ed in 3.3 % mortality as opposed to 23.3 % in the control group ( P = 0.05 ) . In conclusion , JF is feasible and effective in postoperative treatment of patients due to secondary peritonitis or severe pancreatitis . Improved bowel and peritoneal function could be the main impact of JF OBJECTIVE To compare metabolic , nutritional and epidemiological data in two groups of patients , one receiving total enteral nutrition , via nasoenteric tube , and one receiving both enteral and parenteral nutrition . DESIGN A prospect i ve , r and omized study . SETTING A general ICU , with both medical and surgical patients , in a big regional University and National Health Service hospital . PATIENTS 24 patients requiring Intensive Care after major surgery or because suffering from severe head injury or major neurological impairment . INTERVENTIONS All patients initially received total parenteral nutrition : after 4 days 12 patients were " weaned " to total enteral nutrition and 12 stayed on mixed parenteral and enteral nutrition . LABORATORY INVESTIGATIONS AND OBSERVATIONAL DATA : Blood levels of albumin , prealbumin , transferrin , ALT , AST , bilirubin , blood urea , blood glucose , total linfocite count , and nutritional and epidemiological data such as nitrogen balance , calorie intake , diarrhea incidence , blood and sputum cultures and radiologic evidence of pneumonia are analysed . RESULTS At T1 , NET patients were able to reduce their nitrogen losses ( 0.27.1 g/kg + /-0.12 vs 0.35 + /- 0.13 at TO ; p < 0.05 ) and improve nitrogen balance ( -9 + /- 7 vs -2 + /- 6 at T0 ; p < 0.05 ) ; they also had a better total linfocite count ( 2034 + /- 304 vs. 1413 + /- 360 of the MISTA group ; p < 0.05 ) , and a lower incidence of pneumonia as documented by sputum cultures and radiograms . CONCLUSIONS Patients fed with both parenteral and enteral nutrition did no better than those on total enteral nutrition as far as nutritional and metabolic indices were concerned ; they also seemed more prone to infections than those on total enteral nutrition , indicating that mixed nutrition may result in more stable feeding , but this does not seem to have any beneficial nutritional , immunological and metabolic effect BACKGROUND Direct experimental evidence suggests that total enteral nutrition ( TEN ) reduces septic morbidity compared with bowel rest and total parenteral nutrition ( TPN ) and that mucosal support and maintenance of gut barrier function is a key mechanism . This effect is supported indirectly by clinical studies , but this question has not previously been investigated directly in the postoperative patient . This study examined the hypothesis that early enteral feeding after major upper gastrointestinal surgery may modulate gut barrier function and decrease the risk of major infective complications compared with bowel rest and parenteral nutrition . METHODS A r and omized clinical trial of 67 patients ( TPN = 34 ; TEN = 33 ) fed postoperatively for 7 days was performed . Thirty-day major morbidity and mortality were monitored . Intestinal permeability was measured using the lactulose/mannitol test preoperatively and on postoperative days 1 and 7 . Systemic anti-endotoxin core immunoglobulin G and M antibodies and serum albumin and C-reactive protein were quantified at these time points . RESULTS No clinical benefit was observed in patients fed enterally compared with the parenterally fed group . Intestinal permeability was increased on the 1st postoperative day in association with evidence of endotoxin exposure . By day 7 , enteral feeding compared with parenteral feeding had failed to significantly influence any of the gut barrier or systemic parameters . CONCLUSIONS This r and omized controlled trial of TEN vs TPN after major upper gastrointestinal surgery failed to show a clinical benefit for the enteral route . Moreover , enteral nutrition did not modulate gut barrier function postoperatively Introduction The optimal nutritional strategy remains controversial , particularly in severely septic patients . Our aim was to analyze the effect of three nutritional strategies — enteral ( EN ) , parenteral ( PN ) , and combined nutrition (EN+PN)—on the outcome of patients with severe sepsis or septic shock . Patients and methods This secondary analysis of the prospect i ve , r and omized – controlled , multicenter “ Intensive Insulin Therapy and Pentastarch Resuscitation in Severe Sepsis ( VISEP ) ” trial only included patients with a length of stay in the intensive care unit ( ICU ) of more than 7 days . Besides patient characteristics , data on nutrition therapy were collected daily for up to 21 days . Morbidity as measured by the mean Sequential Organ Failure Assessment ( SOFA ) score , incidence of secondary infections , renal replacement therapy , ventilator-free days and severe hypoglycemia , length of ICU stay , and mortality at 90 days were compared between the three nutritional strategies . Results In all , 353 patients were included in the analysis with the majority ( 68.5 % ) receiving EN+PN , 24.4 % receiving EN , and only 7.1 % receiving PN . Median caloric intake was 918 kcal/day ( EN ) , 1,210 kcal/day ( PN ) , and 1,343 kcal/day ( EN+PN ; p < 0.001 ) . In the latter group , calories were predominantly administered via the parenteral route within the first week . The rate of death at 90 days was lower with EN than with EN+PN ( 26.7 % vs. 41.3 % , p = 0.048 ) , as was the rate of secondary infections , renal replacement therapy , and duration of mechanical ventilation . In the adjusted Cox regression analysis , the effect on mortality [ hazard ratio ( HR ) = 1.86 , 95 % confidence interval ( CI ) : 1.16–2.98 , p = 0.010 ] and the rate of secondary infections ( HR = 1.89 , 95 % CI : 1.27–2.81 , p = 0.002 ) remained different between EN and EN+PN . Conclusion In patients with severe sepsis or septic shock and prolonged ICU stay , EN alone was associated with improved clinical outcome compared to EN+PN . This hypothesis-generating result has to be confirmed by a r and omized-controlled trial in this specific patient population .ZusammenfassungHintergrundEine optimale Ernährungsstrategie für Patienten mit schwerer Sepsis ist nach wie vor nicht eindeutig geklärt . Wir untersuchten den Einfluss unterschiedlicher Ernährungsstrategien ( enteral , EN ; parenteral , PN ; und kombinierte Ernährung , EN+PN ) auf den klinischen Verlauf bei Patienten mit schwerer Sepsis und septischem Schock . Patienten und Method enDie vorliegende Sekundäranalyse der prospektiven , r and omisierten , kontrollierten , multizentrischen Studie „ Intensive Insulin Therapy and Pentastarch Resuscitation in Severe Sepsis ( VISEP ) “ wurde auf Patienten mit einer Intensivliegedauer > 7 Tage beschränkt . Neben den Patientencharakteristika wurden Date n zur täglichen Ernährungstherapie über einen Zeitraum von bis zu 21 Tagen gesammelt . Der Einfluss auf die Morbidität , gemessen an der Höhe des mittleren SOFA-Scores , die Häufigkeit von Sekundärinfektionen , Nierenersatztherapie , beatmungsfreien Tagen und schweren Hypoglykämien , Länge des Aufenthalts auf der Intensivstation sowie die 90-Tage-Sterblichkeit wurden zwischen den angewendeten Ernährungsstrategien verglichen . ErgebnisseVon 353 in die Analyse einbezogenen Patienten erhielten 68,5 % EN+PN , 24,4 % EN und 7,1 % PN . Die täglich zugeführte Kalorienmenge lag i m Median bei 918 kcal ( EN ) , 1210 kcal ( PN ) und 1343 kcal ( EN+PN ; p < 0,001 ) . Hierbei wurden die Kalorien innerhalb der ersten Woche den Patienten mit EN+PN überwiegend parenteral zugeführt . Die 90-Tage-Sterblichkeit war bei Patienten mit EN verglichen mit EN+PN niedriger ( 26,7 vs. 41,3 % ; p = 0,048 ) , ebenso die Rate infektiöser Komplikationen , die Notwendigkeit einer Nierenersatztherapie wie auch die Beatmungsdauer . In einer u. a. für die Krankheitsschwere adjustierten Cox-Regressionsanalyse blieb der Unterschied i m Sterblichkeitsrisiko ( Hazard Ratio , HR : 1,86 ; 95 % -Konfidenzintervall , 95%-KI : 1,16–2,98 ; p = 0,010 ) und bei den infektiösen Komplikationen ( HR : 1,89 ; 95 % -KI : 1,27–2,81 ; p = 0,002 ) zwischen den Patienten mit EN+PN und EN bestehen . SchlussfolgerungBei Patienten mit schwerer Sepsis und prolongierter Intensivliegedauer war EN verglichen mit EN+PN mit einem besseren klinischen Verlauf assoziiert . Diese i m Kontext der vorliegenden Sekundäranalyse generierte Hypothese sollte anh and einer r and omisiert-kontrollierten Studie in dieser spezifischen Patienten population überprüft werden OBJECTIVE To evaluate the impact of the route of administration of artificial nutrition and the composition of the diet on outcome . DESIGN Prospect i ve , r and omized , clinical trial . SETTING Department of surgery , university hospital . PATIENTS One hundred sixty-six consecutive patients undergoing curative surgery for gastric or pancreatic cancer . INTERVENTIONS At operation , the patients were r and omized into three groups to receive : a ) a st and ard enteral formula ( control group ; n = 55 ) ; b ) the same enteral formula enriched with arginine , RNA , and omega-3 fatty acids ( enriched group ; n = 55 ) ; and c ) total parenteral nutrition ( TPN group ; n = 56 ) . The three regimens were isocaloric and isonitrogenous . Enteral nutrition was started within 12 hrs following surgery . The infusion rate was progressively increased to reach the nutritional goal ( 25 kcal/kg/day ) on postoperative day 4 . MEASUREMENTS AND MAIN RESULTS Tolerance of enteral feeding , rate and severity of postoperative complications , and length of hospital stay were recorded . Early enteral infusion was well tolerated . Side effects were recorded in 22.7 % of the patients , but only 6.3 % did not reach the nutritional goal . The enriched group had a lower severity of infection than the parenteral group ( 4.0 vs. 8.6 ; p < .05 ) . In subgroups of malnourished ( n = 78 ) and homologous transfused patients ( n = 42 ) , the administration of the enriched formula significantly reduced both severity of infection and length of stay compared with the parenteral group ( p < .05 ) . Moreover , in transfused patients , the rate of septic complications was 20.0 % in the enriched group , 38.4 % in the control group , and 42.8 % in the TPN group . CONCLUSIONS Early enteral feeding is a suitable alternative to TPN after major abdominal surgery . The use of the enriched diet appears to be more beneficial in malnourished and transfused patients Nasogastric tube-assisted enteral feeding and parenteral feeding are utilized for nutritional support after major surgery . Although these nutritional supports have been compared before , there have been no comparative trials following surgery for laryngeal and pharyngeal cancer . In this study , 81 patients were r and omized to total parenteral nutrition ( TPN ) or nasogastric tube nutrition ( NGTN ) after laryngopharyngeal cancer surgery . The two groups were well-matched demographically and clinical ly . Clinical outcomes such as time of commencement of oral feeding and hospital stay and complications such as fistula were similar in both groups . One case in the TPN group had catheter-related sepsis , whereas aspiration pneumonia occurred in four cases ( 9.8 % ) in the NGTN group . The daily cost of NGTN was $ 11.81 cheaper than that of TPN . Subjective symptoms of nasal and pharyngeal discomfort and scores on subjective swallowing were more severe in the NGTN group within the first postoperative week but became similar thereafter . Although there was no difference in objective postoperative outcomes between both groups , these results imply that each method had particular advantages and disadvantages . Nutritional support after laryngopharyngeal cancer surgery should be determined after full consideration of each patient ’s conditions and surgical details along with economics OBJECTIVE To evaluate the protective effect of enteral nutrition on organ function in critically ill patients . METHODS Forty-two critically ill patients were r and omly divided into enteral nutrition group ( n=14 ) , total parenteral nutrition group ( n=14 ) , and control group ( n=14 ) . The partial pressure of oxygen in artery ( PaO(2 ) ) , partial pressure of carbon dioxide in artery ( PaCO(2 ) ) , white blood cell count ( WBC ) and the plasma contents of serum alanine aminotransferase ( ALT ) , blood urea nitrogen ( BUN ) , and the percentage of gastrointestinal haemorrhage were determined one week after the nutritional support was initiated . RESULTS The WBC , the plasma contents of ALT , and the incidence of gastrointestinal haemorrhage were significantly higher in control group patients [ (11.70+/-2.85)x10(9)/L , ( 59.69+/-20.32 ) U/L , 42.9 % ] than those in enteral nutrition group patients [ (9.62+/-3.30)x10(9)/L , ( 40.68+/-22.11 ) U/L , 21.4 % , P<0.05 ] and total parenteral nutrition group[(9.82+/-3.50)x10(9)/L , ( 40.98+/-21.87 ) U/L , P<0.05 , 42.9 % ] , However , PaO(2 ) in control group patients ( 62.78+/-4.95 ) mm Hg was markedly lower than those in enteral nutrition group and parenteral nutrition group patients [ ( 80.85+/-14.03 ) mm Hg , ( 79.88+/-13.73 ) mm Hg , both P<0.05 ] . There was no significant difference in PaCO(2 ) and the plasma contents of BUN among the three groups 1 week after treatment were given ( all P>0.05 ) . CONCLUSION Early stage enteral nutrition could well surpass total parenteral nutrition . It is conducive to protecting gastrointestinal function , preventing bacterial translocation , alleviating systemic inflammatory response and subsequent multiple organ failure among critically ill patients Objective To compare the mortality of critically ill patients given either enteral feeding with an immune-enhancing formula or parenteral nutrition ( PN ) . We report the results of a planned interim analysis on patients with severe sepsis which was undertaken earlier than planned once a meta- analysis suggested excess mortality in patients with severe sepsis given enteral immunonutrition . Design R and omised multicentre unblinded controlled clinical trial . Setting Thirty-three General Intensive Care Units in Italy . Patients and participants Among the 237 recruited patients , 39 had severe sepsis or septic shock ; 21 of them received PN . Interventions Eligible patients received either total PN or enteral nutrition , the latter containing extra L-arginine , omega-3 fatty acids , vitamin E , beta carotene , zinc , and selenium . Measurements and results The primary endpoint for the subgroup analysis on patients with severe sepsis was mortality on Intensive Care Unit ( ICU ) . The ICU mortality of patients with severe sepsis given enteral nutrition ( EN ) was higher than for those given PN ( 44.4 % vs 14.3 % ; p=0.039 ) . More patients given EN than patients given PN still had severe sepsis when they died ( 38.9 % vs 9.5 % , p=0.055 ) . Recruitment of patients with severe sepsis was subsequently stopped . Conclusions Our results show that enteral immunonutrition , compared to PN , may be associated with excess mortality in patients with severe sepsis Hypercatabolism after operations has a negative influence on nutritional status , the healing process , infective complications and hospital stay . Moreover , the immune status of the patient has been shown to be equally important for septic morbidity and mortality . It is extensively accepted that in critical situations , an adequate nutritional support ( enteral or parenteral ) is absolutely necessary , but subjects such as the best way of feeding , the kind of nutrients to be used and the administration time are still debatable issues . Our aim was to evaluate the effectiveness ( nutritional and immunological features ) and clinical outcomes ( septic morbidity and mortality ) of total parenteral nutrition ( TPN ) , early enteral nutrition and early enteral immunonutrition ( EEN , EEIN ) in 171 patients undergoing major abdominal and urological surgery for neoplastic pathology . Our prospect i ve , r and omised study showed no significant differences among the 3 nutritional supports ( TPN , EEN , EEIN ) with regard to restoration of normal nitrogen balance during the acute phase of surgical stress . No correlations were found in the 3 groups with immunoglobulin percentage , lymphocyte sub population s and their functional patterns as studied by specific immunological tests . The skin test , on the other h and , seems to be more representative of the immune condition of the patients , demonstrating a faster improvement in immunological status in the EEIN group as compared to the control group . A smaller percentage of septic morbidity and mortality was found in both enteral nutritional groups ( EEN and EEIN ) , although there was a statistically significant difference only between the TPN and EEIN groups . The hospital stay was 3.5 days shorter in enteral feeding patients ( EEN , EEIN ) . Finally , EEN was less expensive than the other nutritional conditions , this result depending on the cost of the different material s used ( infusion sets , linear filters , prepacked diets , etc . ) Purpose To determine whether nutritional support guided by repeated measurements of resting energy requirements improves the outcome of critically ill patients . Methods This was a prospect i ve , r and omized , single-center , pilot clinical trial conducted in an adult general intensive care ( ICU ) unit . The study population comprised mechanically ventilated patients ( n = 130 ) expected to stay in ICU more than 3 days . Patients were r and omized to receive enteral nutrition ( EN ) with an energy target determined either ( 1 ) by repeated indirect calorimetry measurements ( study group , n = 56 ) , or ( 2 ) according to 25 kcal/kg/day ( control group , n = 56 ) . EN was supplemented with parenteral nutrition when required . Results The primary outcome was hospital mortality . Measured pre- study resting energy expenditure ( REE ) was similar in both groups ( 1,976 ± 468 vs. 1,838 ± 468 kcal , p = 0.6 ) . Patients in the study group had a higher mean energy ( 2,086 ± 460 vs. 1,480 ± 356 kcal/day , p = 0.01 ) and protein intake ( 76 ± 16 vs. 53 ± 16 g/day , p = 0.01 ) . There was a trend towards an improved hospital mortality in the intention to treat group ( 21/65 patients , 32.3 % vs. 31/65 patients , 47.7 % , p = 0.058 ) whereas length of ventilation ( 16.1 ± 14.7 vs. 10.5 ± 8.3 days , p = 0.03 ) and ICU stay ( 17.2 ± 14.6 vs. 11.7 ± 8.4 , p = 0.04 ) were increased . Conclusions In this single-center pilot study a bundle comprising actively supervised nutritional intervention and providing near target energy requirements based on repeated energy measurements was achievable in a general ICU and may be associated with lower hospital mortality BACKGROUND There appears to be an emerging consensus that early postoperative nutritional support benefits the high-risk patient by decreasing septic morbidity , maintaining immunocompetence and improving wound healing . Enteral nutrition via a feeding jejunostomy has been associated with serious complications , with a reported mortality rate as high as 10 % , while total parenteral nutrition has also been associated with a wide variety of complications . METHODS Ninety-seven patients undergoing oesophagectomy or gastrectomy underwent pre-operative nutritional assessment and were r and omized to receive either total parenteral nutrition ( 47 patients ) or enteral nutrition ( 50 patients ) . RESULTS There was no significant difference in the number of catheter-related complications between the two groups , but 9 ( 45 % ) patients in the total parenteral nutrition group had major morbidity ( potentially fatal in two patients ) requiring active intervention . CONCLUSIONS This study demonstrates enteral nutrition to be safe and associated with mainly reversible minor complications . It is probable that immediate postoperative enteral feeding conserves the gut 's integrity . Whether this leads to a reduction in postoperative septic complications has not been demonstrated by this study although there appears to be a trend in this direction , supporting the concept of enteral feeding as ' primary therapy ' . This can be safely , simply and economically achieved using a feeding jejunostomy placed at the time of surgery BACKGROUND Controversy exists about the timing of the initiation of parenteral nutrition in critically ill adults in whom caloric targets can not be met by enteral nutrition alone . METHODS In this r and omized , multicenter trial , we compared early initiation of parenteral nutrition ( European guidelines ) with late initiation ( American and Canadian guidelines ) in adults in the intensive care unit ( ICU ) to supplement insufficient enteral nutrition . In 2312 patients , parenteral nutrition was initiated within 48 hours after ICU admission ( early-initiation group ) , whereas in 2328 patients , parenteral nutrition was not initiated before day 8 ( late-initiation group ) . A protocol for the early initiation of enteral nutrition was applied to both groups , and insulin was infused to achieve normoglycemia . RESULTS Patients in the late-initiation group had a relative increase of 6.3 % in the likelihood of being discharged alive earlier from the ICU ( hazard ratio , 1.06 ; 95 % confidence interval [ CI ] , 1.00 to 1.13 ; P=0.04 ) and from the hospital ( hazard ratio , 1.06 ; 95 % CI , 1.00 to 1.13 ; P=0.04 ) , without evidence of decreased functional status at hospital discharge . Rates of death in the ICU and in the hospital and rates of survival at 90 days were similar in the two groups . Patients in the late-initiation group , as compared with the early-initiation group , had fewer ICU infections ( 22.8 % vs. 26.2 % , P=0.008 ) and a lower incidence of cholestasis ( P<0.001 ) . The late-initiation group had a relative reduction of 9.7 % in the proportion of patients requiring more than 2 days of mechanical ventilation ( P=0.006 ) , a median reduction of 3 days in the duration of renal-replacement therapy ( P=0.008 ) , and a mean reduction in health care costs of € 1,110 ( about $ 1,600 ) ( P=0.04 ) . CONCLUSIONS Late initiation of parenteral nutrition was associated with faster recovery and fewer complications , as compared with early initiation . ( Funded by the Methusalem program of the Flemish government and others ; EPaNIC Clinical Trials.gov number , NCT00512122 . ) BACKGROUND / AIMS Early enteral nutrition ( EEN ) has benefits in reducing infectious complication , length of stay ( LOS ) and preserving liver function . There are few data about the effect of EEN in the patients who had total gastrectomy . The aim of this r and omized and prospect i ve study was to evaluate the effect of EEN after total gastrectomy on nutritional status , liver function , complications and LOS , compared to total parenteral nutrition ( TPN ) in patients with gastric cancer . METHODS Among 56 patients with gastric cancer , 36 and 20 were r and omly assigned to EEN and TPN groups , and finally 17 and 16 completed EEN and TPN schedules , respectively . The nutritional parameters , liver function , LOS and abdominal symptoms were compared between 2 groups on pre-operative day and post-operative 7th day . RESULTS There was no significant difference in the nutritional parameters , liver function between EEN and TPN groups . Vomiting and abdominal distention were more frequent in EEN than TPN group ( 2 vs. 0 cases , p=0.485 ; 1 vs. 0 case , p=1.000 , respectively ) , while increased AST , ALT and total bilirubin were more common in TPN than EEN group ( 4 vs. 2 cases , p=0.398 ; 1 vs. 0 case , p=0.485 , respectively without statistical significance ) . LOS was shorter in EEN than TPN group without statistical significance ( 12 vs. 13 days , p=0.289 ) . CONCLUSIONS No significant differences were found in the nutritional status parameters , liver function , complications and LOS between EEN and TPN groups on 7th day after total gastrectomy . Further large scale studies on the advantages and disadvantages of EEN after total gastrectomy are warranted BACKGROUND Uncertainty exists about the most effective route for delivery of early nutritional support in critically ill adults . We hypothesized that delivery through the parenteral route is superior to that through the enteral route . METHODS We conducted a pragmatic , r and omized trial involving adults with an unplanned admission to one of 33 English intensive care units . We r and omly assigned patients who could be fed through either the parenteral or the enteral route to a delivery route , with nutritional support initiated within 36 hours after admission and continued for up to 5 days . The primary outcome was all-cause mortality at 30 days . RESULTS We enrolled 2400 patients ; 2388 ( 99.5 % ) were included in the analysis ( 1191 in the parenteral group and 1197 in the enteral group ) . By 30 days , 393 of 1188 patients ( 33.1 % ) in the parenteral group and 409 of 1195 patients ( 34.2 % ) in the enteral group had died ( relative risk in parenteral group , 0.97 ; 95 % confidence interval , 0.86 to 1.08 ; P=0.57 ) . There were significant reductions in the parenteral group , as compared with the enteral group , in rates of hypoglycemia ( 44 patients [ 3.7 % ] vs. 74 patients [ 6.2 % ] ; P=0.006 ) and vomiting ( 100 patients [ 8.4 % ] vs. 194 patients [ 16.2 % ] ; P<0.001 ) . There were no significant differences between the parenteral group and the enteral group in the mean number of treated infectious complications ( 0.22 vs. 0.21 ; P=0.72 ) , 90-day mortality ( 442 of 1184 patients [ 37.3 % ] vs. 464 of 1188 patients [ 39.1 % ] , P=0.40 ) , in rates of 14 other secondary outcomes , or in rates of adverse events . Caloric intake was similar in the two groups , with the target intake not achieved in most patients . CONCLUSIONS We found no significant difference in 30-day mortality associated with the route of delivery of early nutritional support in critically ill adults . ( Funded by the United Kingdom National Institute for Health Research ; CALORIES Current Controlled Trials number , IS RCT N17386141 . ) BACKGROUND The CALORIES trial is a pragmatic , open , multicentre , r and omised controlled trial ( RCT ) of the clinical effectiveness and cost-effectiveness of early nutritional support via the parenteral route compared with early nutritional support via the enteral route in unplanned admissions to adult general critical care units ( CCUs ) in the United Kingdom . The trial derives from the need for a large , pragmatic RCT to determine the optimal route of delivery for early nutritional support in the critically ill . OBJECTIVE To describe the proposed statistical analyses for the evaluation of the clinical effectiveness in the CALORIES trial . METHODS With the primary and secondary outcomes defined precisely and the approach to safety monitoring and data collection summarised , the planned statistical analyses , including prespecified subgroups and secondary analyses , were developed and are described . RESULTS The primary outcome is all-cause mortality at 30 days . The primary analysis will be reported as a relative risk and absolute risk reduction and tested with the Fisher exact test . Prespecified subgroup analyses will be based on age , degree of malnutrition , acute severity of illness , mechanical ventilation at admission to the CCU , presence of cancer and time from CCU admission to commencement of early nutritional support . Secondary analyses include adjustment for baseline covariates . CONCLUSION In keeping with best trial practice , we have developed , described and published a statistical analysis plan for the CALORIES trial and are placing it in the public domain before inspecting data from the trial Recent animal models suggest that enteral feeding ( TEN ) compared to parenteral nutrition ( TPN ) improves resistance to infection . This prospect i ve clinical trial examined the impact of early TEN vs. TPN in the critically injured . Seventy-five patients with an abdominal trauma index ( ATI ) greater than 15 and less than 40 were r and omized at initial laparotomy to receive either TEN ( Vivonex TEN ) or TPN ( Freamine HBC 6.9 % and Trophamine 6 % ) ; both regimens contained 2.5 % fat , 33 % branched chain amino acids , and had a calorie to nitrogen ratio of 150:1 . TEN was delivered via a needle catheter jejunostomy . Nutritional support was initiated within 12 hours postoperatively in both groups , and infused at a rate sufficient to render the patients in positive nitrogen balance . The study groups ( TEN = 29 vs TPN = 30 ) were comparable in age , injury severity and initial metabolic stress . Jejunal feeding was tolerated unconditionally in 25 ( 86 % ) of the TEN group . Nitrogen balance remained equivalent throughout the study period , at day 5 TEN = -0.3 + /- 1.0 vs. TPN 0.1 + /- 0.8 gm/day . Traditional nutritional protein markers ( albumin , transferrin , and retinol binding protein ) were restored better in the TEN group . Infections developed in 5 ( 17 % ) of the TEN patients compared to 11 ( 37 % ) of the TPN group . The incidence of major septic morbidity was 3 % ( 1 = abdominal abscess ) in the TEN group contrasted to 20 % ( 2 = abdominal abscess , 6 = pneumonia ) with TPN . This clinical study demonstrates that TEN is well tolerated in the severely injured , and that early feeding via the gut reduces septic complications in the stressed patient A.S.P.E.N. and SCCM are both nonprofit organizations composed of multidisciplinary healthcare professionals . The mission of A.S.P.E.N. is to improve patient care by advancing the science and practice of clinical nutrition and metabolism . The mission of SCCM is to secure the highest quality care for all critically ill and injured patients . Guideline Limitations : These A.S.P.E.N.−SCCM Clinical Guidelines are based on general conclusions of health professionals who , in developing such guidelines , have balanced potential benefits to be derived from a particular mode of medical therapy against certain risks inherent with such therapy . However , practice guidelines are not intended as absolute requirements . The use of these practice guidelines does not in any way project or guarantee any specific benefit in outcome or survival . The judgment of the healthcare professional based on individual circumstances of the patient must always take precedence over the recommendations in these guidelines . The guidelines offer basic recommendations that are supported by review and analysis of the current literature , other national and international guidelines , and a blend of expert opinion and clinical practicality . The population of critically ill patients in an intensive care unit ( ICU ) is not homogeneous . Many of the studies on which the guidelines are based are limited by sample size , patient heterogeneity , variability in disease severity , lack of baseline nutritional status , and insufficient statistical power for analysis . Periodic Guideline Review and Up date : This particular report is an up date and expansion of guidelines published by A.S.P.E.N. and SCCM in 2009 ( 1 ) . Governing bodies of both A.S.P.E.N. and SCCM have m and ated that these guidelines be up date d every three to five years . The data base of r and omized controlled trials ( RCTs ) that served as the platform for the analysis of the literature was assembled in a joint “ harmonization process ” with the Canadian Clinical Guidelines group . Once completed , each group operated separately in their interpretation of the studies and derivation of guideline recommendations ( 2 ) . The current A.S.P.E.N. and SCCM guidelines included in this paper were derived from data obtained via literature search es by the authors through December 31 , 2013 . Although the committee was aware of l and mark studies published after this date , these data were not included in this manuscript . The process by which the literature was evaluated necessitated a common end date for the search review . Adding a last-minute l and mark trial would have introduced bias unless a formalized literature search was re-conducted for all sections of the manuscript . Target Patient Population for Guideline : The target of these guidelines is intended to be the adult ( ≥ 18 years ) critically ill patient expected to require a length of stay ( LOS ) greater than 2 or 3 days in a medical ICU ( MICU ) or surgical ICU ( SICU ) . The current guidelines were exp and ed to include a number of additional subsets of patients who met the above criteria , but were not included in the previous 2009 guidelines . Specific patient population s addressed by these exp and ed and up date d guidelines include organ failure ( pulmonary , renal , and liver ) , acute pancreatitis , surgical subsets ( trauma , traumatic brain injury [ TBI ] , open abdomen [ OA ] , and burns ) , sepsis , postoperative major surgery , chronic critically ill , and critically ill obese . These guidelines are directed toward generalized patient population s but , like any other management strategy in the ICU , nutrition therapy should be tailored to the individual patient . Target Audience : The intended use of these guidelines is for all healthcare providers involved in nutrition therapy of the critically ill , primarily physicians , nurses , dietitians , and pharmacists . Methodology : The authors compiled clinical questions reflecting key management issues in nutrition therapy . A committee of multidisciplinary experts in clinical nutrition composed of physicians , nurses , pharmacists , and dietitians was jointly convened by the two societies OBJECTIVES : The aims of this study were to define the indications for , and to evaluate the cost-effectiveness of , nutritional support in patients with acute pancreatitis . METHODS : All admissions during the 12-month period from January through December 2000 , were entered into a common management protocol consisting of an initial 48-h fast with i.v . fluids and analgesics . After 48 h , those patients who were improving were restarted on oral feeding ( group O ) . The remaining patients were r and omized to receive naso-jejunal ( group EN ) or parenteral feeding ( group TPN ) . The r and omization study was continued until 50 patients had been accrued . Outcomes in the three groups were compared with respect to length of hospital stay , duration of feeding , complications , and hospital costs . RESULTS : A total of 156 admissions were evaluated in the first 12 months . Of these , 87 % patients had mild disease , 10 % moderate , and 3 % severe ; 62 % were related to alcohol abuse , 18 % gallstones , and 8 % idiosyncratic drug reactions . Of the patients , 75 % improved on 48 h bowel rest and i.v . fluids , and were discharged within 4 days . The remainder were r and omized to jejunal elemental ( n = 26 ) or parenteral ( n = 27 ) feeding . Duration of feeding was shorter with EN ( 6.7 vs 10.8 days , p < 0.05 ) and nutrition costs were lower , representing an average cost saving of $ 2362.00 per patient fed . EN was less effective in meeting estimated nutritional requirements ( 54 vs 88 % , p < 0.0001 ) , but metabolic ( p < 0.003 ) and septic complications ( p = 0.01 ) were lower . Subgroup analysis of patients with severe disease showed similar findings . CONCLUSION : Despite concerns that metabolic expenditure is increased and that food-stimulated pancreatic secretion might exacerbate the disease process , hypocaloric enteral feeding seems to be safer and less expensive than parenteral feeding and bowel rest in patients with acute pancreatitis UNLABELLED Thirty-seven ventilator-dependent blunt trauma patients ( ISS 36 + /- 15 ) were r and omized at 24 hours after injury to receive parenteral ( TPN ) ( n = 15 ) , enteral ( TEN ) ( n = 12 ) , or parenteral plus enteral ( PN/EN ) ( n = 10 ) nutrition . The TEN and PN/EN patients had endoscopically placed transpyloric feeding tubes . Patients who had nutritional complications were two TPN ( 13 % ) , three TEN ( 25 % ) , and five PN/EN ( 50 % ) . Enteral complications were tube occlusion ( two ) , failed duodenal intubation ( one ) , patient extubation of feeding tube ( one ) , gastric reflux ( two ) , and abdominal distention ( two ) . Mortality rates were not different between the groups , but were significantly related to the nutrition-associated complications ( p = 0.01 ) : four deaths in ten ( 40 % ) with complications and one death in 27 ( 3.7 % ) without complications . All four deaths associated with complications occurred in the four with gastric reflux or abdominal distention . No deaths occurred in the other 18 TEN or PN/EN patients ( p = 0.0001 ) . Of the four deaths , three were associated with ARDS and respiratory infection ( 75 % ) . CONCLUSIONS In mechanically ventilated blunt trauma patients , endoscopic transpyloric tube placement and feeding has a substantial failure rate ( 36 % ) . Intolerance to duodenal feeding has a remarkably high mortality ( 100 % ) in patients in whom gut dysfunction may be a manifestation of injury severity or directly affect survival BACKGROUND Withholding enteral feeds after an elective gastrointestinal surgery is based on the hypothesis that this period of " nil by mouth " provides rest to the gut and promotes healing . AIMS To assess whether early postoperative naso-gastric tube feeding in the form of a balanced diet formula is safe in and beneficial to patients who have undergone surgical intervention for perforation of the gut . SETTING A surgical unit of a Medical College Hospital . DESIGN AND SUBJECTS Prospect i ve r and omised open control study . METHODS AND MATERIAL Patients undergoing surgical intervention for peritonitis following perforation of the gut were r and omised to the study group receiving feedings of a balanced diet formula through a naso-gastric tube from the second postoperative day , or the control group in which patients were managed with the conventional regimen of intravenous fluid administration . The groups were compared for incidence and duration of complications , biochemical measurements and other characteristics like weight loss/gain . STATISTICAL ANALYSIS Chi square test and " T " test . RESULTS One hundred patients were enrolled in each group . 88 % subjects in the study group achieved positive nitrogen balance on the eighth postoperative day as compared to none in the conventionally managed group . The relative risks ( 95 % confidence interval ) of morbidity from wound infection , wound dehiscence , pneumonia , leakage of anastomoses and septicaemia were 0.66 ( 0.407 - 1.091 ) , 0.44 ( 0.141 - 1.396 ) , 0.70 ( 0.431 - 1.135 ) , 0.54 ( 0.224 - 1.293 ) and 0.66 ( 0.374 - 1.503 ) respectively . Average loss of weight between the first and tenth day was 3.10 kg in the study group as compared to 5.10 kg in the conventionally managed group ( " P " value < 0.001 , 95 % Confidence Interval - 2.46 - 1.54 ) . CONCLUSION Early enteral nutrition is safe and is associated with beneficial effects such as lower weight loss , early achievement of positive nitrogen balance as compared to the conventional regimen of feeding in operated cases of gut perforation OBJECTIVE To compare the efficacy and cost of enteral and parenteral feeding after total gastrectomy . DESIGN Prospect i ve r and omised open study . SETTING University hospital , Finl and . SUBJECTS 29 patients undergoing curative total gastrectomy for gastric cancer . INTERVENTIONS 13 patients were given early enteral feeding by nasojejunal tube and 16 patients parenteral nutrition by central venous catheter . MAIN OUTCOME MEASURES Postoperative complications , duration of hospital stay , serum CRP and albumin concentrations , cost , and postoperative abdominal symptoms . RESULTS One patient in the enteral feeding group discontinued the study on day 1 . Oesophagojejunal leaks developed in one patient in each group . Infective complications occurred in 3 ( 23 % ) in the enteral group and 5 ( 31 % ) in the parenteral group . Serum CRP concentration on day six was lower in the enteral feeding group than in the parenteral feeding group ( 32 ( 16 ) g/L compared with 61 ( 41 ) g/L ; p = 0.02 ) . Enteral feeding was well tolerated . Diarrhoea developed earlier in the enteral than in the parenteral group ( days 3 - 5 compared with 5 - 7 , respectively ) but there was a tendency to an increased risk of diarrhoea in the parenteral group . Parenteral feeding was more than four times as expensive as enteral feeding . CONCLUSION Enteral nasojejunal feeding is safe and well tolerated after total gastrectomy . It is also cheaper than parenteral nutrition Background : According to international guidelines , artificial nutrition may be indicated after pancreaticoduodenectomy ( PD ) . This clinical study was design ed to evaluate whether the route of administration and the composition of the postoperative nutritional support could affect outcome . Methods : One hundred patients who underwent PD for cancer of the pancreatic head were prospect ively studied . Patients were r and omized to receive a st and ard enteral formula ( SEN ; n = 35 ) or immunonutrition with an enteral formula enriched with arginine , ω-3 fatty acids , and RNA ( IEN group ; n = 33 ) , or total parenteral nutrition ( TPN ; n = 32 ) . Postoperative feeding was started within 12 h after surgery . The three regimens were isoenergetic and isonitrogenous . Tolerance of enteral feeding , rate and severity of postoperative complications , and length of hospital stay ( LOS ) were evaluated . Results : Full nutritional goal ( 25 kcal/kg ) was achieved in 84 % of enterally fed patients versus 96 % in the parenteral group ( p = NS ) . The rate of postoperative complications was lower in the IEN group ( 33 % ) than in the SEN ( 40 % ) and TPN groups ( 59 % ) . The severity of infectious complications ( sepsis score ) was lower in the IEN ( 5.5 ) than the SEN ( 7.9 ) and TPN groups ( 10.4 ; p < 0.05 ) . LOS was shorter in the IEN than in the SEN and TPN groups ( 16.3 vs. 17.8 vs. 19.3 days , respectively ; p < 0.05 ) . Conclusions : In patients undergoing PD the established nutritional goal can be obtained by enteral feeding . Immunonutrition seems to improve outcome AIM This study aims to investigate and evaluate the efficacy and safety of early enteral nutrition ( EN ) in maintaining and improving the postoperative nutritional status in patients undergoing esophagectomy . METHODS A r and omized , controlled clinical trial was conducted in 120 adult patients with esophageal cancer and undergoing esophagectomy . Patients were r and omly divided into two groups receiving either EN ( N.=64 ) or parenteral nutrition ( PN ) ( N.=56 ) postoperatively . The nutritional intake was isonitrogenic and isocalorie for both groups . Nutritional status was evaluated preoperatively as well as on postoperative day I and day 8 . Daily nitrogen balance was measured and 7-day cumulative nitrogen balance was calculated . The levels of serum markers including d-lactate , diamine oxidase ( DAO ) , and endotoxin were determined on 1st , 4th and 8th postoperative day for analyzing intestinal barrier function . Postoperative infection rate and the incidence of nutrition support-related complications were examined . RESULTS The concentrations of serum albumin and prealbumin in patients of EN group were significantly higher than those in PN group and the concentrations of blood glucose , γ-GT , AKP , TB , and DB were significantly lower compared to those in the PN group ( P<0.05 ) . Both daily nitrogen balance and cumulative nitrogen balance of EN group were better than those of PN group since postoperative day III . The serum levels of d-lactate , DAO , and endotoxin of EN group were significantly lower than those of PN group on postoperative day VIII ( P<0.01 ) . The incidence of postoperative infections in blood , lung , and intestinal tract in EN group was lower compared to PN group ( P<0.05 ) . No severe complications associated with nutritional support occurred in EN group . The time to flatus passage in EN group was significantly shorter , and the cost of nutritional support was significantly less compared to PN group ( P<0.05 ) . CONCLUSION Postoperative early enteral nutrition was safe and feasible for patients undergoing esophagectomy . Compared to PN , EN more efficiently ameliorated postoperational nutritional status of the patients undergoing esophagectomy , played an important role in restoring intestinal barrier function postoperatively , reduced the incidence of postoperative infection , and decreased the cost of hospital stay BACKGROUND & AIMS Malnourished surgical patients are supposed to benefit from perioperative nutrition . It is unclear , however , whether enteral intervention really surpasses the parenteral one , and whether the modification of st and ard formula matters . The aim of the study was to evaluate the clinical value of the route and type of perioperative nutritional support . METHODS A group of 167 malnourished patients ( 91 M , 76 F , mean age 61.4 years ) operated between June 2001 and December 2008 was r and omly assigned during postoperative period to four groups according to nutritional intervention : enteral and parenteral , st and ard or immunomodulating . All patients received parenteral nutrition before surgery for 14 days , which provided homogenous groups for the postoperative evaluation . The trial was design ed to test the hypothesis that enteral nutrition and /or immunonutrition can reduce the incidence of postoperative complications . RESULTS The incidence of individual complications was comparable among all four groups ( p > 0.05 ) . Infectious complications occurred in 23 of 84 patients with st and ard diets and in 20 of 83 patients receiving immunomodulatory formula ( odds ratio 0.84 ; 95 % CI 0.42 to 1.69 ) . There were no significant differences in infectious complications ' ratio in patients receiving enteral ( 24/84 patients ) and parenteral formulas ( 19/83 patients ) . Neither immunomodulating formulas nor enteral feeding significantly affected the length of hospitalization , overall morbidity and mortality rates . CONCLUSIONS Results demonstrated that postoperative nutritional intervention generates comparable results regardless of the route and formula used and that preoperative intervention is of the utmost importance . The study was registered in the Clinical Trials Data base - number : NCT 00558155 BACKGROUND Nonocclusive bowel necrosis ( NOBN ) has been associated with early enteral nutrition ( EN ) . The purpose of this study was to determine the incidence of this complication in our trauma intensive care unit population and to define a typical patient profile vulnerable to NOBN . METHODS Thirteen cases of NOBN were identified among 4,311 patients ( 0.3 % ) over a 64-month period ending October 1998 . Their charts were analyzed for a variety of clinical data , including prospect i ve EN tolerance data in 4 . RESULTS Twelve ( 92 % ) patients were enterally fed prior to diagnosis for 10 + /- 8 days ( range 3 to 21 ) . Tachycardia ( n = 12 , 92 % ) ; fever/hypothermia , ( n = 12 , 92 % ) , and an abnormal white blood cell count ( n = 11 , 85 % ) were consistently present . Abdominal distention was common but tended to be a late sign ( n = 12 ) . Seven ( 56 % ) survived . In 4 patients with tolerance data , 3 reached the goal rate of feeds prior to diagnosis . Two became distended at > 12 hours from diagnosis . Gastric tonometry demonstrated a decreased NgpHi ( < 7.30 ) after starting EN in all 3 in whom it was monitored . CONCLUSIONS NOBN developed in 0.3 % of our trauma patients . Onset occurs in the second week in high-acuity patients who have had a period of EN tolerance . Clinical findings resemble bacterial sepsis with tachycardia , fever , and leukocytosis . Gastrointestinal specific signs are not consistent or occur late . Thus , we could not identify an early , useful clinical indicator . Gastric carbon dioxide tonometry may detect a vulnerable subgroup of patients Controversy persists as to the optimal means of providing adjuvant nutritional support . The aim of this study was to compare enteral nutrition ( EN ) and parenteral nutrition ( TPN ) in terms of adequacy of nutritional intake , septic and nonseptic morbidity , and mortality . This was a prospect i ve pragmatic study , whereby the route of delivery of nutritional support was determined by the attending clinician 's assessment of gastrointestinal function . Patients considered to have inadequate gastrointestinal function were given TPN ( group 1 ) , while those deemed to have a functioning gastrointestinal tract received EN ( group 2 ) . Patients in whom there was reasonable doubt as to the adequacy of intestinal function were r and omized to receive either TPN ( group 3 ) or EN ( group 4 ) . The trial setting was a large district general hospital with a dedicated nutrition team . A total of 562 patients were included in the study ( 331 males ; median age 67 y ) . Gastrointestinal function on entry into the study was considered inadequate in 267 patients who were given TPN ( group 1 ) and adequate in 231 whom received EN ( group 2 ) . There was clinical uncertainty about the adequacy of gut function in 64 patients ( 11.4 % ) who were r and omized to receive either TPN ( group 3 , 32 patients ) or EN ( group 4 , 32 patients ) . The incidence of inadequate nutritional intake was significantly higher in group 4 compared with group 3 ( 78.1 % versus 25 % , P < 0.001 ) . Complications related to the delivery system and other feed-related morbidity were significantly more frequent in both EN groups compared with the respective TPN groups . EN was associated with a higher overall mortality in both nonr and omized and r and omized patients . There were no significant differences observed in the incidences of septic morbidity between patients receiving TPN and those given EN . EN is associated with a higher incidence of inadequate nutritional intake , complications related to the delivery system , and other feed-related morbidity than TPN . There is no evidence from this study to support a difference between the two modalities in terms of septic morbidity . Patients in whom there is reasonable doubt as to the adequacy of gastrointestinal function should be fed by the parenteral route Background Nutritional support is crucial to the management of patients receiving invasive mechanical ventilation ( IMV ) and the most commonly prescribed treatment in intensive care units ( ICUs ) . International guidelines consistently indicate that enteral nutrition ( EN ) should be preferred over parenteral nutrition ( PN ) whenever possible and started as early as possible . However , no adequately design ed study has evaluated whether a specific nutritional modality is associated with decreased mortality . The primary goal of this trial is to assess the hypothesis that early first-line EN , as compared to early first-line PN , decreases day 28 all-cause mortality in patients receiving IMV and vasoactive drugs for shock . Methods / Design The NUTRIREA-2 study is a multicenter , open-label , parallel-group , r and omized controlled trial comparing early PN versus early EN in critically ill patients requiring IMV for an expected duration of at least 48 hours , combined with vasoactive drugs , for shock . Patients will be allocated at r and om to first-line PN for at least 72 hours or to first-line EN . In both groups , nutritional support will be started within 24 hours after IMV initiation . Calorie targets will be 20 to 25 kcal/kg/day during the first week , then 25 to 30 kcal/kg/day thereafter . Patients receiving PN may be switched to EN after at least 72 hours in the event of shock resolution ( no vasoactive drugs for 24 consecutive hours and arterial lactic acid level below 2 mmol/L ) . On day 7 , all patients receiving PN and having no contraindications to EN will be switched to EN . In both groups , supplemental PN may be added to EN after day 7 in patients with persistent intolerance to EN and inadequate calorie intake . We plan to recruit 2,854 patients at 44 participating ICUs . Discussion The NUTRIREA-2 study is the first large r and omized controlled trial design ed to assess the hypothesis that early EN improves survival compared to early PN in ICU patients . Enrollment started on 22 March 2013 and is expected to end in November 2015.Trial registration Clinical Trials.gov Identifier : NCT01802099 ( registered 27 February 2013 BACKGROUND Malnutrition is a common problem in critically ill patients in UK NHS critical care units . Early nutritional support is therefore recommended to address deficiencies in nutritional state and related disorders in metabolism . However , evidence is conflicting regarding the optimum route ( parenteral or enteral ) of delivery . OBJECTIVES To estimate the effect of early nutritional support via the parenteral route compared with the enteral route on mortality at 30 days and on incremental cost-effectiveness at 1 year . Secondary objectives were to compare the route of early nutritional support on duration of organ support ; infectious and non-infectious complications ; critical care unit and acute hospital length of stay ; all-cause mortality at critical care unit and acute hospital discharge , at 90 days and 1 year ; survival to 90 days and 1 year ; nutritional and health-related quality of life , re source use and costs at 90 days and 1 year ; and estimated lifetime incremental cost-effectiveness . DESIGN A pragmatic , open , multicentre , parallel-group r and omised controlled trial with an integrated economic evaluation . SETTING Adult general critical care units in 33 NHS hospitals in Engl and . PARTICIPANTS 2400 eligible patients . INTERVENTIONS Five days of early nutritional support delivered via the parenteral ( n = 1200 ) and enteral ( n = 1200 ) route . MAIN OUTCOME MEASURES All-cause mortality at 30 days after r and omisation and incremental net benefit ( INB ) ( at £ 20,000 per quality -adjusted life-year ) at 1 year . RESULTS By 30 days , 393 of 1188 ( 33.1 % ) patients assigned to receive early nutritional support via the parenteral route and 409 of 1195 ( 34.2 % ) assigned to the enteral route had died [ p = 0.57 ; absolute risk reduction 1.15 % , 95 % confidence interval ( CI ) -2.65 to 4.94 ; relative risk 0.97 ( 0.86 to 1.08 ) ] . At 1 year , INB for the parenteral route compared with the enteral route was negative at -£1320 ( 95 % CI -£3709 to £ 1069 ) . The probability that early nutritional support via the parenteral route is more cost-effective - given the data - is < 20 % . The proportion of patients in the parenteral group who experienced episodes of hypoglycaemia ( p = 0.006 ) and of vomiting ( p < 0.001 ) was significantly lower than in the enteral group . There were no significant differences in the 15 other secondary outcomes and no significant interactions with pre-specified subgroups . LIMITATIONS Blinding of nutritional support was deemed to be impractical and , although the primary outcome was objective , some secondary outcomes , although defined and objective ly assessed , may have been more vulnerable to observer bias . CONCLUSIONS There was no significant difference in all-cause mortality at 30 days for early nutritional support via the parenteral route compared with the enteral route among adults admitted to critical care units in Engl and . On average , costs were higher for the parenteral route , which , combined with similar survival and quality of life , result ed in negative INBs at 1 year . FUTURE WORK Nutritional support is a complex combination of timing , dose , duration , delivery and type , all of which may affect outcomes and costs . Conflicting evidence remains regarding optimum provision to critically ill patients . There is a need to utilise rigorous consensus methods to establish future priorities for basic and clinical research in this area . TRIAL REGISTRATION Current Controlled Trials IS RCT N17386141 . FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 20 , No. 28 . See the NIHR Journals Library website for further project information AIM To investigate the effect of early postoperative enteral nutrition enriched with arginine , RNA and omega-3 fatty acids on immunological and nutritional variables after elective curative operations for gastric or pancreatic cancer . DESIGN R and omised controlled trial . SETTING University hospital , Italy . SUBJECTS 78 Consecutive patients who were to undergo curative operations for gastric or pancreatic cancer , 60 of whom were suitable for the study . INTERVENTIONS Patients were r and omly allocated to three groups ( n = 20 each ) according to the type of postoperative nutritional support : st and ard enteral diet , the same diet enriched with arginine , RNA , and omega-3 fatty acids or total parenteral nutrition . The daily nutritional goal was 25 kcal ( 105 kJ)/kg and 0.25 g nitrogen/kg for all patients . MAIN OUTCOME MEASURES Serum concentrations of immunoglobulins , albumin , transferrin , prealbumin , retinol binding protein ( RBP ) ; cholinesterase activity , weight loss , duration of operation , operative blood loss ; blood transfusion ; delayed hypersensitivity responses , number of lymphocyte subsets , phagocytic ability of monocytes , number of interleukin-2 ( IL-2 ) plasma receptors , interleukin-6 ( IL-6 ) plasma concentrations , postoperative infections and sepsis scores . RESULTS All enterally fed patients but one completed the nutritional programme . There were significant postoperative reductions in both nutritional and immunological variables in all groups . On postoperative days 4 and 8 prealbumin concentration ( p < 0.05 ) , RBP concentration ( p < 0.05 ) , delayed hypersensitivity responses ( p < 0.05 ) , phagocytic ability of monocytes ( p < 0.01 ) and concentration of IL-2 receptors ( p < 0.009 ) had all recovered more in the group receiving the enriched solution . There was no difference in the postoperative infection rates among the three groups , but the infections were less severe in the enriched group ( p < 0.005 ) . CONCLUSION Early enteral feeding was well tolerated . Patients who received the enriched solution recovered both their nutritional and immunological status quicker than those in the other two groups OBJECTIVE To evaluate the effect of the early postoperative administration of an enriched enteral diet in cancer patients . DESIGN R and omised controlled study . SETTING Surgical intensive care unit of a university hospital . PATIENTS 77 consecutive patients undergoing curative surgery for gastric or pancreatic cancer . INTERVENTIONS Patients were r and omised into 3 groups to receive : a st and ard enteral formula ( n=24 ) ; the same formula enriched with arginine , RNA , and omega-3 fatty acids ( n = 26 ) , isonitrogen isocaloric total parenteral nutrition ( n = 27 ) . Enteral nutrition was started within 12 h following surgery . Infusion rate was progressively increased reaching the full regimen on postoperative day ( POD ) 4 . On admission and on POD 1 and 8 , the following measurements were performed : serum level of total iron-binding capacity , albumin , prealbumin , retinol-binding protein ( RBP ) , and cholinesterase . Delayed hypersensitivity response ( DHR ) , IgG , IgM , IgA , lymphocyte subsets . and monocyte phagocytosis ability were also evaluated . Bioelectrical impedance analysis was performed preoperatively and on POD 2 , 7 , and 11 . The rate and severity of postoperative infections and the length of hospital stay were evaluated . RESULTS In all patients , a significant drop of nutritional and immunologic parameters was observed on POD 1 . A significant increase of prealbumin ( p<0.02 ) , RBP ( p<0.005 ) , monocyte phagocytosis ability ( p<0.001 ) , and DHR ( p<0.005 ) was found on POD 8 only in the group fed with the enriched diet . A significant reduction of severity of postoperative infections and length of postoperative stay was found in the group with the enriched diet compared to the other groups . CONCLUSIONS These data are suggestive of an improvement of the nutritional and immunologic status and clinical outcome in cancer patients who receive an enriched enteral diet in the early postoperative course Although different studies suggest that early enteral nutrition ( EEN ) has benefits in reducing infectious complications , there is no data that addresses whether delayed enteral nutrition ( EN ) is detrimental and if it may have effects on inflammatory responses and immune function . Forty-five critically ill patients with long fasting were r and omly allocated in two groups according to the type of nutritional support . The first group included patients assuming a st and ard enteral nutrition ( EN , n = 22 ) and the second group assuming a parenteral nutrition ( PN , n = 23 ) . The daily nutritional amount was 25 kcal ( 105 kJ)/kg for all patients . The inflammatory markers white blood cells ( WBC ) , C-reactive protein ( CRP ) , TNF-α , IL-1-β , IL-6 , IL-4 , IL- 10 and the immune T-lymphocyte sub- population s CD3 + , CD4 + , CD8 + , and HLA-DR+ were evaluated at day 1 , and after 2 , 3 and 7 days . IL-4 , IL-10 , CD3 + , CD4 + , CD8 + and the CD4+/CD8 + ratio were not statistically different between the two groups . WBC and TNF-α in EN patients were higher than those in PN after 3 and 7 days ( P < 0.05 ) . CRP and IL-6 levels were higher in EN patients than those assuming a PN after 2 and 3 days ( P < 0.05 ) . HLA-DR levels in patients assuming an EN were found higher than those in PN at day 7 ( P < 0.05 ) . Delayed EN for critically ill patients with long-term fasting increased systemic inflammatory responses , whereas EN could modify immune function , therefore reducing hospital stay and costs Over the past 10 years , several clinical and experimental studies report the potential benefit of enteral nutrition as primary therapy after multiple system trauma . In this study , 98 patients sustaining blunt and penetrating trauma were r and omised to receive either enteral or parenteral feeding for 15 days . There were significantly fewer infectious complications in patients r and omised to receive enteral feeding with particular benefit shown in the most severely injured patients . Serum protein concentrations correlated with the clinical outcome with an increase in constitutive protein and decrease in acute phase protein concentrations occurring in the enteral group through a decrease in septic complications and possible direct hepatic ' reprioritisation ' . Enteral feeding serves as a primary therapy affecting the outcome of critically ill patients Background and Aim : Immunomodulating nutrition is supposed to reduce the number of complications and lengthen of hospital stay during the postoperative period in patients after major gastrointestinal surgery . The aim of the study was to assess the clinical effect of immunostimulatory enteral and parenteral nutrition in patients undergoing resection for gastrointestinal cancer in the group of well-nourished patients . Material and Methods : Between June 1 , 2001 , and December 31 , 2005 , a group of 214 well-nourished patients was initially assessed ( 150 men , 64 women , mean age 61.2 years ) to participate in the study . Nine patients were subsequently excluded and the remaining 205 subjects were r and omly assigned in a 2 × 2 factorial design into 4 study groups , ie , st and ard enteral nutrition ( n = 53 ) , immunomodulating enteral nutrition ( n = 52 ) , st and ard parenteral nutrition ( n = 49 ) , and immunomodulating enteral nutrition ( n = 51 ) . The study was design ed to test the hypothesis that immunonutrition and enteral nutrition would reduce the incidence of infectious complications after upper gastrointestinal surgery ; the secondary objective of the study was to evaluate the effect of nutritional intervention on overall morbidity and mortality rates , and hospital stay . The study was registered in the Clinical Trials Data base – number NCT 00558155 . Results : The overall morbidity rate was 33 % and the incidence of individual complications was comparable between all groups . Infectious complications occurred in 26 of 102 patients given st and ard diets and in 22 of 103 patients receiving immunomodulatory formulas ( odds ratio 0.81 ; 95 % CI , 0.43–1.50 ) . There were no significant differences between infectious complications in patients using parenteral nutrition ( 22 of 100 patients ) and parenteral formulas ( 26 of 105 , odds ratio 1.14 ; 95 % CI , 0.61–2.14 ) . Neither immunostimulating formulas nor enteral feeding significantly affected secondary outcome measures , including overall morbidity and mortality rates , and hospital stay . Conclusions : Our study failed to demonstrate any clear advantage of routine postoperative immunonutrition in patients undergoing elective upper gastrointestinal surgery . Both enteral and parenteral treatment options showed similar efficacy , tolerance , and effects on protein synthesis . Parenteral nutrition composed according to contemporary rules showed similar efficiency to enteral nutrition . However , because of its cost-efficiency , enteral therapy should be considered as the treatment of choice in all patients requiring nutritional therapy BACKGROUND The abnormal metabolism caused by cirrhosis always results in a complex problem about nutritional support , which will be more intricate while patients with portal hypertension are treated with pericardial devascularization . Comparing the effects of early enteral and parenteral nutritional support in patients with cirrhotic portal hypertension after pericardial devascularization , we try to realize the advantages and disadvantages of the two nutritional therapies and to guide our clinical practice . METHODS After pericardial devascularization , 40 patients with cirrhotic portal hypertension were divided r and omly into 2 groups : enteral and parenteral nutritional support , respectively . The general nutritional condition , capability of producing protein , liver function , blood velocity of the portal vein , gut function , bowel bacterial translocation , mortality , complication rate , stay in ICU , duration of hospitalization and costs of treatment were determined in all the patients and compared between the 2 groups . RESULTS Both enteral and parenteral nutritional supports could improve the general nutrition condition of the patients ; but patients receiving enteral nutritional support had fewer complications . Enteral nutrition was more effective than parenteral nutrition in increasing the blood velocity of the portal vein , stimulating gut motion , preventing bowel bacterial translocation , shortening the stay in ICU and the duration of hospitalization , and saving costs of treatment . CONCLUSION After pericardial devascularization , patients with cirrhotic portal hypertension should be treated with enteral nutritional support as early as possible OBJECTIVE To evaluate the effect of the combined use of Shenmai Injection ( SMI ) and enteral nutrition on postoperative fatigue syndrome ( POFS ) in patients with gastric cancer ( GC ) . METHODS Fifty-eight GC patients were r and omized into the parenteral nutrition group ( PNG , 19 cases ) , enteral nutrition group ( ENG , 19 cases ) and combined treatment group ( CTG , 20 cases ) . The post-operative recovery in patients was observed ; patients ' conditions of fatigue , mood and sleep were evaluated respectively by visual analogue scale of fatigue , profile of mood states ( POMS ) and Pittsburgh sleep quality index ( PSQI ) . Meanwhile , nutritional variables , such as serum contents of total protein , albumin , pre-albumin , were measured at different time points : before operation ( d0 ) and the 1st , 5th , and 9th day ( d1 , d5 and d9 ) after operation . Immune variables such as subsets of lymphocytes ( CD3 , CD4 , CD8 ) , serum immunoglobulins ( IgG , IgM , IgA ) were also determined . RESULTS Conditions of recovery , POMS and PSQI were better and the postoperative fatigue reduced more significantly in CTG than those in the other two groups ( P < 0.05 ) . On d9 , levels of pre-albumin , CD3 , CD4 , CD4/CD8 in CTG were significantly higher than those in the PNG and ENG ( P < 0.05 ) , meantime , levels of albumin and IgA were higher in CTG than those in PNG ( P < 0.05 ) . CONCLUSION Combined treatment of SMI and enteral nutrition can regulate mood and sleep to some extents , and reduce the postoperative fatigue through improving nutritional status and immune function , thus speeding up the recovery of patients BACKGROUND Early enteral nutrition ( EN ) in patients receiving mechanical ventilation commonly has been advocated , based mainly on studies conducted in mixed population s of trauma and surgery patients . In this study , ventilator-associated pneumonia rates and outcomes were compared in mechanically ventilated medical intensive care unit ( ICU ) patients receiving enteral versus parenteral nutrition . METHODS Patients fulfilling inclusion criteria between February 1 , 2004 , and January 31 , 2006 , were included . Patients were r and omized to enteral or parenteral nutrition ( PN ) within 48 hours of intubation . Development of ventilator-associated pneumonia , assessment as to whether day feeding goal was attained , duration of mechanical ventilation , ICU and hospital length of stay ( LOS ) , and mortality rates were recorded . RESULTS Of 249 consecutive patients receiving mechanical ventilation , 71 patients were included . Thirty ( 42.3 % ) patients received EN , and 41 ( 57.7 % ) received PN . There was no difference between groups for age , sex , body mass index , and scores on the Acute Physiology and Chronic Health Evaluation II . Ventilator-associated pneumonia rate , ICU and hospital LOS , and mortality rates were similar for both groups . In the parenterally fed group , duration of mechanical ventilation was longer ( p = .023 ) , but the feeding goal was attained earlier ( p = .012 ) . CONCLUSIONS In mechanically ventilated patients in the medical ICU , ventilator-associated pneumonia rates , ICU and hospital lengths of stay , and ICU and hospital mortality rates of patients receiving PN are not significantly different than those in patients receiving EN , and feeding goals can more effectively be attained by PN . Yet , duration of mechanical ventilation is slightly longer in patients receiving PN BACKGROUND Sepsis and the route of nutrient administration are clearly related to visceral protein levels ; however , the mechanisms and amount of influence are not completely defined . METHODS Constitutive and acute-phase protein levels were measured on days 1 , 4 , 7 , and 10 in 68 severely injured patients with abdominal trauma indexes of 15 or more r and omized to enteral or parenteral feeding . Groups were matched for age , abdominal trauma index , injury severity score , and length of stay . RESULTS Significantly higher levels of constitutive proteins and lower levels of acute-phase proteins were found in patients r and omized to enteral feeding . Although some " hepatic protein reprioritization " appeared to be caused by nutrient route , this appeared only in the less severely injured patients . A more important factor in visceral protein levels is a reduction in septic morbidity associated with enteral feeding . CONCLUSIONS Enteral feeding produces greater increase in constitutive proteins and greater decreases in acute-phase proteins after severe trauma primarily caused by reduced septic morbidity with enteral feeding CONTEXT The amount of enteral nutrition patients with acute lung injury need is unknown . OBJECTIVE To determine if initial lower-volume trophic enteral feeding would increase ventilator-free days and decrease gastrointestinal intolerances compared with initial full enteral feeding . DESIGN , SETTING , AND PARTICIPANTS The EDEN study , a r and omized , open-label , multicenter trial conducted from January 2 , 2008 , through April 12 , 2011 . Participants were 1000 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition at 44 hospitals in the National Heart , Lung , and Blood Institute ARDS Clinical Trials Network . INTERVENTIONS Participants were r and omized to receive either trophic or full enteral feeding for the first 6 days . After day 6 , the care of all patients who were still receiving mechanical ventilation was managed according to the full feeding protocol . MAIN OUTCOME MEASURES Ventilator-free days to study day 28 . RESULTS Baseline characteristics were similar between the trophic-feeding ( n = 508 ) and full-feeding ( n = 492 ) groups . The full-feeding group received more enteral calories for the first 6 days , about 1300 kcal/d compared with 400 kcal/d ( P < .001 ) . Initial trophic feeding did not increase the number of ventilator-free days ( 14.9 [ 95 % CI , 13.9 to 15.8 ] vs 15.0 [ 95 % CI , 14.1 to 15.9 ] ; difference , -0.1 [ 95 % CI , -1.4 to 1.2 ] ; P = .89 ) or reduce 60-day mortality ( 23.2 % [ 95 % CI , 19.6 % to 26.9 % ] vs 22.2 % [ 95 % CI , 18.5 % to 25.8 % ] ; difference , 1.0 % [ 95 % CI , -4.1 % to 6.3 % ] ; P = .77 ) compared with full feeding . There were no differences in infectious complications between the groups . Despite receiving more prokinetic agents , the full-feeding group experienced more vomiting ( 2.2 % vs 1.7 % of patient feeding days ; P = .05 ) , elevated gastric residual volumes ( 4.9 % vs 2.2 % of feeding days ; P < .001 ) , and constipation ( 3.1 % vs 2.1 % of feeding days ; P = .003 ) . Mean plasma glucose values and average hourly insulin administration were both higher in the full-feeding group over the first 6 days . CONCLUSION In patients with acute lung injury , compared with full enteral feeding , a strategy of initial trophic enteral feeding for up to 6 days did not improve ventilator-free days , 60-day mortality , or infectious complications but was associated with less gastrointestinal intolerance . TRIAL REGISTRATION clinical trials.gov Identifiers : NCT00609180 and NCT00883948 IMPORTANCE Systematic review s suggest adult patients in intensive care units ( ICUs ) with relative contraindications to early enteral nutrition ( EN ) may benefit from parenteral nutrition ( PN ) provided within 24 hours of ICU admission . OBJECTIVE To determine whether providing early PN to critically ill adults with relative contraindications to early EN alters outcomes . DESIGN , SETTING , AND PARTICIPANTS Multicenter , r and omized , single-blind clinical trial conducted between October 2006 and June 2011 in ICUs of 31 community and tertiary hospitals in Australia and New Zeal and . Participants were critically ill adults with relative contraindications to early EN who were expected to remain in the ICU longer than 2 days . INTERVENTIONS R and om allocation to pragmatic st and ard care or early PN . MAIN OUTCOMES AND MEASURES Day-60 mortality ; quality of life , infections , and body composition . RESULTS A total of 1372 patients were r and omized ( 686 to st and ard care , 686 to early PN ) . Of 682 patients receiving st and ard care , 199 patients ( 29.2 % ) initially commenced EN , 186 patients ( 27.3 % ) initially commenced PN , and 278 patients ( 40.8 % ) remained unfed . Time to EN or PN in patients receiving st and ard care was 2.8 days ( 95 % CI , 2.3 to 3.4 ) . Patients receiving early PN commenced PN a mean of 44 minutes after enrollment ( 95 % CI , 36 to 55 ) . Day-60 mortality did not differ significantly ( 22.8 % for st and ard care vs 21.5 % for early PN ; risk difference , -1.26 % ; 95 % CI , -6.6 to 4.1 ; P = .60 ) . Early PN patients rated day-60 quality of life ( R AND -36 General Health Status ) statistically , but not clinical ly meaningfully , higher ( 45.5 for st and ard care vs 49.8 for early PN ; mean difference , 4.3 ; 95 % CI , 0.95 to 7.58 ; P = .01 ) . Early PN patients required fewer days of invasive ventilation ( 7.73 vs 7.26 days per 10 patient × ICU days , risk difference , -0.47 ; 95 % CI , -0.82 to -0.11 ; P = .01 ) and , based on Subjective Global Assessment , experienced less muscle wasting ( 0.43 vs 0.27 score increase per week ; mean difference , -0.16 ; 95 % CI , -0.28 to -0.038 ; P = .01 ) and fat loss ( 0.44 vs 0.31 score increase per week ; mean difference , -0.13 ; 95 % CI , -0.25 to -0.01 ; P = .04 ) . CONCLUSIONS AND RELEVANCE The provision of early PN to critically ill adults with relative contraindications to early EN , compared with st and ard care , did not result in a difference in day-60 mortality . The early PN strategy result ed in significantly fewer days of invasive ventilation but not significantly shorter ICU or hospital stays . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN012605000704695 Background : Early postoperative enteral nutrition has been suggested to improve the nutritional status of patients after esophageal surgery . However , whether enteral nutrition decreases rates of surgical complications and increases the completion rate of the clinical management pathway is unclear . Methods : We analyzed 154 patients who were r and omly assigned to either an enteral or parenteral nutrition group after undergoing esophagectomy , compared the incidence of surgical complications , and evaluated the completion rate of the clinical pathway . In these 2 patient groups , perioperative management was performed through identical clinical pathways , except for nutrition . Results : The overall rate of surgical complications of any type did not differ between patients who received early enteral nutrition and those who did not ( p = 0.50 ) ; however , the rate of life-threatening surgical complications was significantly lower in patients who received early enteral nutrition ( p = 0.02 ) . The rate of non-life-threatening surgical complications did not differ between the groups ( p = 0.98 ) . In patients who received enteral nutrition , the completion rate of the clinical pathway was higher ( p = 0.03 ) , and the postoperative hospital stay was shorter ( p = 0.04 ) . Conclusions : Early enteral nutrition reduces the incidence of life-threatening surgical complications and improves the completion rate of the clinical pathway for thoracic esophagectomy |
610 | 30,561,133 | RESULTS A general trend of increased glucose and insulin is seen and likely to be caused by weight gain and /or changes in body composition as a consequence of adjuvant treatment of BC . | INTRODUCTION Breast cancer ( BC ) is the most common cancer among women worldwide .
With increasing survival rates , focus has exp and ed to long-term adverse effects of adjuvant chemotherapy and /or aromatase inhibitors .
Weight gain during chemotherapy has been well documented , but the underlying mechanisms remain unclear .
A change in glucose and insulin metabolism is a possible consequence . | PURPOSE The purpose of this study was to evaluate associations between hormonal therapy for breast cancer and subsequent diabetes incidence . METHODS The Surveillance , Epidemiology and End Results -Medicare linked data were used . Stage I-III breast cancer patients 65 years or older who filled at least two prescriptions for an aromatase inhibitor ( AI ) or tamoxifen by the end of 2008 , and within 12 months of breast cancer diagnosis , were selected . Women without cancer from a 5 % r and om sample of Medicare beneficiaries were frequency matched to patients by age group , and new onset diabetes was monitored for 24 months postbaseline in both groups of women . RESULTS Cox-proportional hazards analysis failed to show an association between AI use and subsequent diabetes onset after adjusting for age , race , and comorbidity ( hazard ratio : 0.99 ; 95 % confidence interval : 0.84 - 1.18 ) . This study also failed to show an association between tamoxifen use and diabetes onset ( hazard ratio : 0.79 ; 95 % confidence interval : 0.54 - 1.17 ) . CONCLUSIONS Study findings provide evidence that postmenopausal AI and tamoxifen users do not experience an increased risk of diabetes in the 2 years after treatment initiation . Whether these findings will hold with longer duration follow-up deserves a closer look PURPOSE Obesity increases risk for all-cause and breast cancer mortality and comorbidities in women who have been diagnosed and treated for breast cancer . The Exercise and Nutrition to Enhance Recovery and Good Health for You ( ENERGY ) study is the largest weight loss intervention trial among survivors of breast cancer to date . METHODS In this multicenter trial , 692 overweight/obese women who were , on average , 2 years since primary treatment for early-stage breast cancer were r and omly assigned to either a group-based behavioral intervention , supplemented with telephone counseling and tailored newsletters , to support weight loss or a less intensive control intervention and observed for 2 years . Weight and blood pressure were measured at 6 , 12 , 18 , and 24 months . Longitudinal mixed models were used to analyze change over time . RESULTS At 12 months , mean weight loss was 6.0 % of initial weight in the intervention group and 1.5 % in the control group ( P<.001 ) . At 24 months , mean weight loss in the intervention and control groups was 3.7 % and 1.3 % , respectively ( P<.001 ) . Favorable effects of the intervention on physical activity and blood pressure were observed . The weight loss intervention was more effective among women older than 55 years than among younger women . CONCLUSION A behavioral weight loss intervention can lead to clinical ly meaningful weight loss in overweight/obese survivors of breast cancer . These findings support the need to conduct additional studies to test methods that support sustained weight loss and to examine the potential benefit of intentional weight loss on breast cancer recurrence and survival OBJECTIVE To evaluate insulin values , insulin resistance , growth factors and cytokine levels in women suffering from breast cancer and the effect of chemotherapy on these parameters . DESIGN In a prospect i ve study , glucose and insulin values were determined in ten previously undiagnosed diabetic postmenopausal women with stage IV breast cancer ( hepatic metastases excluded ) during an oral glucose tolerance test ( OGTT ) carried out after a glucose load of 75 g. At baseline , leptin , Interleukin-1 ( IL-1 ) , Interleukin-6 ( IL-6 ) , Interleukin-8 ( IL-8 ) , Insulin-Growth Factor-1 ( IGF-1 ) , Tumor-Necrosis-Factor-alpha ( TNF-alpha ) , Vascular Endothelial Growth Factor ( VEGF ) and Platelet Derived Growth Factor ( PDGF ) levels were also determined using appropriate method olody . Insulin resistance and beta-cell function were calculated ( HOMA-model ) . All women were evaluated prior to and after chemotherapy applied for 6 months . RESULTS 1 ) Insulin levels at 120 minutes of the OGTT were higher before compared to post-chemotherapy ( Mean+/-SD : 170.39+/-78.07 vs 111.75+/-76.19 , p=0.037 ) . 2 ) Body mass index ( BMI ) was an important predictor of post-glucose load insulin levels both before ( coefficient=1.051 , p=0.004 ) and after chemotherapy ( coefficient=0.711 , p=0.003 ) . 3 ) Before chemotherapy BMI values were positively related to PDGF levels ( rs=0.685 , p=0.029 ) , while after chemotherapy this relationship became non-significant ( rs=0.188 , p=0.603 ) . Before chemotherapy there was a negative relationship between VEGF and waist circumference ( coefficient= -0.542 , p=0.023 ) . CONCLUSIONS Post-glucose load insulin values significantly decrease after chemotherapy . There is a positive relationship between BMI and post-glucose load insulin before and after chemotherapy . The contribution of the reduction in insulin , a known growth factor , to the outcome of chemotherapy in these patients remains speculative at present Tamoxifen is a nonsteroidal anti-estrogenic drug used for adjuvant treatment of breast cancer and recently as a chemopreventative agent for breast cancer and , on an investigational basis , for other cancers . To date there are case reports of hypertriglyceridemia and fatty liver disease in tamoxifen users . Fatty liver is associated with visceral obesity and other components of the metabolic syndrome . Here we evaluated steatosis and adipose tissue distribution by CT scan in a cross-sectional study of 32 women on tamoxifen and 39 control women . Tamoxifen users had more visceral adipose tissue ( VAT ) and more liver fat than controls . This is the first study to demonstrate that fatty liver and intra-abdominal fat accumulation are common in breast cancer patients receiving tamoxifen . Prospect i ve studies of tamoxifen should monitor metabolic changes in obese women with or without breast cancer Introduction Research has been limited in circadian activity rhythms and their relationship with health status in early-stage breast cancer survivors . Maintaining strong circadian parameters may reduce symptoms and improve physical functioning and disease-free survival . Methods This is a descriptive , correlational , secondary analysis of data from a r and omized controlled trial collected 1 year after the first chemotherapy treatment ; n = 156 cases with 7 days of wrist actigraph data of six circadian activity rhythm parameters ; measures of function , fatigue , sleep , and anxiety/depression ; and demographic/medical data including body mass index ( BMI ) . Results In the total sample and three BMI categories , acrophase was the only circadian parameter that reached means established in healthy adults . In the total sample , phase-delayed acrophase was associated with higher depression ( r = 0.180 , p = 0.025 ) and lower morning energy ( r = −0.194 , p = 0.016 ) and trended for higher fatigue ( r = 0.153 , p = 0.057 ) . Lower morning energy was also associated with a lower circadian quotient ( r = 0.158 , p = 0.05 ) . As BMI increased , weaker circadian parameters were recorded consistently . When compared with women in normal BMI categories , obese women ’s amplitude and 24-h autocorrelation coefficient were significantly weaker ( p = 0.011–0.015 ) . In obese women , phase-delayed acrophase was correlated with higher fatigue and anxiety and with lower morning energy and physical functioning . Discussion / conclusions Amplitude and 24-h autocorrelation parameters were significantly weaker , and phase-delayed acrophase was linked to several more intense symptoms and lower physical functioning in obese women . Implication s for cancer survivorsClinicians need to target high-risk women with phase-delayed rhythms , higher symptoms , and lower physical functioning for intervention Obese breast cancer patients have a higher risk of lymph node metastasis and a poorer prognosis compared to patients with normal weight . For obese women with node-positive breast cancer , an association between body weight and prognosis remains unclear . In this retrospective study , we analyzed patient data from the Phase-III ADEBAR trial , in which high-risk breast cancer patients ( pT1–4 , pN2–3 , pM0 ) were r and omized into a docetaxel-based versus epirubicin-based chemotherapy regimen . Patients were grouped according to their BMI value as underweight/normal weight ( BMI < 25 kg/m2 ; n = 543 ) , overweight ( BMI 25–29.9 kg/m2 ; n = 482 ) or obese ( BMI ≥ 30 kg/m2 ; n = 285 ) . Overweight and obese patients were older , had larger tumors and were more likely to be postmenopausal at the time of diagnosis compared to underweight/normal-weight patients ( all p < 0.001 ) . Multivariate Cox regression analyses adjusting for age and histopathological tumor features showed that obese patients had a significantly shorter disease-free survival ( DFS ; HR 1.43 ; 95 % CI 1.11–1.86 ; p = 0.006 ) and overall survival ( OS ; HR 1.56 ; 95 % CI 1.14–2.14 ; p = 0.006 ) than non-obese patients . Subgroup analyses revealed that the differences in DFS and OS were significant for postmenopausal but not for premenopausal patients , and that the survival benefit of non-obese patients was more pronounced in women with hormone-receptor-positive disease . Obesity constitutes an independent , adverse prognostic factor in high-risk node-positive breast cancer patients , in particular for postmenopausal women and women with hormone-receptor-positive disease Certain food groups are often rejected during chemotherapy ( CT ) due to the side effects of treatment , which may interfere with adequate diet and nutritional status . The aim of this study was to evaluate the treatment impact on the diet and nutritional status of women with breast cancer ( BC ) . In this prospect i ve longitudinal study , conducted in 2014–2015 , 55 women diagnosed with BC , with a mean age 51.5±10.1 years , were followed and data were collected at three different times . Anthropometric and dietary assessment s were performed , the latter by applying nine 24h dietary recalls , by using the Brazilian Healthy Eating Index Revised ( BHEI-R ) , and calculating the prevalence of inadequacy by the EAR cut-off point method . Regarding the BHEI-R analysis , the majority of women had a “ diet requires modification ’ , both at the beginning ( T0 , 58.2 % , n = 32 ) and during treatment ( T1 , 54.5 % , n = 30 ) . However , after the end of the CT , the greater percentage of patients ( T2 , 49.1 % , n = 27 ) were classified as having an " inadequate diet " , since the Total Fruit consumption as well as the Dark Green and Orange Vegetable and Legume consumption decreased significantly during treatment ( p = 0.043 and p = 0.026 , respectively ) . There was a significant reduction in the intake of macro and micronutrients , with a high prevalence of inadequacy , of up to 100 % , for calcium , iron , phosphorus , magnesium , niacin , riboflavin , thiamin , vitamin B6 , vitamin C and zinc . Assessment of the nutritional status indicated that 56 % ( n = 31 ) of patients were overweight at these three different times . Weight , BMI and Waist Circumference increased significantly , indicating a worse nutritional status , and there was a correlation between poor diet quality and higher values for BMI , Waist-Hip Ratio and Waist-to-Height Ratio . Chemotherapy interferes in the patients ’ diet generating a negative impact on the quality and intake of micro and macronutrients , as well as an impact on their nutritional status , with an increase in anthropometric measurements Purpose Breast cancer treatments have been associated with an increased risk of multiple health-related adverse outcomes , but the relationship with diabetes remains unclear . This study investigated the association between hormone therapy and diabetes risk in breast cancer survivors . Patients and Methods We performed a case-cohort study of 2,246 female survivors recruited from the Leumit health care fund who were diagnosed with primary nonmetastatic invasive breast cancer in 2002 through 2012 . A 20 % r and om subcohort was sample d at baseline , and all diabetes cases were identified . Adjusted hazard ratios ( HRs ) with 95 % CIs were estimated by weighted Cox proportional hazards regression models . Results Of 2,246 breast cancer survivors , 324 developed diabetes over a mean follow-up of 5.9 years . The crude cumulative incidence of diabetes that accounted for death as a competing risk was 20.9 % ( 95 % CI , 18.3 % to 23.7 % ) . In multivariable-adjusted models , hormone therapy was associated with increased diabetes risk ( HR , 2.40 ; 95 % CI , 1.26 to 4.55 ; P = .008 ) . The hazard for tamoxifen use ( HR , 2.25 ; 95 % CI , 1.19 to 4.26 ; P = .013 ) was less pronounced than the use of aromatase inhibitors ( HR , 4.27 , 95 % CI , 1.42 to 12.84 ; P = .010 ) . Conclusion Active hormone therapy is a significant risk factor of diabetes among breast cancer survivors . Although cessation of treatment is not recommended because the survival benefits of hormone therapy outweigh the risks , preventive strategies aim ed at lifestyle modifications may minimize the risk Chemotherapy is a st and ard treatment method for the patients with locally advanced breast cancer . Lately , cyclophosphamide ( CYP ) and doxorubicin ( DOX ) are used as the major chemotherapeutic agents especially for the treatment of breast cancer . Till date , no serum biomarker has been able to provide an early diagnosis of breast cancer . This study aim ed to assess inflammatory , cardiac , renal and hematological markers in 56 breast cancer patients ( BCP ) before , during and after termination of chemotherapy with CYP and DOX . Blood sample s were collected from the patients at the each treatment stages mentioned above . These sample s were assessed for interleukin 6 ( IL-6 ) , interleukin 10 ( IL-10 ) , lactate dehydrogenase ( LDH ) , creatine kinase ( CK ) , creatinine , hemoglobin ( Hb ) , leukocyte , platelet and Na+ /K+ -ATPase levels either by ELISA or colorimetric methods . The results suggest a significant increase in IL-6 level at all the stages in BCP as compared to control group . On the other h and , IL-10 , CK and Na+ /K+ -ATPase levels were found to be significantly declined during all the stages . Moreover , the majority of hematological parameters remained unchanged throughout the treatment period with the exception of creatinine and Hb which showed slight modulation in their level at different stages . Based on the results , we conclude that breast cancer and co-treatment with CYP and DOX , interfere arious biological markers , thereby , showing the physiological imbalance PURPOSE Overweight or obese breast cancer patients have a worse prognosis compared with normal-weight patients . This may be attributed to hyperinsulinemia and dysregulation of adipokine levels associated with overweight and obesity . Here , we evaluate whether low levels of adiponectin and a greater level of insulin resistance are associated with breast cancer mortality and all-cause mortality . PATIENTS AND METHODS We measured glucose , insulin , and adiponectin levels in fasting serum sample s from 527 women enrolled in the Health , Eating , Activity , and Lifestyle ( HEAL ) Study , a multiethnic , prospect i ve cohort study of women diagnosed with stage I-IIIA breast cancer . We evaluated the association between adiponectin and insulin and glucose levels ( expressed as the Homeostatic Model Assessment [ HOMA ] score ) represented as continuous measures and median split categories , along with breast cancer mortality and all-cause mortality , using Cox proportional hazards models . RESULTS Increasing HOMA scores were associated with reduced breast cancer survival ( hazard ratio [ HR ] , 1.12 ; 95 % CI , 1.05 to 1.20 ) and reduced all-cause survival ( HR , 1.09 ; 95 % CI , 1.02 to 1.15 ) after adjustment for possible confounders . Higher levels of adiponectin ( above the median : 15.5 μg/mL ) were associated with longer breast cancer survival ( HR , 0.39 ; 95 % CI , 0.15 to 0.95 ) after adjustment for covariates . A continuous measure of adiponectin was not associated with either breast cancer-specific or all-cause mortality . CONCLUSION Elevated HOMA scores and low levels of adiponectin , both associated with obesity , were associated with increased breast cancer mortality . To the best of our knowledge , this is the first demonstration of the association between low levels of adiponectin and increased breast cancer mortality in breast cancer survivors BACKGROUND Vascular endothelial growth factor ( VEGF ) plays a pivotal role in the pathogenesis of malignant pleural effusion ( MPE ) . Here , a multicenter phase II trial to evaluate bevacizumab in non-squamous non-small cell lung carcinoma patients with MPE was conducted . METHODS Patients having MPE with no prior treatment and performance status of 0 - 2 received carboplatin ( area under the curve : AUC 6 ; up to 6 cycles ) and pemetrexed ( 500mg/m(2 ) ) with bevacizumab ( 15mg/kg ) every 3 weeks . The primary endpoint was the control rate of MPE without pleurodesis at 8 weeks after treatment . VEGF levels in plasma and MPE were measured by enzyme immunoassay . RESULTS Of 30 patients entered ( median 66 years ; 24 males ; adenocarcinoma ; 4 epidermal growth factor receptor : EGFR mutations ) , 28 patients ( 2 withdrawn patients ) were given a median of 4 cycles of carboplatin , and 68 % of the patients received maintenance pemetrexed with bevacizumab ( median 8 cycles ) . At eight weeks , MPE was controlled without pleurodesis in 93 % of treated patients ( 95 % confidence interval : 77 - 99 % ) . At the median follow-up time of 12.8 months , 78.6 % of the cases required no pleurodesis . Response rate was 46 % , and median progression-free survival ( PFS ) and overall survival ( OS ) were 8.2 months and 18.6 months , respectively . Toxicities of grade ≥3 included neutropenia ( 28.6 % ) , thrombocytopenia ( 28.6 % ) , proteinuria ( 3.6 % ) , and hypertension ( 3.6 % ) . Assessment of VEGF levels before treatment indicated that patients with low VEGF ( < 1000pg/ml ) in MPE frequently needed pleurodesis ( p=0.011 ) , and that high VEGF ( ≥100pg/ml ) in plasma was indicative of poor prognosis in the context of PFS ( p=0.012 ) . CONCLUSION The combination of bevacizumab with carboplatin and pemetrexed demonstrated efficacy with acceptable toxicities in patients with MPE Six hundred forty-six women with node-positive breast cancer from two prospect i ve , r and omized , adjuvant breast cancer trials were evaluated for changes in weight during and after receiving 60 weeks of chemotherapy , chemohormonal therapy , or observation . The median weight change in the 545 patients remaining on protocol at 60 weeks for observed postmenopausal patients was + 1.8 kg , for treated postmenopausal patients + 3.6 kg , and for treated premenopausal patients + 5.9 kg ( P less than .001 ) . After a median follow-up of 6.6 years , premenopausal women who gained more than the median weight at 60 weeks had a risk of relapse 1.5 times greater ( covariate P = .17 ) and a risk of death 1.6 times greater ( covariate P = .04 ) than premenopausal women who had gained less than the median weight . In the postmenopausal patients , the trend for inferior relapse-free and overall survival in those who gained more than the median weight at 60 weeks was not significant ( P = .05 ) . We conclude that , relative to observation , adjuvant chemotherapy is associated with greater weight gain in node-positive , postmenopausal breast cancer patients ; the amount of weight gain appears greater for premenopausal than postmenopausal women , and in premenopausal women , excessive weight gain may be associated with an increase in relapse and cancer-related deaths in the selected patients who show no evidence of recurrence during 60 weeks of adjuvant chemotherapy . This last point must be interpreted with caution because of the exploratory nature of the analyses Objective Polymorphisms in the CYP19A1 ( aromatase ) gene influence disease-free survival and bone loss in patients taking aromatase inhibitors ( AIs ) for estrogen receptor-positive ( ER+ ) breast cancers . Because AI use results in severe estrogen deficiency that may lead to changes in body composition , the aim of this study was to determine the effect of the rs700518 polymorphism in the CYP19A1 gene on the changes in body composition among postmenopausal women who were treated with AIs for ER+ breast cancer . Patients and methods This was a 1-year prospect i ve study of changes in body composition in postmenopausal women who were initiated on third-generation AIs for ER+ breast cancer . Body composition was measured by dual-energy absorptiometry at 6 and 12 months , serum estradiol by radioimmunoassay , and genotyping by a TaqMan single-nucleotide polymorphism allelic discrimination assay . Results Eighty-two women could provide at least one follow-up body composition measurement . Women with the GG genotype for the rs700518 ( G/A at Val80 ) developed a significant increase in truncal fat mass index ( P=0.03 ) and a significant decrease in fat-free mass index ( P=0.01 ) at 12 months relative to patients carrying the A allele ( GA/AA ) . There was no significant difference in the changes in estradiol levels among the genotypes . Conclusion Patients with the GG genotype for the rs700518 polymorphism in the CYP19A1 gene are at risk for significant loss of fat-free mass and increase in truncal fat with AI therapy . Whether there are associated metabolic abnormalities and whether changes would persist with long-term AI therapy need to be confirmed in a larger study with a longer duration of follow-up Adipose tissue-derived hormones ( adipocytokines ) , such as adiponectin , leptin , resistin and visfatin , and the pancreatic hormone insulin , have been suggested to play a role in carcinogenesis . we therefore hypothesized that the oncological treatment of breast cancer may alter the serum levels of these adipocytokines and insulin . In this study , we aim ed to compare the serum levels of adipocytokines and insulin between the pre- and post-treatment period in patients with breast cancer . In this prospect i ve study , 20 consecutive patients with stage II and III breast cancer underwent breast-conserving surgery or total mastectomy and /or axillary dissection . The patients received adjuvant chemotherapy and radiotherapy , if necessary . Blood sample s were obtained during the preoperative period and postoperatively after completion of the adjuvant therapy . There was no statistically significant difference between the pre- and post-treatment levels of visfatin , adiponectin and leptin . However , the serum insulin and resistin levels and insulin resistance were found to be statistically significantly increased following treatment ( P<0.05 ) . Post-treatment resistin levels were positively correlated with insulin resistance ( r=0.45 , P<0.05 ) . Therefore , oncological treatment of stage II and III breast cancer did not affect visfatin , adiponectin and leptin levels , but statistically significantly increased resistin levels and insulin resistance . In addition , the post-treatment resistin levels were positively correlated with insulin resistance , suggesting that resistin may be involved in the development of insulin resistance in breast cancer patients following treatment OBJECTIVE To investigate prospect ively changes in weight , skin-fold measurements , waist circumference and waist/hip ratio in relation to changes in menopausal status , hormone therapy use and life-style factors . METHOD The study was a 5-year follow-up of volunteers from a population -based cohort of Australian-born women aged 46 - 57 years at baseline : 106 premenopausal , 106 perimenopausal and 21 hormone therapy users . RESULTS Mean ( SD ) weight gain of the entire cohort over 5 years was 2.1 ( 5.1 ) kg . Baseline age was negatively associated with weight change ( regression coefficient = -0.4 , SE 0.1 , p < 0.05 ) . After 5 years , 20 women remained premenopausal , 80 were perimenopausal , 112 had become naturally postmenopausal and 21 remained on hormone therapy . Changes in weight were greater than zero ( p < 0.05 ) in all groups except for the women who remained on hormone therapy . There was no significant difference in weight gain between women who remained premenopausal and those who had a natural menopause . Increases in suprailiac skin-fold measurements ( p < 0.05 ) and in waist circumference and waist/hip ratio occurred in women who experienced the menopausal transition but not in those who took hormone therapy continuously . There was no association between weight change and baseline weight , exercise , alcohol intake or smoking . CONCLUSION Weight gain was not related to change in menopausal status nor to any life-style factors measured . Women who were older at baseline gained less weight than the younger members . Suprailiac skin-fold measurements , waist circumference and waist/hip ratio all increased during the menopausal transition . Continuous hormone therapy users showed no gain in mean weight , suprailiac skin-fold measurements or waist measurements over the follow-up period BACKGROUND Older women with early-stage breast cancer experience higher rates of non-breast cancer-related death . We examined factors associated with cause-specific death in a large cohort of breast cancer patients treated with extended adjuvant endocrine therapy . METHODS In the MA.17 trial , conducted by the National Cancer Institute of Canada Clinical Trials Group , 5170 breast cancer patients ( median age = 62 years ; range = 32 - 94 years ) who were disease free after approximately 5 years of adjuvant tamoxifen treatment were r and omly assigned to treatment with letrozole ( 2583 women ) or placebo ( 2587 women ) . The median follow-up was 3.9 years ( range 0 - 7 years ) . We investigated the association of 11 baseline factors with the competing risks of death from breast cancer , other malignancies , and other causes . All statistical tests were two-sided likelihood ratio criterion tests . RESULTS During follow-up , 256 deaths were reported ( 102 from breast cancer , 50 from other malignancies , 100 from other causes , and four from an unknown cause ) . Non-breast cancer deaths accounted for 60 % of the 252 known deaths ( 72 % for those > or = 70 years and 48 % for those < 70 years ) . Two baseline factors were differentially associated with type of death : cardiovascular disease was associated with a statistically significant increased risk of death from other causes ( P.002 ) , and osteoporosis was associated with a statistically significant increased risk of death from other malignancies ( P.05 ) . An increased risk of breast cancer-specific death was associated with lymph node involvement ( P < .001 ) . Increased risk of death from all three causes was associated with older age ( P < .001 ) . CONCLUSIONS Non-breast cancer-related deaths were more common than breast cancer-specific deaths in this cohort of 5-year breast cancer survivors , especially among older women |
611 | 31,404,410 | Conclusions Progression of PAD in IC patients is probably underestimated in the literature due to study design issues .
Predicting which patients with claudication are likely to deteriorate to critical limb ischaemia is difficult since there is a lack of evidence related to lower limb prognosis . | Background Intermittent claudication ( IC ) is the most common symptom of peripheral arterial disease and is generally treated conservatively due to limited prognostic evidence to support early revascularisation in the individual patient .
This approach may lead to the possible loss of opportunity of early revascularisation in patients who are more likely to deteriorate to critical limb ischaemia .
The aim of this review is to evaluate the available literature related to the progression rate of symptomatic peripheral arterial disease . | OBJECTIVE The aim was to determine long-term mortality rates and the underlying cause of death for subjects with different peripheral arterial disease ( PAD ) stages in a population based setting . METHODS A r and omly selected population sample of 5080 subjects was enrolled in the study in 2004 - 2005 . Participants completed health state question naires and underwent ankle brachial index ( ABI ) measurements for classification into PAD severity stages and reference subjects . A follow-up was conducted by the end of 2015 using data from Swedish governmental national registers for cause of death , which was then compared with PAD stage determined at baseline in 2005 . RESULTS The 10 year all cause mortality was 27 % for reference cases , 56 % for asymptomatic PAD ( APAD ) , 63 % for intermittent claudication ( IC ) , and 75 % for severe limb ischaemia ( SLI ) . Among all PAD subjects , cardiovascular ( CV ) causes were the most common main cause of death ( 45 % ) and a CV event was present as either the main or one of the three most common contributing causes of death in 64 % of the cases . The age adjusted hazard ratios for a main cause of death by a CV event were 1.9 ( 95 % CI 1.5 - 2.3 ) for APAD , 2.6 ( 95 % CI 2.1 - 3.4 ) for IC , and 3.5 ( 95 % CI 2.3 - 5.2 ) for SLI . CONCLUSION PAD subjects , including the APAD subjects , are still at high risk of CV death . The mortality risks are more than doubled in symptomatic PAD patients compared with reference subjects and increase by severity of PAD stage . Awareness and improved risk reduction management of PAD are still warranted BACKGROUND Patients with lower extremity peripheral artery disease ( PAD ) are at increased risk of major adverse cardiovascular events ( MACE ) and major adverse limb events ( MALE ) . There is limited information on the prognosis of patients who experience MALE . OBJECTIVES Among participants with lower extremity PAD , this study investigated : 1 ) if hospitalizations , MACE , amputations , and deaths are higher after the first episode of MALE compared with patients with PAD who do not experience MALE ; and 2 ) the impact of treatment with low-dose rivaroxaban and aspirin compared with aspirin alone on the incidence of MALE , peripheral vascular interventions , and all peripheral vascular outcomes over a median follow-up of 21 months . METHODS We analyzed outcomes in 6,391 patients with lower extremity PAD who were enrolled in the COMPASS ( Cardiovascular Outcomes for People Using Anticoagulation Strategies ) trial . COMPASS was a r and omized , double-blind placebo-controlled study of low-dose rivaroxaban and aspirin combination or rivaroxaban alone compared with aspirin alone . MALE was defined as severe limb ischemia leading to an intervention or major vascular amputation . RESULTS A total of 128 patients experienced an incident of MALE . After MALE , the 1-year cumulative risk of a subsequent hospitalization was 61.5 % ; for vascular amputations , it was 20.5 % ; for death , it was 8.3 % ; and for MACE , it was 3.7 % . The MALE index event significantly increased the risk of experiencing subsequent hospitalizations ( hazard ratio [ HR ] : 7.21 ; p < 0.0001 ) , subsequent amputations ( HR : 197.5 ; p < 0.0001 ) , and death ( HR : 3.23 ; p < 0.001 ) . Compared with aspirin alone , the combination of rivaroxaban 2.5 mg twice daily and aspirin lowered the incidence of MALE by 43 % ( p = 0.01 ) , total vascular amputations by 58 % ( p = 0.01 ) , peripheral vascular interventions by 24 % ( p = 0.03 ) , and all peripheral vascular outcomes by 24 % ( p = 0.02 ) . CONCLUSIONS Among individuals with lower extremity PAD , the development of MALE is associated with a poor prognosis , making prevention of this condition of utmost importance . The combination of rivaroxaban 2.5 mg twice daily and aspirin significantly lowered the incidence of MALE and the related complications , and this combination should be considered as an important therapy for patients with PAD . ( Cardiovascular Outcomes for People Using Anticoagulation Strategies [ COMPASS ] ; NCT01776424 ) Principled methods with which to appropriately analyze missing data have long existed ; however , broad implementation of these methods remains challenging . In this and 2 companion papers ( Am J Epidemiol . 2018;187(3):576 - 584 and Am J Epidemiol . 2018;187(3):585 - 591 ) , we discuss issues pertaining to missing data in the epidemiologic literature . We provide details regarding missing- data mechanisms and nomenclature and encourage the conduct of principled analyses through a detailed comparison of multiple imputation and inverse probability weighting . Data from the Collaborative Perinatal Project , a multisite US study conducted from 1959 to 1974 , are used to create a masked data -analytical challenge with missing data induced by known mechanisms . We illustrate the deleterious effects of missing data with naive methods and show how principled methods can sometimes mitigate such effects . For example , when data were missing at r and om , naive methods showed a spurious protective effect of smoking on the risk of spontaneous abortion ( odds ratio ( OR ) = 0.43 , 95 % confidence interval ( CI ) : 0.19 , 0.93 ) , while implementation of principled methods multiple imputation ( OR = 1.30 , 95 % CI : 0.95 , 1.77 ) or augmented inverse probability weighting ( OR = 1.40 , 95 % CI : 1.00 , 1.97 ) provided estimates closer to the " true " full- data effect ( OR = 1.31 , 95 % CI : 1.05 , 1.64 ) . We call for greater acknowledgement of and attention to missing data and for the broad use of principled missing- data methods in epidemiologic research CONTEXT Among individuals with lower-extremity peripheral arterial disease ( PAD ) , specific leg symptoms and the ankle brachial index ( ABI ) are cross-sectionally related to the degree of functional impairment . However , relations between these clinical characteristics and objective ly measured functional decline are unknown . OBJECTIVE To define whether PAD , ABI , and specific leg symptoms predict functional decline at 2-year follow-up . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study among 676 consecutively identified individuals ( aged > or = 55 years ) with and without PAD ( n = 417 and n = 259 , respectively ) , with baseline functional assessment s occurring between October 1 , 1998 , and January 31 , 2000 , and follow-up assessment s scheduled 1 and 2 years thereafter . PAD was defined as ABI less than 0.90 , and participants with PAD were categorized at baseline into 1 of 5 mutually exclusive symptom groups . MAIN OUTCOME MEASURES Mean annual changes in 6-minute walk performance and in usual-paced and fast-paced 4-m walking velocity , adjusted for age , sex , race , prior-year functioning , comorbid diseases , body mass index , pack-years of cigarette smoking , and patterns of missing data . RESULTS Lower baseline ABI values were associated with greater mean ( 95 % confidence interval ) annual decline in 6-minute walk performance ( -73.0 [ -142 to -4.2 ] ft for ABI < 0.50 vs -58.8 [ -83.5 to -34.0 ] ft for ABI 0.50 to < 0.90 vs -12.6 [ -40.3 to 15.1 ] ft for ABI 0.90 - 1.50 , P = .02 ) . Compared with participants without PAD , PAD participants with leg pain on exertion and rest at baseline had greater mean annual decline in 6-minute walk performance ( -111 [ -173 to -50.0 ] ft vs -8.67 [ -36.9 to 19.5 ] ft , P = .004 ) , usual-pace 4-meter walking velocity ( -0.06 [ -0.09 to -0.02 ] m/sec vs -0.01 ( -0.03 to 0.003 ] m/sec , P = .02 ) , and fastest-pace 4-meter walking velocity ( -0.07 [ -0.11 to -0.03 ] m/sec vs -0.02 [ -0.04 to -0.006 ] m/sec , P = .046 ) . Compared with participants without PAD , asymptomatic PAD was associated with greater mean annual decline in 6-minute walk performance ( -76.8 ( -135 to -18.6 ] ft vs -8.67 ( -36.9 to 19.5 ] ft , P = .04 ) and an increased odds ratio for becoming unable to walk for 6 minutes continuously ( 3.63 ; 95 % confidence interval , 1.58 - 8.36 ; P = .002 ) . CONCLUSIONS Baseline ABI and the nature of leg symptoms predict the degree of functional decline at 2-year follow-up . Previously reported lack of worsening in claudication symptoms over time in patients with PAD may be more related to declining functional performance to than lack of disease progression OBJECTIVE To determine changes over time in the ankle brachial index ( ABI ) among subjects with and without intermittent claudication in the general population . DESIGN OF STUDY Population cohort study . SETTING General population in Edinburgh , Scotl and . SUBJECTS A total of 1592 men and women aged 55 to 74 years selected at r and om from age-sex registers of 11 general practice s and followed up over 12 years . Main outcome measures Changes in ABI for each leg recorded at baseline in 1988 and at subsequent 5-year and 12-year clinical examinations . RESULTS Overall , 695 subjects ( 348 men and 347 women ) had valid ABI measurements on both legs at all three examinations . At baseline , the ABI was on average.03 higher in the right leg than the left ( P < or = .001 ) . Men had a mean ABI that was.07 higher than women ( P < or = .001 ) . Mean ABI in the worse leg showed little change over 12 years in both men and women . However , in the whole population , the ABI in the better leg showed a significant drop , 1.15 to 1.08 ( P < or = .001 ) . A total of 179 cases of intermittent claudication were identified during the 12-year follow-up . At baseline , ABI in the worse leg of the claudicants was significantly lower than in healthy subjects ( .99 vs 1.08 ; P < or = .01 ) . In claudicants , mean ABI in the worse leg fell by.04 over 5 years ( P < or = .05 ) and in the better leg showed a highly significant drop of.09 ( P < or = .001 ) to levels similar to those of the worse leg . CONCLUSIONS The mean ABI in the worse leg of study subjects showed little progression over 12 years . Individuals with intermittent claudication experienced a greater decline in both legs compared with those without claudication . Deterioration occurred more rapidly in the limb with a higher ABI at baseline , which possibly indicates a systemic tendency to atherosclerosis Observational longitudinal research is particularly useful for assessing etiology and prognosis and for providing evidence for clinical decision making . However , there are no structured reporting requirements for studies of this design to assist authors , editors , and readers . The authors developed and tested a checklist of criteria related to threats to the internal and external validity of observational longitudinal studies . The checklist criteria concerned recruitment , data collection , biases , and data analysis and descriptive issues relevant to study rationale , study population , and generalizability . Two raters independently assessed 49 r and omly selected articles describing stroke research published from 1999 to 2003 in six journals : American Journal of Epidemiology , Journal of Epidemiology and Community Health , Stroke , Annals of Neurology , Archives of Physical Medicine and Rehabilitation , and American Journal of Physical Medicine and Rehabilitation . On average , 17 of the 33 checklist criteria were reported . Criteria describing the study design were better reported than those related to internal validity . No relation was found between study type ( etiologic or prognostic ) or word count and quality of reporting . A flow diagram for summarizing participant flow through a study was developed . Editors and authors should consider using a checklist and flow diagram when reporting on observational longitudinal research BACKGROUND The use of physical training in the treatment of intermittent claudication is well established . However , current data do not provide enough information about the prognosis for each case , and there are no data on how walking distances evolve over time with conservative treatment . The goal of this study was to evaluate improvement in walking capacity among patients with intermittent claudication who underwent unsupervised clinical treatment , observing whether sustained treatment would increase or decrease maximum walking distance , whether after 6 months there was a change in the maximum distance , and whether abstinence from smoking and well-conducted walking exercise had independent effects on the outcome . METHODS Five hundred patients with intermittent claudication were surveyed in a prospect i ve , nonr and omized , and uncontrolled study . Maximum walking distance and treatment compliance over time were analyzed . RESULTS Nonsmoking patients who walked achieved a mean increase during the first 6 months of 33.70 m/mo and a mean increase thereafter of 4.24 m/mo . Smokers who walked achieved an increase during the first 6 months only ( mean , 42.92 m/mo ) . Patients who did not practice physical training exhibited no effect ( smokers ) or negligible effect ( nonsmokers ) from the treatment ( mean , 7.58 m/mo ) . CONCLUSIONS Patients who adhered to physical training exhibited a significant increase in maximum walking distance during the first 6 months of treatment only . Patients who did not practice physical training exhibited no effect ( smokers ) or negligible effect ( ex-smokers ) from the treatment OBJECTIVE The purpose of this study was to delineate the natural history of claudication and determine risk factors for ischemic rest pain ( IRP ) and ischemic ulceration ( IU ) among patients with claudication . METHODS We prospect ively collected data on 1244 men with claudication during a 15-year period , including demographics , clinical risk factors , and ankle-brachial index ( ABI ) . We followed these patients serially with ABIs , self-reported walking distance ( WalkDist ) , and monitoring for IRP and IU . We used Kaplan-Meier and proportional hazards modeling to find independent predictors of IRP and IU . RESULTS Mean follow-up was 45 months ; statistically valid follow-up could be carried out for as long as 12 years . ABI declined an average of 0.014 per year . WalkDist declined at an average rate of 9.2 yards per year . The cumulative 10-year risks of development of IU and IRP were 23 % and 30 % , respectively . In multivariate analysis using several clinical risk factors , we found that only DM ( relative risk [ RR ] , 1.8 ) and ABI ( RR , 2.2 for 0.1 decrease in ABI ) predicted the development of IRP . Similarly , only DM ( RR , 3.0 ) and ABI ( RR , 1.9 for 0.1 decrease in ABI ) were significant predictors of IU . CONCLUSION This large serial study of claudication is , to our knowledge , the longest of its kind . We documented an average rate of ABI decline of 0.014 per year and a decline in WalkDist of 9.2 yards per year . Two clinical factors , ABI and DM , were found to be associated with the development of IRP and IU . Our findings may be useful in predicting the clinical course of claudication AIM The aim of this study was to compare ankle brachial indices ( APBI ) with pedal waveforms utilizing the continuous wave Doppler in a population with diabetes mellitus . METHODS A prospect i ve study design was employed to investigate the ABPI in a cohort of 49 people with type 2 diabetes mellitus . ABPI assessment was completed using a portable h and held Doppler and ankle pressures of < 0.9 were taken as suggestive of peripheral arterial disease ( PAD ) . Arterial spectral waveforms in each foot were also recorded and compared to the ABPI readings . RESULTS Inconsistencies were identified between ABPIs and waveform interpretations in the study population . Approximately 35 % of subjects had inconsistencies between their ABPI result and waveform interpretation in their right or left foot . CONCLUSIONS Both ABPIs and Doppler waveforms should be used in the assessment of people with diabetes in order to screen for PAD . This would ensure an accurate assessment of PAD and would allow initiation of appropriate secondary risk factor control measures OBJECTIVES To determine differences between PTA and conventional medical treatment in treadmill distance until onset of claudication , treadmill maximum walking distance , patient reported maximum walking distance , ankle brachial pressure index ( ABPI ) , quality of life ( Nottingham Health Profile , NHP ) and Duplex measured extent of occlusive disease . DESIGN R and omised controlled clinical trial . METHODS Six hundred claudicants were screened . Fifty-one men and 11 women with intermittent claudication due to short femoral stenoses or occlusions ( n = 47 ) and iliac stenoses ( n = 15 ) were r and omised to either PTA plus medical treatment ( PTA group , n = 30 ) or to medical treatment alone ( control group , n = 32 ) . Medical treatment consisted of daily low dose aspirin and advice on smoking and exercise . RESULTS At 6 month follow up : In the PTA group more patients reported no claudication ( p < or = 0.05 ) and were asymptomatic on the treadmill ( p < or = 0.01 ) compared to the control group . The ABPI was significantly higher in the PTA group . More of the PTA group reported lower NHP pain scores ( p < or = 0.05 ) . In the control group there were more occluded arteries ( p < or = 0.001 ) , and the stenosis velocity ratio of patient arteries was significantly higher ( p < or = 0.001 ) . CONCLUSIONS Only 10 % of claudicants had discrete lesions suitable for PTA . Treatment of these patients with PTA produces a greater short-term improvement in walking and quality of life than medical treatment alone and is associated with less progression of disease PURPOSE To compare clinical success , functional capacity , and quality of life during 12 months after revascularization or supervised exercise training in patients with intermittent claudication . MATERIAL S AND METHODS This study had institutional review board approval , and all patients gave written informed consent . Between September 2002 and September 2005 , 151 consecutive patients who presented with symptoms of intermittent claudication were r and omly assigned to undergo either endovascular revascularization ( angioplasty-first approach ) ( n = 76 ) or hospital-based supervised exercise ( n = 75 ) . The outcome measures were clinical success , functional capacity , and quality of life after 6 and 12 months . Clinical success was defined as improvement in at least one category in the Rutherford scale above the pretreatment level . Significance of differences between the groups was assessed with the unpaired t test , chi(2 ) test , or Mann-Whitney U test . To adjust outcomes for imbalances of baseline values , multivariable regression analysis was performed . RESULTS Immediately after the start of treatment , patients who underwent revascularization improved more than patients who performed exercise in terms of clinical success ( adjusted odds ratio [ OR ] , 39 ; 99 % confidence interval [ CI ] : 11 , 131 ; P < .001 ) , but this advantage was lost after 6 ( adjusted OR , 0.9 ; 99 % CI : 0.3 , 2.3 ; P = .70 ) and 12 ( adjusted OR , 1.1 ; 99 % CI : 0.5 , 2.8 ; P = .73 ) months . After revascularization , fewer patients showed signs of ipsilateral symptoms at 6 months compared with patients in the exercise group ( adjusted OR , 0.4 ; 99 % CI : 0.2 , 0.9 ; P < .001 ) , but no significant differences were demonstrated at 12 months . After both treatments , functional capacity and quality of life scores increased after 6 and 12 months , but no significant differences between the groups were demonstrated . CONCLUSION After 6 and 12 months , patients with intermittent claudication benefited equally from either endovascular revascularization or supervised exercise . Improvement was , however , more immediate after revascularization PURPOSE The purpose of the current study was to determine whether hemostatic and rheologic factors are associated with the deterioration of peripheral arterial disease in patients with intermittent claudication and the influence of smoking and severity of underlying disease on these relationships . METHODS We conducted a prospect i ve cohort study with a 6-year follow-up period of a consecutive series of 607 patients with uncomplicated intermittent claudication . The study setting was the Peripheral Vascular Clinic , Royal Infirmary of Edinburgh . The main outcome measures were peripheral vascular intervention or onset of severe chronic leg ischemia ( rest pain , ulceration , gangrene ) . RESULTS A total of 210 patients died during follow-up . Two hundred three patients did not have a vascular event or deterioration of limb ischemia , 45 patients underwent a peripheral vascular intervention , and 64 progressed to severe chronic leg ischemia . Median levels ( interquartile ranges ) of whole blood viscosity were significantly higher in the vascular intervention group ( 3.75 mPa/sec ; range , 3.38 to 4.13 mPa/sec ) than in those who did not deteriorate 3.48 mPa/sec ; range , 3.06 to 3.83 mPa/sec ) ( p < or = 0.05 ) , and plasma von Willebr and factor was higher in those with severe chronic leg ischemia ( 154.0 IU/dl ; range , 122.0 to 187.0 IU/dl ) than in those who did not deteriorate ( 131.0 IU/dl ; range , 106.0 to 165.0 IU/dl ) ( p < or = 0.01 ) . After adjustment for age , sex , cigarette smoking , and ankle brachial pressure index , the levels of plasma fibrinogen and blood and plasma viscosities were each associated with an increased risk of vascular intervention ( all p < or = 0.05 ) . There were no significant associations between any of the hemorheologic factors and the risk of severe chronic leg ischemia on multivariate analyses . CONCLUSION Elevations in rheologic factors may have important effects on further reduction of blood flow in the legs of patients with claudication and promote worsening ischemia and clinical progression of symptoms OBJECTIVE To determine the fatal and non-fatal cardiovascular event rate in patients with intermittent claudication treated with antiplatelet agents . METHODS AND DESIGN Patients with PAD-II stage Fontaine ( n=223 ) and sex and age matched controls ( n=446 ) were followed up from 1974 to 1998 . All patients were treated with antiplatelet agents ( aspirin , 325 mg once daily or ticlopidine , 250 mg twice daily ) and for risk factors , if present . The end points were death for any cause ( vascular event , cancer , and others ) and non-fatal vascular events ( myocardial infa rct ion , ischemic/hemorrhagic stroke , and leg amputation ) . RESULTS PAD patients had a significantly higher mortality rate than controls ( 3.99 vs. 2.53 deaths for 100 patients per year , respectively ) , cancer ( mostly lung , stomach and colon ) and vascular mortality accounted for such difference . The incidence of non-fatal vascular events was three times higher in patients than in controls ( 1.7 vs. 0.56 , 100 patients per year , respectively , p<0.05 ) even considering amputation separately ( 0.28 vs. 0.00 , 100 patients per year , p<0.05 ) . No difference between patients treated with aspirin or ticlopidine could be found in both end points . CONCLUSIONS Vascular mortality and morbidity , despite the use of antiplatelet agents , are still higher than sex and age matched controls ; however , the commonest cause of death is cancer |
612 | 31,531,971 | There was very limited evidence available for adverse effects and quality of life ( QoL ) .
There is very limited evidence for adverse effects , patient satisfaction , QoL , and compliance rates .
There is low-certainty evidence favouring use of intermittent pneumatic compression devices compared to a control device for the treatment of severity owing to different measurements used by the studies reporting on this outcome and small studies of short duration .
There is moderate-certainty evidence of improved QoL but possible increased adverse effects related to compression device use owing to small studies of short duration . | BACKGROUND Post-thrombotic syndrome ( PTS ) is a long-term complication of deep vein thrombosis ( DVT ) characterised by chronic complaints such as oedema and skin changes including ; venous ectasia , varicose veins , redness , eczema , hyperpigmentation , and in severe cases fibrosis of the subcutaneous adipose in the affected limb .
These chronic complaints are the effects of venous outflow restriction that can cause symptoms such as heaviness , itching , pain , cramps , and paraesthesia .
Twenty to fifty percent of people with DVT develop post-thrombotic complications .
Several non-pharmaceutical measures are used for prevention of PTS during the acute phase of DVT .
These include elevation of the legs and compression therapy .
There have been limited studies regarding the effectiveness of compression therapy for prevention or treatment of PTS .
As a result , clinicians and guidelines differ in their assessment of compression therapy during treatment of DVT and in the treatment of PTS .
This is an up date of a review first published in 2003 .
OBJECTIVES To assess the effectiveness of compression therapy for treatment of post-thrombotic syndrome , including elastic compression stockings and mechanical devices compared with no intervention , placebo and with each other . | Objective The purpose of this r and omized study was to evaluate the influence of immediate multilayer compression b and ages before application of elastic stockings in the acute phase of deep-vein thrombosis ( DVT ) on development of the post-thrombotic syndrome ( PTS ) . Methods Sixty-nine patients with acute symptomatic DVT were r and omized to immediate b and aging ( n = 34 ) or no b and aging ( n = 35 ) . After reduction of edema sized-to-fit elastic stockings were applied in all patients after 7–14 days . Follow-up visits and non-invasive examinations were planned after 7 , 30 and 90 days and 1 year . Venous outflow resistance ( VOR ) was measured by strain gauge plethysmography . Thrombosis score ( TS ) and reflux were measured by duplex scanning . After one year patients were evaluated for clinical PTS using both the clinical scale of the CEAP classification and the Villalta score . Results Improvement of clinical symptoms and decrease of leg circumference was better on day 7 in the b and aging group , but after 1 and 3 months clinical symptoms had improved equally in both groups . In 7 patients in the no-b and aging group a b and age was applied after all because of persistent edema after 10 days . There were no differences in VOR , TS and reflux . Using the CEAP classification the incidence of PTS was 39 % in patients with b and ages and 42 % in patients without b and ages ( RR 0.91 , 95 % CI 0.50–1.66 ) . Using the Villalta score the incidence of PTS was resp . 29 and 33 % ( RR 0.87 , 95 % CI 0.41–1.8 ) . There was no difference in severity of PTS . Conclusion Immediate multilayer compression b and aging in the acute phase of DVT is effective in reducing edema and complaints in the first week , but has no effect on thrombus regression , valve incompetence and the development of clinical PTS after 1 year BACKGROUND Post-thrombotic syndrome varies from mild oedema to incapacitating swelling with pain and ulceration . We investigated the rate of post-thrombotic syndrome after a first episode of deep-vein thrombosis and assessed the preventive effect of direct application of a sized-to-fit grade d compression stocking . METHODS Patients with a first episode of venogram-proven proximal deep-vein thrombosis were r and omly assigned no stockings ( the control group ) or made-to-measure grade d compression elastic stockings for at least 2 years . Post-thrombotic syndrome was assessed with a st and ard scoring system that combined clinical characteristics and objective leg measurements . Patients were assessed every 3 months during the first 2 years , and every 6 months thereafter for at least 5 years . The cumulative incidence of mild-to-moderate post-thrombotic syndrome was the primary outcome measure . FINDINGS Of the 315 consecutive out patients considered for inclusion , 44 were excluded and 77 did not consent to take part . 194 patients were r and omly assigned compression stockings ( n = 96 ) or no stockings ( n = 98 ) . The median follow-up was 76 months ( range 60 - 96 ) in both groups . Mild-to-moderate post-thrombotic syndrome ( score > or = 3 plus one clinical sign ) occurred in 19 ( 20 % ) patients in the stocking group and in 46 ( 47 % ) control-group patients ( p < 0.001 ) . 11 ( 11 % ) patients in the stocking group developed severe post-thrombotic syndrome ( score > or = 4 ) , compared with 23 ( 23 % ) patients in the control group ( p < 0.001 ) . In both groups , most cases of post-thrombotic syndrome occurred within 24 months of the acute thrombotic event . INTERPRETATION About 60 % of patients with a first episode of proximal deep-vein thrombosis develop post-thrombotic syndrome within 2 years . A sized-to-fit compression stocking reduced this rate by about 50 % BACKGROUND Graduated elastic compression ( GEC ) stockings have been demonstrated to reduce the morbidity associated with post-thrombotic syndrome . The ideal length or compression strength required to achieve this is speculative and related to physician preference and patient compliance . The aim of this study was to evaluate the hemodynamic performance of four different stockings and determine the patient 's preference . METHODS Thirty-four consecutive patients ( 40 legs , 34 male ) with post-thrombotic syndrome were tested with four different stockings ( Mediven plus open toe , Bayreuth , Germany ) of their size in r and om order : class 1 ( 18 - 21 mm Hg ) and class II ( 23 - 32 mm Hg ) , below-knee ( BK ) and above-knee thigh-length ( AK ) . The median age , Venous Clinical Severity Score , Venous Segmental Disease Score , and Villalta scale were 62 years ( range , 31 - 81 years ) , 8 ( range , 1 - 21 ) , 5 ( range , 2 - 10 ) , and 10 ( range , 2 - 22 ) , respectively . The C of C0 - 6EsAs , d , pPr , o was C0 = 2 , C2 = 1 , C3 = 3 , C4a = 12 , C4b = 7 , C5 = 12 , C6 = 3 . Obstruction and reflux was observed on duplex in 47.5 % legs , with deep venous reflux alone in 45 % . Air plethysmography was used to measure the venous filling index ( VFI ) , venous volume , and time to fill 90 % of the venous volume . Direct pressure measurements were obtained while lying and st and ing using the PicoPress device ( Microlab Elettronica , Nicolò , Italy ) . The pressure sensor was placed underneath the test stocking 5 cm above and 2 cm posterior to the medial malleolus . At the end of the study session , patients stated their preferred stocking based on comfort . RESULTS The VFI , venous volume , and time to fill 90 % of the venous volume improved significantly with all types of stocking versus no compression . In class I , the VFI ( mL/s ) improved from a median of 4.9 ( range , 1.7 - 16.3 ) without compression to 3.7 ( range , 0 - 14 ) BK ( 24.5 % ) and 3.6 ( range , 0.6 - 14.5 ) AK ( 26.5 % ) . With class II , the corresponding improvement was to 4.0 ( range , 0.3 - 16.2 ) BK ( 18.8 % ) and 3.7 ( range , 0.5 - 14.2 ) AK ( 24.5 % ) . Median stocking pressure ( mm Hg ) as measured with the PicoPress in class I was 23 ( range , 12 - 33 ) lying and 27 ( range , 19 - 39 ) st and ing ( P < .0005 ) and in class II was 28 ( range , 21 - 40 ) lying and 32 ( range , 23 - 46 ) st and ing ( P < .0005 ) . There was a significant but weak correlation ( Spearman ) between stocking interface pressure measured directly with the PicoPress and the VFI improvement ( baseline VFI-compression VFI ) at r = .237 ; P = .005 . Twenty-one patients ( legs ) changed their preference of compression and 38 % of these ( 8/21 patients , 9/21 legs ) preferred an AK-GEC stocking . CONCLUSIONS Compression significantly improved all hemodynamic parameters on air plethysmography . However , the hemodynamic benefit did not significantly change with the class or length of stocking . These results support the liberal selection of a GEC stocking based on patient preference Although below-knee compression elastic stockings ( CES ) are effective for the prevention of the postthrombotic syndrome ( PTS ) , a substantial number of patients with deep venous thrombosis still develop PTS . In the present open-label , r and omized clinical trial , we compared thigh-length with below-knee CES for the prevention of PTS . A total of 267 patients with the first episode of proximal deep venous thrombosis were r and omized to wear either thigh-length or below-knee CES for 2 years . After 3 , 6 , 12 , 18 , 24 , and 36 months , they were assessed for PTS manifestations according to the Villalta scale . PTS developed in 44 ( 32.6 % ) of the 135 patients r and omized to thigh-length CES and in 47 ( 35.6 % ) of the 132 allocated to below-knee CES , for an adjusted hazard ratio of 0.93 ( 95 % confidence interval , 0.62 - 1.41 ) . Severe PTS developed in 3 patients in each group . CES-related side effects developed in 55 ( 40.7 % ) of the 135 patients allocated to thigh-length CES and in 36 ( 27.3 % ) of those r and omized to the below-knee group ( P = .017 ) , and led to premature discontinuation of their use in 29 ( 21.5 % ) and 18 ( 13.6 % ) patients , respectively . We conclude that thigh-length CES do not offer a better protection against PTS than below-knee CES and are less well tolerated Objective Post-thrombotic syndrome is a chronic complication of acute deep venous thrombosis in the lower extremity . The role of graduated compression stockings in the prevention of post-thrombotic syndrome has been studied with opinion being divided on the beneficial effects . We aim to answer this question with a r and omized controlled study that uses multiple scoring instruments to assess post-thrombotic syndrome . Methods Sixty-nine consecutive patients with acute deep venous thrombosis diagnosed by duplex ultrasonography were r and omized to treatment with graduated compression stockings or no graduated compression stockings . Venous Clinical Severity Score and Villalta-Pr and oni Score , commonly used scoring systems , were used to appraise post-thrombotic syndrome at 3 , 6 , 12 , 18 , and 24 months following diagnosis of deep venous thrombosis . In both scoring systems , the individual either had post-thrombotic syndrome or no post-thrombotic syndrome . Cumulative incidence was computed using Kaplan – Meier analysis . Relative risk was assessed for age , obesity , varicose veins , and iliofemoral deep venous thrombosis . Results As measured by both Villalta-Pr and oni Score and Venous Clinical Severity Score instruments , the graduated compression stockings group had a lower incidence of post-thrombotic syndrome compared to the control group , but only when one month was used as cut off time for the first diagnosis of post-thrombotic syndrome . When 6 or 12 months were used , there was no difference in the incidence of post-thrombotic syndrome between the two groups . The burden of post-thrombotic syndrome was significantly more when the Villalta-Pr and oni Score instrument ( ∼75 % ) was used as compared to the Venous Clinical Severity Score instrument ( ∼30 % ) at 24 months ’ follow-up . Obesity was the only statistically significant predictor for the development of post-thrombotic syndrome . Conclusion As assessed by both Villalta-Pr and oni Score and Venous Clinical Severity Score instruments , use of graduated compression stockings does not reduce the incidence of post-thrombotic syndrome . There is a significant difference in the incidence post-thrombotic syndrome as detected by Villalta-Pr and oni Score and Venous Clinical Severity Score instruments with incidence of post-thrombotic syndrome dependent on instrument and cut off time interval used to assess post-thrombotic syndrome . However , larger prospect i ve studies are required to confirm these differences Objective To study whether stopping elastic compression stockings ( ECS ) after 12 months is non-inferior to continuing them for 24 months after proximal deep venous thrombosis . Design Multicentre single blind non-inferiority r and omised controlled trial . Setting Outpatient clinics in eight teaching hospitals in the Netherl and s , including one university medical centre . Participants Patients compliant with compression therapy for 12 months after symptomatic , ultrasound proven proximal deep venous thrombosis of the leg . Interventions Continuation or cessation of ECS 12 months after deep venous thrombosis . Main outcome measures The primary outcome was the incidence of post-thrombotic syndrome 24 months after diagnosis of deep venous thrombosis , as assessed by the st and ardised Villalta scale in an intention to treat analysis . The predefined non-inferiority margin was 10 % . The main secondary outcome was quality of life ( VEINES-QOL/Sym ) . Results 518 patients compliant with ECS and free of post-thrombotic syndrome were r and omised one year after diagnosis of deep venous thrombosis to stop or continue ECS therapy for another year . In the stop-ECS group , 51 of 256 patients developed post-thrombotic syndrome , with an incidence of 19.9 % ( 95 % confidence interval 16 % to 24 % ) . In the continue-ECS group , 34 of 262 patients developed post-thrombotic syndrome ( incidence 13.0 % , 9.9 % to 17 % ) , of whom 85 % used ECS six or seven days a week during the study period , for an absolute difference of 6.9 % ( 95 % confidence interval upper limit 12.3 % ) . Because the upper limit of the 95 % confidence interval exceeds the predefined margin of 10 % , non-inferiority was not reached . The number needed to treat to prevent one case of post-thrombotic syndrome by continuing ECS was 14 ( 95 % confidence interval lower limit 8) . Quality of life did not differ between the two groups . Conclusion Stopping ECS after one year in compliant patients with proximal deep venous thrombosis seemed not to be non-inferior to continuing ECS therapy for two years in this non-inferiority trial . Trial registration Netherl and s Trial Register NTR1442 PURPOSE A new intermittent pneumatic compression device ( SCD Response System ) has recently been shown in healthy volunteers to have the ability to detect the postcompression refilling of the calf veins and to respond by initiating the subsequent cycle when these veins are full . This has proven to be more effective in expelling blood proximally than the conventional intermittent pneumatic compression device ( SCD Sequel System ) . The aim of this study was to test the influence of venous disease on the postcompression refill time detected by means of the SCD Response and the effectiveness of the new system in expelling blood in patients who have venous reflux caused by post-thrombotic syndrome or varicose veins . METHODS This open , controlled trial was conducted in an academic vascular unit with 10 patients who had post-thrombotic syndrome and 10 patients who had varicose veins . The new SCD Response System was tested against the existing SCD Sequel System in both legs in the supine , semirecumbent , and sitting positions . The refilling time sensed by means of the device was correlated with the venous filling index by using air plethysmography . The total volume of blood expelled per hour during compression was compared with that expelled by the SCD Sequel System in the same volunteers and in the same positions . RESULTS An inverse association was found between the mean postcompression refilling time in the sitting position and the venous filling index of the apparently healthy or less severely affected leg ( r = -0.52 , P = .019 ) , the refill time being significantly shorter in patients with advanced venous disease . The SCD Response System increased the volume expelled per hour in the post-thrombotic leg , when compared with the SCD Sequel System , by 109.9 % ( P = .005 ) in the supine position , by 85.1 % ( P = .009 ) in the semirecumbent position , and by 40.2 % ( P = .005 ) in the sitting position . The corresponding results in the more severely affected leg in patients with varicose veins were 71.9 % ( P = .005 ) in the supine position , 77.9 % ( P = .005 ) in the semirecumbent position , and 55.7 % ( P = .013 ) in the sitting position . Similar improved results were also found in the contralateral leg in both groups . CONCLUSIONS The deflation setting s of the new SCD Response System are able to be adjusted selectively , correlating with the physiological severity of chronic venous insufficiency . By achieving more frequent compression cycles , the new system is more effective than the current one in expelling blood proximally , confirming our earlier findings in healthy volunteers . Further studies testing a possible improved efficacy in preventing deep venous thrombosis in this high-risk group are justified Severe post-thrombotic syndrome ( PTS ) is responsible for considerable disability , reduced quality of life and increased health care costs . Current therapies are limited and often ineffective . We performed a two-centre , r and omized , cross-over controlled trial to evaluate Venowave , a novel lower-limb venous-return assist device , for the treatment of severe PTS . Eligible subjects were allocated to receive , in r and omized order , Venowave for eight weeks and a control device for eight weeks . The eight-week treatment periods were separated by a four-week period when no device was used ( i.e. wash-out period ) . The primary outcome measure was a ' clinical success ' defined as : i ) reported benefit from the device ; and ii ) moderate or greater improvement in symptoms of PTS ; and iii ) willingness to continue using the device . Secondary outcome measures included quality of life ( QOL ) as measured by VEINES-QOL question naire ( higher scores indicate better QOL ) , and PTS severity as measured by the Villalta PTS scale ( higher scores indicate more severe PTS ) . The study was registered with Clinical Trials . gov ( NCT00182208 ) . Thirty-two patients were enrolled . Of these , 26 ( 80 % ) were also using graduated compression stockings . Twenty-six participants completed both trial periods . Clinical success occurred in 10 ( 31 % ) participants receiving Venowave and four ( 13 % ) participants receiving the control device , with two ( 6 % ) participants reporting a clinical success with both devices ( P = 0.11 ) . Mean VEINES-QOL score at the end of study period was significantly greater ( P = 0.004 ) for Venowave ( 52.5 ; SD 5.8 ) compared to control ( 50.2 ; SD 6.2 ) . Mean Villalta scale score at the end of study period was significantly decreased ( P = 0.004 ) for Venowave ( 12.2 ; SD 6.3 ) compared to control ( 15.0 ; SD 6.1 ) . In conclusion , Venowave appears to be a very promising new therapy for patients with severe PTS , which may be used alone or in combination with graduated compression stockings BACKGROUND Post-thrombotic syndrome ( PTS ) is a common and burdensome complication of deep venous thrombosis ( DVT ) . Previous trials suggesting benefit of elastic compression stockings ( ECS ) to prevent PTS were small , single-centre studies without placebo control . We aim ed to assess the efficacy of ECS , compared with placebo stockings , for the prevention of PTS . METHODS We did a multicentre r and omised placebo-controlled trial of active versus placebo ECS used for 2 years to prevent PTS after a first proximal DVT in centres in Canada and the USA . Patients were r and omly assigned to study groups with a web-based r and omisation system . Patients presenting with a first symptomatic , proximal DVT were potentially eligible to participate . They were excluded if the use of compression stockings was contraindicated , they had an expected lifespan of less than 6 months , geographical inaccessibility precluded return for follow-up visits , they were unable to apply stockings , or they received thrombolytic therapy for the initial treatment of acute DVT . The primary outcome was PTS diagnosed at 6 months or later using Ginsberg 's criteria ( leg pain and swelling of ≥1 month duration ) . We used a modified intention to treat Cox regression analysis , supplemented by a prespecified per- protocol analysis of patients who reported frequent use of their allocated treatment . This study is registered with Clinical Trials.gov , number NCT00143598 , and Current Controlled Trials , number IS RCT N71334751 . FINDINGS From 2004 to 2010 , 410 patients were r and omly assigned to receive active ECS and 396 placebo ECS . The cumulative incidence of PTS was 14·2 % in active ECS versus 12·7 % in placebo ECS ( hazard ratio adjusted for centre 1·13 , 95 % CI 0·73 - 1·76 ; p=0·58 ) . Results were similar in a prespecified per- protocol analysis of patients who reported frequent use of stockings . INTERPRETATION ECS did not prevent PTS after a first proximal DVT , hence our findings do not support routine wearing of ECS after DVT . FUNDING Canadian Institutes of Health Research Calf muscle pump function was assessed in 41 limbs after venous ulcers had healed . Treatment was then r and omized either to ligation of incompetent lower leg communicating veins and ablation of incompetent superficial veins combined with permanent graduated compression elastic stockings , or to graduated compression elastic stockings only . Half volume refilling time ( TV1/2 ) and relative expelled volume ( EVrel ) measured on foot volume plethysmography were used to assess calf muscle pump function . This was repeated after 12 months . The initial TV1/2 and EVrel were significantly lower than for normal limbs . There was no significant improvement in TV1/2 in either treatment group ( Student 's t test , P = 0.78 , P = 0.19 ) . EVrel did not improve significantly in limbs treated with elastic stockings alone ( P = 0.94 ) , but there was a slight but significant improvement in EVrel in limbs treated with surgery and elastic stockings ( P = 0.048 ) ; however , this was still significantly below the normal range ( P<0.001 ) . In limbs without phlebographic evidence of post‐thrombotic changes , treated with the combination of surgery and elastic stockings , there was a significant improvement in EVrel ( P = 0.035 ) , but no improvement was found in limbs with post‐thrombotic changes . This small but significant improvement in EVrel in limbs without post‐thrombotic changes treated by surgery and elastic stockings may explain the reduced incidence of reulceration that has been found following surgical eradication of the superficial and communicating veins Graduated elastic compression stockings ( ECS ) are often prescribed after deep venous thrombosis ( DVT ) to alleviate acute symptoms and to prevent and treat post-thrombotic syndrome ( PTS ) . In patients with DVT , leg symptoms tend to worsen with exercise . The effects of ECS use during exercise have not been studied . Objectives were to determine whether ECS improve symptoms and signs and increase exercise capacity when worn during treadmill exercise by patients with prior DVT , with or without PTS . The methods employed a r and omized cross-over trial . We recruited subjects who had a first episode of unilateral DVT at least 1 year earlier and categorized them as having , or not having , the PTS using a vali date d scale . Subjects underwent two identical treadmill exercise sessions at least 1 week apart , and were r and omly assigned to wear knee-length 30 mmHg ECS on the affected leg during one of the two sessions . Venous symptoms , leg volume , leg circumference and calf muscle flexibility were measured in the affected leg before and after both exercise sessions . Subjects achieved similar percentage maximum predicted heart rates during both sessions . Comparing the ECS to no ECS session , there were no significant differences in treadmill time ( 21.2 vs. 21.2 min , P = 0.94 ) , gain in leg volume ( 71 vs. 73 mL , P = 0.83 ) , or change in soleus or gastrocnemius flexibility , whether or not PTS was present . Symptoms in general worsened slightly with exercise regardless of whether or not ECS were worn and did not differ according to PTS status . Per-subject analysis showed that use of ECS result ed in global improvement of symptoms in 25 % of subjects , global worsening in 33 % of subjects , and had no or inconsistent effects in 42 % of subjects . Whether or not PTS was present , the use of ECS during exercise by patients with prior DVT did not improve symptoms and signs during exercise or increase exercise capacity Deep venous thrombosis of the lower extremity is a serious disorder ; the estimated incidence is 1 per 1000 persons per year [ 1 - 3 ] . The disease can occur after surgical procedures and trauma and in the presence of cancer or inherited coagulation disorders ; it can also develop without any of these factors [ 3 ] . The clinical course of deep venous thrombosis might be complicated by pulmonary embolism , recurrent episodes of deep venous thrombosis , and the development of serious post-thrombotic sequelae , such as venous ulceration , debilitating pain , and intractable edema [ 3 ] . Patients with deep venous thrombosis are usually treated with an initial course of heparin ( 5 to 10 days ) followed by 3 to 6 months of oral anticoagulant therapy . This treatment regimen reduces the risk for short-term thromboembolic complications to approximately 5 % [ 4 , 5 ] . The long-term risk for recurrent venous thromboembolism and the incidence and severity of post-thrombotic sequelae in patients with symptomatic deep venous thrombosis have not been well documented . In a recent large r and omized , clinical trial comparing 6 weeks of oral anticoagulant therapy with 6 months of therapy [ 6 ] , patients with symptomatic deep venous thrombosis were followed for 2 years for recurrences and death . This trial showed a substantial reduction in the risk for recurrent venous thromboembolism among patients in the 6-month oral anticoagulant group , but the investigators did not report on the occurrence of the post-thrombotic syndrome . Another recent study [ 7 ] reported the 8-year incidence of recurrences and post-thrombotic manifestations in patients with confirmed symptomatic deep venous thrombosis . However , only a few patients were included in this study , and data were collected retrospectively . We assessed the clinical course of a first episode of symptomatic deep venous thrombosis in a large consecutive series of patients who had long-term follow-up . We assessed mortality and the long-term incidences of recurrent venous thromboembolism and the post-thrombotic syndrome . We also evaluated the potential risk factors for these three outcomes . Methods Identification of Inception Cohort The Department of Internal Medicine of the University of Padua , Padua , Italy , is a diagnostic facility for out patients with clinical ly suspected venous thromboembolism in a community of approximately 350 000 persons . All consecutive out patients with a first episode of clinical ly suspected deep venous thrombosis who were referred by their general practitioners between January 1986 and December 1991 had noninvasive testing [ 8 ] . Patients were potentially eligible for the study if confirmatory venography showed deep venous thrombosis . Patients were excluded from the study if they had been referred because of recurrent venous thrombosis , were geographically inaccessible for follow-up , or refused to give informed consent . The Institutional Review Board of the hospital of the University of Padua approved the study . Baseline Assessment At the time of referral , demographic characteristics were recorded and a medical history was taken ; information was elicited on the period between the onset of symptoms and presentation to the thrombosis service ( patientphysician delay ) , the presence of risk factors for thrombosis ( that is , cancer , surgery , trauma or fracture , immobilization for more than 7 days , pregnancy or childbirth , or estrogen use ) , and symptoms of pulmonary embolism . Information was also obtained on the history of venous thromboembolism in first-degree relatives . Antithrombin , protein C and S , and lupus-like anticoagulant levels were subsequently measured . Assays were done , and previously described criteria for abnormality and deficiency were used [ 9 ] . The venograms obtained at baseline were divided into those representing proximal venous thrombosis ( with or without concurrent venous thrombosis of the calf ) and those indicating isolated venous thrombosis of the calf . Proximal venous thrombosis was defined as thrombosis located above the trifurcation of the calf veins that involved at least the popliteal vein , superficial femoral vein , common femoral vein , or iliac vein . The location and occlusiveness of proximal thrombi were also determined . A patient was considered to have nonocclusive deep venous thrombosis if contrast material was seen between the thrombus and the vessel wall along the entire thrombus . Treatment Patients were admitted to the hospital and treated with an initial course of high-dose intravenous st and ard heparin ( a bolus of 5000 U followed by continuous infusion of 30 000 U/d , subsequently adjusted to maintain an activated partial thromboplastin time between 1.5 and 2.5 times the normal value ) or subcutaneous low-molecular-weight heparin ( 90 U of anti-factor Xa/kg of body weight twice daily ) . Therapy with oral anticoagulant agents ( warfarin ) was started on day 5 to 7 of treatment and was continued for 3 months . The oral anticoagulant dose was adjusted daily to maintain an international normalized ratio between 2.0 and 3.0 . Treatment with low-molecular-weight heparin was discontinued on day 10 or later if the international normalized ratio was less than 2.0 . This treatment strategy deviated in the following groups of patients : those with cancer , protein deficiencies , or lupus anticoagulant , in whom oral anticoagulation therapy was prolonged ; those with small isolated venous thrombosis of the calf , who received oral anticoagulation alone ; those with contraindications to anticoagulant treatment , who received no treatment or an inferior caval-vein filter ; those who refused to be hospitalized , who received low-dose heparin and oral anticoagulant agents ; and those with threatened viability of the leg , who received thrombolytic therapy . The actual type and duration of treatments were recorded . All patients were instructed to wear elastic graduated compression stockings ( providing 40 mm Hg of pressure at the ankle ) for at least 2 years . Follow-up All patients were seen 3 and 6 months after the initial referral and thereafter returned to the study center every 6 months for follow-up assessment s. Patients were asked to return to the thrombosis center immediately if symptoms suggestive of recurrent venous thromboembolism developed . Follow-up was continued for as long as 8 years or until July 1995 . To avoid diagnostic suspicion bias , the medical history on general health , symptoms of recurrent venous thromboembolism , and the post-thrombotic syndrome was obtained by using a st and ardized form . Patients who could not attend the follow-up sessions were visited at home . For all patients who died during follow-up , the date and cause of death were documented . Diagnosis of Recurrent Venous Thromboembolism and Hemorrhage Contrast venography of the symptomatic leg or legs was done as described previously [ 10 ] . The criteria for deep venous thrombosis were a constant intraluminal filling defect confirmed in at least two different projections or nonvisualization of a vein or a segment thereof , despite adequate technique and repeated injections with contrast material . The presence or absence of venous thrombosis was assessed by a panel of independent observers who were unaware of the patient 's other clinical features or previous test results . If a patient presented with clinical ly suspected recurrent venous thrombosis of the leg , venography was done . The criterion for recurrent venous thrombosis of the leg was a new intraluminal filling defect on the venogram . If the venogram was not diagnostic , recurrent venous thrombosis was diagnosed on the basis of an abnormal 125I-fibrinogen leg scan or results of noninvasive tests that had changed from normal to abnormal [ 11 , 12 ] . Patients with suspected pulmonary embolism had venography if they had concurrent leg symptoms or perfusion lung scanning in the absence of leg symptoms . Pulmonary embolism was excluded if the perfusion scan was normal . Because ventilation lung scanning was not available during the first years of the study and because pulmonary angiography could not routinely be done , we could not definitively diagnose pulmonary embolism in some patients . If a definitive diagnosis could not be made , patients were classified as not having recurrent venous thromboembolism . Perfusion lung scanning and pulmonary angiography were done and their results were interpreted according to st and ard procedures [ 13 ] . Hemorrhagic episodes were classified as major or minor , as reported previously [ 14 ] . The documentation of all patients suspected of having a recurrent venous thromboembolic or bleeding event was review ed by a three-member adjudication committee that was unaware of further clinical details of the patient . Criteria for the Post-Thrombotic Syndrome Presence of the post-thrombotic syndrome was assessed by investigators who were unaware of previous post-thrombotic manifestations and further clinical details of the patient . The presence of leg symptoms ( pain , cramps , heaviness , pruritus , and paresthesia ) and signs ( pretibial edema , in duration of the skin , hyperpigmentation , new venous ectasia , redness , and pain during calf compression ) was scored . For each item , the investigators assigned a score of 0 ( not present or minimal ) to 3 ( severe ) . The presence of a venous ulcer of the lower limb was recorded . In patients with bilateral thrombosis , the higher score was used . A total score of 15 or more on two consecutive visits or the presence of a venous ulcer indicated severe post-thrombotic syndrome , and a total score of 5 to 14 on two consecutive visits indicated mild post-thrombotic syndrome . This score has been shown to have good reproducibility , and it correlates well with the patient 's perception of the interference of leg symptoms with daily life [ 15 ] . Statistical Analysis We calculated Kaplan-Meier estimates and 95 % CIs for a visual assessment of survival and calculated the risk for recurrent venous thromboembolism and mild and severe Context Although physicians often recommend elastic stockings to help prevent the post-thrombotic syndrome , few studies have evaluated the stockings ' effectiveness . Contribution One hundred eighty patients with proximal deep venous thrombosis ( DVT ) were r and omly assigned to wear or not wear below-knee elastic compression stockings for 2 years . More than 90 % of the patients assigned to elastic stockings wore them daily during the 2-year period , but 5 of 90 patients stopped using them because of itching , redness , or discomfort . Twenty-six percent of the patients in the elastic stockings group developed the post-thrombotic syndrome compared with 49 % of controls . Implication s Below-knee elastic compression stockings reduce post-thrombotic sequelae in patients with proximal DVT . The Editors One of every 3 to 4 patients with symptomatic proximal deep venous thrombosis ( DVT ) of the lower extremities will develop post-thrombotic sequelae ( 1 - 5 ) . The incidence of the post-thrombotic syndrome is highest in elderly patients and after recurrent episodes of ipsilateral thrombosis ( 1 , 3 , 4 , 6 ) . This syndrome usually appears within 1 year after the index thrombosis ( 1 , 2 ) . Clinical presentation may vary from minor signs , including skin discoloration , venous ectasia , discomfort , and swelling , to severe manifestations , such as chronic pain , intractable edema , or leg ulcer ( 7 , 8) . Post-thrombotic sequelae have a substantial negative impact on quality of life ( 9 ) and have considerable socioeconomic consequences for both the individual patient and the health care system ( 10 ) . There is indirect evidence that the incidence of the post-thrombotic syndrome is reduced when anticoagulation for the index episode of DVT is adequate in intensity and duration ( 1 ) . Graduated elastic compression stockings assist the calf muscle pump and reduce venous hypertension and reflux , thereby reducing edema and improving tissue microcirculation ( 11 - 14 ) . However , evidence supporting the effectiveness of elastic stockings comes primarily from the results of a single r and omized study conducted in patients with proximal DVT , which assessed the post-thrombotic syndrome by using a nonvali date d scale ( 2 ) . Use of tailor-made and sized-to-fit elastic stockings decreased the incidence of mild or moderate sequelae from 47 % to 20 % and decreased the incidence of severe sequelae from 23 % to 11 % ( 2 ) . In practice , however , such stockings are difficult to use because they are not widely available and are relatively expensive . The limitations of the available evidence have hindered widespread implementation of compression elastic stockings for prevention of the post-thrombotic syndrome after DVT (15).We performed a r and omized study to evaluate the efficacy of off-the-rack elastic compression stockings for prevention of post-thrombotic sequelae in patients with a first episode of acute symptomatic proximal DVT . Methods Study Design and Outcomes Our r and omized , controlled trial evaluated the efficacy of below-knee compression elastic stockings , worn for 2 years , in preventing the post-thrombotic syndrome in patients with a first episode of proximal DVT . The main aim of the study was to compare the 5-year cumulative incidence of the post-thrombotic syndrome in patients who were assigned to the elastic stockings group and those who were not . We also assessed risk factors for the development of late sequelae . Patients Consecutive patients referred to the 2nd Division of Internal Medicine of the University of Padua , Padua , Italy , between January 1997 and March 2000 with clinical ly symptomatic proximal DVT , as confirmed by compression ultrasonography , were considered for the study . One of the trial physicians assessed eligibility criteria . Patients were excluded if they had recurrent ipsilateral DVT , preexisting leg ulcers or signs of chronic venous insufficiency , bilateral thrombosis , a short life expectancy , or a contraindication for use of stockings ( for example , advanced-stage peripheral arterial insufficiency ) . Patients who met the inclusion criteria and had no exclusion criteria received detailed written information about the study hypotheses and procedures and were asked to participate . In detail , they were informed that the value of elastic stockings for prevention of post-thrombotic sequelae was uncertain and that they would be r and omly assigned to wear or not wear a supplied elastic stocking during the daytime . Patients had to give written informed consent to participate in the study . The Institutional Review Board of the University of Padua approved the study protocol . Anticoagulant Treatment Patients were treated with unfractionated or low-molecular-weight heparin , followed by at least 3 months of vitamin K antagonist therapy ( target international normalized ratio , 2.0 to 3.0 ) . Heparin treatment was discontinued when the international normalized ratio remained above 2.0 for 2 consecutive days and patients had received heparin for at least 5 days . All patients received initial treatment and began taking vitamin K antagonists while in the hospital . Patients with transient risk factors were scheduled to receive up to 3 months of oral anticoagulant therapy , while patients with idiopathic thrombosis received at least 6 months of treatment . Patients with permanent risk factors , such as active cancer , were treated for the entire study period . The duration of anticoagulant treatment followed international guidelines and was adapted to conform to each patient 's preferences and risk profile . The individual quality of oral anticoagulation was considered satisfactory if the international normalized ratio was within or above the therapeutic range in more than 70 % of measurements . Study Procedures At hospital discharge , an average of 1 week after admission ( range , 5 to 10 days ) , patients were r and omly assigned in blocks of 20 to the elastic stockings group ( that is , to wear a below-knee , grade d compression stocking on the affected leg ) or to the control group . Study group assignment was based on a computer-generated list that was accessible only to a trial nurse , who informed study physicians about treatment allocation after patients had provided informed consent . New Medical Service , Linea Flebologica Flebysan , Rovigo , Italy , supplied the elastic stockings . The stockings , which were flat-knitted , applied 30 to 40 mm Hg of pressure at the ankle ; they were made of cotton , latex , and rubberpolyamide and were available in 5 sizes . Patients received 2 stockings , which were replaced by identical stockings every 6 months . The stockings had to be used during the day or longer for a period of 2 years . The elastic stockings used in this study are currently sold in Europe for approximately 35.00 euros ( $ 42 U.S. ) each . At baseline , a clinical history was taken detailing risk factors for venous thrombosis : malignant disease , recent trauma or surgery ( within 3 months ) , prolonged immobilization ( > 7 days ) due to medical illnesses , pregnancy or puerperium , ongoing hormonal therapy , and previous contralateral venous thrombosis . In all patients , we search ed for a thrombophilic abnormality ( that is , antithrombin , protein C or S deficiency , factor V Leiden mutation , prothrombin G20210 gene mutation , and lupus-like anticoagulants ) before anticoagulation was started or at least 2 weeks after anticoagulation was completed , according to st and ard procedures ( 16 ) . Patients were discharged with a letter for their family physician indicating that they had agreed to participate in a r and omized study assessing the value of elastic stockings and specifying treatment allocation . Patients and their family physicians were given a card that listed the telephone numbers of the thrombosis clinic . Follow-up and Assessment of Recurrent Thromboembolism All patients were followed for a maximum of 5 years . The study was to be stopped when the last recruited patient reached 3 years of follow-up . All patients were asked to attend regular examinations at the study center at 3 and 6 months from the index event and every 6 months thereafter . In the interval between scheduled visits , patients were asked to report to the study center if symptoms or signs worsened . Patients who could not attend follow-up examinations at the study center were visited at home . Patients were asked to return to the center if they developed symptoms suggestive of recurrent venous thromboembolism . Recurrent thromboembolic events were diagnosed as described elsewhere ( 17 - 19 ) . Date and cause of death were documented for all patients who died during follow-up . Assessment of the Post-Thrombotic Syndrome Patients were instructed not to wear their stockings on the day of assessment and not to reveal their treatment allocation to the assessor . Therefore , each assessment was performed by an investigator who was aware of the side of the index DVT but did not know the treatment allocation or the results of previous measurements . Only the side of the index DVT was considered for development of the post-thrombotic syndrome . The presence and severity of post-thrombotic signs and symptoms were scored by using a st and ardized scale , the same as that used in our previous investigations ( 1 , 20 , 21 ) . The presence of 5 leg symptoms ( pain , cramps , heaviness , pruritus , and paresthesia ) and 6 objective signs ( pretibial edema , in duration of the skin , hyperpigmentation , new venous ectasia , and redness and pain during calf compression ) was scored . For each item , a score of 0 to 3 was assigned by using the contralateral unaffected leg as the denominator for all evaluations . A lower-limb venous ulcer indicated severe post-thrombotic syndrome regardless of the sum of the remaining signs and symptoms . In the absence of a venous ulcer , patients were classified as having severe post-thrombotic syndrome if they had a score of 15 or more on 2 consecutive visits at least 3 months apart . A total score of 5 to 14 on 2 consecutive visits at least 3 months apart indicated mild AIM Treatment of acute deep venous thrombosis ( DVT ) with low-molecular-weight heparin and vitamin K-antagonists reduces the risk of thrombus progression and pulmonary embolism but has no immediate effect on signs and symptoms . We addressed the question whether adding compression and walking would lead to a more rapid clinical improvement than bed rest . METHODS Fifty-three symptomatic out patients with proximal DVT were r and omly treated , in addition to dalteparin and phenprocoumon , with either firm inelastic b and ages ( n=18 ) , elastic compression stockings ( n=18 ) , both combined with immediate deliberate ambulation , or bed rest without any compression ( n=17 ) . We assessed daily walking distance , well-being , quality of life , pain , swelling and clinical scores over a period of 9 days . Lung scans and ultrasound of the leg were performed on days 0 and 9 . RESULTS In the compression groups the walking distance increased with time to 4 km/day on average . Improvement of well-being and DVT-related quality of life was significantly faster and more pronounced with compression than with bed rest ( p<0.05 for stockings , p<0.001 for b and ages ) . Pain monitored by visual analogue scale decreased with time in a linear pattern in all groups ( p<0.001 ) . There was a significant difference between the groups ( p<0.01 ) , the best effect being achieved with b and ages . Pain assessed by a provocation test was reduced by half on day 3 with bed rest but remained constantly present over the subsequent 6 days . With compression it was reduced to near baseline on day 3 . Swelling was almost completely removed with compression and clinical scores also improved more than with bed rest ( p<0.001 ) . Thrombus progression , as studied with ultrasound , was less frequent and less pronounced in the compression groups than with bed rest . There was no difference of new pulmonary embolism on repeat lung scans . CONCLUSION Leg compression combined with walking is the better alternative to bed rest for the treatment of symptomatic out patients with proximal DVT AIM The aim of this r and omized clinical trial was to investigate a cryotherapy ( cooling ) gel wrap applied to lower leg skin affected by chronic venous disorders to determine whether therapeutic cooling improves skin microcirculation . BACKGROUND Chronic venous disorders are under-recognized vascular health problems that result in severe skin damage and ulcerations of the lower legs . Impaired skin microcirculation contributes to venous leg ulcer development , thus new prevention therapies should address the microcirculation to prevent venous leg ulcers . METHODS Sixty participants ( n = 30 per group ) were r and omized to receive one of two daily 30-minute interventions for four weeks . The treatment group applied the cryotherapy gel wrap around the affected lower leg skin , or compression and elevated the legs on a special pillow each evening at bedtime . The st and ard care group wore compression and elevated the legs only . Laboratory pre- and post- measures included microcirculation measures of skin temperature with a thermistor , blood flow with a laser Doppler flowmeter , and venous refill time with a photoplethysmograph . Data were collected between 2008 2009 and analysed using descriptive statistics , paired t-tests or Wilcoxon signed ranks tests , logistic regression analyses , and mixed model analyses . RESULTS Fifty-seven participants ( treatment = 28 ; st and ard care = 29 ) completed the study . The mean age was 62 years , 70 % female , 50 % African American . In the final adjusted model , there was a statistically significant decrease in blood flow between the two groups ( -6.2[-11.8 ; -0.6 ] , P = 0.03 ) . No statistically significant differences were noted in temperature or venous refill time . CONCLUSION Study findings suggest that cryotherapy improves blood flow by slowing movement within the microcirculation and thus might potentially provide a therapeutic benefit to prevent leg ulcers BACKGROUND Although uncommon , severe post-phlebitic syndrome may be associated with persistent , intractable pain and swelling that interfere with work and leisure activities . This study was performed to determine whether intermittent compression therapy with an extremity pump benefits patients with this condition and , if so , whether the benefit is sustained . METHODS The study was a r and omized crossover trial . Over the period 1990 to 1996 , all patients in the clinical thromboembolism program of an Ontario teaching hospital who had a history of deep vein thrombosis and intractable symptoms of post-phlebitic syndrome were recruited into the study . The study involved using an extremity pump twice daily for a total of 2 months ( 20 minutes per session ) . The patients were r and omly assigned to use either a therapeutic pressure ( 50 mm Hg ) or a placebo pressure ( 15 mm Hg ) for the first month . For the second month , the patients used the other pressure . A question naire assessing symptoms and functional status served as the primary outcome measure and was administered at the end of each 1-month period . A symptom score was derived by summing the scores for individual questions . At the end of the 2-month study , patients were asked to indicate their treatment preference and to rate the importance of the difference between the 12 pressures . Treatment was considered successful if the patient preferred the therapeutic pressure and stated that he or she would continue using the extremity pump and that the difference between the therapeutic and placebo pressures was of at least slight importance . All other combinations of responses were considered to represent treatment failure . Patients whose treatment was classified as successful were offered the opportunity to keep the pump and to alter pressure , frequency and duration of pump use to optimize symptom management . In July 1996 the authors contacted all study participants whose treatment had been classified as successful to determine whether they were still using the pump and , if so , whether they were still deriving benefit . RESULTS In total 15 consecutive patients ( 12 women and 3 men ) were enrolled in the study . The symptom scores were significantly better with the therapeutic pressure ( mean 16.5 ) than with the placebo pressure ( mean 14.4 ) ( paired t-test , p = 0.007 ) . The treatment for 12 of the patients ( 80 % , 95 % confidence interval 52 % to 96 % ) was considered successful . Of these , 9 patients continued to use the pump beyond the crossover study and to derive benefit . INTERPRETATION The authors conclude that a trial of pump therapy is worthwhile for patients with severe post-phlebitic syndrome and that a sustained beneficial response can be expected in most such patients OBJECTIVE Compression stockings are widely applied after acute proximal deep vein thrombosis , but their efficacy in preventing the post-thrombotic syndrome remains controversial . This study assessed the effect of prolonged compression therapy after a st and ard treatment of 6 months after acute deep vein thrombosis . METHODS Of 900 patients screened , we r and omly allocated 169 patients with a first or recurrent proximal deep vein thrombosis after receiving 6 months of st and ard treatment to wear compression stockings or not . Primary efficacy analysis was performed on the end point of emerging skin changes ( C4-C6 according to the CEAP classification ) . Secondary analysis was done on symptoms associated with post-thrombotic syndrome . All analyses were done according to the intention-to-treat principle . RESULTS The primary end point occurred in 11 patients ( 13.1 % ) in the treatment group compared with 17 ( 20.0 % ) in the control group ( hazard ratio [ HR ] , 0.60 ; 95 % confidence interval [ CI ] , 0.28 - 1.28 ; P = .19 ) . Mean follow-up was 3.2 years and 2.9 years , respectively . Five additional patients in the control group required compression therapy owing to post-thrombotic signs and symptoms not included in the primary end point . No venous ulceration was observed in either group . Within subgroup analyses of the primary end point , we observed a large sex-specific difference between women ( HR , 0.11 ; 95 % CI , 0.02 - 0.91 ) and men ( HR , 1.07 ; 95 % CI , 0.42 - 2.73 ) . Symptom relief was significant in favor of compression treatment during the first year but not thereafter . CONCLUSION Prolonged compression therapy after proximal deep vein thrombosis significantly reduces symptoms and may prevent post-thrombotic skin changes . Whether these findings translate to the prevention of advanced disease states with ulcerations remains unclear BACKGROUND The true incidence of postphlebitic syndrome ( PPS ) following proximal deep venous thrombosis ( DVT ) and the efficacy of graduated compression stockings in preventing and treating PPS are unknown . METHODS A 3-part study of 202 patients evaluated 1 year after proximal DVT : 2 r and omized placebo-controlled trials of stockings and 1 prospect i ve cohort of untreated patients . Patients were evaluated for PPS , using a st and ardized question naire , and for venous valvular incompetence , using photoplethysmography and venous Doppler . They were enrolled in study 1 or study 2 if they did not have symptomatic PPS and did not have or had venous valvular incompetence , respectively , and into study 3 if they had symptomatic PPS . Study 1 patients were left untreated and followed up for development of PPS every 6 months for a mean of 55 months . Study 2 patients were r and omized to a below-knee stocking ( 20 - 30 mm Hg ) or a matched placebo stocking , and followed up for development of PPS every 6 months for a mean of 57 months . Study 3 patients were r and omized to an active stocking ( 30 - 40 mm Hg ) or a matched placebo stocking and followed up every 3 months for treatment failure , defined a priori . RESULTS In study 1 , 6 ( 5.0 % ) of 120 patients were categorized as treatment failures , a rate similar to placebo-treated study 2 patients ( P = .10 ) . In study 2 , 0 ( 0 % ) of 24 active and 1 ( 4.3 % ) of 23 placebo-treated patients were categorized as treatment failures ( P = .49 ) . In study 3 , 11 ( 61.1 % ) of 18 active and 10 ( 58.8 % ) of 17 placebo-treated patients were categorized as treatment failures ( P>.99 ) . CONCLUSIONS Most patients do not have PPS 1 year after proximal DVT , and do not require stockings . We failed to show a benefit of stockings in patients with PPS , but the small numbers preclude definitive conclusions Background Post thrombotic syndrome ( PTS ) is a burdensome and costly complication of deep venous thrombosis ( DVT ) that develops in 20–40 % of patients within 1–2 years after symptomatic DVT . Affected patients have chronic leg pain and swelling and may develop ulcers . Venous valve disruption from the thrombus itself or thrombus-associated mediators of inflammation is considered to be a key initiating event for the development of venous hypertension that often underlies PTS . As existing treatments for PTS are extremely limited , strategies that focus on preventing the development of PTS in patients with DVT are more likely to be effective and cost-effective in reducing its burden . Elastic compression stockings ( ECS ) could be helpful in preventing PTS ; however , data on their effectiveness are scarce and conflicting . Methods / Design The SOX Trial is a r and omized , allocation concealed , double-blind multicenter clinical trial . The objective of the study is to evaluate ECS to prevent PTS . A total of 800 patients with proximal DVT will be r and omized to one of 2 treatment groups : ECS or placebo ( inactive ) stockings worn on the DVT-affected leg daily for 2 years . The primary outcome is the incidence of PTS during follow-up . Secondary outcomes are severity of PTS , venous thromboembolism ( VTE ) recurrence , death from VTE , quality of life and cost-effectiveness . Outcomes will be evaluated during 6 clinic visits and 2 telephone follow ups . At baseline , 1 and 6 months , blood sample s will be obtained to evaluate the role of inflammatory mediators and genetic markers of thrombophilia in the development of PTS ( Bio-SOX sub study ) . Discussion The SOX Trial will be the largest study and the first with a placebo control to evaluate the effectiveness of ECS to prevent PTS . It is design ed to provide definitive data on the effects of ECS on the occurrence and severity of PTS , as well as DVT recurrence , cost-effectiveness and quality of life . This study will also prospect ively evaluate the predictive role of biomarkers that are reflective of putative underlying pathophysiological mechanisms in the development of clinical PTS . As such , our results will impact directly on the care of patients with DVT.Trial Registration NCT00143598 and IS RCT |
613 | 22,459,604 | There was no consensus on the advantages of including proprioceptive training in the rehabilitation of this population for swelling , postural sway , joint position sense , ankle range of motion or return to sport outcomes . | The purpose of this study was to assess the effectiveness of such proprioceptive exercise following ankle ligament injury . | STUDY DESIGN R and omized controlled trial with pretraining , posttraining , and follow-up repeated measures . OBJECTIVE To determine the effectiveness of a 4-week elastic resistance exercise program on balance in subjects with and without a history of sprained ankles . BACKGROUND Several research ers have suggested that improving balance may help alleviate the symptoms of functional ankle instability and reduce the rate of recurrent ankle sprains . METHODS AND MEASURES Forty subjects ( 20 males , 20 females ; 20 subjects with chronic ankle instability [ CAI ] , 20 healthy ) participated in the study . Ten subjects ( 5 males , 5 females ) from each CAI and healthy group were r and omly assigned to either the exercise or control group , result ing in a total of 4 groups . Total travel distance of the center of pressure , monitored using a force platform , was measured before training , after 4 weeks of training , and at a 4-week follow-up . RESULTS There were no interactions between gender , ankle sprain history , or training groups . Balance significantly improved in subjects with and without a history of ankle sprains following 4 weeks of elastic resistance exercises . Mean improvement in balance for the exercise group following training , reflected through a decrease in total travel distance , was -11.1 cm ( 95 % confidence interval : -14.0 to -8.2 cm ) . These improvements in balance were retained 4 weeks after training . CONCLUSIONS Balance was improved after 4 weeks of elastic resistance exercise in subjects with and without a history of lateral ankle sprains . Balance improvements persisted 4 weeks following the treatment cessation Background Ankle sprains are common injuries that often lead to functional ankle instability ( FAI ) , which is a pathology defined by sensations of instability at the ankle and recurrent ankle sprain injury . Poor postural stability has been associated with FAI , and sports medicine clinicians rehabilitate balance deficits to prevent ankle sprains . Subsensory electrical noise known as stochastic resonance ( SR ) stimulation has been used in conjunction with coordination training to improve dynamic postural instabilities associated with FAI . However , unlike static postural deficits , dynamic impairments have not been indicative of ankle sprain injury . Therefore , the purpose of this study was to examine the effects of coordination training with or without SR stimulation on static postural stability . Improving postural instabilities associated with FAI has implication s for increasing ankle joint stability and decreasing recurrent ankle sprains . Methods This study was conducted in a research laboratory . Thirty subjects with FAI were r and omly assigned to either a : 1 ) conventional coordination training group ( CCT ) ; 2 ) SR stimulation coordination training group ( SCT ) ; or 3 ) control group . Training groups performed coordination exercises for six weeks . The SCT group received SR stimulation during training , while the CCT group only performed coordination training . Single leg postural stability was measured after the completion of balance training . Static postural stability was quantified on a force plate using anterior/posterior ( A/P ) and medial/lateral ( M/L ) center-of-pressure velocity ( COPvel ) , M/L COP st and ard deviation ( COPsd ) , M/L COP maximum excursion ( COPmax ) , and COP area ( COParea ) . Results Treatment effects comparing posttest to pretest COP measures were highest for the SCT group . At posttest , the SCT group had reduced A/P COPvel ( 2.3 ± 0.4 cm/s vs. 2.7 ± 0.6 cm/s ) , M/L COPvel ( 2.6 ± 0.5 cm/s vs. 2.9 ± 0.5 cm/s ) , M/L COPsd ( 0.63 ± 0.12 cm vs. 0.73 ± 0.11 cm ) , M/L COPmax ( 1.76 ± 0.25 cm vs. 1.98 ± 0.25 cm ) , and COParea ( 0.13 ± 0.03 cm2 vs. 0.16 ± 0.04 cm2 ) than the pooled means of the CCT and control groups ( P < 0.05 ) . Conclusion Reduced values in COP measures indicated postural stability improvements . Thus , six weeks of coordination training with SR stimulation enhanced postural stability . Future research should examine the use of SR stimulation for decreasing recurrent ankle sprain injury in physically active individuals with FAI STUDY DESIGN Single-group repeated measures with 2 raters . OBJECTIVES To determine the interrater and intrarater reliability of water volumetry and the figure of eight method on subjects with ankle joint swelling . BACKGROUND Measurements of ankle swelling are commonly performed to determine the nature and stage of injury and to monitor progress made during rehabilitation . Water volumetry and the figure of eight method are 2 techniques used to measure ankle swelling . METHODS AND MEASURES Twenty-nine subjects with ankle swelling were measured by 2 raters with the hypothesis that both measurement techniques would be reliable . Each rater performed 3 measurements of the swollen ankle using both measurement techniques during a single test session . The order of the rater and of the measurement technique was r and omized , and the raters were blinded to each other 's measurements . RESULTS We found high interrater reliability for both the water volumetry ( ICC [ intraclass correlation coefficient ] = 0.99 ) and figure of eight methods ( ICC = 0.98 ) . Additionally , intrarater reliability was high for both raters using both methods ( ICCs = 0.98 - 0.99 ) . CONCLUSIONS Both methods are reliable measures of ankle swelling . The authors recommend the figure of eight method because of its ease of use , time efficiency , and cost effectiveness . However , water volumetry may be more appropriate when measuring diffuse lower-extremity swelling . Reliability of these 2 methods was established using subjects with foot or ankle pathology . Therefore , the results are applicable and generalizable to the clinical setting Exercises to improve joint proprioception and coordination of the functionally unstable ankle are advocated throughout the literature , yet there is little evidence that these exercise have any effect on proprioception and balance . The purpose of this study was to determine the effects of a 6-week coordination and balance training program on proprioception of subjects with functional ankle instability . Forty-five subjects ( age = 22.53 + /- 3.95 years , height = 172.04 + /- 10.0 cm , weight = 71.72 + /- 15.7 kg ) were r and omly placed into a control ( Group 1 ) , sham ( Group 2 ) , or experimental ( Group 3 ) group . The experimental group trained 3 days per week , 10 minutes each day , performing various balance and proprioception exercises . Postural sway and active and passive joint position sense were assessed . Analysis of variance for postural sway modified equilibrium score for anterior and posterior sway , as well as medial and lateral sway revealed significant four-way interactions . Tukey post hoc analyses revealed that Group 3 performed significantly better ( p < .05 ) than Group 1 and Group 2 on the posttests . There were no significant differences for joint position sense or postural sway index . Results suggest that balance and coordination training can improve some measures of postural sway . It is still unclear if joint position sense can be improved in the functionally unstable ankle STUDY DESIGN Prospect i ve , r and omized controlled trial . OBJECTIVE To examine the effects of a 4-week rehabilitation program for chronic ankle instability ( CAI ) on postural control and lower extremity function . BACKGROUND CAI is associated with residual symptoms , performance deficits , and reinjury . Managing CAI is challenging and more evidence is needed to guide effective treatment . METHODS AND MEASURES Subjects with unilateral CAI were r and omly assigned to the rehabilitation ( CAI-rehab , n=16 ) or control ( CAI-control , n=13 ) group . Subjects without CAI were assigned to a healthy group ( n=19 ) . Baseline testing included the ( 1 ) center of pressure velocity ( COPV ) , ( 2 ) star excursion balance test ( SEBT ) , and ( 3 ) Foot and Ankle Disability index ( FADI ) and FADI-Sports Subscale ( FADI-Sport ) . The CAI-rehab group completed 4 weeks of rehabilitation that addressed range of motion , strength , neuromuscular control , and functional tasks . After 4 weeks , all subjects were retested . Nonparametric analyses for group differences and between-group comparisons were performed . RESULTS Subjects with CAI demonstrated deficits in postural control and SEBT reach tasks of the involved limb compared to the uninvolved limb and reported functional deficits of the involved limb compared to healthy subjects . Following rehabilitation , the CAI-rehab group had greater SEBT reach improvements on the involved limb than the other groups and greater improvements in FADi and FADI-Sport scores . CONCLUSIONS These results demonstrate postural control and functional limitations exist in individuals with CAl . In addition , rehabilitation appears to improve these functional limitations . Finally , there is evidence to suggest the SEBT may be a good functional measure to monitor change after rehabilitation for CAI Objective To evaluate the effectiveness of an unsupervised proprioceptive training programme on recurrences of ankle sprain after usual care in athletes who had sustained an acute sports related injury to the lateral ankle ligament . Design R and omised controlled trial , with one year follow-up . Setting Primary care . Participants 522 athletes , aged 12 - 70 , who had sustained a lateral ankle sprain up to two months before inclusion ; 256 ( 120 female and 136 male ) in the intervention group ; 266 ( 128 female and 138 male ) in the control group . Intervention Both groups received treatment according to usual care . Athletes allocated to the intervention group additionally received an eight week home based proprioceptive training programme . Main outcome measure Self reported recurrence of ankle sprain . Results During the one year follow-up , 145 athletes reported a recurrent ankle sprain : 56 ( 22 % ) in the intervention group and 89 ( 33 % ) in the control group . Nine athletes needed to be treated to prevent one recurrence ( number needed to treat ) . The intervention programme was associated with a 35 % reduction in risk of recurrence . Cox regression analysis showed significantly fewer recurrent ankle sprains in the intervention than in the control group . This effect was found for self reported recurrent ankle sprains ( relative risk 0.63 , 95 % confidence interval 0.45 to 0.88 ) , recurrent ankle sprains leading to loss of sports time ( 0.53 , 0.32 to 0.88 ) , and recurrent ankle sprains result ing in healthcare costs or lost productivity costs ( 0.25 , 0.12 to 0.50 ) . No significant differences were found between medically treated athletes in the intervention group and medically treated controls . Athletes in the intervention group who were not medically treated had a significantly lower risk of recurrence than controls who were not medically treated . Conclusions The use of a proprioceptive training programme after usual care of an ankle sprain is effective for the prevention of self reported recurrences . This proprioceptive training was specifically beneficial in athletes whose original sprain was not medically treated . Trial registration Ankle sprains are often complicated by functional instability and repeated sprains . Rehabilitation with wobble boards in patients with functional instability has been tested , and significant improvement has been found compared to no training . The aim of this study was to investigate whether the number of patients with residual symptoms following ankle sprains could be reduced by training on a wobble board during 12-week recovery period . In addition , the influence of training in the time course reduction of edema was investigated . We performed a prospect i ve study including 61 patients , all active in sports for more than 2 hours a week with primary ankle sprains . The effect of a 12-week training program with wobble board was compared with no training . Forty-eight patients completed the study . In the follow-up period ( mean X = 230 days ) , we found significantly fewer recurrent sprains , and significantly fewer patients in the training group had functional instability of the ankle compared with the no training group . There were no differences in the two groups in the time which elapsed before patients were painless at walking , during running , or at sports . Volumetric measurements revealed no difference in the speed of reduction of hematoma and edema of the ankle and foot between the two groups . We conclude that training on a wobble board early after primary stage 2 ankle sprains is effective in reducing residual symptoms following this lesion and that training does not seem to affect the time course reduction in edema PURPOSE The aim of the present study was to investigate the effects of a 6-wk multi-station proprioceptive exercise program that is easy to integrate in normal training programs . METHODS Patients with chronic ankle instability were used , and results of three testing procedures before and afterward were compared : joint position sense , postural sway , and muscle reaction times to sudden inversion events on a tilting platform . A total of 30 subjects with 48 unstable feet were evaluated ( exercise group : N = 31 ; control group : N = 17 ) . RESULTS In the exercise group , the results showed a significant improvement in joint position sense and postural sway as well as significant changes in muscle reaction times . CONCLUSION Based on the present results , a multi-station proprioceptive exercise program can be recommended for prevention and rehabilitation of recurrent ankle inversion injuries Background : A search of the literature shows that the effect of surgery on ankle proprioception has been hardly investigated . Objective : To examine the effect of anatomical reconstruction of the anterolateral capsuloligamentous complex on ankle joint position sense . Methods : A prospect i ve study using the “ slope box ” test . Ten consecutive patients were included in the study , and 10 healthy athletes represented the control group . Results : Similar test-retest reliability rates ( overall reliability 0.92 ; p = 0.0013 ) were obtained to those of the original design ers of the method . There were no significant differences with respect to side dominance ( p = 0.9216 ) . Investigation of the characteristics of mean absolute estimate errors showed that the controls tested became error prone in the range of slope altitudes 7.5–25 ° in every direction , compared with the range 0–5 ° ( range of p values 0.00003–0.00072 ) . The results of the intervention group showed that , for the two main directions of interest ( anterior and lateral ) , preoperative differences in mean absolute estimate errors between injured ( anterior 3.91 ( 2.81 ) ° ; lateral 4.06 ( 2.85 ) ° ) and healthy ( anterior 2.94 ( 2.21 ) ° , lateral 3.19 ( 2.64 ) ° ) sides ( anterior , p = 0.0124 ; lateral , p = 0.0250 ) had disappeared ( postoperative differences : anterior , p = 0.6906 ; lateral , p = 0.4491 ) . The afflicted ankle had improved significantly after surgery in both important directions ( anterior , p<0.0001 ; lateral , p = 0.0023 ) . Conclusions : The study shows that differences in joint position sense between healthy and injured ankles disappeared as the result of surgery . Preoperative data show that proprioceptive malfunction is a cause of functional instability . If treatment is by means of surgery , the retensioning of the original anterolateral structures is inevitable , even if other grafting or surgical techniques are used The effect of an early rehabilitation program , including postural training , on ankle joint function after an ankle ligament sprain was investigated prospect ively . Ninety-two subjects , matched for age , sex , and level of sports activity , were r and omized to a control or training group . All subject received the same st and ard information regarding early ankle mobilization . In addition , the training group participated in supervised physical therapy rehabilitation ( 1 h , twice weekly ) with emphasis on balance training . Postural sway , position sense and isometric ankle strength were measured 6 weeks and 4 months after the injury , and at 12 months re-injury data were obtained . In the training group , there was a significant difference between the injured and uninjured side for plantar flexion ( P < 0.01 ) , eversion ( P < 0.01 ) and inversion ( P < 0.05 ) , but not for dorsiflexion at 6 weeks . In the control group , there was a significant difference between the injured and uninjured side for plantar flexion ( P < 0.01 ) , eversion ( P < 0.01 ) , inversion ( P < 0.01 ) , and dorsiflexion ( P < 0.05 ) at 6 weeks . Postural sway , but not position sense , differed between the injured and uninjured side in both groups ( P < 0.01 ) at 6 weeks . The side-to-side percent differences were similar in both groups for all variables ( P > 0.05 ) at 6 weeks , and there were no side-to-side differences at 4 months in either group . In the control group , 11/38 ( 29 % ) suffered a re-injury , while this number was only 2/29 ( 7 % ) in the training group ( P < 0.05 ) . These data showed that an ankle injury result ed in reduced ankle strength and postural control at 6 weeks , but that these variables had normalized at 4 months , independent of the supervised rehabilitation . However , the findings also demonstrated that supervised rehabilitation may reduce the number of re-injuries , and therefore may play a role in injury prevention Functional instability is a common complication following an acute ankle sprain . Three potential contributing factors underlying the ankle which chronically gives way are proprioceptive deficits , muscle weakness , and ligamentous laxity . This study 's purpose was to document the presence or absence of these concerns in a sample of subjects with unilateral functional ankle instability . Both ankles of 42 subjects were r and omly assessed for passive movement sense into inversion and generation of peak torque by the evertors isokinetically . Thirty-four subjects were available for documentation of talar tilt of both ankles through inversion stress radiographs . Analysis found significantly greater mean values for passive movement sense and talar tilt for the involved ankles compared with the uninvolved , while no significant strength differences in peak torque of the evertors were present . Fifty-eight percent of the sample demonstrated clinical impairments in at least one of these three categories . In conclusion , deficits in passive movement sense and anatomic stability are greater concerns than strength deficits when managing the ankle with functional instability |
614 | 30,342,843 | BCR was associated with worse survival rates , mainly in patients with short prostate-specific antigen doubling time ( PSA-DT ) and a high final Gleason score after RP , or a short interval to biochemical failure ( IBF ) after RT and a high biopsy Gleason score .
BCR has an impact on survival , but this effect appears to be limited to a subgroup of patients with specific clinical risk factors .
Short PSA-DT and a high final Gleason score after RP , and a short IBF after RT and a high biopsy Gleason score are the main factors that have a negative impact on survival .
For many men , rising PSA does not mean that they are at a high risk of death from prostate cancer in the longer term .
Men with PSA that rises shortly after they were treated with radiotherapy or rapidly rising PSA after surgery and a high tumor grade for both treatment modalities are at the highest risk of death . | CONTEXT In men with prostate cancer ( PCa ) treated with curative intent , controversy exists regarding the impact of biochemical recurrence ( BCR ) on oncological outcomes .
OBJECTIVE To perform a systematic review of the existing literature on BCR after treatment with curative intent for nonmetastatic PCa .
Objective 1 is to investigate whether oncological outcomes differ between patients with or without BCR .
Objective 2 is to study which clinical factors and tumor features in patients with BCR have an independent prognostic impact on oncological outcomes .
PATIENT SUMMARY This review looks at the risk of death in men who shows rising prostate-specific antigen ( PSA ) in the blood test performed after curative surgery or radiotherapy . | Purpose Physicians sometimes make management recommendations on the basis of early results from r and omized controlled trials ( RCTs ) relating to reduced prostate-specific antigen ( PSA ) failure , yet whether this early end point is associated with all-cause mortality ( ACM ) , particularly in men with competing risks , is unknown . Using a vali date d metric in men treated within the context of an RCT , we aim ed to determine whether PSA failure is associated with the risk of ACM stratified by comorbidity score . Patients and Methods Between 1995 and 2001 , 206 men with localized ( T1b to 2b ) intermediate- and high-risk prostate cancer ( PC ) were r and omly assigned to receive radiation therapy or radiation therapy and 6 months of ADT . Cox regression analyses were performed to evaluate whether PSA failure modeled as a time-dependent covariate was associated with an increased risk of ACM among men with Adult Comorbidity Evaluation-27-defined no or minimal versus moderate-to-severe comorbidity adjusting for age , PC prognostic factors , and treatment . Results After a median follow-up of 16.62 years , 156 men ( 76 % ) died , 29 of whom ( 19 % ) died as a result of PC . PSA failure was associated with an increased ACM risk among men with no or minimal ( adjusted hazard ratio , 1.59 ; 95 % CI , 1.03 to 2.46 ; P = .04 ) , but not moderate or severe comorbidity ( adjusted hazard ratio , 1.75 ; 95 % CI , 0.76 to 3.99 ; P = .19 ) . Conclusion Recommending treatment on the basis of reduced PSA failure observed from early results of RCTs is unlikely to prolong survival in men with moderate-to-severe comorbidity but may prolong survival in men with no or minimal comorbidity , providing evidence to support discussing the early results with these men BACKGROUND The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen ( PSA ) testing remains uncertain . METHODS We compared active monitoring , radical prostatectomy , and external-beam radiotherapy for the treatment of clinical ly localized prostate cancer . Between 1999 and 2009 , a total of 82,429 men 50 to 69 years of age received a PSA test ; 2664 received a diagnosis of localized prostate cancer , and 1643 agreed to undergo r and omization to active monitoring ( 545 men ) , surgery ( 553 ) , or radiotherapy ( 545 ) . The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up . Secondary outcomes included the rates of disease progression , metastases , and all-cause deaths . RESULTS There were 17 prostate-cancer-specific deaths overall : 8 in the active-monitoring group ( 1.5 deaths per 1000 person-years ; 95 % confidence interval [ CI ] , 0.7 to 3.0 ) , 5 in the surgery group ( 0.9 per 1000 person-years ; 95 % CI , 0.4 to 2.2 ) , and 4 in the radiotherapy group ( 0.7 per 1000 person-years ; 95 % CI , 0.3 to 2.0 ) ; the difference among the groups was not significant ( P=0.48 for the overall comparison ) . In addition , no significant difference was seen among the groups in the number of deaths from any cause ( 169 deaths overall ; P=0.87 for the comparison among the three groups ) . Metastases developed in more men in the active-monitoring group ( 33 men ; 6.3 events per 1000 person-years ; 95 % CI , 4.5 to 8.8 ) than in the surgery group ( 13 men ; 2.4 per 1000 person-years ; 95 % CI , 1.4 to 4.2 ) or the radiotherapy group ( 16 men ; 3.0 per 1000 person-years ; 95 % CI , 1.9 to 4.9 ) ( P=0.004 for the overall comparison ) . Higher rates of disease progression were seen in the active-monitoring group ( 112 men ; 22.9 events per 1000 person-years ; 95 % CI , 19.0 to 27.5 ) than in the surgery group ( 46 men ; 8.9 events per 1000 person-years ; 95 % CI , 6.7 to 11.9 ) or the radiotherapy group ( 46 men ; 9.0 events per 1000 person-years ; 95 % CI , 6.7 to 12.0 ) ( P<0.001 for the overall comparison ) . CONCLUSIONS At a median of 10 years , prostate-cancer-specific mortality was low irrespective of the treatment assigned , with no significant difference among treatments . Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring . ( Funded by the National Institute for Health Research ; ProtecT Current Controlled Trials number , IS RCT N20141297 ; Clinical Trials.gov number , NCT02044172 . ) PURPOSE We evaluated predictors of prostate cancer-specific mortality ( PCSM ) after prostate-specific antigen ( PSA ) failure after radical prostatectomy ( RP ) or radiation therapy ( RT ) . PATIENTS AND METHODS A total of 1,159 men with clinical ly localized prostate cancer treated with RP ( n = 498 ) or RT ( n = 661 ) developed PSA failure , and they formed the study cohort . Competing risk regression analyses were used to evaluate whether previously identified predictors of time to metastasis , including post-treatment PSA doubling time ( PSA-DT ) , Gleason score , and interval to PSA failure , could also predict time to PCSM after PSA failure . The cumulative incidence method was used to estimate PCSM after PSA failure . RESULTS A post-RP PSA-DT of less than 3 months ( hazard ratio [ HR ] , 54.9 ; 95 % CI , 16.7 to 180 ) , a post-RT PSA-DT of less than 3 months ( HR , 12.8 ; 95 % CI , 7.0 to 23.1 ) , and a biopsy Gleason score of 8 to 10 ( HR , 6.1 ; 95 % CI , 3.4 to 10.7 ) for patients treated with RT were significantly associated with PCSM . Post-RP estimated rates of PCSM 5 years after PSA failure were 31 % ( 95 % CI , 17 % to 45 % ) v 1 % ( 95 % CI , 0 % to 2 % ) for patients with PSA-DT of less than 3 months v > or = 3 months . Post-RT estimated rates of PCSM 5 years after PSA failure were 75 % ( 95 % CI , 59 % to 92 % ) v 35 % ( 95 % CI , 24 % to 47 % ) for patients with a biopsy Gleason score of > or = 8 v < or = 7 , respectively , and PSA-DT of less than 3 months ; these rates were 15 % ( 95 % CI , 0.8 % to 28 % ) v 4 % ( 95 % CI , 1 % to 6 % ) , respectively , for patients with a PSA-DT > or = 3 months . CONCLUSION Patients at high risk for PCSM after PSA failure can be identified based on post-RP PSA-DT or post-RT PSA-DT and biopsy Gleason score . These parameters may be useful in identifying patients for a r and omized trial evaluating hormonal therapy with or without docetaxel Background : The optimal management of men with PSA failure following initial prostate cancer ( PC ) therapy stratified by comorbidity is unknown . We investigated the impact that PSA doubling time ( DT ) and comorbidity had on the risk of all-cause mortality ( ACM ) , prostate cancer-specific mortality ( PCSM ) and other-cause mortality ( OCM ) following PSA failure . Methods : Between 1995 and 2001 , 206 men with unfavorable-risk PC were r and omized to receive radiation therapy alone or in combination with 6 months of and rogen deprivation therapy ( ADT ) ; 108 men experienced PSA failure and formed the study cohort . Cox and Fine – Gray regression analysis was used to determine whether PSA DT was associated with the risk of ACM and PCSM/OCM , respectively , stratified by comorbidity status using a vali date d metric . Results : After a median follow-up of 13.71 years following PSA failure , 81 of the 108 men ( 75 % ) died . Longer PSA DT was associated with a decreased risk of PCSM in men with no/minimal ( adjusted hazard ratio ( AHR ) 0.33 , 95 % confidence interval ( CI ) 0.17–0.65 , P=0.001 ) and moderate/severe comorbidity ( AHR 0.014 , 95 % CI 0.002–0.129 , P=0.0002 ) . However , because of the different contributions of the risk of OCM to risk of ACM within comorbidity subgroups , increasing PSA DT was only associated with a decreased risk of ACM in men with no/minimal ( AHR 0.69 , 95 % CI 0.50–0.96 , P=0.03 ) but not moderate/severe comorbidity ( AHR 0.95 , 95 % CI 0.51–1.78 , P=0.87 ) . Conclusions : Both the extent of comorbidity and the PSA DT should be taken into consideration when deciding on appropriate management and /or clinical trial eligibility at the time of PSA failure BACKGROUND Hormonal manipulation concomitant to salvage radiotherapy ( SRT ) given for biochemical recurrence ( BCR ) after radical prostatectomy ( RP ) improved outcomes in two r and omized trials . However , neither of these studies focused on men treated at low prostate-specific antigen ( PSA ) levels . OBJECTIVE To test if the impact of and rogen deprivation therapy ( ADT ) on metastasis in patients undergoing early SRT varies according to prostate cancer ( PCa ) features . DESIGN , SETTING , AND PARTICIPANTS A total of 525 patients received SRT at PSA levels ≤2ng/ml . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES Multivariable Cox regression analyses assessed factors associated with metastasis . We tested the hypothesis that the impact of ADT varied according to the risk of metastasis . An interaction with groups ( concomitant ADT vs no ADT ) and the probability of distant metastasis according to a newly developed model was tested . A nonparametric curve explored the relationship between the risk of metastasis and 10-yr metastasis rates according to ADT . RESULTS AND LIMITATIONS Median PSA and radiotherapy dose were 0.42ng/ml and 66Gy , respectively . Overall , 178 ( 34 % ) patients received ADT . At a median follow-up of 104 mo , 71 patients experienced metastasis . Grade group ≥4 ( hazard ratio [ HR ] : 1.66 ; 95 % confidence interval [ CI ] : 1.01 - 3.30 ) , pT3b/4 ( HR : 2.61 ; 95 % CI : 1.51 - 4.52 ) , and dose ( HR : 0.82 ; 95 % CI : 0.76 - 0.89 ) were associated with metastasis . The impact of ADT differed according to the risk of metastasis calculated using a multivariable model ( p=0.01 ) . This was confirmed when considering patients treated with early SRT ( p=0.046 ) , where ADT was associated with a reduction in the rate of metastasis only in eSRT ; patients with more aggressive characteristics ( ie , pT3b/4 and grade group ≥4 , or pT3b/4 and PSA at eSRT ≥0.4ng/ml ) . CONCLUSIONS The beneficial effect of ADT concomitant to eSRT varied significantly according to disease characteristics , such that only men with more aggressive PCa features benefit from ADT in the eSRT setting for BCR after RP . PATIENT SUMMARY The oncological benefits of concomitant and rogen deprivation therapy ( ADT ) in patients undergoing salvage radiotherapy ( SRT ) vary according to pathological characteristics . Only patients with more aggressive disease characteristics seemed to benefit from the use of hormonal manipulation at the time of early SRT . Conversely , the potential side effects of ADT could be spared in patients with low prostate-specific antigen levels and favorable pathological features BACKGROUND Patients with lymph node (LN)-positive prostate cancer ( PCa ) at radical prostatectomy ( RP ) face a high risk of cancer recurrence . Nevertheless , recurrence patterns of LN-positive PCa and their prognostic significance remain understudied in the literature . OBJECTIVE To analyze a large single-institution series with long-term follow-up to eluci date the various clinical recurrence patterns of LN-positive PCa and their association with oncologic outcomes . DESIGN , SETTING , AND PARTICIPANTS Years 1987 - 2012 of a prospect ively maintained institutional RP registry were queried for men with LN-positive PCa at RP . Clinical recurrences were categorized as local , nodal , skeletal , or visceral . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS In addition to descriptive statistics and Kaplan-Meier analysis , univariable and multivariable Cox proportional hazards models were constructed to predict recurrence and to quantify the impact of recurrence patterns on cancer-specific mortality ( CSM ) . RESULTS AND LIMITATIONS Data from 1011 men with LN-positive PCa at RP were analyzed with 17.6 yr of median follow-up . The 15-yr clinical recurrence rate was 33 % ( 95 % confidence interval [ CI ] , 31 - 35 % ) for all patients and 52.2 % ( 95 % CI , 47.3 - 57.1 % ) for patients with biochemical recurrence . The solitary locations were skeletal ( n=94 , 55 % ) , nodal ( n=59 , 34 % ) , local soft tissue ( n=29 , 17 % ) , and visceral ( n=8 , 5 % ) . Significant multivariable predictors of recurrence were Gleason score 8 - 10 , number of positive nodes , pathologic Gleason score , and more recent year of surgery . The 15-yr CSM after clinical recurrence was 80 % , with a mean overall survival of 30 mo after recurrence . On multivariable analysis , recurrences after 5 yr from RP ( hazard ratio [ HR ] : 0.05 ) , multiple recurrences ( HR : 1.97 ) , skeletal ( HR : 3.13 ) , and visceral metastases ( HR : 7.43 ) were independently associated with CSM ( all p<0.05 ) . CONCLUSIONS Recurrences after RP for LN-positive PCa are heterogeneous in terms of time from RP , location , and number of concomitant lesions . PATIENT SUMMARY We found that impact of recurrence patterns on cancer-specific mortality varies significantly and allows these patients to be stratified for purpose s of prognostication , follow-up , and therapy Whether biochemical recurrence ( BR ) is a significant predictive factor of mortality after definitive radiation therapy for prostate cancer remains unknown . The aim of the current study was to investigate the relation between BR and overall mortality ( OAM ) in high‐risk prostate cancer patients who were treated with carbon‐ion radiotherapy ( CIRT ) and had long‐term follow‐up in 2 prospect i ve trials Purpose . Survival following biochemical failure is highly variable . Using a r and omized trial data set , we sought to define a risk stratification scheme in men with locally advanced prostate cancer ( LAPC ) . Methods . The TROG 96.01 trial r and omized 802 men with LAPC to radiation ± neoadjuvant and rogen suppression therapy ( AST ) between 1996 and 2000 . Ten-year follow-up data was used to develop three-tier post-biochemical failure risk stratification schemes based on cutpoints of time to biochemical failure ( TTBF ) and PSA doubling time ( PSADT ) . Schemes were evaluated in univariable , competing risk models for prostate cancer-specific mortality . The performance was assessed by c-indices and internally vali date d by the simple bootstrap method . Performance rankings were compared in sensitivity analyses using multivariable models and variations in PSADT calculation . Results . 485 men developed biochemical failure . c-indices ranged between 0.630 and 0.730 . The most discriminatory scheme had a high risk category defined by PSADT < 4 months or TTBF < 1 year and low risk category by PSADT > 9 months or TTBF > 3 years . Conclusion . TTBF and PSADT can be combined to define risk stratification schemes after biochemical failure in men with LAPC treated with short-term AST and radiotherapy . External validation , particularly in long-term AST and radiotherapy data sets , is necessary Importance Several surrogates for prostate cancer – specific mortality satisfying the Prentice criteria exist , but whether these are surrogates for all-cause mortality , and how their performance compares , is unknown . Objective To ascertain and compare the performance of 4 c and i date surrogates ( prostate-specific antigen [ PSA ] failure , PSA nadir > 0.5 ng/mL , PSA doubling time < 9 months , and interval to PSA failure < 30 months ) for all-cause mortality using the proportion of treatment-effect metric . Design , Setting , and Participants For this r and omized clinical trial , 206 men with unfavorable-risk prostate cancer who were seen at a Harvard-affiliated academic hospital or an associated community hospital between December 1 , 1995 , to April 15 , 2001 , were identified , r and omized to radiation therapy alone or radiation therapy followed by 6 months of and rogen deprivation therapy , and followed for a median 16.62 years . This analysis looks at the subgroup of 157 men with minimal comorbidities or no comorbidity ( median follow-up , 16.49 months ) . Interventions Patients were previously r and omized to receive radiation therapy or radiation and 6 months of and rogen deprivation therapy . Main Outcomes and Measures Risk of all-cause mortality . Results Overall , a cohort of 157 men ( median [ interquartile range ] age , 72.43 [ 68.75 - 75.53 ] ) with unfavorable-risk prostate cancer and minimal or no comorbidities were selected for this study . Three tested metrics met all 4 Prentice criteria for surrogacy for the surrogate covariate in the adjusted model for all-cause mortality : PSA nadir greater than 0.5 ng/mL ( adjusted hazard ratio [ aHR ] , 1.72 ; 95 % CI , 1.17 - 2.52 ; P = .01 ) , PSA doubling time less than 9 months ( aHR , 2.06 ; 95 % CI , 1.29 - 3.28 ; P = .003 ) , and interval to PSA failure less than 30 months ( aHR , 1.76 ; 95 % CI , 1.06 - 2.92 ; P = .03 ) ; while PSA failure did not . For the 3 successful surrogates , the proportion of treatment effect values were 103.86 % , 43.09 % , and 41.26 % , respectively . Conclusions and Relevance A PSA nadir value of greater than 0.5 ng/mL following radiation and and rogen deprivation therapy appears to identify men prior to PSA failure who are at high-risk for death . This could be used to select men for entry at the time of PSA nadir onto r and omized trials evaluating the impact on survival of salvage and rogen deprivation therapy with or without agents shown to prolong survival in men with castrate-resistant metastatic prostate cancer . Trial Registration clinical trials.gov Identifier : Holmberg L , Bill-Axelson A , Helgesen F , Salo JO , Folmerz P , Haggman M , et al. A r and omized trial comparing radical prostatectomy with watchful waiting in early prostate cancer . N Engl J Med 2002;347 : 781 - 9 . Background : The clinical importance and disease burden of prostate cancer — the PURPOSE Hormonal therapy ( HT ) is the current mainstay of systemic treatment for prostate specific antigen ( PSA ) only recurrence ( PSAR ) , however , there is virtually no published literature comparing HT to observation in the clinical setting . The goal of this study was to examine the Department of Defense Center for Prostate Disease Research observational data base to compare clinical outcomes in men who experienced PSAR after radical prostatectomy by early versus delayed use of HT and by a risk stratified approach . MATERIAL S AND METHODS Of 5,382 men in the data base who underwent primary radical prostatectomy ( RP ) , 4,967 patients were treated in the PSA-era between 1988 and December 2002 . Of those patients 1,352 men who had PSAR ( PSA after surgery greater than 0.2 ng/ml ) and had postoperative followup greater than 6 months were used as the study cohort . These patients were further divided into an early HT group in which patients ( 355 ) received HT after PSA only recurrence but before clinical metastasis and a late HT group for patients ( 997 ) who received no HT before clinical metastasis or by current followup . The primary end point was the development of clinical metastases . Of the 1,352 patients with PSAR clinical metastases developed in 103 ( 7.6 % ) . Patients were also stratified by surgical Gleason sum , PSA doubling time and timing of recurrence . Univariate and multivariate Cox proportional hazard models were used to evaluate the effect of early and late HT on clinical outcome . RESULTS Early HT was associated with delayed clinical metastasis in patients with a pathological Gleason sum greater than 7 or PSA doubling time of 12 months or less ( Hazards ratio = 2.12 , p = 0.01 ) . However , in the overall cohort early HT did not impact clinical metastases . Race , age at RP and PSA at diagnosis had no effect on metastasis-free survival ( p > 0.05 ) . CONCLUSIONS The retrospective observational multicenter data base analysis demonstrated that early HT administered for PSAR after prior RP was an independent predictor of delayed clinical metastases only for high-risk cases at the current followup . Further study with longer followup and r and omized trials are needed to address this important issue The value of pretreatment ( initial ) prostate‐specific antigen ( iPSA ) and biochemical recurrence ( BR ) as prognostic factors for survival remains unclear . The authors sought to determine why using r and omized trial data with 7‐year minimum follow‐up |
615 | 16,179,785 | Results : In addition to st and ard markers such as pepsinogens , we confirmed the close relationship between the levels of several biomarkers including gastrin , interleukin-8 , HLA class II molecules , reactive oxygen species , and the histological grade s. Conclusions : This review provides valuable information describing the clinical implication of these biomarkers for evaluating the static conditions or dynamic alterations of human gastric inflammation | Background : The importance of examining the status of gastric inflammation has been acknowledged ; the new classification by the up date d Sydney system ( USS ) allows us to evaluate the quantitative status of gastric inflammation .
However , this system is based on the histological classification derived from biopsy specimens .
Therefore , more convenient , objective and practical biomarkers are recommended .
Aim : We undertook a systematic review to find out potential biomarkers by summarizing the relationship between biomarkers and grade s of inflammation . | Previous studies have shown that the bisphosphonates ( BP ) vary in their damaging effect on the gastric mucosa , and endoscopy scores ( erosions or erosions plus ulcers ) after 1 and 2 weeks use of BP were significantly lower in H. pylori-positive versus -negative subjects . The mechanism of this damaging effect of BP and the interaction with H. pylori is unknown . As part of a separately reported study of the incidence of gastric damage after 2 weeks of treatment of healthy female postmenopausal volunteers with risedronate ( 5 mg/day ) or alendronate ( 10 mg/day ) , gastric aspirates were taken at the time of the baseline esophagogastroduodenoscopy ( EGD ) , and again at 1 and 2 weeks after daily intake of a BP . At the time of the third EGD , when the volunteers had been on risedronate or alendronate for 2 weeks , antral biopsies were taken from normal-appearing mucosa . Gastric juice and antral biopsies were assessed for their concentration of the cytokines interleukin-1α ( IL-1α ) , IL-8 , IL-13 , and epidermal growth factor ( EGF ) . H. pylori , the use of BP , and development of gastric mucosal lesions had no effect on gastric mucosal concentrations of IL-1α , IL-13 , or EGF . In contrast , the concentration of IL-8 in antral mucosal biopsies of volunteers given BP for 2 weeks was higher in the presence than in the absence of an H. pylori infection and was increased further in those who develop lesions associated with the use of BP . There was no correlation between gastric mucosal and gastric juice concentrations of IL-8 . Gastric juice concentrations of IL-8 and EGF were not affected by H. pylori status , the use of BP , or the development of lesions . However , gastric juice concentrations of IL-1α were numerically lower in those who were negative for H. pylori with no mucosal lesions ( Hp−L− ) , intermediate in those who were H. pylori-negative with lesions ( Hp−L+ ) , and highest in those who were positive for H. pylori and had lesions ( Hp+L+ ) . The gastric juice concentration of IL-13 was threefold higher in the absence than in the presence of H. pylori , and the relative abundance of IL-13 was : Hp−L− > Hp−L+ > Hp+L−1 > Hp+L+ . The prostagl and in E2 concentration in gastric antral biopsies was similar in the four groups and was unchanged with the in vitro biopsy incubation with celecoxib . We speculate that the higher gastric endoscopy scores observed with the use of BP in H. pylori negative as compared with H. pylori positive individuals is due to their lower mucosal concentration of IL-8 as well as the lower gastric juice concentration of IL-1α and higher concentration of IL-13 BACKGROUND This study characterized the phenotypic subsets of isolated gastric lymphocytes and the cellular immune response in cultured gastric biopsy specimens . METHODS Endoscopy specimens from 40 Helicobacter pylori-positive and 40 H. pylori-negative patients were studied . a ) Isolated gastric lymphocytes were analysed for CD4 + , CD8 + T-lymphocyte subsets , activated T cells , and natural killer cells on a fluorescence-activated cell sorter , using monoclonal antibodies . b ) The supernatant of cultured gastric biopsy specimens were assayed for interleukin (IL)-2 , IL-4 , and IL-6 levels . RESULTS In H. pylori-positive patients there was ( a ) a decrease in CD4+/CD8 + T cells , no change in activated T cells , and an increase in natural killer cells , and ( b ) no change in IL-2 levels and a significant increase in IL-4 and IL-6 levels . CONCLUSIONS There is an increase in CD8 + lymphocytes and natural killer cells , and the observed increase in IL-4 and IL-6 might be important in H. pylori-associated gastritis Objectives : In order to test the hypothesis that H. pylori infections in the gastric antrum increase pepsinogen I release , fasting serum pepsinogen I concentrations were compared in peptic ulcer patients with and without H. pylori infection . A r and omized prospect i ve study was performed to determine whether the increased serum pepsinogen I concentrations associated with H. pylori infection respond to treatment that eradicates H. pylori . Methods : Fasting serum pepsinogen I concentrations were measured by RIA in 736 patients with endoscopically and histologically confirmed benign peptic ulcer with and without H. pylori infection . Out of 511 patients with H. pylori infection , 110 patients ( group 1 ) were r and omly selected and were treated with metronidazole and tripotassium dicitrato bismuthate combined with ranitidine and antacid , and 97 patients ( group 2 ) were treated only with ranitidine and antacid . The third group , 54 patients free of H. pylori infection , was design ed to evaluate the influence of H2-receptor antagonist and antacid on the change of pepsinogen I. Fasting pepsinogen I concentration and H. pylori status were compared before and after the treatment . Results : Patients infected by H. pylori ( gastric ulcer 208 , duodenal ulcer 303 ; total 511 ) had significantly higher fasting serum pepsinogen I concentrations than H. pylori negative patients ( gastric ulcer 110 , duodenal ulcer 115 : total 225 ) . Mean pepsinogen I level of the former was 124.3±46.9 and that of the latter was 77.9±25.8 ng/ml . ( p<0.0001 ) The difference in serum pepsinogen I concentrations according to the location of ulcer crater was significant only in non-infected subjects e.g. , mean pepsinogen I level H. pylori-negative gastric ulcer was significantly lower than that of H. pylori-negative duodenal ulcer patients . H. pylori was eradicated in all the patients who had received antibacterial therapy for 4 weeks and serum pepsinogen I concentrations were significantly decreased from 129.8 + 43.0 to 82.4±24.0 ng/ml after eradication of the organism . ( p<0.0001 ) In contrast , H. pylori-positive patients who had not received antibacterial therapy were still infected at the completion of the study and there was no significant change in the serum pepsinogen I concentrations after the treatment ( 120.8±40.9 vs 126.3± 40.4 ng/ml ) . ( p>0.57 ) None of the patients who were initially H. pylori-negative has been reinfected during the period of the study and their serum pepsinogen I concentrations were not changed . ( pre-treatment value 75.1±8.0 ; post-treatment value 77.3±24.5 mg/ml)(p<0.75 ) Four-to six-week therapy of H2-receptor antagonist and antacid did not exert any influence on serum pepsinogen I concentrations . Conclusions : On the basis of our results , we have confirmed that the chronic infection of H. pylori of gastric antrum in peptic ulcer patients causes increased pepsinogen I release into the circulation , and eradication of the organism results in significant fall in serum pepsinogen I concentrations The aim of the present study was to determine the efficacy of a new combination regimen including antioxidant , proton pump inhibitor , and antibiotics against Helicobacter pylori and to document the changes of oxidative stress and cytokines involved in H. pylori-associated gastritis . From each of 57 patients with endoscopically diagnosed gastric and /or duodenal ulcers associated with H. pylori infection , five gastric antral biopsy specimens were taken for the diagnosis of H. pylori and for experimental measures . The patients were then treated either with lansoprozole 30 mg + amoxicillin 1.5 g ( LA group ; 21 patients ) or lansoprazole 30 mg + amoxicillin 1.5 g + rebamipide 300 mg ( LAM group ; 36 patients ) for two weeks . Four weeks after the initiation of treatment , the patients were endoscoped again and biopsy specimens were obtained . Mucosal malondialdehyde ( MDA ) levels ; myeloperoxidase ( MPO ) activities ; superoxide dismutase ; catalase ; glutathione peroxidase ; cytokines IL-1 , IL-6 , TNF-alpha ; and chemokines IL-8 , GRO-alpha , RANTES ( regulated on activation normal T expressed and secreted ) were measured . Using paraffin-embedded tissue sections , in situ terminal deoxyribonucleotide transferase ( TdT ) -mediated dUTP nick end labeling ( TUNEL ) for apoptosis and immunohistochemical staining for inducible nitric oxide synthase ( iNOS ) were performed . Two weeks of treatment with the LA regimen result ed in 57.4 % eradication rates of H. pylori , whereas two weeks of treatment with the LAM regimen result ed in 75.0 % eradication rates . Eradication rates between these two groups were statistically significantly different ( P < 0.05 ) . Mucosal MDA levels and MPO activities were significantly lower in the LAM group than the LA group . Mucosal levels of cytokines IL-1 , IL-6 , and TNF-alpha and of chemokines IL-8 , GRO-alpha , and RANTES were all significantly decreased after the treatment of H. pylori , especially in the LAM-treated group . The apoptotic index and iNOS score were significantly reduced after the eradication of H. pylori . The addition of the antioxidative drug rebamipide to the eradication regimen against H. pylori has quantitative and qualitative advantages such as either augmenting the eradication rates of H. pylori or decreasing oxidative stress and cytokines levels generated by H. pylori infection Helicobacter pylori ( H pylori ) raises serum gastrin but it is unclear whether this stimulates increased acid secretion . Gastrin mediated acid secretion and plasma gastrin after the intravenous infusion of gastrin releasing peptide was studied in nine H pylori negative and nine H pylori positive healthy volunteers , and in 11 duodenal ulcer patients . Nine of the last group were re-examined one month after eradication of H pylori . The median acid output ( mmol/h ) to gastrin releasing peptide ( 40 pmol/kg/h ) in the H pylori positive healthy volunteers was 15.1 ( range 3.3 - 38.3 ) , which was three times that of the H pylori negative healthy volunteers ( median = 5.5 , range 1.0 - 9.0 ) ( p < 0.02 ) . The median acid output in the duodenal ulcer patients with H pylori was 37 ( range 8.5 - 57 ) , which was > six times that of the H pylori negative healthy volunteers . Eradication of H pylori in the duodenal ulcer patients lowered their acid secretion by a median of 66 % ( range 30%-80 % ) ( p < 0.01 ) and to values equivalent to the H pylori positive healthy volunteers . The pepsin output in response to gastrin releasing peptide followed the same pattern as the acid output . The median plasma gastrin concentrations during gastrin releasing peptide were similar in the H pylori positive duodenal ulcer patients ( 150 ng/l , range 95 - 400 ) and H pylori positive healthy volunteers ( 129 ng/l , range 23 - 420 ) and both were appreciably higher than H pylori negative healthy volunteers ( 60 ng/l , range 28 - 135 ) ( p < 0.005 for each ) . Eradication of H pylori lowered the plasma gastrin in the duodenal ulcer patients to values equivalent to the H pylori negative healthy volunteers . These findings show a threefold increase in acid secretion in H pylori positive healthy volunteers that is explained by H pylori induced hypergastrinaemia and a sixfold increase in acid secretion in the duodenal ulcer patients that is explained by the combination of H pylori induced hypergastrinaemia and an exaggerated acid response to stimulation by gastrin . Eradicating H pylori lowers gastrin mediated acid secretion by 66 % in duodenal ulcer patients as a result of the resolution of the hypergastrinaemia . Increased gastrin mediated acid secretion seems to be the key factor in the pathophysiology of duodenal ulceration and explains the role of H pylori infection in the disorder Ascorbic acid , the reduced form of vitamin C , may protect against gastric cancer and is secreted by the normal stomach . Secretion is impaired in Helicobacter pylori ( H pylori ) associated chronic gastritis . This study examined if eradication of H pylori improves gastric juice ascorbate values . Fasting gastric juice and plasma sample s were collected at endoscopy from patients participating in trials of H pylori eradication for duodenal ulcer disease and intestinal metaplasia before and up to 15 months after attempted eradication . Ascorbic acid and total vitamin C concentrations were determined by high performance liquid chromatography . In 12 patients in whom H pylori was successfully eradicated gastric juice ascorbate and total vitamin C concentrations and the ratio of juice to plasma vitamin C rose after treatment . Analysis after treatment suggested that the rise was greatest in patients with high final plasma vitamin C concentrations , even though these did not change with treatment . By contrast , in 22 patients in whom H pylori eradication was unsuccessful there were no significant changes in juice or plasma concentrations after treatment . It is concluded that successful eradication of H pylori improves secretion of vitamin C into gastric juice . It is speculated that this increases protection against gastric cancer BACKGROUND To determine the accuracy of blood tests in predicting normal gastric mucosa confirmed by histological examination of gastric biopsy specimens . METHODS In total , 207 consecutive patients referred for upper endoscopy were included . Two biopsy specimens each from the antrum and corpus were assessed histologically for the presence of Helicobacter pylori , gastritis , and atrophy . Serum sample s were studied for H. pylori antibodies by enzyme immunoassay ( Pyloriset EIA-G and EIA-A ) and by a rapid latex agglutination test ( Pyloriset Dry ) ; pepsinogen I was measured by an immunoenzymometric assay ( Gastroset PGI ) , gastrin by radioimmunoassay , and parietal cell antibodies by indirect immunofluorescence . RESULTS In 101 ( 49 % ) of 207 patients , the gastric mucosa on histologic examination was normal . In the 63 patients aged 45 years or less , H. pylori IgG serology was negative in all 47 patients with normal gastric mucosa and none had low serum pepsinogen I levels . Among 144 patients over age 45 years , 72 had negative H. pylori IgG serology . Combining the serum pepsinogen I assay with the results of H. pylori IgG serology , 12 patients with normal serology but low serum pepsinogen I were found . Thus , 60 patients , 52 of whom showed normal gastric histology , had normal IgG serology and serum pepsinogen 1 . In the remaining eight patients with normal blood tests , the histologic changes were very mild . CONCLUSIONS Although negative H. pylori IgG serology alone in younger patients , and in combination with normal serum pepsinogen I levels in older patients , reliably predicted the presence of normal gastric mucosa , gastroscopy is still recommended for patients over 45 years BACKGROUND Although many studies have found an association between Helicobacter pylori infection and the development of gastric cancer , many aspects of this relation remain uncertain . METHODS We prospect ively studied 1526 Japanese patients who had duodenal ulcers , gastric ulcers , gastric hyperplasia , or nonulcer dyspepsia at the time of enrollment ; 1246 had H. pylori infection and 280 did not . The mean follow-up was 7.8 years ( range , 1.0 to 10.6 ) . Patients underwent endoscopy with biopsy at enrollment and then between one and three years after enrollment . H. pylori infection was assessed by histologic examination , serologic testing , and rapid urease tests and was defined by a positive result on any of these tests . RESULTS Gastric cancers developed in 36 ( 2.9 percent ) of the infected and none of the uninfected patients . There were 23 intestinal-type and 13 diffuse-type cancers . Among the patients with H. pylori infection , those with severe gastric atrophy , corpus-predominant gastritis , and intestinal metaplasia were at significantly higher risk for gastric cancer . We detected gastric cancers in 21 ( 4.7 percent ) of the 445 patients with nonulcer dyspepsia , 10 ( 3.4 percent ) of the 297 with gastric ulcers , 5 ( 2.2 percent ) of the 229 with gastric hyperplastic polyps , and none of the 275 with duodenal ulcers . CONCLUSIONS Gastric cancer develops in persons infected with H. pylori but not in uninfected persons . Those with histologic findings of severe gastric atrophy , corpus-predominant gastritis , or intestinal metaplasia are at increased risk . Persons with H. pylori infection and nonulcer dyspepsia , gastric ulcers , or gastric hyperplastic polyps are also at risk , but those with duodenal ulcers are not BACKGROUND This study investigates the cell proliferation and the expression of p53 protein in Helicobacter pylori ( H. pylori)-associated gastritis and assesses the effect of bacterial eradication on these epithelial factors . MATERIAL AND METHODS Seventy-nine patients with H. pylori-associated gastritis were r and omized into the control group ( n = 38 ) and anti-H. pylori group ( n = 41 ) . Each patient received endoscopic examinations with gastric biopsy before and 8 weeks after the treatment . The specimens from gastric antrum were immunostained for monoclonal antibodies against the proliferating cell nuclear antigen ( PCNA ) and p53 protein . RESULTS In the control group , the total labeling index ( L.I. ) of PCNA and the positive index ( P.I. ) of p53 in the whole foveolar epithelium were unchanged after treatment . In the anti-H. pylori group , 35 of 41 cases ( 85.3 % ) achieved eradication of H. pylori . Amongst the H. pylori-eradicated cases , the total L.I. of PCNA in the whole foveolar epithelium did not meaningfully alter after H. pylori elimination ( p > 0.05 ) . However , a significant reduction of L.I. was observed in the middle compartments of the gastric pits ( before vs. after treatment : 14.0 vs. 7.3 , p < 0.05 ) . With regard to the p53 expression , the P.I.s were significantly decreased in the whole foveolar epithelium ( before vs. after treatment : 0.57 vs. 0.17 , p < 0.05 ) and in each compartment of the gastric pits ( before vs. after treatment : [ upper compartment ] : 0.34 vs. 0.15 , p < 0.05 ; [ middle compartment ] : 0.67 vs. 0.23 , p < 0.05 ; [ lower compartment ] : 0.71 vs. 0.20 , p < 0.05 ) after eradication of H. pylori . CONCLUSIONS Bacterial eradication reverses the hyperproliferating status of the foveolar epithelium in patients with H. pylori gastritis and leads to a decrease in p53 accumulation in the epithelial cells The effects of H. pylori eradication on atrophic body gastritis are controversial Background : A r and omized prospect i ve study on the response of fasting serum gastrin concentrations in peptic ulcer patients was performed in order to test the hypothesis that H. pylori infection in the gastric antrum increases gastrin release , and to examine whether the high fasting serum gastrin concentrations respond to treatment that eradicates H. pylori . Methods : One hundred and twenty-seven patients with gastric or duodenal ulcer were included in this study . Patients were divided into three groups on the basis of antral H. pylori status and therapeutic modalities . The first group , 58 patients infected by H. pylori , was treated with metronidazole and tripotassium dicitrato bismuthate combined with ranitidine and mylanta . The second group , 40 patients also infected by H. Pylori , was treated with ranitidine and mylanta . The third group , 29 patients , free of H. pylori infection , was design ed to evaluate the influence of H2-receptor antagonist on the change of gastrin . When ulcers were completely healed , changes of gastrin concentrations and H. pylori status were re-examined . Results : H. pylori was eradicated in all patients who have received antibacterial therapy in 4 weeks , and serum gastrin concentrations were significantly decreased after eradication of the organism both in gastric and in duodenal ulcer diseases . ( Gastric ulcer : 129.3±47.0 pg/ml before and 63.7±21.6 pg/ml after treatment . Duodenal ulcer : 108.3±35.0 pg/ml and 66.5±21.9 pg/ml , respectively . Total : 112.7±38.2 pg/ml vs 66.0±21.6 pg/ml ) ( p<0.01 ) . In contrast , H. pylori-positive patients who have not received antibacterial therapy were still infected at the completion of the study , and serum gastrin concentrations increased even though the difference was not significant . ( Gastric ulcer : 118.4±51.2 pg/ml vs 124.0±56.5 pg/ml . Duodenal ulcer : 85.4±35.1 pg/ml vs 104.6±43.5 . Total : 99.5±45.3 vs 112.9±48.7 pg/ml . ) ( p>0.05 ) None of the patients who were initially H. pylori-negative has been reinfected during the period of the study , and their serum gastrin concentrations were not changed . ( Gastric ulcer : 69.8±38.0 pg/ml . Total : 63.2±31.1 pg/ml . Duodenal ulcer : 55.1±17.6 pg/ml vs 55.8±13.8 pg/ml . Total : 63.2±31.1 pg/ml vs 63.4±30.0 pg/ml ) Four- to six-week therapy of H2-receptor antagonist and antacid had no influence on serum gastrin concentrations . Conclusions : On the basis of the above results , we confirmed that the chronic infection of H. pylori of gastric antrum in peptic ulcer patients causes increased release of serum gastrin , and eradication of the organism results in a significant fall in serum gastrin BACKGROUND To clarify the possible role of CagA positive ( CagA+ ) Helicobacter pylori strains in the development of atrophic gastritis , the prevalence of antibodies to H. pylori and CagA ( 120 kD protein ) was studied among subjects with atrophic and non-atrophic gastritis . METHODS The study population was r and omly selected among 12,252 Finnish men who were screened for atrophic corpus gastritis with serum pepsinogen I-assay ( S-PGI ) . S-PGI level was used as a selection criterion . Group A consisted of 295 subjects with S-PGI < 25 microg/l ( low ) , group B of 320 subjects with S-PGI 25 - 100 microg/l ( normal ) and group C of 338 subjects with S-PGI > 100 microg/l ( high ) . Antibodies to H. pylori were measured with EIA and immunoblot analysis and antibodies to CagA with immunoblot analysis . Endoscopical and histological examinations were performed for 203 patients from group A. RESULTS The prevalence of antibodies to H. pylori was significantly lower in group B than in groups A or C ( P < 0.0001 , chi-squared test ) . There was a significant association between the prevalence of antibodies to CagA and the lowered level of S-PGI ( P < 0.0001 , Jonckheere-Terpstra trend test ) . There was also a linear decrease in the prevalence of antibodies to CagA as the atrophic corpus gastritis became more severe ( P < 0.0001 , linear-by-linear trend test ) . CONCLUSION The presence of antibodies to CagA seems to be associated with development of atrophic corpus gastritis Objective As Helicobacter pylori infection is associated with an elevation in plasma gastrin with normal antral gastrin cell counts , an abnormality in antral somatostatin cells may be associated with the infection . We evaluated the effect of eradication of H. pylori on antral somatostatin cell density in the light of antral gastrin cell density and plasma gastrin levels . Design Prospect i ve study Methods Of 25 dyspeptic patients with H. pylori infection , nine had H. pylori successfully eradicated and the rest remained infected . Antral biopsies were immunostained for somatostatin cells and plasma gastrin measured before and 4 weeks after H. pylori eradication therapy . Ten other dyspeptic patients without H. pylori infection had their somatostatin cell density evaluated as controls . Results Somatostatin cell density in the patients without H. pylori infection at the outset was significantly higher than that in the patients with H. pylori infection at the outset ( median 57 [ 18–83 ] vs. 37 [ 6–80 ] cells/mm ) respectively ( P < 0.05 ) . Somatostatin cell density increased after H. pylori eradication ( before treatment , median 50 [ 15–72 ] ; after treatment 71 [ 39–107 ] cells/mm ) ( P < 0.05 ) but was unchanged with persistent H. pylori infection . Plasma gastrin decreased after H. pylori eradication ( before treatment , median 70 [ 45–100 ] ; after treatment 30 [ 10–100 ] ng/l ) ( P < 0.05 ) but was unchanged with persistent H. pylori infection . Conclusion Following eradication of H. pylori , there is an increase in somatostatin cell density with a fall in plasma gastrin . This supports the theory that H. pylori infection results in a decrease in somatostatin cell density and , as the latter is an inhibitor of gastrin cells , this results in an increased plasma gastrin BACKGROUND Helicobacter pylori plays a key role in production of reactive oxygen metabolites ( ROMs ) . However , the importance of virulent CagA-positive H. pylori strains remains to be determined . The aim of this study was to assess ROMs production in gastric biopsies of patients infected by H. pylori . Results were correlated to CagA status and acute inflammatory infiltration . METHODS Patients undergoing gastroscopy were enrolled . H. pylori infection was assessed by histology and 13C urea breath test . CagA status was assessed through serology . ROMs were assayed in gastric biopsies by luminol-enhanced chemiluminescence ( CLS ) . Gastric mucosal inflammation was histologically grade d and neutrophils were individually counted . Macroscopical damage was scored according to a modified Lanza score . RESULTS 40 out of 60 patients evaluated were H. pylori ( HP ) positive . Of the 40 infected patients , 24 were CagA-positive . CLS emission was significantly higher in HP-CagA-positive patients than in HP-CagA-negatives and uninfected . ROMs production showed a significant correlation to neutrophil infiltrate in all groups . CONCLUSIONS Gastric mucosa of patients infected by HP-CagA-positive strains is characterized by a higher generation of ROMs and by greater neutrophil counts than that observed in HP-CagA-negative subjects . Since ROMs production is associated with DNA oxidative damage , a long-term stimulation by these strains might be relevant in the pathogenesis of gastric malignancies . Assessment of CagA status might be useful to discriminate patients in which H. pylori eradication is advisable |
616 | 28,916,152 | The results demonstrated that IMT performed at low intensities can chronically promote an increase in the parasympathetic modulation and /or reduction of sympathetic cardiac modulation in patients with diabetes , hypertension , chronic heart failure and gastroesophageal reflux , when assessed by HRV spectral analysis . | PURPOSE To carry out a systematic review to determine if inspiratory muscle training ( IMT ) promotes changes in cardiovascular autonomic responses in humans . | Background Hypertension is a complex chronic condition characterized by elevated arterial blood pressure . Management of hypertension includes non-pharmacologic strategies , which may include techniques that effectively reduce autonomic sympathetic activity . Respiratory exercises improve autonomic control over cardiovascular system and attenuate muscle metaboreflex . Because of these effects , respiratory exercises may be useful to lower blood pressure in subjects with hypertension . Methods / design This r and omized , double-blind clinical trial will test the efficacy of inspiratory muscle training in reducing blood pressure in adults with essential hypertension . Subjects are r and omly allocated to intervention or control groups . Intervention consists of inspiratory muscle training loaded with 40 % of maximum inspiratory pressure , readjusted weekly . Control sham intervention consists of unloaded exercises . Systolic and diastolic blood pressures are co- primary endpoint measures assessed with 24 h ambulatory blood pressure monitoring . Secondary outcome measures include cardiovascular autonomic control , inspiratory muscle metaboreflex , cardiopulmonary capacity , and inspiratory muscle strength and endurance . Discussion Previously published work suggests that inspiratory muscle training reduces blood pressure in persons with hypertension , but the effectiveness of this intervention is yet to be established . We propose an adequately sized r and omized clinical trial to test this hypothesis rigorously . If an effect is found , this study will allow for the investigation of putative mechanisms to mediate this effect , including autonomic cardiovascular control and metaboreflex . Trial registration Clinical Trials.gov NCT02275377 . Registered on 30 September 2014 Objective : To evaluate heart rate variability during an inspiratory muscle endurance protocol at three different load levels [ 30 % , 60 % and 80 % of maximal inspiratory pressure ] , in patients who had previously undergone coronary artery bypass grafting . Methods : Nineteen late postoperative myocardial revascularization patients participating in a cardiovascular rehabilitation program were studied . Maximal inspiratory pressure maneuvers were performed . An inspiratory muscle endurance protocol at 30 % , 60 % and 80 % of maximal inspiratory pressure was applied for four minutes each , in r and om order . Heart rate and RR intervals were recorded and heart rate variability was analyzed by time ( RMSSD-the mean of the st and ard deviations for all R-R intervals , and RMSM-root-mean square differences of successive R-R intervals ) and frequency domains indices ( high and low frequency ) in normalized units . ANOVA for repeated measurements was used to compare heart rate variability indices and Student t-test was used to compare the maximal inspiratory pressure and maximal expiratory pressure values . Results : Heart rate increased during performance of maximal respiratory pressures maneuvers , and the maximal inspiratory pressure and maximal expiratory pressure mean values were significantly lower than predicted values ( P<0.05 ) . RMSSD increased significantly at 80 % in relation to rest and 30 % of maximal inspiratory pressure and RMSM decreased at 30 % and 60 % of maximal inspiratory pressure in relation to rest ( P<0.05 ) . Additionally , there was significant and progressive decrease in low frequency and increase in high frequency at 30 % , 60 % and 80 % of maximal inspiratory pressure in relation to the resting condition . Conclusion : These results suggest that respiratory muscle training at high intensities can promote greater parasympathetic activity and it may confer important benefits during a rehabilitation program in post-coronary artery bypass grafting Introduction Cardiac surgery is a highly complex procedure which generates worsening of lung function and decreased inspiratory muscle strength . The inspiratory muscle training becomes effective for muscle strengthening and can improve functional capacity . Objective To investigate the effect of inspiratory muscle training on functional capacity submaximal and inspiratory muscle strength in patients undergoing cardiac surgery . Methods This is a clinical r and omized controlled trial with patients undergoing cardiac surgery at Instituto Nobre de Cardiologia . Patients were divided into two groups : control group and training . Preoperatively , were assessed the maximum inspiratory pressure and the distance covered in a 6-minute walk test . From the third postoperative day , the control group was managed according to the routine of the unit while the training group underwent daily protocol of respiratory muscle training until the day of discharge . Results 50 patients , 27 ( 54 % ) males were included , with a mean age of 56.7±13.9 years . After the analysis , the training group had significant increase in maximum inspiratory pressure ( 69.5±14.9 vs. 83.1±19.1 cmH2O , P=0.0073 ) and 6-minute walk test ( 422.4±102.8 vs. 502.4±112.8 m , P=0.0031 ) . Conclusion We conclude that inspiratory muscle training was effective in improving functional capacity submaximal and inspiratory muscle strength in this sample of patients undergoing cardiac surgery Background Physical exercise reduces glucose levels and glucose variability in patients with type 2 diabetes . Acute inspiratory muscle exercise has been shown to reduce these parameters in a small group of patients with type 2 diabetes , but these results have yet to be confirmed in a well- design ed study . The aim of this study is to investigate the effect of acute inspiratory muscle exercise on glucose levels , glucose variability , and cardiovascular autonomic function in patients with type 2 diabetes . Methods / design This study will use a r and omized clinical trial crossover design . A total of 14 subjects will be recruited and r and omly allocated to two groups to perform acute inspiratory muscle loading at 2 % of maximal inspiratory pressure ( PImax , placebo load ) or 60 % of PImax ( experimental load ) . Discussion Inspiratory muscle training could be a novel exercise modality to be used to decrease glucose levels and glucose variability . Trial registration Clinical Trials.gov NCT02292810 BACKGROUND The cardiovascular system is noticeably affected by respiration . However , whether different inspiratory resistive loading intensities can influence autonomic heart rate ( HR ) modulation remains unclear . OBJECTIVE The objective was to investigate HR modulation at three different inspiratory resistive loading intensities in healthy elderly men . METHOD This was a prospect i ve , r and omized , double-blind study that evaluated 25 healthy elderly men . Cardiac autonomic modulation was assessed using heart rate variability ( HRV ) indices . All of the volunteers underwent maximal inspiratory pressure ( MIP ) measurements according to st and ardized pulmonary function measurements . Three r and omly-applied inspiratory resistive loading ( 30 , 60 and 80 % of MIP ) intensities were then applied using an inspiratory resistance device ( POWERbreathe , Southam , UK ) , during which the volunteers were asked to inhale for 2 seconds and exhale for 3 seconds and complete 12 breaths per minute . Each effort level was performed for 4 minutes , and HR and the distance between 2 subsequent R waves of electrocardiogram ( R-R intervals ) were collected at rest and at each intensity for further HRV analysis . RESULTS The parasympathetic HRV ( rMSSD , SD1 and HF ) indices demonstrated lower values at 80 % ( rMSSD : 19±2 ms , SD1 : 13±2 ms and HF : 228±61 ms2 ) than at 30 % MIP ( rMSSD : 25±3 ms , SD1 : 18±2 ms and HF : 447±95 ms2 ; p<0.05 ) . CONCLUSIONS Lower inspiratory resistive loading intensities promoted a marked and positive improvement of parasympathetic sinus node modulation The crural diaphragm ( CD ) is an essential component of the esophagogastric junction ( EGJ ) , and inspiratory exercises may modify its function . This study 's goal is to verify if inspiratory muscle training ( IMT ) improves EGJ motility and gastroesophageal reflux ( GER ) . Twelve GER disease [ GERD ; 7 males , 20 - 47 yr , 9 esophagitis , and 3 nonerosive reflex disease ( NERD ) ] and 7 healthy volunteers ( 3 males , 20 - 41 yr ) performed esophageal pH monitoring , manometry , and heart rate variability ( HRV ) studies . A 6-cm sleeve catheter measured average EGJ pressure during resting , peak inspiratory EGJ pressures during sinus arrhythmia maneuver ( SAM ) and inhalations under 17- , 35- , and 70-cmH2O loads ( TH maneuvers ) , and along 1 h after a meal . GERD patients entered a 5-days-a-week IMT program . One author scored heartburn and regurgitation before and after IMT . IMT increased average EGJ pressure ( 19.7 ± 2.4 vs. 29.5 ± 2.1 mmHg ; P < 0.001 ) and inspiratory EGJ pressure during SAM ( 89.6 ± 7.6 vs. 125.6 ± 13.3 mmHg ; P = 0.001 ) and during TH maneuvers . The EGJ-pressure gain across 35- and 70-cmH2O loads was lower for GERD volunteers . The number and cumulative duration of the transient lower esophageal sphincter relaxations decreased after IMT . Proximal progression of GER decreased after IMT but not the distal acid exposure . Low-frequency power increased after IMT and the higher its increment the lower the increment of supine acid exposure . IMT decreased heartburn and regurgitation scores . In conclusion , IMT improved EGJ pressure , reduced GER proximal progression , and reduced GERD symptoms . Some GERD patients have a CD failure , and IMT may prove beneficial as a GERD add-on treatment OBJECTIVES This study sought to evaluate the effects of inspiratory muscle training in inspiratory muscle strength , as well as in functional capacity , ventilatory responses to exercise , recovery oxygen uptake kinetics , and quality of life in patients with chronic heart failure ( CHF ) and inspiratory muscle weakness . BACKGROUND Patients with CHF may have reduced strength and endurance in inspiratory muscles , which may contribute to exercise intolerance and is associated with a poor prognosis . METHODS Thirty-two patients with CHF and weakness of inspiratory muscles ( maximal inspiratory pressure [ Pi(max ) ] < 70 % of predicted ) were r and omly assigned to a 12-week program of inspiratory muscle training ( IMT , 16 patients ) or to a placebo-inspiratory muscle training ( P-IMT , 16 patients ) . The following measures were obtained before and after the program : Pi(max ) at rest and 10 min after maximal exercise ; peak oxygen uptake , circulatory power , ventilatory oscillations , and oxygen kinetics during early recovery ( VO2/t-slope ) ; 6-min walk test ; and quality of life scores . RESULTS The IMT result ed in a 115 % increment Pi(max ) , 17 % increase in peak oxygen uptake , and 19 % increase in the 6-min walk distance . Likewise , circulatory power increased and ventilatory oscillations were reduced . The VO2/t-slope was improved during the recovery period , and quality of life scores improved . CONCLUSIONS In patients with CHF and inspiratory muscle weakness , IMT results in marked improvement in inspiratory muscle strength , as well as improvement in functional capacity , ventilatory response to exercise , recovery oxygen uptake kinetics , and quality of life Autonomic dysfunction , including baroreceptor attenuation and sympathetic activation , has been reported in patients with myocardial infa rct ion ( MI ) and has been associated with increased mortality . We tested the hypotheses that exercise training ( ET ) in post-MI patients would normalize arterial baroreflex sensitivity ( BRS ) and muscle sympathetic nerve activity ( MSNA ) , and long-term ET would maintain the benefits in BRS and MSNA . Twenty-eight patients after 1 month of uncomplicated MI were r and omly assigned to 2 groups , ET ( MI-ET ) and untrained . A normal control group was also studied . ET consisted of three 60-minute exercise sessions per week for 6 months . We evaluated MSNA ( microneurography ) , blood pressure ( automatic oscillometric method ) , heart rate ( ECG ) , and spectral analysis of RR interval , systolic arterial pressure ( SAP ) , and MSNA . Baroreflex gain of SAP-RR interval and SAP-MSNA were calculated using the & agr;-index . At 3 to 5 days and 1 month after MI , MSNA and low-frequency SAP were significantly higher and BRS significantly lower in MI patients when compared with the normal control group . ET significantly decreased MSNA ( bursts per 100 heartbeats ) and the low-frequency component of SAP and significantly increased the low-frequency component of MSNA and BRS of the RR interval and MSNA . These changes were so marked that the differences between patients with MI and the normal control group were no longer observed after ET . MSNA and BRS in the MI-untrained group did not change from baseline over the same time period . ET normalizes BRS , low-frequency SAP , and MSNA in patients with MI . These improvements in autonomic control are maintained by long-term ET . These findings highlight the clinical importance of this nonpharmacological therapy based on ET in the long-term treatment of patients with MI PURPOSE Patients with type 2 diabetes mellitus may present weakness of the inspiratory muscles . We tested the hypothesis that inspiratory muscle training ( IMT ) could improve inspiratory muscle strength , pulmonary function , functional capacity , and autonomic modulation in patients with type 2 diabetes and weakness of the inspiratory muscles . METHODS Maximal inspiratory muscle pressure ( PImax ) was evaluated in a sample of 148 patients with type 2 diabetes . Of these , 25 patients with PImax<70 % of predicted were r and omized to an 8-wk program of IMT ( n=12 ) or placebo-IMT ( n=13 ) . PImax , inspiratory muscle endurance time , pulmonary function , peak oxygen uptake , and HR variability were evaluated before and after intervention . RESULTS The prevalence of inspiratory muscle weakness was 29 % . IMT significantly increased the PImax ( 118 % ) and the inspiratory muscle endurance time ( 495 % ) , with no changes in pulmonary function , functional capacity , or autonomic modulation . There were no significant changes with placebo-IMT . CONCLUSIONS Patients with type 2 diabetes may frequently present inspiratory muscle weakness . In these patients , IMT improves inspiratory muscle function with no consequences in functional capacity or autonomic modulation BACKGROUND Autonomic imbalance , characterized by sympathetic hyperactivity and diminished vagal tone , is a known mechanism for essential hypertension . Inspiratory muscle training ( IMT ) demonstrates beneficial outcomes in a number of cardiovascular population s , which may potentially extend to patients with hypertension . The aim of this study was to further eluci date the effects of IMT on blood pressure and autonomic cardiovascular control in patients with essential hypertension . METHODS Thirteen patients with hypertension were r and omly assigned to an eight-week IMT program ( 6 patients ) or to a placebo-IMT ( P-IMT , 7 patients ) protocol . We recorded RR interval for posterior analysis of heart rate variability and blood pressure , by ambulatory blood pressure monitoring ( ABPM ) , before and after the program . RESULTS There was a significant increase in inspiratory muscle strength in the IMT group ( 82.7 ± 28.8 vs 121.5 ± 21.8 cmH2O , P<0.001 ) , which was not demonstrated by P-IMT ( 93.3 ± 25.3 vs 106.1 ± 25.3 cmH2O , P>0.05 ) . There was also a reduction in 24-hour measurement of systolic ( 133.2 ± 9.9 vs 125.2 ± 13.0 mm Hg , P=0.02 ) and diastolic ( 80.7 ± 12.3 vs 75.2 ± 1.0 mm Hg , P=0.02 ) blood pressure , as well as in daytime systolic ( 136.8 ± 12.2 vs 127.6 ± 14.2 mm Hg , P=0.008 ) and diastolic ( 83.3 ± 13.1 vs. 77.2 ± 12.2 mm Hg , P = 0.01 ) blood pressure in the IMT group . In relation to autonomic cardiovascular control , we found increased parasympathetic modulation ( HF : 75.5 ± 14.6 vs. 84.74 ± 7.55 n.u , P=0.028 ) and reduced sympathetic modulation ( LF : 34.67 ± 20.38 vs. 12.81 ± 6.68 n.u ; P=0.005 ) . Moreover , there was reduction of cardiac sympathetic discharge ( fLF ) in IMT group ( P=0.01 ) . CONCLUSIONS IMT demonstrates beneficial effects on systolic and diastolic blood pressure as well as autonomic cardiovascular control in hypertensive patients BACKGROUND Resistance exercise ( RE ) is an important part of cardiac rehabilitation . However , it is not known about the low intensity of RE training that could modify the heart rate variability ( HRV ) , muscular strength and endurance in patients with coronary artery disease ( CAD ) . AIM To investigate the effects of high repetition/low load resistance training ( HR/LL-RT ) program on HRV and muscular strength and endurance in CAD patients . DESIGN R and omized and controlled trial . SETTING Patients seen at the Cardiopulmonary Physical Therapy Laboratory between May 2011 and November 2013 . POPULATION Twenty male patients with CAD were r and omized to a training group ( 61.3±5.2 years ) or control group ( 61±4.4 years ) . METHODS 1 repetition maximum ( 1-RM ) maneuver , discontinuous exercise test on the leg press ( DET-L ) , and resting HRV were performed before and after 8 weeks of HR/LL-RT on a 45 ° leg press . RMSSD , SD1 , mean HR and ApEn indices were calculated . The HR/LL-RT program consisted of a lower limb exercise using a 45 ° leg press ; 3 sets of 20 repetitions , two times a week . The initial load was set at 30 % of the 1-RM load and the duration of the HR/LL-RT program was performed for 8 weeks . RESULTS After 8 weeks of HR/LL-RT there were significant increases of RMSSD and SD1 indices in the training group only ( P<0.05 ) . There was a significant decrease in mean HR after HR/LL-RT in the training group ( P<0.05 ) . There was a significantly higher ApEn after in the training group ( P<0.05 ) . There were significantly higher values in the training group in contrast to the control group ( P<0.05 ) . CONCLUSION These results show positive improvements on HRV , as well as muscle strength and endurance in CAD patients . CLINICAL REHABILITATION IMPACT Eight weeks of HR/LL-RT is an effective sufficient to beneficially modify important outcomes as HRV , muscle strength and endurance in CAD patients Reduced heart rate variability ( HRV ) in older patients with heart failure ( HF ) is common and indicates poor prognosis . Exercise training ( ET ) has been shown to improve HRV in younger patients with HF . However , the effect of ET on HRV in older patients with HF is not known . Sixty-six participants ( 36 % men ) , aged 69±5 years , with HF and both preserved ejection fraction ( HFPEF ) and reduced ejection fraction ( HFREF ) , were r and omly assigned to 16 weeks of supervised ET ( ET group ) vs attention-control ( AC group ) . Two HRV parameters ( the st and ard deviation of all normal RR intervals [ SDNN ] and the root mean square of successive differences in normal RR intervals [ RMSSD ] ) were measured at baseline and after completion of the study . When compared with the AC group , the ET group had a significantly greater increase in both SDNN ( 15.46±5.02 ms in ET vs 2.37±2.13 ms in AC , P=.016 ) and RMSSD ( 17.53±7.83 ms in ET vs 1.69±2.63 ms in AC , P=.003 ) . This increase was seen in both sexes and HF categories . ET improved HRV in older patients with both HFREF and HFPEF |
617 | 12,804,390 | REVIEW ER 'S CONCLUSIONS There is no strong evidence to support the everyday use of any of the agents included in this review . | BACKGROUND Tardive dyskinesia is a disabling movement disorder associated with the prolonged use of neuroleptic medication .
This review , one in a series examining the treatment of tardive dyskinesia , will cover miscellaneous treatments not covered elsewhere .
OBJECTIVES To determine whether the following interventions were associated with a reduction of neuroleptic induced tardive dyskinesia : botulin toxin , endorphin , essential fatty acid , EX11582A , ganglioside , insulin , lithium , naloxone , oestrogen , periactin , phenylalanine , piracetam , stepholidine , tryptophan , neurosurgery , or ECT . | A single blind trial and a placebo controlled double blind trial of lithium were carried out in elderly patients with tardive dyskinesia . In the pilot study , neuroleptics were continued : in the controlled trial , neuroleptics were discontinued . The results of both studies were essentially negative . Thus , the suppression effect of neuroleptics is much more dramatic than anything seen in the two studies . Several reasons for this were discussed namely , the severity and chronicity of the symptoms Eleven patients with tardive dyskinesia were treated with lithium carbonate in a placebo-controlled double-blind crossover study . No significant effect of lithium on either tardive dyskinesia or blood prolactin concentrations was demonstrated , but 5 patients developed pseudo-Parkinsonian features Psychiatric in patients with tardive dyskinesia ( TD ) were treated with either lithium alone ( n = 9 ) or with a combination of lithium and lecithin ( n = 9 ) for 5 weeks in a double-blind , placebo-controlled experiment . A statistically significant but clinical ly unimportant improvement of TD occurred during both treatments . The addition of lecithin to lithium had no effect The effectiveness of a once-weekly i.m . injection of ceruletide ( 0.8 microgram/kg ) in suppressing the symptoms of neuroleptic-induced tardive dyskinesia ( TD ) was evaluated in a double-blind , placebo-controlled , matched-pairs study . Global evaluation of the severity of TD symptoms over the 8-week study period revealed a significant improvement with ceruletide as compared with placebo . Analysis of the therapeutic response to ceruletide over the course of treatment revealed a slow , but long-lasting improvement of TD symptoms . Side effects , which were mild and transient , consisted mainly of nausea and epigastric discomfort . The incidence of side effects did not differ between the ceruletide- and placebo-treated groups . Ceruletide appears to be a novel and practical treatment that can substantially alleviate the symptoms of dyskinesia The beneficial effect of estrogens on L -dopa-induced dyskinesias and on tardive dyskinesia has recently been reported . In this open pilot study , conjugated estrogens ( CE ) were Eight psychiatric patients with tardive dyskinesia ( TD ) were treated with single doses of the synthetic met-enkephalin analogue FK 33 - 824 ( 1 , 2 , and 3 mg IM ) morphine ( 10 mg SC ) and naloxone , an opiate receptor antagonist ( 0.8 mg IM ) . The drug effects were assessed by blind evaluation of r and omly sequenced videotapes made before and during treatment . FK 33 - 824 ( 1,2 , and 3 mg IM ) slightly reduced TD ( P<0.05 ) and increased preexisting bradykinesia . The effect on TD , however , was pronounced only in patients concurrently treated with neuroleptics in relatively high doses . Morphine had a similar although weaker antihyperkinetic effect , whereas naloxone had no effect . Side effects of FK 33 - 824 included dizziness , heaviness in the extremities , slurred speech , and dryness of mouth . Morphine caused drowsiness , dizziness , ataxia , and nausea , and naloxone had no side effects . The results do not point to a primary role of enkephalin in the pathophysiology of TD , but enkephalin may interact with dopamine functions and potentiate some of the effects of neuroleptic drugs The unique role of ganglioside GM1 in neuronal plasticity led two centers , New York University and McLean Hospital , to study the effect of GM1 or placebo in patients with tardive dyskinesia . Results from the NYU cohort have already been published . We now present data from the entire cohort , allowing us to evaluate the effects of GM1 in the elderly compared to young adults . Subjects with tardive dyskinesia were r and omly assigned to single-blind placebo injections for 1 week , followed by 1 month of double-blind intramuscular placebo or GM1100 mg . The final sample included 29 patients : 12 younger than 55 years of age and 17 older . There was no GM1-versus-placebo difference observed in either-age group , or in the total group . However , whether on placebo or GM1 , repeated measures analysis of variance ( RANOVA ) found a significant difference in response between Abnormal Involuntary Movement Scale scores , taken baseline and week 4 , in the elderly compared to young adults . Scores for the young adults show initial improvement then deterioration back to baseline , and those for the elderly show continuing improvement during the 4-week trial . The importance of the placebo effect in the elderly and its meaning for studies of GM1 in tardive dyskinesia are discussed OBJECTIVE The study investigated the efficacy and tolerability of ethyl-eicosapentaenoic acid ( E-EPA ) as add-on treatment in chronic , severe schizophrenia . METHOD A r and omized , parallel-group , double-blind , placebo-controlled , fixed-dose , add-on study was conducted over 12 weeks . Forty patients with persistent symptoms after at least 6 months of stable antipsychotic treatment received E-EPA or placebo , in addition to their existing treatment . RESULTS At 12 weeks , the E-EPA group had significantly greater reduction of Positive and Negative Syndrome Scale total scores and of dyskinesia scores than the placebo group . CONCLUSIONS EPA may be an effective and well-tolerated add-on treatment in schizophrenia The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas Estrogen have been reported in animal studies to both enhance and block central dopaminergic activity and in one clinical report to improve tardive dyskinesia . In the present study estrogen ( Premarin , 2.5 mg per day ) administration caused varying degrees of improvement in less than one-third of 21 patients with chorea due to Huntington 's disease and tradive dyskinesia and had no effect in eight patients with dystonia . Estrogens appear to have an antidopaminergic effect in humans but poses only limited efficacy in the treatment of dyskinetic disorders In an attempt to determine the role of serotoninergic mechanisms in the pathophysiology of tardive dyskinesia , the serotonin precursor 5-hydroxytryptophan ( 5HTP ) with carbidopa , a peripheral decarboxylase inhibitor , were given in a double-blind crossover design to seven patients with longst and ing tardive dyskinesia . In the five patients who completed the study , there was no change in dyskinetic movements . Most of the patients had worsening of psychotic symptoms with 5HTP . The data suggest that serotonin precursors have no therapeutic effects in tardive dyskinesia . The implication s for the role of serotonin in the pathophysiology of tardive dyskinesia are discussed Tardive dyskinesia ( TD ) is thought to result from nigrostriatal dopaminergic supersensitivity secondary to prolonged neuroleptic exposure . Pre clinical studies have demonstrated that the opiate antagonist naloxone can acutely reverse a haloperidol-induced hyperdopaminergic state . In a trial of high-dose naloxone , 20 patients with TD received i.v . naloxone ( 20 mg , 40 mg , and placebo ) under double-blind conditions . At baseline and at regular postdrug intervals , patients were evaluated using a battery of motor , clinical , and neuropsychological measures to study effects on neurological , behavioral , and cognitive functions . There was a significant improvement in involuntary movements at 30 min postnaloxone , together with improvement in clinical ratings at that time point , as well as some cognitive changes . The implication s of these findings for the putative functional relationship between dopaminergic and enkephalinergic systems in the nigrostriatal area are discussed Pre clinical and clinical observations suggest that enhancement of prostagl and in activity inhibits catecholamine release and may have antidyskinetic effects . A double-blind therapeutic trial with prostagl and in precursor essential fatty acids was conducted in 16 patients with tardive dyskinesia . No beneficial effects were seen The subjects were 13 psychiatric in patients with tardive dyskinesia . Each subject participated in two sessions . Either naloxone ( 10 mg ) or placebo was administered intravenously during each session . In a subset of subjects ( n = 7 ) , blood sample s for beta-endorphin were drawn before and at 30 and 60 minutes after the injection . The Abnormal Involuntary Movement Scale was administered before and at 10 , 20 , 40 , 60 , 120 , and 360 minutes after the injection . Double-blind procedures were maintained throughout the experiment . Neither naloxone nor placebo had any appreciable effect on the involuntary movements . Naloxone elicited a significant increase in the plasma beta-endorphin Tardive dyskinesia ( TD ) induced by antipsychotic drugs represents a great concern for patients and psychiatrists . Considering its pathophysiological mechanisms , there exists a convergence towards the development of postsynaptic dopaminergic hypersensitivity as a possible cause of TD . Hypersensitivity following receptor blockade is the consequence of an increased number of receptors and such a synthesis is energy-dependent . In the brain , under normal conditions , energy is almost exclusively provided by glucose utilization . We thus hypothesized that , if glucose availability were reduced , the metabolically hyperactive structures should represent the best functional target of a reduction in fuel availability . Twenty chronic schizophrenic out patients ( 13 males , 7 females ) , aged 20 - 67 ( mean : 38.3 ) , accepted to participate in this double-blind , placebo-controlled study . They were r and omly assigned to either the insulin treatment group ( 10 patients ) or to the insulin-placebo group ( 10 patients ) . They received a subcutaneous injection of 10 units of st and ard insulin or placebo at 10 a.m. From day 1 to day 15 , injections were performed daily and , thereafter , every other week for 5 weeks totalizing 20 injections in 90 days . At day 7 , the insulin treatment group showed a sharp decrease in the intensity of TD symptoms which persisted throughout the duration of the study . By contrast , no change in TD symptomatology was observed in the insulin-placebo-treated group . Although a direct effect on DA neurones , or at least the participation of such an effect , can not be excluded , our data favor a role of decreased glucose availability in reversing receptor hypersensitivity Despite continued research , the influences that promote or exacerbate tardive dyskinesia ( TD ) symptoms remain incompletely understood . Recent findings ( Gardos et al. 1992 ; Richardson et al. 1989 ) suggest that ingestion of the dietary constituent , phenylalanine , might exacerbate TD symptoms , but a double-blind , placebo-controlled challenge had not previously been conducted in schizophrenic patients . On two different mornings , in counterbalanced order , 18 male schizophrenic patients with TD were challenged with either 100 mg/kg phenylalanine or placebo . Effects on abnormal involuntary movements , recall memory , and plasma phenylalanine were measured 90 minutes post-challenge . The results supported the hypothesis in that involuntary movements increased to a statistically and clinical ly meaningful degree after the phenylalanine challenge , but not after placebo . No effects on memory were detected . Significant order effects characterized the plasma findings but not the behavioral data . Results indicate that a dietary constituent , the amino acid phenylalanine , can potentially exacerbate tardive dyskinesia symptoms in schizophrenic patients . The influence of phenylalanine and other ingested substances on clinical symptomatology warrants further investigation A double-blind r and omized clinical trial was conducted among 10 post-menopausal women with tardive dyskinesia ( TD ) to test the effect of estrogen replacement of the severity of abnormal movements and other outcome variables . After 3 weeks of treatment , the mean Abnormal Involuntary Movement Scale ( AIMS ) score decreased by 38 % in the estrogen group and by 9 % in the placebo group ; the difference between groups was marginally significant ( p less than 0.10 ) . However , the small sample size and the imbalance between groups in baseline AIMS scores do not allow us to rule out the confounding effects of other prognostic factors . There were no significant differences between treatment groups for parkinsonian and psychological symptoms at any visit or for changes in these variables between visits . The findings of this preliminary trial are consistent with the results of other human and animal investigations , and they support the need for future research to underst and the role of estrogens in the neuropathology and treatment of TD The efficacy of electromyographic feedback training in reducing the magnitude and frequency of the oral-lingual movements associated with tardive dyskinesia ( TD ) was investigated in a groups design . Twenty adult male in patients diagnosed as having TD using the Abnormal Involuntary Movements Scale ( AIMS ) were r and omly assigned to one of two treatment conditions . Following identification , all participants were initially reduced to the lowest effective dosage of neuroleptics , and then discontinued from anticholinergics . Following one month on this regimen , they were given a course of feedback training consisting of ten 14-minute sessions . Group one participants were provided with a tone contingent upon oral-lingual movements above a yoked threshold . Group two participants were given noncontingent feedback tones generated r and omly . Weekly AIMS were administered as well as an initial baseline during each session to determine current level of oral-lingual activity . An analysis of session effects indicated significantly more suppression of oral-lingual activity in the contingent group versus the noncontingent feedback group . Jaw and forehead activity also measured showed reductions of similar magnitudes for both groups Patients with tardive dyskinesia showed no significant difference in CSF HVA when compared with groups of schizophrenic or depressives . CSF cAMP in the tardive dyskinesia group was significantly lower when compared to schizophrenics but not depressives . These results do not support a dopamine-receptor supersensitivity hypothesis in permanent tardive dyskinesia In a double-blind crossover placebo controlled trial the effectivity of piracetam in neuroleptic-induced extrapyramidal side effects was confirmed . 40 psychotic patients treated with neuroleptics in an average daily dose equal to 600 mg of chlorpromazine were included in this study . Akathisia , tremor , muscle rigidity and dyskinesia were evaluated on a 4-point scale . The patients were r and omly divided into two subgroups--40 g of piracetam or placebo from identic ampoules were given i.v . with a crossover readministration after 60 min . The intensity of the extrapyramidal side effects was evaluated at 30-min intervals during 2 h. Piracetam was proved to be significantly effective in both subgroups , the onset of its action being between 30 and 60 min after i.v . administration . Possible interpretations of the observed piracetam effectivity are considered . Further trials with piracetam in neurologic complications during neuroleptic treatment , tardive dyskinesia included , are suggested This study reports the results of a trial of essential fatty acid ( EFA ) supplementation in psychiatric patients ( predominantly schizophrenics ) with movement disorders . Evidence of EFA deficiency in these patients was observed . The antidyskinetic effect of EFA supplementation was marginally significant but not clinical ly important . However , active treatment produced highly significant improvements in total psychopathology scores and schizophrenia subscale scores , and a significant improvement in memory Augmentation of excitatory neuronal activity by enkephalins may be achieved by depression of firing of inhibitory γ-aminobutyric acid-ergic ( GABAergic ) neurons ( 1–3 ) . The latter findings and consideration of roles of GABAergic neurons in information processing in the central nervous system ( 4–7 ) led one of us ( E.R. ) to propose that the effects of low doses of naloxone be investigated in disorders in which there may be excessive disinhibition , among which may be tardive dyskinesia ( TD ) . We now report results obtained with two schizophrenic women with TD who were given naloxone in a short-term , double-blind study BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials 15 hospitalized patients suffering from neuroleptic-induced tardive dyskinesias participated in a double-blind cross-over study of lithium sulphate and placebo . Each drug was given for 3 weeks . The results were evaluated by means of the video-tape technique . Lithium sulphate induced a slight , but significant reduction in the tardive dyskinesia . Lithium had , in addition , a suppressive effect on psychomotor agitation and aggression . The concentrations of homovanillic acid and 5-hydroxyindoleacetic acid were determined in the cerebro-spinal fluid from five patients . It is concluded that lithium can be used with advantage in the treatment of tardive dyskinesia with only moderate intensity , particularly when the movement disturbances are accompanied by psychomotor restlessness . Finally , the effect of lithium on the central aminergic transmitter substances is discussed in relation to the existing hypotheses on the pathophysiology of tardive dyskinesia Preliminary results on a small number of patients indicate that naloxone might have a beneficial effect in tardive dyskinesia ( TD ) ( Blum et al. 1983 , 1984 ; S and yk and Snider 1985 , 1986 ) . In order to examine this assumption , this study was performed in 13 patients suffering from chronic schizophrenia and long st and ing TD . The patients ( eight women and five men ) were aged 61 - 75 years . Their pertinent clinical data are shown in Table 1 . One week prior to naloxone administrat ion all other forms of medication except phenothiazines and butyrophenones were stopped . Naloxone was administered intravenously ( IV ) in a dosage of 0.8 mg . One day prior to or after naloxone administration , an equal volume of saline was administered in a similar fashion , in a double blind manner , so that patients served as their own controls . The intensity of dyskinetic movements was scored according to the Abnormal Involuntary Movement Scale ( AIMS ) . The dyskinetic movements were recorded before and at 5 , 10 , 20 and 60 rain after the IV injection . The changes in the intensity of dyskinetic movements after naloxone administrat ion are shown in Table 1 . In three patients , one man and two women , naloxone induced a dramatic improvement in dyskinetic movements . In two patients ( Nos 1 and 2 ) the movements were abolished . In another case ( patient No. 3 ) the intensity of the movements was decreased . The amelioration was observed immediately after naloxone administrat ion and diminished after 1 h. In the other ten patients no change was observed in dyskinetic movements . The change in intensity did not seem to be correlated to age or sex , but positive results were observed in three patients who developed TD less than 3 years prior to naloxone administration . No side effects of naloxone were observed . Saline administrat ion produced no changes in the intensity or frequency of the dyskinetic movements . The results obtained during the present study showed that naloxone treatment was effective only in those patients in whom the disease was of relatively short duration . It is possible that long st and ing TD is accompanied by Objective : Treatment of dyskinetic disorders , in general , and of tardive dyskinesia ( TD ) , in particular , is difficult . The opiate peptide enkephalin coexits with gamma aminobutyric acid in the projection neurons of striatum forming the " indirect " pathway . Several lines of pre clinical evidence implicate this enkephalin-comediated pathway in the pathophysiology and therapeutics of dyskinesia . However , previous studies , most using relatively low doses of opioid antagonists , showed mixed results . The goal of the current study was to test whether moderately high doses of naltrexone , alone or in combination with a subtherapeutic dose of a gamma aminobutyric acid agonist , improve TD . Methods : In 2 double-blind , placebo-controlled , r and omized , crossover trials , effects of naltrexone alone ( n = 9 ) and in combination with clonazepam ( n = 14 ) were tested on TD . In both trials , patients ' antipsychotic medication and dose remained unchanged through the trial . Naltrexone dose was increased over a period of 3 weeks to 200 mg/d and maintained at that dose for another week . In the second study , patients were first stabilized on low dose ( 0.25 to 0.5 mg ) of clonazepam for 4 weeks or longer . In addition to the TD scores , saccadic peak velocity and latency , as measures of vigilance , and antisaccade error rate were obtained during the fourth week of placebo and naltrexone in a subgroup of patients . Results : There were no significant effects of naltrexone alone on TD ( mean ± SD decrease in TD score = 0.1 ± 4.8 ) , psychosis scores , or eye movement measures . Low dose of clonazepam had no effect on TD . However , addition of naltrexone significantly improved TD ( mean , SD decrease in TD score 4.0 ± 3.6 ) . There was no clinical or laboratory evidence of increased sedation during treatment with naltrexone compared to placebo . There were no significant effects on the antisaccade error rate or psychosis scores . Conclusion : These findings suggest effectiveness of a strategy of combining a GABA(gamma aminobutyric acid)mimetic drug with an enkephalin antagonist to treat dyskinesia A double-blind crossover study on the effects of deanol and lithium carbonate was conducted on a sample of 29 chronic schizophrenic patients with tardive dyskinesia . In addition to his usual treatment with different neuroleptics , each patient received during an 8-week period either deanol , lithium carbonate or placebo . A 4-week wash-out period was inserted between each of the 8-week periods of experimental treatment of the tardive dyskinesia . The administration of either deanol , lithium carbonate or placebo added to the neuroleptic treatment did not produce a statistically significant improvement of tardive dyskinesia in our patient population as a whole . Favorable and unfavorable responses are discussed 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 |
618 | 29,682,344 | Conclusions and Recommendation The pooled estimate prevalence of depression among PLWHIV was higher than that in the general population .
It is better to offer special attention to these population | Background Depression is a substantial contributor to the global burden of disease and affects people in all communities across the globe .
Depression is the most common psychiatric problem associated with HIV/AIDS and half of all PLWHIV with depression go underdiagnosed and untreated .
Psychiatric complications of HIVAIDS delay mental health services in less affluent countries .
However , there is lack of study with regard to the pooled estimation prevalence of depression in PLWHIV in Ethiopia .
Objectives The aim of this systematic review and meta- analysis is to summarize the most current available evidence from 2010 to March 2017 among adult PLWHIV in Ethiopia . | Background Malnutrition hastens progression to Acquired Human Immunodeficiency Syndromes ( AIDS ) related illnesses ; undermines adherence and response to antiretroviral therapy ( ART ) in re source -poor setting s. However , nutritional status of people living with HIV ( PLHIV ) can be affected by various psychosocial factors which have not been well explored in Ethiopia . Therefore , the objective of this study was to determine psychosocial correlates of nutritional status among people living with HIV ( PLHIV ) on ART in Central zone of Tigray , Northern Ethiopia . Methods A matched case-control study design was conducted to assess psychosocial correlates of nutritional status among PLHIV on ART . Data were collected by an interviewer-administered technique using structured pre-tested question naire , record review using a checklist and anthropometric measurements . Cases were selected by simple r and om sampling and controls purposively to match the selected cases . Conditional logistic regression was used to compute relevant associations by STATA version 12 . Results The psychosocial factors independently associated with malnutrition were ever consuming alcohol after starting ART [ AOR = 4.7 , 95 % CI : 1.8–12.3 ] , ever smoking cigarette after starting ART [ AOR = 7.6 , 95 % CI : 2.3–25.5 ] , depression [ AOR = 2.8 , 95 % CI : 1.3 , 6.1 ] , not adhering to ART [ AOR = 6.8,95 % CI : 2.0–23.0 ] and being in the second lowest wealth quintile [ AOR = 4.3,95 % CI : 1.1–17.7 ] . Conclusion Ever consuming alcohol and ever smoking cigarette after starting ART , depression , not adhering to ART and being in the second lowest wealth quintile were significantly associated with malnutrition . Therefore ; policies , strategies , and programs targeting people living with HIV should consider psychosocial factors that can impact nutritional status of people living with HIV enrolled on ART Background The devastating impact of AIDS in the world especially in sub-Saharan Africa has led to an unprecedented global effort to ensure access to antiretroviral ( ARV ) drugs . Given that medication-taking behavior can immensely affect an individual 's response ; ART adherence is now widely recognized as an ' Achilles heel ' for the successful outcome . The present study was undertaken to investigate the rate and predictors of adherence to antiretroviral therapy among HIV-infected persons in southwest Ethiopia . Methods The study was conducted in the antiretroviral therapy unit of Jimma University Specialized Hospital . A prospect i ve study was undertaken on a total of 400 HIV infected person . Data were collected using a pre-tested interviewer-administered structured question naire at first month ( M0 ) and third month ( M3 ) follow up visits . Results A total of 400 and 383 patients at baseline ( M0 ) and at follow up visit ( M3 ) respectively were interviewed . Self-reported dose adherence in the study area was 94.3 % . The rate considering the combined indicator ( dose , time and food ) was 75.7 % . Within a three month follow up period , dose adherence decreased by 2 % and overall adherence rate decreased by more than 3 % . Adherence was common in those patients who have a social support ( OR , 1.82 , 95%CI , 1.04 , 3.21 ) . Patients who were not depressed were two times more likely to be adherent than those who were depressed ( OR , 2.13 , 95%CI , 1.18 , 3.81 ) . However , at the follow up visit , social support ( OR , 2.42 , 95%CI , 1.29 , 4.55 ) and the use of memory aids ( OR , 3.29 , 95%CI , 1.44 , 7.51 ) were found to be independent predictors of adherence . The principal reasons reported for skipping doses in this study were simply forgetting , feeling sick or ill , being busy and running out of medication in more than 75 % of the cases . Conclusion The self reported adherence rate was high in the study area . The study showed that adherence is a dynamic process which changes overtime and can not reliably be predicted by a few patient characteristics that are assumed to vary with time . Adherence is a process , not a single event , and adherence support should be integrated into regular clinical follow up Health-related quality of life ( HRQoL ) is an important outcome measure among HIV-infected patients receiving combination antiretroviral therapy ( cART ) , but has not been studied extensively in re source -limited setting s. Insight in the predictors or correlates of poor HRQoL may be helpful to identify patients most in need of additional support and to design appropriate interventions . A cross-sectional study was conducted between September 2012 and April 2013 in 10 healthcare facilities in Addis Ababa , Ethiopia . Patients who were at least 6 months on cART were r and omly selected and individual patient data were retrieved from medical records . HRQoL was measured by the WHOQoL-HIVBREF , depressive-symptoms by the Kessler-6 scale , and stigma by the Kalichman internalized AIDS-related stigma scale . Multivariate linear regression analysis was carried-out to examine associations between HRQoL and the other variables . A total of 664 patients ( response-rate 95 % ) participated in the study . A higher level of depressive-symptoms was most strongly and consistently associated with a lower HRQoL , both in terms of the magnitude of the relationship and in the number of HRQoL domains associated with it . Also , a higher level of HIV-stigma was associated with a lower HRQoL except for the physical domain , while obtaining sufficient nutritious food and job opportunity were associated with a better HRQoL except for the spiritual and social domains , respectively . Demographics , clinical , and treatment characteristics yielded few significant associations with HRQoL. Our study findings suggest that interventions to improve HRQoL should focus on reducing depressive-symptoms and HIV-stigma , and on enhancing food security and job opportunity ABSTRACT Developing appropriate strategies to sustain optimal medication adherence among the increasing number of HIV-positive patients taking antiretroviral therapy ( ART ) in sub-Saharan Africa is a major challenge . The objective of this study was to determine patient , regimen , disease , patient-provider , and healthcare-related factors associated with adherence with ART over a one-year period , and assess the impact of adherence on treatment outcomes . We performed a prospect i ve , observational study among 246 patients who were initiated on ART in Ethiopia . Of 172 who completed follow-up , 130 ( 75.6 % ) had ≥95 % adherence . In the multivariate analyses , a higher baseline BMI ( OR , 1.2 ; 95 % CI 1.0 , 1.4 ) and use of reminder devices ( OR , 9.1 ; 95 % CI 2.0 , 41.6 ) remained positively associated with adherence , while a higher HIV symptom and adverse drug reaction distress score was an independent negative predictor of adherence ( OR , 0.90 ; 95 % CI 0.9 , 1.0 ) CD4 count increase was significantly higher in the adherent patients compared to non-adherent patients at 12 months ( 159 cells/µL [ interquartile range ( IQR ) , 72–324 cells/µL ] vs. 132 cells/µL [ IQR , 43–190 cells/µL ] ; p = 0.026 ) . Our findings indicate that interventions aim ed at improving adherence and thereby treatment outcomes in patients initiated on ART should promote the use of reminder devices , and monitor HIV symptoms and adverse reaction distress and nutritional status |
619 | 23,460,248 | The results of the meta-analyses showed that operative mortality and morbidity were not significantly different between the two procedures ( preservation vs. non-preservation of duodenum ) .
However , operative time was considerably prolonged by preserving the duodenal passage .
Patients in the preservation group had an improved nutritional parameters ( body weight , levels of serum iron and hemoglobin ) in the short term ( < 6 months ) after surgery .
Beneficial effect on preventing postgastrectomy symptom ( heartburn , dumping syndrome ) was not found by maintaining the duodenal passage throughout a 2-year follow-up .
Moreover , a qualitative measurement showed that no significant quality of life improvement for patients with a preserved duodenal passage .
Conclusion This systematic review failed to demonstrate obvious advantage in preserving duodenal passage after total gastrectomy | Background Various reconstruction procedures have been proposed for restoring the alimentary tract continuity after total gastrectomy .
However , so far there is no consensus on the ideal post-gastrectomy reconstruction procedure .
The necessity of preserving the duodenal passage is one of the major focuses of the debate concerning gastrointestinal reconstruction and is the objective of this study . | This is an interim report of a r and omized clinical trial on esophagojeju-nostomy ( EJ ) versus Hunt-Lawrence-Rodino ( HLR ) pouch as reconstruction techniques following total gastrectomy and systematic lymphadenectomy for gastric cancer treatment . The r and omized trial preceded a pilot study comparing the Longmire-Gütgemann interposition and the HLR . The pilot study included 7 patients , the r and omized trial 38 patients ( 60 planned ) . The main outcome variables in the pilot study were food resorption , caloric intake , and body weight . Survival probability and general well-being ( quality of life ) were measured in the r and omized trial . A score was composed of disease-specific and socio-personal variables with well-being ranging from 0 ( worst ) to 14 ( best ) points . Concerning food resorption in the pilot study , no relevant advantage of the duodenal passage was found . The main postoperative disorder was insufficient food intake . Despite a radical operation , a hospital mortality rate of 16 % , and a complication rate of 37 % , gastric cancer still has a poor prognosis . In the r and omized trial only 15 ( 39 % ) of 38 patients were alive 1 year after operation , but the survival probability was higher ( 58 % ) after HLR than after EJ ( 24 % ) ( p<0.05 ) . Hunger and appetite were strongly reduced during the first 6 months after operation . Food intake was less than half of the preoperative values , which was reflected by an average decrease in body weight of 7 kg . Patients dying within the first year after total gastrectomy suffered an irreversible loss of quality of life ( scoring 7 points ) . They had no objective benefit from the operation . Patients surviving this period regained quality of life and exceeded preoperative values , especially after HLR.We conclude that HLR-operated patients who have a chance of surviving for at least 1 year benefit from total gastrectomy in regard to quality of life . RésuméCet article est consacré au bilan provisoire d'une étude clinique r and omisée de l'oesophago-jéjunostomie ( EJ ) par rapport à l'opération de Hunt-Lawrence-Rodino ( HLR ) comme technique de reconstruction après gastrectomie totale et lymphadénectomie systématique pour cancer de l'estomac . Le bilan a été établi à partir d'une étude pilote comparant l'interposition Longmire-Gütgemann et la HLR . Cette première étude a porté sur 7 patients et le étude r and omisée sur 38 patients ( 60 sont prévues ) . Dans l'étude pilote la réabsorption intestinale , le poids et l'absorption calorique furent les variables essentielles pour mesurer l'avenir des malades . Dans le étude r and omisée la probabilité de survie et la qualité de la vie ont été ajoutées . L'état général a été représenté par un score comprenant des variables spécifiques de la maladie et socio-personnelles allant de 0 ( très mal ) à 14 ( très bien ) points . Dans l'étude pilote le passage duodénal n'a pas montré d'avantage concernant la réabsorption intestinale . Le malaise post-opératoire essentiel a été l'insuffisance de l'absorption calorique . L'opération radicale a une mortalité hospitalière de 16 % et comprend un taux de complication de 37 % . Le cancer de l'estomac est de prognostic peu favorable . Seuls 15 ( 39 % ) des 38 patients ont survécu la première année dans le étude r and omisée mais la probabilité de survie après HLR ( 58 % ) dépasse celle après EJ ( 24 % ) ( p<0.05 ) . La f aim et l'appétit ont été sévèrement réduits pendant les 6 premiers mois post-opératoires . Comparée à la situation pré-opératoire , la quantitié de nourriture a diminué d'au moins 50 % ce qui correspond à une perte de poids de 7 kilos en moyenne . Les malades qui ne survivent pas la première année subissent une perte importante et irréversible de leur qualité de vie . Ceci nous amène à dire qu'ils ne profitent pas de l'intervention chirurgicale contraitement aux autres qui regagnent une qualité de vie égale ou même supérieure aux valeurs pré-opératoires . Au total nous pouvons affirmer que ce sont essentiellement les patients opérés qui ont subi une HLR qui survivent un an ou plus et qui tirent profit de la gastrectomie totale . ResumenEste es un informe provisional de un ensayo clínico aleatorizado para comparar la esofagoyeyunostomía ( EY ) con la bolsa de Hunt-Lawrence-Rodino ( HLR ) como técnicas de reconstrucción gástrica después de gastrectomía total con linfadenectomía sistemática como tratamiento del cáncer gástrico . El ensayo aleatorizado fue precedido de un estudio piloto para comparar el procedimiento de interposición de Longmire-Gütgemann con la HLR . El estudio piloto incluyó 7 pacientes y el ensayo aleatorizado 38 pacientes ( 60 fueron planeados ) . Las principales variables analizadas en el estudio piloto fueron la resorción de alimentos , la ingesta calórica , y el peso corporal . En el ensayo aleatorizado fueron analizadas , además , la probabilidad de supervivencia y el estado de bienestar general ( calidad de la vida ) . Se construyó un puntaje a partir de variables específicas de la enfermedad y sociopersonales para calificar el estado de bienestar general ( calidad de la vida ) entre 0 ( peor ) y 14 (óptimo).En el estudio piloto el paso a través del duodeno no demostró ventaja significativa en cuanto a la resorción intestinal . La principal alteración postoperatoria fue la ingesta alimenticia insuficiente . A pesar de una operación radical , una mortalidad de 16 % , y una tasa de complicaciones de 37 % , el cáncer gástrico mantiene un pronóstico poco favorable . En el ensayo aleatorizado sólo 15 ( 39 % ) de 38 pacientes sobrevivían 1 año después de la operación , con una probabilidad de supervivencia mayor ( 58 % ) después de la HLR que después de la EY ( 24 % ) ( p<0.05 ) . El hambre y el apetito aparecieron notoriamente disminuidos durante el primer semestre después de la operación . La ingesta de alimento fue menos de la mitad del valor preoperatorio , lo cual se manifestó en una disminución del peso corporal de 7 kg en promedio . Los pacientes que murieron en el curso del primer año después de la gastrectomía total exhibieron una disminución importante e irreversible de la calidad de la vida ( cerca de 7 puntos ) y no demostraron beneficio objetivo de la operación , en comparación con los que sobrevivieron tal período , quienes recuperaron una buena calidad de la vida con valores iguales o superiores a los preoperatorios , especialmente después de HLR.Nuestra conclusión es que los pacientes sometidos al procedimiento HLR que sobreviven por lo menos 1 año , se benefician de la gastrectomía total en lo relativo a la calidad de la vida Background The double tract ( DT ) method was compared with the Roux-en-Y ( R-Y ) method to identify the optimal reconstruction procedure after total gastrectomy for patients with gastric cancer . The DT reconstruction is as simple as the R-Y , and it can be safely performed even after total gastrectomy . However , these have been no studies evaluating the usefulness of DT reconstruction in comparison to R-Y reconstruction . Methods A group of 44 patients with gastric cancer were intraoperatively r and omized for R-Y ( n = 23 ) or DT reconstruction ( n = 21 ) after total gastrectomy ( TG ) . Body weight , food intake , nutritional conditions , and quality of life ( QOL ) were determined at 3 and 12 months after the operation . This study is registered with Clinical Trials.gov , no. NCT00746161 . Results Food intake significantly decreased soon after the operation . No differences were observed between the DT and R-Y groups . The body weight decreased throughout the ensuing period ( P < 0.05 ) and thereafter gradually recovered . However , no differences were observed between the two groups . Among the nutritional laboratory parameters , serum prealbumin , retinol-binding protein , total cholesterol , and triglyceride were decreased soon after the operation . The changes of those parameters were not substantially different between the two groups . The postoperative QOL was evaluated , and no differences were observed between those groups . Conclusions There were no particular advantages in the DT method after TG in comparison to the simple R-Y method in terms of body weight , QOL , and nutritional conditions , suggesting that the DT method might not be recommended after TG for patients with gastric cancer Out of 74 consecutive patients with gastric carcinoma only 39 patients fulfilled the inclusion criteria for this r and omized study . These patients were divided into two groups intraoperatively , 21 were reconstructed with and 18 without performing a stapled interposed jejunal pouch . Quality of life was evaluated using Spitzer 's QL index and Cuschieri 's assessment for 6 months . Spitzer 's QL index showed -- as expected -- no differences concerning the specific reconstruction in gastrointestinal complaints , whereas Cuschieri 's assessment revealed an advantage in the pouch group . Cuschieri 's assessment needs to be vali date d by larger comparable groups to prove its suitability for the determination of specific gastrointestinal complaints concerning the type of reconstruction in gastric cancer patients BACKGROUND Although more than 50 methods of gastric replacement after total gastrectomy have been used , none of them has demonstrated a substantial nutritional advantage . The Roux-en-Y esophagojejunostomy is still the preferred type of reconstruction , more because of its simplicity than the lack of postpr and ial disturbances . STUDY DESIGN A r and omized controlled trial was conducted to compare two reconstructive procedures , Roux-en-Y esophagojejunostomy ( n = 24 ) and Hunt-Rodino-Lawrence pouch ( HRL , n = 24 ) , by evaluating nutritional status ( body weight , arm circumference , and serum nutritional parameters ) , nutritional habits ( number of meals , energy intake , and postpr and ial disturbances ) , and emptying time of the jejunal loop . RESULTS Twenty-seven patients were studied two years after operation ( 12 had undergone Roux-en-Y and 15 had undergone HRL ) . No difference was found in either postoperative morbidity or mortality , emptying time , frequency of meals , or variation of body weight . Postpr and ial disturbances were more frequent in patients having Roux-en-Y. In a subset of patients , there was a correlation between nutrient intake and change of body weight , but not between nutrient intake and type of reconstruction . CONCLUSIONS The simple use of a reservoir such as the HRL pouch after total gastrectomy is of no benefit to the patient as compared with the Roux-en-Y reconstruction Patients with carcinoma of the stomach who underwent curative resection were r and omized to total gastrectomy ( n = 49 ) , total gastrectomy and an S‐shaped gastric substitute ( n = 28 ) or subtotal gastrectomy ( n = 12 ) ; all had a Roux‐en‐Y reconstruction . The gastric substitute and gastric remnant allowed a volume of 400–500 ml to be installed without increments in basal pressures . The corresponding volume in the Roux limb was 100 ml . Energy intake was approximately 120 kJ/kg preoperative weight per day 3 months after operation , and then remained constant . Patients who had subtotal gastrectomy ate less ( 91.7 kJ/kg preoperative weight ) 3 months after operation , but thereafter increased their intake . Patients allocated to have a gastric pouch or subtotal gastrectomy complained more frequently of adverse postpr and ial symptoms ( P < 0.03 ) as a major cause of reduced calorie intake . The construction of a gastric reservoir did not improve nutritional adaptation after surgery for gastric carcinoma Controversial results have been reported regarding the importance of the duodenal food passage after total gastrectomy . There are a number of experimental and clinical studies showing an advantage for the jejunal interposition between esophagus and duodenum . Others favor the Roux-en-Y reconstruction , as it is technically less dem and ing . The purpose of this study was the r and omized comparison between two major reconstruction principles after total gastrectomy for gastric cancer ( i.e. , jejunal interposition with pouch versus Roux-en-Y pouch reconstruction ) . A group of 120 patients with gastric cancer were r and omized and operated on during a 5-year period according to st and ardized operative protocol s , using either a jejunal interposition with pouch ( JIP ) or the Roux-en-Y reconstruction with pouch ( RYP ) . Endpoints of this study were operation time , intra- and postoperative problems and complications , patients ' body weight , functional assessment , and quality of life . Of the 120 patients , 14 had to be withdrawn during the operation because only the Roux-en-Y reconstruction was technically possible . Finally , 53 patients with JIP were compared with 53 patients with RYP for the perioperative course . There were no significant differences between the two procedures ( RYP and JIP ) regarding complications ( 24.5 % and 26.4 % , respectively ) , mortality ( 3.8 % and 1.9 % , respectively ) , and operation time ( 4.35 hours and 4.40 hours , respectively ) . For long-term functional comparison 46 ( RYP , n=26 ; JIP , n=20 ) patients were without recurrence after 3 years of survival . Comparison of body weight , Visick scoring , and the Spitzer Index also did not reveal any significant difference between the two operation methods . In conclusion , patients with gastric cancer after total gastrectomy do not benefit from reconstructing the duodenal food passage by a jejunal interposition with pouch regarding their postoperative quality of life when compared to the widely used and technically less dem and ing Roux-en-Y reconstruction with pouch . Differences between the two reconstruction principles , documented by sophisticated functional assessment , may well exist , but the have no major clinical importance .RésuméDes résultats controversés ont été rapportés en ce qui concerne F importance des passages d'aliments dans le duodénum après gastrectomie totale . II existe bon nombre d'études expérimentales et cliniques en faveur de la reconstruction par montage d'interposition intestinale entre l'esophage et le duodénum . D'autres préferent le montage par une anse en-Y , techniquenment plus facile . Le but de cette étude r and omisée a été de comparer ces deux méthodes de reconstruction après gastrectomie totale pour cancer gastrique , i.e. interposition jéjunale avec néogastre vs. reconstruction par anse-en-Y avec néogastre . Méthodes : 120 patients avec un cancer gastrique ont été r and omisés pour avoir comme reconstruction un néogastre et rétablissement de continuité soit par une interposition jéjunale ( IJ ) soit par anse-en-Y ( AY ) . Les critères de jugements ont été la durée de l'intervention , les incidents et complications per-et postopératoires , le poids du sujet , l'évaluation fonctionnelle et la qualité de vie du patient . Résultats : Parmi les 120 patients r and omisés , 14 ont du être exclus pendant l'intervention car seule la reconstruction par anse en Y a été possible . Pour l'analyse , 53 patients dans chaque groupe ont été comparés/Il n'y avait aucune différence significative entre les deux méthodes en ce qui concerne le taux de complications ( 24.5%/26.4 % , respectivement ) ou la mortalité ( 3.8%/1.9 % ; respectivement ) ou la durée de l'intervention ( 4h.35 vs. 4h:40 , respectivement ) . En ce qui concerne la fonction à long terme , 46 patients ( 20 IJ et 26 RY ) sont en vie sans récidive à 3 ans . La comparaison du poids corporel , le score de Visick et de Spitzer n'ont également pas détecté de différence statistiquement significative entre les deux méthodes opératoires . En conclusion , il n'y a aucun avantage en termes de qualité de vie pour le patient d'avoir une reconstruction par anse-jéjunale interposée après gastrectomie totale pour cancer en ce qui concerne le retablissement de continuité par IJ ou par RY . Des différences obtenues par des méthodes d'évaluation sophistiquées existent peut-être , mais en pratique , elles n'ont aucune importance clinique . Resumen Result ados controvertibles han sido informados en relación a la importancia del paso de los alimentos a través del duodeno luego de una gastrectomía total . Existe un número de estudios experi-mentales y clínicos que demuestran la ventaja de la interposición veyunal entre el esófago y el duodeno , en tanto que otros demuestran la ventaja de la reconstrucción de Roux-en-Y , procedimiento que es técnicamente menos oneroso . El propósito del presente estudio fue realizar una comparación r and omizada entre dos métodos principales de reconstrucción después de gastrectomía total para cáncer gástrico : la interposición con bolsa yeyunal vs. la reconstrucción de Roux-en-Y. Se r and omizaron 120 pacientes con cáncer gástrico , los cuales fueron intervenidos en un período de 5 años siguiendo los protocol os operatorios est and arizados , utiliz and o bien la interposición yeyunal con bolsa ( IYB ) o la reconstrucción de Roux-en-Y ( IRB ) . Los puntos de análisis fueron el tiempo operatorio , los problemas y complicaciones intra y postoperatorios , el peso corporal , la valoración funcional y la calidad de la vida . De los 120 pacientes , 14 tuvieron que ser retirados en el curso de la operación porque la reconstrucción de Roux-en-Y era el único procedimiento posible . Finalmente , se pudieron comparar 53 pacientes con IYB con 53 pacientes con IRB . No se hallaron diferencias entre los dos procedimientos en relación a complicaciones ( 24.5 % y 26.4 % , respectivamente ) , mortalidad ( 3.8 % y 1.9 % , respectivamente ) y tiempo operatorio ( 4.35 horas y 4.40 horas , respectivamente ) . En cuanto a la comparación de los result ados funcionales a largo plazo , se encontraron 46 pacientes ( IRB : n=26 ; IYB : n=20 ) libres de recurrencia a los 3 años de sobrevida ; la comparación del peso corporal , el índice de Visick y el índice de Spitzer tampoco exhibieron diferencias significativas entre los dos métodos . En conclusión , los pacientes con cáncer gástrico sometidos a reseción no se benefician , en cuanto a calidad de la vida , de la conbolsa al compararlos con los sometidos a reconstrucción de tipo Roux-en-Y con bolsa , procedimiento que es de tan amplio favoritismo y que es técnicamente menos oneroso . Aunque es posible que entre los dos métodos de reconstrucción existan diferencias documentadas mediante evaluaciones funcionales sofisticadas , éstas pueden no tener mayor importancia clínica OBJECTIVE To investigate the emptying of solids after total gastrectomy with pouch reconstruction . DESIGN R and omised , prospect i ve study . SETTING University hospital , Finl and . SUBJECTS 49 patients with gastric carcinoma operated on for cure between 1988 and 1992 . INTERVENTIONS After total gastrectomy 26 patients were r and omised to have a pouch reconstruction and 23 a Roux-en-Y reconstruction . 15 months after the operation 24 patients with a pouch ( pouch group ) and 21 patients with a simple Roux-en-Y reconstruction ( Roux-en-Y group ) were alive and available to have an emptying test by the solid isotope method . Emptying of the pouch and Roux-en-Y limb was assessed by measuring the activity at 3 hours . MAIN OUTCOME MEASURES Postoperative symptoms , size of meal , and postoperative nutrition . RESULTS Emptying was significantly slower after pouch reconstruction than after Roux-en-Y ( mean activity at 3 hours 82 % and 44 % , respectively , p < 0.01 ) . Early satiety occurred in 10 ( 48 % ) of the patients after Roux-en-Y reconstruction and 6 ( 25 % ) in the pouch group . Dumping was more common in the Roux-en-Y group ( n = 12 , 57 % compared with n = 6 , 25 % , p = 0.04 ) . 19 ( 79 % ) of the patients in the pouch group were able to eat normal sized meals compared with 3 ( 14 % ) in the Roux-en-Y group ( p < 0.0001 ) . Weight gain and haemoglobin and albumin concentrations were similar in the two groups . CONCLUSION Jejunal pouch reconstruction after total gastrectomy delays passage of solid food in the upper intestine compared with Roux-en-Y reconstruction . It is associated with better eating capacity and fewer postoperative symptoms Abstract . Background : Many reconstruction procedures have been developed in efforts to resolve patients ' complaints after total gastrectomy . However , there have been few reports of longterm comparisons between reconstruction procedures , especially with regard to the prevention of duodenal food passage . This study was undertaken to compare the longterm subjective and functional results among Roux-en-Y esophagojejunostomy ( R-Y ) , R-Y with pouch ( P-Y ) , and jejunal interposition with pouch ( P-I ) after total gastrectomy . Methods : Consecutive patients requiring curative total gastrectomy were enrolled in this prospect i ve study by the envelope method . Results : Hospital stay was longer following a P-I than an R-Y or a P-Y. Over 50 % of R-Y patients complained of heartburn , and 20 % of R-Y patients showed dumping syndrome throughout the postoperative period , with this rate being significantly different from rates in the other two groups . P-Y patients complained of early satiety in the late postoperative period , while P-I patients complained of early satiety in the early postoperative period . The nutritional index in P-I patients was higher than those in patients with the other two procedures . Gastrointestinal and hepatobiliary dual scintigraphy ( GHDS ) showed that the rate of bile reflux with an R-Y was relatively high after surgery . Food reflux with a P-Y was increased ( 9.4 % to 11.1 % ) , but with a P-I food reflux was decreased at 3 years after surgery ( 13.3 % to 9.9 % ) . Patients with a P-Y had a faster recovery of body , weight in the early postoperative period ; however , at 5 years after operation , body weight recovery with a P-I was greatest . Conclusion : Reconstruction should be performed with pouch formation after total gastrectomy with curative intent Abstract . The objective of this r and omized study was to examine which reconstruction method and which pouch volume offer the best preconditions for a good quality of life and extensive physiologic regulation of gastrointestinal hormones after total gastrectomy . Up to now there is no general agreement with regard to the ideal reconstruction after total gastrectomy . The importance of the duodenal passage , the need for a pouch reconstruction , and the ideal pouch volume are matters of controversy . A total of 60 patients underwent the following reconstructions : Ulm pouch ( pouch reconstruction with preservation of the duodenal passage ) , Hunt-Lawrence-Rodino pouch , or Roux-en-Y reconstruction without pouch . The clinical course , quality of life , and regulation of gastrointestinal hormones in correlation to reconstruction type and pouch volume were documented . Quality of life was assessed by means of a st and ardized specific question naire . Blood glucose , insulin , cholecystokinin , motilin , secretin , and pancreatic polypeptide were measured after stimulation by a st and ardized test meal . Six months after total gastrectomy those patients with an Ulm pouch were found to have a significantly better life quality ( p < 0.01 ) , higher body weight , and better physiologic regulation of gastrointestinal hormones ; moreover , they developed ( in contrast to all other reconstruction types ) no pathologic glucose tolerance . Our conclusion is that all patients with a postoperative life expectancy of at least 6 months ( i.e. , tumor stages UICC I and II ) should undergo pouch reconstruction with preservation of the duodenal passage Objective The authors determined the optimum reconstruction procedure after total gastrectomy in terms of the quality of life of the patients . Summary Background Data Gastric replacement with various enteric reservoirs has been used to improve the postpr and ial symptoms and nutrition of patients after total gastrectomy . However , the effect of each is uncertain because no prospect i ve r and omized studies have been conducted . Methods A r and omized controlled trial was conducted to compare the usefulness of the three reconstruction procedures of simple Roux-en-Y ( RY ; N = 10 ) , pouch and Roux-en-Y ( PR ; N = 10 ) , and pouch and interposition ( PI ; N = 10 ) . In each subject , the postpr and ial symptoms , food intake in a single meal , body weight , serum nutritional parameters , and emptying time of the gastric substitute were evaluated . Results The PR group showed significantly greater food intake in a single meal than the RY and PI groups , and greater weight recovery than the PI group . A gastric emptying test also revealed satisfactory retention capacity and emptying time of the gastric substitute in the PR group . Conclusions Pouch and Roux-en-Y reconstruction is the most useful of the three procedures for improving the postoperative quality of life . In patients with pouch and interposition reconstruction , the clinical assessment was quite poor , even though it is a physiologic route BACKGROUND / AIMS To determine the optimum pouch reconstruction after total gastrectomy , we conducted a r and omized trial to compare the usefulness between PR and PI in terms of quality of life . METHODOLOGY Thirty patients younger than 70 years of age were selected and r and omly classified into the following 2 groups : pouch and Roux-en-Y ( PR ; n = 15 ) and pouch and interposition ( PI ; n = 15 ) . In each subject , the postoperative symptoms , food intake in a single meal , body weight , serum nutritional parameters , endoscopy , emptying time of the gastric substitute , and gallstone formation were evaluated . RESULTS There were no significant differences in terms of the postpr and ial symptoms , food intake , body weight , and serum nutritional parameters until 2 years postoperative . Endoscopy showed a tendency of food stasis in the PR group , although this was not significant . The gastric emptying test in the PR group indicated that the retention capacity was slightly superior to that in the PI group . CONCLUSIONS The impact of the duodenal passage on symptoms and nutrition could not be ascertained AIMS The aboral pouch , a new type of gastric substitute , has been introduced after total gastrectomy and compared to simple Roux-en-Y reconstruction in a prospect i ve , r and omized study . Anthropometric data , serum nutritional parameters , small intestinal passage , lipid and carbohydrate absorption and quality of life were measured 6 and 12 months after total gastrectomy . PATIENTS AND METHODS Between September 1997 and April 2000 46 patients entered the study , 24 to the aboral pouch group and 22 to the control , simple Roux-en-Y group . RESULTS Interim analysis of the data revealed significantly higher serum cholesterol levels , better lipid absorption and quality of life in patients who underwent aboral pouch construction . CONCLUSION Aboral pouch construction is a feasible reconstruction method after total gastrectomy providing better lipid absorption and quality of life for patients after total gastrectomy Background : Fifty-one patients were operated on during 1988 - 1992 and r and omized after total gastrectomy to one of two reconstruction types . Twenty patients with jejunal pouch reconstruction and 14 patients with Roux-en-Y reconstruction ( 67 % of all ) survived at least 3 years after total gastrectomy . We studied symptoms , eating capacity , and nutrition in these patients during the clinical follow-up ; 21 patients were assessed by mail question naire 8 years after total gastrectomy . Methods : Postoperative symptoms , number of meals , and eating capacity were assessed by st and ard question naire during 3 years ' follow-up . Weight loss and nutritional laboratory variables were measured , and upper intestinal endoscopy with biopsy was performed during the follow-up . Eight years after the operation symptoms , ability to eat , and number of meals consumed were studied by means of a mail question naire . Results : Three years postoperatively dumping ( 64 % compared with 10 % , P < 0.05 ) and early satiety ( 86 % compared with 5 % , P < 0.05 ) were commoner in the Roux-en-Y group . In the pouch group eating capacity was better ( 96 % of normal compared with 67 % , P < 0.05 ) , and the patients ate fewer meals per day ( mean , 2.7 versus 5.3 , P < 0.05 ) at 3 years . Mean weight loss at 3 years was 9.9 kg in the Roux-en-Y group compared with 1.5 kg in the pouch group ( P < 0.05 ) . 25 ( OH ) vitamin D concentration tended to be higher in the pouch group ( 47.3 nmol/l compared with 33.9 nmol/l ) . In the Roux-en-Y group serum alkaline phosphatase activity increased significantly during the 3 postoperative years ( from mean163 U/l to 248 U/l , P < 0.01 ) and tended to be higher ( 248 U/l compared with 216 U/l in the pouch group ) . None of the patients developed oesophagitis or pouchitis during the follow-up . One patient developed a bezoar in the pouch 5 years after gastrectomy . Conclusions : Pouch reconstruction after total gastrectomy is associated with diminished postoperative symptoms , better eating capacity , and decreased weight loss compared with Roux-en-Y reconstruction . Jejunal pouch reconstruction is thus the recommended surgical method after total gastrectomy BACKGROUND The postoperative clinical superiority of the interposition of jejunum reconstruction ( INT ) to Roux-en-Y reconstruction ( RY ) after total gastrectomy has not been clarified . Postoperative quality of life ( QOL ) was evaluated between the 2 methods by a multi-institutional prospect i ve r and omized trial . METHODS A total of 103 patients with gastric cancer were prospect ively r and omly divided into groups for RY ( n = 51 ) or INT reconstruction ( n = 52 ) after total gastrectomy . They were stratified by sex , age , institute , histology , and degree of lymph node dissection . Postoperatively , body mass index ( BMI ) and nutritional conditions were measured serially , and QOL and postoperative squalor scores were evaluated at 3 , 12 , and 60 months and compared between the 2 groups . RESULTS After removing patients who did not complete the follow-up survey or censured cases , 24 patients in the RY group and 18 patients in the INT group were clinical ly available and their postoperative status was assessed . QOL scores were increased and complication scores were improved in the postoperative periods ( P < .01 ) . Postoperative BMI significantly deteriorated compared with preoperative BMI in each group . The postoperative QOL and complication scores at 60 months after surgery were significantly better than those at 3 months after surgery in each group ( P < .01 ) . However , there was no significant difference of QOL scores and postoperative complication scores between the 2 reconstruction groups . The nutritional condition in the INT group was nearly the same as that in the RY group . CONCLUSIONS Although our patient sample was small and patients who did not complete the follow-up survey were present , we could not identify any clinical difference between INT and RY after total gastrectomy 60 months after surgery . The safer and simpler RY method may be a more suitable reconstruction method than INT after total gastrectomy |
620 | 26,292,280 | While most cases of prevalent cerebrovascular disease can be detected using 430 - 438/I60-I69 collectively , acute stroke must be defined using more specific codes .
Most in-hospital deaths and death certificates with stroke as a cause-of-death correspond to true stroke deaths .
Linking vital statistics and hospitalization data may improve the ascertainment of fatal stroke | OBJECTIVE To conduct a systematic review of studies reporting on the validity of International Classification of Diseases ( ICD ) codes for identifying stroke in administrative data . | Background There is little information on the validity of using record linkage with routinely collected data for case ascertainment of stroke in large population -based studies in the UK . We examined the accuracy of these routine record linkage approaches for identifying incident stroke cases in a large UK population -based study , the European Prospect i ve Investigation into Cancer (EPIC)-Norfolk cohort . Methods We examined a sample of hospital records of incident stroke cases identified by linkage with two routine data sources , death certificates and a national hospital record linkage system ( ENCORE ) , using predefined study criteria . Two senior Specialist Registrars with clinical experience in stroke medicine examined the hospital records and search ed for the evidence of stroke recorded in these records between 1993/97–2003 . Results Of 520 incident strokes identified between 1993/1997–2003 using record linkage systems in the EPIC-Norfolk , a sample of 250 medical case notes were examined between March and July 2004 . Using the predefined study criteria , there were 191 definite strokes ( 76 % ) , 20 probable strokes ( 8 % ) , 11 possible strokes and 11 cases of transient ischaemic attacks ( 4 % each ) i.e. 233/250 ( 93 % ) with possible or definite stroke or transient ischaemic attacks . Stroke could not be verified using hospital records in 13 cases ( 5 % ) and 4 cases ( 2 % ) had other diagnoses : 3 cases of vascular dementia and 1 case of benign intracranial hypertension . The diagnosis of stroke in 185 out of 250 cases identified in the EPIC-Norfolk ( 74.0 % ) was supported by radiological evidence using WHO criteria . Conclusion Death certificates and hospital record linkage in this British prospect i ve study have a high accuracy or positive predictive value in correctly identifying incident stroke cases BACKGROUND AND PURPOSE The Greater Cincinnati/Northern Kentucky Stroke Study was design ed to be the first large , population -based metropolitan study of temporal trends in stroke incidence rates and outcome within a biracial population . METHODS We are identifying all hospitalized and autopsied cases of stroke and transient ischemic attack ( TIA ) among the 1.3 million inhabitants of a five-county region of Greater Cincinnati/Northern Kentucky for the period 7/1/93 - 6/30/94 . We have already prospect ively monitored for out-of-hospital stroke and TIAs for this same time period at 128 screening sites , including a r and om sample of all primary care physicians and nursing homes in the region . We have already identified all hospitalized and autopsied cases of stroke and TIA among blacks for 1/1/93 - 6/30/93 and report preliminary incidence rates for this 6-month period . RESULTS The overall incidence rate for all first-ever hospitalized or autopsied stroke ( excluding TIAs ) among blacks in the Greater Cincinnati region was 288 per 100000 ( 95 % CI , 250 to 325 , age- and sex-adjusted to 1990 US population ) . The overall incidence rate for first-ever and recurrent stroke ( excluding TIAs ) was 411 per 100000 ( 95 % CI , 366 to 456 ) . By comparison , the overall incidence rate of first-ever stroke among whites in Rochester , Minn , during the period 1985 - 1989 was 179 per 100000 ( 95 % CI , 164 to 194 , age- and -sex adjusted to 1990 US population ) . The incidence rates among blacks in Greater Cincinnati were substantially greater than the rates among whites in Rochester , Minn , for all age categories except ages 75 and older , for which the rates were similar . CONCLUSIONS We conservatively estimate that 731100 first-ever or recurrent strokes occurred in the United States during 1996 . Studies of first-ever as well as total stroke among biracial and representative population s are critical for underst and ing temporal trends in the incidence rate and the burden of stroke in the US population Background and Purpose — Many studies use medical record review for ascertaining outcomes . One large , longitudinal study , the Women ’s Health Initiative ( WHI ) , ascertains strokes using participant self-report and subsequent physician review of medical records . This is re source -intensive . Herein , we assess whether Medicare data can reliably assess stroke events in the WHI . Methods — Subjects were WHI participants with fee-for-service Medicare . Four stroke definitions were created for Medicare data using discharge diagnoses in hospitalization cl aims : definition 1 , stroke codes in any position ; definition 2 , primary position stroke codes ; and definitions 3 and 4 , hemorrhagic and ischemic stroke codes , respectively . WHI data were r and omly split into training ( 50 % ) and test sets . A concordance matrix was used to examine the agreement between WHI and Medicare stroke diagnosis . A WHI stroke and a Medicare stroke were considered a match if they occurred within ±7 days of each other . Refined analyses excluded Medicare events when medical records were unavailable for comparison . Results — Training data consisted of 24 428 r and omly selected participants . There were 577 WHI strokes and 557 Medicare strokes using definition 1 . Of these , 478 were a match . With regard to algorithm performance , specificity was 99.7 % , negative predictive value was 99.7 % , sensitivity was 82.8 % , positive predictive value was 85.8 % , and & kgr;=0.84 . Performance was similar for test data . Whereas specificity and negative predictive value exceeded 99 % , sensitivity ranged from 75 % to 88 % and positive predictive value ranged from 80 % to 90 % across stroke definitions . Conclusions — Medicare data seem useful for population -based stroke research ; however , performance characteristics depend on the definition selected BACKGROUND Surveillance for stroke/transient ischemic attack ( TIA ) using administrative data has traditionally been limited to reporting patients who had an acute event and were hospitalized . This underestimates the true prevalence because many events do not result in hospitalization . We examined whether the accuracy of administrative data for identifying prevalent stroke/TIA could be improved by using data from both inpatient and outpatient visits . METHODS An administrative data validation reference st and ard was developed through chart abstract ion of 5000 adult patients r and omly sample d from 73,014 patients of 83 family physicians who participate in the Electronic Medical Record Administrative Data Linked Data base ( EMRALD ) , in Ontario , Canada . RESULTS The prevalence of stroke/TIA in our adult population was 3.0 % . An algorithm of 1 hospital record had a sensitivity of 35.3 % ( 27.7%-43.0 % ) and specificity of 99.8 % ( 99.7%-99.9 % ) , whereas an algorithm of 2 physician billings within 1 year or 1 hospitalization had a sensitivity of 68.0 % ( 95 % confidence interval [ CI ] , 60.5%-75.5 % ) and specificity of 98.9 % ( 95 % CI , 98.6%-99.2 % ) for the identification of patients who had ever had a stroke/TIA . We found that hospitalization data underestimated the prevalence of stroke by > 50 % and TIA by > 66 % compared with using both hospitalization and physician cl aims data . CONCLUSIONS The use of outpatient physician cl aims data in addition to hospitalization data improves the sensitivity of administrative data for the identification of prevalent stroke/TIA and may be used to estimate the prevalence of cerebrovascular events in large population s and over time Background Kappa is commonly used when assessing the agreement of conditions with reference st and ard , but has been criticized for being highly dependent on the prevalence . To overcome this limitation , a prevalence-adjusted and bias-adjusted kappa ( PABAK ) has been developed . The purpose of this study is to demonstrate the performance of Kappa and PABAK , and assess the agreement between hospital discharge administrative data and chart review data conditions . Methods The agreement was compared for r and om sampling , restricted sampling by conditions , and case-control sampling from the four teaching hospitals in Alberta , Canada from ICD10 administrative data during January 1 , 2003 and June 30 , 2003 . A total of 4,008 hospital discharge records and chart view , linked for personal unique identifier and admission date , for 32 conditions of r and om sampling were analyzed . The restricted sample for hypertension , myocardial infa rct ion and congestive heart failure , and case-control sample for those three conditions were extracted from r and om sample . The prevalence , kappa , PABAK , positive agreement , negative agreement for the condition was compared for each of three sample s. Results The prevalence of each condition was highly dependent on the sampling method , and this variation in prevalence had a significant effect on both kappa and PABAK . PABAK values were obviously high for certain conditions with low kappa values . The gap between these two statistical values for the same condition narrowed as the prevalence of the condition approached 50 % . Conclusion Kappa values varied more widely than PABAK values across the 32 conditions . PABAK values should usually not be interpreted as measuring the same agreement as kappa in administrative data , particular for the condition with low prevalence . There is no single statistic measuring agreement that captures the desired information for validity of administrative data . Research ers should report kappa , the prevalence , positive agreement , negative agreement , and the relative frequency in each cell ( i.e. a , b , c and d ) to enable the reader to judge the validity of administrative data from multiple aspects Background and Purpose — Because acute ischemic strokes ( ISs ) are mainly hospitalized , hospital discharge data could be used to routinely follow their incidence management . We aim ed to assess sensitivity and positive predictive value of the French hospital discharge data base ( HDD ) to identify patients with acute IS using a prospect i ve and exhaustive cohort ( AVC69 ) of acute IS cases . Methods — A selection algorithm based on IS diagnosis coded with the International Classification of Diseases ( ICD-10 ) and cerebral imaging codes was used to identify all hospital stays with the primary diagnosis of IS in the HDD of the university hospitals of the Rhône area . Cases identified through HDD search were compared with IS cases identified through an exhaustive cohort study conducted in the Rhône district and confirmed on medical records review . Results — There were 465 confirmed cases of IS hospitalized in 1 of the 4 university hospitals during the study period . The HDD search identified 313 among those ( true-positive cases ) but missed 152 cases ( false-negative cases ) . The sensitivity of the HDD search was 67.3 % ( 95 % confidence interval , 63.1–71.5 ) , and the positive predictive value was 95.1 % ( 95 % confidence interval , 92.8–97.4 ) . Additionally , HDD search retrieved 16 cases , which were not eventually IS ( false positives ) . Sensitivity was better when patients were hospitalized in neurological departments . Conclusions — The lack of sensitivity to identify acute IS patients through HDD search does not seem to be accurate enough to vali date the use of these data for incidence estimates . Efforts have to be made to improve the coding quality Background and Purpose — Surveillance is necessary to underst and and meet the future dem and s stroke will place on health care . Administrative data are the most accessible data source for stroke surveillance in Canada . The International Classification of Diseases , 10th revision ( ICD-10 ) coding system has potential improvements over ICD-9 for stroke classification . Our purpose was to compare hospital discharge abstract coding using ICD-9 and ICD-10 for stroke and its risk factors . Methods — We took advantage of a switch in coding systems from ICD-9 to ICD-10 to independently review stroke patient charts . From time periods April 2000 to March 2001 , 717 charts , and from April 2002 to March 2003 , 249 charts were r and omly selected for review . Using a before- and -after time period design , the accuracy of hospital coding of stroke ( part I ) and stroke risk factors ( part II ) using ICD-9 and ICD-10 was compared . We used careful definitions of stroke and its types based on ICD-9 using the fourth and fifth digit modifier codes . Results — Stroke coding was equally good with ICD-9 ( 90 % [ CI95 86 to 93 ] correct ) and ICD-10 [ 92 % ( CI95 88 to 95 correct ) with ICD-10 . There were some differences in coding by stroke type , notably with transient ischemic attack , but these differences were not statistically significant . Atrial fibrillation , coronary artery disease/ischemic heart disease , diabetes mellitus , and hypertension were coded with high sensitivity ( 81 % to 91 % ) and specificity ( 83 % to 100 % ) . ICD-10 was as good as ICD-9 for stroke risk factor coding . Conclusions — Passive surveillance using administrative data are a useful tool for identifying stroke and its risk factors using both ICD-9 and ICD-10 Background The burden of stroke is high and increasing in China . We modelled variations in , and predictors of , the costs of hospital care for patients with acute stroke in China . Methods and Findings Baseline characteristics and hospital costs for 5,255 patients were collected using the prospect i ve register-based ChinaQUEST study , conducted in 48 Level 3 and 14 Level 2 hospitals in China during 2006–2007 . Ordinary least squares estimation was used to determine factors associated with hospital costs . Overall mean cost of hospitalisation was 11,216 Chinese Yuan Renminbi ( CNY ) ( ≈US$1,602 ) per patient , which equates to more than half the average annual wage in China . Variations in cost were largely attributable to stroke severity and length of hospital stay ( LOS ) . Model forecasts showed that reducing LOS from the mean of 20 days for Level 3 and 18 days for Level 2 hospitals to a duration of 1 week , which is common among Western countries , afforded cost reductions of 49 % and 19 % , respectively . Other lesser determinants varied by hospital level : in Level 3 hospitals , health insurance and the occurrence of in-hospital complications were each associated with 10 % and 18 % increases in cost , respectively , whilst treatment in a teaching hospital was associated with approximately 39 % decrease in cost on average . For Level 2 hospitals , stroke due to intracerebral haemorrhage was associated with a 19 % greater cost than for ischaemic stroke . Conclusions Changes to hospital policies to st and ardise re source use and reduce the variation in LOS could attenuate costs and improve efficiencies for acute stroke management in China . The success of these strategies will be enhanced by broader policy initiatives currently underway to reform hospital reimbursement systems The validity of stroke diagnosis in the National Hospital Discharge Register and the Register of Causes of Death was examined among 546 middle-aged men in Finl and . The subjects were cases of cerebrovascular diseases of the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study and identified by record linkage to the registers . In all , 375 events with cerebrovascular disease as hospital discharge diagnosis and 218 events with cerebrovascular disease as the underlying cause of death were review ed using specific criteria modified from the classifications of the National Survey of Stroke and the WHO MONICA Study . For hospital stroke diagnoses , there was agreement on diagnosis for all strokes in 90 % , for subarachnoid hemorrhage in 79 % , intracerebral hemorrhage in 82 % , and cerebral infa rct ion in 90 % . The respective agreement rates for stroke as the underlying cause of death were 97 % , 95 % , 91 % , and 92 % . The data were insufficient for review in 1 % and 3 % of the stroke events , respectively . Age , observation year and trial supplementation with alpha-tocopherol or beta-carotene had no effect on validity . In conclusion , the validity of stroke diagnosis was good in registers of hospital diagnoses and causes of death justifying their use for endpoint assessment in epidemiological studies We evaluated the accuracy of administrative data for identifying complications and comorbidities of diabetes using International Classification of Diseases , 9th edition , Clinical Modification and Current Procedural Terminology codes . The records of 471 r and omly selected diabetic patients were review ed for complications from January 1 , 1993 to December 31 , 1995 ; chart data served to vali date automated data . The complications with the highest sensitivity determined by a diagnosis in the medical records identified within + /-60 days of the data base date were myocardial infa rct ion ( 95.2 % ) ; amputation ( 94.4 % ) ; ischemic heart disease ( 90.3 % ) ; stroke ( 91.2 % ) ; osteomyelitis ( 79.2 % ) ; and retinal detachment , vitreous hemorrhage , and vitrectomy ( 73.5 % ) . With the exception of amputation ( 82.9 % ) , positive predictive value was low when based on a diagnosis identified within + /-60 days of the data base date but increased with relaxation of the time constraints to include confirmation of the condition at any time during 1993 - 1995 : ulcers ( 88.5 % ) ; amputation ( 85.4 % ) ; and retinal detachment , vitreous hemorrhage and vitrectomy ( 79.8 % ) . Automated data are useful for ascertaining potential cases of some diabetic complications but require confirmatory evidence when they are to be used for research purpose Background and Purpose : The economic impact of hemorrhagic stroke , including subarachnoid hemorrhage ( SAH ) and intracerebral hemorrhage ( ICH ) , has not been well characterized compared to the more prevalent ischemic stroke ( IS ) . Methods : Patients diagnosed with SAH , ICH or IS in 1997 were identified in a 5 % national r and om sample of all Medicare beneficiaries . Medical care patterns and associated Medicare reimbursements were analyzed from one year prior to the index event through four years following that event . Results : 11,430 patients were identified with SAH ( n = 342 ) , ICH ( n = 1,957 ) or IS ( n = 9,131 ) . Average Medicare expenditures , from the initial event through four years , were USD 48,327 for SAH , USD 38,023 for ICH and USD 39,396 for IS . Conclusions : Long-term healthcare costs of SAH and ICH are substantial . With the expected increase in the elderly population over the coming decades , these results emphasize the need for effective preventive and acute medical care BACKGROUND AND PURPOSE The underlying reasons for the decline in stroke mortality in the United States are not well understood and have been the subject of ongoing debate . This study was undertaken to determine whether survival of hospitalized stroke patients has changed during the 1980s , thereby contributing to the decline in stroke mortality during that period . METHODS For the years 1980 , 1985 , and 1990 , we obtained listings of discharge diagnoses from hospitals in the Minneapolis-St Paul metropolitan area and identified all hospitalizations with a discharge diagnosis code of acute cerebrovascular disease according to the International Classification of Diseases , 9th Revision . A 50 % r and om sample of men and women aged 30 to 74 years was selected in each survey for detailed medical record abstract ion . St and ardized sets of criteria for stroke were then used to vali date acute stroke events throughout the 1980s . Each of the three period cohorts of hospitalized stroke patients ( 1980 , 1985 , and 1990 ) was followed for at least 2 years for all-cause mortality end point . RESULTS A total of 1853 patients met minimal criteria for acute stroke : 564 patients in 1980 , 598 patients in 1985 , and 691 patients in 1990 . Controlling for age , the odds of death within 2 years after stroke were approximately 40 % lower in 1990 than in 1980 . The relative odds of 2-year death in 1990 ( versus 1980 ) were 0.65 ( 95 % confidence interval , 0.47 to 0.89 ) and 0.60 ( 95 % confidence interval , 0.42 to 0.85 ) for men and women , respectively . The improved survival was evident in the short term ( 28 days ) as well as for stroke patients who survived that period . Analysis according to stroke subtype revealed that improved survival of ischemic stroke and specifically of stroke with no apparent cardioembolic source largely accounted for the overall trend . The prognosis of stroke patients who were admitted in a comatose state has not changed during that decade . CONCLUSIONS Despite the absence of any clear major advances in acute stroke therapy , survival of stroke patients substantially improved during the 1980s . The underlying reasons for this unexpected yet remarkable trend remain uncertain but may include improved supportive and rehabilitative care of stroke victims as well as a change in the natural history of the disease The sparseness of prospect i ve data about hemorrhagic stroke ( HS ) risk among Asian American ethnic groups led to the investigation of 128,934 persons with self-classified ethnicity at health examinations in 1978–1985 . Subsequently , 431 persons were hospitalized for HS ; 31 % for subarachnoid hemorrhage ( SAH ) and 69 % for intracerebral hemorrhage ( ICH ) . Ethnic predictors of HS were studied by Cox proportional hazard models with 7 covariates . With whites as reference , the adjusted relative risk ( 95 % CI ) of all Asians for HS was 1.6 ( 1.1–2.3 , p = 0.01 ) , due substantially to increased risks of SAH in Japanese people and ICH in Filipinos . These data m and ate emphasis upon preventive measures in these groups Objectives – The geographic inequity and the wide variation in the patterns of care of stroke found across Europe together with the lack of health economics evaluation in Greece led to this prospect i ve study , aim ing to provide data on in‐hospital direct cost of patients with an acute stroke in Greece , and to identify independent prognostic factors PURPOSE To vali date ICD 9 codes with a high positive predictive value ( PPV ) for incident strokes . The study population consisted of Tennessee Medicaid enrollees aged from 50 to 84 years . METHODS We identified all patients who were hospitalized with a discharge diagnosis of stroke between 1999 and 2003 using highly specific codes ( ischemic stroke ICD 9-CM codes 433.x1 , 434 [ excluding 434.x0 ] , or 436 ; intracerebral hemorrhage [ 431 ] ; and subarachnoid hemorrhage [ 430 ] ) . We review ed medical records of a systematic sample of 250 cohort members . We r and omly selected 10 - 30 eligible records for review from hospitals with at least 10 stroke hospitalizations . RESULTS We review ed 231 charts ( 93 % of total sample d ) , and 205 ( 89 % ) met study criteria for new outpatient stroke . Of the 205 confirmed new outpatient strokes , 196 had stroke listed as the primary discharge diagnosis ( PPV = 96 % ) . However , 46 ( 23 % ) of the 196 patients identified by the primary diagnosis also had a remote stroke history ( recurrent stroke not incident ) . Thus the PPV of the primary discharge diagnosis for identifying incident stroke decreased to 74 % . When we applied an algorithm that restricted our population to those with stroke as the primary diagnosis and excluded patients with any prior outpatient diagnosis of stroke , we identified incident stroke events with more precision ( PPV = 80 % ) . CONCLUSION The PPV of incident strokes was 80 % using our strategy of primary discharge diagnosis and excluding prior outpatient diagnoses of stroke . Although an unknown percentage of incident strokes are missed , this group of proven incident stroke patients can be used for etiologic studies of medication exposures BACKGROUND In Japan , the healthcare expenditure has increased to 8.0 % of the gross domestic products in 2001 . Stroke care is costly . OBJECTIVE To examine hospital costs and clinical outcomes of ischemic stroke ( IS ) and intracerebral hemorrhage ( ICH ) in Japanese stroke centers . DESIGN A prospect i ve non-interventional multi-center study . SETTING Ten Japanese stroke centers . STUDY PERIOD Fourteen months between October 2000 and December 2001 . PATIENTS Patients were those who were consecutively hospitalized with acute IS or ICH within 72 h of onset , excluding subarachnoid hemorrhage . Stroke was defined as focal neurological deficits lasting more than 24 h and the relevant lesions were to be confirmed by brain CT and /or MRI . METHODS We examined demography , in-hospital cares , length of hospital stay , clinical outcomes at discharge , and direct hospital medical costs including physician 's fees . The hospital medical cost data were collected from official hospital medical cost charts for reimbursement to the healthcare insurance systems . RESULTS There were a total of 1113 patients with a mean age of 70 years , of whom 913 ( 82 % ) patients had an IS and 200 ( 18 % ) patients had an ICH . The 317 patients ( 28 % ) experienced a recurrent stroke . Patients with ICH had the higher baseline stroke severity , result ing in longer hospitalization ( 39 days for IS and 46 days for ICH ; P<0.001 ) , lower independence rate at discharge ( 55 and 40 % ; P<0.001 ) , higher mortality rate ( 5 and 10 % ; P=0.03 ) , and higher medical costs ( US dollar 8662 and US dollar 10,260 ; P<0.001 ) than those with IS . Patients with recurrent stroke had significantly older age , higher stroke severity , and lower independence rate at discharge than those with first-ever stroke . The length of stay , in-hospital mortality , and hospital medical costs were similar among first-ever and recurrent strokes . In subtype of IS , patients with cardioembolic stroke had the worst neurological deficits , poorest outcomes , and highest medical costs . The hospital costs had a greatest association with length of stay . CONCLUSIONS Stroke care is costly in Japan . ICH is more likely to impose substantial physical and economic burden than IS . Because the cares of both first-ever and recurrent stroke were costly , primary and secondary prevention of stroke is important on the healthcare aspects BACKGROUND Hospital discharge abstract s could be used to identify complications of warfarin if coding for bleeding and thromboembolic events are accurate . OBJECTIVES To measure the accuracy of International Classification of Diseases , Ninth Revision , Clinical Modification ( ICD-9CM ) codes for bleeding and thromboembolic diagnoses . SETTING University affiliated , tertiary care hospital in Ottawa , Canada . PATIENTS A r and om sample of patients discharged between September 1999 and September 2000 with an ICD-9-CM code indicating a bleeding or thromboembolic diagnosis . METHODS Gold-st and ard coding was determined by a trained chart abstract or using explicit st and ard diagnostic criteria for bleeding , major bleeding , and acute thromboembolism . The abstract or was blinded to the original coding . We calculated the sensitivity , specificity , positive , and negative predictive values of the original ICD-9CM codes for bleeding or thromboembolism diagnoses . RESULTS We review ed 616 medical records . 361 patients ( 59 % ) had a code indicating a bleeding diagnosis , 291 patients ( 47 % ) had a code indicating a thromboembolic diagnosis and 36 patients ( 6 % ) had a code indicating both . According to the gold st and ard criteria , 352 patients experienced bleeding , 333 experienced major bleeding , and 188 experienced an acute thromboembolism . For bleeding , the ICD-9CM codes had the following sensitivity , specificity , positive and negative predictive values [ 95 % CI ] : 93 % [ 90 - 96 ] , 88 % [ 83 - 91 ] , 91 % [ 88 - 94 ] , and 91 % [ 87 - 94 ] , respectively . For major bleeding , the ICD-9CM codes had the following sensitivity , specificity , positive and negative predictive values : 94 % [ 91 - 96 ] , 83 % [ 78 - 87 ] , 87 % [ 83 - 90 ] , and 92 % [ 88 - 95 ] , respectively . For thromboembolism , the ICD-9CM codes had the following sensitivity , specificity , positive and negative predictive values : 97 % [ 94 - 99 ] , 74 % [ 70 - 79 ] , 62 % [ 57 - 68 ] , and 98 % [ 96 - 99 ] , respectively . By selecting a sub-group of ICD-9CM codes for thromboembolism , the positive predictive value increased to 87 % . CONCLUSION In our centre , the discharge abstract could be used to identify and exclude patients hospitalized with a major bleed or thromboembolism . If coding quality for bleeding is similar in other hospitals , these ICD-9-CM diagnostic codes could be used to study population -based warfarin-associated hemorrhagic complications using administrative data bases While previous prospect i ve multicenter studies have conducted cardiovascular disease surveillance , few have detailed the techniques relating to the ascertainment of and data collection for events . The Cardiovascular Health Study ( CHS ) is a population -based study of coronary heart disease and stroke in older adults . This article summarizes the CHS events protocol and describes the methods of surveillance and ascertainment of hospitalized and nonhospitalized events , the use of medical records and other support documents , organizational issues at the field center level , and the classification of events through an adjudication process . We present data on incidence and mortality , the classification of adjudicated events , and the agreement between classification by the Events Subcommittee and the medical records diagnostic codes . The CHS techniques are a successful model for complete ascertainment , investigation , and documentation of events in an older cohort |
621 | 19,093,923 | CONCLUSION Exercise can prevent falls in older people .
Greater relative effects are seen in programs that include exercises that challenge balance , use a higher dose of exercise , and do not include a walking program . | OBJECTIVES To determine the effects of exercise on falls prevention in older people and establish whether particular trial characteristics or components of exercise programs are associated with larger reductions in falls . | OBJECTIVE To use two different exercise programs over a 2-year period to reduce falls and their sequelae among residents of two long-term care facilities . DESIGN R and omized , controlled trial . SETTING The study took place at two long-term care facilities with services ranging from independent living to skilled nursing . PARTICIPANTS One hundred and ten participants whose average age was 84 and who were capable of ambulating with or without assistive devices and could follow simple directions . INTERVENTION Participants were r and omized to one of two exercise groups ( resistance/endurance plus basic enhanced programming or tai chi plus basic enhanced programming ) or to a control group ( basic enhanced programming only ) . Exercise classes were held three times per week throughout the study . MEASUREMENTS Participants were evaluated for cognitive and physical functioning at baseline and 6 , 12 , and 24 months . Falls were determined from incident reports filed by the nursing staffs at the facilities . RESULTS Time to first fall , time to death , number of days hospitalized , and incidence of falls did not differ among the treatment and control groups ( P>.05 ) . Among all participants , those who fell had significantly lower baseline Folstein Mini-Mental State Examination and instrumental activities of daily living scores and experienced significantly greater declines in these measures over the 2-year program . CONCLUSION There were no significant differences in falls among the two exercise groups and the control group . Lack of treatment differences and low adherence rates suggest that residents of long-term care facilities may require individualized exercise interventions that can be adapted to their changing needs BACKGROUND Although exercise has been shown to relieve depression , little is known about its mechanism or dose-response characteristics . We hypothesized that high intensity progressive resistance training ( PRT ) would be more effective than either low intensity PRT or st and ard care by a general practitioner ( GP ) in depressed elderly persons , and that high intensity PRT would provide superior benefits in quality of life , sleep quality , and self-efficacy . METHODS Sixty community-dwelling adults > 60 years with major or minor depression were r and omized to supervised high intensity PRT ( 80 % maximum load ) or low intensity PRT ( 20 % maximum load ) 3 days per week for 8 weeks , or GP care . RESULTS A 50 % reduction in the Hamilton Rating Scale of Depression score was achieved in 61 % of the high intensity , 29 % of the low intensity , and 21 % of the GP care group ( p = .03 ) . Strength gain was directly associated with reduction in depressive symptoms ( r = 0.40 , p = .004 ) , as was baseline social support network type ( F = 3.52 , p = .015 ) , whereas personality type , self-efficacy , and locus of control were unrelated to the antidepressant effect . Vitality quality -of-life scale improved more in the high intensity group than in the others ( p = .04 ) . Sleep quality improved significantly in all participants ( p < .0001 ) , with the greatest relative change in high intensity PRT ( p = .05 ) . CONCLUSIONS High intensity PRT is more effective than is low intensity PRT or GP care for the treatment of older depressed patients STUDY OBJECTIVE In the causative mechanism of falls among older community dwellers , slips and trips have been found to be significant precursors . The purpose of the two year trial was to assess the effectiveness of multi-component interventions targeting major risk factors for falls in reducing the incidence of slips , trips and falls among the well , older community . DESIGN Four groups with approximately equal numbers of participants were r and omly allocated to interventions . The prevention strategies included education and awareness raising of falls risk factors , exercise sessions to improve strength and balance , home safety advice to modify environmental hazards , and medical assessment to optimise health . The interventions combined the strategies in an add on approach . The first intervention group receiving the information session only was regarded as the control . The outcome of interest was the occurrence of a slip , trip or fall , monitored prospect ively using a daily calendar diary . PARTICIPANTS AND SETTING Two hundred and fifty two members of the National Seniors Association in the Brisbane district agreed to participate . National Seniors clubs provide a forum for active , community dwelling Australians aged 50 and over to participate in policy , personal development and recreation . MAIN RESULTS Using Cox 's proportional hazards regression model , adjusted hazard ratios comparing intervention groups with the control ranged from 0.35 ( 95 % CI 0.17 , 0.73 ) to 0.48 ( 0.25 , 0.91 ) for slips ; 0.29 ( 0.16 , 0.51 ) to 0.45 ( 0.27 , 0.74 ) for trips ; and 0.60 ( 0.36 , 1.01 ) to 0.82 ( 0.51 , 1.31 ) for falls . While calendar monitoring recorded outcome , it was also assessed as a prevention strategy by comparing the intervention groups with a hypothetical non-intervened group . At one year after intervention , reductions in the probability of slips , trips and falls ( 61(95%CI 54 , 66)% ; 56 ( 49 , 63)% ; 29 ( 22 , 36)% respectively ) were demonstrated . CONCLUSIONS This study makes an important contribution to the priority community health issue of falls prevention by showing that effective , sustainable , low cost programmes can be introduced through community-based organisations to reduce the incidence of slips , trips and falls in well , older people OBJECTIVE To assess the effectiveness of psychotropic medication withdrawal and a home-based exercise program in reducing falls in older people . DESIGN A r and omized controlled trial with a two by two factorial design . SETTING Seventeen general practice s in Dunedin , New Zeal and . PARTICIPANTS Women and men aged 65 years registered with a general practitioner and currently taking psychotropic medication ( n = 93 ) . INTERVENTIONS Two interventions : ( 1 ) gradual withdrawal of psychotropic medication versus continuing to take psychotropic medication ( double blind ) and ( 2 ) a home-based exercise program versus no exercise program ( single blind ) . MEASUREMENTS Number of falls and falls risk during 44 weeks of follow-up . Analysis was on an intent to treat basis . RESULTS After 44 weeks , the relative hazard for falls in the medication withdrawal group compared with the group taking their original medication was .34 ( 95 % CI , .16-.74 ) . The risk of falling for the exercise program group compared with those not receiving the exercise program was not significantly reduced . CONCLUSIONS Withdrawal of psychotropic medication significantly reduced the risk of falling , but permanent withdrawal is very difficult to achieve OBJECTIVES This r and omized controlled trial studied the effects of a low- to moderate-intensity group exercise program on strength , endurance , mobility , and fall rates in fall-prone elderly men with chronic impairments . METHODS Fifty-nine community-living men ( mean age = 74 years ) with specific fall risk factors ( i.e. , leg weakness , impaired gait or balance , previous falls ) were r and omly assigned to a control group ( n = 28 ) or to a 12-week group exercise program ( n = 31 ) . Exercise sessions ( 90 minutes , three times per week ) focused on increasing strength and endurance and improving mobility and balance . Outcome measures included isokinetic strength and endurance , five physical performance measures , and self-reported physical functioning , health perception , activity level , and falls . RESULTS Exercisers showed significant improvement in measures of endurance and gait . Isokinetic endurance increased 21 % for right knee flexion and 26 % for extension . Exercisers had a 10 % increase ( p < .05 ) in distance walked in six minutes , and improved ( p < .05 ) scores on an observational gait scale . Isokinetic strength improved only for right knee flexion . Exercise achieved no significant effect on hip or ankle strength , balance , self-reported physical functioning , or number of falls . Activity level increased within the exercise group . When fall rates were adjusted for activity level , the exercisers had a lower 3-month fall rate than controls ( 6 falls/1000 hours of activity vs 16.2 falls/1000 hours , p < .05 ) . DISCUSSION These findings suggest that exercise can improve endurance , strength , gait , and function in chronically impaired , fall-prone elderly persons . In addition , increased physical activity was associated with reduced fall rates when adjusted for level of activity Background : The knowledge concerning balance training actually lowering fall rates among frail older persons is limited . Objective : The aim of this study was to examine the effects of a 4-week individualized visual feedback-based balance training on the fall incidence during 1-year follow-up among frail older women living in residential care . Methods : Twenty-seven older women from 2 residential care homes were r and omized into exercise ( n = 20 ) and control ( n = 7 ) groups . Balance measurements were carried out before and after a 4-week training period and falls were monitored by monthly diaries for 1 year . An interview about fear of falling and physical activity was completed before and after the intervention and after the 1-year follow-up . Results : A positive effect of balance training on fall incidence was found . A dynamic Poisson regression model showed that during the follow-up the monthly risk of falling was decreased in the exercise group compared to controls ( risk ratio 0.398 , 95 % CI 0.174–0.911 , p = 0.029 ) . In addition , the exercise group reported a reduced fear of falling and increased physical activity after a training period but these changes declined during the follow-up period . Conclusion : Individualized visual feedback-based balance training was shown to be a promising method for fall prevention among frail older women . High compliance ( 97.5 % ) with the training program showed that carefully targeted training programs can be carried out among older people with health limitations Community trials involve the assignment of intact social groups to study conditions and are becoming increasingly common in epidemiologic research . In both the design and analysis of these studies , whether cross-sectional or cohort , allowance must be made for the dependence of elements within intact groups if variances are to be properly estimated . In the design phase , the statistician needs estimates of the level of dependence likely to be encountered . In the analysis phase , external estimates of the level of dependence may be useful in preventing the erosion of power associated with small numbers of intact groups assigned to each condition . We report the intraclass correlation coefficients of the city-year component of variance as estimated in the Minnesota Heart Health Program for a variety of community survey variables and illustrate their use in both design and analysis . Of 23 variables assessed , all but two showed positive estimates of city-year intraclass correlations . In these data , estimates of intraclass correlation coefficients generally were in the range 0.002–0.012 OBJECTIVE To evaluate the effects of two exercise approaches , Tai Chi ( TC ) and computerized balance training ( BT ) , on specified primary outcomes ( biomedical , functional , and psychosocial indicators of frailty ) and secondary outcomes ( occurrence of falls ) . DESIGN The Atlanta FICSIT ( Frailty and Injuries : Cooperative Studies of Intervention Techniques ) , a prospect i ve , r and omized , controlled clinical trial with three arms ( TC , BT , and education [ ED ] . Intervention length was 15 weeks , with primary outcomes measured before and after intervention and at 4-month follow-up . Falls were monitored continuously throughout the study . SETTING Persons aged 70 and older living in the community . PARTICIPANTS A total of 200 participants , 162 women and 38 men ; mean age was 76.2 . MEASUREMENTS Biomedical ( strength , flexibility , cardiovascular endurance , body composition ) , functional ( IADL ) , and psychosocial well-being ( CES-D scale , fear of falling question naire , self-perception of present and future health , mastery index , perceived quality of sleep , and intrusiveness ) variables . RESULTS Grip strength declined in all groups , and lower extremity range of motion showed limited but statistically significant changes . Lowered blood pressure before and after a 12-minute walk was seen following TC participation . Fear of falling responses and intrusiveness responses were reduced after the TC intervention compared with the ED group ( P = .046 and P = .058 , respectively ) . After adjusting for fall risk factors , TC was found to reduce the risk of multiple falls by 47.5 % . CONCLUSIONS A moderate TC intervention can impact favorably on defined biomedical and psychosocial indices of frailty . This intervention can also have favorable effects upon the occurrence of falls . Tai Chi warrants further study as an exercise treatment to improve the health of older people BACKGROUND Community physiotherapy is often prescribed for stroke patients with long-term mobility problems . We aim ed to assess the effectiveness of this treatment in patients who had mobility problems 1 year after stroke . METHODS We screened 359 patients older than 50 years for a single-masked , r and omised controlled trial to assess the effects of community physiotherapy . Assessment s were made at baseline , 3 , 6 , and 9 months in 170 eligible patients assigned treatment or no intervention . The primary outcome measure was mobility measured by the Rivermead mobility index . Secondary outcome measures were gait speed , number of falls , daily activity ( Barthel index scores ) , social activity ( Frenchay activities index ) , hospital anxiety and depression scale , and emotional stress of carers ( general health question naire 28 ) . Analyses were by intention to treat . FINDINGS Follow-up was available for 146 patients ( 86 % ) . Changes in scores on the Rivermead mobility index ( score range 0 - 15 ) differed significantly between treatment and control groups at 3 months ( p=0.018 ) , but only by a median of 1 point ( 95 % CI 0 - 1 ) , with an interpolated value of 0.55 ( 0.08 - 1.04 ) . Gait speed was 2.6 m/min ( 0.30 - 4.95 ) higher in the treatment group at 3 months . Neither treatment effect persisted at 6-months ' and 9-months ' follow-up . Treatment had no effect on patients ' daily activity , social activity , anxiety , depression , and number of falls , or on emotional stress of carers . INTERPRETATION Community physiotherapy treatment for patients with mobility problems 1 year after stroke leads to significant , but clinical ly small , improvements in mobility and gait speed that are not sustained after treatment ends Frequent or recurrent fallers are more likely to have chronic medical conditions and physiological impairments , exhibit functional decline and have poor outcomes , than single fallers [ 1 ] . Fractures are also more common in recurrent fallers than single fallers [ 2 ] . Modern surgery for hip fracture can no longer improve on its outcomes [ 3 ] and therefore , effective prevention of falls [ 4 , 5 ] is the key to preventing disability and death . There is still no published evidence that a single intervention ( tailored group exercise ) can prevent falls or injuries in a high risk group of frequent fallers . This r and omised controlled trial ( RCT ) aim ed to investigate the impact of a 36 week individualised and tailored group and home exercise intervention , compared with a control intervention , in reducing falls and injuries in communitydwelling , independent-living , frequent falling women aged 65 years and over . Preliminary results have been published in abstract form [ 6 ] . The primary outcome was falls and fallrelated injuries . The secondary outcome was the number of frequent fallers who had died , had moved into residential care or were in hospital compared with the group they were in OBJECTIVE To determine the safety and efficacy of an exercise protocol design ed to improve strength , mobility , and balance and to reduce subsequent falls in geriatric patients with a history of injurious falls . DESIGN A r and omized controlled 3-month intervention trial , with an additional 3-month follow-up . SETTING Out-patient geriatric rehabilitation unit . PARTICIPANTS Fifty-seven female geriatric patients ( mean age 82 + /- 4.8 years ; range 75 - 90 ) admitted to acute care or inpatient rehabilitation with a history of recurrent or injurious falls including patients with acute fall-related fracture . INTERVENTION Ambulatory training of strength , functional performance , and balance 3 times per week for 3 months . Patients of the control group attended a placebo group 3 times a week for 3 months . Both groups received an identical physiotherapeutic treatment 2 times a week , in which strengthening and balance training were excluded . MEASUREMENTS Strength , functional ability , motor function , psychological parameters , and fall rates were assessed by st and ardized protocol s at the beginning ( T1 ) and the end ( T2 ) of intervention . Patients were followed up for 3 months after the intervention ( T3 ) . RESULTS No training-related medical problems occurred in the study group . Forty-five patients ( 79 % ) completed all assessment s after the intervention and follow-up period . Adherence was excellent in both groups ( intervention 85.4 + /- 27.8 % vs control 84.2 + /- 29.3 % ) . The patients in the intervention group increased strength , functional motor performance , and balance significantly . Fall-related behavioral and emotional restrictions were reduced significantly . Improvements persisted during the 3-month follow-up with only moderate losses . For patients of the control group , no change in strength , functional performance , or emotional status could be documented during intervention and follow-up . Fall incidence was reduced nonsignificantly by 25 % in the intervention group compared with the control group ( RR:0.753 CI:0.455 - 1.245 ) . CONCLUSIONS Progressive resistance training and progressive functional training are safe and effective methods of increasing strength and functional performance and reducing fall-related behavioral and emotional restrictions during ambulant rehabilitation in frail , high-risk geriatric patients with a history of injurious falls OBJECTIVES To determine the effects of moderate intensity group-exercise programs on falls , functional performance , and disability in older adults ; and to investigate the influence of frailty on these effects . DESIGN A 20-week , multicenter r and omized controlled trial , with 52-week follow-up . SETTING Fifteen homes for the elderly . PARTICIPANTS Two hundred seventy-eight men and women ( mean age + /- st and ard deviation , 85+/-6y ) . INTERVENTIONS Two exercise programs were r and omly distributed across 15 homes . The first program , functional walking ( FW ) , consisted of exercises related to daily mobility activities . In the second program , in balance ( IB ) , exercises were inspired by the principles of Tai Chi . Within each home participants were r and omly assigned to an intervention or a control group . Participants in the control groups were asked not to change their usual pattern of activities . The intervention groups followed a 20-week exercise program with 1 meeting a week during the first 4 weeks and 2 meetings a week during the remaining weeks . MAIN OUTCOME MEASURES Falls , Performance Oriented Mobility Assessment ( POMA ) , physical performance score , and the Groningen Activity Restriction Scale ( GARS ) ( measuring self-reported disability ) . RESULTS Fall incidence rate was higher in the FW group ( 3.3 falls/y ) compared with the IB ( 2.4 falls/y ) and control ( 2.5 falls/y ) groups , but this difference was not statistically significant . The risk of becoming a faller in the exercise groups increased significantly in the subgroup of participants who were classified as being frail ( hazard ratio [ HR ] = 2.95 ; 95 % confidence interval [ CI ] , 1.64 - 5.32 ) . For participants who were classified as being pre-frail , the risk of becoming a faller decreased ; this effect became significant after 11 weeks of training ( HR = .39 ; 95 % CI , .18-.88 ) . Participants in both exercise groups showed a small , but significant improvement in their POMA and physical performance scores . In the FW group , this held true for the GARS score as well . Post hoc analyses revealed that only the pre-frail participants improved their POMA and physical performance scores . CONCLUSIONS Fall-preventive moderate intensity group-exercise programs have positive effects on falling and physical performance in pre-frail , but not in frail elderly BACKGROUND Exercise programs improve balance , strength and agility in elderly people and thus may prevent falls . However , specific exercise programs that might be widely used in the community and that might be " prescribed " by physicians , especially for patients with osteoporosis , have not been evaluated . We conducted a r and omized controlled trial of such a program design ed specifically for women with osteoporosis . METHODS We identified women 65 to 75 years of age in whom osteoporosis had been diagnosed by dual-energy X-ray absorptiometry in our hospital between 1996 and 2000 and who were not engaged in regular weekly programs of moderate or hard exercise . Women who agreed to participate were r and omly assigned to participate in a twice-weekly exercise class or to not participate in the class . We measured baseline data and , 20 weeks later , changes in static balance ( by dynamic posturography ) , dynamic balance ( by a timed figure-eight run ) and knee extension strength ( by dynamometry ) . RESULTS Of 93 women who began the trial , 80 completed it . Before adjustment for covariates , the intervention group tended to have greater , although nonsignificant , improvements in static balance ( mean difference 4.8 % , 95 % confidence interval [ CI ] -1.3 % to 11.0 % ) , dynamic balance ( mean difference 3.3 % , 95 % CI -1.7 % to 8.4 % ) and knee extension strength ( mean difference 7.8 % , 95 % CI -5.4 % to 21.0 % ) . Mean crude changes in the static balance score were -0.85 ( 95 % CI -2.91 to 1.21 ) for the control group and 1.40 ( 95 % CI -0.66 to 3.46 ) for the intervention group . Mean crude changes in figure-eight velocity ( dynamic balance ) were 0.08 ( 95 % CI 0.02 to 0.14 ) m/s for the control group and 0.14 ( 95 % CI 0.08 to 0.20 ) m/s for the intervention group . For knee extension strength , mean changes were -0.58 ( 95 % CI -3.02 to 1.81 ) kg/m for the control group and 1.03 ( 95 % CI -1.31 to 3.34 ) kg/m for the intervention group . After adjustment for age , physical activity and years of estrogen use , the improvement in dynamic balance was 4.9 % greater for the intervention group than for the control group ( p = 0.044 ) . After adjustment for physical activity , cognitive status and number of fractures ever , the improvement in knee extension strength was 12.8 % greater for the intervention group than for the control group ( p = 0.047 ) . The intervention group also had a 6.3 % greater improvement in static balance after adjustment for rheumatoid arthritis and osteoarthritis , but this difference was not significant ( p = 0.06 ) . INTERPRETATION Relative to controls , participants in the exercise program experienced improvements in dynamic balance and strength , both important determinants of risk for falls , particularly in older women with osteoporosis INTRODUCTION Frequent falls and risk of injury are evident in individuals with Parkinson 's disease ( PD ) as the disease progresses . There have been no reports of any interventions that reduce the incidence of falls in idiopathic PD . PURPOSE Assess the benefit of gait and step perturbation training in individuals with PD . DESIGN R and omized , controlled trial . SETTING Outpatient research , education and clinical center in a tertiary care Veterans Affairs Medical Center . OUTCOME MEASURES Gait parameters , 5-step test , report of falls . SUBJECTS Eighteen men with idiopathic PD in stage 2 or 3 of the Hoehn and Yahr staging . METHODS Subjects were r and omly assigned to a trained or control group . They were asked about any falls 2 weeks prior to and after an 8 week period . Gait speed , cadence , and step length were tested on an instrumented walkway . Subjects were timed while stepping onto and back down from an 8.8 cm step for 5 consecutive steps . Gait training consisted of walking on a treadmill at a speed greater than over ground walking speed while walking in 4 directions and while supported in a harness for safety . Step training consisted of suddenly turning the treadmill on and off while the subject stood in the safety harness facing either forwards , backwards , or sideways . Training occurred 1 hour per day , three times per week for 8 weeks . A two-factor ( time and group ) analysis of variance with repeated measures was used to compare the groups . RESULTS Substantial reduction occurred in falls in the trained group , but not in the control group . Gait speed increased in the trained group from 1.28+/-0.33 meters/sec to 1.45+/-0.37 meters/sec , but not in the control group ( from 1.26 to 1.27 m/s ) . The cadence increased for both groups : from 112.8 to 120.3 steps/min for the trained group and 117.7 to 124.3 steps/min for the control group . Stride lengths increased for the trained group , but not the control group . The 5-step test speed increased in the trained group from 0.40+/-0.08 steps/sec to 0.51+/-0.12 steps/sec , and in the control group ( 0.36+/-0.11 steps/sec to 0.42+/-0.11 steps/sec ) . CONCLUSION Gait and step perturbation training result ed in a reduction in falls and improvements in gait and dynamic balance . This is a promising approach to reduce falls for patients with PD BACKGROUND recent studies have found that moderate intensity exercise is an effective intervention strategy for preventing falls in older people . However , research is required to determine whether supervised group exercise programmes , conducted in community setting s with at-risk older people referred by their health care practitioner are also effective in improving physical functioning and preventing falls in this group . OBJECTIVES to determine whether participation in a weekly group exercise programme with ancillary home exercises over one year improves balance , muscle strength , reaction time , physical functioning , health status and prevents falls in at-risk community-dwelling older people . METHODS the sample comprised 163 people aged over 65 years identified as at risk of falling using a st and ardised assessment screen by their general practitioner or hospital-based physiotherapist , residing in South Western Sydney , Australia . Subjects were r and omised into either an exercise intervention group or a control group . Physical performance and general health measures were assessed at baseline and repeated 6-months into the trial . Falls were measured over a 12-month follow-up period using monthly postal surveys . RESULTS at baseline both groups were well matched in their physical performance , health and activity levels . The intervention subjects attended a median of 23 exercise classes over the year , and most undertook the home exercise sessions at least weekly . At retest , the exercise group performed significantly better than the controls in three of six balance measures ; postural sway on the floor with eyes open and eyes closed and coordinated stability . The groups did not differ at retest in measures of strength , reaction time and walking speed or on Short-Form 36 , Physical Activity Scale for the Elderly or fear of falling scales . Within the 12-month trial period , the rate of falls in the intervention group was 40 % lower than that of the control group ( IRR=0.60 , 95 % CI 0.36 - 0.99 ) . CONCLUSIONS these findings indicate that participation in a weekly group exercise programme with ancillary home exercises can improve balance and reduce the rate of falling in at-risk community dwelling older people Abstract Objective : To test the effectiveness of , and explore interactions between , three interventions to prevent falls among older people . Design : A r and omised controlled trial with a full factorial design . Setting : Urban community in Melbourne , Australia . Participants : 1090 aged 70 years and over and living at home . Most were Australian born and rated their health as good to excellent ; just over half lived alone . Interventions : Three interventions ( group based exercise , home hazard management , and vision improvement ) delivered to eight groups defined by the presence or absence of each intervention . Main outcome measure : Time to first fall ascertained by an 18 month falls calendar and analysed with survival analysis techniques . Changes to targeted risk factors were assessed by using measures of quadriceps strength , balance , vision , and number of hazards in the home . Results : The rate ratio for exercise was 0.82 ( 95 % confidence interval 0.70 to 0.97 , P=0.02 ) , and a significant effect ( P<0.05 ) was observed for the combinations of interventions that involved exercise . Balance measures improved significantly among the exercise group . Neither home hazard management nor treatment of poor vision showed a significant effect . The strongest effect was observed for all three interventions combined ( rate ratio 0.67 ( 0.51 to 0.88 , P=0.004 ) ) , producing an estimated 14.0 % reduction in the annual fall rate . The number of people needed to be treated to prevent one fall a year ranged from 32 for home hazard management to 7 for all three interventions combined . Conclusions : Group based exercise was the most potent single intervention tested , and the reduction in falls among this group seems to have been associated with improved balance . Falls were further reduced by the addition of home hazard management or reduced vision management , or both of these . Cost effectiveness is yet to be examined . These findings are most applicable to Australian born adults aged 70–84 years living at home who rate their health as good At 16 senior centers , we studied the effectiveness of exercise and cognitive-behavioral programs , compared with a discussion control program , in reducing falls and injuries among 230 older adults . After 1 year of the programs , we observed no significant difference in time to first fall . Even though a relatively high percentage ( 38.6 % ) suffered at least one fall , only 7.8 % of these community-residing elderly required medical attention . Secondary outcome measures such as strength , balance , fear of falling , and perceived health did not significantly change OBJECTIVES To determine the effectiveness of a 16-week community-based tai chi program in reducing falls and improving balance in people aged 60 and older . DESIGN R and omized , controlled trial with waiting list control group . SETTING Community in Sydney , Australia . PARTICIPANTS Seven hundred two relatively healthy community-dwelling people aged 60 and older ( mean age 69 ) . INTERVENTION Sixteen-week program of community-based tai chi classes of 1 hour duration per week . MEASUREMENTS Falls during 16 and 24 weeks of follow-up were assessed using a calendar method . Balance was measured at baseline and 16-week follow-up using six balance tests . RESULTS Falls were less frequent in the tai chi group than in the control group . Using Cox regression and time to first fall , the hazard ratio after 16 weeks was 0.72 ( 95 % confidence interval (CI)=0.51 - 1.01 , P=.06 ) , and after 24 weeks it was 0.67 ( 95 % CI=0.49 - 0.93 , P=.02 ) . There was no difference in the percentage of participants who had one or more falls . There were statistically significant differences in changes in balance favoring the tai chi group on five of six balance tests . CONCLUSION Participation in once per week tai chi classes for 16 weeks can prevent falls in relatively healthy community-dwelling older people BACKGROUND Among elderly persons , falls account for 87 % of all fractures and are contributing factors in many nursing home admissions . This study evaluated the effect of an easily implemented , low-intensity exercise program on the incidence of falls and the time to first fall among a clinical ly defined population of elderly men and women . METHODS This community-based , r and omized trial compared the exercise intervention with a no-intervention control . The participants were 294 men and women , aged 60 years or older , who had either a hospital admission or bed rest for 2 days or more within the previous month . Exercise participants were scheduled to attend exercise sessions lasting 45 minutes , including warm-up and cool-down , 3 times a week for 8 weeks ( 24 sessions ) . Assessment s included gait and balance measures , self-reported physical function , the number of medications being taking at baseline , participant age , sex , and history of falling . Falls were tracked for 1 year after each participant 's baseline assessment . RESULTS 29 % of the study participants reported a fall during the study period . The effect of exercise in preventing falls varied significantly by baseline physical function level ( p < or = .002 ) . The risk for falls decreased for exercise participants with low baseline physical functioning ( hazard ratio,.51 ) but increased for exercise participants with high baseline physical functioning ( hazard ratio , 3.51 ) . CONCLUSIONS This easily implemented , low-intensity exercise program appears to reduce the risk for falls among elderly men and women recovering from recent hospitalizations , bed rest , or both who have low levels of physical functioning Introduction The purpose of this study was to investigate the effect of a 12-month Balance Training Program on balance , mobility and falling frequency in women with osteoporosis . Methods Sixty-six consecutive elderly women were selected from the Osteometabolic Disease Outpatient Clinic and r and omized into 2 groups : the ‘ Intervention ’ , su bmi tted for balance training ; and the ‘ Control ’ , without intervention . Balance , mobility and falling frequency were evaluated before and at the end of the trial , using the Berg Balance Scale ( BBS ) , the Clinical Test Sensory Interaction Balance ( CTSIB ) and the Timed “ Up & Go ” Test ( TUGT ) . Intervention used techniques to improve balance consisting of a 1-hour session each week and a home-based exercise program . Results Sixty women completed the study and were analyzed . The BBS difference was significant higher in the Intervention group compared to Control ( 5.5 ± 5.67 vs −0.5 ± 4.88 score , p < 0.001 ) . Similarly , the number of patients in the Intervention group presented improvement in two conditions of CTSIB compared to Control ( eyes closed and unstable surface condition : 13 vs one patient , p < 0.001 and eyes open , visual conflict and unstable surface condition : 12 vs one patient , p < 0.001 ) . Additionally , the differences between the TUGT were reduced in the Intervention group compared to Control ( −3.65 ± 3.61 vs 2.27 ± 7.18 seconds , p < 0.001 ) . Notably , this improvement was paralleled by a reduction in the number of falls/patient in the Intervention group compared to Control ( −0.77 ± 1.76 vs 0.33 ± 0.96 , p = 0.018 ) . Conclusion This longitudinal prospect i ve study demonstrated that an intervention using balance training is effective in improving functional and static balance , mobility and falling frequency in elderly women with osteoporosis BACKGROUND The authors ' objective was to evaluate the efficacy of a 6-month Tai Chi intervention for decreasing the number of falls and the risk for falling in older persons . METHODS This r and omized controlled trial involved a sample of 256 physically inactive , community-dwelling adults aged 70 to 92 ( mean age , 77.48 years ; st and ard deviation , 4.95 years ) who were recruited through a patient data base in Portl and , Oregon . Participants were r and omized to participate in a three-times-per-week Tai Chi group or to a stretching control group for 6 months . The primary outcome measure was the number of falls ; the secondary outcome measures included functional balance ( Berg Balance Scale , Dynamic Gait Index , Functional Reach , and single-leg st and ing ) , physical performance ( 50-foot speed walk , Up&Go ) , and fear of falling , assessed at baseline , 3 months , 6 months ( intervention termination ) , and at a 6-month postintervention follow-up . RESULTS At the end of the 6-month intervention , significantly fewer falls ( n=38 vs 73 ; p=.007 ) , lower proportions of fallers ( 28 % vs 46 % ; p=.01 ) , and fewer injurious falls ( 7 % vs 18 % ; p=.03 ) were observed in the Tai Chi group compared with the stretching control group . After adjusting for baseline covariates , the risk for multiple falls in the Tai Chi group was 55 % lower than that of the stretching control group ( risk ratio,.45 ; 95 % confidence interval , 0.30 to 0.70 ) . Compared with the stretching control participants , the Tai Chi participants showed significant improvements ( p<.001 ) in all measures of functional balance , physical performance , and reduced fear of falling . Intervention gains in these measures were maintained at a 6-month postintervention follow-up in the Tai Chi group . CONCLUSIONS A three-times-per-week , 6-month Tai Chi program is effective in decreasing the number of falls , the risk for falling , and the fear of falling , and it improves functional balance and physical performance in physically inactive persons aged 70 years or older OBJECTIVES To compare the effects of three fall-prevention programs ( education ( ED ) , home safety assessment and modification ( HSAM ) , and exercise training ( ET ) ) on quality of life ( QOL ) , functional balance and gait , activities of daily living ( ADLs ) , fear of falling , and depression in adults aged 65 and older . DESIGN A 4-month r and omized trial . SETTING R and omized , controlled trial . PARTICIPANTS One hundred fifty participants who had experienced a recent fall . MEASUREMENTS QOL was assessed according to the brief version of the World Health Organization Quality of Life instrument ( WHOQOL-BREF ) , functional balance and gait according to functional reach and Tinetti balance and gait , ADLs according to the Older Americans Re sources and Services question naire , fear of falling according to a visual analog scale , and depression level according to the Geriatric Depression Scale . RESULTS The score changes for the ET group were 2.1 points greater on the physical domain ( 95 % confidence interval (CI)=-1.2 - 5.3 ) , 3.8 points greater on the psychological domain ( 95 % CI=0.7 - 7.0 ) , and for the WHOQOL-BREF , 3.4 points greater on the social domain ( 95 % CI=0.7 - 6.1 ) and 3.2 points greater on the environmental domain ( 95 % CI=0.6 - 5.7 ) than for the ED group . The score change for each domain of the WHOQOL-BREF for the HSAM group was greater than that for the ED group , although these results were not statistically significant . The ET group also had greater improvements in functional reach , Tinetti balance and gait , and fear of falling than the ED group . CONCLUSION The QOL outcome supports the superiority of ET over the other two interventions in older people who have recently fallen . This finding also parallels those gathered from the functional measures BACKGROUND Past studies suggest multidisciplinary interventions that include physical therapy ( PT ) can improve function of nursing home residents . This trial specifically evaluates effects of PT for frail long-stay nursing home residents . DESIGN R and omized , controlled trial . SETTING One academic nursing home and eight community nursing homes . PATIENTS A total of 194 elderly nursing home residents dependent in at least two activities of daily living residing in the nursing home for at least 3 months . INTERVENTIONS Patients were r and omized to individually tailored one-on-one PT sessions or friendly visits ( FVs ) three times a week for 4 months . Physical therapy included range-of-motion , strength , balance , transfer , and mobility exercises . MAIN OUTCOME MEASURES Performance-based physical function assessed by the Physical Disability Index ; self-perceived health status assessed with the Sickness Impact Profile ; observer-reported activities of daily living ; and falls . RESULTS Eighty-nine percent and 92 % of PT and FV sessions , respectively , were attended ; 5 % and 9 % of subjects dropped out in the PT group and FV group , respectively . Compared with the FV group , the PT group experienced no significant improvements in overall Physical Disability Index , Sickness Impact Profile , or activities of daily living scores . A 15.5 % improvement in the mobility subscale of the Physical Disability Index was seen ( 95 % confidence interval [ CI ] , 6.4 % to 24.7 % ) ; no benefits in range-of-motion , strength , or balance subscales were found . Compared with the FV group , the PT group used assistive devices for bed mobility tasks less often ( P = .06 ) and were less likely to use assistive devices and wheelchairs for locomotion ( P < .005 ) . There were 79 falls in the PT group vs 60 falls in the FV group ( P = .11 ) . Charge for the 4-month PT program was $ 1220 per subject ( 95 % CI , $ 412 to $ 1832 ) . CONCLUSION This st and ardized physical therapy program provided modest mobility benefits for very frail long-stay nursing home residents with physical disability due to multiple comorbid conditions BACKGROUND The beneficial role of exercise in improving bone mineral density , muscle strength and balance , has been documented predominantly in younger population s. These findings may not apply to elderly population s with limited ability to perform exercises of high intensity . OBJECTIVE To examine the effects of Tai Chi ( TC ) and resistance exercise ( RTE ) on bone mineral density ( BMD ) , muscle strength , balance and flexibility in community living elderly people . DESIGN R and omised controlled trial , using blocked r and omization with stratification by sex . SETTING A community in the New Territories Region of Hong Kong , China . SUBJECTS One hundred eighty subjects ( 90 men , 90 women ) aged 65 - 74 , were recruited through advertisements in community centres . METHODS Subjects were assigned to participate in TC , RTE three times a week , or no intervention ( C ) for 12 months . Measurements were carried out at baseline , 6 and 12 months . Analyses of covariance ( ANCOVA ) adjusted for age , and baseline values of variables that were significantly different between groups : i.e. smoking and flexibility for men ; quadriceps strength for women . RESULTS Compliance was high ( TC 81 % , RTE 76 % ) . In women , both TC and RTE groups had less BMD loss at total hip compared with controls . No effect was observed in men . No difference in either balance , flexibility or the number of falls was observed between either intervention or controls after 12 months . CONCLUSION The beneficial effects of TC or RTE on musculoskeletal health are modest and may not translate into better clinical outcomes OBJECTIVE to evaluate the effects of brisk walking on bone mineral density in women who had suffered an upper limb fracture . DESIGN r and omized placebo-controlled trial . Assessment s of bone mineral density were made before and at 1 and 2 years after intervention . St and ardized and vali date d measures of physical capacity , self-rated health status and falls were used . SETTING district general hospital outpatient department . SUBJECTS 165 women drawn from local accident and emergency departments with a history of fracture of an upper limb in the previous 2 years . Women were r and omly allocated to intervention ( self-paced brisk walking ) or placebo ( upper limb exercises ) groups . INTERVENTION both groups were seen at 3-monthly intervals to assess progress , measure physical capacity and maintain enthusiasm . The brisk-walking group were instructed to progressively increase the amount and speed of walking in a manner that suited them . The upper limb exercise placebo group were asked to carry out a series of exercises design ed to improve flexibility and fine h and movements , appropriate for a past history of upper limb fracture . RESULTS drop-outs from both intervention and placebo groups were substantial ( 41 % ) , although there were no significant differences in bone mineral density , physical capacity or health status between drop-outs and participants . At 2 years , among those completing the trial , bone mineral density at the femoral neck had fallen in the placebo group to a greater extent than in the brisk-walking group [ mean net difference between intervention and placebo groups 0.019 g/cm2 , 95 % confidence interval ( CI ) -0.0026 to + 0.041 g/cm2 , P = 0.056 ] . Lumbar spine bone mineral density had increased to a similar extent ( + 0.017 g/cm2 ) in both groups . The cumulative risk of falls was higher in the brisk-walking group ( excess risk of 15 per 100 person-years , 95 % CI 1.4 - 29 per 100 person-years , P < 0.05 ) . There were no significant differences in clinical or spinal x-ray fracture risk or self-rated health status between intervention and placebo groups . CONCLUSION the promotion of exercise through brisk-walking advice given by nursing staff may have a small , but clinical ly important , impact on bone mineral density but is associated with an increased risk of falls . Self-paced brisk walking is difficult to evaluate in r and omized controlled trials because of drop-outs , placebo group exercise , limited compliance and lack of st and ardization of the duration and intensity of walking . Further work is needed to evaluate the best means of safely achieving increased activity levels in different groups , such as older women and those at high risk of fractures BACKGROUND The study tested the effect of strength and endurance training on gait , balance , physical health status , fall risk , and health services use in older adults . METHODS The study was a single-blinded , r and omized controlled trial with intention-to-treat analysis . Adults ( n = 105 ) age 68 - 85 with at least mild deficits in strength and balance were selected from a r and om sample of enrollees in a health maintenance organization . The intervention was supervised exercise ( 1-h sessions , three per week , for 24 - 26 weeks ) , followed by self-supervised exercise . Exercise groups included strength training using weight machines ( n = 25 ) , endurance training using bicycles ( n = 25 ) , and strength and endurance training ( n = 25 ) . Study outcomes included gait tests , balance tests , physical health status measures , self-reported falls ( up to 25 months of follow-up ) , and inpatient and outpatient use and costs . RESULTS There were no effects of exercise on gait , balance , or physical health status . Exercise had a protective effect on risk of falling ( relative hazard = .53 , 95 % CI = .30-.91 ) . Between 7 and 18 months after r and omization , control subjects had more outpatient clinic visits ( p < .06 ) and were more likely to sustain hospital costs over $ 5000 ( p < .05 ) . CONCLUSIONS Exercise may have beneficial effects on fall rates and health care use in some subgroups of older adults . In community-living adults with mainly mild impairments in gait , balance , and physical health status , short-term exercise may not have a restorative effect on these impairments Abstract Objective : To assess the effectiveness of a home exercise programme of strength and balance retraining exercises in reducing falls and injuries in elderly women . Design : R and omised controlled trial of an individually tailored programme of physical therapy in the home ( exercise group , n=116 ) compared with the usual care and an equal number of social visits ( control group , n=117 ) . Setting : 17 general practice s in Dunedin , New Zeal and . Subjects : Women aged 80 years and older living in the community and registered with a general practice in Dunedin . Main outcome measures : Number of falls and injuries related to falls and time between falls during one year of follow up ; changes in muscle strength and balance measures after six months . Results : After one year there were 152 falls in the control group and 88 falls in the exercise group . The mean ( SD ) rate of falls was lower in the exercise than the control group ( 0.87 ( 1.29 ) v 1.34 ( 1.93 ) falls per year respectively ; difference 0.47 ; 95 % confidence interval 0.04 to 0.90 ) . The relative hazard for the first four falls in the exercise group compared with the control group was 0.68 ( 0.52 to 0.90 ) . The relative hazard for a first fall with injury in the exercise group compared with the control group was 0.61 ( 0.39 to 0.97 ) . After six months , balance had improved in the exercise group ( difference between groups in change in balance score 0.43 ( 0.21 to 0.65 ) . Conclusions : An individual programme of strength and balance retraining exercises improved physical function and was effective in reducing falls and injuries in women 80 years and older . Key messages Modifiable risk factors for falls in elderly people have been well defined ; they include loss of muscle strength and impaired balance A programme to improve strength and balance in women aged 80 years and older can be set up safely with four home visits from a physiotherapist This programme reduced falls and moderate injuries appreciably over the subsequent year in Dunedin , New Zeal and The benefit was most noticeable in elderly people who fell OBJECTIVES To determine whether an intervention that combines low-intensity exercise and incontinence care offsets some of its costs by reducing the incidence of selected health conditions in nursing home residents . DESIGN R and omized , controlled trial with the incidence and costs of selected , acute conditions compared between a 6-month baseline and an 8-month intervention phase . SETTING Four nursing homes . PARTICIPANTS One hundred ninety incontinent , long-stay nursing home residents . INTERVENTION Low-intensity , functionally oriented exercise and incontinence care were provided every 2 hours from 8:00 a.m. to 4:00 p.m. for 5 days a week for 8 months . MEASUREMENTS Predefined acute conditions hypothesized to be related to physical inactivity , incontinence , or immobility were abstract ed from residents ' medical records by blinded observers during a 6-month baseline period and throughout the 8-month intervention . Conditions included those in the dermatological , genitourinary , gastrointestinal , respiratory and cardiovascular systems ; falls ; pain ; and psychiatric and nutritional disturbances . Costs were determined using Current Procedural Terminology Center and Medicare allowable cost reimbursement at a rate of 80 % . RESULTS The intervention group had significantly better functional outcomes than the control group ( strength , mobility endurance , urinary and fecal incontinence ) and a reduction of 10 % in the incidence of the acute conditions , which was not significant . There were no significant differences between groups in the cost of assessing and treating these acute conditions between baseline and intervention . CONCLUSION The intervention , which is consistent with federal and clinical practice guidelines , significantly improved functional outcomes but did not reduce the incidence and costs of selected acute health conditions . The cost of implementing these labor-intensive interventions for frail nursing home residents will have to be justified based on functional and quality -of-life outcomes and are unlikely to be offset by savings in medical care costs in this population OBJECTIVE To determine whether a 12-month program of regular exercise can improve balance , reaction time , neuromuscular control , and muscle strength and reduce the rate of falling in older women . DESIGN A r and omized , controlled trial of 12 months duration . SETTING Conducted as part of the R and wick Falls and Fractures Study in Sydney , Australia . PARTICIPANTS One hundred ninety-seven women aged 60 to 85 years ( mean age 71.6 , SD = 5.4 ) who were r and omly recruited from the community . OUTCOME MEASURES Accidental falls , postural sway , reaction time , neuromuscular control , and lower limb muscle strength . MAIN RESULTS Exercise and control subjects were tested before , midway through , and at the end of the trial . At initial testing , exercisers and controls performed similarly in all tests and were well matched in relevant health and lifestyle factors . The mean number of classes attended for the 75 exercise subjects who completed the program was 60.0 ( range 26 - 82 ) . At the end of the trial , the exercise subjects showed improved performance in all five strength measures , in reaction time , neuromuscular control , body sway on a firm surface with the eyes open , and body sway on a compliant surface with the eyes open and closed . In contrast , there were no significant improvements in any of the test measures in the controls . In one test measure , hip flexion strength , the exercisers showed continued improvement throughout the study year . There was no significant difference in the proportion of fallers between the exercise and control subjects . Interesting trends were evident , however , between falls frequency and adherence to the exercise program . CONCLUSIONS These findings show that exercise can produce long-term benefits with regard to improving sensorimotor function in older persons . The findings also suggest that high compliance to an exercise program may reduce falls frequency , although further studies are required to conclusively demonstrate that exercise offers an effective means of preventing falls Means KM , Rodell DE , O’Sullivan PS : Balance , mobility , and falls among community-dwelling elderly persons : Effects of a rehabilitation exercise program . Am J Phys Med Rehabil 2005;84:238–250 . Objective : To assess the short-term effect of an exercise-based rehabilitation intervention on balance , mobility , falls and injuries . Design : This r and omized , controlled trial with repeated measures was performed at an outpatient rehabilitation center . Elderly , ambulatory , community-dwelling volunteers underwent 6 wks of supervised stretching , balance , endurance , coordination , and strengthening exercises . Controls attended seminars . Data were recorded for time and quality performance on a functional obstacle course and for self-reported falls and injuries . Results : From baseline through 6-mo follow-up , participants in the exercise group ( n = 122 ) significantly outperformed those in the control group ( n = 83 ) . The exercise group ’s functional obstacle course quality improved 2.3 % postintervention and 1.57 % at follow-up compared with 0.3 % for the control group for each time period ( P = 0.001 ) . Functional obstacle course completion time improved 7.69 % at postintervention and 8.35 % at follow-up for the exercise group compared with 4.0 % and 3.4 % for the control group . Of baseline fallers in the intervention group , 87 % ( compared with 34.5 % for the controls ) reported no falls in the subsequent 6 mos . Of those reporting injuries in the 6 mos preintervention , 89.7 % in the intervention group ( compared with 55.6 % for controls ) reported no injury at 6 mos postintervention . Conclusions : Our intervention can improve functional performance and protect against falls and fall-related injuries OBJECTIVES To compare the effectiveness of group resistance and agility-training programs in reducing fall risk in community-dwelling older women with low bone mass . DESIGN A r and omized , controlled , single-blind 25-week prospect i ve study with assessment s at baseline , midpoint , and trial completion . SETTING Community center . PARTICIPANTS Community-dwelling women aged 75 to 85 with low bone mass . INTERVENTION Participants were r and omly assigned to one of three groups : resistance training ( n=32 ) , agility training ( n=34 ) , and stretching ( sham ) exercises ( n=32 ) . The exercise classes for each study arm were held twice weekly . MEASUREMENTS The primary outcome measure was fall risk ( derived from weighted scores from tests of postural sway , reaction time , strength , proprioception , and vision ) , as measured using a Physiological Profile Assessment ( PPA ) . Secondary outcome measures were ankle dorsiflexion strength , foot reaction time , and Community Balance and Mobility Scale score . RESULTS Attendance at the exercise sessions for all three groups was excellent : resistance training ( 85.4 % ) , agility training ( 87.3 % ) , and stretching program ( 78.8 % ) . At the end of the trial , PPA fall-risk scores were reduced by 57.3 % and 47.5 % in the resistance and agility-training groups , respectively , but by only 20.2 % in the stretching group . In the resistance and agility groups , the reduction in fall risk was mediated primarily by improved postural stability , where sway was reduced by 30.6 % and 29.2 % , respectively . There were no significant differences between the groups for the secondary outcomes measures . Within the resistance-training group , reductions in sway were significantly associated with improved strength , as assessed using increased squat load used in the exercise sessions . CONCLUSION These findings support the implementation of community-based resistance and agility-training programs to reduce fall risk in older women with low bone mass . Such programs may have particular public health benefits because it has been shown that this group is at increased risk of falling and sustaining fall-related fractures Evidence of the effect of exercise on bone loss comes mainly from studies in voluntary postmenopausal women , and no population -based , long-term interventions have been performed . The purpose of this population -based , r and omized , controlled trial was to determine the effect of long-term impact exercise on bone mass at various skeletal sites in elderly women with low bone mineral density ( BMD ) at the radius and hip . Participants ( n = 160 ) were r and omly assigned to 30 months either of supervised and home-based impact exercise training or of no intervention . The primary outcome measures were femoral neck , trochanter and total hip BMD , and the secondary outcomes were bone density measures at the radius and calcaneum . Outcomes were assessed at baseline , 12 months and 30 months using blinded operators . The analyses were performed on an intention-to-treat analysis . Mean femoral neck and trochanter BMD decreased in the control group [ −1.1 % , 95 % confidence interval ( CI ) −0.1 % to −2.1 % and −1.6 % , 95 % CI −0.4 % to −2.7 % ] , while no change occurred in the exercise group . Mean trochanter BMC decreased more in the control group ( −7.7 % , 95 % CI −9.7 % to −5.6 % vs. −2.9 % , 95 % CI −5.3 to −0.9 ) . There were six falls that result ed in fractures in the exercise group and 16 in the control group during the 30-month intervention ( P = 0.019 ) . A significant bone loss occurred in both groups at the radius and calcaneum . In multivariate analysis , weight gain was associated with increased BMD and BMC at all femur sites both in the exercise group and in the pooled groups . In conclusion , impact exercise had no effect on BMD , while there was a positive effect on BMC at the trochanter . Exercise may prevent fall-related fractures in elderly women with low bone mass Seven hundred and four women aged between 65 and 99 years ( mean age 74.6 years ) , who were r and omly selected from the community , took part in a study to determine whether health and lifestyle factors were associated with falls . In the 12 months before the survey , 66.1 per cent of the subjects experienced no falls , 19.7 per cent fell once and 14.2 per cent fell on two or more occasions . The proportion of women who fell outside the home decreased with age , with a corresponding increase in the proportion who fell inside the home on a level surface . The most common causes of falls reported were trips , slips and loss of balance . Some ( 27 per cent ) suffered injuries as a result of a fall , and the proportion suffering injuries increased with age . Those who rated their health and balance as impaired , those with a limitation in activities of daily living , those receiving community services , those taking psychoactive drugs , and those taking four or more drugs had significantly more falls . On the other h and , those taking part in planned exercise and those active for seven or more hours per week had fewer falls . Smoking and alcohol consumption were not significantly associated with falls . Stepwise logistic regression analysis revealed poor vision , inactivity and subjective fall risk as variables that were independently and significantly associated with falling . These findings highlight possible intervention strategies for reducing falls risk in older people Abstract Objectives To assess the efficacy and cost effectiveness of a home safety programme and a home exercise programme to reduce falls and injuries in older people with low vision . Design R and omised controlled trial . Setting Dunedin and Auckl and , New Zeal and . Participants 391 women and men aged ≥(1 ) 75 with visual acuity of 6/24 or worse who were living in the community ; 92 % ( 361 of 391 ) completed one year of follow-up . Interventions Participants received a home safety assessment and modification programme delivered by an occupational therapist ( n = 100 ) , an exercise programme prescribed at home by a physiotherapist plus vitamin D supplementation ( n = 97 ) , both interventions ( n = 98 ) , or social visits ( n = 96 ) . Main outcome measures Numbers of falls and injuries result ing from falls , costs of implementing the home safety programme . Results Fewer falls occurred in the group r and omised to the home safety programme but not in the exercise programme ( incidence rate ratios 0.59 ( 95 % confidence interval 0.42 to 0.83 ) and 1.15 ( 0.82 to 1.61 ) , respectively ) . However , within the exercise programme , stricter adherence was associated with fewer falls ( P = 0.001 ) . A conservative analysis showed neither intervention was effective in reducing injuries from falls . Delivering the home safety programme cost $ NZ650 ( £ 234 , 344 euros , $ US432 ) ( at 2004 prices ) per fall prevented . Conclusion The home safety programme reduced falls and was more cost effective than an exercise programme in this group of elderly people with poor vision . The Otago exercise programme with vitamin D supplementation was not effective in reducing falls or injuries in this group , possibly due to low levels of adherence . Trial registration number IS RCT N15342873 BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . Objective : This paper provides intraclass correlation coefficients ( ICCs ) for estimation of sample size inflation required in future cluster r and omised trials in primary or residential care OBJECTIVES To determine whether an intense tai chi ( TC ) exercise program could reduce the risk of falls more than a wellness education ( WE ) program in older adults meeting criteria for transitioning to frailty . DESIGN R and omized , controlled trial of 48 weeks duration . SETTING Twenty congregate living facilities in the greater Atlanta area . PARTICIPANTS Sample of 291 women and 20 men aged 70 to 97 . MEASUREMENTS Demographics , time to first fall and all subsequent falls , functional measures , Sickness Impact Profile , Centers for Epidemiologic Studies -Depression Scale , Activities-specific Balance Confidence Scale , Falls Efficacy Scales , and adherence to interventions . RESULTS The risk ratio ( RR ) of falling was not statistically different in the TC group and the WE group ( RR=0.75 , 95 % confidence interval (CI)=0.52 - 1.08 ) , P=.13 ) . Over the 48 weeks of intervention , 46 % ( n=132 ) of the participants did not fall ; the percentage of participants that fell at least once was 47.6 % for the TC group and 60.3 % for the WE group . CONCLUSION TC did not reduce the RR of falling in transitionally frail , older adults , but the direction of effect observed in this study , together with positive findings seen previously in more-robust older adults , suggests that TC may be clinical ly important and should be evaluated further in this high-risk population OBJECTIVES To assess the effectiveness of an intervention planned and implemented by regional geriatric care teams in order to prevent falls in an elderly population . METHODS The study was conducted among 555 ( 67 % ) home-dwelling Finnish persons aged 85 years or older of a representative population sample ( N=827 ) in 2000 - 2003 . Altogether 486 subjects ( 88 % ) had a history of recurrent falls or at least one risk factor for disability in the activities of daily living or mobility and were r and omly assigned to receive suggestions for a programme consisting of home exercise , walking exercise , group activities or self-care exercise or alternatively routine care . Falls were monitored for a median of 16 months during the intervention . RESULTS The time to first four falls and all falls did not significantly differ in the targeted intervention group ( N=217 ) ; compared to controls ( N=220 ) , hazard ratio 0.88 ( 95 % CI 0.74 to 1.04 ) and 0.93 ( 0.80 - 1.09 ) , respectively . Among those able to move outdoors , the corresponding hazard ratios in the intervention group ( N=168 ) compared to the controls ( N=178 ) were 0.78 ( 0.64 - 0.94 ) and 0.88 ( 0.74 - 1.05 ) . After the intervention period , impaired balance was less common in the intervention than in the control subjects ; 64 ( 45 % ) and 89 ( 59 % ) ( p<0.05 ) . CONCLUSIONS A pragmatic intervention was not effective in reducing the falling risk at the population level , but slowed down the reduction of balance performance . Among those able to move outdoors , the intervention was also effective in reducing the risk of first four falls OBJECTIVES To determine whether a 12-month program of group exercise can improve physical functioning and reduce the rate of falling in frail older people . DESIGN Cluster r and omized , controlled trial of 12 months duration . SETTING Retirement villages in Sydney and Wollongong , Australia . PARTICIPANTS Five hundred fifty-one people aged 62 to 95 ( mean+/-st and ard deviation=79.5+/-6.4 ) who were living in self- and intermediate-care retirement villages . MEASUREMENTS Accidental falls , choice stepping reaction time , 6-minute walk distance postural sway , leaning balance , simple reaction time , and lower-limb muscle strength . RESULTS Two hundred eighty subjects were r and omized to the weight-bearing group exercise ( GE ) intervention that was design ed to improve the ability of subjects to undertake activities for daily living . Subjects r and omized to the control arm ( n=271 ) attended flexibility and relaxation ( FR ) classes ( n=90 ) or did not participate in a group activity ( n=181 ) . In spite of the reduced precision of cluster r and omization , there were few differences in the baseline characteristics of the GE and combined control ( CC ) subjects , although the mean age of the GE group was higher than that of the CC group , and there were fewer men in the GE group . The mean number of classes attended was 39.4+/-28.7 for the GE subjects and 31.5+/-25.2 for the FR subjects . After adjusting for age and sex , there were 22 % fewer falls during the trial in the GE group than in the CC group ( incident rate ratio=0.78 , 95 % confidence interval (CI)=0.62 - 0.99 ) , and 31 % fewer falls in the 173 subjects who had fallen in the past year ( incident rate ratio=0.69 , 95 % CI=0.48 - 0.99 ) . At 6-month retest , the GE group performed significantly better than the CC group in tests of choice stepping reaction time , 6-minute walking distance , and simple reaction time requiring a h and press . The groups did not differ at retest in tests of strength , sway , or leaning balance . CONCLUSION These findings show that group exercise can prevent falls and maintain physical functioning in frail older people The purpose of this research was to explore the role of exercise in preventing falls , specifically assessing the effectiveness of an ankle strengthening and walking program to improve balance , ankle strength , walking speed , and falls efficacy and to decrease falls and subjects ' fear of falling . Sixteen individuals participated in the study which was conducted at two nursing homes . Subjects were assigned r and omly to an intervention or control group . The participants in the intervention group completed a 3-month supervised program of ankle strengthening exercises and walking . Descriptive statistics were used to characterize the sample , and differences in the least square means were used to assess the outcome variables ( i.e. , balance , ankle strength , walking speed , falls , fear of falling , falls efficacy ) before the exercise program , and again at 3 months and 6 months after the program for the intervention and control subjects . Findings for the intervention group from pretest to 3-month posttest were , for the most part , maintained or in the predicted direction , suggesting that regular exercise shows promise for preventing deterioration and improving fall-related outcomes for elderly nursing home residents Studies of the effects of different exercise programmes on bone in postmenopausal women have produced different conclusions , but few have targeted elderly women specifically.1 We report a controlled trial of weight bearing exercise in this clinical ly important population . The study was approved by the local ethics committee . We recruited volunteers by advertising in the local press . After excluding subjects with conditions or drug treatment likely to affect bone , we r and omly allocated 118 volunteers ( mean age 64.5 ( range 60 - 73 ) years ) to either a group taking calcium supplementation ( 1000 mg calcium daily , as calcium carbonate ) or to an exercise group taking the same calcium supplementation . We monitored compliance with calcium by a tablet count every six months . We asked volunteers in the calcium group taking exercise to attend the University of Dundee 's exercise class for people aged over 60 three times weekly for each of three 10 Background The aim of this study was to assess the effectiveness of the unipedal st and ing balance exercise for 1 min to prevent falls and hip fractures in high-risk elderly individuals with a r and omized controlled trial . This control study was design ed as a 6-month intervention trial . SubjectsSubjects included 553 clinical ly defined high-risk adults who were living in residences or in the community . They were r and omized to an exercise group and a control group . Methods R and omization to the subjects was performed by a table of r and om numbers . A unipedal st and ing balance exercise with open eyes was performed by st and ing on each leg for 1 min three times per day . As a rule , subjects of the exercise group stood on one leg without holding onto any support , but unstable subjects were permitted to hold onto a bar during the exercise time . Falls and hip fractures were reported by nurses , physical therapists , or facility staff with a survey sheet every month . This survey sheet was required every month for both groups . Results Registered subjects were 553 persons ranging in age from 37 to 102 years ( average , 81.6 years of age ) . Twenty-six subjects dropped out . The number of falls and hip fractures for the 6-month period after the trial for 527 of the 553 subjects for whom related data were available were assessed . The exercise group comprised 315 subjects and the control group included 212 subjects . The cumulative number of falls of the exercise group , with 1 multiple faller omitted , was 118 , and the control group recorded 121 falls . A significant intergroup difference was observed . However , the cumulative number of hip fractures was only 1 case in both groups . This difference was not statistically significant . Conclusions The unipedal st and ing balance exercise is effective to prevent falls but was not shown to be statistically significant in the prevention of hip fracture in this study OBJECTIVES To determine the effectiveness of vitamin D and home-based quadriceps resistance exercise on reducing falls and improving the physical health of frail older people after hospital discharge . DESIGN Multicenter , r and omized , controlled trial with a factorial design . SETTING Five hospitals in Auckl and , New Zeal and , and Sydney , Australia . PARTICIPANTS Two hundred forty-three frail older people . INTERVENTIONS Patients were r and omized to receive a single dose of vitamin D ( calciferol , 300,000 IU ) or placebo tablets and 10 weeks of high-intensity home-based quadriceps resistance exercise or frequency-matched visits . MEASUREMENTS The primary endpoints were physical health according to the short-form health survey at 3 months and falls over 6 months . Physical performance and self-rated function were secondary endpoints . Assessment s took place in the participants ' homes at 3 and 6 months after r and omization and were performed by blinded assessors . RESULTS There was no effect of either intervention on physical health or falls , but patients in the exercise group were at increased risk of musculoskeletal injury ( risk ratio = 3.6 , 95 % confidence interval = 1.5 - 8.0 ) . Vitamin D supplementation did not improve physical performance , even in those who were vitamin D deficient ( < 12 ng/mL ) at baseline . CONCLUSION Neither vitamin D supplementation nor a home-based program of high-intensity quadriceps resistance exercise improved rehabilitation outcomes in frail older people after hospitalization . There was no effect of vitamin D on physical performance , and the exercises increased the risk of musculoskeletal injury . These findings do not support the routine use of these interventions at these dosages in the rehabilitation of frail older people Abstract Objectives : To assess the effectiveness of a trained district nurse individually prescribing a home based exercise programme to reduce falls and injuries in elderly people and to estimate the cost effectiveness of the programme . Design : R and omised controlled trial with one year 's follow up . Setting : Community health service at a New Zeal and hospital . Participants : 240 women and men aged 75 years and older . Intervention : 121 participants received the exercise programme ( exercise group ) and 119 received usual care ( control group ) ; 90 % ( 211 of 233 ) completed the trial . Main outcome measures : Number of falls , number of injuries result ing from falls , costs of implementing the programme , and hospital costs as a result of falls . Results : Falls were reduced by 46 % ( incidence rate ratio 0.54 , 95 % confidence interval 0.32 to 0.90 ) . Five hospital admissions were due to injuries caused by falls in the control group and none in the exercise group . The programme cost $ NZ1803 ( £ 523 ) ( at 1998 prices ) per fall prevented for delivering the programme and $ NZ155 per fall prevented when hospital costs averted were considered . Conclusion : A home exercise programme , previously shown to be successful when delivered by a physiotherapist , was also effective in reducing falls when delivered by a trained nurse from within a home health service . Serious injuries and hospital admissions due to falls were also reduced . The programme was cost effective in participants aged 80 years and older compared with younger participants BACKGROUND to develop a physical training programme to improve balance in dependent , demented , people with a history of falling , and so decrease falls and increase autonomy . METHODS the study was undertaken on 20 demented elderly people with a history of falling with an average age of 81.4+/-4.7 years and an average mini mental state score of 16.3+/-6.5 . They had all passed ' get up and go ' , ' chair sit and reach ' , walking speed and static balance tests . They were assigned to a control group or a training group ; the latter were trained with two sessions a week for 16 weeks . RESULTS walking , mobility , flexibility and static balance were significantly improved in the training group ( P<0.05 ) , but not in the controls . The trained subjects did not suffer a relapse , while the controls did during the training period . CONCLUSION the balance of frail , demented , elderly patients with a history of falling can be improved by training The purpose of this study was to test the feasibility of the WALC intervention ( Walk ; Address pain , fear , fatigue during exercise ; Learn about exercise ; Cue by self-modeling ) , and determine its effects on self-efficacy and outcome expectations , exercise activity and free living activity , physical and mental health status , and falls and fall-related injuries . A total of 17 sedentary older women with a mean age of 88 + /- 3.7 years were r and omly assigned to receive either the WALC intervention or routine care . Ninety percent of those in the treatment group initiated and engaged in a regular exercise program during the 6 months of the study . There was a statistically significant difference in self-efficacy expectations , exercise behavior , and overall activity between the two groups . Those in the treatment group had stronger self-efficacy expectations related to exercise ; engaged in more exercise and more free living activity ; and although not statistically significant , had stronger outcome expectations following exposure to the WALC intervention when compared with those who received routine care . To help older adults initiate and adhere to an exercise program , nurses can easily implement the WALC intervention in a variety of setting Falls are common in elderly people . Possible consequences include serious injuries and the post-fall syndrome , with functional decline and limitation of physical activity . The present r and omized controlled study sought to clarify the benefits of a combined long-term and home-based fall prevention program for elderly Japanese women . The subjects were individuals aged over 73 years , living at home in a western suburb of Tokyo , who had attended a comprehensive geriatric health check . Persons with a marked decline in the basic activities of daily living ( ADL ) , hemiplegia , or those missing baseline data were excluded . Fifty-two subjects who expressed a wish to participate in the trial were r and omized , 28 to an exercise-intervention group and 24 to a control group . Baseline data for age , h and grip force , walking speed , total serum cholesterol , serum albumin , basic ADL , visual and auditory impairments , self-rated health , and experience of falls did not differ significantly between the two groups . Beginning from June 2000 , the intervention group attended a 6-month program of fall-prevention exercise classes aim ed at improving leg strength , balance , and walking ability ; this was supplemented by a home-based exercise program that focused on leg strength . The control group received only a pamphlet and advice on fall prevention . The average rate of attendance at exercise class was 75.3 % ( range , 64 % to 86 % ) . Participants showed significant improvements in t and em walk and functional reach after the intervention program , with enhanced self confidence . At the 8-month follow-up , the proportion of women with falls was 13.6 % ( 3/22 ) in the intervention group and 40.9 % ( 9/22 ) in the control group . At 20 months , the proportion remained unchanged , at 13.6 % in the intervention group , but had increased to 54.5 % ( 12/22 ) in the control group , which showed a statistically significant difference between the two groups ( Fisher ’s exact test ; P = 0.0097 ) . The total number of falls during the 20-month follow-up period was 6 in the intervention group and 17 in the control group . We conclude that a moderate exercise intervention program plus a home-based program significantly decreases the incidence of falls in both the short and the long term , contributing to improved health and quality of life in the elderly |
622 | 18,658,035 | RESULTS Although the mechanisms of protection for both therapeutic strategies are multifold , both share features of downregulating metabolism . | BACKGROUND AND PURPOSE The search for effective neuroprotectants remains frustrating , particularly with regard to specific pharmaceuticals .
However , laboratory studies have consistently shown remarkable neuroprotection with 2 nonpharmacological strategies-therapeutic hypothermia and ischemic preconditioning .
Recent studies have shown that the mechanism of protection underlying both of these treatments is correlated to downregulation of cellular and tissue metabolism .
Thus , underst and ing the mechanisms underlying such robust protective effects could lead to appropriate translation at the clinical level .
In fact , hypothermia is already being used at many centers to improve neurological outcome from cardiac arrest . | BACKGROUND Induction of hypothermia in patients with brain injury was shown to improve outcomes in small clinical studies , but the results were not definitive . To study this issue , we conducted a multicenter trial comparing the effects of hypothermia with those of normothermia in patients with acute brain injury . METHODS The study subjects were 392 patients 16 to 65 years of age with coma after sustaining closed head injuries who were r and omly assigned to be treated with hypothermia ( body temperature , 33 degrees C ) , which was initiated within 6 hours after injury and maintained for 48 hours by means of surface cooling , or normothermia . All patients otherwise received st and ard treatment . The primary outcome measure was functional status six months after the injury . RESULTS The mean age of the patients and the type and severity of injury in the two treatment groups were similar . The mean ( + /-SD ) time from injury to r and omization was 4.3+/-1.1 hours in the hypothermia group and 4.1+/-1.2 hours in the normothermia group , and the mean time from injury to the achievement of the target temperature of 33 degrees C in the hypothermia group was 8.4+/-3.0 hours . The outcome was poor ( defined as severe disability , a vegetative state , or death ) in 57 percent of the patients in both groups . Mortality was 28 percent in the hypothermia group and 27 percent in the normothermia group ( P=0.79 ) . The patients in the hypothermia group had more hospital days with complications than the patients in the normothermia group . Fewer patients in the hypothermia group had high intracranial pressure than in the normothermia group . CONCLUSIONS Treatment with hypothermia , with the body temperature reaching 33 degrees C within eight hours after injury , is not effective in improving outcomes in patients with severe brain injury BACKGROUND Cardiac arrest with widespread cerebral ischemia frequently leads to severe neurologic impairment . We studied whether mild systemic hypothermia increases the rate of neurologic recovery after resuscitation from cardiac arrest due to ventricular fibrillation . METHODS In this multicenter trial with blinded assessment of the outcome , patients who had been resuscitated after cardiac arrest due to ventricular fibrillation were r and omly assigned to undergo therapeutic hypothermia ( target temperature , 32 degrees C to 34 degrees C , measured in the bladder ) over a period of 24 hours or to receive st and ard treatment with normothermia . The primary end point was a favorable neurologic outcome within six months after cardiac arrest ; secondary end points were mortality within six months and the rate of complications within seven days . RESULTS Seventy-five of the 136 patients in the hypothermia group for whom data were available ( 55 percent ) had a favorable neurologic outcome ( cerebral-performance category , 1 [ good recovery ] or 2 [ moderate disability ] ) , as compared with 54 of 137 ( 39 percent ) in the normothermia group ( risk ratio , 1.40 ; 95 percent confidence interval , 1.08 to 1.81 ) . Mortality at six months was 41 percent in the hypothermia group ( 56 of 137 patients died ) , as compared with 55 percent in the normothermia group ( 76 of 138 patients ; risk ratio , 0.74 ; 95 percent confidence interval , 0.58 to 0.95 ) . The complication rate did not differ significantly between the two groups . CONCLUSIONS In patients who have been successfully resuscitated after cardiac arrest due to ventricular fibrillation , therapeutic mild hypothermia increased the rate of a favorable neurologic outcome and reduced mortality Background and Purpose — We undertook this study to evaluate the feasibility of inducing and maintaining moderate hypothermia with the use of endovascular rather than surface cooling . Methods — Six patients with severe acute ischemic stroke were treated with moderate hypothermia . This was induced and maintained by circulating temperature-adjusted normal saline in a closed-loop system entailing 3 balloons located near the tip of a central line , which dwelled in the inferior vena cava . Results — The mean±SD initial temperature of the patients was 37±1 ° C ( range , 35.5 ° C to 38.4 ° C ) . The pace of cooling was 1.4±0.6 ° C/h , and target temperature was reached after 3±1 hours ( range , 2 to 4.5 hours ) . During hypothermia , the maximal temperature observed was 33.4 ° C , and the minimal temperature was 32.2 ° C . Temperature deviations > 0.2 ° C or > 0.3 ° C were observed during 21 % or 10 % of the hours under hypothermia , respectively . Singultus was the only device-related complication encountered . Pulmonary infection , arterial hypotension , bradycardia , arrhythmia , and thrombocytopenia were the most common side effects . Conclusions — Induction and maintenance of hypothermia with an intravenous cooling device are feasible . The safety of this approach remains to be evaluated Objective : To report results of a r and omized pilot clinical feasibility trial of endovascular cooling in patients with ischemic stroke . Methods : Forty patients with ischemic stroke presenting within 12 hours of symptom onset were enrolled in the study . An endovascular cooling device was inserted into the inferior vena cava of those r and omized to hypothermia . A core body temperature of 33 ° C was targeted for 24 hours . All patients underwent clinical assessment and MRI initially , at days 3 to 5 and days 30 to 37 . Results : Eighteen patients were r and omized to hypothermia and 22 to receive st and ard medical management . Thirteen patients reached target temperature in a mean of 77 ± 44 minutes . Most tolerated hypothermia well . Clinical outcomes were similar in both groups . Mean diffusion-weighted imaging ( DWI ) lesion growth in the hypothermia group ( n = 12 ) was 90.0 ± 83.5 % compared with 108.4 ± 142.4 % in the control group ( n = 11 ) ( NS ) . Mean DWI lesion growth in patients who cooled well ( n = 8) was 72.9 ± 95.2 % ( NS ) . Conclusions : Induced moderate hypothermia is feasible using an endovascular cooling device in most patients with acute ischemic stroke . Further studies are needed to determine if hypothermia improves outcome Background and Purpose — Moderate hypothermia decreases ischemic damage in experimental stroke models . This multicenter study was performed to evaluate ( 1 ) the safety and feasibility of moderate hypothermia and ( 2 ) its potential to reduce intracranial hypertension in acute stroke patients . Methods — Fifty prospect i ve patients with cerebral infa rct ion involving at least the complete middle cerebral artery territory treated with moderate hypothermia were evaluated . Hypothermia was induced with the use of cooling blankets as well as alcohol and ice bags within 22±9 hours after stroke onset and maintained for 24 to 72 hours ; subsequently , patients passively rewarmed over a mean duration of 17 hours . Outcome was assessed at 4 weeks and at 3 months . Results — Time required for cooling to < 33 ° C varied from 3.5 to 11 hours . The most frequent complications of hypothermic therapy were thrombocytopenia ( 70 % ) , bradycardia ( 62 % ) , and pneumonia ( 48 % ) . Four patients ( 8 % ) died during hypothermia as a result of severe coagulopathy , cardiac failure , or uncontrollable intracranial hypertension . An additional 15 patients ( 30 % ) died during or after rewarming because of rebound increase in intracranial pressure ( ICP ) and fatal herniation . A shorter ( < 16 hours ) rewarming period was associated with a more pronounced rise of ICP . Elevated ICP values were significantly reduced under hypothermia . Neurological outcome according to the National Institutes of Health Stroke Scale score 4 weeks after stroke was 29 , and Rankin Scale score 3 months after stroke was 2.9 . Conclusions — Moderate hypothermia is feasible in patients with acute stroke , although it is associated with several side effects . Most deaths occur during rewarming as a result of excessive ICP rise . Our preliminary observation that a longer duration of the rewarming period limits the ICP increase remains to be confirmed in future studies Objective : To study the effects of mild hypothermia and associated changes in temperature-corrected PaCO2 ( cPaCO2 ) on intracranial pressure ( ICP ) , mean velocity of the middle cerebral artery ( Vm ) , and venous jugular saturation in O2 ( SjvO2 ) in patients with severe traumatic brain injury (TBI).¶ Design : Prospect i ve , observational study .¶ Setting : Intensive care unit.¶ Patients : Severe TBI patients mechanically ventilated , se date d and paralyzed.¶ Interventions : Twenty patients were subjected to four consecutive periods : ( a ) normocapnia-normothermia ; ( b ) hypocapnia-normothermia , where hypocapnia was induced by an increase in minute volume ; ( c ) hypocapnia-hypothermia , where hypocapnia was induced by hypothermia maintaining the ventilatory setting s constant ; ( d ) normocapnia-hypothermia , where normocapnia was achieved by a decrease in minute volume.¶ Measurements and results : cPaCO2 was 41 ± 8 mmHg in periods 1 and 4 , and 31 ± 7 mmHg in periods 2 and 3 . Core temperature was 37.1 ± 0.8 ° C in periods 1 and 2 , and 34.1 ± 1.1 ° C in periods 3 and 4 . End-tidal CO2 and cPaCO2 values showed no difference between periods 1 and 4 and periods 2 and 3 . ICP and Vm were dependent on cPaCO2 but independent of core temperature values . SjvO2 was related to cPaCO2 and was significantly higher during period 3 than during period 2 ( P < 0.05).¶ Conclusion : The decrease in ICP was similar when hypocapnia was induced by hyperventilation or as a result of hypothermia alone . The relationship between cPaCO2 and ICP might predict variations in ICP during changes in core temperature . Further studies are needed to confirm the cerebral metabolic effects of moderate hypothermia in TBI patients BACKGROUND Cardiac arrest outside the hospital is common and has a poor outcome . Studies in laboratory animals suggest that hypothermia induced shortly after the restoration of spontaneous circulation may improve neurologic outcome , but there have been no conclusive studies in humans . In a r and omized , controlled trial , we compared the effects of moderate hypothermia and normothermia in patients who remained unconscious after resuscitation from out-of-hospital cardiac arrest . METHODS The study subjects were 77 patients who were r and omly assigned to treatment with hypothermia ( with the core body temperature reduced to 33 degrees C within 2 hours after the return of spontaneous circulation and maintained at that temperature for 12 hours ) or normothermia . The primary outcome measure was survival to hospital discharge with sufficiently good neurologic function to be discharged to home or to a rehabilitation facility . RESULTS The demographic characteristics of the patients were similar in the hypothermia and normothermia groups . Twenty-one of the 43 patients treated with hypothermia ( 49 percent ) survived and had a good outcome --that is , they were discharged home or to a rehabilitation facility -- as compared with 9 of the 34 treated with normothermia ( 26 percent , P=0.046 ) . After adjustment for base-line differences in age and time from collapse to the return of spontaneous circulation , the odds ratio for a good outcome with hypothermia as compared with normothermia was 5.25 ( 95 percent confidence interval , 1.47 to 18.76 ; P=0.011 ) . Hypothermia was associated with a lower cardiac index , higher systemic vascular resistance , and hyperglycemia . There was no difference in the frequency of adverse events . CONCLUSIONS Our preliminary observations suggest that treatment with moderate hypothermia appears to improve outcomes in patients with coma after resuscitation from out-of-hospital cardiac arrest Ischaemic preconditioning ( short periods of ischaemia with intermittent reperfusion ) has been shown paradoxically to protect the myocardium from a subsequent longer ischaemic insult . The protection associated with preconditioning is one of the most powerful mechanisms of protection known and has been shown in every animal species investigated . However , there is no direct evidence that ischaemic preconditioning occurs in the human heart . We studied whether it was possible to precondition the human heart in a setting of coronary artery bypass surgery . The measurement of adenosine triphosphate in biopsy specimens was used as our endpoint . We believe that our results are the first to show that it may be possible to precondition and protect the human myocardium with short controlled periods of intermittent ischaemia and reperfusion Background : We hypothesized that previous transient ischemic attack ( TIA ) had a favorable effect on early outcome after acute nonlacunar ischemic stroke . Methods : Data of 1,753 consecutive patients with ischemic stroke collected from a prospect i ve hospital-based stroke registry were studied . A comparison was made of the groups with and without previous TIA . Favorable outcome included spontaneous neurological recovery or grade s 0–2 of the modified Rankin scale at hospital discharge . Results : Previous TIA occurred in 55 ( 11.5 % ) of 484 patients with lacunar stroke and in 166 ( 13.1 % ) of 1,269 patients with nonlacunar stroke . The percentage of nonlacunar ischemic stroke patients with favorable outcome was 21.7 % in those with a history of TIA compared to 15 % without TIA ( p < 0.03 ) . In the lacunar stroke group , differences were not significant . In the multivariate analysis , TIA was an independent predictor of spontaneous in-hospital recovery . Conclusions : Prior TIA was associated with a favorable outcome in nonlacunar ischemic stroke , suggesting a neuroprotective effect of TIA possibly by inducing a phenomenon of ischemic tolerance allowing better recovery from a subsequent ischemic stroke Objective External cooling is commonly used to force induction of mild hypothermia but requires equipment , has a slow onset of action , and must be prolonged to provide permanent neurologic benefits after hypoxic-ischemia . It is unknown whether the method for inducing mild hypothermia affects neurologic outcome after near-drowning . The objective of the study was to induce mild hypothermia with neurotensin analog NT77 or external cooling in a rat model of near-drowning . We hypothesize that NT77 would be more effective for improving neurologic outcome than external cooling of the same duration . Design Rats were r and omized to a normothermic control , neurotensin-induced hypothermia , brief external cooling , or prolonged external cooling group after asphyxial cardiac arrest . Setting Laboratory investigation . SubjectsForty-eight rats . Interventions Mild hypothermia was induced by external cooling for 4 hrs ( brief external cooling ) or 24 hrs ( prolonged external cooling ) or by neurotensin-induced hypothermia administration 30 mins after asphyxial cardiac arrest in rats . Measurements Outcome was assessed by a neurologic deficit score , the Morris water maze , and CA1 hippocampus histology 15 days after resuscitation . Main Results Neurologic deficit score at 72 hrs after asphyxial cardiac arrest was lower with neurotensin-induced hypothermia ( score , 0 ) and prolonged external cooling ( score , 0 ) vs. normothermic control ( score , 20 ) and brief external cooling ( score , 18 ; p < .05 ) . Latency time in the Morris water maze 15 days after asphyxial cardiac arrest was decreased with neurotensin-induced hypothermia ( 14 ± 11 secs ) and prolonged external cooling ( 18 ± 9 secs ) vs. normothermic control ( 74 ± 17 secs ) and brief external cooling ( 78 ± 18 secs , p < .05 ) . There was less ischemic neuronal damage with neurotensin-induced hypothermia ( 28 ± 24 % ) and prolonged external cooling ( 21 ± 14 % ) vs. normothermic control ( 61 ± 32 % ) and brief external cooling ( 51 ± 32 % ) . Conclusions Neurotensin-induced hypothermia improved neurologic outcome after asphyxial cardiac arrest in rats vs. brief external cooling but was comparable to prolonged external cooling |
623 | 19,370,695 | The studies demonstrated an initial improvement in respiratory status ( improved oxygenation and decreased need for ventilator support ) .
AUTHORS ' CONCLUSIONS Infants with established respiratory distress syndrome who receive animal derived surfactant extract treatment have a decreased risk of pneumothorax , a decreased risk of pulmonary interstitial emphysema , a decreased risk of mortality , and a decreased risk of bronchopulmonary dysplasia or death | BACKGROUND Respiratory distress syndrome ( RDS ) is caused by a deficiency or dysfunction of pulmonary surfactant .
A wide variety of surfactant products have been formulated and studied in clinical trials .
These include synthetic surfactants and animal derived surfactant extracts .
Trials of surfactant replacement have either tried to prevent the development of respiratory distress in high-risk premature infants or treat established respiratory distress in premature infants .
OBJECTIVES To assess the effect of administration of animal derived surfactant extract on mortality , chronic lung disease and other morbidities associated with prematurity in preterm infants with established respiratory distress syndrome . | We performed a r and omized , prospect i ve clinical trial comparing intratracheal administration of human surfactant with conventional treatment with intermittent m and atory mechanical ventilation alone for treatment of severe respiratory distress syndrome in preterm infants of less than 30 weeks gestation . Twenty-two infants ( mean gestational age 27.0 weeks , mean birth weight 987 gm ) were given surfactant , and 23 infants ( mean gestational age 27.2 week , mean birth weight 1055 gm ) received intermittent m and atory ventilation . Infants given surfactant required less FiO2 during the first week , had lower mean airway pressure during the first 48 hours , and had improved ventilatory index and a/A PO2 ratio . Death or the occurrence of bronchopulmonary dysplasia was significantly less among infants given surfactant ( P = 0.019 ) . Pneumothorax , pulmonary interstitial emphysema , and need for FiO2 greater than or equal to 0.3 for greater than 30 days was significantly less in the surfactant group . This trial confirms the efficacy of treatment with human surfactant in preterm infants with severe respiratory distress syndrome We carried out a multicenter r and omized , placebo-controlled trial to evaluate the efficacy and safety of surfactant in the treatment of respiratory distress syndrome . The study population was made up of newborn infants weighing 750 to 1750 g who were receiving assisted ventilation with 40 percent or more oxygen . The eligible infants received a single dose of either surfactant ( 100 mg of phospholipid per kilogram of body weight [ 4 ml per kilogram ] ) or an air placebo ( 4 ml per kilogram ) , administered into the trachea within eight hours of birth by an investigator not involved in the clinical care of the infant . When compared with the infants who received the placebo ( n = 81 ) , the infants who were treated with surfactant ( n = 78 ) had a 0.12 greater average increase in the ratio of arterial to alveolar oxygen tension ( P less than 0.0001 ) , a 0.20 greater average decrease in the fractional inspiratory oxygen concentration ( P less than 0.0001 ) , and a 0.26-kPa greater average decrease in the mean airway pressure ( P less than 0.0001 ) during the 72 hours after treatment . Pneumothorax was less frequent among the infants treated with surfactant than in the control group ( 13 percent vs. 37 percent ; P = 0.0005 ) . There were no statistically significant differences between the groups in the proportion of infants in each of five ordered clinical -status categories on day 7 ( P = 0.08 ) or day 28 ( P = 0.75 ) after treatment . There were also no significant differences between the groups in the frequency of bronchopulmonary dysplasia , patent ductus arteriosus , necrotizing enterocolitis , or periventricular-intraventricular hemorrhage . In each group , 17 percent of the infants died by day 28 . We conclude that treatment with the single-dose surfactant regimen used in this study reduces the severity of respiratory distress during the 72 hours after treatment and decreases the frequency of pneumothorax , but that it does not significantly improve clinical status later in the neonatal period and does not reduce neonatal mortality . Further study of different surfactant regimens and patient- selection criteria will be required to determine whether this initial improvement can be translated into reductions in mortality or serious morbidity In a double-blind clinical trial the effects of a single dose of reconstituted bovine surfactant ( ' Surfactant TA ' ) were assessed in 30 premature infants ( birthweight 751 - 1750 g ) with severe hyaline membrane disease . 17 infants had a sonicated saline suspension of 100 mg/kg surfactant phospholipid instilled into the trachea at 5.0 ( SD 0.7 ) hours of age and 13 infants received saline by the same route at 4.3 ( 1.1 ) hours of age . In the surfactant-treated group there was early improvement in oxygenation and ventilation . Haemodynamically significant patent ductus arteriosus occurred more often in the surfactant group ; pneumothorax and pulmonary interstitial emphysema occurred less often . The combined incidence of death and severe bronchopulmonary dysplasia was significantly lower in the surfactant group ( 3/17 ) than in the placebo group ( 9/13 ) The postnatal growth , respiratory status and neurodevelopmental outcome of surviving babies enrolled in the first European multicentre trial of porcine surfactant ( Curosurf ) replacement for severe neonatal respiratory distress syndrome , were assessed at corrected ages of 1 and 2 years . Follow up rates of survivors were 93 % at 1 year and 89 % at 2 years . Treated and control groups were similar at both 1 and 2 years in terms of physical growth , the prevalence of persistent respiratory symptoms and the occurrence of major and minor disability . Serum antibodies recognising Curosurf and surfactant-anti-surfactant immune complexes were detected in both treated and control babies , the titres showing no difference between groups . Examination of histological lung sections from non-survivors revealed a higher incidence of severe pulmonary interstitial emphysema in control babies than in those treated with surfactant . Surfactant treatment for severe respiratory distress syndrome reduces neonatal mortality and air leaks and is not associated with an increase in disability 2 years later Treatment with bovine surfactant ( SF-RI 1 ) was shown to be efficacious in improving pulmonary function and in increasing survival rate without BPD in very premature infants . Surfactant therapy did not affect the risk of major complications of prematurity We conducted a prospect i ve , r and omized , unblinded , controlled trial of exogenous bovine surfactant ( surfactant TA ) in premature infants requiring ventilator support for the treatment of severe hyaline membrane disease . Forty-one low birth weight infants with severe hyaline membrane disease were r and omly assigned to saline or surfactant therapy and treated within eight hours of birth . Significant improvements in oxygenation ( increased arterial/alveolar PO2 ) and respiratory support ( decreased mean airway pressure ) were seen in the group receiving surfactant within four hours after treatment . These improvements were maintained in the surfactant-treated infants , who also had fewer pneumothoraces and fewer number of days in environments of fractional inspiratory oxygen greater than 0.4 mm Hg . No problems were associated with administration of surfactant , and no acute side effects were detected . We conclude that exogenous surfactant , administered early in the course of severe hyaline membrane disease , is an effective therapy that can diminish the amount of respiratory support required during the first 48 hours of life The results obtained with porcine surfactant ( Curosurf ) administration for the treatment of hyaline membrane disease ( HMD ) are reported . Thirty premature infants weighing 700 to 2,000 g with severe HMD ( mechanical ventilation and oxygen requirement ( FiO2 ) greater than 60 % were r and omly allocated at 2 to 15 hours postnatal age . Eight of the 30 patients included in this group participated in a multicenter european trial . The fifteen infants with mean gestational age ( GA ) of 29.5 weeks included in the treatment group ( T ) , were treated at 8.6 hours of life with a single dose of 200 mg/kg Curosurf given intratracheally while 15 infants of mean GA 30 weeks formed the control group ( C ) . Infants in the T group showed an immediate , dramatic and sustained improvement of oxygenation as reflected by increased PaO2/FiO2 and arterial to alveolar PO2 ratios within 1 hour . This significant improvement in favor of T group ( p less than 0.005 ) persisted for 2 days when control infants began to recover . This improvement in oxygenation allowed a significant decrease of FiO2 ( p less than 0.005 ) and mean airway pressure ( p less than 0.01 ) in the T group within 1 hour and up till the second day . Despite this early improvement obtained with Curosurf the survival rate at 28 days of life and the incidence of associated HMD complications were not significantly modified . However the tendency was towards decreased respiratory morbidity . The discussion will consider the value of multiple doses We investigated the clinical efficacy of a new surfactant product , Curosurf , isolated from porcine lungs by liquid-gel chromatography . Ten premature newborn infants ( birth weight 850 - 1850 g ) , all ventilated artificially for severe hyaline membrane disease categorized radiologically as stage III-IV , received a single dose of Curosurf ( 200 mg/kg ) via the tracheal tube . This treatment result ed in a rapid improvement of oxygenation , similar to that observed by other teams collaborating in the study and , in an astonishingly fast resolution of the radiological changes . In comparison with a control group of 8 infants , the surfactant-treated babies also had a lower incidence of acute and chronic complications In a r and omized , controlled study , human surfactant derived from amniotic fluid was administered within 12 hours of birth to infants with severe respiratory distress syndrome who were born at 24 to 32 weeks of gestation weighing less than or equal to 1500 gm . A second dose of surfactant was given to patients in the treatment group if they met ventilator requirements indicating relapse or lack of response to the initial dose . No significant improvement was observed in mortality rate ( 9/28 vs 15/31 ) or incidence of bronchopulmonary dysplasia ( 5/28 vs 3/31 ) when surfactant-treated infants were compared with control subjects , although there was a significant reduction in initial respirator and inspired oxygen requirements and the arterial/alveolar oxygen ratio improved . In addition , there was a significant reduction in pulmonary air leak in treated infants ( 10/28 vs 20/31 ; p less than 0.05 ) . Retreatment was associated with an attenuated ventilatory response and with a higher mortality rate ( 7/14 ) than that of infants who did not require a second dose ( 2/14 ; p = 0.05 ) , indicating a more severe form of disease . Multiple discriminant analysis , including eight independent variables , revealed that increasing birth weight , earlier age at surfactant treatment , and female gender were significantly associated with survival . These data suggest that early surfactant treatment may reduce mortality rates in very low birth weight infants with severe respiratory distress syndrome , as well as reduce ventilator requirements and the incidence of pulmonary air leaks To determine if outcomes of low birth weight neonates with respiratory distress syndrome can be improved by the administration of multiple doses of bovine surfactant , we conducted two identical multicenter , controlled trials , and the results were combined for analysis . Seven hundred and ninety-eight neonates weighing 600 to 1750 g at birth who had developed respiratory distress syndrome within 6 hours of birth were assigned r and omly to receive either 100 mg of phospholipid/kg of Survanta , a modified bovine surfactant ( n = 402 ) , or a sham dosing procedure ( n = 396 ) . Neonates whose respiratory distress persisted could be given up to three more doses , with all doses to be given in the first 48 hours after birth . Dosing was performed by investigators not involved in the clinical care of the neonates ; nursery staff were kept blinded as to the treatment assignment . Fewer Survanta-treated neonates died of any cause ( 18.4 % vs 27.3 % , P = .002 ) , died of respiratory distress syndrome ( 9.0 % vs 20.3 % , P less than .001 ) , and either died or developed bronchopulmonary dysplasia due to respiratory distress syndrome ( 51.2 % vs 64.6 % , P less than .001 ) . Neonates who received Survanta also had greater improvement in their oxygenation and ventilatory status from baseline to 72 hours than did control neonates . Survanta-treated neonates were at lowered risk for developing pulmonary interstitial emphysema ( 18.6 % vs 39.3 % , P less than .001 ) and other pulmonary air leaks ( 11.5 % vs 25.9 % , P less than .001 ) . We conclude that multiple doses of Survanta given after diagnosis of respiratory distress syndrome reduce mortality and morbidity We assessed postnatal growth , neurodevelopmental outcome , and occurrence of respiratory illnesses in 46 infants of very low birth weight who were enrolled in a r and omized , controlled , bicenter clinical trial of human surfactant treatment for respiratory distress syndrome . No long-term adverse effects of human surfactant treatment were detected between control and human surfactant-treated infants with respect to growth , neurologic , or developmental outcome . Infants with chronic lung disease , regardless of treatment group , had poorer growth and were more likely to have neurodevelopmental abnormalities at 12 to 24 months of age Several r and omized clinical trials have shown that surfactant therapy improves the pulmonary status of infants with respiratory distress syndrome and has the potential to reduce morbidity and mortality in these infants . Relatively little is known , however , about the long-term consequences of surfactant treatment . In this report , the results of health and developmental assessment are described at 1 and 2 years of age of 32 survivors of an initial group of 41 infants enrolled in a r and omized clinical trial of bovine surfactant therapy . The frequencies of abnormal findings were comparable in the two groups although there was a trend toward a greater frequency of allergic manifestations in the control group ( 6 of 16 ( 38 % ) vs 1 of 15 ( 7 % ) , P = .08 ) . Similarly , no differences were seen in the mental and motor scores of the Bayley Scales of Infant Development at either 1 or 2 years of age . This study and other recently published reports of follow-up studies of infants treated with surfactant provide encouraging evidence that major long-term side effects do not result from surfactant therapy We performed a multicenter prospect i ve r and omized controlled trial to determine the efficacy and safety of the surfactant preparation , Survanta ( Abbott Laboratories , Chicago , USA ) , for 750–1750 g infants with idiopathic respiratory distress syndrome , ( IRDS ) receiving assisted ventilation with 40 % or more oxygen . One hundred and six eligible infants from the eight participating centers were r and omly assigned between March 1986 and June 1987 to receive either surfactant ( 100 mg phospholipid/kg , 4 ml/kg ) or air ( 4 ml/kg ) administered into the trachea within 8 h of brith ( median time of treatment 6.2 h , range 3.2–9.1 h ) . The study was stopped before enrollment was completed at the request of the United States Food and Drug Administration when significant differences were observed in incidence of periventricular-intraventricular hemorrhage ( PIH ) , between the surfactant treated and control infants . Surfactant treated infants had larger average increases in the arterial-alveolar oxygen ratio , ( a/A ratio ) ( P<0.0001 ) , and larger average decreases in FiO2 ( P<0.0001 ) and mean airway pressure , ( MAP ) ( P<0.017 ) than controls over the 48 h following treatment . The magnitude of the differences between the surfactant and control groups were 0.19 ( SE=0.03 ) for a/A ratio , −0.28 ( SE=0.04 ) for FiO2 and −1.7 cm H2O ( SE=0.70 ) for MAP . The clinical status on days 7 and 28 after treatment was classified using four predefined ordered categories : ( 1 ) no respiratory support ; ( 2 ) supplemental O2 with or without continuous positive airway pressure ( CPAP ) ; ( 3 ) intermittent m and atory ventilation ; and ( 4 ) death . There were no statistically significant differences in the status categories on days 7 or 28 between surfactant and control infants . There were no significant differences between the groups with respect to the incidence of patent ductus arteriosus , bronchopulmonary dysplasia , necrotizing entero-colitis , air leaks or death . There was a statistically significant difference between treated and control infants in the frequency and severity of periventricular-intraventricular hemorrhage ( PIH ) ( Cochran-Mantel-Haenszelχ2adj=6.36,P=0.01 ) . Hemorrhages occurred in 59.6 % of surfactant treated infants and 26.9 % of controls . Severe hemorrhages ( grade s 3 or 4 ) occurred in 38.5 % of surfactant treated infants and 15.4 % of controls ( χ2adj=4.01,P=0.045 ) . We conclude that the intratracheal administration of Survanta prior to 8 h of age to infants with IRDS receiving assisted ventilation with 40 % or more oxygen results in a reduction in the severity of respiratory distress during the 48 h after therapy . Because of the difference in incidence of PIH between surfactant and control infants in this study , we recommend that future clinical trials of surfactant include more frequent prospect i ve serial ultrasound evaluations for diagnosis of hemorrhage Lung surfactant replacement has been tested clinical ly in recent years . In this study the outcome of 31 premature infants with moderate to severe neonatal respiratory distress syndrome ( RDS ) treated with surfactant was compared to that of 74 prematures with RDS treated conventionally by positive pressure ventilation and supportive care . The groups were well matched for gestational age , birthweight , sex , and Apgar scores at 1 and 5 min . Surfactant treatment result ed in a significant decrease in mortality -- from 36.6 % in the untreated group to 12.9 % in the surfactant-treated group ( P < 0.04 ) . This improvement in survival was seen also in prematures with a birthweight < 1,000 g ; in the untreated group mortality was 57.6 % compared to 23.5 % in the treated group ( P < 0.05 ) . The incidence of pneumothorax was lower in the treated group--42 % vs. 13 % ( P < 0.01 ) . Surfactant treatment result ed in a trend of more survivors without bronchopulmonary dysplasia or intraventricular hemorrhage , even though surfactant therapy did not change the incidence of either OBJECTIVE To determine the effect of bovine surfactant ( SF-RI 1 , Alveofact ) administered during the first hour following birth to very premature infants [ gestational age ( GA ) , 25 - 30 weeks ] in a multicenter , controlled trial . HYPOTHESIS Survival without bronchopulmonary dysplasia ( BPD ; definition : ventilator dependency or FiO2 greater than 0.3 during spontaneous respiration ) at day 28 is increased in surfactant-treated infants ( sequential analysis ) . PATIENTS AND METHODS Thirty-four infants [ GA 28.0 + /- 1.5 SD weeks , birth weight ( BW ) , 1,048 + /- 299 g ] received 50 mg/kg BW surfactant , whereas 35 infants ( GA , 27.6 + /- 1.5 weeks , BW 969 + /- 269 g ) served as controls . Retreatment with surfactant ( up to three identical doses ) 12 - 24 hours after the previous dose was permitted if FiO2 was greater than 0.5 . RESULTS Survival without BPD was significantly higher in surfactant treated infants ( 26/34 ) compared to controls ( 14/35 ; P = 0.003 ) , but in the incidence of pulmonary air leaks , patent ductus arteriosus , intracranial hemorrhage , and nosocomial infections they were not different . CONCLUSION Bovine surfactant treatment improves survival without BPD in very premature infants at risk for neonatal respiratory distress syndrome ( RDS ) We investigated the effects of a bovine surfactant ( SF-RI 1 , Alveofact ) in very low birth weight infants ( VLBW , b.w . 500 - 1500 g ) with established respiratory distress syndrome ( RDS ; definition : FiO2 greater than or equal to 0.6 or peak inspiratory pressure greater than 22 - 28 cm H2O ) . Fifty mg/kg b.w . bovine surfactant was administered intratracheally as a bolus , if the acute response was unsatisfactory ( FiO2 greater than 0.5 ) , further administrations of surfactant up to a maximum cumulative dose of 200 mg/kg b.w . were permitted . One hundred and sixty-four VLBW infants ( gestational age 28.0 + /- 2 wks ; b.w . 1054 + /- 251 g ; mean + /- SD ) with a mean FiO2 of 0.84 + /- 0.15 were enrolled in the study . Maximum improvement in oxygen requirements was observed 1/2 h post administration ( FiO2 0.53 + /- 0.22 ) ; incidence of complications during the neonatal period : pulmonary interstitial emphysema 26 % , pneumothorax 10 % , patent ductus arteriosus 37 % , intracranial hemorrhage 47 % . The overall survival rate was 61 % , survival rate without bronchopulmonary dysplasia ( BPD ) was 47 % . A multiple regression analysis was performed in order to identity factors determining survival without BPD ( p less than or equal to 0.05 ) . We observed a positive correlation for gestational age and birth weight and a negative correlation for pretreatment oxygen requirements . For further optimizing surfactant-therapy in VLBW infants with RDS , studies are m and atory using intervention criteria at lower FiO2-values and higher initial doses of bovine surfactant |
624 | 24,875,092 | RESULTS There was no evidence of association between diagnostic group and prescribing or clinical outcomes .
All tests had limitations .
We found no evidence that POCTs for influenza or S. pneumoniae , or PCR for influenza or RSV influenced antimicrobial prescribing or clinical outcomes .
The total costs and QALYs of each diagnostic strategy were similar , although , incrementally , PCR was the most cost-effective strategy .
The analysis does not support routine use of POCTs for either influenza or pneumococcal antigen for adults presenting with acute cardiopulmonary conditions , but suggests that conventional viral culture for clinical diagnosis should be replaced by PCR . | BACKGROUND Western industrialised nations face a large increase in the number of older people .
People over the age of 60 years account for almost half of the 16.8 million hospital admissions in Engl and from 2009 to 2010 .
During 2009 - 10 , respiratory infections accounted for approximately 1 in 30 hospital admissions and 1 in 20 of the 51.5 million bed-days .
OBJECTIVE To determine the diagnostic accuracy and clinical effectiveness and cost-effectiveness of rapid molecular and near-patient diagnostic tests for influenza , respiratory syncytial virus ( RSV ) and Streptococcus pneumoniae infections in comparison with traditional laboratory culture .
METHODS We carried out a r and omised controlled trial ( RCT ) to evaluate impact on prescribing and clinical outcomes of point-of-care tests ( POCTs ) for influenza A and B and pneumococcal infection , reverse transcriptase-polymerase chain reaction ( RT-PCR ) tests for influenza A and B and RSV A and B , and conventional culture for these pathogens .
We evaluated diagnostic accuracy of POCTs for influenza and pneumococcal infection , RT-PCR for influenza and sputum culture for S. pneumoniae using sample s collected during the RCT . | Background —Diagnostic strategies with ECG and serum cardiac markers have been used to rule out acute myocardial infa rct ion in 6 to 12 hours . The present study evaluated whether a multimarker strategy that used point-of-care measurement of myoglobin , creatine kinase (CK)-MB , and troponin I could exclude acute myocardial infa rct ion in ≤3 hours . Methods and Results —We prospect ively enrolled consecutive patients ( n=817 ) in the emergency department who were evaluated for possible acute myocardial infa rct ion . In patients with nondiagnostic ECGs , we measured CK-MB , troponin I , and myoglobin with a point-of-care device at presentation and at 90 minutes , 3 hours , and 9 hours . St and ard central laboratory testing of CK-MB was done at the same time intervals , and triage decisions were made by emergency physicians who were unaware of point-of-care results . Sensitivity and negative predictive value were compared for both the multimarker , point-of-care approach and the central laboratory strategy . Sensitivity and negative predictive value for point-of-care combination of myoglobin and troponin I by 90 minutes was 96.9 % and 99.6 % , respectively . CK-MB measurements and blood sampling at 3 hours did not improve sensitivity or negative predictive value . Median time from sampling to reporting of results was 71.0 minutes for the central laboratory versus 24.0 minutes for the point-of-care device ( P < 0.001 ) . Conclusions —Acute myocardial infa rct ion can be excluded rapidly in the emergency department by use of point-of-care measurements of myoglobin and troponin I during the first 90 minutes after presentation ABSTRACT The diagnosis of severe pneumococcal infections is inadequate , relying heavily on culture of Streptococcus pneumoniae from blood or other normally sterile fluids , and is severely limited by prior administration of antibiotics . We evaluated prospect ively the Binax NOW S. pneumoniae urinary antigen test , a rapid immunochromatographic assay , for the diagnosis of bacteremic pneumococcal infections in hospitalized adult patients . Antigen was detected in 88 of 107 cases overall , result ing in a test sensitivity of 82 % ( 95 % confidence interval [ 95 % CI ] , 74 to 89 % ) . Antigen detection was greater in those with pneumonia ( 67 of 77 [ 87 % ] ) than in those without pneumonia ( 21 of 30 [ 70 % ] ) ( P = 0.04 ) . Urinary antigen was also detected in 3 of 106 adult patients with community-acquired septicemic infections caused by other organisms , giving a test specificity of 97 % ( 95 % CI , 92 to 99 % ) . For 45 pneumococcal bacteremia patients with a positive test on treatment day 1 , urinary antigen excretion was monitored for the first week of antibiotic treatment . Antigen was still detectable in 83 % ( 29 of 35 tested ; 95 % CI , 66 to 93 % ) on treatment day 3 . Detection of urinary antigen is a valuable , sensitive , and rapid test for the early diagnosis of bacteremic pneumococcal infections in adult patients , even after antibiotic treatment has commenced BACKGROUND : The rapidly evolving p and emic of novel 2009 swine-origin influenza A ( H1N1 ) virus ( S-OIV ) dem and s that accurate and practical diagnostics be urgently evaluated for their potential clinical utility . OBJECTIVE : To determine the diagnostic accuracy of a rapid influenza diagnostic test ( RIDT ) and direct fluorescent antibody ( DFA ) assay for S-OIV by using reverse-transcription polymerase chain reaction ( RT-PCR ) as the reference st and ard . METHODS : We prospect ively recruited children ( aged 0–17 years ) assessed in the emergency department of a pediatric referral hospital and a community pediatric clinic for influenza-like illness between May 22 and July 25 , 2009 . RIDT ( performed on-site ) and DFA were compared with RT-PCR to determine their sensitivity and specificity for S-OIV . We also compared the sensitivity of RIDT for S-OIV to that for seasonal influenza over 2 preceding seasons . RESULTS : Of 820 children enrolled , 651 were from the emergency department and 169 were from the clinic . RIDT sensitivity was 62 % ( 95 % confidence interval [ CI ] : 52%–70 % ) for S-OIV , with a specificity of 99 % ( 95 % CI : 92%–100 % ) . DFA sensitivity was 83 % ( 95 % CI : 75%–89 % ) and was superior to that of RIDT ( P < .001 ) . RIDT sensitivity for S-OIV was comparable to that for seasonal influenza when using DFA supplemented with culture as the reference st and ard . RIDT sensitivity for influenza viruses was significantly higher in children 5 years of age or younger ( P = .003 ) and in patients presenting ≤2 days after symptom onset ( P < .001 ) . CONCLUSIONS : The sensitivity of RIDT for detection of S-OIV is higher than recently reported in mixed adult-pediatric population s but remains suboptimal INTRODUCTION The cost-effectiveness of blood cultures in community-acquired pneumonia ( CAP ) has been question ed . Although penicillin-resistant Streptococcus pneumoniae is an increasing problem , penicillin therapy , where appropriate , reduces cost and may reduce antibiotic resistance . Blood cultures , however , can only reduce cost if physicians are prepared to alter therapy based on the results . We review ed our experience to determine how often physicians changed management based on blood culture results positive for S pneumoniae . METHODS Retrospective chart review was performed of all CAP admissions between January 1996 and December 1998 with blood culture results positive for S pneumoniae . RESULTS Seventy-four patients out of 1,805 patients admitted with CAP during this period had pneumococcemia . Penicillin resistance was identified in 15 cases ( 20.3 % ; high grade in 4 cases ) with cephalosporin resistance in 4 of these cases ( 1 high grade ) . Fifty-one patients had initial empiric therapy with a third-generation cephalosporin , and 58 patients had empiric coverage of atypical organisms ; no patient received empiric penicillin therapy . Blood culture results altered management in 31 patients ( 41.9 % ) , but in only 2 cases was this due to antibiotic resistance . Fifty-one patients without penicillin allergy grew penicillin-sensitive pneumococci ; only 11 patients ( 21.6 % ) were changed to penicillin therapy . Thirteen of 35 patients ( 37.1 % ) who were given an additional antibiotic for atypical coverage had this antibiotic ceased . CONCLUSION Despite evidence of penicillin-sensitive pneumococcal CAP , physicians were reluctant to narrow antibiotic therapy , potentially adding to treatment cost and reducing the impact of blood culture results on management . The impact of penicillin resistance was reduced by the usual empiric choice of a third-generation cephalosporin . While positive blood culture results can clearly be useful in the management of patients with CAP , their cost-effectiveness needs to be assessed in prospect i ve clinical trials Background With the current influenza A H1N1 p and emic ( H1N1pdm ) , it is extremely important that clinicians can quickly and accurately identify influenza cases . Methodology /Principal Findings To investigate the performance of the QuickVue Influenza A+B rapid test , we conducted a prospect i ve study of the diagnostic accuracy of the QuickVue Influenza A+B test compared to real-time reverse transcriptase-polymerase chain reaction ( RT-PCR ) for influenza A H1N1pdm in Nicaraguan children aged 2 to 14 years . Rapid test sensitivity and specificity compared to real-time RT-PCR were 64.1 % ( 95 % CI 53.5 , 73.9 ) and 98.3 % ( 95.0 , 99.6 ) , respectively . Agreement between the two tests was 86.4 % ( 95 % CI 81.7 , 90.3 ) , and kappa was calculated to be 0.67 ( 95 % CI 0.56 , 0.76 ) . Performance of the rapid test varied by day of presentation , with a sensitivity of 41.7 % ( 95 % CI 22.1 , 63.4 ) for sample s from children presenting on the day of symptom onset and a sensitivity of 72.1 % ( 95 % CI 59.9 , 82.3 ) for sample s from children presenting one or more days post-symptom onset . Conclusions / Significance We found that the rapid test performed with moderate sensitivity and high specificity . Test performance varied by day of onset , with lower sensitivity on the day of symptom onset BACKGROUND Little is known about the impact of community-acquired respiratory coinfection in patients with p and emic 2009 influenza A(H1N1 ) virus infection . METHODS This was a prospect i ve , observational , multicenter study conducted in 148 Spanish ICUs . RESULTS Severe respiratory syndrome was present in 645 ICU patients . Coinfection occurred in 113 ( 17.5 % ) of patients . Streptococcus pneumoniae ( in 62 patients [ 54.8 % ] ) was identified as the most prevalent bacteria . Patients with coinfection at ICU admission were older ( 47.5±15.7 vs 43.8±14.2 years , P<.05 ) and presented a higher APACHE ( Acute Physiology and Chronic Health Evaluation ) II score ( 16.1±7.3 vs 13.3±7.1 , P<.05 ) and Sequential Organ Failure Assessment ( SOFA ) score ( 7.0±3.8 vs 5.2±3.5 , P<.05 ) . No differences in comorbidities were observed . Patients who had coinfection required vasopressors ( 63.7 % vs 39.3 % , P<.05 ) and invasive mechanical ventilation ( 69 % vs 58.5 % , P<.05 ) more frequently . ICU length of stay was 3 days longer in patients who had coinfection than in patients who did not ( 11 [ interquartile range , 5 - 23 ] vs 8 [ interquartile range 4 - 17 ] , P=.01 ) . Coinfection was associated with increased ICU mortality ( 26.2 % vs 15.5 % ; OR , 1.94 ; 95 % CI , 1.21 - 3.09 ) , but Cox regression analysis adjusted by potential confounders did not confirm a significant association between coinfection and ICU mortality . CONCLUSIONS During the 2009 p and emics , the role played by bacterial coinfection in bringing patients to the ICU was not clear , S pneumoniae being the most common pathogen . This work provides clear evidence that bacterial coinfection is a contributor to increased consumption of health re sources by critical patients infected with the virus and is the virus that causes critical illness in the vast majority of cases BACKGROUND The role of pneumococcal urinary antigen detection in the treatment of adults with community-acquired pneumonia ( CAP ) is not well defined . We assessed the usefulness of pneumococcal urinary antigen detection in the diagnosis and antimicrobial guidance in patients hospitalized with CAP . METHODS A prospect i ve study of all adults hospitalized with CAP was performed from February 2007 through January 2008 . To evaluate the accuracy of the test , we calculated its sensitivity , specificity , positive and negative predictive values , and positive and negative likelihood ratios . The gold st and ard used for diagnosis of pneumococcal pneumonia was isolation in blood or pleural fluid ( definite diagnosis ) and isolation in sputum ( probable diagnosis ) . Antibiotic modifications , complications , and mortality were analyzed . RESULTS A total of 474 episodes of CAP were included . Streptococcus pneumoniae was the causative pathogen in 171 cases ( 36.1 % ) . It was detected exclusively by urinary antigen test in 75 cases ( 43.8 % ) . Sixty-nine patients had CAP caused by a pathogen other than S pneumoniae . Specificity was 96 % , positive predictive value ranged from 88.8 % to 96.5 % , and the positive likelihood ratio ranged from 14.6 to 19.9 . The results of the test led the clinicians to reduce the spectrum of antibiotics in 41 patients . Pneumonia was cured in all of them . Potentially , this optimization would be possible in the 75 patients diagnosed exclusively by the test . CONCLUSION When its findings are positive , the pneumococcal urinary antigen test is a useful tool in the treatment of hospitalized adult patients with CAP because it may allow the clinician to optimize antimicrobial therapy with good clinical outcomes Background : Mucosal coinfections with respiratory viruses and Streptococcus pneumoniae are common , but the role of rhinovirus infections in the development of invasive pneumococcal disease ( IPD ) in children has not been studied . Methods : During 1995 and 2007 , we analyzed the association of IPD in children less than 5 years of age with respiratory virus epidemics by combining data from the National Infectious Disease Register , 3 prospect i ve epidemiologic studies , and the data base of the Department of Virology , University of Turku , Finl and . Results : The mean IPD rate in children younger than 5 years of age in Finl and was 2.9 cases per week ( 95 % confidence interval [ CI ] , 2.5–3.3 ) during periods of high rhinovirus activity , and 1.4 ( 95 % CI , 1.2–1.6 ) during periods of low rhinovirus activity ( P < 0.001 ) . The IPD rate correlated with the rhinovirus activity recorded at the Department of Virology ( correlation coefficient , 0.23 ; P = 0.001 ) and in the epidemiologic studies ( correlation coefficients , 0.28 , 0.25 , and 0.31 ) . The IPD rate was moderately increased during periods of high respiratory syncytial virus activity ( mean , 2.1 cases per week ; 95 % CI , 1.8–2.3 ) compared with periods of low respiratory syncytial virus activity ( mean , 1.7 ; 95 % CI , 1.6–1.9 ; P = 0.008 ) . There were no differences in the IPD rate between the periods of high and low influenza activity . Conclusions : Rhinovirus circulation in the community had an association with IPD in children younger than 5 years of age . This study suggests that rhinovirus infection may be a contributor in the development of IPD in the population of young children Background Influenza is major public health threat worldwide , yet the diagnostic accuracy of rapid tests in developing country setting s is not well described . Methodology /Principal Findings To investigate the diagnostic accuracy of the QuickVue Influenza A+B test in a primary care setting in a developing country , we performed a prospect i ve study of diagnostic accuracy of the QuickVue Influenza A+B test in comparison to reverse transcriptase-polymerase chain reaction ( RT-PCR ) in a primary healthcare setting in children aged 2 to 12 years in Managua , Nicaragua . The sensitivity and specificity of the QuickVue test compared to RT-PCR were 68.5 % ( 95 % CI 63.4 , 73.3 ) and 98.1 % ( 95 % CI 96.9 , 98.9 ) , respectively , for children with a fever or history of a fever and cough and /or sore throat . Test performance was found to be lower on the first day that symptoms developed in comparison to test performance on days two or three of illness . Conclusions / Significance Our study found that the QuickVue Influenza A+B test performed as well in a developing country primary healthcare facility setting as in developed country setting STUDY OBJECTIVE Although it is considered st and ard of care to obtain blood cultures on patients hospitalized for pneumonia , several studies have question ed the utility and cost-effectiveness of this practice . The objective of this study is to determine the impact of emergency department ( ED ) blood cultures on antimicrobial therapy for patients with pneumonia . METHODS We performed a prospect i ve , observational , cohort study of consecutive adult ( age > or = 18 years ) patients treated at an urban university ED between February 1 , 2000 and February 1 , 2001 . Inclusion criteria were radiographic evidence of pneumonia , clinical evidence of pneumonia , and blood culture obtained . Blood cultures were classified as positive , negative , or contaminant based on previously established criteria . Additionally , data were collected on antimicrobial sensitivities , empiric antibiotic therapy , antibiotic changes , and reasons for changes . RESULTS There were 3,926 ED visits with blood cultures obtained for any reason , of which 3,762 ( 96 % ) were available for review . Of these , 414 of 3,762 ( 11 % ) patients met pneumonia study inclusion criteria , and blood cultures identified 29 of 414 ( 7.0 % ) patients with true bacteremia . In the 414 patients , blood culture results altered therapy for 15 patients ( 3.6 % ) with suspected pneumonia , of which 11 ( 2.7 % ) patients had their coverage narrowed ; only 4 ( 1.0 % ) patients had their coverage broadened because of resistance to empiric therapy . For the 11 patients with bacteremia whose therapy was not altered , culture results actually supported narrowing therapy in 8 ( 1.9 % ) cases , but this was not done . CONCLUSION Blood cultures rarely altered therapy for patients presenting to the ED with pneumonia . More discriminatory blood culture use may potentially reduce re source utilization OBJECTIVE To describe a nosocomial influenza A outbreak , how it was managed , what impact it had on subsequent delivery of health care , and the additional charges attributable to it DESIGN Prospect i ve cohort study and microbiological investigation . SETTING One internal medicine unit in an acute care , university-affiliated hospital . PARTICIPANTS Twenty-three patients and 22 staff members from February 28 to March 6 , 1999 . RESULTS Attack rates were 41 % ( 9 of 22 ) among patients and 23 % ( 5 of 22 ) among staff members , with 3 of 14 cases being classified as " certain . " The influenza virus isolates were typed as A/SYDNEY/5/97 ( H3N2 ) . The index case was a patient who shared a room with the first nosocomial case . Vaccination rates for influenza virus were 43 % ( 10 of 23 ) among patients and 36 % ( 8 of 22 ) among staff members . The outbreak result ed in staff members ' taking 14 person-days of sick leave . Furthermore , 8 scheduled admissions were postponed and all emergency admissions were suspended for 11 days . Hospital charges attributable to the influenza outbreak totaled $ 34,179 and the average extra charge per infected patient was $ 3,798 . CONCLUSIONS Nosocomial influenza outbreaks increase charges and alter the quality of care delivered in acute care setting s. Strategies for their prevention need to be evaluated in acute care setting STUDY OBJECTIVES We evaluated the role of sputum examination in the management of patients with community-acquired pneumonia ( CAP ) in a primary -care hospital without microbiologic laboratory facilities . DESIGN AND INTERVENTIONS A diagnostic strategy using regular collection of sputum sample s , Gram staining in a local laboratory , and mailing of sample s to a commercial laboratory for culture analysis . SETTING A 200-bed primary -care hospital without subspeciality physicians . PATIENTS One hundred sixteen consecutive patients with a diagnosis of CAP were prospect ively evaluated during a 12-month period . RESULTS Of 116 patients , 42 patients ( 36 % ) were capable of producing a sputum sample . Age > or = 75 years ( odds ratio [ OR ] , 0.4 ; 95 % confidence interval [ CI ] , 0.18 to 0.93 ) and prior ambulatory antimicrobial treatment ( OR , 3.2 ; 95 % CI , 1.2 to 8.4 ) were independent predictors of sputum production . A delay in collection and processing of sputum sample s of > 24 h was present in 31 % and 39 % , respectively . A delay in collection yielded an increased number of Gram-negative enteric bacilli and nonfermenters ( 44 % vs. 7 % , p = 0.056 ) . A delay in processing was associated with an increased number of C and ida spp isolates ( 33 % vs. 9 % , p = 0.16 ) . The overall diagnostic yield was low ( 10 of 116 patients , 9 % ) due to a limited number of valid sample s ( n = 23 of 42 patients , 55 % ) and a limited number of definitely or probably positive sample s on Gram 's stain and culture ( n = 10 of 42 patients , 24 % ) . Prior ambulatory antimicrobial treatment was associated with a reduction in diagnostic yield ( 14 % vs. 56 % , p = 0.09 ) . The impact of diagnostic results on antimicrobial treatment decisions was minimal , with antimicrobial treatment directed to diagnostic results in only one patient . CONCLUSIONS We conclude that in this setting representative of primary -care hospitals in Germany , sputum had a low diagnostic yield and did not contribute significantly to patient management Objectives Although blood cultures are commonly ordered in the emergency department , there is controversy about their utility . This study aim ed to determine the usefulness of blood cultures in the management of patients presenting to a tertiary adult teaching hospital emergency department in Perth , Western Australia . Methods A detailed chart review was undertaken of all blood cultures taken in our emergency department over a 2-month period . All patients within the hospital having blood cultures taken were identified ; from this group , blood cultures originating from the emergency department were review ed . Data were collected concerning patient demographics , culture indication , vital signs , culture outcome , disposition and alterations in management result ing from the blood culture . Results 218 blood cultures were ordered from the emergency department during the study period . This represented 4.0 % ( 218/5478 ) of the total number of patients seen . Of the 218 cultures , only 30 were positive ( 13 % of the study population ) , with 16 ( 7.3 % ) probable contaminants and 14 ( 6.4 % ) true positives . No anaerobic isolates were identified . Of the 14 significantly positive blood cultures , the result influenced management in six patients , result ing in a useful culture rate of 2.8 % ( 6/218 ) . Conclusion Blood cultures are ordered on a significant number of patients seen in the emergency department but rarely alter management . Our findings in conjunction with other studies suggest that eliminating blood cultures in immunocompetent patients with common illnesses such as urinary tract infection , community acquired pneumonia and cellulitis , may significantly reduce the number of blood cultures , producing substantial savings without jeopardizing patient care . This needs prospect i ve study and validation Directigen FLU-A , an enzyme immunoassay membrane test , was compared prospect ively to isolation in cell culture and direct immunofluorescence ( IF ) for the detection of influenza A virus . One hundred ninety specimens were evaluated by Directigen FLU-A and cell culture ; 184 of these specimens were also tested by direct IF . The sensitivity of Directigen FLU-A compared to isolation in cell culture and direct IF was 100 % . The specificities of Directigen FLU-A compared to isolation and direct IF were identical , 91.6 % . Fourteen specimens that were positive by Directigen FLU-A did not yield virus in culture ; two of the specimens , however , were positive by direct IF , and four other specimens were not specimens of choice for the test . A positive Directigen result had positive predictive values of 62.6 and 75.0 % compared to isolation and direct IF , respectively ; a positive Directigen result with an intensity reading of 2 + or greater , however , had positive predictive values of 85 and 100 % compared to isolation and direct IF , respectively . In all comparisons , the negative predictive value was 100 % . There was no evidence that cross-reactivity occurred with non-influenza A antigens . Directigen FLU-A should serve as a convenient screening test for influenza A and as a rapid test supported by isolation in cell culture during an influenza outbreak Background The aim of this study was to investigate factors affecting clinical outcomes of adults hospitalised with severe seasonal influenza . Methods A prospect i ve , observational cohort study was conducted over 24 months ( 2007–2008 ) in two acute , general hospitals . Consecutive , hospitalised adult patients were recruited and followed once their laboratory diagnosis of influenza A/B was established ( based on viral antigen detection and virus isolation from nasopharyngeal aspirates collected per protocol ) . Outcomes studied included in-hospital death , length of stay and duration of oxygen therapy . Factors affecting outcomes were analysed using multivariate Cox proportional hazards models . Sequencing analysis on the neuraminidase gene was performed for available H1N1 isolates . Results 754 patients were studied ( influenza A , n=539 ; > 75 % H3N2 ) . Their mean age was 70±18 years ; co-morbidities and serious complications were common ( 61–77 % ) . Supplemental oxygen and ventilatory support was required in 401 ( 53.2 % ) and 41 ( 5.4 % ) patients , respectively . 39 ( 5.2 % ) patients died ; pneumonia , respiratory failure and sepsis were the causes . 395 ( 52 % ) patients received antiviral ( oseltamivir ) treatment . Omission of antiviral treatment was associated with delayed presentation or negative antigen detection results . The mortality rate was 4.56 and 7.42 per 1000 patient-days in the treated and untreated patients , respectively ; among those with co-morbidities , it was 5.62 and 11.64 per 1000 patient-days , respectively . In multivariate analysis , antiviral use was associated with reduced risk of death ( adjusted HR ( aHR ) 0.27 ( 95 % CI 0.13 to 0.55 ) ; p<0.001 ) . Improved survival was observed with treatment started within 4 days from onset . Earlier hospital discharge ( aHR 1.28 ( 95 % CI 1.04 to 1.57 ) ; p=0.019 ) and faster discontinuation of oxygen therapy ( aHR 1.30 ( 95 % CI 1.01 to 1.69 ) ; p=0.043 ) was associated with early treatment within 2 days . Few ( n=15 ) H1N1 isolates in this cohort had the H275Y mutation . Conclusions Antiviral treatment for severe influenza is associated with reduced mortality and improved clinical outcomes To evaluate the efficacy of a rapid immunochromatographic membrane test ( ICT ) for the detection of Streptococcus pneumoniae urinary antigen for diagnosing S. pneumoniae pneumonia , ICT was performed with urine sample s using the Binax NOW Streptococcus pneumoniae kit at the time of admission . The results were compared with those from conventional microbiological studies . Three hundred and forty-nine adult patients with CAP who were admitted to the hospital were studied prospect ively between February 2001 and January 2004 . The ICT test was positive in 115 ( 33.0 % ) of 349 patients enrolled into the study and in 63 ( 75.9 % ) of 83 patients with pneumococcal pneumonia confirmed by conventional methods . The test revealed a sensitivity of 75.9 % and a specificity of 94.0 % with conventional microbiological criteria used as the reference st and ard . The positive predictive value was 91.3 % , and the negative predictive value was 82.6 % . The clinical features of 53 patients in whom ICT was positive and no pathogen was identified showed no significant difference from those of 83 patients who had pneumococcal pneumonia identified by conventional methods . The diagnostic yield of pneumococcal pneumonia was increased up to 38.9 % using ICT combined with conventional methods . The Binax NOW ICT to detect S. pneumoniae urinary antigen is therefore a rapid and useful method for diagnosing pneumococcal pneumonia . Induction of ICT will prove the predominance of S. pneumoniae in the etiology of CAP Background Most antibiotic prescriptions for acute cough due to lower respiratory tract infections ( LRTI ) in primary care are not warranted . Diagnostic uncertainty and patient expectations and worries are major drivers of unnecessary antibiotic prescribing . A C-reactive protein ( CRP ) point of care test may help GPs to better guide antibiotic treatment by ruling out pneumonia in cases of low test results . Alternatively , enhanced communication skills training to help clinicians address patients ' expectations and worries could lead to a decrease in antibiotic prescribing , without compromising clinical recovery , while enhancing patient enablement . The aim of this paper is to describe the design and methods of a study to assess two interventions for improving LRTI management in general practice . Methods / Design This cluster r and omised controlled , factorial trial will introduce two interventions in general practice ; point of care CRP testing and enhanced communication skills training for LRTI . Twenty general practice s with two participating GPs per practice will recruit 400 patients with LRTI during two winter periods . Patients will be followed up for at least 28 days . The primary outcome measure is the antibiotic prescribing rate . Secondary outcomes are clinical recovery , cost-effectiveness , use of other diagnostic tests and medical services ( including reconsultation ) , and patient enablement . Discussion This trial is the first cluster r and omised trial to evaluate the influence of point of care CRP testing in the h and s of the general practitioner and enhanced communication skills , on the management of LRTI in primary care . The pragmatic nature of the study , which leaves treatment decisions up to the responsible clinicians , will enhance the applicability and generalisability of findings . The factorial design will allow conclusion to be made about the value of CRP testing on its own , communication skills training on its own , and the two combined . Evaluating a biomedical and communication based intervention ( ' hard ' and ' soft ' technologies ) together in this way makes this trial unique in its field BACKGROUND Successful treatment of influenza depends on an accurate diagnosis of the illness and prompt intervention . However , there is a lack of data comparing clinical diagnosis vs laboratory diagnostic techniques . OBJECTIVE To compare the clinical diagnosis of community cases of influenza with various laboratory diagnostic techniques including multiplex , reverse transcription polymerase chain reaction . METHODS Clinical diagnosis , viral isolation , hemagglutinin inhibition serology , and multiplex , reverse transcription polymerase chain reaction were used to diagnose influenza in patients enrolled in international phase 3 studies design ed to investigate the efficacy and safety of an anti-influenza drug ( inhaled zanamivir ) . Patients clinical ly diagnosed with influenza were enrolled at centers across North America and Europe . RESULTS A total of 791 ( 77 % ) of 1033 patients with laboratory results from all 3 methods were confirmed positive for influenza by 1 or more test results . For 692 patients ( 67 % ) , the results of all 3 tests agreed . Total symptom scores at baseline showed a significant association toward greater severity of symptoms with an increasing number of positive test results ( P<.001 ) . An increasing number of positive test results also showed a significant correlation with a longer time to alleviation of symptoms of influenza in the placebo group ( P = .001 ) . CONCLUSIONS During a time when influenza was known to be circulating and clinical diagnostic criteria were applied , diagnosis of influenza in these trials was accurate in approximately 77 % of adults on clinical grounds alone . This highlights the need for primary care physicians to be alerted to circulating influenza and to be aware that presentation with cough and fever provide the most predictive symptoms In a previous prospect i ve study , Streptococcus pneumoniae was identified as the causative agent in 148 ( 42.8 % ) of 346 adult patients hospitalized over the course of one year with community-acquired pneumonia ( CAP ) in the Soroka Medical Center , Beer-Sheva , Israel . The present study characterizes those cases in whichStreptococcus pneumoniae was the only pathogen and those in which additional etiological agents were identified . Pneumococcal CAP was diagnosed by st and ard blood cultures or positive serological tests by one of two laboratory methods . In 100 ( 67.6 % ) patients , at least one other etiological agent of CAP was identified in addition toStreptococcus pneumoniae . Compared with patients who were not infected byStreptococcus pneumoniae , patients withStreptococcus pneumoniae CAP were older and had a higher rate of comorbidity ( 39.5 % vs. 29.8%).Streptococcus pneumoniae CAP had a more severe clinical course and a higher mortality rate , especially whenStreptococcus pneumoniae was the only pathogen . Community-acquired pneumonia due toStreptococcus pneumoniae only was more similar in its clinical manifestations to classic typical pneumococcal pneumonia . When an additional etiological agent was identified , the clinical characteristics could not be distinguished from those of atypical pneumonia . It is concluded thatStreptococcus pneumoniae remains the principal cause of CAP in this region . The frequency of additional etiological agents of CAP and the difficulty in differentiating clinical ly between cases due toStreptococcus pneumoniae only and those due toStreptococcus pneumoniae plus other organisms necessitates initial empirical treatment that coversStreptococcus pneumoniae as well as other causative agents of atypical pneumonia BACKGROUND The drug of choice for treatment of Streptococcus pneumoniae infection is generally a penicillin ( including amoxicillin ) . Targeted therapy is , however , rarely used , because results of definitive diagnostic tests for pneumonia are not available for several days . Thus , broad-spectrum antibiotics are used for empirical treatment of pneumonia to cover both typical and atypical pathogens . Our purpose was to assess the usefulness of a strategy of targeted antimicrobial therapy based on the results of a rapid urinary antigen test for S. pneumoniae . METHODS Military trainees with pneumonia were prospect ively assigned to 2 groups : patients with positive urinary antigen test results who were treated with amoxicillin ( 1000 mg 3 times per day ) , and patients with negative urinary antigen test results who were treated with clarithromycin ( 500 mg 2 times per day ) . The duration of therapy was 5 - 10 days for both groups . RESULTS A total of 219 evaluable patients were enrolled in the study . The most common causes of pneumonia were S. pneumoniae , Chlamydia pneumoniae , and Mycoplasma pneumoniae . Patients with positive urinary antigen test results had illness of greater severity at the time of study entry . Twenty-two percent of patients had positive urinary antigen test results ( i.e. , the amoxicillin group ) , and 78 % had negative urinary antigen test results ( i.e. , the clarithromycin group ) . The clinical success rates were 94 % for the clarithromycin group and 90 % for the amoxicillin group ( P = not significant ) . None of the patients who were classified as having treatment failure died . Resolution of clinical manifestations was slower for patients with pneumococcal pneumonia defined by a positive urinary antigen test result . CONCLUSIONS The urine antigen test allowed targeted use of a penicillin ( amoxicillin ) for young immunocompetent individuals with nonsevere , community-acquired pneumonia . Clarithromycin was highly effective against both S. pneumoniae pneumonia and pneumonia due to atypical pathogens Objective To assess the cost effectiveness of different management strategies for urinary tract infections . Design Cost effectiveness analysis alongside a r and omised controlled trial with a one month follow-up . Setting Primary care . Participants 309 non-pregnant adult women aged 18 - 70 presenting with suspected urinary tract infection . Interventions Patients were r and omised to five basic management approaches : empirical antibiotics , empirical delayed ( by 48 hours ) antibiotics , or targeted antibiotics based on either a high symptom score ( two or more of urine cloudiness , smell , nocturia , dysuria ) , dipstick results ( nitrite or leucocytes and blood ) , or receipt of a positive result on midstream urine analysis . Main outcome measure Duration of symptoms and cost of care . Results Management with targeted antibiotics with midstream urine analysis was more costly over the period of one month . Costs for the midstream urine analysis and dipstick management groups were £ 37 and £ 35 , respectively ; these compared with £ 31 for immediate antibiotics . Cost effectiveness acceptability curves suggested that if avoiding a day of moderately bad symptoms was valued at less than £ 10 , then immediate antibiotics is likely to be the most cost effective strategy . For values over £ 10 , targeted antibiotics with dipstick testing becomes the most cost effective strategy , though because of the uncertainty we can never be more than 70 % certain that this strategy truly is the most cost effective . Conclusion Dipstick testing with targeted antibiotics is likely to be cost effective if the value of saving a day of moderately bad symptoms is £ 10 or more , but caution is required given the considerable uncertainty surrounding the estimates The Streptococcus pneumoniae ( SP ) urinary antigen ( UAg ) test is a commonly used assay . The purpose of this study was to evaluate the test 's actual performance in the clinical setting and determine the effects of renal function , grade of bacteremia , and severity-of-illness scores on its outcome . Patients with pneumococcal bacteremia were retrospectively identified and stratified on the basis of glomerular filtration rates , number of positive blood cultures , and CURB-65 scores . Logistic regression was used to determine the effect that these 3 variables had on test outcomes . SP UAg testing was performed in 65 of 129 patients with pneumococcal bacteremia and was positive in 42 of 65 ( 64.5 % ) . Impaired renal function was the only variable to have a significant effect on test outcome ( P = 0.03 ) . Test performance was less sensitive than prospect i ve studies indicate . Patients with impaired renal function were significantly more likely to have positive UAg tests Abstract Background The goal of this study was to characterize viral loads and factors affecting viral clearance in persons with severe influenza Methods This was a 1-year prospect i ve , observational study involving consecutive adults hospitalized with influenza . Nasal and throat swabs were collected at presentation , then daily until 1 week after symptom onset . Real-time reverse-transcriptase polymerase chain reaction to determine viral RNA concentration and virus isolation were performed . Viral RNA concentration was analyzed using multiple linear or logistic regressions or mixed-effect models Results One hundred forty-seven in patients with influenza A ( H3N2 ) infection were studied ( mean age ± st and ard deviation , 72±16 years ) . Viral RNA concentration at presentation positively correlated with symptom scores and was significantly higher than that among time-matched out patients ( control subjects ) . Patients with major comorbidities had high viral RNA concentration even when presenting > 2 days after symptom onset ( mean ± st and ard deviation , 5.06±1.85 vs 3.62±2.13 log10 copies/mL ; P=.005 ; β , + 0.86 [ 95 % confidence interval , + 0.03 to + 1.68 ] ) . Viral RNA concentration demonstrated a nonlinear decrease with time ; 26 % of oseltamivir-treated and 57 % of untreated patients had RNA detected at 1 week after symptom onset . Oseltamivir started on or before symptom day 4 was independently associated with an accelerated decrease in viral RNA concentration ( mean β [ st and ard error ] , −1.19 [ 0.43 ] and −0.68 [ 0.33 ] log10 copies/mL for patients treated on day 1 and days 2–3 , respectively ; P<.05 ) and viral RNA clearance at 1 week ( odds ratio , 0.10 [ 95 % confidence interval , 0.03–0.35 ] and 0.30 [ 0.10–0.90 ] for patients treated on day 1–2 and day 3–4 , respectively ) . Conversely , major comorbidities and systemic corticosteroid use for asthma or chronic obstructive pulmonary disease exacerbations were associated with slower viral clearance . Viral RNA clearance was associated with a shorter hospital stay ( 7.0 vs 13.5 days ; P=.001 ) Conclusion Patients hospitalized with severe influenza have more active and prolonged viral replication . Weakened host defenses slow viral clearance , whereas antivirals started within the first 4 days of illness enhance viral OBJECTIVE To evaluate four methods of rapid diagnosis of respiratory syncytial virus ( RSV ) infection in older adults and to compare sensitivities with serologic analysis . DESIGN Prospect i ve comparative analysis . SETTING Two adult daycenters . PATIENTS Frail older persons attending the daycenter who developed signs or symptoms of acute respiratory illness between the months of December and February . MEASUREMENTS Viral cultures performed by st and ard technique and bedside inoculation : antigen detection by indirect immunofluorescence assay ( IFA ) and Directigen enzyme immunoassay ( EIA ) on nasal brush sample s ; serologic analysis of acute and convalescent sera using EIA . RESULTS RSV infection was documented by serology in 11 of 54 ( 20 % ) subjects during the study period . Bedside viral cultures were the most sensitive assay and were positive in 6/9 infections . St and ard viral culture detected 5/11 cases . Both methods of rapid antigen detection were found to be insensitive , with 1/11 detected by IFA and 0/11 detected by EIA . CONCLUSION Rapid antigen tests for the diagnosis of RSV in older persons should be used with caution BACKGROUND : The purpose of this study was to assess the causes of community-acquired pneumonia in adult patients admitted to hospital . METHODS : A prospect i ve study was performed on 346 consecutive adult patients ( 54 % men ) of mean ( SD ) 49.3 ( 19.5 ) years ( range 17 - 94 ) admitted to a university affiliated regional hospital in southern Israel with community-acquired pneumonia over a period of one year . Convalescent serum sample s were obtained from 308 patients ( 89 % ) . The aetiological diagnosis for community-acquired pneumonia was based on positive blood cultures and /or significant changes in antibody titres to Streptococcus pneumoniae , Haemophilus influenzae , Moraxella catarrhalis , respiratory viruses , Coxiella burnetii , Mycoplasma pneumoniae , Chlamydia pneumoniae , and Legionella sp. RESULTS : The aetiology of community-acquired pneumonia was identified in 279 patients ( 80.6 % ) . The distribution of causal agents was as follows : S pneumoniae , 148 patients ( 42.8 % ) ; M pneumoniae , 101 ( 29.2 % ) ; C pneumoniae , 62 ( 17.9 % ) ; Legionella sp , 56 ( 16.2 % ) ; respiratory viruses , 35 ( 10.1 % ) ; C burnetii , 20 ( 5.8 % ) ; H influenzae 19 ( 5.5 % ) ; and other causes , 21 patients ( 6.0 % ) . In patients above the age of 55 years C pneumoniae was the second most frequent aetiological agent ( 25.5 % ) . In 133 patients ( 38.4 % ) more than one causal agent was found . CONCLUSIONS : The causal agents for community-acquired pneumonia in Israel are different from those described in other parts of the world . In many of the patients more than one causal agent was found . In all these patients treatment should include a macrolide antibiotic , at least in the first stage of their illness BACKGROUND We conducted a prospect i ve cohort study to assess the impact of antiviral therapy on outcomes of patients hospitalized with influenza in southern Ontario , Canada . METHODS Patients admitted to Toronto Invasive Bacterial Diseases Network hospitals with laboratory-confirmed influenza from 1 January 2005 through 31 May 2006 were enrolled in the study . Demographic and medical data were collected by patient and physician interview and chart review . The main outcome evaluated was death within 15 days after symptom onset . RESULTS Data were available for 512 of 541 eligible patients . There were 185 children ( < 15 years of age ) , none of whom died and none of whom were treated with antiviral drugs . The median age of the 327 adults was 77 years ( range , 15 - 98 years ) , 166 ( 51 % ) were male , 245 ( 75 % ) had a chronic underlying illness , and 216 ( 71 % ) had been vaccinated against influenza . Of the 327 adult patients , 184 ( 59 % ) presented to the emergency department within 48 h after symptom onset , 52 ( 16 % ) required intensive care unit admission , and 27 ( 8.3 % ) died within 15 days after symptom onset . Most patients ( 292 patients ; 89 % ) received antibacterial therapy ; 106 ( 32 % ) were prescribed antiviral drugs . Treatment with antiviral drugs active against influenza was associated with a significant reduction in mortality ( odds ratio , 0.21 ; 95 % confidence interval , 0.06 - 0.80 ; n=100 , 260 ) . There was no apparent impact of antiviral therapy on length of stay in survivors . CONCLUSIONS There is a significant burden of illness attributable to influenza in this highly vaccinated population . Treatment with antiviral drugs was associated with a significant reduction in mortality STUDY OBJECTIVE To assess the clinical usefulness of blood cultures ( BCs ) in the management of patients hospitalized with community-acquired pneumonia ( CAP ) . DESIGN A prospect i ve , observational study to investigate the contribution of BCs to the management and outcomes of adult patients presenting with CAP . SETTING Nineteen Canadian hospitals . PATIENTS Adults admitted to the hospital with CAP between January 1 , 1998 , and July 31 , 1998 . INTERVENTIONS The courses of therapy in patients for whom BC results yielded organisms considered to be clinical ly significant were analyzed to determine whether the BCs had contributed to management or outcome . MEASUREMENTS AND RESULTS Forty-three of 760 patients had significantly positive BC results . Patients with CAP who had BCs performed had a 1.97 % chance ( 15 of 760 patients ) of having a change of therapy directed by BC results . Patients in whom BCs yielded positive results had a 34.8 % chance ( 15 of 43 patients ) of having a change in therapy determined by BC results , and had a 58.1 % chance ( 25 of 43 patients ) of having a course of therapy contraindicated by BC results . Severity of illness , as measured by the pneumonia severity index , correlated poorly with the yield of BCs . BC results were positive in 8.0 % of patients in risk classes I and II , 6.2 % of patients in risk class III , 4.6 % of patients in risk class IV , and 5.2 % of patients in risk class V. CONCLUSION BCs have limited usefulness in the routine management of patients admitted to the hospital with uncomplicated CAP BACKGROUND Respiratory syncytial virus ( RSV ) is an increasingly recognized cause of illness in adults . Data on the epidemiology and clinical effects in community-dwelling elderly persons and high-risk adults can help in assessing the need for vaccine development . METHODS During four consecutive winters , we evaluated all respiratory illnesses in prospect i ve cohorts of healthy elderly patients ( > or = 65 years of age ) and high-risk adults ( those with chronic heart or lung disease ) and in patients hospitalized with acute cardiopulmonary conditions . RSV infection and influenza A were diagnosed on the basis of culture , reverse-transcriptase polymerase chain reaction , and serologic studies . RESULTS A total of 608 healthy elderly patients and 540 high-risk adults were enrolled in prospect i ve surveillance , and 1388 hospitalized patients were enrolled . A total of 2514 illnesses were evaluated . RSV infection was identified in 102 patients in the prospect i ve cohorts and 142 hospitalized patients , and influenza A was diagnosed in 44 patients in the prospect i ve cohorts and 154 hospitalized patients . RSV infection developed annually in 3 to 7 percent of healthy elderly patients and in 4 to 10 percent of high-risk adults . Among healthy elderly patients , RSV infection generated fewer office visits than influenza ; however , the use of health care services by high-risk adults was similar in the two groups . In the hospitalized cohort , RSV infection and influenza A result ed in similar lengths of stay , rates of use of intensive care ( 15 percent and 12 percent , respectively ) , and mortality ( 8 percent and 7 percent , respectively ) . On the basis of the diagnostic codes of the International Classification of Diseases , 9th Revision , Clinical Modification at discharge , RSV infection accounted for 10.6 percent of hospitalizations for pneumonia , 11.4 percent for chronic obstructive pulmonary disease , 5.4 percent for congestive heart failure , and 7.2 percent for asthma . CONCLUSIONS RSV infection is an important illness in elderly and high-risk adults , with a disease burden similar to that of nonp and emic influenza A in a population in which the prevalence of vaccination for influenza is high . An effective RSV vaccine may offer benefits for these adults Abstract Objective : To evaluate the disease burden of upper respiratory infections in elderly people living at home . Design : Prospect i ve surveillance of elderly people . Intervention : None . Setting : Leicestershire , Engl and Subjects : 533 subjects 60 to 90 years of age . Main outcome measures : Pathogens , symptoms , restriction of activity , duration of illness , medical consultations , interval between onset of illness and medical consultation , antibiotic use , admission to hospital , and death . Results : 231 pathogens were identified for 211 ( 43 % ) of 497 episodes for which diagnostic specimens were available : 121 ( 52 % ) were rhinoviruses , 59 ( 26 % ) were coronaviruses , 22 ( 9.5 % ) were influenza A or B , 17 ( 7 % ) were respiratory syncytial virus , 7 ( 3 % ) were parainfluenza viruses , and 3 ( 1 % ) were Chlamydia species ; an adenovirus and Mycoplasma pneumoniae caused one infection each . Infections occurred at a rate of 1.2 episodes per person per annum ( 95 % confidence interval 1.0 to 1.7 ; range 0 - 10 ) and were clinical ly indistinguishable . Lower respiratory tract symptoms complicated 65 % of upper respiratory infections and increased the medical consultation rate 2.4-fold ( χ2 test P<0.001 ) . The median interval between onset of illness and medical consultation was 3 days for influenza and 5 days for other infections . Rhinoviruses caused the greatest disease burden overall followed by episodes of unknown aetiology , coronaviruses , influenza A and B , and respiratory syncytial virus . Conclusions : Respiratory viruses cause substantial morbidity in elderly people . Although respiratory syncytial virus and influenza cause considerable individual morbidity , the burden of disease from rhinovirus infections and infections of unknown aetiology seems greater overall . The interval between onset of illness and consultation together with diagnostic difficulties raises concern regarding the role of antiviral drugs in treating influenza . Key messages There are few data on the morbidity associated with respiratory viruses other than influenza in elderly people Respiratory virus infections in elderly people are clinical ly indistinguishable , and patients with influenza will be difficult to target for antiviral treatment without a near patient diagnostic test Overall , two thirds of elderly people with colds and four fifths of those with influenza and respiratory syncytial virus can be expected to develop lower respiratory illness Although influenza and respiratory syncytial virus cause substantial morbidity in elderly people , the disease burden from rhinovirus infections and colds of unknown aetiology is greater overall Most elderly patients seek medical attention beyond 48 hours when the benefits of antiviral treatment of influenza remain OBJECTIVE To determine whether a point-of-care rapid influenza test impacts the diagnostic evaluation and treatment of children with acute respiratory illnesses . DESIGN R and omized controlled trial . SETTING Pediatric emergency department and acute care clinic of a children 's hospital . PARTICIPANTS Children aged younger than 5 years with fever or acute respiratory symptoms during 2 influenza seasons ( 2002 through 2004 ) . INTERVENTIONS Surveillance days were r and omized to performance or no performance of a point-of-care rapid influenza test . All children had a nasal and throat swab obtained for laboratory tests . The rapid test group had another nasal swab obtained for the QuickVue Influenza Test ( Quidel Corp , San Diego , Calif ) , which was performed by nurses ; results were shared immediately with treating physicians . MAIN OUTCOME MEASURES Rapid test results were compared with results of the viral culture or 2 polymerase chain reaction assays for influenza . Diagnostic test ordering and antibiotic prescribing were compared for the groups . RESULTS Of 468 enrolled children , 306 were from the emergency department and 162 from the clinic . Overall , 88 children ( 19 % ) had influenza infection . Of 205 children in the rapid test group , 51 ( 25 % ) had influenza infection . The rapid influenza test was 82 % sensitive and 99 % specific . In the emergency department , fewer children in the rapid test group had diagnostic tests ordered than in the no rapid test group ( 39 % vs 51 % , P = .03 ) . There was no difference in test ordering in the clinic or in antibiotic prescribing in either setting . The use of antivirals was low . CONCLUSIONS Point-of-care rapid influenza tests were sensitive and specific and were associated with less diagnostic testing in the emergency department The value of antibiotics was assessed in a r and omised , double-blind study of amoxycillin and placebo in sixty adults admitted to hospital with acute exacerbations of asthma . 37 exacerbations were treated with amoxycillin and 34 were treated with placebo . Response to treatment was closely monitored but no significant difference in improvement was demonstrated between groups for length of hospital stay , time taken for 50 % improvement in symptoms , patient 's self assessment and respiratory function , and symptoms and respiratory function at time of discharge from hospital . Antibiotics should not be given routinely to patients admitted to hospital with acute exacerbations of asthma Limited information exists on the performance of antigen-based rapid influenza diagnostic tests ( RIDT ) in diagnosing the novel influenza A p and emic ( H1N1 ) 2009 virus . Large studies evaluating these tests in consecutive patients with a broad clinical spectrum of influenza-like illnesses are needed . We assessed the ClearView ® Exact Influenza A & B test ( Inverness Medical , Cologne , Germany ) in comparison with real-time (r)RT-PCR for detection of the novel influenza A ( H1N1 ) in a population -based prospect i ve study of 1016 adults and children with suspected influenza in Spain . Three hundred and one ( 29.6 % ) patients had a positive sample with the rRT-PCR assay for influenza A and B viruses , with 297 ( 29.2 % ) confirmed cases of the novel influenza A p and emic ( H1N1 ) 2009 virus . Fifty ( 16.8 % ) patients with confirmed A ( H1N1 ) 2009 virus were admitted to hospital , with six of them to the intensive care unit . In comparison with rRT-PCR , the ClearView ® Exact Influenza A & B test had a sensitivity of 19 % ( 95 % CI 14 - 23 ) , a specificity of 100 % , a positive predictive value of 100 % , and a negative predictive value of 75 % ( 95 % CI 72 - 78 ) . The sensitivity of the test remained low across all demographic and clinical strata . Although a positive RIDT performed well in predicting PCR-confirmed infection with p and emic H1N1 virus , the sensitivity was very low and a negative test result was a poor predictor of the absence of infection Introduction The influenza A ( H1N1 ) 2009 outbreak caused death and a disruption of public health services . Rapid influenza diagnostic tests ( RIDT ) could be helpful to ease the triage of patients and prevent an overload of emergency and laboratory facilities . Objectives To compare the sensitivity and specificity of the Clearview Exact Influenza A&B test and real-time reverse transcription(RT)–PCR to detect influenza A ( H1N1 ) 2009 in a paediatric emergency department of a paediatric teaching hospital in Paris , France . Methods 76 children with an influenza-like illness and either severe symptoms or an underlying medical condition were prospect ively recruited between July 2009 and October 2009 . RIDT and RT – PCR were simultaneously performed and compared . Results Among 39 influenza A ( H1N1 ) 2009 RT – PCR-positive children ( median age 5 years ) , 23 Clearview Exact Influenza A&B tests were positive . Sensitivity was 59 % ( 95 % CI 42.2 to 74 ) and specificity was 94.6 % ( 95 % CI 80.5 to 99.1 ) . Conclusions This study shows a sensitivity of RIDT of 59 % , in agreement with other prospect i ve studies , which could be useful in clinical practice for diagnosis influenza A ( H1N1 ) 2009 in children . In outbreaks of a high prevalence , such as the 2009 outbreak , this test can help to prevent an overload of public health services |
625 | 30,101,552 | The majority of papers reporting on antiviral prescription found that a positive POCT result significantly increased use of antivirals for influenza compared with negative POCT results and st and ard supportive care .
A positive POCT result also led to decreased antibiotic use .
The studies assessed in this systematic review support the use of POCT for diagnosis of influenza in patients suffering an acute respiratory infection .
Diagnosis using POCT may lead to more appropriate prescription of treatments for infectious agents . | Acute respiratory tract infections are a major cause of morbidity and mortality and represent a significant burden on the health care system .
Laboratory testing is required to definitively distinguish infecting influenza virus from other pathogens , result ing in prolonged emergency department ( ED ) visits and unnecessary antibiotic use .
Recently available rapid point-of-care tests ( POCT ) may allow for appropriate use of antiviral and antibiotic treatments and decrease patient lengths of stay .
We undertook a systematic review to assess the effect of POCT for influenza on three outcomes : ( 1 ) antiviral prescription , ( 2 ) antibiotic prescription , and ( 3 ) patient length of stay in the ED . | Managing children with influenza-like illness is associated with costly and painful interventions because , in order to distinguish viral from bacterial infections , diagnostic tests ( including routine blood examinations and chest radiographs ) are frequently performed,1,2 and the empirical use of antimicrobial agents is common.3 Various rapid diagnostic techniques for the detection of influenza viruses have been developed , but few data are available on their impact on child care.2,4,5 The aim of this study was to assess the effect of a rapid diagnosis of influenza infection on the management of children with influenza-like illness in an emergency department . All patients seen for influenza-like illness from 6 January to 27 February 2002 , at the paediatric emergency department of the University of Milan , Italy , were enrolled and blindly r and omly assigned in a 1:1 ratio to undergo a rapid test for the detection of influenza viruses or no rapid test . Influenza-like illness was defined as an axillary temperature of ⩾37.8 ° C and at least one symptom of acute upper or lower respiratory tract disease.6 The patients who underwent the test had their throats swabbed after vigorously rubbing both tonsillar surfaces and the posterior pharynx ; the swab was then immediately su bmi tted to the Quickvue influenza test ( Quidel , Milan , Italy ) for the rapid detection of influenza A and B viruses . The test , which has an overall sensitivity of 74–95 % and an overall specificity of 76–98%,5,7,8 was performed by a postgraduate student in accordance with the manufacturer ’s recommendations . The results were available after 10 OBJECTIVE To determine the impact of the rapid diagnosis of influenza on physician decision-making and patient management , including laboratory tests and radiographs ordered , patient charges associated with these tests , antibiotics/antivirals prescribed , and length of time to patient discharge from the emergency department . METHODS Patients aged 2 months to 21 years presenting to an urban children 's teaching hospital emergency department were screened for fever and cough , coryza , myalgias , headache , and /or malaise . After obtaining informed consent , patients were r and omized to 1 of 2 groups : 1 ) physician receives ( physician aware of ) the rapid influenza test result ; or 2 ) physician does not receive ( physician unaware of ) the result . For patients in the physician aware group , nasopharyngeal swabs were obtained , immediately tested with the FluOIA test for influenza A and B , and the result was placed on the chart before patient evaluation by the attending physician . For the physician unaware group , nasopharyngeal swabs were obtained , stored according to manufacturer 's directions , and tested within 24 hours . Results for the physician unaware group were not disclosed to the treating physicians at any time . The 2 result ant influenza-positive groups ( aware and unaware ) were compared for laboratory and radiograph studies and their associated patient charges , antibiotic/antiviral prescriptions , and length of stay in the emergency department . RESULTS A total of 418 patients were enrolled , and 391 completed the study . Of these , 202 tested positive for influenza . Comparison of the 96 influenza-positive patients whose physician was aware of the result with the 106 influenza-positive patients whose physician was unaware of the result revealed significant reductions among the former group in : 1 ) numbers of complete blood counts , blood cultures , urinalyses , urine cultures , and chest radiographs performed ; 2 ) charges associated with these tests ; 3 ) antibiotics prescribed ; and 4 ) length of stay in the emergency department . The number of influenza-positive patients who received prescriptions for antiviral drugs was significantly higher among those whose physician was aware of the result . CONCLUSIONS Physician awareness of a rapid diagnosis of influenza in the pediatric emergency department significantly reduced the number of laboratory tests and radiographs ordered and their associated charges , decreased antibiotic use , increased antiviral use , and decreased length of time to discharge Summary Background Respiratory virus infection is a common cause of hospitalisation in adults . Rapid point-of-care testing ( POCT ) for respiratory viruses might improve clinical care by reducing unnecessary antibiotic use , shortening length of hospital stay , improving influenza detection and treatment , and rationalising isolation facility use ; however , insufficient evidence exists to support its use over st and ard clinical care . We aim ed to assess the effect of routine POCT on a broad range of clinical outcomes including antibiotic use . Methods In this pragmatic , parallel-group , open-label , r and omised controlled trial , we enrolled adults ( aged ≥18 years ) within 24 h of presenting to the emergency department or acute medical unit of a large UK hospital with acute respiratory illness or fever higher than 37·5 ° C ( ≤7 days duration ) , or both , over two winter seasons . Patients were r and omly assigned ( 1:1 ) , via an internet-based allocation sequence with r and om permuted blocks , to have a molecular POC test for respiratory viruses or routine clinical care . The primary outcome was the proportion of patients who received antibiotics while hospitalised ( up to 30 days ) . Secondary outcomes included duration of antibiotics , proportion of patients receiving single doses or brief courses of antibiotics , length of stay , antiviral use , isolation facility use , and safety . Analysis was by modified intention to treat , excluding patients who declined intervention or were withdrawn for protocol violations . This study is registered with IS RCT N , number 90211642 , and has been completed . Findings Between Jan 15 , 2015 , and April 30 , 2015 , and between Oct 1 , 2015 , and April 30 , 2016 , we enrolled 720 patients ( 362 assigned to POCT and 358 to routine care ) . Six patients withdrew or had protocol violations . 301 ( 84 % ) of 360 patients in the POCT group received antibiotics compared with 294 ( 83 % ) of 354 controls ( difference 0·6 % , 95 % CI −4·9 to 6·0 ; p=0·84 ) . Mean duration of antibiotics did not differ between groups ( 7·2 days [ SD 5·1 ] in the POCT group vs 7·7 days [ 4·9 ] in the control group ; difference −0·4 , 95 % CI −1·2 to 0·4 ; p=0·32 ) . 50 ( 17 % ) of 301 patients treated with antibiotics in the POCT group received single doses or brief courses of antibiotics ( < 48 h ) compared with 26 ( 9 % ) of 294 patients in the control group ( difference 7·8 % , 95 % CI 2·5 to 13·1 ; p=0·0047 ; number needed to test=13 ) . Mean length of stay was shorter in the POCT group ( 5·7 days [ SD 6·3 ] ) than in the control group ( 6·8 days [ 7·7 ] ; difference −1·1 , 95 % CI −2·2 to −0·3 ; p=0·0443 ) . Appropriate antiviral treatment of influenza-positive patients was more common in the POCT group ( 52 [ 91 % ] of 57 patients ) than in the control group ( 24 [ 65 % ] of 37 patients ; difference 26·4 % , 95 % CI 9·6 to 43·2 ; p=0·0026 ; number needed to test=4 ) . We found no differences in adverse outcomes between the groups ( 77 [ 21 % ] of 360 patients in the POCT group vs 88 [ 25 % ] of 354 patients in the control group ; −3·5 % , −9·7 to 2·7 ; p=0·29 ) . Interpretation Routine use of molecular POCT for respiratory viruses did not reduce the proportion of patients treated with antibiotics . However , the primary outcome measure failed to capture differences in antibiotic use because many patients were started on antibiotics before the results of POCT could be made available . Although POCT was not associated with a reduction in the duration of antibiotics overall , more patients in the POCT group received single doses or brief courses of antibiotics than did patients in the control group . POCT was also associated with a reduced length of stay and improved influenza detection and antiviral use , and appeared to be safe . Funding University of Southampton OBJECTIVE To present our experience regarding the use of a rapid diagnostic test for seasonal influenza A and B. METHODS We systematic ally collected and analyzed our data regarding the use of a rapid diagnostic test for seasonal influenza A and B in patients with specific respiratory symptoms that sought medical services , during the time period from 01/01/2009 to 30/05/2009 , from a network of physicians ( SOS Doctors ) who perform house-call visits in the area of Attica , Greece . RESULTS From the total of 16,335 house-call visits performed during the evaluated period , 3412 ( 20.8 % ) were due to respiratory/influenza symptoms ; 197 ( 5.8 % ) patients were tested for influenza . From the 184 patients with available data regarding the test result , 97 ( 52.7 % ) were positive for influenza . Significantly more oseltamivir and less antibiotic treatment were prescribed to patients with positive test result compared with those with a negative test result . Additionally , the impact of the test in the participating physicians ' decision making was obvious , as doctors who used the test systematic ally prescribed significantly more oseltamivir and less antibiotic treatment compared to the doctors who did n't use the test . CONCLUSION The use of a rapid test for seasonal influenza enabled the targeted treatment with oseltamivir , as well as a reduction in antibiotic treatment , in patients found positive for influenza in our clinical setting BACKGROUND Influenza affects many people worldwide each year and has many troublesome symptoms . We investigated the efficacy and safety of the inhaled antiviral agent zanamivir as a treatment for influenza A and B infection . METHODS In a r and omised , double-blind , placebo-controlled trial , we recruited 455 patients aged 12 years and older with influenza-like symptoms of 36 h duration or less who lived in Australia , New Zeal and , and South Africa . Eligible patients were r and omly assigned 10 mg inhaled zanamivir ( n=227 ) or placebo ( n=228 ) twice daily for 5 days . All patients recorded symptoms on diary cards four times daily during treatment and twice daily for 9 days after treatment . We analysed all patients by intention to treat , influenza-positivity , and high risk of developing complications . FINDINGS Compared with placebo , zanamavir relieved influenza symptoms a median of 1.5 days earlier in the intention-to-treat ( p=0.011 ) and influenza-positive ( p=0.004 ) population s , and 2 days earlier in patients who were febrile at entry [ corrected ] . In high-risk patients treated with zanamivir , symptoms were alleviated a median of 2.5 days earlier ( p=0.048 ) , fewer had complications ( p=0.004 ) , and fewer used complication-associated antibiotics ( p=0.025 ) compared with placebo . The adverse event profiles were similar for zanamivir and placebo . INTERPRETATION Zanamivir was well-tolerated and effective in decreasing the duration and severity of symptoms . Complications were also decreased in high-risk patients but these findings need to be confirmed in future studies due to the limited number of patients [ corrected ] OBJECTIVES Acute respiratory tract infections represent a significant burden on pediatric emergency departments ( ED ) and families . We hypothesized that early and rapid diagnosis of a viral infection alleviates the need for ancillary testing and antibiotic treatment . STUDY DESIGN We conducted a r and omized , controlled trial of children 3 to 36 months of age with febrile acute respiratory tract infections at a pediatric ED . Two hundred four subjects were r and omly assigned to receive rapid respiratory viral testing on admission or a routine ED admission protocol . Outcome measures were : mean length of visits , rate of ancillary tests , and antibiotic prescription in the ED . A follow-up call was made to all study subjects to inquire about further healthcare visits , ancillary testing , and antibiotic prescription after ED discharge . RESULTS We did not find a statistically significant difference in ED length of visits , rate of ancillary testing , or antibiotic prescription rate in the ED between the study groups . There was , however , a significant reduction in antibiotic prescription after ED discharge ( in the group who had rapid viral testing RR = 0.36 ; 95 % CI = 0.14 , 0.95 ) . CONCLUSIONS Rapid multi-viral testing in the ED did not significantly affect ED patient treatment but may reduce antibiotic prescription in the community after discharge from the ED , suggesting a novel strategy to alter community physician antibiotic prescription patterns BACKGROUND Fever is a frequent cause of medical consultation among returning travelers . The objectives of this study were to assess whether physicians were able to identify patients with influenza and whether the use of an influenza rapid diagnostic test ( iRDT ) modified the clinical management of such patients . METHODS R and omized controlled trial conducted at 2 different Swiss hospitals between December 2008 and November 2012 . Inclusion criteria were 1 ) age ≥ 18 years , 2 ) documented fever of ≥ 38 ° C or anamnestic fever + cough or sore throat within the last 4 days , 3 ) illness occurring within 14 days after returning from a trip abroad , 4 ) no definitive alternative diagnosis . Physicians were asked to estimate the likelihood of influenza on clinical grounds , and a single nasopharyngeal swab was taken . Thereafter patients were r and omized into 2 groups : i ) patients with iRDT ( BD Directigen A + B ) performed on the nasopharyngeal swab , ii ) patients receiving usual care . A quantitative PCR to detect influenza was done on all nasopharyngeal swabs after the recruitment period . Clinical management was evaluated on the basis of cost of medical care , number of X-rays requested and prescription of anti-infective drugs . RESULTS 100 eligible patients were referred to the investigators . 93 patients had a naso-pharyngeal swab for a PCR and 28 ( 30 % ) swabs were positive for influenza . The median probability of influenza estimated by the physician was 70 % for the PCR positive cases and 30 % for the PCR negative cases ( p < 0.001 ) . The sensitivity of the iRDT was only 20 % , and specificity 100 % . Mean medical cost for the patients managed with iRDT and without iRDT were USD 581 ( 95%CI 454 - 707 ) and USD 661 ( 95%CI 522 - 800 ) respectively . 14/60 ( 23 % ) of the patients managed with iRDT were prescribed antibiotics versus 13/33 ( 39 % ) in the control group ( p = 0.15 ) . No patient received antiviral treatment . CONCLUSION Influenza was a frequent cause of fever among these febrile returning travelers . Based on their clinical assessment , physicians had a higher level of suspicion for influenza in PCR positive cases . The iRDT used in this study showed a disappointingly low sensitivity and can therefore not be recommended for the management of these patients . TRIAL REGISTRATION Clinical Trials.gov NCT00821626 Background : The objective of this study was to assess the effect of rapid testing for influenza virus on management of febrile young infants . Methods : During 2 influenza seasons ( November to December 2003 and December 2004 to February 2005 ) , we studied prospect ively infants who were 0 to 36 months of age who presented to the emergency department ( ED ) with fever in the absence of signs of focal infection . The Directigen Flu A+B test was used to determine infection with influenza virus types A or B. Confirmatory viral cultures were not done . Results : Rapid influenza testing was performed in 206 infants and 84 ( 40.7 % ) of them were influenza-positive . Infants with a positive and a negative influenza test showed a similar mean ( st and ard deviation ) age ( 6.86 [ 6.3 ] versus 6.55 [ 6.8 ] months ) and mean temperature ( 39.38 ° C [ 0.6 ] versus 39.32 ° C [ 0.8 ] ) , but there were significant differences ( P < 0.01 ) in the percentage of patients undergoing blood tests ( 33.3 % versus 100 % ) , urinalysis ( 80.9 % versus 100 % ) , chest roentgenogram ( 14.2 % versus 32 % ) , cerebrospinal fluid analysis ( 1.33 % versus 21.3 % ) , mean length of stay in the ED ( 116.2 [ 75.5 ] versus 192.9 [ 76.3 ] minutes ) , admission to the ED observation ward ( 8.3 % versus 21.3 % ) , inpatient care ( 2.3 % versus 16.4 % ) and antibiotic treatment ( 0 % versus 38.5 % ) . All positive bacterial cultures occurred among influenza-negative patients . Conclusions : The inclusion of rapid influenza testing for the evaluation of febrile young infants without signs of focal infection during influenza season decreases the need for additional studies and reduces the length of stay in the ED , the use of antibiotic treatment and unnecessary hospitalizations OBJECTIVES To determine the effect of point-of-care testing ( POCT ) for influenza on the physician management of febrile children who are at risk for serious bacterial illness ( SBI ) on the basis of age and temperature and who are presenting to a pediatric emergency department ( ED ) during an influenza outbreak . METHODS Patients 2 - 3 months of age with temperature of > or = 38 degrees C and patients 3 - 24 months of age with temperature of > or = 39 degrees C who were presenting to a pediatric ED during an influenza outbreak were enrolled into a prospect i ve , quasi-r and omized , controlled trial . Influenza testing was performed on enrolled patients by either the POCT or the st and ard-testing ( ST ) methods . The two groups were compared in terms of laboratory testing , chest radiography , antibiotic use , visit-associated costs , pediatric ED lengths of stay , inpatient admission , and return visits to the pediatric ED . Similar analyses also were performed on the result ing subgroups of patients on the basis of method of testing ( POCT or ST ) and test result ( positive or negative ) . RESULTS Of 767 eligible patients , 700 ( 91 % ) completed the study . No significant differences were demonstrated between the POCT and ST groups with respect to laboratory tests ordered , chest radiographs obtained , antibiotic administration , inpatient admission , return visits to the pediatric ED , lengths of stay , or visit-associated costs . In the subgroup analysis , the adjusted odds ratios ( ORs ) for blood culture in influenza test-positive to -negative patients were 0.59 and 0.71 in the POCT and ST groups , respectively ( p = 0.088 ) . The adjusted ORs for urine culture in influenza test-positive to -negative patients were 0.46 and 0.67 in the POCT and ST groups , respectively ( p = 0.005 ) . CONCLUSIONS When using a strategy of performing influenza testing on all patients at risk for SBI who presented to a pediatric ED during an influenza outbreak , the method of testing ( POCT or ST ) did not appear to significantly alter physician management , cost , or length of stay in the pediatric ED . However , if the interaction of the method of testing and the test result ( positive or negative ) were considered , a positive POCT for influenza was associated with a significant reduction in orders for urinalyses and urine cultures OBJECTIVE To determine whether a point-of-care rapid influenza test impacts the diagnostic evaluation and treatment of children with acute respiratory illnesses . DESIGN R and omized controlled trial . SETTING Pediatric emergency department and acute care clinic of a children 's hospital . PARTICIPANTS Children aged younger than 5 years with fever or acute respiratory symptoms during 2 influenza seasons ( 2002 through 2004 ) . INTERVENTIONS Surveillance days were r and omized to performance or no performance of a point-of-care rapid influenza test . All children had a nasal and throat swab obtained for laboratory tests . The rapid test group had another nasal swab obtained for the QuickVue Influenza Test ( Quidel Corp , San Diego , Calif ) , which was performed by nurses ; results were shared immediately with treating physicians . MAIN OUTCOME MEASURES Rapid test results were compared with results of the viral culture or 2 polymerase chain reaction assays for influenza . Diagnostic test ordering and antibiotic prescribing were compared for the groups . RESULTS Of 468 enrolled children , 306 were from the emergency department and 162 from the clinic . Overall , 88 children ( 19 % ) had influenza infection . Of 205 children in the rapid test group , 51 ( 25 % ) had influenza infection . The rapid influenza test was 82 % sensitive and 99 % specific . In the emergency department , fewer children in the rapid test group had diagnostic tests ordered than in the no rapid test group ( 39 % vs 51 % , P = .03 ) . There was no difference in test ordering in the clinic or in antibiotic prescribing in either setting . The use of antivirals was low . CONCLUSIONS Point-of-care rapid influenza tests were sensitive and specific and were associated with less diagnostic testing in the emergency department Children are an important vector for spreading influenza and they are at increased risk for complications . The appropriate diagnosis of influenza may help start early antiviral treatment and may optimize the use of antibiotics and additional laboratory tests . The objective of this study was to describe the influence of rapid influenza detection test ( RIDT ) on clinical management of children with acute febrile respiratory tract infections . The method consisted of a prospect i ve , open , cohort study conducted in three primary care clinics in Warsaw , Pol and , during the epidemic influenza seasons of 2009/2010 and 2010/2011 . A total number of 256 children of the age 0 - 5 years with symptoms of febrile respiratory tract infection were enrolled into the study . A 115 of them were tested with RIDT ( BD Directigen EZ FluA + B ) and another 141 children , who were not tested , constituted a control group . We found that RIDT gave positive results in 35 ( 30 % ) out of the 115 tested children . Antibiotics , additional blood tests and urinalysis were administered more often in the control group compared with the rapid test group ( 16 % vs. 7 % ; 14 % vs. 5 % , and 47 % vs. 32 % , respectively ) . Chest radiograms were made only in six cases of children from the control group . We conclude that in children with symptoms of acute febrile respiratory tract infection , the rapid influenza detection test provides a rational use of antivirals , reduces an inappropriate use of antibiotics , and decreases a number of additional tests conducted AIM Influenza causes a large burden of disease in children . Point-of-care testing ( POCT ) can rapidly diagnose influenza with the potential to reduce investigation and hospital admission rates , but information on its use in an Australian setting is limited . METHODS Through a retrospective review of laboratory-confirmed influenza cases presenting at a paediatric emergency department ( ED ) in 2009 , we evaluated children diagnosed by POCT versus st and ard testing ( direct fluorescent antibody , polymerase chain reaction or viral culture ) and assessed differences in investigations , admission requirements , length-of-stay ( LOS ) in ED/hospital and antibiotic/antiviral prescription . The rate of serious bacterial infection was examined . RESULTS Compared with st and ard testing ( n = 65 ) , children diagnosed by positive POCT ( n = 236 ) had a shorter median hospital LOS by 1 day ( P = 0.006 ) , increased antiviral prescription ( odds ratio 3.31 , P < 0.001 ) and a reduction in the time to influenza diagnosis ( 2.4 vs. 24.4 h , P < 0.001 ) ; however , a negative POCT result ( n = 63 ) result ed in delayed diagnosis ( 44.0 h , P = 0.001 ) . POCT did not decrease LOS in ED . Interpretation of reductions in admission and investigations with POCT may be limited by possible confounding . Approximately 4 % of influenza patients had a serious bacterial infection ; urinary tract infections were commonest ( 2.7 % ) , but no cerebrospinal fluid cultures were positive . A single positive blood culture was seen among 332 immunocompetent influenza patients . CONCLUSIONS Influenza diagnosis by POCT was quicker and reduced LOS of hospitalised children , whereas negative results delayed diagnosis . Negative POCT should not alter usual investigations if influenza remains suspected . A controlled prospect i ve study during the influenza season is needed to clarify the direct benefits of POCT BACKGROUND The clinical diagnosis of influenza is difficult in the younger children . OBJECTIVES Evaluate the impact of rapid influenza diagnostic test ( RIDT ) on clinicians ' estimation of the clinical probability of influenza in children . STUDY DESIGN This prospect i ve study included children aged from 1 month to 5 years who were admitted in a university paediatric emergency department during an influenza epidemic period and presented with fever without source . The RIDT Quickvue ( ® ) was performed on nasopharyngeal aspiration and results were confirmed with immunofluorescence and /or PCR . The clinical probability of influenza and serious bacterial infection ( SBI ) was evaluated for each child before and after the physician(s ) was informed of the RIDT results . RESULTS 170 children were included from January 15th through March 18th , 2013 . After the only clinical examination , the overall clinical probability of influenza was 66.0 % [ CI 95 % : 63.04 - 68.4 ] , and was significantly increased at 92.4 % [ CI 95 % : 89.5 - 95.3 ] in case of positive RIDT and significantly decreased at 30.8 % [ CI 95 % : 29.0 - 32.5 ] in case of negative RIDT without knowing the results of laboratory tests . Whereas the initial clinical probability of influenza were appropriate regarding the prevalence ( 66.0 % vs. 57.0 % ) , the probability of SBI was overestimated ( 30.2 % vs. 8.8 % ) . The RIDT result positive enabled a significant decrease in orders for chest X-rays ( 64,4 % vs. 45.8 % , p<0,05 ) and laboratory tests ( 71,1 % vs. 41.1 % , p<0,05 ) . CONCLUSIONS The RIDT seems to be a useful diagnostic tool for ED clinicians in epidemic conditions . Improving clinician estimation of flu probability would reduce orders for imaging and testing Acute respiratory tract infections ( ARTIs ) are a common reason for unnecessary antibiotic prescriptions worldwide . Our objective was to determine if providing access to rapid influenza test results could reduce antibiotic prescriptions for ARTIs in a re source -limited setting . We conducted a prospect i ve , pre-post study from March 2013 to October 2014 . Out patients presenting to a hospital in Sri Lanka were surveyed for influenza-like illness-onset of fever ≥ 38.0 ° C and cough in prior 7 days . Enrolled patients were administered a structured question naire , physical examination , and nasal/nasopharyngeal sampling for rapid influenza A/B testing . Influenza test results were released only during phase 2 ( January-October 2014 ) . We enrolled 571 patients with ILI-316 in phase 1 and 241 in phase 2 . The proportion positive for influenza was 46.5 % in phase 1 and 28.6 % in phase 2 , P < 0.001 . Between phases , antibiotic prescriptions decreased from 81.3 % to 69.3 % ( P = 0.001 ) among all patients and from 83.7 % to 62.3 % ( P = 0.001 ) among influenza-positive patients . On multivariable analysis , a positive influenza result during phase 2 was associated with lower odds of antibiotic prescriptions ( OR = 0.50 , 95 % CI = 0.26 - 0.95 ) . This prospect i ve study suggests that providing access to rapid influenza testing may reduce unnecessary antibiotic prescriptions in re source -limited setting |
626 | 30,721,242 | None of the studies defined adequacy of dialysis as a patient relevant outcome such as survival or quality of life .
Patients had a substantially different underst and ing of the construct dialysis adequacy than the biochemical interpretation reported in the literature .
Being alive , time spent while being on dialysis , fatigue and friendliness of staff were the most prominent themes that patients linked to the construct of dialysis adequacy .
Conclusion Adequacy of dialysis as reported in the literature refers to biochemical outcome measures , most of which are not related with patient relevant outcomes .
For patients , adequate dialysis is a dialysis that enables them to spend as much quality time in their life as possible | Background Clinical trials are most informative for evidence -based decision-making when they consistently measure and report outcomes of relevance to stakeholders , especially patients , clinicians , and policy makers .
However , sometimes terminology used is interpreted differently by different stakeholders , which might lead to confusion during shared decision making .
The construct dialysis adequacy is frequently used , suggesting it is an important outcome both for health care professionals as for patients .
Objective To assess the scope and consistency of the construct dialysis adequacy as reported in r and omised controlled trials in hemodialysis , and evaluate whether these align to the insights and underst and ing of this construct by patients . | BACKGROUND Protein requirements in stable , adequately dialysed haemodialysis patients are not known and recommendations vary . It is not known whether increasing the dialysis dose above the accepted adequate level has a favourable effect on nutrition . The aim of this study was to determine whether prescribing a high protein diet and increasing the dose of dialysis would have a favourable effect on dietary protein intake and nutritional status in stable , adequately dialysed haemodialysis patients . Effects on hyperphosphataemia and acidosis were also studied . METHODS Patients were r and omized to a high dialysis dose ( HDD ) group ( target Kt/V(eq ) of 1.4 ) or a regular dialysis dose ( RDD ) group ( target Kt/V(eq ) of 1.0 ) . All patients were prescribed a high protein ( HP ) diet [ 1.3 g/kg of ideal body weight (IBW)/day ] and a regular protein ( RP ) diet ( 0.9 g/kg/day ) , each during 40 weeks in a crossover design . In 50 patients , 23 in the HDD and 27 in the RDD group follow-up was > or = 10 weeks . These patients , aged 56+/-15 years , were included in the analysis . Nutritional status was assessed by anthropometry , plasma albumin and a nutritional index . RESULTS Delivered Kt/V(eq ) in the HDD group ( 1.26+/-0.14 ) was significantly higher than in the RDD group ( 1.02+/-0.08 ) . Protein intake estimated from total nitrogen appearance ( PNA ) measurements and food records ( DPI ) was significantly higher during the HP diet ( PNA(IBW ) , 1.01+/-0.18 g/kg/day ; DPI(IBW ) , 1.15+/-0.18 g/kg/day ) than during the RP diet ( PNA(IBW ) , 0.90+/-0.14 g/kg/day ; DPI(IBW ) , 0.94+/-0.11 g/kg/day ) . Increasing the dialysis dose did not increase protein intake either during the HP or RP diet . Plasma albumin ( 41.9+/-3.0 g/l ) lean body mass ( 107+/-15 % of normal values ) and the nutritional index did not differ between the dialysis dose groups or protein diets and remained stable overtime . Dry body weight ( 97+/-14 % ) and total fat mass increased over time in the HDD group , but remained stable in the RDD group suggesting an effect of dialysis dose on energy balance . There was no effect of the protein diets on dry body weight or total fat mass . Plasma phosphate levels and oral bicarbonate supplements were lower in the HDD group , but were comparable between the protein diets . CONCLUSIONS Prescribing a HP diet result ed in a modest increase in actual protein intake , but increasing dialysis dose did not have a contributing effect . A HP diet or increasing the dialysis dose did not have a favourable effect on the nutritional status . A dietary protein intake of at least 0.9 g/kg IBW/day appears to be sufficient for adequately dialysed haemodialysis patients without overt malnutrition BACKGROUND Dialysis adequacy targets frequently are difficult to achieve in large hemodialysis patients . Dual dialyzers can be used to improve clearance . It is unknown whether series or parallel configurations are superior . METHODS Eighteen large hemodialysis patients ( mean weight , 92.4 kg ) were enrolled in a r and omized , crossover trial to directly compare dual dialyzers in parallel and series configurations . Treatment times , blood flow rates , and dialysate flow rates were kept constant . RESULTS Compared with a single dialyzer , parallel dual dialyzers increased the single-pool Kt/V ( spKt/V ) from 1.25 + /- 0.22 to 1.43 + /- 0.29 ( P < 0.003 ) . Series dual dialyzers improved urea clearance measured by spKt/V ( spKt/V(urea ) ) to 1.46 + /- 0.26 ( P < 0.0003 compared with a single dialyzer ) . Kt/V and urea reduction ratio of dual dialyzers in parallel were not significantly different from those of dual dialyzers in series . Half the subjects failed to meet the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative recommended adequacy target for spKt/V(urea ) of 1.2 or less using a single dialyzer . With the use of dual dialyzers , 83 % of subjects achieved this adequacy target . Serum levels of a middle molecule , beta2-microglobulin , were reduced 34 % after 2 months of dual-dialyzer therapy . Cost analysis estimates annual net savings of 1,260 dollars with dual-dialyzer therapy , primarily from projected savings in inpatient expenses . CONCLUSION In large hemodialysis patients , our study shows that dual dialyzers in parallel and series are equally effective at improving urea clearance without prolonging dialysis treatment times BACKGROUND Half of the dialysis population suffers from hyperphosphataemia , which is now recognized as a major factor of haemodialysis ( HD ) morbidity and mortality . Current control is focussed on reducing dietary phosphate intake and diminishing absorption using phosphate binders , whereas control and quantification of phosphate removal by HD is undervalued . The aim of this prospect i ve study was to develop a simple , bedside formula to estimate dialytic phosphate removal in stable HD patients . METHODS This was a prospect i ve , r and omized trial . Phosphate and urea elimination were assessed in a representative group of patients at two dialysis centres using r and omly different dialysers ( 1.3 - 2.4 m(2 ) ) . Quantification was performed by partial dialysate collection , concentration measurements in blood and effluent dialysate spot sample s , and Kt/V(urea ) during st and ard high-flux HD . Multiple linear regression analyses were used in 77 % of all data sets to generate an equation to predict phosphate removal . The formula was vali date d in the remaining 23 % of data sets , in the same group of patients using a large capillary filter , and in diabetic patients treated with a small dialyser at different blood flows ( 200 , 250 , and 300 ml/min ) . RESULTS A formula allowing quantification of phosphate removal within one HD session was developed in 18 of 74 patients during 41 treatments ( 137 out of 177 data sets ) and was determined as : M(PO4pred)=0.1 t -17 + 50c(ds60)+11c(b60 ) , where t is treatment time in min , c(ds60 ) and c(b60 ) are phosphate concentrations in dialysate and plasma measured 60 min into HD in mmol/l , and M(PO4pred ) is estimated phosphate removed in mmol . The precision was remarkable ( r(2)=0.92 - 0.94 ) . The comparison of phosphate and Kt/V(urea ) showed a significant association ( r(2)=0.28 ) , albeit with remarkable scatter . CONCLUSIONS We present the first approach to quantify phosphate removal during high-flux HD by a bedside formula . Only 28 % of the variation in phosphate removal was explained by Kt/V(urea ) . It appears that other factors not adequately accounted for by Kt/V(urea ) affect phosphate removal . Therefore , we propose an individual control and quantification of phosphate removal in HD Dialysis is measured as Kt/V , which scales the dose ( Kt ) to body water content ( V ) . Scaling dialysis dose to body surface area ( S(dub ) ) has been advocated , but the implication s of such rescaling have not been examined . We developed a method of rescaling measured Kt/V to S(dub ) and studied the effect of such alternative scaling on the minimum adequacy values that might then be applied in male and female patients of varying body size . We examined anthropometric estimates of V and S ( Watson vs. Dubois estimates ) in 1765 patients enrolled in the HEMO study after excluding patients with amputations . An S-normalized target stdKt/V was defined , and an adequacy ratio ( R ) was computed for each patient as R = D/N where D = delivered stdKt/V ( calculated using the Gotch-Leypoldt equation for stdKt/V ) and N = the S-normalized minimum target value . In the HEMO data set , we determined the extent to which baseline ( prer and omization ) stdKt/V values would have exceeded such an S-based minimum target stdKt/V. The median V(wat):S(dub ) ratios were significantly higher in men ( 21.34 ) than in women ( 18.50 ) . The average of these ( 20 ) was used to normalize the current suggested minimally adequate value ( stdKt/V > or = 2.0/week ) to the S-normalized target value ( stdKt/S > or = 40 L/M(2 ) ) , assuming that average modeled V = average anthropometric V. To achieve this S-normalized target , the required single-pool ( sp ) Kt/V was always higher in women than in men at any level of body size . For small patients ( V(wat ) = 25L ) , required stdKt/V values were 2.05 and 2.21/week for men and women , respectively , corresponding to spKt/V values of 1.31 and 1.52/session . On the other h and , large ( V(wat ) = 50L ) male patients would need spKt/V values of only 1.0/session . Prer and omization baseline dialysis sessions in the HEMO study were found to meet such a new S-based st and ard in almost all ( 766/773 ) men and in 885/992 women . An analysis of scaling dose to anthropometrically estimated liver size ( L ) showed similar gender ratios for V(wat):L and V(wat):S(dub ) , providing a potential physiologic explanation underpinning S-based scaling . S-based scaling of the dialysis dose would require considerably higher doses in small patients and in women , and would allow somewhat lower doses in larger male patients . Current dialysis practice would largely meet such an S-based adequacy st and ard if the dose were normalized to a V(wat):S(dub ) ratio of 20 BACKGROUND Using st and ard hemodialysis regimens , overweight patients often do not reach Kidney Disease Outcomes Quality Initiatives ( KDOQI ) Kt/V targets , and this has been associated with lower health-related quality of life ( HRQL ) . Whether increasing dialysis adequacy in large patients not achieving KDOQI targets improves HRQL is unknown . STUDY DESIGN R and omized blinded crossover study . SETTING & PARTICIPANTS Overweight ( > 80 kg ) underdialyzed patients from 6 dialysis units in 2 Canadian dialysis programs . INTERVENTIONS Six-week treatment periods with a st and ard dialysis regimen ( 4 hours 3 times weekly ) and 3 augmented regimens : 4.5 hours of hemodialysis , 4 hours of hemodialysis with increased dialysate flow , and 4 hours of hemodialysis with 2 dialyzers in parallel . OUTCOMES & MEASUREMENTS The End-Stage Renal Disease Symptom domain of the Kidney Disease Quality -of-Life Short-Form question naire ( primary outcome ) and the Health Utilities Index Mark 2 ( secondary outcome ) . RESULTS We enrolled 18 patients ( mean weight , 109.7 + /- 16.2 [ SD ] kg ) ; 12 completed all 4 regimens . Mean Kt/Vs during the study were 1.27 ( 95 % confidence interval [ CI ] , 1.19 to 1.35 ) , 1.41 ( 95 % CI , 1.32 to 1.50 ) , 1.31 ( 95 % CI , 1.22 to 1.39 ) , and 1.41 ( 95 % CI , 1.33 to 1.49 ) for patients receiving st and ard dialysis , 4.5 hours of hemodialysis , hemodialysis with increased dialysate flow , and hemodialysis with 2 dialyzers , respectively . Kidney Disease Quality -of-Life End-Stage Renal Disease Symptom domain and Health Utilities Index Mark 2 scores were 75.9 ( 95 % CI , 70.7 to 81.2 ) and 0.69 ( 95 % CI , 0.56 to 0.81 ) for patients receiving st and ard dialysis , respectively . These did not differ when patients received the 3 augmented dialysis regimens ( P = 0.2 and P = 0.5 , respectively ) . LIMITATIONS Small sample size and inability to fully blind patients to the treatment they were receiving . CONCLUSION Improving hemodialysis adequacy for large underdialyzed patients did not lead to improved HRQL . Our findings suggest that augmentation of the dialysis regimen is not required for these patients in the absence of overt uremic symptoms BACKGROUND Muscle cramp is a common complication of haemodialysis . The exact mechanism of this complication is still unknown . Many approaches have been used to relieve the muscle cramping but have had variable effects . One of the possible mechanisms of haemodialysis-associated muscle cramps ( HAMC ) is the disturbance of muscle energy metabolism . Creatine monohydrate can enhance muscle metabolism . We evaluated the clinical effect of creatine monohydrate on HAMC . METHODS Ten patients with frequent muscle cramps during haemodialysis were r and omly selected into two groups , control and placebo . In a double-blind manner , 12 mg of creatine monohydrate or placebo was given to each patient before each dialysis session for 4 weeks . The incidence of muscle cramp during haemodialysis was compared between the two groups . Dialysis adequacy , haemodynamic status , and side-effects were also evaluated . We continued to observe and compare the patients during a 4-week washout period to verify the effect of creatine monohydrate . RESULTS The frequency of symptomatic muscle cramps decreased by 60 % in the creatine monohydrate treatment group ( 6.2+/-0.8 vs 2.6+/-1.8 times/4 weeks , P<0.05 ) during the treatment period . This decreasing incidence of muscle cramps disappeared in the washout period in the creatine group ( 6.6+/-1.1 times/4 weeks ) . There was no difference in the incidence of muscle cramps in the placebo group . The haematocrit , Kt/V , serum albumin , and haemodynamics remained unchanged in both groups during the treatment and washout periods . Serum creatinine increased slightly after creatine monohydrate treatment ( 10.7+/-3.2 vs 12.4+/-3.2 mg/dl , P<0.05 ) . No adverse effect was found in either group during the treatment and washout periods . CONCLUSION These data suggest that creatine monohydrate can reduce the incidence of HAMC and that it may be a safe agent BACKGROUND Anaemia is one of the major clinical characteristics of patients with chronic renal failure , and has a considerable effect on morbidity and mortality . Adequate dialysis is of paramount importance in correcting anaemia by removing small and medium-sized molecules , which may inhibit erythropoiesis . However , high-molecular-weight inhibitors cleared only by means of highly porous membranes have also been found in uraemic serum and it has been cl aim ed from uncontrolled studies that high-flux dialysis could improve anaemia in haemodialysis patients . METHODS We therefore planned this multicentre r and omized controlled trial with the aim of testing whether the use of a large-pore biocompatible membrane for a fixed 12-week follow-up improves anaemia in haemodialysis patients in comparison with the use of a conventional cellulose membrane . Eighty-four ( 5.3 % ) of a total of 1576 adult haemodialysed patients attending 13 Dialysis Units fulfilled the entry criteria and were r and omly assigned to the experimental treatment ( 42 patients ) or conventional treatment ( 42 patients ) . RESULTS Haemoglobin levels increased non-significantly from 9.5+/-0.8 to 9.8+/-1.3 g/dl ( dP=0 . 069 ) in the population as a whole , with no significant difference between the two groups ( P:=0.485 ) . Erythropoietin therapy was given to 32/39 patients ( 82 % ) in the conventional group , and 26/35 ( 74 % ) in the experimental group ( P:=0.783 ) with subcutaneous administration to 26/32 patients in conventional and to 23/26 patients in experimental group , P:=0.495 . Dialysis dose ( Kt/V ) remained constant in both groups ( from 1.30+/-0.17 to 1.33+/-0.20 in the conventional group and from 1.28+/-0.26 to 1.26+/-0.21 in the experimental group , P:=0.242 ) . Median pre- and post-dialysis beta(2)-microglobulin levels remained constant in the conventional group ( 31.9 and 34.1 mg/dl at baseline ) and decreased in the experimental group ( pre-dialysis values from 31.1 to 24.7 mg/dl , P:=0.004 and post-dialysis values from 24.8 to 20.8 mg/dl , P:=0.002 ) . Median erythropoietin doses were not different at baseline ( 70 IU/kg/week in conventional treatment and 90 IU/kg/week in experimental treatment , P:=0.628 ) and remained constant during follow-up ( from 70 to 69 IU/kg/week in the conventional group and from 90 to 91 IU/kg/week in the experimental group , P:=0.410 ) . Median erythropoietin plasma levels were in the normal range and remained constant ( from 12.1 to 12.9 mU/ml in the conventional group and from 13.2 to 14.0 mU/ml in the experimental group , P:=0.550 ) . CONCLUSIONS This study showed no difference in haemoglobin level increase between patients treated for 3 months with a high-flux biocompatible membrane in comparison with those treated with a st and ard membrane . When patients are highly selected , adequately dialysed , and have no iron or vitamin depletion , the effect of a high-flux membrane is much less than might be expected from the results of uncontrolled studies Purpose Central venous catheters for maintenance hemodialysis ( HD ) are design ed to attain the required dialysis dose through sustained high blood flow rates ( BFR ) . The authors studied the immediate and long-term performance and complications of two twin-catheter systems , the Tesio catheter ( TC ) and the LifeCath Twin ( LC ) , to inform clinical practice . Methods This single-center r and omized controlled parallel-group trial allocated 80 incident patients ( 1:1 ) to receive either a TC ( MedComp ) or LC ( Vygon ) . Patients were dialyzed to target BFR 450 mL/min and followed up for 12 months . The primary outcome was achievement of target BFR during the first HD session . Secondary outcomes included thrombotic dysfunction , displacement and catheter-related infection . Catheter dysfunction was defined by a BFR ≤ 250 mL/min . Results More LCs reached the primary endpoint ( 44 % vs. 10 % , p=0.001 ) delivering a higher BFR ( mean 383±82 vs. 277±79 mL/min , p<0.001 ) . Significant differences in BFR persisted until the fourth dialysis session . Rates of catheter-related bacteremia ( 0.40 vs. 0.51/1,000 catheter days , p=0.7 ) and exit site infection were similar between groups ( 0.24 vs. 0.09/1,000 catheter days , p=0.4 ) . Overall rates of catheter dysfunction were 2.8/1,000 catheter days ( 95 % CI 2.1 - 3.5 ) , with no differences in thrombolytic lock use although the LC group required more thrombolytic infusions ( 6 vs. 0 , p=0.01 ) . Conclusions The LC can deliver greater BFRs in the first three HD sessions following insertion although this did not translate into differences in performance , dialysis adequacy or complication rates with long-term use . Both catheter types can consistently deliver high BFRs over an extended period of time Background and Objective Low molecular weight heparins ( LMWHs ) are small enough to pass large pore dialysis membranes . Removal of LMWH if injected before the start of the session is possible during high-flux dialysis and hemodiafiltration . The aim of this study was to determine the optimal mode ( place and time ) of tinzaparin administration during postdilution hemodiafiltration . Study Design , Setting , Patients In 13 chronic hemodiafiltration patients , 3 approaches of injection were compared in a r and omised cross over trial : i ) before the start of the session at the inlet blood line filled with rinsing solution ( IN0 ) , ii ) 5 min after the start at the inlet line filled with blood ( IN5 ) and iii ) before the start of the session at the outlet blood line ( OUT0 ) . Anti-Xa activity , thrombin generation , visual clotting score and reduction ratios of urea and beta2microglobulin were measured . Results Anti-Xa activity was lower with IN0 compared with IN5 and OUT0 , and also more thrombin generation was observed with IN0 . No differences were observed in visual clotting scores and no clinical ly relevant differences were observed in solute reduction ratio . An anti-Xa of 0.3 IU/mL was discriminative for thrombin generation . Anti-Xa levels below 0.3 IU/mL at the end of the session were associated with worse clotting scores and lower reduction ratio of urea and beta2microglobulin . Conclusions Injection of tinzaparin at the inlet line before the start of postdilution hemodiafiltration is associated with loss of anticoagulant activity and can therefore not be recommended . Additionally , we found that an anti-Xa above 0.3 IU/mL at the end of the session is associated with less clotting and higher dialysis adequacy . Trial Registration Clinical trials.gov Anemia in hemodialysis patients is effectively treated by intravenous ( IV ) injections of recombinant human erythropoietin ( rHuEPO ) at each dialysis session . Because the hormone is effective by subcutaneous ( SC ) administration , it was decided that this study would evaluate low-dose weekly SC rHuEPO therapy . To determine the safety and efficacy of weekly SC rHuEPO administration to hemodialysis patients , only one third the weekly IV dose was given and the effects were compared with those from an age- , gender- , and nephrologic disease-matched control group treated in the st and ard fashion . Forty-four patients entered the trial and 27 completed the protocol along with 27 control subjects . During Phase 1 , experimental and control subjects received st and ard IV rHuEPO at dialysis for 6 months . During Phase 2 , experimental patients received weekly SC rHuEPO at one third the weekly IV dose for 10 months ; control subjects continued to receive IV therapy . In Phase 3 , both groups were treated for 6 more months with IV rHuEPO . In Phase 2 , there was no significant reduction in hematocrit value , reticulocyte count , transferrin saturation , or ferritin level in the experimental group , even with only one third the weekly rHuEPO IV dose over the 10-month period . There were no significant differences between IV and SC rHuEPO administration or between experimental and control subjects in blood pressure , serum chemistries , or parameters of " dialysis adequacy . " It was concluded that low-dose weekly SC rHuEPO administration is a safe and effective method for maintaining the hematocrit level of stable hemodialysis patients . This therapy could enhance the efficacy of rHuEPO and substantially reduce costs while preserving patient care outcomes BACKGROUND Increased hemoglobin ( Hb ) levels and higher blood viscosity could reduce hemodialyzer clearance . We examined hemodialysis ( HD ) adequacy after treatment with epoetin alfa aim ed at normalizing Hb levels . METHODS Thirty-three HD patients were r and omly allocated to achieve a normal Hb level ( 135 - 160 g/L ) or a subnormal ( control ) Hb level of 90 - 120 g/L. HD adequacy was assessed by Kt/V measurement . RESULTS In the 24 evaluable patients , Hb levels reached 144 + /- 11 g/L in the normal Hb group ( n=10 ) and 109 + /- 10 g/L in the subnormal group ( n=14 ) . Single-pool Kt/V decreased from 1.25 + /- 0.19 to 1.15 + /- 0.13 ( p<0.01 ) in the normal Hb group , but remained constant in the subnormal group ( 1.26 + /- 0.26 and 1.26 + /- 0.28 ) . CONCLUSIONS Normalization of Hb with epoetin alfa in HD patients result ed in a slight but statistically significant reduction in Kt/V. Therefore , when Hb is normalized , an increased dialysis dose could be necessary to maintain dialysis adequacy CONTEXT Mortality rates among US hemodialysis patients are the highest in the industrialized world at 23 % per year . Measures of dialysis dose ( Kt/V ) correspond strongly with survival and are inadequate in one sixth of patients . Inadequate dialysis is also associated with increased hospitalizations and high inpatient costs . Our previous work identified 3 barriers to adequate hemodialysis : dialysis underprescription , catheter use , and shortened treatment time . OBJECTIVE To determine the effect of a tailored intervention on adequacy of hemodialysis . DESIGN AND SETTING Community-based r and omized controlled trial with recruitment from April 1999 to June 2000 at 29 hemodialysis facilities in northeast Ohio . PARTICIPANTS Forty-four nephrologists and their 169 r and omly selected adult patients receiving inadequate hemodialysis . INTERVENTION Nephrologists were r and omly assigned to an intervention ( n = 21 ) or control ( n = 23 ) group . For patients in the intervention group ( n = 85 ) , depending on the barrier(s ) present , a study coordinator gave nephrologists recommendations about optimizing dialysis prescriptions , expedited conversion of catheters to surgically created grafts or fistulas , and educated patients about the importance of compliance with treatment time . Patients in the control group ( n = 84 ) continued to receive usual care . MAIN OUTCOME MEASURES Changes in Kt/V and specific barriers after 6 months . RESULTS At baseline , intervention and control patients had similar Kt/V measurements , specific barriers , and demographic and medical characteristics . After 6 months , intervention patients had 2-fold larger increases in Kt/V compared with control patients ( + 0.20 vs + 0.10 ; P<.001 ) and were more likely to achieve their facility Kt/V goal ( 62 % vs 42 % ; P = .01 ) . Intervention patients also had nearly 3-fold larger increases in dialysis prescription ( + 0.16 vs + 0.06 ; P<.001 ) and were 4 times more likely to change from use of catheters to use of fistulas/grafts ( 28 % vs 7 % ; P = .04 ) . CONCLUSIONS An intervention tailored to patient-specific barriers result ed in increased hemodialysis dose . Extending this approach to the 33 000 persons in the United States receiving inadequate hemodialysis may substantially enhance patient survival , diminish hospitalizations , and decrease inpatient expenditures Background Protein-energy malnutrition is a common problem in hemodialysis patients and has different outcomes such as reduced quality of life , longer hospitalization time , lower dialysis adequacy , and higher mortality rate . Investigation of dialysis adequacy is an important method for assessing hemodialysis patients , and improving the dialysis adequacy is an important healthcare team goal . Objectives The present study aims to investigate and compare the effects of BCAA and ISO-WHEY oral nutritional supplements on dialysis adequacy . Methods In a clinical trial study , 66 hemodialysis patients were r and omly divided into three groups : Group A ( n = 22 ) , Group B ( n = 22 ) , and Group C or the control group ( n = 22 ) . In Groups A and B , as prescribed and controlled by nutritionists and nephrologists , respectively , ISO-WHEY and BCAA protein powder were used for 2 months on a daily basis . For all groups , before intervention and 1 and 2 months after intervention , the dialysis adequacy was measured using URR and Kt/V. Finally , the data were analyzed using IBM SPSS Statistics Base 21.0 software . Results Out of 66 patients , 61 ( 19 in Group A , 20 in Group B , and 22 in Group C ) completed the study period , and before intervention , all groups were equal in terms of quality and quantity variables ( P > 0.05 ) . After intervention , there was a significant difference between the three groups with regard to the variables of dialysis adequacy based on Kt/V and URR to independent-t test and repeated measures ANOVA ( P < 0.05 ) . Conclusions Results show that the intake of oral nutritional supplements leads to an improvement in the dialysis adequacy of hemodialysis patients . Therefore , the use of nutritional supplements along with patients ' training and regular consultation will be helpful in improving the nutritional status , dialysis adequacy , and eventually the quality of life BACKGROUND Several studies already stressed the importance of haemodialysis ( HD ) time in the removal of uraemic toxins . In those studies , however , also the amount of dialysate and /or processed blood was altered . The present study aim ed to investigate the isolated effect of the factor time t ( by processing the same total blood and dialysate volume in two different time schedules ) on the removal and kinetic behaviour of some small , middle and protein-bound molecules . METHODS The present study had a crossover design : 11 stable anuric HD patients underwent two bicarbonate HD sessions ( ~ 4 and ~ 8 h ) in a r and om sequence , at least 1 week apart . The GENIUS single-pass batch dialysis system and the high-flux FX80 dialysers ( Fresenius Medical Care , Bad Homburg , Germany ) were used . The volume of blood and dialysate processed , volume of ultrafiltration , and dialysate composition were prescribed to be the same . For each patient , blood was sample d from the arterial line at 0 , 60 , 120 , 180 and 240 min ( all sessions ) , and at 360 and 480 min ( 8-h sessions ) . Dialysate was sample d at the end of HD from the dialysate tank . The following solutes were investigated : ( i ) small molecules : urea , creatinine , phosphorus and uric acid ; ( ii ) middle molecule : β(2)M ; and ( iii ) protein-bound molecules : homocysteine , hippuric acid , indole-3-acetic acid and indoxyl sulphate . Total solute removals ( solute concentration in the spent dialysate of each analyte × 90 L - the volume of dialysate ) ( TSR ) , clearances ( TSR of a solute/area under the plasma water concentration time curve of the solute ) ( K ) , total cleared volumes ( K × dialysis time ) ( TCV ) , and dialyser extraction ratios ( K/blood flow rate ) ( ER ) were determined . The percent differences of TSR , K , TCV and ER between 4- and 8-h dialyses were calculated . Single-pool Kt/Vurea , and post-dialysis percent rebounds of urea , creatinine and β(2)M were computed . RESULTS TSR , TCV and ER were statistically significantly larger during prolonged HD for all small and middle molecules ( at least , P < 0.01 ) . Specifically , the percent increases of TSR ( 8 h vs 4 h ) were : for urea 22.6.0 % ( P < 0.003 ) , for creatinine 24.8 % ( P < 0.002 ) , for phosphorus 26.6 % ( P < 0.001 ) , and for β(2)M 39.2 % ( P < 0.005 ) . No statistically significant difference was observed for protein-bound solutes in any of the parameters being studied . Single-pool Kt/Vurea was 1.41 ± 0.19 for the 4-h dialysis sessions and 1.80 ± 0.29 for the 8-h ones . The difference was statistically significant ( P < 0.0001 ) . Post-dialysis percent rebounds of urea , creatinine and β(2)M were statistically significantly greater in the 4-h dialysis sessions ( at least , P < 0.0002 ) . CONCLUSIONS The present controlled study using a crossover design indicates that small and middle molecules are removed more adequately from the deeper compartments when performing a prolonged HD , even if blood and dialysate volumes are kept constant . Hence , factor time t is very important for these retention solutes . The kinetic behaviour of protein-bound solutes is completely different from that of small and middle molecules , mainly because of the strength of their protein binding BACKGROUND Gender and body size have been associated with survival in hemodialysis population s. In recent observational studies , overall mortality was similar in men and women and higher in small patients . The effect of dialysis dose in each of these subgroups has not been tested in a clinical trial . METHODS The HEMO Study was a controlled trial of dialysis dose and membrane flux in 1846 hemodialysis patients followed up for 6.6 years in 15 centers throughout the United States . We examined the effect of dialysis dose on mortality and on selected secondary outcomes in subgroups of patients . RESULTS Adjusting for age only , overall mortality was lower in patients with higher body weight ( P < 0.001 ) , higher body mass index ( P < 0.001 ) , and higher body water content determined by the Watson formula ( Vw ) ( P < 0.001 ) , but was not associated with gender ( P= 0.27 ) . The RR of mortality comparing the high dose with the st and ard dose group was related to gender ( P= 0.014 ) . Women r and omized to the high dose had a lower mortality rate than women r and omized to the st and ard dose ( RR = 0.81 , P= 0.02 ) , while men r and omized to the high dose had a nonsignificant trend for a higher mortality rate than men r and omized to the st and ard dose ( RR = 1.16 , P= 0.16 ) . Analysis of both genders combined showed no overall dose effect ( R = 0.96 , P= 0.52 ) , as reported previously . Vw was greater than 35 L in 84 % of men compared with 17 % of women . However , the RR of mortality for the high versus st and ard dose remained lower in women than in men after adjustment for the interaction of dose with Vw or with other size parameters , including weight and body mass index . Conversely , the dose effect was not significantly related to size parameters after controlling for the relationship of the dose comparison with gender . CONCLUSION The data suggest that mortality and morbidity might be reduced by increasing the dialysis dose above the current st and ard in women but not in men . This effect was not explained by differences between men and women in age , race , or in several indices of body size . Because multiple comparisons were considered in this analysis , the role of gender on the effect of dialysis dose is suggestive and invites further study Patients with end-stage renal disease ( ESRD ) undergoing hemodialysis ( HD ) are typically sedentary and functionally limited as a consequence of their condition . The purpose of this study is to test the effect of a lifestyle physical rehabilitation program ( The Life Readiness Program ) on physical function in patients with ESRD undergoing HD . Physical function was measured by the Kidney Disease Quality of Life Short Form ( KDQOL-SF ) physical function score ( range , 0 to 100 ) . Eighty-two patients were r and omly assigned to a 6-month rehabilitation program ( intervention ; n = 39 ) or to st and ard clinical management alone ( control ; n = 43 ) . The groups were frequency matched by age , sex , ethnicity , and diabetes as the cause of ESRD . General linear modeling of the change in physical function score was used for multivariate analysis . Physical function scores were not different between groups at baseline . Change in physical function score increased significantly in the intervention group compared with the control group when data were adjusted for the matching variables and adequacy of dialysis ( 3.2 , -3.6 ; P = 0.04 ) . Additionally , the control group reported more problems with work or daily functions because of emotional problems ( P : < /= 0.05 ) . In this brief 6-month intervention , The Life Readiness Program showed the therapeutic benefit of a lifestyle rehabilitation program on functional outcomes and health-related quality of life for patients with ESRD undergoing hemodialysis Numerous design s for tunneled hemodialysis catheter have been developed in an effort to improve catheter function and survival . In this prospect i ve r and omized controlled study , 97 patients were r and omized into the palindrome catheter group ( PC , n = 47 ) and step-tip catheter group ( SC , n = 50 ) . Demographic characteristics were not different between the two groups . The effective blood flow rates at different pump speeds were comparable between the two groups . The recirculation was low within acceptable range in both types of catheter , and hemodialysis adequacy was not different between the two groups . However , when arterial and venous blood lines were reversed , while the recirculation was significantly increased in SC , it was not increased at all in PC . The catheter dysfunction-free survival rate was significantly higher in PC than in SC ( 78.9 % vs. 54.4 % at 2 months , p = 0.008 ) . The overall catheter survival rate was also higher in PC than in SC ( 90.6 % vs. 68.8 % at 2 months , p = 0.015 ) . We conclude that both catheters are equally effective on the adequate hemodialysis and low recirculation . However , the PCs have advantages over the SCs in terms of lower catheter dysfunction rate , lower recirculation with reversed blood lines , higher short-term catheter survival rate Background / Aims : According to mathematical modeling , intradialytic exercise of sufficient intensity and duration implemented in the second half of dialysis should be as efficacious as increasing dialysis time for dialysis adequacy . This assumption has not been tested in vivo . Methods : In this controlled trial , 11 hemodialysis ( HD ) patients ( mean ( SD ) age 56 ( 13 ) years ) were recruited . Each patient completed three trial arms in a r and omized order : routine care ( CONT ) , increased HD time of 30 min ( TIME ) , and intradialytic exercise ( EXER ) , 60 min of cycling at 90 % of the lactate threshold in the last 90 min of HD . The primary outcome was eKt/Vurea . Secondary outcomes included reduction and rebound ratios of urea , creatinine , phosphate and β2-microglobulin . Outcomes were calculated from blood sampling collected pre- , post- and 30 min post-HD and confirmed with dialysate sampling . Results : Exercise was not as efficacious as increased HD time for eKt/Vurea ( EXER vs. CONT , mean change ( 95 % CI ) : 0.03 ( -0.05 to 0.12 ) ; TIME vs. CONT : 0.15 ( 0.05 - 0.26 ) ) . Exercise was less efficacious at improving reduction ratios of urea and creatinine . However , exercise was more efficacious than increased dialysis time for phosphate reduction ratio ( EXER vs. CONT : 8.6 % ( 0.5 - 16.7 ) ; TIME vs. CONT : 5.0 % ( -1.0 to 11.1 ) ) . Conclusion : This study utilized a rigorously controlled in vivo design to test mathematical models and assumptions regarding dialysis adequacy . Intradialytic exercise towards the end of HD can not replace the prescription of increased HD time for dialysis adequacy , but may be an adjunctive therapy for serum phosphate control BACKGROUND Hemodialysis requires effective anticoagulation to avoid blood circuit clotting . In patients at high risk for bleeding , several alternative methods have been developed . STUDY DESIGN Multicenter , prospect i ve , r and omized , crossover study evaluating the noninferiority of vitamin E-coated compared with heparin-coated dialyzers in a 4-hour heparin-free hemodialysis strategy . SETTING S & PARTICIPANTS 32 adult long-term hemodialysis patients from 2 French hemodialysis units with well-functioning fistulas or double-lumen catheters . INTERVENTION Patients were r and omly allocated to a first period using either vitamin E- or heparin-coated dialyzers . After a washout period of 2 hemodialysis sessions , each patient was switched to the alternative dialyzer for a second period . Each study period started with 2 hemodialysis sessions with reduced heparin dose ( 50 % and 25 % of usual heparin dose , respectively , for sessions 1 and 2 ) followed by 2 heparin-free sessions . OUTCOMES The primary end point was the percentage of successful study periods , defined as no circuit-clotting event leading to premature interruption of any of the 4 dialysis sessions . Secondary end points included total number and cumulative duration of hemodialysis sessions without clotting , number of saline solution flushes , dialysis circuit bubble trap status and dialyzer membrane status by visual inspection , and dialysis adequacy . RESULTS The percentage of success with vitamin E-coated dialyzers ( 25/32 study periods [ 78 % ] ) was not inferior to that with heparin-coated dialyzers ( 26/32 study periods [ 81 % ] ) . Visual inspection showed equal numbers of clean dialysis circuit bubble traps ( vitamin E-coated , 34/121 ; heparin-coated , 32/120 ) , whereas clean fiber bundles were more frequently noted with the vitamin E-coated compared with heparin-coated dialyzers ( 25/121 vs 2/120 ; P=0.002 ) . LIMITATIONS Results may not extrapolate to critically ill patients . Differences in dialyzer transparency may account for visual inspection scores . CONCLUSIONS The success rate of 4-hour heparin-free hemodialysis sessions is lower than that previously cl aim ed in uncontrolled studies . Vitamin E-coated and heparin-coated dialyzers exposed patients to similar and unacceptable high failure rates . Further studies are required to improve heparin-free hemodialysis BACKGROUND Short- duration high-efficiency haemodialysis has been utilized increasingly in recent years to deliver adequate blood urea clearances per dialysis session . However , high-efficiency and st and ard- duration haemodialysis schedules , which achieve equal patient urea clearances , may not represent equivalent dialytic therapy due to solute differences in intercompartmental dysequilibrium during dialysis and differences in dialysis mechanics . METHODS To circumvent the effects of intercompartmental dysequilibrium and postdialysis rebound solute clearances were measured by direct dialysis quantification ( total and partial dialysate collection s ) rather than blood clearances . High-efficiency haemodialysis ( dialyser blood flow rate = 400 ml/min ; dialysis time = 170.67 min ) was compared with st and ard haemodialysis ( dialyser blood flow rate = 200 ml/min ; dialysis time = 240 min ) performed in r and om order in six anuric patients using Fresenius F8 dialysers and the same haemodialysis machine . Such haemodialysis schedules were prescribed to provide equivalent urea clearances . RESULTS Patient plasma water urea clearances measured by direct dialysis quantification were equivalent , whereas high efficiency haemodialysis achieved significantly lower phosphate clearances ( P = 0.01 ) , less net bicarbonate absorption ( P = 0.01 ) , and lower beta 2 microglobulin removal ( P < 0.001 ) than st and ard haemodialysis . Estimated total dialysate effluent volumes with partial dialysate collection and total dialysate collection correlated closely ( r = 0.95 ) and there were no differences between patient urea , creatinine and phosphate clearances measured by partial and total dialysate quantification . CONCLUSIONS The data indicate that even if high-efficiency and st and ard haemodialysis provide equal whole-body urea clearances , delivered dialysis therapy is not equivalent . The partial dialysate collection method is as accurate as the cumbersome total dialysate collection approach and may be applied to assess delivered dialysis dose by minor modification of current haemodialysis machines BACKGROUND Several studies have indicated that the improved elimination of middle molecules by convective renal replacement procedures might be associated with a better outcome in end-stage renal disease ( ESRD ) . On-line mid-dilution hemodiafiltration ( HDF ) with the Nephros OLpur MD 190 hemodiafilter represents a novel extracorporeal renal replacement therapy concept to increase the removal of middle molecules . METHODS In a prospect i ve cross-over study in 10 ESRD patients , this technique was compared to on-line post-dilution HDF with a conventional synthetic high-flux dialyzer , operated at its technical limit , concerning small and middle molecular solute removal . Each patient was treated 3 times for 4.0 + /- 0.4 hours with both filters . Blood flow was 400 mL/min , substitution flow ( Q(S ) ) during mid-dilution HDF 200 mL/min , and during post-dilution HDF 100 mL/min , and effective dialysate flow of 700 - Q(S ) mL/min . Instantaneous clearances , reduction ratios ( RR ) , and middle molecule mass transfer in continuously collected dialysate were determined . RESULTS While urea and creatinine clearances were significantly lower ( 6.4 % and 3.9 % , respectively ) , middle molecule removal was much more efficient in mid-dilution HDF over the whole range of investigated proteins : compared to post-dilution HDF , beta(2)-microglobulin ( 11.8 kD ) clearance ( 165.8 + /- 26.59 vs. 201.9 + /- 20.63 mL/min ; P < 0.001 ) , RR ( 80.0 + /- 5.4 % vs. 82.2 + /- 5.7 % ; P < 0.001 ) , and dialysate mass transfer ( 53 % higher ; P < 0.001 ) were significantly higher . For the larger middle molecules , cystatin C ( 13.4 kD ) and retinol-binding protein ( 21.2 kD ) , mid-dilution HDF result ed in an even more superior performance , indicated by significantly higher values of all investigated parameters . CONCLUSION On-line mid-dilution HDF with the Nephros OLpur MD 190 hemodiafilter appears to be a true technologic step ahead in terms of improved middle molecule removal . This efficient procedure gives hope to play a role in preventing or at least retarding dialysis-related long-term complications , such as beta(2)m amyloidosis , in ESRD patients , and may contribute to a more adequate dialysis therapy Delivered dose of hemodialysis ( HD ) in large patients with end-stage renal disease is often less than adequate . Fourteen chronic HD patients with weights greater than 80 kg participated in a prospect i ve , cross-over study comparing urea reduction ratio ( URR + /- SEM ) and the fractional clearance index for urea ( eKt/V(urea ) + /- SEM ) on a single polysulfone dialyzer for a control ( HDC ) period of 4 weeks versus clearances obtained with two dialyzers in parallel during an intervention ( HDP ) period of 4 weeks . Clearance of the surrogate middle molecule iohexol ( C(Io ) ) was also measured . Health status was assessed with the SF-36 . Blood and dialysate flow rates and duration of HD sessions were constant . URR increased from 0.67 + /- 0.006 during HDC to 0.72 + /- 0.006 with HDP ( P < 0.0001 ) . eKt/V(urea ) increased from 1.16 + /- 0.021 to 1.34 + /- 0.021 ( P < 0.0001 ) . Increased URR and eKt/V(urea ) occurred in all 14 during HDP ( P < 0.05 ) . C(Io ) during HDP averaged 182 + /- 7.7 mL/min compared with 131 + /- 5.4 mL/min in HDC sessions ( P < 0.00001 ) . Health status improved in six of eight categories . Expense increased approximately $ 14.27 per dialysis with HDP . In 11 of 14 patients continued on two dialyzers in parallel for 1 year , monthly eKt/V averaged 1.46 + /- 0.066 , and health status further improved in five of eight categories . In large patients , two dialyzers in parallel increased urea and iohexol clearance . Increased urea clearance was maintained for 1 year , and health status improved OBJECTIVES This multicentre , prospect i ve , open label , r and omised controlled trial was to determine whether buttonhole cannulation technique in new and established haemodialysis fistula reduced complications and prolonged the access life compared to usual practice . METHOD Seventy subjects were recruited for this study . Subjects r and omised to the buttonhole group had their fistula cannulated by the same staff member for two to four weeks at the same angle and direction with sharp needles . Once the tunnel was developed , blunt needles were used . The control group continued with usual practice ( rope ladder rotation technique ) . RESULTS Infection at the cannulation site occurred in four patients in the buttonhole group and one in the rope ladder rotation group ( p = 0.11 ) . Haematomas at the cannulation site and site pain experienced during the dialysis session were more often recorded for the buttonhole group ( p < 0.05 ) . CONCLUSIONS This study showed that buttonhole cannulation result ed more infections , haematoma formation and site pain during dialysis than with the rope ladder rotation group . A further larger scale longitudinal study is recommended BACKGROUND Innovative modifications have been introduced in several types of dialyser membranes to improve adequacy and permselectivity . Which aspects of removal are modified and how this relates to different diffusive or convective strategies has , however , been insufficiently investigated . METHODS In a prospect i ve cross-over study , 14 chronic kidney disease ( Stage 5D ) patients were dialysed with a second-generation high-flux dialyser ( Polynephron ) in comparison to a first-generation type ( DIAPES-HF800 ) . Both dialysers were assessed in haemodialysis , in online pre-dilution and in post-dilution haemodiafiltration . Reduction ratio ( RR , % ) of small water-soluble compounds ( urea and uric acid ) , low-molecular weight proteins ( LMWPs ) ( β(2)-microglobulin , cystatin C , myoglobin and retinol-binding protein ) and protein-bound solutes ( hippuric acid , indole acetic acid , indoxylsulphate and p-cresylsulphate ) was assessed , together with albumin losses into the dialysate . RESULTS Comparing the two types of membranes , the second-generation dialyser demonstrated a higher RR for LMWPs , whilst at the same time exhibiting lower albumin losses but only during post-dilution haemodiafiltration . No differences in RR were detected for both the small water-soluble and the protein-bound compounds . Comparing dialysis strategies , convection removed the same amount of solute or more as compared to diffusion . CONCLUSIONS The second-generation membrane result ed in a higher removal of LMWPs compared to the first-generation membrane , but for the other solutes , differences were less prominent . Convection was superior in removal of a broad range of uraemic retention solutes especially with the first-generation membrane Venous stenosis and occlusion are a major cause of vascular access dysfunction and failure . The HeRO Graft bypasses occlusion and traverses stenosis with outflow directly into the central venous circulation . A r and omized , multicenter study was conducted to evaluate the efficacy and safety of the HeRO Graft relative to conventional AV grafts . The design was to enroll 143 patients in a 2:1 r and omization ratio between HeRO and conventional AV control groups . Data on 72 subjects ( 52 HeRO Graft and 20 AV graft controls ) were obtained . The HeRO Graft and control cohorts were comparable in baseline characteristics . Adequacy of dialysis , bacteremia rates , and adverse events were consistent between groups . Twelve month Kaplan-Meier estimates for primary and secondary patency rates were 34.8 % and 67.6 % in the HeRO Graft cohort , and 30.6 % and 58.4 % in the control cohort . There was no statistical difference in terms of patency between groups . The rates of intervention were 2.2/year for HeRO Graft and 1.6/year for the control ( p = 0.100 ) . Median days to loss of secondary patency was 238 for HeRO Graft versus 102 for the control ( p = 0.032 ) . The HeRO Graft appears to provide similar patency , adequacy of dialysis , and bacteremia rates to those of conventional AV grafts Aim : To evaluate the effects of short-term restriction of dietary protein intake ( DPI ) supplemented with keto acids on hyperphosphatemia in maintenance hemodialysis ( MHD ) patients . Methods : Forty MHD patients with uncontrolled hyperphosphatemia were r and omized to either low DPI with keto acid-supplemented ( sLP ) or normal DPI ( NP ) group for 8 weeks . After 8 weeks , the sLP group was shifted to NP for another 8 weeks . Low-protein diet ( LPD ) was individualized with total caloric intake 30–35 kcal/kg/day , protein intake of 0.8 g/kg/day and phosphate intake of 500 mg/day . Keto acids were supplied in a dosage of 12 pills per day . Calcium phosphorous metabolism index and nutritional index ( serum albumin , total protein , somatometric measurements , 3-day diaries and Mini-Nutritional Assessment score ) were recorded . C-reactive protein , CO2 combining power and Kt/V were measured to evaluate the inflammation , metabolic acidosis and dialysis adequacy , respectively . Results : Serum phosphorus level and calcium-phosphate product were significantly decreased at the end of the first 8 weeks in the sLP group compared to the basal value and the NP group ( p < 0.001 ) . No difference was observed in C-reactive protein , Kt/V and nutritional index , while CO2 combining power was significantly higher at week 8 in the sLP group ( p < 0.001 ) . Conclusion : Short-term restriction of DPI supplemented with keto acids could decrease hyperphosphatemia and calcium-phosphate product , while keeping stable nutritional status among MHD patients UNLABELLED Cuffed central -venous haemodialysis catheters are emerging as an alternative permanent haemodialysis vascular access . There is limited data regarding the adequacy of dialysis with prolonged used of these catheters . We conducted a prospect i ve study comparing three commonly used cuffed central -venous haemodialysis catheters : ( 1 ) PermCath , Quinton Instrument Co , Seattle ; ( 2 ) Tesio , Med Comp , Inc , Harleysville PA ; ( 3 ) VasCath Soft Cell , Bard Instrument Company , Toronto , and compared them with control patients dialysing with arteriovenous access ( AV ) access . We r and omly assigned 64 patients who needed prolonged temporary vascular access to placement of one of three catheters . The control group comprised 222 patients dialysing simultaneously in the same units with AV access . METHODS All patients were dialysed with identical machines and kidneys . Maximal effort were made with every catheter to optimize achievable blood flow . Catheters with mechanical problems were treated first with urokinase and then fibrin sheath catheter stripping . The mean blood flow was determined by averaging mean blood flows from 30 consecutive treatments . Reliability of catheter was defined as percentage of treatments that were performed at a median blood flow of 350 ml/min or above during these 30 treatments . Kt/V was measured monthly and calculated using the single-pool Daugirdas formula . Haemodialysis prescription were adjusted for Kt/V above 1.2 . Recirculation was measured using two-needle low-blood-flow technique . RESULTS The mean blood flows were ( PermCath 383.6 ml/min , Tesio 396.3 ml/min , VasCath 320.4 ml/min ) . PermCath and Tesio had comparable mean blood flows and were significantly higher than VasCath ( P<0.005 ) . Reliability of catheters were ( PermCath 86.9 % , Tesio 81.6 % , VasCath 42.3 % ) . Tesio and PermCath were equally reliable and both were more reliable than VasCath ( P<0.005 ) . Had the target for reliability been 300 ml/min all three catheters would have been equally reliable . Negative arterial pressure in excess of 300 mmHg prevented faster blood flows in 98 % of instances . None of the catheters performed as well as the control population with AV access ( mean blood flow 437ml/min , reliability 96 % , P<0.005 ) . Recirculation rates were 3.7 % for PermCath 3.9 % for Tesio , and 4 % for VasCath . All patients weighing less than 85 kg acheived a Kt/V of 1.2 with a 4-h treatment . For comparison purpose s when Kt/V was normalized to a 70-kg patient the results were PermCath 1.42 . Tesio 1.44 , VasCath 1.19 , AV access 1.64 . SUMMARY All three catheters are capable of providing adequate haemodialysis although large patients will need extended treatment times . The PermCath and Tesio provide blood flow and reliability superior to the VasCath . Blood flow is limited in all catheters by inflow , as evidence d by negative arterial pressure . All catheters had acceptable recirculation . AV access is superior in terms of blood flow and reliability to all tested catheters This report summarizes morbidity in 151 patients in a cooperative trial design ed to evaluate the clinical effects of different dialysis prescriptions . Four treatment groups were divided along two dimensions : dialysis treatment time ( long or short ) , and blood urea nitrogen ( BUN ) concentration averaged with respect to time ( TACurea ) ( high or low ) . Dietary protein was not restricted . There was no difference in mortality between the groups . Withdrawal of patients from the high-BUN groups for medical reasons was significantly greater than withdrawal from the low-BUN groups . Hospitalization was also greater in the high-BUN groups , but dialysis treatment time had no significant effects . The data indicate that the occurrence of morbid events is affected by the dialysis prescription . Increased morbidity appears to accompany prescriptions associated with a relatively high BUN . Conversely , morbidity may be decreased by prescriptions associated with more efficient removal of urea if the dietary intake of protein and other nutrients is adequate BACKGROUND Membrane biocompatibility has long been thought to be relevant to hemodialysis outcomes and , possibly , renal anemia . METHODS We performed a r and omized , controlled , single-center study comparing the consequences on renal anemia of 2 dialyzers of equivalent performance , but different composition , during 7 months . Two hundred eleven patients of an unselected dialysis population of 235 patients gave informed consent to undergo r and om assignment to either group A ( SF170E ; modified cellulose triacetate/midflux membrane ; Nipro , Osaka , Japan ) or group B ( HF80LS ; polysulfone/high-flux membrane ; Fresenius , Bad Homburg , Germany ) . Anemia management was identical in both treatment groups and followed strict clinical protocol s managed by computer algorithms . Dialysis adequacy , hemoglobin ( Hb ) level , ferritin level , percentage of red blood cell hypochromicity , C-reactive protein ( CRP ) level , and intravenous iron and epoetin doses were monitored monthly . RESULTS One hundred seventy-seven patients completed the 7-month study . Equilibrated Kt/V increased in both groups . Hb outcome improved overall , but did not differ between the 2 study groups . Epoetin dose was not significantly different after 7 months compared with baseline in either group . Hb level , epoetin dose , iron status , CRP level , dialysis Kt/V , and residual renal function did not differ between the 2 groups . A slight but significant negative correlation was identified between dialysis Kt/V and Hb level in the population as a whole ( Spearman 's correlation , -0.16 ; P = 0.04 ) . CONCLUSION No significant epoetin-sparing effect was identified through the use of the high-flux polysulfone HF80LS membrane over the modified cellulose triacetate SF170E membrane . Although not a primary outcome for this study , there was a suggestion of benefit of improved Hb level , without increased need for epoetin , through increasing delivered dialysis dose Hemodialysis with reprocessed dialyzers has been associated with an increased mortality in patients on chronic dialysis , but the causes for this increased mortality have not been identified thus far . The aim of this study was to compare the qualitative and /or quantitative differences in activation of cellular and plasma elements , intradialytic signs and symptoms , adequacy of dialysis , and serum biochemistry and hematology in patients dialyzed with new or reprocessed cellulose dialyzers . This study measured the plasma levels and production of interleukin-1 receptor antagonist ( IL-1Ra ) by peripheral blood mononuclear cells ( P BMC ) , indices of cytokine synthesis ; plasma C3a levels , an index of complement activation ; plasma levels of lipopolysaccharide binding protein ( LBP ) , an acute phase reactant ; and plasma levels of bactericidal-permeability increasing factor ( BPI ) , a neutrophil primary granule protein , in 37 patients on chronic hemodialysis with glutaraldehyde and bleach-reprocessed cellulose dialyzers after r and om assignment to 12 wk of dialysis with new ( single use ) or reprocessed ( reuse ) cellulose dialyzers . These indices were studied before dialysis , 15 min after the start of dialysis , and at the conclusion of dialysis in both groups . Intradialytic clinical symptoms and signs , urea reduction ratios , monthly blood chemistry , and hematology were also studied during the 12-wk period . Before r and omization , clinical and laboratory characteristics and IL-1Ra production by P BMC were similar in the two groups . During the 12-wk study , the mean number of dialyzer reuses was 7 + /- 1 in the reuse group and there were no breaks in protocol in the single-use group . At the end of the study , plasma levels of IL-1Ra , cell content and production of IL-1Ra by unstimulated , endotoxin-stimulated , and lgG-stimulated P BMC among patients assigned to reuse were not significantly different from those in the single-use group either before dialysis , at 15 min , or at the conclusion of dialysis . Similarly , plasma levels of C3a , LBP , and BPl were not significantly different between groups at any of the three time points . During the 12-wk study , none of the patients in either arm of the study experienced chills , rigors , or fever , and there were no differences in the number of episodes of symptomatic hypotension in patients on reused dialyzers ( 11 + /- 3 ) compared with patients on single-use dialyzers ( 8 + /- 2 ) . The mean monthly urea reduction ratio during the 3 months of the study was 63 + /- 2 % and 65 + /- 2 % for reuse and single-use dialyzers , respectively ( not significant ) . Similarly , the hematocrit , white blood cell count , serum calcium , phosphorus , cholesterol , triglycerides , total protein , and albumin levels were also not significantly different between the two groups at the end of the 12-wk study period . These results suggest that the reprocessing of cellulose dialyzers with glutaraldehyde and bleach does not affect indices of blocompatibility , intradialytic symptoms and signs , adequacy of dialysis , or serum biochemistry and hematology End-stage renal disease ( ESRD ) Networks are quality improvement organizations that collect , analyze , and report information to clinicians and allied health providers about discrepancies between observed patterns of care of ESRD patients and what has been recommended by clinical practice guidelines . The Networks facilitate response to this information by assisting ESRD treatment centers to develop quality improvement programs to redress inadequate care . The authors evaluated this process of quality improvement by selecting 42 treatment centers in a single ESRD Network with the lowest facility-specific mean urea reduction ratio ( URR ) . The treatment centers were r and omly assigned to two intervention strategies : ( 1 ) feedback alone ; ( 2 ) an intensive intervention that included feedback , workshops , distribution of educational material s and clinical practice guidelines , technical assistance with the development of quality improvement plans , and continued monitoring . The intensive intervention had greater improvement in the increased proportions of patients dialyzed with prescribed blood flow ( P = 0.02 ) and documented review of prescription ( P = 0.01 ) . Furthermore , the mean center URR increased nearly 3 % among intensive intervention centers ( from 68.1 to 70.9 ) but only 0.09 % among the feedback centers ( 68.2 to 69.1 ) ( P = 0.002 ) . Similarly , time on dialysis increased 7.5 min on average among patients in intervention centers but decreased 2 min for patients in comparison centers ( P = 0.03 ) . These results demonstrate that Network feedback , coupled with the intensive intervention , result ed in improvement in care that would otherwise not have occurred In the intention-to-treat analysis of the Hemodialysis Study , all-cause mortality did not differ significantly between the high versus st and ard hemodialysis dose groups . The association of mortality with delivered dose within each of the two r and omized treatment groups was examined , and implication s for observational studies were considered . Time-dependent Cox regression was used to relate the relative risk ( RR ) for mortality to the running mean of the achieved equilibrated Kt/V ( eKt/V ) over the preceding 4 mo . eKt/V was categorized by quintiles within each dose group . Analyses were controlled for case-mix factors and baseline anthropometric volume . Within each r and omized dose group , mortality was elevated markedly when achieved eKt/V was in the lowest quintile ( RR , 1.93 ; 95 % confidence interval [ CI ] , 1.40 to 2.66 ; P < 0.0001 in the st and ard-dose group ; RR , 2.04 ; 95 % CI , 1.50 to 2.76 ; P < 0.0001 in the high-dose group ; RR relative to the middle quintiles ) . The mortality rate in the lowest eKt/V quintile of the high-dose group was higher than in the full st and ard-dose group ( RR , 1.59 ; 95 % CI , 1.29 to 1.96 ; P < 0.0001 ) . Each 0.1 eKt/V unit below the group median was associated with a 58 % higher mortality in the st and ard-dose group ( P < 0.001 ) and a 37 % higher mortality in the high-dose group ( P < 0.001 ) . The magnitude of these dose-mortality effects was seven- to 12-fold higher than the upper limit of the 95 % CI from the intention-to-treat analysis . The effects were attenuated in lagged analyses but did not disappear . When dialysis dose is targeted closely , as under the controlled conditions of the Hemodialysis Study , patients with the lowest achieved dose relative to their target dose experience markedly increased mortality , to a degree that is not compatible with a biologic effect of dose . The possibility of similar ( albeit smaller ) biases should be considered when analyzing observational data sets relating mortality to achieved dose of dialysis R and omized trials provide the most reliable evidence about the safety and effectiveness of interventions to improve health care and patient outcomes . Unfortunately , the potential for trials to inform treatment decisions remains limited because the outcomes reported often do not resonate with what is directly meaningful and relevant to patients and their clinicians [ 1–3 ] . Further , inconsistent reporting of outcomes across trials prevents assessment of the comparative effect of interventions [ 4 ] . Outcome reporting bias , whereby authors cherry-pick the outcomes they report on the basis of favourable results , may also occur when there is not a st and ardized list of outcomes measured and reported [ 5 , 6 ] . Collectively these problems may undermine the reliability of published trials , leading to inefficient use of scarce research and health care re sources and unintended harm to patients [ 6 ] . Such dissonance in outcomes reported in trials is widespread and evident across all medical specialties . The growing recognition of the problem has prompted large-scale efforts to establish core outcome sets . Core outcome sets are an agreed st and ardized set of outcomes for a specific clinical area that are to be reported as a minimum in all trials in that area [ 7 ] . Outcomes are selected because they are critically important to all stakeholders — namely patients , their clinicians and policymakers— for decision making . Core outcome sets are not design ed to be comprehensive or exclusive . Typically they include only three to five outcomes . Other outcomes that are identified to be important ( i.e. to some stakeholder groups ) may also be recommended for some trials ( Figure 1 ) . The design ated primary outcome of any given trial may be outside the core outcome set and research ers may also opt to add other , trial-specific outcomes , chosen for reasons including responsiveness to the intervention and feasibility . Attempts to st and ardize outcomes began 50 years ago when the World Health Organization published recommendations for the minimum requirements for data collection in cancer trials [ 8 ] . In the 1990s , the Outcome Measures in Rheumatology ( OMERACT ) initiative was formed , and is perhaps the most widely recognized and largest initiative in the field of core outcome development . OMERACT engages patients and health professionals to st and ardize outcome measures for trials in rheumatology [ 9 ] and has pioneered method ologies for developing core outcome sets . The uptake of the OMERACT core outcome sets has improved the consistency of outcomes reported in trials [ 10 ] . In the past decade , core outcome sets in diverse medical specialties , including cardiology , dermatology , surgery , oncology , women ’s health and respiratory disease , have progressively been developed [ 7 , 9–11 ] . The use of core outcome sets is also increasingly being advocated by funders to ensure the relevance and potential impact of research . In the UK , funding organizations , including the National Institute for Health Research and the Health Research Board ( Irel and ) , advise research ers to include core outcome sets if they are available and highlight the Core Outcome Measures in Effectiveness ( COMET ) data base of core outcomes as a key re source [ 7 ] . The COMET initiative was recently launched to facilitate the development , implementation and evaluation of core outcome sets [ 7 ] . There has been a long-st and ing need in nephrology to develop core outcomes [ 12–14 ] . More than 14 000 r and omized trials are available in the Cochrane Kidney and Transplant Specialised Register [ 15 ] and a search of Clinical Trials.gov trials for ‘ kidney disease ’ yields > 3000 ongoing trials . Despite this considerable investment in trials in nephrology , improvements in outcomes for patients with kidney disease have been modest at best . Across all stages of chronic kidney disease ( CKD ) , patients still have a markedly higher risk of mortality and serious comorbidities , including cardiovascular disease , diabetes , cancer and infection , compared with the general population [ 16–18 ] . Patients with CKD have poor quality of life , particularly if they are on dialysis , to the extent that many patients || || || || || || || || || || || || || || || || || || || || || || || || || || || || || || || || || || || || || || || || || || || || || || || || || || || |
627 | 31,018,007 | The main findings were : 1 ) conformity to norms associated with traditional masculine role ( dominance , womanising , aggressiveness , risk behaviours ) is related to greater alcohol use ; 2 ) conformity to norms associated with traditional feminine role ( interest in home life and family care ) is related with lower alcohol use .
These findings provide evidence of the relationship between dimensions associated with gender and drinking . | There are different profiles of alcohol consumption for men and women , and different courses and prognoses associated with problems caused by alcohol abuse .
There is evidence of these differences by sex , but research on their links to differences associated with gender dimensions is scarcer .
In order to know what has been research ed on the subject , this article review s the literature regarding the relationship between conformity with gender norms and alcohol use and /or abuse in adults . | Health statistics routinely show higher morbidity and health services use for women , while mortality rates are higher for men . This analysis empirically identifies reasons for women 's poorer health . It is based on retrospective ( interview ) and prospect i ve ( health diaries ) data from the Health In Detroit Study . Three kinds of risk factors , which may help explain females ' excess , are considered : acquired risks , psychosocial aspects , and health-reporting behavior . Men and women differ markedly in acquired risks : smoking and job hazards are higher for men , but inactivity , nonemployment , stress , and many other factors are higher for women . Psychosocial aspects predispose women to more illness and health care . Women also had keener interest in the survey . When all of the risk factors are controlled , the morbidity gap narrows considerably . In fact , indicators of general and chronic health reverse to reveal higher morbidity for men . Similarly , females ' excesses for therapeutic care ( short- and long-term disability , medical visits , lay consultation , drug use ) diminish when risks and morbidity level are controlled . They actually reverse to a male excess for disability and medical care . Though most of the unveiled male excesses are statistically nonsignificant , their pattern allows a reasonable interpretation . Our results are closely compatible with recent analyses of sex mortality differences in several California sites , which could not eliminate men 's mortality excess by controlling for social factors . In conclusion , contemporary women 's poorer health profile stems largely from their roles and stress ( acquired risks ) , and to a smaller degree from their health attitudes . When social factors are taken into account , health data suggest a disadvantage for men , and mortality data maintain men 's disadvantage . Do the reasons lie in biology R. Lorraine Collins State University of New York at Stony Brook George A. Parks and G. Alan Marlatt University of Washington Two studies were conducted to assess variables related to the social determinants of alcohol consumption . In Study 1 , moderate- and heavy-drinking male under- graduates were paired with confederates who behaved in a sociable or unsociable manner while modeling either light or heavy consumption . Modeling occurred in the sociable conditions but not in the unsociable conditions , where subjects tended to drink heavily . In Study 2 , a similar group of subjects was exposed to one of three social status conditions crossed with light versus heavy consumption . The results indicated a modeling effect in all social status conditions . These studies provide further support for the existence of a modeling effect that can be disrupted by a lack of rapport between drinking partners . This latter finding has implication s for the etiology of problem drinking because it suggests that increased alcohol consumption may serve as a strategy for coping with aversive social interactions . Initial research on the effect of modeled consumption rates on social drinking ( Caudill & Marlatt , 1975 ) suggested that heavy-drink- ing men tended to match the consumption of their drinking partner whether his con- sumption was heavy or light . Subsequent examinations of this phenomenon replicated these findings in laboratory analogue drinking tasks such as the taste-rating task ( Cooper , Waterhouse , & Sobell , 1979 ; Hendricks , So- bell , & Cooper , 1978 ; Lied & Marlatt , 1979 ; Watson & Sobell , 1982 ) , natural bar setting s ( Reid , 1978 ) , and seminaturalistic bar setting s ( Caudill & Lipscomb , 1980 ) . Much of the research concerning the mod- eling of alcohol consumption has focused on manipulating characteristics of the model , including the nature of the social interaction between the model and the subject . The effects of manipulating social interaction are unclear . In the Caudill and Marlatt study , model 's drinking rate ( light vs. heavy ) and |
628 | 31,344,211 | We conclude that exercise training is associated with reductions of HbA1c in patients with DM2 .
Thus , it can be a complementary tool in the management of these patients | Physical training is recommended in several studies and guidelines for the control of type 2 diabetes mellitus ( DM2 ) and its complications . | OBJECTIVE Physical fitness is inversely related to mortality in the general population and in subjects with type 2 diabetes . Here , we present data concerning the relationship between changes in physical fitness and modifiable cardiovascular risk factors in subjects with type 2 diabetes from the Italian Diabetes and Exercise Study . RESEARCH DESIGN AND METHODS Sedentary patients with type 2 diabetes ( n = 606 ) were enrolled in 22 outpatient diabetes clinics and r and omized to twice-a-week supervised aerobic and resistance training plus exercise counseling versus counseling alone for 12 months . Baseline to end-of- study changes in cardiorespiratory fitness , strength , and flexibility , as assessed by Vo2max estimation , a 5–8 maximal repetition test , and a hip/trunk flexibility test , respectively , were calculated in the whole cohort , and multiple regression analyses were applied to assess the relationship with cardiovascular risk factors . RESULTS Changes in Vo2max , upper and lower body strength , and flexibility were significantly associated with the variation in the volume of physical activity , HbA1c , BMI , waist circumference , high-sensitivity C-reactive protein ( hs-CRP ) , coronary heart disease ( CHD ) risk score , and inversely , HDL cholesterol . Changes in fitness predicted improvements in HbA1c , waist circumference , HDL cholesterol , hs-CRP , and CHD risk score , independent of study arm , BMI , and in case of strength , also waist circumference . CONCLUSIONS Physical activity/exercise-induced increases in fitness , particularly muscular , predict improvements in cardiovascular risk factors in subjects with type 2 diabetes independently of weight loss , thus indicating the need for targeting fitness in these individuals , particularly in subjects who struggle to lose weight Objective : We have previously reported insignificant changes in HbA1c after exercise in patients with both type 2 diabetes and coronary artery disease . In this study , we investigated the effect of exercise on endothelial function and possible associations between changes in endothelial function and HbA1c . Methods : Patients with type 2 diabetes and coronary artery disease ( n = 137 ) were r and omised to 12 months exercise or st and ard follow-up . Endothelial function was assessed by circulating biomarkers ( E-selectin , intercellular adhesion molecule-1 , vascular cell adhesion molecule-1 , von Willebr and factor , tissue plasminogen activator antigen , asymmetric dimethylarginine and L-arginine/asymmetric dimethylarginine ratio ) . Differences between the r and omised groups were analysed by analysis of covariance and correlations by Spearman ’s rho or Pearson ’s correlation . Results : No effect of exercise on endothelial function was demonstrated . The changes in HbA1c in the exercise group correlated with changes in E-selectin ( r = 0.56 , p < 0.001 ) , intercellular adhesion molecule-1 ( r = 0.27 , p = 0.052 ) , vascular cell adhesion molecule-1 ( r = 0.32 , p = 0.022 ) and tissue plasminogen activator antigen ( r = 0.35 , p = 0.011 ) . HbA1c decreased significantly more in patients with versus without a concomitant reduction in E-selectin ( p = 0.002 ) , intercellular adhesion molecule-1 ( p = 0.011 ) , vascular cell adhesion molecule-1 ( p = 0.028 ) and tissue plasminogen activator antigen ( p = 0.009 ) . Conclusion : Exercise did not affect biomarkers of endothelial function in patients with both type 2 diabetes and coronary artery disease . However , changes in biomarkers of endothelial activation correlated with changes in HbA1c , and reduced endothelial activation was associated with improved HbA1c after exercise Importance It is unclear whether a lifestyle intervention can maintain glycemic control in patients with type 2 diabetes . Objective To test whether an intensive lifestyle intervention results in equivalent glycemic control compared with st and ard care and , secondarily , leads to a reduction in glucose-lowering medication in participants with type 2 diabetes . Design , Setting , and Participants R and omized , assessor-blinded , single-center study within Region Zeal and and the Capital Region of Denmark ( April 2015-August 2016 ) . Ninety-eight adult participants with non – insulin-dependent type 2 diabetes who were diagnosed for less than 10 years were included . Participants were r and omly assigned ( 2:1 ; stratified by sex ) to the lifestyle group ( n = 64 ) or the st and ard care group ( n = 34 ) . Interventions All participants received st and ard care with individual counseling and st and ardized , blinded , target-driven medical therapy . Additionally , the lifestyle intervention included 5 to 6 weekly aerobic training sessions ( duration 30 - 60 minutes ) , of which 2 to 3 sessions were combined with resistance training . The lifestyle participants received dietary plans aim ing for a body mass index of 25 or less . Participants were followed up for 12 months . Main Outcomes and Measures Primary outcome was change in hemoglobin A1c ( HbA1c ) from baseline to 12-month follow-up , and equivalence was prespecified by a CI margin of ±0.4 % based on the intention-to-treat population . Superiority analysis was performed on the secondary outcome reductions in glucose-lowering medication . Results Among 98 r and omized participants ( mean age , 54.6 years [ SD , 8.9 ] ; women , 47 [ 48 % ] ; mean baseline HbA1c , 6.7 % ) , 93 participants completed the trial . From baseline to 12-month follow-up , the mean HbA1c level changed from 6.65 % to 6.34 % in the lifestyle group and from 6.74 % to 6.66 % in the st and ard care group ( mean between-group difference in change of −0.26 % [ 95 % CI , −0.52 % to −0.01 % ] ) , not meeting the criteria for equivalence ( P = .15 ) . Reduction in glucose-lowering medications occurred in 47 participants ( 73.5 % ) in the lifestyle group and 9 participants ( 26.4 % ) in the st and ard care group ( difference , 47.1 percentage points [ 95 % CI , 28.6 - 65.3 ] ) . There were 32 adverse events ( most commonly musculoskeletal pain or discomfort and mild hypoglycemia ) in the lifestyle group and 5 in the st and ard care group . Conclusions and Relevance Among adults with type 2 diabetes diagnosed for less than 10 years , a lifestyle intervention compared with st and ard care result ed in a change in glycemic control that did not reach the criterion for equivalence , but was in a direction consistent with benefit . Further research is needed to assess superiority , as well as generalizability and durability of findings . Trial Registration clinical trials.gov Identifier : OBJECTIVE To investigate the associations between changes in body composition and fitness after exercise training and changes in hemoglobin A1c ( HbA1c ) in individuals with type 2 diabetes . RESEARCH DESIGN AND METHODS Participants ( n = 201 ) were r and omized to aerobic , resistance , or combined training for 9 months . HbA1c , waist circumference , total and trunk fat mass , appendicular fat mass , lean body mass , isokinetic leg muscle strength , peak O2 uptake , and estimated METs were assessed at baseline and follow-up . Change in HbA1c was evaluated across quartiles of change in body composition and fitness . RESULTS Change in HbA1c was associated with changes in body weight ( r = 0.13 , P = 0.052 ) , waist circumference ( r = 0.17 , P = 0.013 ) , trunk fat mass ( r = 0.19 , P = 0.005 ) , and estimated METs ( r = −0.16 , P = 0.023 ) . There was a trend in change in HbA1c across quartiles of waist circumference ( P = 0.011 ) , trunk fat mass ( P = 0.020 ) , and estimated METs ( P = 0.011 ) . Participants with increased estimated METs and reduced trunk fat mass had greater odds of having reduced HbA1c after training ( 3.48 , 1.46–8.31 ) . Finally , participants with increased estimated METs and reduced waist circumference were 2.81 ( 1.13–6.98 ) times more likely to have reduced HbA1c and type 2 diabetes medication use than those without improved fitness and central adiposity . CONCLUSIONS In patients with type 2 diabetes , a reduction in central adiposity and increase in fitness were the most prominent predictors of the change in HbA1c in response to exercise training CONTEXT Exercise guidelines for individuals with diabetes include both aerobic and resistance training although few studies have directly examined this exercise combination . OBJECTIVE To examine the benefits of aerobic training alone , resistance training alone , and a combination of both on hemoglobin A(1c ) ( HbA(1c ) ) in individuals with type 2 diabetes . DESIGN , SETTING , AND PARTICIPANTS A r and omized controlled trial in which 262 sedentary men and women in Louisiana with type 2 diabetes and HbA(1c ) levels of 6.5 % or higher were enrolled in the 9-month exercise program between April 2007 and August 2009 . INTERVENTION Forty-one participants were assigned to the nonexercise control group , 73 to resistance training 3 days a week , 72 to aerobic exercise in which they expended 12 kcal/kg per week ; and 76 to combined aerobic and resistance training in which they expended 10 kcal/kg per week and engaged in resistance training twice a week . Main Outcome Change in HbA(1c ) level . Secondary outcomes included measures of anthropometry and fitness . RESULTS The study included 63.0 % women and 47.3 % nonwhite participants who were a mean ( SD ) age of 55.8 years ( 8.7 years ) with a baseline HbA(1c ) level of 7.7 % ( 1.0 % ) . Compared with the control group , the absolute mean change in HbA(1c ) in the combination training exercise group was -0.34 % ( 95 % confidence interval [ CI ] , -0.64 % to -0.03 % ; P = .03 ) . The mean changes in HbA(1c ) were not statistically significant in either the resistance training ( -0.16 % ; 95 % CI , -0.46 % to 0.15 % ; P = .32 ) or the aerobic ( -0.24 % ; 95 % CI , -0.55 % to 0.07 % ; P = .14 ) groups compared with the control group . Only the combination exercise group improved maximum oxygen consumption ( mean , 1.0 mL/kg per min ; 95 % CI , 0.5 - 1.5 , P < .05 ) compared with the control group . All exercise groups reduced waist circumference from -1.9 to -2.8 cm compared with the control group . The resistance training group lost a mean of -1.4 kg fat mass ( 95 % CI , -2.0 to -0.7 kg ; P < .05 ) and combination training group lost a mean of -1.7 ( -2.3 to -1.1 kg ; P < .05 ) compared with the control group . CONCLUSIONS Among patients with type 2 diabetes mellitus , a combination of aerobic and resistance training compared with the nonexercise control group improved HbA(1c ) levels . This was not achieved by aerobic or resistance training alone . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00458133 Aim /hypothesisIn people with type 2 diabetes , exercise improves glucose control ( as reflected in HbA1c ) and physical fitness , but it is not clear to what extent these exercise-induced improvements are correlated with one another . We hypothesised that reductions in HbA1c would be related : ( 1 ) to increases in aerobic fitness and strength respectively in patients performing aerobic training or resistance training ; and ( 2 ) to changes in strength and aerobic fitness in patients performing aerobic and resistance training . Methods We r and omly allocated 251 type 2 diabetes patients to aerobic , resistance , or aerobic plus resistance training , or to a sedentary control group . Peak oxygen consumption ( $ $ \mathop {V}\limits^\cdot { { \text{O}}_{\text{2 peak } } } $ $ ) , workload , treadmill time and ventilatory threshold measurements from maximal treadmill exercise testing were measured at baseline and 6 months . Muscular strength was measured as the maximum weight that could be lifted eight times on the leg press , bench press and seated row exercises . Results With aerobic training , significant associations were found between changes in both $ $ \mathop {V}\limits^\cdot { { \text{O}}_{\text{2 peak } } } $ $ ( p = 0.040 ) and workload ( p = 0.022 ) , and changes in HbA1c . With combined training , improvements in $ $ \mathop {V}\limits^\cdot { { \text{O}}_{\text{2 peak } } } $ $ ( p = 0.008 ) , workload ( p = 0.034 ) and ventilatory threshold ( p = 0.003 ) were significantly associated with changes in HbA1c . Increases in strength on the seated row ( p = 0.006 ) and in mid-thigh muscle cross-sectional area ( p = 0.030 ) were significantly associated with changes in HbA1c after resistance exercise , whereas the association between increases in muscle cross-sectional area and HbA1c in participants doing aerobic plus resistance exercise ( p = 0.059 ) was of borderline significance . Conclusions /interpretationThere appears to be a link between changes in fitness and HbA1c . The improvements in cardiorespiratory fitness with aerobic training may be a better predictor of changes in HbA1c than improvements in strength Purpose : To investigate whether a home-based resistance training ( RT ) program that supplied high- quality equipment and qualified exercise specialists could provide benefits to obese patients with type 2 diabetes . Methods : A total of 48 obese individuals with type 2 diabetes were r and omly assigned to either an RT ( n=27 ) or a control group ( n=21 ) . Those in the RT group received a multigym and dumbbells and performed RT 3 days per week for 16 weeks at home . A qualified exercise specialist supervised training , with supervision being gradually decreased throughout the study . Primary outcome measures included strength and hemoglobin-A1C , whereas secondary outcome measures included other cardiovascular risk markers , key social-cognitive constructs and health-related quality of life . Results : Intention-to-treat analyses indicated a significant increase in upper and lower body strength for the RT group compared with controls ( 20–37 % mean increases in the RT group ) . No significant reduction in A1C levels was observed . The RT group had unchanged high-density lipoprotein cholesterol levels in comparison to declines in the control group . Significant reductions in fasting insulin , and increases in RT-related self-efficacy and intentions , were also observed in the RT group . Conclusions : Supervised home-based RT with high- quality equipment was effective for improving strength , along with other secondary outcomes in obese patients with type 2 diabetes BACKGROUND Clinical guidelines seldom provide in depth information about the most suitable type and intensity of exercise to obtain optimal benefit in different subgroups of T2D individuals . The aim of this study was to examine the effect of group exercise training on exercise capacity , insulin sensitivity and HbA1c in women with diabetes . METHODS Twenty-two women with T2D participated in a supervised group exercise program for six months . The program combined endurance and resistance exercise . The duration and intensity of exercise for each subject was recorded . The volume of exercise was calculated as the product of exercise duration and intensity . Exercise capacity , insulin sensitivity and HbA1c were measured at baseline and after six months of training . The subjects were dichotomized with respect to training volume in a high training volume group and a low training volume group . RESULTS Exercise capacity did not change significantly during the training period . Insulin sensitivity increased significantly and HbA1c decreased significantly from baseline in the high volume group but not in the low volume group . The increase in insulin sensitivity was explained with the intensity of exercise by 30 % . The reduction in HbA1c was explained with exercise by 25 % . CONCLUSION Improvement in insulin sensitivity after six months combined supervised group training in female diabetic subjects is related to exercise intensity , whereas the reduction in HbA1c is related mainly to training volume . Metabolic effects of training may be seen in the absence of improved exercise capacity |
629 | 22,258,983 | We could not find convincing evidence that NBI is significantly better than high definition WLC for the detection of patients with colorectal polyps , or colorectal adenomas .
We found evidence that NBI might be better than st and ard definition WLC and equal to high definition WLC for detection the patients with colorectal polyps , or colorectal adenomas | BACKGROUND It has been suggested that narrow b and imaging colonoscopy ( NBI ) might be better for detection of colorectal polyps than white light colonoscopy ( WLC ) .
OBJECTIVES To compare st and ard or high definition white light colonoscopy with narrow b and imaging colonoscopy for detection of colorectal polyps . | BACKGROUND Chromoendoscopy can accurately differentiate neoplastic from nonneoplastic polyps in the colon . Narrow b and imaging ( NBI ) has been described as " electronic chromoendoscopy , " but it is unclear whether pit patterns seen with chromoendoscopy are identical to those with NBI . OBJECTIVE Pilot study to compare features of diminutive polyps assessed with magnification NBI and chromoendoscopy . DESIGN Prospect i ve polyp series . SETTING Single tertiary referral center in the United Kingdom . PATIENTS Twenty patients seen for routine colonoscopy . INTERVENTION Digital images of each polyp recorded with NBI and chromoendoscopy were subsequently assessed as single images in a r and om order and as paired polyp images by experienced European- and Japanese-trained endoscopists . MAIN OUTCOME MEASUREMENTS Pit pattern ( Kudo classification ) ; vascular pattern intensity ( weak , normal , strong ) ; predicted histology ; pit pattern and vessel network clarity ( scale 1 - 3 , 1 poor , 3 excellent ) . RESULTS A total of 33 polyps < or=6 mm were assessed . Chromoendoscopic and NBI pit patterns were different for 12 and 20 of 33 polyps ( Japanese and European , respectively ) , combined kappa 0.23 , P < .001 compared with published intraobsever variation . Sensitivity , specificity , and accuracy for neoplasia were comparable for chromoendoscopic and NBI pit patterns and vascular pattern intensity for both observers . Vessel network clarity was better with NBI , P < .001 ( both ) , as was pit pattern clarity , P = .04 ( European ) . LIMITATIONS Small sample size ; pilot study . CONCLUSIONS Pit patterns were not always identical with NBI and chromoendoscopy . The Kudo classification may need to be modified and revali date d before it can be used with confidence with NBI . Vascular pattern intensity , a simple color change , appears as accurate as pit pattern Context How often does colonoscopy miss adenomas ? Contribution During a multicenter screening trial , experienced colonoscopists performed same-day optical ( OC ) and virtual colonoscopy ( VC ) on 1233 asymptomatic adults . Optical colonoscopy performed without knowledge of the VC findings missed 55 of 511 polyps ; 21 of these polyps were adenomas measuring 6 mm or greater . Adenomas missed by OC were usually on the proximal side of a fold or near the anal verge . Virtual colonoscopy missed 14 % of the adenomas that measured 6 mm or greater that were de-tected by OC . Implication s Neither OC nor VC is a perfect test : Each misses 10 % to 14 % of adenomas that measure 6 mm or greater . The Editors Optical colonoscopy ( OC ) is widely accepted as the gold st and ard for detecting colorectal neoplasia ( 1 , 2 ) . However , even in the most experienced h and s , this skilled examination is underst and ably not infallible . Retrospective analysis has suggested that the OC miss rate for adenomas 10 mm or greater is approximately 10 % ( 3 ) . More recently , prospect i ve back-to-back or t and em colonoscopy studies have reported miss rates for 10-mm adenomas ranging from 0 % to 6 % ( 4 , 5 ) . However , in addition to evaluating relatively small population s of patients with a high prevalence of polyps , a notable weakness common to these studies was that they used OC as its own reference st and ard . In a large , prospect i ve , multicenter trial that was primarily intended to evaluate the performance of virtual colonoscopy ( VC ) in asymptomatic adults ( 6 ) , we also had a unique opportunity to evaluate the adenoma miss rate on OC by segmentally unblinding the results from same-day VC . By using a reference st and ard other than OC itself for comparison , we could uncover lesions that may be systematic ally missed on repeated colonoscopies . These data not only provide novel insight into OC miss rates but also indicate the relative blind spots where more attention could be focused . Methods Study Design The institutional review boards at all 3 participating medical centers approved the study protocol for same-day VC and OC , and all patients provided written informed consent . We recruited asymptomatic adults who were referred for colorectal cancer screening . Exclusion criteria were a positive stool guiaic test result or iron deficiency anemia within the past 6 months ; rectal bleeding , hematochezia , or unintentional weight loss of more than 10 pounds within the past 12 months ; OC within the past 10 years or barium enema within the past 5 years ; personal history of adenomatous polyps , colorectal cancer , or inflammatory bowel disease ; and family history of familial adenomatous polyposis or nonpolyposis cancer syndromes . Between May 2002 and June 2003 , 1253 asymptomatic adults enrolled in the study . Eight patients were excluded because of failure to reach the cecum at OC , 6 patients were excluded because of inadequate colonic preparation , and another 6 patients were excluded because of computed tomography ( CT ) system failure . The final study group comprised 1233 asymptomatic adults ( 728 men and 505 women ; mean age , 57.8 years ) who successfully completed same-day VC and OC . Study participants underwent colonic preparation with oral intake of 90 mL of phospho-soda and 10 mg of bisacodyl . To opacify residual colonic fluid and stool for VC examination , patients also consumed dilute oral contrast as previously described ( 7 ) . Our CT protocol and VC technique have also been detailed previously ( 6 ) . To briefly summarize , we obtained supine and prone CT acquisitions on multidetector scanners after patient-controlled rectal insufflation of room air . One of 6 trained radiologists interpreted VC studies by using a commercially available CT colonography system ( Viatronix V3D-Colon , version 1.2 , Viatronix , Inc. , Stony Brook , New York ) . We used the 3-dimensional endoluminal fly-through view primarily for detecting polyps and 2-dimensional images for confirmation and problem solving . We measured polyps on the 3-dimensional view and recorded them by segment ( cecum , ascending colon , hepatic flexure , transverse colon , splenic flexure , descending colon , sigmoid colon , or rectum ) . We defined the proximal colon as including the cecum to the splenic flexure . We prospect ively rated diagnostic confidence for each detected lesion on a 3-point scale ( most certain , intermediate , and least certain ) . One of 17 experienced colonoscopists performed OC immediately after VC interpretation by using st and ard commercial video colonoscopes ( Olympus , Inc. , Melville , New York ) . The colonoscope was advanced to the cecum and then sequentially withdrawn into more distal segments for polyp detection . The colonoscopist measured polyps by using a calibrated linear probe , which is more accurate than either visual or biopsy forceps estimation ( 8) . Our polyp-matching algorithm requires VC and OC agreement according to size ( within a 50 % margin of error ) and location ( within the same or adjacent segment ) . After the colonoscopist evaluated a given segment , a study nurse unblinded the VC results for the previous segment . For any suspected polyp seen on VC that measured 5 mm or greater but was not seen on the initial blinded OC , the colonoscopist closely reexamined that segment and could review the VC images for guidance . We sent all retrieved polyps for histologic examination . For all cases in which a colorectal neoplasm measuring 6 mm or greater was found on second-look OC , we retrospectively review ed both the VC and OC images . We recorded polyp characteristics , such as size , morphologic characteristic ( sessile , pedunculated , or flat ) , and location on VC . If the polyp was situated on a colonic fold on VC , we further subcategorized it as being located on the back ( proximal ) side , front ( distal ) side , or edge of the fold . We analyzed both supine and prone VC sets for all cases . The primary reason that diminutive polyps measuring 5 mm at VC were included for potential unblinding at OC was that , given the relative error in polyp measurement , such polyps found on second-look OC might , in fact , measure 6 mm or greater . This allows for more accurate assessment of the OC miss rate at the 6-mm threshold . We did not include unblinded polyps that measured 5 mm or less on both VC and OC examinations in the final analysis . All study participants completed a detailed question naire on their personal and family medical history . For the purpose s of this study , particular attention was given to the question about previous abdominal or pelvic surgery , since adhesions could conceivably result in a more difficult colonoscopic examination . Statistical Analysis Prospect i ve OC performance was compared against the enhanced reference st and ard of second-look OC after segmental unblinding of VC results . We estimated exact binomial 95 % CIs for OC miss rates . We used the chi-square test to compare the frequency of previous abdominal surgery among patients with and without polyps missed at OC and also to compare the OC miss rates among the 3 medical centers . We calculated the 95 % CIs by using Stata software , version 7.0 for Windows ( Stata Corp. , College Station , Texas ) , and performed the chi-square tests by using SAS software , version 8.0 for Windows ( SAS Institute , Inc. , Cary , North Carolina ) . Role of the Funding Source The funding source 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 The performance characteristics of VC from this prospect i ve , multicenter screening trial , using OC as the reference st and ard , have been previously reported ( 6 ) . Our technique of segmental unblinding also allows for a separate assessment of OC by using the blinded VC results for comparison , which is the focus of this study . We identified 1310 polyps at OC in the 1233 asymptomatic adults ; 511 ( 39.0 % ) of these polyps measured 5 mm or greater ( Figure 1).Of these 511 polyps , 55 ( 10.8 % ) were found only on second-look OC after segmental unblinding of VC results . Twenty-four ( 43.6 % ) of the 55 unblinded lesions were nonadenomatous , including 16 hyperplastic polyps . Of the 31 missed neoplasms , 10 adenomas that measured only 5 mm were excluded from further analysis because of their diminutive size ( 9 ) . Including unblinded lesions , 554 adenomas were detected on OC in this screening sample ; 210 of these measured 6 mm or greater and 51 measured 10 mm or greater . Figure 1 . Polyp flowchart . In 20 patients ( 17 men and 3 women ; mean age , 58.2 years ) , 21 adenomas measuring 6 mm or greater ( range , 6 mm to 17 mm ; mean , 8.1 mm ) were found on OC only after the VC results were unblinded , which represent the lesions of primary interest for this study ( Table ) . The corresponding adenoma miss rate on prospect i ve OC examination was 10.0 % ( 95 % CI , 6.3 % to 14.9 % ) ( 21 of 210 adenomas ) at a 6-mm cutoff . The 20 patients with missed adenomas that measured 6 mm or greater represented only 1.6 % of the study sample ( 20 of 1233 patients ) but 11.9 % of patients with adenomas 6 mm or greater ( 20 of 168 patients ) . At 8-mm and 10-mm thresholds , the OC adenoma miss rates by polyp were 10.5 % ( CI , 5.2 % to 18.5 % ) ( 10 of 95 adenomas ) and 11.8 % ( CI , 4.4 % to 23.9 % ) ( 6 of 51 adenomas ) , respectively . The 10 patients with missed adenomas 8 mm or greater represented 12.2 % ( 10 of 82 patients ) of all patients with neoplasms of this size or greater ; the 6 patients with missed adenomas 8 mm or greater represented 12.5 % of all patients with neoplasms 10 mm or greater . Table . Characteristics of Neoplasms Missed at Prospect i ve Colonoscopic Evaluation Seventeen ( 81.0 % ) of the 21 unblinded neoplasms 6 mm or greater were tubular adenomas , 3 ( 14.3 % ) were tubulovillous adenomas , and 1 ( 4.8 % ) was an adenocarcinoma . Seven ( 33.3 % ) of the 21 unblinded polyps were classified as advanced lesions ( that is , size 10 mm or high- grade dysplasia , prominent villous component , or focus of malignancy ) . There were 15 sessile lesions , 4 pedunculated lesions , and 2 flat An important determinant in interpreting the results of colorectal polyp chemoprevention trials is the rate of polyps missed during colonscopic examination . We prospect ively examined 90 patients by t and em colonoscopy performed by two alternating examiners . In 69 ( 76.7 % ) patients , 221 neoplastic lesions were documented histologically . Of a total of 58 lesions detected in 31 patients , no neoplastic lesion greater than or equal to 10 mm in size was missed ; 16 % of diminutive ( less than or equal to 5 mm ) neoplastic polyps and 12.3 % of medium-sized ( 6 - 9 mm ) neoplastic polyps were missed by the first examiner . We conclude that an experienced colonoscopist will miss about 15 % of colorectal neoplastic polyps less than 10 mm in size in the setting of adequate bowel preparation . Large ( greater than or equal to 10 mm ) polyps were rarely missed , however , with the " miss " rate in our study equal to 0 , with a 95 % confidence limit of 4.64 % BACKGROUND AND STUDY AIMS A newly developed narrow-b and imaging ( NBI ) technique , in which modified optical filters were used in the light source of a video endoscope system , was applied during colonoscopy in a clinical setting . This pilot study evaluated the clinical feasibility of the NBI system for evaluating colorectal lesions . PATIENTS AND METHODS A total of 43 colorectal lesions in 34 patients were included in the study . The quality of visualization of colorectal lesions and the accuracy of differentiation between neoplastic and non-neoplastic lesions using the NBI system were evaluated in comparison with results from conventional colonoscopy and with chromoendoscopy . RESULTS For pit pattern delineation , NBI was superior to conventional endoscopy ( P < 0.001 ) , but inferior to chromoendoscopy ( P < 0.05 ) . NBI achieved better visualization of the mucosal vascular network and of the hue of lesions than conventional endoscopy ( P < 0.05 ) . However there was no significant difference between NBI and chromoendoscopy in differentiating neoplastic from non-neoplastic lesions ( both techniques had a sensitivity of 100 % and a specificity 75 % ) . This was better than the results of conventional colonoscopy ( sensitivity 83 % , specificity 44 % ; P < 0.05 for specificity ) . CONCLUSIONS These results suggest that in the examination of colonic lesions the NBI system provides imaging features additional to those of both conventional endoscopy and chromoendoscopy . For distinguishing neoplasms from non-neoplastic lesions , NBI was equivalent to chromoendoscopy BACKGROUND & AIMS Colonoscopic polypectomy is considered effective for preventing colorectal cancer ( CRC ) , but the incidence of cancer in patients under colonoscopic surveillance has rarely been investigated . We determined the incidence of CRC in patients under colonoscopic surveillance and examined the circumstances and risk factors for CRC and adenoma with high- grade dysplasia . METHODS Patients were drawn from 3 adenoma chemoprevention trials . All underwent baseline colonoscopy with removal of at least one adenoma and were deemed free of remaining lesions . We identified patients subsequently diagnosed with invasive cancer or adenoma with high- grade dysplasia . The timing , location , and outcome of all cases of cancer and high- grade dysplasia identified are described and risks associated with their development explored . RESULTS CRC was diagnosed in 19 of the 2915 patients over a mean follow-up of 3.7 years ( incidence , 1.74 cancers/1000 person-years ) . The cancers were located in all regions of the colon ; 10 were at or proximal to the hepatic flexure . Although most of the cancers ( 84 % ) were of early stage , 2 participants died of CRC . Seven patients were diagnosed with adenoma with high- grade dysplasia during follow-up . Older patients and those with a history of more adenomas were at higher risk of being diagnosed with invasive cancer or adenoma with high- grade dysplasia . CONCLUSIONS CRC is diagnosed in a clinical ly important proportion of patients following complete colonoscopy and polypectomy . More precise and representative estimates of CRC incidence and death among patients undergoing surveillance examinations are needed 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 OBJECTIVES : St and ard white light colonoscopy has limited ability to differentiate between polyp types ( adenomatous vs. hyperplastic ) . Narrow b and imaging ( NBI ) highlights the superficial mucosal/vascular patterns on polyps and may facilitate real-time characterization of polyp histology . The aim of this study was to prospect ively evaluate and compare the diagnostic characteristics of high-definition white light colonoscopy ( HDWL ) and NBI without magnification in the real-time prediction of polyp histology ( adenomatous vs. hyperplastic ) by evaluating the surface mucosal and vascular patterns . METHODS : We conducted a prospect i ve comparative study in a tertiary referral center . A total of 100 patients referred for screening or surveillance colonoscopy were prospect ively enrolled and underwent colonoscopy using a high-definition colonoscope with NBI capability . Every polyp detected was initially evaluated with HDWL followed by NBI for the presence of surface mucosal/vascular patterns . Based on these patterns , polyp histology was predicted by both modalities . The main outcome measurements were : ( i ) diagnostic characteristics of HDWL and NBI in predicting polyp histology and ( ii ) impact of polyp size and learning effect ( first half of study vs. second half ) on the ability of NBI to predict adenomas . RESULTS : A total of 236 polyps were detected in 100 patients —143 adenomas , 77 hyperplastic , and 16 others . Surface patterns ( type A : hyperplastic ; type B : adenomatous ) were recognized in all polyps with NBI ( 100 % ) compared to 45 % with HDWL . For predicting adenomas , NBI had a significantly higher sensitivity and greater accuracy ( 96 and 93 % respectively ) compared with HDWL ( 38 and 61 % respectively ) ( all P<0.0001 ) . Although the accuracy of NBI for predicting adenomas improved with increasing polyp size ( ≤5 mm ; 6–9 mm ; ≥10 mm ) and in the second half compared with the first half of the study , these differences were not statistically significant . CONCLUSIONS : Using a simple surface mucosal/vascular pattern classification , NBI without magnification was highly accurate and significantly superior to HDWL for the real-time prediction of adenomas Background Removal of colorectal neoplastic polyps can reduce the incidence of colorectal cancers . It is important to distinguish neoplastic from nonneoplastic polyps . We compared the ability of a trainee and an experienced endoscopist in distinguishing between neoplastic polyps and nonneoplastic polyps by conventional white-light , magnifying narrow-b and imaging ( NBI ) , and magnifying chromoendoscopy . Material s and methods One hundred and sixty-three small colorectal polyps from 104 patients were studied . All polyps were diagnosed by trainees and experienced endoscopists using conventional white-light , magnifying NBI , and magnifying chromoendoscopy . The kappa values of interobserver agreement between trainees and experienced endoscopists were evaluated before this study . Sensitivity , specificity , and diagnostic accuracy were assessed by reference to histopathology . The first 50 polyps were diagnosed by the trainee as the first stage and the rest 113 polyps were diagnosed as the second stage . Results Magnifying NBI and magnifying chromoendoscopy were significant better than conventional white-light by the experienced endoscopist ( diagnostic accuracy : NBI 85.3 % , chromoendoscopy 87.7 % , conventional view 74.8 % ) . No significant differences were found for the trainee . The kappa values ( 0.77~0.85 ) were good for each endoscopic modality for the experienced endoscopist . However , only NBI and chromoendoscopy had acceptable kappa values ( 0.40~0.48 ) for the trainee . The trainee improved diagnostic accuracy in the second stage , but not yielded the level of the experienced endoscopist . Conclusion Magnifying NBI and magnifying chromoendoscopy had a better interobserver agreement than conventional white-light among trainees and experienced endoscopists . The trainee needs learning time to improve diagnostic ability , even using a new modality such as magnifying NBI BACKGROUND Interval colorectal cancer ( CRC ) occasionally is detected in patients who have recently undergone colonoscopy . Systematic evaluation of CRC detected after colonoscopy could identify ways to improve the quality and the outcome of colonoscopy . METHODS This study examined cancer diagnoses in the course of the dietary Polyp Prevention Trial , a r and omized study of a dietary intervention on recurrence of adenomatous polyps . An algorithm was developed to classify each cancer into one of 4 etiologies : ( 1 ) incomplete removal ( cancer at the site of previous adenoma ) , ( 2 ) failed biopsy detection ( cancer in an area of suspected neoplasia with negative biopsy specimens ) , ( 3 ) missed cancer ( large , advanced stage cancer found at a short interval after colonoscopy ) , or ( 4 ) new cancer ( small , early stage cancer after a longer time interval ) . RESULTS Of 2079 patients , 13 had cancer detected over 5810 person years of observation ( PYO ) ( 2.2 cases/1000 PYO ) ; 7/13 or 53.8 % of patients had either a potentially " avoidable " cancer or one detectable at an earlier time interval because of incomplete removal ( 4/13 ) or missed cancer ( 3/13 ) . CONCLUSIONS Interval cancer occurs despite colonoscopy . Improved quality of colonoscopy may have reduced cancer prevalence or result ed in earlier cancer detection in over 50 % of prevalent cancers in the dietary Polyp Prevention Trial BACKGROUND & AIMS The miss rate of colonoscopy for neoplasms is poorly understood . The aim of this study was to determine the miss rate of colonoscopy by same day back-to-back colonoscopy . METHODS Two consecutive same day colonoscopies were performed in 183 patients . The patients were r and omized to undergo the second colonoscopy by the same or a different endoscopist and in the same or different position . RESULTS The overall miss rate for adenomas was 24 % , 27 % for adenomas < or = 5 mm , 13 % for adenomas 6 - 9 mm , and 6 % for adenomas > or = 1 cm . Patients with two or more adenomas at the first examination were more likely than patients with no or one adenoma detected at the first examination to have one or more adenomas at the second examination ( odds ratio , 3.3 ; 95 % confidence interval , 1.69 - 6.46 ) . Right colon adenomas were missed more often ( 27 % ) than left colon adenomas ( 21 % ) , but the difference was not significant . There was evidence of variation in sensitivity between endoscopists , but significant miss rates for small adenomas were found among essentially all endoscopists . CONCLUSIONS Using current colonoscopic technology , there are significant miss rates for adenomas < 1 cm even with meticulous colonoscopy . Miss rates are low for adenomas > or = 1 cm . The results suggest the need for improvements in colonoscopic technology 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 . OBJECTIVES : Endoscopic tri-modal imaging incorporates high-resolution white-light endoscopy ( HR-WLE ) , narrow-b and imaging ( NBI ) , and autofluorescence imaging ( AFI ) . Combining these advanced techniques may improve endoscopic differentiation between adenomas and non-neoplastic polyps . In this study , we aim ed to assess the interobserver variability and accuracy of HR-WLE , NBI , and AFI for polyp differentiation and to evaluate the combined use of AFI and NBI . METHODS : First , still images of 50 polyps ( 22 adenomas ; median 3 mm ) were r and omly displayed to three experienced and four non-experienced endoscopists . All HR-WLE and NBI images were scored for Kudo classification and AFI images for color . Second , the combined AFI and NBI images were assessed using a newly developed algorithm by six additional non-experienced endoscopists . RESULTS : The outcomes measured were interobserver agreement and diagnostic accuracy using histopathology as reference st and ard . Experienced endoscopists had better interobserver agreement for NBI ( κ=0.77 ) than for AFI ( κ=0.33 ) , whereas non-experienced endoscopists had better agreement for AFI ( κ=0.58 ) than for NBI ( κ=0.33 ) . The accuracies of HR-WLE , NBI , and AFI among experienced endoscopists were 65 , 70 , and 74 , respectively . Figures among non-experienced endoscopists were 57 , 63 , and 77 . The algorithm was associated with a significantly higher accuracy of 85 % among all observers ( P<0.023 ) . These figures were confirmed in the second evaluation study . CONCLUSIONS : Non-experienced endoscopists have better interobserver agreement and accuracy for AFI than for HR-WLE or NBI , indicating that AFI is easier to use for polyp differentiation in non-experienced setting . The newly developed algorithm , combining information of AFI and NBI together , had the highest accuracy and obtained equal results between experienced and non-experienced endoscopists BACKGROUND AND STUDY AIMS Chromoendoscopy in combination with magnifying endoscopy is useful in distinguishing neoplastic from non-neoplastic colorectal polyps . Narrow b and imaging ( NBI ) has been developed as a new technique to differentiate tissue patterns in vivo . The aim of the present study was to directly compare the diagnostic values of chromoendoscopy and NBI for the differentiation of neoplastic from non-neoplastic colorectal polyps . PATIENTS AND METHODS In total , 200 colorectal polyps from 99 patients were distributed in a 1 : 1 ratio in order to analyze the surface according to the pit pattern classification and vascular patterns by either magnifying chromoendoscopy or NBI magnification . Histologic analysis was performed on all lesions . RESULTS Using the Kudo classification of mucosal patterns , NBI with magnification result ed in a sensitivity of 90.5 % and a specificity of 89.2 % for the differentiation of neoplastic vs. non-neoplastic lesions . This performance was comparable to magnifying chromoendoscopy with a sensitivity of 91.7 % and a specificity of 90 % , respectively . Using vascular patterns for differentiation , NBI with magnification correctly identified 93.7 % of neoplastic polyps and 89.2 % of non-neoplastic colorectal lesions , whereas magnifying chromoendoscopy had a specificity of 95 % but a sensitivity of only 66.7 % . CONCLUSION NBI in combination with magnifying endoscopy is a promising tool for the differentiation of neoplastic from non-neoplastic colorectal polyps in vivo without the necessity of using dye . The detection of capillary vessels with NBI allows the evaluation of colorectal lesions based on the vascular patterns with high diagnostic accuracy 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 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 Colonoscopy is the preferred screening method for colorectal cancer . However , it has a substantial miss rate for colon polyps , and several techniques have been attempted to improve this limitation . Narrow-b and imaging ( NBI ) is a novel technology that enhances the visualization of surface mucosal and vascular patterns . OBJECTIVE The aim of this study was to determine the detection rate of additional polyps by NBI after removal of polyps visualized by st and ard white light colonoscopy ( WLC ) and to correlate the surface mucosal and vascular patterns with polyp histologic diagnosis . DESIGN This was a prospect i ve pilot feasibility study . SETTING Kansas City Veterans Affairs Medical Center . PATIENTS Subjects referred for screening colonoscopy were prospect ively enrolled . METHODS Subjects underwent colonoscopy after enrollment . After intubation of the cecum , colonic segments were sequentially examined , initially with WLC with removal of polyps followed by re-examination of the same segment with NBI . Additional polyps seen with NBI were photographed for their surface patterns and then removed . The total number of polyps visualized by WLC and NBI was calculated and the surface patterns were then correlated with polyp histologic features . RESULTS Forty patients were enrolled in the study , all men , 32 white . The mean age was 62 years . A total of 72 polyps were detected by WLC ( 43 tubular adenoma , 28 hyperplastic polyps ) , whereas NBI detected an additional 51 polyps , of which 29 were tubular adenomas and 22 were hyperplastic . Five different surface/vascular patterns were observed : fine capillary network with absent mucosal pattern , circular pattern with dots , round/oval pattern , tubular pattern , and gyrus pattern . The sensitivity , specificity , and overall accuracy of the first two patterns for hyperplastic polyps were 86 % , 96 % , and 92 % , respectively , and of the latter three patterns for tubular adenomas were 96 % , 86 % , and 92 % , respectively . CONCLUSIONS This pilot study demonstrates the feasibility of polyp detection and histologic correlation with NBI . These findings need to be confirmed in future r and omized controlled trials BACKGROUND AND STUDY AIM Polyp miss rates during colonoscopy have been calculated in a few t and em or back-to-back colonoscopy studies . Our objective was to assess the adenoma miss rate while limiting technique or operator expertise biases , i. e. by performing a large multicenter study , with same-day back-to-back video colonoscopy , done by two different operators in r and omized order and blinded to the other examination . PATIENTS AND METHODS 294 patients at 11 centers were included . Among the 286 analyzable t and em colonoscopies , miss rates were calculated in both a lesion- and patient-based analysis . Each of these rates was determined for polyps overall , for adenomas , and then for lesions larger than 5 mm , and for advanced adenomas . Univariate and logistic regression analysis were performed to define independent variables associated with missed polyps or adenomas . RESULTS The miss rates for polyps , adenomas , polyps > or = 5 mm , adenomas > or = 5 mm , and advanced adenomas were , respectively , 28 % , 20 % , 12 % , 9 % and 11 % . None of the masses with a carcinomatous ( n = 3 ) or carcinoid component ( n = 1 ) was missed . The specific lesion miss rates for patients with polyps and adenomas were respectively 36 % and 26 % but the corresponding rates were 23 % and 9.4 % when calculated for all 286 patients . The diameter ( 1-mm increments ) and number of polyps ( > or = 3 ) were independently associated with a lower polyp miss rate , whereas sessile or flat shape and left location were significantly associated with a higher miss rate . Adequacy of cleansing , presence of diverticula , and duration of withdrawal for the first procedure were not associated with adenoma miss rate . CONCLUSIONS We confirm a significant miss rate for polyps or adenoma during colonoscopy . Detection of flat polyps is an issue that must be focused on to improve the quality of colonoscopy Background : Discrimination between neoplastic and non-neoplastic lesions is crucial in colorectal cancer screening . Application of narrow-b and imaging ( NBI ) in colonoscopy visualises mucosal vascular networks in neoplastic lesions and may improve diagnostic accuracy . Aim : To compare the diagnostic efficacy of NBI in differentiating neoplastic from non-neoplastic colorectal lesions with diagnostic efficacies of st and ard modalities , conventional colonoscopy , and chromoendoscopy . Methods : In this prospect i ve study , 180 colorectal lesions from 133 patients were observed with conventional colonoscopy , and under low-magnification and high-magnification NBI and chromoendoscopy . Lesions were resected for histopathological analysis . Endoscopic images were stored electronically and r and omly allocated to two readers for evaluation . Sensitivity , specificity and diagnostic accuracy of each endoscopic modality were assessed by reference to histopathology . Results : NBI and chromoendoscopy scored better under high magnification than under low magnification in comparison with conventional colonoscopy . The diagnostic accuracy of NBI with low or high magnification was significantly higher than that of conventional colonoscopy ( low magnification : p = 0.0434 for reader 1 and p = 0.004 for reader 2 ; high magnification : p<0.001 for both readers ) and was comparable to that of chromoendoscopy . Conclusion : Both low-magnification and high-magnification NBI were capable of distinguishing neoplastic from non-neoplastic colorectal lesions ; the diagnostic accuracy of NBI was better than that of conventional colonoscopy and equivalent to that of chromoendoscopy . The role of NBI in screening colonoscopy needs further evaluation BACKGROUND AND STUDY AIMS Narrow b and imaging ( NBI ) with optical magnification is useful in predicting colon polyp histology . As magnifying endoscopes are not routinely available , we investigated the use of NBI and high definition white light imaging in determining polyp histology , using images obtained with colonoscopes without optical magnification . PATIENTS AND METHODS Images ( white light and NBI ) of colon polyps less than 10 mm in diameter were collected prospect ively from patients undergoing screening colonoscopy and digitally stored . Two endoscopists later review ed all images and predicted polyp histology as neoplastic or non-neoplastic using a modified Kudo classification . Comparison was made with histopathology . RESULTS Separate white light and NBI images of 80 polyps ( 49 neoplastic , 31 non-neoplastic ) from 63 patients were recorded . Mean polyp size was 5.1 + /- 2.1 mm ( 5.4 + /- 2.2 neoplastic ; 4.4 + /- 1.8 non-neoplastic ; P = 0.02 ) . In a pooled analysis , NBI correctly predicted neoplastic histology in 93 of 98 images ( sensitivity 95 % , positive predictive value [ PPV ] 94 % ) whereas white light did so in 58 of 98 images ( sensitivity 59 % , PPV 79 % ) . NBI correctly predicted non-neoplastic histology in 56 of 62 images ( specificity 90 % , negative predictive value [ NPV ] 92 % ) whereas white light did so in 47 of 62 images ( specificity 76 % , NPV 54 % ) . CONCLUSIONS NBI without optical magnification was more accurate in predicting colon polyp histology compared with white light imaging . Image quality and confidence in histology were significantly higher in the NBI group . NBI without optical magnification may be useful in predicting colon polyp histology BACKGROUND There is no widely adopted , easily applied method for distinguishing between adenomatous and nonadenomatous polyps during real-time colonoscopy . OBJECTIVE To compare white light ( WL ) with narrow-b and imaging ( NBI ) for the differentiation of colorectal polyps in vivo and to assess for a learning curve . DESIGN A prospect i ve polyp series . PATIENTS AND SETTING A total of 302 patients referred for colonoscopy , between August 2006 and July 2007 , to a single tertiary-referral center in the United States . INTERVENTION St and ard WL colonoscopy was performed with Olympus 180-series colonoscopes . Each detected polyp was first characterized by WL and then by NBI . Modified Kudo pit pattern and vascular color intensity ( VCI ) were recorded , and the histology was predicted . Endoscopists were given feedback every 2 weeks . MAIN OUTCOME MEASUREMENTS Overall accuracy and sensitivity and specificity of endoscopic diagnosis by using WL alone and with NBI , as well as improvement in endoscopists ' performance . RESULTS A total of 265 polyps were found in 131 patients . Diagnostic accuracy was 80 % with NBI and 77 % with WL ( P = .35 ) . NBI performed better than WL in diagnosing adenomas ( sensitivity 80 % vs 69 % , P < .05 ) . Nonadenomatous polyps were more likely to have a " light " VCI compared with adenomas ( 71 % vs 29 % , P < .001 ) . During the second half of the study , NBI accuracy improved , from 74 % to 87 % , and outperformed an unchanged WL accuracy of 79 % ( P < .05 ) . CONCLUSIONS Overall , NBI was not more accurate than WL in differentiating colorectal polyps in vivo ; however , once a learning curve was achieved , NBI performed significantly better . Further refinements of an NBI pit-pattern classification and VCI scale are needed before broad application to clinical decisions regarding the necessity of polypectomy AIM : To identify the feasibility of the narrow-b and imaging ( NBI ) method compared with that of conventional colonoscopy and chromoendoscopy for distinguishing neoplastic and nonneoplastic colonic polyps . METHOD : This study enrolled consecutive patients who underwent colonoscopy using a conventional colonoscope between January and February 2006 at Chang-Gung Memorial Hospital , Linkou Medical Center , Taiwan . These 78 patients had 110 colorectal polyps . During the procedure , conventional colonoscopy first detected lesions , and then the NBI system was used to examine the capillary networks . Thereafter indigo carmine ( 0.2 % ) was sprayed directly on the mucosa surface prior to evaluating the crypts using a conventional colonoscope . The pit patterns were characterized using the classification system proposed by Kudo . Finally , a polypectomy or biopsy was performed for histological diagnosis . RESULTS : Of the 110 colorectal polyps , 65 were adenomas , 40 were hyperplastic polyps , and five were adenocarcinomas . The NBI system and pit patterns for all lesions were analyzed . For differential diagnosis of neoplastic ( adenoma and adenocarcinoma ) and nonneoplastic ( hyperplastic ) polyps , the sensitivity of the conventional colonoscope for detecting neoplastic polyps was 82.9 % , specificity was 80.0 % and diagnostic accuracy was 81.8 % , significantly lower than those achieved with the NBI system ( sensitivity 95.7 % , specificity 87.5 % , accuracy 92.7 % ) and chromoendoscopy ( sensitivity 95.7 % , specificity 87.5 % , accuracy 92.7 % ) . Therefore , no significant difference existed between the NBI system and chromoendoscopy during differential diagnosis of neoplastic and nonneoplastic polyps . CONCLUSION : The NBI system identified morphological details that correlate well with polyp histology by chromoendoscopy 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 & 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 AND STUDY AIMS Narrow b and imaging ( NBI ) can accurately characterize colonic polyps using microvascular appearances . We aim ed to assess whether the Kudo pit pattern classification is accurate when used with NBI ( without dye-spray ) , and if microvascular appearances or NBI pit patterns maintain accuracy for polyp characterization at sizes < 10 mm . PATIENTS AND METHODS 116 polyps < 10 mm in size were detected in 62 patients undergoing surveillance colonoscopy . The polyps were prospect ively assessed using NBI and magnification for Kudo pit pattern ( III-V neoplastic , I-II non-neoplastic ) and vascular pattern intensity ( VPI ) , a measure of microvascular density ( strong VPI , neoplastic ; normal or weak VPI , non-neoplastic ) . Sensitivity , specificity , and accuracy were calculated and compared with results from histopathology . RESULTS The mean polyp size was 3.4 mm ( range 1 - 9 mm ) . Overall , NBI pit pattern sensitivity , specificity , and accuracy were 0.88 , 0.91 , and 89.6 % , respectively . Equivalent values for VPI were 0.94 , 0.89 , and 91.4 % . Results were similar when polyps were subdivided into diminutive polyps ( size < or= 5 mm ) and flat polyps . Combining both pit pattern and VPI improved the sensitivity ( 0.98 , P = 0.06 versus NBI pit pattern alone ) . There was very good agreement between NBI pit pattern and VPI for prediction of dysplasia ( kappa = 0.83 ) . No evidence of a learning curve for VPI was found . The NBI pit pattern was better than the VPI at subclassifying hyperplastic from other non-neoplastic polyps ( sensitivity 0.79 versus 0.56 , respectively , P = 0.02 ) , but accuracy was poor . CONCLUSION The NBI pit pattern and VPI are both highly accurate in characterizing neoplastic colonic polyps of < 10 mm , with VPI appearing to be simple to learn . NBI has the potential to replace conventional histology for small polyps BACKGROUND & AIMS Narrow-b and imaging ( NBI ) has been implemented in gastrointestinal endoscopy to improve the contrast of endoluminal pathologic structures , one of the aims being to increase colonic adenoma detection . Previous studies from referral centers have yielded variable and conflicting results with regard to improvement in adenoma detection rates by using NBI . The present large r and omized trial was design ed to finally settle this issue . METHODS In a prospect i ve study performed exclusively in a multicenter private practice setting involving 6 examiners with substantial lifetime experience ( > 10,000 colonoscopies ) , 1256 patients ( men : women , 47%:53 % ; mean age , 64.4 y ) were r and omized to HDTV screening colonoscopy with either NBI or white-light imaging on instrument withdrawal . The primary outcome measure was the adenoma detection rate ( ie , number of adenomas/total number of patients ) . RESULTS There was no difference between the 2 groups in terms of the general adenoma detection rate ( 0.32 vs 0.34 ) , the total number of adenomas ( 200 vs 216 ) , or in detection in subgroups of adenomas . This was despite a minimal , but significantly longer , withdrawal time in the NBI group ( 8.5 vs 7.9 min ; P < .05 ) . Only hyperplastic polyps were found more frequently in the NBI group ( P = .03 ) . CONCLUSIONS This large r and omized trial in a homogeneous private practice screening setting could not show any objective advantage of the NBI technique over white-light high definition television imaging in terms of improved adenoma detection rate . Contrast enhancement therefore likely will not contribute to a reduction in adenoma miss rates among experienced colonoscopists |
630 | 22,700,446 | This review demonstrates some efficacy of meditative therapies in reducing anxiety symptoms , which has important clinical implication s for applying meditative techniques in treating anxiety .
However , most studies measured only improvement in anxiety symptoms , but not anxiety disorders as clinical ly diagnosed | BACKGROUND Anxiety disorders are among the most common psychiatric disorders and meditative therapies are frequently sought by patients with anxiety as a complementary therapy .
Although multiple review s exist on the general health benefits of meditation , no review has focused on the efficacy of meditation for anxiety specifically . | BACKGROUND AND OBJECTIVE To develop a checklist of items measuring the quality of reports of r and omized clinical trials ( RCTs ) assessing nonpharmacological treatments ( NPTs ) . STUDY DESIGN AND SETTING The Delphi consensus method was used to select and reduce the number of items in the checklist . A total of 154 individuals were invited to participate : epidemiologists and statisticians involved in the field of methodology of RCTs ( n = 55 ) , members of the Cochrane Collaboration ( n = 41 ) , and clinicians involved in planning NPT clinical trials ( n = 58 ) . Participants ranked on a 10-point Likert scale whether an item should be included in the checklist . RESULTS Fifty-five experts ( 36 % ) participated in the survey . They were experienced in systematic review s ( 68 % were involved in the Cochrane Collaboration ) and in planning RCTs ( 76 % ) . Three rounds of the Delphi method were conducted to achieve consensus . The final checklist contains 10 items and 5 subitems , with items related to the st and ardization of the intervention , care provider influence , and additional measures to minimize the potential bias from lack of blinding of participants , care providers , and outcome assessors . CONCLUSIONS This tool can be used to critically appraise the medical literature , design NPT studies , and assess the quality of trial reports included in systematic review Background Although several studies have reported positive effects of mindfulness-based stress reduction ( MBSR ) intervention on psychological well-being , it is not known whether these effects are attributable to a change in mindfulness . Purpose The aim of this study is to compare the effects of MBSR to a waiting-list control condition in a r and omized controlled trial while examining potentially mediating effects of mindfulness . Methods Forty women and 20 men from the community with symptoms of distress ( mean age 43.6 years , SD = 10.1 ) were r and omized into a group receiving MBSR or a waiting-list control group . Before and after the intervention period , question naires were completed on psychological well-being , quality of life , and mindfulness . Results Repeated measures multiple analysis of variance ( MANCOVAs ) showed that , compared with the control group , the intervention result ed in significantly stronger reductions of perceived stress ( p = 0.016 ) and vital exhaustion ( p = 0.001 ) and stronger elevations of positive affect ( p = 0.006 ) , quality of life ( p = .009 ) , as well as mindfulness ( p = 0.001 ) . When mindfulness was included as a covariate in the MANCOVA , the group effects on perceived stress and quality of life were reduced to non significance . Conclusion Increased mindfulness may , at least partially , mediate the positive effects of mindfulness-based stress reduction intervention Objective : The underlying changes in biological processes that are associated with reported changes in mental and physical health in response to meditation have not been systematic ally explored . We performed a r and omized , controlled study on the effects on brain and immune function of a well‐known and widely used 8‐week clinical training program in mindfulness meditation applied in a work environment with healthy employees . Methods : We measured brain electrical activity before and immediately after , and then 4 months after an 8‐week training program in mindfulness meditation . Twenty‐five subjects were tested in the meditation group . A wait‐list control group ( N = 16 ) was tested at the same points in time as the meditators . At the end of the 8‐week period , subjects in both groups were vaccinated with influenza vaccine . Results : We report for the first time significant increases in left‐sided anterior activation , a pattern previously associated with positive affect , in the meditators compared with the nonmeditators . We also found significant increases in antibody titers to influenza vaccine among subjects in the meditation compared with those in the wait‐list control group . Finally , the magnitude of increase in left‐sided activation predicted the magnitude of antibody titer rise to the vaccine . Conclusions : These findings demonstrate that a short program in mindfulness meditation produces demonstrable effects on brain and immune function . These findings suggest that meditation may change brain and immune function in positive ways and underscore the need for additional research OBJECTIVE To evaluate the efficacy of Qigong in rehabilitation for patients with burnout . DESIGN Prospect i ve , r and omized controlled trial . SUBJECTS Eighty-two patients ( 68 women and 14 men , mean age 44.3 ( st and ard deviation 9.1 ) years ) diagnosed with burnout . METHODS Basic care was offered to both the intervention and the control group . Patients in the intervention group received basic care and , in addition , performed Qigong twice a week for 12 weeks . Psychological variables , health-related quality of life , perceived relaxation and physical measurements were assessed at baseline and after the intervention period . RESULTS No significant difference in treatment efficacy between the groups was found by either intention-to-treat or per- protocol analyses . Both groups improved significantly over time , with reduced levels of burnout , fatigue , anxiety and depression , and increased dynamic balance and physical capacity . CONCLUSION In this study , a Qigong intervention twice a week for 12 weeks had no additional effect beyond basic care for patients with burnout Objective This study tests the hypothesis that stress reduction methods based on mindfulness meditation can positively influence the rate at which psoriasis clears in patients undergoing phototherapy or photochemotherapy treatment . Methods Thirty-seven patients with psoriasis about to undergo ultraviolet phototherapy ( UVB ) or photochemotherapy ( PUVA ) were r and omly assigned to one of two conditions : a mindfulness meditation-based stress reduction intervention guided by audiotaped instructions during light treatments , or a control condition consisting of the light treatments alone with no taped instructions . Psoriasis status was assessed in three ways : direct inspection by unblinded clinic nurses ; direct inspection by physicians blinded to the patient 's study condition ( tape or no-tape ) ; and blinded physician evaluation of photographs of psoriasis lesions . Four sequential indicators of skin status were monitored during the study : a First Response Point , a Turning Point , a Halfway Point , and a Clearing Point . Results Cox-proportional hazards regression analysis showed that subjects in the tape groups reached the Halfway Point ( p = .013 ) and the Clearing Point ( p = .033 ) significantly more rapidly than those in the no-tape condition , for both UVB and PUVA treatments . Conclusions A brief mindfulness meditation-based stress reduction intervention delivered by audiotape during ultraviolet light therapy can increase the rate of resolution of psoriatic lesions in patients with psoriasis CONTEXT Qigong is a traditional Chinese health practice believed to have special healing and recovery power . Little scientific documentation was found on qigong and its effectiveness , and no literature was found on qigong as a treatment of substance addiction . OBJECTIVE To explore the effectiveness of qigong therapy on detoxification of heroin addicts compared to medical and nonmedical treatment . DESIGN Participants were r and omly assigned to 1 of 3 groups : qigong treatment group ( n = 34 ) , medication group ( n = 26 ) , and no-treatment control group ( n = 26 ) . PARTICIPANTS Eighty-six male heroin addicts , aged 18 to 52 years , who met the substance-dependence criteria of the Diagnostic and Statistical Manual of Mental Disorders , Third Edition Revised , with a history of heroin use from .5 to 11 years . All were residents at a m and atory drug-treatment center in the People 's Republic of China . INTERVENTION The qigong group practice d Pan Gu qigong and received qi adjustments from a qigong master daily . The medication group received the detoxification drug lofexidine-HCl by a 10-day gradual reduction method . The control group received only basic care and medications to treat severe withdrawal symptoms . MEASURES Urine morphine test , electrocardiogram , Hamilton Anxiety Scale , and a withdrawal-symptom evaluation scale were applied before and during the 10-day intervention . RESULTS Reduction of withdrawal symptoms in the qigong group occurred more rapidly than in the other groups . From day 1 , the qigong group had significantly lower mean symptom scores than did the other groups ( P < .01 ) . Both the qigong and medication groups had much lower anxiety scores than did the control group ( P<.01 ) , and the qigong group had significantly lower anxiety scores than did the medication group ( P<.01 ) . All subjects had a positive response to the urine morphine test before treatment . Fifty percent of the qigong group had negative urine tests on day 3 , compared to 23 % in the control group and 8 % in the medication group ( P < .01 ) . By day 5 of treatment , all subjects in the qigong group had negative urine tests , compared to day 9 for the medication group and day 11 for the control group . CONCLUSIONS Results suggest that qigong may be an effective alternative for heroin detoxification without side effects , though we can not completely eliminate the possibility of the placebo effect from the current study Background There is increasing recognition of mindfulness and mindfulness training as a way to decrease stress and increase psychological functioning . Purpose The aims of this study were to examine the effects of mindfulness stress reduction training on perceived stress and psychological well-being and to examine if changes in mindfulness mediate intervention effects on these outcomes . Methods Seventy women and one man with a previous cancer diagnosis ( mean age 51.8 years , st and ard deviation = 9.86 ) were r and omized into an intervention group or a wait-list control group . The intervention consisted of an 8-week mindfulness training course . Results Compared to participants in the control group , participants in the mindfulness training group had significantly decreased perceived stress and posttraumatic avoidance symptoms and increased positive states of mind . Those who participated in the intervention reported a significant increase in scores on the five-facet mindfulness question naire ( FFMQ ) when compared to controls . The increase in FFMQ score mediated the effects of the intervention on perceived stress , posttraumatic avoidance symptoms , and positive states of mind . Conclusions This study indicates that the improvements in psychological well-being result ing from mindfulness stress reduction training can potentially be explained by increased levels of mindfulness as measured with the FFMQ . The importance of these findings for future research in the field of mindfulness is discussed BACKGROUND Psychological distress contributes to the development of hypertension in young adults . This trial assessed the effects of a mind-body intervention on blood pressure ( BP ) , psychological distress , and coping in college students . METHODS This was a r and omized controlled trial ( RCT ) of 298 university students r and omly allocated to either the Transcendental Meditation ( TM ) program or wait-list control . At baseline and after 3 months , BP , psychological distress , and coping ability were assessed . A subgroup of 159 subjects at risk for hypertension was analyzed similarly . RESULTS Changes in systolic BP (SBP)/diastolic BP ( DBP ) for the overall sample were -2.0/-1.2 mm Hg for the TM group compared to + 0.4/+0.5 mm Hg for controls ( P = 0.15 , P = 0.15 , respectively ) . Changes in SBP/DBP for the hypertension risk subgroup were -5.0/-2.8 mm Hg for the TM group compared to + 1.3/+1.2 mm Hg for controls ( P = 0.014 , P = 0.028 , respectively ) . Significant improvements were found in total psychological distress , anxiety , depression , anger/hostility , and coping ( P values < 0.05 ) . Changes in psychological distress and coping correlated with changes in SBP ( P values < 0.05 ) and DBP ( P values < 0.08 ) . CONCLUSIONS This is the first RCT to demonstrate that a selected mind-body intervention , the TM program , decreased BP in association with decreased psychological distress , and increased coping in young adults at risk for hypertension . This mind-body program may reduce the risk for future development of hypertension in young adults OBJECTIVE The aim of this study was to investigate the potential of mindfulness-based stress reduction ( MBSR ) as a treatment for chronic primary insomnia . DESIGN A r and omized controlled trial was conducted . SETTING The study was conducted at a university health center . PATIENTS Thirty adults with primary chronic insomnia based on criteria of the Diagnostic and Statistical Manual of Mental Disorders , Text Revision , 4th Edition were r and omized 2:1 to MBSR or pharmacotherapy ( PCT ) . INTERVENTIONS Mindfulness-based stress reduction , a program of mindfulness meditation training consisting of eight weekly 2.5 hour classes and a daylong retreat , was provided , with ongoing home meditation practice expectations during three-month follow-up ; PCT , consisting of three milligrams of eszopiclone ( LUNESTA ) nightly for eight weeks , followed by three months of use as needed . A 10-minute sleep hygiene presentation was included in both interventions . MAIN OUTCOMES The Insomnia Severity Index ( ISI ) , Pittsburgh Sleep Quality Index ( PSQI ) , sleep diaries , and wrist actigraphy were collected pretreatment , posttreatment ( eight weeks ) , and at five months ( self-reports only ) . RESULTS Between baseline and eight weeks , sleep onset latency ( SOL ) measured by actigraphy decreased 8.9 minutes in the MBSR arm ( P < .05 ) . Large , significant improvements were found on the ISI , PSQI , and diary-measured total sleep time , SOL , and sleep efficiency ( P < .01 , all ) from baseline to five-month follow-up in the MBSR arm . Changes of comparable magnitude were found in the PCT arm . Twenty-seven of 30 patients completed their assigned treatment . This study provides initial evidence for the efficacy of MBSR as a viable treatment for chronic insomnia as measured by sleep diary , actigraphy , well-vali date d sleep scales , and measures of remission and clinical recovery OBJECTIVES Considerable morbidity persists among survivors of breast cancer ( BC ) including high levels of psychological stress , anxiety , depression , fear of recurrence , and physical symptoms including pain , fatigue , and sleep disturbances , and impaired quality of life . Effective interventions are needed during this difficult transitional period . METHODS We conducted a r and omized controlled trial of 84 female BC survivors ( Stages 0-III ) recruited from the H. Lee Moffitt Cancer and Research Institute . All subjects were within 18 months of treatment completion with surgery and adjuvant radiation and /or chemotherapy . Subjects were r and omly assigned to a 6-week Mindfulness-Based Stress Reduction ( MBSR ) program design ed to self-regulate arousal to stressful circumstances or symptoms ( n=41 ) or to usual care ( n=43 ) . Outcome measures compared at 6 weeks by r and om assignment included vali date d measures of psychological status ( depression , anxiety , perceived stress , fear of recurrence , optimism , social support ) and psychological and physical subscales of quality of life ( SF-36 ) . RESULTS Compared with usual care , subjects assigned to MBSR(BC ) had significantly lower ( two-sided p<0.05 ) adjusted mean levels of depression ( 6.3 vs 9.6 ) , anxiety ( 28.3 vs 33.0 ) , and fear of recurrence ( 9.3 vs 11.6 ) at 6 weeks , along with higher energy ( 53.5 vs 49.2 ) , physical functioning ( 50.1 vs 47.0 ) , and physical role functioning ( 49.1 vs 42.8 ) . In stratified analyses , subjects more compliant with MBSR tended to experience greater improvements in measures of energy and physical functioning . CONCLUSIONS Among BC survivors within 18 months of treatment completion , a 6-week MBSR(BC ) program result ed in significant improvements in psychological status and quality of life compared with usual care Background Bipolar disorder is highly recurrent and rates of comorbidity are high . Studies have pointed to anxiety comorbidity as one factor associated with risk of suicide attempts and poor overall outcome . This study aim ed to explore the feasibility and potential benefits of a new psychological treatment ( Mindfulness-based Cognitive Therapy : MBCT ) for people with bipolar disorder focusing on between-episode anxiety and depressive symptoms . Methods The study used data from a pilot r and omized trial of MBCT for people with bipolar disorder in remission , focusing on between-episode anxiety and depressive symptoms . Immediate effects of MBCT versus waitlist on levels of anxiety and depression were compared between unipolar and bipolar participants . Results The results suggest that MBCT led to improved immediate outcomes in terms of anxiety which were specific to the bipolar group . Both bipolar and unipolar participants allocated to MBCT showed reductions in residual depressive symptoms relative to those allocated to the waitlist condition . Limitations Analyses were based on a small sample , limiting power . Additionally the study recruited participants with suicidal ideation or behaviour so the findings can not immediately be generalized to individuals without these symptoms . Conclusions The study , although preliminary , suggests an immediate effect of MBCT on anxiety and depressive symptoms among bipolar participants with suicidal ideation or behaviour , and indicates that further research into the use of MBCT with bipolar patients may be warranted & NA ; Mindfulness‐based stress reduction ( MBSR ) is a structured 8‐week group program teaching mindfulness meditation and mindful yoga exercises . MBSR aims to help participants develop nonjudgmental awareness of moment‐to‐moment experience . Fibromyalgia is a clinical syndrome with chronic pain , fatigue , and insomnia as major symptoms . Efficacy of MBSR for enhanced well‐being of fibromyalgia patients was investigated in a 3‐armed trial , which was a follow‐up to an earlier quasi‐r and omized investigation . A total of 177 female patients were r and omized to one of the following : ( 1 ) MBSR , ( 2 ) an active control procedure controlling for nonspecific effects of MBSR , or ( 3 ) a wait list . The major outcome was health‐related quality of life ( HRQoL ) 2 months post‐treatment . Secondary outcomes were disorder‐specific quality of life , depression , pain , anxiety , somatic complaints , and a proposed index of mindfulness . Of the patients , 82 % completed the study . There were no significant differences between groups on primary outcome , but patients overall improved in HRQoL at short‐term follow‐up ( P = 0.004 ) . Post hoc analyses showed that only MBSR manifested a significant pre‐to‐post‐intervention improvement in HRQoL ( P = 0.02 ) . Furthermore , multivariate analysis of secondary measures indicated modest benefits for MBSR patients . MBSR yielded significant pre‐to‐post‐intervention improvements in 6 of 8 secondary outcome variables , the active control in 3 , and the wait list in 2 . In conclusion , primary outcome analyses did not support the efficacy of MBSR in fibromyalgia , although patients in the MBSR arm appeared to benefit most . Effect sizes were small compared to the earlier , quasi‐r and omized investigation . Several method ological aspects are discussed , e.g. , patient burden , treatment preference and motivation , that may provide explanations for differences . In a 3‐armed r and omized controlled trial in female patients suffering from fibromyalgia , patients benefited modestly from a mindfulness‐based stress reduction intervention We conducted a study of a group therapy based on exposure and mindfulness in the treatment of irritable bowel syndrome ( IBS ) . Out of 49 out patients , most of whom were referred from gastroenterological clinics , 34 entered into the 10-week treatment . Patients were assessed before , immediately after and 6 months after treatment . The assessment s consisted of a gastrointestinal symptom diary , self-report question naires covering quality of life , gastrointestinal specific anxiety , general functioning , and a psychiatric interview . At post-treatment , the mean reduction in symptoms was 41 % and 50 % of patients showed clinical ly significant improvement in symptom level . Patients also showed marked improvement on other outcome measures . Treatment gains were maintained at follow-up . The results support the use of exposure and mindfulness based strategies in the treatment of IBS , but further r and omised studies are needed to confirm the efficacy of the treatment OBJECTIVE Treatment of breast cancer is usually associated with significant psychological stress . In this study , we examined the effects of relaxation and visualization therapy ( RVT ) on psychological distress , cortisol levels , and immunological parameters of breast cancer patients undergoing radiotherapy . METHODS Participants were r and omly assigned to either the experimental ( n=20 ) who underwent group RVT for 24 consecutive days or control group ( n=14 ) who were on radiotherapy only . Psychological scores ( stress , anxiety , and depression ) were measured by structured clinical interviews . Salivary cortisol was assessed along the day . Lymphocytes were isolated and cultured to measure T-cell proliferation and sensitivity to glucocorticoids ( GCs ) . RESULTS RVT was effective to reduce stress , anxiety , and depression scores ( all P<.05 ) . However , cortisol levels as well as proliferation remained unchanged following RVT . Although T cells of experimental group were more sensitive to GCs than cells of controls at baseline , no changes were noted following RVT . Cortisol levels were positively correlated to anxiety and depression scores and inversely correlated to T-cell proliferation and sensitivity to GCs . CONCLUSION We conclude that the psychological intervention was capable to attenuate the emotional distress presented during radiotherapy treatment . A longer RVT or worse psychological morbidity at baseline may be necessary to translate psychological into biological changes The inability to cope successfully with the enormous stress of medical education may lead to a cascade of consequences at both a personal and professional level . The present study examined the short-term effects of an 8-week meditation-based stress reduction intervention on premedical and medical students using a well-controlled statistical design . Findings indicate that participation in the intervention can effectively ( 1 ) reduce self-reported state and trait anxiety , ( 2 ) reduce reports of overall psychological distress including depression , ( 3 ) increase scores on overall empathy levels , and ( 4 ) increase scores on a measure of spiritual experiences assessed at termination of intervention . These results ( 5 ) replicated in the wait-list control group , ( 6 ) held across different experiments , and ( 7 ) were observed during the exam period . Future research should address potential long-term effects of mindfulness training for medical and premedical students Objective : To determine the effect of yoga and of aerobic exercise on cognitive function , fatigue , mood , and quality of life in multiple sclerosis ( MS ) . Methods : Subjects with clinical ly definite MS and Exp and ed Disability Status Score less than or equal to 6.0 were r and omly assigned to one of three groups lasting 6 months : weekly Iyengar yoga class along with home practice , weekly exercise class using a stationary bicycle along with home exercise , or a waiting-list control group . Outcome assessment s performed at baseline and at the end of the 6-month period included a battery of cognitive measures focused on attention , physiologic measures of alertness , Profile of Mood States , State-Trait Anxiety Inventory , Multi-Dimensional Fatigue Inventory ( MFI ) , and Short Form (SF)-36 health-related quality of life . Results : Sixty-nine subjects were recruited and r and omized . Twelve subjects did not finish the 6-month intervention . There were no adverse events related to the intervention . There were no effects from either of the active interventions on either of the primary outcome measures of attention or alertness . Both active interventions produced improvement in secondary measures of fatigue compared to the control group : Energy and Fatigue ( Vitality ) on the SF-36 and general fatigue on the MFI . There were no clear changes in mood related to yoga or exercise . Conclusion : Subjects with MS participating in either a 6-month yoga class or exercise class showed significant improvement in measures of fatigue compared to a waiting-list control group . There was no relative improvement of cognitive function in either of the intervention groups Objectives . This study compares the effects of an integrated yoga program with brief supportive therapy in breast cancer out patients undergoing adjuvant radiotherapy at a cancer center . Methods . Eighty-eight stage II and III breast cancer out patients are r and omly assigned to receive yoga ( n = 44 ) or brief supportive therapy ( n = 44 ) prior to radiotherapy treatment . Assessment s include diurnal salivary cortisol levels 3 days before and after radiotherapy and self-ratings of anxiety , depression , and stress collected before and after 6 weeks of radiotherapy . Results . Analysis of covariance reveals significant decreases in anxiety ( P < .001 ) , depression ( P = .002 ) , perceived stress ( P < .001 ) , 6 a.m. salivary cortisol ( P = .009 ) , and pooled mean cortisol ( P = .03 ) in the yoga group compared with controls . There is a significant positive correlation between morning salivary cortisol level and anxiety and depression . Conclusion . Yoga might have a role in managing self-reported psychological distress and modulating circadian patterns of stress hormones in early breast cancer patients undergoing adjuvant radiotherapy This study was conducted to evaluate the comparative effect of yogic and conventional treatment in diarrhea-predominant irritable bowel syndrome ( IBS ) in a r and omized control design . The patients were 22 males , aged 20–50 years , with confirmed diagnosis of diarrhea-predominant IBS . The conventional group ( n=12 , 1 dropout ) was given symptomatic treatment with loperamide 2–6 mg/day for 2 months , and the yogic intervention group ( n=9 ) consisted of a set of 12 asanas ( yogic poses , i.e. , Vajrasana , Shashankasana , Ushtrasana , Marjariasana , Padhastasana , Dhanurasana , Trikonasana in two variations , Pawanmuktasana , and Paschimottanasana ) along with Surya Nadi pranayama ( right-nostril breathing ) two times a day for 2 months . All participants were tested at three regular intervals , at the start of study —0 month , 1 month , and 2 months of receiving the intervention— and were investigated for bowel symptoms , autonomic symptoms , autonomic reactivity ( battery of five st and ard tests ) , surface electrogastrography , anxiety profile by Spielberger 's Self Evaluation Question naire , which evaluated trait and state anxiety . Two months of both conventional and yogic intervention showed a significant decrease of bowel symptoms and state anxiety . This was accompanied by an increase in electrophysiologically recorded gastric activity in the conventional intervention group and enhanced parasympathetic reactivity , as measured by heart rate parameters , in yogic intervention group . The study indicates a beneficial effect of yogic intervention over conventional treatment in diarrhea-predominant IBS BACKGROUND Emotional stress triggers and exacerbates asthma in children . Reducing anxiety in adults by relaxation-breathing techniques has been shown in clinical trials to produce good asthma outcomes . However , more evidence is needed on using this intervention with asthmatic children . OBJECTIVE To evaluate the effectiveness of combined self-management and relaxation-breathing training for children with moderate-to-severe asthma compared to self-management-only training . DESIGN Two-group experimental design . SETTING AND PARTICIPANTS Pediatric outpatient clinic of a medical center in central Taiwan . Participants were 48 children , ages 6 - 14 years , with moderate-to-severe asthma and their parents . METHODS Participants were r and omly assigned to an experimental or comparison group and matched by gender , age , and asthma severity . Both groups participated in an asthma self-management program . Children in the experimental group were also given 30 min of training in a relaxation-breathing technique and a CD for home practice . Data on anxiety levels , self-perceived health status , asthma signs/symptoms , peak expiratory flow rate , and medication use were collected at baseline and at the end of the 12-week intervention . Effects of group , time , and group-time interaction were analyzed using the Mixed Model in SPSS ( 12.0 ) . RESULTS Anxiety ( especially state anxiety ) was significantly lower for children in the experimental group than in the comparison group . Differences in the other four physiological variables were also noted between pre- and post-intervention , but these changes did not differ significantly between groups . CONCLUSIONS A combination of self-management and relaxation-breathing training can reduce anxiety , thus improving asthmatic children 's health . These results can serve as an evidence base for psychological nursing practice with asthmatic children OBJECTIVE To compare yoga and relaxation as treatment modalities at 10 and 16 weeks from study baseline to determine if either of modality reduces subject stress , anxiety , blood pressure and improve quality of life . DESIGN A r and omised comparative trial was undertaken comparing yoga with relaxation . PARTICIPANTS One hundred and thirty-one subjects with mild to moderate levels of stress were recruited from the community in South Australia . INTERVENTIONS Ten weekly 1- h sessions of relaxation or hatha yoga . MAIN OUTCOME MEASURES Changes in the State Trait Personality Inventory sub-scale anxiety , General Health Question naire and the Short Form-36 . RESULTS Following the 10 week intervention stress , anxiety and quality of life scores improved over time . Yoga was found to be as effective as relaxation in reducing stress , anxiety and improving health status on seven domains of the SF-36 . Yoga was more effective than relaxation in improving mental health . At the end of the 6 week follow-up period there were no differences between groups in levels of stress , anxiety and on five domains of the SF-36 . Vitality , social function and mental health scores on the SF-36 were higher in the relaxation group during the follow-up period . CONCLUSION Yoga appears to provide a comparable improvement in stress , anxiety and health status compared to relaxation PURPOSE The r and omized study aim ed to determine the efficacy of psychological intervention consisting of relaxation and guided imagery to reduce anxiety and depression in gynecologic and breast cancer patients undergoing brachytherapy during hospitalization . METHODS AND MATERIAL S Sixty-six patients programmed to receive brachytherapy in two hospitals in Barcelona ( Spain ) were included in this study . The patients were r and omly allocated to either the study group ( n=32 ) or the control group ( n=34 ) . Patients in both groups received training regarding brachytherapy , but only study group patients received training in relaxation and guided imagery . After collection of sociodemographic data , all patients were given a set of question naires on anxiety and depression : the Hospital Anxiety and Depression Scale ( HADS ) , and on quality of life : Cuestionario de Calidad de Vida QL-CA-AFex ( CCV ) , prior to , during and after brachytherapy . RESULTS The study group demonstrated a statistically significant reduction in anxiety ( p=0.008 ) , depression ( p=0.03 ) and body discomfort ( p=0.04 ) compared with the control group . CONCLUSIONS The use of relaxation techniques and guided imagery is effective in reducing the levels of anxiety , depression and body discomfort in patients who must remain isolated while undergoing brachytherapy . This simple and inexpensive intervention enhances the psychological wellness in patients undergoing brachytherapy . State : This study has passed Ethical Committee review Mindfulness-based stress reduction ( MBSR ) is an established program shown to reduce symptoms of stress , anxiety , and depression . MBSR is believed to alter emotional responding by modifying cognitive-affective processes . Given that social anxiety disorder ( SAD ) is characterized by emotional and attentional biases as well as distorted negative self-beliefs , we examined MBSR-related changes in the brain-behavior indices of emotional reactivity and regulation of negative self-beliefs in patients with SAD . Sixteen patients underwent functional MRI while reacting to negative self-beliefs and while regulating negative emotions using 2 types of attention deployment emotion regulation-breath-focused attention and distraction-focused attention . Post-MBSR , 14 patients completed neuroimaging assessment s. Compared with baseline , MBSR completers showed improvement in anxiety and depression symptoms and self-esteem . During the breath-focused attention task ( but not the distraction-focused attention task ) , they also showed ( a ) decreased negative emotion experience , ( b ) reduced amygdala activity , and ( c ) increased activity in brain regions implicated in attentional deployment . MBSR training in patients with SAD may reduce emotional reactivity while enhancing emotion regulation . These changes might facilitate reduction in SAD-related avoidance behaviors , clinical symptoms , and automatic emotional reactivity to negative self-beliefs in adults with SAD Although research has found that long-term mindfulness meditation practice promotes executive functioning and the ability to sustain attention , the effects of brief mindfulness meditation training have not been fully explored . We examined whether brief meditation training affects cognition and mood when compared to an active control group . After four sessions of either meditation training or listening to a recorded book , participants with no prior meditation experience were assessed with measures of mood , verbal fluency , visual coding , and working memory . Both interventions were effective at improving mood but only brief meditation training reduced fatigue , anxiety , and increased mindfulness . Moreover , brief mindfulness training significantly improved visuo-spatial processing , working memory , and executive functioning . Our findings suggest that 4days of meditation training can enhance the ability to sustain attention ; benefits that have previously been reported with long-term meditators & NA ; A mounting body of literature recommends that treatment for fibromyalgia ( FM ) encompass medications , exercise and improvement of coping skills . However , there is a significant gap in determining an effective counterpart to pharmacotherapy that incorporates both exercise and coping . The aim of this r and omized controlled trial was to evaluate the effects of a comprehensive yoga intervention on FM symptoms and coping . A sample of 53 female FM patients were r and omized to the 8‐week Yoga of Awareness program ( gentle poses , meditation , breathing exercises , yoga‐based coping instructions , group discussion s ) or to wait‐listed st and ard care . Data were analyzed by intention to treat . At post‐treatment , women assigned to the yoga program showed significantly greater improvements on st and ardized measures of FM symptoms and functioning , including pain , fatigue , and mood , and in pain catastrophizing , acceptance , and other coping strategies . This pilot study provides promising support for the potential benefits of a yoga program for women with FM Depression and anxiety are associated with increased risk of postoperative cardiac events and death in patients who have undergone coronary artery bypass graft surgery . These risks persist even several months after the procedure . Guided imagery has been used with cardiac surgery patients for some time and with numerous anecdotal reports of considerable benefit . In addition , this therapy is low-cost and easy to implement , and the literature holds ample evidence for its efficacy in symptom reduction in various patient population s. It was thus hypothesized that preoperative use of guided imagery would reduce postoperative distress in patients undergoing coronary artery bypass graft . Fifty-six patients scheduled to undergo coronary artery bypass graft at Columbia University Medical Center were r and omized into 3 groups : guided imagery , music therapy , and st and ard care control . Patients in the imagery and music groups listened to audiotapes preoperatively and intraoperatively . All patients completed psychological , complementary medicine therapies use , and other assessment s preoperatively and at 1 week and 6 months postoperatively . Only preoperative distress was predictive of postoperative distress at follow-up . Use of complementary medicine therapies was high in all groups and this fact , in addition to the small sample size , may have accounted for the lack of significant relationship between imagery and postoperative distress . Regardless , this complementary and alternative medicine therapy remains palatable to patients . Given its efficacy in other patient population s , it is worth exploring its potential utility for this population with a larger sample Exercise and relaxation decrease blood pressure . Qigong is a traditional Chinese exercise consisting of breathing and gentle movements . We conducted a r and omised controlled trial to study the effect of Guolin qigong on blood pressure . In all , 88 patients with mild essential hypertension were recruited from the community and r and omised to Goulin qigong or conventional exercise for 16 weeks . The main outcome measurements were blood pressure , health status ( SF-36 scores ) , Beck Anxiety and Depression Inventory scores . In the qigong group , blood pressure decreased significantly from 146.3±7.8/93.0±4.1 mmHg at baseline to 135.5±10.0/87.1±7.7 mmHg at week 16 . In the exercise group , blood pressure also decreased significantly from 140.9±10.9/93.1±3.5 mmHg to 129.7±11.1/86.0±7.0 mmHg . Heart rate , weight , BMI , waist circumference , total cholesterol , renin and 24 h urinary albumin excretion significantly decreased in both groups after 16 weeks . General health , bodily pain , social functioning and depression also improved in both groups . No significant differences between qigong and conventional exercise were found . In conclusion , Guolin qigong and conventional exercise have similar effects on blood pressure in patients with mild hypertension . While no additional benefits were identified , it is nevertheless an alternative to conventional exercise in the nondrug treatment of hypertension The objective of this study was to examine the usefulness of a mindfulness-based cognitive therapy ( MBCT ) for treating insomnia symptoms in patients with anxiety disorder . Nineteen patients with anxiety disorder were assigned to an 8-week MBCT clinical trial . Participants showed significant improvement in Pittsburgh Sleep Quality Index ( Z = −3.46 , p = 0.00 ) , Penn State Worry Question naire ( Z = −3.83 , p = 0.00 ) , Ruminative Response Scale ( Z = −3.83 , p = 0.00 ) , Hamilton Anxiety Rating Scale ( Z = −3.73 , p = 0.00 ) , and Hamilton Depression Rating Scale scores ( Z = −3.06 , p = 0.00 ) at the end of the 8-week program as compared with baseline . Multiple regression analysis showed that baseline Penn State Worry Question naire scores were associated with baseline Pittsburgh Sleep Quality Index scores . These findings suggest that MBCT can be effective at relieving insomnia symptoms by reducing worry associated sleep disturbances in patients with anxiety disorder . However , well- design ed , r and omized , controlled trials are needed to confirm our findings Background : Mindfulness‐based cognitive therapy ( MBCT ) has been widely used to treat patients with depressive disorder to prevent relapse . The objective of this study was to examine the effectiveness of newly developed MBCT program as an adjuvant to pharmacotherapy in the treatment of patients with panic disorder or generalized anxiety disorder . Methods : Forty‐six patients with panic disorder or generalized anxiety disorder were assigned to either MBCT or an anxiety disorder education ( ADE ) program for a period of 8 weeks . The Hamilton Anxiety Rating Scale ( HAM‐A ) , Hamilton Depression Rating Scale ( HAM‐D ) , Beck Anxiety Inventory ( BAI ) , Beck Depression Inventory ( BDI ) , and Symptom Checklist‐90‐Revised ( SCL‐90‐R ) were used to assess the patients at 0 week and after the two programs had been running for 2 , 4 , and 8 weeks . Results : The MBCT group demonstrated significantly more improvement than the ADE group according to all anxiety ( HAM‐A , p<0.01 ; BAI , p<0.01 ; anxiety subscale of SCL‐90‐R , p=0.01 ) and depression ( HAM‐D , p<0.01 ; BDI , p<0.01 ; depression subscale of SCL‐90‐R , p<0.01 ) scale scores . The obsessive‐compulsive and phobic subscales of the SCL‐90‐R also showed significantly more improvement in the MBCT group . However , no significant improvement was observed in the MBCT group versus the ADE group in terms of the somatization , interpersonal sensitivity , paranoid ideation , or psychoticism subscale scores of the SCL‐90‐R. Conclusions : MBCT may be effective at relieving anxiety and depressive symptoms in patients with panic disorder or generalized anxiety disorder . However , well‐ design ed , r and omized controlled trials are needed . Depression and Anxiety , 2009 . © 2009 Wiley‐Liss , OBJECTIVES To evaluate the effects on blood pressure , lipid profile , and anxiety status on subjects received a 12-week Tai Chi Chuan exercise program . DESIGN R and omized controlled study of a Tai Chi Chuan group and a group of sedentary life controls . SETTING Taipei Medical University Hospitals and University campus in the Taipei , Taiwan , area . SUBJECTS Two ( 2 ) selected groups of 76 healthy subjects with blood pressure at high-normal or stage I hypertension . INTERVENTION A 12-week Tai Chi Chuan exercise training program was practice d regularly with a frequency of 3 times per week . Each session included 10-minute warm-up , 30-minute Tai Chi exercise , 10-minute cool-down . Exercise intensity was estimated to be approximately 64 % of maximal heart rate . OUTCOME MEASURES Blood pressure , lipid profile and anxiety status ( State-Trait Anxiety Inventory ; STAI ) were evaluated . RESULTS After 12-weeks of Tai Chi training , the treatment group showed significant decrease in systolic blood pressure of 15.6 mm Hg and diastolic blood pressure 8.8 mm Hg . The serum total cholesterol level decreased 15.2 mg/dL and high-density lipoprotein cholesterol increased 4.7 mg/dL. By using STAI evaluation , both trait anxiety and state anxiety were decreased . CONCLUSIONS This study shows that under well- design ed conditions , Tai Chi exercise training could decrease blood pressure and results in favorable lipid profile changes and improve subjects ' anxiety status . Therefore , Tai Chi could be used as an alternative modality in treating patients with mild hypertension , with a promising economic effect OBJECTIVE This study evaluated the effectiveness of mindfulness-based cognitive therapy ( MBCT ) for individuals with a diagnosis of cancer . METHOD Participants ( N = 115 ) diagnosed with cancer , across site and stage , were r and omly allocated to either the treatment or the wait-list condition . Treatment was conducted at 1 site , by a single therapist , and involved participation in 8 weekly 2-hr sessions that focused on mindfulness . Participants meditated for up to 1 hr daily and attended an additional full-day session during the course . Participants were assessed before treatment and 10 weeks later ; this second assessment occurred immediately after completion of the program for the treatment condition . The treatment condition was also assessed at 3 months postintervention . All postinitial assessment s were completed by assessors who were blind to treatment allocation . RESULTS There were large and significant improvements in mindfulness ( effect size [ ES ] = 0.55 ) , depression ( ES = 0.83 ) , anxiety ( ES = 0.59 ) , and distress ( ES = 0.53 ) as well as a trend for quality of life ( ES = 0.30 ) for MBCT participants compared to those who had not received the training . The wait-list group was assessed before and after receiving the intervention and demonstrated similar change . CONCLUSIONS These improvements represent clinical ly meaningful change and provide evidence for the provision of MBCT within oncology setting BACKGROUND Numerous studies have explored the effectiveness of complementary and alternative medicine in the treatment of migraine but there is no documented investigation of the effectiveness of yoga therapy for migraine management . OBJECTIVES To investigate the effectiveness of holistic approach of yoga therapy for migraine treatment compared to self-care . DESIGN A r and omized controlled trial . METHODS Seventy-two patients with migraine without aura were r and omly assigned to yoga therapy or self-care group for 3 months . Primary outcomes were headache frequency ( headache diary ) , severity of migraine ( 0 - 10 numerical scale ) and pain component ( McGill pain question naire ) . Secondary outcomes were anxiety and depression ( Hospital anxiety depression scale ) , medication score . RESULTS After adjustment for baseline values , the subjects ' complaints related to headache intensity ( P < .001 ) , frequency ( P < .001 ) , pain rating index ( P < .001 ) , affective pain rating index ( P < .001 ) , total pain rating index ( P < .001 ) , anxiety and depression scores ( P < .001 ) , symptomatic medication use ( P < .001 ) were significantly lower in the yoga group compared to the self-care group . CONCLUSION The study demonstrated a significant reduction in migraine headache frequency and associated clinical features , in patients treated with yoga over a period of 3 months . Further study of this therapeutic intervention appears to be warranted CONTEXT Despite the growing popularity of qigong in the West , few well-controlled studies using a sham master to assess the clinical efficacy of qigong have been conducted . OBJECTIVE To study the effect of qigong on treatment-resistant patients with late-stage complex regional pain syndrome type I. DESIGN Block-r and om placebo-controlled clinical trial . SETTING Pain Management Center at New Jersey Medical School . PATIENTS 26 adult patients ( aged 18 to 65 years ) with complex regional pain syndrome type I. INTERVENTIONS The experimental group received qi emission and qigong instruction ( including home exercise ) by a qigong master . The control group received a similar set of instructions by a sham master . The experimental protocol included 6 forty-minute qigong sessions over 3 weeks , with reevaluation at 6 and 10 weeks . Assessment included comprehensive medical history , physical exam , psychological evaluation , necessary diagnostic testing . Symptom Check List 90 , and the Carleton University Responsiveness to Suggestion Scale . MAIN OUTCOME MEASURES Thermography , swelling , discoloration , muscle wasting , range of motion , pain intensity rating , medication usage , behavior assessment ( activity level and domestic disability ) , frequency of pain awakening , mood assessment , and anxiety assessment . RESULTS 22 subjects completed the protocol . Among the genuine qigong group , 82 % reported less pain by the end of the first training session compared to 45 % of control patients . By the last training session , 91 % of qigong patients reported analgesia compared to 36 % of control patients . Anxiety was reduced in both groups over time , but the reduction was significantly greater in the experimental group than in the control group . CONCLUSIONS Using a credible placebo to control for nonspecific treatment effects , qigong training was found to result in transient pain reduction and long-term anxiety reduction . The positive findings were not related to preexperimental differences between groups in hypnotizability . Future studies of qigong should control for possible confounding influences and perhaps use clinical disorders more responsive to psychological intervention The purpose of this investigation was to evaluate the effects of guided imagery on postoperative outcomes in patients undergoing same-day surgical procedures . Forty-four adults scheduled for head and neck procedures were r and omly assigned into 2 groups for this single-blind investigation . Anxiety and baseline pain levels were documented preoperatively . Both groups received 28 minutes of privacy , during which subjects in the experimental group listened to a guided imagery compact disk ( CD ) , but control group patients received no intervention . Data were collected on pain and narcotic consumption at 1- and 2-hour postoperative intervals . In addition , discharge times from the postoperative anesthesia care unit ( PACU ) and the ambulatory procedure unit and patient satisfaction scores were collected . The change in anxiety levels decreased significantly in the guided imagery group ( P = .002 ) . At 2 hours , the guided imagery group reported significantly less pain ( P = .041 ) . In addition , length of stay in PACU in the guided imagery group was an average of 9 minutes less than in the control group ( P = .055 ) . The use of guided imagery in the ambulatory surgery setting can significantly reduce preoperative anxiety , which can result in less postoperative pain and earlier PACU discharge times Objective The objective of this study was to assess the effects of participation in a mindfulness meditation – based stress reduction program on mood disturbance and symptoms of stress in cancer out patients . Methods A r and omized , wait-list controlled design was used . A convenience sample of eligible cancer patients enrolled after giving informed consent and were r and omly assigned to either an immediate treatment condition or a wait-list control condition . Patients completed the Profile of Mood States and the Symptoms of Stress Inventory both before and after the intervention . The intervention consisted of a weekly meditation group lasting 1.5 hours for 7 weeks plus home meditation practice . Results Ninety patients ( mean age , 51 years ) completed the study . The group was heterogeneous in type and stage of cancer . Patients ’ mean preintervention scores on dependent measures were equivalent between groups . After the intervention , patients in the treatment group had significantly lower scores on Total Mood Disturbance and subscales of Depression , Anxiety , Anger , and Confusion and more Vigor than control subjects . The treatment group also had fewer overall Symptoms of Stress ; fewer Cardiopulmonary and Gastrointestinal symptoms ; less Emotional Irritability , Depression , and Cognitive Disorganization ; and fewer Habitual Patterns of stress . Overall reduction in Total Mood Disturbance was 65 % , with a 31 % reduction in Symptoms of Stress . Conclusions This program was effective in decreasing mood disturbance and stress symptoms in both male and female patients with a wide variety of cancer diagnoses , stages of illness , and ages Summary : Heart disease is the leading cause of death among Americans each year , yet the misperception still exists that cardiovascular disease is not a serious health problem for women . Evidence indicates that anxiety contributes to the development of heart disease . The primary purpose of this study was to assess the effectiveness of Kabat-Zinn 's mindfulness-based stress reduction program to reduce anxiety in women with heart disease . Anxiety , emotional control , coping styles , and health locus of control were compared in a treatment and control group of women with heart disease . Post-intervention analyses provide initial support for beneficial effects of this program OBJECTIVES This study compares the anxiolytic effects of a yoga program and supportive therapy in breast cancer out patients undergoing conventional treatment at a cancer centre . METHODS Ninety-eight stage II and III breast cancer out patients were r and omly assigned to receive yoga ( n=45 ) or brief supportive therapy ( n=53 ) prior to their primary treatment i.e. , surgery . Only those subjects who received surgery followed by adjuvant radiotherapy and six cycles of chemotherapy were chosen for analysis following intervention ( yoga , n=18 , control , n=20 ) . Intervention consisted of yoga sessions lasting 60min daily while the control group was imparted supportive therapy during their hospital visits as a part of routine care . Assessment s included Speilberger 's State Trait Anxiety Inventory and symptom checklist . Assessment s were done at baseline , after surgery , before , during , and after radiotherapy and chemotherapy . RESULTS A GLM-repeated measures ANOVA showed overall decrease in both self-reported state anxiety ( p<0.001 ) and trait anxiety ( p=0.005 ) in yoga group as compared to controls . There was a positive correlation between anxiety states and traits with symptom severity and distress during conventional treatment intervals . CONCLUSION The results suggest that yoga can be used for managing treatment-related symptoms and anxiety in breast cancer out patients BACKGROUND Hypertension occurs in nearly 10 percent of pregnancies , and is associated with higher risk of infant and maternal morbidity and mortality than in normal pregnancies . Previous studies have suggested that relaxation therapies reduce blood pressure in nonpregnant adults . The objectives of this pilot r and omized trial were to provide preliminary evidence of whether relaxation by means of guided imagery would reduce blood pressure in hypertensive pregnant women , and to assess the feasibility of a larger trial . METHODS A total of 69 pregnant women with hypertension were r and omized to periods of guided imagery or of quiet rest , twice daily for 4 weeks or until delivery , whichever came first . Daytime ambulatory mean arterial pressure , systolic and diastolic blood pressure , and anxiety were measured weekly for up to 4 weeks . RESULTS Women allocated to guided imagery had lower mean arterial pressure elevations over time than those allocated to quiet rest ( guided imagery : M = 1.58 mmHg , SD = 7.63 ; quiet rest : M = 5.93 mmHg , SD = 6.55 ; t = 2.36 , p = 0.02 ) . However , when adjusted for baseline mean arterial pressure and gestation , the effect was not significant ( p = 0.14 ) . Numbers of women prescribed antihypertensive medication postr and omization were similar ( guided imagery : n = 16 ; quiet rest : n = 13 , χ(2 ) = 0.74 , p = 0.46 ) . There was also no evidence of an effect on women 's anxiety . Nearly 90 percent ( n = 26 ) of the guided imagery group indicated that they would use it again . CONCLUSIONS Further rigorous study is warranted to determine effects of guided imagery on maternal blood pressure and perinatal health outcomes OBJECTIVES The aim of the current study was to evaluate and compare two different behavioral rehabilitation programs in improving the quality of life in cardiac patients in Hong Kong . DESIGN AND SETTING The current study was carried out in the outpatient unit of Occupational Therapy Department in the United Christian Hospital , Hong Kong . Convenience sampling with referral from the cardiac specialty was used in the present study . SUBJECTS A total of 65 subjects , with a mean age 65 ( range , 42 to 76 ) , were recruited in the study . The cardiac diseases included myocardial infa rct , postcoronary intervention , valve replacement , and also ischemic heart disease . INTERVENTIONS Patients were alternately allocated to the two groups . The first group of patients received instructions and practice d on progressive relaxation . The second group of patients underwent training in qigong . A total of eight sessions were conducted and each session lasted 20 minutes . OUTCOME MEASURES Demographic and clinical data such as gender , age , and systolic and diastolic blood pressure were recorded . The psychological and Quality of Life assessment was performed using the Chinese versions of Short Form 36 ( C-SF36 ) , State-Trait Anxiety Inventory ( C-STAI ) , and General Health Question naire ( C-GHQ-12 ) . RESULTS Fifty-nine ( 59 ) subjects ( 44 men and 15 women ) completed all eight rehabilitation sessions in the study . Patients allocated to the two treatment groups had comparable baseline characteristics . Progressive relaxation was more effective in reducing blood pressures compared to qigong . Relaxation appeared to be particularly beneficial in somatic domains . qigong group demonstrated greater improvement in psychologic measures in addition to reduction in systolic blood pressure . CONCLUSIONS Progressive relaxation and qigong exercise improved the quality of life for cardiac patients with reference to certain physiologic and psychologic measures . The result was supported by previous studies and literature review s on qigong in terms of its effect on the psychologic dimension CONTEXT Patients who have received solid organ transplants continue to experience a myriad of complex symptoms related to their underlying disease and to chronic immunosuppression that reduce the quality of life . Beneficial nonpharmacologic therapies to address these symptoms have not been established in the transplant population . OBJECTIVE Assess the efficacy of mindfulness-based stress reduction ( MBSR ) in reducing symptoms of anxiety , depression , and poor sleep in transplant patients . DESIGN , SETTING , AND PATIENTS Controlled trial with a two-staged r and omization . Recipients of kidney , kidney/pancreas , liver , heart , or lung transplants were r and omized to MBSR ( n=72 ) or health education ( n=66 ) initially or after serving in a waitlist . Mean age was 54 years ( range 21 - 75 ) ; 55 % were men , and 91 % were white . INTERVENTIONS MBSR , a mindfulness meditation training program consisting of eight weekly 2.5-hour classes ; health education , a peer-led active control . PRIMARY OUTCOME MEASURES Anxiety ( State-Trait Anxiety Inventory ) , depression ( Center for Epidemiologic Studies Depression Scale ) , and sleep quality ( Pittsburgh Sleep Quality Index ) scales assessed by self-report at baseline , 8 weeks , 6 months , and 1 year . RESULTS Benefits of MBSR were above and beyond those afforded by the active control . MBSR reduced anxiety and sleep symptoms ( P < .02 ) , with medium treatment effects ( .51 and .56 ) at 1 year compared to health education in intention-to-treat analyses . Within the MBSR group , anxiety , depression , and sleep symptoms decreased and quality -of-life measures improved by 8 weeks ( P < .01 , all ) , and benefits were retained at 1 year ( P < .05 , all ) . Initial symptom reductions in the health education group were smaller and not sustained . Comparisons to the waitlist confirmed the impact of MBSR on both symptoms and quality of life , whereas health education improvements were limited to quality -of-life ratings . CONCLUSIONS MBSR reduced distressing symptoms of anxiety , depression , and poor sleep and improved quality of life . Benefits were sustained over 1 year . A health education program provided fewer benefits , and effects were not as durable . MBSR is a relatively inexpensive , safe , and effective community-based intervention BACKGROUND Cerebral vascular disorder ( CVD ) might result in a quantifiable decrease in quality of life , which is determined not only by the neurological deficits but also by impairment of cognitive functions . There are few studies that report on the cognitive effect of Tai Chi exercise ( Tai Chi ) on the elderly with CVD . The purpose of the present study was to examine the cognitive effect of Tai Chi on the elderly with CVD using P300 measurement , in addition to the General Health Question naire ( GHQ ) and Pittsburgh Sleep Quality Index ( PSQI ) . METHODS A total of 34 patients with CVD were recruited from outpatient Akistu-Kounoike Hospital and r and omly assigned to receive Tai Chi ( n= 17 ) or rehabilitation ( n= 17 ) in group sessions once a week for 12 weeks . To examine the time courses of each score ( P300 amplitude , P300 latency , GHQ score and PSQI score ) , repeated- measures analysis of variance was carried out with groups and time as factors . RESULTS For the time courses of P300 amplitudes and latencies , there were no significant effects of interaction between group and time . However , significant time-by-group interactions were found for Sleep Quality ( P= 0.006 ) , GHQ total score ( P= 0.005 ) , anxiety/insomnia score ( P= 0.034 ) , and severe depression score ( P= 0.020 ) . CONCLUSIONS Tai Chi might therefore be considered a useful non-pharmacological approach , along with rehabilitation , for the maintenance of cognitive function in the elderly with CVD and might be a more useful non-pharmacological approach for the improvement of sleep quality and depressive symptoms in the elderly with CVD than rehabilitation A student under optimal stress does bring out his or her best , However extremes of stress can result in stress induced disorders and deteriorating performance . Can yoga be of benefit in stress induced effects in medical students ? The present study was conducted in first MBBS students ( n = 50 ) to determine the benefit if any of yogic practice s on anxiety status during routine activities and prior to examination . Feedback scores were assessed to determine how the students had benefited from the practice s. Anxiety status as assessed by Spillberger 's anxiety scale showed a statistically significant reduction following practice . In addition the anxiety score which rose prior to exams showed a statistically significant reduction on the day of exam after practice . These results point to the beneficial role of yoga in not only causing reduction in basal anxiety level but also attenuating the increase in anxiety score in stressful state such as exams . The results of the exam indicated a statistically significant reduction in number of failures in yoga group as compared to the control group . The improvement in various parameters such as better sense of well being , feeling of relaxation , improved concentration , self confidence , improved efficiency , good interpersonal relationship , increased attentiveness , lowered irritability levels , and an optimistic outlook in life were some of the beneficial effects enjoyed by the yoga group indicated by feedback score OBJECTIVES This study investigated the relationships between a mindfulness-based stress reduction meditation program for early stage breast and prostate cancer patients and quality of life , mood states , stress symptoms , and levels of cortisol , dehydroepi and rosterone-sulfate ( DHEAS ) and melatonin . METHODS Fifty-nine patients with breast cancer and 10 with prostate cancer enrolled in an eight-week Mindfulness-Based Stress Reduction ( MBSR ) program that incorporated relaxation , meditation , gentle yoga , and daily home practice . Demographic and health behavior variables , quality of life , mood , stress , and the hormone measures of salivary cortisol ( assessed three times/day ) , plasma DHEAS , and salivary melatonin were assessed pre- and post-intervention . RESULTS Fifty-eight and 42 patients were assessed pre- and post-intervention , respectively . Significant improvements were seen in overall quality of life , symptoms of stress , and sleep quality , but these improvements were not significantly correlated with the degree of program attendance or minutes of home practice . No significant improvements were seen in mood disturbance . Improvements in quality of life were associated with decreases in afternoon cortisol levels , but not with morning or evening levels . Changes in stress symptoms or mood were not related to changes in hormone levels . Approximately 40 % of the sample demonstrated abnormal cortisol secretion patterns both pre- and post-intervention , but within that group patterns shifted from " inverted-V-shaped " patterns towards more " V-shaped " patterns of secretion . No overall changes in DHEAS or melatonin were found , but nonsignificant shifts in DHEAS patterns were consistent with healthier profiles for both men and women . CONCLUSIONS MBSR program enrollment was associated with enhanced quality of life and decreased stress symptoms in breast and prostate cancer patients , and result ed in possibly beneficial changes in hypothalamic-pituitary-adrenal ( HPA ) axis functioning . These pilot data represent a preliminary investigation of the relationships between MBSR program participation and hormone levels , highlighting the need for better-controlled studies in this area A community-based nursing study was conducted in Sydney , Australia , to compare the effects of progressive muscle relaxation and guided imagery on anxiety , depression , and quality of life in people with advanced cancer . In this study , 56 people with advanced cancer who were experiencing anxiety and depression were r and omly assigned to 1 of 4 treatment conditions : ( 1 ) progressive muscle relaxation training , ( 2 ) guided imagery training , ( 3 ) both of these treatments , and ( 4 ) control group . Subjects were tested before and after learning muscle relaxation and guided imagery techniques for anxiety , depression , and quality of life using the Hospital Anxiety and Depression scale and the Functional Living Index — Cancer scale . There was no significant improvement for anxiety ; however , significant positive changes occurred for depression and quality of life Background Despite an increase in the occurrence of burnout , there is no agreement on what kind of rehabilitation these patients should be offered . Purpose Primary aim of this study was to evaluate effects on psychological variables and sick leave rates by two different group rehabilitation programs for patients on long-term sick leave because of burnout . Rehabilitation program A ( Cognitively oriented Behavioral Rehabilitation ( CBR ) and Qigong ) was compared with rehabilitation program B ( Qigong only ) . Method In a r and omized clinical trial , 96 women and 40 men with a mean age of 41.6 ± 7.4 years were allocated to one of the two rehabilitation programs . Results A per- protocol analysis showed no significant difference in treatment efficacy between the groups . Both groups improved significantly over time with reduced levels of burnout , self-rated stress behavior , fatigue , depression , anxiety , obsessive – compulsive symptoms , and sick leave rates . In an intention-to-treat analysis , patients in program A had fewer obsessive – compulsive symptoms and larger effect sizes in self-rated stress behavior and obsessive – compulsive symptoms compared to patients in program B. Conclusion This study showed no differences in effect between CBR and Qigong compared with Qigong only in a per- protocol analysis . Both rehabilitation programs showed positive effect for patients with burnout |
631 | 27,838,461 | Reasons for both adherence and non-adherence were largely similar ; medication efficacy , compatibility with personal medication or religious beliefs , side-effects and the influence of relationships with other people . | People diagnosed with psychosis , such as those with schizophrenia-related disorders , are routinely prescribed neuroleptic medication as a primary treatment .
Despite reported benefits of neuroleptic treatment for symptom remission and relapse prevention , discontinuation rates are high .
Research examining factors associated with neuroleptic non-adherence report inconsistent findings .
Reasons for adherence to neuroleptic medication are under- research ed .
The current review aim ed to synthesis e evidence exploring service-user self-reported reasons for adherence and non-adherence to neuroleptic medication . | BACKGROUND Patient nonadherence is common for the st and ard mental health treatments in primary care : antidepressants and referrals to specialty mental health treatment . This is one of few studies to prospect ively identify predictors of nonadherence . METHODS We observed 95 veterans attending an internal medicine clinic prescribed antidepressant medication or referred to mental health treatment . We collected information on sociodemographic factors , health beliefs , preferences about treatment , past experiences , and treatment knowledge . RESULTS At 1 month , medication adherence was greater when patients experienced previous pharmacy trouble and traveled for less than 30 minutes to reach the clinic . Appointment attendance improved when patients were ready for treatment , perceived benefits , and saw their physician as collaborative . At 6 months , medication adherence was greater when patients reported a preference for medicine treatment , traveled for less than 30 minutes , and perceived greater benefits . Fewer negative effects from previous mental health treatment improved adherence to appointments . In multivariate analyses examining adherence to all treatments , greater readiness for treatment predicted 1-month adherence , whereas being unmarried and seeing the physician as more collaborative improved 6-month adherence . CONCLUSIONS Adherence to antidepressant medications and to mental health referrals should be examined separately . A brief initial assessment for nonadherence risk factors may identify persons for targeted adherence promoting interventions BACKGROUND Many patients recovering from a first psychotic episode will discontinue medication against medical advice , even before a 1-year treatment course is completed . Factors associated with treatment adherence in patients with chronic schizophrenia include beliefs about severity of illness and need for treatment , treatment with typical versus atypical antipsychotic and medication side effects . METHOD In this 2-year prospect i ve study of 254 patients recovering from a first episode of schizophrenia , schizophreniform , or schizoaffective disorder we examined the relationship between antipsychotic medication non-adherence and patient beliefs about : need for treatment , antipsychotic medication benefits , and negative aspects of antipsychotic medication treatment . We also examined the relationship between medication non-adherence and treatment with either haloperidol or olanzapine , and objective measures of symptom response and side effects . RESULTS The likelihood of becoming medication non-adherent for 1 week or longer was greater in subjects whose belief in need for treatment was less ( HR=1.75 , 95 % CI 1.16 , 2.65 , p=0.0077 ) or who believed medications were of low benefit ( HR=2.88 , 95 CI 1.79 - 4.65 , p<0.0001 ) . Subjects r and omized to haloperidol were more likely to become medication non-adherent for > or=1 week than subjects r and omized to olanzapine ( HR-1.51 , 95 % CI 1.01 , 2.27 , p=0.045 ) . CONCLUSION Beliefs about need for treatment and the benefits of antipsychotic medication may be intervention targets to improve likelihood of long-term medication adherence in patients recovering from a first episode of schizophrenia , schizoaffective , or schizophreniform disorder Objective : To evaluate the efficacy of two community‐based programs that combined antipsychotic medication , family interventions and social skills training Dropout from prophylactic neuroleptic treatment is one major reason for relapse in schizophrenia patients . There is a lack of prospect i ve studies on factors that predict medication adherence . We investigated factors suspected to predict dropout from continuous neuroleptic treatment in a 2-year prospect i ve study involving 122 out patients with a DSM-III-R diagnosis of schizophrenia . Forty-two ( 34.4 % ) were classified as patient-related dropouts . No significant difference between compliant patients and dropouts was found with regard to sociodemographic variables , except that compliant patients were significantly older . Also , no differences in psychopathology were seen at the beginning of treatment , but compliant patients had a longer duration of illness . Compliant patients had higher doses of neuroleptics in the initial stabilization phase and correspondingly showed more extrapyramidal signs . Physicians rated compliant patients from the beginning as more cooperative . These patients also showed significantly higher scores in positive treatment expectations . In a stepwise regression analysis , positive illness concepts , the global assessment of functioning ( GAF ) , and the physicians ' view of patients ' cooperation predicted 19 percent of the variance . We concluded that the prediction of dropouts is insufficient and remains largely an unsolved problem . Future research should focus more on context factors in the search for clinical ly meaningful explanations of patient dropout from treatment RATIONALE Most first-episode schizophrenia patients will stop their medication after their acute symptoms improve . Underst and ing the salient motivations and attitudes that drive adherence -- as well as nonadherence -- is an important part of developing strategies to prevent or delay nonadherence during the early phases of the illness . METHODS Self-reported reasons for adherence and nonadherence among first-episode and multi-episode patients with schizophrenia were obtained from cross-sectional adherence interviews from two prospect i ve adherence studies : one composed of a first-episode sample ( n=33 ) and the other with recently relapsing multi-episode patients ( n=16 ) . Both groups received the Rating of Medication Influences ( ROMI ) Scale at approximately 16 to 20 weeks after an acute psychotic episode . The specific ROMI items were ranked in order of percentage ( % ) strong , and were compared both within each patient group for rank order of importance , and also compared between groups to determine the differences in specific adherence and nonadherence influences . RESULTS The doctor-patient relationship was more likely to be endorsed as a strong adherence influence in the first-episode sample ( 74 % ) than in the multi-episode sample ( 13 % , X²=18.07 , p<.01 ) . Change in physical appearance attributed to medication was a more commonly endorsed nonadherence influence for the multi-episode sample ( 25 % ) relative to the first-episode sample ( 0 % , X²=9.2 , p<.01 ) . CONCLUSIONS The doctor-patient relationship st and s out as being the major reason for ongoing adherence for first-episode schizophrenia patients . Our post hoc interpretation is that lack of prior experience with medication and treatment elevates the importance of the relationship with the treating clinician for first-episode patients Abstract Objective : To identify reasons for discontinuation and continuation of antipsychotic medications in the treatment of schizophrenia from the patients ’ and their clinicians ’ perspectives . Research design and methods : Two measures were previously developed to assess the Reasons for Antipsychotic Discontinuation/Continuation ( RAD ) , one from the patient 's perspective and another from the clinician 's perspective . These measures were administered to acutely ill schizophrenia patients enrolled in a 12-week study of antipsychotic medications ( N = 596 ) and to their clinicians . The RAD was assessed at baseline and at endpoint . Reasons were rated on a 5-point scale from ‘ primary reason ’ to ‘ not a reason . ’ The single most important reason was also identified . The ‘ single most important reason ’ and the ‘ primary reasons ’ for discontinuing the drug used prior to enrollment , and for discontinuing or continuing the study drug were identified . Levels of concordance between patients ’ and clinicians ’ reasons were assessed . Clinical trial registration : The data source for this study is a clinical trial registered at www . clinical trials.gov ( NCT00337662 ) . Main outcome measures : Reasons for Antipsychotic Discontinuation/Continuation ( RAD ) . Results : Patients and clinicians identified several reasons for medication discontinuation and continuation ( 2.3 to 6.3 reasons , on average ) . The top ‘ single most important ’ reason for discontinuing the drug used prior to enrollment and for discontinuing the study drug was ‘ positive symptoms not sufficiently improved or made worse , ’ followed by ‘ medication-related adverse events . ’ The most frequent ‘ single most important ’ reason for medication continuation was ‘ improved positive symptoms , ’ followed by ‘ patient 's perception of improvement , ’ and ‘ functional improvement . ’ A high level of concordance was observed between patients ’ and clinicians ’ ratings . Conclusions : Medication efficacy appears to be the core driver of medication discontinuation and continuation , especially with regard to positive symptoms . There was a high level of concordance between patients ’ and clinicians ’ perspectives . Limitations include the study requirement that patients be at least moderately ill and experiencing acute psychotic exacerbation , a potential selection bias in the readiness to respond to measures , and small sample sizes for some analyses . Further research is needed to replicate findings in patients who are not acutely ill ABSTRACT Objectives : During a schizophrenia treatment episode , persistence with the initial antipsychotic may indicate optimal pharmacotherapy and be a precursor to longer-term effectiveness and other positive outcomes . The objective of this study was to examine the ability of selected variables to predict antipsychotic persistence among patients receiving olanzapine or risperidone as initial treatment . Research design and methods : Data for this analysis , which was not defined in the original study protocol , came from a naturalistic , r and omized , open-label trial comparing costs and effectiveness of first-line antipsychotic treatment options in schizophrenia . Predictor variables were as follows : ( 1 ) patients ’ initial antipsychotic ( olanzapine [ n = 222 ] or risperidone [ n = 218 ] ) ; ( 2 ) current ( within 30 days ) comorbid diagnosis of substance abuse ; and ( 3 ) nine self-report items from the Rating of Medication Influence ( ROMI ) scale , including an item assessing patients ’ perceptions of the role of their therapeutic alliance in their adherence . Main outcome measures : For the primary analysis , a stepwise logistic regression was used in predicting antipsychotic persistence of at least 180 days . Variables found to be significantly predictive were included in a second analysis that assessed persistence at additional thresholds ( > 90 days , > 270 days , and completion of the 1‑year study ) . Results : Four variables predicted longer antipsychotic persistence ; olanzapine as initial antipsychotic ( p = 0.004 ) , absence of comorbid substance abuse ( p = 0.025 ) , and two of the ROMI items representing patients ’ subjective response to treatment – positive relationship with clinical staff ( p = 0.048 ) and fulfillment of life goals ( p = 0.050 ) . Conclusions : Within a r and omized trial design , this study corroborated the influence of several factors on antipsychotic persistence in schizophrenia . Results support the importance of the initial antipsychotic treatment option , presence of a comorbid substance abuse diagnosis , and the role of patients ’ subjective responses . Additional research is needed to further explore these and other factors as predictors of antipsychotic persistence , and of subsequent treatment outcomes OBJECTIVE Time to all-cause treatment discontinuation is considered a composite proxy measure of treatment efficacy , safety , and tolerability . Longer time to discontinuation of antipsychotic medication for any cause has been shown to be associated with greater symptom improvements in the treatment of schizophrenia . This study examines whether longer time to all-cause medication discontinuation is also linked to better functional outcomes . METHOD Using pooled data from 4 r and omized , double-blind antipsychotic trials of 24- to 28-weeks ' duration , this study examined the association between time to all-cause treatment discontinuation and functional outcomes , as assessed by a disease-specific , clinician-rated measure ( Quality of Life Scale [ QLS ] ) and a generic , patient-reported measure ( Medical Outcomes Study Short Form 36 [ SF-36 ] ) . Patients in these trials had a DSM-IV diagnosis of schizophrenia , schizophreniform disorder , or schizoaffective disorder . This post hoc analysis used Pearson partial correlations to assess relationships between time to treatment discontinuation and changes in functional scores , adjusting for baseline scores . Repeated measures analyses were also conducted to compare post-baseline functional outcome change over time between completers and noncompleters . RESULTS Longer time to all-cause treatment discontinuation was found to be significantly associated with greater improvements in all assessed functional domains ( p < .05 ) . Patients who completed their respective trials ( 46.8 % , 761/1627 ) experienced significantly greater improvement in functional outcome measures ( in 4 QLS domains and SF-36 mental health component summary score ; all , p < .001 ) compared to patients who discontinued for any cause . In addition , greater symptom improvement was significantly associated with greater functional improvements in assessed domains . CONCLUSIONS Findings from this post hoc analysis illustrate the importance of longer treatment duration with antipsychotics for improving functional outcomes in the treatment of patients with schizophrenia |
632 | 32,204,620 | The certainty of evidence was low to very low , and the results are insufficient to support the routine use laser therapy for Achilles tendinopathy | OBJECTIVE The purpose of this study was to determine the benefits and harms of low-level laser therapy for Achilles tendinopathy . | 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 The common regime of eccentric exercise in use for Achilles tendinopathy is somewhat arduous and compliance issues can arise . This is the first study to investigate the effectiveness of a regime of fewer exercise sessions combined with photobiomodulation for the treatment of Achilles tendinopathy . Methods A double blind r and omized controlled trial and intention-to-treat analysis were performed . Eighty participants , 18–65 years with Achilles tendinopathy and symptoms for longer than 3 months , were included in the trial . Participants r and omized into one of four groups ; 1 ( Placebo + Ex Regime 1 ) or 2 ( Laser + Ex Regime 1 ) or 3 ( Placebo + Ex Regime 2 ) or 4 ( Laser + Ex Regime 2 ) . The primary outcome measure was the Victorian Institute of Sports Assessment -Achilles ( VISA-A ) question naire . Outcomes were collected at baseline , week 4 and week 12 . Results Sixteen participants were lost to follow-up at 12 weeks , 4 of which due to adverse reactions . As per intention to treat , missing data were imputed , 80 participants were included in the final analysis . For VISA-A at 12 weeks , group 4 achieved significant gains over the other 3 groups : group 1 ( 18.5 [ 9.1 , 27.9 ] ) , group 2 ( 10.4 [ 1.5 , 19.2 ] ) , group 3 ( 11.3 [ 3.0 , 19.6 ] ) . There was a moderate effect size in favour of exercise twice per week ( 7.2 [ −1.8 , 16.2 ] , ES .7 ) . Conclusions Twice-daily exercise sessions are not necessary as equivalent results can be obtained with two exercise sessions per week . The addition of photobiomodulation as adjunct to exercise can bring added benefit Background Synthesis of multiple r and omized controlled trials ( RCTs ) in a systematic review can summarize the effects of individual outcomes and provide numerical answers about the effectiveness of interventions . Filtering of search es is time consuming , and no single method fulfills the principal requirements of speed with accuracy . Automation of systematic review s is driven by a necessity to expedite the availability of current best evidence for policy and clinical decision-making . We developed Rayyan ( http://rayyan.qcri.org ) , a free web and mobile app , that helps expedite the initial screening of abstract s and titles using a process of semi-automation while incorporating a high level of usability . For the beta testing phase , we used two published Cochrane review s in which included studies had been selected manually . Their search es , with 1030 records and 273 records , were uploaded to Rayyan . Different features of Rayyan were tested using these two review s. We also conducted a survey of Rayyan ’s users and collected feedback through a built-in feature . Results Pilot testing of Rayyan focused on usability , accuracy against manual methods , and the added value of the prediction feature . The “ taster ” review ( 273 records ) allowed a quick overview of Rayyan for early comments on usability . The second review ( 1030 records ) required several iterations to identify the previously identified 11 trials . The “ suggestions ” and “ hints , ” based on the “ prediction model , ” appeared as testing progressed beyond five included studies . Post rollout user experiences and a reflexive response by the developers enabled real-time modifications and improvements . The survey respondents reported 40 % average time savings when using Rayyan compared to others tools , with 34 % of the respondents reporting more than 50 % time savings . In addition , around 75 % of the respondents mentioned that screening and labeling studies as well as collaborating on review s to be the two most important features of Rayyan . As of November 2016 , Rayyan users exceed 2000 from over 60 countries conducting hundreds of review s totaling more than 1.6 M citations . Feedback from users , obtained mostly through the app web site and a recent survey , has highlighted the ease in exploration of search es , the time saved , and simplicity in sharing and comparing include-exclude decisions . The strongest features of the app , identified and reported in user feedback , were its ability to help in screening and collaboration as well as the time savings it affords to users . Conclusions Rayyan is responsive and intuitive in use with significant potential to lighten the load of review ers Background : Low level laser therapy ( LLLT ) has gained increasing popularity in the management of tendinopathy and arthritis . Results from in vitro and in vivo studies have suggested that inflammatory modulation is one of several possible biological mechanisms of LLLT action . Objective : To investigate in situ if LLLT has an anti-inflammatory effect on activated tendinitis of the human Achilles tendon . Subjects : Seven patients with bilateral Achilles tendinitis ( 14 tendons ) who had aggravated symptoms produced by pain inducing activity immediately before the study . Method : Infrared ( 904 nm wavelength ) LLLT ( 5.4 J per point , power density 20 mW/cm2 ) and placebo LLLT ( 0 J ) were administered to both Achilles tendons in r and om blinded order . Results : Ultrasonography Doppler measurements at baseline showed minor inflammation through increased intratendinous blood flow in all 14 tendons and measurable resistive index in eight tendons of 0.91 ( 95 % confidence interval 0.87 to 0.95 ) . Prostagl and in E2 concentrations were significantly reduced 75 , 90 , and 105 minutes after active LLLT compared with concentrations before treatment ( p = 0.026 ) and after placebo LLLT ( p = 0.009 ) . Pressure pain threshold had increased significantly ( p = 0.012 ) after active LLLT compared with placebo LLLT : the mean difference in the change between the groups was 0.40 kg/cm2 ( 95 % confidence interval 0.10 to 0.70 ) . Conclusion : LLLT at a dose of 5.4 J per point can reduce inflammation and pain in activated Achilles tendinitis . LLLT may therefore have potential in the management of diseases with an inflammatory component A linear analogue for rating pain with 10 , 15 and 20 cm lines is significantly less variable than a 5 cm line ( mean error of 15 cm line is 0 - 19 % , 95 % confidence limits for the group + /- 2 % and an inood correlation between repeated ratins of a recalled pain distant in time . The variance of the rating is significantly less than the repeated rating of a r and om mark . The linear analogue rating of a constant pain stimulus is reproducible and changes in rating are likely to be real changes of opinion . Pethidine 150 mg intramuscularly had no significant effect , tested 30 minutes after the administration , on the accuracy or reproducibility of the analogue rating . A linear analogue seems a suitable method of recording the patient 's opion of a severe pain such as that of labour Background Eccentric exercises ( EEs ) are recommended for the treatment of Achilles tendinopathy , but the clinical effect from EE has a slow onset . Hypothesis The addition of low-level laser therapy ( LLLT ) to EE may cause more rapid clinical improvement . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods A total of 52 recreational athletes with chronic Achilles tendinopathy symptoms were r and omized to groups receiving either EE + LLLT or EE + placebo LLLT over 8 weeks in a blinded manner . Low-level laser therapy ( Λ = 820 nm ) was administered in 12 sessions by irradiating 6 points along the Achilles tendon with a power density of 60 mW/cm2 and a total dose of 5.4 J per session . Results The results of the intention-to-treat analysis for the primary outcome , pain intensity during physical activity on the 100-mm visual analog scale , were significantly lower in the LLLT group than in the placebo LLLT group , with 53.6 mm versus 71.5 mm ( P = .0003 ) at 4 weeks , 37.3 mm versus 62.8 mm ( P = .0002 ) at 8 weeks , and 33.0 mm versus 53.0 mm ( P = .007 ) at 12 weeks after r and omization . Secondary outcomes of morning stiffness , active dorsiflexion , palpation tenderness , and crepitation showed the same pattern in favor of the LLLT group . Conclusion Low-level laser therapy , with the parameters used in this study , accelerates clinical recovery from chronic Achilles tendinopathy when added to an EE regimen . For the LLLT group , the results at 4 weeks were similar to the placebo LLLT group results after 12 weeks OBJECTIVE To test the feasibility of a r and omized controlled trial to assess the clinical effectiveness of low-level laser therapy ( LLLT ) when used in addition to eccentric exercise in the management of Achilles tendinopathy . BACKGROUND DATA LLLT has emerged as a possible treatment modality for tendon injuries . Over the past 20 years only three human studies have investigated LLLT for Achilles tendinopathy . MATERIAL S AND METHODS Twenty patients were r and omized into an active laser or placebo group ; all patients , therapists , and investigators were blinded to allocation . All patients were given a 12-week eccentric exercise program and irradiated three times per week for 4 wk with either an active or placebo laser at st and ardized points over the affected tendons . Irradiation parameters in the active treatment group were : 810 nm , 100 mW , applied to six points on the tendon for 30 s , for a total dose of 3 J per point and 18 J per session . Outcome measures were the VISA-A question naire , pain , and isokinetic strength . Patients were measured before treatment and at 4 and 12 wk . Analysis of covariance was used to analyze data , using the effects of baseline measurements as a covariate . RESULTS Within groups , there were significant improvements ( p < 0.05 ) at 4 and 12 wk for all outcome measures , except eccentric strength for the placebo group at 4 wk ( p = 0.11 ) . Based on the results of the current study , recruitment of 20 subjects per group would be required to perform an adequately powered study based on minimally important clinical differences in VISA-A scale . CONCLUSION This study has demonstrated the feasibility of undertaking a r and omized controlled trial of LLLT for Achilles tendinopathy . Conclusions regarding effectiveness can not be made due to the low statistical power of this pilot study & 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 OBJECTIVE To investigate the effectiveness of low-level laser therapy ( LLLT ) as an adjunct to a program of eccentric exercises for the treatment of Achilles ' tendinopathy . DESIGN R and omized controlled trial with evaluations at baseline and 4 , 12 , and 52 weeks . SETTING Primary care clinic . PARTICIPANTS Participants with midportion Achilles ' tendinopathy were r and omly assigned to 2 groups ( LLLT n=20 : mean age ± SD , 45.6±9.1y ; placebo n=20 : mean age ± SD , 46.5±6.4y ) . The 12-week evaluation was completed by 36 participants ( 90 % ) , and 33 participants ( 82.5 % ) completed the 52-week evaluation . INTERVENTION Both groups of participants performed eccentric exercises over a 3-month period . In addition , they received either an active or placebo application of LLLT 3 times per week for the first 4 weeks ; the dose was 3J per point . MAIN OUTCOME MEASURES The primary outcome was the Victorian Institute of Sport Assessment -Achilles ' question naire ( VISA-A ) score at 12 weeks ; secondary outcome was a visual analog scale for pain . Outcomes were measured at baseline and 4 , 12 , and 52 weeks . RESULTS Baseline characteristics exhibited no differences between groups . At the primary outcome point , there was no statistically significant difference in VISA-A scores between groups ( P>.05 ) . The difference in VISA-A scores at the 4-week point significantly favored the placebo group ( F(1)=6.411 , sum of squares 783.839 ; P=.016 ) ; all other outcome scores showed no significant difference between the groups at any time point . Observers were blinded to groupings . CONCLUSIONS The clinical effectiveness of adding LLLT to eccentric exercises for the treatment of Achilles ' tendinopathy has not been demonstrated using the parameters in this study The effects of low level laser treatment in soldiers with achilles tendinitis were studied in a prospect i ve , r and omized and double blind trial . Eighty-nine soldiers were enrolled in the study . Forty-six were r and omized to treatment with active laser and 43 to treatment with placebo laser . No statistically significant differences in the number of consultations , morning stiffness , tenderness , crepitation , swelling , redness , VAS-score of pain and degree of unfitness for duty were found between the two treatment groups |
633 | 29,526,664 | Self‐report measures were the most frequently used , followed by electronic lid devices and pharmacy records .
St and ardized self‐report measures such as Morisky , Green , and Levine Self‐Reported Medication Taking Scale ( MGLS ) and Antidepressant Adherence Scale ( AAS ) demonstrated acceptable reliability and validity , while medication cl aims data showed good reliability as a long‐term measure .
Conclusions : Although the psychometric properties of various measures have been evaluated across the three phases of adherence , a st and out measure with strong reliability and validity was not apparent .
No single measure demonstrated reliability and validity throughout the adherence process . | Objective : To identify and evaluate the range of adherence measures used to assess different phases of medication adherence ( initiation , implementation , and discontinuation ) to antidepressants , including the psychometric properties of the measures . | BACKGROUND In chronic diseases adherence is a problem . Little is known about adherence to antidepressants after the acute phase in recurrent depression . This study evaluates adherence to antidepressants in the continuation and maintenance phase in remitted recurrently depressed patients . METHODS We prospect ively assessed adherence to continuation and maintenance antidepressant use , the longest phase in antidepressant treatment , over 2 years and the association of adherence with future recurrence in 131 recurrently depressed patients remitted on antidepressants . LIMITATIONS Self reported non-adherence . RESULTS Non-adherence ranged from 39.7 % to 52.7 % ; 20.9 % were always non-adherent , 48.4 % were intermittently non-adherent and 30.8 % were always adherent . Adherence rates did not significantly differ between intermittent and continuous antidepressant users ( 37.2 % vs. 25 % ) . Non-adherence predicted time to recurrence . CONCLUSION Non-adherence to continuation and maintenance antidepressant treatment in recurrent depression is frequent , like in other chronic diseases , and a potential risk of recurrence . Doctors continuously have to be aware of this problem and should keep on discussing it with their patients . Finally , as many patients do n't seem to be able or willing to take AD as prescribed , alternatives to prevent relapse deserve more attention AIMS To assess the advantages and disadvantages of four methods for study ing compliance with antidepressants : self-report scores , tablet counts , a microprocessor ( MEMS ) container system and the assay of nordothiepin and dothiepin concentrations in plasma . METHODS The techniques were used in 88 patients commencing tricyclic antidepressants in the setting of UK general practice . RESULTS The MEMS system proved to be the most informative technique allowing identification of the precise time of container opening , the demonstration of ' drug holidays ' and early cessation of therapy . Self-report scores ( Morisky ) proved a useful screening technique with a sensitivity of 72.2 % and specificity of 74.1 % for > or = 80 % compliance . Although tablet counts were possible in 84 patients ( 95 . 5 % ) they were unreliable in 19 ( 21.6 % ) . Blood concentration assays proved the least acceptable method to patients and were possible in only 53 ( 60.2 % ) . A ratio of nordothiepin : dothiepin > or = 1.1 cl aim ed , by others , to identify noncompliance was only reliable when concentrations were low . CONCLUSIONS Both the MEMS system and self-report scores proved useful methods for identifying noncompliant patients in the setting of UK general practice . Although compliance was higher than reported in previous studies with 70 patients ( 79.5 % ) completing 6 weeks treatment , general practitioners tended to prescribe subtherapeutic doses BACKGROUND This research study evaluates the effectiveness of a multifaceted intervention program to improve the management of depression in primary care . METHODS One hundred fifty-three primary care patients with current depression were entered into a r and omized controlled trial . Intervention patients received a structured depression treatment program in the primary care setting that included both behavioral treatment to increase use of adaptive coping strategies and counseling to improve medication adherence . Control patients received " usual " care by their primary care physicians . Outcome measures included adherence to antidepressant medication , satisfaction with care of depression and with antidepressant treatment , and reduction of depressive symptoms over time . RESULTS At 4-month follow-up , significantly more intervention patients with major and minor depression than usual care patients adhered to antidepressant medication and rated the quality of care they received for depression as good to excellent . Intervention patients with major depression demonstrated a significantly greater decrease in depression severity over time compared with usual care patients on all 4 outcome analyses . Intervention patients with minor depression were found to have a significant decrease over time in depression severity on only 1 of 4 study outcome analyses compared with usual care patients . CONCLUSION A multifaceted primary care intervention improved adherence to antidepressant regimens and satisfaction with care in patients with major and minor depression . The intervention consistently result ed in more favorable depression outcomes among patients with major depression , while outcome effects were ambiguous among patients with minor depression Measurement of adherence is complex and many methods , both direct and indirect are used ; there is no universal gold st and ard . In this article , we share our experiences in a r and omised controlled study , the Hypertension Adherence Program in Pharmacy trial , evaluating a community pharmacy-based intervention for improving adherence to antihypertensive medication . Several objective and subjective measures of adherence ( Morisky score , TABS score , MedsIndex , Medicines Possession Ratio ) were used , but produced varying results , limiting confidence in the conclusions that could be drawn . Despite using a specifically design ed data mining software program to identify potentially nonadherent patients from dispensing records , many participants were found to be adherent by the self reported Morisky scale . A lesson to be learned when targeting people for interventions to improve adherence is that information from dispensing records should be supplemented by other methods in order to identify patients most in need of assistance 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 BACKGROUND A new formulation of enteric-coated fluoxetine given once weekly could be a useful option for the long-term treatment of depression , but compliance to once-weekly fluoxetine treatment has not been assessed . METHOD Patients were adults from the United Kingdom who had responded to fluoxetine treatment for a current episode of depression ( DSM-IV criteria ) . In the baseline assessment phase , all patients ( N = 117 ) were continued on 20 mg of open-label fluoxetine once daily for 4 weeks . In the follow-up phase , patients ( N = 109 ) were r and omly assigned to once-weekly or once-daily fluoxetine for 3 months . Patient compliance was monitored by electronic devices during both phases of the study . RESULTS Compliance to once-weekly fluoxetine treatment was higher than compliance to once-daily fluoxetine ( 85.9 % vs. 79.4 % , respectively ) . CONCLUSION Once-weekly fluoxetine treatment allows for new flexibility for both the clinician and the patient , and this study alleviates the concern that patients will forget weekly doses The goals of this study were to examine how physician communication style impacts client beliefs and medication taking behavior during treatment for depression . The study uses a communication framework and prospect i ve design to examine physician communication and client beliefs as treatment is initiated and again 2 months later . Two telephone interviews were conducted with 100 clients enrolled from 23 community pharmacies . Clients report that physician communication styles vary . In follow-up , 25 % of the clients were not satisfied with their medication and 82 % reported missing doses or stopping treatment earlier than recommended . Path analysis showed that physician initial communication style positively influences client knowledge and initial beliefs about the medication . Clients with more positive beliefs about the treatment are more likely to see the physician in follow-up and are more satisfied with treatment after attempting medication use . Physician follow-up communication style and client satisfaction are both predictive of better medication adherence Abstract Objectives : To evaluate two different methods of improving adherence to antidepressant drugs . Design : Factorial r and omised controlled single blind trial of treatment leaflet , drug counselling , both , or treatment as usual . Setting : Primary care in Wessex Participants : 250 patients starting treatment with tricyclic antidepressants . Main outcome measures : Adherence to drug treatment ( by confidential self report and electronic monitor ) ; depressive symptoms and health status . Results : 66 ( 63 % ) patients continued with drugs to 12 weeks in the counselled group compared with 42 ( 39 % ) of those who did not receiving counselling ( odds ratio 2.7 , 95 % confidence interval 1.6 to 4.8 ; number needed to treat=4 ) Treatment leaflets had no significant effect on adherence . No differences in depressive symptoms were found between treatment groups overall , although a significant improvement was found in patients with major depressive disorder receiving drug doses of at least 75 mg ( depression score 4 ( SD 3.7 ) counselling v 5.9 ( SD 5.0 ) no counselling , P=0.038 ) . Conclusions : Counselling about drug treatment significantly improved adherence , but clinical benefit was seen only in patients with major depressive disorder receiving doses ≥75 mg . Further research is required to evaluate the effect of this approach in combination with appropriate targeting of treatment and advice about dosage . Key messages Non-adherence is a serious problem in the treatment of depression by general practitioners In this study a brief psychosocial intervention delivered by a nurse greatly improved adherence Clinical benefit was apparent only in patients with major depressive episodes on higher doses of drugs Counselling should be targeted at patients with symptoms of at least moderate severity and combined with therapeutic drug Medication non-adherence is a major obstacle in the treatment of affective disorders . The primary objective of this study was to evaluate two different interventions to improve adherence to antidepressant drugs . Secondary objectives included response to treatment , relation between adherence and response , patient satisfaction and tolerability . A r and omized controlled design was used to assess the effect of a patient educational compliance enhancing programme ( CP ) and therapeutic drug monitoring in 1031 major depressed patients treated with sertraline for 24 weeks and managed by their general practitioner . Adherence was measured by question ing , measurable serum levels of sertraline and desmethylsertraline , appointments kept and a composite index including all three methods . Treatment adherence was found in 37–70 % of patients , depending on the method used . Neither of the interventions result ed in a significant increase in adherence rate . However , significantly more patients in the CP group had responded at week 24 compared to patients in the control group . Overall , significantly more adherent patients responded to treatment compared to non-adherent patients , regardless of method used to determine adherence . This large study demonstrates that treatment response increases when using an educational compliance programme and that a strong relationship between treatment adherence and response exists The effects on adherence and depressive symptoms of a community pharmacy-based coaching program , including a take-home videotape , were evaluated in a r and omized controlled trial in the Netherl and s. A total of 147 depressed primary care patients who had a new antidepressant prescription were included in the study . Adherence was measured with an electronic pill container and was also derived from pharmacy medication records ; the latter method was associated with an overestimation of adherence of only 5 percent . Intention-to-treat analyses showed no intervention effect on adherence ( 73 percent compared with 76 percent ) , whereas analyses of patients who received the intervention ( per protocol ) showed improved adherence ( 73 percent compared with 90 percent ) . Neither analysis showed effects on depressive symptoms Background : Medication adherence is suboptimal , and clinicians and research ers struggle with identifying nonadherent patients . Various measures of medication adherence exist , but there is controversy regarding which measures provide acceptable data and how nonadherence should be defined . Objective : To assess agreement among patient self-report , pharmacy refill , and electronic adherence measures and compare the sensitivity and specificity of different cut-points for defining nonadherence . Methods : Data were analyzed from 2 similarly design ed r and omized controlled trials that assessed a pharmacist 's intervention to improve medication adherence among patients with hypertension or heart failure . For each participant , adherence was measured by patient self-report , prescription refill records , and electronic lids on medication containers . Agreement among measures was assessed using Spearman 's correlation coefficient rho . Correlation coefficients were compared by patient characteristics using Fisher 's Z transformation , The sensitivity and specificity of different cut-points for defining nonadherence were calculated . Results : Median adherence was 84 % for self-report , 86 % for electronic , and 91 % for prescription refill adherence measurement . Refill and electronic adherence demonstrated the best agreement among measures ( rho = 0.48 ) . Age , depression , and other comorbid conditions influenced agreement among measures . Measures were generally in agreement , regardless of how nonadherence was defined . A cut-point of 80 % illustrated a fair balance between sensitivity and specificity for all measures . Conclusions : All measures provided similar estimates of overall adherence , although refill and electronic measures were in highest agreement . In selection of a measure , practitioners should consider population and disease characteristics , since measurement agreement could be influenced by these and other factors . The commonly used , clinical ly based cut-point of 80 % had a reasonable balance between sensitivity and specificity in studies of adherence in patients with heart failure or hypertension 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 To identify predictors of nonadherence to continuation and maintenance antidepressant medication among patients with remitted recurrent depression . METHOD We used data of 91 remitted , recurrently depressed patients ( at least 2 major depressive episodes as assessed by the Structured Clinical Interview for DSM-IV Axis I Disorders ) treated with continuation and maintenance antidepressant medication in a 2-year prospect i ve study . Patients were recruited at psychiatric centers and through media announcement from February 2000 through September 2000 . Adherence was assessed with the Medication Adherence Question naire . Nonadherence on this scale indicates that patients missed 20 % or more of their antidepressant medication . We determined nonadherence point prevalences at the 7 assessment points . Based upon these 7 assessment s , we found nonadherence percentages ranging from 39.7 % to 52.7 % with a mean of 46.5 % over 2 years . We examined a set of potential risk factors ( patient-related , disease-related , and treatment-related ) measured at baseline . RESULTS In univariate analysis using a stringent significance level ( p < or= .005 ) , we found no independently related predictors of nonadherence over a 2-year period . In a multivariate analysis with backward elimination , the baseline predictors for nonadherence over a 2-year period were a higher level of personality pathology and a higher level of education . CONCLUSION There are no clear predictors of nonadherence to antidepressants in the continuation and maintenance phases in remitted , recurrently depressed patients . Further research should focus on the process of becoming nonadherent to antidepressants in the longest phase of antidepressant use to maximize the potential protective effect of these medications |
634 | 11,525,697 | Low-molecular-weight heparin initiated 12 hours before surgery or 12 to 24 hours postoperatively was not more effective than oral anticoagulants .
Low-molecular-weight heparin initiated postoperatively in close proximity to surgery at half the usual dose was not associated with a clinical ly or statistically significant increase in major bleeding rates ( P = .16 ) .
The timing of initiating low-molecular-weight heparin significantly influences antithrombotic effectiveness .
The practice of delayed initiation of low-molecular-weight heparin prophylaxis results in suboptimal antithrombotic effectiveness without a substantive safety advantage | BACKGROUND Perioperative and postoperative venous thrombosis are common in patients undergoing elective hip surgery .
Prophylactic regimens include subcutaneous low-molecular-weight heparin 12 hours or more before or after surgery and oral anticoagulants .
Recent clinical trials suggest that low-molecular-weight heparin initiated in closer proximity to surgery is more effective than the present clinical practice .
We performed a systematic review of the literature to assess the efficacy and safety of low-molecular-weight heparin administered at different times in relation to surgery vs oral anticoagulant prophylaxis . | The efficacy of low-dose heparin in preventing fatal postoperative pulmonary embolism has been investigated in a multicentre prospect i ve r and omised trial . 4121 patients over the age of forty years undergoing a variety of elective major surgical procedures were included in the trial ; 2076 of these were in the control group and 2045 patients received heparin . The two groups were well matched for age , sex , weight , blood-group , and other factors which could predispose to the development of venous thromboembolism . 180 ( 4 - 4 % ) patients died during the postoperative period , 100 in the control and 80 in the heparin group : 72 % of deaths in the control and 66 % in the heparin group had necropsy examination . 16 patients in the control group and 2 in the heparin group were found at necropsy to have died due to acute massive pulmonary embolism ( P smaller than 0 - 005 ) . In addition , emboli found at necropsy in 6 patients in the control group and 3 in the heparin group were considered either contributory to death or an incidental finding since death in these patients was attributed to other causes . Taking all pulmonary emboli together , the findings were again significant ( P smaller than 0 - 005 ) . Of 1292 patients in whom the 125-I-fibrinogen test was performed to detect deep-vein thrombosis ( D.V.T. ) 667 were in the control group and 625 in the heparin group . The frequency of isotopic D.V.T. was reduced from 24 - 6 % in the control group 7 - 7 % in the heparin group ( P smaller 0 - 005 ) . In 30 patients D.V.T. was detected at necropsy ; 24 in the control and 6 in the heparin group ( P smaller 0 - 005 ) . 32 patients in the control group and 11 in the heparin group developed clinical ly diagnosed D.V.T. which was confirmed by venography ( P smaller than 0 - 005 ) . In addition , 24 patients in the control and 8 in the heparin group were treated for clinical ly suspected pulmonary emoblism . The difference in the number of patients requiring treatment for D.V.T. and /or pulmonary embolism in the two groups was again significant ( P smaller than 0 - 005 ) . 9 patients were found at necropsy to have died from haemorrhage ; 5 were in the control and 4 in the heparin group . A careful objective analysis of operative and postoperative bleeding in 1475 patients showed no statistically significant difference in the blood-transfusion requirements or in the fall in the postoperative haemoglobin level either in the individual operative groups or in the group as a whole . However , the difference in the number of patients who developed wound haematoma in the heparin and control groups was significant ( P smaller 0 - 01 ) . The results of the trial indicate that this form of prophylaxis can now be recommended for use on a large scale in " high-risk " patients undergoing major surgery BACKGROUND The risk of deep-vein thrombosis ( DVT ) and pulmonary embolism after total hip replacement ( THR ) surgery may persist after hospital discharge , but the extent of the risk is not known . We carried out a single-centre , prospect i ve , r and omised , double-blind trial with the aims of quantifying this risk and assessing the efficacy of continued prophylactic treatment . METHODS At hospital discharge 13 - 15 days after surgery , we recruited 179 consecutive THR patients who had no DVT visible on bilateral ascending venography of the legs . The patients were r and omly assigned subcutaneous enoxaparin ( 40 mg , once daily ; n = 90 ) or placebo ( n = 89 ) for 21 ( 19 - 23 ) days . The primary endpoint was the occurrence of DVT or pulmonary embolism . Venography was repeated at the end of 21 days ' treatment or earlier if necessary . FINDINGS There were no deaths and no symptomatic pulmonary embolisms during the study or follow-up periods . Of 173 patients with evaluable venograms , intention-to-treat analysis of efficacy showed that the rate of DVT at day 21 after discharge was significantly lower in the enoxaparin group than in the placebo group ( 6 [ 7.1 % ] vs 17 [ 19.3 % ] , p = 0.018 ) . Distal DVT was detected in one ( 1.2 % ) patient in the enoxaparin group and in ten ( 11.4 % ) patients in the placebo group ( p = 0.006 ) . Proximal DVT was observed in five ( 5.9 % ) patients in the enoxaparin group and in seven ( 7.9 % ) patients in the placebo group ( p = 0.592 ) . A per protocol analysis of efficacy in 155 patients confirmed these findings . Safety was good ; three minor bleeding episodes occurred in the enoxaparin group and one in the placebo group , but none of these episodes necessitated withdrawal from the study . INTERPRETATION In patients who have undergone THR surgery , are without venogram-proven DVT at hospital discharge , and do not receive antithrombotic prophylaxis after discharge , the risk of late-occurring DVT remains high at least until day 35 after surgery . Continued prophylaxis with enoxaparin is effective and safe in reducing this risk In a r and omized , prospect i ve trial of 100 patients , we have studied the safety and efficacy of warfarin sodium in comparison with that of dextran 40 in the prevention of venous thrombosis in patients at high risk for deep vein thrombosis after elective total hip or knee replacement . Warfarin was given in a new two-step regimen design ed to avoid bleeding complications while still preventing venous thrombosis . A low dose of warfarin was started ten to 14 days preoperatively , and the prothrombin time was regulated to between 1.5 and 3 seconds longer than control at the time of surgery ; immediately after surgery , the dose was increased to prolong the prothrombin time to 1.5 times control . The overall incidence of venous thrombosis as documented by venography was less in the 53 patients treated with warfarin than in the 37 treated with dextran ( 21 % v 51 % ) , as was the incidence of thrombi in the femoral or popliteal veins ( 2 % v 16 % ) . Objective measures of blood loss showed no difference between patients treated with warfarin or dextran , and excessive postoperative bleeding was infrequent and similar in both treatment groups . This study demonstrates that two-step warfarin therapy provides highly effective prophylaxis of postoperative venous thrombosis after elective hip or knee prosthetic surgery without excessive risk of perioperative bleeding The effect of low-dose heparin prophylaxis on venous thrombosis and bleeding after major elective surgery was studied in a prospect i ve controlled study of 820 patients . The total incidence of venous thrombosis detected with leg-scanning using fibrinogen labeled with radioactive iodine ( 125I ) was reduced from 16.0 % in the control group to 4.2 % in treated patients . More important , the incidence of popliteal or femoral vein thrombosis was reduced from 2.9 % to 1.0 % . Prophylaxis result ed in a slight increase in bleeding-minor wound hematoma , mean volume of blood transfused , and a post-operative hematocrit fall in treated patients . However , increased bleeding was clinical ly minor , and prophylaxis was well tolerated Discontinuation of thromboprophylaxis a few days after surgery may unmask delayed hypercoagulability and contribute to late formation of deep venous thrombosis ( DVT ) . To investigate whether thromboprophylaxis should be prolonged beyond the hospital stay , a prospect i ve , double-blind r and omised study was conducted in 308 patients . All patients received initial thromboprophylaxis with dalteparin , dextran and grade d elastic stockings . On day 7 , patients were r and omised to receive dalteparin ( Fragmin ) 5000 i.u . once daily , or placebo , for 4 weeks . All patients were subjected to bilateral venography , perfusion ventilation scintigraphy and chest X-ray on days 7 and 35 . Patients with venographically verified proximal DVT on day 7 were withdrawn from the r and omised study to receive anticoagulant treatment . The overall prevalence of DVT on day 7 was 15.9 % . On day 35 , the prevalence of DVT was 31.7 % in placebo-treated patients compared with 19.3 % in dalteparin-treated patients ( p = 0.034 ) . The incidence of DVT from day 7 to day 35 was 25.8 % in the placebo-treated group versus 11.8 % in the dalteparin-treated group ( p = 0.017 ) . The incidence of symptomatic pulmonary embolism ( PE ) from day 7 to day 35 was 2.8 % in the placebo-treated group compared with zero in the dalteparin-treated group . This included one patient who died from PE . No patients experienced serious complications related to the injections of dalteparin or placebo . This study shows that prolonged thromboprophylaxis with dalteparin . 5000 IU , once daily for 35 days significantly reduces the frequency of DVT and should be recommended for 5 weeks after hip replacement surgery OBJECTIVE To compare efficacy , safety , and feasibility of adjusted-dose oral anticoagulants ( OAC ) versus fixed-dose subcutaneous low molecular weight heparin ( LMWH ) for the prevention of deep venous thrombosis ( DVT ) in patients who have undergone elective hip or knee replacement . DESIGN Multicentre , single blind r and omised trial . OAC ( acenocoumarol , target International Normalised Ratio , 2.0 - 3.0 ) and LMWH ( nadroparine , 60 aXa IU/kg once daily ) were started preoperatively and continued for 10 days . All outcome measures were adjudicated by an independent committee unaware of treatment allocation . SUBJECTS 672 consecutive patients scheduled for elective hip or knee replacement surgery . All patients wore bilateral graduated compression stockings . MAIN OUTCOME MEASURES The endpoint for the assessment of efficacy was venography confirmed DVT or confirmed symptomatic pulmonary embolism . The endpoint for the assessment of safety was clinical ly important bleeding during study treatment or within 48 h of the end of treatment . RESULTS Among the 517 patients with interpretable venograms , 391 had a hip replacement and 126 had a knee implant . DVT was demonstrated in 50 ( 20 % ) of 257 patients allocated to OAC and 43 ( 17 % ) of 260 patients allocated to nadroparine ( p = 0.45 ) , for an absolute difference in DVT incidence of 2.9 % in favour of nadroparine ( 95 % CI , -3.7 - 9.5 ) . Clinical ly important bleeding occurred in eight ( 2.3 % ) of the 342 oral anticoagulant treated patients and in five ( 1.5 % ) of the 330 nadroparine treated patients ( p = 0.62 ) , for an absolute difference in favour of nadroparine of 0.8 % ( 95 % Cl , -1.3 - 2.9 ) . CONCLUSION Patients who undergo major orthopaedic operations have a high risk of venous thromboembolism . Once daily fixed-dose subcutaneous nadroparine is at least as efficacious and safe as daily adjusted OAC for prophylaxis against DVT after hip or knee implantation but is more simple to administer Abstract The efficacy of small doses of peri-operative subcutaneous heparin in preventing deep venous thrombosis has been studied in a controlled clinical trial involving 251 patients undergoing major operations . The results indicate that the regimen of sodium heparin used was safe . It reduced the frequency of postoperative deep venous thrombosis from 24 % in the control group to 0·8 % in the test group as detected by the 125 I-fibrinogen test . In addition it reduced the frequency of the dangerous extensive thrombi often responsible for pulmonary emboli from 7.4 % to In a prospect i ve study all positive phlebographies within the well-defined population of the city of Malmö , Sweden , during 1987 were studied in order to determine the incidence of deep venous thrombosis ( DVT ) . Epidemiological data were analysed for the detection of patient groups at increased risk of DVT . The incidence was found to be equal for both sexes , i.e. 1.6 per 1000 inhabitants a year . Risk factors were found to be in accordance with earlier studies . The median age for men was 66 years , compared to 72 years for women . At diagnosis of DVT , 19 % of subjects had a known malignancy and within 1 year 5 % ( 19 cases ) developed a new malignancy . Of the men , 29 % had postoperative or post-traumatic ( fracture ) DVT , compared to 46 % of the women . Fewer patients with DVT than expected ( 39 % ) belonged to blood group 0 ( 31 % ) ( P less than 0.005 ) . Pulmonary embolism ( PE ) was clinical ly suspected in only 5 % of cases , and diagnosis was verified scintigraphically in 2 % of cases . None of these died of PE , but of 6 patients who were found to have PE at autopsy , four died about 4 weeks after the DVT was diagnosed BACKGROUND This study provides an estimate of the prevalence of risk factors for venous thromboembolism among hospital patients . METHODS The presence of risk factors for venous thromboembolism was determined from a retrospective review of the medical records of 1,000 r and omly selected patients in 16 acute care hospitals in central Massachusetts . RESULTS The most common risk factors for venous thromboembolism were age 40 years ( 59 % ) or more , obesity ( 28 % ) , and major surgery ( 23 % ) . The average number of risk factors increased with increasing age . One or more risk factors for venous thromboembolism were present in 78 % of hospital patients , two or more in 48 % , three or more in 19 % , four or more in 6 % , and five or more in 1 % . CONCLUSION Risk factors for venous thromboembolism are common among hospital patients , suggesting that prophylaxis should be widely employed . The cost-effectiveness and risk benefit of prophylaxis is well established in patients undergoing major surgery . Further studies are needed to confirm the benefit of prophylaxis in patients with nonsurgical risk factors for venous thromboembolism In a prospect i ve , r and omized , double-blind study , the efficacy and safety of a low-molecular-weight heparin were compared with those of unfractionated sodium heparin ( st and ard heparin ) in 136 patients who had elective total hip replacement . The patients received subcutaneous injection of either 5000 international units of low-molecular-weight heparin once daily or 5000 international units of st and ard heparin three times a day . Treatment with low-molecular-weight heparin began twelve hours before the operation , and treatment with st and ard heparin began two hours preoperatively ; both regimens were continued for ten days . Twelve days postoperatively , bilateral ascending phlebography was performed in 122 patients , sixty-three in the treatment group that received low-molecular-weight heparin and fifty-nine in the treatment group that received st and ard heparin . Pulmonary scintigraphy was performed in 127 patients . Deep-vein thrombosis was diagnosed in forty-four patients : nineteen ( 30 per cent ) of the sixty-three who received low-molecular-weight heparin and twenty-five ( 42 per cent ) of the fifty-nine who received st and ard heparin . All but four patients , two from each treatment group , were asymptomatic . The difference in the total rate of thrombosis in the two groups was not significant ( p = 0.189 ) . However , thrombosis occurred in the thigh in only six ( 10 per cent ) of the patients who received low-molecular-weight heparin but in eighteen ( 31 per cent ) of those who received st and ard heparin , a significant difference ( p = 0.011 ) . Pulmonary embolism was detected in twenty-seven patients : eight ( 12.3 per cent ) of those who received low-molecular-weight heparin and nineteen ( 30.6 per cent ) of those who received st and ard heparin . Only three patients had clinical signs of embolism . Pulmonary embolism was significantly more frequent in the group that received st and ard heparin ( p = 0.016 ) . Total loss of blood and the total amount of blood that was transfused were significantly reduced in the patients who received low-molecular-weight heparin compared with those who received st and ard heparin . Prophylaxis was not discontinued because of hemorrhage in any patient . The efficacy of low-molecular-weight heparin was superior to that of st and ard heparin in the prevention of femoral thrombosis and pulmonary embolism , although the over-all incidence of deep-vein thrombosis was not statistically different . ( ABSTRACT TRUNCATED AT 400 WORDS There is experimental evidence that low-molecular-weight fractions of heparin are as effective as the st and ard form but cause less bleeding . We therefore performed a double-blind , r and omized trial comparing PK10169 low-molecular-weight heparin with placebo for the prevention of venous thrombosis in patients undergoing elective hip surgery . Prophylactic treatment with a fixed dose was begun postoperatively and continued for 14 days . Fifty patients in each treatment group underwent surveillance with [125I]fibrinogen leg scanning and impedance plethysmography . In the first 24 patients , venography was performed only if either surveillance test was positive . Because the rate of venous thrombosis detected in those patients was unexpectedly low , venography was requested in the remaining 76 patients , even if the screening tests were negative . In this latter group , venous thrombosis occurred in 4 patients ( 10.8 percent ) given PK10169 heparin and 20 patients ( 51.3 percent ) given placebo ( P = 0.0002 ) ; the corresponding rates for proximal-vein thrombosis were 5.4 percent and 23.1 percent , respectively ( P = 0.029 ) . In the entire group of 100 patients , venous thrombosis occurred in 12 percent of those given PK10169 heparin and 42 percent of those given placebo ( P = 0.0007 ) , and the corresponding rates for proximalvein thrombi were 4 percent and 20 percent , respectively ( P = 0.014 ) . The observed hemorrhagic rate was 4 percent in each treatment group . We conclude that prophylaxis with fixed-dose PK10169 heparin is effective and safe for patients undergoing elective hip replacement Summary In a double-blind , r and omized multicentre trial , the efficacy and safety of two regimens for the prevention of postoperative venous thrombo-embolism , low-molecular-weight heparin ( LMWH ) CY 216 and unfractionated heparin ( UH ) , were compared in 341 patients undergoing elective total hip replacement . A group of 169 patients received one subcutaneous injection of 48 mg ( ≈ 10 000 anti-Xa IC units ) LMWH and two placebo injections per day and 172 patients received a fixed dose of 5000 IU UH t.i.d . Deep vein thrombosis was assessed by bilateral phlebography on day 14 ± 1 after surgery . Phlebography was successfully performed in 136 patients in the LMWH group and 137 patients in the UH group . Deep vein thrombosis occurred in 45 of 137 patients ( 33.1 % ) treated with LMWH CY 216 and in 47 of 136 patients ( 34.3 % ) who received UH . Pulmonary embolism occurred in 2 of 167 evaluable patients ( 1.2 % ) in the LMWH group and in 6 of 168 patients ( 3.6 % ) in the UH group . In addition , the incidence of proximal deep vein thrombosis was evaluated and was found to be 10.3 % ( 14/137 patients ) in the LMWH group and 19 % ( 26/136 patients ) in the UH group ( P = 0.044 , two-sided ) . The safety of the treatments , as assessed by the incidence of major haemorrhage , intra- and postoperative blood loss , transfusion requirements , haemoglobin drop and frequency of wound haematomata , was similar in the two groups . It is concluded that prophylaxis of postoperative thrombo-embolism in hip surgery with one subcutaneous injection ( 48 mg ) of LMWH CY 216 is as effective and as safe as prevention with fixed low-dose heparin ( 5000 IU t.i.d ) . A tendency to reduced rates of pulmonary embolism ( 3.6 % vs. 1.2 % ) and proximal deep vein thrombosis ( 19 % vs. 10.3 % ) was observed in favour of LMWH CY 216 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 BACKGROUND Venous thromboembolic disease in the form of deep venous thrombosis and pulmonary embolism is a major risk after a total hip arthroplasty . Enoxaparin , a low-molecular-weight heparin , has been shown to reduce the prevalence of deep venous thrombosis after total hip arthroplasty . Warfarin , an orally administered anticoagulant , has been used historically to reduce the risk of deep venous thrombosis after total hip arthroplasty . METHODS We compared enoxaparin and adjusted-dose warfarin with respect to their safety and their efficacy in the prevention of clinical ly important venous thromboembolic disease , defined as distal or proximal deep venous thrombosis or pulmonary embolism , or both , during hospitalization after total hip arthroplasty . We also evaluated the prevalence of complications and mortality from venous thromboembolic disease within three months after discharge . RESULTS Three thous and and eleven patients at 156 centers were r and omly assigned to prophylactic treatment with injection of enoxaparin or oral administration of adjusted-dose warfarin during hospitalization . During the study , fifty-five ( 3.6 percent ) of the 1516 patients who were managed with enoxaparin and fifty-six ( 3.7 percent ) of the 1495 patients who were managed with warfarin had venous thromboembolic disease . Twenty-one patients ( 0.7 percent ) , which included four ( 0.3 percent ) of those managed with enoxaparin and seventeen ( 1.1 percent ) of those managed with warfarin ( p = 0.0083 ) , had venous thromboembolic disease during hospitalization . After discharge from the hospital , venous thromboembolic disease developed in ninety patients ( 3.0 percent ) : fifty-one ( 3.4 percent ) of those managed with enoxaparin and thirty-nine ( 2.6 percent ) of those managed with warfarin . One patient who had been managed with enoxaparin died because of a pulmonary embolism , which was confirmed at autopsy . Three additional patients ( one who had been managed with enoxaparin and two who had been managed with warfarin ) died , and the deaths were attributed to venous thromboembolic disease ; however , no autopsies were performed . Twenty-six patients ( 0.9 percent ) ( eighteen managed with enoxaparin and eight managed with warfarin ) had clinical ly important bleeding . CONCLUSIONS Inpatient programs providing treatment with either enoxaparin ( thirty milligrams every twelve hours ) or adjusted-dose warfarin for a mean of 7.3 days afforded protection against venous thromboembolic disease , with overall rates of morbidity and mortality of 3.7 and 0.6 percent , respectively , and a very low rate of major bleeding complications ( 0.9 percent ) for three months after total hip arthroplasty . During hospitalization , the patients managed with enoxaparin had a lower rate of venous thromboembolic disease than those managed with adjusted-dose warfarin ( p = 0.0083 ) . This benefit was lost after the medication was discontinued , with no difference in the prevalences of venous thromboembolic disease between the two groups at three months after discharge from the hospital A quantitative systematic review , or meta- analysis , uses statistical methods to combine the results of multiple studies . Meta-analyses have been done for systematic review s of therapeutic trials , diagnostic test evaluations , and epidemiologic studies . Although the statistical methods involved may at first appear to be mathematically complex , their purpose is simple : They are trying to answer four basic questions . Are the results of the different studies similar ? To the extent that they are similar , what is the best overall estimate ? How precise and robust is this estimate ? Finally , can dissimilarities be explained ? This article provides some guidance in underst and ing the key technical aspects of the quantitative approach to these questions . We have avoided using equations and statistical notations ; interested readers will find implementations of the described methods in the listed references . We focus here on the quantitative synthesis of reports of r and omized , controlled , therapeutic trials because far more meta-analyses on therapeutic studies than on other types of studies have been published . For practical reasons , we present a stepwise description of the tasks that are performed when statistical methods are used to combine data . These tasks are 1 ) deciding whether to combine data and defining what to combine , 2 ) evaluating the statistical heterogeneity of the data , 3 ) estimating a common effect , 4 ) exploring and explaining heterogeneity , 5 ) assessing the potential for bias , and 6 ) presenting the results . Deciding Whether To Combine Data and Defining What To Combine By the time one performs a quantitative synthesis , certain decisions should already have been made about the formulation of the question and the selection of included studies . These topics were discussed in two previous articles in this series [ 1 , 2 ] . Statistical tests can not compensate for lack of common sense , clinical acumen , and biological plausibility in the design of the protocol of a meta- analysis . Thus , a reader of a systematic review should always address these issues before evaluating the statistical methods that have been used and the results that have been generated . Combining poor- quality data , overly biased data , or data that do not make sense can easily produce unreliable results . The data to be combined in a meta- analysis are usually either binary or continuous . Binary data involve a yes/no categorization ( for example , death or survival ) . Continuous data take a range of values ( for example , change in diastolic blood pressure after antihypertensive treatment , measured in mm Hg ) . When one is comparing groups of patients , binary data can be summarized by using several measures of treatment effect that were discussed earlier in this series [ 3 ] . These measures include the risk ratio ; the odds ratio ; the risk difference ; and , when study duration is important , the incidence rate . Another useful clinical measure , the number needed to treat ( NNT ) , is derived from the inverse of the risk difference [ 3 ] . Treatment effect measures , such as the risk ratio and the odds ratio , provide an estimate of the relative efficacy of an intervention , whereas the risk difference describes the intervention 's absolute benefit . The various measures of treatment effect offer complementary information , and all should be examined [ 4 ] . Continuous data can be summarized by the raw mean difference between the treatment and control groups when the treatment effect is measured on the same scale ( for example , diastolic blood pressure in mm Hg ) , by the st and ardized mean difference when different scales are used to measure the same treatment effect ( for example , different pain scales being combined ) , or by the correlation coefficients between two continuous variables [ 5 ] . The st and ardized mean difference , also called the effect size , is obtained by dividing the difference between the mean in the treatment group and the mean in the control group by the SD in the control group . Evaluating the Statistical Heterogeneity of the Data This step is intended to answer the question , Are the results of the different studies similar ( homogeneous ) ? It is important to answer this question before combining any data . To do this , one must calculate the magnitude of the statistical diversity ( heterogeneity ) of the treatment effect that exists among the different sets of data . Statistical diversity can be thought of as attributable to one or both of two causes . First , study results can differ because of r and om sampling error . Even if the true effect is the same in each study , the results of different studies would be expected to vary r and omly around the true common fixed effect . This diversity is called the within- study variance . Second , each study may have been drawn from a different population , depending on the particular patients chosen and the interventions and conditions unique to the study . Therefore , even if each study enrolled a large patient sample , the treatment effect would be expected to differ . These differences , called r and om effects , describe the between- study variation with regard to an overall mean of the effects of all of the studies that could be undertaken . The test most commonly used to assess the statistical significance of between- study heterogeneity is based on the chi-square distribution [ 6 ] . It provides a measure of the sum of the squared differences between the results observed and the results expected in each study , under the assumption that each study estimates the same common treatment effect . A large total deviation indicates that a single common treatment effect is unlikely . Any pooled estimate calculated must account for the between- study heterogeneity . In practice , this test has low sensitivity for detecting heterogeneity , and it has been suggested that a liberal significance level , such as 0.1 , should be used [ 6 ] . Estimating a Common Effect The questions that this step tries to answers are , 1 ) To the extent that data are similar , what is their best common point estimate of a therapeutic effect , and 2 ) how precise is this estimate ? The mathematical process involved in this step generally involves combining ( pooling ) the results of different studies into an overall estimate . Compared with the results of individual studies , pooled results can increase statistical power and lead to more precise estimates of treatment effect . Each study is given a weight according to the precision of its results . The rationale is that studies with narrow CIs should be weighted more heavily than studies with greater uncertainty . The precision is generally expressed by the inverse of the variance of the estimate of each study . The variance has two components : the variance of the individual study and the variance between different studies . When the between- study variance is found to be or assumed to be zero , each study is simply weighted by the inverse of its own variance , which is a function of the study size and the number of events in the study . This approach characterizes a fixed-effects model , as exemplified by the Mantel-Haenszel method [ 7 , 8 ] or the Peto method [ 9 ] for dichotomous data . The Peto method has been particularly popular in the past . It has the advantage of simple calculation ; however , although it is appropriate in most cases , it may introduce large biases if the data are unbalanced [ 10 , 11 ] . On the other h and , r and om-effects models also add the between- study variance to the within- study variance of each individual study when the pooled mean of the r and om effects is calculated . The r and om-effects model most commonly used for dichotomous data is the DerSimonian and Laird estimate of the between- study variance [ 12 ] . Fixed- and r and om-effects models for continuous data have also been described [ 13 ] . Pooled results are generally reported as a point estimate and CI , typically a 95 % CI . Other quantitative techniques for combining data , such as the Confidence Profile Method [ 14 ] , use Bayesian methods to calculate posterior probability distributions for effects of interest . Bayesian statistics are based on the principle that each observation or set of observations should be viewed in conjunction with a prior probability describing the prior knowledge about the phenomenon of interest [ 15 ] . The new observations alter this prior probability to generate a posterior probability . Traditional meta- analysis assumes that nothing is known about the magnitude of the treatment effect before r and omized trials are performed . In Bayesian terms , the prior probability distribution is noninformative . Bayesian approaches may also allow the incorporation of indirect evidence in generating prior distributions [ 14 ] and may be particularly helpful in situations in which few data from r and omized studies exist [ 16 ] . Bayesian analyses may also be used to account for the uncertainty introduced by estimating the between- study variance in the r and om-effects model , leading to more appropriate estimates and predictions of treatment efficacy [ 17 ] . Exploring and Explaining Heterogeneity The next important issue is whether the common estimate obtained in the previous step is robust . Sensitivity analyses determine whether the common estimate is influenced by changes in the assumptions and in the protocol for combining the data . A comparison of the results of fixed- and r and om-effects models is one such sensitivity analysis [ 18 ] . Generally , the r and om-effects model produces wider CIs than does the fixed-effects model , and the level of statistical significance may therefore be different depending on the model used . The pooled point estimate per se is less likely to be affected , although exceptions are possible [ 19 ] . Other sensitivity analyses may include the examination of the residuals and the chi-square components [ 13 ] and assessment of the effect of deleting each study in turn . Statistically significant results that depend on a single study may require further exploration . Cumulative Meta- Analysis The aim of this study was to compare the efficacy and safety of prolonged ( 35 days ) thromboprophylaxis with a st and ard length ( 7 days ) regimen of a low molecular weight heparin in patients undergoing total hip arthroplasty . The study was multicentre , r and omised , double-blind , and prospect i ve with two groups . Following seven days on a st and ard length regimen of dalteparin ( 5000 antifactor Xa units subcutaneously once daily starting 12 h before surgery ) , patients were r and omized to continue the prophylaxis with either subcutaneous injections of dalteparin or placebo injections for a further 28 days . Efficacy was evaluated at the end of the study ( day 35 ) in all patients with bilateral ascending phlebography to detect deep vein thrombosis . Bleeding complications and other adverse events were registered throughout the study period . Three hundred consecutive patients agreed to participate before the operation : 281 were finally r and omised and 215 completed the study ; two patients died before r and omisation ; 17 developed deep vein thrombosis ; none developed pulmonary embolism ; and five of 113 patients ( 4.4 % , 95 % CI 1 - 10 % ) developed deep vein thrombosis in the dalteparin group , compared with 12 of 102 ( 11.8 % ; 95 % CI 6 - 20 % ) in the placebo group ( p=0.039 ) . Deep vein thrombosis in the proximal veins was diagnosed in one patient ( 0.9 % ; 95 % CI 0 - 5 % ) in the dalteparin group , and in five ( 5.0 % ; 95 % CI 2 - 11 % ) in the placebo group ( p=0.076 ) . Major bleeding was observed in one patient in the placebo group ; minor bleeding complications and adverse events were equally distributed between the groups . We concluded that prolonged ( 35 days ) thrombo prophylaxis with dalteparin is more effective than a st and ard length ( 7 days ) regimen without increased risk of bleeding complications or other adverse events In a double-blind , r and omised study of thromboprophylaxis in patients undergoing total hip replacement , we compared a low-molecular-weight heparin with a placebo . Of the 120 patients enrolled , 112 completed the trial ; 58 in the treatment group and 54 in the placebo group . Nine ( 16 % ) patients in the treatment group and 19 ( 35 % ) in the placebo group developed deep venous thrombosis , diagnosed by the 125I-fibrinogen uptake test ( p < 0.02 ) . Verification was obtained by phlebography in 86 % of the patients . Prolonged surgery increased the risk of thrombosis in the placebo group but not in the treatment group ( p < 0.05 ) . There were significantly more cases of deep venous thrombosis in the placebo group during the first four postoperative days ( p < 0.02 ) . The groups did not differ with respect to peroperative and postoperative bleeding . Low-molecular-weight heparin offers safe and easily administered thromboprophylaxis in total hip replacement 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 A study of equivalence was performed between two low molecular weight heparins , reviparin-sodium ( Clivarin ) and enoxaparin ( Lovenox ) in the prevention of deep vein thrombosis ( DVT ) after total hip replacement . Nineteen orthopaedic centres participated in the trial . Four hundred and ninety-eight patients were r and omized ; 247 received reviparin-sodium and 251 enoxaparin ; 58 patients were excluded . Each patient received subcutaneous prophylaxis begun 10 - 12 h pre-operatively and the second injection 10 - 12 h post-operatively and thereafter every 24 h. In the enoxaparin group 18 DVT were observed ( 9 % ) ; of these 13 ( 6 % ) were proximal . In the reviparin-sodium group 21 DVT were observed ( 10 % ) ; 12 ( 6 % ) were proximal . The study showed that the efficacy of both LMWHs was equivalent as was the clinical tolerance . There was a slight trend in favour of reviparin-sodium as regards haemoglobin level , and wound haematoma . Anti-factor Xa activity was significantly different despite similar injected doses Review articles are an important element of most medical journals and a popular source of information for clinicians ( 1 ) . Given the increasing volume of medical literature and the limited time for reading that busy clinicians have , reliance on review articles is likely to increase . However , concerns have been raised that narrative , non systematic review articles may produce biased conclusions ( 2 , 3 ) . Mulrow ( 4 ) examined 50 review articles published in four major medical journals ( The New Engl and Journal of Medicine , Annals of Internal Medicine , JAMA , and Archives of Internal Medicine ) in 1985 - 1986 and found that none fulfilled 8 explicit criteria for scientifically sound summaries of the evidence . As a result , she and others ( 5 , 6 ) proposed criteria for conducting and evaluating review articles that would improve their quality ; these criteria are the first 10 listed in the Appendix Table . In a study of 36 review articles done by nine content experts and method ologists , these criteria were shown to yield reliable and valid estimates of the scientific quality of review s ( 7 , 8) . We sought to describe the methods used in recently published review articles and determine whether the attention paid to the method ologic shortcomings of review articles has led to improvements in their scientific quality . Methods By using the Science Citation Index ( 9 ) , we stratified the 12 general medicine journals that are considered core journals for ACP Journal Club ( 10 ) into those with high impact factors ( scores 5 ) and those with lower impact factors . We r and omly selected 3 ( The New Engl and Journal of Medicine , Annals of Internal Medicine , and JAMA ) of the 4 high-impact core journals and 3 ( British Medical Journal , American Journal of Medicine , and Journal of Internal Medicine ) of the 8 core journals with lower impact factors . The sampling frame included 3 of the 4 journals examined in Mulrow 's original study ( 4 ) . All 6 journals were h and - search ed by two of the investigators independently , and review articles published between January and December 1996 were retrieved . Review articles were defined as full-text articles published under the banner review that dealt with disease states ; had the words review , overview , or meta- analysis in the title or abstract ; or indicated in the text that the intention was to review or summarize the literature about a clinical topic . Editorials , correspondence , and conference summaries were excluded . Disagreements on article eligibility ( which occurred in five cases ) were resolved by consensus . After training with a test set of articles , five of the authors used explicit criteria ( Appendix Table ) to rate the identified review articles . So that the raters ' assessment s would be blinded , the articles ' authors , author affiliations , and sources of articles were masked . The first 10 criteria in the Appendix Table ( hereafter referred to as method ologic criteria ) have been previously vali date d ( 7 ) and assess method ologic rigor , whereas the last five criteria were developed for this study to evaluate the scientific basis of treatment recommendations . Because inter-rater agreement was excellent on the test set ( overall agreement , 94 % ) , each rater was assigned a r and om sample of 20 % of the articles . One rater independently evaluated a r and om sample of five articles from each rater to assess inter-rater reliability for the criteria . The mean value was 0.79 , indicating substantial agreement ; overall agreement was 95 % and ranged from 84 % for criteria 1 and 6 to 100 % for criteria 2 , 3 , and 5 . After we determined the number of criteria fulfilled by each article , the number of articles meeting each criterion was ascertained . The proportion of review s from high-impact journals and from lower-impact journals that met each criterion were compared . Only the subset of review s containing treatment recommendations were used for the comparisons for criteria 7 to 15 . The chi-square test was used and 95 % CIs for the observed differences were calculated for all comparisons . In addition , articles identified as meta-analyses , systematic review s , or overviews in their title , abstract , or text were compared with the remaining review articles for each criterion ( again by using the chi-square test and by limiting analysis to those that included treatment recommendations for criteria 7 to 15 ) . Logistic regression analysis was used to adjust for journal of publication . The funding organizations were not involved in the design , conduct , analysis , or reporting of this study . Results A total of 158 review articles were identified : 60 from The New Engl and Journal of Medicine , 33 from Annals of Internal Medicine , 24 from British Medical Journal , 18 from American Journal of Medicine , 13 from JAMA , and 10 from Journal of Internal Medicine . ( A full list of the included articles is available from Dr. McAlister on request . ) Most review s were written by more than one author ( median number of authors , 2 [ range , 1 to 10 authors ] ) , and 111 review s ( 70 % ) made treatment recommendations . Although most articles had sections review ing the relevant pathophysiology and pharmacodynamics , 19 articles ( 12 % ) were largely basic science review s. Only 2 review s met all 10 method ologic criteria ; the median number of criteria fulfilled was one ( Figure ) . Nineteen ( 12 % ) of the review articles were described as meta- analysis , systematic review , or overview in the title or abstract ; 12 of these 19 articles were published in high-impact journals . A higher proportion of these articles met the method ologic criteria ( Appendix Table ) ; the comparisons for all but criterion 6 were statistically significant , even after adjustment for journal of publication ( P<0.005 for all comparisons ) . Although there was significant heterogeneity among journals ( P<0.005 for criteria 1 to 5 , 7 , and 8) , review articles published in high-impact journals did not meet method ologic criteria more frequently than those published in other journals ( Table ) . Exclusion of the review s from one journal with method ologic scores that were significantly lower than the rest ( P<0.001 for all comparisons ) resolved much of the interjournal heterogeneity and revealed that review s published in the remaining high-impact journals more often met some ( but not all ) of the method ologic criteria ( Table ) . Figure . Percentage of 158 review articles published in 1996 that fulfilled specific method ologic criteria . Table . Comparison of Methods Used in 1996 Review Articles , by Journal Impact Factor The 44 articles that described how evidence was located used the following sources ( which were not mutually exclusive ) : MEDLINE ( 42 articles ) , h and search of reference lists from published studies or review articles ( 30 articles ) , other electronic data bases ( 14 articles ) , contact with experts in the field ( 10 articles ) , h and search of relevant journals ( 7 articles ) , and contact with the pharmaceutical industry ( 5 articles ) . Of the 22 review s that included a description of the electronic search strategy , the search was restricted to English- language publications in 11 . Of the 111 review s in which treatment recommendations were made , a median of 3 therapies ( range , 1 to 23 therapies ) were discussed . The 16 meta-analyses that included treatment recommendations were more focused , examining a median of 1 therapy ( range , 1 to 6 therapies ) . The scientific basis of these recommendations is outlined in the last five criteria of the Appendix Table . Discussion In summary , only a minority of the review articles published in six widely read general medical journals specified rigorous , systematic methods of identifying , evaluating , and synthesizing the evidence , thereby raising concerns about the validity of their conclusions and recommendations ( 11 ) . Furthermore , although most review articles made recommendations for therapeutic options , their clinical relevance may be limited : Only one third discussed benefits and harms of the treatment options , only 6 % mentioned the relative or absolute costs of the various options , less than half provided an estimate of the anticipated treatment effect , and very few presented the results in clinical ly relevant formats that would be easily understood by clinicians . Although there is still substantial room for improvement , these results do represent progress from the situation in 1985 - 1986 ( Appendix Table ) . A higher proportion of recently published review s specify how the evidence was identified and synthesized . This same pattern was observed in a recent study of oncology review articles published in a single journal between 1983 and 1995 ( 12 ) . Similarly , our findings for meta-analyses published in these journals in 1996 are consistent with contemporaneous investigations in other fields and represent substantial improvement over the state of affairs in the mid-1980s ( 13 , 14 ) . Our study had several potential limitations . First , the authors of articles in which systematic methods were not specified may have used such methods but not reported them ( or the journal may have removed the details of the methods in prepublication ) . However , preliminary evidence suggests that there is little difference between the conduct of studies and their published methods ( 7 , 15 ) . In other words , if what was done is not reported , there is a good chance that it was not done rigorously ( 7 ) . Second , our finding that meta-analyses are more scientifically rigorous than other review s may be seen as tautological because the criteria used in this study may be used by meta-analysts in performing their studies . However , meta-analysts disagree over some issues of methodology , and published meta-analyses often vary in the quality of their reports ( 13 ) . Third , the practical importance of the method ologic flaws identified in these review s is difficult to ascertain . We lack empirical evidence that review s with explicit , systematic methods yield results closer to the truth , but it is known that non systematic review s are more prone to r and om and Prophylactic efficacy and safety of a low molecular weight ( LMW ) heparin against postoperative thromboembolic complications were investigated in a double-blind , r and omized study . Totally , 210 consecutive patients undergoing total hip replacement were allocated to two groups . Patients in the heparin group received 50 IU anti-Xa per kilo body weight of Logiparin once daily , and patients in the placebo group received one daily injection of saline . Additional prophylaxis in all the patients was thigh-length compression stockings beginning on the day of the operation . Deep vein thrombosis was diagnosed by bilateral ascending phlebography between Days 8 and 10 after the operation . Twenty patients were excluded from the evaluation . Thirty of 93 patients in the heparin group compared with 45 of 97 patients in the placebo group suffered a thromboembolic complication during the study ( P = 0.02 ) . The postoperative blood loss and total number of blood transfusions in the heparin group were higher than in the placebo group . However , the observed differences were of no clinical importance . Adverse effects , including bleeding complications and wound hematomas , were observed in 13 heparin patients and 7 placebo patients ( NS ) . One patient in each group died . Thrombo-prophylaxis with LMW heparin once daily was safe and more effective than the placebo in patients undergoing total hip replacement The efficacy and safety of RD heparin , a low-molecular-weight heparin , for the prevention of venous thromboembolic disease among patients managed with an elective total hip or total knee arthroplasty were compared with the efficacy and safety of warfarin in an open-label prospect i ve , multicenter trial . Patients were r and omized to receive either a fixed dose of fifty anti-factor-Xa units of RD heparin per kilogram of body weight , administered subcutaneously twice daily , beginning postoperatively ; a fixed dose of ninety anti-factor-Xa units of RD heparin per kilogram of body weight , administered subcutaneously once daily , beginning postoperatively ; or five milligrams of warfarin , administered orally preoperatively , followed by a daily adjusted dose of warfarin to prolong the prothrombin time ratio to 1.2 to 1.5 . The primary measure of efficacy was contrast venography of the treated limb , performed by local radiologists blinded to the type of treatment that had been assigned . Nine hundred and sixty-nine patients had a complete assessment for the presence of deep-vein thrombosis . The over-all rates of venous thromboembolic disease were 16 percent ( 95 pecent confidence interval , 13 to 21 percent ) ( fifty-three ) for the 328 patients who received RD heparin twice daily , 21 percent ( 95 percent confidence interval , 17 to 26 percent ) ( sixty-eight ) for the 320 patients who received RD heparin once daily , and 27 percent ( 95 percent confidence interval , 22 to 32 percent ) ( eighty-seven ) for the 321 patients who received warfarin ( p < 0.001 for RD heparin administered twice daily compared with warfarin ; p = 0.13 for RD heparin administered once daily compared with warfarin ) . Compared with warfarin , RD heparin administered twice daily and RD heparin administered once daily reduced the risk of venous thromboembolic disease by 41 percent ( 95 percent confidence interval , 20 to 56 percent ) and 18 percent ( 95 percent confidence interval , -6 to 37 percent ) , respectively . The rates of venous thromboembolic disease after 523 total hip arthroplasties were 8 , 14 , and 14 percent for the patients who received RD heparin twice daily , those who received it once daily , and those who received warfarin ( p = 0.07 for RD heparin administered twice daily compared with warfarin ; p = 0.82 for RD heparin administered once daily compared with warfarin ) . ( ABSTRACT TRUNCATED AT 400 WORDS Enoxaparin , a low-molecular-weight heparin , has been used together with spinal or general anaesthesia in a prospect i ve , r and omised study of 188 consecutive elective hip replacements . Bilateral venography was performed on all patients on day 13 after operation . Group I ( 65 patients ) received spinal anaesthesia and no immediate injection of enoxaparin . Group II ( 61 patients ) received spinal anaesthesia and 20 mg of enoxaparin one hour after the onset of anaesthesia . Group III ( 62 patients ) was operated on under general anaesthesia and received 40 mg of enoxaparin 12 hours prior to surgery . This group acted as the control group . In all three groups , 40 mg of enoxaparin was given 12 hours after the end of surgery and continued on a once-daily basis . Proximal DVT occurred in 6 % of group I , 6.7 % of group II and 6.5 % of group III , not a significant difference . Distal DVT was present in 11 % of group I , 5 % of group II and 0 % of group III ; this was a highly significant difference ( p = 0.007 ) . Tolerance was good and the incidence of bleeding low in the three groups . Our results confirm the low rate of DVT in patients operated on under general anaesthesia with the st and ard procedure of 40 mg of enoxaparin on a once-daily basis started pre-operatively . The 40 mg-dose is also safe and effective in association with spinal anaesthesia if half the dose ( 20 mg ) is injected an hour after the lumbar puncture BACKGROUND The risk of venous thromboembolism in patients undergoing total hip replacement is known to be high . However , the optimal duration of prophylaxis with anticoagulant agents after this procedure is unknown . We sought to determine whether one month of anticoagulant therapy with the low-molecular-weight heparin enoxaparin is more effective than enoxaparin therapy given only during the hospitalization for surgery . METHODS Two hundred sixty-two patients undergoing total hip replacement received enoxaparin during their hospitalizations ( average stay , 10 to 11 days ) . They were then r and omly assigned to receive enoxaparin or placebo ( 131 patients each ) . Blinded outpatient therapy ( or placebo ) was continued long enough that the total treatment period , inpatient plus outpatient , was one month for each patient . Bilateral ascending phlebography was performed 19 to 23 days after discharge , with deep-vein thrombosis as the primary end point . Distal and proximal thrombosis , pulmonary embolism , and hemorrhage were also recorded , as were deaths . RESULTS Venography was adequate in 116 patients in the placebo group and 117 in the enoxaparin group . We observed 43 episodes of deep-vein thrombosis and 2 episodes of pulmonary embolism in the placebo group , but only 21 episodes of deep-vein thrombosis and no episodes of pulmonary embolism in the enoxaparin group ( incidence of thromboembolism , 39 percent and 18 percent , respectively ; P<0.001 ) . The difference in the incidence of proximal deep-vein thrombosis was also significant ( 24 percent and 7 percent in the placebo and enoxaparin groups , respectively ; P<0.001 ) . Six enoxaparin groups , respectively ; P<0.001 ) . Six patients in the enoxaparin group and one patient in the placebo group had hematomas at their injection sites . No patients died or had major complications . CONCLUSIONS There were significantly fewer venous thromboembolic complications in patients undergoing elective hip replacement when prophylaxis with enoxaparin was given for a total of one month , rather than only during the hospitalization A prospect i ve , r and omized trial was conducted to compare the effectiveness and safety of warfarin given in two regimens in prevention of venous thrombosis after total knee replacement . Adult patients scheduled for primary or revision total knee replacement were r and omly assigned to receive either a " two-step " warfarin regimen beginning 10 - 14 days pre-operatively or , alternatively , to begin warfarin the night before surgery . Post-operatively , the dose was adjusted in both groups to achieve a target International Normalized Ratio ( INR ) of 2.2 and prophylaxis was continued until venography on post-operative days five through nine . Bleeding was assessed by surgical blood loss , transfusion requirements , changes in hematocrit , and clinical ly identified bleeding complications . The occurrence of deep vein thrombosis was nearly the same in the two treatment groups , 39 % in patients r and omized to the two-step regimen as compared to 38 % in those beginning the night before surgery . The occurrence of proximal vein thrombosis was also similar , 5 % versus 7 % ( p = NS ) . Patients in the two-step group received 1.33 + /- 1.26 transfusions compared to 0.95 + /- 1.22 in the night before group ( p < 0.05 ) and also had a lower nadir post-operative hematocrit of 26.7 + /- 3.1 as compared to 28.5 + /- 3.2 ( p < 0.0001 ) . Major bleeding complications were associated with excessively prolonged INRs and occurred in five patients in the two-step group and two in the night before group . Patients in both groups who developed thrombosis had a significantly lower INR on post-operative days two and three compared to those without thrombosis . We conclude that a prophylactic warfarin regimen for prevention of deep vein thrombosis after total knee replacement beginning the night before surgery is more convenient and may be associated with less bleeding than a regimen beginning warfarin 10 - 14 days pre-operatively . Careful control of anticoagulant intensity is needed to achieve maximum effectiveness and avoidance of bleeding complications BACKGROUND Patients who undergo total hip replacement have a high risk of thromboembolic complications . Recombinant hirudin ( desirudin ) , a specific inhibitor of thrombin , represents a new development in antithrombotic therapy . We compared the efficacy and safety of desirudin with those of a low-molecular-weight heparin ( enoxaparin ) for the prevention of thromboembolic complications in patients undergoing primary total hip replacement . METHODS Both treatments , which were assigned in a r and omized , double-blind manner , were started preoperatively : enoxaparin on the evening before surgery , and desirudin within 30 minutes before the start of surgery . The dose of desirudin was 15 mg subcutaneously twice daily , and the dose of enoxaparin was 40 mg subcutaneously once daily . The duration of treatment was 8 to 12 days . Deep-vein thrombosis was verified by bilateral venography performed at the end of the treatment period or earlier , if there were clinical signs of deep-vein thrombosis . RESULTS At 31 centers in 10 European countries , 2079 eligible patients were r and omly assigned to receive desirudin or enoxaparin . A total of 1587 patients were included in the primary analysis of efficacy . In the desirudin group , as compared with the enoxaparin group , there was a significantly lower rate of proximal deep-vein thrombosis ( 4.5 vs. 7.5 percent , P=0.01 ; relative reduction in risk , 40.3 percent ) and a lower overall rate of deep-vein thrombosis ( 18.4 vs. 25.5 percent , P=0.001 ; relative reduction in risk , 28.0 percent ) . The safety profiles were similar in the two treatment groups . CONCLUSIONS When administered 30 minutes before total hip replacement surgery , desirudin is more effective than enoxaparin in preventing deep-vein thrombosis |
635 | 28,543,086 | This was robust to a prespecified sensitivity analyses , but there was evidence suggestive of publication bias .
For secondary outcomes , subcutaneous immunotherapy ( SCIT ) improved quality of life and decreased allergen-specific airway hyperreactivity ( AHR ) , but this was not the case for sublingual immunotherapy ( SLIT ) .
There were no consistent effects on asthma control , exacerbations , lung function , and nonspecific AHR .
AIT result ed in a modest increased risk of adverse events ( AEs ) .
Although relatively uncommon , systemic AEs were more frequent with SCIT ; however no fatalities were reported .
The limited evidence on cost-effectiveness was mainly available for sublingual immunotherapy ( SLIT ) and this suggested that SLIT is likely to be cost-effective .
AIT can achieve substantial reductions in short-term symptom and medication scores in allergic asthma .
It was however associated with a modest increased risk of systemic and local AEs . | BACKGROUND To inform the development of the European Academy of Allergy and Clinical Immunology 's ( EAACI ) Guidelines on Allergen Immunotherapy ( AIT ) for allergic asthma , we assessed the evidence on the effectiveness , cost-effectiveness and safety of AIT . | The present study aim ed to evaluate the efficacy of three-year subcutaneous SQ-st and ardized specific immunotherapy ( SCIT ) in house dust mite (HDM)-allergic children with asthma . Ninety children with allergic asthma to HDMs , with or without allergic rhinitis , were r and omly divided into two groups , the treatment group and the control group . The treatment group received SCIT combined with st and ardized glucocorticoid management and the control group received st and ardized glucocorticoid management alone for a period of three years . The mean daily dose of inhaled corticosteroids ( ICSs ) , a four-week diary recording the symptom scores of asthma , peak expiratory flow ( PEF ) measurements , skin prick test results and serum immunoglobulin E ( IgE ) levels were assessed prior to treatment and following one , two and three years of treatment . The median dose of ICS was reduced in the treatment group after two and three years of treatment compared with that of the control group . After three years of treatment , the discontinuation percentage of ICS in the treatment group was higher than that in the control group . The treatment group demonstrated significantly reduced daytime and night-time asthmatic symptom scores , increased PEF values and reduced serum IgE levels after two and three years of treatment compared with those in the control group ( P<0.05 ) . In conclusion , three-year SCIT treatment combined with ICS is an effective immunotherapy for children with allergic asthma and result ed in a reduction of the required ICS dose Forty‐six asthmatics with verified allergy to the house dust mite , D. pteronyssinus ( Dp ) , participated in a double‐blind study comparing the effect of 2 years ' hyposensitization with two different Dp extracts . Two groups received either monomethoxypolyethylene glycol modified ( mPEG ) Dp extract or the corresponding non‐modified extract , and a third group acted as controls receiving no injections . Medicine consumption , symptom scores , and peak expiratory flow ( PEF ) were recorded daily from September to December prior to and after 6 and 18 months of treatment . Changes were calculated choosing changes 10 % as relevant . In addition , patients were asked to give their direct assessment of the clinical effect at the end of the study . After 6 months , there was an improvement in symptoms + medication in 11/14 of Dp‐treated , 6/17 of the mPEG‐Dp group ( P > 0.05 ) and 3/15 of openly treated controls . Few patients had changed in PEF . During the second year , several Dp‐treated relapsed and some controls improved . At the end of the study the same improvement rate was seen in all groups . Similarly , the retrospective question naire data did not disclose any significant differences between groups after 2 years . In conclusion , hyposensitization with unmodified Dp extract seemed to have a favourable short‐term effect on bronchial symptoms + medication in the majority of patients . When mainly on maintenance dose , the beneficial effect was reduced . The mPEG modification of the extract had reduced not only allergenicity but also the clinical effect of equal doses . Changes in medicine and symptom scores only partly correlated to retrospective assessment , thus stressing the problems in this kind of evaluation A double-blind clinical trial of hyposensitization with aqueous extracts of Dermatophagoides pteronyssinus ( the house-dust mite ) and human skin scales showed a substantial improvement in symptoms in 11 asthmatics allergic to house dust treated with the D. pteronyssinus extract and a reduction in their need for other therapy . Five patients were well for a year but six relapsed . These results contrasted with the generally unfavourable course of the patients treated with the extract of human skin scales . Asthma due to house-dust allergy may be substantially improved by hyposensitization with D. pteronyssinus extract 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 Cockroach allergy is a key contributor to asthma morbidity in children living in urban environments . OBJECTIVE We sought to document immune responses to cockroach allergen and provide direction for the development of immunotherapy for cockroach allergy . METHODS Four pilot studies were conducted : ( 1 ) an open-label study to assess the safety of cockroach sublingual immunotherapy ( SLIT ) in adults and children ; ( 2 ) a r and omized , double-blind biomarker study of cockroach SLIT versus placebo in adults ; ( 3 ) a r and omized , double-blind biomarker study of 2 doses of cockroach SLIT versus placebo in children ; and ( 4 ) an open-label safety and biomarker study of cockroach subcutaneous immunotherapy ( SCIT ) in adults . RESULTS The adult SLIT trial ( n = 54 ; age , 18 - 54 years ) found a significantly greater increase in cockroach-specific IgE levels between the active and placebo groups ( geometric mean ratio , 1.92 ; P < .0001 ) and a trend toward increased cockroach-specific IgG4 levels in actively treated subjects ( P = .09 ) but no evidence of functional blocking antibody response . The pediatric SLIT trial ( n = 99 ; age , 5 - 17 years ) found significant differences in IgE , IgG , and IgG4 responses between both active groups and the placebo group but no consistent differences between the high- and low-dose groups . In the SCIT study the treatment result ed in significant changes from baseline in cockroach IgE , IgG4 , and blocking antibody levels . The safety profile of cockroach immunotherapy was reassuring in all studies . CONCLUSIONS The administration of cockroach allergen by means of SCIT is immunologically more active than SLIT , especially with regard to IgG4 levels and blocking antibody responses . No safety concerns were raised in any age group . These pilot studies suggest that immunotherapy with cockroach allergen is more likely to be effective with SCIT Continuing study for a second year and further analysis of a double‐blind placebo controlled trial , already briefly reported , of injections of tyrosine‐adsorbed , glutaraldehyde‐modified Dermatophagoides pteronyssinus antigen in fifty‐one children with perennial asthma and positive bronchial challenge to the antigen , confirms that the patients receiving the treatment reduced their symptomatic medication more than controls , without deterioration of symptoms . Some became symptom‐free , when off all treatment BACKGROUND The safety and efficacy of specific immunotherapy for mold allergy are not known in children and adolescents . OBJECTIVE We evaluated the efficacy and safety of specific immunotherapy with a st and ardized allergen extract in a r and omized , double-blind , placebo-controlled , 3-year prospect i ve study of patients who were allergic to only Alternaria alternata . METHODS Fifty children and adolescents ( 25 girls ; 5 - 18 years of age ) with A alternata-induced seasonal allergic rhinoconjunctivitis and /or bronchial asthma were r and omly assigned to groups given treatment ( Novo-Helisen Depot , A alternata 100 % ) or placebo . The primary end point was the combined symptom medication score . Secondary end points included safety , quality of life , and sensitivity to allergen-specific nasal challenge . RESULTS Forty-five children completed the 3-year study . Although there was no significant change in year 1 , the combined symptom medication score decreased in years 2 and 3 of the study ( by 38.7 % and 63.5 % , respectively ; P < .001 for each ) . The reduction in symptoms was associated with a significant improvement in quality of life ( P < .05 ) and decrease in sensitivity after allergen-specific nasal challenge . Side effects were observed in 7 patients ; the most common ( edema at the site of injection ) occurred after 11 injections . CONCLUSIONS Allergen-specific immunotherapy with st and ardized A alternata extract reduces symptoms of asthma and rhinoconjunctivitis in children and adolescents without serious side effects Hyposensitisation with Dermatophagoides pteronyssinus tyrosine absorbate in asthmatic children with bronchial sensitivity to D. pteronyssinus was effective in a 12-month double-blind controlled clinical trial . Compared with controls , treated children used a smaller quantity of drugs while maintaining clinical and lung function improvements . In most children who improved there was no change in immediate response to D. pteronyssinus on bronchial provocation test , but the late reaction was lost in half the patients and these showed the greatest improvement in symptoms BACKGROUND Cells producing a T(H2)-cytokine profile play an important role in the onset and maintenance of atopic diseases , and therefore specific immunotherapy is aim ed to induce a switch to cells producing a T(H1)- or T(H0)-cytokine profile . Recently , a novel form of immunotherapy making use of synthetic peptides from the major cat allergen Fel d 1 has been developed , but its mechanisms of action are unknown . OBJECTIVES We examined the effects of immunotherapy with Fel d 1 peptides on the response to bronchial provocation tests ( PD20FEV1 ) with a st and ardized Fel d 1 cat extract on Fel d 1-specific serum IgE and IgG levels and in vitro IL-4 and IFN-gamma production . METHODS Patients allergic to cats received 6 weekly injections of 7.5 micro(g ) ( low dose ) , 75 micro(g ) ( medium dose ) , or 750 micro(g ) ( high dose ) of Fel d 1 peptides ( 25 patients ) or a placebo ( 6 patients ) . RESULTS Six weeks after ending immunotherapy , posttreatment PD20FEV1 was not significantly different between the treated and placebo groups . However , in the medium- and high-dose groups there was a significant improvement between baseline and posttreatment days . IL-4 release was significantly reduced in the high dose-treated group ( P < .005 , Wilcoxon W test ) , whereas it was unchanged in the low or medium dose- and in the placebo-treated groups . In all groups , IFN-gamma , IgE , and IgG levels remained unchanged . CONCLUSION There was no correlation between the improvement of PD20FEV1 and the decrease in IL-4 production . These data suggest that peptide immunotherapy may act by shifting the Fel d 1-induced response of P BMC s in vitro from the T(H2)-like to the T(H0)-like phenotype Results from one immunotherapy study can be difficult to extrapolate when physicians use products or dose schedules that differ from the ones used in that particular study . The purpose of this study was to determine if an alum absorbed Alpare D. pteronyssinus extract administered in a maintenance dose of 10,000 - 12,500 BU 's could be shown to improve symptoms in asthmatic patients allergic to D. pteronyssinus . Previous studies using higher doses of extracts suggested efficacy but frequent side effects were noted . A double blind placebo controlled study was performed which included 24 active and 25 placebo patients . We measured skin reactivity , methacholine challenge changes , symptoms by visual analog score , specific IgE levels , and end of study assessment . The results showed significantly greater improvement in actively treated patients versus those given placebo in specific IgE levels , symptoms by visual analog score , and end of study status . We saw no significant differences in skin reactivity , methacholine challenge , or diary medication scores . In addition , no difference in side effects was noted between the two groups . We conclude that the dose administered in this study was safe and well tolerated . Some clinical improvement did seem to occur but the study suggests that higher doses may be indicted in certain patients OBJECTIVE To evaluate the safety and efficacy of sublingual immunotherapy with ' Dermatophagoides Farinae Drops ' in D. farinae allergic asthma and /or rhinitis patients . METHODS A 25-week double-blind , placebo-controlled , multi-centered trail was conducted in 278 children ( aged 4 - 18 yr ) with mite-induced asthma and /or rhinitis . Patients were r and omly assigned to receive sublingual immunotherapy ( SLIT ) with ' Dermatophagoides Farinae Drops ' ( n = 139 ) or placebo ( n = 139 ) for 25 weeks and the dosage and administration strictly followed the manufacturer 's instructions . At the beginning of the 2nd , 3rd , 4th , 6th , 10th , 14th , 18th , 22nd week of the treatment , the patients were asked to accept follow-up visit , during the clinical trial all patients and parents were asked to keep a daily record of their asthma symptom scores , rescue medicine use , rhinitis symptom scores , morning and evening peak expiratory flow . Asthma symptom scores , reduction in use of rescue medicine , rhinitis symptom scores , lung function tests , skin sensitivity to mite , mite-specific immunoglobulin ( Ig ) E and IgG4 , and quality of life and adverse effect were assessed during the study . RESULT ( 1 ) Of the 278 children , 27 dropped out before the study completion . ( 2 ) After 25 weeks of treatment , the median variability of PEFR was -1.38 for SLIT group and -0.90 for the placebo ( P < 0.05 ) . ( 3 ) Besides , the mean variability of medicine score of asthma was -0.08 for SLIT group and 0.52 for the plcebo ( P < 0.05 ) . ( 4 ) The median variability of rhinitis symptom score was -1.96 for SLIT group and -1.03 for the placebo ( P < 0.01 ) . ( 5 ) The rescue medicine usage of SLIT reduced but did not show significant differences between SLIT and placebo . ( 6 ) After 25 weeks treatment , the increase of D. farinae specific IgE antibody of two groups were similar , while specific IgG4 increased significantly in SLIT compared to the patients in control one ( P < 0.01 ) ; ( 7 ) No severe adverse events happened in the trial and the most-likely adverse events were mild asthma and local rash . CONCLUSION Dermatophagoides Farinae Drops is safe and effective in treating allergic asthma and atopic rhinitis BACKGROUND Immunotherapy has been shown to reduce allergen sensitivity to allergens such as cat and dust mite . The aim of this study was to investigate the effect of cat or dust mite immunotherapy on bronchial hyperreactivity and the need for inhaled corticosteroids in children with asthma , cat or dust mite allergy , and hay fever . SUBJECTS Twenty-nine children , 7 to 16 years old , completed the 3-year study . They were r and omly allocated to receive cat/dust mite or placebo and birch/timothy immunotherapy . METHODS Before immunotherapy was begun and then once each year , bronchial histamine challenges were performed . Bronchial allergen challenge with the perennial allergen was done before and after the 3-year study . Pharmacotherapy was given according to a st and ardized protocol . RESULTS PC20 allergen increased significantly in both the active immunotherapy group ( P < .001 ) and in the placebo-pollen group ( P < .05 ) . PC20 histamine increased continuously in the active immunotherapy group ( P < .05 and P = .002 after 1 and 3 years , respectively ) and had also increased after 3 years in the placebo-pollen group ( P < .05 ) . The difference between the 2 groups was significant for PC20 allergen ( P = .001 ) but not for PC20 histamine . There was no significant change in the dose of inhaled budesonide needed for symptom control in either of the groups . CONCLUSION Pollen immunotherapy combined with inhaled corticosteroids results in improvement of both cat/dust mite bronchial sensitivity and hyperresponsiveness to histamine . The combination of cat or dust mite , pollen immunotherapy , and inhaled budesonide enhances this improvement . Cat immunotherapy also induces cat allergen tolerance Inl and areas of northern California have an intense grass pollination in the spring of each year . This is accompanied by a stirking rise in the incidence of asthma . We documented this relationship and design ed a trial to test the efficacy of immunotherapy for grass-pollen asthma . Aeroallergen counts were performed on the roof of the allergy clinic of David Grant Medical Center from January 1981 to December 1984 by a gravity collector . These counts were compared to counts done on a Rotorod at a nearby hospital from July 1982 to September 1984 . Climatologic factors were also tabulated . Visits for asthma and rhinitis to our emergency room and asthma admissions to our hospital were counted for the 4-year period . A r and omized , double-blinded , placebo-controlled trial of immunotherapy with grass-pollen extract was performed from November 1984 to June 1985 . Two groups of clinical ly and immunologically well-matched subjects were started on an accelerated preseasonal trial of immunotherapy . One group received a st and ardized grass extract , and the other group did not . Both groups received other extracts of aeroallergens to which they were skin test positive that occur locally in the spring and summer . This was done because of our dissatisfaction with a histamine placebo used in a previous pilot study . Symptom medication scores ( SMS ) and immunologic parameters were followed . For the 4-year period , grass-pollen count ( GPC ) correlated strongly with asthma emergency room visits ( r = 0.90 ; p less than 0.001 ) and for rhinitis ( r = 0.92 ; p less than 0.001 ) . Asthma admissions also correlated strongly with GPC ( r = 0.72 ; p less than 0.001 ) . Other aeroallergens either did not correlate significantly or occurred in such small numbers that they could not be seriously considered . Rotorod counts supported these conclusions with the exceptions of some Basidiomycetes . Climatologic factors demonstrated no relationship to the incidence of asthma . Asthma SMS were lower in the grass-treated group , p less than 0.05 . Rhinitis SMS were also lower but did not reach significance , p = 0.11 . RGGI sIgE did not rise significantly in the grass-treated group but did in the placebo-treated group . RGGI sIgE rose in both groups , although to significantly higher levels in the grass-treated group , p less than 0.001 . The asthma SMS were inversely related to increasing RGGI cumulative dose , p less than 0.10 . Linear regression analysis of the dose-response scattergram suggests that a cumulative dose of approximately 90 micrograms of RGGI may be desirable . ( ABSTRACT TRUNCATED AT 400 WORDS Background : There is only very limited documentation of the efficacy and safety of high‐dose subcutaneous birch pollen immunotherapy ( IT ) in double‐blind , placebo‐controlled ( DBPC ) studies . Birch pollen is a major cause of allergic morbidity in northern Europe and in eastern parts of North America 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 A double‐blind controlled study of the effect of house dust hyposensitization was conducted in 93 patients allergic to house dust . The allergy diagnosis was established by bronchial provocation tests , and the degree of bronchial sensitivity to house dust extracts ( bronchial threshold dose for allergen ) was assessed before and after 2 1/2–3 years ' injection treatment Ten asymptomatic patients with normal pulmonary function were selected for a double-blind trial of immunotherapy in cat-induced asthma . Each patient had a positive prick test to cat pelt extract and also a positive bronchial challenge response to the same extract . Patients were r and omly assigned to active treatment or placebo groups and received weekly or biweekly injections over a 3 to 4-month period . The 5 patients who received the active treatment received a cumulative dose of cat pelt extract that ranged from 16.4 to 44.8 mg of total solid containing 1.7 to 4.7 mg of cat allergen 1 . Apparent systemic reactions were observed in 3 patients who received the placebo and 3 patients who received the active treatment . The 5 patients who received the active treatment showed a reduction in skin reactivity to cat pelt extract as well as a significant mean reduction in bronchial sensitivity to the same extract . The 5 patients who received the placebo showed no significant changes in skin reactivity or bronchial sensitivity to cat pelt extract . Bronchial response to histamine did not change significantly in either the active treatment of the placebo group 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 RATIONALE Heterogeneity in asthma expression is multidimensional , including variability in clinical , physiologic , and pathologic parameters . Classification requires consideration of these disparate domains in a unified model . OBJECTIVES To explore the application of a multivariate mathematical technique , k-means cluster analysis , for identifying distinct phenotypic groups . METHODS We performed k-means cluster analysis in three independent asthma population s. Clusters of a population managed in primary care ( n = 184 ) with predominantly mild to moderate disease , were compared with a refractory asthma population managed in secondary care ( n = 187 ) . We then compared differences in asthma outcomes ( exacerbation frequency and change in corticosteroid dose at 12 mo ) between clusters in a third population of 68 subjects with predominantly refractory asthma , clustered at entry into a r and omized trial comparing a strategy of minimizing eosinophilic inflammation ( inflammation-guided strategy ) with st and ard care . MEASUREMENTS AND MAIN RESULTS Two clusters ( early-onset atopic and obese , noneosinophilic ) were common to both asthma population s. Two clusters characterized by marked discordance between symptom expression and eosinophilic airway inflammation ( early-onset symptom predominant and late-onset inflammation predominant ) were specific to refractory asthma . Inflammation-guided management was superior for both discordant subgroups leading to a reduction in exacerbation frequency in the inflammation-predominant cluster ( 3.53 [ SD , 1.18 ] vs. 0.38 [ SD , 0.13 ] exacerbation/patient/yr , P = 0.002 ) and a dose reduction of inhaled corticosteroid in the symptom-predominant cluster ( mean difference , 1,829 mug beclomethasone equivalent/d [ 95 % confidence interval , 307 - 3,349 mug ] ; P = 0.02 ) . CONCLUSIONS Cluster analysis offers a novel multidimensional approach for identifying asthma phenotypes that exhibit differences in clinical response to treatment algorithms Abstract Background The occurrence of allergic multimorbidity ( coexistence of asthma , allergic rhinitis and eczema ) has not been evaluated longitudinally from early childhood up to adulthood in a population ‐based study sample . We aim ed to determine the prevalence of allergic multimorbidity up to age 20 stratified by parental allergies and sex/gender using extensive prospect i ve follow‐up data from two decades of a birth cohort study . Methods In 1990 , we recruited 1314 healthy newborns from 6 maternity wards across Germany for the population ‐based MAS birth cohort study . The sample was purpose ly risk‐enriched by increasing the proportion of children at high allergy risk ( i.e. at least 2 allergic family members among parents and siblings ) from 19 % in the source population to 38 % in the final sample . The remaining 62 % of all MAS children had a low or no allergy risk . Symptoms , medication and doctor 's diagnoses of allergic diseases have been assessed using st and ardized question naires including vali date d ISAAC questions in 19 follow‐up assessment s up to age 20 . Allergic multimorbidity at each time point was defined as the coexistence of at least 2 of the following diseases in one participant : asthma , allergic rhinitis and eczema . Results Response at age 20 was 72 % ( n = 942 ) of all recruited participants . At age 20 , 18.5 % ( 95 % CI , 15.0–22.5 % ) of all participants with allergic parents had 2 or 3 concurrent allergies as compared to only 6.3 % ( 95 % CI , 4.3–9.0 % ) of those with non‐allergic parents . At this age , allergic multimorbidity was similar in women and men ( 12.7 % ( 95 % CI , 9.7–16.2 % ) vs. 11.6 % ( 95 % CI , 8.9–14.8 % ) ) , whereas single allergic diseases were slightly more common in women than men ( 24.2 % ( 95 % CI , 20.2–28.5 % ) vs. 20.1 % ( 95 % CI , 16.6–24.0 % ) ) . Asthma occurred more frequently with coexisting allergic rhinitis and /or eczema than as a single entity from pre‐puberty to adulthood . Conclusion Having parents with allergies is not only a strong predictor to develop any allergy , but it strongly increases the risk of developing allergic multimorbidity . In males and females alike , coexisting allergies were increasingly common throughout adolescence up to adulthood . Particularly asthma occurred in both sexes more frequently with coexisting allergies than as a single entity Abstract Objective : To evaluate the efficacy of homoeopathic immunotherapy on lung function and respiratory symptoms in asthmatic people allergic to house dust mite . Design : Double blind r and omised controlled trial . Setting : 38 general practice s in Hampshire and Dorset . Participants : 242 people with asthma and positive results to skin prick test for house dust mite ; 202 completed clinic based assessment s , and 186 completed diary based assessment s. Intervention : After a four week baseline assessment , participants were r and omised to receive oral homoeopathic immunotherapy or placebo and then assessed over 16 weeks with three clinic visits and diary assessment s every other week . Outcome measure : Clinic based assessment s : forced expiratory volume in one second ( FEV1 ) , quality of life , and mood . Diary based assessment s : morning and evening peak expiratory flow , visual analogue scale of severity of asthma , quality of life , and daily mood . Results : There was no difference in most outcomes between placebo and homoeopathic immunotherapy . There was a different pattern of change over the trial for three of the diary assessment s : morning peak expiratory flow ( P=0.025 ) , visual analogue scale ( P=0.017 ) , and mood ( P=0.035 ) . At week three there was significant deterioration for visual analogue scale ( P=0.047 ) and mood ( P=0.013 ) in the homoeopathic immunotherapy group compared with the placebo group . Any improvement in participants ' asthma was independent of belief in complementary medicine . Conclusion : Homoeopathic immunotherapy is not effective in the treatment of patients with asthma . The different patterns of change between homoeopathic immunotherapy and placebo over the course of the study are unexplained BACKGROUND Although several studies support the efficacy of specific immunotherapy in allergic asthma , its benefit compared with that of st and ardized pharmacologic intervention remains unknown . OBJECTIVE A double-blind , placebo-controlled trial in 72 patients with mild-to-moderate asthma and allergy to house dust mite ( HDM ; Dermatophagoides species ) was conducted to assess the effects of specific immunotherapy added to guideline -adjusted pharmacologic treatment and allergen avoidance . METHODS After 1 observational year of pharmacologic treatment and st and ard measures of HDM avoidance , 2 groups of asthmatic subjects were r and omly assigned to receive specific immunotherapy consisting of subcutaneous injections of either a mixture of Dermatophagoides pteronyssinus and Dermatophagoides farinae vaccine ( n=41 ) or placebo ( n=31 ) for 3 years . Medications were adjusted every 3 months according to the Global Initiative for Asthma guidelines . RESULTS The adjustment of treatment was associated with a reduction in asthma symptom scores in all subjects . The addition of specific immunotherapy was associated with a decrease in the number of subjects requiring rescue bronchodilators , an increase in morning and evening peak expiratory flow , and a reduced skin sensitivity to HDM extracts . The addition of specific immunotherapy had no significant effects on the cumulative dose of inhaled corticosteroids , asthma symptoms , lung volumes , or bronchial responsiveness to methacholine . CONCLUSION These results suggest that specific immunotherapy added to pharmacologic treatment and HDM avoidance provides marginal but statistically significant clinical benefits , possibly by reducing the allergic response of asthmatic patients sensitized to HDM 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 A placebo‐controlled , double‐blind study of immunotherapy with the mould species Cladosporium was performed in 22 adult asthmatics . The diagnosis of Cladosporium allergy was based on a combination of bronchial provocation test and daily symptom score in the Cladosporium season . An aqueous preparation of a potent , biologically st and ardized and purified extract was used in a clustered dose‐increase regimen . The clinical efficacy was evaluated by a combination of symptoms ( asthma score + peak flow ) and consumption of antiasthmatic medication . The mean changes in symptoms and medication consumption over a 10–week registration period ( peak Cladosporium season ) in 1982 after 5–7 months of immunotherapy were compared with the corresponding 1981 pretreatment 10‐week period A significant ( P= 0.03 ) difference in terms of “ improved ” , “ unchanged ” and “ deteriorated ” patients in favour of Cladosporium treatment was found . Approximately 80 % in the Cladosporium group showed improved/unchanged symptoms contrary to 30 % of the placebo treated . Side effects were observed frequently but only in the Cladosporium‐treated . About 70 % experienced a large local reaction and 100 % had episodes of asthma during dose‐increase phase . Only a few severe systemic reactions occurred . Based on the clinical efficacy of the treatment we consider immunotherapy with Cladosporium feasible for highly specialized clinics Dermatophagoides pteronyssinus ( Dp ) is the major allergen in allergic asthma in France . St and ardized and lyophilized Dp extracts are available , and their effectiveness after a short course of rush immunotherapy was examined in a placebo-controlled , double-blind study . Twenty patients received the Dp st and ardized extract , and 10 other patients received a placebo extract . Before and 7 weeks after rush immunotherapy , in vivo and in vitro parameters were examined . Bronchial provocation tests performed in a st and ardized manner demonstrated that a provocative dose causing a 20 % fall in FEV1 , a 25 % fall in maximum mild expiratory flow rate , a 25 % fall in maximum flow when 50 % of the forced vital capacity has been expired , and a 35 % fall in specific airway conductance were significantly ( p less than 0.005 to p less than 0.01 , Wilcoxon W test ) improved in the treated group and remained unchanged in the placebo group . Skin test titration demonstrated that patients placed in the treated group had a significant ( p less than 0.001 , Wilcoxon W test ) decrease of both end point titer and size of the largest wheal . No significant difference was observed in the placebo group . Serum Dp-IgE did not vary significantly in either group . Serum Dp antigen P1-IgG was significantly ( p less than 0.001 , Wilcoxon W test ) increased in the treated group and slightly increased in the placebo-treated group . This study demonstrated that a Dp st and ardized extract administered by a rush protocol elicits a rapid and significant immune response and leads to a significant protection of the patients BACKGROUND Although the efficacy of allergen immunotherapy has been demonstrated in seasonal pollen allergy , there is no report of a double-blind placebo-controlled trial with st and ardized pollen extract in seasonal respiratory allergy from India . In the agricultural area of eastern India , Phoenix sylvestris Roxb or date sugar palm is grown or cultivated and seasonal allergic rhinitis is common during the pollen season . OBJECTIVE The objective of the present study was to observe the clinical and immunological changes during a 2-year double-blind placebo-controlled trial of immunotherapy with st and ardized P sylvestris pollen extract in respiratory patients sensitive to pollen from this wild date palm . Thirty-five subjects with typical seasonal allergic rhinitis with or without bronchial asthma were selected . A symptom-medication score ( based on a question naire and diary ) was correlated with pollen counts as recorded in a Burkard sample r. Eighteen subjects were r and omized to a specific immunotherapy ( SIT ) group receiving regular injections containing st and ardized allergen extract and 17 to a placebo control group . Changes in the level of specific immunoglobulin ( Ig ) E , IgG1 , and IgG4 were recorded at 3-month intervals . Measurement of wheal diameter , total IgE level and forced expiratory volume in 1 second ( FEV1 ) were performed before starting and a month after finishing therapy . RESULTS The SIT group showed decreases of 33.5 % and 57 % from the baseline symptom-medication scores during the first and second treatment season , respectively . This group showed significant decreases in skin-reactivity to P sylvestris pollen extract and in specific IgE levels , and significant increases in FEV , , specific IgGI ( 1.95 - 3.2 times higher ) and IgG4 ( 21.24 - 30.83 times higher ) . There were no significant changes in total IgE levels . The control group showed no significant changes for any parameter except the development of new sensitization in 2 cases ( to Saccharum officinarum pollen grain and Alternaria species spores ) . The rate of local adverse reactions was 0.024 % . CONCLUSION After a 2-year study , allergen immunotherapy with st and ardized P sylvestris pollen extract was found to be effective in seasonal respiratory allergic subjects susceptible to P sylvestris pollen with a narrow range of sensitization 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 Sublingual immunotherapy ( SLIT ) has been recommended as a viable alternative to subcutaneous injection therapy in the treatment of airway allergies , though more data is needed from well-controlled studies for documenting its efficacy in different ethnic population s. Ninety-seven children ( age range 6 - 12 years ) , mild-to-moderate asthma with a single sensitization to mite allergen , were enrolled from 5 medical centers in Taiwan to evaluate the efficacy and safety of SLIT with st and ardized mite extracts , which contain Dermatophagoides pteronyssinus ( D.p . ) and Dermatophagoides farinae ( D.f . ) . Patients were double blinded and r and omly assigned to either a SLIT or placebo group . Following 24 weeks of study period , symptom and medication scores , lung function tests , skin prick tests , total serum IgE , and specific IgE to D.p . and D.f . were recorded . The results showed that there was statistically significant difference between these two groups in the analysis of daily ( P=0.011 ) , nighttime ( P=0.028 ) , and daytime ( P=0.009 ) asthmatic scores after 24 weeks of treatment . Patients receiving SLIT improved their forced vital capacity ( FVC ) , forced expiratory volume in 1s ( FEV1 ) , and peak expiratory flow ( PEF ) as compared to baseline ( P=0.042 , P=0.048 , and P=0.001 , respectively ) . No differences were found in skin prick test , total serum IgE and specific IgE to D.p . and D.f . Tolerance with high-dose SLIT was good with few minor adverse events reported . Our results indicated that a 24-week SLIT is of clinical benefit to mite-sensitive asthmatic children in Taiwan Background Allergen vaccination is effective in mite‐allergic asthma . Liposomes are immunological adjuvants that can act as allergen carriers Background Immunotherapy is a recognized treatment for allergic respiratory diseases BACKGROUND Mite sensitivity is highly prevalent in tropical and subtropical regions , such as the Canary Isl and s. OBJECTIVES To evaluate the clinical efficacy and safety of a depigmented polymerized allergen vaccine containing a 50 % mixture of Dermatophagoides pteronyssinus and Dermatophagoides farinae . METHODS Sixty-four patients participated in the study . It was prospect i ve , double-blind , and placebo-controlled , with r and om allocation of patients to receive active treatment or placebo . The active group received a mixture of modified allergen extracts containing 50 % D pteronyssinus and 50 % D farinae ; the control group received placebo . All individuals were diagnosed with mild/moderate asthma and rhinoconjunctivitis caused by sensitization to D pteronyssinus and D farinae . Bronchial provocation test ( BPT ) was considered the main outcome to document clinical efficacy . RESULTS Fifty-four patients completed the study . The active group experienced a significant improvement in BPT ( P < .001 ) , whereas the placebo group did not ( P = .648 ) . At the end of the study , 20 patients in the active versus 9 in the placebo group ( P = .013 ; odds ratio , 5.71 [ 1.76 , 18.51 ] ) needed more than twice the amount of allergen to obtain a positive BPT . The median improvement in the active group over placebo was 53.76 % in total symptom and 58.09 % in medication scores . CONCLUSION Immunotherapy with a mixture of modified allergen extracts of D pteronyssinus and D farinae is safe and efficacious to treat mite-allergic asthma . CLINICAL IMPLICATION S This immunotherapy modifies the natural course of the illness because it improves all clinical outcomes measured and prevents the worsening of specific bronchial hyperreactivity BACKGROUND First reports on sublingual immunotherapy were published in 1980 . OBJECTIVE To compare safety and effectiveness of sublingual immunotherapy , as compared with placebo , in asthmatic patients . MATERIAL S In a blinded r and omized controlled trial asthmatic patients with positive skin prick tests to Dermatophagoides pteronyssinus , and with serum IgE at least 200 UI were included . According to GINA , asthma severity was mild persistent and moderate . All patients improved their baseline FEV1 at least by 14 % after inhaled albuterol . Spirometry was performed again after three and six months after initiating treatment . Patients were r and omized to receive for six months either sublingual immunotherapy with Der p 1 st and ardized allergens ( IPI-ASAC , México ) at a total dose of 10,469 UBE or identically looking and tasting placebo . Both groups received conventional pharmacological therapy . RESULTS Sixty four patients enter the study ; four were excluded because of systemic oral steroid therapy . Sixty patients underwent r and omization . Both groups ( 30 patients in each one ) were similar in their baseline characteristics . After six months , patients that received sublingual immunotherapy had less exacerbations than those in the control group ( 61 vs 123 , T 2.61 , p<0.001 , IC 1.8 - 7.2 ) , better FEV1 as compared with baseline values ( 25 % vs 9 % , Z=0.66 , p=0.03 ) , and less need of albuterol ( 50 % of initial dose , vs 21 % ( Z=1.4 , p=0.03 , IC 1.39 - 1.49 ) . CONCLUSION Sublingual immunotherapy improves patient symptoms and pulmonary functional tests , makes exacerbations less frequent , and reduces albuterol needs . It may improve asthma related quality of life Twenty-seven dog-allergic asthmatic children with no pets in the home were included in the study . The clinical trial was performed as a double-blind study using a commercial st and ardized aluminum hydroxide-bound dog d and er and hair extract or histamine-placebo . The patients were r and omized into the active treatment or the placebo group on the basis of the RAST ( e5 ) and the provocation test with aqueous dog d and er and hair extract . The good clinical response of immunotherapy with dog d and er and hair extract has been reported earlier . The specific immunotherapy result ed in an increase in the serum level of antigen-specific IgG antibodies ( P less than .01 ) and a decrease in the skin sensitivity to dog extract ( P less than .001 ) in the active treatment group when compared with the placebo group . The treatment was well-tolerated . No systemic reactions occurred and local reactions were mild . The results show a good immunologic response with a st and ardized dog d and er and hair extract . There were no major changes in the course of bronchial asthma in either group . After 1 year of immunotherapy the subjects had no symptoms on a dog-exposure of short duration . This must be carefully emphasized when considering the indications for immunotherapy Eighteen asymptomatic Artemisia pollen asthma patients with normal pulmonary function were selected for a double-blind trial of oral immunotherapy . Each patient had a positive skin test to Artemisia pollen extract and also a positive bronchial challenge response to the same extract . The patients were r and omly assigned to active treatment or placebo group and received intensive oral administration of Artemisia pollen extract over a 50-day course . The nine patients who received the active treatment ingested a cumulative dose of 396,652 PNU and showed a significant decrease in serum-specific IgE antibodies ( P less than .05 ) and a significant reduction in bronchial sensitivity to the same extract ( P less than .01 ) . The changes in these two variables correlated well ( r = .8787 , P less than .01 ) . The nine patients who received the placebo showed no significant changes in serum-specific IgE or bronchial sensitivity to Artemisia pollen extract . Follow-up of two cases with the same extract showed that the reductions in serum-specific IgE as well as bronchial sensitivity induced by oral immunotherapy were maintained for 3 months To evaluate the efficacy of specific sublingual immunotherapy ( SLIT ) , we enrolled 15 children with asthma and rhinitis ( 7 girls , 8 boys , mean + /- SD age of 11.7 + /- 3.3 ) allergic to house dust mite ( HDM ) into a double-blind , placebo-controlled study . After a run-in period , patients were r and omized to receive either placebo ( n = 7 ) or SLIT ( n = 8) with a st and ardized Dermatophagoides pteronyssinus ( D. pteronyssinus ) + Dermatophagoides farinea ( D. farinea ) 50/50 extract . They received increasing doses up to 100 index units of reactivity ( IR ) every day for 4 weeks , then 100 IR/day for another 4 weeks , followed by maintenance therapy consisting of 20 drops 2 times a week for 4 months . Efficacy was assessed at the end of 6 months of therapy according to symptom and medication scores , serum total IgE levels , results of lung function tests , methacholine provocation tests , and skin prick tests . Daily means for the asthma score and use of inhaled beta-2-mimetics decreased significantly in the SLIT group ( P = 0.05 , P = 0.028 , respectively ) , whereas no such difference was observed in the placebo group . At the end of follow-up , mean daily doses of intranasal steroids needed for control of rhinitis symptoms decreased significantly in the SLIT group ( P = 0.04 ) . Baseline skin sensitivity to D. pteronyssinus and D. farinea was not significantly different between in the two groups , whereas end-point wheal diameter obtained with D. pteronyssinus extract was significantly less in the SLIT vs. the placebo group ( P = 0.026 ) . At the end of 6 months , peak expiratory flow ( PEF ) values in the placebo group was significantly lower than in the SLIT group ( P = 0.049 ) . Throughout the treatment period , the SLIT group was found to have less asthma exacerbations than the placebo group ( P = 0.007 ) . The provocation concentration causing a 20 % drop in forced expired volume in 1 sec did not change throughout the treatment period in either groups . None of the patients reported local or systemic side effects from SLIT . Results of this study suggests that SLIT may be a useful alternative or additional therapy in the treatment of children with asthma/rhinitis due to HDM Twenty-seven asthmatic children allergic to dog were included in the study . Their allergy to dog was confirmed by positive results from the skin prick , radioallergosorbent and provocation tests . The subjects were r and omly assigned to active and placebo groups . Fifteen subjects received immunotherapy with a commercial st and ardized aluminum hydroxide-bound dog d and er extract and 12 subjects received placebo injections containing histamine . After one year 's therapy the conjunctival sensitivity to dog d and er extract had decreased significantly ( p less than 0.001 ) in the active treatment group compared to the placebo group . The hyposensitization effect was already observable after six to eight months of treatment . The decrease in bronchial sensitivity was less marked than that in conjunctival sensitivity and statistically not significant . Immunotherapy was observed to be safe and effective . No systemic adverse reactions occurred and local reactions were mild A double‐blind histamine placebo controlled immunotherapy trial was performed to investigate the clinical effect of a purified and st and ardized Cladosporium herbarum allergen preparation . Thirty children with a clinical history suggesting mould‐induced asthma and /or rhinoconjuctivitis were included . The diagnosis was confirmed by positive skin prick test and Phadebas RAST ® as well as positive bronchial and /or conjunctival provocation test to Cladosporium herbarum . Immunotherapy was given for 10 months in a double‐blind manner to r and omized groups with either Pharmalgen ® /Cladosporium herbarum preparation or histamine placebo . Allergic side effects to injections were common , especially during the peak of the mould season ( July‐September in Sc and inavia ) . In the active group , 13/16 patients experienced general reactions during the first 10 months of treatment . After 6 months of treatment , eye , nose and bronchial symptom scores and peak expiratory flow rates were similar for the groups , maybe because most of the children were also sensitive to many other allergens , including Alternaria alternala . However , medication scores were significantly lower in the treated group ( P < 0.01 ) . Bronchial ( P < 0.01 ) and conjunctival sensitivity ( P= 0.01 ) were significantly reduced in the Cladosporium‐treated group but not in the placebo group after 10 mouths of treatment . This is the first double‐blind clinical trial showing the clinical efficacy of immunotherapy in children with mould‐induced asthma The efficacy of immunotherapy in cat-induced asthma was studied by use of a purified fraction of cat-pelt extract and a double-blind protocol . Nine active-treatment subjects who received a mean cumulative dose of cat allergen , 1 of 10.9 units , and eight placebo-treatment subjects completed the study . Active treatment result ed in significant reductions in bronchial sensitivity ( p less than 0.05 ) and prick test titer ( p less than 0.01 ) . In addition , active treatment result ed in a significant delay in the onset of ocular ( p less than 0.05 ) and pulmonary ( p less than 0.02 ) symptoms on exposure to living cats . Significant increases in IgG antibody to cat allergen 1 ( p less than 0.001 ) and cat albumin ( p less than 0.01 ) also occurred with active treatment . There was no significant change in bronchial reactivity to methacholine or in the sensitivity of circulating basophils . These results confirm the validity of immunotherapy in allergic asthma where there is careful patient selection and well defined treatment preparations BACKGROUND Few studies have investigated the use of specific immunotherapy ( SIT ) for childhood seasonal allergic asthma . OBJECTIVE We sought to examine the efficacy and safety of SIT with Alutard SQ grass pollen ( Phleum pratense Alutard SQ ; ALK-Abelló , Hørsholm , Denmark ) in children with seasonal allergic asthma . METHODS A r and omized , double-blind , placebo-controlled study assessing the efficacy of grass pollen SIT over 2 pollen seasons was performed . Children ( 3 - 16 years ) with a history of seasonal allergic asthma sensitized to grass pollen ( P pratense ) and requiring at least 200 microg of inhaled beclomethasone equivalent per day were enrolled . Subjects with symptomatic asthma or rhinoconjunctivitis outside the grass pollen season were excluded . The primary outcome measure was a combined asthma symptom-medication score during the second pollen season . Secondary outcome measures included end-point titration skin prick testing and conjunctival and bronchial provocation testing to allergen , sputum eosinophilia , exhaled nitric oxide , and adverse events . RESULTS Thirty-nine subjects were enrolled . Thirty-five subjects provided data for analysis . The use of SIT was associated with a substantial reduction in asthma symptom-medication score compared with that after placebo ( P = .04 ) . There were also significant reductions in cutaneous ( P = .002 ) , conjunctival ( P = .02 ) , and bronchial ( P = .01 ) reactivity to allergen after SIT compared with that after placebo . The 2 groups had similar levels of airway inflammation , despite a trend toward less inhaled steroid use in the active group . No serious adverse events were reported , and no subjects withdrew because of adverse events . CONCLUSION The study has shown that SIT is effective and well tolerated in children with seasonal allergic asthma to grass pollen Twenty-eight patients were included in a double-blind placebo-controlled study of a vaccine containing tyrosine-adsorbed Dermatophagoides pteronyssinus antigen ( Migen(R ) ) . The aim of the trial was to show the efficacy and safety of Migen as a 6-injection course , with or without a follow-up course of 6 maintenance doses , for the treatment of bronchial asthma . The patients selected had suffered from perennial asthma for at least 2 years and gave a strong skin reaction to house dust mite . The subjects in the study were divided into two groups : one of twelve patients receiving only a st and ard course of six grade d injections at weekly intervals and the other of sixteen patients receiving the same course followed by a maintenance course comprising six injections of the highest strength ( 400 N.U. ) . Approximately half the patients in each of these groups were on placebo . Assessment was based on the patient 's and doctor 's impression of the response to the treatment using a daily symptom record card and clinical observation of the patient at regular intervals . The overall assessment was grade d in accordance with the following four point scale : very good , good , same and worse . Results showed that the pa tients receiving Migen as a 6-injection course responded better than patients receiving placebo ; moreover , patients who received 6 maintenance injections of Migen gave a very good or good response compared to those who were su bmi tted to 12 injections of placebo and also compared to those receiving the st and ard course . Particular notice was taken of the side effects of the vaccine . Migen proved to be a good and and safe method of treating bronchial asthma due to house dust mite ( D. pteronyssinus ) Fifteen grass pollen -- sensitive asthmatic patients were selected from 200 patients with grass pollenosis on the basis of positive SPTs and RASTs that were restricted to grass pollens ( except Bermuda grass ) , no previous IT , and residence and occupation in an area monitored by serial pollen counts . They underwent a double-blind trial of specific IT with a mixture of three grass pollen -- aqueous extracts ( velvet , sweet vernal , and timothy ) or placebo . After 10 mo , the mean maintenance dose of pollen extract ( assayed by RAST inhibition ) in eight actively treated patients was 6000 RAST units ( range 3000 to 8000 ) and the mean total dose was 18,700 RAST units ( range 10,200 to 30,000 ) . Results were assessment done by the following clinical and immunological data : ( 1 ) during the pollen season , daily symptom scores ; ( 2 ) PD 20 % FEV1 , IgE antibody to timothy by RAST in serum and in nasal secretions , serum IgG antibody to purified timothy allergen D by solid-phase radioimmunoassay , and the four IgG subclass antibodies by enzyme immunoassay were all measured before treatment and before and after the pollen season . Symptom scores of both treated patients and controls correlated with pollen counts ( R = 0.88 , p less than 0.05 and R = 0.71 , p less than 0.05 , respectively ) . There was a significant difference between the mean symptom score values of treated patients versus controls ( Kruskal-Wallis test , p less than 0.001 ) . No significant differences or changes either in the PD 20 % FEV1 or IgE antibody to timothy in serum and nasal secretions were found in the two groups before or after IT . ( ABSTRACT TRUNCATED AT 250 WORDS 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 A double-blind controlled trial of house dust mite hyposensitization was carried out in 14 patients with asthma , who were hypersensitive on skin testing to the house dust mite alone . Measurements were made , using a Wright 's peak flowmeter , during the 15-month trial period . Pre caution s were taken in the home to reduce the mite population . At the end of the trial , no clinical improvement was noted subjectively or objective ly , despite a reduced bronchial sensitivity to allergen in the treated group . The role of the house dust mite as a cause of asthma is discussed In 22 patients with cat asthma who were highly sensitive to cat , we compared , double-blind , the effects of immunotherapy with cat-hair and d and er extract ( 11 patients ) with effects of placebo ( 11 patients ) . Patients were matched by the dose of the cat extract expressed in Food and Drug Administration ( FDA ) units of Fel d I ( previously called cat allergen 1 ) required for end point reaction in intradermal skin test end point titration ( STEPT ) , for in vitro leukocyte histamine release ( LHR ) , and for the dose of cat extract producing a 20 % fall in FEV1 ( cat-extract PD20 ) in bronchoprovocation test . Patients were matched also for bronchoprovocation dose of methacholine producing a 20 % fall in FEV1 ( methacholine PD20 ) . Patients were r and omly assigned to one of two treatment groups . During immunotherapy , doses were increased to maintenance dose of 4.56 FDA units of Fel d I , or , if this were less , to the highest tolerated dose . Systemic reactions to cat-extract immunotherapy were mild and infrequent . Before and during immunotherapy , we measured ( in FDA units of Fel d I ) cat-extract PD20 , cat-extract intradermal STEPT , cat-extract in vitro LHR , serum levels of cat IgG and cat IgE , and methacholine PD20 . After they had received 1 year of immunotherapy , patients receiving cat extract , in comparison to patients receiving placebo , had decreased cat-extract PD20 ( p less than 0.01 ) , diminished responses to cat-extract intradermal STEPT ( p less than 0.025 ) , increased IgE antibodies toward cat extract ( p less than 0.01 ) , increased IgG antibodies toward cat extract , Fel d I , and cat albumin ( p less than 0.001 ) , but no significant change in cat-extract in vitro LHR or in methacholine PD20 . We conclude that cat-extract immunotherapy was well tolerated , significantly decreased skin and bronchial responses to cat extract , and significantly increased IgE antibodies to cat extract and IgG antibodies to cat extract , Fel d I , and cat albumin A double blind controlled trial of a house mile fortified house dust vaccine was carried out in forty‐two asthmatic patients between the ages of 6 and 15 years . Improvement in height and weight was shown in eight of twenty‐one children receiving the active therapy compared with one of twenty‐one children receiving placebo injections . No difference between the two groups was shown by respiratory function testing or chest examination BACKGROUND The prevalence of allergy to natural rubber latex proteins has increased over recent years among healthcare professionals but also in children undergoing multiple operations . Exposure to the antigen mainly occurs through the respiratory mucosa and the percutaneous route . Clinical manifestations range from urticaria to angioedema , rhinoconjunctivitis , bronchial asthma , or anaphylactic shock . Preventive measures have been proposed to reduce the risk of sensitization by using only powder-free or synthetic gloves and latex-free material in operating units , but this is not always possible . OBJECTIVE The aim of this study was to investigate the efficacy and safety of specific immunotherapy in sensitized workers . METHODS Seventeen patients with latex skin allergy and rhinitis ( 9 of whom also had asthma ) were included in this r and omized , double-blind , placebo-controlled trial ( 9 in the active group and 8 in the placebo group ) for 1 year . Treatment started with a 2-day course of rush immunotherapy in hospital . Treatment efficacy was assessed after 6 and 12 months by means of symptom and medication scores recorded on diary cards . Conjunctival provocation tests were also performed . RESULTS Patients in the active treatment group had a significantly lower total rhinitis score after 6 ( P < . 04 ) and 12 months ( P < .05 ) , conjunctivitis score after 6 months ( P < . 02 ) , and cutaneous score after 12 months ( P < .03 ) than in the placebo group . Asthma symptoms after 6 or 12 months of treatment were not significantly different between the two groups after adjustment for baseline values . The global medication score was markedly decreased in the latex-treated group . A significant difference in conjunctival reactivity was observed in favor of the active group : the number of patients for whom the threshold dose was increased after 12 months of treatment was significantly greater in the active group than in the placebo group ( P < .02 ) . Most injections were well tolerated , but several adverse effects , including hypotension , urticaria , wheezing , and pharyngeal edema , were observed . CONCLUSION The clinical benefits observed during the present study included a significant improvement of rhinitis , conjunctivitis , and cutaneous symptoms . Immunotherapy also decreased allergen-specific conjunctival reactivity . Latex-specific immunotherapy may allow sensitized personnel to remain at work , but further trials need to be conducted in a larger number of patients We evaluated the clinical efficacy and immunologic changes associated with the administration of tyrosine-adsorbed Dermatophagoides pteronyssinus ( Dpt ) extract . The study was carried out in a double-blind , placebo-controlled fashion in 18 patients with Dpt-induced asthma during a trial period of at least 12 mo . Patients initially received six increasing doses once a week ; the top dose of 400 Noon units was repeated at monthly intervals . Clinical response was on the basis of diary cards on which symptoms and medication scores were recorded ; daily lung function measurements were made by use of a mini Wright 's peak flow meter . The entire spectrum of physiologic measurements , medications , and symptoms were taken into account by computing daily scores over a 2-week period . Total IgE , Dpt-specific IgE antibodies , and leukocyte histamine release were measured before treatment and during hyposensitization . Changes in Dpt-specific IgG were evaluated with a double antibody antigen-binding assay by use of the purified fraction of mite extract F4P1 . All patients had measurable levels of IgG antibodies to F4P1 before treatment . Treatment with tyrosine-adsorbed Dpt extract result ed in a significant increase of specific-IgG antibodies in the treated group at 2 and 6 mo only ( nonparametric rank sum test ) . Variations relative to the pretreatment values of total and specific IgE were not significantly different in the treated and in the control patients after 2.6 and 12 mo . No significant decrease in leukocyte sensitivity was observed after treatment . It was only possible to demonstrate a significant diminution in the mean medication score ( nonparametric sign test ) in the first 6 mo for the treated group ; independently of the beginning of the treatment , the treated group demonstrated a reduction of the mean medication score and an improvement in peak expiratory flow rate lung function before the midsummer months when seasonal increase in mite density can occur . Particular attention was paid to the method ological problems raised during this study and inherent in a trial in house dust-mite asthma 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 The clinical efficacy of sublingual immunotherapy ( SLIT ) has been demonstrated , but its mechanism of action is still controversial . The most recent experimental observations suggest that a critical role in the modulation of immune response is sustained by Th2 cytokines , such as interleukin-4 ( IL-4 ) , IL-5 and IL-13 , by co-stimulatory molecules , such as CD40 on B cells , and by hormones and neuropeptides . To better underst and whether SLIT affects immune responses we used a double-blind placebo-controlled design . Eighty-six children with mild asthma due to allergy to Dermatophagoides pteronyssinus ( 33 of whom also had rhinoconjunctivitis ) were r and omly assigned SLIT ( n = 47 ) or placebo ( n = 39 ) . We assessed symptom scores using diary cards of each patient and determined the expression of CD40 on B cells and the serum concentration of ECP , IL-13 , prolactin ( PRL ) and ACTH at enrolment and after 6 months of therapy . We observed a significant reduction in asthma and rhinitis scores in the immunotherapy group compared with the placebo group , no variation in CD40 and ACTH , but a significant decrease in ECP , IL-13 and PRL after 6 months of therapy ( p < 0.01 ) . Our results confirm the efficacy and safety of SLIT , and lead us to believe that it could modulate the synthesis of Th2 cytokines , as revealed from the decrease of IL-13 . In addition , the reduction of PRL might be a signal of reduced activation of T lymphocytes BACKGROUND Both specific immunotherapy ( SIT ) and nasal steroid ( NS ) have been shown to effectively reduce symptoms of allergic rhinitis . Although a number of investigators have convincingly shown anti-inflammatory effects of both treatments in separate studies , few comparative studies have been performed . OBJECTIVE The purpose of this study was to compare the effects of preseason SIT with a st and ardized allergen extract and NS in seasonal allergic disease ( rhinoconjunctivitis and asthma ) . METHODS We examined 41 patients allergic to birch pollen , 21 with rhinoconjunctivitis and 20 with both rhinoconjunctivitis and asthma ; they were treated in a r and omized , double-blinded comparative study with birch SIT and NS ( budesonide 400 microg daily ) . Bronchial hyperresponsiveness was measured before and during the season . Changes in eosinophil number , eosinophil cationic protein , and eosinophil chemotactic activity ( ECA ) in peripheral blood were investigated . RESULTS Symptoms of rhinoconjunctivitis increased significantly less in the NS-treated patients than in the SIT-treated patients during the final 2 weeks of the season ( P = .03 and P = .04 , respectively ) . Seasonal peak expiratory flow values decreased significantly only in the NS-treated patients ( P = .01 ) . In the NS-treated patients , bronchial hyperresponsiveness increased significantly during the season ( P = .0001 ) ; however , SIT treatment prevented seasonal PC(20 ) increase in the asthmatic patients . Measurement of blood eosinophils , eosinophil cationic protein , and eosinophil chemotactic activity demonstrated significant seasonal increase only in the NS-treated asthmatic patients . CONCLUSION Treatment with NS was more effective than short-course preseason SIT in reducing symptoms of rhinoconjunctivitis ; however , the 2 therapies were equivalent in terms of the need for rescue medication . SIT prevented seasonal increase in bronchial hyperresponsiveness , eosinophil number , eosinophil cationic protein , and eosinophil chemotactic activity only in asthmatic patients . The mechanisms underlying bronchial hyperresponsiveness developing during allergen exposure in rhinitis might be different from those operating in asthma A double‐blind statistically controlled study was carried out on ninety‐six patients with Type I allergy to D. pteronyssinus and a history of perennial asthma and /or rhinitis . Forty‐eight received injections of an extract of Dermatophagoides pteronyssinus and forty‐eight controls received injections of carbol saline . Both groups were closely comparable in all respects . Ninety‐one were available for assessment , forty‐six controls , and forty‐five treated Forty-one patients ( 21 adults and 20 children ) with cat d and er-or dog d and er-induced asthma were selected for immunotherapy with st and ardized and partially purified cat- or dog-d and er extracts by use of a double-blind protocol . Based on sex , age , clinical history , results of bronchial challenge , and crossed radioimmunoelectrophoresis studies , the patients were stratified in matched pairs , and the treatment alternatives were distributed r and omly among the pairs . Twenty-two patients treated with allergen ( 15 with cat allergen and seven with dog allergen ) and 17 patients receiving placebo therapy completed the first year of treatment . In the cat allergen-treated group , the bronchial sensitivity toward cat and histamine decreased ( p less than 0.001 and p less than 0.05 , respectively ) . Measured by bronchial challenge , the cat allergen-treated patients could tolerate 11 times more allergen at the end than at the start of the study , and they also demonstrated a tendency toward less pronounced symptoms after exposure to cat and dog allergens . No significant changes were observed in the dog allergen treated- or placebo-treated groups . The adverse effects in general were negligible except for some systemic side effects during rush hyposensitization , especially among the children , but these were mild and responded promptly to treatment Allergen-specific immunotherapy ( ASIT ) with fungal extracts has been beset by safety and efficacy problems , which result mainly from qualitative and quantitative variations . Little has been published on the safety and efficacy of these extracts . The objective was to analyze the safety and efficacy of ASIT with an Alternaria alternata extract . A total of 28 patients were selected with rhinitis and /or bronchial asthma because of Alternaria allergy and monosensitization to molds . The patients were r and omized to an active ASIT or placebo group , both groups on a conventional immunotherapy schedule ( increasing weekly doses until maintenance dose and then monthly doses ) . Adverse reactions were classified with the European Academy of Allergology and Clinical Immunology system . Clinical efficacy was analyzed for a year with symptom/medication diary cards , peak expiratory flow ( PEF ) measures , clinical severity score , severity of symptoms ( visual analog scale ) , subjective evaluation of treatment by the patient and the physician , and a quality of life question naire . Twenty-three patients completed the study ; all reached the established maintenance dose with only two mild adverse reactions in the whole sample . Significant improvements were found after 6 months in respiratory symptoms in the active treatment group , and in all symptoms in both groups . PEF increased significantly in the active treatment group but not in the placebo group . The severity of asthma decreased in the active treatment group , and the severity of rhinitis decreased in both groups . Visual analog scale scores for severity of symptoms improved in all phases in the active treatment group , but only after 12 months in the placebo group . Physicians judged the disease course as significantly better in the active treatment group . ASIT with the A. alternata extract was safe , with clinical improvements after one year of treatment A multicenter , double blind clinical study on two homogeneous , treated and untreated groups , has allowed an objective appreciation of the results of specific immunotherapy using the alpha-fraction of D. pteronyssinus in asthma . A statistically significant difference was seen of the consumption of drugs in the treated group and in infants of less than 5 years ( p = 0.047 ) . Tolerance , evaluated as a function of local and secondary effects was excellent and comparable in the two groups The effect of hyposensitization ( HS ) upon the allergen evoked immediate asthmatic reaction ( IAR ) , late asthmatic reaction ( LAR ) and upon bronchial reactivity towards histamine was examined . Eighteen young asthmatic patients were studied using a double-blind , placebo-controlled design . All were allergic to house dust mite ( HDM ) and demonstrated an IAR and a LAR after bronchial provocation with HDM . Furthermore , all , except one child , demonstrated bronchial hyperreactivity towards histamine ( median provocative dose producing a 20 % fall in forced expiratory volume in one second ( PD20 ) histamine = 0.19 mg.ml-1 , range : 0.02 - 8 mg.ml-1 ) . The subjects were r and omly divided into two groups to receive HDM or placebo injections during one year . After the one year period , the IAR was less severe in the subjects who received HDM injections ( p = 0.02 ) , while this reduction was not observed in the subjects who received placebo injections . Also , in the HDM group a small but significant increase of the median PD20 HDM was observed ( p = 0.04 ) . Furthermore , the LAR was less severe in the subjects who received HDM injections ( p = 0.02 ) , while the subjects who received placebo injections showed the same severity of LAR after one year ( p = 0.44 ) . Histamine reactivity did not change after HDM injections or after placebo injections . Thus , HS reduces the severity of the IAR and LAR without any change in histamine reactivity 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 BACKGROUND Liposomes are potent immunologic adjuvants and have been proposed as allergen carriers in allergy vaccination . OBJECTIVE We sought to investigate the efficacy and safety of vaccination with Dermatophagoides pteronyssinus encapsulated in liposomes . METHODS We conducted a double-blind , placebo-controlled study . Fifty-five asthmatic patients sensitized to mites were r and omly assigned vaccination with D pteronyssinus extract encapsulated in liposomes or empty liposomes for a period of 12 months . The principal parameters were symptom and medication-consumption scores . The percentage of healthy days ( ie , days without medication and with absent or mild symptoms ) was calculated . Immediate and late skin test results , allergen bronchial challenge test results , and allergen-specific serum immunoglobulin levels were evaluated before and after treatment . RESULTS All clinical scores were markedly lower in the active group than in the placebo group after vaccination . Nearly half ( 45.8 % ) of the patients actively treated reduced their symptom and medication scores by at least 60 % versus only 12 % of patients receiving placebo treatment ( P = .0388 ) . The percentage of healthy days in the active group rose from 10.5 % before treatment to 64.5 % afterward ( P = .0008 ) . Reduction in organ sensitivity was demonstrated by skin prick test responses ( P < .01 ) , late-phase response after intradermal testing ( P = .009 ) , and bronchial challenge test results ( P = .026 ) in the active group . Serum levels of specific IgG increased throughout the treatment , whereas specific IgE levels showed only an initial transient increase . No change in these parameters was observed in the placebo group . Vaccination was well tolerated , and no subcutaneous nodules appeared . CONCLUSION Vaccination with D pteronyssinus encapsulated in liposomes is an effective and safe treatment for allergy-induced asthma OBJECTIVE To study the efficacy and safety of specific sublingual immunotherapy with dermatophagoides farinae drops in the treatment of cough variant asthma in children . METHODS A total of 106 children aged 4 - 14 years old with cough variant asthma and positive skin prick test responses to dermatophagoides farinae allergens were r and omly divided into two groups : SLIT group ( n=53 ) , which received specific sublingual immunotherapy with dermatophagoides farinae drops as well as st and ardized treatment and conventional treatment group ( n=53 ) , which received st and ardized treatment alone . Improvement in cough/asthma symptom scores and the time taken for symptoms to improve were observed after treatment . Serum eosinophil ( EOS ) level and peak expiratory flow ( PEF ) were measured after treatment . The side effects were observed . RESULTS Compared with the conventional treatment group , the SLIT group showed significant decrease in symptom scores and serum EOS level and significant increase in PEF ( P<0.05 ) . The time at which symptoms began to improve in the SLIT group was earlier than in the conventional treatment group ( P<0.05 ) . The effective rate in the SLIT group was significantly higher than in the conventional treatment group ( 85 % vs 68 % ; P<0.05 ) . Local reactions such as redness , swelling , and itching occurred in some children of the SLIT group but disappeared on the following day . CONCLUSIONS Specific sublingual immunotherapy with dermatophagoides farinae drops is an effective and highly safe treatment for cough variant asthma in children BACKGROUND The worldwide increased prevalence of allergic diseases , and especially of respiratory allergy , is paralleled by increased health costs . This requires consideration of the cost to efficacy ratio of the available treatment to identify the optimal choice . OBJECTIVE To compare the different economic relevance , over a long evaluation time , of symptomatic pharmacologic therapy and sublingual immunotherapy ( SLIT ) in patients with allergic asthma . METHODS Seventy patients with perennial allergic asthma , sensitized to dust mites , were enrolled ; 50 of these patients were treated with SLIT against house dust mites and 20 were treated with symptomatic drugs . The patients were evaluated for 2 years after discontinuing immunotherapy , which was performed for 3 years , to obtain a more complete follow-up . Symptom scores , medication scores , and all other direct medical costs were evaluated with a specific question naire . RESULTS Patients treated with SLIT plus drugs had a higher mean annual cost in the first year of SLIT treatment compared with patients only receiving drug treatment , but the mean annual cost became significantly lower since the end of SLIT both in the whole population and in the subgroups defined by disease severity . CONCLUSION The economic advantage measured alongside this prospect i ve observational study was long lasting and still present at the fifth year of the follow-up ( 2 years after discontinuing SLIT ) and could positively be related to the persistent good clinical control of patients Background : A r and omized double‐blind , placebo‐controlled study was conducted in patients allergic asthma sensitized to Dermatophagoides pteronyssinus We carried out a double-blind clinical trial of immunotherapy on 35 patients sensitized to the storage mite Lepidoglyphus destructor ( Ld ) . Before and after 12 months of specific hyposensitization ( Abelló Lab . , Spain ) we performed in vivo ( skin tests with Ld , methacholine and challenge tests ) , and in vitro tests ( specific IgE , IgG , IgG1 and IgG4 to Ld and specific IgE , IgG , IgG1 and IgG4 to their major allergen Lep dI ) . We also monitored the efficacy and safety of the immunotherapy with clinical and analytical controls ( symptoms and medication score , detection of immune complexes ) . After therapy we found a significant decrease in specific skin reactivity , dose of positive challenge tests , and hyperresponsiveness to methacholine . Sputum eosinophilia decreased . Specific IgE to Ld was increased and we also observed an increase in specific IgG1 and IgG4 to Ld and Lep DI . The placebo group showed no changes in these variables . There were no severe secondary reactions after treatment with the extract . Patients -self-evaluation was favourable and their labour absence decreased . No development of circulating immune complexes was associated with this immunotherapy Thirty‐one adult patients with asthma caused by house‐dust mites ( HDM ) were included in this placebo‐controlled , double‐blind study to evaluate the efficacy and safety of specific immunotherapy ( SIT ) with biologically st and ardized extracts of HDM . The specific diagnosis was confirmed by skin prick tests , specific IgE , and bronchial provocation tests with HDM allergens . The patients were r and omized to receive active treatment with extracts of either Dermatophagoides pteronyssinus ( Dpt ) or D. farinae ( Dfa ) ( Alutard ® SQ , ALK , Denmark ) or placebo injections . Twenty‐three patients completed the study . After 1 year of treatment , we found a clinical ly important and significant reduction in both asthma medicine consumption ( inhaled steroids 38 % and p2–agonists 46 % ) and symptom score ( 57 % ) in the actively treated group , but not the placebo group . These findings were confirmed by a significant decrease in skin and bronchial sensitivity to HDM in the active group . Additionally , there was a significant difference in the patients ' scores for effect in favor of the actively treated group . Total IgE and specific IgE to HDM showed no significant changes before and after treatment for either group . Spirometric lung‐function measurements showed a significant increase in forced expiratory volume in 1 s ( FEV1 ) from 85 % before to 89 % of predicted values after treatment for the actively treated group . Peak‐flow measurements at home showed no significant changes during the study . It is concluded that allergen SIT is an effective treatment in adult patients suffering from asthma due to HDM 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 Injections of allergens are widely prescribed for patients with asthma , but little is known about the effectiveness of immunotherapy . METHODS We conducted a double-blind , placebo-controlled trial of multiple-allergen immunotherapy in 121 allergic children with moderate-to-severe , perennial asthma . The children , who required daily medication for their asthma , were r and omly assigned to receive subcutaneous injections of either a mixture of up to seven aeroallergen extracts or a placebo . Maintenance injections were continued for 18 months or longer . Medications were adjusted every two to three weeks on the basis of peak flow rates and symptoms . The principal outcome was the daily medication score . Bronchial sensitivity to methacholine ( the concentration provoking a 20 percent decrease in the forced expiratory volume in one second [ PC20 ] ) was measured twice yearly . RESULTS The median medication score declined from 5.4 to 4.9 in the immunotherapy group ( P<0.001 ) and from 5.2 to 5.0 in the placebo group ( P<0.001 ) , but there was no significant difference between the groups ( P>0.6 ) . The number of days on which oral corticosteroids were used was similar in the two groups . Partial or complete remission of asthma occurred in 31 percent of the immunotherapy group and in 28 percent of the placebo group ( P>0.5 ) . There was no difference between the groups in the use of medical care , symptoms , or peak flow rates . The median PC20 increased significantly in both groups , but again with no difference between the two groups . CONCLUSIONS Immunotherapy with injections of allergens for over two years was of no discernible benefit in allergic children with perennial asthma who were receiving appropriate medical treatment This study investigated the specificity and efficacy of immunotherapy with Artemisia vulgaris ( Artemisia ) extract . We studied 25 patients with a more than two year lasting history of seasonal rhinoconjunctivitis and who had only two clinical ly important allergies , either to Artemisia and Betula verrucosa ( Betula ) or to Artemisia and Phleum pratense ( Phleum ) . Patient selection was r and omized and evaluation of results was conducted in double blind fashion . Twenty patients completed two years of specific immunotherapy . Nine patients were treated with extracts of Artemisia and 11 with extracts of either Betula ( n = 3 ) or Phleum ( n = 8) . Treatment with Artemisia was followed by a significant decrease in skin sensitivity ( p < 0.05 ) and eye sensitivity ( p < 0.01 ) to Artemisia but not to Betula/phleum . No significant decrease was observed in medicine consumption or symptom scores . Patients treated with Betula or Phleum experienced a significant decrease in skin sensitivity to Betula or Phleum ( p < 0.001 ) , and eye sensitivity to Betula or Phleum ( p < 0.05 ) , but not to Artemisia and had significant decreases in medicine and symptom scores ( p < 0.05 ) in Betula/phleum seasons but not in the Artemisia season . The treatment was both effective and specific with the one unexplained exception that both patient groups ( Artemisia and Betula/Phleum ) decreased their skin sensitivity to Artemisia A double‐blind study on hyposensitization ( HS ) with two extracts prepared from the house dust mite Dermatophagoides pteronyssinus ( Dp ) was performed on a group of asthmatics with bronchial sensitivity to Dp . In 18 patients , aluminiumhydroxide was added to the Dp‐extract to give a depot effect ( Dp‐group ) . Nineteen patients were treated with a similar extract in which allergenicity had been reduced by coupling to monomethoxy‐polyethylene glycol ( mPEG‐Dp‐group ) . This extract had previously been shown to have less effect on clinical symptoms and skin sensitivity compared to the Dp‐extract . In the Dp‐ and mPEG‐Dp‐groups , 778 and 675 injections were administered . Fifteen and 12 patients in the Dp‐ and mPEG‐Dp‐groups had systemic reactions ( P > 0.05 ) . The frequency of injections giving systemic reactions was reduced in the mPEG‐Dp‐group : 5.1 % compared to 9.0 % in the Dp‐group ( P < 0.01 ) . In the mPEG‐Dp‐group , reactions were mild to moderate , mainly late‐occurring asthma and urticaria , whereas two episodes of anaphylaxis and four of severe asthma occurred in the Dp‐group . The reduction in side effects seems promising , but a further dose increase in the mPEG‐Dp‐group would be necessary to compare the side effects of doses with equal therapeutic effectiveness . High frequency of late local reactions made dose increase impossible with the present slightly modified extract . The systemic side effects occurred more frequently in patients highly skin test‐sensitive to Dp prior to treatment . All patients skin test‐positive to : ≤ 100 BU had systemic reactions . Systemic side effects could not be predicted from the size of previous local reactions 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 Specific immunotherapy is still widely used in grass-pollen allergy , but its side effects may limit its use . We tested the safety and efficacy of a formalinized high-molecular-weight allergoid prepared from a mixed grass-pollen extract with two injection schedules in a double-blind , placebo-controlled study . Eighteen patients received placebo , 19 received the low-dose schedule ( maximal dose : 2000 PNU ) and 20 received the high-dose schedule ( maximal dose : 10,000 PNU ) . Only one patient presented a systemic reaction of moderate severity for a dose of 1200 PNU . Before the onset of the pollen season , patients had a nasal challenge with orchard grass-pollen grains , a skin test titration , and the titration of serum-specific IgG. Both groups of patients presented a significant reduction in nasal and skin sensitivities and a significant increase in IgG compared to placebo . Symptoms and medications for rhinitis and asthma were studied during the season , and both groups receiving allergoids had a significant reduction of symptom-medication scores for nasal and bronchial symptoms . There was a highly significant correlation between nasal symptom-medication scores during the season and the results of nasal challenges . High-molecular-weight allergoids are safe and effective 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 Thirty patients with asthma and /or monosensitized allergic rhinitis caused by grass pollen whose ages ranged from 15 to 35 years were selected . Two groups were established at r and om : an active group and a placebo group , and a double‐blind study was done on treatment with immunotherapy for a period of 3 continuous years , with initiation doses administered according to the rush immunotherapy technique . Grass‐pollen allergen extract Alutard SQ and histamine as a placebo were used . The objective parameters of efficacy evaluated were end‐point cutaneous tests , conjunctival provocation , bronchial provocation , and symptom/medication scores , as well as specific immunoglobulin determinations . The statistical evaluation of the results was significant for the differences existing between the initial and final time of the active group , and there were significant differences between the two groups for all of the parameters considered . We found no relationship between clinical improvement and the range of specific immunoglobulin E values . Regarding the safety of the treatment , systemic adverse effects were manifested only in the initial phase ( rush immunotherapy ) . and were easily controlled by treatment . We conclude that the efficacy and safety of immunotherapy with grass pollen make it possible to consider this treatment fundamental in these patients Twenty‐four asthmatics allergic to cat and /or dog d and er were included in a study to examine the efficacy and safety of immunotherapy ( IT ) with partially purified , st and ardized extracts of cat or dog d and er . In the first placebo controlled , double‐blind part of the study , 10 patients were treated with extracts of both eat and dog , 12 with cat extracts and 2 with dog extracts . Fifteen patients received active IT and 9 placebo injections . Patients treated with both extracts received active extracts only , or placebo only . Bronchial allergen challenge after 5 months demonstrated a significant fall in sensitivity to eat ( P = 0.04 ) in patients treated with cat extracts . No significant changes were found in sensitivity to dog after treatment with dog d and er extract or in the placebo groups . During this period , bronchial sensitivity to histamine did not change significantly in any of the groups . To examine the effect of more prolonged IT , 19 patients allergic to cat ( 17 ) and /or dog ( 9 ) were treated for 12 months . Bronchial sensitivity to cat decreased further ( P = 0.003 ) , while no significant change was found in dog extract‐treated patients . In cat extract‐treated patients a significant decrease in bronchial histamine sensitivity developed ( P = 0.02 ) . Systemic side effects were few , but in some eases , local side effects were a dose‐limiting factor . This study demonstrated that IT with cat extract may benefit cat‐allergic asthmatics , whereas no influence of IT with dog extract was detected in dog‐sensitive asthmatics OBJECTIVE To compare the efficacy of sublingual immunotherapy ( SLIT ) combined with inhaled corticosteroids ( ICS ) versus ICS alone in children with mild and moderate dust mite allergic asthma . METHODS Thirty-two children with mild and moderate dust mite allergic asthma were r and omly divided into two groups : SLIT+ICS ( n=18 ) and ICS alone ( n=14 ) . A total of 30 children completed the one year clinical observation . The amount of ICS administration , the day and night symptom scores , skin-prick test and pulmonary function test results , serum specific immunoglobulin E ( sIgE ) and G4 ( sIgG4 ) levels and visual analog scale ( VAS ) scores were compared between the two groups . RESULTS By the end of one year the SLIT+ICS group had significantly decreased amount of ICS administration than the ICS alone group . Compared with the ICS alone group , the day and night symptom scores decreased , FEF25 - 75 % increased significantly , and serum sIgE levels and VAS scores were significantly reduced in the SLIT+ICS group . There were no statistical differences in the skin-prick test results , and FEV1 and sIgG4 levels between the two groups . No severe adverse events occurred in both groups during the follow-up period . CONCLUSIONS SLIT combined with ICS may produce a better efficacy than ICS alone in the improvement of day and night symptoms , pulmonary function and VAS scores in children with dust mite-allergic asthma Background : Few placebo‐controlled studies have examined the effect of allergen specific immunotherapy ( SIT ) on early and late phase asthmatic reactions . In this placebo‐controlled study we have investigated the effect of 1 year of SIT with st and ardized birch pollen extract on early and late phase asthmatic reactions in adult asthmatic patients Background : We assessed the efficacy of preseasonal local allergoid immunotherapy in a group of children with asthma and /or rhinitis and /or rhinoconjunctivitis due to grass pollen The effect of immunotherapy on the production of histamine-releasing factor ( HRF ) by mononuclear cells ( MNC ) from patients with seasonal asthma was investigated in a double-blind , placebo-controlled , r and omized study . Twenty-four patients with asthma were r and omly divided into a placebo-treated group and a grass pollen-treated group . In vitro production of HRF by MNCs and the provocative concentration of histamine that causes 20 % fall in FEV1 were measured before and after immunotherapy , and symptoms were monitored during the pollen season . MNCs from the patients were either cultured alone , spontaneous HRF production ( spHRF ) , or in the presence of grass allergens ( grass-stimulated HRF production ) , and the supernatants were assayed for HRF activity with basophils from a single donor after the study . We found that MNCs from patients with seasonal asthma to grass pollen spontaneously produce substantial amounts of HRF . The group of patients treated with placebo developed typical symptoms in the pollen season and also an increase in HRF production . In contrast , patients treated with grass pollen demonstrated reduced symptoms and no increase in spHRF production . A high degree of correlation between spHRF productions and symptom scores in both treated groups was noted . After 2 years of immunotherapy , allergen-stimulated HRF production decreased significantly , whereas spHRF production decreased significantly only in the patients who were clinical ly benefitted . The change in the provocative concentration of histamine that causes 20 % fall in FEV1 during the pollen season highly correlated with the change in HRF production . The results of this study suggest that HRF might be involved in the pathogenesis of atopic asthma Twenty-eight patients ( 14 in an active treatment group and 14 in a placebo group ) with rhinoconjunctivitis and asthma caused by cat hypersensitivity took part in a placebo-controlled , r and omized , double-blind study to evaluate the risk-benefit quotient of the maintenance dose corresponding to 13.2 micrograms Fel d I antigen . The cat extract was biologically st and ardized and quantified with monoclonal antibodies ( 100 biological units : 33 microgram of Fel d I antigen , 650 micrograms of albumin , and 99 micrograms of Fel d Bd/K30 antigen ) . After 1 year of treatment , the systemic reactions to cat extract immunotherapy were mild and infrequent . Improvement was observed in the active treatment group in comparison with the placebo group in the medication-symptoms score ( p < 0.001 ) ; in skin prick test ( p < 0.001 ) , conjunctival provocation test ( p < 0.001 ) , and allergen bronchoprovocation test ( p < 0.05 ) results , and in nonspecific bronchial hyperreactivity measured with methacholine , which was not statistically significant . This study demonstrates the favorable risk-benefit quotient of the dose of 13.2 micrograms of Fel d I antigen , which may serve as a future reference in defining the optimum dose and appropriate proportion of antigens that should be administered in cat extract immunotherapy 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 |
636 | 29,121,288 | The primary outcomes were 24 h morphine i.v .
Based on trials with low risk of bias , pregabalin may have a minimal opioid-sparing effect , but the risk of SAEs seems increased . | Pregabalin has demonstrated anti-hyperalgesic properties and was introduced into acute pain treatment in 2001 .
Our aim was to evaluate the beneficial and harmful effects of pregabalin in postoperative pain management . | BACKGROUND Although various analgesics have been used , postoperative pain remains one of the most troublesome aspects of tonsillectomy for patients . OBJECTIVE The aim of the present study was to evaluate the effectiveness of premedication using pregabalin compared with placebo ( diazepam ) on postoperative pain control in patients undergoing tonsillectomy . METHODS Forty-eight adult patients were r and omly divided into a control group and a pregabalin group . Preoperatively , patients in the control group received 4 mg diazepam orally as placebo , whereas those in the pregabalin group received 300 mg pregabalin orally . All participants were provided with patient-controlled analgesia using fentanyl for 24 hours after surgery . Postoperative pain treatment included acetaminophen 650 mg three times daily for 8 postoperative days . The primary outcome measure was the total amount of patient-controlled fentanyl consumption after tonsillectomy . Secondary outcome measures were the number of injections of ketorolac tromethamine ( each 30 mg ) requested by patients , pain scores , overall satisfaction scores , drowsiness , nausea , dizziness , headache , and vomiting after the surgery . P < 0.05 was considered statistically significant . RESULTS The total amount of fentanyl dem and ed decreased significantly in the pregabalin group ( P < 0.001 ) . There were no significant differences in the number of ketorolac tromethamine injections , pain scores , overall satisfaction scores , drowsiness , nausea , dizziness , headache , and vomiting between the two groups . CONCLUSION Administration of 300 mg pregabalin prior to tonsillectomy decreases fentanyl consumption compared with that after 4 mg diazepam , without an increased incidence of adverse effects . TRIAL REGISTRATION KCT0001215 STUDY OBJECTIVE To investigate the efficacy of pregabalin for the relief of postoperative shoulder pain after laparoscopic gynecologic surgery . DESIGN Prospect i ve , r and omized , double-blind , placebo-controlled trial ( Canadian Task Force classification I ) . SETTING Tertiary referral center , university hospital . PATIENTS Fifty-six women undergoing elective laparoscopic gynecologic surgery between June 2012 and March 2013 . INTERVENTIONS Women in the study group received 75 mg pregabalin 2 hours before surgery and then every 12 hours for 2 doses , and women in the control group received an identical capsule and the same dosage of placebo . MEASUREMENTS AND MAIN RESULTS Visual analog scale ( VAS ) scores for shoulder pain and surgical pain at 24 and 48 hours after surgery were evaluated as primary outcome . Postoperative analgesics used and drug-related adverse events were also monitored . Patients in the pregabalin group had significantly lower postoperative VAS scores for shoulder pain at 24 hours , compared with the placebo group ( median , 23.14 [ range , 13.67 - 32.61 ] vs. 37.22 [ 27.75 - 46.64 ] ; p = .04 ) , and required less analgesic ( p = .01 ) . There were no significant differences in VAS scores for surgical pain and adverse events between the 2 groups ( p = .56 ) . CONCLUSIONS Perioperative administration of 75 mg pregabalin significantly reduced postoperative laparoscopic shoulder pain and amount of analgesic used Abstract We aim ed to investigate the role of preoperative single dose of pregabalin for attenuating postoperative pain and analgesic consumption in patients undergoing septoplasty . One hundred forty-three patients with ASA physical status I who underwent elective septoplasty were included in this prospect i ve , r and omized , and controlled study . Subjects were r and omized to receive pregabalin 75 mg , pregabalin 150 mg , and control group . All the medications were administered orally 1 hour before surgery . A st and ard septoplasty technique was used for all patients . Postoperative pain intensity was evaluated by a 0- to 100-mm horizontal visual analog scale ( VAS ) ( 0 , no pain ; 100 , worst imaginable pain ) . Total analgesic consumption 1 to 24 h after operation was also recorded . Visual analog scale scores in the 1st , 2nd , 4th , 6th , 12th , and 24th hour were significantly decreased in 75 and 150 mg pregabalin group compared with the control group , and VAS scores in the 12th and 24th hour were significantly decreased in pregabalin 150 mg compared with 75 mg . The 24th total analgesic consumption was significantly decreased in pregabalin 75 mg and 150 mg groups compared with the control group . In conclusion , a single preoperative oral dose pregabalin 75 or 150 mg is an effective method for reducing postoperative pain and total analgesic consumption in patients undergoing septoplasty BACKGROUND Preoperative administration of pregabalin is proposed as a promising way of enhancing postoperative pain control . Whereas a few studies have investigated the effect of pregabalin on postoperative opioid consumption , no study has focused on the influence on postoperative hyperalgesia . In this r and omized , triple-blinded , placebo-controlled study , we aim ed to demonstrate that a single , preoperative dose of pregabalin reduces postoperative opioid consumption , mechanical hyperalgesia , and pain sensitivity . METHODS Patients undergoing elective transperitoneal nephrectomy received 300 mg pregabalin or placebo 1 h before anaesthesia . After operation , patients received piritramide via a patient-controlled analgesia device . Pain levels and side-effects were documented . The area of hyperalgesia for punctuate mechanical stimuli around the incision was measured 48 h after the operation with a h and -held von Frey filament . Mechanical pain threshold was tested before and 48 h after surgery with von Frey filaments with increasing diameters . RESULTS In each group , 13 patients were recruited . Total piritramide consumption [ 77 ( 16 ) vs 52 ( 16 ) mg , P=0.0004 ] and the normalized area of hyperalgesia [ 143 ( 87 ) vs 84 ( 54 ) cm(2 ) , P=0.0497 ] were significantly decreased in the pregabalin group . There were no significant differences in mechanical pain threshold levels [ 1.20 ( 0.56 ) log(g ) vs 1.05 ( 0.58 ) log(g ) , P=0.6738 ] . No case of severe sedation was reported in both groups . No other side-effects were observed . CONCLUSIONS Our study has shown that preoperative administration of 300 mg pregabalin in patients undergoing transperitoneal nephrectomy reduces postoperative opioid consumption and decreases the area of mechanical hyperalgesia Prevention and treatment of postoperative pain continues to be a major challenge in postoperative care . Opioid analgesics , with their well-known side effects , continue to represent a cornerstone in postoperative pain control . Anticonvulsant medications are established treatments for neuropathic pain . Pregabalin ( S-[+]-3-isobutylgaba ) , a structural analog of gamma-Aminobutyric acid , has been used for the treatment of various neuropathic pain and also as an adjunctive therapy for adults with partial onset seizures . This study was thus taken up to primarily assess and compare the analgesic and anxiolytic effects of administering pregabalin and tramadol preoperatively for patients undergoing elective decompressive lumbar laminectomy . The study group included 75 patients between the ages of 20–60 years belonging to American Society of Anesthesiology-1 ( ASA ) and ASA-2 patients . The patients were r and omly allocated into three groups of 25 patients each . The placebo group received a placebo capsule , the tramadol group received a 100 mg capsule , while the pregabalin group received a 150 mg capsule orally 1 hour before anesthetic induction . Pregabalin showed statistically significant analgesic effects compared to placebo , but the effect was found to be less prevalent compared to tramadol . The need for rescue analgesia was the least prevalent in tramadol patients followed by pregabalin patients , and reached a maximum in the control group . Pregabalin showed statistically significant anxiolytic effects compared to placebo , and this was associated with less sedation in comparison to tramadol . Pregabalin had fewer numbers of postoperative complications of nausea , vomiting , and drowsiness in comparison to tramadol . The results of this study support the clinical use of pregabalin in the postsurgical setting for pain relief , as it is well tolerated , and usually presents with transient adverse effects BACKGROUND This was a r and omized , double-blinded clinical trial to study the effects of a single oral dose of pregabalin 150 mg in postoperative pain management after mastectomy . METHODS DESIGN forty nine patients ASA I or II , aged between 20 - 60 years , scheduled for mastectomy with or without axillary lymph nodes dissection ( ALND ) were recruited into this study . They were r and omized into two groups , placebo ( n = 24 ) or pregabalin ( n = 25 ) receiving either oral pregabalin 150 mg or placebo when called to operation theatre ( OT ) . The assessment of pain score were performed at recovery , 2 , 4 , 6 and 24 hours postoperatively at rest and on movement , using the verbal numeral rating score ( VNRS ) . RESULTS VNRS scores for pain at rest were lower in the pregabalin group at 2 ( p = 0.024 ) , 4 ( p = 0.006 ) and 6 ( p = 0.003 ) hours postoperatively , and also at 4 ( p = 0.005 ) and 6 ( p = 0.016 ) hours postoperatively on movement compared to the placebo group . Incidences . of dizziness were common , however , side effects such as nausea and vomiting , headache , somnolence and visual disturbance were low and comparable in both groups . CONCLUSION A single dose of 150 mg pregabalin given preoperatively compared to placebo significantly reduced postoperative pain scores after mastectomy BACKGROUND AND OBJECTIVES Adding novel adjunctive drugs like gabapentinoids to multimodal analgesic regimen might be reasonable for lessening postoperative pain scores , total opioid consumption and side effects after percutaneous nephrolithotomy . We aim ed to evaluate the effect of pregabalin on postoperative pain scores , analgesic consumption and renal functions expressed by creatinine clearance ( CrCl ) and blood neutrophil gelatinase-associated lipocalin ( NGAL ) and cystatin C ( Cys C ) levels in patients undergoing percutaneous nephrolithotomy ( PCNL ) . METHODS 60 patients undergoing elective PCNL were enrolled in the study . Patients were r and omized to oral single dose 75 mg pregabalin group and a control group . Visual Analog Scale pain scores ( VAS ) , postoperative intravenous morphine consumption during the first 24 postoperative hours , serum NGAL , Cys C levels and creatinine clearance ( CrCl ) was measured preoperatively and post-operatively at 2nd and 24th hour . RESULTS Postoperative VAS scores were significantly decreased in the pregabalin group at the postoperative 30th min , 1st , and 2nd hour ( p = 0.002 , p = 0.001 and p = 0.027 , respectively ) . Postoperative mean morphine consumption was statistically significantly decreased for all time intervals in the pregabalin group ( p = 0.002 , p = 0.001 , p = 0.001 , p = 0.001 , p < 0.001 , respectively ) . No statistically significant differences were found between the two groups with regard to CrCl , or Cys C at preoperative and postoperative 2nd and 24th hour . Postoperative 24th hour NGAL levels were significantly decreased in the pregabalin group ( p = 0.027 ) . CONCLUSIONS Oral single-dose preemptive 75 mg pregabalin was effective in reducing early postoperative pain scores and total analgesic consumption in patients undergoing PCNL without leading to hemodynamic instability and side effects INTRODUCTION Gabapentin and pregabalin have been compared in studies conducted on management of neuropathic and postoperative pain . In neuropathic pain studies , the analgesic effects of the two drugs were compared , and pregabalin has been found to be more potent . However , in postoperative pain studies , the effects of each drug were examined separately . This study compared the analgesic effects of pregabalin ( 300 mg day-1 ) , gabapentin ( 1,200 mg day-1 ) and a placebo in managing postoperative pain following laminectomy and discectomy . METHODS 90 patients were r and omly assigned to three groups ( pregabalin , gabapentin and placebo ) of 30 patients each . Pregabalin 150 mg , gabapentin 600 mg and a placebo were administered every 12 hours , two times pre- and post surgery . Study data collected included morphine consumption , Visual Analogue Scale records , preoperative anxiety , patient satisfaction , adverse effects and observation notes . RESULTS In the gabapentin and pregabalin groups , overall morphine consumption , preoperative anxiety , pruritus , postoperative shivering were significantly lower ( p-value less than 0.05 for all ) , and patient satisfaction was significantly higher than those in the placebo group ( p-value less than 0.05 ) . CONCLUSION This study showed that both pregabalin 300 mg day-1 and gabapentin 1,200 mg day-1 have more analgesic , anxiolytic and opioid-sparing effects , higher patient satisfaction and are more effective for preventing postoperative shivering than the placebo following lumbar laminectomy and discectomy . The findings revealed that pregabalin 300 mg day-1 had equivalent analgesic , adverse and opioid-sparing effects and patient satisfaction as gabapentin 1,200 mg day-1 Objectives : To evaluate the efficacy and tolerability of pregabalin in postoperative pain management after laparoscopic cholecystectomy ( LC ) . Patients and Methods : A prospect i ve , r and omized , placebo , controlled , double-blinded study was conducted at Anesthesia Department , Laparoscopy Surgery Unit , Ain Shams University Hospital . Ninety patients with ASA physical status I-II scheduled for elective LC under general anesthesia were included . Patients were r and omly assigned to the following groups ( n=30 each ) : pregabalin group ( P ) , received 150 mg pregabalin capsules 2 hours preoperatively , 12 hours postoperatively , and twice daily for 2 days ; gabapentin group ( G ) , received 1200 mg gabapentin capsules ( 400 mg , ×3 ) 2 hours preoperatively , 12 hours postoperatively , and 400 mg three times daily for 2 days ; and control group ( C ) , received placebo capsules . Postoperative pain scores were recorded on a visual analogue scale . The following data were recorded : total daily pethidine and diclofenac consumption , numeric sedation score , and the postoperative nausea , vomiting , and dizziness scores . Results : The 24-hour pethidine consumption was significantly lower ( P<0.001 ) in both pregabalin and gabapentin groups versus control . Both groups had significantly less ( P<0.001 ) patients with postoperative nausea , vomiting , sedation , and dizziness versus control . Overall patient satisfaction with pain management was significantly higher ( P<0.001 ) in pregabalin group versus gabapentin or control groups . Conclusions : Gabapentin 1200 mg and pregabalin 150 mg are effective and safe analgesics for reducing postoperative pain in LC . The perioperative oral administration of pregabalin 150 mg in patients undergoing LC is an effective and safe method of analgesia with a low incidence of adverse effects and reduces postoperative pethidine consumption STUDY OBJECTIVE We hypothesized that oral administration of a single dose of pregabalin 2 hours before modified radical mastectomy ( MRM ) would produce dose-related reduction in postoperative opioid consumption . DESIGN Prospect i ve r and omized controlled clinical trial . SETTING Postanesthesia care unit . PATIENTS One hundred twenty adult women scheduled for unilateral ( MRM ) with axillary evacuation . INTERVENTIONS Patients were r and omized to receive either , placebo capsule , pregabalin 75 mg , pregabalin 150 mg , or pregabalin 300 mg . MEASUREMENTS The assessment parameters were the postoperative analgesic effect using visual analog scale ( VAS ) pain scores , the subsequent 24-hour morphine consumption , and the systemic adverse effects of pregabalin doses . MAIN RESULTS The VAS score at rest and movement was significantly decreased only in group P300 and group P150 in comparison to group P0 and group P75 at 0 hour ( P<.01 ) . The median ( interquartile range ) consumption of morphine in the first postoperative 24 hours was significantly decreased in group P300 in comparison to group P0 and group P75 ( P300 vs P0 : 6.5 [ 5 - 6.5 ] vs 20.5 [ 15.8 - 20.5 ] [ P<.001 ] ; P300 vs P75 : 6.5 [ 5 - 6.5 ] vs 20 [ 14 - 20 ] [ P<.001 ] ) , but there was no significant difference between group P300 and group P150 . In addition , there was a significant decrease in consumption of morphine in group P150 in comparison to group P0 and group P75 ( P150 vs P0 : 7 [ 5 - 7 ] vs 20.5 [ 15.8 - 20.5 ] [ P<.001 ] ; P150 vs P75 : 7 [ 5 - 7 ] vs 20 [ 14 - 20 ] [ P<.001 ] ) . There were statistical significant increase in dizziness and blurred vision in group P300 in comparison to other groups ( P<.05 ) . CONCLUSIONS A single preoperative oral dose of pregabalin 150 mg is an optimal dose for reducing postoperative pain and morphine consumption in patients undergoing MRM Background We investigated the effect of a combination of pregabalin and dexamethasone , when used as part of a multimodal analgesic regimen , on pain control after rhinoplasty operations . Methods Sixty patients were enrolled in this study . They were r and omly assigned into three groups : Group C ( placebo + placebo ) , Group P ( pregabalin + placebo ) , and Group PD ( pregabalin + dexamethasone ) . Patients received either pregabalin 300 mg orally 1 h before surgery , dexamethasone 8 mg intravenously during induction , or placebo according to their allocation . Postoperative pain was treated with intravenous patient-controlled analgesia ( tramadol , 20-mg bolus dose , 45-min lockout time ) . The numeric rating scale ( NRS ) , side effects , and consumption of tramadol , pethidine , and ondansetron were assessed . Results The median NRS scores at 0 , 1 , and 6 h after surgery were significantly higher in Group C than in Group PD ( p < 0.001 for all ) . The 24-h consumption of tramadol and pethidine was significantly reduced in Groups P and PD compared to Group C ( p < 0.01 and p < 0.01 ) . The total tramadol consumption was decreased by 54.5 % in Group P and 81.9 % in Group PD compared to Group C ( p < 0.001 for both ) . The incidence of nausea was higher in Group C than in Groups P and PD between the postoperative 0–2 and 0–24-h periods ( p < 0.05 for both ) . The frequency of blurred vision was significantly higher in Groups P and PD than in Group C within the 0–24-h period ( p < 0.05 for both ) . Conclusion We found that the addition of a single dose of pregabalin and dexamethasone to multimodal analgesia in rhinoplasty surgeries provided efficient analgesia and thus decreased opioid consumption . Level of Evidence IThis journal requires that authors assign a level of evidence to each article . For a full description of these Evidence -Based Medicine ratings , please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 Purpose The purpose of the current study was to evaluate the effects of pregabalin administration as an adjunct to fentanyl-based intravenous patient-controlled analgesia on opioid consumption and postoperative pain following arthroscopic shoulder surgery . Methods In this r and omized controlled trial , 60 adult patients undergoing arthroscopic shoulder surgery were r and omly assigned to receive either pregabalin 150 mg ( Pregabalin group , n = 30 ) or placebo ( Control group , n = 30 ) one hour before anesthetic induction . The primary outcome was the cumulative amount of fentanyl consumption during 48 hr postoperatively . Secondary outcomes were pain intensity , the number of rescue analgesics administered , and adverse effects related to the analgesic regimen , which were serially assessed during 48 hr postoperatively . Results The cumulative fentanyl consumption during 48 hr postoperatively was significantly lower in the Pregabalin group than in the Control group ( [ 1,126.0 ( 283.6 ) μg vs 1,641.4 ( 320.3 ) μg , respectively ; mean difference , 515.4 μg ; 95 % confidence interval [ CI ] , 359.0 to 671.8 ; P = < 0.001 ) . Numeric rating scores for pain ( 0 to 10 ) were significantly lower in the Pregabalin group at six hours ( mean difference , 2.9 ; 95 % CI , 1.8 to 4.0 ) , 24 hr ( mean difference , 2.9 ; 95 % CI , 1.9 to 3.8 ) , and 48 hr ( mean difference , 1.5 ; 95 % CI , 0.6 to 2.3 ) . The incidence of adverse effects related to the analgesic regimens , including nausea , sedation , and dizziness , were similar between the two groups . Conclusion A preoperative dose of pregabalin 150 mg administered before arthroscopic shoulder surgery result ed in significant analgesic efficacy for 48 hr in terms of opioid-sparing effect and improved pain intensity scores without influencing complications . This trial was registered at : http://cris.nih.go.kr , number CT0000578.RésuméObjectifL’objectif de cette étude était d’évaluer les effets d’une administration de prégabaline comme supplément à une analgésie contrôlée par le patient intraveineuse à base de fentanyl sur la consommation d’opioïdes et la douleur postopératoire après une arthroscopie de l’épaule . MéthodeDans cette étude r and omisée contrôlée , 60 patients adultes subissant une arthroscopie de l’épaule ont été r and omisés à recevoir soit 150 mg de prégabaline ( groupe prégabaline , n = 30 ) , ou un placebo ( groupe témoin , n = 30 ) une heure avant l’induction de l’anesthésie . Le critère d’évaluation principal était la quantité cumulée de fentanyl consommée durant les premières 48 h postopératoires . Les critères secondaires comprenaient l’intensité de la douleur , le nombre d’analgésiques de sauvetage administrés et les effets secondaires liés au régime analgésique , lesquels ont été évalués en série pendant 48 h après l’intervention . RésultatsLa consommation cumulée de fentanyl pendant 48 h postopératoires était significativement plus basse dans le groupe prégabaline que dans le groupe témoin ( [ 1126,0 ( 283,6 ) µg vs 1641,4 ( 320,3 ) µg , respectivement ; différence moyenne , 515,4 µg ; intervalle de confiance [ IC ] 95 % , 359,0 à 671,8 ; P = < 0,001 ) . Les scores d’évaluation numérique de la douleur ( 0 à 10 ) étaient significativement plus bas dans le groupe prégabaline à six heures ( différence moyenne , 2,9 ; IC 95 % , 1,8 à 4,0 ) , 24 h ( différence moyenne , 2,9 ; IC 95 % , 1,9 à 3,8 ) , et 48 h ( différence moyenne , 1,5 ; IC 95 % , 0,6 à 2,3 ) . L’incidence d’effets secondaires néfastes liés aux régimes analgésiques , y compris la nausée , la sédation et les étourdissements , étaient semblables dans les deux groupes . Conclusion Une dose préopératoire de 150 mg de prégabaline administrée avant une arthroscopie de l’épaule a entraîné une efficacité analgésique significative durant 48 h en termes de réduction en besoin d’opioïdes et a amélioré les scores d’intensité de la douleur sans influencer les complications . Cette étude a été enregistrée au : http://cris.nih.go.kr , numéro CT0000578 The clinical study was design ed to evaluate and compare single preoperative dose of pregabalin to a placebo regarding hemodynamic responses to laryngoscopy and endotracheal intubation , to assess perioperative fentanyl requirement and any side-effects . It was a r and omized , double-blind , placebo-controlled , parallel assignment , efficacy study . The study was done at a tertiary university hospital . This study was a comparison between two groups of 30 adult patients scheduled for elective off pump coronary artery bypass surgery . In the control group , the patients were given placebo capsules , and in the pregabalin group , the patients were given pregabalin 150 mg capsule orally 1 h before surgery . The patients were compared for hemodynamic changes before the start of the surgery , after induction , 1 , 3 , and 5 min after intubation . Additionally , fentanyl requirement during surgery and the first postoperative day was also compared . The present study shows that a single oral dose of 150 mg pregabalin given 1 h before surgery attenuated the pressor response to tracheal intubation in adults , but the drug did not show any effect on perioperative opioid consumption and was devoid of side-effects in the given dose Objectives : In this r and omized-controlled study , we investigated the effects of combined administration of pregabalin and dexamethasone on postoperative pain and analgesic requirements , and functional outcome in patients who underwent lumbar spinal surgery . Methods : One hundred eight patients were r and omized to group C ( placebo+placebo ) , group P ( pregabalin+placebo ) , or group PD ( pregabalin+dexamethasone ) . According to their allocated group , patients received placebo or pregabalin 150 mg every 12 hours starting 1 hour before anesthetic induction for a total of 8 doses . Dexamethasone 16 mg or normal saline was injected before the induction of anesthesia . The pain intensity , analgesic requirements , and side effects were assessed in the postoperative period : postanesthesia care unit , 12 , 24 , 48 , and 72 hours . Pain intensity and daily activity performance were also assessed 1 , 3 , and 6 months after surgery . Results : Compared with group C , the pain scores were lower in group PD at 24 hours after surgery ( P=0.011 ) . The frequency of additional rescue analgesic administration was significantly lower in group PD until 48 hours after surgery ( P<0.05 ) and in group P at 24 to 48 hours ( P=0.005 ) relative to group C. Back pain intensity at work was lower ( P=0.048 ) and daily activity performance was better ( P=0.006 ) in group PD compared with group C at 1 month after surgery . Conclusions : Combined administration of pregabalin and dexamethasone conferred analgesic benefits superior to those of pregabalin alone . This regimen also helped facilitate return to normal daily activity after surgery STUDY OBJECTIVE To determine the efficacy of two different doses ( 150 mg and 300 mg ) of preoperative pregabalin on pain relief and total opioid consumption after laparoscopic cholecystectomy . DESIGN Prospect i ve , r and omized , placebo-controlled , double-blinded study . SETTING Training and research hospital . PATIENTS 90 adult , ASA physical status 1 and 2 patients . INTERVENTIONS Patients were r and omly assigned to three groups to receive orally one hour before surgery , a placebo ( Group 1 ) , pregabalin 150 mg ( Group 2 ) , or pregabalin 300 mg ( Group 3 ) . Patients were observed for pregabalin side effects , somnolence via Ramsay Sedation Scale , dizziness , confusion , and ataxia . MEASUREMENTS In the operating room , heart rate and noninvasive systolic and diastolic blood pressures were measured . Visual analog scale ( VAS ) , Ramsay Sedation Scale , and Aldrete scores were also recorded on arrival at the Postanesthesia Care Unit ( time 0 ) , 15 , 30 , 60 , 120 minutes and 3 , 4 , 6 , 8 , 10 , 12 and 24 hours after surgery . Additional doses of drugs ( fentanyl and /or metoclopramide ) were also recorded . MAIN RESULTS Preemptive pregabalin decreased pain scores and postoperative fentanyl consumption in patients after laparoscopic cholecystectomy in a dose-dependent manner . There were no differences between the groups in side effects . CONCLUSION Preoperative pregabalin may be a useful analgesic for patients after laparoscopic cholecystectomy , as it lowers pain intensity and opiod consumption , and does not increase the frequency of side effects OBJECTIVE Adjuvant agents , given with local anesthetics or via venous , oral , or rectal routes for peripheral nerve blocking , have been in use for a long time . Literature studies about pregabalin usage in peripheral nerve blocking are limited in number . In this study , we aim ed to reveal the blocking quality of pregabalin administered orally in various doses as an anxiolytic agent and its effective dose range . PATIENTS AND METHODS Eighty patients who underwent upper extremity bone surgery were included in the study . The cases were divided into 4 r and omized groups of 20 patients . The group that did not receive any medication before the surgery was named the Control Group ( Group C ) , the group that received 75 mg pregabalin per os was named Group P75 , the group that received 150 mg pregabalin per os was named Group P150 , and the group that received 300 mg pregabalin per os was named Group P300 . The study had a controlled and double-blind design . Before , during and after routine peripheral nerve blocking , vital signs , Ramsey Sedation Scale , Patient Satisfaction , Visual Analog Scale , and termination duration s of sensorial and motor blocks were recorded . RESULTS Motor block initiation duration s of all groups given pregabalin were significantly shorter than those of Group C. Sensorial block termination duration s were similar in Group P150 and Group P300 , and both were significantly longer than those in Group C and Group P75 . First analgesic requirement time for Group P150 and Group P300 were significantly longer than that of Group P75 . Although there was no significant difference between postoperative patient satisfaction and VAS values , first analgesic requirement times of the pregabalin administered groups were longer than those of the control group . CONCLUSIONS The patients , who are about to undergo surgery , generally develop anxiety about death , not waking up from anesthesia , disability , pain and loss of ability to work . Pregabalin is an anti-epileptic , analgesic and anxiolytic agent . With these characteristics , it can be used to reduce pre-operative anxiety , for prophylaxis against convulsions and post-operative analgesia . One hundred fifty mg of pregabalin provides sufficient and effective analgesia , and this dose positively affects the quality of the block Background Postoperative pain is the dominant complaint and the most common cause of delayed discharge after laparoscopic cholecystectomy . The aim of this study is to evaluate the potential of preoperative administration of pregabalin to reduce postoperative pain and opioid consumption . Methods Fifty American Society of Anesthesiologists ( ASA ) I and II adult patients with symptomatic gallstone disease scheduled for elective laparoscopic cholecystectomy were r and omized into two groups : group I patients ( n = 25 ) were given 600 mg pregabalin per os divided in two doses , the night before surgery and 1 h preoperatively , respectively , while group II patients ( n = 25 ) received a matching to pregabalin placebo at the same scheme . Postoperative pain , morphine consumption , and complications were compared between the two groups . Results Postoperative pain ( static and dynamic assessment ) was significantly less at 0 , 1 , 8 , 16 , and 24 h ( p < 0.001 ) after the procedure for group I ( pregabalin ) compared with the placebo group . Postoperative patient-controlled morphine consumption during hospital stay was also significantly less in the pregabalin group compared with the placebo group . Side-effects were similar in both groups expect for dizziness , which was significantly higher ( p < 0.0001 ) in the pregabalin group . Conclusions Administration of 600 mg pregabalin per os , divided in two preoperative doses , significantly reduces postoperative pain as well as opioid consumption in patients undergoing laparoscopic cholecystectomy , at the cost of increased incidence of dizziness BACKGROUND There has been a recent , growing concern regarding narcotic use in surgical patients . This issue , coupled with an ongoing desire to lessen postoperative discomfort , has prompted the search for alternative analgesic regimens . OBJECTIVE The purpose of this study was to determine whether the addition of pregabalin , an anticonvulsant indicated for the management of neuropathic pain , to an analgesic regimen reduced narcotic use and reported pain following augmentation mammaplasty . METHODS Eighty patients underwent submuscular augmentation mammaplasty with smooth shell saline mammary prostheses in an outpatient surgical facility . The patients were r and omized into two groups . Group A ( n = 40 ) used 5-mg hydrocodone tablets as needed to manage postoperative pain . Group B ( n = 40 ) used pregabalin , 75 mg , twice daily in addition to 5-mg hydrocodone tablets as needed for postoperative pain management . Narcotic use was recorded and pain assessed daily using the Rogers Pain Scale from 1 ( mild ) to 10 ( severe ) . Patients were surveyed for nausea and quality of pain . RESULTS Group A used 115 + /- 32 mg hydrocodone during the immediate 7 day postoperative period and reported an average pain scale score of 5.3 . Likewise , group B used 33 + /- 27 mg hydrocodone as well as the prescribed pregabalin dosage and reported an average pain scale score of 3.4 . Patients in group B reported less nausea . These differences were statistically significant ( P < .05 ) . Patient age , implant size , and postoperative complications were similar between the two groups . CONCLUSIONS Perioperative pregabalin administration in patients undergoing augmentation mammaplasty reduced postoperative narcotic use by 70 % . There was also significantly less reported pain and a 46 % reduction in nausea in the pregabalin-treated group . Pregabalin has few side effects , no drug interactions , and should be considered safe in an analgesic regimen Preoperative anxiety can increase postoperative pain and is therefore important to avoid . Different approaches have already been tested for preoperative anxiolysis . Gabapentinoids might be a useful alternative to benzodiazepines . Pregabalin is used for treating generalized anxiety disorders and shows a favourable pharmacokinetic profile after oral administration ; however , its anxiolytic effect preoperatively in healthy out patients is still unclear . In this r and omised , double-blind , placebo-controlled trial the anxiolytic effect of pregabalin in 40 out patients undergoing st and ardised general anaesthesia and postoperative pain therapy for minor orthopaedic surgery was analysed . Patients received preoperatively either 300 mg pregabalin or placebo orally . The primary outcome was anxiety before anaesthesia induction , the secondary outcome the postoperative pain , both assessed using a visual analogue scale from 0 to 100 . Without any side effects pregabalin reduced preoperative anxiety compared with the control group ( 23 ± 10 vs. 38 ± 17 ; p = 0.003 ) . Pain scores did not differ between groups ; however , need of piritramide in the postanaesthesia care unit was reduced to half by pregabalin compared with the control group . A single preoperative dose of 300 mg pregabalin reduces anxiety in patients undergoing minor orthopaedic surgery without any side effects like dizziness or persisting sedation result ing in a prolonged stay in the postanaesthesia care unit Background Pregabalin is an antiepileptic drug that is effective for treating postoperative pain , neuropathic pain , anxiety , and hemodynamic instability . The aim of this study was to investigate the effect of a single preoperative dose of pregabalin in patients with opioid-induced hyperalgesia ( OIH ) . Methods Ninety ASA I-II patients undergoing laparoendoscopic single-site urologic surgery were r and omly assigned to one of the following three groups that received either pregabalin or placebo 1 h before anesthesia and an intraoperative remifentanil infusion . Group plL received placebo and 0.05 µg/kg/min remifentanil , group plH received placebo and 0.3 µg/kg/min remifentanil , and group prH received 300 mg pregabalin plus 0.3 µg/kg/min remifentanil . The primary endpoint was pain intensity upon movement 1 , 6 , 12 , and 24 h after surgery . Secondary endpoints were the area of hyperalgesia and mechanical hyperalgesia threshold 24 h after surgery , time to first postoperative analgesic requirement , and cumulative postoperative volume of morphine administered via a patient-controlled analgesia ( PCA ) pump over 24 h. Results The time to first postoperative analgesic requirement in group plH was significantly shorter than that in group plL. The injected PCA volume was significantly greater in group plH than that in the other two groups . Postoperative pain intensity in group plH was significantly greater than that in the other two groups at 6 , 12 , and 24 h after surgery . The mechanical hyperalgesia threshold and the area of hyperalgesia around the surgical incision 24 h after surgery in group plH differed significantly from those in the other two groups , which were not significantly different . Adverse effects were comparable among groups . Conclusions High-dose remifentanil induced hyperalgesia , including increased pain intensity , increased area of hyperalgesia , and decreased mechanical hyperalgesia threshold . These effects were attenuated by oral administration of a single preoperative dose of pregabalin ( 300 mg ) in patients undergoing laparo-endoscopic single-site urologic surgery Purpose Multimodal analgesia increases the chance of successful discharge and pain control after surgery , and pregabalin is being promoted as an effective analgesic , based on placebo-controlled studies . We investigated whether adding pregabalin improved pain control and reduced opioid requests when it was added to a multimodal analgesic regimen for cosmetic surgery . Methods One hundred and ten women who underwent same-day cosmetic surgery were r and omized to receive oral pregabalin , 75 mg q12 h for five consecutive days starting the night before surgery , or identical placebos . Participants , outcomes assessors , and the statistician were blinded . The primary outcome was postoperative numerical movement-evoked pain scores at 2 , 24 , 48 , 72 , and 96 h after surgery . The secondary outcomes included pain scores at rest ; incidence of moderate to severe pain ; and analgesic and antiemetic requirements ; as well as the incidence of nausea , vomiting , and somnolence . Results Based on 99 patients who completed the study , we found no difference between the groups in the primary outcome ; 72 h after surgery , movement-evoked median pain scores were < 4/10 in both groups . We found no differences in opioid requirements ( p = 0.95 ) or anti-inflammatory requirements ( p = 0.45 ) , and no difference in opioid-related adverse events . Conclusion Perioperative pregabalin 75 mg twice a day does not increase benefit when it is added to an already multimodal analgesic regimen for patients undergoing cosmetic surgery . Several factors could explain our findings , including the possibility of publication bias in the current literature BACKGROUND Pregabalin may reduce postoperative pain and opioid use . Higher doses may be more effective , but may cause sedation and confusion . This prospect i ve , r and omized , blinded , placebo-controlled study tested the hypothesis that pregabalin reduces pain at 2 weeks after total knee arthroplasty , but increases drowsiness and confusion . METHODS Patients ( 30 per group ) received capsules containing pregabalin ( 0 , 50 , 100 , or 150 mg ) ; two capsules before surgery , one capsule twice a day until postoperative day ( POD ) 14 , one on POD15 , and one on POD16 . Multimodal analgesia included femoral nerve block , epidural analgesia , oxycodone-paracetamol , and meloxicam . The primary outcome was pain with flexion ( POD14 ) . RESULTS Pregabalin did not reduce pain at rest , with ambulation , or with flexion at 2 weeks ( P=0.69 , 0.23 , and 0.90 , respectively ) . Pregabalin increased POD1 drowsiness ( 34.5 , 37.9 , 55.2 , and 58.6 % in the 0 , 50 , 100 , and 150 mg arms , respectively ; P=0.030 ) , but did not increase confusion ( 0 , 3.5 , 0 , and 3.5 % , respectively ; P=0.75 ) . Pregabalin had no effect on acute or chronic pain , opioid consumption , or analgesic side-effects . Pregabalin reduced POD14 patient satisfaction [ 1 - 10 scale , median ( first quartile , third quartile ) : 9 ( 8 , 10 ) , 8 ( 7 , 10 ) , 8 ( 5 , 9 ) , and 8 ( 6 , 9.3 ) , respectively ; P=0.023 ) . Protocol compliance was 63 % by POD14 ( 50.0 , 70.0 , 76.7 , and 56.7 % compliance , respectively ) , with no effect of dose on compliance . Per- protocol analysis of compliant patients showed no effect of pregabalin on pain scores . CONCLUSIONS Pregabalin had no beneficial effects , but increased sedation and decreased patient satisfaction . This study does not support routine perioperative pregabalin for total knee arthroplasty patients . CLINICAL TRIAL REGISTRATION Clinical Trials.gov : http://www . clinical trials.gov/ct2/show/ study /NCT01333956 Background : Optimal pain treatment with minimal side effects is essential for early mobility and recovery in patients undergoing total knee arthroplasty ( TKA ) . We investigated the effect of pregabalin as an adjuvant for postoperative analgesia provided by opioid-based patient-controlled epidural analgesia ( PCEA ) in such patients . Material s and Methods : Forty patients undergoing unilateral primary TKA were r and omly assigned to two equal groups , to receive either placebo or pregabalin 75 mg twice a day . The drug was administered orally starting before surgery and was continued for 2 days after surgery . Anesthetic technique was st and ardized . Postoperatively , static and dynamic pain was assessed by verbal rating score . Mean morphine consumption , PCEA usage , rescue analgesic requirement , and overall patient satisfaction were also assessed . Treatment emergent adverse drug reactions were recorded . Results : Mean morphine consumption was significantly reduced by pregabalin . Postoperative pain ( both static and dynamic ) and PCEA consumption too was significantly reduced in the pregabalin group during the first 48 h after surgery . This group needed fewer rescue analgesics and recorded higher overall patient satisfaction . Pregabalin-treated patients had fewer opioid-related adverse reactions like nausea , vomiting , and constipation . Dizziness was noted in two of the patients receiving pregabalin . There was no statically significant difference in the incidence of sedation in the two groups . Conclusions : Oral pregabalin 75 mg started preoperatively is a useful adjunct to epidural analgesia following TKA . It reduces opioid consumption , improves postoperative analgesia , and yields higher patient satisfaction levels Background and Objectives Pregabalin is often used as a perioperative analgesic adjunct ; some studies show benefit , but others do not . Adverse effects , such as confusion and sedation , have been attributed to perioperative use of pregabalin . We tested the hypothesis that pregabalin , when used as part of a multimodal analgesic regimen , reduces the duration of moderate to severe pain in the first 24 hrs following foot or ankle surgery . Secondary outcomes included measures of opioid and pregabalin adverse effects . Methods Sixty patients scheduled for hospital admission after foot or ankle surgery entered this r and omized , double-blind , placebo-controlled trial . Patients received a neuraxial anesthetic , a popliteal fossa sciatic nerve block using 30 mL 0.375 % bupivacaine with clonidine 100 µg and epinephrine , a saphenous nerve block , postoperative hydromorphone intravenous patient-controlled analgesia , and oral analgesics ( oxycodone/acetaminophen ) . Patients were r and omized to receive pregabalin ( 100 mg preoperatively , then 50 mg every 12 hrs ) or a placebo for 3 days . The primary outcome was the number of hours that patients reported moderate to severe pain . Results Both groups reported a similar number of hours of moderate to severe pain during the first 24 hrs : 4.1 ( SD , 4.1 ) hrs ( pregabalin ) versus 4.5 ( SD , 3.5 ) hrs ( placebo ) . Pain scores , opioid use , and adverse effects were also similar in both groups . Conclusions No clinical benefit was obtained from perioperative administration of pregabalin ( 100 mg preoperative , then 50 mg every 12 hrs ) as part of a multimodal postoperative analgesic regimen following foot and ankle surgery BACKGROUND : Despite the enormous success of total knee arthroplasty ( TKA ) , chronic neuropathic pain can develop postoperatively and is both distressing and difficult to treat once established . We hypothesized that perioperative treatment with pregabalin , a chronic pain medication , would reduce the incidence of postsurgical neuropathic pain . METHODS : We performed a r and omized , placebo-controlled , double-blind trial of pregabalin ( 300 mg ) administered before TKA and for 14 days after TKA ( 150–50 mg twice daily ) . Patients were screened for the presence of neuropathic pain at 3 and 6 mo postoperatively using the Leeds Assessment of Neuropathic Symptoms and Signs scale . Secondary outcomes included postsurgical recovery and rehabilitation measures , including knee range of motion , opioid consumption , postoperative pain scores , sleep disturbance , and time to discharge as well as the occurrence of postoperative systemic complications . RESULTS : Of the 240 patients r and omly assigned to the 2 treatment groups ( 120 in each ) , data for the primary outcome were obtained from 113 pregabalin patients and 115 placebo patients . At both 3 and 6 mo postoperatively , the incidence of neuropathic pain was less frequent in the pregabalin group ( 0 % ) compared with the placebo group ( 8.7 % and 5.2 % at 3 and 6 mo , respectively ; P = 0.001 and P = 0.014 ) . Patients receiving pregabalin also consumed less epidural opioids ( P = 0.003 ) , required less oral opioid pain medication while hospitalized ( P = 0.005 ) , and had greater active flexion over the first 30 postoperative days ( P = 0.013 ) . There were no differences in the actual recorded duration of hospitalization between the 2 groups , although time to achieve hospital discharge criteria was longer for placebo patients , 69.0 ± 16.0 h ( mean ± sd ) , than that of pregabalin patients , 60.2 ± 15.8 h ( P = 0.001 ) . Sedation ( P = 0.005 ) and confusion ( P = 0.013 ) were more frequent on the day of surgery and postoperative day 1 in patients receiving pregabalin . CONCLUSION : Perioperative pregabalin administration reduces the incidence of chronic neuropathic pain after TKA , with less opioid consumption and better range of motion during the first 30 days of rehabilitation . However , in the doses tested , it is associated with a higher risk of early postoperative sedation and confusion BACKGROUND This study examined whether a perioperative regimen of pregabalin added to celecoxib improved pain scores and functional outcomes postdischarge up to 3 months after total hip arthroplasty ( primary outcome ) and acute postoperative pain and adverse effects ( secondary outcomes ) . METHODS One hundred and eighty-four patients were enrolled in a r and omized , double-blind , placebo-controlled study . Two hours before receiving a spinal anaesthetic and undergoing surgery , patients received celecoxib 400 mg p.o . and were r and omly assigned to receive either pregabalin 150 mg p.o . or placebo p.o . After surgery , patients received pregabalin 75 mg or placebo twice daily in hospital and for 7 days after discharge . Patients also received celecoxib 200 mg every 12 h for 72 h and morphine i.v . patient-controlled analgesia for 24 h. Pain and function were assessed at baseline , 6 weeks , and 3 months after surgery . RESULTS There was no difference between groups in physical function or incidence and intensity of chronic pain 3 months after total hip arthroplasty . The pregabalin group used less morphine [ mean ( sd ) : 39.85 ( 28.1 ) mg ] than the placebo group [ 54.01 ( 31.2 ) mg ] in the first 24 h after surgery ( P<0.01 ) . Pain scores were significantly lower in the pregabalin group vs the placebo group on days 1 - 7 after hospital discharge , and the pregabalin group required less adjunctive opioid medication ( Percocet ) 1 week after hospital discharge ( P<0.05 ) . CONCLUSIONS Perioperative administration of pregabalin did not improve pain or physical function at 6 weeks or 3 months after total hip arthroplasty . Perioperative administration of pregabalin decreased opioid consumption in hospital and reduced daily pain scores and adjunct opioid consumption for 1 week after discharge Background : For coronary artery bypass grafting ( CABG ) sternotomy should be performed . The pain after surgery is severe and requires medical intervention . Use of the analgesics is limited by their side effects and studies suggest that prevention with some medications before surgery is effective in controlling the postoperative pain . Objectives : We investigated the efficacy of pregabalin administration before surgery in the treatment of acute postoperative pain after CABG surgery . Patients and Methods : Sixty patients indicated for elective CABG surgery were r and omly allocated to two groups . One group received placebo and the other received 150 mg of oral pregabalin before surgery . Heart rates , blood pressure , respiratory rate , intensive care unit ( ICU ) stay duration , morphine consumption , and pain score according to the visual analog scale ( VAS ) were measured and recorded at 4 , 12 , and 24 hours of surgery . Results : Pregabalin consumption did not alter hemodynamic parameters and was safe in patients after CABG . Its consumption was associated with significant reduction in the pain score ( P values were 0.035 , 0.026 , and 0.047 respectively at 4 , 12 , and 24 hours of surgery ) . Its use was not associated with changes in the morphine consumption at 4 , 12 , and 24 hours of surgery ( P > 0.05 ) . Conclusions : Premedication with studied dose of pregabalin is effective for the prevention of postoperative pain in patients after CABG and has no adverse effects . Trials with other treating schedule and doses of the drug should be performed to determine the best treatment plan Background Pregabalin has been shown to have analgesic effect in acute pain models . The primary objective was to examine the efficacy a single dose of pregabalin , would have on morphine consumption following lumbar discectomy . Methods With ethical approval a r and omized , placebo-controlled prospect i ve trial was undertaken in 32 patients ( ASA I-II , 18 - 65 years ) with radicular low back pain for > 3 months undergoing elective lumbar discectomy . Patients received either oral pregabalin 300 mg ( PG Group ) or placebo ( C Group ) one hour before surgery . Pain intensity , the accumulative morphine consumption and adverse effects were recorded for 24 hours following surgery . Functional , psychological and quantitative sensory testing were also assessed . Results Fourteen patients out of the 32 recruited were r and omized to receive pregabalin . Morphine consumption was reduced ( absolute difference of 42.3 % ) between groups with medium effect size . ( Mann-Whitney ; U = 52.5 , z-score= 2.84 , P = 0.004 , r = 0.14 ) . This was not associated with a significant difference in the incidence of adverse effects between the two groups . The median pain intensity ( VAS ) on movement was not significantly different between groups . Conclusions A single pre-operative dose of pregabalin ( 300 mg ) did not result in a reduction in pain intensity compared to placebo in this patient cohort but the significant reduction in morphine consumption suggests that a fixed peri-operative dosing regime warrants investigation Objectives Pregabalin is used to treat neuropathic pain and has shown analgesic properties in postoperative pain . The aim of this study was to investigate the effectiveness and safety of pregabalin in reducing postoperative pain in patients after septoplasty . Methods Forty-seven patients scheduled for elective septoplasty were r and omly assigned to groups that received either pregabalin ( 150 mg ) or placebo , both one hour before surgery and 12 hours after the initial dose . Pain ( verbal numerical rating scale , VNRS ) and side effect assessment s were performed at 6 , 12 , 12 to 24 , and 24 to 48 hours postoperatively . Results From 1 to 12 hours postoperatively , VNRS scores for pain were lower in the pregabalin group ( n=24 ) than in the placebo group ( n=23 ; P<0.05 ) . The number of patients who needed rescue analgesics was lower in the pregabalin group ( P=0.042 ) . The incidence of nausea and vomiting did not differ between groups ( P=0.666 ) , and the incidence of sedation was higher in the placebo groups ( P=0.022 ) . Conclusion The perioperative administration of oral pregabalin ( 150 mg twice ) is an effective and safe way to reduce early postoperative pain in patients undergoing septoplasty BACKGROUND The objective of this study was to examine the effects of low-dose pregabalin on the analgesic efficacy , side-effects , and recovery profile in patients undergoing laparoscopic cholecystectomy . METHODS One hundred and sixty-two patients aged 18 - 65 yr , of ASA physical status I-III , undergoing elective outpatient laparoscopic cholecystectomy were recruited and r and omized in this prospect i ve , placebo-controlled , double-blind study to receive one of the following study medications orally : pregabalin 50 mg , pregabalin 75 mg , or placebo , 1 h before surgery and then every 12 h after operation for a total of three doses . Postoperative numeric pain scores , analgesic consumption , recovery score ( QoR-40 ) , and side-effects ( opioid-related symptom distress scale ) were assessed in the early postoperative period ( every 15 min during the first hour , at 90 , 120 min , 6 , and 12 h ) and at days 1 , 2 , and 7 . Data were analysed using an intention-to-treat method . RESULTS Compared with the placebo group , the pain scores were lower in the pregabalin 75 mg group in the first 90 min after surgery ( P<0.05 ) . Pregabalin 50 mg result ed in pain reduction at 30 and 45 min ( P<0.05 ) relative to placebo . The analgesic consumption , side-effects , and recovery scores were similar among the three groups . CONCLUSIONS Perioperative administration of pregabalin 75 mg provided limited analgesic benefit in the postoperative period . An up date d meta- analysis confirms this finding ( see Supplementary material ) Background Postoperative pain of dacryocystorhinostomy ( DCA ) surgery is one of the serious issues to be considered . Administrating opioids to relieve postoperative pain and facing their increasing side effects in eye surgeries , make the use of non-opioid drugs inevitable . Objectives The present study examined the efficacy of pregabalin in alleviating the postoperative pain of DCA surgery . Patients and Methods The present study has been carried out as a double-blind , r and omized clinical trial on the patient c and i date s for DCR . The patients were r and omly divided in to two groups of pregabalin and placebo . Patients in pregabalin group received 300 mg of pregabalin , an hour before the operation in the morning of the surgery . Pain intensity on visual analog scale ( VAS ) was recorded until 24 hours after the operation ; also the rate of administrated opioids and nausea/vomiting frequency were recorded during the first 24-hour period after the operation and the results of the two groups were compared . Results Postoperative pain intensity in the pregabalin group at the time of recovery was significantly lower than that of the placebo group ( P = 0.001 ) until 24 hours after the surgery . In the pregabalin group 17.5 % of the patients received opioids while in the placebo group the figure was 52.5 % ( P = 0.001 ) . Nausea frequency was also higher in the placebo group than the pregabalin group ( P = 0.003 ) . Conclusions A single 300 mg dose of pregabalin , an hour before DCA can effectively reduce pain intensity and also reduce opioid dose and nausea/vomiting Background : Pregabalin is a potent lig and for alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system , which exhibits potent anticonvulsant , analgesic and anxiolytic activity . The pharmacological activity of pregabalin is similar to that of gabapentin and shows possible advantages . Although it shows analgesic efficacy against neuropathic pain , very limited evidence supports its postoperative analgesic efficacy . We investigated its analgesic efficacy in patients experiencing acute pain after abdominal hysterectomy and compared it with gabapentin and placebo . Methods : A r and omized , double-blind , placebo-controlled study was conducted in 90 women undergoing abdominal hysterectomy who were anaesthetized in a st and ardized fashion . Patients received 300 mg pregabalin , 900 mg gabapentin or placebo , 1–2 hours prior to surgery . Postoperative analgesia was administered at visual analogue scale ( VAS ) ≥3 . The primary outcome was analgesic consumption over 24 hours and patients were followed for pain scores , time to rescue analgesia and side effects as secondary outcomes . Results : The diclofenac consumption was statistically significant between pregabalin and control groups , and gabapentin and control groups ; however , pregabalin and gabapentin groups were comparable . Moreover , the consumption of tramadol was statistically significant among all the groups . Patients in pregabalin and gabapentin groups had lower pain scores in the initial hour of recovery . However , pain scores were subsequently similar in all the groups . Time to first request for analgesia was longer in pregabalin group followed by gabapentin and control groups . Conclusion : A single dose of 300 mg pregabalin given 1–2 hours prior to surgery is superior to 900 mg gabapentin and placebo after abdominal hysterectomy . Both the drugs are better than placebo Objectives . The aim of this study was to explore effect of a combination of pregabalin and dexamethasone on pain control after septoplasty operations . Methods . In this study , 90 patients who were scheduled for septoplasty under general anesthesia were r and omly assigned into groups that received either placebo ( Group C ) , pregabalin ( Group P ) , or pregabalin and dexamethasone ( Group PD ) . Preoperatively , patients received either pregabalin 300 mg one hour before surgery , dexamethasone 8 mg intravenously during induction , or placebo according to their allocation . Postoperative pain treatment included tramadol and diclofenac sodium 30 minutes before the end of the operation . Numeric rating scale ( NRS ) for pain assessment , side effects , and consumption of tramadol , pethidine , and ondansetron were recorded . Results . The median NRS score at the postoperative 0 and the 2nd h was significantly higher in Group C than in Group P and Group PD ( P ≤ 0.004 for both ) . The 24 h tramadol and pethidine , consumptions were significantly reduced in Groups P and PD compared to Group C ( P < 0.001 and P < 0.001 ) . The incidence of blurred vision was significantly higher in Group PD compared to Group C within both 0–2 h and 0–24 h periods ( P = 0.002 and P < 0.001 , resp . ) . Conclusions . We conclude that administration of 300 mg pregabalin preoperatively may be an adequate choice for pain control after septoplasty . Addition of dexamethasone does not significantly reduce pain in these patients Background Pregabalin , a structural analogue of gamma amino butyric acid ( GABA ) , is shown to be effective in treatment of several types of neuropathic pain , incisional injury , and inflammatory injury . Objectives The aim of the present study is to compare the efficacy of two doses ( 75 mg or 150 mg ) of pregabalin with the administration of a placebo for post-operative analgesia in patients undergoing hysterectomy under spinal anesthesia . Patients and Methods A r and omized , placebo-controlled trial was conducted on 135 patients undergoing vaginal hysterectomy under spinal anesthesia . The patients were divided in three groups of 45 patients each : group 0 , placebo ; group 1 , 75 mg pregabalin ; and group 2 , 150 mg pregabalin ; each treatment of which was administered one hour before surgery . The Ramsay sedation scale ( RSS ) was used for pre-operative assessment and the visual analog scale ( VAS ) was used to determine pain at rest and for cough on the first post-operative day . The time for the requirement of rescue analgesics on the first post-operative day was also assessed . Results The RSS scores were significantly higher in groups 1 and 2 as compared to the controls ( P < 0.001 ) . Postoperative VAS scores for pain both at rest and on cough were significantly reduced in groups 1 and 2 ( P < 0.001 ) . Rescue analgesic consumption decreased significantly in groups 1 and 2 ( P < 0.001 ) . The time at which rescue analgesia was administered ( first dose ) was 4.45 hours in group 0 , 10.86 hours in group 1 , and 16.82 hours in group 2 ( P < 0.001 ) . Conclusions Pregabalin administered as premedication provided significant postoperative pain relief and decreased the requirement of other parenteral analgesics . Pregabalin doses of 150 mg had a better analgesic profile , but the advantages of their use may be limited by side effects such as dizziness . Thus , it is concluded that pregabalin doses of 75 mg may be the optimal pre-emptive dose Background : Post-operative pain is one of the problems , wherein lack of control on it has many side-effects such as tachycardia , hypertension , myocardial ischemia , decreased alveolar ventilation , and poor wound healing . Aims : In this study , we evaluated the pre-operative administration of pregabalin sufficiency and security in relieving post-operative pain after lower limb orthopedic surgery and reducing the need for opioids and their possible side-effects . Material s and Methods : This study is a r and omized , double-blind clinical trial . It was performed on 60 patients under lower limb surgery by spinal anesthesia . Patients were r and omly allocated to two groups , one group has received a 150 mg pregabalin capsule 2 h before surgery and the other group has received placebo as a control . In both groups at 2 , 6 , 12 , and 24 h after surgery , the patients were evaluated and the pain score , the score of sedation , incidence of nausea and vomiting was recorded in the checklists . Then , the data were analyzed by SPSS v16 . Results : Visual analog pain scores at all hours in pregabalin group significantly reduced compared to the placebo group ( P < 0.0001 ) . Also , in the pregabalin group nausea and vomiting scores at all hours , sedation levels at 2 h and 6 h post-operatively , and pethidine consumption in all hours have significantly been reduced . Conclusion : A single pre-operative oral dose of pregabalin 150 mg is an effective method for reducing post-operative pain and pethidine consumption in patients undergoing orthopedic surgery BACKGROUND Achieving post operative pain management is difficult with the use of only opioids analgesia . Multimodal pain management is a method to improve post operative analgesia with minimal side effects . Pregabalin has an analgesic and opioids sparing effects in post operative analgesia . OBJECTIVE The objective of the present study was to evaluate the effect of premedication with pregabalin 300 mg compared with lorazepam 0.5 mg on post operative morphine consumption in women undergoing abdominal hysterectomy with/without salphingo-oophorectomy . MATERIAL AND METHOD Eighty ASA I-III , aged 18 - 65 year patients undergoing elective abdominal hysterectomy with/without salphingo-oophorectomy were r and omized to receive either lorazepam 0.5 mg or pregabalin 300 mg 1 hr before surgery . Anesthesia was induced with thiopental ( 3 - 5 mg/kg ) and atracurium ( 0.6 mg/kg ) and maintained with sevoflurane with a fresh gas flow of 2 L/min ( 50 % N2O in O2 ) and morphine 0.1 - 0.2 mg/kg . All patients received patient-controlled analgesia with morphine with a 1 mg incremental dose , 5-min lockout interval , and 4-hr limit of 40 mg post operative . Patients were studied at 0 , 1 , 4 , 12 and 24 hours post operatively for verbal numerical rating scale ( VNRS ) , morphine consumption , satisfaction score and side effects . RESULTS The VNRS scores of the pregabalin group were significantly lower than the control group at 1 , 4 , 12 and 24 hours after surgery . The total morphine consumption at 24 hours post operatively of pregabalin group ( 7.11 + /- 5.57 ) was significantly lower than the control group ( 21.18 + /- 7.12 ) ( p < 0.01 ) . There were no differences between groups in somnolence and dizziness ( p = 0.93 ) and nausea-vomiting ( p = 0.11 ) . The satisfaction score was higher in the pregabalin group . CONCLUSION A 300 mg pregabalin administered 1 hr preoperatively before abdominal hysterectomy with/without salphingo-oophorectomy significantly reduced morphine consumption , VNRS pain score and improved satisfaction score at 24 hr post operatively without any significant differences in side effects . Pregabalin is an alternative combination to opioids as multimodal analgesia Background : Hemodynamic responses of laryngoscopy and laparoscopy should be attenuated by the appropriate premedication , smooth induction , and rapid intubation . The present study evaluated the clinical efficacy of oral premedication with pregabalin or clonidine for hemodynamic stability during laryngoscopy and laparoscopic cholecystectomy . Methods : A total of 180 healthy adult consented patients aged 35 to 52 years with American Society of Anesthesiologist ( ASA ) physical status I and II of both gender , who met the inclusion criteria for elective laparoscopic cholecystectomy , were r and omized to receive placebo Group I , pregabalin ( 150 mg ) Group II , or clonidine ( 200 μg ) Group III , given 75 to 90 minutes before surgery as oral premedication . All groups were compared for preoperative sedation and anxiety level along with changes of heart rate and mean arterial pressure prior to premedication , before induction , after laryngoscopy , pneumoperitoneum , release of carbon dioxide , and extubation . Intraoperative analgesic drug requirement and any postoperative complications were also recorded . Results : Pregabalin and clonidine proved to have sedative and anxiolytic effects as oral premedicants and decreased the need of intraoperative analgesic drug requirement . Clonidine was superior to pregabalin for attenuation of the hemodynamic responses to laryngoscopy and laparoscopy , but it increased the incidence of intra- and postoperative bradycardia . No significant differences in the parameters of recovery were observed between the groups . None of the premedicated patient has suffered from any postoperative side effects . Conclusion : Oral premedication with pregabalin 150 mg or clonidine 200 μg causes sedation and anxiolysis with hemodynamic stability during laryngoscopy and laparoscopic cholecystectomy , without prolongation of recovery time and side effects BACKGROUND : Patient outcome after lumbar discectomy for radicular low back pain is variable and the benefit is inconsistent . Many patients continue to experience pain 3 months after surgery . Pregabalin , a membrane stabilizer , may decrease perioperative central sensitization and subsequent persistent pain . METHODS : Forty patients undergoing lumbar discectomy were r and omly allocated to receive either pregabalin ( 300 mg at 90 minutes preoperatively and 150 mg at 12 and 24 hours postoperatively ) or placebo at corresponding times in a double-blinded manner . Our primary outcome was the change in the present pain intensity ( PPI ) ( visual analog scale [ VAS ] , 0–100 mm [ PPI-VAS , McGill Pain Question naire ] ) from preoperatively to 3 months postoperatively . RESULTS : The decrease in PPI-VAS score at 3 months was greater in patients who received pregabalin ( 37.6 ± 19.6 mm ) ( mean ± SD ) than those who received placebo ( 25.3 ± 21.9 mm ) ( P = 0.08 ) . The Rol and Morris disability score at 3 months was less in patients who received pregabalin ( 2.7 ± 2.4 ) than in those who received placebo ( 5.6 ± 4.8 ) ( P = 0.032 ) . Pregabalin administration was associated with greater pain tolerance thresholds in both lower limbs compared with placebo at 24 hours postoperatively . CONCLUSION : Perioperative pregabalin administration is associated with less pain intensity and improved functional outcomes 3 months after lumbar discectomy Purpose Early postoperative pain is a common complaint after elective laparoscopic cholecystectomy . The use of non-opioid medications as a part of multimodal analgesia has been increasingly advocated in the management of acute post-surgical pain . This r and omized , double-blinded , placebo-controlled study evaluated the efficacy of pregabalin , celecoxib , and their combination in the management of acute postoperative pain in patients undergoing elective laparoscopic cholecystectomy . Methods One hundred ASA I/II patients scheduled to undergo elective laparoscopic cholecystectomy were assigned to receive two perioperative doses , 12 h apart , of either pregabalin alone , celecoxib alone , their combination , or a placebo . St and ard anesthetic protocol was followed . The primary outcomes were postoperative pain at rest and with movement . Secondary outcomes were fentanyl requirements and side effects , which were assessed at 1 , 2 , 4 , 8 , 12 , and 24 h following surgery . Patient satisfaction with pain relief was recorded at discharge . Differences in main outcomes were analyzed using an intention-to-treat approach . Results There was no statistically significant difference ( p > 0.05 ) between the four groups in terms of outcomes such as rest pain , movement pain , postoperative fentanyl requirements , or changes in anxiety scores . Patients who had only celecoxib had significantly higher satisfaction with pain management ( p = 0.013 ) . Patients who had only pregabalin were at three-times-higher odds of having drowsiness ( p = 0.040 ) and four-times-higher odds of having lightheadedness ( p = 0.019 ) when compared with the placebo group . Conclusions Pregabalin , celecoxib alone , or in combination offers no analgesic superiority over st and ard opioid care in the treatment of postoperative pain following laparoscopic cholecystectomy Background Postthoracotomy pain syndrome ( PTPS ) is a frequent cause of chronic postoperative pain . Pregabalin might reduce the incidence of chronic postoperative pain . The goal of this study was to evaluate the impact of perioperative pregabalin on the occurrence of PTPS , defined as any surgical site pain 3 months after surgery . Methods We conducted a r and omized , placebo-controlled , double-blind trial in patients undergoing elective thoracotomy . Patients received either pregabalin 150 mg orally twice a day initiated 1 hour before thoracotomy and continued until 4 days after thoracotomy ( 10 doses total ) or a placebo using the same protocol . All patients received preincision thoracic epidural analgesia . Postthoracotomy pain syndrome was evaluated using the Brief Pain Inventory question naire through a telephone interview . Secondary outcomes included evaluation of neuropathic characteristics through the Leeds Assessment of Neuropathic Symptoms and Signs question naire , analgesic use 3 months after surgery , and evaluation of acute postoperative pain and opioid consumption . Results One hundred fourteen patients were r and omized , and 99 patients completed the study ( placebo , n = 49 ; pregabalin , n = 50 ) . Postthoracotomy pain syndrome occurred in 49 ( 49.5 % ) of 99 patients and more frequently in the pregabalin group ( 31/50 [ 62 % ] vs 18/49 [ 37 % ] in the placebo group , P = 0.01 ) . However , among patients with PTPS , those in the pregabalin group required significantly less analgesics , reported less moderate to severe average pain , and presented significantly less neuropathic characteristics than patients in the placebo group 3 months after surgery . Conclusions Pregabalin did not reduce the incidence of PTPS in this study . Future research on PTPS should focus on the impact of regional analgesia on central sensitization BACKGROUND : Although pregabalin shows efficacy against neuropathic pain , very limited evidence supports postoperative analgesic efficacy . Our study objective was to investigate analgesic efficacy in an ambulatory day surgical population experiencing acute visceral pain . The null hypothesis was that there was no significant difference in pain relief between pregabalin and placebo . METHODS : A r and omized , double-blind , parallel-group , placebo-controlled trial was performed in 90 women having minor gynecological surgery involving the uterus . Patients received either oral pregabalin 100 mg ( Group PG ) or placebo ( Group C ) approximately 1 h before surgery . The primary outcome was pain score in the recovery unit and patients were followed for 24 h. RESULTS : There was no significant difference between groups for pain experienced in the recovery room ( median , interquartile range 16 , 0–36 vs 10 , 6.5–36 for Groups PG and C , respectively , P = 0.80 ) or thereafter ; nor for recovery room fentanyl requirement ( 42 % Group PG versus 27 % Group C , P = 0.12 ) or the quality of recovery at 24 h postoperatively ( median , interquartile range score 17 , 17–18 Group PG versus 18 , 16.5–18 Group C , P = 0.75 ) . The incidence of posthospital discharge light-headedness , visual disturbance , and difficulty with walking was significantly higher in the pregabalin group . CONCLUSIONS : A single preoperative dose of 100 mg pregabalin does not reduce acute pain or improve recovery after minor surgery involving only the uterus BACKGROUND : Pregabalin is a gabapentinoid compound , which has been alleged to possess anxiolytic , analgesic , and anticonvulsant properties . We hypothesized that premedication with oral pregabalin would produce dose-related reductions in acute ( state ) anxiety and increases in sedation ( sleepiness ) before induction of general anesthesia . A secondary objective was to determine if premedication with pregabalin would reduce postoperative pain . METHODS : One hundred eight ASA I – III out patients undergoing elective surgery were r and omly assigned to one of the four premedication treatment groups : 1 ) control group received placebo capsules , 2 ) pregabalin 75 group received pregabalin 75 mg , po , 3 ) pregabalin 150 group received pregabalin 150 mg , po , and 4 ) pregabalin 300 group received pregabalin 300 mg , po . The effects of the study drug on the patients ’ level of anxiety , sedation , and pain were assessed at baseline ( immediately before study drug administration ) , at 30 and 60 min after drug administration , and immediately before induction of anesthesia , as well as at 30-min intervals in the postanesthesia care unit ( PACU ) using st and ardized 11-point verbal rating scales , with 0 = none to 10 = maximal effect . The need for postoperative opioid analgesic medication , incidence of nausea and vomiting , requirement for rescue antiemetics , and times to discharge from the PACU and hospital , as well as the patients ’ quality of recovery scores , and late recovery outcomes ( e.g. , resumption of dietary intake and recovery of bowel function ) were assessed at a 7-day follow-up interview . RESULTS : Demographic characteristics , times between study drug administration to anesthetic induction , type of surgical procedures , duration of anesthesia , PACU and hospital discharge time , as well as the requirement for fentanyl in the PACU , did not differ among the four study groups . Anxiety levels remained unchanged during the preoperative evaluation period , and did not differ among the four study groups . Sedation scores were significantly higher in the pregabalin 300 group at the preinduction assessment interval and at 90 and 120 min after surgery compared with the control group ( 5 ± 3 vs 3 ± 2 , 7 ± 4 vs 5 ± 3 , 8 ± 4 vs 4 ± 4 , respectively , P < 0.05 ) . CONCLUSION : Preoperative pregabalin administration ( 75–300 mg po ) increased perioperative sedation in a dose-related fashion , but failed to reduce preoperative state anxiety , postoperative pain , or to improve the recovery process after minor elective surgery procedures BACKGROUND Optimal pain treatment with minimal side-effects is essential for early mobility and recovery in patients undergoing total hip arthroplasty . We investigated the analgesic effect of pregabalin and dexamethasone in this surgical procedure . METHODS One hundred and twenty patients were r and omly allocated to either Group A ( placebo ) , Group B ( pregabalin 300 mg ) , or Group C ( pregabalin 300 mg+dexamethasone 8 mg ) . The medication and acetaminophen 1 g were given before operation . Spinal anaesthesia was performed . Postoperative pain treatment was with acetaminophen 1 g three times daily and patient-controlled i.v morphine , 2.5 mg bolus . Nausea was treated with ondansetron . Morphine consumption , pain intensity at rest and during mobilization , nausea and vomiting , sedation , dizziness , and consumption of ondansetron were recorded 2 , 4 , and 24 h after operation . P<0.05 was considered statistically significant . RESULTS Twenty-four hour morphine consumption was significantly reduced in Groups B [ mean ( SD ) 24 ( 14 ) mg ] and C [ 25 ( 19 ) mg ] compared with Group A [ 47 ( 28 ) mg ] . Vomiting was reduced in Group C compared with Group B ( P=0.03 ) . Sedation was significantly increased in Group B compared with the other groups . CONCLUSIONS Pregabalin result ed in a 50 % reduction in 24 h postoperative morphine requirements . This was not associated with a reduced incidence of nausea or vomiting . Pregabalin result ed in increased levels of sedation . Combining pregabalin and dexamethasone provided no additional effects on pain or opioid requirements AIMS AND OBJECTIVES We evaluated the efficacy of perioperative pregabalin on acute and chronic post-operative pain after off-pump coronary artery bypass ( OPCAB ) surgery . MATERIAL S AND METHODS Forty patients undergoing elective OPCAB surgery were r and omized to pregabalin and control groups . Pregabalin group received 150 mg pregabalin 2 h prior to induction of anesthesia and 75 mg twice daily for 2 post-operative days whereas the control group received placebo at similar timings ; pregabalin and placebo were administered by an anesthesiologist blinded to the drugs . Pain scores ( visual analogue scale [ VAS ] ) and sedation scores were observed at 0 , 4 , 6 , 12 , 24 , 36 and 48 h after extubation . Time to extubation , tramadol consumption and side-effects were noted . VAS score was analyzed by Mann-Whitney U test . The analysis of variance test for repeated measures was used for comparison of the means of continuous variables . Group comparisons were made using the Chi-square-test . RESULTS Pain-scores at 6 , 12 , 24 and 36 h from extubation at rest and at deep breath were less in pregabalin treated patients ( P < 0.05 ) . Tramadol consumption was reduced by 60 % in pregabalin group ( P < 0.001 ) . Extent of sedation , extubation times and incidence of nausea were comparable . The effect on chronic post-operative pain was not significant . CONCLUSIONS Perioperative pregabalin reduced pain scores at rest and deep breath and reduced consumption of tramadol in the post-operative period without delaying extubation and causing excessive sedation BACKGROUND Pregabalin has a similar pharmacologic profile to that of its developmental predecessor gabapentin but has shown greater analgesic activity in rodent models of neuropathic pain . OBJECTIVE The objective of the study was to compare the effects of 2 different doses of pregabalin and placebo on postoperative pain and morphine consumption . METHODS Ninety patients who underwent abdominal hysterectomy were included in the study and r and omly divided into 3 groups in a doubled-blinded manner . They were given 150 mg of pregabalin ( group P300 , n = 30 ) , 300 mg of pregabalin ( group P600 , n = 30 ) , or placebo capsules ( group C , n = 30 ) 4 hours before the induction of anesthesia ; they received a second dose of the drug 12 hours postoperatively . Morphine consumption , nausea , and vomiting , visual analogue scale-pain intensity ( VAS-PI ) , sedation scores , and dissatisfaction scores were recorded in the postanesthesia care unit ( PACU ) and at 2 , 4 , 6 , and 24 hours after operation . RESULTS Morphine consumption at 24 hours was 40.80 ( 3.42 ) mg , 33.79 ( 5.77 ) mg , and 46.97 ( 6.67 ) mg in groups P300 , P600 , and C , respectively ( P < 0.001 ) . VAS-PI scores at movement and at rest in the PACU and at 2 , 4 , and 6 hours decreased in group P600 ( P < 0.01 ) . In the PACU and at 2 , 4 , and 6 hours , the sedation scores were increased in group P600 compared with the scores in group C ( P < 0.001 , P < 0.001 , P = 0.01 , P = 0.006 , respectively ) . Patient satisfaction was higher in group P600 than in group C for all time points ( P < 0.001 , P < 0.001 , P < 0.001 , P = 0.001 , P < 0.001 , respectively ) . There were no statistically significant differences between the groups for side effects such as nausea , vomiting , and dizziness ( P = 0.58 ) . CONCLUSIONS Pregabalin at a total dose of 600 mg , administered before operation and at 12 hours postoperatively after abdominal hysterectomy , reduced morphine consumption and pain intensity and increased patient satisfaction . No significant differences in side effects were observed between the study groups BACKGROUND Pregabalin , an antiepileptic and chronic pain medication , has been used by various authors for preoperative analgesia . We have assessed the effect of pre-emptive administration of the drug to patients scheduled for elective abdominal hysterectomy . METHODS Seventy-four ASA I and II patients were included in this prospect i ve , double blind study . They were r and omised to receive 75 , 150 , or 300 mg of pregabalin , or 7.5 mg of midazolam as a placebo , one hour before anaesthesia and surgery . Anaesthesia was induced with propofol and maintained with sevoflurane or desflurane . Fentanyl was used for analgesia and rocuronium for muscle relaxation . Immediately after surgery , patients received morphine intravenously in 2 mg increments until the NRS score was below 3 . This was then followed by PCA . RESULTS Morphine consumption and pain scores were only significantly lower in the 300 mg pregabalin group , when compared to the placebo and other treatment groups ; there were no differences between placebos and lower doses of pregabalin . CONCLUSION We conclude that pre-emptive administration of 300 mg pregabalin reduces postoperative pain and morphine consumption . Further studies on higher doses would appear to be justified Ketamine and pregabalin each provide postoperative analgesia , although the combination has yet to be evaluated . One hundred and forty‐two patients undergoing total hip arthroplasty were r and omly assigned to receive ketamine alone , pregabalin alone , ketamine and pregabalin combined , or placebo . Pain scores at rest and on movement , morphine consumption , side‐effects , pressure pain thresholds and secondary hyperalgesia were evaluated . Mean ( SD ) total 48‐h morphine use was reduced in patients given ketamine alone ( 52 ( 22 ) mg ) and pregabalin alone ( 44 ( 20 ) mg ) compared with placebo ( 77 ( 36 ) mg ) p < 0.001 . Morphine use was further reduced in patients given both ketamine and pregabalin ( 38 ( 19 ) mg ) with an interaction between ketamine and pregabalin ( ANOVA factorial ; p = 0.028 ) . Secondary hyperalgesia was reduced by ketamine . There were no differences between groups in pain scores after surgery , pressure pain thresholds or side‐effects . The combination of pregabalin and ketamine has a small , beneficial clinical effect STUDY OBJECTIVE To determine whether single preoperative administration of 2 different doses of pregabalin ( 75 and 150 mg ) could decrease postoperative pain intensity and opioid consumption following posterior lumbar interbody fusion surgery . DESIGN Prospect i ve , r and omized , active placebo-controlled , double-blinded study . SETTING Postoperative recovery area and patients ' room . PATIENTS Ninety-seven adult , American Society of Anesthesiologists physical status 1 and 2 patients . INTERVENTIONS Patients were r and omly assigned to receive diazepam 5 mg as an active placebo ( D5 ) , pregabalin 75 mg ( P75 ) , or pregabalin 150 mg ( P150 ) . The study drug was orally administered 2 hours prior to surgery and a st and ard anesthetic technique was used . Postoperative pain was managed using intravenous patient-controlled analgesia with morphine . MEASUREMENT The visual analog scale at rest was used to measure pain intensity immediately after extubation at the postanesthesia care unit , and then 2 , 4 , 6 , 12 , 18 , 24 , 36 , and 48 hours after surgery . Morphine consumption and adverse effects were assessed until 48 hours after surgery . MAIN RESULTS The visual analog scale score at rest was lower in the P150 group than in the D5 group until 2 hours after surgery . Morphine consumption was lower in the P150 group than in the D5 from 0 to 12 hours after surgery . CONCLUSIONS Single preoperative administration of 150 mg of pregabalin 2 hours prior to surgery reduced postoperative pain intensity and morphine consumption compared with 5 mg diazepam in patients who underwent posterior lumbar interbody fusion PURPOSE The effect of a single-dose of pre-emptive pregabalin is still unknown , although it is used as an adjuvant in controlling acute postoperative pain . The purpose of this study was to evaluate the effects of pre-emptive single-dose pregabalin on postoperative acute pain and 24-hour opioid consumption in patients who underwent double-jaw surgery . PATIENTS AND METHODS Forty patients ( 18 to 45 yr old ; American Society of Anesthesiologists status I to II ) for whom elective double-jaw surgery was planned under general anesthesia were included in this study , which had been planned as a prospect i ve , r and omized , and double-blinded study . Patients were r and omly divided into 2 groups : the pregabalin group ( n = 20 ) was given pregabalin 150 mg orally 1 hour before general anesthesia and the placebo group ( n = 20 ) was given an oral placebo capsule . The groups were administered the routine general anesthesia protocol . Postoperative analgesia was performed intravenously in the 2 groups twice a day with dexketoprofen trometamol 50 mg and patient-controlled analgesia with fentanyl . Postoperative analgesia was evaluated using the visual analog scale ( VAS ) . Fentanyl consumption , additional analgesia requirement , and side-effects were recorded during the first 24 hours after surgery . Descriptive and bivariate statistics were computed , and significance was set at a P value less than .05 . RESULTS Compared with placebo , the VAS score was statistically lower in the pregabalin group during the early postoperative period ( P < .05 ) . The 24-hour opioid consumption was significantly higher in the placebo group compared with the pregabalin group ( 509.40 ± 261.56 vs. 260.10 ± 246.53 μq , respectively ; P = .004 ) . In addition , the analgesia requirement was statistically lower in the pregabalin group ( P < .05 ) . Nausea or vomiting was observed more often in the placebo group , whereas other side-effects were similar for the 2 groups . CONCLUSION A single 150-mg dose of pre-emptive pregabalin decreased postoperative opioid consumption in the first 24 hours after double-jaw surgery . Multimodal analgesia techniques that contain pre-emptive analgesia can be used successfully in preventing postoperative pain caused by orthognathic surgery Background Bunionectomy has been used as a model of postoperative pain for opioids and nonsteroidal anti-inflammatory drugs/cyclooxygenase-2 inhibitors with a fast onset of analgesia . The present study was conducted to assess whether the utility of the model can be broadened in assessing the efficacy of analgesics with diverse mechanisms and pharmacokinetic profiles in drug development and to enhance the sensitivity of a bunionectomy model . Methods This was a single center , r and omized , double-blind , placebo-controlled , three-arm , parallel group methodology study to evaluate the effects of pregabalin and naproxen sodium on postoperative pain following bunionectomy . Patients ( n=100 ) were r and omized 1:1:1 to three treatments ( administered 1 hour before and at defined intervals after surgery ) : pregabalin 300 mg before surgery and 150 mg every 8 hours ; naproxen sodium 550 mg before surgery and 550 mg every 12 hours ; or placebo in a double-dummy fashion . Primary endpoints were patient-controlled analgesic ( PCA ) hydromorphone consumption and the time to first PCA hydromorphone use postsurgery over 24 hours . Results Of the 100 patients r and omized , 96 completed the study . Relative to placebo , pregabalin and naproxen sodium , respectively , reduced PCA hydromorphone consumption by 51 % ( P=0.005 ) and 65 % ( P<0.001 ) and increased the median time to first use of PCA hydromorphone by 1.5 hours ( P=0.004 ) and 3.7 hours ( P<0.001 ) . Both drugs significantly ( P<0.050 ) decreased use of oral opioid rescue medication over 24–48 hours postsurgery relative to placebo . Although there were no statistically significant differences between naproxen sodium and pregabalin in opioid consumption and global evaluation of medication , overall naproxen sodium appeared to be more effective at reducing pain . Conclusions The model provided a sensitive method for evaluating efficacy of compounds with diverse mechanisms and pharmacokinetic profiles . The robustness of the enhanced pain model renders bunionectomy pain a valuable tool to assess novel analgesic compounds in small numbers of subjects early in drug development Background : Pregabalin and gabapentin are the gamma-aminobutyric acid analogs used as a part of multimodal analgesic regimen . Aim : To compare the postoperative analgesic benefits of gabapentin or pregabalin as a premedication for lower limb orthopedic surgery under combined spinal-epidural techniques . Setting s and Design : R and omized double-blind study . Material s and Methods : A total of 90 patients were divided into three groups : G , P , C who received gabapentin 1200 mg , pregabalin 300 mg , and placebo , respectively 1.5 h before surgery . All patients received combined spinal-epidural block with 3 ml of 0.5 % intrathecal bupivacaine . Assessment of pain was made with visual analog scale ( VAS ) . Postoperative analgesia was provided with epidural top-ups with 2.5 ml of 0.5 % bupivacaine and fentanyl 25 μg when VAS > 3 . Rescue analgesia in the form of injection diclofenac ( 75 mg ) intramuscularly was given if VAS > 3 even after epidural top-up . A total number of epidural top-ups , rescue analgesia , pain-free interval postspinal anesthesia , and sedation score were noted . Statistical Analysis : This was done using SPSS version 17 . Mean and st and ard deviation were calculated using Chi-square test and analysis of variance . Results : The total postoperative analgesic time was 7.23 h in Group G , 14.80 h in Group P , and 4.17 h in Group C. A total number of epidural top-ups were 2.43 in Group G , 0.77 in Group P , and 4.43 in Group C. Conclusion : Pregabalin 300 mg and gabapentin 1200 mg significantly reduce the need of postoperative rescue analgesia , epidural top-ups , and increase the duration of postspinal anesthesia without altering hemodynamics with sedation as a major side effect Purpose To evaluate the efficacy of pregabalin and gabapentin for reducing post – photorefractive keratectomy ( PRK ) pain . Methods In this r and omized clinical trial , 150 subjects undergoing PRK were allocated into 3 groups . In addition to the routine regimen , pregabalin 75 mg , gabapentin 300 mg , and placebo were administered 3 times daily for 3 days , in groups 1 , 2 , and 3 , respectively . Subjects could take acetaminophen-codeine 300/10 mg tablets every 4 hours as needed . Patients completed a pain assessment survey ( visual analogue scale ranging from 0 = no pain to 10 = most severe pain ) 7 times in the first 3 days following PRK and also recorded the number of consumed acetaminophen-codeine tablets . Results Age , sex , refractive error , ablation depth , and mitomycin-C ( MMC ) application were similar in the 3 study groups ( all p values>0.05 ) . Overall pain scores in the placebo group were 0.9 and 1 unit higher than the pregabalin ( p=0.029 ) and gabapentin ( p=0.023 ) groups , respectively . Severe pain ( score > 7 ) was more frequent in the placebo group on the morning of the first postoperative day ( p=0.043 ) . The difference in the number of consumed acetaminophen-codeine tablets was statistically borderline ( p=0.061 ) and less in the pregabalin ( 7.9±5.2 ) and gabapentin ( 9.0±4.1 ) groups in comparison to the placebo group ( 10.3±5.6 ) . Conclusions Pregabalin and gabapentin seem to be helpful in alleviating post-PRK pain when combined with other measures . Depending on availability , either compound can be used as an adjuvant for pain control in this setting OBJECTIVE The aim of this study was to assess in-hospital ( immediate ) postoperative pain scores and analgesic consumption ( primary goals ) and preoperative anxiety and sleep quality ( secondary goals ) in patients who underwent craniotomy and were treated with pregabalin ( PGL ) . Whenever possible , out-of-hospital pain scores and analgesics usage data were obtained as well . METHODS This prospect i ve , r and omized , double-blind and controlled study was conducted in consenting patients who underwent elective craniotomy for brain tumor resection at Tel Aviv Medical Center between 2012 and 2014 . Patients received either 150 mg PGL ( n = 50 ) or 500 mg starch ( placebo ; n = 50 ) on the evening before surgery , 1.5 hours before surgery , and twice daily for 72 hours following surgery . All patients spent the night before surgery in the hospital , and no other premedication was administered . Opioids and nonsteroidal antiinflammatory drugs were used for pain , which was self-rated by means of a numerical rating scale ( score range 0 - 10 ) . RESULTS Eighty-eight patients completed the study . Data on the American Society of Anesthesiologists class , age , body weight , duration of surgery , and intraoperative drugs were similar for both groups . The pain scores during postoperative Days 0 to 2 were significantly lower in the PGL group than in the placebo group ( p < 0.01 ) . Analgesic consumption was also lower in the PGL group , both immediately and 1 month after surgery . There were fewer requests for antiemetics in the PGL group , and the rate of postoperative nausea and vomiting was lower . The preoperative anxiety level and the quality of sleep were significantly better in the PGL group ( p < 0.01 ) . There were no PGL-associated major adverse events . CONCLUSIONS Perioperative use of twice-daily 150 mg pregabalin attenuates preoperative anxiety , improves sleep quality , and reduces postoperative pain scores and analgesic usage without increasing the rate of adverse effects . Clinical trial registration no. : NCT01612832 ( clinical trials.gov ) & NA ; Pregabalin has anticonvulsant , antihyperalgesic , and anxiolytic properties . In this study we evaluated the control of pain after perioperative administration of pregabalin 300 or 600 mg , compared with diazepam 10 mg . Altogether 91 women scheduled for laparoscopic hysterectomy were r and omized to receive diazepam 10 mg ( D10 ) , pregabalin 150 mg ( P300 ) or 300 mg ( P600 ) for premedication , and the dose was repeated after 12 h , except for the D10 group , in which the patients received placebo . Up until the 1st postoperative morning , analgesia was provided by oxycodone using patient controlled analgesia . The visual analogue scale scores for pain and side effects , and the amounts of the analgesics were recorded for three days after surgery . The doses of oxycodone during hours 0–12 after surgery were similar in the three groups , whereas the dose of oxycodone during hours 12–24 after surgery was smaller in the P600 group than in the P300 group ( 0.09 vs. 0.16 mg kg−1 ; P = 0.025 ) . The total dose of oxycodone ( 0–24 h after surgery ) was smaller in the P600 group than in the D10 group ( 0.34 vs. 0.45 mg kg−1 ; P = 0.046 ) . The incidence of dizziness ( 70 % vs. 35 % ; P = 0.012 ) , blurred vision ( 63 % vs. 14 % ; P = 0.002 ) and headache ( 31 % vs. 7 % ; P = 0.041 ) were higher in the P600 group than in the D10 group . In conclusion , perioperative administration of pregabalin 600 mg decreases oxycodone consumption compared with diazepam 10 mg , but is associated with an increased incidence of adverse effects Purpose : To examine the effect of a 1-time dose of pregabalin ( Lyrica ) on the perception of pain and analgesic consumption after oculofacial plastic surgery . Methods : In this prospect i ve , r and omized , double-blind , placebo-controlled trial , patients presenting to the oculofacial plastic surgery service at University of Colorado Eye Center for functional eyelid surgery and who met the study criteria were consecutively enrolled between October 2011 and September 2012 . Subjects were r and omized to either placebo or 150 mg pregabalin administered 15 minutes to an hour prior to the procedure . The procedure was then performed under the usual st and ard of care . Postoperatively , study subjects recorded pain scores on visual analog scales ( range 0–100 ) at 1 to 2 hours , 2 to 4 hours , 8 to 12 hours , 20 to 28 hours , and 36 to 48 hours and the amount of acetaminophen consumed . Data were analyzed with Statistical Analysis System software using mixed-effects linear models . Results : Fifty-two patients were enrolled . Three patients were excluded due to incomplete follow up ( n = 2 ) and postoperative course requiring early unblinding ( n = 1 ) . Twenty-six subjects were men . Average age was 68 years ( range , 25–89 ) . Eyelid procedures performed included blepharoplasty ( 18 ) , canthoplasty ( 11 ) , ptosis repair ( 15 ) , eyelid retraction repair ( 2 ) , pentagonal wedge resection ( 1 ) , and MOHS reconstruction ( 2 ) . Twenty-six patients were r and omized to receive pregabalin , while the remainder received placebo . There was no significant difference in demographics between the 2 groups . The pregabalin group reported pain scores that were 5.5 points lower on average compared with the placebo group ( p = 0.0307 ) . Patients in the pregabalin group also consumed half as much acetaminophen ( 1.3 g ) on average as the placebo group ( 2.6 g ) during the postoperative period . Conclusions : Pregabalin is effective in reducing postoperative pain after oculoplastic procedures when compared with placebo . It may be a useful adjunct for pain control in selected patients Background : Pregabalin is used for the treatment of neuropathic pain and has shown analgesic efficacy in post‐operative pain . The aim of this r and omized , double‐blinded , placebo‐controlled trial ( Clinical Trials.gov ID NCT00938548 ) was to investigate the efficacy and safety of pregabalin for reducing post‐operative pain in patients after mastectomy BACKGROUND : Total knee replacement ( TKR ) is of enormous benefit to patients with osteoarthritis of the knee ; however , the acute postoperative pain can be severe and difficult to manage . The role of major spinal cord neurotransmitters in this acute postoperative period is not clear , although there are a few studies in humans . We performed the first prospect i ve clinical study undertaken to delineate the changes in the spinal neurotransmitters after a surgery such as TKR . Furthermore , we also determined whether antihyperalgesic drugs at clinical ly acceptable doses modulate spinal neurotransmitter concentrations in patients during the perioperative period . METHODS : All patients had a spinal needle placed in the lumbar region and cerebrospinal fluid ( CSF ) obtained for baseline measurement of the neurotransmitters . An intrathecal catheter was then placed for spinal anesthesia for st and ard TKR and for continuous spinal postoperative analgesia . The spinal catheter was also used postoperatively to sample CSF at 2 , 4 , 8 , 12 , 24 , and 32 hours after catheter placement . CSF sample s were assayed for norepinephrine , substance P , calcitonin gene-related peptide ( CGRP ) , and glutamate concentrations . SF-36 ( 36-item Short Form Health Survey ) was measured preoperatively . Numerical rating scale ( NRS ) pain scores and intrathecal analgesic consumption were recorded postsurgery at 4-hour intervals for 32 hours . We performed a r and omized , placebo-controlled , double-blind trial with 3 drug groups ( n = 16 per group ) : placebo ; single-dose pregabalin ( 150 mg administered before surgery ) ; and multidose pregabalin ( 150 mg administered presurgery and 12 and 24 hours later ) , to determine the effect of an antihyperalgesic drug such as pregabalin on spinal neurotransmitters . RESULTS : Forty-eight patients were r and omly assigned to the 3 perioperative treatment groups , and multiple CSF sample s were successfully obtained from 44 patients . Before surgery , increased bodily pain ( from preoperative SF-36 measure ) was correlated with increased CSF norepinephrine concentration ( P = 0.044 ) . Compared with presurgery values , norepinephrine levels were lower in the placebo group at the 2- and 4-hour time points ( P < 0.005 ) whereas in the single and multidose groups , the reduction ( P < 0.001 ) continued until 12 and 24 hours , respectively . Substance P CSF levels had an early peak value ( at 2 hours ) in all 3 groups , and then returned to baseline . Compared with baseline value , the CGRP CSF levels only decreased at the 32-hour time point in the placebo group , but in both pregabalin groups , CGRP levels decreased over the 4- to 32-hour period . In the placebo group only , CSF glutamate decreased over 4 to 32 hours compared with presurgery values . However , there was no difference in the CSF neurotransmitter concentrations among the 3 treatment groups over the 32-hour sampling period . In the placebo group , the early NRS pain score area under the curve , AUC [ 0–12 hours ] , was positively correlated ( R = 0.67 , P = 0.0088 ) with the CSF norepinephrine concentration AUC [ 12–24 hours ] , but none of the other neurotransmitters was correlated with the NRS . None of the CSF neurotransmitter concentrations correlated with postoperative analgesic consumption . CONCLUSION : In the perioperative period , the concentration changes of the 4 spinal neurotransmitters have a distinct time course . CSF substance P seems to increase very rapidly with surgical intervention , whereas the CSF norepinephrine concentration tends to decrease . At clinical doses , pregabalin does not seem to modulate these spinal neurotransmitter concentrations Purpose Acute pain after open abdominal hysterectomy limits the function of patients in the postoperative period , but data regarding the analgesic efficacy of a low dose of pregabalin ( 75 or 150 mg ) have been conflicting . This study was performed to determine if a low dose of pregabalin could decrease postoperative opioid use following abdominal hysterectomy when compared with placebo . Methods American Society of Anesthesiologists I-II patients older than 18 yr and scheduled for open elective abdominal hysterectomy were recruited for participation and r and omized to one of three groups : pregabalin 75 mg ( P75 ) , pregabalin 150 mg ( P150 ) , or placebo . The study drug was administered two hours prior to surgery and 12 hr following the initial dose . Anesthetic technique and postoperative analgesia were st and ardized . Postoperative pain was managed using patient-controlled analgesia with morphine . Pain at rest and movement as well as nausea were assessed with an 11-point numeric rating scale . Results One hundred and one patients were recruited , and 89 patients completed the study . Mean ( SD ) cumulative morphine consumption at 24 hr postoperatively was 54.0 ( 26.2 ) mg for the placebo group , 53.1 ( 22.7 ) mg for the P75 group , and 44.3 ( 20.9 ) mg for the P150 group . Independent Student ’s t tests indicated no difference between the placebo group and either the P75 group ( 95 % confidence interval [ CI ] : −11.75 to 13.44 ; P = 0.8937 ) or the P150 group ( 95 % CI : −2.74 to 22.15 ; P = 0.1238 ) . Conclusions At the doses used in this study , pregabalin treatment may not be effective in reducing opioid use up to 24 hr postoperatively following abdominal hysterectomy . This trial was registered at www . Clinical Trials.gov : NCT00781131.RésuméObjectifLa douleur aiguë faisant suite à une hystérectomie par voie abdominale limite les fonctions des patients au cours de la période postopératoire , mais les données concernant l’efficacité analgésique d’une faible dose de prégabaline ( 75 ou 150 mg ) ont été contradictoires . Cette étude a été menée pour déterminer si une faible dose de prégabaline pouvait diminuer l’utilisation postopératoire des morphiniques après hystérectomie par voie abdominale , comparativement au placebo . MéthodesDes patientes , âgées de plus de 18 ans , de type I-II selon les critères de l’American Society of Anesthesiologists , et devant subir une hystérectomie programmée par voie abdominale ont été recrutées et r and omisées dans l’un des trois groupes suivants : prégabaline 75 mg ( P75 ) , prégabaline 150 mg ( P150 ) , ou placebo . Le médicament étudié a été administré deux heures avant l’intervention chirurgicale et 12 h après la dose initiale . La technique anesthésique et l’analgésie postopératoire ont été st and ardisées . La douleur postopératoire a été gérée en utilisant une analgésie par morphine contrôlée par le patient . La douleur au repos et au mouvement ainsi que les nausées ont été évaluées au moyen d’une échelle d’évaluation numérique de 11 points . RésultatsCent une patientes ont été incluses et 89 patientes ont terminé l’étude . Les consommations cumulées moyennes ( ET ) de morphine à 24 heures en postopératoire étaient de 54,0 ( 26,2 ) mg pour le groupe placebo , 53,1 ( 22,7 ) mg pour le groupe P75 et 44,3 ( 20,9 ) mg pour le groupe P150 . Des tests t de Student indépendants n’ont pas fait apparaître de différence entre le groupe placebo et soit le groupe P75 ( intervalle de confiance [ IC ] à 95 % : −11,75 à 13,44 ; p = 0,8937 ) , soit le groupe P150 ( IC à 95 % : −2,74 à 22,15 ; p = 0,1238 ) . Conclusions Aux doses utilisées dans cette étude , le traitement par prégabaline ne semble pas être efficace dans la réduction de la consommation de morphine à 24 heures postopératoires après hystérectomie par voie abdominale . Cette étude a été enregistrée sur le site www . clinical trials.gov : NCT00781131 Background : 80 % of patients undergoing surgical procedures experience postoperative pain1 and requires adequate pain relief . Nowadays drugs like COX2 inhibitors and calcium channel modulators ( Pregabalin and Gabapentin ) are been increasingly used for postoperative pain management effectively . We conducted this study to find whether preoperative pregabalin has any effect in postoperative analgesic requirement in patients undergoing hysterectomy under spinal anaesthesia . Patients & Methods : This r and omized , double-blind , placebo-controlled trial was conducted in 150 patients undergoing hysterectomy under spinal anaesthesia , divided in three groups - Group I ( PO ) - Control group , Group II ( P150 ) received 150 mg pregabalin and Group III ( P300 ) received 300 mg pregabalin . We used VAS for anxiety , Ramsay sedation scale and VAS for patient satisfaction regarding pain relief . Results : There was significant reduction in anxiety in groups P ( 150 ) and P ( 300 ) than placebo group P ( 0 ) during intraoperative and postoperative period than preoperative period . There was significant sedation seen in groups P ( 150 ) and P ( 300 ) than placebo group P ( 0 ) . First rescue analgesia in group P ( 300 ) was202.42±6.77 and in group P ( 150 ) was176.38±4.80on average , group P ( 0 ) was131.38±5.15 . Dizziness was 44.44 % in group P ( 300 ) , 36.11 % in group P ( 150 ) , and 19.44 % in group P ( 0 ) . Patient satisfaction was better in P ( 300 ) group than other two groups . Conclusions : Pregabalin being an oral drug which would be easy for the patients to take and also its prolongation of the neuraxial block helps in immediate postoperative analgesia and further reduction of other parentral analgesics . Pregabalin 150 mg would be the optimal preemptive dose for hysterectomy under spinal anaesthesia INTRODUCTION We hypothesised that preoperative administration of a single-dose of pregabalin would be associated with lower morphine consumption after uncomplicated caesarean delivery . METHODS After Institutional Ethics Committee approval , 135 parturients scheduled for elective caesarean delivery under spinal anaesthesia were r and omly allocated to receive either placebo , or oral pregabalin 150 mg or 300 mg , one hour before induction of anaesthesia . Maternal cumulative morphine requirement at 24h , pain scores , sedation scores , nausea and vomiting , pruritus , pregabalin-related adverse effects , Apgar scores , Neurologic and Adaptive Capacity scores and umbilical cord acid-base status were recorded . RESULTS Compared with placebo or pregabalin 150 mg , the use of a preoperative dose of pregabalin 300 mg result ed in significantly lower cumulative morphine consumption at 24h ( mean dose : placebo 12.9 mg [ 95 % CI 11.6 to 14.2 ] ; pregabalin 150 mg 11.9 mg ; [ 95 % CI 10.7 to 13.1 ] ; pregabalin 300 mg 6 mg [ 95 % CI 5.4 to 7.3 ] ; P<0.001 ) . Pregabalin 300 mg result ed in lower pain scores at 4h and 6h after delivery ( P<0.001 ) , and fewer instances of nausea , vomiting and pruritus ( P<0.009 ) . Dizziness and abnormal vision were observed most frequently in the pregabalin 300 mg group ( P<0.05 and P<0.009 , respectively ) . The three groups were similar in terms of maternal sedation , Apgar scores , Neurologic and Adaptive Capacity scores and umbilical cord acid-base status . Three babies in the pregabalin 300 mg group ( 6.7 % ) experienced short-term poor latching-on for breastfeeding . CONCLUSION In our study , preoperative administration of pregabalin 300 mg reduced postoperative morphine consumption and early postoperative pain in parturients undergoing elective caesarean delivery , although maternal side effects were more common Study Design . Prospect i ve , double-blind study , r and omized control trial . Objective . To evaluate and compare the analgesic efficacy , adverse effects , and clinical utility of gabapentin and pregabalin in postoperative pain management , long-term functional outcome , and quality of life in patients undergoing spinal surgery . Summary of Background Data . Patient outcome after lumbar discectomy for radicular low back pain is variable and the benefit is inconsistent . The most common persistent symptoms are pain , motor deficit , and decreased functional status . Methods . This study was conducted in 90 patients belonging to the 18 to 75 age group of either sex undergoing spinal surgery under general anesthesia . Group A received 300 mg of gabapentin , group B received 75 mg of pregabalin , whereas group C received placebo 1 dose 1 hour before surgery and 8 hourly for 7 days , thereafter . The outcome of postoperative static and dynamic pain and functional outcome was recorded using 3 question naires — visual analogue scale , Prolo functional and economic score , Oswestry Disability Index score from preoperative period to 3 months postoperatively . Results . Among the 3 groups , subjects receiving pregabalin showed consistently reduced static and dynamic pain intensity and also required lesser amount of rescue drug throughout the postoperative period . There was statistically significant difference ( P < 0.05 ) in the Prolo score and Oswestry Disability Index score at all time intervals between group B and group C. Although , significant difference in the functional outcome between group A and group B was seen at 3 months . Conclusion . Preoperative pregabalin administration is associated with less pain intensity and improved functional outcomes 3 months after lumbar discectomy followed by gabapentin and then placebo . Level of Evidence : OBJECTIVE To evaluate the analgesic effect of perioperative administration of pregabalin in patients undergoing arthroscopic anterior cruciate ligament reconstruction . MATERIAL AND METHOD Fifty-six patients were r and omly assigned to receive either pregabalin 75 mg or a matching placebo , one hour prior to spinal anesthesia , with the second dose repeated 12 hours after the first dose in this comparative study . The means of postoperative pain intensity measured by a verbal rating scale ( VRS ) of 0 to 10 , sedation score of 0 to 3 , requirement for morphine using a patient-controlled analgesia ( PCA ) device , and the median respiratory rate , as well as adverse effect were recorded every four-hour up to 24 hours . RESULTS Twenty-seven patients received pregabalin , and 29 cases got placebo . Characteristics were not significantly different between the two groups , except for the ages of 29.3 years in the pregabalin group , and 33.8 years in the placebo group . The means of postoperative pain severity , sedation score , consumption of PCA morphine , median respiratory rate , and adverse effects were not significantly different between the two groups . CONCLUSION Perioperative administration of pregabalin was not superior to placebo in terms of reducing postoperative pain intensity and PCA morphine requirement in patients undergoing arthroscopic anterior cruciate ligament reconstruction INTRODUCTION Conquering postoperative pain which has significant impact on the surgery outcome can be challenging for the clinicians . Pregabalin is a GABA analogue used for various neuropathic pain syndromes . Very few studies are there with the use of pregabalin as a preemptive analgesic for orthopedic surgeries . AIM To compare pregabalin 150 mg with placebo for postoperative pain control in patients undergoing elective lower limb orthopedic surgeries under spinal anaesthesia and to assess any side effects . MATERIAL S AND METHODS A r and omized double blinded prospect i ve study was undertaken . Ninety patients with ASA physical status I , II , aged between 18 - 50 years were enrolled in the study . One hour prior to spinal anaesthesia Group C - received colour matched empty capsules , Group P - received 150 mg of oral pregabalin . Spinal anaesthesia was administered in sitting position in L3-L4 space with Inj . Bupivacaine heavy ( 0.5 % ) at a dose of 0.3mg/kg body weight with 20 mg being the maximum dose using 25 gauge spinal needle . Rescue analgesia was provided with using Inj . Diclofenac 1.5 mg/kg intramuscular . RESULTS Time for rescue analgesia ( VAS score > 3 ) was significantly increased in Group P than in Group C. The total dose of diclofenac required in the 24 hour postoperative period was significantly lower in Group P than in Group C. The sedation scores and patient satisfaction scores were also more in Group P than in Group C. CONCLUSION Preemptive pregabalin in an oral dose of 150 mg offers good postoperative analgesia in lower limb orthopedic surgeries under spinal anaesthesia Context The antiepileptics gabapentin and pregabalin are used as adjuvants to control postoperative pain . Objective The aim of the present study was to investigate the effect of perioperative administration of pregabalin on postoperative acute and chronic pain and analgesic requirements . Setting Department of Anaesthesiology , Aretaieio University Hospital , Athens , Greece . Patients Eighty patients scheduled for abdominal hysterectomy or myomectomy were r and omly assigned to the pregabalin or to the control group . Intervention The pregabalin group received 150 mg of pregabalin 8-hourly , starting on the afternoon before surgery and continued until the fifth postoperative day . The control group was similarly treated , but received placebo capsules instead . Measurements Postoperative intravenous morphine and Lonalgal ( 30 mg codeine with 500 mg paracetamol ) tablet consumption , visual analogue pain scores at rest and on coughing , sedation , anxiety , dizziness , ataxia , blurred vision and diplopia were recorded . One and 3 months postoperatively patients were interviewed for the presence of pain and analgesic needs due to surgery . Results The pregabalin-treated patients consumed less morphine during the first 48 h postoperatively ( P = 0.0001 ) . However , consumption of Lonalgal tablets and visual analogue scores for pain at rest and on coughing did not differ between the groups . No difference was found in sedation and anxiety scores between the patients who received placebo or pregabalin . Patients in the control group had lower incidences of dizziness ( 29 versus 58 % , P = 0.015 ) , ataxia ( 0 versus 18 % , P = 0.011 ) , blurred vision ( 6 versus 26 % , P = 0.028 ) and diplopia ( 0 versus 16 % , P = 0.023 ) . Presence of pain , analgesic intake due to surgery and decreased or absent sensation around the wound did not differ between the groups 1 and 3 months postoperatively . Conclusion Pregabalin in the doses given decreased morphine requirements for the first 48 h postoperatively , but neither altered the analgesic requirements beyond 48 h nor had any effect on acute , late or chronic pain Background The treatment of pain in obese patients is always a challenge . These patients have low pain thresholds , and the use of opioids can be especially harmful . Intraoperative nervous fiber section and the high temperatures of electrical scalpels probably contribute to the generation of postoperative neuropathic pain . We hypothesized that an antineuropathic pain drug like pregabalin could be helpful to optimize postoperative analgesia by reducing the requirement for opioids and their associated side effects . Methods Eighty adults undergoing laparoscopic sleeve gastrectomy were r and omly assigned to orally receive either placebo capsules ( control ) or pregabalin ( 150 mg ) 2 h before surgery . Postoperative morphine consumption during the first 24 postoperative hours was registered . Visual analog pain scores ( VAS ) were assessed at 1 , 2 , 4 , 6 , 8 , 12 , 16 , and 24 h after surgery . Both the incidence of adverse reactions and patient satisfaction were also assessed . Results Over a 24-h period , the morphine consumption in the pregabalin group was 11.51 ± 7.93 mg , whereas in the control group , it was 23.07 ± 9.57 mg ( p < 0.0001 ) . VAS scores were significantly lower in the pregabalin group . Postoperative nausea and vomiting and the consumption of antiemetics were reduced in the pregabalin group . Conclusions A single preoperative oral dose of 150 mg pregabalin is useful for reducing morphine consumption after a sleeve gastrectomy , and it guarantees effective and safe analgesia with a low incidence of adverse effects Objectives : Pregabalin and clonidine have anti-nociceptive properties . This study assesses their efficacy in prolonging the analgesic effect of spinal anesthesia and post-operative analgesic requirement in patients undergoing vaginal hysterectomy . Material s and Methods : A total of 90 females in the age group of 30 - 60 years were r and omly allocated in to three groups of 30 each , to receive either oral clonidine ( 150 μg ) or oral pregabalin ( 150 mg ) or oral multivitamin as placebo 1.5 h before spinal anesthesia with 3ml ( 15 mg ) of 0.5 % hyperbaric bupivacaine . Intensity of pain was measured on a visual analog scale ( VAS ) at the end of operation ( 0 h ) then at 1,2,4,6,12 and 24 h thereafter . Diclofenac sodium intramuscularly 1 mg/kg was provided when the VASscore was > 4 in the study period . Sedation was defined by Ramsay sedation scale at 0,6,12 and 24 h. Side-effects such as nausea and vomiting , respiratory depression and dryness of mouth were noted . Results : The VAS scores were significantly less in the pregabalin group compared with the clonidine group at 6,12 and 24 h post-operatively with a P < 0.0001 . More sedation was seen in the clonidine group than in the pregabalin group ( P < 0.05 ) . Analgesic consumption and VAS scores were lower in clonidine and pregabalin group compared with the placebo group ( P < 0.05 ) . Conclusion : Oral pregabalin ( 150 mg ) prolongs the post-operative pain relief after spinal anesthesia but produces less sedation compared with oral clonidine ( 150 μg ) Background and Aims : Preemptive analgesia is an antinociceptive treatment that prevents establishment of altered processing of afferent input . Pregabalin has been cl aim ed to be more effective in preventing neuropathic component of acute nociceptive pain of surgery . We conducted a study to compare the effect of oral gabapentin and pregabalin with control group for post-operative analgesia Material s and Methods : A total of 90 ASA grade I and II patients posted for elective gynecological surgeries were r and omized into 3 groups ( group A , B and C of 30 patients each ) . One hour before entering into the operation theatre the blinded drug selected for the study was given with a sip of water . Group A- received identical placebo capsule , Group B- received 600 mg of gabapentin capsule and Group C — received 150 mg of pregabalin capsule . Spinal anesthesia was performed at L3-L4 interspace and a volume of 3.5 ml of 0.5 % bupivacaine heavy injected over 30sec through a 25 G spinal needle . VAS score at first rescue analgesia , mean time of onset of analgesia , level of sensory block at 5min and 10 min interval , onset of motor block , total duration of analgesia and total requirement of rescue analgesia were observed as primary outcome . Hemodynamics and side effects were recorded as secondary outcome in all patients . Results : A significantly longer mean duration of effective analgesia in group C was observed compared with other groups ( P < 0.001 ) . The mean duration of effective analgesia in group C was 535.16 ± 32.86 min versus 151.83 ± 16.21 minutes in group A and 302.00 ± 24.26 minutes in group B. The mean numbers of doses of rescue analgesia in the first 24 hours in group A , B and C was 4.7 ± 0.65 , 4.1 ±0.66 and 3.9±0.614 . ( P value < 0.001 ) . Conclusion : We conclude that preemptive use of gabapentin 600 mg and pregabalin 150 mg orally significantly reduces the postoperative rescue analgesic requirement and increases the duration of postoperative analgesia in patients undergoing elective gynecological surgeries under spinal |
637 | 24,910,940 | Comparisons of all outcomes in N RCTs and RCTs failed to show statistical significance .
Prospect ive/retrospective cohort studies , case series , and RCTs did not differ significantly in their estimates .
Adjusted testing for metaregression disclosed that rerecurrence among N RCTs was independent of the study design .
The number of included patients and study setting were independent predictors of outcome . | To examine , if case series considered together with observational studies tend to produce similar results as r and omized-controlled trials ( RCTs ) , on recurrent hernia repair . | INTRODUCTION Since 1994 we perform laparoscopic total extraperitoneal hernia repair ( TEP ) for primary and recurrent inguinal hernias at our institution . The aim of this study was to investigate and compare the results of TEP in primary inguinal hernias and recurrent inguinal hernias and to determine whether there are differences in patient data , complication rates and outcome between these two groups . METHODS In a prospect i ve trial 338 patients were analyzed who underwent 500 laparoscopic TEP repairs . In all , 431 TEP repairs were performed for primary inguinal hernias , and 69 for recurrent inguinal hernias . For data acquisition the SALTC study protocol was used . All patients were clinical ly examined 3 and 12 months after the operation . RESULTS The mean operation time was 67.3 min for TEP repair of primary hernias and 68.1 min for TEP repair of recurrent hernias , respectively . The conversion rate to an open procedure was 0 % . Conversion from TEP into TAPP was required in 0.5 % of patients with primary inguinal hernias and 1.4 % of patients with recurrent inguinal hernias . As the sole difference between the two groups the intraoperative complication rate could be identified . In the TEP repair group of recurrent inguinal hernias a higher incidence of injury to the peritoneum and a higher occurrence of bleeding from the epigastric vessels was found ( P = 0.03 ) . The postoperative complication rate was identical in the two groups , amounting to 5.1 % and 5.7 % , respectively . No differences were found in the 1 year follow-up between the two groups . The 1-year recurrence rate was 0.5 % for primary hernias . However , in the group of recurrent hernias there have been no recurrences to date . CONCLUSIONS The use of laparoscopic TEP repair has proven to be a safe and effective treatment in patients with primary and recurrent inguinal hernias . Because of scar tissue with possible adhesions a higher intraoperative complication rate was observed in the TEP repair of recurrent hernias than in TEP repair of primary inguinal hernias . However , no single recurrence was observed in the TEP repair group of recurrent hernias . In our opinion TEP is the optimal hernia repair for recurrent and bilateral inguinal hernias 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 Background : A variety of procedures with substantial differences in results are employed to treat recurrent inguinal hernia . The advantages of totally extraperitoneal patch repair ( TEP ) are even more evident when it is applied to recurrent compared to primary hernias . To investigate the superiority of this method more closely , we review ed our results obtained for recurrent inguinal hernias over a period of 2 years . Methods : We performed a prospect i ve single-center study using data obtained in consecutive patients with recurrent inguinal hernia who were operated on in 1997 and 1998 . Results : A total of 179 patients with recurrent inguinal hernia were recruited . Overall , 1329 patients with inguinal hernia were treated in the 2-year period , of whom 1270 underwent TEP . The percentage of recurrent hernias was 14 % . The average age of the patients was 56 years . The follow-up rate was 87.5 % , and the mean follow-up period was 2.3 years . The 154 patients who were followed up underwent a total of 225 hernia repairs , of which 181 were for recurrent hernias . The average operating time was 57 min . In 68 % ( 104/154 ) of the patients , adhesions , adherent epigastric vessels , or cicatricial changes were found , which result ed in the inadvertant opening of the peritoneum in 26.3 % of the patients . All the openings in the peritoneum were closed by endoscopic suturing . Intraoperative complications developed in 4 patients ( 2.3 % ) , including one injury to the bladder and three cases of bleeding from side branches of the epigastric vessels . The conversion rate was 0 % . The sole postoperative complication was treatment requiring hematomas in 7 patients , in 2 of whom reoperation became necessary . In both cases , a diffuse hemorrhage due to a preoperatively undiagnosed coagulation disorder was found . No cases of wound or patch infection were observed . In a patient undergoing both primary and recurrent hernia repair , displacement of a mesh led to a recurrence on the primary hernia side ( recurrence rate , 0.4 % ; re-recurrence rate , 0 % ) . Conclusions : Although for its definitive management , recurrent hernia requires a reliable operative technique , current data do not support the recommendation of any of the currently available procedures as the gold st and ard . In a representative patient population with recurrent hernia , we were able to demonstrate that TEP achieves very good results in terms of re-recurrence rate , intraoperative and postoperative complications , and rehabilitation . Prerequisites for the reliable and low-complication application of the method are a high level of st and ardization of the procedure and an advanced learning curve Evidence -based medicine ( EBM ) ranks different medical research methods on a hierarchy , at the top of which are r and omized controlled trials ( RCTs ) and systematic review s or meta-analyses of RCTs . Any study that does not r and omly assign patients to a treatment or a control group is automatically placed at a lower level on the hierarchy . This article argues that what matters is whether the treatment and control groups are similar with respect to potential confounding factors , not whether they got that way through r and omization . Moreover , nonr and omized studies tend to have other characteristics that make them useful sources of evidence , in that they tend to last longer and to enroll more patients than do r and omized trials . Replacing the sharp dichotomy between r and omized and nonr and omized studies with a continuum from “ clean ” studies ( which have high internal validity but whose results do not readily generalize to clinical practice ) to pragmatic studies ( which are design ed to more closely reflect clinical practice ) would also make a place for outcomes research and research using clinical data bases , which are not included in the current hierarchy of evidence but which can provide important information about the safety and efficacy of treatments Background : The aim of this study was to investigate the outcome of preperitoneal repair using laparoscopic ( TEP ) and open ( OPM ) approach in recurrent inguinal hernia . Methods : We performed a prospect i ve controlled nonr and omized clinical study in 188 patients with 207 recurrent inguinal hernias over a period of 5 years . TEP repair was employed for 86 repairs , and OPM was used in 121 procedures . The main outcome measurements were : recurrence rate , operating time , hospital stay , and postoperative complications . Results : There were three recurrences ( 1.7 % ) . Two in the OPM group ( 1.8 % ) and one ( 1.3 % ) in the TEP group [ P = NS ( not significant ) ] . The TEP procedure was faster than OPM for unilateral repair ( 40.8 vs 46.3 min ) ( P<0.001 ) . Postoperative complications were more frequent in the OPM group ( 23.9 % ) than the TEP group ( 13.9 % ) ( P = NS ) . Hospital stay was significantly shorter in the TEP group ( 1.2 vs 3.9 days ) ( P<0.001 ) . Conclusions : Preperitoneal approach ( open or laparoscopic ) seems to be a good option in recurrent inguinal hernia when these procedures are done by experienced surgeons Introduction The Lichtenstein hernioplasty for the repair of primary inguinal hernia in male patients is well established and constitutes the current gold st and ard . However a gold st and ard technique for the repair of recurrent inguinal hernia has not been established . The aim of this study was to analyze the outcomes of Lichtenstein hernioplasty for the repair of primary inguinal hernia and recurrent inguinal hernia , applying for that purpose the Qualitative and Quantitative Measurement Instrument ( QQMI ) . Methods We studied 75 recurrent inguinal hernia patients and 287 primary inguinal hernia patients with a follow-up period ranging from 60 to 107 months . Results The final QQMI score demonstrated that most patients in both groups reached scores between 8 and 11 points , with a significant difference in the maximum score ( 11 points ) favoring primary hernia patients . Conclusions All evaluated parameters showed better outcomes in primary hernia patients . Applying the QQMI , we have demonstrated that the outcomes of Lichtenstein hernioplasty are not similar between primary and recurrent inguinal hernia ; there is a tendency toward better outcomes for primary inguinal hernia patients , although the Lichtenstein hernioplasty st and s as a safe option for repair of recurrent inguinal hernias Objective : To compare the Lichtenstein hernioplasty with a totally extraperitoneal preperitoneal laparoscopic technique ( TEP ) in treatment of recurrent inguinal hernias . Summary Background Data : Only a few studies thus far have compared an open and laparoscopic approach with the treatment of recurrent inguinal hernia in a prospect i ve r and omized study setting . Methods : Ninety-nine patients undergoing surgery for recurrent inguinal hernia were prospect ively r and omized into having either open or laparoscopic mesh repair . Pre , peri- and postoperative factors were recorded in addition to 3-year follow-up data at the outpatient clinic . At 5–10 years , the patients were interviewed via telephone for recurrent symptoms . The primary end-points chosen were hernia recurrence and chronic pain . Results : Preoperative factors did not differ between the 2 groups . Rerecurrence rates were 3 in the Lichtenstein group and none in the TEP group ( 6.4 % versus 0.0 % , respectively ) , but this difference was statistically not significant . Chronic pain was more prevalent in the Lichtenstein group compared with the TEP group ( 13 [ 27.7 % ] versus 4 [ 8.2 % ] patients , respectively , P = 0.02 ) . Postoperatively , the Lichtenstein group needed more pain medication than the TEP group ( 4.4 versus 3.0 doses , respectively , P = 0.02 ) and returned to work later ( 17.9 versus 14.8 days , respectively , P = 0.05 ) . Conclusions : The laparoscopic technique with mesh in the treatment of recurrent inguinal hernia was proven superior to the open mesh repair in several important clinical aspects , with concomitant improvement in patient satisfaction Background Recurrences continue to be seen after repair of inguinal hernias . The repair of these recurrent hernias is a more complex and dem and ing procedure , with a high re-recurrence rate . Definite advantage has been demonstrated with endoscopic repair of these hernias . Methods The results for this prospect i ve study from January 2003 to December 2006 were evaluated after laparoscopic repair of 65 recurrent hernias in 61 patients . The patients were followed up for 1 year . Longer follow-up evaluation was performed for the patients who underwent surgery in the initial 3 years . Results In this study , 37 recurrent hernias were managed using the transabdominal preperitoneal technique ( TAPP ) technique and 28 using the totally extraperitoneal ( TEP ) technique . There was no conversion and no cases of postoperative wound infection . Of the 12 metachronous hernias repaired simultaneously , 3 were occult . Seroma developed in five patients . At a follow-up assessment after 1 year , one patient had groin pain , and there was one re-recurrence . A longer follow-up period with a mean of 35.11 months failed to show any new re-recurrence . Conclusions Laparoscopic repair of recurrent inguinal hernia is safe and effective . The morbidity and recurrence rates for the procedure are as low as for laparoscopic repair of primary hernias . Laparoscopic repair should be the gold st and ard for these hernias Background The optimal treatment for recurrent inguinal hernia is of concern due to the high frequency of recurrence . Methods This r and omized multicenter study compared the short- and long-term results for recurrent inguinal hernia repair by either the laparoscopic transabdominal preperitoneal patch ( TAPP ) procedure or the Lichtenstein technique . Results A total of 147 patients underwent surgery ( 73 TAPP and 74 Lichtenstein ) . The operating time was 65 min ( range , 23–165 min ) for the TAPP group and 64 min ( range , 25–135 min ) for the Lichtenstein group . Patients who underwent TAPP reported significantly less postoperative pain and shorter sick leave ( 8 vs 16 days ) . The recurrence rate 5 years after surgery was 19 % for the TAPP group and 18 % for the Lichtenstein group . Conclusion The short-term advantage for patients who undergo the laparoscopic technique is less postoperative pain and shorter sick leave . In the long term , no differences were observed in the chronic pain or recurrence rate Observational studies have a record of extremely successful contributions to medicine . They are essential for our knowledge about causes and pathogenesis — eg , genetic , environmental , or infectious causes of disease . Additionally , for medical practice we rely on observational studies of prognosis and diagnosis . Nevertheless , over the past years , we have seen recurrent debates about the merit of observational versus r and omised research . The debates have been fuelled recently because of seeming total failures , in which the results of observational studies were completely overturned by r and omised studies . Hormone replacement therapy showed protection from myocardial infa rct ion in observational studies , but a small increase was seen in r and omised trials ; a similar reversal happened for carotene and lung cancer . Such discrepancies raise the question : in what circumstances can observational comparisons be as convincing as r and omised experiments ? To answer that question : I will first recall what is expected from r and omisation . I will then describe two specific issues , adverse effects of drugs and genetic causes of disease , to eluci date under what circumstances evidence from observational research is as good as that from r and omised trials . This description can be generalised to other areas of clinical and epidemiological research , and leads to a proposal for a three-pronged restriction to give observational research the best chance to be as credible as r and omised controlled trials . Benefits of r and omisation Two benefits are expected from r and omisation : unbiased allocation of treatment , because of easier concealment of the allocation scheme , 1 and application of statistical theory on the basis of r and om sampling . Background The current prospect i ve r and omized controlled clinical study aim ed to assess the short- and long-term results of recurrent inguinal hernia repair , and to compare the results for transabdominal preperitoneal ( TAPP ) and totally extraperitoneal ( TEP ) procedures with those for open tension-free repair . Methods For this study , 82 patients were r and omly assigned to undergo TAPP ( group A , n = 24 ) , TEP ( group B , n = 26 ) , or open Lichtenstein hernioplasty ( group C , n = 32 ) . All the patients with recurrent inguinal hernias had undergone previous repair using conventional open procedures . Physical examination showed Nyhus type II hernia in the vast majority of the patients ( 59 % ) . High-risk patients ( American Society of Anesthesiology [ ASA ] III or IV ) ; coagulation disorders ; previous abdominal or pelvic surgery ; and irreducible , congenital , and massive scrotal or sliding hernias were excluded from the study . Results There was a statistically significant difference ( p = 0.001 ) in operating time favoring the open procedure . The intensity of postoperative pain was greater in the open hernia repair group 24 h , 48 h , and 7 days after surgery ( p = 0.001 ) , with a greater consumption of pain medication among these patients ( p < 0.004 ) . The median time until return to work was 14 days for group A , 13 days for Group g , and 20 days for group C. The comparison was in favor of laparoscopically treated patients . Nine recurrences ( 4 in the laparoscopic groups and 5 in the open group ) were documented within 3 years of follow-up evaluation . Conclusion Laparoscopic inguinal hernia repair ( TAPP or TEP ) is the method of choice for dealing with recurrent inguinal hernia BACKGROUND Groin hernia repair is one of the most frequent operations , but there is no consensus about surgical or anaesthetic technique . Furthermore , no nationwide studies have been done . Our aim was to investigate outcome results of groin hernia surgery to improve quality of treatment . METHODS We prospect ively recorded 26304 groin hernia repairs done in Denmark from Jan 1 , 1998 , to June 30 , 2000 , in a nationwide Danish hernia data base . FINDINGS 93 % of all groin herniorrhaphies done in Denmark in the 30 months of the study were recorded in the data base . Kaplan-Meier estimates of reoperation rates 30 months after anterior mesh repair and laparoscopic repair were significantly lower than after sutured posterior wall repairs in primary inguinal hernia ( 2.2 % and 2.6 % vs 4.4 % ; p<0.0001 ) . Reoperation rates were also lower with anterior mesh repair ( 6.1 % ; p<0.0001 ) and laparoscopic repair ( 3.4 % ; p<0.0001 ) than with sutured posterior wall repair ( 10.6 % ) after recurrent hernia . Use of Lichtenstein mesh repair increased from 33 % in January , 1998 , to 62 % in June , 2000 , whereas use of laparoscopic repair remained constant at about 5 % . Kaplan-Meier estimates of reoperation rates were 2.8 % in the first 15 months and 1.6 % in the second ( p=0.03 ) . For elective repairs , only 59 % of patients were treated on an outpatient basis , and only 18 % had local anaesthesia . INTERPRETATION Mesh repairs have a lower reoperation rate than conventional open repairs . Systematic prospect i ve recording of treatment and outcome variables in a national clinical data base improved the overall quality of surgical care . However , there is a large potential for cost savings and more efficient patient care with extended use of mesh techniques , outpatient surgery , and local anaesthesia INTRODUCTION Favourable short-term results , with respect to less postoperative pain and earlier return to physical activity , have been demonstrated with laparoscopic totally extraperitoneal ( TEP ) hernia repair compared with open mesh repair . However , there is limited data regarding long-term results . PATIENTS AND METHODS The study cohort consisted of 275 consecutive patients undergoing TEP repair between 1996 and 2002 . Patient demographics , details of surgery , postoperative complications , recurrence and chronic pain were collected from patient records and from a prospect i ve data base . All patients were seen at 6 weeks and then annually for 5 years following surgery . RESULTS A total of 430 repairs were performed in the 275 patients ( median age , 56 years ; range , 20 - 94 years ; men , 97.5 % ) . Bilateral repair was performed in 168 patients ( 61.1 % ) and recurrent hernia repair in 79 patients ( 28.7 % ) . Two patients were converted to an open procedure . Five-year follow-up was achieved in 72 % of patients . Eleven patients ( 4 % ) died during the follow-up period due to unrelated causes . Hernia recurrence rate at 5 years was 1.1 % per patient ( three repairs ) . Recurrences were noted at 7 months , 2 years and 4 years following surgery . Chronic groin pain was reported by 21 patients ( 7.6 % ) , seven of whom required referral to the pain team . CONCLUSIONS TEP hernia repair is associated with a recurrence rate of 1 % at 5 years in this series . Chronic groin symptoms are also acceptably few . This recurrence rate following TEP repair compares extremely favourably with open mesh repair , particularly as it includes a high proportion of recurrent repairs . As well as the proven early benefits , TEP repair can be considered a safe and durable procedure with excellent long-term results Surgical treatment of recurrent inguinal hernia is controversial . This is a prospect i ve study of 50 patients who had laparoscopic total extraperitoneal repair ( n = 25 ) or Lichtenstein repair ( n = 25 ) for recurrent inguinal hernia . The two groups of patients were comparable in age , sex and type of hernia . Post-operatively , a seroma or a wound haematoma developed in 12 patients after Lichtenstein repair and in 4 patients after laparoscopic repair ( p < 0.05 ) . On average , analgesia was taken for 6.4 days after Lichtenstein repair compared with 3.4 days after laparoscopic repair ( p < 0.05 ) . In our unit , laparoscopic repair was associated with fewer complications and a significantly shorter duration of post-operative analgesia than Lichtenstein repair for recurrent inguinal hernia Laparoscopic repair is considered by many to be the operation of choice for a recurrent hernia . The aim of this study was to compare long-term outcome of laparoscopic and open preperitoneal repair of recurrent groin hernias . All patients operated on by one surgeon for recurrent groin hernia between January 1994 and December 2001 were review ed . Forty-five percent had their data collected prospect ively , while in 55 % the data was collected retrospectively . Over the study period 128 patients underwent repair of a recurrent groin hernia of whom 99 had either a laparoscopic or open preperitoneal repair . The mean age was 60 years ( range 15–88 ) , 93 were men while 6 were women . Forty-five had their hernia repaired laparoscopically while 54 had an open preperitoneal repair . Patients have been followed for a median of 5 years ( range 2–9 years ) . There has been no recurrence in either group of patients . Two patients in the laparoscopic group and four in the open group suffered from chronic groin pain . One patient in either group developed a Hydrocele that was dealt with surgically . Laparoscopic and open preperitoneal repair of a recurrent groin hernia are associated with similar long-term outcomes Background Inguinal hernia recurrence after surgical repair is a major concern . The authors report their experience with open and laparoscopic repair of recurrent inguinal hernias . Methods After institutional review board approval , a retrospective review was performed with the charts of 197 patients who had undergone surgical repair of recurrent inguinal hernias from January 2000 through August 2009 , and the data for 172 patients who met the inclusion criteria were analyzed . Surgical variables and clinical outcomes were compared using Student ’s t test , the Mann – Whitney U test , chi-square , and Fisher ’s exact test as appropriate . Results The review showed that 172 patients had undergone either open mesh repair ( n = 61 ) or laparoscopic mesh repair ( n = 111 ) for recurrent inguinal hernias . Postoperative complications were experienced by 8 patients in the open group and 17 patients in laparoscopic group ( p = 0.70 ) . Five patients ( 8.2 % ) in the open group and four patients ( 3.6 % ) in the laparoscopic group had re-recurrent inguinal hernias ( p = 0.28 ) . Four patients in the open group ( 9.5 % ) and no patients in the laparoscopic group had recurrence during long-term follow-up evaluation ( p = 0.046 ) . In the laparoscopic group , 76 patients ( 68.5 % ) underwent total extraperitoneal ( TEP ) repair , and 35 patients ( 31.5 % ) had transabdominal preperitoneal ( TAPP ) repair . Postoperative complications were experienced by 13 patients in the TEP group and 4 patients in the TAPP group ( p = 0.44 ) . Two patients ( 2.6 % ) in the TEP group and two patients ( 5.7 % ) in the TAPP group had re-recurrent inguinal hernias ( p = 0.59 ) . Conclusions This retrospective review showed no statistical difference in the re-recurrence rate between the two techniques during short-term follow-up evaluation . However , the laparoscopic technique had a significantly lower re-recurrence rate than the open technique during long-term follow-up evaluation . Both procedures were comparable in terms of intra- and postoperative complications . Among laparoscopic techniques , TEP and TAPP repair are acceptable methods for the repair of recurrent inguinal hernia . A multicenter prospect i ve r and omized control trial is needed to confirm the findings of this study BACKGROUND Repair of recurrent inguinal hernias is associated with recurrence rates as high as 30 % and complication rates higher than for primary hernias . PATIENTS AND METHODS In a prospect i ve study , results were evaluated after laparoscopic transabdominal preperitoneal hernia repair in 192 patients with 200 recurrent inguinal hernias . A total of 132 hernia repairs followed one previous repair , 41 followed two repairs , 17 followed three repairs , 6 followed four , 3 followed five , and 1 followed six previous repairs . The surgical technique is described . RESULTS Follow-up ranged from 9 to 31 months ( mean 18.4 ) . Twelve patients ( 6 % ) had groin seromas or hematomas ; 3 ( 1.5 % ) had transient thigh numbness . One patient ( 0.5 % ) underwent laparoscopy a second time because of a large hematoma . In 1 patient ( 0.5 % ) , a staple on the n. cutaneus femoris lateralis was removed laparoscopically . Patients described postoperative pain as being much less severe compared with their previous operation . Of the total group , 76 % of patients were able to return to work within 2 weeks of surgery . One recurrence ( 0.5 % ) occurred after 6 months because of too small a prosthetic mesh . CONCLUSIONS This laparoscopic technique can be applied to recurrent hernias , even in difficult cases , with low morbidity rates . Recurrence rates as low as for laparoscopic repair of primary hernias can be expected 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 We analysed the results of 221 comparisons of an innovation with a st and ard treatment in surgery published in six leading surgery journals in 1983 to relate features of study design to the magnitude of gain . For each comparison we measured the gain attributed to the innovation over the st and ard therapy by the Mann-Whitney statistic and the difference in proportion of treatment successes . For primary treatments ( aim ed at curing or ameliorating a patient 's principal disease ) , an average gain of 0.56 was produced by 20 r and omized controlled trials . This was less than the 0.62 average for four non-r and omized controlled trials , 0.63 for 19 externally controlled trials , and 0.57 for 73 record review s ( 0.50 represents a toss-up between innovation and st and ard ) . For secondary therapies ( used to prevent or treat complications of therapy ) , the average gain was 0.53 for 61 r and omized controlled trials , 0.58 for eleven non-r and omized controlled trials , 0.54 for eight externally controlled trials , and 0.55 for 18 record review s. Readers of studies evaluating new treatments , particularly for primary treatments , may consider adjustment of the gain according to the study type BACKGROUND Even though the introduction of endoscopic surgical techniques to inguinal hernia therapy date s back 10 years , only a few data exist concerning the problem of development of a recurrence after endoscopic repair . Similarly there are only anecdotal reports on the feasibility of an endoscopic reintervention for this situation . For the first time we are able to present data of a prospect i ve study on both issues . STUDY DESIGN We analyzed the data of a prospect ively documented series of 46 transperitoneal hernia repair re interventions after endoscopic hernia repair . In 33 patients from our own clinic we evaluated the cause of recurrence after transperitoneal hernia repair . Together with these and 13 more patients sent to us from external clinics we examined the efficiency of an endoscopic reoperation . RESULTS When implanting a 13 x 8-cm mesh with an incision ( phase I ) we found the main cause of recurrence to be that the mesh was too small ( 47.4 % ) and the region of the mesh incision was insufficient ( 42.1 % ) . After a change to a 15 x 10-cm implant without incision ( phase II ) the main cause of recurrence was found to be a mesh dislocation ( 38.9 % ) and the rate of recurrence dropped from 2.8 % ( phase I ) to 0.36 % ( phase II ) . The transperitoneal reoperation lasted for a median of 75 minutes ( range 45 to 170 minutes ) for the medial recurrence and a median of 110 minutes ( range 65 to 190 minutes ) for the lateral recurrence ( p = 0.009 ) . The total rate of complications was 10.9 % , and the rate of re-recurrence was 0 % after a median followup of 26 months ( range 2 to 72 months ) . CONCLUSIONS To avoid hernia recurrence after transperitoneal hernia repair operations a sufficiently large mesh ( at least 15 x 10 cm ) has to be implanted , preferably without an incision , after an extensive parietalization . The endoscopic reoperation for recurrence can be done only in a transperitoneal way and is effective with comparably low complication rates . The procedure is significantly easier for a medial recurrence compared with a lateral recurrence . This method of reoperation should be reserved for endoscopically experienced surgeons The Authors report their three-year experience in the laparoscopic management of bilateral or recurrent hernia using a polypropylene mesh through a transabdominal extraperitoneal approach : out of a total of 500 laparoscopic hernioplasties performed , 162 patients with bilateral hernias and 51 with recurrent hernia underwent this procedure . In bilateral hernias a single wide patch was used to cover both the myopectineal foramen , therefore performing a Stoppa procedure by laparoscopy . Two major complications were registered in this series : 1 bleeding and 1 intestinal obstruction , both managed laparoscopically . Minor complications were : 2 cases of neuralgia and 6 seromas which required single or multiple evacuations . Patients were carefully followed up ( 1 - 31 months ) , and no relapses were recorded . Although the follow up is still too short , the Authors stress the characteristics of this technique which shows great advantages mainly represented by a good compliance , quick return to normal work and sport activity ; in fact , recovery is obtained in a shorter period as compared to traditional surgery even when the latter includes the use of prosthetic mesh The aim of our study was the comparative analysis of the results of two surgical methods : tension-free repair by the Lichtenstein technique and laparoscopic transabdominal preperitoneal ( TAPP ) repair . In total 52 patients with recurrent inguinal hernia were r and omly assigned to the two groups : Lichtenstein ( 28 patients ) and TAPP ( 24 patients ) . Comparisons between these groups were done by several preoperative , intraoperative , and postoperative factors . For postoperative factors both short-term and long-term results were considered . Average operation time for Lichtenstein group was 59.6 + /- 9.9 minutes , compared with 64.4 + /- 8.4 minutes for TAPP patients ( P = 0.068 ) . In TAPP patients there was less pain in the postoperative period ( P = 0.002 ) and fewer sick-leave days ( 13.4 + /- 1.7 versus 17.5 + /- 2.6 days ; P < 0.001 ) and , correspondingly , faster recovery . In the Lichtenstein group a total of 4 postoperative complications ( infection , hematoma , seroma , urinary retention ) were observed , compared with 8 in the TAPP group ( P = 0.19 ) . Statistically significant difference was only by urinary retention ( 0 for Lichtenstein , 4 for TAPP ; P = 0.039 ) . There were no cases of hernia recurrence observed during the followup . Chronic pain developed in 5 patients from the Lichtenstein group ( 17.9 % ) and 2 patients from the TAPP group ( 8.3 % ; P = 0.28 ) more than 1 year after the operation ; 4 Lichtenstein patients ( 14.3 % ) and 1 TAPP patient ( 4.2 % ; P = 0.23 ) more than 2 years after the operation ; and 3 Lichtenstein patients ( 10.7 % ) and 1 TAPP patient ( 4.2 % ; P = 0.36 ) more than 3 years after the operation . For the treatment of recurrent inguinal hernias , which are developed after use of conventional ( nonmesh ) methods , the first choice should be given to the laparoscopic method , especially for young , physically active , nonobese patients , and if there are any contraindications for the laparoscopy , the Lichtenstein approach should be recommended |
638 | 27,907,224 | There was a wide variation in the individual antibiotics used in each trial . | BACKGROUND Choice of antibiotic , and the use of single or combined therapy are controversial areas in the treatment of respiratory infection due to Pseudomonas aeruginosa in cystic fibrosis ( CF ) .
Advantages of combination therapy include wider range of modes of action , possible synergy and reduction of resistant organisms ; advantages of monotherapy include lower cost , ease of administration and reduction of drug-related toxicity .
Current evidence does not provide a clear answer and the use of intravenous antibiotic therapy in cystic fibrosis requires further evaluation .
This is an up date of a previously published review .
OBJECTIVES To assess the effectiveness of single compared to combination intravenous anti-pseudomonal antibiotic therapy for treating people with cystic fibrosis . | RATIONALE Inhaled tobramycin has been shown to transiently clear Pseudomonas from lower airways in early cystic fibrosis ( CF ) , but does not markedly reduce lung inflammation , a key factor in disease progression . OBJECTIVE Test the hypothesis that systemic antibiotics are more effective than inhaled antibiotics for reducing lower airways inflammation . METHODS Clinical ly stable CF children with recent Pseudomonas were r and omized to receive 4 weeks of inhaled tobramycin or 2 weeks of systemic antibiotics ( intravenous ceftazidime and tobramycin ) . Bronchoalveolar lavage fluid was obtained just before and 4 - 6 weeks after treatment . The primary outcome was change in % neutrophils in lavage fluid . RESULTS Fifteen subjects ( inhaled = 6 , systemic = 9 ) completed the protocol . Three Systemic Group subjects could not have central venous access established and were treated with oral ciprofloxacin ( plus inhaled tobramycin ) for 2 weeks as an alternative " systemic " regimen , per protocol . Groups were well matched in age , markers of disease severity , and initial % neutrophils . The Systemic Group showed a modest median change in percent neutrophils ( -7 % ) which was not statistically significant compared to inhaled ( + 5.4 % , P = 0.07 ) . However , the Systemic Group had significantly greater reductions in total cells ( -50 % vs. -3 % , P < 0.01 ) and neutrophils ( -74 % vs. -10 % , P = 0.02 ) per ml lavage fluid . Both groups had reduced bacterial quantity after treatment , but there was no significant difference between groups . CONCLUSIONS In clinical ly stable children with CF , systemic antibiotics result in greater short-term reduction in lower airways inflammation than inhaled antibiotics ABSTRACT The present multicenter , r and omized crossover study compared the safety and efficacy of continuous infusion with those of short infusions of ceftazidime in patients with cystic fibrosis . Patients with chronic Pseudomonas aeruginosa colonization received two successive courses of intravenous tobramycin and ceftazidime ( 200 mg/kg of body weight/day ) for pulmonary exacerbation administered as thrice-daily short infusions or as a continuous infusion . The primary endpoint was the variation in the forced expiratory volume in 1 s ( FEV1 ) during the course of antibiotic treatment . Sixty-nine of the 70 patients enrolled in the study received at least one course of antibiotic treatment . The improvement in FEV1 at the end of therapy was not statistically different between the two treatment procedures ( + 7.6 % after continuous infusion and + 5.5 % after short infusions ) but was better after continuous ceftazidime treatment in patients harboring resistant isolates ( P < 0.05 ) . The interval between the course of antibiotic treatments was longer after the continuous infusion than after the short infusion of ceftazidime ( P = 0.04 ) . The mean serum ceftazidime concentration during the continuous infusion was 56.2 ± 23.2 μg/ml ; the mean peak and trough concentrations during the short infusions were 216.3 ± 71.5 and 12.1 ± 8.7 μg/ml , respectively . The susceptibility profiles of the P. aeruginosa isolates remained unchanged and were similar for both regimens . Quality -of-life scores were similar whatever the treatment procedure , but 82 % of the patients preferred the continuous-infusion regimen . Adverse events were not significantly different between the two regimens . In conclusion , the continuous infusion of ceftazidime did not increase its toxicity and appeared to be as efficient as short infusions in patients with cystic fibrosis as a whole , but it gave better results in patients harboring resistant isolates of P. aeruginosa Purpose : We hypothesized that a single intravenous ( iv ) tobramycine infusion ( treatment B ) would have equivalent anti-infectious efficacy in chronic Pseudomonas aeruginosa ( PA ) infection in cystic fibrosis ( CF ) as the commonly performed treatment of three doses ( treatment A ) . Toxicity and practicability may even be improved in the single-dose regimen . Methods : This was a r and omized crossover study comparing outcome after 14 and 35 days . The primary end-point was a decrease in the leukocyte count , and the secondary end-points were clinical and lung function parameters , Pseudomonas quantification in sputum , and inflammation markers ( immunoglobulin G , C-reactive protein ) in serum . 30 patients ( 20 female , mean age 11.2 years , mean age range 1.7–18.1 years ) received elective 14-day courses of treatments A or B , followed by the alternative treatment after a mean interval of 37 ( ± 21 ) weeks . Results : With the exception of PA density , there were no significant differences between both treatment strategies after 14 days of treatment . After 35 days of treatment , there were no significant changes in the leukocyte count and inflammation markers . Both treatment strategies reduced the bacterial load in the airways , as reflected by a decreased PA density in sputum . Nephrotoxicity was equal in both groups , with a transient slight elevation of urinary N-acetyl-β-glucosaminidase concentrations . St and ard audiometry tests revealed no evidence of a hearing impairment in any patient following therapy . Mean body weight increased during the study period by 0.5 kg . Forced expiratory volume increased by approximately 5 % of the predicted volume , forced vital capacity increased by 2 % of predicted capacity , and forced mid expiratory flow rate increased by 7 % ( A ) or 4 % ( B ) of the predicted normal value , although these changes were not statistically significant . Conclusion : We conclude that tobramycin given in a daily single dose ( with the advantage of being more practical in a home environment ) has an efficacy equal to that of three daily doses in terms of elective antipseudomonal therapy in clinical ly stable patients with CF To evaluate whether the addition of an aminoglycoside might enhance the clinical efficacy of ceftazidime in cystic fibrosis patients with acute exacerbations of chronic Pseudomonas lung infections we carried out a prospect i ve , comparative , r and omized blind study with three schedules : ceftazidime vs. ceftazidime plus sisomicin ( C/S ) vs. piperacillin plus sisomicin , for a total of 60 courses of 14 days of treatment . Each treatment led to clinical and radiologic improvement with marked reduction of signs of acute infection . Statistically there was no significant difference in clinical responses among the schedules . No side effect appeared during treatments with ceftazidime or C/S. Hyperpyrexia was seen in 35 % of patients receiving piperacillin . Decrease in Pseudomonas aeruginosa count to less than 10(5 ) colony-forming units/ml of sputum was achieved in 60 % of patients treated with C/S and in 30 % of patients who received ceftazidime or piperacillin plus sisomicin ( statistically not significant ) . A transient increase in mean geometric minimal inhibitory concentrations for ceftazidime and piperacillin was observed at the end of the combined therapies . A larger percentage of persistent resistant strains of P. aeruginosa was seen after the combined therapies . We conclude that ceftazidime as monotherapy may be an effective alternative in Pseudomonas lung infections in cystic fibrosis patients . Its clinical efficacy seems not to be enhanced by the addition of an aminoglycoside , although reduction of Pseudomonas in the sputum was better achieved by the combination of Thirteen patients with cystic fibrosis ( aged 11 to 32 years ) who were hospitalized for exacerbation and who had sputum cultures positive for Pseudomonas organisms were treated initially for 4 days with bronchodilators and physiotherapy followed by the addition of antibiotic ( 14 days , n = 8) or placebo ( 14 days , n = 4 ; 7 days , n = 1 ) . Tc-99 m DTPA aerosol scintigraphy was performed on the day before bronchodilators and physiotherapy , on the day before antibiotic or placebo , and on the day after completion of antibiotic or placebo therapy . Scintigrams were evaluated for change in the number of nonventilated segments and change in the number of bronchial deposits of aerosol . Sixty-nine percent of patients showed improvement after bronchodilators and physiotherapy alone . Sixty-two percent showed further improvement after antibiotic or placebo was added ; this improvement was independent of whether antibiotic or placebo was administered ( P > 0.1 ) . These aerosol scintigraphy results failed to demonstrate that the effectiveness of bronchodilators and physiotherapy is enhanced by antibiotics in the treatment of cystic fibrosis exacerbations The aim of this study was to test the equivalence of once- and thrice-daily dosing with tobramycin by comparing efficacy and safety in adult patients with cystic fibrosis . Sixty adult patients with an acute respiratory exacerbation were r and omized to receive either 10 mg·kg−1 tobramycin once-daily or 3.3 mg·kg−1 tobramycin thrice-daily . Primary efficacy and safety endpoints were defined as changes in respiratory function and changes in renal function and hearing . Both groups showed a significant increase in respiratory function without a clinical ly significant change in renal function . For changes in forced vital capacity % predicted and serum potassium and magnesium levels , equivalence was demonstrated . For the variables forced expiratory volume in one second and forced mid-expiratory flow % pred and serum creatinine levels , there was insufficient power to demonstrate equivalence . One patient in each group showed bilateral impairment in pure tone audiogram after treatment . This study demonstrated significant clinical improvement with both once- and thrice-daily tobramycin dosing . Equivalence between the two regimens was shown for some , but not all primary endpoints . Once-daily dosing should be used with careful monitoring of safety and efficacy until large multicentre studies confirm these encouraging results ABSTRACT Linezolid is a treatment option for methicillin-resistant Staphylococcus aureus ( MRSA ) infections in cystic fibrosis ( CF ) patients . Little is known , however , about its pharmacokinetics in this population . Eight adults with CF were r and omized to receive intravenous ( i.v . ) and oral linezolid at 600 mg twice daily for 9 doses in a crossover design with a 9-day washout . Plasma sample s were collected after the first and ninth doses of each phase . Population pharmacokinetic analyses were performed by nonlinear mixed-effects modeling using a previously described 2-compartment model with time-dependent clearance inhibition . Monte Carlo simulation was performed to assess the activities of the linezolid dosing regimens against 42 contemporary MRSA isolates recovered from CF patients . The following pharmacokinetic parameter estimates were observed for the population : absorption rate constant , 1.91 h−1 ; clearance , 9.54 liters/h ; volume of central compartment , 26.8 liters ; volume of peripheral compartment , 17.3 liters ; and intercompartmental clearance , 104 liters/h . Linezolid demonstrated nonlinear clearance after 9 doses , which was reduced by a mean of 38.9 % ( range , 28.8 to 59.9 % ) . Mean bioavailability was 85 % ( range , 47 to 131 % ) . At steady state , 600 mg given twice daily produced 93.0 % and 87.2 % probabilities of obtaining the target pharmacodynamic exposure against the MRSA isolates for the i.v . and oral formulations , respectively . Thrice-daily dosing increased the probabilities to 97.0 % and 95.6 % , respectively . Linezolid pharmacokinetics in these adults with CF were well described by a 2-compartment model with time-dependent clearance inhibition . St and ard i.v . and oral dosing regimens should be sufficient to reliably attain pharmacodynamic targets against most MRSA isolates ; however , more frequent dosing may be required for isolates with MICs of ≥2 μg/ml Aminoglycosides are often prescribed as part of the treatment regimen for acute pulmonary exacerbations due to their potent activity and low potential for development of resistance . Preliminary evidence from r and omized controlled trials in patients with cystic fibrosis ( CF ) suggests that once-daily administration of aminoglycosides results in similar efficacy and a low risk for toxicity compared with traditional dosing . The pharmacokinetics of aminoglycosides administered once daily in CF patients are currently not well described . In this study we compare the distribution and elimination patterns of traditional dosing ( 3.3 mg/kg q8h ) versus once-daily dosing ( 10 mg/kg q24h ) of tobramycin in six adult patients with CF . The pharmacokinetics of tobramycin administered either once daily or every 8 h were best described by a two-compartment model . No statistically significant differences in any of the pharmacokinetic parameter values between regimens were noted . The distribution phase half-lives of 32 and 24 min following the q8h and q24h regimens were longer than expected . The use of a one-compartment model requires clinical peak levels to be drawn 2 h after initiation of either a 30 min infusion for multiple daily dosing or a 60 min infusion with once-daily dosing , to ensure completion of the distribution phase . Our data indicate that a dose of 10 mg/kg/day provides post-distributional phase peak concentrations that achieve the desired goal for susceptible organisms ( > 20 mg/L ) and AUC(24 ) values at the upper end of the desired range ( 70 - 100 mg.h/L ) During a 22-month period 35 children with cystic fibrosis received 52 courses of antibiotic therapy for acute pulmonary exacerbations , including 26 cases of therapy with piperacillin and 26 courses with ticarcillin plus tobramycin . Groups were similar in age ( 5 vs. 5.4 years ) , disease severity based on Schwachman scores and presenting symptoms . Pseudomonas aeruginosa was the most common organism isolated in 90 % of sputum cultures . Mean minimal inhibitory concentrations for piperacillin , ticarcillin and tobramycin were 8 , 64 and 1 microgram/ml , respectively . Piperacillin pharmacokinetic data revealed an average half-life in serum of 36 minutes . Peak serum concentrations averaged 144 micrograms/ml , and after 4 hours serum concentrations continued to exceed the P. aeruginosa 90 % minimal inhibitory concentration in 50 % of children . The dosage requirement for tobramycin was quite variable , necessitated monitoring of aminoglycoside serum concentrations and in most cases result ed in at least one dosage adjustment . Emergence of resistant bacteria was not seen in 26 courses of piperacillin therapy . Both regimens were effective and well-tolerated . Single agent therapy has the advantage of providing reliable serum concentrations and , in contrast to the st and ard therapy , does not necessitate monitoring of serum drug concentrations BACKGROUND Although anti-pseudomonal antibiotics are routinely used in the treatment of acute respiratory exacerbations of adult cystic fibrosis ( CF ) , the specific efficacy of such treatment remains uncertain , the mechanism of action of these agents is not fully understood , and the role of sputum susceptibility testing in clinical decision making is controversial . AIMS We investigated the relationship between susceptibility testing and clinical outcome in adult CF patients colonised with Pseudomonas aeruginosa . METHODS Sputum sample s were collected before , during and after respiratory exacerbations from 31 admissions ( 17 patients ) . Sputum colony counts and MIC of P. aeruginosa were performed . RESULTS Sputum colony counts did not change significantly during or after intravenous ( IV ) antibiotic therapy . Clinical outcome parameters ( lung function , 12-minute walking distance , sputum weight and quality of life ) were compared with susceptibility of P. aeruginosa colonies isolated at admission to the antibiotics used , and no correlation was evident . There was no evidence for the development of cross-resistance and there was no change in the proportion of mucoid colonies with therapy . CONCLUSIONS While this study has a small patient sample size , it highlights the inconsistency of the role of antipseudomonal drugs also shown in other similar studies . The presence of P. aeruginosa in sputum of acutely ill CF patients prompts us to prescribe i.v . antipseudomonal drugs . If this approach was valid , we would expect to find a reduction in sputum colony counts and improvement in clinical parameters with the use of antibiotics to which the organisms were sensitive . The fact that such a relationship can not be consistently demonstrated in this and other studies suggests that the use of antipseudomonal therapy in these patients requires more critical bacteriological and clinical evaluation Our objective was to compare the efficacy , safety , and microbiology of once-daily intravenous ( IV ) tobramycin with conventional 8-hourly tobramycin/ceftazidime IV therapy for acute Pseudomonas aeruginosa ( PA ) pulmonary exacerbations in cystic fibrosis ( CF ) . CF patients with PA-induced pulmonary exacerbations were allocated to receive either once-daily tobramycin ( Mono ) or conventional therapy with tobramycin/ceftazidime given 8-hourly ( Conv ) . The two longitudinal groups received therapy in a double-blind , r and omized manner over a period of 2 years . Tobramycin doses were adjusted to achieve a daily area under the time-concentration curve of 100 mg x hr/L in both groups . Results were assessed for both short-term changes ( efficacy and safety after 10 days of IV antibiotics during acute exacerbations ) and long-term changes ( efficacy , safety , and sputum microbiology between study entry and exit ) . Pulmonary function tests ( PFTs ) on admission were similar in both groups . After 10 days of IV antibiotics , absolute mean improvements in percent of predicted PFTs were 12.8 , 12.1 , and 13.7 for forced expiratory volume in 1 sec ( FEV(1 ) ) , forced vital capacity ( FVC ) , and forced expired flow between 25 - -75 % of FVC ( FEF(25 - -75 % ) ) in the Conv group ( n = 51 admissions ) compared to 10.6 , 9.9 , and 10.6 in the Mono group ( n = 47)(P<0.05 for all ) . Sixteen percent in the Conv group and 15 % of patients in the Mono group did not respond to therapy by day 10 . Long-term PFT patterns were similar for the Conv and Mono groups . The time between admissions did not differ . The Mono group showed a significant increase in tobramycin minimum inhibitory concentrations ( MICs ) against PA from study entry to study exit ( P = 0.02 , n = 27 strains ) ; this failed to reach significance in the Conv group ( P = 0.08 , n = 25 ) . There was no significant increase in the number of isolates , with MIC > or = 8 mg/L in both groups . No short- or long-term changes in audiology or serum creatinine were found in either group . After 10 days of IV therapy , the urinary enzyme N-acetyl-beta-d-glucosaminidase/creatinine ratios increased in both groups ( P0.05 ) . This increase was greater in the Conv compared to the Mono group ( P < 0.05 ) . We conclude that this pilot study indicates once-daily tobramycin therapy to be as effective and safe as conventional 8-hourly tobramycin/ceftazidime therapy . Combination antibacterial therapy appears to offer no clinical advantage over once-daily tobramycin monotherapy . Tobramycin once-daily monotherapy is a potential alternative to conventional IV antibacterial therapy which deserves further investigation , including the impact on susceptibility of PA to tobramycin 20 patients with cystic fibrosis and chronic bronchopulmonary infection due to Pseudomonas aeruginosa entered a r and omized cross-over study comparing ceftazidime ( 150 mg/kg body weight/24 h ) plus tobramycin ( 10 mg/kg body weight/24 h ) to ceftazidime alone ( 150 mg/kg body weight/24 h ) , both given intravenously for 2 weeks . 17 patients completed the study ; both treatment regimens improved lung function and decreased the WBC count . No difference in clinical efficacy was found between the treatments . Pulmonary function returned to pre-treatment levels 3 months later with no difference between the treatments . No changes were seen in minimal inhibitory concentrations during treatment . None of the patients developed hypersensitivity or experienced serious adverse reactions to the drugs The effectiveness of ticarcillin against Pseudomonas aeruginosa in acute exacerbations of pulmonary infection in patients with cystic fibrosis was evaluated . Seventy-one percent of patients treated with ticarcillin alone responded favorably . The response rate was similar in patients treated with a combination of ticarcillin plus gentamicin or with gentamicin alone . Severity of the underlying disease was the most important determinant of response to treatment . Ticarcillin-resistant organisms were recovered during treatment in 50 % of patients who received this drug ; recovery of them was not prevented by the inclusion of gentamicin in the therapeutic regimen nor did they interfere with clinical improvement . The ticarcillin-resistant strains persisted at follow-up , two to six months after completion of therapy , in only one of ten patients . No serious toxicity to ticarcillin was noted during the study period Patients with cystic fibrosis hospitalized because of deterioration in their pulmonary disease were r and omly assigned to receive ten days of intravenous antibiotic therapy with either ticarcillin plus tobramycin ( previously the st and ard regimen at our hospital ) , azlocillin plus tobramycin or azlocillin plus placebo . Pulmonary function and microbiological responses were similar in the three treatment groups , although patients receiving azlocillin and placebo tended to have a smaller reduction in the concentration of bacteria in the sputum and a greater rate of acquisition of antibiotic-resistant organisms . Overall , in-hospital treatment was associated with a significant improvement in Shwachman score , pulmonary function tests , and PO2 . Improvement was noted by day 5 of therapy , continued through day 10 , and was partially maintained at follow-up clinic visit one month after discharge . There was also a statistically significant reduction in sputum bacterial concentration , but patients cultured at the conclusion of antibiotic therapy still had a mean of 10(7 ) cfu/ml in sputum . Pseudomonas aeruginosa , the principal pathogen recovered from sputum cultures in this study , was transiently suppressed to sub-detectable levels in only one patient . There was no correlation between microbiological response and change in any parameter of pulmonary function . By follow-up clinic visit , sputum bacteria had returned to pre-treatment levels , and antibiotic-resistant organisms persisted in all patients from whom they had been recovered during hospitalization A r and omized controlled trial was undertaken to compare ceftazidime vs. the combination of ticarcillin and tobramycin in the treatment of acute respiratory exacerbations of mild to moderate severity in patients with cystic fibrosis . The two antibiotic regimens were equally effective in terms of clinical improvement : 16 of 17 in the ceftazidime group and 11 of 13 in the ticarcillin/tobramycin group were judged to be improved by the patients and attending physicians and were observed to show improvement in symptom scores , vital signs , body weight and pulmonary function . Ceftazidime was more effective bacteriologically in reducing colony counts of Pseudomonas aeruginosa in the sputum . Neither regimen affected Pseudomonas cepacia . Resistance to multiple antibiotics developed in six of 12 isolates of nonmucoid P. aeruginosa in patients receiving ticarcillin/tobramycin , which was significantly more than occurred in the ceftazidime group . There was no correlation between clinical and bacteriologic outcomes in either treatment group . No clinical ly important adverse effects were observed A controlled study was design ed to clarify the indications for antibiotic therapy in children with advanced cystic fibrosis hospitalized with respiratory exacerbations . Twenty-two children with severe CF and signs of acute lower respiratory infection were r and omly assigned to receive either cloxacillin or carbenicillin plus gentamicin administered intravenously for ten days . Other aspects of therapy were constant . The groups were comparable in all respects and Pseudomonas aeruginosa was the predominant sputum pathogen in most patients . Clinical improvement , chest radiograph changes , evidence of airway obstruction , and bacteriologic flora of sputum were no different regardless of the regimen used . These results suggest that the use of anti-Pseudomonas medication in these children may not always be necessary . These observations need to be confirmed by blind-controlled studies in larger numbers of patients with mild as well as severe respiratory involvement We evaluated patients with cystic fibrosis ( CF ) and moderate obstructive lung disease in pulmonary exacerbation in a double-blind placebo-controlled trial to determine the contribution of antibiotic-mediated reduction in sputum bacterial density to clinical improvement . For the first 4 days of study , all patients received bronchodilating aerosols and chest physiotherapy but no antibiotics . During this time , the patients showed significant improvement in mean FVC , FEV1 , and maximal midexpiratory flow rate ( FEF25 - 75 ) . In 12 of 13 trials , the patients showed no significant increases in the density of Pseudomonas aeruginosa during these first 4 days . In these 12 trials , the patients were stratified by their initial FVC and r and omized to receive either parenteral tobramycin and ticarcillin ( n = 7 ) or placebo ( n = 5 ) , in addition to continued aerosol and chest physiotherapy . In the remaining trial , the patient had a significant rise in the density of P. aeruginosa and was assigned to the antibiotic group . During the next 14 days of therapy , the antibiotic group showed significantly ( p less than 0.01 ) greater reductions in log10 colony-forming units ( cfu ) of P. aeruginosa per gram of sputum and greater increases in FVC , FEV1 , and FEF25 - 75 than did the placebo group . The degree of decrease in log10 cfu P. aeruginosa/g sputum correlated significantly ( p less than 0.001 ) with the degree of improvement in FVC , FEV1 , and FEF25 - 75 . ( ABSTRACT TRUNCATED AT 250 WORDS Seventeen patients with cystic fibrosis ( CF ) and pulmonary exacerbations were r and omly assigned to two treatment groups : piperacillin 600 mg/kg/day ( P ) , and piperacillin 600 mg/kg/day plus tobramycin ( PT ) , in order to determine the safety and pharmacokinetics of high-dose piperacillin and whether piperacillin alone was effective for the treatment of Pseudomonas infections . The mean half-life of piperacillin was 0.54 hours , with a peak concentration of 232 micrograms/ml . No differences between P and PT groups were noted in clinical assessment , as judged by Shwachman scores , pulmonary function testing , or weight gain . However , during the course of treatment , quantitative sputum cultures decreased by greater than 10(2 ) colony-forming units in only 5 out of 19 Pseudomonas isolates from the P group , compared with 12 of 19 isolates from the PT group ( P less than 0.03 , Chi-square ) . Although emergence of resistance was not seen , one isolate had an increase in minimum inhibitory concentration from 8 to 128 micrograms/ml . There were no serious adverse reactions to piperacillin ; only one patient developed fever possibly related to piperacillin . Therapy with high-dose piperacillin was safe in children with CF . Treatment with piperacillin alone was less effective than combination therapy with gentamicin for reduction in titer of Pseudomonas in sputum . However , the role of antimicrobial agents in the treatment of CF remains undefined . A double-blind placebo-controlled trial is indicated BACKGROUND Cystic fibrosis ( CF ) is characterized by chronic pulmonary infection with acute pulmonary exacerbations ( APEs ) requiring IV antibiotic treatment . We report on a blinded comparative trial of IV meropenem ( 40 mg/kg to 2 g q8h ) or ceftazidime ( 5 mg/kg to 2 g q8h ) , each of which was administered with IV tobramycin ( at a serum peak of > or = 8 microg/mL and a trough of < 2 microg/mL ) , as treatment for CF patients with APEs . METHODS Patients who were > or = 5 years of age who were infected with ceftazidime-susceptible Pseudomonas aeruginosa were stratified by lung function and r and omized to treatment with meropenem/tobramycin or ceftazidime/tobramycin . Patients infected with Burkholderia cepacia complex or ceftazidime-resistant P aeruginosa were assigned to receive open-label meropenem/tobramycin . Clinical response was assessed by spirometry to determine the change in percent predicted FEV1 and by a clinical acute change score ( ACS ) . RESULTS One hundred two patients were r and omized to meropenem/tobramycin ( n = 50 ) or ceftazidime/tobramycin ( n = 52 ) . Nineteen patients received open-label meropenem/tobramycin . FEV1 was improved at the end of treatment ( EOT ) with meropenem/tobramycin ( mean [ + /- SD ] increase , 38.8 + /- 52.3 % ) and with ceftazidime/tobramycin ( mean increase , 29.4 + /- 35.1 % ; p < 0.0001 vs baseline values ) . The proportion of patients with > or = 15 % relative increase from baseline FEV1 ( satisfactory response ) at day 7 was 62 % for the meropenem/tobramycin group and 44 % for the ceftazidime/tobramycin group ( p = 0.04 ) . The median time to FEV1 response was 4 days for meropenem/tobramycin therapy vs 6 days for ceftazidime/tobramycin therapy . Similarly , FEV1 improved in the open-label group ( mean increase , 12.5 + /- 25.7 % ; p = 0.05 ) . ACS improved in all three groups at EOT ( p < 0.0001 vs baseline values ) . CONCLUSIONS Therapy with both meropenem/tobramycin and ceftazidime/tobramycin improved pulmonary and clinical status and reduced sputum bacterial burden in CF patients with APEs . A larger proportion of patients receiving meropenem/tobramycin therapy demonstrated a satisfactory FEV1 response at day 7 . Resistant P aeruginosa emerged infrequently during treatment with both regimens A controlled prospect i ve study was undertaken to compare the efficacy and benefits of home and hospital treatment for patients with exacerbations of pulmonary disease caused by cystic fibrosis . A total of 41 home and 41 hospital treatments were analyzed . Home and hospital patients were matched according to sex , age , pulmonary function tests , and arterial blood gas values . Both home and hospital treatments result ed in statistically significant improvement in pulmonary function . A comparison of these values did not show any statistically significant difference between groups at admission or discharge . Furthermore , the mean number of treatment days for both groups , individually determined by the primary physician , was equivalent ( home 17.7 + /- 1.1 days , hospital 18.1 + /- 4.1 ) . The mean charge for a home treatment was approximately $ 10,000 , and for a hospital treatment $ 18,000 . Sixty-five percent of home care patients and 68 % of hospital patients required retreatment for pulmonary exacerbations within the study period ; the interval between pulmonary exacerbations for the two groups was not significantly different . In addition , 85 % of patients receiving treatment at home were able to maintain at least some of their school or work activities . These data indicate that home therapy for cystic fibrosis patients with pulmonary exacerbations is less costly and is as effective as in-hospital therapy In a r and omized , double-blind study , cystic fibrosis patients 11 - 30 years of age with an acute exacerbation of their pulmonary disease were treated with either ticarcillin-tobramycin , azlocillin-tobramycin , or azlocillin-placebo for 10 days . There was significant improvement in Shwachman scores and pulmonary function tests . Concentrations of sputum bacteria were significantly reduced , but after therapy patients had a mean of 10(7 ) bacteria/ml of sputum . Pseudomonas was transiently eliminated in only one patient . The three regimens had similar impacts on pulmonary function and sputum bacterial concentration . Antibiotic resistance was noted more frequently in the azlocillin-placebo group , but this trend was not statistically significant . Improvement in pulmonary function did not correlate with bacteriological response . Four weeks after discharge , 62 % of the improvement in forced expiratory volume in one second and 75 % of the improvement in vital capacity remained , but concentrations of sputum bacteria had returned to pretreatment levels , and antibiotic-resistant bacteria persisted A non-blinded , r and omized , cross-over investigation of the pharmacokinetic interaction between tobramycin and ticarcillin was performed in 18 healthy cystic fibrosis ( CF ) patients with normal renal function . On consecutive mornings the patients were given either tobramycin intravenously ( i.v . ) over 3 - 5 min ( TOB phase ) , or tobramycin i.v . over 3 - 5 min followed immediately by ticarcillin infused i.v . over 20 - 30 min ( TOB+TIC phase ) . Capillary blood sample s were taken 30 min and 330 min after administration of the tobramycin dose in each phase . Tobramycin was measured in serum by fluorescence polarization immunoassay ( TDx ) . There were decreases in serum tobramycin concentrations of 11 % at 30 min ( P < 0.001 ) and 330 min ( P = 0.012 ) when measured in the presence of ticarcillin . No difference in elimination half-life was found ( TOB phase 95 + /- 13 min , TOB+TIC phase 95 + /- 13 min , P = 0.86 ) . The volume of distribution and clearance of tobramycin increased by 14 % ( P < 0.001 ) and 13 % ( P < 0.001 ) , respectively , in the presence of ticarcillin . This interaction appears to be of minor clinical importance but pharmacokinetic studies of tobramycin should exclude concurrent use of ticarcillin BACKGROUND Cystic fibrosis patients have chronic bacterial infections of the respiratory tract , most commonly Pseudomonas aeruginosa . Although controversial , administration of antibiotic therapy during acute pulmonary exacerbations is st and ard practice . Fluoroquinolones are currently not indicated for use in young children because of the observation of arthropathy and damage to growing cartilage in beagle puppies . Because of its activity against P. aeruginosa and excellent oral bioavailability , ciprofloxacin offers a unique therapeutic alternative for this patient population . OBJECTIVE This prospect i ve , r and omized , double blind study compared the efficacy and safety of sequential intravenous/oral ciprofloxacin vs. ceftazidime/tobramycin in hospitalized pediatric cystic fibrosis patients with an acute pulmonary exacerbation associated with P. aeruginosa infection . METHODS One hundred thirty patients ( ages 5 to 17 years ) were r and omized to receive either i.v . ciprofloxacin 10 mg/kg every 8 h for 7 days followed by oral ciprofloxacin 20 mg/kg every 12 h for a minimum of 3 days or i.v . ceftazidime 50 mg/kg every 8 h plus i.v . tobramycin 3 mg/kg every 8 h for a minimum of 10 days . Clinical , bacteriologic and safety responses were assessed throughout the study . RESULTS All 84 patients ( median age , 11 years ; range , 5 to 17 years ) valid for efficacy in both treatment groups demonstrated clinical improvement . Five patients experienced clinical relapses ( 3 ciprofloxacin , 2 ceftazidime/tobramycin ) by the 2- to 4-week follow-up . Intent-to-treat analysis demonstrated similar clinical findings between the two treatment groups at both the end of therapy and follow-up . Clinical improvement correlated with improvement in pulmonary function studies and the acute clinical scoring system but not with bacteriologic eradication of Pseudomonas . DNA profiles demonstrated that irrespective of colony morphology , usually one clonal strain was associated with each patient 's pulmonary exacerbation . Treatment-associated musculoskeletal events occurred with equal frequency ( 22 % vs. 21 % ) in both study drug groups ( n = 129 ) , and arthralgias were within the range of rates for cystic fibrosis arthropathy . None of these events required study drug discontinuation . CONCLUSION Sequential i.v./oral ciprofloxacin monotherapy offers a safe and efficacious alternative to st and ard parenteral therapy for acute pulmonary exacerbations in pediatric cystic fibrosis patients Fourteen children with cystic fibrosis and pulmonary lung infection due to Pseudomonas aeruginosa were treated with piperacillin ( 300 mg/kg/day ) alone or piperacillin and tobramycin ( 7 mg/kg/day ) iv . The outcome with respect to clinical state , chest X-ray and lung function tests was better with combination therapy than with piperacillin alone . Bacteriological response was the same with both regimens : leucocyte content of the sputum decreased , non-mucoid Ps . aeruginosa strains were eliminated , but mucoid strains were only suppressed ( 11 children ) . Peak serum levels of piperacillin averaged 102 mg/l , the overall serum elimination was 0.75 h and the mean sputum concentrations ranged from 1.07 to 2.2 mg/l . Peak serum levels of tobramycin averaged 5.15 mg/l , the half life was 1.25 h and the mean sputum concentrations ranged from 0.57 to 0.68 mg/l . The clearance of piperacillin and tobramycin was increased significantly . Drug-resistance did not develop during therapy The antimicrobial prescribing practice s of 26 physicians from the U.K. and Eire who care for patients with cystic fibrosis ( CF ) were assessed by postal question naire . Our main aim was to delineate divergent practice s which may reveal a need for controlled prospect i ve studies . For first-line intravenous ( i.v . ) therapy of acute exacerbations associated with Pseudomonas aeruginosa , 20 physicians ( 76.9 % ) combine a penicillin derivative with an aminoglycoside , in contrast to five ( 19.2 % ) who regularly use i.v . monotherapy with ceftazidime and one who combines i.v . ceftazidime with an aminoglycoside . When i.v . therapy is considered inappropriate , oral ciprofloxacin is sometimes used by all clinicians and oral broad spectrum agents are used in addition by 13 , chloramphenicol being prescribed most often . Excluding allergy , the most important factor influencing choice of agents by 19 ( 73.1 % ) physicians is the most recent sputum susceptibility results . For maintenance therapy , 21 prescribe oral anti-staphylococcal agents if Staphylococcus aureus is isolated ; of these , eight do so only if lung function deteriorates , nine after repeated isolation and four after first isolation of S. aureus . The remaining five physicians give anti-staphylococcal drugs to all patients once the diagnosis of CF is made . For maintenance of lung function in patients with persistent P. aeruginosa , all physicians used nebulized antibiotics , the indications for which vary between units . There was general concordance in the therapy of exacerbations associated with P. aeruginosa , whereas the use of agents to maintain lung function is more varied . We suggest that prospect i ve studies address practice s which vary greatly , such as the route , the duration and the timing of initiating antibiotic therapy given to maintain lung function BACKGROUND Patients with cystic fibrosis have received more intravenous antibiotic courses as median survival has steadily increased . A number of centres have adopted a policy of regular ( three monthly ) rather than on dem and intravenous antipseudomonal antibiotics . More widespread bacterial antibiotic resistance has result ed from this increased antibiotic use . Most Pseudomonas aeruginosa strains remain fully sensitive to colistin but its use has been resisted owing to concerns about neurotoxicity and nephrotoxicity . A study was carried out to assess the safety and efficacy of intravenous colistin in the treatment of acute respiratory exacerbations in adult patients with cystic fibrosis . METHODS Patients with chronic Pseudomonas aeruginosa colonisation who presented with protocol defined respiratory tract exacerbations were r and omised to receive treatment for 12 days with either colistin ( 2 MU tds intravenously ) alone or with a second anti-pseudomonal antibiotic . Comparisons of the absolute values of respiratory function tests on days 1 , 5 , and 12 and of overnight oxygen saturation on days 1 and 12 were the primary outcome measures . Patient 's weight , clinical and chest radiographic scores , and peripheral blood markers of inflammation were also documented . The effect of each treatment regimen individually was assessed by the change in clinical measurements from baseline values . Adverse renal effects were monitored by measurement of serum levels of urea and electrolytes , creatinine clearance , and ward urine testing . Neurotoxicity was monitored by direct question ing for symptoms . RESULTS Fifty three patients , 18 of whom entered the study twice , were enrolled . The mean forced expiratory volume in one second ( FEV1 ) increased significantly in both groups , mean forced vital capacity ( FVC ) only with dual therapy . Both groups showed a non-significant increase in overnight oxygen saturation . All patients showed clinical improvement . Thirty seven adverse neurological events ( two severe ) were reported in 33 patients in the monotherapy group and 37 ( none severe ) in 36 patients in the dual therapy group . One patient withdrew because of severe weakness and dizziness . All other adverse neurological events were well tolerated and resolved during or shortly after treatment . Significant changes were seen in mean serum urea levels in both groups , but in only four patients to a level above the normal range , and in creatinine clearance in the dual therapy group . At 24 month follow up no long term adverse consequences from intravenous colistin were found in patients who completed the study . CONCLUSIONS Intravenous colistin is an effective treatment for Pseudomonas aeruginosa associated pulmonary exacerbations in patients with cystic fibrosis . Assessment of the individual effect of each treatment regimen suggests a greater efficacy when colistin is combined with a second antibiotic to which the pseudomonas shows in vitro sensitivity . Changes in renal function should be monitored Two open r and omized cross-over studies were undertaken comparing ceftazidime to tobramycin and ceftazidime to tobramycin plus carbenicillin in 13 and 15 cystic fibrosis ( CF ) patients , respectively , with chronic bronchopulmonary Pseudomonas aeruginosa infection . The difference in lung function improvement was statistically better in terms of FEV1 and FVC for the ceftazidime group in the study versus tobramycin plus carbenicillin . Patients receiving ceftazidime showed a tendency for a greater long-term benefit in lung function as measured at 1 and 2 months after treatment than patients receiving the other antibiotics . Development of resistance against both ceftazidime and carbenicillin was seen regularly and was not prevented by combination therapy with tobramycin . No resistance developed when tobramycin was used as monotherapy . Serum concentration curves for ceftazidime fitted a two compartment first order open model in CF patients and showed a distribution volume of 40 % of the body weight and a final serum half-life of 1.8 h. One case of Type III hypersensitivity reaction was seen during ceftazidime treatment . Ceftazidime seems to be an effective and safe antibiotic in the treatment of Ps . aeruginosa bronchopulmonary infection in CF patients , although these bacteria could not be eradicated Background / aim : We hypothesized that a continuous 24-h infusion of 100 mg/kg per day ceftazidime ( treatment C ) would result in equivalent or even superior anti-infectious efficacy in chronic Pseudomonus aeruginosa ( PA ) infection in patients with cystic fibrosis ( CF ) in comparison to the usual application of 200 mg/kg per day ceftazidime in three doses ( treatment T ) . Methods : This was a r and omized crossover study comparing outcome after 14 days and 35 days . Tobramycin administered once daily ( 10 mg/kg per day ) was administered concomitantly in both groups . The primary end-point was a decrease in the leukocyte count , and the secondary endpoints were clinical and lung function parameters , Pseudomonas quantification in sputum , and inflammation markers ( immunogloblulin [ Ig ] G , C-reactive protein [ CRP ] ) in serum . All patients received antibiotics electively as 14-day courses on a regular basis , not for acute exacerbations . Results : Fifty-six patients ( 29 females , mean patient age 14.4 years , age range 5–37 ) initially received treatments C or T , followed by the alternative treatment after amean interval of 37 ( ± 21 ) weeks . After 2 weeks of antibiotic treatment , the overall study group showed significant improvements compared to baseline for body weight , leukocyte counts , CRP , forced expiratory volume in 1 s ( FEV1 ) , FVC ( forced vital capacity ) , and bacterial load in the airways , with no significant differences between treatment groups . Both regimens were well tolerated . Threeweeks after cessation of antimicrobial therapy , leukocytes and PA density had returned to pre-treatment values . Conclusion : We conclude that continuous or thrice-daily dosing of intravenous ceftazidime , both combined with once-daily tobramycin , are equally effective application regimens for elective antipseudomonal therapy in clinical ly stable patients with CF Twenty-one patients with cystic fibrosis and chronic Pseudomonas lung infection were treated at r and om with ceftazidime , 150 mg/kg/day , or with piperacillin , 300 mg/kg/day , and tobramycin , 10 and more mg/kg/day for 14 days . On admission and at discharge , body weight , erythrocyte sedimentation rate , white blood cell count , and differential were determined . Pulmonary function analysis and chest X-rays were also obtained on both occasions as was sputum bacteriology . After hospitalization , the patients were followed in the outpatient department for 14 - 26 months . Both treatments were associated with significant improvement in most of the parameters that were studied , but neither treatment was superior A double-blind controlled trail of anti-Pseudomonas chemotherapy was carried out in 24 exacerbations of pulmonary disease in patients with cystic fibrosis . Fifteen exacerbations were treated with oxacillin plus sisomicin and carbenicillin ( treatment group ) ; nine were treated with oxacillin alone ( control group ) . The planned length of treatment was 14 days . The difference between the failure rate in the treatment group ( 3/15 ) and the control group ( 7/9 ) was statistically significant ( P less than 0.015 ) . The difference in improvement of forced expiratory volume in 1 second was also significant ( P less than 0.025 ) . At the end of the study , Pseudomonas aeruginosa was still present in the sputum of all nine patients in the control group , but was not isolated from six of the 15 patients in the treatment group . The data suggest a beneficial role for anti-Pseudomonas chemotherapy in the treatment of acute pulmonary exacerbations in patients with cystic fibrosis BACKGROUND Once daily dosing of aminoglycosides is widely used but is limited by the inconvenience of the slow infusion it requires and the associated three-times daily infusion of a beta-lactam . Twice daily tobramycin can be given as a slow IV bolus and may be more convenient . This study compares twice with three-times daily dosing of both tobramycin and ceftazidime . METHODS This was a r and omised , open-label , parallel group trial . CF patients presenting with an infective exacerbation were r and omised to either twice or three-times daily ceftazidime and tobramycin . Markers of treatment efficacy and safety were measured in the two groups . The primary outcome measure was improvement in FEV1 . RESULTS 146 patients were r and omised into the study . There was no significant difference in the two groups for improvement in FEV1 % predicted ( 9.93 % and 7.98 % for twice daily and three-times daily respectively ) and similar times to next exacerbation . There were no differences in the incidence of treatment failure , nephrotoxicity and ototoxicity . DISCUSSION This study confirms that twice daily dosing of both tobramycin and ceftazidime is safe and effective and may be considered more convenient than current dosing schedules The efficacy of aztreonam was compared to that of st and ard therapy consisting of tobramycin and azlocillin in the treatment of acute pulmonary exacerbations of cystic fibrosis in a r and omized , open trial . Fifteen patients were r and omized to each treatment . Responses were assessed based on changes in pulmonary and clinical scores , white blood cell counts , pulmonary function tests and quantitative bacteriology of sputum which were performed before , every 5 to 7 days during and on the last day of therapy . Patients in both groups responded to therapy and there were no statistically significant differences in changes in the above indicators of response with therapy between the two groups ( P greater than 0.05 ) . The incidence of detection of Pseudomonas aeruginosa isolates resistant to all three study antibiotics increased with therapy . Side effects were limited to transient elevations of liver enzymes ( both groups ) and rash and fever in one patient treated with azlocillin . Aztreonam represents effective therapy for pulmonary exacerbations of cystic fibrosis associated with susceptible pathogens |
639 | 16,034,888 | Operative time was longer in laparoscopic surgery , but intraoperative blood was less than in conventional surgery .
Intensity of postoperative pain and duration of postoperative ileus was shorter after laparoscopic colorectal resection and pulmonary function was improved after a laparoscopic approach .
Total morbidity and local ( surgical ) morbidity was decreased in the laparoscopic groups .
General morbidity and mortality was not different between both groups .
Until the 30th postoperative day , quality of life was better in laparoscopic patients .
Postoperative hospital stay was less in laparoscopic patients .
Under traditional perioperative treatment , laparoscopic colonic resections show clinical ly relevant advantages in selected patients . | BACKGROUND Colorectal resections are common surgical procedures all over the world .
Laparoscopic colorectal surgery is technically feasible in a considerable amount of patients under elective conditions .
Several short-term benefits of the laparoscopic approach to colorectal resection ( less pain , less morbidity , improved reconvalescence and better quality of life ) have been proposed .
OBJECTIVES This review compares laparoscopic and conventional colorectal resection with regards to possible benefits of the laparoscopic method in the short-term postoperative period ( up to 3 months post surgery ) . | Laparoscopy-assisted colectomy istechnically feasible , but objective evidence of its benefits remainsscarce . This study was done to evaluate the outcomes and operativestress of laparoscopy-assisted colectomy versus the traditional open method in the management of sigmoid complex polyps that can not besafely or adequately removed by colonofibroscopy . Between January 1997 and December 1999 , a total of 42 patients were equally r and omizedto the laparoscopy group and the laparotomy group by the blockedr and omization method . Three patients r and omized to the laparoscopygroup did not complete the trial ; therefore 18 patients treated bylaparoscopy-assisted sigmoidectomy and the other 21 treated by the open method were prospect ively evaluated . These two groups of patients werewell matched in age , gender , symptoms , tumor location , localization method , tumor size , morphology , histopathology , and the accuracy of the clinical diagnosis . Two st and ardized surgical strategies , thelateral-to-medial and medial-to-lateral dissection sequences , wereperformed in 14 and 4 patients of the laparoscopy group , respectively , according to whether their tumors were located above or below 20 cmabove the anal verge . After evaluating the surgical outcomes , we foundthat the laparoscopy group was significantly better than the laparotomygroup in regard to parameters that included severity of postoperativepain , wound size , postoperative complication rate , and the duration ofpostoperative ileus , hospitalization , and disability . There was nosignificant difference in the operating times for these two groups . However , the costs of the laparoscopy group were significantly higher . To evaluate the surgical stress , we measured the serum C-reactiveprotein ( CRP ) level , erythrocyte sedimentation rate ( ESR ) , totallymphocyte count , and CD4+/CD8 + ratio 24 hoursbefore and after surgery . We found that the postoperative serum CRPlevel and the ESR were significantly less elevated and the totallymphocyte counts and CD4+/CD8 + ratio weresignificantly less depressed in the laparoscopy group than in thelaparotomy group . We thus concluded that laparoscopy-assistedsigmoidectomy can be safely performed with shorter convalescence and less operative stress but at a higher cost . We strongly recommended theuse of this technique in the management of sigmoid complex polyps ifthe patient 's economic status permits 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 Background : The magnitude of surgical trauma after laparoscopic and open colonic resection was evaluated by examining postoperative serum values of interleukin-6 ( IL-6 ) , IL-10 , C-reactive protein ( CRP ) , and granulocyte elastase ( GE ) for further evidence of the benefit realized with minimally invasive approaches in colonic surgery . Methods : Altogether , 42 patients with Crohn 's disease ( n = 20 ) or colon carcinomas/adenomas ( n = 22 ) were matched by age , gender , body mass index ( BMI ) , and Crohn 's Disease Activity Index for either a laparoscopic ( n = 21 ) or an open colonic resection ( n = 21 ) . In both groups the postoperative serum levels of IL-6 , IL-10 , C-RP , and granulocyte elastase were determined , as indicators of surgical stress . Results : Laparoscopic and open colonic resection caused a significant increase in serum IL-6 , IL-10 , CRP , and granulocyle elastase levels . The comparison between laparoscopic and open colonic resections , however , showed significantly lower serum IL-6 , IL-10 , CRP , and granulocyte elastase levels after laparoscopic colonic resection , which was most evident for IL-6 and granulocyte elastase . Conclusions : Our study demonstrated that IL-6 and granulocyte elastase may be appropriated particularly to monitor surgical stress . By using these parameters , we found a significant reduction in surgical trauma after laparoscopic surgery , was compared with the open procedure . This supports the clinical findings of a clear benefit for patients undergoing laparoscopic colonic surgery 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 INTRODUCTION : Surgeons have been reluctant to apply laparoscopic techniques to Crohn 's disease surgery because of concerns with evaluating and excising inflamed tissue using laparoscopic methods Additionally in Crohn 's disease surgery , laparoscopic techniques have not been demonstrated to have clear advantages over conventional ones . METHOD : We conducted a prospect i ve , r and omized trial in one surgical department comparing laparoscopic vs. conventional techniques in 60 patients ( 25 males ) , median age 34.4 ( range 10–60.1 ) years , undergoing elective ileocolic resection for refractory Crohn 's disease . Postoperatively , all patients underwent measurement of pulomnary 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 31 patients assigned to laparoscopic and 29 to the conventional group , all had isolated Crohn 's disease of the terminal ileum plus or minus the cecum . Median length of the incision was 5 cm in the laparoscopic group and 12 cm in the conventional group . Overall recovery of 80 percent of forced expiratory volume ( one second ) and forcec vital capacity was a median of 2.5 days for laparoscopic and 3.5 days for conventional ( P=0.03 ) . There was no difference in the amount of morphine equivalents used between groups postoperatively . Flatus and first bowel movement returned a median of 3 and 4 days , respectively , after conventional roscopicvs . 3.3 and 4 days , respectively , after conventional surgery ( P=0.21 ) . Median length of stay was five ( range , 4–30 ) days for laparoscopic , and six ( range , 4–18 ) days for conventional surgery . Major complications occurred in one patient in each group . Minor complications occurred in four laparoscopic and eight conventional patients ( P<0.05 ) . There were no deaths . Two laparoscopic patients were converted to conventional as a result of adhesions or inflammation . All patients recovered well and there were no clinical resurrences in the follow-up period ( median , 20 ; range , 12–45 months ) . CONCLUSIONS : Within a single insititution , single surgical team , prospect i ve , r and omized trial , laparoscopic techniques offered a faster recovery of pulomary function , fewer complications , and shorter length of stay compared with conventional surgery for selected patients undergoing ileocolic resection for Crohn 's disease UNLABELLED We compared the effects of a laparoscopic ( n = 23 ) versus laparotomic ( n = 21 ) technique for major abdominal surgery on temperature control in 44 patients undergoing colorectal surgery during a combined epidural/general anesthesia . A thoracic epidural block up to T4 was induced with 6 - 10 mL of 0.75 % ropivacaine ; general anesthesia was induced with thiopental , fentanyl , and atracurium IV and maintained with isoflurane . Core temperature was measured with a bladder probe and recorded every 15 min after the induction . In both groups , core temperature decreased to 35.2 degrees C ( range , 34 degrees C-36 degrees C ) at the end of surgery . After surgery , normothermia returned after 75 min ( 60 - 120 min ) in the Laparoscopy group and 60 min ( 45 - 180 min ) in the Laparotomy group ( P = 0.56 ) . No differences in postanesthesia care unit discharge time were reported between the two groups . The degree of pain during coughing was smaller after laparoscopy than laparotomy from the 24th to the 72nd observation times ( P < 0.01 ) . Morphine consumption was 22 mg ( 2 - 65 mg ) in the Laparotomy group and 5 mg ( 0 - 45 mg ) in the Laparoscopy group ( P = 0.02 ) . The time to first flatus was shorter after laparoscopy ( 24 h [ 16 - 72 h ] ) than laparotomy ( 72 h [ 26 - 96 h ] ) ( P = 0.0005 ) , and the first intake of clear liquid occurred after 48 h ( 24 - 72 h ) in the Laparoscopy group and after 96 h ( 90 - 96 h ) in the Laparotomy group ( P = 0.0005 ) . Although laparoscopic surgery provides positive effects on the degree of postoperative pain and recovery of bowel function , the reduction in heat loss produced by minimizing bowel exposure with laparoscopic surgery does not compensate for the anesthesia-related effects on temperature control , and active patient warming must also be used with laparoscopic techniques . IMPLICATION S This prospect i ve , r and omized , controlled study demonstrates that laparoscopic colorectal surgery results in less postoperative pain and earlier recovery of bowel function than conventional laparotomy but does not reduce the risk for perioperative hypothermia . Accordingly , active warming must be provided to patients also during laparoscopic procedures 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 The objectives of this study were to compare both subjective clinical outcomes and the objective stress response of laparoscopic and open abdominal rectopexy in patients with full‐thickness rectal prolapse . Abdominal rectopexy for patients with rectal prolapse is well suited for a laparoscopic approach as no resection or anastomosis is necessary Abstract . Previous analyses of non- prospect ively r and omized trials have suggested that early oral postoperative feeding might be a benefit unique to laparoscopic surgery . However , some authors have indicated that early feeding can be tolerated by the majority of patients after elective open surgery . Aim : This prospect i ve r and omized study was undertaken to assess whether the time prior to oral intake of food after laparoscopy-assisted surgery is shorter than that after st and ard laparotomy . Methods : This trial included 40 patients who were divided r and omly into two groups before operation . Group I included 20 patients ( mean age , 52 years ; range , 15 – 77 years ) who underwent a laparoscopy-assisted colon or rectal procedure ( LAP ) . Group II consisted of 20 patients ( mean age , 56 years , range , 41 – 74 years ) who underwent surgery with a st and ard midline incision ( SMI ) . On the evening after surgery , patients were allowed clear liquids ab libitum . This regimen was continued until the first postoperative day at which time they could elect to start eating a regular diet . If a patient had two episodes of vomiting , a nasogastric tube was inserted . Results : Five laparoscopic procedures were converted to SMI because of adhesions ( 25 % ) and an equal number of patients was excluded from the group that was treated in the traditional manner . Therefore , only 30 patients were included in the analysis . There were no deaths in this trial . Complications appeared in four of the patients in the LAP group and in two of the patients in the SMI group ( no significant difference ) . There were no statistically significant differences between the two groups in terms of the ability to tolerate the early oral intake of food , in the frequency of vomiting or in the incidence of insertion of a nasogastric tube . The time to the first bowel movement was 5.4 days in LAP and 5.5 days in SMI , and the difference was not significant . Conclusion : This study invali date s the cl aim by laparoscopic surgeons that earlier oral intake of food is tolerated by their patients than by patients who undergo st and ard procedures .Résumé . Des études r and omisées non prospect ives ont suggéré que la reprise précoce de l'alimentation orale peut être un bénéfice particulier à la chirurgie laparoscopique . Certains auteurs ont indiqué que la reprise précoce de l'alimentation orale peut être bien tolérée par la plupart des patients après chirurgie élective ouverte . Cette étude prospect i ve r and omisée a été entreprise pour déterminer si la reprise orale de l'alimentation après chirurgie laparoscopique peut être plus précoce qu'après une laparotomie st and ard . Quarante patients ont été inclus dans cette étude et ont été divisés de manière r and omisée en deux groupes avant chirurgie . Le groupe 1 comporte 20 patients ( 15 à 77 ans , moyenne d'âge 52 ans ) qui ont subi une résection colique ou rectale laparoscopique ( LAP ) . Le groupe II comporte 20 patients ( 41 à 74 ans , moyenne d'âge 56 ans ) qui ont subi une chirurgie par une incision médiane st and ard ( SMI ) . Le soir de l'intervention chirurgicale , les patients ont été autorisés à boire librement . Ce régime a été continué le premier jour postopératoire à partir duquel les patients pouvaient débuter une alimentation normale . Si un patient présente deux épisodes de vomissements , une sonde naso-gastrique a été mise en place . Cinq interventions laparaoscopiques ont dûêtre converties en chirurgie ouverte en raison d'adhérences ( 25 % ) et un nombre égal de patients ont été exclus du groupe qui a été traité de manière traditionelle . En conséquence , 30 patients ont été inclus dans l'analyse . Aucun décès n'est à déplorer . Quatre complications sont survenues chez des patients du groupe laparoscopique et deux dans le collectif des patients ayant subi un chirurgie ouverte ( pas de différence statistique significative ) . Il n'y a pas de différence statistique significative entre les deux groupes en ce qui concerne la tolérance à la reprise orale de l'alimentation , à la fréquence des vomissements ou à la nécessité de réinsérer un tube naso-gastrique . La première exonération est survenue au 5.4 jour dans le groupe laparoscopique et au 5,5 jour dans le groupe de chirurgie ouverte sans que la différence ne soit significative . En conclusion : Cette étude infirme l'idée que la chirurgie laparoscopique permet une reprise précoce et bien tolérée de l'alimentation en comparaison à la chirrugie ouverte Background : Laparoscopic surgery has proven to be safe and effective . However , the value of laparoscopic resection for malignancy in terms of cancer outcome can only be assessed by large prospect i ve r and omized clinical trials with sufficient follow-up . Methods : COLOR ( COlon carcinoma Laparoscopic or Open Resection ) is a European multicenter r and omized trial which has started in September 1997 . In 24 hospitals in Sweden , The Netherl and s , Germany , France , Italy and Spain , 1,200 patients will be included . The primary end point of the study is cancer-free survival after 3 years . Results : Within < 2 years , more than 540 patients have been r and omized for right hemicolectomy ( 45 % ) , left hemicolectomy ( 10 % ) and sigmoidectomy ( 45 % ) . 33 patients ( 6 % ) were excluded after r and omization . The accrual rate is approximately 25 patients /month . Current survival rates for the whole study group are : stage I : 95 % , stage II : 98 % , stage III : 93 % , stage IV : 64 % . For all patients with stage I disease , the mortality was not cancer related . Conclusions : Although laparoscopic surgery appears of value in colorectal malignancy , results of r and omized trials have to be awaited to determine the definitive place of laparoscopy in colorectal cancer . Considering the current accrual rate , the COLOR study will be completed in 2002 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 Laparotomy causes a significant reduction of pulmonary function , and atelectasis and pneumonia occur after elective conventional colorectal resections . OBJECTIVE To evaluate the hypothesis that pulmonary function is less restricted after laparoscopic than after conventional colorectal resection . DESIGN A r and omized clinical trial . SETTING The surgical department of an academic medical center . PATIENTS Sixty patients underwent laparoscopic ( n = 30 ) or conventional ( n = 30 ) resection of colorectal tumors . The 2 groups did not differ significantly in age , sex , localization or stage of tumor , or preoperative pulmonary function . MAIN OUTCOME MEASURES Forced vital capacity , forced expiratory volume in 1 second , peak expiratory flow , mid-expiratory phase of forced expiratory flow , and oxygen saturation of arterial blood . RESULTS The forced vital capacity ( mean + /- SD values : conventional resection group , 1.73+/-0.60 L ; laparoscopic surgery group , 2.59+/-1.11 L ; P<.01 ) and the forced expiratory volume in 1 second ( conventional resection group , 1.19+/-0.51 L/s ; laparoscopic surgery group , 1.80+/-0.80 L/s ; P<.01 ) were more profoundly suppressed in the patients having conventional resection than in those having laparoscopic surgery . Similar results were found for the peak expiratory flow ( conventional resection group , 2.51+/-1.37 L/s ; laparoscopic resection group , 3.60+/-2.22 L/s ; P<.05 ) and the midexpiratory phase of forced expiratory flow ( conventional resection group , 1.87+/-1.12 L/s ; laparoscopic surgery group , 2.67+/-1.76 L/s ; P<.05 ) . The oxygen saturation of arterial blood , measured while the patients were breathing room air , was lower after conventional than after laparoscopic resections ( P<.01 ) . The recovery of the forced vital capacity and forced expiratory volume in 1 second to 80 % of the preoperative value took longer in patients having conventional resection than in those having laparoscopic resection ( P<.01 ) . Pneumonia developed in 2 patients having conventional resection , but no pulmonary infection occurred in the laparoscopic resection group ( P>.05 ) . CONCLUSIONS Pulmonary function is better preserved after laparoscopic than after conventional colorectal resection . Pulmonary complications may be reduced after laparoscopic resections because of the better postoperative pulmonary function PURPOSE : All types of trauma to the organism produce a systemic response that is proportional to the severity of the lesion caused . The more rapid clinical recovery during the postoperative period of patients undergoing laparoscopic-assisted colectomyvs . patients receiving conventional surgery suggests that laparoscopic surgery produces less surgical trauma . The aim of this r and omized , prospect i ve study was to compare acute phase postoperative response in patients diagnosed with colon neoplasm undergoing open segmentary colectomyvs . laparoscopic-assisted colectomy . METHODS : From June 1994 to July 1997 the results of 97 patients ( 58 su bmi tted to open colectomy and 39 undergoing laparoscopic-assisted colectomy ) were analyzed . Blood determinations of cortisol , prolactin , C-reactive protein and interleukin-6 were performed before surgery and at 4 , 12 , 24 , and 72 hours after surgery . RESULTS : The plasma levels of cortisol and prolactin were higher in the postoperative period with both surgical techniques with no significant differences being observed . The levels of interleukin-6 achieved a maximum peak at 4 hours after surgery , later showing a decrease and practically achieving basal levels at 72 hours in both groups . The levels of interleukin-6 were higher with significant differences at 4 , 12 , and 24 hours in the patients undergoing open colectomy . The plasma levels of C-reactive protein were significantly lower at 72 hours in patients receiving laparoscopic-assisted colectomy . CONCLUSIONS : The results obtained in this r and omized , prospect i ve study suggest that acute phase systemic response is attenuated in patients undergoing laparoscopic-assisted colectomy in comparison with patients receiving open colectomy HYPOTHESIS Gasless laparoscopy produces smaller cardiopulmonary and systemic changes than carbon dioxide ( CO2 ) laparoscopy during colonic surgery . DESIGN Prospect i ve r and omized trial . SETTING Department of Surgery in a university hospital . PATIENTS Twenty-two patients scheduled for laparoscopic colonic resection ; 5 patients were excluded because of conversion to open surgery ( N = 17 ) . INTERVENTIONS Patients were r and omized to either gasless ( n = 9 ) or conventional CO2 ( n = 8) surgery . MAIN OUTCOME MEASURES Intraoperative assessment of hemodynamic factors and pulmonary function , and postoperative assessment of pain , pulmonary function , convalescence , and various injury factors were done several times until 30 days after surgery . Surgical complications were noted . RESULTS Descending aorta blood flow after 30 minutes ( P=.03 ) and heart rate after 150 minutes were higher in the CO2 group ( P=.009 ) . Central venous pressure , PaCO2 inspiration pressure , and end tidal CO2 level were significantly higher in the CO2 group ( P = .05 , .03 , .04 , and .01 , respectively ) . Patients in the CO2 group had less pain during mobilization and coughing ( P = .008 and .006 , respectively ) , and were significantly more fatigued ( P = .04 ) . No other important differences were observed in intraoperative hemodynamic factors , postoperative convalescence , immunocompetence , or pulmonary function . CONCLUSION No clinical ly important differences in cardiovascular and systemic response were observed between patients undergoing CO2 or gasless laparoscopy for colonic disease 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 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 Abstract Background : We prospect ively studied the recovery of gastrointestinal motility in patients undergoing laparoscopic ( LAP , n=7 ) or open ( OPEN , n=7 ) colon resections . Methods : At operation , bipolar recording electrodes were placed on the proximal and distal antrum , the proximal site of the colonic anastomosis , and the rectosigmoid for postoperative myoelectric recordings . Results : Shorter postoperative hospitalization and earlier resumption of a regular diet of the LAP group just barely failed to achieve significant differences when compared with the OPEN group ( p=0.091 , p=0.050 , respectively ) . There were no differences between groups for slow wave frequency , amplitude , or dysrhythmias in the antrum , nor for return of discrete ( DERA ) and continuous ( CERA ) electrical response activity in the colon . Percentage of slow waves with spike activity tended to increase with passage of time postoperatively in both groups . There was a significant difference between POD 3 and 7 + in the LAP group ( p<0.05 ) . However , there were no significant differences in the percentage of slow waves with spike activities between groups on any postoperative day . Conclusions : The potential benefits of using a laparoscopic approach to colon resection are not clearly confirmed by these data . While such an approach may possibly result in shorter hospitalization , it appears to offer at best only modest increases in the rapidity of recovery of gastrointestinal function Abstract PURPOSE : This study was design ed to evaluate differences in both the peritoneal and systemic immune response after laparoscopic and conventional surgical approaches . METHODS : Patients with a primary carcinoma were prospect ively r and omized to curative laparoscopic ( n = 12 ) or conventional ( n = 14 ) colon resection . The proinflammatory cytokines interleukin-6 , interleukin-8 , and tumor necrosis factor-alpha were measured in the peritoneal drain fluid and in the serum . C-reactive protein and leukocyte counts and the differences in leukocyte sub population s and expression of human leukocyte antigen-DR on monocytes were measured perioperatively . RESULTS : Significantly higher levels of proinflammatory cytokine were found in the peritoneal drain fluid than in the circulation after both procedures . Serum interleukin-6 and interleukin-8 levels were significantly lower 2 hours after laparoscopic surgery than with the conventional procedure . Postoperative cellular immune counts and human leukocyte antigen-DR expression normalized earlier after the laparoscopic approach . CONCLUSIONS : The systemic proinflammatory concentrations after both surgical approaches represent only a small fragment of what is generated in the peritoneal drain fluid . Even if the immediate levels of proinflammatory cytokines in the serum are significantly lower in the laparoscopic group , the same cytokines locally produced showed no differences , which suggests that the two intra-abdominal approaches are equally traumatic . No differences in cellular response were observed between the groups The authors examined the impact of the laparoscopic approach on the early outcome of resected colon carcinomas . The role of laparoscopic techniques in the treatment of colon carcinomas is question able . Previous studies have suggested technical feasibility of surgical resections of these cancers by laparoscopic means and have implied a benefit to laparoscopic technique for patients undergoing colorectal resections . A prospect i ve , r and omized study was conducted comparing laparoscopic assisted colectomy ( LAC ) open colectomy ( OC ) for colon cancer . We present the preliminary results in relation to the short-term outcome and judge the feasibility of the laparoscopic procedure to as a way of performing accurate oncologic resection and staging . Benefit has been demonstrated with LAC in this setting . Passing flatus , oral intake , and discharge from hospital occurred earlier in LAC- than OC-treated patients The mean operative time was significantly longer in the LAC group than in the OC group . The overall morbidity was significantly lower in the LAC group . No significant differences were observed between both groups in the number of lymph nodes removed or the pathological stage following the Astler-Coller modification of the Dukes classification . The laparoscopic approach improves the short-term outcome of segmental colectomies for colon cancer . However , the further follow-up of these patients will allow us to answer in the near future whether or not the LAC may influence the long-term outcome 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 Background : Surgical trauma and anesthesia are known to cause transient postoperative suppression of the immune system . In r and omized controlled trials , it has been shown that laparoscopic colorectal resections have short-term benefits not observed with conventional colorectal resections . We hypothesized that these benefits were due to the reduction in surgical trauma , leading to a diminished cytokine response and less depression of cell-mediated immunity after laparoscopy . Methods : In a prospect i ve r and omized trial , colorectal cancer patients without evidence of metastatic disease underwent either laparoscopic ( n = 20 ) or conventional ( n = 20 ) tumor resection . Postoperative immune function was assessed by measuring the white blood cell ( WBC ) count , the CD4 + and CD8 + lymphocytes , the CD4+/CD8+/ratio , and the HLA-DR expression of CD14 + monocytes . In addition , the production of interleukin-6 ( IL = 6 ) and TNF-a were measured after ex vivo stimulation of mononuclear blood cells with lipopolysaccharide ( LPS ) and compared to the plasma levels of these cytokines . Postoperative mean levels of the immunologic parameters for the two groups were calculated and compared using the Mann-Whitney U test . Results : Preoperatively , there were no differences between the two groups in terms of patient characteristics or immunologic parameters . Although the postoperative peak concentrations of white blood cells were significant lower in the laparoscopic group than the conventional group ( p < 0.05 ) , there were no differences between the two groups in the sub population of lymphocytes ( CD4 + , CD8 + ) . HLA-DR expression of CD14 + monocytes was lower in the conventional group on the 4th postoperative day ( p < 0.05 ) . The laparoscopic group showed higher values in cytokine production of mononuclear blood cells after LPS stimulation . Postoperative plasma peak concentrations of IL-6 and TNF-a were lower after laparoscopic resection . Conclusion : Postoperative cell-mediated immunity was better preserved after laparoscopic than after conventional colorectal resection . Cellular cytokine production was preserved only in the laparoscopic group , while cytokine plasma levels were significantly higher in the conventional group . These findings may have important implication s for the use of laparoscopic colorectal resection , especially in patients with malignant disease 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 We devised 33 rules for the evaluation of r and om control trials ( RCT ) and used them to assess 56 RCTs listed in Index Medicus during 1980–82 on antibiotic prophylaxis of surgical wound infection . We asked 15 questions about design and conduct , 10 about analysis and 8 about presentation . Out of a maximum score of 100 only 16 papers scored over 70 , the highest being 89 and the lowest 34 . Defects in presentation were not common , and 17 papers scored over 90 per cent . Defects in analysis included the incorrect use of statistical tests and ignoring the Type II error in ‘ negative ’ trials ; only 13 papers scored over 70 per cent . Defects in design and conduct included transgressions of ethical principles , inappropriate regimens , ill‐defined end points and biased r and omization or assessment ; only 20 papers scored over 70 per cent . We conclude that there is room for improvement in the performance of RCT and that the application of the 33 rules would be helpful not only to research ers but also to editors and referees of scientific journals , and to their readers 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 OBJECTIVE To compare the systemic cytokine response in patients after laparoscopic-assisted resection with those after open resection of rectosigmoid carcinoma . SUMMARY BACKGROUND DATA Laparoscopic resection of colorectal carcinoma is technically feasible , but objective evidence of its benefit is scarce . Systemic cytokines are accepted as markers of postoperative tissue trauma and mediators of the host immune response . METHODS Thirty-four patients with rectosigmoid carcinoma , without evidence of metastatic disease and suitable for laparoscopic resection , were r and omized to undergo either laparoscopic ( n = 17 ) or conventional open ( n = 17 ) resection of the tumor . Clinical parameters were recorded . Sera were collected before surgery and at appropriate time points afterward and assayed for interleukin-1beta , tumor necrosis factor-alpha , interleukin-6 , and C-reactive protein . The primary end points were the cytokine and C-reactive protein levels . Data were analyzed by intention to treat . RESULTS The demographic data of the two groups were comparable . The clinical outcome of both groups was satisfactory , with no surgical deaths and a reasonable complication rate . Both interleukin-1beta and interleukin-6 levels peaked 2 hours after surgery , with the responses in the laparoscopic group significantly less than those in the open group . C-reactive protein levels peaked at 48 hours , and the difference was also statistically significant . Levels of tumor necrosis factor-alpha were not elevated after surgery , and there was no difference between the groups . CONCLUSIONS Tissue trauma , as reflected by systemic cytokine response , was less after laparoscopic resection than after open resection of rectosigmoid carcinoma . The difference in the systemic cytokine response may have implication s on the long-term survival PURPOSE : Operating room time and anastomosis-related morbidity of laparoscopic-assisted sigmoid resection with anastomosis performed in an open fashion through a horizontal suprapubic incision or laparoscopically after re-establishing pneumoperitoneum were compared . METHODS : A r and omized trial was performed on patients with recurrent uncomplicated diverticulitis of the sigmoid colon during a 14-month period . Inclusion criteria were persistence of symptoms despite medical treatment and two previous admissions . Exclusion criteria included complicated diverticulitis , suspected cancer , and previous extensive abdominal surgery . Because skin incisions were similar and patients were r and omly assigned in the operating room , the trial was performed as double blind . RESULTS : There were no deaths . Two patients were excluded before r and omization . Three patients were not treated as allocated because of conversion to open surgery . Aside from previous abdominal-surgery rates , 16 patients with laparoscopic-assisted sigmoid resections after re-establishing pneumoperitoneum and 15 patients with laparoscopic-assisted sigmoid resections with anastomosis performed in an open fashion through a horizontal suprapubic incision were well-matched for age , gender , weight , American Society of Anesthesiology class , previous admissions , skin-incision length , size of circular stapler , and mobilization of splenic flexure . There were no significant differences in morbidity rates ( 3/16vs . 3/15 ) , complete doughnuts ( 16/16vs . 15/15 ) , blood loss ( 300vs . 200 ml ) , flatus ( 4vs . 4 days ) , solid-food resumption ( 5vs . 6 days ) , stay ( 8.5vs . 9 days ) in laparoscopic-assisted sigmoid resection after re-establishing pneumoperitoneum and laparoscopic-assisted sigmoid resection with anastomosis performed in an open fashion through a horizontal suprapubic incision groups , respectively . Patients with laparoscopic-assisted sigmoid resection after re-establishing pneumoperitoneum had statistically longer operating room time ( 295vs . 190 minutes;P<0.01 ) . Median follow-up was 12 and 10 months in 10 patients with laparoscopic-assisted sigmoid resection after reestablishing pneumoperitoneum and 11 patients with laparoscopic-assisted sigmoid resection with anastomosis performed in an open fashion through a horizontal suprapubic incision , respectively . One patient with laparoscopic-assisted sigmoid resection with anastomosis performed in an open fashion through a horizontal suprapubic incision had an anastomotic stenosis endoscopically dilated . CONCLUSIONS : Nonrestoration of pneumoperitoneum after laparoscopic-assisted sigmoid resection allows a decrease in operating room time and a similar outcome Objective The primary endpoint was to compare the impact of laparoscopic and open colorectal surgery on 30-day postoperative morbidity . Lymphocyte proliferation to mitogens and gut oxygen tension were surrogate endpoints . Summary Background Data Evidence -based proof of the effect of laparoscopic colorectal surgery on immunometabolic response and clinical ly relevant outcome variables is scanty . Further r and omized trials are desirable before proposing laparoscopy as a superior technique . Methods Two hundred sixty-nine patients with colorectal disease were r and omly assigned to laparoscopic ( n = 136 ) or open ( n = 133 ) colorectal resection . Four trained members of the surgical staff who were not involved in the study registered postoperative complications . Lymphocyte proliferation to C and ida albicans and phytohemagglutinin was evaluated before and 3 and 15 days after surgery . Operative gut oxygen tension was monitored continuously by a polarographic microprobe . Results In the laparoscopic group the conversion rate was 5.1 % . The overall morbidity rate was 20.6 % in the laparoscopic group and 38.3 % in the open group . Postoperative infections occurred in 15 of the 136 patients in the laparoscopic group and 31 of the 133 patients in the open group . The mean length of hospital stay was 10.4 ± 2.9 days in the laparoscopic group and 12.5 ± 4.1 days in the open group . On postoperative day 3 , lymphocyte proliferation was impaired in both groups . Fifteen days after surgery , the proliferation index returned to baseline values only in the laparoscopic group . Intraoperative gut oxygen tension was higher in the laparoscopic than in the open group . Conclusions Laparoscopic colorectal surgery result ed in a significant reduction of 30-day postoperative morbidity . Lymphocyte proliferation and gut oxygen tension were better preserved in the laparoscopic group than in the open group There has been no r and omized clinical trial of the costs of laparoscopic colonic resection ( LCR ) compared with those of open colonic resection ( OCR ) in the treatment of colonic cancer Abstract PURPOSE : The aim of the study was to investigate the effect of surgical trauma in terms of approach ( laparoscopic vs. conventional surgery ) and extent of bowel resection ( ileocolic resection vs. colectomy ) on interleukin-6 level , C-reactive protein level , and expression of human leukocyte antigen-DR on peripheral blood mononuclear cells . Second , the length of the incision was correlated with the inflammatory response . METHODS : Thirty-four patients were analyzed as part of a r and omized trial comparing laparoscopically assisted vs. open bowel resection for Crohn ’s disease , ulcerative colitis , and familial adenomatous polyposis . C-reactive protein levels and expression of human leukocyte antigen-DR on peripheral blood mononuclear cells were measured preoperatively and one day after surgery . Interleukin-6 was measured preoperatively and on Days 1 and 7 postoperatively . RESULTS : Four of the 34 patients were excluded because of blood transfusion after surgery . One day postoperatively , the interleukin-6 level peaked significantly within the laparoscopic and conventional group . There was no significant difference between the conventional and laparoscopic groups at Day 1 postoperatively . At Day 7 postoperatively , interleukin-6 levels were similar in both groups and returned to baseline levels . There was a higher C-reactive protein level in the conventional group one day after surgery than in the laparoscopic group , although the difference was not significant . Preoperative and postoperative human leukocyte antigen-DR expression on monocytes and postoperative percentage of lymphocytes expressing human leukocyte antigen-DR did not differ between the conventional and laparoscopic groups . No differences in immune response with respect to the measured parameters were noticed in patients with a large or small bowel resection segment or in patients with a small ( ≤8 cm ) or large ( > 8 cm ) incision . CONCLUSIONS : These data suggest that surgical trauma did not significantly affect the immune status of patients with respect to the measured parameters in terms of either the approach or the extent of bowel resection |
640 | 27,653,623 | AIT appeared to have an acceptable side effect profile .
CONCLUSIONS AIT did not result in a statistically significant reduction in the risk of developing a first allergic disease .
There was , however , evidence of a reduced short-term risk of developing asthma in those with allergic rhinitis , but it is unclear whether this benefit was maintained over the longer term .
We are unable to comment on the cost-effectiveness of AIT | BACKGROUND There is a need to establish the effectiveness , cost-effectiveness , and safety of allergen immunotherapy ( AIT ) for the prevention of allergic disease . | BACKGROUND The natural history of allergic sensitization is complex and poorly understood . A prospect i ve nonr and omized study was carried out in a population of asthmatic children younger than 6 years of age whose only allergic sensitivity was to house dust mites ( HDMs ) . OBJECTIVES The study was design ed to determine whether specific immunotherapy ( SIT ) with st and ardized allergen extracts could prevent the development of new sensitizations over a 3-year follow-up survey . METHODS We studied 22 children monosensitized to HDM who were receiving SIT with st and ardized allergen extracts and 22 other age-matched control subjects who were monosensitized to HDM . The initial investigation included a full clinical history , skin tests with a panel of st and ardized allergens , and the measurement of allergen-specific IgE , depending on the results of skin tests . Children were followed up on an annual basis for 3 years , and the development of new sensitizations in each group was recorded . RESULTS Ten of 22 children monosensitized to HDM who were receiving SIT did not have new sensitivities compared with zero of 22 children in the control group ( p = 0.001 , chi square test ) . CONCLUSIONS This study suggests that SIT in children monosensitized to HDM alters the natural course of allergy in preventing the development of new sensitizations Background : Although widely practice d for over 80 years , the role of specific immunotherapy ( SIT ) in pediatric asthma treatment is still controversial . We assessed the effects of a 3‐year period of subcutaneous administration of a st and ardized preparation of Dermatophagoides pteronyssinus ( D pt ) on the respiratory health in a group of asthmatic children monosensitized to house dust mite ( HDM ) BACKGROUND Previous studies have suggested that single-allergen-specific immunotherapy ( SIT ) may prevent sensitization to other airborne allergens in monosensitized children . We aim ed to assess the prevention of new sensitizations in monosensitized children treated with single-allergen SIT injections in comparison with monosensitized patients given appropriate pharmacologic treatment for their disease . METHODS A total of 147 children with rhinitis and /or asthma monosensitized to house dust mite were studied ; 45 patients underwent SIT with adsorbed extracts and 40 patients underwent SIT with aqueous extracts for 5 years . The control group was comprised of 62 patients given only pharmacologic treatment for at least 5 years . Skin prick tests , medication scores for rhinitis and asthma , and atopy scores according to skin prick tests were evaluated at the beginning and after 5 years of treatment . RESULTS All groups were comparable in terms of age , sex , and disease characteristics . At the end of 5 years , 64 out of 85 ( 75.3 % ) in the SIT group showed no new sensitization , compared to 29 out of 62 children ( 46.7 % ) in the control group ( P = .002 ) . There were no differences between the SIT subgroups with regard to onset of new sensitization ( P = .605 ) . The patients developing new sensitizations had higher atopy scores ( P = .002 ) and medication scores for both rhinitis ( P = .008 ) and asthma ( P = .013 ) in comparison to patients not developing new sensitizations after 5 years of SIT . CONCLUSION According to our data , SIT has the potential to prevent the onset of new sensitizations in children with rhinitis and /or asthma monosensitized to house dust mite BACKGROUND Sublingual immunotherapy ( SLIT ) has been proved to be effective in allergic rhinitis and asthma , but there are few data on its preventive effects , especially in children . OBJECTIVE To evaluate the clinical and preventive effects of SLIT in children by assessing onset of persistent asthma and new sensitizations , clinical symptoms , and bronchial hyperreactivity . METHODS A total of 216 children with allergic rhinitis , with or without intermittent asthma , were evaluated and then r and omized to receive drugs alone or drugs plus SLIT openly for 3 years . The clinical score was assessed yearly during allergen exposure . Pulmonary function testing , methacholine challenge , and skin prick testing were performed at the beginning and end of the study . RESULTS One hundred forty-four children received SLIT and 72 received drugs only . Dropouts were 9.7 % in the SLIT group and 8.3 % in the controls . New sensitizations appeared in 34.8 % of controls and in 3.1 % of SLIT patients ( odds ratio , 16.85 ; 95 % confidence interval , 5.73 - 49.13 ) . Mild persistent asthma was less frequent in SLIT patients ( odds ratio , 0.04 ; 95 % confidence interval , 0.01 - 0.17 ) . There was a significant decrease in clinical scores in the SLIT group vs the control group since the first year . The number of children with a positive methacholine challenge result decreased significantly after 3 years only in the SLIT group . Adherence was 80 % or higher in 73.8 % of patients . Only 1 patient reported systemic itching . CONCLUSIONS In everyday clinical practice , SLIT reduced the onset of new sensitizations and mild persistent asthma and decreased bronchial hyperreactivity in children with respiratory allergy BACKGROUND Allergic rhinitis ( AR ) is a main risk factor for the development of asthma . Two r and omized open-label trials indicated that allergy immunotherapy ( AIT ) prevents the onset of asthma in patients with AR . However , these trials have method ological limitations , and it is unclear to what extent this experimental efficacy translates into clinical effectiveness . OBJECTIVES We sought to investigate the effectiveness of AIT to prevent asthma in patients with AR . METHODS Using routine health care data from German National Health Insurance beneficiaries , we identified a consecutive cohort of 118,754 patients with AR but without asthma who had not received AIT in 2005 . These patients were stratified into one group starting AIT in 2006 and one group receiving no AIT in 2006 . Both groups were observed regarding the risk of incident asthma in 2007 to 2012 . Risk ratios ( RRs ) were calculated with generalized linear models by using a Poisson link function with robust error variance and adjustment for age , sex , health care use because of AR , and use of antihistamines . RESULTS In a total of 2431 ( 2.0 % ) patients , AIT was started in 2006 . Asthma was newly diagnosed from 2007 - 2012 in 1646 ( 1.4 % ) patients . The risk of incident asthma was significantly lower in patients exposed to AIT ( RR , 0.60 ; 95 % CI , 0.42 - 0.84 ) compared with patients receiving no AIT in 2006 . Sensitivity analyses suggested significant preventive effects of subcutaneous immunotherapy ( RR , 0.54 ; 95 % CI , 0.38 - 0.84 ) and AIT including native ( nonallergoid ) allergens ( RR , 0.22 ; 95 % CI , 0.02 - 0.68 ) . AIT for 3 or more years tended to have stronger preventive effects than AIT for less than 3 years . CONCLUSION AIT effectively prevents asthma in patients with AR in a real-world setting . Confounding by indication can not be excluded but would lead to an underestimation of the true preventive effects of AIT BACKGROUND We wondered whether short-term coseasonal sublingual immunotherapy ( SLIT ) can reduce the development of asthma in children with hay fever in an open r and omized study . OBJECTIVE We sought to determine whether SLIT is as effective as subcutaneous immunotherapy in reducing hay fever symptoms and the development of asthma in children with hay fever . METHODS One hundred thirteen children aged 5 to 14 years ( mean age , 7.7 years ) with hay fever limited to grass pollen and no other clinical ly important allergies were r and omized in an open study involving 6 Italian pediatric allergy centers to receive specific SLIT for 3 years or st and ard symptomatic therapy . All of the subjects had hay fever symptoms , but at the time of study entry , none reported seasonal asthma with more than 3 episodes per season . Symptomatic treatment was limited to cetirizine , loratadine , nasal budesonide , and salbutamol on dem and . The hay fever and asthma symptoms were quantified clinical ly . RESULTS The actively treated children used less medication in the second and third years of therapy , and their symptom scores tended to be lower . From the second year of immunotherapy , subjective evaluation of overall allergy symptoms was favorable in the actively treated children . Development of asthma after 3 years was 3.8 times more frequent ( 95 % confidence limits , 1.5 - 10.0 ) in the control subjects . CONCLUSIONS Three years of coseasonal SLIT improves seasonal allergic rhinitis symptoms and reduces the development of seasonal asthma in children with hay fever BACKGROUND Allergen specific immunotherapy is the only specific and curative approach in the treatment of IgE-mediated allergic diseases such as bronchial asthma and allergic rhinitis . The safety and clinical efficacy of this treatment are well documented but data on the prevention of new sensitizations remain scarce . OBJECTIVE To demonstrate the efficacy of specific immunotherapy in allergic respiratory diseases in childhood and to determine whether this treatment prevents the development of new sensitizations in children sensitized to house dust mite or pollen species . METHODS Fifty-six patients received specific immunotherapy ( 43 sensitive to house dust mite and 13 sensitive to pollen ) . Fifty-one patients not receiving immunotherapy but treated with pharmacotherapy were enrolled in the control group . The patients were followed-up for at least 4 years and treatment efficacy and the development of new sensitizations were compared between the two groups . RESULTS The number of patients with symptoms was significantly decreased in both groups at the end of the treatment period . No new sensitizations were found in 35 of the 43 ( 81.39 % ) patients in the house dust mite immunotherapy group and in 10 of 13 ( 76.92 % ) patients in the pollen immunotherapy group . In contrast , 20 of 51 ( 39.21 % ) patients in the control group showed new sensitizations . The difference between the house dust mite and pollen immunotherapy groups and the control group in this parameter was statistically significant ( p = 0.033 ) . CONCLUSION Our data demonstrate that administration of specific immunotherapy in allergic patients significantly reduced symptoms and the development of new sensitivities BACKGROUND Children with allergic rhinitis are likely to develop asthma . OBJECTIVE The purpose of this investigation was to determine whether specific immunotherapy can prevent the development of asthma and reduce bronchial hyperresponsiveness in children with seasonal allergic rhinoconjunctivitis . METHODS From 6 pediatric allergy centers , 205 children aged 6 to 14 years ( mean age , 10.7 years ) with grass and /or birch pollen allergy but without any other clinical ly important allergy were r and omized either to receive specific immunotherapy for 3 years or to an open control group . All subjects had moderate to severe hay fever symptoms , but at inclusion none reported asthma with need of daily treatment . Symptomatic treatment was limited to loratadine , levocabastine , sodium cromoglycate , and nasal budesonide . Asthma was evaluated clinical ly and by peak flow . Methacholine bronchial provocation tests were carried out during the season(s ) and during the winter . RESULTS Before the start of immunotherapy , 20 % of the children had mild asthma symptoms during the pollen season(s ) . Among those without asthma , the actively treated children had significantly fewer asthma symptoms after 3 years as evaluated by clinical diagnosis ( odds ratio , 2.52 ; P < .05 ) . Methacholine bronchial provocation test results improved significant in the active group ( P < .05 ) . CONCLUSION Immunotherapy can reduce the development of asthma in children with seasonal rhinoconjunctivitis Background : Limited data exist regarding extended , long-term immunologic effects of immunotherapy in polysensitized individuals . To study possible long-term effects , skin tests and specific IgE levels were obtained from subjects who had previously received broad-spectrum aeroallergen immunotherapy years before . Methods : Eighty-two subjects ( 78 % male , mean age 23 years ) previously enrolled in a r and omized , placebo-controlled trial of immunotherapy for treatment of childhood allergic asthma were reevaluated in adulthood ( mean follow-up interval , 10.8 years ) by puncture skin tests and CAP-RAST levels for major aeroallergens . All completed at least 18 months ( median 27 months ) of maintenance active treatment or placebo injections without subsequent immunotherapy . Results : At adult follow-up , 36 % of all skin tests to treatment allergens among subjects who received immunotherapy ( n = 41 ) had significantly reduced intensity versus 26 % of skin tests among placebo recipients ( n = 41 ; p = 0.03 ) . No significant differences were noted for individual treatment allergens . No significant differences were observed in the long-term changes of serum-specific IgE antibody levels for all treatment allergens between immunotherapy treatment and placebo groups ( p = 0.43 ) . The treatment and placebo groups had a similar acquisition of new skin test sensitivities from time of r and omization in the original childhood trial to debriefing ( 15 vs. 20 % ; p = 0.28 ) and to adult follow-up ( 30 vs. 31 % ; p = 0.75 ) . Conclusions : Immunotherapy suppresses skin test sensitivity 8–16 years after discontinuation of treatment , but long-term effects on specific IgE levels in serum are not observed . Broad-spectrum immunotherapy does not appear to affect the acquisition of new inhalant sensitivities BACKGROUND Allergic rhinoconjunctivitis is a risk factor for asthma development . Treating the underlying allergy may represent an attractive method of asthma prevention . No regulatory guidance exists in this area , and , to our knowledge , no clinical investigations meeting modern regulatory st and ards have been published . OBJECTIVE The objective of this publication is to describe the rationale behind the design of and report on the recruitment for the ongoing pediatric Grazax Asthma Prevention ( GAP ) trial . METHODS The trial was design ed for assessment of the preventive effect of an SQ-st and ardized grass allergy immunotherapy tablet ( AIT ) on asthma development , both during treatment and after the end of treatment . ( The st and ardized quality [ SQ ] procedure is a st and ardization procedure comprising 3 components : total potency , major allergen content , and assessment of extract complexity . ) The trial design was discussed with several European Competent Authorities . RESULTS The GAP trial is a multinational , parallel-group , double-blind , placebo-controlled r and omized trial . Main eligibility criteria were age of 5 to 12 years , grass pollen-induced allergic rhinoconjunctivitis , no asthma , and no overlapping symptomatic allergies . The children have been r and omized 1:1 to receive the grass AIT or placebo once daily for 3 years , followed by a blinded observational period of 2 years . Asthma is assessed by the investigators according to specific diagnostic criteria , used at screening visits before r and omization to exclude children with existing asthma , and evaluated at least half-yearly during the trial . Seven months of screening result ed in 812 r and omized children at 101 centers in 11 countries . CONCLUSIONS To our knowledge , the GAP trial represents the first double-blind , placebo-controlled r and omized trial to assess the preventive effect of allergen-specific immunotherapy on asthma development . A total of 812 children were successfully recruited into the trial . EudraCT number : 2009 - 011235 - 12 Background Subcutaneous immunotherapy for respiratory allergy has shown a long‐lasting efficacy after its discontinuation , whereas this evidence is still lacking for sublingual immunotherapy , despite the fact that it is widely used Allergic rhinitis can be associated with bronchial hyperresponsiveness ( BHR ) , and carries an increased risk for the development of asthma . The aim of this study was to evaluate the ability of specific immunotherapy ( SIT ) to reduce the progression of allergic rhinitis to asthma and prevent the associated increase in BHR . Forty-four subjects monosensitized to Dermatophagoides pteronyssinus , with perennial rhinitis and BHR to methacholine , were r and omly assigned to receive SIT or placebo in a double-blind study conducted over a period of 2 yr . After 1 yr of treatment , a 2.88-fold increase in the provocative dose of methacholine producing a 20 % decrease in FEV(1 ) ( PD(20)FEV(1 ) ) was recorded in the SIT-treated group ( 95 % confidence interval [ CI ] : 3.98- to 2.09-fold ; p < 0.001 ) , with a further increase to fourfold at the end of Year 2 ( 95 % CI : 2.9- to 5.7-fold ; p < 0.001 ) . At the end of the study , the methacholine PD(20)FEV(1 ) was within the normal range in 50 % of treated subjects ( p < 0.0001 ) , and was significantly higher in this group than in the group receiving placebo ( p < 0.0001 ) . In contrast , no changes in methacholine PD(20)FEV(1 ) were found in the placebo group throughout the study . Although 9 % of subjects given placebo developed asthma , none of those treated with SIT did . This study suggests that SIT , when administered to carefully selected , monosensitized patients with perennial allergic rhinitis , reduces airway responsiveness in subjects with rhinitis , and may be an appropriate prophylactic treatment for rhinitic patients with hyperreactive airways BACKGROUND This study aims to examine the immunological parameters , focusing IL-10 productivity , in prophylactic sublingual immunotherapy ( SLIT ) in asymptomatic subjects sensitized to Japanese cedar pollen ( JCP ) . METHODS This study was conducted as part of a r and omized , double-blind , placebo-controlled , multiple center trial , and was performed for two consecutive pollen seasons in 2012 and 2013 . The present results were based only on our institution . We recruited 29 participants with specific IgE against JCP of at class 2 and higher levels without history of the pollinosis symptoms at the time of JCP scattering . The SLIT group received st and ardized JCP extract for five months over the pollen season . We observed and judged development of the symptoms in the pollen season . The percentage of IL-10 producing CD4(+ ) T ( Trl ) cells , B cells and monocytes were analyzed by flow cytometry . JCP specific IgE and total IgE were also measured . RESULTS The ratio of development of cedar pollinosis was significantly lower in the SLIT group compared to the placebo group in 2013 . In 2012 , the percentage of circulating Tr1 cells and IL-10 producing monocytes significantly increased in the SLIT group . In 2013 , the percentage of circulating Tr1 cells and IL-10 producing B cells increased significantly in the SLIT group . The percentage of circulating IL-10 producing monocytes significantly decreased in the placebo group . CONCLUSIONS Prophylactic SLIT is effective for prevention of the development of pollinosis . Induction of IL-10 producing T cells , B cells and monocytes is an important mechanism of SLIT for prevention of pollinosis in asymptomatic but sensitized subjects OBJECTIVE To evaluate the efficacy of mite allergen specific immunotherapy ( SIT ) to patients of allergic rhinitis . METHOD A total of 102 patients with mite allergy were recruited into the study . They were r and omly divided into two groups : SIT group ( n = 51 ) and ST ( symptomatic therapy ) group ( n = 51 ) . They were given SIT with st and ardized allergen vaccine for 3 years or only symptomatic therapy respectively . Observation items include : rhinitis symptom scores , drug score , skin prick test result , serum specificity IgE ( sIgE ) , peripheral eosinophil counting . The development of asthma and new allergens sensitization was also assessed . RESULT The blood eosinophil numbers , skin test index , rhinitis symptom scores and drug scores were all decreased significantly after the treatment with SIT for 3 years compared to that of ST group ( P < 0.01 ) . Although the level of serum slgE was decreased , no statistic diferences were found . No patients developed asthma in SIT group , and only 2.1 % of patients had new allergen sensitization ; 17.4 % of those in ST group developed asthma , 32.6 % had new sensitization . No severe adverse events occurred . CONCLUSION Keeping long-term SIT is effective and safe for patients with allergic rhinitis induced by mite , which can also prevent new allergen sensitization and development for asthma Allergic rhinitis is often associated with bronchial hyperresponsiveness ( BHR ) and airway inflammation , and it seems to be an important risk factor for the development of asthma . Specific immunotherapy ( SIT ) reduces symptoms and medication requirements in subjects with allergic rhinitis , but the mechanisms by which SIT promotes these beneficial effects are less clear . We have investigated the effects of Parietaria-SIT on rhinitis symptoms , BHR to inhaled methacholine , eosinophilic inflammation and cytokine production ( interferon gamma and interleukin-4 ) in the sputum . The effect on asthma progression was also examined . Thirty non-asthmatic subjects with seasonal rhinitis and monosensitized to Parietaria judaica participated in a r and omized , double-blind , placebo-controlled , parallel group study . Participants were r and omly assigned to receive injections of a Parietaria pollen vaccine ( n = 15 ) or matched placebo injections ( n = 15 ) in a rapid updosing cluster regimen for 7 weeks , followed by monthly injections for 34 months . Throughout the 3-year study we collected data on symptoms and medication score , airway responsiveness to methacholine , eosinophilia and soluble cytokines in sputum , followed by a complete evaluation of the clinical course of atopy . Hay fever symptom and medication scores were well controlled by SIT . By the end of the study , in the placebo group , symptom and medication scores significantly increased by a median ( interquartile range ) of 121 % ( 15 - 280 % ) and 263 % ( 0 - 4400 % ) respectively ( p < 0.01 ) , whereas no significant difference was observed in the SIT group . We found no significant changes in the sputum parameters and methacholine PC15 values in both groups throughout the study . By the end of the investigation , a total of 9 out of 29 participants developed asthma symptoms ; of these , seven ( 47 % ) belonged to the placebo group , whereas only 2 ( 14 % ) to the SIT-treated group ( p = 0.056 ) . In conclusion , Parietaria-SIT is effective in controlling hay fever symptoms and rescue medications , but no changes in the BHR to methacholine or sputum eosinophilia were observed . Moreover , Parietaria-SIT appears to prevent the natural progression of allergic rhinitis to asthma , suggesting that SIT should be considered earlier in the management of this condition Background : Some aspects of sublingual immunotherapy ( SLIT ) still need to be addressed : magnitude of the clinical efficacy , effect on the bronchial hyperreactivity adherence to treatment , preventive effect . We attempted to clarify these points in a r and omized open , controlled , two parallel group study in a real‐life setting BACKGROUND Prevention of new IgE sensitizations has been described during allergen-specific immunotherapy . However , prospect i ve data using a preventive approach in very young children who would benefit most are missing . We initiated a prospect i ve pilot study investigating the safety , immunomodulatory , and sensitization-preventive effect of sublingual immunotherapy ( SLIT ) in mono/oligoclonally sensitized , clinical ly asymptomatic children 2 - 5 yr of age . METHODS In this double-blinded , r and omized , placebo-controlled pilot study , 31 mono-/oligosensitized children to house-dust mite or grass pollen were included . SLIT with the respective source ( n = 15 ) or placebo ( n = 16 ) was applied . After dose-up-phase therapy was continued for 2 yr . Parents recorded clinical events , vaccinations , and drug intake in a diary . Skin prick testing and specific IgE and IgG measurements were recorded at baseline , 12 and 24 months . At the same time , allergen-specific proliferation and IL10- and TGFβ-dependent Treg function were measured . RESULTS Preventive application of SLIT in young children was safe ( no relevant side effects in 21,170 single applications ) . After 12 and 24 months of treatment , the rate of allergen-specific sensitization ( specific IgE and SPT reactivity ) was comparable in the treatment and the placebo group . However , verum-treated patients displayed a significant up-regulation of allergen-specific IgG ( p < 0.05 ) . Furthermore , IL10-dependent inhibition ( p < 0.05 ) was observed in vitro in the treatment group but not in the placebo group . CONCLUSION Preventive SLIT is safe in children 2 - 5 yr of age and induces regulatory mechanisms involving allergen-specific IgG and IL10 . Based on this pilot study , large-scale trials will need to investigate the modulation of sensitization and clinical ly relevant allergy BACKGROUND Children born to atopic parents are at increased risk of sensitization to environmental allergens . OBJECTIVE We sought to demonstrate proof of concept for oral immunotherapy to high-dose house dust mite ( HDM ) allergen in infancy in the prevention of allergen sensitization and allergic diseases . METHODS This was a prospect i ve , r and omized , double-blind , placebo-controlled , proof-of-concept study involving 111 infants less than 1 year of age at high risk of atopy ( ≥ 2 first-degree relatives with allergic disease ) but with negative skin prick test responses to common allergens at r and omization . HDM extract ( active ) and appropriate placebo solution were administered orally twice daily for 12 months , and children were assessed every 3 months . Co primary outcomes were cumulative sensitization to HDM and sensitization to any common allergen during treatment , whereas development of eczema , wheeze , and food allergy were secondary outcomes . All adverse events were recorded . RESULTS There was a significant ( P = .03 ) reduction in sensitization to any common allergen ( 16.0 % ; 95 % CI , 1.7 % to 30.4 % ) in the active ( 5 [ 9.4 % ] ) compared with placebo ( 13 [ 25.5 % ] ) treatment groups . There was no treatment effect on the co primary outcome of HDM sensitization and the secondary outcomes of eczema , wheeze , and food allergy . The intervention was well tolerated , with no differences between active and placebo treatments in numbers or nature of adverse events . CONCLUSION Prophylactic HDM oral immunotherapy is well tolerated in children at high heredity risk . The results met the trial 's prespecified criteria for proof of concept in reducing sensitization to any allergen ; however , no significant preventive effect was observed on HDM sensitization or allergy-related symptoms |
641 | 31,328,353 | Effects of other rTMS protocol s on craving were not significant .
However , when examining substance consumption , excitatory rTMS of the left DLPFC and excitatory deep TMS ( dTMS ) of the bilateral DLPFC and insula revealed significant consumption-reducing effects , compared with sham stimulation .
Excitatory repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex appears to have an acute effect on reducing craving and substance consumption in patients with substance dependence .
The anti-craving effect may be associated with stimulation dose | BACKGROUND AND AIMS Repetitive transcranial magnetic stimulation ( rTMS ) is increasingly used as an intervention for treating substance dependence .
We aim ed to assess evidence of the anti-craving and consumption-reducing effects of rTMS in patients with alcohol , nicotine , and illicit drug dependence . | UNLABELLED Recent animal studies demonstrate that compulsive cocaine seeking strongly reduces prelimbic frontal cortex activity , while optogenetic stimulation of this brain area significantly inhibits compulsive cocaine seeking , providing a strong rationale for applying brain stimulation to reduce cocaine consumption . Thus , we employed repetitive transcranial magnetic stimulation ( rTMS ) , to test if dorsolateral prefrontal cortex ( DLPFC ) stimulation might prevent cocaine use in humans . Thirty-two cocaine-addicted patients were r and omly assigned to either the experimental group ( rTMS ) on the left DLPFC , or to a control group ( pharmacological agents ) during a 29-day study ( Stage 1 ) . This was followed by a 63-day follow-up ( Stage 2 ) , during which all participants were offered rTMS treatment . Amongst the patients who completed Stage 1 , 16 were in the rTMS group ( 100 % ) and 13 in the control group ( 81 % ) . No significant adverse events were noted . During Stage 1 , there were a significantly higher number of cocaine-free urine drug tests in the rTMS group compared to control ( p=0.004 ) . Craving for cocaine was also significantly lower in the rTMS group compared to the controls ( p=0.038 ) . Out of 13 patients who completed Stage 1 in the control group , 10 patients received rTMS treatment during Stage 2 and showed significant improvement with favorable outcomes becoming comparable to those of the rTMS group . The present preliminary findings support the safety of rTMS in cocaine-addicted patients , and suggest its potential therapeutic role for rTMS-driven PFC stimulation in reducing cocaine use , providing a strong rationale for developing larger placebo-controlled studies . Trial name : Repetitive transcranial magnetic stimulation ( rTMS ) in cocaine abusers , URL : 〈http://www.is rct n.com/IS RCT N15823943?q=&filters=&sort=&offset=8&total Results = 13530&page=1&pageSize=10 & search Type = basic- search 〉 , REGISTRATION NUMBER IS RCT N15823943 BACKGROUND Tobacco smoking is the leading cause of preventable death in developed countries . Our previous studies in animal models and humans suggest that repeated activation of cue-induced craving networks followed by electromagnetic stimulation of the dorsal prefrontal cortex ( PFC ) can cause lasting reductions in drug craving and consumption . We hypothesized that disruption of these circuitries by deep transcranial magnetic stimulation ( TMS ) of the PFC and insula bilaterally can induce smoking cessation . METHODS Adults ( N = 115 ) who smoke at least 20 cigarettes/day and failed previous treatments were recruited from the general population . Participants were r and omized to receive 13 daily sessions of high-frequency , low-frequency or sham stimulation following , or without , presentation of smoking cues . Deep TMS was administered using an H-coil version targeting the lateral PFC and insula bilaterally . Cigarette consumption was evaluated during the treatment by measuring cotinine levels in urine sample s and recording participants ' self-reports as a primary outcome variable . Dependence and craving were assessed using st and ardized question naires . RESULTS High ( but not low ) frequency deep TMS treatment significantly reduced cigarette consumption and nicotine dependence . The combination of this treatment with exposure to smoking cues enhanced reduction in cigarette consumption leading to an abstinence rate of 44 % at the end of the treatment and an estimated 33 % 6 months following the treatment . CONCLUSIONS This study further implicates the lateral PFC and insula in nicotine addiction and suggests the use of deep high-frequency TMS of these regions following presentation of smoking cues as a promising treatment strategy AIMS As alcohol dependency is characterized by severe executive function deficits , we examined the influence of high-frequency ( HF ) repetitive transcranial magnetic stimulation ( rTMS ) applied to the right dorsolateral prefrontal cortex ( DLPFC ) on executive functioning in recently detoxified alcohol-dependent patients . METHODS In this r and omized , single blind , sham (placebo)-controlled , crossover study , we included 50 detoxified alcohol-dependent patients . We examined the effect of a single right DLPFC HF-rTMS session on commission errors , mean reaction times ( RTs ) and intra-individual reaction time variability ( IIRTV ) during a Go-NoGo task ( 50 % Go/50 % NoGo condition ) in 29 alcohol-dependent patients . Patients completed this cognitive task immediately before and immediately after the stimulation session . In order to avoid carry-over effects between stimulation sessions , a 1-week inter-session interval was respected . Because rTMS treatment has been shown to affect subjective craving , all patients were also assessed with the Obsessive Compulsive Drinking Scale ( OCDS ) . RESULTS After both stimulation conditions , we observed a significant decrease of commission errors , without differences between active and sham HF-rTMS stimulation . No significant difference was observed between active and sham stimulation on mean RT . However , only active stimulation result ed in a significant decrease in IIRTV . No effects of stimulation were found for the craving measurements . CONCLUSION Our findings suggest that in recently detoxified alcohol-dependent patients , one right-sided HF-rTMS session stabilizes cognitive performance during executive control tasks , implying that active stimulation reduces patients ' proneness to attentional lapses Drug-related cues induce craving , which may perpetuate drug use or trigger relapse in addicted individuals . Craving is also under the influence of other factors in daily life , such as drug availability and self-control . Neuroimaging studies using drug cue paradigms have shown frontal lobe involvement in this context ual influence on cue reactivity , but have not clarified how and which frontal area accounts for this phenomenon . We explored frontal lobe contributions to cue-induced drug craving under different intertemporal drug availability conditions by combining transcranial magnetic stimulation and functional magnetic resonance imaging in smokers . We hypothesized that the dorsolateral prefrontal cortex ( DLPFC ) regulates craving during changes in intertemporal availability . Subjective craving was greater when cigarettes were immediately available , and this effect was eliminated by transiently inactivating the DLPFC with transcranial magnetic stimulation . Functional magnetic resonance imaging demonstrated that the signal most proportional to subjective craving was located in the medial orbitofrontal cortex across all context s , whereas the DLPFC most strongly encoded intertemporal availability information . The craving-related signal in the medial orbitofrontal cortex was attenuated by inactivation of the DLPFC , particularly when cigarettes were immediately available . Inactivation of the DLPFC also reduced craving-related signals in the anterior cingulate and ventral striatum , areas implicated in transforming value signals into action . These findings indicate that DLPFC builds up value signals based on knowledge of drug availability , and support a model wherein aberrant circuitry linking dorsolateral prefrontal and orbitofrontal cortices may underlie addiction BACKGROUND Addiction is associated with dorso-lateral prefrontal cortex ( DLPFC ) dysfunction and altered brain-oscillations . High frequency repetitive transcranial magnetic stimulation ( HFrTMS ) over DLPFC reportedly reduces drug craving . Its effects on neuropsychological , behavioural and neurophysiological are unclear . METHODS We assessed psychological , behavioural and neurophysiological effects of 4 sessions of 10-min adjunctive HFrTMS over the left DLPFC during two weeks during a residential programme for alcohol detoxification . Participants were r and omized to active HFrTMS ( 10 Hz , 100 % motor threshold ) or sham . Immediately before the first and after the last session , 32-channels EEG was recorded and alcohol craving Visual Analogue Scale , Symptom Check List-90-R , Numeric Stroop task and Go/No-go task administered . Tests were repeated at 1-month follow-up . RESULTS 17 subjects ( mean age 44.7 years , 4 F ) were assessed . Active rTMS subjects performed better at Stroop test at end of treatment ( p=0.036 ) and follow up ( p=0.004 ) and at Go-NoGo at end of treatment ( p=0.05 ) and follow up ( p=0.015 ) . Depressive symptoms decreased at end of active treatment ( p=0.036 ) . Active-TMS showed an overall decrease of fast EEG frequencies after treatment compared to sham ( p=0.026 ) . No significant modifications over time or group emerged for craving and number of drinks at follow up . CONCLUSION 4 HFrTMS sessions over two weeks on the left DLPFC can improve inhibitory control task and selective attention and reduce depressive symptoms . An overall reduction of faster EEG frequencies was observed . Nonetheless , this schedule is ineffective in reducing craving and alcohol intake BACKGROUND Prior research in substance dependence has suggested potential anti-craving effects of repetitive transcranial magnetic stimulation ( rTMS ) when applied to the dorsolateral prefrontal cortex ( DLPFC ) . However , no single sham-controlled session studies applied to the right DLPFC have been carried-out in recently detoxified alcohol-dependent patients . Furthermore , no studies examined the effect of a single HF-rTMS session on craving in these patients ' natural habitat . METHODS To further investigate the effect of high-frequency (HF)-rTMS of the right DLPFC on alcohol craving , we performed a prospect i ve , single-blind , sham-controlled study involving 36 hospitalized patients with alcohol dependence syndrome . After successful detoxification , patients were allocated receiving one active or one sham HF-rTMS session . The obsessive-compulsive drinking scale ( OCDS ) was administered to evaluate the extent of craving just before and after the HF-rTMS session ( on Friday ) , on Saturday and Sunday during the weekend at home , and on Monday when the patient returned to the hospital . RESULTS One single blind sham-controlled HF-rTMS session applied to the right DLPFC did not result in changes in craving ( neither immediately after the stimulation session , nor in patients ' natural environment during the weekend ) . CONCLUSIONS One HF-rTMS stimulation session applied to the right DLPFC had no significant effects on alcohol craving in alcohol dependent patients . One such session could have been too short to alter alcohol craving in a sample of alcohol dependent patients Dopamine is implicated in movement , learning , and motivation , and in illnesses such as Parkinson 's disease , schizophrenia , and drug addiction . Little is known about the control of dopamine release in humans , but research in experimental animals suggests that the prefrontal cortex plays an important role in regulating the release of dopamine in subcortical structures . Here we used [(11)C]raclopride and positron emission tomography to measure changes in extracellular dopamine concentration in vivo after repetitive transcranial magnetic stimulation ( rTMS ) of the dorsolateral prefrontal cortex in healthy human subjects . Repetitive TMS of the left dorsolateral prefrontal cortex caused a reduction in [(11)C]raclopride binding in the left dorsal cau date nucleus compared with rTMS of the left occipital cortex . There were no changes in binding in the putamen , nucleus accumbens , or right cau date . This shows that rTMS of the prefrontal cortex induces the release of endogenous dopamine in the ipsilateral cau date nucleus . This finding has implication s for the therapeutic and research use of rTMS in neurological and psychiatric disorders BACKGROUND Positron emission tomography ( PET ) imaging studies have shown that addiction to a number of substances of abuse is associated with a decrease in dopamine D(2/3 ) receptor binding and decreased presynaptic dopamine release in the striatum . Some studies have also shown that these reductions are associated with the severity of addiction . For example , in cocaine dependence , low dopamine release is associated with the choice to self-administer cocaine . The goal of the present study was to investigate these parameters of striatal dopamine transmission in heroin dependence and their association with drug seeking behavior . METHODS Heroin-dependent and healthy control subjects were scanned with [(11)C]raclopride before and after stimulant administration ( methylpheni date ) to measure striatal D(2/3 ) receptor binding and presynaptic dopamine release . After the PET scans , the heroin-dependent subjects performed heroin self-administration sessions . RESULTS Both striatal D(2/3 ) receptor binding and dopamine release were reduced in the heroin-dependent subjects compared with healthy control subjects . However , neither PET measure of dopamine transmission predicted the choice to self-administer heroin . CONCLUSIONS These findings show that heroin addiction , like addiction to other drugs of abuse , is associated with low D(2/3 ) receptor binding and low presynaptic dopamine . However , neither of these outcome measures was associated with the choice to self-administer heroin We used PET (15)O and a modified version of the Stroop task to determine if 25-day abstinent heavy marijuana ( MJ ) users have persistent deficits in executive cognitive functioning ( ECF ) and brain activity . Performance on a modified version of the Stroop task and brain activity was compared between 25-day abstinent , heavy marijuana users ( n = 11 ) , and a matched comparison group ( n = 11 ) . The 25-day abstinent marijuana users showed no deficits in performance on the modified version of the Stroop task when compared to the comparison group . Despite the lack of performance differences , the marijuana users showed hypoactivity in the left perigenual anterior cingulate cortex ( ACC ) and the left lateral prefrontal cortex ( LPFC ) and hyperactivity in the hippocampus bilaterally , when compared to the comparison group . These results suggest that marijuana users display persistent metabolic alterations in brain regions responsible for ECF . It may be that marijuana users recruit an alternative neural network as a compensatory mechanism during performance on a modified version of the Stroop task . These differences in brain activity may be a common denominator in the evolution of maladaptive behaviors such as substance abuse and other neuropsychiatric disorders Background Chronic cocaine consumption is associated with a decrease in mesolimbic dopamine transmission that maintains drug intake . transcranial magnetic stimulation ( TMS ) is gaining reliability , a useful therapeutic tool in drug addiction , since it can modulate cortico-limbic activity result ing in reduction of drug craving . Aims In the present study , we investigated the therapeutic effect of bilateral TMS of prefrontal cortex ( PFC ) in reducing cocaine intake , in a sample of treatment-seeking patients with current cocaine use disorder ( DSM-V ) . Methods Ten cocaine addicts ( DSM-V ) were r and omly assigned to the active or sham stimulation protocol in a double-blind experimental design . Twelve repetitive TMS ( rTMS ) sessions were administered three times a week for 4 weeks at 100 % of motor threshold , over bilateral PFC . Cocaine intake ( ng/mg ) was assessed by hair analysis at baseline ( before treatment , T0 ) , after 1 month ( end of treatment , T1 ) , 3 ( T2 ) , and 6 ( T3 ) months later . All subjects received psychological support weekly . Results The two-way ANOVA for repeated measures did not show a significant effect of the interaction between time and treatment ( F4,32 = 0.35 ; p = 0.87 ) . Despite that result indicated no difference in the effect of the two conditions ( active vs. sham ) along time , a decreasing trend in cocaine consumption in active TMS group ( F3,23 = 3.42 ; p = 0.04 ) vs. sham ( F3,15 = 1.88 ; p = 0.20 ) was observed when we performed exploratory analysis with time as factor . Indeed , Post hoc comparisons showed a significant reduction in the amount of cocaine detected from the onset to 3 months later ( T0–T2 ; p = 0.02 ) and to the end of treatment ( T0–T3 ; p = 0.01 ) in addicts from the active group . Conclusion Bilateral rTMS of PFC at 10 Hz did not show a significant effect on cocaine intake compared to sham . However , a long-term reduction on cocaine intake in active TMS-treated patients was observed when we considered the time as factor . Further studies are required to confirm these encouraging but preliminary findings , in order to consoli date rTMS as a valid tool to treat cocaine addiction BACKGROUND Repetitive transcranial magnetic stimulation ( rTMS ) can temporarily interrupt or facilitate activity in a focal brain region . Several lines of evidence suggest that rTMS of the dorsolateral prefrontal cortex ( DLPFC ) can affect processes involved in drug addiction . We hypothesized that a single session of low-frequency rTMS of the left DLPFC would modulate cue-induced craving for methamphetamine ( MA ) when compared to a sham rTMS session . METHODS In this single-blind , sham-controlled crossover study , 10 non-treatment seeking MA-dependent users and 8 healthy controls were r and omized to receive 15 min of sham and real ( 1 Hz ) DLPFC rTMS in two experimental sessions separated by 1h . During each rTMS session , participants were exposed to blocks of neutral cues and MA-associated cues . Participants rated their craving after each cue block . RESULTS In MA users , real rTMS over the left DLPFC increased self-reported craving as compared to sham stimulation ( 17.86 ± 1.46 vs. 24.85 ± 1.57 , p=0.001 ) . rTMS had no effect on craving in healthy controls . One Hertz rTMS of the left DLPFC was safe and tolerable for all participants . CONCLUSIONS Low frequency rTMS of the left DLPFC transiently increased cue-induced craving in MA participants . These preliminary results suggest that 1 Hz rTMS of the left DLPFC may increase craving by inhibiting the prefrontal cortex or indirectly activating subcortical regions involved in craving AIMS To evaluate the effect of repeated high-frequency transcranial magnetic stimulation ( rTMS ) of the left dorsolateral prefrontal cortex ( DLPFC ) , combined with either smoking or neutral cues , on cigarette consumption , dependence and craving . DESIGN Participants were divided r and omly to real and sham stimulation groups . Each group was subdivided r and omly into two subgroups presented with either smoking-related or neutral pictures just before the daily TMS intervention . Ten daily rTMS sessions were applied every week-day and then a maintenance phase was conducted in which rTMS sessions were less frequent . SETTING Single-site , out-patient , r and omized , double-blind , sham-controlled . PARTICIPANTS Forty-eight chronic smokers who smoked at least 20 cigarettes per day and were motivated to quit smoking . Healthy males and females were recruited from the general population using advertisements in newspapers and on internet websites . INTERVENTION Ten daily rTMS sessions were administered using a st and ard figure-8 coil over the DLPFC . Stimulation included 20 trains/day at 100 % of motor threshold . Each train consisted of 50 pulses at 10 Hz with an inter-train interval of 15 seconds . MEASUREMENTS Cigarette consumption was evaluated objective ly by measuring cotinine levels in urine sample s and subjectively by participants ' self-reports . Dependence and craving were evaluated by st and ard question naires . FINDINGS Ten daily rTMS sessions over the DLPFC reduced cigarette consumption and nicotine dependence . Furthermore , treatment blocked the craving induced by daily presentation of smoking-related pictures . However , these effects tended to dissipate over time . CONCLUSIONS Multiple high-frequency rTMS of the DLPFC can attenuate nicotine craving BACKGROUND Repetitive transcranial magnetic stimulation ( rTMS ) can noninvasively stimulate the brain and transiently amplify or block behaviors mediated through a region . We hypothesized that a single high-frequency rTMS session over the left dorsolateral prefrontal cortex ( DLPFC ) would reduce cue craving for cigarettes compared with a sham TMS session . METHODS Sixteen non-treatment-seeking , nicotine-dependent participants were r and omized to receive either real high-frequency rTMS ( 10 Hz , 100 % resting motor threshold , 5-sec on , 10-sec off for 15 min ; 3000 pulses ) or active sham ( eSham ) TMS over the DLPFC in two visits with 1 week between visits . The participants received cue exposure before and after rTMS and rated their craving after each block of cue presentation . RESULTS Stimulation of the left DLFPC with real , but not sham , rTMS reduced craving significantly from baseline ( 64.1±5.9 vs. 45.7±6.4 , t = 2.69 , p = .018 ) . When compared with neutral cue craving , the effect of real TMS on cue craving was significantly greater than the effect of sham TMS ( 12.5±10.4 vs. -9.1±10.4 ; t = 2.07 , p = .049 ) . More decreases in subjective craving induced by TMS correlated positively with higher Fagerström Test for Nicotine Dependence score ( r = .58 , p = .031 ) and more cigarettes smoked per day ( r = .57 , p = .035 ) . CONCLUSIONS One session of high-frequency rTMS ( 10 Hz ) of the left DLPFC significantly reduced subjective craving induced by smoking cues in nicotine-dependent participants . Additional studies are needed to explore rTMS as an aid to smoking cessation OBJECTIVE To study the anticraving efficacy of high-frequency repetitive transcranial magnetic stimulation ( rTMS ) of the right dorsolateral pre-frontal cortex ( DLPFC ) in patients with alcohol dependence . METHODS We performed a prospect i ve , single-blind , sham-controlled study involving 45 patients with alcohol dependence syndrome ( according to ICD-10 DCR ) , with Clinical Institute of Withdrawal Assessment in Alcohol Withdrawal ( CIWA-Ar ) scores < or=10 . Patients were allocated to active and sham rTMS in a 2 : 1 ratio , such that 30 patients received active and 15 patients sham rTMS to the right DLPFC ( 10 Hz frequency , 4.9 seconds per train , inter-train interval of 30 seconds , 20 trains per session , total 10 sessions ) . The Alcohol Craving Question naire ( ACQ-NOW ) was administered to measure the severity of alcohol craving at baseline , after the last rTMS session and after 1 month of the last rTMS session . RESULTS Two-way repeated- measures analysis of variance ( ANOVA ) showed significant reduction in the post-rTMS ACQ-NOW total score and factor scores in the group allocated active rTMS compared to the sham stimulation . The effect size for treatment with time interaction was moderate ( eta(2 ) = 0.401 ) . CONCLUSIONS Right dorsolateral pre-frontal high-frequency rTMS was found to have significant anticraving effects in alcohol dependence . The results highlight the potential of rTMS which , combined with other anticraving drugs , can act as an effective strategy in reducing craving and subsequent relapse in alcohol dependence BACKGROUND Previous functional magnetic resonance imaging studies have shown strong correlations between cue-elicited craving for cigarettes and activation of the superior frontal gyrus ( SFG ) . Repetitive transcranial magnetic stimulation ( rTMS ) offers a noninvasive means to reversibly affect brain cortical activity , which can be applied to testing hypotheses about the causal role of SFG in modulating craving . METHODS Fifteen volunteer smokers were recruited to investigate the effects of rTMS on subjective responses to smoking versus neutral cues and to controlled presentations of cigarette smoke . On different days , participants were exposed to three conditions : 1 ) high-frequency ( 10 Hz ) rTMS directed at the SFG ; 2 ) low-frequency ( 1 Hz ) rTMS directed at the SFG ; and 3 ) low-frequency ( 1 Hz ) rTMS directed at the motor cortex ( control condition ) . RESULTS Craving ratings in response to smoking versus neutral cues were differentially affected by the 10-Hz versus 1-Hz SFG condition . Craving after smoking cue presentations was elevated in the 10-Hz SFG condition , whereas craving after neutral cue presentations was reduced . Upon smoking in the 10-Hz SFG condition , ratings of immediate craving reduction as well as the intensity of interoceptive airway sensations were also attenuated . CONCLUSIONS These results support the view that the SFG plays a role in modulating craving reactivity ; moreover , the results suggest that the SFG plays a role in both excitatory and inhibitory influences on craving , consistent with prior research demonstrating the role of the prefrontal cortex in the elicitation as well as inhibition of drug-seeking behaviors Despite the dictionary definition of " craving " ( a strong desire ) , two studies indicate that a substantial percentage of persons with alcohol and drug problems use the word " craving " to mean any desire or urge , even a weak one , to use substances . Research ers and clinicians are advised to beware of this ambiguity of " craving " and to consider the conceptual status of " craving " in their work BACKGROUND Further evidence suggests that repetitive Transcranial Magnetic Stimulation ( rTMS ) is an effective method to reduce tobacco craving among smokers . HYPOTHESIS As relapse is common within a few days after smoking cessation , we hypothesized that combining the anti-craving effects of rTMS with Nicotine replacement therapy ( NRT ) to attenuate withdrawal symptoms could increase abstinence rates in smokers with severe nicotine dependence who quit smoking . METHODS Thirty-seven smokers who failed to quit with the usual treatments were r and omly assigned to two treatment groups to receive either active ( n = 18 ) or sham ( n = 19 ) 1-Hz rTMS of the right dorsolateral prefrontal cortex . The day after quitting smoking , each patient combined NRT ( 21-mg patch ) with active or sham rTMS ( 10 sessions ) for 2 weeks . Cessation support was then continued with NRT alone using lower-dose patches . Abstinence rates and self-report craving scales were used to assess the therapeutic results during the combined treatment and for up to 12 weeks after quitting . RESULTS At the end of the combined treatment , there were significantly more abstinent participants in the active rTMS group ( n = 16 ) than in the sham rTMS group ( n = 9 ) ( P = 0.027 ) . The craving scales analysis revealed that active rTMS ( P = 0.011 ) but not sham rTMS ( P = 0.116 ) led to a significant decrease in the compulsive factor . However , no lasting rTMS effect was found . CONCLUSIONS 1-Hz rTMS combined with NRT improved the success rate of abstinence in smokers during tobacco cessation . The stimulation-induced reduction in compulsivity may explain this result Smoking is among the leading causes of mortality worldwide . Discontinuing smoking can increase life expectancy to the presmoking level . Unaided attempts are often ineffective , strengthening the necessity of cognitive-behavioral therapy ( CBT ) , nicotine replacement or pharmacotherapy . Still , relapse rates are high . Recently , a modulation of nicotine craving , which predicts relapse , through transcranial magnetic stimulation to the prefrontal cortex was shown . In a pilot study , we investigated whether 4 sessions of intermittent theta burst stimulation ( iTBS ) as add-on treatment to CBT reduces nicotine craving and improves long-term abstinence ( at 3 , 6 and 12 months ) . Smokers were r and omly assigned to a treatment ( n = 38 ) or a sham group ( n = 36 ) . Although we did not find reduced craving , we could show higher abstinence rates in the treatment group at 3 months . At 6 and 12 months abstinence rates did not differ significantly . Results at 12 months , however , have to be interpreted cautiously due to significant differences in the dropout rates between the two groups at this time point . We provide first evidence for a beneficial effect of additional iTBS on intermediate nicotine abstinence ; however , the low number of iTBS sessions might have prevented longer effects . More lasting effects might be achieved by iTBS maintenance sessions in analogy to the treatment of depression 70 - 80 % of regular smokers fulfill the ICD-10- criteria of dependence . In Germany , approximately 120 000 deaths per year are caused by tobacco-associated diseases . In contrast , therapeutic interventions , such as nicotine substitution or bupropione , yield poor abstinence rates of 30 % after 12 months , at best . In animal experiments , repetitive transcranial magnetic stimulation ( rTMS ) exhibited modulatory effects on dopaminergic neurotransmission in regions of the so-called reward system . This pilot study should evaluate , if rTMS could modulate subjective craving for tobacco , which quite often leads to relapse to smoking . Therefore , 11 tobacco-dependent cigarette smokers were r and omly assigned to a course of verum- and placebo-rTMS on consecutive days . Craving , as measured by a visual analogue scale , is significantly decreased after Verumstimulation compared to placebostimulation intra-individually . This encourages further studies to clarify , if rTMS might be helpful in achieving higher tobacco abstinence rates in smokers willing to quits BACKGROUND Repetitive transcranial magnetic stimulation ( rTMS ) is a brain stimulation and modulation electrophysiological technique , it can change cortical excitability of target brain region , modulate neuron plasticity and brain connections . Previous research es indicated that rTMS could reduce cue-induced craving in drug addiction . OBJECTIVE In this study , we employed real and sham rTMS of the left dorsolateral prefrontal cortex ( DLPFC ) to test whether it could reduce cue-induced craving for methamphetamine ( MA ) and influence cognitive function in a r and omised clinical trial . METHODS Thirty MA-addicted patients were r and omized to receive 5 sessions of 8min sham or 10Hz rTMS to the left DLPFC . Subjects rated their craving at baseline , after exposed to MA-associated cues and after rTMS sessions . RESULTS Real rTMS over the left DLPFC reduced craving significantly after 5 sessions of rTMS as compared to sham stimulation . Furthermore , real rTMS improved verbal learning and memory and social cognition in MA-addicted patients . CONCLUSIONS The present study suggests that 10Hz rTMS of the left DLPFC may reduce craving and have no negative effects on cognitive function in MA-addicted patients , supporting the safety of rTMS in treating MA addiction TargetingWithdrawal Symptoms inMenAddicted toMethamphetamineWith TranscranialMagnetic Stimulation : A R and omized Clinical Trial Drugwithdrawal isassociatedwithaversiveexperiences , which promotes relapse . Different neurotransmitters , neuropeptides , signal transduction pathways , and brain regions ( especially the nucleus accumbens ) have been implicated in the occurrence of withdrawal syndrome during abstinence from addictive drugs . Withdrawal frommethamphetamine results in fatigue , irritability , disturbed sleep , exhaustion , and symptomsofdepression and anxiety , whichmight last formonths . Currently , limitedpharmaceutical tools are available for detoxification from methamphetamine ; vitamins , antidepressants , and antipsychotics have been used to ameliorate withdrawal symptoms in clinical practice s. In an animal study , optogenetic stimulation of the thalamic-accumbensdopamineD2mediumspinyneuronpathway alleviated somatic signs induced by opiate withdrawal . However , it is unknown ifnoninvasivebrain stimulationcould facilitate detoxification during the withdrawal period in humans . In this study , we used repetitive transcranial magnetic stimulation ( rTMS ) targeting the left dorsal-lateral prefrontal cortex ( DLPFC ) to modulate symptoms of withdrawal from methamphetamine The hypothalamic pituitary adrenal axis and dopamine have a key role in transition from alcohol social use to addiction . The medial prefrontal cortex was shown to modulate dopaminergic activity and cortisol releasing factor ( CRF ) release in hypothalamic and extra-hypothalamic systems . The recent advancements in non-invasive neurostimulation technologies has enabled stimulation of deeper brain regions using H-coil transcranial magnetic stimulation ( TMS ) in humans . This r and omized double-blind placebo-controlled pilot study aims to evaluate H-coil efficacy in stimulating the medial prefrontal cortex . Cortisolemia and prolactinemia were evaluated as effectiveness markers . Alcohol intake and craving were considered as secondary outcomes . Eighteen alcoholics were recruited and r and omized into 2 homogeneous groups : 9 in the real stimulation group and 9 in the sham stimulation group . Repetitive TMS ( rTMS ) was administered through a magnetic stimulator over 10 sessions at 20 Hz , directed to the medial prefrontal cortex . rTMS significantly reduced blood cortisol levels and decreased prolactinemia , thus suggesting dopamine increase . Craving visual analogic scale ( VAS ) in treated patients decreased , as well as mean number of alcoholic drinks/day and drinks on days of maximum alcohol intake ( DMAI ) . In the sham group there was no significant effect observed on cortisolemia , prolactinemia , mean number of alcoholic drinks/day , or drinks/DMAI . Thus , deep rTMS could be considered a potential new treatment for alcoholism BACKGROUND Previous studies reported that repetitive transcranial magnetic stimulation ( rTMS ) can reduce cue-elicited craving and decrease cigarette consumption in smokers . The mechanism of this effect however , remains unclear . We used resting-state functional magnetic resonance imaging ( rsfMRI ) to test the effect of rTMS in non-treatment seeking smokers . METHODS We used a single blinded , sham-controlled , r and omized counterbalanced crossover design where participants underwent two visits separated by at least 1 week . Participants received active rTMS over the left dorsolateral prefrontal cortex ( DLPFC ) during one of their visits , and sham rTMS during their other visit . They had two rsFMRI scans before and after each rTMS session . We used the same rTMS stimulation parameters as in a previous study ( 10Hz , 5s-on , 10s-off , 100 % resting motor threshold , 3000 pulses ) . RESULTS Ten non-treatment-seeking , nicotine-dependent , cigarette smokers ( 6 women , an average age of 39.72 and an average cigarette per day of 17.30 ) finished the study . rsFMRI results demonstrate that as compared to a single session of sham rTMS , a single session of active rTMS inhibits brain activity in the right insula and thalamus in fractional amplitude of low frequency fluctuation ( fALFF ) . For intrinsic brain connectivity comparisons , active TMS result ed in significantly decreased connectivity from the site of rTMS to the left orbitomedial prefrontal cortex . CONCLUSIONS This data suggests that one session of rTMS can reduce activity in the right insula and right thalamus as measured by fALFF . The data also demonstrates that rTMS can reduce rsFC between the left DLPFC and the medial orbitofrontal cortex |
642 | 31,660,966 | ConclusionS ervices sited in community setting s are feasible and can deliver increased uptake of treatment .
Such clinics are able to demonstrate similar SVR rates to published studies and real-world clinics in secondary care . | Background Direct Acting Antiviral ( DAAs ) drugs have a much lower burden of treatment and monitoring requirements than regimens containing interferon and ribavirin , and a much higher efficacy in treating hepatitis C ( HCV ) .
These characteristics mean that initiating treatment and obtaining a virological cure ( Sustained Viral response , SVR ) on completion of treatment , in non-specialist environments should be feasible .
We investigated the English- language literature evaluating community and primary care-based pathways using DAAs to treat HCV infection . | Background Direct-acting antiviral ( DAA ) therapy for hepatitis C virus ( HCV ) infection has result ed in high rates of disease cure ; however , not enough specialists currently are available to provide care . Objective To determine the efficacy of HCV treatment independently provided by nurse practitioners ( NPs ) , primary care physicians ( PCPs ) , or specialist physicians using DAA therapy . Design Nonr and omized , open-label clinical trial initiated in 2015 . ( Clinical Trials.gov : NCT02339038 ) . Setting 13 urban , federally qualified health centers ( FQHCs ) in the District of Columbia . Patients A referred sample of 600 patients , of whom 96 % were black , 69 % were male , 82 % were treatment naive , and 20 % had cirrhosis . Seventy-two percent of the patients had HCV genotype 1a infection . The baseline characteristics of patients seen by each provider type were similar . Intervention Patients were assigned in a nonr and omized but specified manner to receive treatment from 1 of 5 NPs , 5 PCPs , or 6 specialists . All providers underwent an identical 3-hour training session based on guidelines . Patients received treatment with ledipasvir-sofosbuvir , which was provided on site , according to U.S. Food and Drug Administration labeling requirements . Measurements Sustained virologic response ( SVR ) . Results 516 patients achieved SVR , a response rate of 86 % ( 95 % CI , 83.0 % to 88.7 % ) , with no major safety signals . Response rates were consistent across the 3 provider types : NPs , 89.3 % ( CI , 83.3 % to 93.8 % ) ; PCPs , 86.9 % ( CI , 80.6 % to 91.7 % ) ; and specialists , 83.8 % ( CI , 79.0 % to 87.8 % ) . Patient loss to follow-up was the major cause of non-SVR . Limitation Nonr and omized patient distribution ; possible referral bias . Conclusion In a real-world cohort of patients at urban FQHCs , HCV treatment administered by nonspecialist providers was as safe and effective as that provided by specialists . Nurse practitioners and PCPs with compact didactic training could substantially exp and the availability of community-based providers to escalate HCV therapy , bridging existing gaps in the continuum of care for patients with HCV infection . Primary Funding Source National Institutes of Health and Gilead Sciences BACKGROUND Direct-acting antiviral therapy ( DAAs ) for hepatitis C infection ( HCV ) have a much smaller burden of treatment than interferon-based regimes , require less monitoring and are very effective . New pathways are required to increase access to treatment amongst people prescribed opioid substitution therapy ( OST ) . METHODS An exploratory cluster r and omised controlled trial with mixed methods evaluation was undertaken to compare the uptake of dried blood spot testing ( DBST ) and treatment of people with genotype 1 HCV infection in a conventional service pathway versus a pharmacist-led pathway in a population receiving OST . RESULTS Pharmacies r and omised to the conventional pathway obtained 58 DBST from 244 patients (24%):15 new reactive tests and 33 new negative tests were identified . Within the pharmacist-led pathway , 94 DBST were obtained from 262 patients ( 36 % ) : 26 new reactive tests and 54 new negative tests were identified . Participants in the pharmacist-led pathway were more likely to take a DBST ( p<0.003 ) . Of participants referred for treatment through the conventional pathway , 4 patients from 15 with new reactive tests ( 27 % ) attended clinic for assessment . In the pharmacist-led treatment pathway , 20 patients from 26 with new reactive tests ( 77 % ) attended for assessment blood tests . Participants in the pharmacist-led pathway were more likely to proceed through the assessment for treatment ( p<0.002 ) . One participant completed treatment through the conventional pathway and three patients completed treatment through the pharmacist-led pathway . The process evaluation identified key themes important to service user completers and staff participants . CONCLUSION The study provides evidence that testing and treatment for HCV in a pharmacist led-pathway is a feasible treatment pathway for people who receive supervised OST consumption through community pharmacies . This feasibility trial therefore provides sufficient confirmation to justify proceeding to a full trial OBJECTIVES To revise 2010 guidance on grading the strength of evidence ( SOE ) of the effectiveness of drugs , devices , and other preventive and therapeutic interventions in systematic review s produced by the Evidence -based Practice Center ( EPC ) program , established by the US Agency for Healthcare Research and Quality ( AHRQ ) . STUDY DESIGN AND SETTING A cross-EPC working group review ed authoritative systems for grading SOE [ primarily the approach from the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) working group ] and conducted extensive discussion s with GRADE and other experts . RESULTS Up date d guidance continues to be conceptually similar to GRADE . Review ers are to evaluate SOE separately for each major treatment comparison for each major outcome . We added reporting bias as a required domain and retained study limitations ( risk of bias ) , consistency , directness , and precision ( and three optional domains ) . Additional guidance covers scoring consistency , precision , and reporting bias , grading bodies of evidence with r and omized controlled trials and observational studies , evaluating single study bodies of evidence , using studies with high risk of bias , and presenting findings with greater clarity and transparency . SOE is grade d high , moderate , low , or insufficient , reflecting review ers ' confidence in the findings for a specific treatment comparison and outcome . CONCLUSION No single approach for grading SOE suits all review s , but a more consistent and transparent approach to reporting summary information will make review s more useful to the broad range of audiences that AHRQ 's work aims to reach . EPC working groups will consider ongoing challenges and modify guidance as needed , on issues such as combining trials and observational studies in bodies of evidence , weighting domains , and combining qualitative and quantitative syntheses BACKGROUND Though direct acting antivirals ( DAAs ) promise high cure rates , many providers and payers remain concerned about successful treatment for people who use drugs ( PWUD ) , even among those engaged in opioid agonist treatment ( OAT ) . The efficacy of DAAs among PWUD in real-world setting s is unclear . METHODS We conducted a cohort study of patients initiating HCV treatment between January 2014 and August 2015 ( n=89 ) at a primary care clinic in the Bronx , NY . Onsite HCV treatment with DAAs was performed by an HCV specialist , with support from a care coordinator funded by the NYC Department of Health . We identified four categories of drug use and drug treatment : ( 1 ) no active drug use/not receiving OAT ( defined as non-PWUD ) ; ( 2 ) no active drug use/receiving OAT ; ( 3 ) active drug use/not receiving OAT ; and ( 4 ) active drug use/receiving OAT . The primary outcome was SVR at 12 weeks post-treatment . RESULTS Overall SVR rates were 95 % ( n=41/43 ) for non-PWUD and 96 % ( n=44/46 ) for patients actively using drugs and /or receiving OAT [ p=0.95 ] . There were no differences in SVR rates by drug use or drug treatment category . Compared to non-PWUD , those with no active drug use/receiving OAT had 100 % SVR ( n=15/15 ; p=1.0 ) , those actively using drugs/not receiving OAT had 90 % SVR ( n=9/10 ; p=0.47 ) , and those actively using drugs/receiving OAT had 95 % SVR ( 20/21 ; p=1.0 ) . CONCLUSION Regardless of active drug use or OAT , patients who received DAA therapy at an urban primary care clinic achieved high HCV cure rates . We found no clinical evidence to justify restricting access to HCV treatment for patients actively using drugs and /or receiving OAT Introduction Hepatitis C virus ( HCV ) infection affects 0.7 % of the general population , and up to 40 % of people prescribed opioid substitution therapy ( OST ) in Scotl and . In conventional care , less than 10 % of OST users are tested for HCV and less than 25 % of these initiate treatment . Community pharmacists see this group frequently to provide OST supervision . This study examines whether a pharmacist-led ‘ test & treat ’ pathway increases cure rates for HCV . Methods and analysis This protocol describes a cluster-r and omised trial where 60 community pharmacies provide either conventional or pharmacy-led care . All pharmacies offer dried blood spot testing ( DBST ) for HCV . Participants have attended the pharmacy for OST for 3 months ; are positive for HCV genotype 1 or 3 ; are not co-infected with HIV and /or hepatitis B ; have no decompensated liver disease ; are not pregnant . For conventional care , pharmacists refer HCV-positive participants to a local centre for assessment . In the pharmacy-led arm , pharmacists assess participants themselves in the pharmacy . Drug prescribing is by nurse prescribers ( conventional arm ) or pharmacist prescribers ( pharmacy-led arm ) . Treatment in both arms is delivered as daily modified directly observed therapy in a pharmacy . Primary trial outcome is number of sustained virological responses at 12 weeks after treatment completion . Secondary trial outcomes are number of tests taken ; treatment uptake ; completion ; adherence ; re-infection . An economic evaluation will assess potential cost-effectiveness . Qualitative research interviews with clients and health professionals assess acceptability of a pharmacist-led pathway . Ethics and dissemination This protocol has been ethically approved by the East of Scotl and Research Ethics Committee 2 ( 15/ES/0086 ) and complies with the Declaration of Helsinki and principles of Good Clinical Practice . Caldicott guardian approval was given on 16 December 2016 to allow NHS Tayside to pass information to the cluster community pharmacies about the HCV test status of patients that they are seeing to provide OST supervision . NHS R&D approvals have been obtained from each health board taking part in the study . Informed consent is obtained before study enrolment and only anonymised data are stored in a secured data base , enabling an audit trail . Results will be su bmi tted to international peer- review ed journals and presented at international conferences . Trial registration number NCT02706223 ; Pre- results BACKGROUND To achieve the World Health Organization hepatitis C elimination targets , it is essential to increase access to direct acting antivirals ( DAAs ) - especially amongst people who inject drugs ( PWID ) . We aim ed to determine the effectiveness of providing DAAs in primary care compared with hospital-based specialist care . METHODS We r and omised PWID with hepatitis C attending primary care sites in Australia or New Zeal and to receive DAAs at their primary care site or local hospital ( st and ard of care ( SOC ) ) . The primary outcome was to determine if people treated in primary care had a non-inferior sustained virologic response at week 12 ( SVR12 ) rate compared to historical controls ( consistent with DAA trials at the time of study design ) ; secondary outcomes included comparison of treatment initiation , SVR12 rates , and the care cascade by study arm . RESULTS We recruited 140 participants and r and omised 136 ; 70 to primary care and 66 to SOC . The SVR12 rate ( 100 % , 95 % CI , 87.7 - 100 ) of people treated in primary care was non-inferior when compared to historical controls ( 85 % assumed ) . Intention to treat analysis revealed that the proportion of participants commencing treatment in primary care ( 75 % , 43/57 ) was significantly higher than in SOC ( 34 % , 18/53 ) ( p<0.001 ; RR 2.48 ; 95 % CI , 1.54 - 3.95 ) , and the proportion of participants with SVR12 was significantly higher in primary care compared to SOC ( 49 % , 28/57 and 30 % , 16/53 ) ( p=0.043 ; RR 1.63 ; 95 % CI,1.0 - 2.65 ) . CONCLUSION Providing hepatitis C treatment in primary care increases treatment uptake and cure . Approaches that increase treatment uptake amongst PWID will accelerate elimination strategies |
643 | 24,474,683 | The barriers that were identified are not all unique to participants from ethnic minorities , although the way in which they manifest themselves is often distinct in minority groups . | Disparities in the prevalence of mental illness are widely reported for people from ethnic minorities .
Unlike the United States , there is no legislation for clinical research in the UK to m and ate the inclusion of ethnic minorities and they are underrepresented in European trials compared with those conducted in the United States .
This restricts generalization of research findings . | OBJECTIVE Latino family caregivers of older people with memory problems are a rapidly growing group . However , their participation in intervention research is disproportionately low . The authors compared the participant retention rates of three different recruitment strategies in a sample of Latino and Caucasian family caregivers . METHODS A total of 310 caregivers ( 195 Latino and 105 Caucasian ) were screened for participation in one of two clinical intervention trials . Potential participants were recruited from one of three sources : 1 ) non-professional ( e.g. , health fairs ) ; 2 ) professional ( e.g. , community agencies ) ; and 3 ) advertisements . Reasons for non-participation were also obtained . RESULTS Caucasians were significantly more likely to be successfully retained across all recruitment strategies ( 52 % versus 31 % , respectively ) . However , logistic regression revealed a recruitment strategy -by-ethnicity interaction : Latinos were highly similar in retention rates to Caucasians when recruited through professional referrals , and far less likely to participate with other strategies . Descriptive analyses also revealed ethnic differences for non-participation . CONCLUSION Partnership of Latino family caregivers with community agencies may result in the highest recruitment rates among this group . Latino cultural values likely play a role in the success of these partnerships in participant recruitment PURPOSE This article review s the problems associated with recruiting older minorities into mental health research studies and proposes a consumer-centered model of research methodology that addresses the barriers to recruitment and retention in this population . DESIGN AND METHODS The authors discuss and compare the results of recruitment and retention interventions for two geriatric mental health studies , one that used traditional methods of recruitment and retention and another that used consumer-centered methods . RESULTS Although the consumer-centered methods result in better recruitment of older minorities in general ( chi(2 ) = 54.90 , p < .001 ) , it was not superior to the traditional method in recruiting older minorities ( chi(2 ) = 0.82 , ns ) . However , the consumer-centered approach yielded better retention of older minorities ( chi(2 ) = 6.20 , p < .05 ) than did the traditional method . Within both methods , recruitment through provider referral and face-to-face contact were the superior recruitment methods ( chi(2 ) = 6.78 , p < .05 ) . Having an experienced recruiter or a community recruiter result ed in greater agreement to participate than simply having an ethnically matched recruiter ( chi(2 ) = 36.00 , p < .001 ) . IMPLICATION S Although these data are observational , and rigorous research on the best methods for recruiting and retaining older minorities is still necessary , the results suggest that a consumer-centered model of research yields greater overall recruitment and retention rates than do traditional research methods The negative consequences of untreated depression on the health and well-being of women and their children are well-documented , underscoring the need to develop effective interventions to prevent the onset of major depression during the perinatal period . This article describes recruitment data from two r and omized controlled trials of preventive interventions for postpartum depression : one conducted with immigrant Latinas in Washington , DC , United States , and the other with women in Mexico City , Mexico . In both countries , pregnant women met a priori eligibility criteria and were r and omized into an 8-week theory-based group intervention . Two hundred and seventeen Latinas in the U.S. and 377 women born and raised in Mexico were enrolled in their respective countries . The recruitment rates ( i.e. , the number of participants who met eligibility criteria , consented , and r and omized into the study ) were 70 % in the U.S. and in Mexico . Issues and recommendations related to recruiting Hispanic women into preventive intervention trials for postpartum depression are discussed OBJECTIVE Ethnic minority patients often receive poorer quality care and have worse outcomes than white patients , yet practice -based approaches to reduce such disparities have not been identified . We determined whether practice -initiated quality improvement ( QI ) interventions for depressed primary care patients improve care across ethnic groups and reduce outcome disparities . STUDY SETTING The sample consists of 46 primary care practice s in 6 U.S. managed care organizations ; 181 clinicians ; 398 Latinos , 93 African Americans , and 778 white patients with probable depressive disorder . STUDY DEIGN : Matched practice s were r and omized to usual care or one of two QI programs that trained local experts to educate clinicians ; nurses to educate , assess , and follow-up with patients ; and psychotherapists to conduct Cognitive Behavioral Therapy . Patients and physicians selected treatments . Interventions featured modest accommodations for minority patients ( e.g. , translations , cultural training for clinicians ) . DATA EXTRACTION METHODS Multilevel logistic regression analyses assessed intervention effects within and among ethnic groups . PRINCIPAL FINDINGS At baseline , all ethnic groups Latino , African American , white ) had low to moderate rates of appropriate care and the interventions significantly improved appropriate care at six months ( by 8 - 20 percentage points ) within each ethnic group , with no significant difference in response by ethnic group . The interventions significantly decreased the likelihood that Latinos and African Americans would report probable depression at months 6 and 12 ; the white intervention sample did not differ from controls in reported probable depression at either follow-up . While the intervention significantly improved the rate of employment for whites and not for minorities , precision was low for comparing intervention response on this outcome . It is important to note that minorities remained less likely to have appropriate care and more likely to be depressed than white patients . CONCLUSIONS Implementation of quality improvement interventions that have modest accommodations for minority patients can improve quality of care for whites and underserved minorities alike , while minorities may be especially likely to benefit clinical ly . Further research needs to clarify whether employment benefits are limited to whites and if so , whether this represents a difference in opportunities . Quality improvement programs appear to improve quality of care without increasing disparities , and may offer an approach to reduce health disparities BACKGROUND Rates of self-harm appear high in South Asian young women in the United Kingdom ( UK ) although previous studies were mostly small . Data on treatment and outcomes for South Asians are lacking . This study compared rates of self-harm , socio-demographic and clinical characteristics , provision of services and risk of repetition by ethnicity . METHOD A prospect i ve cohort of adult self-harm attendees ( n = 7185 ) , aged 15 and over presenting to four emergency departments in the cities of Manchester and Salford , UK over a 4-year period . RESULTS The study included 299 South Asians . South Asian women aged 16 - 24 years were more likely to self-harm than Whites of the same age group ( 1010.9 vs. 754 per 100,000 ) . Across all age groups the rates of self-harm were lower in South Asian men compared to White men and to South Asian women . South Asian women were significantly more likely to report relationship problems within the family than White women ( 32 % vs. 19 % , P = < 0.001 ) . South Asians were less likely than Whites to report depressive symptoms and to be offered specialist mental health services ( Rate ratio = 0.75 ) , and more likely to be referred back to the GP ( Rate ratio = 1.83 ) . South Asians were less likely to attend with a repeat episode ( Rate ratio = 0.56 ) . CONCLUSIONS Young South Asian women are at high risk of self-harm , but their clinical risk appears to be lower in terms of the accepted context ual factors contributing to risk . Potentially useful service provision may include an interpersonal problem solving approach although to be effective , interventions would need to be acceptable to South Asian women and culturally appropriate |
644 | 32,112,250 | There were minimal side effects without serious adverse effects .
Er : YAG laser is shown to be effective in a way to reduce snoring without significant AHI or RDI changes . | A new outpatient non-surgical method using Er : YAG laser for snoring has been demonstrated .
The aim of this systematic review and meta- analysis was to investigate the effects of this treatment on snoring . | OBJECTIVES /HYPOTHESIS The effect of the Pillar implant on mild sleep-disordered breathing ( SDB ) has been assessed in various studies . However , most of these were conducted among a non-Asian population at a single institution . Therefore , the aim of this study was to prospect ively evaluate the efficacy of the Pillar implant in Asian patients with simple snoring and mild obstructive sleep apnea ( OSA ) at multiple centers . STUDY DESIGN Multicenter prospect i ve clinical trials . METHODS This study included consecutive subjects with simple snoring or mild OSA . We examined subjective symptoms ( snoring intensity , frequency , witnessed apnea , and daytime sleepiness ) and objective snoring and respiratory parameters ( snoring duration [ proportion of sleep while snoring louder than 50 dB ] , snoring loudness , apnea-hypopnea index , respiratory disturbance index , minimum arterial oxygen saturation , and oxygen desaturation index ≥ 4 % ) at 3 to 6 months after surgery . Adverse events were also investigated . RESULTS Twenty-nine subjects with mild SDB completed the study . Whole group analysis found significant improvements in various subjective symptoms , but not in the objective snoring and respiratory parameters . A subgroup analysis of subjects with mild OSA ( n = 11 ) found significant alleviation in various subjective symptoms , apnea-hypopnea index , respiratory disturbance index , and oxygen desaturation index ≥ 4 % . No major complication related to surgery was observed , and most minor adverse effects were resolved without morbidity . CONCLUSIONS In selected Korean patients , the Pillar implant significantly improved not only subjective symptoms of mild SDB but also respiratory disturbances in mild OSA . LEVEL OF EVIDENCE 2b BACKGROUND Limited data have suggested that sleep-disordered breathing , a condition of repeated episodes of apnea and hypopnea during sleep , is prevalent among adults . Data from the Wisconsin Sleep Cohort Study , a longitudinal study of the natural history of cardiopulmonary disorders of sleep , were used to estimate the prevalence of undiagnosed sleep-disordered breathing among adults and address its importance to the public health . METHODS A r and om sample of 602 employed men and women 30 to 60 years old were studied by overnight polysomnography to determine the frequency of episodes of apnea and hypopnea per hour of sleep ( the apnea-hypopnea score ) . We measured the age- and sex-specific prevalence of sleep-disordered breathing in this group using three cutoff points for the apnea-hypopnea score ( > or = 5 , > or = 10 , and > or = 15 ) ; we used logistic regression to investigate risk factors . RESULTS The estimated prevalence of sleep-disordered breathing , defined as an apnea-hypopnea score of 5 or higher , was 9 percent for women and 24 percent for men . We estimated that 2 percent of women and 4 percent of men in the middle-aged work force meet the minimal diagnostic criteria for the sleep apnea syndrome ( an apnea-hypopnea score of 5 or higher and daytime hypersomnolence ) . Male sex and obesity were strongly associated with the presence of sleep-disordered breathing . Habitual snorers , both men and women , tended to have a higher prevalence of apnea-hypopnea scores of 15 or higher . CONCLUSIONS The prevalence of undiagnosed sleep-disordered breathing is high among men and is much higher than previously suspected among women . Undiagnosed sleep-disordered breathing is associated with daytime hypersomnolence OBJECTIVE We sought to find a combination of noninvasive treatments for snoring by adding weight loss to previously studied treatments , including the combination of sleeping on one 's side and using a decongestant nasal spray . STUDY POPULATION Twenty asymptomatic men who snore heavily were studied previously on a control night and on a night when they slept on their side and used a nasal spray . With these two treatments , minor improvements in apnea/hypopnea index ( AHI ) were seen , but no improvement occurred in snoring frequency . Nineteen of these subjects subsequently completed a 6-month weight loss program , and 12 lost weight . These 19 subjects comprise the study population of this report . STUDY DESIGN At the conclusion of the weight loss program , a repeated sleep study was done from which the effect of adding weight loss to the two previously studied treatments could be assessed . RESULTS Those 12 subjects who lost any amount of weight showed a very mild reduction in snores per hour from 328 using two modalities of treatment to 232 per hour with the addition of weight loss ( p = 0.15 ) . The nine subjects who lost > or = 3 kg reduced the number of snores per hour from 320 to 176 ( p = 0.0496 ) . Three subjects losing an average of only 7.6 kg showed virtual elimination of snoring after weight loss . Subjects who gained weight had no improvement in snoring . Weight loss added to the other two modalities of treatment had no effect on the AHI . CONCLUSION In most cases , the combination of weight loss , sleeping on one 's side , and the administration of a nasal decongestant significantly reduces the frequency of snoring in asymptomatic men who snore heavily . The major effect appears to be related to weight loss OBJECTIVE The aim of this study was to assess the effects of laser irradiation with a novel snoring h and piece on the histological structures of the soft palate in a rat model . BACKGROUND Snoring is a common problem and studies have shown that 20 - 50 % of the population is affected . An apnea-hypopnea index of < 5/h without daytime somnolence is documented as simple snoring . No snoring treatment should ever be attempted until a sleep study has been completed to rule out sleep apnea . METHODS Twenty adult Wistar rats , weighing 200 - 250 g , were used in this study . Rats were r and omized into two groups : experimental group ( n = 10 ) and control group ( n = 10 ) . Laser energy was delivered in a horizontal direction to the surface of the soft palate of each rat in the experimental group for 2 min with an Er : YAG laser ( LightWalker AT ; Fotona ) with snoring h and piece ( PS04 ) in a noncontact mode ( 1.15 W , 2 Hz , 1.5 J/cm(2 ) ) . The animals were sacrificed after 24 h , 1 week , 3 weeks , or 5 weeks . The soft palate of each rat was removed by excisional biopsy . The specimens underwent histological examination . Contractions and fibrosis were reported as grading from 1 + to 3 + , while edema and hyperemia were evaluated according to the absence ( 0 ) or presence ( 1 ) of any changes . Statistical analysis was done with the Mann-Whitney U and Spearman 's rho tests . RESULT A noticeable contraction of the soft palate occurred immediately after laser application . Inflammatory changes were observed histologically at 3 weeks postoperatively . Keratinization appeared after the procedure in both groups and decreased gradually . Statistically , there was a strong correlation among inflammation and time and also keratinization and time ( p < 0.05 ) . CONCLUSIONS The present study indicates that Er : YAG laser irradiation with snoring h and piece ( PS04 ) causes acute shrinkage of the mucosa . This contraction decreases gradually but is still present at the end of fifth week Introduction : Adenotonsillar hypertrophy ( AH ) is considered the most common cause of upper respiratory tract obstruction among children . It results in a spectrum of symptoms from mouth breathing , nasal obstruction , hyponasal speech , snoring , and obstructive sleep apnea ( OSA ) to growth failure and cardiovascular morbidity . Adenotonsillectomy is a typical strategy for patients with AH , but may lead to serious complications such as bleeding ( 4–5 % ) and postoperative respiratory compromise ( 27 % ) , especially among young children , as well as recurrence of adenoid tissue ( 10–20 % ) . Thus , non-surgical therapies have attracted considerable attention as an alternative strategy . The inflammatory mechanism proposed for AH has lead to the use of anti-inflammatory drugs to manage this condition . The present study aim ed to evaluate the effect of chewable tablets of montelukast , a cysteinyl- leukotriene receptor antagonist , in children with AH . Material s and Methods : Sixty children between the ages of 4–12 years with > 75 % choanal obstruction on primary nasal endoscopy were recruited in this r and omized , placebo-controlled trial and r and omly divided into two groups . The study group was treated with montelukast 5 mg daily for 12 weeks while the control group received matching placebo for the same period of time . A question naire was completed by each child ’s parent/guardian to assess the severity of sleep discomfort , snoring , and mouth breathing before and after the intervention . Results : Adenoid size decreased in 76 % of the study group compared with 3 % of the placebo group after 12 weeks . A statically significant improvement was observed in the study group compared with the placebo group in terms of sleep discomfort , snoring , and mouth breathing . The symptoms average total score dropped from 7.7 to 3.3 in the study group , while in the placebo group the total score changed from 7.4 to 6.7 . Conclusion : Montelukast chewable tablets achieved a significant reduction in adenoid size and improved the related clinical symptoms of AH and can therefore be considered an effective alternative to surgical treatment in children with adenoid hypertrophy Snoring is a sleep phenomenon due to the partial upper airway obstruction during sleep which causes vibration of the tissues of the rhino-oro-hypopharynx and less frequently the larynx . This study evaluated the use and effectiveness of the erbium : YAG 2940-nm laser as an adjunctive in providing treatment for patients suffering from chronic snoring-related sleep disorders . A prospect i ve study of 40 consecutive patients with snoring and sleep disorders was performed , assessing data before and after three Er : YAG laser treatment sessions . During laser treatment , the pain was almost absent . There were no side effects , except a very mild sore throat in 1 out of 40 patients . The patient ’s evaluation of satisfaction of the results obtained after the treatments showed that 85 % of cases were very satisfied , 5 patients ( 12.5 % ) reported being fairly satisfied with the treatment and only 1 subject ( 2.5 % ) was not satisfied . Mallampati , Friedman Tongue Position , and degree of O ( oropharynx ) at nose oropharynx hypopharynx and larynx classification were significantly decreased after the laser sessions . The decrease of Epworth Sleepiness Scale and Visual Analogue Scale for loudness of snoring , waking up during sleep because of snoring , dry mouth on waking , and choking was all statistically significant . The incidence of dreaming during the night also raised significantly ; 30/40 ( 75 % ) of cases perceived less tightness in their throat and better breathing after treatment . These results were stable at 20 months follow-up ( 14–24 q ) in 72 % of cases . Nonsurgical and non-invasive Er : YAG laser treatment demonstrated to be a valid procedure in reducing the loudness of snoring In a prospect i ve study aim ed at evaluating objective ly the compliance with nasal continuous positive airway pressure ( CPAP ) treatment , 233 obstructive sleep apnea ( OSA ) ( apnea index , > 10 apneas/hour ) patients and 36 nonapneic snorers were studied . The compliance to treatment was measured by the mean rate of use of the CPAP device , obtained from a built-in time counter . The follow-up period was 874 + /- 48 in OSA patients and 675 + /- 83 in snorers . CPAP was proposed to all OSA patients but only to those snorers who felt improved after an initial laboratory night on CPAP . Nineteen OSA patients refused CPAP . Of the 214 OSA patients who accepted CPAP , 181 are still on treatment , with a mean daily rate of use of 5.6 + /- 0.1 hours ( mean + /- SEM ) ; 22 patients stopped CPAP after a variable period of time ; 10 patients died and one acromegalic patient was considered cured after hypophysectomy for a pituitary adenoma . Depending upon the definition of acceptable compliance , the compliance rate in this group was between 77 % and 89 % . The mean rate of use was correlated with indices of disease severity ( apnea index , apnea+hypopnea index , minimal SaO2 during sleep , daytime PaO2 , pulmonary artery pressure ) . Thirty-six nonapneic snorers accepted CPAP . In this group , 26 are still on CPAP , with a mean daily rate of use of 5.4 + /- 0.5 hours ; one patient died ; one underwent uvolopalatopharyngoplasty without follow-up ; and eight stopped CPAP . The compliance rate in this group was between 58 % and 78 % . This study shows that CPAP is reasonably accepted by OSA patients as well as by nonapneic snorers . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVES To develop and vali date a new risk-of-bias tool for nonr and omized studies ( NRSs ) . STUDY DESIGN AND SETTING We developed the Risk of Bias Assessment Tool for Nonr and omized Studies ( RoBANS ) . A validation process with 39 NRSs examined the reliability ( interrater agreement ) , validity ( the degree of correlation between the overall assessment s of RoBANS and Method ological Index for Nonr and omized Studies [ MINORS ] , obtained by plotting the overall risk of bias relative to effect size and funding source ) , face validity with eight experts , and completion time for the RoBANS approach . RESULTS RoBANS contains six domains : the selection of participants , confounding variables , the measurement of exposure , the blinding of the outcome assessment s , incomplete outcome data , and selective outcome reporting . The interrater agreement of the RoBANS tool except the measurement of exposure and selective outcome reporting domains ranged from fair to substantial . There was a moderate correlation between the overall risks of bias determined using RoBANS and MINORS . The observed differences in effect sizes and funding sources among the assessed studies were not correlated with the overall risk of bias in these studies . The mean time required to complete RoBANS was approximately 10 min . The external experts who were interviewed evaluated RoBANS as a " fair " assessment tool . CONCLUSIONS RoBANS shows moderate reliability , promising feasibility , and validity . The further refinement of this tool and larger validation studies are required Four hundred forty-one subjects 34 to 69 yr of age were recruited from a r and om sample of the community . They answered a question naire and were monitored in their homes for sleep-disordered breathing ( SDB ) . This report concerns the association between observed SDB and arterial hypertension and vascular disease . Hypertension was defined as self-report of a diagnosis of hypertension made by a physician , current treatment for hypertension , or a systolic pressure greater than 150 mm Hg or a diastolic pressure greater than 90 mm Hg . Coronary artery disease was defined by self-report of angina or myocardial infa rct ion of " heart attack . " There were few cases of stroke or claudication , and a category of " occlusive vascular disease " was defined by self-report of coronary artery disease or of " blocked arteries " or stroke . Subjects were classified as snorers ( n = 289 ) or nonsnorers ( n = 73 ) by self-report of regular snoring , and as having SDB ( n = 79 ) if more than 15 abnormal respiratory events were recorded per hour of recording . There were significant increases in the prevalence of hypertension , coronary artery disease , and occlusive vascular disease from nonsnorers ( 26 , 7 , and 10 % , respectively ) through snorers ( 39 , 12 , and 17 % ) to subjects with SDB ( 57 , 20 , and 28 % ) . The crude odds ratio for SDB versus nonsnorers was 3.8 ( 95 % CI , 1.9 to 7.5 ) for hypertension , 3.5 ( 1.2 to 10.0 ) for coronary artery disease , and 3.7 ( 1.5 to 9.1 ) for occlusive vascular disease . ( ABSTRACT TRUNCATED AT 250 WORDS |
645 | 23,255,684 | Conclusions NIPPV could be used to reduce endotracheal ventilation , increase successful extubation , decrease the rate of apnea of prematurity , and have better outcome indicated by fewer death and /or bronchopulmonary dysplasia in preterm and term newborn infants | Objective To compare the efficacy and safety of Nasal intermittent positive pressure ventilation ( NIPPV ) and Nasal continuous positive airway pressure ( nCPAP ) in neonates . | A prospect i ve , r and omized , cross-over trial was performed to compare the efficacy of nasal intermittent positive-pressure ventilation with nasal continuous positive airway pressure in infants of less than 32 weeks of gestation . Continuous positive airway pressure was delivered at end-expiratory pressures of 4 cm H2O , while peak pressures of 20 cm H2O and end-expiratory pressures of 4 cm H2O were used during nasal intermittent positive-pressure ventilation at ventilatory rates of 20 breaths per minute . The frequency and extent of apnea and bradycardia during a 6-hour period in a patient receiving nasal continuous positive airway pressure were compared with a similar crossover period of nasal intermittent positive-pressure ventilation . Although the infants had slightly less frequent episodes of apnea per hour ( 0.6 + /- 0.7 vs 0.5 + /- 0.7 ) and bradycardia per hour ( 1.2 + /- 1.3 vs 0.9 + /- 1.0 ) during nasal intermittent positive-pressure ventilation , these differences were not significant . There were no significant differences in the severity of these events as assessed by the duration and fall in transcutaneous oxygen pressure during apnea and heart rate during bradycardia . There were no significant changes in blood gases throughout the study . Nasal intermittent positive-pressure ventilation appears to have no advantages over nasal continuous positive airway pressure in preventing apnea and does not alter gas exchange in infants of less than 32 weeks of gestation CONTEXT : Strategies for reducing exposure to endotracheal ventilation through the use of early noninvasive ventilation has proven to be safe and effective , but the option with the greatest benefits needs to be determined . OBJECTIVE : To determine , in infants with respiratory distress syndrome , if early nasal intermittent positive-pressure ventilation ( NIPPV ) compared with nasal continuous positive airway pressure ( NCPAP ) decreases the need for mechanical ventilation . PATIENTS AND METHODS : In this single-center , r and omized controlled trial , infants ( gestational ages 26 to 3367 weeks ) with respiratory distress syndrome were r and omly assigned to receive early NIPPV or NCPAP . Surfactant was administered as rescue therapy . The primary outcome was the need for mechanical ventilation within the first 72 hours of life . RESULTS : A total of 200 infants , 100 in each arm , were r and omly assigned . Rates of the primary outcome did not differ significantly between the NIPPV ( 25 % ) and NCPAP ( 34 % ) groups ( relative risk [ RR ] : 0.71 [ 95 % confidence interval ( CI ) : 0.48–1.14 ] ) . In posthoc analysis , from 24 to 72 hours of life , significantly more infants in the NIPPV group remained extubated compared with those in the NCPAP groups ( 10 vs 22 % ; RR : 0.45 [ 95 % CI : 0.22–0.91 ] ) . This difference was also noted in the group of infants who received surfactant therapy , NIPPV ( 10.9 % ) , and NCPAP ( 27.1 % ) ( RR : 0.40 [ 95 % CI : 0.18–0.86 ] ) . CONCLUSIONS : Early NIPPV did not decrease the need for mechanical ventilation compared with NCPAP , overall , in the first 72 hours of life . However , further studies to assess the potential benefits of noninvasive ventilation are warranted , especially for the most vulnerable or preterm infants Objective : Comparison of outcomes of infants with respiratory distress syndrome ( RDS ) , post-surfactant , extubated to synchronized nasal intermittent positive pressure ventilation ( SNIPPV ) or continued on conventional ventilation ( CV ) . Study Design : Prospect i ve post-surfactant r and omized controlled trial of primary mode SNIPPV compared with CV in infants ( born from July 2000 to March 2005 ) with birth weights ( BW ) of 600 to 1250 g. Primary mode SNIPPV was defined as its use in the acute phase of RDS , following the administration of the first dose of surfactant . Result : There were no significant differences in the maternal demographics , antenatal steroid use , mode of delivery , BW , gestational age , gender or Apgar at 5 min between infants continued on CV ( n=21 ) and those extubated to primary mode SNIPPV ( n=20 ) . Significantly , more babies in the CV group had the primary outcome of bronchopulmonary dysplasia (BPD)/death , compared to the SNIPPV group ( 52 versus 20 % , P=0.03 ) . There was no difference in the incidence of other common neonatal morbidities . There were no differences in the Mental or Psychomotor Developmental Index scores on follow-up between the two groups . Conclusion : Infants of BW 600 to 1250 g with RDS receiving surfactant with early extubation to SNIPPV had a significantly lower incidence of BPD/death . Primary mode SNIPPV is a feasible method of ventilation in small premature infants OBJECTIVE To compare the rate of reintubation within 7 days after extubation and study the complications in premature infants who were r and omized in the immediate postextubation period to either nsNIMV or NCPAP . MATERIAL AND METHOD This study was conducted in the neonatal unit of Queen Sirikit National Institute of Child Health between June 1 and November 30 , 2006 . Intubated premature infants born at GA < or = 34 weeks or with birth weight < or = 1500 gm , ready to be extubated before 4 weeks of age were recruited . Infants were r and omized to either nsNIMV or NCPAP after extubation . Non-synchronized NIMV setting was the same as ventilator setting before extubation and NCPAP pressure was set at the same mean airway pressure of pre extubation ventilator value . Extubation was performed after intravenous loading dose of aminophylline . Primary outcome measurement was reintubation within 7 days of initial extubation and the secondary outcome was possible complications such as apnea , abdominal distension , gastrointestinal ( GI ) perforation , necrotizing enterocolitis ( NEC ) , sepsis and death . RESULTS A total of 70 VLBW infants were admitted to the neonatal unit during the study period . A total of 57 infants were intubated of which 48 infants were recruited for the study ; 24 were in the nsNIMV group and 24 were in the NCPAP group . Infants in the nsNIMV group had mean birth weight and body weight at the start of study less than that in the NCPAP group ( 984.8 + /- 218 vs. 1067 + /- 214 and 1185 + /- 219 vs. 1205 + /-191 , p = 0.003 , 0.02 ) . The nsNIMV group also had a higher rate of RDS and antenatal steroid used when compared to the NCPAP group ( 19/24 vs. 12/24 and 17/24 vs. 8/24 , p = 0.03 , 0.01 ) . The nsNIMV group had fewer males than in the NCPAP group ( 8/24 vs. 17/24 , p = 0.01 ) . Reintubation was similar in both groups but atelectasis and sepsis were statistically significant risk factor for reintubation in NCPAP group . There were no significant differences in treatment related complications between the two groups , with respect to incidence of apnea ( 41.7 % in nsNIMV vs. 62.5 % in NCPAP ) , abdominal distensions ( 8.3 % in nsNIMVvs . 16.7 % in NCPAP ) , NEC ( 4.2 % in nsNIMVvs . 12.5 in NCPAP ) , sepsis ( 4.2 % in nsNIMVvs . 8.3 % NCPAP ) . No GI perforation was observed in both groups . CONCLUSION Non-invasive mode of ventilation , both NIMV and NCPAP , for weaning ofpre-term infants from ventilator may reduce the rate of reintubation in this group . Both modes seem to be equally safe . We believe that the use of non-invasive ventilator techniques will significantly reduce neonatal morbidity in the future . Additional prospect i ve evaluation of these approaches should be conducted in the future OBJECTIVE To determine whether synchronized nasal intermittent positive pressure ventilation ( SNIPPV ) would decrease extubation failure compared with nasal continuous positive airway pressure ( NCPAP ) in preterm infants being ventilated for respiratory distress syndrome ( RDS ) . METHODS Infants who were < /=34 weeks ' gestational age and who were ventilated for RDS were r and omized to either SNIPPV or NCPAP after extubation . The criteria for extubation were peak inspiratory pressure of < /=16 cm H(2)O , positive end expiratory pressure of < /=5 cm H(2)O , intermittent m and atory ventilation rate of 15 to 25 , and fraction of inspired oxygen < /=0.35 . Pulmonary function tests ( PFT ) were obtained before extubation . After extubation , blood gases were monitored for a minimum of 72 hours . Success was defined as remaining in the selected mode of treatment or demonstrating improvement ( switching to oxyhood/nasal cannula/room air ) by 72 hours . RESULTS Thirty-two ( 94 % ) of 34 infants were extubated successfully with the use of SNIPPV versus 18 ( 60 % ) of 30 with the use of NCPAP ( P < .01 ) . There was no difference in apnea/bradycardia episodes in the 2 groups during the 72-hour study period . Among 55 infants who had PFT , 80 % ( 8 of 10 ) with dynamic lung compliance of > /=0.5 mL/kg/cm H(2)O and expiratory airway resistance of < /=70 cm H(2)O/L/s were extubated successfully . In infants with poor lung function ( dynamic lung compliance : < 0.5 mL/kg/cm H(2)O ; expiratory airway resistance : > 70 cm H(2)O/L/s ) , successful extubation was seen in 93 % ( 27 of 29 ) in the SNIPPV group and 60 % ( 15 of 25 ) in the NCPAP group . When weight was controlled for at the time of extubation , the odds of success in the SNIPPV group were 21.1 times higher ( 95 % confidence interval : 3.4 , 130.1 ) than that of the NCPAP group . CONCLUSIONS SNIPPV is more effective than NCPAP in weaning infants with RDS from the ventilator . PFT may be useful in predicting successful extubation OBJECTIVE : To compare the outcome of infants with respiratory distress syndrome ( RDS ) in the neonatal intensive care unit ( NICU ) who were extubated to synchronized nasal intermittent positive pressure ventilation ( SNIPPV ) or continued on conventional ventilation ( CV ) , immediately postsurfactant . STUDY DESIGN : Prospect i ve observational study of postsurfactant ventilatory management of consecutive infants ( born between 10/99 and 12/02 ) of 28 to 34 weeks gestation . Extubation to SNIPPV was at the attending neonatologists ' discretion . Babies in the CV group remained intubated , postsurfactant . RESULTS : There were no significant differences in the maternal demographics , antenatal steroid use , mode of delivery , birth weight ( BW ) , gestational age ( GA ) , gender , Apgar at 5 minutes , age at surfactant instillation , or oxygenation index ( OI ) prior to surfactant administration , between infants continued on CV ( n=35 ) and those extubated to SNIPPV ( n=24 ) . The total duration of endotracheal intubation ( mean±SEM ; CV versus SNIPPV ; 2.4±0.4 versus 0.3±0.0 days , p=0.001 ) and duration of supplemental oxygen exposure ( 15±3.2 versus 8.2±3.3 days , p=0.04 ) were significantly shorter in the SNIPPV group . Furthermore , the duration of parenteral nutrition ( 12.1±1.6 versus 8.4±0.8 days , p=0.02 ) and length of stay ( 37.5±3.0 versus 29.1±3.3 days , p=0.04 ) were also significantly shorter in the SNIPPV group . There were no differences between the two groups in blood gas or OI values postsurfactant ( up to 48 hours ) . There was no statistical difference in the incidence of intraventricular hemorrhage grade I ( three ( 9 % ) in the CV group and two infants ( 8 % ) in the SNIPPV group ) . No infant died in either group or had patent ductus arteriosus , air leaks , necrotizing enterocolitis , periventricular leukomalacia , retinopathy of prematurity or bronchopulmonary dysplasia . CONCLUSIONS : Infants of 28 to 34 weeks GA with RDS requiring surfactant with early extubation to SNIPPV had a shorter duration of intubation , and decreased need for oxygen as compared to CV . There was also a significant decrease in the duration of parenteral nutrition and hospitalization . SNIPPV is a safe and effective primary mode of ventilation in larger premature infants The efficacy of nasal intermittent positive pressure ventilation ( NIPPV ) in treating apnea of prematurity was evaluated . Apneic preterm infants were r and omly assigned to receive either NIPPV or continuous positive airway pressure ( NCPAP ) for 4 hr when they failed to respond to conservative therapy . The amount of reduction in apneic spells and bradycardia in the two groups after treatment was compared . Thirty-four infants ( 18 with NIPPV , 16 with NCPAP ) were enrolled . Their birth weights ranged from 590 - 1,880 g ( mean , 1,021 g ) and gestational ages from 25 - 32 weeks ( mean , 27.6 weeks ) . The baseline characteristics were comparable in the two groups . Frequency of apnea and bradycardia was reduced during both forms of treatments . However , the infants receiving NIPPV had a greater reduction of apneic spells ( P = 0.02 ) and a tendency to greater decrease in bradycardia ( P = 0.09 ) than those receiving NCPAP . We conclude that NIPPV is more effective than NCPAP in reducing apnea in preterm infants . NIPPV may reduce bradycardia ; however , this needs to be vali date d by a larger number of observations AIM Nasal continuous positive airway pressure and nasal intermittent positive pressure ventilation have both been proposed as a form of gentle respiratory support for neonatal respiratory distress syndrome . We have compared these two respiratory support methods in the management of early stages of mild-moderate , neonatal respiratory distress syndrome . METHODS A prospect i ve , r and omized trial was performed enrolling 88 consecutive preterm infants with mild to moderate respiratory distress syndrome matched for birthweight , gestational age , sex , admission FiO2 and Apgar scores . Nasal continuous positive airway pressure was delivered at a pressure of 4 - 6 cmH2O . Infants on intermittent pressure were put on ventilatory rates of 40 breaths per minute . Peak pressures of 14 - 20 cmH2O and end-expiratory pressures of 4 - 6 cmH2O were used judging clinical ly the chest cage expansion . RESULTS Although there were no differences in the PaO2 values between the groups , infants treated with nasal intermittent positive pressure ventilation showed a significantly lower pCO2 values than those in the continuous pressure group ( 40+/-2 vs 58+/-4 mmHg , P<0.05 ) . Also a significantly lower incidence of apnoeic episodes ( number of episodes/hour 0.4+/-0.2 vs 0.9+/-03 ; P<0.05 ) and a shorter respiratory support in the nasal intermittent positive pressure ventilation group were observed . No difference in severe abdominal distension or need of endotracheal intubation was noted . CONCLUSIONS In the present clinical setting , the use of nasal positive airway pressure in an intermittent way is associated to a more physiological arterial carbon dioxide tension , less apnoea and a shorter duration of respiratory support when compared with continuous pressure delivery by the same route Background : Apnoea of prematurity ( AOP ) is a common problem in preterm infants which can be treated with various modes of nasal continuous positive airway pressure ( NCPAP ) or nasal intermittent positive pressure ventilation ( NIPPV ) . It is not known which mode of NCPAP or NIPPV is most effective for AOP . Objective : To assess the effect of four NCPAP/NIPPV systems on the rate of bradycardias and desaturation events in very low birthweight infants . Methods : Sixteen infants ( mean gestational age at time of study 31 weeks , 10 males ) with AOP were enrolled in a r and omised controlled trial with a crossover design . The infants were allocated to receive nasal pressure support using four different modes for 6 h each : NIPPV via a conventional ventilator , NIPPV and NCPAP via a variable flow device , and NCPAP delivered via a constant flow underwater bubble system . The primary outcome was the cumulative event rate of bradycardias ( ⩽80 beats per minute ) and desaturation events ( ⩽80 % arterial oxygen saturation ) , which was obtained from cardio-respiratory recordings . Results : The median event rate was 6.7 per hour with the conventional ventilator in NIPPV mode , and 2.8 and 4.4 per hour with the variable flow device in NCPAP and NIPPV mode , respectively ( p value<0.03 for both compared to NIPPV/conventional ventilator ) . There was no significant difference between the NIPPV/conventional ventilator and the underwater bubble system . Conclusion : A variable flow NCPAP device may be more effective in treating AOP in preterm infants than a conventional ventilator in NIPPV mode . It remains unclear whether synchronised NIPPV would be even more effective Objective : Physiologic and pathologic comparison of two modes of assisted ventilation , nasal intermittent positive-pressure ventilation ( NIPPV ) and synchronized intermittent m and atory ventilation ( SIMV ) , in spontaneously breathing term newborn piglets with saline lavage-induced lung injury . Design : After inducing acute lung injury via repetitive saline lavage , piglets were r and omized to NIPPV ( n = 12 ) or SIMV ( n = 11 ) and treated for 6 hrs . Setting : Clinical laboratory . Subjects : Spontaneously breathing term newborn piglets . Interventions : Invasive ( SIMV ) or noninvasive ( NIPPV ) assisted ventilation for 6 hrs . Measurements : Physiologic parameters and arterial blood gases were continuously monitored . At the conclusion of the study , lung tissue was obtained to analyze for evidence of inflammation , including myeloperoxidase , interleukin-8 , and hydrogen peroxide levels , as well as for evidence of pathologic injury . Main Results : Piglets treated with NIPPV demonstrated higher arterial blood gas pH ( p < .001 ) , lower Paco2 ( p < .05 ) , and a lower set respiratory rate ( p < .0001 ) as compared with the SIMV-treated piglets . The piglets in the SIMV group had higher Pao2/Pao2 ratio than those in the NIPPV group ( p = .001 ) . There was significantly more interstitial inflammation ( p = .04 ) in the SIMV-treated piglets compared with the NIPPV-treated piglets . Total respiratory rate , heart rate , blood pressure , oxygen saturation , and biochemical markers of lung inflammation were not different between the groups . Conclusion : In surfactant-deficient term newborn piglets , NIPPV offers an effective and noninvasive ventilatory strategy with the potential for less pathologic lung inflammation BACKGROUND : Synchronized nasal intermittent positive-pressure ventilation ( SNIPPV ) use reduces reintubation rates compared with nasal continuous positive airway pressure ( NCPAP ) . Limited information is available on the outcomes of infants managed with SNIPPV . OBJECTIVES : To compare the outcomes of infants managed with SNIPPV ( postextubation or for apnea ) to infants not treated with SNIPPV at 2 sites . METHODS : Clinical retrospective data was used to evaluate the use of SNIPPV in infants ≤1250 g birth weight ( BW ) ; and 3 BW subgroups ( 500–750 , 751–1000 , and 1001–1250 g , decided a priori ) . SNIPPV was not assigned r and omly . Bronchopulmonary dysplasia ( BPD ) was defined as treatment with supplemental oxygen at 36 weeks ' postmenstrual age . RESULTS : Overall , infants who were treated with SNIPPV had significantly lower mean BW ( 863 vs 964 g ) and gestational age ( 26.4 vs 27.9 weeks ) , more frequently received surfactant ( 85 % vs 68 % ) , and had a higher incidence of BPD or death ( 39 % vs 27 % ) ( all P < .01 ) compared with infants treated with NCPAP . In the subgroup analysis , SNIPPV was associated with lower rates of BPD ( 43 % vs 67 % ; P = .03 ) and BPD/death ( 51 % vs 76 % ; P = .02 ) in the 500- to 750-g infants , with no significant differences in the other BW groups . Logistic regression analysis , adjusting for significant covariates , revealed infants with 500–700-g BW who received SNIPPV were significantly less likely to have the outcomes of BPD ( OR : 0.29 [ 95 % CI : 0.11–0.77 ] ; P = .01 ) , BPD/death ( OR : 0.30 [ 95 % CI : 0.11–0.79 ] ; P = .01 ) , neurodevelopmental impairment ( NDI ) ( OR : 0.29 [ 95 % CI : 0.09–0.94 ] ; P = .04 ) , and NDI/death ( OR : 0.18 [ 95 % CI : 0.05–0.62 ] ; P = .006 ) . CONCLUSION : SNIPPV use in infants at greatest risk of BPD or death ( 500–750 g ) was associated with decreased BPD , BPD/death , NDI , and NDI/death when compared with infants managed with NCPAP OBJECTIVE : To prospect ively compare the incidence of respiratory failure in premature infants r and omized to receive either nasopharyngeal continuous positive airway pressure ( NPCPAP ) or nasopharyngeal-synchronized intermittent m and atory ventilation ( NP-SIMV ) in the immediate postextubation period . STUDY DESIGN : This is a prospect i ve study of very low birth weight ( VLBW ) infants r and omized at the time of extubation to receive either NPCPAP or NP-SIMV in a university-based level III neonatal intensive care unit . Statistical analysis were performed with the Mann-Whitney U test for continuous and ordinal variables , and with the χ-squared test or Fisher ’s exact test for categorical variables . RESULTS : A total of 41 VLBW infants were studied ; 19 were in the NPCPAP group , and 22 were in the NP-SIMV group . Respiratory failure after extubation in the NP-SIMV group was significantly lower than in the NPCPAP group ( 5 % vs 37 % , respectively ) ( p = 0.016 ) . No statistically significant differences between groups with regard to demographics , severity of initial illness and associated complications , time to extubation , ventilatory management before extubation , weight , age , or nutritional status at the time of extubation were noted . CONCLUSION : NP-SIMV applied to VLBW infants upon extubation is more effective in preventing respiratory failure than NPCPAP BACKGROUND Nasal flow-synchronized intermittent positive pressure ventilation ( NFSIPPV ) is a new non-invasive ventilatory mode that delivers synchronized mechanical breaths through the nasal prongs . An unmasked , prospect i ve r and omized controlled trial was conducted to compare the efficacy of NFSIPPV and conventional nasal continuous positive airway pressure ( NCPAP ) in increasing the likelihood for successful extubation in very low-birthweight infants . METHODS Consecutive infants who weighed < 1251 g at birth , required endotracheal intubation within 48 h of birth and met specific predetermined criteria for extubation by day 14 of life were recruited . Each infant was r and omized to receive either NFSIPPV or NCPAP soon after extubation . Extubation was deemed successful if re-intubation was not needed for at least 72 h. Criteria for re-intubation were persistent severe respiratory acidosis ( arterial pH < 7.20 with pCO2 > 70 mmHg ) , severe recurrent apneic episodes not responding to increased ventilatory setting s and then requiring bag ventilation , and hypoxemia ( SaO2 < 90 % or pO2 < 60 mmHg with FiO2 > or = 0.70 ) . RESULTS There were no significant differences in clinical characteristics between the two groups at r and omization . Ninety-four percent ( 30/32 ) infants were successfully extubated to NFSIPPV but only 61 % ( 19/31 ) to conventional NCPAP ( P > 0.005 ) . Infants assigned to NCPAP failed extubation mainly because of apnea and hypercapnia , and those assigned to NFSIPPV because of hypoxia . Neither procedure induced major adverse effects . CONCLUSIONS NFSIPPV in the post-extubation period is safe and more effective than NCPAP in preventing re-ventilation OBJECTIVE To compare the efficacy of nasal synchronized intermittent m and atory ventilation ( nSIMV ) and nasal continuous positive airway pressure ( nCPAP ) in preterm infants with respiratory distress syndrome ( RDS ) . METHODS Fifty preterm infants with RDS who received pulmonary surfactant were r and omized to nSIMV and nCPAP groups after extubation . Clinical signs , symptoms and blood gas results following nSIMV or nCPAP were compared in the two groups . RESULTS Compared with the nCPAP group , the nSIMV group had a lower incidence of failure respiratory support ( 24 % vs 60 % ; P<0.05 ) , a lower incidence of hypercarbonia ( 12 % vs 40 % ; P<0.05 ) and a lower incidence of hypoxia ( 24 % vs 36 % ; P<0.05 ) . CONCLUSIONS nSIMV is more effective in respiratory support in preterm infants with RDS OBJECTIVE To evaluate whether nasal intermittent m and atory ventilation ( NIMV ) compared with nasal continuous positive airway pressure ( NCPAP ) would decrease the requirement for endotracheal ventilation in the treatment of respiratory distress syndrome ( RDS ) in preterm infants < 35 weeks . STUDY DESIGN R and omized , controlled , prospect i ve , single-center study . Forty-one infants were r and omized to NCPAP and 43 comparable infants to NIMV ( birth weight 1533 + /- 603 vs 1616 + /- 494 g , gestational age 30.6 + /- 3.0 vs 31.1 + /- 2.3 weeks , P = .5 , respectively ) . RESULTS Infants treated with NIMV and with NCPAP had comparable cardio-respiratory status at study entry . In the total cohort , infants treated initially with NIMV needed less endotracheal ventilation than infants treated with NCPAP ( 25 % vs 49 % , P < .05 ) with a similar trend in infants < 1500 g ; 31 % vs 62 % , P = . 06 ) . When controlling for weight and gestational age , NIMV was more successful in preventing endotracheal ventilation ( P < .05 ) . Infants treated with NIMV had a decreased incidence of bronchopulmonary dysplasia ( BPD ) compared with those treated with NCPAP ( 2 % vs 17 % , P < . 05 , in the total cohort and 5 % vs 33 % , P < . 05 , for infants < 1500 g ) . CONCLUSIONS NIMV compared with NCPAP decreased the requirement for endotracheal ventilation in premature infants with RDS . This was associated with a decreased incidence of BPD Objective . To determine whether noninvasive , nasal synchronized intermittent m and atory ventilation ( nSIMV ) improves the likelihood that very low birth weight infants will be successfully extubated . Methods . Infants of < 1251-g birth weight who were due to be extubated before 6 weeks of age were eligible once they were receiving < 35 % oxygen and were on a ventilator rate of < 18 breaths per minute ( bpm ) . Extubation was performed following intravenous loading with aminophylline , after a successful trial of 12 hours of endotracheal synchronized intermittent m and atory ventilation at a rate of 8 . Infants were r and omized to either nasal continuous positive airway pressure ( nCPAP ) at 6 cm H2O or nSIMV after extubation . nSIMV was commenced at a rate of 12 bpm with pressure on the ventilator set to achieve a delivered pressure of at least 12 cm H2O and a peak end expiratory pressure of 6 cm H2O . Continuous recording for diagnosis of apnea was performed for 72 hours after extubation . Objective criteria for failure of extubation were as follows : a Paco 2 > 70 ; Fio 2 > 0.7 ; or severe recurrent apnea ( > 2 apneas requiring intermittent positive-pressure ventilation in 24 hours or > 6 apneas > 20 seconds per day ) . The study ended after 72 hours postextubation or when infants satisfied failure criteria . A sample size of 54 was determined by power analysis . Results . Mean birth weight ( 831 st and ard deviation [ SD ] : 193 g ) and gestation ( 26.3 SD : 1.8 weeks ) did not differ between groups . Mean age at extubation was 7.6 ( SD : 9.7 ) days , range 1 to 40 days . The nSIMV group had a lower incidence of failed extubation 4/27 compared with the continuous positive airway pressure group , 12/27 . This was attributable to both a decreased incidence of apnea and a decreased incidence of hypercarbia . There was no increase in the incidence of abdominal distension or feeding intolerance . Discussion . nSIMV is effective in preventing extubation failure in very low birth weight infants in the first 72 hours after extubation . Noninvasive ventilation may have other roles in the care of the very low birth weight infant |
646 | 29,177,977 | This systematic review highlighted a number of key findings in 16 sporting activities .
Overall , NIRS information can be used as a marker of skeletal muscle oxidative capacity and for analyzing muscle performance factors . | Background Since the introduction ( in 2006 ) of commercially available portable wireless muscle oximeters , the use of muscle near-infrared spectroscopy ( NIRS ) technology is gaining in popularity as an application to observe changes in muscle metabolism and muscle oxygenation during and after exercise or training interventions in both laboratory and applied sports setting s. Objectives The objectives of this systematic review were to highlight the application of muscle oximetry in evaluating oxidative skeletal muscle performance to sport activities and emphasize how this technology has been applied to exercise and training . | Prior peripheral hypoxia induced via remote ischemic preconditioning ( IPC ) can improve physical performance in male athletes through improved O2 delivery and utilization . Since females may have an innate protective mechanism against ischemia-reperfusion injury , and since muscle metabolism during contraction differs between sexes , it is relevant to examine the impact of sex in response to IPC to determine whether it is also ergogenic in females . In a r and omized , crossover , single-blind study , we investigated muscle performance , hemodynamic and O2 uptake in strength-trained males ( n = 9 ) and females ( n = 8) performing five sets of 5 maximum voluntary knee extensions on an isokinetic dynamometer , preceded by either IPC ( 3 × 5-min ischemia/5-min reperfusion cycles at 200 mmHg ) or SHAM ( 20 mmHg ) . Changes in deoxy-hemoglobin ( Δ[HHb ] , expressed in percentage of arterial occlusion and considered an index of O2 extraction ) , and total hemoglobin ( Δ[THb ] ) concentrations of the vastus lateralis muscle were continuously monitored by near-infrared spectroscopy . The metabolic efficiency of the contractions was calculated as the average force/Δ[HHb]avg ratio . Cohen 's effect sizes ( ES ) ± 90 % confidence limits were used to estimate IPC-induced changes and sex differences . IPC increased total muscular force in males only ( 13.0 % , ES 0.64 , 0.37;0.90 ) , and this change was greater than in females ( 10.4 % difference , ES 0.40 , 0.10;0.70 ) . Percent force decrement was only attenuated in females ( −19.8 % , ES −0.38 , −0.77;0.01 ) , which was clearly different than males ( sex difference : ES 0.45 , −0.16;1.07 ) . IPC also induced different changes between sexes for average muscle O2 uptake in set 2 ( males : 6.4 % vs. females : −16.7 % , ES 0.21 , −0.18;0.60 ) , set 3 ( males : 7.0 % vs. females : −44.4 % , ES 0.56 , −0.17;1.29 ) , set 4 ( males : 9.1 % vs. females : −40.2 % , ES 0.51 , −0.10;1.13 ) , and set 5 ( males : 10.2 % vs. females : −40.4 % , ES 0.52 , −0.04;1.09 ) . However , metabolic efficiency was not meaningfully different between conditions and sexes . IPC increased muscle blood volume ( ↑[THb ] ) at rest and during recovery between sets , to the same extent in both sexes . Despite a similar IPC-induced initial increase in O2 delivery in both sexes , males displayed greater peripheral O2 extraction and greater strength enhancement . This ergogenic effect appears to be mediated in part via an up regulated oxidative function in males . We conclude that strength-trained males might benefit more from IPC than their female counterparts during repeated , maximal efforts The potential purpose of near‐infrared spectroscopy ( NIRS ) as a clinical application in patients with chronic heart failure ( CHF ) is the identification of limitations in O2 delivery or utilization during exercise . The objective of this study was to evaluate absolute and relative test – retest reliability of skeletal muscle oxygenation measurements in patients with CHF . Thirty patients with systolic heart failure ( left ventricular ejection fraction 31 ± 8 % ) performed 6‐min constant‐load cycling tests at 80 % of the anaerobic threshold ( AT ) with tissue saturation index ( TSI ) measurement at the vastus lateralis . Tests were repeated after 10 ± 5 days to evaluate reliability . Absolute reliability was assessed with limits of agreement ( LoA , expressed as bias ± r and om error ) and coefficients of variation ( CV ) for absolute values ( LoA range : 0·4 ± 6·2 % to 0·6 ± 7·9 % ; CV range : 4·7–7·1 % ) , amplitudes ( LoA range −0·5 ± 5·8 % to −0·7 ± 6·8 % ; CV range : 26·2–42·1 % ) , onset and recovery kinetics ( mean response times ; LoA 0·4 ± 9·5 s , CV 23·5 % and LoA −5·8 ± 50·8 s , CV 67·4 % respectively ) and overshoot characteristics ( CV range 45·7–208·6 % ) . Relative reliability was assessed with intraclass correlation coefficients for absolute values ( range 0·74–0·90 ) , amplitudes ( range 0·85–0·92 ) , onset and recovery kinetics ( 0·53 and 0·51 , respectively ) and overshoot characteristics ( range 0·17–0·74 ) . In conclusion , absolute reliability of absolute values and onset kinetics seems acceptable for serial within‐subject comparison , and as such , for evaluation of treatment effects . Absolute reliability of amplitudes and recovery kinetics is considered unsatisfactory . Relative reliability of absolute values and amplitudes is sufficient for purpose s of physiological distinction between patients with CHF . Despite lower relative reliability , kinetics may still be useful for clinical application This study examined the effects of Sprint Interval Cycling ( SIT ) on muscle oxygenation kinetics and performance during the 30 - 15 intermittent fitness test ( IFT ) . Twenty-five women hockey players of Olympic st and ard were r and omly selected into an experimental group ( EXP ) and a control group ( CON ) . The EXP group performed six additional SIT sessions over six weeks in addition to their normal training program . To explore the potential training-induced change , EXP subjects additionally completed 5 x 30s maximal intensity cycle testing before and after training . During these tests near-infrared spectroscopy ( NIRS ) measured parameters ; oxyhaemoglobin + oxymyoglobin ( HbO2 + MbO2 ) , tissue deoxyhaemoglobin + deoxymyoglobin ( HHb+HMb ) , total tissue haemoglobin ( tHb ) and tissue oxygenation ( TSI % ) were taken . In the EXP group ( 5.34±0.14 to 5.50±0.14m.s-1 ) but not the CON group ( pre = 5.37±0.27 to 5.39±0.30m.s-1 ) significant changes were seen in the 30 - 15IFT performance . EXP group also displayed significant post-training increases during the sprint cycling : ΔTSI ( −7.59±0.91 to −12.16±2.70 % ) ; ΔHHb+HMb ( 35.68±6.67 to 69.44±26.48μM.cm ) ; and ΔHbO2 + MbO2 ( −74.29±13.82 to −109.36±22.61μM.cm ) . No significant differences were seen in ΔtHb ( −45.81±15.23 to −42.93±16.24 ) . NIRS is able to detect positive peripheral muscle oxygenation changes when used during a SIT protocol which has been shown to be an effective training modality within elite athletes Introduction : The aim of this study was to determine whether calf compression sleeves ( CS ) affects physiological and biomechanical parameters , exercise performance , and perceived sensations of muscle fatigue , pain and soreness during prolonged ( ~2 h 30 min ) outdoor trail running . Methods : Fourteen healthy trained males took part in a r and omized , cross-over study consisting in two identical 24-km trail running sessions ( each including one bout of running at constant rate on moderately flat terrain , and one period of all-out running on hilly terrain ) wearing either degressive CS ( 23 ± 2 mmHg ) or control sleeves ( CON , < 4 mmHg ) . Running time , heart rate and muscle oxygenation of the medial gastrocnemius muscle ( measured using portable near-infrared spectroscopy ) were monitored continuously . Muscle functional capabilities ( power , stiffness ) were determined using 20 s of maximal hopping before and after both sessions . Running biomechanics ( kinematics , vertical and leg stiffness ) were determined at 12 km·h−1 at the beginning , during , and at the end of both sessions . Exercise-induced Achilles tendon pain and delayed onset calf muscles soreness ( DOMS ) were assessed using visual analog scales . Results : Muscle oxygenation increased significantly in CS compared to CON at baseline and immediately after exercise ( p < 0.05 ) , without any difference in deoxygenation kinetics during the run , and without any significant change in run times . Wearing CS was associated with ( i ) higher aerial time and leg stiffness in running at constant rate , ( ii ) with lower ground contact time , higher leg stiffness , and higher vertical stiffness in all-out running , and ( iii ) with lower ground contact time in hopping . Significant DOMS were induced in both CS and CON ( > 6 on a 10-cm scale ) with no difference between conditions . However , Achilles tendon pain was significantly lower after the trial in CS than CON ( p < 0.05 ) . Discussion : Calf compression did not modify muscle oxygenation during ~2 h 30 of trail running but significantly changed running biomechanics and lower limb muscle functional capabilities toward a more dynamic behavior compared to control session . However , wearing compression sleeves did not affect performance and exercise-induced DOMS , while it minimized Achilles tendon pain immediately after running The effects of intermittent hypoxic exposure ( IHE ) on cerebral and muscle oxygenation , arterial oxygen saturation ( SaO2 ) , and respiratory gas exchange during a 20-km cycle time trial ( 20TT ) were examined ( n=9 ) in a placebo-controlled r and omized design . IHE ( 7:3 min hypoxia to normoxia ) involved 90-min sessions for 10 days , with SaO2 clamped at ~80 % . Prior to , and 2 days after the intervention , a 20TT was performed . During the final minute of the 20TT , in the IHE group only , muscle oxyhemoglobin ( oxy-Hb ) was elevated ( mean+/-95 % confidence interval 1.3+/-1.2 ΔmicroM , p=0.04 ) , whereas cerebral oxy-Hb was reduced ( -1.9%+/-1.0 % , p<0.01 ) post intervention compared with baseline . The 20TT performance was unchanged between groups ( p=0.7 ) . In the IHE group , SaO2 was higher ( 1.0+/-0.7Δ% , p=0.006 ) and end-tidal PCO2 was lower ( -1.2+/-0.1 mm Hg , p=0.01 ) during the final stage of the 20TT post intervention compared with baseline . In summary , reductions in muscle oxy-Hb and systemic SaO2 occurring at exercise intensities close to maximal at the end of a 20TT were offset by IHE , although this was not translated into improved performance Abstract In this study , we wished to determine whether the observed reduction in quadriceps muscle oxygen availability , reported during repetitive bouts of isometric exercise in simulated sailing efforts ( i.e. hiking ) , is because of restricted muscle blood flow . Six national-squad Laser sailors initially performed three successive 3-min hiking bouts followed by three successive 3-min cycling tests sustained at constant intensities reproducing the cardiac output recorded during each of the three hiking bouts . The blood flow index ( BFI ) was determined from assessment of the vastus lateralis using near-infrared spectroscopy in association with the light-absorbing tracer indocyanine green dye , while cardiac output was determined from impedance cardiography . At equivalent cardiac outputs ( ranging from 10.3±0.5 to 14.8±0.86 L · min−1 ) , the increase from baseline in vastus lateralis BFI across the three hiking bouts ( from 1.1±0.2 to 3.1±0.6 nM · s−1 ) was lower ( P = 0.036 ) than that seen during the three cycling bouts ( from 1.1±0.2 to 7.2±1.4 nM · s−1 ) ( Cohen 's d : 3.80 nM · s−1 ) , whereas the increase from baseline in deoxygenated haemoglobin ( by ∼17.0±2.9 μM ) ( an index of tissue oxygen extraction ) was greater ( P = 0.006 ) during hiking than cycling ( by ∼5.3±2.7 μM ) ( Cohen 's d : 4.17 μM ) . The results suggest that reduced vastus lateralis muscle oxygen availability during hiking arises from restricted muscle blood flow in the isometrically acting quadriceps muscles Muscle ischemia and reperfusion induced by ischemic preconditioning ( IPC ) can improve performance in various activities . However , the underlying mechanisms are still poorly understood . The purpose of this study was to examine the effects of IPC on muscle hemodynamics and oxygen ( O2 ) uptake during repeated maximal contractions . In a cross-over , r and omized , single-blind study , 10 strength-trained men performed 5 sets of 5 maximal voluntary knee extensions of the right leg on an isokinetic dynamometer , preceded by either IPC of the right lower limb ( 3 × 5-min compression/5-min reperfusion cycles at 200 mm Hg ) or sham ( 20 mm Hg ) . Changes in deoxyhemoglobin , expressed as a percentage of arterial occlusion , and total hemoglobin ( [ THb ] ) concentrations of the vastus lateralis muscle were monitored continuously by near-infrared spectroscopy . Differences between IPC and sham were analyzed using Cohen 's effect size ( ES ) ± 90 % confidence limits , and magnitude-based inferences . Compared with sham , IPC likely increased muscle blood volume at rest ( ↑[THb ] , 46.5 % ; ES , 0.56 ; 90 % confidence limits for ES , -0.21 , 1.32 ) . During exercise , peak force was almost certainly higher ( 11.8 % ; ES , 0.37 ; 0.27 , 0.47 ) , average force was very likely higher ( 12.6 % ; ES , 0.47 ; 0.29 , 0.66 ) , and average muscle O2 uptake was possibly increased ( 15.8 % ; ES , 0.36 ; -0.07 , 0.79 ) after IPC . In the recovery periods between contractions , IPC also increased blood volume after sets 1 ( 23.6 % ; ES , 0.30 ; -0.05 , 0.65 ) and 5 ( 25.1 % ; ES , 0.32 ; 0.09 , 0.55 ) . Three cycles of IPC immediately increased muscle perfusion and O2 uptake , conducive to higher repeated force capacity in strength-trained athletes . This maneuver therefore appears relevant to enhancing exercise training stimulus Abstract While the effect of lower body compression garments on performance and physiological responses are well documented , no studies have examined the effect of upper body compression garments ( UBCG ) on upper-body dominant exercise . This study examined the effects of wearing UBCG on performance and physiological responses during simulated flat-water kayaking . Five male ( mean values±s : 21.8±2.8 years ; 83.5±9.2 kg ; 63.0±5.5 ml·kg−1·min−1 ) and two female ( mean values±s : 25.0±4.2 years ; 71.4±2.7 kg ; 51.0±4.8 ml·kg-1·min-1 ) elite flat-water kayakers completed a six-step incremental test followed by a four-minute maximal performance test ( 4minPT ) in both UBCG and control ( no shirt or sports training bra ) conditions in a r and omized counter-balanced order . Heart rate and oxygen consumption ( O2 ) as well as performance measures ( power , distance covered , stroke rate ) were recorded during the tests , and blood lactate was measured immediately after each incremental step and three minutes following the 4minPT . Near-infrared spectroscopy-derived measures of blood flow and oxygenation of the flexor carpi radialis were monitored continuously for all tests . No significant differences between the UBCG and control conditions were evident for any performance , cardiorespiratory or oxygenation measure across the incremental step test and 4minPT . It was concluded that wearing UBCG did not provide any significant physiological or performance benefits during simulated flat-water kayaking The objective of this study was to test how low-frequency electrical stimulation ( LFES ; Veinoplus Sport ( AdRem Technology , Paris , France ) ) of the calf muscles affects recovery indices compared with 2 other commonly used recovery methods ( active , ACT ; passive , PAS ) . The tests used assessed predominantly anaerobic performance after short-term ( 15 min ) recovery , and the kinetics of blood markers . Fourteen highly trained female h and ball players completed 2 Yo-Yo Intermittent Recovery tests ( level 2 ; YYIR2 ) separated by a 15-min recovery period . During recovery , 1 of 3 recovery methods ( ACT , LFES or PAS ) was r and omly selected . Performance ( i.e. , distance run ) was measured at the end of each YYIR2 test . Blood lactate , pH , bicarbonate concentrations , heart rate , respiratory gas exchange and tissue saturation index for the lateral gastrocnemius were recorded . LFES showed a very likely beneficial effect on performance during the second YYIR2 relative to PAS and a possible beneficial effect relative to ACT ( distance Pre vs. Post ; LFES : -1.8 % ; ACT : -7.6 % ; PAS : -15.9 % ) . Compared with PAS recovery , LFES and ACT recovery clearly showed a faster return to baseline for blood lactate , pH and bicarbonate concentrations during the recovery period . LFES of the calf muscles and , to a lesser extent , ACT recovery appear to effectively improve short-term recovery between 2 bouts of exhausting exercises . These methods could be of benefit if applied during half-time , for sports involving successive rounds , or where only a limited recovery period is available |
647 | 27,049,603 | Reported relationships were facilitated by healthcare professionals , social supporters , motivation and encouragement , reduced fear and seeing benefits and hindered by changing physical health , environment , lack of motivation , fear and social isolation .
The associations between increased levels of PA and quality of life , respiratory function and dyspnoea are largely based on 6MWD and PA question naires .
Initial benefits from PR decline after program completion .
Following PR , increased levels of physical activity in people with COPD undertaking exercise maintenance programmes are positively related with improvements in exercise capacity , quality of life and dyspnoea . | AIM To investigate the relationship between physical activity ( PA ) and measures of health-related quality of life ( HRQoL ) and hospital admissions in people with chronic obstructive pulmonary disease ( COPD ) following pulmonary rehabilitation ( PR ) . | In recent years quality of life instruments have been featured as primary outcomes in many r and omized trials . One of the challenges facing the investigator using such measures is determining the significance of any differences observed , and communicating that significance to clinicians who will be applying the trial results . We have developed an approach to elucidating the significance of changes in score in quality of life instruments by comparing them to global ratings of change . Using this approach we have established a plausible range within which the minimal clinical ly important difference ( MCID ) falls . In three studies in which instruments measuring dyspnea , fatigue , and emotional function in patients with chronic heart and lung disease were applied the MCID was represented by mean change in score of approximately 0.5 per item , when responses were presented on a seven point Likert scale . Furthermore , we have established ranges for changes in question naire scores that correspond to moderate and large changes in the domains of interest . This information will be useful in interpreting question naire scores , both in individuals and in groups of patients participating in controlled trials , and in the planning of new trials STUDY OBJECTIVES The purpose s of this study were as follows : ( 1 ) to determine whether physical performance , quality of life , and dyspnea with activities of daily living improved following both short-term and long-term pulmonary rehabilitation ( PR ) across multiple hospital outpatient programs ; ( 2 ) to examine the differences in these parameters between men and women ; and ( 3 ) to determine what relationships existed between the psychosocial parameters and the results of the 6-min walk ( 6MW ) test performance across programs . DESIGN Non-experimental , prospect i ve , and comparative . SETTING Seven outpatient hospital PR programs from urban and rural setting s across North Carolina . PARTICIPANTS Three hundred nine women and 281 men who were 20 to 93 years of age ( mean [ + /- SD ] age , 66.7 + /- 11.1 years ) with chronic lung disease . INTERVENTIONS All 6MW tests and health surveys were administered prior to and immediately following 12 and 24 weeks of supervised PR participation . Scores from the 6MW tests , the Ferrans and Powers quality of life index-pulmonary version III ( QLI ) , the Medical Outcomes Study 36-item short form ( SF-36 ) , and the University of California at San Diego shortness of breath question naire ( SOBQ ) were compared at PR entry , at 12 weeks , and at 24 weeks for differences by gender with repeated- measures analysis of variance . The study entry and follow-up SF-36 physical and mental component summary scores , the QLI health/function and overall scores , and the SOBQ scores were also compared to the 6MW test scores with Pearson correlation coefficient analysis . RESULTS The mean summary scores on the SF-36 and the QLI increased after 12 weeks of PR ( p < 0.05 ) , and improvements were maintained by 24 weeks of PR participation ( p < 0.05 ) . Scores on the SOBQ improved after 12 weeks ( p < 0.001 ) among the short-term participants , but not until after 24 weeks among the long-term participants ( p = 0.009 ) . The 6MW test performance improved after 12 weeks ( p < 0.001 ) and again from 12 to 24 weeks ( p = 0.002 ) in the long-term participants . No relevant correlational relationships were found between 6MW scores and the summary scores of the administered surveys ( r = -0.43 to 0.36 ) . CONCLUSIONS Physical performance , as measured by the 6MW test , continued to improve with up to 24 weeks of PR participation . Quality -of-life measures and the perception of dyspnea improved after 12 weeks of PR participation , with improvements maintained by 24 weeks of PR participation . It is recommended that PR patients participate in supervised PR for at least 24 weeks to gain and maintain optimal health benefits The purpose of this study was to investigate the effects on activities of daily living , quality of life , and exercise tolerance of a comprehensive out-patient rehabilitation programme for patients with moderate-to-severe chronic obstructive pulmonary disease . In this r and omized and controlled trial , the main outcome measures were Activities of Daily Living ( ADL ) score , York Quality of Life Question naire ( YQLQ ) score , Chronic Respiratory Disease Question naire ( CRDQ ) score , 6 min walking distance ( 6MWD ) , forced expiratory volume in one second ( FEV1 ) , and forced vital capacity ( FVC ) . The rehabilitation programme included physical training , occupational therapy , education , and smoking cessation therapy , and lasted for 12 weeks . The patients were evaluated at entry , halfway through , and at the end of the programme . Follow-up was at 24 weeks . Forty seven patients were recruited , and 16 in each group completed the trial . There were significant differences in the improvements in ADL and CRDQ between the control and the treatment groups at 12 and 24 weeks , and at 24 weeks , respectively . At 6 , 12 and 24 weeks , improvements in the 6MWD were 21.6 versus 79.8 , 36.1 versus 113.1 and 21.4 versus 96.2 for control and treatment groups , respectively ( p<0.004 ) . A correlation matrix showed only ADL and 6MWD to be significantly correlated ; the matrix was also used to vali date the translated question naires . The programme required 124 staff-hours in total . An inexpensive , comprehensive out-patient rehabilitation programme can produce long-term improvement in activities of daily living , quality of life , and exercise tolerance in patients with moderate-to-severe chronic obstructive pulmonary disease Maintenance of physical activity following pulmonary rehabilitation remains a challenge for patients with chronic obstructive pulmonary disease ( COPD ) . The objectives of this study were to identify patterns of endurance activity after completion of pulmonary rehabilitation and to characterise people who succeed and those who have difficulty maintaining endurance activity . In a longitudinal study embedded within a r and omised clinical trial , 206 individuals with COPD underwent a 3-month pulmonary rehabilitation programme . Weekly duration of endurance activity was assessed at 4 , 6 , 8 and 12 months after the start of rehabilitation . Trajectory modelling was used to determine the most common patterns of activity during the post-rehabilitation phase from 4–12 months . Three distinct patterns were identified , two of which indicated difficulty in maintaining endurance activity : 61 individuals reported a high activity level at 4 months ( 2.7 h·week−1 ) and stayed high ; 114 individuals started at a low activity level ( mean 1.0 h·week−1 ) and stayed low ; and 31 individuals started high ( 3.0 h·week−1 ) and declined . The low activity group was characterised by more severe disease and greater respiratory impairment . The high and declined group had less severe disease and respiratory impairment , but reported greater barriers to exercise . Pulmonary rehabilitation should include interventions aim ed at minimising barriers , in order to induce long-term behaviour change 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 The aim of this study was to evaluate the short-term benefits of a pulmonary rehabilitation program in chronic obstructive pulmonary disease ( COPD ) patients . The study was a r and omized controlled trial that included 54 mild and moderate COPD patients . Patients were assigned to either an 8-week-long pulmonary rehabilitation program , which consisted of exercise plus education ( rehabilitation group ) , or were controls . All the patients were evaluated at baseline at the completion of the 8th week of the program and one month after the completion of the pulmonary rehabilitation program using five instruments : arterial blood gas analysis , postbronchodilator pulmonary function test , 6-minute walk test ( 6MWT ) , Saint George Respiratory Question naire ( SGRQ ) , and the dyspnea visual analog scale ( VAS ) There were no statistically significant differences in the pulmonary functions and pulmonary gas analysis between baseline , discharge ( 8th week ) , and the 12th-week visit in both groups ( p > 0.05 ) . Rehabilitation result ed in significant improvements in both the VAS and the 6MWT at the 8th week , but by the 12th week all of these improvements had deteriorated . All of the SGRQ domains improved both at the 8th and the 12th week , with a significant difference between the groups ( p < 0.05 ) . We conclude that rehabilitation result ed in improvements in exercise capacity , health status , and dyspnea . All of these benefits , however , tend to deteriorate in the first month after rehabilitation . Therefore , it is strongly recommended that all patients with COPD be kept motivated in order to continue with rehabilitation and maintain the benefits gained UNLABELLED The central purpose of pulmonary rehabilitation is to reduce morbidity by improving functional capacity through exercise . It is still unknown if improvements in functional capacity are maintained in the long-term and if this leads to increased physical activity levels as measured by a free-living activity monitor . The hypothesis of this study was that pulmonary rehabilitation would lead to a sustained increase in st and ard outcome measures and in daily physical activity . METHODS A prospect i ve study of 47 subjects with COPD was performed , registered at Clinical Trials.gov ( Clinical Trial Number NCT 0112943 ) . The primary outcome was a maintained improvement in st and ard outcome measures with a secondary aim of an increase in daily physical activity . A convenient sample of the cohort ( n = 17 ) was re-evaluated at a third time point at 1 year . RESULTS A seven week hospital based outpatient pulmonary rehabilitation program led to a significant reduction in total energy expenditure ( p < 0.044 ) and breathlessness ( Borg , p < 0.011 ) and improved exercise capacity ( ISWT , p > 0.001 , 6MWT , p > 0.002 ) PiMax ( p > 0.007 ) and quality of life scores ( SGRQ , p > 0.001 , EQ5D , 0.025 ) . However , pulmonary rehabilitation did not significantly change the average number of daily steps taken , time spent sedentary activity , METs consumed or daily physical activity . Indeed , all of the st and ard and freeliving values had returned towards the baseline value at 1 year . DISCUSSION These findings show that while pulmonary rehabilitation increased exercise capacity this was not transmitted into increased daily physical activity . Hence , alternative methods to alter/affect behavioural change need to be addressed OBJECTIVE To establish the minimal important difference ( MID ) for the six-minute walk distance ( 6MWD ) in persons with chronic obstructive pulmonary disease ( COPD ) . DESIGN Analysis of data from an observational study using distribution- and anchor-based methods to determine the MID in 6MWD . SETTING Outpatient pulmonary rehabilitation program at 2 teaching hospitals . PARTICIPANTS Seventy-five patients with COPD ( 44 men ) in a stable clinical state with mean age 70 years ( SD 9 y ) , forced expiratory volume in one second 52 % ( SD 21 % ) predicted and baseline walking distance 359 meters ( SD 104 m ) . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Participants completed the six-minute walk test before and after a 7-week pulmonary rehabilitation program . Participants and clinicians completed a global rating of change score while blinded to the change in 6MWD . RESULTS The mean change in 6MWD in participants who reported themselves to be unchanged was 17.7 meters , compared with 60.2 meters in those who reported small change and 78.4 meters in those who reported substantial change ( P=.004 ) . Anchor-based methods identified an MID of 25 meters ( 95 % confidence interval 20 - 61 m ) . There was excellent agreement with distribution-based methods ( 25.5 - 26.5 m , kappa=.95 ) . A change in 6MWD of 14 % compared with baseline also represented a clinical ly important effect ; this threshold was less sensitive than for absolute change ( sensitivity .70 vs .85 ) . CONCLUSIONS The MID for 6MWD in COPD is 25 meters . Absolute change in 6MWD is a more sensitive indicator than percentage change from baseline . These data support the use of 6MWD as a patient-important outcome in research and clinical practice The outcomes of quantitative investigations examining the effectiveness of exercise interventions for people with COPD are limited by the small number of measurement tools that can be included . In contrast , qualitative inquiry allows broader exploration of the perceived outcomes of an intervention . The purpose of this investigation is to explore the qualitative outcomes of a progressive resistance exercise ( PRE ) program for people with COPD . People with COPD , enrolled in a r and omized controlled trial of PRE , were invited to participate in two semi-structured interviews conducted at the end ( 12 weeks ) and 12 weeks after the training intervention ( 24 weeks ) . Interviews were audiotaped , transcribed and then coded independently by two research ers . Themes relating to training outcomes were then developed and described . Twenty-two participants were interviewed at 12 weeks , and 19 participants at 24 weeks . After PRE , participants reported a range of physical gains , particularly with regard to improved strength and reduced breathlessness during daily activities . Improved control and confidence during activities of daily living were important psychological benefits perceived by people with COPD , as was the social support experienced during group training sessions . At 24 weeks , confidence persisted despite a perceived plateau or dissipation of physical gains . People with COPD reported physical , psychological and social benefits after PRE , which had a positive effect on activity performance . Although the perceived physical benefits of training were not prominent at 24 weeks , feelings of increased confidence and control persisted . Chronic Respiratory Disease 2007 ; 4 : OBJECTIVE To assess whether language of publication restrictions impact the estimates of an intervention 's effectiveness , whether such impact is similar for conventional medicine and complementary medicine interventions , and whether the results are influenced by publication bias and statistical heterogeneity . STUDY DESIGN AND SETTING We set out to examine the extent to which including reports of r and omized controlled trials ( RCTs ) in language s other than English ( LOE ) influences the results of systematic review s , using a broad data set of 42 language -inclusive systematic review s , involving 662 RCTs , including both conventional medicine ( CM ) and complementary and alternative medicine ( CAM ) interventions . RESULTS For CM interventions , language -restricted systematic review s , compared with language -inclusive ones , did not introduce biased results , in terms of estimates of intervention effectiveness ( r and om effects ration of odds rations ROR=1.02 ; 95 % CI=0.83 - 1.26 ) . For CAM interventions , however , language -restricted systematic review s result ed in a 63 % smaller protective effect estimate than language -inclusive review s ( r and om effects ROR=1.63 ; 95 % CI=1.03 - 2.60 ) . CONCLUSION Language restrictions do not change the results of CM systematic review s but do substantially alter the results of CAM systematic review s. These findings are robust even after sensitivity analyses , and do not appear to be influenced by statistical heterogeneity and publication bias BACKGROUND Some r and omised controlled trials ( RCTs ) done in German-speaking Europe are published in international English- language journals and others in national German- language journals . We assessed whether authors are more likely to report trials with statistically significant results in English than in German . METHODS We studied pairs of RCT reports , matched for first author and time of publication , with one report published in German and the other in English . Pairs were identified from reports round in a manual search of five leading German- language journals and from reports published by the same authors in English found on Medline . Quality of methods and reporting were assessed with two different scales by two investigators who were unaware of authors ' identities , affiliations , and other characteristics of trial reports . Main study endpoints were selected by two investigators who were unaware of trial results . Our main outcome was the number of pairs of studies in which the levels of significance ( shown by p values ) were discordant . FINDINGS 62 eligible pairs of reports were identified but 19 ( 31 % ) were excluded because they were duplicate publications . A further three pairs ( 5 % ) were excluded because no p values were given . The remaining 40 pairs were analysed . Design characteristics and quality features were similar for reports in both language s. Only 35 % of German- language articles , compared with 62 % of English- language articles , reported significant ( p < 0.05 ) differences in the main endpoint between study and control groups ( p = 0.002 by McNemar 's test ) . Logistic regression showed that the only characteristic that predicted publication in an English- language journal was a significant result . The odds ratio for publication of trials with significant results in English was 3.75 ( 95 % CI 1.25 - 11.3 ) . INTERPRETATION Authors were more likely to publish RCTs in an English- language journal if the results were statistically significant . English language bias may , therefore , be introduced in review s and meta-analyses if they include only trials reported in English . The effort of the Cochrane Collaboration to identify as many controlled trials as possible , through the manual search of many medical journals published in different language s will help to reduce such bias |
648 | 26,952,020 | Transient elastography is a noninvasive imaging modality with excellent ability to assess for cirrhosis in patients with HIV-HCV coinfection | BACKGROUND AND AIM Patients with HIV-hepatitis C virus ( HCV ) coinfection progress towards liver fibrosis and cirrhosis more rapidly compared with HCV mono-infected individuals .
This necessitates an accurate assessment of liver stiffness with transient elastography to guide treatment . | UNLABELLED Human immunodeficiency virus (HIV)/hepatitis C virus ( HCV ) coinfection is associated with progressive liver disease . However , the rate of progression is variable and the ability to differentiate patients with stable versus progressive HCV disease is limited . The objective of this study was to assess the incidence of and risk factors for fibrosis progression in a prospect i ve cohort of coinfected patients . Overall , 435 liver biopsy pairs from 282 patients without cirrhosis were analyzed . Biopsies were scored according to the METAVIR system by a single pathologist blind to biopsy sequence . Fibrosis progression was defined as an increase of at least one METAVIR fibrosis stage between paired biopsies . The majority of patients were African American ( 84.8 % ) , male ( 67.7 % ) , and infected with HCV genotype 1 ( 93.4 % ) . On initial biopsy , no or minimal fibrosis was identified in 243 patients ( 86 % ) . The median interval between biopsies was 2.5 years . Fibrosis progression was observed in 97 of 282 ( 34 % ) patients and 149 of 435 ( 34 % ) biopsy pairs . After adjustment , greater body mass index ( adjusted odds ratio [ aOR ] : 1.04 per 1 unit increase ) , diabetes ( aOR : 1.56 ) , and hepatic steatosis ( aOR : 1.78 ) at the time of initial biopsy were marginally associated with subsequent fibrosis progression . Between biopsies , elevated serum aspartate and alanine aminotransferase ( AST , ALT ) ( aOR AST : 3.34 , ALT : 2.18 for > 25 % values > 100 U/L versus < 25 % values > 100 U/L ) were strongly associated with fibrosis progression . CONCLUSION Fibrosis progression is common among HIV/HCV coinfected patients ; these data suggest that progression can be rapid . Persistent elevations in serum transaminase levels may serve as important noninvasive markers to identify subsets of patients who are more likely to progress and thus warrant closer monitoring and consideration of HCV treatment BACKGROUND FibroTest , a noninvasive method of measuring biomarkers of liver fibrosis , is an alternative to liver biopsy for determining the severity of chronic hepatitis C virus ( HCV ) infection . We compared the 5-year prognostic value of the FibroTest with biopsy staging for predicting cirrhosis decompensation and survival in patients with chronic HCV infection . METHODS Fibrosis stage was assessed on the same day by FibroTest and biopsy in a prospect i ve cohort of 537 patients . Disease classification at baseline was 157 patients with severe fibrosis ( FibroTest > 0.58 ) , 137 with moderate fibrosis ( FibroTest 0.32 - 0.58 ) , and 243 with no or minimal fibrosis ( FibroTest < 0.32 ) . RESULTS In 64 untreated patients with severe fibrosis , survival without HCV complications was 73 % [ 95 % confidence interval ( CI ) , 59%-086 % ; 13 complications ] , and survival without HCV-related death was 85 % ( 95 % CI , 73%-96 % ; 7 HCV deaths ) . Survival rates were higher in patients with moderate fibrosis , [ 99 % ( 95 % CI , 97%-100 % ; 1 complication ; P < 0.001 ) and 100 % ( no HCV death ; P < 0.001 ) for patients with and without HCV-related complications , respectively ] , and in patients with minimal fibrosis [ 100 % ( no complication ; P < 0.001 vs severe ) and 100 % ( no HCV death ; P < 0.001 vs severe ) , respectively ] . FibroTest was a better predictor than biopsy staging for HCV complications , with area under the ROC curves ( AUROC ) = 0.96 ( 95 % CI , 0.93%-0.97 % ) vs 0.91 ( 95 % CI , 0.85%-0.94 % ; P = 0.01 ) , respectively ; it was also a better predictor for HCV deaths : AUROC = 0.96 ( 95 % CI , 0.93%-0.98 % ) vs 0.87 ( 95 % CI , 0.70%-0.94 % ; P = 0.046 ) , respectively . The prognostic value of FibroTest was still significant ( P < 0.001 ) in multivariate analyses after taking into account histology , treatment , alcohol consumption , and HIV coinfection . CONCLUSION The FibroTest measurement of HCV biomarkers has a 5-year prognostic value similar to that of liver biopsy IMPORTANCE Patients co-infected with human immunodeficiency virus ( HIV ) and hepatitis C virus ( HCV ) are at high risk for liver disease progression . However , interferon-based treatments for HCV infection have significant toxicities , limiting treatment uptake . OBJECTIVE To assess the all-oral 3 direct-acting antiviral ( 3D ) regimen of ombitasvir , paritaprevir ( co-dosed with ritonavir [ paritaprevir/r ] ) , dasabuvir , and ribavirin in HCV genotype 1-infected adults with HIV-1 co-infection , including patients with cirrhosis . DESIGN , SETTING , AND PARTICIPANTS TURQUOISE-I is a r and omized , open-label study . Part 1a of this pilot study was conducted at 17 sites in the United States and Puerto Rico between September 2013 and August 2014 and included 63 patients with HCV genotype 1 and HIV-1 co-infection who were HCV treatment-naive or had history of prior treatment failure with peginterferon plus ribavirin therapy . The study allowed enrollment of patients , including those with cirrhosis , with a CD4 + count of 200/mm3 or greater or CD4 + percentage of 14 % or more and plasma HIV-1 RNA suppressed while taking a stable atazanavir- or raltegravir-inclusive antiretroviral regimen . INTERVENTIONS Ombitasvir/paritaprevir/r , dasabuvir , and ribavirin for 12 or 24 weeks of treatment as r and omized . MAIN OUTCOMES AND MEASURES The primary assessment was the proportion of patients with sustained virologic response ( HCV RNA < 25 IU/mL ) at posttreatment week 12 ( SVR12 ) . RESULTS Among patients receiving 12 or 24 weeks of 3D and ribavirin , SVR12 was achieved by 29 of 31 ( 94 % ; 95 % CI , 79%-98 % ) and 29 of 32 patients ( 91 % ; 95 % CI , 76%-97 % ) , respectively . Of the 5 patients who did not achieve SVR , 1 withdrew consent , 2 had confirmed virologic relapse or breakthrough , and 2 patients had clinical history and phylogenetic evidence consistent with HCV reinfection . The most common treatment-emergent adverse events were fatigue ( 48 % ) , insomnia ( 19 % ) , nausea ( 18 % ) , and headache ( 16 % ) . Adverse events were generally mild , with none reported as serious or leading to discontinuation . No patient had a confirmed HIV-1 breakthrough of 200 copies/mL or greater during treatment . CONCLUSIONS AND RELEVANCE In this open-label , r and omized uncontrolled study , treatment with the all-oral , interferon-free 3D-plus-ribavirin regimen result ed in high SVR rates among patients co-infected with HCV genotype 1 and HIV-1 whether treated for 12 or 24 weeks . Further phase 3 studies of this regimen are warranted in patients with co-infection . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01939197 BACKGROUND / AIMS To examine if serum fibrosis biomarkers could accurately identify the stage of liver disease amongst hepatitis C ( HCV ) and HIV co-infected patients . METHODS One hundred and thirty seven HIV/HCV co-infected persons were r and omly selected from the Johns Hopkins HIV Clinic cohort . Ninety five had complete testing for fibrosis markers in sera collected at the time of liver biopsy . Biopsies were scored according to Ishak modified histological activity index ( F0 no fibrosis to F6 cirrhosis ) . Fibrosis was evaluated against alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) , AST to platelet ratio ( APRI ) , albumin , total bilirubin , hyaluronic acid ( HA ) and YKL-40 . RESULTS Sixty nine ( 73 % ) had no or minimal portal fibrosis ( F0 - 2 ) and were compared with remaining subjects ( F3 - 6 ) . Fibrosis scores > or = F3 were found 27 times more often in persons with HA levels > 86 ng/ml and 5.5 times more often in persons with HA levels 41 - 86 ng/ml . Less substantial associations were detected with levels of albumin < 3.5 g/dl ( OR 4.85 ) and AST > 60 iu ( OR 5.91 ) . All 35 subjects who had favorable results of HA , albumin , and AST had minimal fibrosis ( F0 - 2 ) . CONCLUSIONS Amongst HIV/HCV co-infected patients , serum testing for HA , albumin , and AST ( SHASTA Index ) was able to accurately stage mild and advanced fibrosis Liver biopsy remains the gold st and ard in the assessment of severity of liver disease . Noninvasive tests have gained popularity to predict histology in view of the associated risks of biopsy . However , many models include tests not readily available , and there are limited data from patients with HIV/hepatitis C virus ( HCV ) coinfection . We aim ed to develop a model using routine tests to predict liver fibrosis in patients with HIV/HCV coinfection . A retrospective analysis of liver histology was performed in 832 patients . Liver fibrosis was assessed via Ishak score ; patients were categorized as 0 - 1 , 2 - 3 , or 4 - 6 and were r and omly assigned to training ( n = 555 ) or validation ( n = 277 ) sets . Multivariate logistic regression analysis revealed that platelet count ( PLT ) , age , AST , and INR were significantly associated with fibrosis . Additional analysis revealed PLT , age , AST , and ALT as an alternative model . Based on this , a simple index ( FIB-4 ) was developed : age ( [ yr ] x AST [ U/L ] ) / ( ( PLT [ 10(9)/L ] ) x ( ALT [U/L])(1/2 ) ) . The AUROC of the index was 0.765 for differentiation between Ishak stage 0 - 3 and 4 - 6 . At a cutoff of < 1.45 in the validation set , the negative predictive value to exclude advanced fibrosis ( stage 4 - 6 ) was 90 % with a sensitivity of 70 % . A cutoff of > 3.25 had a positive predictive value of 65 % and a specificity of 97 % . Using these cutoffs , 87 % of the 198 patients with FIB-4 values outside 1.45 - 3.25 would be correctly classified , and liver biopsy could be avoided in 71 % of the validation group . In conclusion , noninvasive tests can accurately predict hepatic fibrosis and may reduce the need for liver biopsy in the majority of HIV/HCV-coinfected patients BACKGROUND / AIMS Transient elastometry ( TE ) is accurate for detecting cirrhosis ( F=4 ) in human immunodeficiency virus (HIV)/hepatitis C virus ( HCV ) co-infected patients . However , this procedure is less precise to differentiate mild ( F < or = 1 ) from moderate to severe ( F > or = 2 ) fibrosis using the cut-off value of 7.2kPa , a level previously proposed by some authors . Because of this , we elaborated and vali date d cut-off values of liver stiffness ( LS ) to better discriminate F < or = 1 from F > or = 2 in HIV/HCV co-infected subjects to aid therapy decisions . METHODS One hundred and ninety-seven co-infected patients with liver biopsy and TE measurement , without prior therapy against HCV infection , were included . RESULTS To diagnose F < or = 2 , a cut-off of 9.0kPa showed a positive predictive value of 87 % . To discard F > or = 2 , a cut-off of 6.0kPa showed a negative predictive value of 90 % . Considering all the patients , 61 ( 31 % ) patients yielded LS values < or = 6.0kPa and 81 ( 41 % ) patients showed LS values > or = 9.0kPa . There were no severe classification errors as the NPV of L < or = S6.0kPa for F > or = 3 was 100 % and the NPV LS > or = 9.0kPa for F=0 was also 100 % . CONCLUSIONS The usefulness of TE can be enhanced using two different cut-off values to identify patients with F < or = 1 and F > or = 2 Background : Chronic hepatitis C in HIV-infected patients is an increasing cause of death dependent on the development of liver fibrosis , which is currently assessed by liver biopsy despite its limitations . Liver stiffness measurement , a new noninvasive method , allows the evaluation of liver fibrosis . The aim of this prospect i ve study was to assess the accuracy of liver stiffness measurement for the detection of fibrosis and cirrhosis in HIV/hepatitis C virus (HCV)-coinfected patients and to compare its accuracy with other noninvasive methods . Methods : We studied 72 consecutive HIV patients with chronic hepatitis C who had a simultaneous liver biopsy and liver stiffness measurement by transient elastography ( FibroScan ; Echosens , Paris , France ) for the assessment of liver fibrosis . Results : Liver stiffness values ranged from 3.0 to 46.4 kilopascal . Liver stiffness was significantly correlated to fibrosis stage ( Kendall τ-b = 0.48 ; P < 0.0001 ) . The area under the receiver operating characteristic ( AUROC ) curve of liver stiffness measurement was 0.72 for F ≥ 2 and 0.97 for F = 4 . For the diagnosis of cirrhosis , AUROC curves of liver stiffness measurement were significantly higher than those for platelet count ( P = 0.02 ) , aspartate aminotransferase (AST)/alanine aminotransferase ( ALT ) ratio ( P = 0.0001 ) , Aspartate aminotransferase-to-Platelet Ratio Index ( APRI ) ( P = 0.01 ) , and FIB-4 ( P = 0.004 ) . Conclusion : Liver stiffness measurement is a promising noninvasive method for the assessment of fibrosis in HIV-infected patients with chronic HCV infection . Its use for the follow-up of these patients should be further evaluated BACKGROUND Hepatitis C virus ( HCV ) infection is a leading cause of morbidity and mortality in patients with HIV-1 . The C-EDGE CO-INFECTION study assessed the efficacy , safety , and tolerability of grazoprevir ( MK-5172 ) plus elbasvir ( MK-8742 ) in patients with HCV and HIV co-infection . METHODS In this uncontrolled , non-r and omised , phase 3 , open-label , single-arm study , treatment-naive patients with chronic HCV genotype 1 , 4 , or 6 infection and HIV co-infection , with or without cirrhosis , were enrolled from 37 centres in nine countries across Europe , the USA , and Australia . Patients were either naive to treatment with any antiretroviral therapy ( ART ) or stable on ART for at least 8 weeks . All patients received grazoprevir 100 mg plus elbasvir 50 mg in a fixed-dose combination tablet once daily for 12 weeks . The primary endpoint was sustained virological response ( HCV RNA < 15 IU/mL ) 12 weeks after the end of therapy ( SVR12 ) . The primary population for efficacy analyses was all patients who received at least one dose of study treatment . This study is registered with Clinical Trials.gov , number NCT02105662 . FINDINGS Between June 11 , 2014 , and Aug 29 , 2014 , 218 patients were enrolled and received grazoprevir plus elbasvir for 12 weeks , all of whom completed follow-up at week 12 . SVR12 was achieved by 210 ( 96 % ) of 218 patients ( 95 % CI 92·9 - 98·4 ) . One patient did not achieve SVR12 because of a non-virological reason , and seven patients without cirrhosis relapsed ( two subsequently confirmed as reinfections ) . All 35 patients with cirrhosis achieved SVR12 . The most common adverse events were fatigue ( 29 ; 13 % ) , headache ( 27 ; 12 % ) , and nausea ( 20 ; 9 % ) . No patient discontinued treatment because of an adverse event . Two patients receiving ART had transient HIV viraemia . INTERPRETATION This HCV treatment regimen seems to be effective and well tolerated for patients co-infected with HIV with or without cirrhosis . These data are consistent with previous trials of this regimen in the monoinfected population . This regimen continues to be studied in phase 3 trials . FUNDING Merck Sharp & Dohme BACKGROUND AND OBJECTIVE Publication bias and other sample size effects are issues for meta-analyses of test accuracy , as for r and omized trials . We investigate limitations of st and ard funnel plots and tests when applied to meta-analyses of test accuracy and look for improved methods . METHODS Type I and type II error rates for existing and alternative tests of sample size effects were estimated and compared in simulated meta-analyses of test accuracy . RESULTS Type I error rates for the Begg , Egger , and Macaskill tests are inflated for typical diagnostic odds ratios ( DOR ) , when disease prevalence differs from 50 % and when thresholds favor sensitivity over specificity or vice versa . Regression and correlation tests based on functions of effective sample size are valid , if occasionally conservative , tests for sample size effects . Empirical evidence suggests that they have adequate power to be useful tests . When DORs are heterogeneous , however , all tests of funnel plot asymmetry have low power . CONCLUSION Existing tests that use st and ard errors of odds ratios are likely to be seriously misleading if applied to meta-analyses of test accuracy . The effective sample size funnel plot and associated regression test of asymmetry should be used to detect publication bias and other sample size related effects BACKGROUND The combination of daclatasvir , a hepatitis C virus ( HCV ) NS5A inhibitor , and the NS5B inhibitor sofosbuvir has shown efficacy in patients with HCV monoinfection . Data are lacking on the efficacy and safety of this combination in patients coinfected with human immunodeficiency virus type 1 ( HIV-1 ) . METHODS This was an open-label study involving 151 patients who had not received HCV treatment and 52 previously treated patients , all of whom were coinfected with HIV-1 . Previously untreated patients were r and omly assigned in a 2:1 ratio to receive either 12 weeks or 8 weeks of daclatasvir at a st and ard dose of 60 mg daily ( with dose adjustment for concomitant antiretroviral medications ) plus 400 mg of sofosbuvir daily . Previously treated patients were assigned to undergo 12 weeks of therapy at the same doses . The primary end point was a sustained virologic response at week 12 after the end of therapy among previously untreated patients with HCV genotype 1 who were treated for 12 weeks . RESULTS Patients had HCV genotypes 1 through 4 ( 83 % with genotype 1 ) , and 14 % had compensated cirrhosis ; 98 % were receiving antiretroviral therapy . Among patients with genotype 1 , a sustained virologic response was reported in 96.4 % ( 95 % confidence interval [ CI ] , 89.8 to 99.2 ) who were treated for 12 weeks and in 75.6 % ( 95 % CI , 59.7 to 87.6 ) who were treated for 8 weeks among previously untreated patients and in 97.7 % ( 95 % CI , 88.0 to 99.9 ) who were treated for 12 weeks among previously treated patients . Rates of sustained virologic response across all genotypes were 97.0 % ( 95 % CI , 91.6 to 99.4 ) , 76.0 % ( 95 % CI , 61.8 to 86.9 ) , and 98.1 % ( 95 % CI , 89.7 to 100 ) , respectively . The most common adverse events were fatigue , nausea , and headache . There were no study -drug discontinuations because of adverse events . HIV-1 suppression was not compromised . CONCLUSIONS Among previously untreated HIV-HCV coinfected patients receiving daclatasvir plus sofosbuvir for HCV infection , the rate of sustained virologic response across all genotypes was 97.0 % after 12 weeks of treatment and 76.0 % after 8 weeks . ( Funded by Bristol-Myers Squibb ; ALLY-2 Clinical Trials.gov number , NCT02032888 . ) BACKGROUND Effective treatment for hepatitis C virus ( HCV ) in patients coinfected with human immunodeficiency virus type 1 ( HIV-1 ) remains an unmet medical need . METHODS We conducted a multicenter , single-group , open-label study involving patients coinfected with HIV-1 and genotype 1 or 4 HCV receiving an antiretroviral regimen of tenofovir and emtricitabine with efavirenz , rilpivirine , or raltegravir . All patients received ledipasvir , an NS5A inhibitor , and sofosbuvir , a nucleotide polymerase inhibitor , as a single fixed-dose combination for 12 weeks . The primary end point was a sustained virologic response at 12 weeks after the end of therapy . RESULTS Of the 335 patients enrolled , 34 % were black , 55 % had been previously treated for HCV , and 20 % had cirrhosis . Overall , 322 patients ( 96 % ) had a sustained virologic response at 12 weeks after the end of therapy ( 95 % confidence interval [ CI ] , 93 to 98 ) , including rates of 96 % ( 95 % CI , 93 to 98 ) in patients with HCV genotype 1a , 96 % ( 95 % CI , 89 to 99 ) in those with HCV genotype 1b , and 100 % ( 95 % CI , 63 to 100 ) in those with HCV genotype 4 . Rates of sustained virologic response were similar regardless of previous treatment or the presence of cirrhosis . Of the 13 patients who did not have a sustained virologic response , 10 had a relapse after the end of treatment . No patient had confirmed HIV-1 virologic rebound . The most common adverse events were headache ( 25 % ) , fatigue ( 21 % ) , and diarrhea ( 11 % ) . No patient discontinued treatment because of adverse events . CONCLUSIONS Ledipasvir and sofosbuvir for 12 weeks provided high rates of sustained virologic response in patients coinfected with HIV-1 and HCV genotype 1 or 4 . ( Funded by Gilead Sciences ; ION-4 Clinical Trials.gov number , NCT02073656 . ) |
649 | 26,697,225 | In this systematic review of published reports , we found that late gastrointestinal toxicity following prostate radiotherapy seems to be statistically and potentially causally related to acute gastrointestinal morbidity as a consequential effect .
We su bmi t that acute gastrointestinal toxicity may be used to identify at-risk patients who may benefit from additional attention for medical interventions and close follow-up to prevent late toxicity . | A small but meaningful percentage of men who are treated with external beam radiation therapy for prostate cancer will develop late gastrointestinal toxicity .
While numerous strategies to prevent gastrointestinal injury have been studied , clinical trials concentrating on late toxicity have been difficult to carry out .
Identification of subjects at high risk for late gastrointestinal injury could allow toxicity prevention trials to be performed using reasonable sample sizes .
Acute radiation therapy toxicity has been shown to predict late toxicity in several organ systems .
Late toxicities may occur as a consequential effect of acute injury . | Background To answer the question if and to which extent acute symptoms at the end and /or several weeks after radiotherapy can predict adverse urinary and gastrointestinal long-term quality of life ( QoL ) . Methods A group of 298 patients has been surveyed prospect ively before ( time A ) , at the last day ( B ) , two months after ( C ) and > one year after ( D ) radiotherapy using a vali date d question naire ( Exp and ed Prostate Cancer Index Composite ) . A subgroup of 10 % with the greatest urinary/bowel bother score decrease at time D was defined as patients with adverse long-term QoL. Results Subgroup and correlation analyses could demonstrate a strong dependence of urinary/bowel QoL after radiotherapy on urinary/bowel QoL before radiotherapy . In contrast to absolute scores , QoL score changes ( relative to baseline scores ) did not correlate with pretreatment scores . Long-term changes could be well predicted by acute changes . Patients reporting great/moderate bother with urinary/bowel problems at time C reported to have great/moderate bother at time D in ≥ 50 % , respectively . In a multivariate analysis of factors for adverse long-term urinary and bowel QoL , score changes at time C were found to be independent predictors , respectively . Additionally , QoL changes at time B were independently predictive for adverse long-term bowel QoL. Conclusions Consequential late effects play a major role after radiotherapy for prostate cancer . Patients with greater and particularly longer non-healing acute toxicity are c and i date s for closer follow-up and possible prophylactic actions to reduce a high probability of long-term problems PURPOSE To compare the toxicity between hypofractionation vs. conventional fractionation schedules in patients with high-risk prostate cancer . METHODS AND MATERIAL S Between January 2003 and December 2007 , 168 patients were r and omized to receive either hypofractionated ( 62 Gy in 20 fractions within 5 weeks , 4 fractions/wk ) or conventionally fractionated ( 80 Gy in 40 fractions within 8 weeks ) three-dimensional conformal radiotherapy to the prostate and seminal vesicles . All patients had undergone a 9-month course of total and rogen deprivation , with radiotherapy starting 2 months after initiation of the total and rogen deprivation . RESULTS The median follow-up was 32 and 35 months in the hypofractionation and conventional fractionation arms , respectively . For the patients developing acute toxicity , no difference between the two fractionation groups was found in either severity or duration of gastrointestinal or genitourinary toxicity . Also , no difference was found in the incidence and severity of late gastrointestinal and genitourinary toxicity between the two treatment schedules , with a 3-year rate of Grade 2 or greater toxicity of 17 % and 16 % for the hypofractionation arm and 14 % and 11 % for the conventional fractionation arm , respectively . A statistically significant correlation between acute and late gastrointestinal toxicity was found only in the conventional fractionation group . CONCLUSION Our findings suggest that the hypofractionation regimen used in our study is safe , with only a slight , nonsignificant increase in tolerable and temporary acute toxicity compared with the conventional fractionation schedule . The severity and frequency of late complications was equivalent between the two treatment groups PURPOSE To report toxicity and preliminary biochemical outcomes with high-dose intensity-modulated radiation therapy ( IMRT ) to a dose of 86.4 Gy for localized prostate cancer . METHODS AND MATERIAL S Between August 1997 and March 2004 , 478 patients were treated with 86.4 Gy using a 5- to 7-field IMRT technique . To adhere to normal tissue constraints , the mean D95 and V100 for the planning target volume were 83 Gy and 87 % , respectively . Toxicity data were scored according to the Common Terminology Criteria for Adverse Events Version 3.0 . Freedom from biochemical relapse was calculated . The median follow-up was 53 months . RESULTS Thirty-seven patients ( 8 % ) experienced acute Grade 2 gastrointestinal ( GI ) toxicity . There was no acute Grade 3 or 4 GI toxicity . One hundred and five patients ( 22 % ) experienced acute Grade 2 genitourinary ( GU ) toxicity and three patients ( 0.6 % ) had Grade 3 GU toxicity . There was no acute Grade 4 GU toxicity . Sixteen patients ( 3 % ) developed late Grade 2 GI toxicity and two patients ( < 1 % ) developed late Grade 3 GI toxicity . Sixty patients ( 13 % ) had late Grade 2 GU toxicity and 12 ( <3 % ) experienced late Grade 3 GU toxicity . The 5-year actuarial PSA relapse-free survival according to the nadir plus 2 ng/mL definition was 98 % , 85 % and 70 % for the low , intermediate , and high risk NCCN prognostic groups . CONCLUSION This report represents the largest data set of patients treated to ultra-high radiation dose levels of 86.4 Gy using IMRT for localized prostate cancer . Our findings indicate that this treatment is well tolerated and the early excellent biochemical control rates are encouraging Background As dose-escalation in prostate cancer radiotherapy improves cure rates , a major concern is rectal toxicity . We prospect ively assessed an innovative approach of hydrogel injection between prostate and rectum to reduce the radiation dose to the rectum and thus side effects in dose-escalated prostate radiotherapy . Methods Acute toxicity and planning parameters were prospect ively evaluated in patients with T1 - 2 N0 M0 prostate cancer receiving dose-escalated radiotherapy after injection of a hydrogel spacer . Before and after hydrogel injection , we performed MRI scans for anatomical assessment of rectal separation . Radiotherapy was planned and administered to 78 Gy in 39 fractions . Results From eleven patients scheduled for spacer injection the procedure could be performed in ten . In one patient hydrodissection of the Denonvillier space was not possible . Radiation treatment planning showed low rectal doses despite dose-escalation to the target . In accordance with this , acute rectal toxicity was mild without grade 2 events and there was complete resolution within four to twelve weeks . Conclusions This prospect i ve study suggests that hydrogel injection is feasible and may prevent rectal toxicity in dose-escalated radiotherapy of prostate cancer . Further evaluation is necessary including the definition of patients who might benefit from this approach . Trial registration : German Clinical Trials Register DRKS00003273 Objective To determine late toxicity and quality of life ( QoL ) in patients with localized prostate cancer after high-dose intensity-modulated radiotherapy (IMRT).Patient and methods This was a prospect i ve study in patients with localized prostate adenocarcinoma who had been treated by IMRT ( 76 Gy ) between February and November 2006 . Physicians scored acute and late toxicity using the Common Terminology Criteria for Adverse Events ( version 3.0 ) . Patients completed cancer and prostate-specific QoL question naires ( EORTC QLQ-C30 and QLQ-PR25 ) before IMRT ( baseline ) and at 2 , 6 , 18 and 54 months . Result Data were available for 38 patients ( median age , 73 years ) ( 18 % low risk ; 60 % intermediate risk ; 32 % high risk ) . The incidence of urinary and gastrointestinal toxicity was respectively : immediately post IMRT : 36.8 % and 23.7 % ( grade 1 ) , 5.3 % and 5.3 % ( grade 2 ) , 2.6 % and 0 % ( grade 3 ) ; at 18 months : 23.7 % and 10.3 % ( grade 1 ) , 26.3 % and 13.2 % ( grade 2 ) , 0 % and 2.6 % ( grade 3 ) ; at 54 months : 34.2 % and 23.7 % ( grade 1 ) , 5.3 % and 15.8 % ( grade 2 ) , 5.3 % and 0 % ( grade 3 ) . At 54 months , significant worsening was reported by patients for 11/19 QoL items but the worsening was clinical ly relevant ( > 10 points ) for 7 items only : physical , role as well as social functioning , fatigue , pain , dyspnoea and constipation . There was no significant difference between 54-month and baseline QoL scores for global health , gastrointestinal symptoms , treatment-related symptoms and sexual function . However , there was significant - but clinical ly non-relevant ( < 10 points ) - worsening of urinary symptom . Conclusion High-dose IMRT to the prostate with accurate patient positioning did not induce any clinical ly relevant worsening in late urinary and gastrointestinal QoL at 54 months . Impaired physical and role functioning may be related to age and comorbidities Purpose : To assess whether the topical use of steroids or 5-aminosalicylic acid ( 5-ASA ) is superior to sucralfate in preventing acute rectal toxicity during three-dimensional conformal radiotherapy ( 3DCRT ) to 76 Gy . Patients and Methods : Patients undergoing 3DCRT for prostate carcinoma at our institution were offered to be r and omized to sucralfate 3 g in 15 ml suspension enema ( Antepsin ® ) , mesalazine 4 g gel enema ( Enterasyn ® ) , or hydrocortisone 100 mg foam enema ( Colifoam ® ) . R and omization was blind to the treating physician but not to the patient . Sucralfate was chosen as control arm . Topical treatment had to be performed once daily , starting on day 1 of 3DCRT . Acute rectal toxicity was scored weekly according to RTOG criteria . Time to occurrence of grade 2 + acute rectal toxicity was taken as endpoint . Results : The trial was opened in August 1999 , and after the first 24 patients had been treated , arm 2 was discontinued because of eight patients receiving mesalazine , seven actually developed acute rectal toxicity ( five patients grade 3 and two patients grade 2).Until May 2001 , 134 consecutive patients were r and omly assigned to sucralfate ( 63 patients ) , mesalazine ( eight patients ) or hydrocortisone ( 63 patients ) . The cumulative incidence of acute rectal toxicity at the end of treatment by arm is 61.9 ± 6.1 % , 87.5 ± 11.7 % , and 52.4 ± 6.2 % for arms 1 , 2 , and 3 , respectively . The difference between the mesalazine group and the sucralfate group is highly significant ( hazard ratio [ HR ] 2.5 , 95 % confidence interval [ CI ] 1.1–5.7 ; p = 0.03 ) . At both uni- and multivariate analysis taking into account several patients and treatment covariates , the difference between hydrocortisone and sucralfate is not significant ( HR 0.7 , 95 % CI 0.5–1.2 ; p = 0.2 ) . Conclusion : Topical mesalazine is contraindicated during radiotherapy . Hydrocortisone enema is not superior to sucralfate in preventing acute rectal toxicity . Fragestellung : R and omisierter Vergleich der lokalen Anwendung von Steroiden oder 5-ASA oder Sucralfat zur Prävention einer akuten Strahlenproktitis unter 3-D-konformaler Radiotherapie ( 3DCRT ) bis 76 Gy . Patienten und Method ik : Patienten , die sich in unserer Klinik wegen eines Prostatakarzinoms einer 3DCRT unterzogen , wurde r and omisiert angeboten eine Vorbeh and lung 1 ) mit Sucralfat ( 3 g suspendiert i m 15-ml-Klysma ) , 2 ) Mesalazin als 4-g-Gelklysma ) oder 3 ) Hydrocortison : 100 mg als Schaumklysma ) . Die R and omisierung zu einem dieser drei Studienarme war dem beh and elnden Arzt unbekannt , nicht aber dem Patienten . Sucralfat wurde als Kontrollarm gewählt . Die jeweilige topische Therapie musste ab dem 1 . Tag der 3DCRT einmal täglich durchgeführt werden . Auf akute Strahlenproktitis wurde jede Woche nach RTOG-Kriterien geprüft . Als Endpunkt wurde das Auftreten einer akuten Strahlenproktitis Grad 2 festgelegt . Ergebnisse : Die Studie begann i m August 1999 . Nachdem die ersten 24 Patienten aufgenommen worden waren , wurde Arm 2 abgebrochen , da sieben Patienten unter Mesalazin eine akute Strahlenproktitis ( Grad 3 bei fünf Patienten und Grad 2 bei zwei Patienten ) entwickelten . Bis zum Mai 2001 wurden 134 Patienten der lokalen Anwendung von Sucralfat ( 63 Patienten ) , Mesalazin ( acht Patienten ) oder Hydrocortison ( 63 Patienten ) zugeführt . Die kumulative Inzidenz akuter Strahlenproktitis betrug jeweils 61,9 ± 6,1 % , 87,5 ± 11,7 % und 52,4 ± 6,2 % . Der Unterschied zwischen Mesalazin- und Sucralfat-Gruppe ist hoch signifikant ( HR : 2,5 ; 95%-CI : 1,1–5,7 ; p = 0,03 ) , der zwischen Hydrocortison und Sucralfat nicht ( HR = 0,7 ; 95%-CI : 0,5–1,2 ; p = 0,2 ) . Schlussfolgerung : Topisches Mesalazin ist unter Radiotherapie kontraindiziert . Hydrocortison-Klysmen und Sucralfat sind zur Prophylaxe einer akuten Strahlenproktitis gleichwertig PURPOSE To determine whether acute radiation-proctitis , diagnosed by proctoscopy after radiation therapy for prostate cancer , can predict late clinical proctitis . METHODS AND MATERIAL S A prospect i ve study of 130 patients who underwent external radiation therapy ( RT ) for stage T1 to T4 prostate cancer between 1997 and 2008 was performed . Treatments were conventional ( 2-dimensional [ 2D ] ) in 61 patients and 3D conformal in 69 , with a median target dose of 72 Gy ( 70 - 74 Gy ) . Within 1 week after RT , proctoscopy was performed to detect possible acute endoscopic proctitis ( AEP ) . Acute clinical proctitis ( ACP ) and late clinical proctitis ( LCP ) were also evaluated . The median follow-up was 84 months ( 20 - 180 months ) . The influence of AEP and ACP on LCP occurrence was studied using the Cox model controlling for age , dose , prostatectomy , RT technique ( 2D vs 3D ) , and hormone therapy . RESULTS AEP was detected in 15 patients ( 11.5 % ) and ACP in 67 ( 51.5 % ) ; in 13 cases ( 10 % ) AEP and ACP occurred simultaneously . Thirty-five cases of LCP were recorded . The 5-year probability of developing LCP was highest in patients with AEP and ACP ( 77 % , 95 % confidence interval [ CI ] 53%-94 % ) and lowest in asymptomatic patients ( 14 % , 95 % CI 7%-26 % ; P<.001 ) . Compared to asymptomatic patients , the 5-year probability also was slightly increased in patients with ACP only ( 26 % , 95 % CI 16%-40 % ; P=.052 ) . In multivariable analysis , the combination of AEP and ACP was the main predictor of LCP : compared to asymptomatic patients , the hazard ratio was 5.6 ( 2.1 - 15.2 ) in patients with AEP plus ACP ( P=.001 ) and 2.1 ( 0.9 - 4.9 ) in those with ACP only ( P=.103 ) . CONCLUSIONS In patients with AEP and ACP , the risk of LCP was more than 5-fold increased compared to those who were asymptomatic , while a much smaller increase in risk occurred in patients with ACP only . Early proctoscopy can provide valuable information regarding the likelihood of late proctitis BACKGROUND AND PURPOSE A limited number of studies have suggested that oral sucralfate reduces the acute and late gastro-intestinal side-effects of pelvic radiotherapy and sucralfate enemas ameliorate symptoms of chronic proctitis . Sucralfate may act via local bFGF at the mucosal level in promoting angiogenesis and reducing epithelial associated microvascular injury . This multi-institutional study was design ed to test the hypothesis that sucralfate given as an enema would have a significant protective effect against acute radiation induced rectal injury by direct application to the mucosa . MATERIAL S AND METHODS Eighty-six patients having radiotherapy for localised carcinoma of the prostate were r and omised in a double-blind placebo-controlled study to receive either 15 ml of placebo suspension or 3 g of sucralfate in 15 ml suspension , given as a once daily enema during and for 2 weeks following radiotherapy . Assessment was based on the EORTC/RTOG acute toxicity criteria and a patient self- assessment diary . RESULTS There was no significant difference between placebo and sucralfate for peak incidences of EORTC/RTOG proctitis . For the placebo and sucralfate arms 95 and 88 % ( difference 7 + /- 11 % ) suffered some degree of proctitis , with 71 and 61 % ( difference 10 + /- 19 % ) reaching grade 2 , respectively . The median period to onset of grade 2 proctitis was 33.5 and 36 days , with the median duration being 9.5 and 15 days , respectively , again these difference being non-significant . Thirty-five and 37 % of patients rated the effect of radiotherapy on bowel habit as ' a lot ' with a moderate or severe effect on normal daily living in 52 and 49 % , respectively . CONCLUSION This study suggests that sucralfate given as a once daily enema does not substantially reduce the incidence of symptoms associated with acute radiation proctitis and its routine clinical use can not be recommended . This cohort of patients will be followed to determine if any difference develops in relation to late toxicity PURPOSE Acute radiation proctitis ( ARP ) is a common side effect of pelvic radiotherapy , and its management is challenging in daily practice . The present phase I/II study evaluates the safety and efficacy of the botulinum toxin A ( BTX-A ) in ARP treatment for rectal cancer patients undergoing neoadjuvant high-dose-rate endorectal brachytherapy ( HDREBT ) . METHODS AND MATERIAL S Fifteen patients , treated with neoadjuvant HDREBT , 26-Gy in 4 fractions , received the study treatment that consisted of a single injection of BTX-A into the rectal wall . The injection was performed post-HDREBT and prior to the development of ARP . The control group , 20 such patients , did not receive the BTX-A injection . Both groups had access to st and ard treatment with hydrocortisone rectal aerosol foam ( Cortifoam ) and anti-inflammatory and narcotic medication . The ARP was clinical ly evaluated by self-administered daily question naires using visual analog scores to document frequency and urgency of bowel movements , rectal burning/tenesmus , and pain symptoms before and after HDREBT . RESULTS At the time of this analysis , there was no observed systemic toxicity . Patient compliance with the self-administered question naire was 100 % from week 1 to 4 , 70 % during week 5 , and 40 % during week 6 . The maximum tolerated dose was established at the 100-U dose level , and noticeable mean differences were observed in bowel frequency ( p = 0.016 ) , urgency ( p = 0.007 ) , and pain ( p = 0.078 ) . CONCLUSIONS This study confirms the feasibility and efficacy of BTX-A intervention at 100-U dose level for study patients compared to control patients . A phase III study with this dose level is planned to vali date these results PURPOSE To evaluate dose reduction caused by the implantation of an interstitial inflatable and biodegradable balloon device aim ing to achieve lower rectal doses with virtual 3D conformal external beam radiation treatment . MATERIAL S AND METHODS An inflatable balloon device was placed , interstitially and under transrectal ultrasound guidance , into the rectal-prostate interspace prior treatment initiation of 26 patients with localized prostate cancer , who elected to be treated with radiotherapy ( 3D CRT or IMRT ) . The pre- and post-implant CT imaging data of twenty two patients were collected ( 44 images ) for the purpose of the 3D conformal virtual planning presented herein . RESULTS The dorsal prostate-ventral rectal wall separation result ed in an average reduction of the rectal V70 % by 55.3 % ( ± 16.8 % ) , V80 % by 64.0 % ( ± 17.7 % ) , V90 % by 72.0 % ( ± 17.1 % ) , and V100 % by 82.3 % ( ± 24.1 % ) . In parallel , rectal D2 ml and D0.1 ml were reduced by 15.8 % ( ± 11.4 % ) and 3.9 % ( ± 6.4 % ) , respectively . CONCLUSIONS Insertion of the biodegradable balloon into the prostate-rectum interspace is similar to other published invasive procedures . In this virtual dose distribution analysis , the balloon insertion result ed in a remarkable reduction of rectal volume exposed to high radiation doses . This effect has the potential to keep the rectal dose lower especially when higher than usual prostate dose escalation protocol s or hypo-fractionated regimes are used . Further prospect i ve clinical investigations on larger cohorts and more conformal radiation techniques will be necessary to define the clinical advantage of the biodegradable interstitial tissue separation device Purpose : To evaluate toxicity after dose-escalated radiotherapy for prostate cancer using intensity-modulated treatment planning ( IMRT ) and image-guided treatment ( IGRT ) delivery . Patients and Methods : 100 patients were treated with simultaneous integrated boost ( SIB ) IMRT for prostate cancer : doses of 76.23 Gy and 60 Gy in 33 fractions were prescribed to the prostate and the seminal vesicles , respectively , for intermediate- and high-risk patients ( n = 74 ) . The total dose was 73.91 Gy in 32 fractions for low-risk patients and after transurethral resection of the prostate ( n = 26 ) . The pelvic lymphatics were treated with 46 Gy in 25 fractions in patients with high risk of lymph node metastases using an SIB to the prostate ( n = 25 ) . IGRT was practice d with cone-beam computed tomography . Acute and late gastrointestinal ( GI ) and genitourinary ( GU ) toxicity was evaluated prospect ively ( CTCAE v3.0 ) . Results : Treatment was completed as planned by all patients . Acute GI and GU toxicity grade ≥ 2 was observed in 12 % and 42 % of the patients , respectively , with 4 % suffering from GU toxicity grade 3 . 6 weeks after treatment , the incidence of acute toxicity grade ≥ 2 had decreased to 12 % . With a median follow-up of 26 months , late GI and GU toxicity grade ≥ 2 was seen in 1.5 % and 7.7 % of the patients at 24 months . Four patients developed late toxicity grade 3 ( GI n = 1 ; GU n = 3 ) . Presence of acute GI and GU toxicity was significantly associated with late GI ( p = 0.0007 ) and GU toxicity ( p = 0.006 ) . Conclusion : High-dose radiotherapy for prostate cancer using IMRT and IGRT result ed in low rates of acute toxicity and preliminary results of late toxicity are promising . ZusammenfassungZiel : Erfassung der Toxizität nach intensitätsmodulierter ( IMRT ) , bildgeführter Strahlentherapie ( IGRT ) des Prostatakarzinoms . Patienten und Method ik:100 Patienten wurden wegen eines Prostatakarzinoms mittels IMRT und simultanen integrierten Boosts ( SIB ) primar bestrahlt : Gesamtdosen von 76,23 Gy bzw . 60 Gy in 33 Fraktionen wurden i m Boostzielvolumen und in den Samenblasen geplant , falls ein hohes oder intermediares Risikoprofil vorlag ( n = 74 ) . Bei niedrigem Risiko und Zust and nach transurethraler Prostataresektion wurde eine Gesamtdosis von 73,91 Gy in 32 Fraktionen angewendet ( n = 26 ) . Das pelvine Lymphabflussgebiet wurde bei hohem Risiko eines Lymphknotenbefalls mit 46 Gy in 25 Fraktionen beh and elt ( n = 25 ) , ebenfalls mit einem SIB auf die Prostata . IGRT wurde mittels Cone-Beam-Computertomographie praktiziert . Die akute und chronische gastrointestinale ( GI ) und urogenitale ( GU ) Toxizitat wurde prospektiv nach CTCAE v3.0 erfasst . Ergebnisse : Die Beh and lung wurde bei allen Patienten planmäßig beendet . Akute GI- und GU-Toxizitat ≥ Grad 2 wurde bei 12 % bzw . 42 % der Patienten beobachtet ; 4 % entwickelten eine GU-Toxizitat Grad 3 . 6 Wochen nach Therapie war die Inzidenz einer Toxizität ≥ Grad 2 auf 12 % zurückgegangen . Nach einer medianen Nachbeobachtungszeit von 26 Monaten wurde eine 2-Jahres-GI-bzw . -GU-Toxizitat ≥ Grad 2 bei 1,5 % bzw . 7,7 % der Patienten beobachtet . Vier Patienten entwickelten eine Spätnebenwirkung Grad 3 ( GI n = 1 ; GU n = 3 ) . Das Vorh and ensein von akuter GI- und GU-Toxizität war mit einer signifikant höheren Inzidenz an späten GI- ( p = 0,0007 ) und GU-Nebenwirkungen ( p = 0,006 ) assoziiert . Schlussfolgerung : Radiotherapie mit hohen Bestrahlungsdosen result ierte in geringer Akuttoxizitat bei Anwendung von IMRT und IGRT ; vorläufige Date n zur chronischen Toxizität sind vielversprechend Background and Purpose : To assess the late effect of a prostagl and in , given rectally during irradiation , on late rectal toxicity . In the acute treatment setting no significant differences in reducing the incidence of acute proctitis symptoms in patients receiving misoprostol , however , significantly more rectal bleeding had been reported . Patients and Methods : A total of 100 patients who had undergone radiotherapy for prostate cancer had been entered into this phase III r and omized , placebo-controlled , double-blind study with misoprostol or placebo suppositories . The toxicity was evaluated yearly after cessation of irradiation by the RTOG/LENT-SOMA scale . Results : The median follow-up was 50 months . 20 patients suffered from grade 1 , four patients from grade 2 as well , and three patients only from grade 2 toxicity . Frequency , bleeding and urgency were the most commonly reported symptoms . In keeping with other studies and clinical experience , the symptoms peaked within the first 2 years with a median for grade 1 of 13 months and for grade 2 of 15 months . The presence of acute toxicity grade 2 showed a correlation with the development of any late toxicity ( p = 0.03 ) . Any acute rectal bleeding was significant correlated with any late rectal bleeding ( p = 0.017 ) . Conclusion : Misoprostol given as once-daily suppository for prevention of acute radiation-induced proctitis does neither influence the incidence and severity of radiation-induced acute nor late rectal toxicity . Misoprostol has no negative impact on the incidence and severity of late rectal bleeding , in contrast to acute rectal bleeding . The routine clinical use of misoprostol suppositories can not be recommended . Hintergrund und Ziel : Diese Untersuchung wurde durchgeführt , um einen potentiellen Einfluss von zur Prophylaxe der akuten Proktitis rektal gegebenem Misoprostol auf radiogene rektale Spätreaktionen zu evaluieren . Patienten und Method ik:100 Patienten , die mit Radiotherapie bei Prostatakarzinom beh and elt wurden , wurden in diese r and omisierte , plazebokontrollierte , doppelblinde Phase-III-Studie mit Misoprostol- bzw . Plazebozäpfchen eingeschlossen . Die Toxizität wurde jährlich anh and der RTOG- und LENT-SOMA-Skalen erhoben . Ergebnisse : Der mediane Nachbeobachtungszeitraum betrug 50 Monate . Bei 20 Patienten trat eine Grad-1- , bei vier ebenfalls eine Grad-2- und bei drei Patienten nur eine Grad-2-Toxizität auf . Frequenz , Blutung und Stuhldrang waren die häufigsten Symptome . Vergleichbar mit and eren Studien und klinischer Erfahrung , traten die Symptome am häufigsten innerhalb der ersten 2 Jahre mit einer medianen Zeit von 13 Monaten für Grad-1- und 15 Monaten für Grad-2-Proktitis auf . Das Vorh and ensein akuter Grad-2-Toxizität zeigte eine Korrelation mit der Entwicklung von später Toxizität ( p = 0,03 ) . Akute Blutung war signifikant korreliert mit später Blutung ( p = 0,017).Schlussfolgerung : Misoprostol , einmal täglich als Zäpfchen zur Prävention der akuten radiotherapieinduzierten Proktitis gegeben , beeinflusst weder die Inzidenz und Schwere der radiotherapieinduzierten akuten noch der späten rektalen Toxizität . Misoprostol hat keinen negativen Einfluss auf die Häufigkeit und Schwere von später rektaler Blutung i m Gegensatz zu akuter Blutung . Der Routineeinsatz von Misoprostolzäpfchen kann nicht empfohlen werden PURPOSE The aim of this study was to investigate prospect ively the rectal wall ( Rwall ) spatial dose distribution , toxicity , and mucosal changes after prostate cancer radiotherapy with or without an endorectal balloon ( ERB ) . METHODS AND MATERIAL S A total of 24 patients with ERB and 24 without ERB ( No-ERB ) were treated with three-dimensional conformal radiotherapy ( 3D-CRT ) to a dose of 67.5 Gy . The Rwall was divided into 16 mucosal areas and Rwall dose surface maps were constructed . After 3 months , 6 months , 1 year , and 2 years a rectosigmoidoscopy was performed , and each mucosal area was scored on telangiectasia , congestion , ulceration , stricture , and necrosis . Late rectal toxicity was correlated with the endoscopic findings . RESULTS The ERB significantly reduced the Rwall volume exposed to doses > 40 Gy . Late rectal toxicity ( grade > or=1 , including excess of bowel movements and slight rectal discharge ) was reduced significantly in the ERB group . A total of 146 endoscopies and 2,336 mucosal areas were analyzed . Telangiectases were most frequently seen and appeared after 6 months . At 1 and 2 years , significantly less high- grade telangiectasia ( T 2 - 3 ) was observed in the ERB group at the lateral and posterior part of the Rwall . In mucosal areas exposed to doses > 40 Gy , less high- grade telangiectases ( T 2 - 3 ) were seen in the ERB group compared with the No-ERB group . CONCLUSIONS An ERB reduced the Rwall volume exposed to doses > 40 Gy , result ing in reduction of late rectal mucosal changes and reduced late rectal toxicity . Although further analysis is needed , these data suggest an ERB-induced increased tolerance for late Rwall damage BACKGROUND AND PURPOSE The late morbidity of a r and omized study was analyzed after a follow up of 2 years . The difference in intestinal morbidity was analyzed as a function of the treatment arm and dose volume parameters . The correlation with acute toxicity and ( pre-existing ) bowel complaints was investigated . PATIENTS AND METHODS 266 T1 - 4N0M0 prostate cancer patients were r and omized for conventional ( open fields ) and 3D conformal radiotherapy using beams eye view blocked fields with the same dose ( 66 Gy ) and gross target volume-planning target volume margin ( 15 mm ) . Apart from the RTOG toxicity scoring system a patient self- assessment question naire was used to obtain detailed information on morbidity . RESULTS At 2 years there is only a trend for less rectal toxicity ( grade > /=1 ) in favor of the conformal radiotherapy ( grade 1 , 47 versus 40 % and grade 2 , 10 versus 7 % for conventional and conformal radiotherapy , respectively ( P=0.1 ) . A significant relation was found between late rectal toxicity ( grade > /=1 ) and the volume of the anus and rectum exposed to > /=90 % tumor dose ( TD ) . A highly significant relationship is observed between acute rectum and anal toxicity and late rectal toxicity . The patient self- assessment question naire analysis revealed that patients are most bothered by compliance related symptoms like urgency , soiling and fecal loss . In a multivariate analysis , all other variables loose significance , when anal volume exposed to > /=90 % TD and pre-treatment defaecation frequency are accounted for . Late anal toxicity is low and related only to acute anal toxicity . Late bladder toxicity is related solely to pre-treatment frequency and overall urological symptoms . The incidence of grade 2 toxicity increases with a factor 2.5 - 4 when ( stool or urine ) frequency is unfavorable at the start of treatment . CONCLUSIONS Conformal radiotherapy at the dose level of 66 Gy does not significantly decrease the incidence of rectal , anal and bladder toxicity compared to conventional radiotherapy . There is a significant relationship between acute and late toxicity and the anal volume exposed to 90 % TD . Intestinal ( and urological ) symptoms at start have a major impact on late toxicity PURPOSE Radiotherapy , a cornerstone in the management of pelvic cancer , is accompanied by intestinal reactions . Therefore , we investigated the possible effects of sucralfate , an aluminium hydroxide complex of sulfated sucrose used in the treatment of gastric ulcer , in preventing radiation-induced diarrhea and bowel discomfort in patients treated with curative intention for pelvic cancer with external radiotherapy . PATIENTS AND METHODS The study was double-blind and placebo-controlled and included 70 patients with carcinoma in the prostate or urinary bladder without distant metastases ( T1 - 4No1xMo ) and a performance status of greater than or equal to 90 % on the Karnofsky scale . Radiotherapy was conventionally delivered with high-energy photons ( four-field technique , the total dose 64 Gy , 2 Gy daily , total treatment time 5 to 6 weeks ) . Dose granules of sucralfate or placebo were dispensed to each patient 2 weeks after radiation started and continued for 6 weeks . All analyses were performed blindly . RESULTS The frequency of defecation and stool consistency were significantly improved by sucralfate . Fourteen patients in the placebo group and three in the sucralfate group required symptomatic therapy with loperamide . One year later , the patients in the sucralfate group displayed significantly less problems with frequency of defecation , mucus , and blood in the stools compared with the placebo group . There was also a lower intake of loperamide and the weight decrease was less pronounced in the sucralfate group . There was no evidence of adverse effects associated with the use of sucralfate . CONCLUSION It is suggested that sucralfate can be of beneficial value in diminishing bowel discomfort during treatment and , most importantly , sucralfate also reduces the late bowel disturbances that follow radiotherapeutic treatment of pelvic malignancies . The earlier proposed mechanisms of action ( eg , protection of denuded mucosa , cytoprotective properties , binding bile acids ) seem adequate to explain the present effects of sucralfate PURPOSE To report the long-term results of a r and omized radiotherapy dose escalation trial for prostate cancer . METHODS AND MATERIAL S From 1993 to 1998 , a total of 301 patients with stage T1b to T3 prostate cancer were accrued to a r and omized external beam dose escalation trial using 70 Gy versus 78 Gy . The median follow-up is now 8.7 years . Kaplan-Meier analysis was used to compute rates of prostate-specific antigen ( PSA ) failure ( nadir + 2 ) , clinical failure , distant metastasis , disease-specific , and overall survival as well as complication rates at 8 years post-treatment . RESULTS For all patients , freedom from biochemical or clinical failure ( FFF ) was superior for the 78-Gy arm , 78 % , as compared with 59 % for the 70-Gy arm ( p = 0.004 , and an even greater benefit was seen in patients with initial PSA > 10 ng/ml ( 78 % vs. 39 % , p = 0.001 ) . The clinical failure rate was significantly reduced in the 78-Gy arm as well ( 7 % vs. 15 % , p = 0.014 ) . Twice as many patients either died of prostate cancer or are currently alive with cancer in the 70-Gy arm . Gastrointestinal toxicity of grade 2 or greater occurred twice as often in the high dose patients ( 26 % vs. 13 % ) , although genitourinary toxicity of grade 2 or greater was less ( 13 % vs. 8 % ) and not statistically significantly different . Dose-volume histogram analysis showed that the complication rate could be significantly decreased by reducing the amount of treated rectum . CONCLUSIONS Modest escalation in radiotherapy dose improved freedom from biochemical and clinical progression with the largest benefit in prostate cancer patients with PSA > 10 ng/ml Aim : To evaluate the cytoprotective effect of amifostine against radiation-induced acute toxicity to the rectal mucosa . Patients and Methods : 36 patients irradiated for prostate or gynecologic cancer were r and omized to receive amifostine ( n = 18 , group A ) or not ( n = 18 , group B ) . The radiation-induced acute rectal toxicity was evaluated by using three different toxicity scales : WHO scale , EORTC/RTOG toxicity criteria , and a modified toxicity scale based on the LENT-SOMA grading scale and the endoscopic terminology of the World Organization for Digestive Endoscopy . The objective measurements were coming from flexible rectosigmoidoscopy performed at baseline and 1–2 days after completion of the radiotherapy schedule . Anterior-posterior fields were used in the gynecologic patients while 3-D conformal 4-field technique was applied in the prostate cancer patients . The area under the curve ( AUC ) for dose-volume histograms ( DVHs ) of the rectum was also assessed during a 3-D treatment planning schedule , and no significant differences were assessed between the two groups , indicating a homogeneous dose-volume effect . Results : Amifostine was well tolerated . No grade 2 or higher WHO and EORTC/RTOG acute toxicity was noted in group A , while acute rectal toxicity ( ≥ grade 1 ) was observed in 16/18 patients of group B versus 2/18 of group A ( p < 0.001 ) . The onset as well as the duration of acute rectal toxicity were significantly improved in group A ( p = 0.002 ) . Rectosigmoidoscopy revealed more severe rectal mucositis in noncytoprotected patients ( group B ) , and modified LENT-SOMA overall mucositis grading score was significantly lower in group A ( p = 0.003 ) . Conclusion : Amifostine seems to have a significant cytoprotective efficacy in acute radiation-induced rectal mucositis in terms of symptomatic and objective endpoints . Ziel : Auswertung der zytoprotektiven Wirkung von Amifostin hinsichtlich der strahlungsinduzierten akuten Toxizität auf die Rektumschleimhaut . Patienten und Method ik : 36 aufgrund eines Prostata- oder gynäkologischen Karzinoms bestrahlte Patienten nahmen an einer r and omisierten Studie teil . Die eine Hälfte ( n = 18 , Gruppe A ) erhielt Amifostin , die and ere Hälfte ( n = 18 , Gruppe B ) nicht . Die strahlungsinduzierte akute Toxizität auf die Rektumschleimhaut wurde mit Hilfe von drei verschiedenen Toxizitätsskalen ausgewertet : der WHO-Skala , den Toxizitätskriterien der EORTC/RTOG und einer modifizierten Toxizitätsskala , die sowohl auf der LENTSOMA-Skala als auch auf der endoskopischen Terminologie der Weltorganisation für intestinale Endoskopie beruht . Zu Beginn und 1 - 2 Tage nach Beendigung der Strahlentherapie wurden mit Hilfe der flexiblen Rektosigmoidoskopie objektive Messungen vorgenommen . Für die gynäkologischen Patienten wurden ventrodorsale Felder benutzt , wohingegen bei den Patienten mit Prostatakarzinom eine 3-D konformale 4-Felder-Technik appliziert wurde . Während des 3-D-Therapieplans wurde auch die Fläche unter der Kurve ( AUC ) für die Auswertung in rektalen Dosis-Volumen-Histogrammen ( DVH ) bestimmt . Zwischen den beiden Gruppen war jedoch kein signifikanter Unterschied festzustellen , was auf eine homogene Dosis-Volumen-Wirkung hindeutet . Ergebnisse : Amifostin war gut verträglich . In Gruppe A wurde der Toxizitätsgrad 2 nach WHO und EORTC/RTOG weder erreicht noch überschritten . In Gruppe A wurde in 16 von 18 Fällen eine akute rektale Toxizität ≥ Grad 1 festgestellt , in Gruppe B dagegen nur in zwei von 18 Fällen ( p < 0.001 ) . Bei Gruppe A war hinsichtlich der Zeit bis zum Auftreten der Proktitis sowie deren Dauer eine deutliche Überlegenheit zu verzeichnen ( p = 0.002 ) . In der Kontrollgruppe ( Gruppe B ) deckte die Rektosigmoidoskopie eine wesentlich schwerere Rektumschleimhautentzündung auf , während dir Toxizität entsprechend der modifizierten LENT-SOMA-Skala in der Amifostingruppe bedeutend niedriger war ( p = 0.003 ) . Schlussfolgerung : Amifostin scheint in Anbetracht der beobachteten Symptome , gemessen an objektiven Endpunkten , bei akuter strahlungsinduzierter Proktitis eine zytoprotektive Wirkung zu PURPOSE Assessing the predictors of late rectal toxicity after high-dose conformal radiotherapy for prostate cancer . METHODS One thous and one hundred thirty-two patients entered a prospect i ve observational multicentric study ; late rectal toxicity was evaluated by a self-reported question naire . Results concerning bleeding and faecal incontinence of 718/1132 patients with a complete follow-up at 36 months were analysed . The correlation between a number of clinical -dosimetric parameters and moderate/severe toxicity was investigated by univariate and multivariate logistic analyses . RESULTS Fifty-two ( 7.2 % ) and 57/718 ( 7.9 % ) patients were scored as moderate/severe bleeders and faecal incontinents , respectively ; 19/57 incontinent patients showed persistent incontinence at 36 months . Bleeding was mainly correlated with V75 Gy while severe bleeding was mainly correlated with the previous abdominal/pelvic surgery ; a different rectal dose-volume relationship in the two groups of patients ( with/without surgery ) was found . Moderate/severe acute toxicity was weakly correlated to late bleeding . The best predictor of faecal incontinence was acute toxicity ( OR=4 and 7 for chronic and actuarial incontinence , respectively ) . CONCLUSION The application of rectal dose-volume constraints limited the incidence of rectal bleeding . The risk of bleeding may be further reduced by limiting V75 Gy<5 % and , in the case of patients previously su bmi tted to abdominal/pelvic surgery , V70 Gy<15 - 20 % . Faecal incontinence seems to be mainly a consequential effect after acute toxicity PURPOSE To evaluate the toxicity and preliminary outcome of patients with localized prostate cancer treated with twice-weekly hypofractionated intensity-modulated radiotherapy ( IMRT ) . METHODS AND MATERIAL S Between 2003 and 2006 , 82 prostate cancer patients with a nodal involvement risk ≤20 % ( Roach index ) have been treated to the prostate with or without seminal vesicles with 56 Gy ( 4 Gy/fraction twice weekly ) and an overall treatment time of 6.5 weeks . Acute and late genitourinary ( GU ) and gastrointestinal ( GI ) toxicities were scored according to the Radiation Therapy Oncology Group ( RTOG ) grading system . Median follow-up was 48 months ( range , 9 - 67 months ) . RESULTS All patients completed the treatment without interruptions . No patient presented with Grade ≥3 acute GU or GI toxicity . Of the patients , 4 % presented with Grade 2 GU or GI persistent acute toxicity 6 weeks after treatment completion . The estimated 4-year probability of Grade ≥2 late GU and GI toxicity-free survival were 94.2 % ± 2.9 % and 96.1 % ± 2.2 % , respectively . One patient presented with Grade 3 GI and another patient with Grade 4 GU late toxicity , which were transitory in both cases . The 4-year actuarial biochemical relapse-free survival was 91.3 % ± 5.9 % , 76.4 % ± 8.8 % , and 77.5 % ± 8.9 % for low- , intermediate- , and high-risk groups , respectively . CONCLUSIONS In patients with localized prostate cancer , acute and late toxicity were minimal after dose-escalation administering twice-weekly 4 Gy to a total dose of 56 Gy , with IMRT . Further prospect i ve trials are warranted to further assess the best fractionation schemes for these patients The purpose of this study was to evaluate the feasibility and the activity of radiotherapy treatment in patients aged ≥75 with prostate cancer ( PC ) . From January 2000 to December 2007 , 107 consecutive patients aged ≥75 years received radiotherapy with radical intent for PC . Eighty-one patients received radiotherapy in combination with a 6 months and rogen suppression therapy . Variables considered were age , stage , co-morbidities according to the adult co-morbidity evaluation index ( ACE-27 ) and performance status ( PS ) . The median age was 79.1 years ( range 76 - 87 ) . The 23.4 % of patients showed no co-morbidities , while the 46.7 % had mild , 23.4 % moderate , and 6.5 % severe co-morbidities , respectively . All patients completed the planned radiation treatment . At a median follow-up of 37.8 months , the 5-year overall survival rate was 78 % . There was a better survival for patients with no or mild co-morbidities ( p<0.0001 ) and a good PS ( p=0.009 ) . The actuarial disease-free survival at 60 months was 75.8 % . Difference in acute and late toxicity rate was detected between ACE-27 classes for diarrhea and marginally for urinary toxicity , but no difference was detected for different age . We conclude that compliance with radiotherapy is good and rate of toxicity is acceptable in elderly patients . Increasing severity of co-morbidity may sufficiently shorten remaining life expectancy to cancel gains with radical radiotherapy . Further prospect i ve trials are needed to confirm these results The therapeutic use of ionizing radiations is predicated on sparing normal tissue effects while attempting to achieve lethal effects on tumor cells . From quite early in the history of radiation therapy , it was apparent that there were striking differences in effects in the panoply of normal tissues . Although there was early appreciation of some late effects in normal tissues , often not predicted by acute reactions , only in recent years has there been full documentation of the slow and progressive increase in severity of late damage . Pathophysiological mechanisms of acute and late radiation effects are better understood today ( 2 ) , but interactions of other modalities with radiation therapy require constant monitoring to recognize and mitigate untoward sequelae . The work of Stone ( 3 ) is a classic example of unanticipated late effects , which result ed from irradiation with ‘ fast neutrons . Acute reactions were moderate and tolerable , but the late sequelae were so marked that there was little interest in pursuing therapy with fast neutrons for nearly three decades . The Late Morbidity Scoring Criteria were developed as a joint effort between physicians with renewed interests in fast neutron therapy and Radiation Therapy Oncology Group ( RTOG ) staff . In the late 1970s the Neutron/Particle Committee was one of several modality committees of the RTOG . Recognizing the results of Stone , this committee , led by Lawrence Davis worked with RTOG staff to establish criteria and scoring for possible late effects from fast neutron radiation therapy . Investigators from the European Organization for Research and Treatment of Cancer ( EORTC ) , led by William Duncan of the Western General Hospital of Edinburgh , wished to have common toxicity criteria in anticipation of joint studies . RTOG Protocol 7929 , an international registry of patients treated with heavy particles , was started in 1980 . At the annual meetings of the international participants in particle studies , there were attempts to monitor interobserver variations in scoring effects in normal tissues and to seek consistency in reporting toxicity , but no publications document these efforts . The first prospect i ve trial to use the Late Morbidity Scoring Criteria was RTOG Protocol 8001 , a study of fast neutron therapy for malignant tumors arising in salivary gl and s. Although the RTOG began to use these criteria in reporting toxicity in patients enrolled in all studies from 198 1 ( beginning with RTOG Protocol 8 115 ) , the criteria only became a published part of protocol s in 1983 . At that time , statistical methods began to be used , which presented time-adjusted estimates of late effects , the rationale for which was described by Cox ( 1 ) . It is now considered st and ard to represent cumulative probabilities of late effects with methods similar to those for estimating local control and survival . The Acute Radiation Morbidity Scoring Criteria were developed in 1985 as complimentary to the Late Effects Scoring Criteria . The National Cancer Institute promulgated st and ard toxicity criteria in 1990 , but late effects were not considered . An abbreviated version of the RTOG/EORTC toxicity criteria was published by Winchester and Cox in 1992 as part of the St and ard for Breast Conservation Treatment . The current RTOG Acute Radiation Morbidity Scoring Criteria are presented in Table 1 . The RTOG/EORTC Late Radiation Morbidity Scoring Scheme is detailed in Table 2 . In both tables , 0 means an absence of radiation effects and 5 means the effects led to death . The BACKGROUND AND PURPOSE Acute radiation-induced diarrhea occurs in approximately 80 % of the patients receiving pelvic radiotherapy . It is caused by gastrointestinal irritation and inflammation . Eicosanoids are thought to be one of the mechanisms of this . Sulphasalazine is an inhibitor of their synthesis in the mucosa . This r and omized clinical trial was undertaken to evaluate its effect in preventing acute radiation enteritis ( ARE ) . MATERIAL S AND METHODS Prospect ively , 87 patients receiving pelvic radiotherapy were r and omized , in a double-blind fashion . Two tablets twice daily of sulphasalazine ( 500 mg ) or placebo were administered orally . Patients were evaluated weekly according to diarrhea grading for the primary study endpoint and according to late effect of normal tissue-subjective objective management analytic ( LENT-SOMA ) criteria for the secondary endpoint during irradiation . RESULTS Groups did not differ for age , gender , tumour site or irradiation procedure . Diarrhea occurred in 55 and 86 % of the sulphasalazine and placebo groups , respectively ( P=0.001 ) . Gastrointestinal toxicity was seen in 80 and 93 % of the sulphasalazine and placebo groups according to the maximum LENT-SOMA score ( P=0.07 ) . According to the maximum LENT-SOMA score between the two groups , significant differences in favor of sulphasalazine were found for each week . CONCLUSION Sulphasalazine ( 2 g/day ) was found to be effective in decreasing the symptoms of ARE PURPOSE A common complication of pelvic radiotherapy ( RT ) is acute radiation-induced proctosigmoiditis ( RIPS ) , for which a multitude of therapies have been tried . The 5-aminosalicylates ( 5-ASA ) , which are traditionally used to treat inflammatory bowel disease , have been tested ; however , all but one prior r and omized attempt to limit or prevent RIPS with 5-ASA-type agents have failed . We sought to evaluate balsalazide , a new 5-ASA drug , for its potential to prevent or limit RIPS in patients undergoing RT for carcinoma of the prostate , as a representative sample of pelvic RT patients . Balsalazide has a unique delivery system in that 99 % of ingested drug is delivered to and activated in the colon , a higher yield than all other oral agents currently available in this class . Furthermore , it lacks the antigenic sulfa moiety present in sulfasalazine , the only other 5-ASA with demonstrated benefit in this setting . Thus , it was deemed an ideal c and i date for preventing or limiting RIPS . METHODS AND MATERIAL S Eligible patients included prostate cancer patients , American Joint Committee on Cancer Stage T1 - 3 , M0 being treated with external beam radiotherapy in the University of Kentucky Department of Radiation Medicine . Between January 1 , 2003 and July 1 , 2004 , 27 eligible patients were enrolled in the study . Patients were administered 2250 mg of balsalazide or an identical-appearing placebo twice daily beginning 5 days before RT and continuing for 2 weeks after completion . Toxicities were grade d weekly according to National Cancer Institute Common Toxicity Criteria v. 2.0 for each of the following : proctitis , diarrhea , dysuria , weight loss , fatigue , nausea , and vomiting . A symptom index was formulated for each toxicity consisting of the toxicity 's numeric grade multiplied by the number of days it was experienced , and summed for each grade experienced throughout the course of RT . RESULTS With the exception of nausea or vomiting , seen in 3 patients on balsalazide and 2 on placebo , all toxicities were appreciably lower in patients taking balsalazide . Proctitis was prevented most significantly with a mean proctitis index of 35.3 in balsalazide patients and 74.1 in placebo patients ( p = 0.04 ) . Placebo patients lost an average of 2.7 pounds , whereas balsalazide patients on average gained weight . Unexpectedly , dysuria was also lower in balsalazide-treated patients . CONCLUSIONS Balsalazide is a new-generation 5-ASA drug that yields a high concentration of active drug to the distal colon . Results of this pilot study suggest that it is able to prevent or reduce symptoms of RIPS in patients undergoing RT for prostate cancer . We feel that these results justify the formation of a cooperative group trial to assess its efficacy in a multi-institutional setting PURPOSE To assess the potential for sucralfate administered rectally to reduce the risk of late rectal morbidity in patients undergoing nonconformal radiotherapy ( RT ) for carcinoma of the prostate and to study the variables potentially contributing to late rectal morbidity and particularly to explore the relationship between acute and late toxicity . METHODS AND MATERIAL S Eighty-six patients with localized prostate carcinoma were r and omized in a double-blind , placebo-controlled study to a daily enema of 3 g of sucralfate in a 15-mL suspension or the same suspension without sucralfate . The enema began the first day of RT and was continued for 2 weeks after treatment completion . The primary end point of the study was acute Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer ( EORTC ) toxicity ; however , the patients were followed for an additional 5 years on a 6-month basis . The evaluation included late RTOG/EORTC toxicity and a patient self- assessment question naire . RESULTS With a median follow-up of 5 years , the Kaplan-Meier probability of late Grade 2 RTOG/EORTC toxicity was 12 % ( 95 % confidence interval [ CI ] 2 - 22 % ) for placebo and 5 % ( 95 % CI 0 - 12 % ) for sucralfate ( p = 0.26 ) . The probability of late rectal bleeding was 59 % ( 95 % CI 45 - 73 % ) for placebo and 54 % ( 95 % CI 40 - 68 % ) for sucralfate . No statistically significant difference was found between the treatment arms for the peak incidence of any of the other patient self- assessment variables . Cox proportional hazards modeling indicated acute RTOG/EORTC toxicity of Grade 2 or greater was associated with a hazard ratio of 2.74 ( 95 % CI 1.31 - 5.73 ) for the development of late toxicity of Grade 1 or greater . Substituting the patient self- assessment variables for acute RTOG/EORTC toxicity revealed that rectal pain of a moderate or severe grade during RT was the best predictor of the subsequent development of late toxicity , with a hazard ratio of 3.44 ( 95 % CI 1.68 - 7 ) . CONCLUSION The results of this study do not support the use of sucralfate administered rectally as a method for reducing the late toxicity of nonconformal RT for prostate cancer . There appears to be an association between the development of acute and subsequent late toxicity , although the nature of this association remains to be determined |
650 | 29,703,670 | This systematic review showed no significant differences between early and immediate loading protocol s in single implant crowns with regard to survival rate or marginal bone loss at 1 or 3 years | Patients prefer to be rehabilitated as soon as possible if the risk of implant failure is not increased .
However , whether immediate loading of single implants is riskier than early loading is not clear .
Purpose .
This systematic review and meta‐ analysis investigated whether the immediate loading protocol has more clinical disadvantages than the early loading protocol for single dental implants in terms of the marginal bone loss and survival rate of single implant crowns . | PURPOSE The primary goal of this stratified r and omized controlled trial ( S RCT ) was to compare the stability of dental implants placed under three different loading regimens during the first 16 weeks of healing following implant placement . Implants were loaded immediately , early ( 6 weeks ) , or with conventional/delayed timing ( 12 weeks ) . Secondary outcomes were to compare marginal bone adaptation for 3 years after placement . MATERIAL S AND METHODS Single posterior implant sites in the maxilla or m and ible were examined . The insertion torque value was the primary determinant of load assignment . Resonance frequency analysis was performed at follow-up appointments for the first 16 weeks ( with results provided as implant stability quotients [ ISQs ] ) . Marginal bone levels were assessed via radiographs . RESULTS Forty patients each received a single 4.0-mm diameter dental implant between 2004 and 2007 . One implant failure occurred in Lekholm and Zarb type 4 bone with insertion torque value ( ITV ) of < 8.1 Ncm ; the cumulative success rate was 97.5 % . All implants , when classified by bone and loading type , increased in stability over time , with a minor reduction of 1.3 ISQ units seen at 4 weeks in the immediate loading group . The mean marginal bone loss over 3 years was 0.22 mm . The mean ITVs at implant placement for bone types 1 and 2 ( grouped together ) , 3 , and 4 were 32 , 17 , and 10 , respectively , and were significantly different ( P < .05 ) . CONCLUSIONS ITV was a good objective measure of bone type . Using an ITV of 20 Ncm as the determinant for immediate loading and an ITV of 10 Ncm or greater as the determinant for early loading provided long-term success for this implant and led to no negative changes in tissue response . All bone type groups and loading groups showed no reduction in stability during the first 4 months of healing PURPOSE The possibility of expediting dental implant therapy by early or immediate loading protocol s requires long-term clinical investigation . The aim of this prospect i ve cohort trial was to determine the 3-year implant success rate and prosthesis complications associated with functional loading 3 weeks after 1-stage placement of Astra Tech single-tooth implants replacing maxillary anterior teeth . A secondary objective was to determine peri-implant tissue responses at these implants . MATERIAL S AND METHODS The peri-implant bone and mucosal conditions of 43 implants in 39 subjects were radiographically and clinical ly measured 3 years after implant placement . RESULTS Of the 48 patients originally treated , 39 patients and 43 implants were examined at the 3-year time point . Three of 54 implants failed within the first year . No additional failures were recorded since the 12-month reporting period . Peri-implant bone levels were stable for the 3-year period following implant placement . The change in marginal bone levels after 3 years was 0.42 + /- 0.59 mm . Papilla growth was measured at 1 and 3 years ( 0.61 + /- 0.95 mm and 0.74 + /- 0.79 mm , respectively ) . The buccal peri-implant tissue dimensions at the gingival zenith also increased at 1 and 3 years ( 0.34 + /- 0.94 mm and 0.51 + /- 1.42 mm , respectively ) . No abutment screw loosening or fracture occurred . DISCUSSION AND CONCLUSIONS Early loading of endosseous dental implants placed in healed ridges offers select benefits to clinicians and their patients BACKGROUND Interest in the use of one-stage surgery and immediate loading of oral implants has lately been increasing . PURPOSE The aim of this study was to compare the 3-year results of one-stage surgery versus two-stage surgery , early loading versus loading after a 3-month healing period , and the use of one-piece implants versus the use of two-piece implants . MATERIAL S AND METHODS The study included 108 patients with edentulous m and ibles . Each patient was treated with four Brånemark System implants ( Nobel Biocare AB , Göteborg , Sweden ) and with full fixed prostheses . Patients were consecutively treated and were distributed in four groups : group A ( one-stage surgery ) , group B ( control group with two-stage surgery ) , group C ( one-piece implants ) , and group D ( early loading ) . In groups A and B Brånemark St and ard implants and st and ard abutments were used . In group C the conical one-piece Brånemark implant was used , and in group D the patients had Brånemark System Mk III implants together with multiunit abutments . All patients were observed for 3 years . RESULTS Of the 432 inserted implants , 24 were lost . Survival rates in the three experimental groups ranged from 93.2 to 93.3 % whereas the survival rate in group B ( the control group with two-stage surgery ) was 97.5 % . The differences between the groups were not statistically significant . The changes in marginal bone level were measured from fixture insertion to the final follow-up at 3 years . The bone loss in group D ( early loading ) was significantly less than in group B ( the control group ) whereas there were no differences in marginal bone change between the other groups . CONCLUSIONS Early loading seemed to give good results in the anterior part of the m and ible . The survival rate of the early-loaded implants did not significantly differ from that of implants inserted with the conventional two-stage procedure , but the mean marginal bone loss around the surviving implants was less with early loading AIM To compare immediate versus early non-occlusal loading of dental implants placed flapless in a 3-year , parallel group , r and omized clinical trial . MATERIAL S AND METHODS The study was conducted in a private dental clinic between July 2005 and July 2010 . Patients 18 years or older were r and omized to receive implants for fixed partial dentures in cases of partial edentulism . The test group was represented by immediate non-occlusal implant loading , whereas the control group was represented by early non-occlusal implant loading . The outcome variables were implant failure , complications and radiographic bone level at implant sites 3 years after loading , measured from the implant-abutment junction to the most coronal point of bone-to-implant contact . R and omization was computer-generated with allocation concealment by opaque sequentially numbered sealed envelopes , and the measurer was blinded to group assignment . RESULTS Sixty patients were r and omized : 30 to the immediately loaded group and 30 to the early loaded group . Four patients dropped out ; however , the data of all patients were included in the analysis . No implant failure occurred . Two complications occurred in the control group and one in the test group . The mean bone level at 3 years was 1.91 mm for test group and 1.59 mm for control group . The adjusted difference in bone level was 0.26 mm ( CI 95 % -0.08 to 0.59 , p = 0.1232 ) . CONCLUSION The null hypothesis of no difference in failure rates , complications and bone level between implants that were loaded immediately or early at 3 years can not be rejected in this r and omized clinical trial PURPOSE To evaluate the medium-term effectiveness of 6.5 mm-long flapless-placed single implants immediately or early loaded at 6 weeks . MATERIAL S AND METHODS Thirty patients received two single NanoTite external hex Biomet 3i implants each , which were then r and omly allocated to be immediately or early loaded according to a splitmouth design . Implants had to be inserted with a minimum torque of > 40 Ncm . Provisional crowns were put in slight occlusal contact and replaced by definitive crowns 3 months after loading . Patients were followed for 4 years after loading . Outcome measures were implant failures , biological and biomechanical complications , peri-implant marginal bone level changes , and patient preference . RESULTS Twenty-nine implants were immediately loaded and 31 early loaded . Four years after loading , no drop-outs occurred . One implant failed in each group within 2 months after loading . Seven patients experienced complications at immediately loaded implants and 6 at early loaded implants . There were no statistically significant differences between groups for implant losses , complications , mean marginal bone level changes and patient preference . CONCLUSIONS Flapless-placed 6.5 mm-long single implants can be immediately loaded and remain successful up to 4 years after loading . Even longer follow-ups are still needed to evaluate the longterm prognosis of short implants PURPOSE To evaluate the efficacy of 7-mm-long flapless placed single implants immediately or early loaded at 6 weeks . MATERIAL S AND METHODS Thirty patients received two single Nanotite External Hex Biomet 3i implants that were then r and omised for immediate or early loading . All implants had to be inserted with a minimum torque > 40Ncm . Provisional crowns were put in slight occlusal contact and replaced by definitive crowns 3 months after loading . Outcome measures were implant failures , biological and biomechanical complications , peri-implant marginal bone level changes and patient preference . RESULTS Twenty-nine implants were immediately loaded and 31 early loaded . Thirteen flaps had to be elevated in 12 patients . Eleven implants in ten patients did not reach the planned insertion torque . Eight implants in seven patients were immediately replaced by implants with a larger diameter , two were loaded anyway , and one implant that was r and omised to immediate loading was early loaded instead . Nine months after loading , no drop-out occurred . One implant failed in each group . There were no statistically significant differences between groups for implant losses , complications , mean marginal bone level changes , and patient preferences . CONCLUSIONS Flapless placed 7-mm-long single implants can be successfully loaded the day of insertion . Longer follow-ups are needed to monitor the long-term prognosis of short implants In this study , 19 patients were treated with 36 Brånemark System MK III TiUnite implants in the maxilla . Definitive implant-supported single crowns were delivered to patients 6 weeks after implant placement . Clinical and radiographic parameters were recorded at baseline , and at 1 , 2 , and 3 years . Both implant and prosthesis success rates were 94 % after 3 years . The average marginal bone loss was 0.97 mm after 3 years . The results of this study indicate that 6-week early loading of TiUnite surface implants in the maxilla was reliable and predictable for this patient population and may offer an alternative to the st and ard loading protocol PURPOSE This study evaluated the survival parameters of single-tooth implants through clinical and radiographic analysis . MATERIAL S AND METHODS Implants were restored within a 24-hour period with a provisional crown design ed to receive an occlusal masticatory load . This approach was compared to implants restored after a healing period ( the control group ) . Forty-six implants were placed in 23 patients who were each treated with 2 Frialit-2 implants placed in sites between the second premolar in the maxilla or m and ible . The manufacturer 's recommended formal surgical procedure was followed , and primary stability was st and ardized with a minimum insertion torque of 20 Ncm . The sites were r and omly selected , and the clinical and radiographic parameters were st and ardized with individual templates . RESULTS Data were collected at 24 h , and at 1 , 3 , 6 , 12 , 18 , and 24 months . The experimental group included 10 failed implants ; 9 of the failed implants had been placed with an insertion torque of 20 Ncm . One implant from the control group failed during the 24-month follow-up period . The survival rate was independent of implant length , site position , and bone quality and quantity . Relative risk for implant failure was associated with insertion torque ( relative risk 0.79 [ CI : 0.66 - 0.930 ] ; Cox regression ) ( P < or = .007 ) , in the experimental group but was not significant for those in the control group ( ie , implants placed after a healing period ; relative risk 0.78 [ CI : 0.34 - 1.78 ] ; Cox regression ) ( P < or = .057 ) . To achieve osseointegration , it was found that an insertion torque above 32 Ncm was necessary ( chi2= 15.68 ; P < or = .004 ) . DISCUSSION A careful evaluation is necessary for a better underst and ing of the survival rates of immediately loaded implants . In this study , insertion torque was associated with the potential for risk , which can be decreased by 20 % per 9.8 Ncm added . CONCLUSION Given these results , and considering the number of patients treated , immediate provisional crowns should only be proposed with early loading if an appropriate initial insertion torque has been applied PURPOSE The aim of this report is to present the implant and clinical outcomes of an immediate-loading protocol of TiUnite implants with m and ibular overdentures in edentulous patients . MATERIAL S AND METHODS Two groups of edentulous patients were selected . Thirty-five consecutively treated patients received 70 immediately loaded TiUnite implants and 69 Brånemark implants as backup ( 1 patient received 1 Brånemark implant ) . The control group was a historical cohort that comprised 42 patients who received 111 Brånemark implants . All overdentures were supported by a resilient bar mechanism . Implant and clinical outcomes , including maintenance events for the first year , were recorded . RESULTS Implant success rates were in excess of 95 % with both protocol s. Immediately loaded implants had less bone loss than did implants loaded with the conventional protocol ( Mann-Whitney U test ; P = .001 ) . Patients in the immediate-loading group required more prosthodontic maintenance , consisting of overdenture remakes and laboratory relining of prostheses ( Chi-square test ; P < .05 ) . Of note , 74 % of patients in the immediate-loading group needed a reline to improve the denture seal around the bar housing ( Chi-square test ; P < .05 ) . CONCLUSION The favorable implant and bone level outcomes with immediate loading attest to its biologic success . The prosthetic maintenance encountered in the immediate-loading group does not negate the clinical potential of the treatment but rather suggests that the protocol may benefit from modifications OBJECTIVE Immediate and early loading of implants can simplify treatment and increase patient satisfaction . This 3-year r and omized-controlled trial will therefore evaluate survival rates and bone-level changes with immediately and early loaded Straumann implants with the SLActive surface . MATERIAL AND METHODS Partially edentulous patients > or=18 years of age were enrolled . Patients received a temporary restoration ( single crown or two to four unit fixed partial denture ) out of occlusal contact either immediately ( immediate loading ) or 28 - 34 days later ( early loading group ) , with permanent restorations placed 20 - 23 weeks after surgery . The primary endpoint was change in crestal bone level from baseline ( implant placement ) to 12 months ; the secondary variables were implant survival and success rates . RESULTS A total of 383 implants ( 197 immediate and 186 early ) were placed in 266 patients ; 41.8 % were placed in type III and IV bone . The mean patient age was 46.3+/-12.8 years . Four implants failed in the immediate loading group and six in the early loading group , giving implant survival rates of 98 % and 97 % , respectively ( P = NS ) . There were no implant failures in type IV bone . The overall mean bone level change from baseline to 12 months was 0.77+/-0.93 mm ( 0.90+/-0.90 and 0.63+/-0.95 mm in the immediate and early groups , respectively ; P<0.001 ) . However , a significant difference in implantation depth between the two groups ( P<0.0001 ) was found . After adjusting for this slight difference in initial surgical placement depth , time to loading no longer had a significant influence on bone-level change . Significant influence was found for : center ( P<0.0001 ) , implant length ( P<0.05 ) and implant position ( P<0.0001 ) . Bone gain was observed in approximately 16 % of implants . CONCLUSIONS The results demonstrated that Straumann implants with the SLActive surface are safe and predictable when used in immediate and early loading procedures . Even in poor- quality bone , survival rates were comparable with those from conventional or delayed loading . The mean bone-level change was not deemed to be clinical ly significant and compared well with the typical bone resorption observed in conventional implant loading PURPOSE The aim of this study was to compare implant-supported restorations placed and loaded immediately or with a delay in a longitudinal case control study . MATERIAL S AND METHODS Seventy-six patients with 222 implants were enrolled in this study . One hundred eleven implants ( 45 patients ) were su bmi tted to immediate functional or nonfunctional loading . These were compared to 111 implants ( 51 patients ) that received delayed loading after submerged healing . The mean observation time was 40.3 months ( 3.36 years ) . Implant success was determined , and peri-implant soft tissue parameters and esthetic outcomes for anterior restorations were evaluated . The implants were divided into four groups according to their treatment protocol : immediate ( I ) or delayed ( D ) implant placement ( P ) or function ( F ) , ie : group 1 = IF+IP , group 2 = IF+DP , group 3 = DF+IP , and group 4 = DF+DP . RESULTS Five implants were lost during healing , giving an overall success rate of 97.7 % . Implants with delayed function showed significantly better results ( 100.0 % ) than implants that were immediately loaded ( 95.5 % ) . Four of the five lost implants had been placed immediately post extraction ( success rate for delayed implant placement , 99.4 % , versus 93.1 % for immediate implant placement ) . Regarding the four treatment protocol s , group 1 showed a success rate of 91.3 % ; group 2 achieved 98.5 % ; and both delayed function groups showed 100 % success . No statistically significant difference was seen between the four groups . Esthetically significant advantages were seen for the implants placed into immediate function . Probing depths and bleeding on probing were significantly lower in the group of implants placed into immediate function . CONCLUSIONS Implants that are loaded immediately can achieve good outcomes . However , the risk of implant loss appears to be increased in cases where immediate function is combined with immediate implant placement PURPOSE To compare the efficacy of immediate nonocclusal loading ( test group ) versus early loading ( control group ) in partially edentulous patients . MATERIAL S AND METHODS Fifty-two patients in 5 Italian private practice s were r and omized to 1 of the treatments : 25 to the immediately loaded group and 27 to the early loaded group . To be immediately loaded , single implants had to be inserted with a torque of > 30 Ncm , and splinted implants had to be inserted with a torque of > 20 Ncm . Implants in the immediately loaded group were provided with full acrylic resin nonoccluding temporary restorations within 48 hours after placement . After 2 months , full occluding provisional restorations were provided . Implants in the early loading group were not submerged and were loaded after 2 months . At 8 months , provisional restorations were replaced with definitive metal-ceramic prostheses . Outcome measures were prosthesis and implant failures as well as biologic and prosthetic complications recorded by nonblinded assessors . The Fisher exact test was used to compare the proportion of implant failures . RESULTS Fifty-two implants were placed in the immediately loaded group and 52 in the early loaded group . No dropouts or complications occurred up to 14 months postinsertion . One single implant failed in the immediately loaded group 2 months after placement . There was no statistically difference for the tested outcome measures between the 2 procedures ( P > .99 ) . CONCLUSIONS The results of this r and omized controlled clinical trial with 25 patients rehabilitated with immediately restored nonocclusally loaded implant-supported prostheses compared to 27 patients restored 2 months following placement suggest that there are no major clinical differences in implant survival between these 2 protocol s. No biologic or prosthetic complications occurred OBJECTIVES The aim of this study was to compare clinical results of immediate and early loading ( EL ) self-tapping implants placed in posterior m and ibles . MATERIAL AND METHODS Twelve patients with bilateral edentulous posterior m and ibular were r and omly assigned to treatment either with immediate ( test ) or early loaded implants ( control ) . Seventy-two self-tapping implants with SLA surface ( Ø 4 , 1/4 , 8 mm ; length 8 and 10 mm ) were analyzed in this study . Test implants ( 36 ) were loaded on the day of surgery and control implants 6 weeks later . The measuring of implant stability quotient ( ISQ ) was performed on 0 , 6th , 12th , and 52nd week after implant insertion . The bone resorption , modified plaque , and bleeding index were notified at 1 and 5 years later . RESULTS After 5 years , survival in the both groups was 100 % . The mean value of primary implant stability was 76.92 ± 0.79 ISQ . In the first 6 weeks , ISQ values significantly increased in the test group ( 77.92 ± 1.16 vs. 79.61 ± 0.90 ) as well as in the control group ( 7.92 ± 1.05 vs. 77.55 ± 0.99 ) . A significant longitudinal increase in ISQ value was recorded in test and control group . The differences between immediate and early loaded implants were statistically insignificant ( P > 0.05 ) . At the 5 years , no statistically significant differences were found between immediate and early loaded implants with respect to mean crestal bone loss measurements ( 0.4 ± 0.24 vs. 0.8 ± 0.15 mm ) , mean bleeding index ( 0.22 ± 0.11 vs. 0.25 ± 0.11 ) , and mean plaque index ( 0.17 ± 0.15 vs. 0.19 ± 0.20 ) . CONCLUSION Based on these results , the self-tapping implants inserted in posterior m and ible can provide adequate primary stability value as the main factor for immediate and EL protocol The aim of this study was to compare the release of bone markers during osseointegration of immediately loaded and nonloaded implants . Forty patients who were indicated for rehabilitation with dental implants r and omly received either implant and prosthesis placement within 72 hours ( group IM ) or implant insertion and no prosthesis placement ( group NL ) . Peri-implant crevicular fluid was collected immediately after implant insertion and 7 , 15 , 30 , 60 , 90 , and 120 days after surgery and levels of osteoprotegerin , transforming growth factors , osteocalcin , osteopontin , and parathyroid hormone were evaluated using Luminex assay . Bleeding index and peri-implantar sulcus depth were also evaluated . The data were compared using statistical tests ( α = 5 % ) . No statistical difference was found regarding demographic and clinical parameters ( p > .05 ) . Transforming growth factors , osteoprotegerin , osteopontin , and parathyroid hormone presented an earlier release peak in group IM than in NL group ( p < .05 ) . Osteocalcin achieved higher levels in group IM versus group NL between 7 and 30 days of evaluation ( p < .05 ) . It may be concluded that earlier loading positively modulates bone mediators release around immediately loaded implants when compared with nonloaded dental implants ( Clinical Trials.gov NCT01909999 ) BACKGROUND There is a lack of well- design ed prospect i ve , r and omized clinical trials evaluating the efficacy of immediate and early loading of implants placed in the partially edentulous posterior maxilla or m and ible . PURPOSE The aim of this study was to evaluate crestal bone level changes over 3 years following immediate or early loading of Straumann implants with a chemically modified surface ( SLActive ® , Institut Straumann AG , Basel , Switzerl and ) placed in the posterior maxilla and m and ible . MATERIAL S AND METHODS Subjects received temporary restorations immediately or 28 to 34 days after surgery , with permanent restorations placed at 20 to 23 weeks . Bone level changes were measured by comparison of st and ardized radiographs taken on the day of implant placement and 5 , 12 , 24 , and 36 months thereafter . RESULTS Two hundred thirty-nine of two hundred sixty-six patients ( 89.9 % ) completed the trial . Implant survival rates were 97.4 % and 96.7 % in the immediate and early loading groups , respectively ( p = not significant ) . Over 36 months , the mean bone level change for immediately loaded implants was 0.88 ± 0.81 mm versus 0.57 ± 0.83 mm for the early-loaded group ( p < .001 ) . After adjusting for a slight difference in initial placement depth , the time of loading had no significant influence on bone level change . CONCLUSIONS Changes in crestal bone level occurred mostly during the first 5 months postloading . After this bone remodeling period , crestal bone level was stable up to 36 months . Implants with a chemically modified surface are safe and predictable for immediate and early loading in the posterior maxilla and m and ible PURPOSE To compare the clinical outcome of single implants which underwent immediate nonocclusal loading with implants subjected to early non-occlusal loading at 3 weeks , and implants conventionally loaded at 4 months . MATERIAL S AND METHODS One hundred and five patients in five private practice s requiring a single implant-supported crown were r and omised to immediate loading ( 35 patients ) , early loading ( 35 patients ) and conventional loading ( 35 patients ) groups . To be immediately or early loaded , implants had to be inserted with a torque superior to 45 Ncm . Immediately and early loaded implants received non-occluding temporary crows , whereas conventionally loaded implants were directly restored with definitive crowns . Temporary crowns were replaced by definitive ones after 4 months . Outcome measures were crown and implant failures , complications and peri-implant marginal bone level changes recorded by a blinded assessor . RESULTS Two patients dropped out from the immediate loading group up to 1-year post-loading . Two implants failed , one in the immediately loaded and one in the early loaded group ( P=0.601 ) . One immediately loaded implant and two early loaded implants were affected by one complication each ( P=0.162 ) . Mean peri-implant marginal bone loss after 1 year was -0.120±0.230 mm ( 95 % CI -0.35 , 0.10 ) for immediate , -0.390±0.840 mm ( 95 % CI -1.23 , 0.45 ) for early and -0.201±0.306 mm ( 95 % CI -0.51 ; 0.11 ) for conventionally loaded implants . There were no statistically significant differences for any of the outcome measures between the three loading strategies up to 1-year post-loading . CONCLUSIONS No major clinical differences were observed with regard to implant survival , complications and marginal bone level changes when loading single implants immediately , early or conventionally AIMS To compare immediate versus early ( 6 weeks ) non-occlusal loading of dental implants placed flapless in partially edentulous patients 1 year after loading . MATERIAL S AND METHODS Sixty patients were r and omised : 30 to the immediately loaded group and 30 to the early loaded group . In order to be immediately loaded , implants were inserted with a minimum torque of > or = 40Ncm . Implants were fully occlusally loaded after 6 months . Outcome measures were prosthesis and implant failures , and biological and biomechanical complications . RESULTS Five implants in five patients r and omised to the immediately loaded group did not reach the required primary implant stability . Three of these implants ( two prostheses ) were not immediately loaded . Two patients who were r and omised to the early loaded group were immediately loaded erroneously . Implants in five patients of the early loaded group were conventionally loaded . No patient dropped out and there were no failures . Two complications occurred in the early and one in the immediately loaded group ( no statistically significant difference ) , but were solved . CONCLUSIONS The use of a flapless technique for placing dental implants in conjunction with non-occlusal immediate or early loading in selected patients can provide excellent clinical results . No differences were observed when comparing implants that were loaded immediately or early . Therefore , when a high primary implant stability is obtained , it might be preferable to load the implants immediately rather than waiting for a few weeks |
651 | 12,142,305 | Smoke-free workplaces not only protect non-smokers from the dangers of passive smoking , they also encourage smokers to quit or to reduce consumption | OBJECTIVE To quantify the effects of smoke-free workplaces on smoking in employees and compare these effects to those achieved through tax increases . | CONTEXT The association between environmental tobacco smoke ( ETS ) exposure and respiratory symptoms has not been well established in adults . OBJECTIVE To study the respiratory health of bartenders before and after legislative prohibition of smoking in all bars and taverns by the state of California . DESIGN Cohort of bartenders interviewed before and after smoking prohibition . SETTING AND PARTICIPANTS Bartenders at a r and om sample of bars and taverns in San Francisco . MAIN OUTCOME MEASURES Interviews assessed respiratory symptoms , sensory irritation symptoms , ETS exposure , personal smoking , and recent upper respiratory tract infections . Spirometric assessment included forced expiratory volume in 1 second ( FEV1 ) and forced vital capacity ( FVC ) measurements . RESULTS Fifty-three of 67 eligible bartenders were interviewed . At baseline , all 53 bartenders reported workplace ETS exposure . After the smoking ban , self-reported ETS exposure at work declined from a median of 28 to 2 hours per week ( P<.001 ) . Thirty-nine bartenders ( 74 % ) initially reported respiratory symptoms . Of those symptomatic at baseline , 23 ( 59 % ) no longer had symptoms at follow-up ( P<.001 ) . Forty-one bartenders ( 77 % ) initially reported sensory irritation symptoms . At follow-up , 32 ( 78 % ) of these subjects had resolution of symptoms ( P<.001 ) . After prohibition of workplace smoking , we observed improvement in mean FVC ( 0.189 L ; 95 % confidence interval [ CI ] , 0.082 - 0.296 L ; 4.2 % change ) and , to a lesser extent , mean FEV1 ( 0.039 L ; 95 % CI , -0.030 to 0.107 L ; 1.2 % change ) . Complete cessation of workplace ETS exposure ( compared with continued exposure ) was associated with improved mean FVC ( 0.287 L ; 95 % CI , 0.088 - 0.486 ; 6.8 % change ) and mean FEV1 ( 0.142 L ; 95 % CI , 0.020 - 0.264 L ; 4.5 % change ) , after controlling for personal smoking and recent upper respiratory tract infections . CONCLUSION Establishment of smoke-free bars and taverns was associated with a rapid improvement of respiratory health Smoking and health are increasingly understood to be incompatible . To evaluate , prospect ively and retrospectively , the attitudes of employees , staff physicians , and patients of a medical institution , a question naire was administered before and after implementation of a no-smoking policy . Of many questions , select ones review ed here focused on the following concerns : ( 1 ) how tobacco smoke affects employees and patients , ( 2 ) employee acceptance of a no-smoking policy before and after its implementation , and ( 3 ) the consequences of the policy on employee smokers . Open-ended questions about smoking were constructed by a committee comprised of clinicians , investigators , and administrators . The question naire was given to 2,000 r and omly selected patients and the institution 's entire staff of 4,200 employees and 225 staff physicians . Data were obtained on three occasions : six months before , six months after , and one year after the implementation of the no-smoking policy . The majority of patients , employees , and physicians indicated that the smoke of others bothered them and ranked the following as most offensive : smell , eye irritation , provocation of sinus problems , coughing , and headache . Approximately 80 percent of employees and patients favored the policy before its inception ; and employees increasingly favored it through the year after its implementation with a favorable attitude increasing by nearly 10 percentage points . One year after implementation , 80 percent of patients were in favor of the policy . In the final survey , 74 percent of respondents indicated the policy had helped them . One year after policy implementation , employee smoking was reduced significantly from 22 to 14 percent ; and of those employees who continued to smoke , 81 percent smoked less than eight cigarettes per day . ( ABSTRACT TRUNCATED AT 250 WORDS In view of the fact that the impact of statewide smoking laws on private worksite policies and the smoking behavior of employees has not been evaluated , two cross-sectional surveys were performed in Vermont to measure compliance with such a law : a r and om-digit telephone survey of employees and a subsequent mail survey of their employers . Employers were not aware that one of their employees had been surveyed . Roughly half ( 56 percent ) of the employees and 66.5 percent of their employers described policies that are in compliance . Among all employers who described policies in compliance with the law , 68.1 percent of their employees also described compliant policies . Among all employees who described non-compliant policies , 48.8 percent had employers who described compliant policies . Overall , employees and employers agreed on how their policies stood with respect to compliance in 67.6 percent of cases . The prevalence and amount of smoking at work declined after the institution of the law but so did the prevalence and amount of smoking at home . Changes toward more restrictive policies were associated with reductions in cigarette consumption at work , but not with quitting . The study suggests that a large fraction of worksite smoking policies may not comply with a statewide worksite smoking law . The proportion of companies complying with such a law may be overestimated if information on compliance is obtained only from employers BACKGROUND AND OBJECTIVES To examine the long term impact of workplace smoking bans on employee smoking cessation and relapse . Over three years we studied a total of 1033 current or former smokers ( intervention group ) employed in smoke-free hospitals and 816 current or former smokers ( comparison group ) employed in non-smoke-free workplaces . The design of this natural experiment is a prospect i ve cohort study . We r and omly selected both hospitals and employees from 12 strata based on hospital size and state tobacco regulations , and sample d employees in the same communities . Main outcome measures were post-ban quit ratio and relapse rate . RESEARCH DESIGN Between groups comparisons were conducted using the Cochran-Mantel-Haenszel statistic for general association , stratified Cox proportional hazards models , and the CMH analysis of variance statistic based on ranks . McNemar 's test and the sign test were used to test for changes over time within each group . RESULTS Differences in the post-ban quit ratio were observed between intervention and comparison groups ( p ⩽ 0.02 ) . For employees whose bans were implemented at least seven years before survey , the post-ban quit ratio was estimated at 0.256 , compared with 0.142 for employees in non-smoke-free workplaces ( p = 0.02 ) . After controlling for a variety of factors , time to quit smoking was shorter for the hospital employees ( p < 0.001 ) , with an overall relative risk of quitting of 2.3 . Contrary to expectations , relapse rates were similar between the groups . CONCLUSION Employees in workplaces with smoking bans have higher rates of smoking cessation than employees where smoking is permitted , but relapse is similar between these two groups of employees . The results of this investigation have international applicability for policy makers , clinicians , employers , and employees . Countries should review smoking policies in workplaces in light of their own smoking patterns and efforts to deal with environmental tobacco smoke STUDY OBJECTIVE : The aim of this study was to evaluate the impact of a smoke free programme implemented at the University of Geneva , Switzerl and , in 1996 . This programme included a prohibition to smoke in university buildings everywhere except in limited areas , and a smoking cessation counselling service . METHODS : Surveys were conducted before and four months after the programme was implemented , in representative sample s of programme participants ( n = 833 ) and university members not exposed to the programme ( n = 1023 ) . RESULTS : In retrospective assessment s , participants reported being less bothered by environmental tobacco smoke after programme implementation , but no between group difference was detected in prospect i ve assessment s. Relationships between smokers and non-smokers improved moderately in the intervention group and remained unchanged in the comparison group ( between group p = 0.001 ) . Proportions of smokers who attempted to quit smoking in the past four months increased from 2.0 % to 3.8 % in the intervention group and remained unchanged at 3.5 % in the comparison group ( between group difference : p = 0.048 ) . No impact on smoking prevalence ( 25 % ) was detected . The programme was appreciated by university members , although some of its modalities were criticised . CONCLUSION : A regulation prohibiting smoking everywhere but in limited areas of university buildings was acceptable and reduced the perception of bother by environmental tobacco smoke . It did not , however , influence smoking habits or attitudes toward smoking Purpose . To determine the prevalence of tobacco use among Centers for Disease Control and Prevention (CDC)/Agency for Toxic Substances and Disease Registry ( ATSDR ) employees and the effect of the smoke-free policy on smoking behavior and air quality at work . Design . A stratified telephone survey of 1181 CDC/ATSDR employees r and omly selected from employee rosters . Setting . CDC/ATSDR work sites in Atlanta , Georgia , and other major CDC locations throughout the United States and Puerto Rico . Subjects . R and omly selected employees of CDC/ATSDR1 , or about 22 % of the total CDC/ATSDR population ; 98 % of eligible persons selected agreed to participate . Measures . Demographic and smoking history variables , attitudes toward and impact of the smoke-free policy on smoking behavior , and self-report changes in air quality were the measures used . Results . Overall cigarette smoking prevalence was only 11.1 % . One percent reported using chewing tobacco , 1.1 % reported smoking a pipe , and 1.4 % reported smoking cigars . Average self-reported , daily cigarette comsumption significantly decreased after the smoking ban took effect . Overall , 90 % of the employees supported the smoke-free policy , and 80 % of the employees believed that smokers were complying with the smoke-free policy . Most employees believed that the air quality of work areas and nonwork areas ( 65 % and 69 % , respectively ) had improved since the smoke-free policy was implemented . Conclusions . These findings are consistent with previous evaluations of smoke-free policies and suggest that most employees are generally supportive of workplace smoking restrictions . Such policies can also have a positive impact on smoking behavior and perceived air quality BACKGROUND This study reports the barriers and challenges for hospital tobacco control efforts after the institution of smoke-free policies . METHODS Surveys of employees and in patients of five hospitals in Augusta , Georgia , were conducted and evaluated 4 months after joint hospital implementation of smoke-free policies . A r and om sample of 1997 employees and a convenience sample of 517 in patients returned usable surveys . RESULTS Although attitudes to the hospital bans on smoking reflected strong support for smoke-free policies , four out of five hospitals reported significant implementation problems . Despite the bans , 49 % of patients who were smokers continued to smoke while hospitalized , and almost one half of all hospitalized smokers had received no advice to quit smoking from a physician or a nurse since admission . Employees and patients both agreed that the smoke-free policies had benefited employees more than patients . CONCLUSIONS Despite achieving a smoke-free status , there are many challenges that remain for comprehensive hospital tobacco-control efforts . Hospitals and health care professionals must remain particularly alert and attentive to the needs of patients and employees still addicted to tobacco OBJECTIVES This study evaluated the biological and subjective consequences observed in individual smokers after implementation of a workplace smoking-restriction policy . METHODS Employees were evaluated for 4 weeks before and 4 weeks after their workplace became smoke-free ( n = 34 ) . A comparison group of smokers whose work-site smoking was unrestricted served as controls ( n = 33 ) . Daily exposure to tobacco constituents and withdrawal effects were measured . RESULTS Smokers at the restricted site had verified smoking reduction ( mean = four cigarettes per day ) and significantly reduced nicotine and carbon monoxide during the work shift . There were increases in ratings of some common withdrawal symptoms ( cravings/urges , concentration difficulties , increased eating , depression ) . No evidence of compensatory smoking during nonwork hours was found . Overall tobacco exposure , as measured in saliva cotinine , showed a nonsignificant 15 % decline . CONCLUSIONS Workplace smoking restriction markedly altered smoking patterns ( i.e. , reduced daytime smoking ) and reduced cotinine levels to an amount consistent with cigarette reduction . Thus , work-site smoking restriction may promote meaningful , albeit limited , reductions in tobacco exposure and consequent health risks OBJECTIVE To determine the effectiveness of laws restricting youth access to cigarettes on prevalence of smoking among teens . METHODS We conducted a systematic review of studies that reported changes in smoking associated with the presence of restrictions on the ability of teens to purchase cigarettes . We calculated the correlation between merchant compliance levels with youth access laws and prevalence ( 30-day and regular ) prevalence of youth smoking , and between changes in compliance and prevalence associated with youth access interventions . We also conducted a r and om effects meta- analysis to determine the change in youth prevalence associated with youth access interventions from studies that included control communities . RESULTS Based on data from 9 studies , there was no detectable relationship between the level of merchant compliance and 30-day ( r = .116 ; n = 38 communities ) or regular ( r = .017 ) smoking prevalence . There was no evidence of a threshold effect . There was no evidence that an increase in compliance with youth access restrictions was associated with a decrease in 30-day ( r = .294 ; n = 18 communities ) or regular ( r = .274 ) smoking prevalence . There was no significant difference in youth smoking in communities with youth access interventions compared with control communities ; the pooled estimate of the effect of intervention on 30-day prevalence was -1.5 % ( 95 % confidence interval : -6.0 % to + 2.9 % ) . CONCLUSIONS Given the limited re sources available for tobacco control , as well as the expense of conducting youth access programs , tobacco control advocates should ab and on this strategy and devote the limited re sources that are available for tobacco control toward other interventions with proven effectiveness OBJECTIVE : To report data on the impact of worksite smoking policies on employee smoking behaviour from a large and heterogeneous sample of smokers and worksites in 22 different communities across North America participating in the COMMIT trial . DESIGN AND SUBJECTS : Data from a population -based survey of 8271 employed adult smokers who completed surveys in 1988 and 1993 . Surveys included questions on tobacco use behaviours , personal/demographic characteristics , and smoking policy and cessation re sources at the workplace . RESULTS : After controlling for potential confounding factors , regression analyses revealed that employees who worked in a smoke-free worksite were over 25 % more likely to make a serious quit attempt between 1988 and 1993 , and over 25 % more likely to achieve cessation than those who worked in a worksite that permitted smoking . Among continuing smokers , employees in smoke-free worksites consumed an average of 2 3/4 fewer cigarettes per day compared with those who worked in places with a non-restrictive smoking policy . A smoke-free worksite policy was not associated with a greater likelihood of using smokeless tobacco . CONCLUSION : These data , from one of the largest and longest smoking cessation studies to date , add support to the conclusion that smoke-free worksite policies help employees to reduce or discontinue use of tobacco A " smoke-free " policy was adopted at the Duke University Medical Center but not at the adjacent University Campus . Three months after the smoking prohibition went into effect , a cross-sectional telephone survey was conducted , using r and omly selected groups of 400 employees from each campus . Subjects were queried about current and previous smoking histories and their opinion of the smoking ban . As determined retrospectively from this survey , at the time of the announcement of the policy and 6 months before implementation , 23.6 % of employees at the Medical Center were smokers , compared with 20.3 % on the University Campus . Three months after implementation of the Medical Center smoking prohibition , smoking cessation rates were 12.6 % at the Medical Center and 6.9 % on the University Campus dating back 9 months to the time of policy announcement ( P less than 0.10 ) . Mean cigarette consumption during work hours declined over this same period from 8.1 + /- 6.8 ( mean + /- SD ) to 4.3 + /- 4.4 at the Medical Center but showed little change on the University Campus ( 9.3 + /- 7.5 v 8.7 + /- 8.0 ) . Overall , 75.8 % of subjects at the Medical Center " somewhat " or " strongly " agreed with the policy compared with 73.2 % on the University Campus . A follow-up survey of the cohort of current or recent ex-smokers identified on the initial survey was conducted 6 months later . This survey revealed a smoking cessation rate of 22.5 % at the Medical Center and 6.9 % on the University Campus , dating back 15 months to the time of policy announcement ( P less than 0.01 ) . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To examine the impact of workplace smoking bans on smoking behavior of employees . PARTICIPANTS A total of 1469 current or former smokers ( intervention group ) employed in smoke-free hospitals and 920 current or former smokers ( comparison group ) employed in non-smoke-free workplaces were surveyed to determine smoking behavior . DESIGN This cross-sectional study is part of a larger , ongoing prospect i ve study . The study design was quasi-experimental . We r and omly selected sites consisting of a hospital and a corresponding community . Furthermore , we r and omly selected subjects from hospitals and their corresponding communities . MAIN OUTCOME MEASURES Postban quit ratio and progression along the stages-of-change continuum . METHODS The Cox proportional hazards model was used to compare the postban quit ratio between the intervention and comparison groups . The Cochran-Mantel-Haenszel analysis of variance statistic was used to compare groups on the stages-of-change variables . RESULTS Beginning with the smoking ban and continuing for 5 years after implementation , statistically significant differences in the postban quit ratio were observed between employees of smoke-free hospitals who were smokers and counterparts in the community ( P<.001 ) . Despite preban differences in smoking intensity , the overall difference in postban quit ratios remained significant even after multivariate adjustment for socioeconomic , demographic , and smoking intensity variables . For those sites that were 5 years postban , the quit ratio was 0.506 in smoke-free workplaces compared with 0.377 in workplaces where smoking was permitted . In all but 1 category , the intervention group was further along the stages-of-change continuum toward quitting smoking than the comparison group ( P<.001 ) . CONCLUSION American hospitals ' experiences with smoking bans , which directly affect more than 5 million workers , should be examined by other industries as a method of improving employee health . Workplace smoking bans could also be effective in saving lives , reducing health care costs , addressing safety concerns , and decreasing operating and maintenance expenses of employers R and om-digit dialing surveys were conducted before ( n = 1543 ) and 8 to 9 months after ( n = 1430 ) implementation of the city of Toronto workplace smoking bylaw . Compared with workers in the rest of metropolitan Toronto and persons not working outside the home , city workers evidence d more positive changes in regard to knowledge of the bylaw , its requirements , and enforcement provisions . City workers reported more changes in workplace restrictions and satisfaction with such restrictions . Patterns of smoking at work changed A r and om sample of employees was surveyed 20 months after a non-smoking policy was implemented at the New Engl and Telephone Company in 1986 . Overall , 21 percent of respondents who were smoking at the time they heard about the policy had quit smoking ; 42 percent of quitters said they stopped smoking because of the policy . Cessation was highest among those who reported less smoke in their work area , but was not related to participation in cessation programs . This study suggests that worksite nonsmoking policies may have favorable effects on smoking cessation This article presents data from a population -based , r and om-digit dialing telephone survey of 1228 employed adults in Washington State , conducted 1989 through 1990 . Eighty-one percent of men and 91 % of women reported work-site smoking restrictions . Employees in work sites with no-smoking policies were less likely to be current smokers ; men in work sites with policies restricting smoking smoked fewer cigarettes on both workdays and nonworkdays . Forty-eight percent of male and 53 % of female smokers reported reduced smoking as a result of work-site policy . Work-site smoking policies , intended to protect against smoke exposure , may also reduce employee smoking BACKGROUND Thirty-two worksites participating in a r and omized trial of worksite health promotion aim ed at reducing smoking and obesity were categorized at baseline and 2 years later as having either restrictive or unrestrictive smoking policies . Between the two assessment points , 16 sites received health promotion interventions . RESULTS At baseline 15 sites had restrictive policies and 17 unrestrictive policies . Smoking restrictions were associated with significantly lower smoking prevalence and higher lifetime quit rates among ever smokers . They also were associated with more recent quit attempts and lower daily cigarette consumption , although these effects were not significant . Between baseline and follow-up , 9 of the 17 worksites that had few smoking restrictions at baseline became restrictive . Although neither baseline smoking policies nor changes in smoking policy predicted change in smoking prevalence or in the frequency of quit attempts , smokers in sites changing from unrestrictive to restrictive policies reported a significant reduction in daily cigarette consumption . CONCLUSIONS The worksite health promotion program was successful in reducing smoking prevalence in intervention sites compared to controls . However , the existence of restrictive smoking policies neither helped nor hindered these intervention efforts . The present data are believed to support the idea that restrictive smoking policies have beneficial effects on the smoking habits of employees , but that the magnitude of this effect is modest OBJECTIVE To assess the impact of attitudes toward secondh and smoke among young people . METHODS Three hundred nonsmokers and 300 smokers ( smoked a cigarette in last 30 days ) 14 through 22 years of age in the United States were surveyed with r and om-digit dialing . The results of this cross-sectional survey were analyzed using logistic regression to determine predictors of nonsmoking and intent to stop among current smokers . RESULTS Controlling for age , ethnicity , and education , nonsmokers were more likely to consider smoking risky than smokers ( odds ratio [ OR ] = 3.46 ) . Nonsmokers were twice as likely to consider secondh and smoke dangerous than smokers ( OR = 1.47 ) . Among the variables in our model , the only statistically significant predictor of planning to stop smoking or having actually stopped was believing that secondh and smoke harmed nonsmokers , which more than doubled the chances of planning to stop or having stopped smoking ( relative risk = 2.17 ) . CONCLUSIONS Educating young people about the dangers of secondh and smoke and empowering nonsmokers to speak out should be a strong element of any tobacco control program An empiric evaluation of a policy ending smoking in a large urban medical center was conducted . The study included a prospect i ve cohort tracking of employees to measure changes in smoking behavior , environmental fires , smoking-related litter , and environmental tobacco pollution exposure . A 25 % decrease in employee smoking prevalence was found ( 21.7 % vs 16.2 % before vs after policy implementation , respectively ) . The daily number of cigarettes reportedly smoked by employees who continued smoking and the total number smoked at work decreased across all occupational categories by an average of 25 % . Significant reductions were noted in the level of public smoking and the amount of cigarette remnants . Nicotine vapor concentrations decreased significantly in all areas except restrooms . These findings suggest that visible smoking and environmental tobacco smoke exposure can be markedly decreased by instituting a policy eliminating smoking in a large medical center |
652 | 26,119,726 | Although these biomarkers show promise , there is not enough evidence to justify their use in routine practice . | Radiotherapy is an essential component of treatment for more than half of newly diagnosed cancer patients .
The response to radiotherapy varies widely between individuals and although advances in technology have allowed the adaptation of radiotherapy fields to tumour anatomy , it is still not possible to tailor radiotherapy based on tumour biology .
A biomarker of intrinsic radiosensitivity would be extremely valuable for individual dosing , aiding decision making between radical treatment options and avoiding toxicity of neoadjuvant or adjuvant radiotherapy in those unlikely to benefit .
This systematic review summarises the current evidence for biomarkers under investigation as predictors of radiotherapy benefit . | BACKGROUND The likelihood of distant recurrence in patients with breast cancer who have no involved lymph nodes and estrogen-receptor-positive tumors is poorly defined by clinical and histopathological measures . METHODS We tested whether the results of a reverse-transcriptase-polymerase-chain-reaction ( RT-PCR ) assay of 21 prospect ively selected genes in paraffin-embedded tumor tissue would correlate with the likelihood of distant recurrence in patients with node-negative , tamoxifen-treated breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-14 . The levels of expression of 16 cancer-related genes and 5 reference genes were used in a prospect ively defined algorithm to calculate a recurrence score and to determine a risk group ( low , intermediate , or high ) for each patient . RESULTS Adequate RT-PCR profiles were obtained in 668 of 675 tumor blocks . The proportions of patients categorized as having a low , intermediate , or high risk by the RT-PCR assay were 51 , 22 , and 27 percent , respectively . The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low-risk , intermediate-risk , and high-risk groups were 6.8 percent ( 95 percent confidence interval , 4.0 to 9.6 ) , 14.3 percent ( 95 percent confidence interval , 8.3 to 20.3 ) , and 30.5 percent ( 95 percent confidence interval , 23.6 to 37.4 ) . The rate in the low-risk group was significantly lower than that in the high-risk group ( P<0.001 ) . In a multivariate Cox model , the recurrence score provided significant predictive power that was independent of age and tumor size ( P<0.001 ) . The recurrence score was also predictive of overall survival ( P<0.001 ) and could be used as a continuous function to predict distant recurrence in individual patients . CONCLUSIONS The recurrence score has been vali date d as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative , estrogen-receptor-positive breast cancer PURPOSE Biomarkers can add substantial value to current medical practice by providing an integrated approach to prediction using the genetic makeup of the tumor and the genotype of the patient to guide patient-specific treatment selection . We discuss and evaluate various clinical trial design s for the validation of biomarker-guided therapy . METHODS Design s for predictive marker validation are broadly classified as retrospective ( ie , using data from previously well-conducted r and omized controlled trials [ RCTs ] ) versus prospect i ve ( enrichment , unselected , hybrid , or adaptive analysis ) . We discuss the salient features of each design in the context of real trials . RESULTS Well- design ed retrospective analysis from well-conducted prospect i ve RCTs can bring forward effective treatments to marker-defined subgroups of patients in a timely manner ( eg , KRAS and colorectal cancer ) . Enrichment design s are appropriate when preliminary evidence suggest that patients with or without that marker profile do not benefit from the treatments in question ; however , this may sometimes leave questions unanswered ( eg , trastuzumab and breast cancer ) . An unselected design is optimal where preliminary evidence regarding treatment benefit and assay reproducibility is uncertain ( eg , epidermal growth factor receptor and lung cancer ) . Hybrid design s are appropriate when preliminary evidence demonstrate the efficacy of certain treatments for a marker-defined subgroup , making it unethical to r and omly assign patients with that marker status to other treatments ( eg , multigene assay and breast cancer ) . Adaptive analysis design s allow for prespecified marker-defined subgroup analyses of data from an RCT . CONCLUSION The implementation of these design strategies will lead to a more rapid clinical validation of biomarker-guided therapy PURPOSE Development of a radiosensitivity predictive assay is a central goal of radiation oncology . We reasoned a gene expression model could be developed to predict intrinsic radiosensitivity and treatment response in patients . METHODS AND MATERIAL S Radiosensitivity ( determined by survival fraction at 2 Gy ) was modeled as a function of gene expression , tissue of origin , ras status ( mut/wt ) , and p53 status ( mut/wt ) in 48 human cancer cell lines . Ten genes were identified and used to build a rank-based linear regression algorithm to predict an intrinsic radiosensitivity index ( RSI , high index = radioresistance ) . This model was applied to three independent cohorts treated with concurrent chemoradiation : head- and -neck cancer ( HNC , n = 92 ) ; rectal cancer ( n = 14 ) ; and esophageal cancer ( n = 12 ) . RESULTS Predicted RSI was significantly different in responders ( R ) vs. nonresponders ( NR ) in the rectal ( RSI R vs. NR 0.32 vs. 0.46 , p = 0.03 ) , esophageal ( RSI R vs. NR 0.37 vs. 0.50 , p = 0.05 ) and combined rectal/esophageal ( RSI R vs. NR 0.34 vs. 0.48 , p = 0.001511 ) cohorts . Using a threshold RSI of 0.46 , the model has a sensitivity of 80 % , specificity of 82 % , and positive predictive value of 86 % . Finally , we evaluated the model as a prognostic marker in HNC . There was an improved 2-year locoregional control ( LRC ) in the predicted radiosensitive group ( 2-year LRC 86 % vs. 61 % , p = 0.05 ) . CONCLUSIONS We vali date a robust multigene expression model of intrinsic tumor radiosensitivity in three independent cohorts totaling 118 patients . To our knowledge , this is the first time that a systems biology-based radiosensitivity model is vali date d in multiple independent clinical data sets Predictive biomarkers to guide therapy for cancer patients are a cornerstone of precision medicine . Discussed herein are considerations regarding the design and interpretation of such predictive biomarker studies . These considerations are important for both planning and interpreting prospect i ve studies and for using specimens collected from completed r and omized clinical trials . Specific issues addressed are differentiation between qualitative and quantitative predictive effects , challenges due to sample size requirements for predictive biomarker assessment , and consideration of additional factors relevant to clinical utility assessment , such as toxicity and cost of new therapies as well as costs and potential morbidities associated with routine use of biomarker-based tests The 70-gene signature ( MammaPrint ™ ) has been developed to predict the risk of distant metastases in breast cancer and select those patients who may benefit from adjuvant treatment . Given the strong association between locoregional and distant recurrence , we hypothesize that the 70-gene signature will also be able to predict the risk of locoregional recurrence ( LRR ) . 1,053 breast cancer patients primarily treated with breast-conserving treatment or mastectomy at the Netherl and s Cancer Institute between 1984 and 2006 were included . Adjuvant treatment consisted of radiotherapy , chemotherapy , and /or endocrine therapy as indicated by guidelines used at the time . All patients were included in various 70-gene signature validation studies . After a median follow-up of 8.96 years with 87 LRRs , patients with a high-risk 70-gene signature ( n = 492 ) had an LRR risk of 12.6 % ( 95 % CI 9.7–15.8 ) at 10 years , compared to 6.1 % ( 95 % CI 4.1–8.5 ) for low-risk patients ( n = 561 ; P < 0.001 ) . Adjusting the 70-gene signature in a competing risk model for the clinicopathological factors such as age , tumour size , grade , hormone receptor status , LVI , axillary lymph node involvement , surgical treatment , endocrine treatment , and chemotherapy result ed in a multivariable HR of 1.73 ( 95 % CI 1.02–2.93 ; P = 0.042 ) . Adding the signature to the model based on clinicopathological factors improved the discrimination , albeit non-significantly [ C-index through 10 years changed from 0.731 ( 95 % CI 0.682–0.782 ) to 0.741 ( 95 % CI 0.693–0.790 ) ] . Calibration of the prognostic models was excellent . The 70-gene signature is an independent prognostic factor for LRR . A significantly lower local recurrence risk was seen in patients with a low-risk 70-gene signature compared to those with high-risk 70-gene signature Radical radiotherapy and surgery achieve similar cure rates in muscle-invasive bladder cancer , but the choice of which treatment would be most beneficial can not currently be predicted for individual patients . The primary aim of this study was to assess whether expression of any of a panel of DNA damage signaling proteins in tumor sample s taken before irradiation could be used as a predictive marker of radiotherapy response , or rather was prognostic . Protein expression of MRE11 , RAD50 , NBS1 , ATM , and H2AX was studied by immunohistochemistry in pretreatment tumor specimens from two cohorts of bladder cancer patients ( validation cohort prospect ively acquired ) treated with radical radiotherapy and one cohort of cystectomy patients . In the radiotherapy test cohort ( n = 86 ) , low tumor MRE11 expression was associated with worse cancer-specific survival compared with high expression [ 43.1 % versus 68.7 % 3-year cause-specific survival ( CSS ) , P = 0.012 ] by Kaplan-Meier analysis . This was confirmed in the radiotherapy validation cohort ( n = 93 ; 43.0 % versus 71.2 % , P = 0.020 ) . However , in the cystectomy cohort ( n = 88 ) , MRE11 expression was not associated with cancer-specific survival , commensurate with MRE11 being a predictive marker . High MRE11 expression in the combined radiotherapy cohort had a significantly better cancer-specific survival compared with the high-expression cystectomy cohort ( 69.9 % versus 53.8 % 3-year CSS , P = 0.021 ) . In this vali date d immunohistochemistry study , MRE11 protein expression was shown and confirmed as a predictive factor associated with survival following bladder cancer radiotherapy , justifying its inclusion in subsequent trial design s. MRE11 expression may ultimately allow patient selection for radiotherapy or cystectomy , thus improving overall cure rates BACKGROUND The efficacy of the ALK inhibitor crizotinib as compared with st and ard chemotherapy as first-line treatment for advanced ALK-positive non-small-cell lung cancer ( NSCLC ) is unknown . METHODS We conducted an open-label , phase 3 trial comparing crizotinib with chemotherapy in 343 patients with advanced ALK-positive nonsquamous NSCLC who had received no previous systemic treatment for advanced disease . Patients were r and omly assigned to receive oral crizotinib at a dose of 250 mg twice daily or to receive intravenous chemotherapy ( pemetrexed , 500 mg per square meter of body-surface area , plus either cisplatin , 75 mg per square meter , or carboplatin , target area under the curve of 5 to 6 mg per milliliter per minute ) every 3 weeks for up to six cycles . Crossover to crizotinib treatment after disease progression was permitted for patients receiving chemotherapy . The primary end point was progression-free survival as assessed by independent radiologic review . RESULTS Progression-free survival was significantly longer with crizotinib than with chemotherapy ( median , 10.9 months vs. 7.0 months ; hazard ratio for progression or death with crizotinib , 0.45 ; 95 % confidence interval [ CI ] , 0.35 to 0.60 ; P<0.001 ) . Objective response rates were 74 % and 45 % , respectively ( P<0.001 ) . Median overall survival was not reached in either group ( hazard ratio for death with crizotinib , 0.82 ; 95 % CI , 0.54 to 1.26 ; P=0.36 ) ; the probability of 1-year survival was 84 % with crizotinib and 79 % with chemotherapy . The most common adverse events with crizotinib were vision disorders , diarrhea , nausea , and edema , and the most common events with chemotherapy were nausea , fatigue , vomiting , and decreased appetite . As compared with chemotherapy , crizotinib was associated with greater reduction in lung cancer symptoms and greater improvement in quality of life . CONCLUSIONS Crizotinib was superior to st and ard first-line pemetrexed-plus-platinum chemotherapy in patients with previously untreated advanced ALK-positive NSCLC . ( Funded by Pfizer ; PROFILE 1014 Clinical Trials.gov number , NCT01154140 . ) PURPOSE To investigate the expression and predictive role of the Mre11/Rad50/Nbs1 ( MRN ) complex and the ataxia-telangiectasia mutated protein ( ATM ) for the outcome of radiotherapy in breast cancer patients . METHODS AND MATERIAL S The protein expression of ATM and the DNA repair proteins in the MRN complex were investigated using immunohistochemistry in tumors from 224 women with early breast cancer , who were r and omized to receive postoperative radiotherapy or adjuvant chemotherapy . RESULTS Compared with normal breast tissue , the staining intensity of Mre11 , Rad50 , Nbs1 , and ATM was reduced in a majority of the tumors . Weak expression of the MRN complex was correlated with high histologic grade and estrogen receptor negativity ( p = 0.01 and p = 0.0001 , respectively ) . Radiotherapy significantly reduced the risk of local recurrence as compared with chemotherapy ( p = 0.04 ) . The greatest benefit of radiotherapy was seen in patients with moderate/strong expression of the MRN complex ( relative risk = 0.27 , 95 % confidence interval = 0.098 - 0.72 , p = 0.009 ) , whereas patients with negative/weak MRN expression had no benefit of radiotherapy compared with adjuvant chemotherapy . These results suggest that an intact MRN complex is important for the tumor cell eradicating effect of radiotherapy . CONCLUSIONS Reduced expression of the MRN complex predicts a poor effect of radiotherapy in patients with early breast cancer BACKGROUND Patients with non-small-cell lung cancer harbouring mutations in the epidermal growth factor receptor ( EGFR ) gene respond well to the EGFR-specific tyrosine kinase inhibitor gefitinib . However , whether gefitinib is better than st and ard platinum doublet chemotherapy in patients selected by EGFR mutation is uncertain . METHODS We did an open label , phase 3 study ( WJTOG3405 ) with recruitment between March 31 , 2006 , and June 22 , 2009 , at 36 centres in Japan . 177 chemotherapy-naive patients aged 75 years or younger and diagnosed with stage IIIB/IV non-small-cell lung cancer or postoperative recurrence harbouring EGFR mutations ( either the exon 19 deletion or L858R point mutation ) were r and omly assigned , using a minimisation technique , to receive either gefitinib ( 250 mg/day orally ; n=88 ) or cisplatin ( 80 mg/m(2 ) , intravenously ) plus docetaxel ( 60 mg/m(2 ) , intravenously ; n=89 ) , administered every 21 days for three to six cycles . The primary endpoint was progression-free survival . Survival analysis was done with the modified intention-to-treat population . This study is registered with UMIN ( University Hospital Medical Information Network in Japan ) , number 000000539 . FINDINGS Five patients were excluded ( two patients were found to have thyroid and colon cancer after r and omisation , one patient had an exon 18 mutation , one patient had insufficient consent , and one patient showed acute allergic reaction to docetaxel ) . Thus , 172 patients ( 86 in each group ) were included in the survival analyses . The gefitinib group had significantly longer progression-free survival compared with the cisplatin plus docetaxel goup , with a median progression-free survival time of 9.2 months ( 95 % CI 8.0 - 13.9 ) versus 6.3 months ( 5.8 - 7.8 ; HR 0.489 , 95 % CI 0.336 - 0.710 , log-rank p<0.0001 ) . Myelosuppression , alopecia , and fatigue were more frequent in the cisplatin plus docetaxel group , but skin toxicity , liver dysfunction , and diarrhoea were more frequent in the gefitinib group . Two patients in the gefitinib group developed interstitial lung disease ( incidence 2.3 % ) , one of whom died . INTERPRETATION Patients with lung cancer who are selected by EGFR mutations have longer progression-free survival if they are treated with gefitinib than if they are treated with cisplatin plus docetaxel . FUNDING West Japan Oncology Group ( WJOG ) : a non-profit organisation supported by unrestricted donations from several pharmaceutical companies The aim of this study was to test the utility of AIM P3 , an upstream regulator of DNA damage response following genotoxic stress , as a clinical biomarker in muscle‐invasive bladder cancer ( MIBC ) . AIM P3 was identified from a meta‐ analysis of a global gene‐expression data set . AIM P3 protein expression was determined by immunohistochemistry on a customised bladder cancer tissue‐microarray ( TMA ) . The mechanism of gene silencing was probed using methylation‐specific PCR . The association between AIM P3 expression , Tp53 transactivity and genomic stability was analysed . In vitro AIM P3 translocation to the nucleus in response to ionising radiation was demonstrated using immunofluorescence . Radiosensitisation effects of siRNA‐mediated AIM P3‐knockdown were measured using colony forming assays . TMAs derived from patients enrolled in BCON , a Phase III multicentre radiotherapy trial in bladder cancer ( IS RCT N45938399 ) were used to evaluate the association between AIM P3 expression and survival . The prognostic value of AIM P3 expression was determined in a TMA derived from patients treated by radical cystectomy . Loss of AIM P3 expression was frequent in MIBC and associated with impaired Tp53 transactivity and genomic instability . AIM P3‐knockdown was associated with an increase in radioresistance . Loss of AIM P3 expression was associated with survival in MIBC patients following radiotherapy ( HR = 0.53 ; 95 % CI : 0.36 to 0.78 , p = 0.002 ) but was not prognostic in the cystectomy set . In conclusion , AIM P3 expression is lost in a subset of bladder cancers and is significantly predictive of survival following radiotherapy in MIBC patients BACKGROUND Trastuzumab emtansine ( T-DM1 ) is an antibody-drug conjugate incorporating the human epidermal growth factor receptor 2 (HER2)-targeted antitumor properties of trastuzumab with the cytotoxic activity of the microtubule-inhibitory agent DM1 . The antibody and the cytotoxic agent are conjugated by means of a stable linker . METHODS We r and omly assigned patients with HER2-positive advanced breast cancer , who had previously been treated with trastuzumab and a taxane , to T-DM1 or lapatinib plus capecitabine . The primary end points were progression-free survival ( as assessed by independent review ) , overall survival , and safety . Secondary end points included progression-free survival ( investigator-assessed ) , the objective response rate , and the time to symptom progression . Two interim analyses of overall survival were conducted . RESULTS Among 991 r and omly assigned patients , median progression-free survival as assessed by independent review was 9.6 months with T-DM1 versus 6.4 months with lapatinib plus capecitabine ( hazard ratio for progression or death from any cause , 0.65 ; 95 % confidence interval [ CI ] , 0.55 to 0.77 ; P<0.001 ) , and median overall survival at the second interim analysis crossed the stopping boundary for efficacy ( 30.9 months vs. 25.1 months ; hazard ratio for death from any cause , 0.68 ; 95 % CI , 0.55 to 0.85 ; P<0.001 ) . The objective response rate was higher with T-DM1 ( 43.6 % , vs. 30.8 % with lapatinib plus capecitabine ; P<0.001 ) ; results for all additional secondary end points favored T-DM1 . Rates of grade 3 or 4 adverse events were higher with lapatinib plus capecitabine than with T-DM1 ( 57 % vs. 41 % ) . The incidences of thrombocytopenia and increased serum aminotransferase levels were higher with T-DM1 , whereas the incidences of diarrhea , nausea , vomiting , and palmar-plantar erythrodysesthesia were higher with lapatinib plus capecitabine . CONCLUSIONS T-DM1 significantly prolonged progression-free and overall survival with less toxicity than lapatinib plus capecitabine in patients with HER2-positive advanced breast cancer previously treated with trastuzumab and a taxane . ( Funded by F. Hoffmann-La Roche/Genentech ; EMILIA Clinical Trials.gov number , NCT00829166 . ) Despite years of research and hundreds of reports on tumor markers in oncology , the number of markers that have emerged as clinical ly useful is pitifully small . Often initially reported studies of a marker show great promise , but subsequent studies on the same or related markers yield inconsistent conclusions or st and in direct contradiction to the promising results . It is imperative that we attempt to underst and the reasons why multiple studies of the same marker lead to differing conclusions . A variety of method ological problems have been cited to explain these discrepancies . Unfortunately , many tumor marker studies have not been reported in a rigorous fashion , and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of study results . The development of guidelines for the reporting of tumor marker studies was a major recommendation of the National Cancer Institute – European Organisation for Research and Treatment of Cancer ( NCI – EORTC ) First International Meeting on Cancer Diagnostics in 2000 . As for the successful CONSORT initiative for r and omized trials and for the STARD statement for diagnostic studies , we suggest guidelines to provide relevant information about the study design , preplanned hypotheses , patient and specimen characteristics , assay methods , and statistical analysis methods . In addition , the guidelines provide helpful suggestions on how to present data and important elements to include in discussion s. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and underst and the context in which the conclusions apply BACKGROUND Radiotherapy is an alternative to cystectomy in patients with muscle-invasive bladder cancer . In other disease sites , synchronous chemoradiotherapy has been associated with increased local control and improved survival , as compared with radiotherapy alone . METHODS In this multicenter , phase 3 trial , we r and omly assigned 360 patients with muscle-invasive bladder cancer to undergo radiotherapy with or without synchronous chemotherapy . The regimen consisted of fluorouracil ( 500 mg per square meter of body-surface area per day ) during fractions 1 to 5 and 16 to 20 of radiotherapy and mitomycin C ( 12 mg per square meter ) on day 1 . Patients were also r and omly assigned to undergo either whole-bladder radiotherapy or modified-volume radiotherapy ( in which the volume of bladder receiving full-dose radiotherapy was reduced ) in a partial 2-by-2 factorial design ( results not reported here ) . The primary end point was survival free of locoregional disease . Secondary end points included overall survival and toxic effects . RESULTS At 2 years , rates of locoregional disease-free survival were 67 % ( 95 % confidence interval [ CI ] , 59 to 74 ) in the chemoradiotherapy group and 54 % ( 95 % CI , 46 to 62 ) in the radiotherapy group . With a median follow-up of 69.9 months , the hazard ratio in the chemoradiotherapy group was 0.68 ( 95 % CI , 0.48 to 0.96 ; P=0.03 ) . Five-year rates of overall survival were 48 % ( 95 % CI , 40 to 55 ) in the chemoradiotherapy group and 35 % ( 95 % CI , 28 to 43 ) in the radiotherapy group ( hazard ratio , 0.82 ; 95 % CI , 0.63 to 1.09 ; P=0.16 ) . Grade 3 or 4 adverse events were slightly more common in the chemoradiotherapy group than in the radiotherapy group during treatment ( 36.0 % vs. 27.5 % , P=0.07 ) but not during follow-up ( 8.3 % vs. 15.7 % , P=0.07 ) . CONCLUSIONS Synchronous chemotherapy with fluorouracil and mitomycin C combined with radiotherapy significantly improved locoregional control of bladder cancer , as compared with radiotherapy alone , with no significant increase in adverse events . ( Funded by Cancer Research U.K. ; BC2001 Current Controlled Trials number , IS RCT N68324339 . ) © 2 0 1 0 T H E A U T H O R S J O U R N A L C O M P I L A T I O N © 2 0 1 0 B J U I N T E R N A T I O N A L 7 5 3 prostate cancer . N Engl J Med 2010 ; 362 : 1192–202 2 Jemal A , Siegel R , Ward E et al . Cancer Statistics 2008 . CA Cancer J Clin 2008 ; 58 : 71–96 3 Thompson IM , Tangen CM , Goodman PJ , Lucia MS , Klein EA . Chemoprevention of prostate cancer . J Urol 2009 ; 182 : 499–508 4 Lippman SM , Klein EA , Goodman PJ et al . Effect of selenium and vitamin E on risk of prostate cancer and other cancers : the Selenium and Vitamin E Cancer Prevention Trial ( SELECT ) . JAMA 2009 ; 301 : 39–51 5 Stranges S , Marshall JR , Natarajan R et al . Effects of long-term selenium supplementation on the incidence of type2 diabetes : a r and omized trial . Ann Intern Med 2007 ; 147 : 217–23 6 Thompson IM , Goodman PJ , Tangen CM et al . The influence of finasteride on the development of prostate cancer . N Engl J Med 2003 ; 349 : 215–24 7 Thompson IM , Chi C , Ankerst DP et al . Effect of finasteride on the sensitivity of PSA for detecting prostate cancer . J Natl Cancer Inst 2006 ; 98 : 1128–33 8 Redman MW , Tangen CM , Goodman PJ , Lucia MS , Coltman CA , Thompson IM . Finasteride does not increase the risk of high- grade prostate cancer : a bias-adjusted modeling approach . Cancer Prev Res ( Phila Pa ) 2008 ; 1 : 174– 81 9 Pinsky P , Parnes H , Ford L. Estimating rates of true high- grade disease in the Prostate Cancer Prevention Trial . Cancer Prev Res ( Phila Pa ) 2008 ; 1 : 182–6 10 Walsh PC . Chemoprevention of prostate cancer . N Engl J Med 2010 ; 362 : 1237– 8 11 Thompson IM , Tangen CM , Goodman PJ et al . Finasteride improves the sensitivity of digital rectal examination for prostate cancer detection . J Urol 2007 ; 177 : 1749– 52 12 And riole GL , Bostwick D , Brawley O et al . The utility of PSA for detection of prostate cancer in men treated with dutasteride : results from the REduction by DUtasteride of prostate Cancer Events ( REDUCE ) study . J Men ’s Health 2009 ; 6 : 269 13 Kirby RS , Eeles RA , Kote-Jarai Z , Guy M , Easton D , Fitzpatrick JM . Screening for prostate cancer : the way ahead . BJU Int 2010 ; 105 : PURPOSE Phase II clinical studies suggest that hypoxic modification with carbogen and nicotinamide ( CON ) may increase the efficacy of radiotherapy ( RT ) . PATIENTS AND METHODS Three hundred thirty-three patients with locally advanced bladder carcinoma were r and omly assigned to RT alone versus RT with CON . A schedule of either 55 Gy in 20 fractions in 4 weeks or 64 Gy in 32 fractions in 6.5 weeks was used . The primary end point was cystoscopic control at 6 months ( CC(6 m ) ) and secondary end points were overall survival ( OS ) , local relapse-free survival ( RFS ) , urinary and rectal morbidity . RESULTS CC(6 m ) was 81 % for RT + CON and 76 % for RT alone ( P = .3 ) ; however , just more than half of patients underwent cystoscopy at that time . Three-year estimates of OS were 59 % and 46 % ( P = .04 ) and 3-year estimates of RFS were 54 % and 43 % ( P = .06 ) for RT + CON versus RT alone . Risk of death was 14 % lower with RT + CON ( P = .04 ) . In multivariate comparison , RT + CON significantly reduced the risk of relapse ( P = .05 ) and death ( P = .03 ) . There was no evidence that differences in late urinary or GI morbidity between treatment groups or between fractionation schedules were significant . CONCLUSION RT + CON produced a small nonsignificant improvement in CC(6 m ) . Differences in OS , risk of death , and local relapse were significantly in favor of RT + CON . Late morbidity was similar in both trial arms . Results indicate a benefit of adding CON to radical RT Purpose : Tumor hypoxia is associated with a poor prognosis , hypoxia modification improves outcome , and hypoxic status predicts benefit from treatment . Yet , there is no universal measure of clinical hypoxia . The aim of this study was to investigate whether a 26-gene hypoxia signature predicted benefit from hypoxia-modifying treatment in both cancer types . Experimental Design : Sample s were available from 157 T2–T4 laryngeal cancer and 185 T1–T4a bladder cancer patients enrolled on the accelerated radiotherapy with carbogen and nicotinamide ( ARCON ) and bladder carbogen nicotinamide ( BCON ) phase III r and omized trials of radiotherapy alone or with carbogen and nicotinamide ( CON ) respectively . Customized TaqMan low density arrays ( TLDA ) were used to assess expression of the 26-gene signature using quantitative real-time PCR . The median expression of the 26 genes was used to derive a hypoxia score ( HS ) . Patients were categorized as TLDA-HS low ( ≤median ) or TLDA-HS high ( > median ) . The primary outcome measures were regional control ( RC ; ARCON ) and overall survival ( BCON ) . Results : Laryngeal tumors categorized as TLDA-HS high showed greater benefit from ARCON than TLDA-HS low tumors . Five-year RC was 81 % ( radiotherapy alone ) versus 100 % ( CON ) for TLDA-HS high ( P = 0.009 ) . For TLDA-HS low , 5-year RC was 91 % ( radiotherapy alone ) versus 90 % ( CON ; P = 0.90 ) . TLDA-HS did not predict benefit from CON in bladder cancer . Conclusion : The 26-gene hypoxia signature predicts benefit from hypoxia-modifying treatment in laryngeal cancer . These findings will be evaluated in a prospect i ve clinical trial . Clin Cancer Res ; 19(17 ) ; 4879–88 . © 2013 AACR |
653 | 27,766,395 | Conclusion Pudendal nerve block , with or without general anaesthesia , is recommended for all patients undergoing haemorrhoidal surgery .
Either closed haemorrhoidectomy , or open haemorrhoidectomy with electrocoagulation of the pedicle is recommended as the primary procedure . | Background The aim of this systematic review was to up date previous PROSPECT ( http://www.postoppain.org ) review recommendations for the management of pain after excisional haemorrhoidectomy . | BACKGROUND Spasm through the internal anal sphincter is one of the supposed causes for pain after hemorrhoidectomy , a common and distressing experience . We hypothesized that the addition of topical nifedipine to lidocaine would improve pain control by causing a relaxation of the smooth muscle of the internal anal sphincter . METHODS We conducted a multicentre r and omized , double-blind trial to compare the efficacy of 0.3 % nifedipine and 1.5 % lidocaine ointment versus 1.5 % lidocaine ointment alone in reducing pain after hemorrhoidectomy . A physician unaware of the treatment arm measured pain by use of the Analogue Chromatic Continuous Scale ( ACCS ) at baseline ; soon after surgery ; at 2 , 4 , 6 , 8 and 24 hours after surgery ; on day 7 after surgery ; and at a final visit 14 days after surgery . The physician also noted the time to first analgesic administration within 24 hours after surgery . RESULTS In all , 135 patients per group participated ( 270 total ) . Evaluation of the delta ACCS score versus basal value , a covariate for rescue analgesic administration time , revealed better pain control in the group that received nifedipine with lidocaine at 6 hours after surgery and on day 7 ( p < 0.011 and p < 0.054 , respectively ) . We noticed no difference between groups for time of administration of rescue analgesic , blood pressure , heart rate or frequency of headache . CONCLUSION Although there was no difference between groups for time of administration of rescue analgesic after open hemorrhoidectomy , the patients ' assessment of pain using ACCS showed that the use of topical nifedipine with lidocaine may provide a slight significant difference in favour of the study group at 6 hours and at day 7 after surgery . Narcotic analgesics and nonsteroidal anti-inflammatory drug administration should continue to be recommended . Further research focusing on these outcomes is warranted Background Milligan-Morgan excision haem-orrhoidectomy remains a very popular treatment modality for third and fourth degree haemorrhoids due to its cost effectiveness and good long-term results . The LigaSure tissue-sealing device is an alternative technique used in haemorrhoidectomy that has been shown to produce favourable results . The aim of this study was to assess the effectiveness of the LigaSure tissue sealing device in comparison with conventional diathermy haemorrhoidectomy Methods A prospect i ve clinical trial was conducted . Patients with newly diagnosed haemorrhoids requiring haemorrhoidectomy were r and omized to either LigaSure haemorrhoidectomy or diathermy haemorrhoidectomy . Surgical technique and postoperative care was st and ardized . Outcome measures were operative time and bleeding , postoperative pain ( measured on a visual analogue scale ) and rate of wound healing Results We r and omized 44 patients , 22 to LigaSure and 22 to diathermy ; 43 patients were evaluated . They were aged between 19 and 71 years . There were no differences in patient demographics or type of haemorrhoid being operated on . LigaSure haemorrhoidectomy had a significantly lower mean operative time and intraoperative bleeding . At 3 weeks after surgery , haemorrhoidectomy performed with LigaSure had an odds ratio for complete epithelialization of 3.1 over diathermy ( 95 % CI 1.2–8.2 ) . There was no difference in postoperative pain Conclusion LigaSure haemorrhoidectomy is superior to diathermy for open Objective To determine whether a combination of topical anesthetic ( EMLA ) and local injection with lidocaine is better than lidocaine alone for pain relief after Ferguson hemorrhoidectomy . Methods Sixty patients scheduled for hemorrhoidectomy were r and omized into 2 groups : ( 1 ) control group ( CG , n=30 ) received neomycin ointment ( 5 g ) , and ( 2 ) EMLA group ( EG , n=30 ) received EMLA ( 5 g ) , both agents applied topically after surgery . Before the surgical incision was made , lidocaine ( 10 mL of a 1 % solution ) was locally injected into all 60 patients . After surgery , analgesics were provided when necessary . The visual analog scale score was recorded at 4 time points : ( 1 ) upon arrival in the postanesthesia room , ( 2 ) 2 hours after arriving in the postanesthesia room , ( 3 ) between 9 and 10 PM on the first postoperative evening , and ( 4 ) on the first postoperative morning . The frequency of meperidine requests , 1-time catheterizations for urinary retention , and patient satisfaction with postoperative pain management , were also recorded . Results The median visual analog scale scores and cumulative dosages of meperidine were significantly lower in the EG than the CG ( P<0.05 ) . Patient satisfaction with postoperative pain control was also significantly higher in the EG than the CG ( P<0.01 ) . No systemic complications occurred . Discussion EMLA is considered a breakthrough in cutaneous analgesia , capable of reducing pain in many cutaneous procedures . Because Ferguson hemorrhoidectomy has been performed for years with ongoing concerns over postoperative pain , we felt that using EMLA could lower postoperative pain intensity and the number of requests for additional medication Purpose We compared the efficacy and side effects of diclofenac and a topical eutectic mixture of local anesthetics ( EMLA ) for pain relief after hemorrhoidectomy . Methods Ninety patients , nominated for elective hemorrhoidectomy , were recruited for this r and omized clinical trial and were r and omly categorized into three groups ( 30 patients in each group ) . After surgery , the patients in the first group received one 100 mg diclofenac suppository , those in the second group received 5 g of EMLA , and those in the third group received 5 g of petrolatum ointment ( control group ) . The pain intensity was measured using a visual analog scale ( VAS ) . Twenty-five mg of intramuscular pethidine was administered upon the patient ’s request . Pain measurements were performed on the patient ’s transfer to the recovery ward , 2 h after surgery , the evening and the morning after surgery . Results The EMLA group yielded the lowest VAS score on transfer to recovery and at 2 h after surgery ( p < 0.05 ) . The diclofenac group reported the lowest VAS score in the evening and the morning after surgery ( p < 0.05 ) . Conclusions Topical use of an EMLA cream is appropriate for short-term pain control following hemorrhoidectomy , while diclofenac yields a more sustainable pain control OBJECTIVES Control of postoperative symptoms is of paramount importance in proctologic surgery . Phlebotropic activity , protective effect on the capillaries and anti-inflammatory properties of the flavonoids have been reported in several studies . They have been used to treat a variety of conditions including chronic venous insufficiency , lymphedema and hemorrhoids . Numerous trials , assessing the effect of phlebotonics in treating the symptoms and signs of haemorrhoidal disease , suggest that there is a potential benefit . Our trial was conducted to evaluate whether the flavonoids reduce postoperative bleeding , pain and other symptoms after hemorrhoidectomy . PATIENTS AND METHODS We compared the results obtained in 24 patients undergoing open hemorrhoidectomy with radiofrequency scalpel . Our study cohort was r and omized in two groups : the Group A received flavonoids in the postoperative period , the Group B has constituted the control group , without administration of study drug . Follow-up outpatient visits were performed on 7 , 15 and 30 postoperative day ( POD ) . During the visits the patients expressed trough a list of specific questions , based on a scoring system ( 1 to 10 ) , their opi-nion about the extent of postoperative symptoms as pain , bleeding , tenesmus , pruritus and perianal weight . RESULTS We observed that the results obtained after 7 days of surgery are similar in both study groups . Even after 15 and 30 days no significant changes were observed between the two groups about pain and bleeding . Instead , we observed significant differences regarding tenesmus ( group A : 8.0±1.1 vs Group B : 5.4 ± 1.5 at 15 POD , p < 0.05 ; group A : 9.1±0.8 vs Group B : 5.7 ± 0.9 at 30 POD , p < 0.05 ) , pruritus ( group A : 7.1 ± 1.4 vs Group B : 4.8 ± 1 at 15 POD , p < 0.05 ; group A : 9.5 ± 0.5 vs Group B : 6.6 ± 0.8 at 30 POD , p < 0.05 ) and perianal weight ( group A : 7.2 ± 0.9 vs Group B : 6.2 ± 0.8 at 15 POD , p < 0.05 ; group A : 9.75 ± 0.4 vs Group B : 7.3 ± 0.9 at 30 POD , p < 0.05 ) . CONCLUSIONS Our results confirm the usefulness of this drug to reduce the prevalence and the importance of post-hemorrhoidectomy symptoms and make more comfortable the postoperative period Background In the past decade , several new surgical tools have revived the hope for an improved technique to treat radically hemorrhoids with less postoperative pain . Among these radiofrequency ( RF ) , excisional surgery seems to be safe , fast , and accompanied by less postoperative pain . The aim of this study was to evaluate and compare RF ( ligasure TM ) to conventional diathermy Milligan-Morgan hemorrhoidectomy ( MMH ) . Patients and methods Between January 2003 and July 2009 , 210 symptomatic patients were r and omized to undergo RF ( 118 patients ) or diathermy MMH ( 92 patients ) . Mean follow-up was 39 ± 16 months . Clinical outcome was assessed by vali date d question naire on postoperative symptoms and satisfaction . Primary endpoints were pain and wound healing . Secondary endpoints were operative time , early and late complications ( including recurrences ) , and patient satisfaction . Data was analyzed using chi-squared test and Fisher ’s exact test . Results Despite postoperative pain was less after RF , this difference was significant only for severe pain ( expressed as VAS score > 7 ) . Significant differences were observed in terms of wound healing . The two techniques were similar in terms of early and late complications . Conclusions RF hemorrhoidectomy is followed by reduced severe pain and better wound healing . However , in our experience , this is not followed by earlier return to daily activities Background Hemorrhoid is one of the most common surgical diseases occurring in the anorectal region . In this study , we evaluated the effect of ischiorectal fossa block on alleviating post hemorrhoidectomy pain . Methods In this study , 90 patients suffering from hemorrhoids were evaluated . They were r and omly divided into 3 groups . The first group had no block , the second group an ischiorectal block with placebo ( normal saline ) , and the third group a preemptive ischiorectal block with bupivacaine . Postoperative variables such as pain intensity , pethidine consumption , nausea , and vomiting were compared between the groups . Results The postoperative pain score in group 1 was 8.5 ± 1.3 and 8.1 ± 0.9 ( P = NS ) in group 2 . The post operative analgesic dem and was 3.1 ± 1.5 and 3.3 ± 1.8 hours in groups 1 and 2 , respectively ( P = NS ) . The post operative pain score and analgesic dem and were 4.2 ± 2.1 and 9.3 ± 2.7 hours , respectively , in group 3 ( P < 0.0001 ) . Conclusions Preemptive ischiorectal block reduces the posthemorrhoidectomy pain and opioid dem and INTRODUCTION Hemorrhoidal disease occurs in 50 % of people aged > 40 years and is the most common reason for anorectal surgery . Pain is the main complication . Multiple topical and systemic drugs have been investigated for pain control , but there is no ideal treatment . Metronidazole has been shown to decrease postoperative pain but is not used widely . OBJECTIVE To evaluate the effect of oral metronidazole versus placebo and to assess postoperative pain following hemorrhoidectomy . MATERIAL AND METHODS Controlled clinical trial in adult patients who underwent elective hemorrhoidectomy for grade III/IV hemorrhoids . Patients were assigned to receive metronidazole ( 500 mg q8 h orally ; study group , SG ) or placebo ( control group , CG ) for 7 days after surgery . Pain was assessed using a visual analog scale after surgery . Analgesic administration ( time and use of analgesics ) and resumption of daily life activities were also assessed . RESULTS Forty-four patients were included , 22 in each group . Postoperative pain differed significantly between the SG and CG at 6 h ( 3.86 ± 0.56 , 6.64 ± 1.49 ) , 12 h ( 5.59 ± 1.33 , 8.82 ± 0.79 ) , 24 h ( 6.86 ± 1.49 , 9.73 ± 0.45 ) , day 4 ( 5.32 ± 2.10 , 9.50 ± 0.59 ) , day 7 ( 3.14 ± 1.03 , 7.36 ± 1.39 ) , and day 14 ( 2.14 ± 0.46 , 5.45 ± 1.29 ) . The first analgesia dose was required at 21.27 ± 5.47 h in the CG and 7.09 ± 2.36 h in the SG ( p < 0.05 ) , the time of analgesic use was 6.86 ± 1.61 days in the CG and 13.09 ± 2.48 days in the SG ( p < 0.05 ) , and resumption of daily activities occurred at 7.59 ± 1.56 days in the CG and 14.73 ± 3.76 days in the SG ( p < 0.05 ) . CONCLUSION Oral administration of metronidazole is effective in pain management after hemorrhoidectomy Background and Objectives : Hemorrhoidectomy usually leads to severe postoperative pain that often causes urinary retention . Topical EMLA cream ( lidocaine 2.5 % and prilocaine 2.5 % ) has been used extensively in the clinical setting . This prospect i ve study tested the effectiveness of EMLA cream for postoperative pain control after hemorrhoidectomy . Methods : Thirty patients admitted for hemorrhoidectomy were enrolled and r and omly assigned into either a control group ( n = 15 ) or EMLA group ( n = 15 ) . Postoperatively , the control group received approximately 5 g of neomycin ointment , and the EMLA group received approximately 5 g of EMLA . A visual analog scale ( VAS ) score was recorded on arrival in the postanesthesia recovery unit ( PAR ) , after 2 hours in the PAR , on the first postoperative evening , and on the first postoperative morning . The requested frequency and dosage of meperidine , the first spontaneous voiding time , the frequency of single urinary catheterization , and a patient satisfaction score were also obtained . Results : The VAS score and frequency and dosage of meperidine injections were significantly lower in the EMLA group than in the control group ( P < .01 ) . The voiding time was significantly later in the control group ( P = .04 ) . The frequency of single catheterization was significantly lower in the EMLA group than in the control group ( P = .03 ) . Patient satisfaction with postoperative pain control was significantly higher in the EMLA group than in the control group ( P < .01 ) . No systemic complications were observed . Conclusions : Topical EMLA cream decreased pain intensity and meperidine requests , reduced the frequency of single catheterizations , and improved patient satisfaction with postoperative pain management after hemorrhoidectomy in adults AIM To assess the efficacy of internal sphincterotomy compared with application of topical 2 % Diltiazem ointment after hemorrhoidectomy for pain relief . SETTING S AND DESIGN Prospect i ve r and omized study . MATERIAL S AND METHODS In an 18-month period , 108 subjects with uncomplicated Grade 3/ 4 hemorrhoids were enrolled in the study and were r and omized into two equal groups : Subjects in Group A underwent internal sphincterotomy at time of primary surgery while those in Group B received 1 g of 2 % Diltiazem ointment locally , thrice daily for seven days . Postoperative pain perception was measured using visual analog score ( VAS ) and on the basis of number of analgesic tablets ( Tab tramadol 50 mg ) required in each group . Time to discharge , time to return to work and incidence of complications measured and compared . STATISTICAL ANALYSIS USED Statistical techniques applied were Student T test , Chi-square and Fisher 's Exact Test . RESULTS There were 102 analyzable subjects ( Group A : 50 and Group B : 52 ) . The mean VAS score was significantly less in the internal sphincterotomy group from the fourth postoperative day onwards compared to topical Diltiazem ( 2.23 vs. 3.72 ; P = 0.031 ) . Similarly , the mean requirement of analgesic tablets [ 10.54 vs. 15.40 ; P = 0.01 ] was much lower in Group A. There was no significant difference in terms of time to discharge and time to return to work between the two groups . The incidence of complications was more with the internal sphincterotomy group ( 11.5 % vs. 3 % ; P = 0.488 ) . CONCLUSIONS In patients undergoing hemorrhoidectomy , addition of surgical internal sphincterotomy results in lesser pain in the postoperative period as compared to those receiving topical application of Diltiazem Purpose This study evaluated the use of adding morphine to bupivacaine in spinal anesthesia for pain control in patients who underwent an open hemorrhoidectomy . Methods Forty patients were prospect ively selected for an open hemorrhoidectomy at the same institution and were r and omized into two groups of 20 patients each : group 1 had a spinal with 7 mg of heavy bupivacaine associated with 80 µg of morphine ( 0.2 mg/mL ) . Group 2 had a spinal with 7 mg of heavy bupivacaine associated with distilled water , achieving the same volume of spinal infusion as that of group 1 . Both groups were prescribed the same pain control medicine during the postoperative period . Pain scores were evaluated at the anesthetic recovery room and at 3 , 6 , 12 , and 24 hours after surgery . Postoperative complications , including pruritus , nausea , headaches , and urinary retention , were also recorded . Results There were no anthropometric statistical differences between the two groups . Pain in the anesthetic recovery room and 3 hours after surgery was similar for both groups . However , pain was better controlled in group 1 at 6 and 12 hours after surgery . Although pain was better controlled for group 1 after 24 hours of surgery , the difference between the groups did n't achieved statistical significance . Complications were more common in group 1 . Six patients ( 6/20 ) presented coetaneous pruritus and 3 with ( 3/20 ) urinary retention . Conclusion A hemorrhoidectomy under a spinal with morphine provides better pain control between 6 and 12 hours after surgery . However , postoperative complications , including cutaneous pruritus ( 30 % ) and urinary retention ( 15 % ) , should be considered as a negative side of this procedure Background Spasm of the internal anal sphincter is considered to be one of the causes of pain in anal diseases . We have evaluated the effects of topical diltiazem on postoperative pain after hemorrhoidectomy . Methods Sixty-two patients were r and omly assigned to receive a 2 % diltiazem gel ( n = 32 ) or a placebo gel ( n = 30 ) after hemorrhoidectomy . Patients applied the gel to the anal region three times per day for 14 days . Pain both in the resting state and on defecation ranged from 0 to 10 on a numerical rating scale , and the number of prescribed loxoprofen tablets ( Loxonin ) were recorded and confirmed daily by telephone . Any morbidity during the follow-up period was recorded . Results Both pain scores during defecation and the number of analgesic tablets consumed tended to be lower in the diltiazem group , although they did not reach statistical significance ( P = 0.09 , P = 0.12 , respectively ) . Total number of complications was significantly higher in the diltiazem group , but each incidence of complications , including itching sensation , headache , and dizziness was not statistically different . Conclusions Perianal application of 2 % diltiazem gel after hemorrhoidectomy has the potential to reduce postoperative pain during defecation Background This prospect i ve r and omized trial was used to compare two different local anesthetic techniques , local perianal anesthesia and pudendal nerve block , used for harmonic scalpel hemorrhoidectomy ( HSH ) . Methods A total of 120 patients with grade III or IV hemorrhoids were r and omly chosen to perform HSH ( 60 patients under local anesthesia — Group A and 60 patients under pudendal nerve block — Group B ) . Results Additional perioperative analgesia during the procedure was needed in 37 patients of group A and 18 patients of group B ( P < 0.001 ) . A total of 27 patients from group A and 8 patients from group B ( P < 0.001 ) required additional postoperative analgesia apart from the st and ard administered analgesics . A statistical significant difference in favor of the second group (B)—(P < 0.003 ) was found regarding the discharge point from the hospital when the number of patients that were able to be discharged from the hospital on the day of the operation and the first postoperative day was the comparison parameter . Group B ( P < 0.001 ) was superior to local group regarding VAS pain score at discharge for the patient group that were discharge on the day of surgery ( 5.1 vs. 2.2 ) . Conclusion These data suggest that HSH performed under pudendal nerve block is a safe and efficient technique Objective To prospect ively compare immediate postoperative results of the surgical treatment of haemorrhoidal disease ( HD ) by Milligan – Morgan technique using either the CO2 laser or cold scalpel OBJECTIVE To compare analgesic effectiveness , postoperative pain , complications , and patients ' satisfaction between two r and omly allocated groups -- one group that had local perianal nerve block and another group that had spinal block following closed hemorrhoidectomy . MATERIAL AND METHOD Sixty-seven patients underwent elective hemorrhoidectomy . Of these , 33 were r and omly allocated to receive spinal anesthesia ( SA ) while 34 received perianal local analgesia ( LA ) with bupivacaine . Pain measurement at 6 and 24 hours following hemorrhoidectomy , the quantity of postoperative analgesic medication administered , patient 's satisfaction and complications were recorded . RESULTS Among the patients who had SA , there were 5 patients ( 15.2 % ) who developed hypotension during surgery . There was no reported case of hypotension among those who had LA . There was no significant difference in degree of median postoperative pain at 6 hours ( LA : 38 vs. SA : 50 with VAS ; p = 0.09 ) and at 24 hours ( LA : 31 vs. SA : 35 with VAS ; p = 0.35 ) between the two groups . Patients had a high satisfaction on both anesthetic methods . Patients in the SA group required more parenteral analgesics ( p = 0.03 ) and had a higher incidence of urinary retention than those in the LA group ( SA : 30.3 % vs. LA : 8.8 % , p = 0.03 ) . CONCLUSION Local perianal nerve block for hemorrhoidectomy is feasible and safe and superior to spinal block due to a lower incidence of post-op urinary retention and less requirement of parenteral analgesics post-op BACKGROUND : Bupivacaine extended-release liposome injection is a novel formulation of bupivacaine design ed to achieve long-acting postoperative analgesia . OBJECTIVE : The aim of this study was to compare the magnitude and duration of postoperative analgesia from a single dose of bupivacaine extended-release injection with placebo administered intraoperatively in patients undergoing hemorrhoidectomy . DESIGN : This evaluation was a multicenter , r and omized , double-blind , parallel-group , placebo-controlled phase 3 study . SETTING S : Data were obtained from 13 centers in the Republic of Georgia , Pol and , and Serbia . PATIENTS : Included in this study were patients aged 18 to 86 years undergoing excisional hemorrhoidectomy . INTERVENTIONS : All patients received either a single dose of bupivacaine extended-release 300 mg or placebo administered intraoperatively via wound infiltration . MAIN OUTCOME MEASURE : The cumulative pain score was assessed by measurement of the area under the curve of pain intensity through 72 hours after study drug administration . RESULTS : One hundred eighty-nine patients were r and omly assigned and treated ; 186 completed the study . Pain intensity scores were significantly lower in the bupivacaine extended-release group in comparison with the group receiving placebo ( 141.8 vs 202.5 , P < .0001 ) . More patients in the bupivacaine extended-release group remained opioid free from 12 hours ( 59 % ) to 72 hours ( 28 % ) after surgery compared with patients receiving placebo ( 14 % and 10 % ; P < .0008 through 72 h ) . The mean total amount of opioids consumed through 72 hours was 22.3 mg and 29.1 mg in the bupivacaine extended-release and placebo groups ( P ≤ .0006 ) . The median time to first opioid use was 14.3 hours in the bupivacaine extended-release group vs 1.2 hours in the placebo group ( P < .0001 ) . A greater proportion of patients in the bupivacaine extended-release group were satisfied with their postsurgical analgesia ( 95 % vs 73 % , P = .0007 ) than in the placebo group . CONCLUSIONS : Bupivacaine extended-release demonstrated a statistically significant reduction in pain through 72 hours , decreased opioid requirements , delayed time to first opioid use , and improved patient satisfaction compared with placebo after hemorrhoidectomy The aim of this r and omized prospect i ve trial was to compare LigaSure ™ and conventional diathermy haemorrhoidectomy Background The present study was conducted to compare operative time , postoperative course and outcome of LigaSure hemorrhoidectomy ( LH ) , and conventional open hemorrhoidectomy ( OH ) for prolapsed hemorrhoids . Methods Eighty-four patients with grade III and IV hemorrhoids were r and omized into two groups of 42 patients each ; group 1 patients underwent LH whereas group 2 patients underwent OH . Data regarding patient demographics , operative details , postoperative pain score , amount of parenteral analgesics required , length of hospital stay , and time until return to work or normal physical activity were all prospect ively collected . Postoperative complications and recurrence of prolapse were also recorded . All patients had regular follow-ups every 2 weeks for the first 8 weeks postoperatively , and at 2-month intervals thereafter , for a total period of 12 months . Results Patient demographics , clinical characteristics , and length of hospital stay were similar in both groups ( P > 0.05 ) . The mean operative time , postoperative pain score ( up to 48 h ) , amount of parenteral analgesics required , time off work , and time needed for complete wound healing were significantly less in patients who underwent LH ( P < 0.001 ) . Both groups had similar postoperative complications except for delayed wound healing that was observed at 4 weeks postoperatively , in seven patients ( 16.67 % ) in the LH group compared to 17 patients ( 40.48 % ) in the OH group ( χ2 = 5.83 , P = 0.016 ) . Although hemorrhoid recurrence , at 1 year , was also lower among the LH group compared to the OH group ( 2.38 vs. 9.14 % , respectively ) , the difference was not statistically significant ( P = 0.167 ) . Conclusions LH is a better alternative than conventional OH in treating prolapsed hemorrhoids ( grade s III and IV ) since it reduces operating time , postoperative pain , and time off work , and allows surgical wounds to heal faster , with minimal comparable side effects and a low recurrence rate Purpose This study was design ed to compare the surgical outcomes of hemorrhoidectomy performed by the Ligasure ™ with that performed by the conventional diathermy . Methods A total of 110 patients were r and omized to Ligasure ™ ( 55 patients ) or diathermy ( 55 patients ) hemorrhoidectomy . The operative time , postoperative pain scores , parenteral analgesic requirements in the first 24 hours , postoperative complications , and wound healing rates at six weeks postoperatively were documented . Results The median operative time was 8 ( range , 7–10 ) minutes for the Ligasure ™ group and 18 ( range , 15–21 ) minutes for the diathermy group ( P < 0.001 ) . Throughout the first postoperative week , the daily median pain score was lower in the Ligasure ™ group than in the diathermy group ( P < 0.001 ) . The median number of analgesic ampoules during the first 24 hours postoperatively was lower in the Ligasure ™ group ( P < 0.001 ) . There was no statistically significant difference in the incidence of postoperative complications . At six weeks postoperatively , more patients in the Ligasure ™ group had complete healing of wounds ( P = 0 ) . Conclusion Ligasure ™ provides a superior alternative to conventional diathermy in hemorrhoidectomy by reducing the operative time , postoperative pain , parenteral analgesic requirements during the first 24 hours postoperatively , and the time to complete healing of wounds Purpose We evaluate the safety and efficacy of a spinal anesthesia with lidocaine versus a local anesthesia of pudendal block with ropivacaine combined with intravenous sedation in the hemorrhoidectomy procedure and also we compared the short- and long-term efficacy of conventional diathermy versus Ligasure ™ diathermy hemorrhoidectomy . Methods Seventy-four patients of grade III or IV hemorrhoids were r and omized to conventional diathermy hemorrhoidectomy under spinal ( n = 19 ) or local anesthesia ( n = 18 ) and Ligasure ™ diathermy hemorrhoidectomy under spinal ( n = 17 ) or local anesthesia ( n = 20 ) . Time of follow-up was 12 months . Results Patients operated under local anesthesia had less pain ( p < 0.01 ) , less analgesic requirements ( p < 0.001 ) , shorter hospital stay ( p < 0.01 ) , and less postoperative complications ( p < 0.05 ) . A shorter operating time ( p < 0.001 ) and less complications at 4 months postoperatively ( p < 0.05 ) was observed in the Ligasure ™ group , but differences at 12 months were not found . Conclusions Hemorrhoidectomy under local anesthesia with pudendal block with ropivacaine and sedation reduced postoperative pain , analgesic requirements , and postoperative complications , and can be performed as day-case procedure . Ligasure ™ diathermy hemorrhoidectomy reduced operating time and was equally effective than conventional diathermy in long-term symptom control Background Performing hemorrhoidectomy with LigaSure vessel sealing system is a relatively new technique . The aim of the study was to evaluate LigaSure hemorrhoidectomy by comparing its results to closed Ferguson technique . Patients and methods Eighty patients with grade s III and IV hemorrhoids were prospect ively r and omized to either LigaSure or Ferguson hemorrhoidectomy . Primary end point was postoperative pain . Secondary end points were operative time , blood loss , morbidity , manometric assessment , need for analgesics , hospital stay , time to achieve complete wound healing , and patient satisfaction . Results The LigaSure group achieved a significant reduction in operative time ( P < 0.001 ) , blood loss ( P < 0.001 ) , first postoperative day pain score ( P < 0.006 ) , seventh day pain score ( P < 0.012 ) , second week pain score ( P < 0.001 ) . Less patients in the LigaSure group required pethidine analgesia on the first postoperative day ( P < 0.006 ) . Hospital stay ( P < 0.001 ) , time to achieve complete wound healing ( P = 0.001 ) were shorter in the LigaSure group , and third month satisfaction score was higher ( P = 0.03 ) . There was no difference in postoperative complications . Postoperative manometric resting ( P = 0.0001 ) and squeeze ( P = 0.001 ) pressures were significantly decreased in the Ferguson group . Conclusion LigaSure hemorrhoidectomy provides a valid alternative to closed hemorrhoidectomy . LigaSure patients gain short-term benefits in terms of reduced postoperative pain , wound healing , and better satisfaction . Based on our preliminary results , future studies addressing long-term functional results are needed to prove that LigaSure hemorrhoidectomy may be safer for the patients OBJECTIVE Role of prophylactic antibiotics in Milligan Morgan hemorrhoidectomy - A prospect i ve , r and omized control trial . DESIGN R and omized control trial . PLACE AND DURATION OF STUDY Combined Military Hospital Malir , Bannu and HIT hospital Taxilla , September 2008 to February 2011 . PATIENTS AND METHODS Patients undergoing Milligan Morgan hemorrhoidectomy for grade III and IV hemorrhoids were r and omized in 2 groups by using computer generated table . Group A did not receive any prophylactic antibiotic whereas group B received 500 mg I/V metronidazole and 1 g Ceftriaxone I/V before induction of anesthesia . All the patients had st and ardized post operative care . Pain scores on 100 mm Visual Analogue Scale and consumption of oral analgesics were noted from 1st to 7th post operative day . Time required for complete healing was also noted . Data was entered on SPSS 16.0 and p value was calculated . RESULTS Out of 100 patients , 96 patients ( 47 in group A and 49 in group B ) completed the study . Demographical data was comparable in both the groups . There was no difference in the pain scores , analgesic consumption and rate of healing between both the groups . CONCLUSION Prophylactic antibiotics have got no role in cases of Milligan Morgan hemorrhoidectomy BACKGROUND : In hemorrhoidectomy , pedicle coagulation has been cl aim ed to be associated with less postoperative pain compared with pedicle ligation . OBJECTIVE : This study was design ed to compare the effects of pedicle ligation vs pedicle coagulation on postoperative pain in patients undergoing diathermy excisional hemorrhoidectomy . DESIGN : The study was conducted as a single-blind prospect i ve r and omized clinical trial . SETTING : Patients were treated at a single tertiary-level teaching hospital ( Main University Hospital ) in Alex and ria , Egypt , from February 2009 to October 2010 . PATIENTS : Patients with symptomatic grade III or IV hemorrhoids were eligible . INTERVENTION : Patients were r and omly allocated to receive either pedicle coagulation or pedicle ligation during 3-quadrant diathermy excision hemorrhoidectomy . MAIN OUTCOME MEASURES : Patients reported postoperative pain daily on a visual analog scale ( 0–10 , with 10 corresponding to the most severe pain ) during the first 10 postoperative days . On-dem and parenteral analgesic requirements were recorded during the first 24 hours after surgery . Operative time , postoperative complications , and wound healing rates at 6 weeks postoperatively were also recorded . LIMITATIONS : No a priori power calculation could be performed , so it was not possible to tell whether nonsignificant differences were real or a result of chance . RESULTS : A total of 136 patients were r and omly assigned , and 120 patients completed the study ( 60 in each group ) . The overall median pain score for the first 10 postoperative days was significantly lower in the pedicle coagulation group than in the pedicle ligation group ( 4.65 vs 6.56 , P < .001 ) , and daily median pain scores were significantly lower for pedicle coagulation than for pedicle ligation throughout the first 6 postoperative days ( P < .001 ) . Postoperative pain scores followed different courses in the 2 groups . In the coagulation group , pain levels were lowest during the first 3 postoperative days , increasing from day 4 and then falling after day 8 . In the ligation group , pain levels were highest during the first 4 postoperative days , then gradually decreased . The median number of analgesic ampoules required during the first 24 hours was also significantly lower for pedicle coagulation than for ligation : 1 ( range , 0–3 ) vs 3 ( range , 1–3 ) ; P < .001 ) . The median operative time was 15 ( range , 14–20 ) minutes with coagulation and 14.5 ( range , 12–18 ) minutes with ligation ( P < .001 ) . No significant differences were observed in the incidence of postoperative complications or wound healing rates at 6 weeks postoperatively . No anal stenoses or recurrences were observed . CONCLUSIONS : Pedicle coagulation is safe and provides a superior alternative to pedicle ligation by decreasing postoperative pain in the first 6 postoperative days , as well as reducing parenteral analgesic requirements during the first 24 hours postoperatively AIM In this r and omized prospect i ve clinical study , we aim ed to evaluate the effect of mechanical bowel preparation ( MBP ) before Milligan-Morgan hemorrhoidectomy on intraoperative procedures and postoperative complication rates to determine whether MBP is adventageous or not before elective anorectal surgeries . METHODS Forty patients who had internal grade III or IV hemorrhoidal disease and who would underwent open hemorrhoidectomy were r and omized into two groups : non-MBP group ( female : male , 11:9 ; mean age , 33.8±9.57 years ) that would not receive MBP before the surgery , and MBP group ( female : male , 12:8 ; mean age , 34.7±11.37 years ) that would be given one Fleet enema on the morning of Milligan-Morgan hemorrhoidectomy . Intraoperative variables and postoperative complications were compared between two groups . RESULTS MPB had no effect on both intraoperative and postoperative variables , such as operating time , intraoperative bleeding , visual analogue scale ( VAS ) score for the comfort of the surgeon during operation , the presence of stool or enema remnants in anal canal , the presence of mucosal edema of the anal canal intraoperatively , the rates of postoperative bleeding and infection , VAS score for the pain on third day postoperatively , time to first stool after the operation , VAS score for the pain during first stool after the operation , and number of analgesics during one week postoperatively ( P>0.05 for all ) . CONCLUSION MBP performed before surgery does not provide introperative or postoperative benefit for Milligan-Morgan hemorrhoidectomy , thus MBP is not necessary before elective anorectal surgeries Background Topical metronidazole ( 10 percent ) has been previously demonstrated to decrease postoperative pain after hemorrhoidectomy . The aim of this study was to evaluate the effect of topical metronidazole ( 10 percent ) in reducing postoperative and after-defecation pain of hemorrhoidectomy . Material s and Methods A double-blind , r and omized trial was conducted to compare posthemorrhoidectomy pain with use of topical metronidazole ( 10 percent ) vs. placebo carrier , applied to surgical site . Forty-seven patients were r and omly allocated to receive metronidazole ( n = 25 ) or placebo ( n = 22 ) . Pain was assessed using a visual analog scale preoperatively and on postoperative hours 6 and 12 and at days 1 , 2 , 7 , and 14 . The use of narcotic , additional analgesics , and complications were recorded . ( Pain scores were calculated and compared with baseline values and control group ( t test , SPSS ver.10 ) . Results Patients in the topical metronidazole group had significantly less postoperative pain than those in the placebo group up to day 14 ( P ≤ 0.04 ) . There was no significant difference in narcotic analgesic requirements between groups , except on hour 12 ( P < 0.05 ) . In the metronidazole group , after-defecation pain was ranked significantly lower at day 2 ( P = 0.016 ) and patients required fewer additional analgesics postoperatively on days 2 and 7 ( P ≤ 0.04 ) . Conclusion These finding indicate that topical 10 percent metronidazole significantly reduce posthemorrhoidectomy discomfort , and postoperative defecation pain is reduced compared with that of the placebo control group Background The aim of the present study was to evaluate the efficacy of cholestyramine ointment ( 15 % ) in reducing postoperative pain at rest and during defecation after open hemorrhoidectomy . Methods A total of 91 patients with third and fourth degree hemorrhoids undergoing open hemorrhoidectomy were included in this prospect i ve , double-blind , r and omized controlled trial . The patients were r and omly assigned to either cholestyramine ointment or placebo immediately after surgery , 12 h after surgery , and then every 8 h for 14 days . The primary outcomes were intensity of pain at rest and during defecation , measured with a visual analog scale , and the analgesic requirement , measured by amount of tramadol consumption . Results The cholestyramine group had less postoperative pain than the placebo group at the 24th hour ( 1.84 ± 2.54 vs. 4.07 ± 3.35 ; P = 0.001 ) and 48th hour ( 0.18 ± 0.88 vs. 3.57 ± 3.45 ; P < 0.001 ) and less pain during defecation starting at the 48th hour ( 2.28 ± 2.96 vs. 4.77 ± 4.09 ; P = 0.001 ) . Similarly , the average tramadol consumption at hours 24 and 48 was significantly lower for the cholestyramine group ( 5.32 ± 21.45 vs. 43.18 ± 61.56 mg at 24 h , and 4.48 ± 16.65 vs. 57.63 ± 65.47 mg at 48 h ; P < 0.001 ) . The only adverse event was pruritus , which had a lower frequency in the cholestyramine group but the difference was not significant until postoperative week 4 ( P < 0.001 ) . Conclusions Compared with placebo , cholestyramine ointment ( 15 % ) reduced postoperative pain at rest and on defecation , and consequently lowered the analgesic requirement after open hemorrhoidectomy Objective : o compare the outcome of Milligan-Morgan ( MMH ) and Ferguson ( FH ) techniques for haemorrhoidectomy with regard to postoperative pain , control of bleeding , early mobilization of patients and wound healing . Methodology : In this prospect i ve , r and omized clinical study conducted between January 2005 to December 2008 , 213 patients with late 2nd degree ; third or fourth degree hemorrhoids were assigned to two groups . One hundred ten patients in group A were operated by an open method and 103 patients in group B were operated by closed method . Results : Age ranged from 22 - 70 years with mean age of 45.5 years . Peak incidence was between 41 - 50 years . Out of 213 patients , 170 ( 79.81 % ) were male and 43 ( 20.18 % ) were females . The mean ± SD operating time was significantly more in group B ( 31.3±4.8 min ) than group A ( 25.2±5.6 ) . The duration of hospitalization and duration off from work was more in group A than the group B. Wound healing was quicker in group B than the group A. Post operative pain scores were significantly low in the Group A than Group B during first 24 hours and at first bowel movements . Reactionary hemorrhage occurred in 4 ( 3.63 % ) patients of group A , no patient in group B developed this complication . Retention of urine was seen in 13 ( 11.81 % ) patients in group A and 4 ( 3.88 % ) in group B. No patient in group A developed anal stenosis , while 3 ( 2.91 % ) patients in group B developed anal stenosis . Wound infection was one ( 0.9 % ) in group A and two ( 1.9 % ) in group B. Two ( 3.63 % ) patients in group A came with recurrent hemorrhoids and in group B , only one ( 0.97 % ) patient reported recurrence . Conclusions : The closed technique is more beneficial with respect to postoperative pain , control of bleeding , early mobilization of patients and wound healing PURPOSE To determine the safety , pain intensity correlated with age and body mass index ( BMI ) , epidural anesthesia with ropivacaine and clonidine in hemorrhoidectomy . METHODS Eighty patients , both genders , 20 - 70 years old , ASA I or II , for hemorrhoidectomy were r and omly divided into two groups : Control ( n=38 ) , epidural anesthesia with 14 mL of ropivacaine 0.75 % plus 0.0266 mL/kg of 0.9 % saline solution ; Experimental ( n=42 ) epidural anesthesia with 14 mL of 0.75 % ropivacaine plus 4.0 mcg/kg of clonidine . In preoperative and postoperative period were evaluated : systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , heart rate ( HR ) , pulse oximetry ( SpO2 ) , electrocardiography ( ECG ) , pain intensity ( VAS ) in four , eight and , 12 hours and analgesic consumption . RESULTS The VAS values differed between four , eight and 12 hours in the Experimental Group , where correlation of VAS 12h with age ( p<0.05 ) occurred and not with BMI and more patients ( p<0.05 ) did not receive analgesics . SBP , DBP , HR changed similarly in both groups at 15 , 30 and 45 min . The ECG and SpO2 remained unchanged . CONCLUSIONS Clonidine ( 4mcg/kg ) in epidural anesthesia with ropivacaine 0.75 % in hemorrhoidectomy showed safety and greater analgesia within four hours . The pain at 12 hours showed correlation with age and not with body mass index Day‐care open haemorrhoidectomy under local anaesthesia ( LH ) may be the most cost‐effective approach to haemorrhoidectomy . This prospect i ve r and omized trial compared outcome after LH from patients ' and clinical perspectives with that after day‐care open haemorrhoidectomy under general anaesthesia ( GH ) AIM To identify a more effective treatment protocol for circumferential mixed hemorrhoids . METHODS A total of 192 patients with circumferential mixed hemorrhoids were r and omized into the treatment group , where they underwent Milligan-Morgan hemorrhoidectomy with anal cushion suspension and partial internal sphincter resection , or the control group , where traditional external dissection and internal ligation were performed . Postoperative recovery and complications were monitored . RESULTS The time to wound healing was 12.96 ± 2.25 d in the treatment group shorter than 19.58 ± 2.71 d in the control group . Slight pain rate was 58.3 % in the treatment group higher than 22.9 % in the control group ; moderate pain rate was 33.3 % in the treatment group lower than 56.3 % in the control group severe pain rate was 8.4 % in the treatment group lower than 20.8 % in the control group . No edema rate was 70.8 % in the treatment group higher than 43.8 % in the control group ; mild local edema rate was 26 % in the treatment group lower than 39.6 % in the control group obvious local edema was 3.03 % in the treatment group lower than 16.7 % in the control group . No stenosis rate was 85.4 % in the treatment group higher than 63.5 % in the control group ; moderate stenosis rate was 14.6 % in the treatment group Lower than 27.1 % in the control group severe anal stenosis rate was 0 % in the treatment group lower than 9.4 % in the control group . CONCLUSION Milligan-Morgan hemorrhoidectomy with anal cushion suspension and partial internal sphincter resection is the optimal treatment for circumferential mixed hemorrhoids and can be widely applied in clinical setting A single dose of caudal lidocaine does not provide a sufficiently long anaesthetic duration and is not generally used for complicated anorectal surgery . This study evaluated the safety and efficacy of a ropivacaine – lidocaine combination for caudal anaesthesia in patients undergoing haemorrhoidectomy . A total of 287 haemorrhoid patients with successful initial caudal anaesthesia were r and omized to receive either a mixture of 0.375 % ropivacaine and 1.0 % lidocaine ( ropi – lido group ; n = 146 ) or 1.0 % lidocaine alone ( placebo-lido group ; n = 141 ) . Significantly fewer patients in the ropi – lido group required intra-operative supplemental anaesthesia than in the placebo-lido group . Patients treated with the ropivacaine – lidocaine combination had significantly lower scores for pain at each post-operative time point , and a longer mean time to the first requirement for post-operative analgesic than patients in the placebo-lido group . These results suggest that caudal anaesthesia with a combination of ropivacaine and lidocaine is a safe and effective method of inducing anaesthesia during haemorrhoidectomy OBJECTIVE To compare the analgesic efficacy and rate of wound healing of combination of 0.2 % Glyceryl Trinitrate and 2 % lignocaine ointments with 0.2 % Glyceryl Trinitrate and 2 % lignocaine ointment separately after Milligan Morgan hemorrhoidectomy . DESIGN R and omized control trial . PLACE AND DURATION OF STUDY Combined Military Hospital , Kharian , Malir and Bannu . November 2007 to August 2011 . PATIENTS AND METHODS Patients undergoing Milligan Morgan hemorrhoidectomy were r and omized into 3 groups by using computer generated table . Group A received combination of 0.2 % Glyceryl Trinitrate and 2 % lignocaine ointment , Group B 2 % lignocaine and Group C received 0.2 % Glyceryl Trinitrate ointment . These ointments were given on twice daily basis . Pain scores were measured on a 100 mm Visual Analog Scale . Pain scores and quantity of oral analgesics used were compared daily until the 7th post-operative day . The time required for complete healing ( in weeks ) was also compared . RESULTS Out of 210 patients , 192 ( 67 Group A , 64 Group B and 61 Group C ) completed the study . Demographic data were comparable in all three groups . There were statistically significant reductions in pain scores and quantity of analgesics used from the first to the fourth post-operative days in Group A. The time required for complete healing was also significantly reduced in the combination group . There were no significant side effects in any group . CONCLUSION The combination of 0.2 % GTN and 2 % lignocaine showed better pain relief result ing in less use of oral analgesics and faster healing of the wound after Milligan Morgan hemorrhoidectomy This r and omized , active-controlled study evaluated the extent and duration of analgesia after administration of liposome bupivacaine ( LB ) , a novel formulation of bupivacaine , compared with bupivacaine HCl given via local infiltration in excisional hemorrhoidectomy . One hundred patients were r and omly assigned to receive a single dose of bupivacaine HCl 75 mg ( 0.25 % with 1:200,000 epinephrine ) or LB 66 , 199 , or 266 mg upon completion of hemorrhoidectomy . Postoperative pain intensity was assessed using a numeric rating scale at rest to calculate a cumulative pain score ( area under the curve ) . Cumulative pain scores were significantly lower with LB at each study dose ( P < 0.05 ) compared with bupivacaine HCl 72 hours after surgery . Post hoc analysis showed that mean total postoperative opioid consumption was statistically significantly lower for the LB 266-mg group compared with the bupivacaine HCl group during the 12- to 72-hour postoperative period ( P = 0.019 ) . Median time to first opioid use was 19 hours for LB 266 mg versus 8 hours for bupivacaine HCl ( P = 0.005 ) . Incidence of opioid-related adverse events was 4 per cent for LB 266 mg compared with 35 per cent for bupivacaine HCl ( P = 0.007 ) . Local infiltration with LB result ed in significantly reduced postsurgical pain compared with bupivacaine HCl in patients after hemorrhoidectomy surgery AIM Milligan-Morgan operation is still considered the treatment of choice for IV-degree haemorrhoids : it is frequently associated with significant postoperative pain and prolonged hospital stay . Many instruments were conceived to reduce these complications , such as the LigaSure ™ ( LS ) system , a combination of radiofrequency and pressure that seems mainly effective where a large tissue demolition is required . This r and omized study is METHODS Fifty-two patients with IV-degree hemorrhoids were r and omly assigned to two different surgical treatments ( conventional diathermy vs. LigaSure ™ hemorrhoidectomy ) . They were evaluated on the basis of the following main outcomes : mean operative time , postoperative pain , day of discharge early and late complications . The time of recovery of work was also assessed . All patients had a minimum follow-up of twelve months ( range 12 - 24 ) . All data were statistically evaluated . RESULTS Twenty-seven patients were treated by conventional diathermy , 25 by LigaSure ™ . The mean operative time was significantly shorter in LS , such as postoperative pain , mainly lower on the third and fourth postoperative day : moreover pain disappeared earlier in LS than CD . The time off-work was shorter in LS , while there was no difference in hospital stay and overall complications rate . CONCLUSION This r and omized prospect i ve controlled trial confirms , according to other large trials in literature , the benefits of the LigaSure ™ hemorrhoidectomy over conventional diathermy when a large tissue demolition is required , supporting the use of this device as treatment of choice in IV degree hemorrhoids , even if the procedure is more expensive than conventional operation Hemorrhoidectomy is used for the surgical treatment of high- grade hemorrhoids . The most prominent complaint after hemorrhoidectomy is pain . Postoperative pain management is still a big problem after surgery in patients with hemorrhoidectomy . The aim of the study was to assess the effect of early application of warm bag on postoperative pain after hemorrhoidectomy . All patients were r and omly divided into warm plastic bag and control groups by using sealed envelopes , which were prepared preoperatively . After st and ard spinal anesthesia , all patients underwent st and ard Milligan-Morgan hemorrhoidectomy using Ligasure ™ . Although the study group received the warm bag application , the control group did not receive such a treatment . Two separate visual analog scale ( VAS ) measurements were performed for postoperative pain assessment s on postoperative days , one during the resting state and the other one during the straining phase after the onset of peristaltic bowel movement . Postoperative VAS scores were significantly lower among the warm plastic bag group as compared with the control group on Days 1 and 3 for the resting state and on Day 3 for defecation . Additionally , a significant difference existed between the two groups in terms of the need for additional anesthesia . Local thermal application appears to be a safe and effective method for pain relief after hemorrhoidectomy AIM To demonstrate the value of Diosmin ( flavonidic fraction ) in the management of post-haemorhoidectomic symptoms . METHODS Eighty-six consecutive patients with grade s III and IV acute mixed hemorrhoids admitted to the Anorectal Surgical Department of First Affiliated Hospital , Xinjiang Medical University from April 2009 to April 2010 , were enrolled in this study . An observer-blinded , r and omized trial was conducted to compare post-haemorhoidectomic symptoms with use of Diosmin flavonidic fraction vs placebo . Eighty-six patients were r and omly allocated to receive Diosmin flavonidic fraction 500 mg for 1 wk ( n = 43 ) or placebo ( n = 43 ) . The Milligan-Morgan open haemorrhoidectomy was performed by a st and ardized diathermy excision method . Pain , bleeding , heaviness , pruritus , wound edema and mucosal discharge were observed after surgery . The postoperative symptoms and hospitalization time were recorded . RESULTS The mean age of the Diosmin group and controls was 53.2 and 51.3 years , respectively . In Diosmin group , haemorrhoid piles were of the third degree in 33 patients and the fourth degree in 10 ; and in the control group , 29 were of the third degree and 14 were of the fourth degree . There was no statistically significance in age , gender distribution , degree and number of excised haemorrhoid piles , and the mean duration of haemorrhoidal disease between the two groups . There was a statistically significant improvement in pain , heaviness , bleeding , pruritus from baseline to the 8th week after operation ( P < 0.05 ) . Patients taking Diosmin had a shorter hospitalization stay after surgery ( P < 0.05 ) . There was also a significant improvement on the proctoscopic appearance ( P < 0.001 ) . However , there was no statistical difference between the two groups in terms of wound mucosal discharge . Two patients experienced minor bleeding at the 8th week in Diosmin group , and underwent surgery . CONCLUSION Diosmin is effective in alleviating postoperational symptoms of haemorrhoids . Therefore , it should be considered for the initial treatment after haemorrhoid surgery . However , further prospect i ve r and omized trials are needed to confirm the findings of this study Background The aim of the present study was to evaluate the efficacy of 10 % sucralfate ointment in the reduction of acute postoperative pain after open hemorrhoidectomy . Methods A total of 48 patients ( 24 men and 24 women ) between 20 and 70 years of age who underwent open hemorrhoidectomy were included in this prospect i ve , double-blind , r and omized , controlled trial and were r and omly divided into two groups ( 24 in each group ) , receiving either sucralfate ointment or placebo immediately after surgery and then every 12 h for 14 days . The primary outcome measure was pain intensity measured by a visual analogue scale at different time points after hemorrhoidectomy . Results The sucralfate group had significantly less pain than the placebo group at 24th h and the 48th h after hemorrhoidectomy ( 4 ± 1.14 vs 5.08 ± 0.97 ; P = 0.001 and 3 ± 0.72 vs 4.41 ± 0.8 ; P < 0.001 , respectively ) , and they consumed lower amounts of analgesics at the same time intervals ( 12.50 ± 16.48 vs 21.87 ± 15.30 mg of pethidine ; P = 0.047 and 152 ± 23 vs 172 ± 29 mg of diclofenac ; P = 0.009 , respectively ) . The same trend continued until the end of the trial . Conclusions Sucralfate ointment reduced the acute postoperative pain after hemorrhoidectomy PURPOSE To study the safety and efficiency of two anesthetic blockages in hemorrhoidectomy and the effect of clonidine on analgesia . METHODS 80 patients were studied , r and omly divided into four groups : l (n=19)- peridural with a 0,75 % ropivacaine ; 2 (n=21)-peridural with a 0,75 % ropivacaine and 150 microg of clonidine ; 3 (n=19)- subarachnoid with a 0,5 % bupivacaine ; 4 (n=21)- subarachnoid with a 0,5 % bupivacaine and 50 microg of clonidine . The intensity of pain was evaluated by the visual analogical scale 8 , 12 and 24 hours after surgery . The use of vasoconstrictors on the transoperatory and the amount of analgesics within the 24 hours were registered . RESULTS The intensity of pain , 8 hours after surgery , was lesser on group 4 , and much lesser on group 4 comparing with groups 1 and 2 , 12 hours ( p=0,022 ; p=0,001 ) and 24 hours ( p=0,03 ; p=0,003 ) . The frequency of vasoconstrictors usage on the transoperatory and the analgesics on the post-operatory showed no difference among the groups . There were no anesthetic complications . CONCLUSIONS The subarachnoid anesthesia with a 0,5 % bupivacaine with clonidine , showed better analgesia comparing with the peridural anesthesia with a 0,75 % ropivacaine with or without clonidine , however all were safe and efficient . The clonidine aided on the decreasing of pain when subarachnoid anesthesia was used Purpose Oral and topical sucralfate is regularly used in ulcers of gastrointestinal tract , vaginal and perianal excoriations , and radiation burns . This study was design ed to determine whether there was any advantage of topical application of sucralfate in reducing postoperative pain and promoting wound healing after open hemorrhoidectomy in patients with Grade s III or IV hemorrhoids . Methods A total of 116 patients were r and omly assigned to receive sucralfate cream ( sucralfate group ) or placebo cream ( control group ) applied to the surgical site . Weekly pain score was evaluated by using Visual Analog Scale . The amount of analgesic tablets consumed in each week also was assessed . At the end of four weeks , two independent surgeons assessed the wound healing . Results There was no significant difference in age , gender distribution , and number of excised hemorrhoid piles between the two groups . Patients in the topical sucralfate group experienced significantly less pain at Day 7 ( Visual Analog Scale ± st and ard error of the mean , 3.7 ± 0.3 vs. 6.1 ± 0.7 ; P < 0.002 ) and at Day 14 ( 1.6 ± 0.2 vs. 3.1 ± 0.6 ; P < 0.01 ) . Likewise patients who received sucralfate cream used less analgesic tablets compared with the placebo group . In the sucralfate group , the overall wound healing ranked significantly better than in controls ( P < 0.02 ) . Conclusions Topical sucralfate significantly reduces pain at Days 7 and 14 after hemorrhoidectomy and promotes faster wound healing compared with that of a placebo INTRODUCTION Surgical excision using Harmonic Scalpel is a modern technique used for ablation of symptomatic third degree and all fourth-degree hemorrhoids . Compared with electrocautery , Harmonic Scalpel causes minimal lateral thermal injury during tissue dissection . The result ing mucosal defect is then either left open or sutured ( closed ) depending on surgeon preference . The aim of this work was to evaluate the value of using Harmonic Scalpel in reducing incidence of postoperative complications following Hemorrhoidectomy . PATIENTS & METHODS This is a single-blind r and omized controlled trial done at Zagazig University hospital during the period from July 2007 to December 2008 . Patients underwent surgical excision of complex grade III or grade IV hemorrhoids . They were divided into two groups : ( A ) Harmonic Scalpel Hemorrhoidectomy group and ( B ) Bipolar Electro-cautery Hemorrhoidectomy group . Pain levels scoring and postoperative complications were analyzed . RESULTS Postoperative pain in Group ( A ) was significantly less with less analgesic requirement . There was no significant difference between both groups regarding other postoperative complications . CONCLUSION This study demonstrates significantly reduced postoperative pain after Harmonic Scalpel Hemorrhoidectomy compared with bipolar electro-cautery Hemorrhoidectomy . Most likely , this result came from the avoidance of excessive lateral thermal injury caused by bipolar electrocautery Abstract Background and objective Perioperative low-dose ketamine has been useful for postoperative analgesia . In this study we wanted to assess the analgesic effect and possible side-effects of perioperative low-dose S ( + ) ketamine when added to a regime of non-opioid multimodal pain prophylaxis . Methods Seventy-seven patients scheduled for haemorrhoidectomy were enrolled in this r and omized , double-blind , controlled study . They received oral paracetamol 1–2 g , total intravenous anaesthesia , intravenous 8 mg dexamethasone , 30 mg ketorolac and local infiltration with bupivacaine/epinephrine . Patients r and omized to S ( + ) ketamine received an intravenous bolus dose of 0.35 mg kg−1 S ( + ) ketamine before start of surgery followed by continuous infusion of 5 μg kg−1 min−1 until 2 min after end of surgery . Patients in the placebo group got isotonic saline ( bolus and infusion ) . BISTM monitoring was used . Pain intensity and side-effects were assessed by blinded nursing staff during PACU stay and by phone 1 , 7 and 90 days after surgery . Results In patients r and omized to S ( + ) ketamine emergence from anaesthesia was significantly longer ( 13.1 min vs. 9.3 min ; p < 0.001 ) . BIS values were significantly higher during anaesthesia ( maximal value during surgery : 62 vs. 57 ; p = 0.01 ) and when opening eyes ( 81 vs. 70 , p < 0.001 ) . Pain scores ( NRS and VAS ) did not differ significantly between groups . Conclusions The addition of perioperative S ( + ) ketamine for postoperative analgesia after haemorrhoidectomy on top of multimodal non-opioid pain prophylaxis does not seem to be warranted , due to delayed emergence and recovery , more side-effects , altered BIS readings and absence of additive analgesic effect AIM The prevalence of symptomatic hemorrhoidal disease is a common disease that usually needs surgery for treatment . Although conservative treatment is often enough for early stages , late stage disease usually needs surgical treatment . The most common and effective approaches used for conventional surgical treatment are harmonic scalpel ( HS ) and Ferguson 's with electrocautery hemorrhoidectomy ( FEH ) . We aim ed to use the HS device for hemorrhoidectomy in Grade III and Grade IV hemorrhoids and compare our results with FEH MATERIAL S AND METHODS : Enrolled into the study were 151 patients who were operated for symptomatic Grade III-IV hemorrhoids . Patients were r and omized into FEH and HS groups . The present review focused on comparing HS hemorrhoidectomy versus FEH with regards to operating time , postoperative pain , duration of disease , number of issued analgesics , length of hospital stay , time to return to normal activity , and postoperative complications . RESULTS The mean ages of patients who underwent HS and FEH were 34.1 ± 9.2 years and 33.7 ± 8.4 years , respectively . The average postoperative stay in the HS group was 1.0 ± 0.1 days and in the FEH group was 1.2 ± 0.4 ( p = 0.001 ) . The time of return to normal activity was less for the HS groups than for the FEH groups ( 10.6 ± 2.1 days vs. 16.0 ± 6.3 days ; p = 0.001 ) . The mean operating time of the HS and FEH groups was 16.8 ± 4.1 minutes and 25.5 ± 7.7 minutes , respectively ( p = 0.001 ) . The total analgesic doses for the HS group were 790 ± 206 mg , 619 ± 234 mg , and 30 ± 99 mg , and for the FEH group were 1096 ± 194 mg , 1000 ± 259 mg , and 40 ± 0 mg for postoperative Day 1 , Day 7 , and Day 28 , respectively . There was no significant difference between the HS group and the FEH group in the terms of the number of excised hemorrhoid masses ( 2.0 ± 0.6 vs. 1.88 ± 0.6 ) . CONCLUSION HS hemorrhoidectomy is safe and effective , causes less blood loss and postoperative pain , and fewer complications compared to FEH Purpose Milligan-Morgan hemorrhoidectomy using radiofrequency dissection ( Ligasure ™ ) has been proposed instead of conventional diathermy in view of its potential benefits in terms of postoperative anal pain and better hemostatic control , but the medical literature is still controversial . This multicenter , r and omized , controlled trial was design ed to compare the outcomes between Ligasure ™ and conventional diathermy hemorrhoidectomy in the Milligan-Morgan procedures in a sufficient number of patients . Methods Patients with Grade s III and IV hemorrhoids were r and omized to two groups : Ligasure ™ hemorrhoidectomy and conventional diathermy . Postoperative anal pain was measured by the Visual Analog Scale ( VAS ) and the analgesia required . Postoperative complications , wound healing , and return to working activities also were evaluated as secondary outcomes . Results A total of 273 patients , well matched for age , gender , working activity and grade of hemorrhoids , were r and omized to two groups : Ligasure ™ 146 , and diathermy 127 . The severity of postoperative anal pain was significantly less in the Ligasure group when measured at least 12 hours after defecation ( P < 0.01 ) , whereas it was similar at the time of defecation . The Ligasure ™ group had significantly lower requirements for painkiller pills . There were no significant differences in early and late complications . Return to work and normal activities was significantly faster in the Ligasure ™ group . Conclusion Ligasure ™ hemorrhoidectomy is an effective procedure for Grade s III and IV hemorrhoids and facilitates a faster return to work and normal activities by reducing postoperative pain ABSTRACT Background : This r and omized study compared results obtained with the Ferguson 's technique for the treatment of hemorrhoids performed with a radiofrequency ( RF ) scalpel and traditional diathermy . Methods : 28 patients affected by grade IV hemorrhoids were r and omized to receive either the Ferguson operation with the RF scalpel ( group A ) or traditional diathermy ( group B ) . The operating time , intra- and postoperative bleeding , postoperative pain , and overall patient satisfaction were all recorded . Results : Six patients ( three for each group ) did not attend follow-up controls . Group A showed a significant reduction of the surgical time ( 23 vs. 33 min ; p < .01 ) , pain at first postoperative day ( Visual Analog Scale [ VAS ] score 3.4 vs. 4.8 ; p < .05 ) , and at the first evacuation ( 3.4 vs. 5.0 ; p < .05 ) . No significant differences were observed for the pain score at the seventh postoperative day , or overall satisfaction scores at the 7th postoperative day , and six months postoperatively ( p = NS ) . No severe complications were recorded . Two patients in group A ( 18.2 % ) and four patients in group B ( 36.4 % ) reported transitory gas incontinence that spontaneously resolved within one month ( p = NS ) . Three patients in group A ( 27.3 % ) and four patients in group B ( 36.4 % ) required postoperative catheterization due to urinary retention ( p = NS ) . Conclusions : RF scalpel shortens the operating time of the Ferguson operation and is less painful in the early postoperative period |
654 | 18,156,884 | Maintaining perioperative normothermia reduces blood loss and transfusion requirement by clinical ly important amounts | BACKGROUND Anesthetic-induced hypothermia is known to reduce platelet function and impair enzymes of the coagulation cascade .
The objective of this meta- analysis and systematic review was to evaluate the hypothesis that mild perioperative hypothermia increases surgical blood loss and transfusion requirement . | Background : Hypothermia during and after major abdominal surgery decreases host defenses , increases the incidence of coagulopathy and may alter blood pressure , cardiac contractility and myocardial stability . Methods : We design ed a prospect i ve r and omized study to compare the benefits of a forced air warming system with warm blanket treatments in minimizing the effects of hypothermia on 64 morbidly obese patients undergoing Roux-en-Y gastric bypass . Results : Patients in the forced air warming group ( n = 32 ) had significantly higher perioperative body core temperature , lower central venous pressure and blood pressure readings , lower incidence of shivering , less blood loss intraoperatively and achieved a higher post anesthesia Aldrete Score than those patients in the warmed blanket group ( n = 32 ) . Conclusion : The forced air warming system is safe , cost effective and beneficial in minimizing the undesirable consequences of hypothermia in morbidly obese patients undergoing Roux-en-Y gastric bypass BACKGROUND Mild perioperative hypothermia , which is common during major surgery , may promote surgical-wound infection by triggering thermoregulatory vasoconstriction , which decreases subcutaneous oxygen tension . Reduced levels of oxygen in tissue impair oxidative killing by neutrophils and decrease the strength of the healing wound by reducing the deposition of collagen . Hypothermia also directly impairs immune function . We tested the hypothesis that hypothermia both increases susceptibility to surgical-wound infection and lengthens hospitalization . METHODS Two hundred patients undergoing colorectal surgery were r and omly assigned to routine intraoperative thermal care ( the hypothermia group ) or additional warming ( the normothermia group ) . The patient 's anesthetic care was st and ardized , and they were all given cefam and ole and metronidazole . In a double-blind protocol , their wounds were evaluated daily until discharge from the hospital and in the clinic after two weeks ; wounds containing culture-positive pus were considered infected . The patients ' surgeons remained unaware of the patients ' group assignments . RESULTS The mean ( + /- SD ) final intraoperative core temperature was 34.7 + /- 0.6 degrees C in the hypothermia group and 36.6 + /- 0.5 degrees C in the normothermia group ( P < 0.001 ) Surgical-wound infections were found in 18 of 96 patients assigned to hypothermia ( 19 percent ) but in only 6 of 104 patients assigned to normothermia ( 6 percent , P = 0.009 ) . The sutures were removed one day later in the patients assigned to hypothermia than in those assigned to normothermia ( P = 0.002 ) , and the duration of hospitalization was prolonged by 2.6 days ( approximately 20 percent ) in hypothermia group ( P = 0.01 ) . CONCLUSIONS Hypothermia itself may delay healing and predispose patients to wound infections . Maintaining normothermia intraoperatively is likely to decrease the incidence of infectious complications in patients undergoing colorectal resection and to shorten their hospitalizations BACKGROUND In-vitro studies indicate that platelet function and the coagulation cascade are impaired by hypothermia . However , the extent to which perioperative hypothermia influences bleeding during surgery remains unknown . Accordingly , we tested the hypothesis that mild hypothermia increases blood loss and allogeneic transfusion requirements during hip arthroplasty . METHODS Blood loss and transfusion requirements were evaluated in 60 patients undergoing primary , unilateral total hip arthroplasties who were r and omly assigned to normothermia ( final intraoperative core temperature 36.6 [ 0.4 ] degrees C ) or mild hypothermia ( 35.0 [ 0.5 ] degrees C ) . Crystalloid , colloid , scavenged red cells , and allogeneic blood were administered by strict protocol . FINDINGS Intra- and postoperative blood loss was significantly greater in the hypothermic patients : 2.2 ( 0.5 ) L vs 1.7 ( 0.3 ) L , p < 0.001 ) . Eight units of allogeneic packed red cells were required in seven of the 30 hypothermic patients , whereas only one normothermic patient required a unit of allogeneic blood ( p < 0.05 for administered volume ) . A typical decrease in core temperature in patients undergoing hip arthroplasty will thus augment blood loss by approximately 500 mL. INTERPRETATION The maintenance of intraoperative normothermia reduces blood loss and allogeneic blood requirements in patients undergoing total hip arthroplasty Background Shivering is rare during general anesthesia . This observation suggests that anesthetics profoundly impair shivering . However , the effects of surgical doses of volatile anesthetics on control of shivering have yet to be evaluated . Furthermore , the effects of desflurane on sweating and thermoregulatory vasoconstriction remain unknown . Accordingly , the authors determined the concentration‐dependent effects of desflurane on sweating , vasoconstriction , and shivering We have investigated patients undergoing cardiac surgery with hypothermic bypass to see if the addition of skin surface warming during systemic rewarming on bypass ( heated group , n = 43 ) would improve perioperative thermal balance compared with conventional management without skin warming ( control group , n = 43 ) in an open , r and omized , controlled study . Intraoperative skin warming with a water mattress and forced warm air over the face , neck and shoulders attenuated the afterdrop in nasopharyngeal temperature after weaning from bypass ( 2.3 ( 1.2 ) degrees C and 1.3 ( 0.5 ) degrees C in the control and heated groups , respectively ) ( P < 0.05 ) and result ed in higher rectal temperature 4 h after surgery . Despite similar st and ard coagulation tests , heated patients had lower blood loss via the chest tubes ( 600 ( 264 ) ml vs 956 ( 448 ) ml in control patients ) ( P < 0.05 ) and less requirements for i.v . colloid infusion ( 1662 ( 404 ) ml vs 1994 ( 389 ) ml ) ( P < 0.05 ) . There was a significant inverse correlation between rectal temperature on arrival in the ICU and postoperative blood loss ( r = 0.57 , P < 0.001 ) . These data suggest that additional skin surface warming with a water mattress and forced warm air helped to preserve perioperative thermal balance and may contribute to reduced bleeding after cardiac surgery OBJECTIVE We evaluated the performance of a new temperature management system ( A rct ic Sun , Medivance , Inc. ) in maintaining normothermia during off-pump coronary artery bypass ( OPCAB ) . PATIENTS AND METHODS Ninety-eight unselected patients were prospect ively r and omized to either a conventional temperature management method ( consisting of a sterile forced-air warming blanket , warm intravenous fluids , and maintenance of a warm OR ) or the new A rct ic Sun system ( two pads , A rct ic Sun Energy Transfer Pads placed on the patient 's back with temperature-controlled water flowing through the pads ) . RESULTS The mean age , body surface area , and total operating time were similar in both groups . Despite significantly lower room temperatures ( p<0.001 ) in the A rct ic Sun group , the system maintained higher bladder and nasopharyngeal temperatures ( p<0.001 and p<0.001 , respectively ) . A core temperature of at least 36 degrees C was achieved in 97 % of the A rct ic Sun patients compared with 42 % in the conventional group . Additionally , intra-operative blood loss for the A rct ic Sun patients was significantly less ( p=0.01 ) . CONCLUSIONS The A rct ic Sun system significantly outperformed conventional techniques in achieving and maintaining normothermia during off-pump coronary artery bypass OBJECTIVE Perioperative hypothermia might be detrimental to the patient undergoing off-pump coronary artery bypass surgery . We assessed the efficacy of the Allon thermoregulation system ( MTRE Advanced Technologies Ltd , Or-Akiva , Israel ) compared with that of routine thermal care in maintaining normothermia during and after off-pump coronary artery bypass surgery . METHODS Patients undergoing off-pump coronary artery bypass surgery were perioperatively and r and omly warmed with the 2 techniques ( n = 45 per group ) . Core temperature , hemodynamics , and troponin I , interleukin 6 , interleukin 8 , and interleukin 10 blood levels were assessed . RESULTS The mean temperature of the patients in the Allon thermoregulation system group ( AT group ) was significantly ( P < .005 ) higher than that of the patients receiving routine thermal care ( the RTC group ) ; less than 40 % of the latter reached 36 degrees C compared with 100 % of the former . The cardiac index was higher and the systemic vascular resistance was lower ( P < .05 ) by 16 % and 25 % , respectively , in the individuals in the AT group compared with in the individuals in the RTC group during the 4 postoperative hours . End-of-surgery interleukin 6 levels and 24-hour postoperative troponin I levels were significantly ( P < .01 ) lower in the patients in the AT group than in the RTC group . The RTC group 's troponin levels closely correlated with their interleukin 6 levels at the end of the operation ( R = 0.51 , P = .002 ) . CONCLUSIONS Unlike routine thermal care , the Allon thermoregulation system maintains core normothermia in more than 80 % of patients undergoing off-pump coronary artery bypass surgery . Normothermia is associated with better cardiac and vascular conditions , a lower cardiac injury rate , and a lower inflammatory response . The close correlation between the increased interleukin 6 and troponin I levels in the routine thermal care group indicates a potential deleterious effect of lowered temperature on the patient 's outcome STUDY OBJECTIVE To evaluate the postoperative hemodynamic and thermoregulatory consequences of intraoperative core hypothermia . DESIGN Prospect i ve , r and omized clinical trial . SETTING Operating room and postanesthesia care unit of a university hospital . PATIENTS 74 healthy , ASA status I , II , and III patients ( average age 58 yrs ) undergoing elective colon surgery . INTERVENTIONS Patients were r and omly assigned to be kept normothermic or approximately 2.5 degrees C hypothermic during surgery . Anesthesia was maintained with isoflurane , nitrous oxide , and fentanyl . Postoperatively , surgical pain was treated with patient-controlled analgesia ( PCA ) opioid . MEASUREMENTS AND MAIN RESULTS An observer blinded to group assignment and core temperatures evaluated shivering , thermal comfort , surgical pain , heart rates ( HRs ) , and blood pressures ( BPs ) during the first six postoperative hours . Morphometric characteristics , oxygen saturation , fluid balance , PCA-administered opioid , and visual analog pain scores were comparable in the two groups . Hypothermic patients felt uncomfortably cold during recovery , and their postoperative core temperatures remained significantly less than in the normothermic patients for more than four hours . Peripheral vasoconstriction and shivering were common in the hypothermic patients but rare in those kept normothermic . HRs and BPs were comparable in the two groups . CONCLUSIONS These data confirm that the effects of intraoperative hypothermia on postoperative HR and BP are modest in relatively young , generally healthy patients . In contrast , intraoperative hypothermia caused substantial postoperative thermal discomfort , and full recovery from hypothermia required many hours . Delayed return to care normothermia apparently result ed largely from postoperative thermoregulatory impairment An attempt was made to reduce heat loss in elderly patients undergoing major abdominal surgery . Two groups were studied . In one group , efforts were made to minimize heat loss by using a hot-water humidifier in the anaesthetic circuit , a hot-water circulating mattress under the patient and warming all i.v . fluids . Otherwise , the surgical and anaesthetic techniques were comparable . The same anaesthetic technique of nitrous oxide , oxygen , pancuronium and fentanyl with intermittent positive pressure ventilation was used in all cases . Nitrogen loss was measured in urine collected over 48 h from an indwelling urinary catheter inserted soon after induction of anaesthesia . Prevention of heat loss during anaesthesia and postoperative recovery caused a significant reduction in nitrogen loss OBJECTIVE To assess the relationship between body temperature and cardiac morbidity during the perioperative period . DESIGN R and omized controlled trial comparing routine thermal care ( hypothermic group ) to additional supplemental warming care ( normothermic group ) . SETTING Operating rooms and surgical intensive care unit at an academic medical center . SUBJECTS Three hundred patients undergoing abdominal , thoracic , or vascular surgical procedures who either had documented coronary artery disease or were at high risk for coronary disease . OUTCOME MEASURE The relative risk of a morbid cardiac event ( unstable angina/ischemia , cardiac arrest , or myocardial infa rct ion ) according to thermal treatment . Cardiac outcomes were assessed in a double-blind fashion . RESULTS Mean core temperature after surgery was lower in the hypothermic group ( 35.4+/-0.1 degrees C ) than in the normothermic group ( 36.7+/-0.1 degrees C ) ( P<.001 ) and remained lower during the early postoperative period . Perioperative morbid cardiac events occurred less frequently in the normothermic group than in the hypothermic group ( 1.4 % vs 6.3 % ; P=.02 ) . Hypothermia was an independent predictor of morbid cardiac events by multivariate analysis ( relative risk , 2.2 ; 95 % confidence interval , 1.1 - 4.7 ; P=.04 ) , indicating a 55 % reduction in risk when normothermia was maintained . Postoperative ventricular tachycardia also occurred less frequently in the normothermic group than in the hypothermic group ( 2.4 % vs 7.9 % ; P=.04 ) . CONCLUSION In patients with cardiac risk factors who are undergoing noncardiac surgery , the perioperative maintenance of normothermia is associated with a reduced incidence of morbid cardiac events and ventricular tachycardia We evaluated the effects of aggressive warming and maintenance of normothermia on surgical blood loss and allogeneic transfusion requirement . We r and omly assigned 150 patients undergoing total hip arthroplasty with spinal anesthesia to aggressive warming ( to maintain a tympanic membrane temperature of 36.5 ° C ) or conventional warming ( 36 ° C ) . Autologous and allogeneic blood were given to maintain a priori design ated hematocrits . Blood loss was determined by a blinded investigator based on sponge weight and scavenged cells ; postoperative loss was determined from drain output . Results were analyzed on an intention-to-treat basis . Average intraoperative core temperatures were warmer in the patients assigned to aggressive warming ( 36.5 ° ± 0.3 ° vs 36.1 ° ± 0.3 ° C , P < 0.001 ) . Mean arterial pressure was similar in each group preoperatively , but was greater intraoperatively in the conventionally warmed patients : 86 ± 12 vs 80 ± 9 mm Hg , P < 0.001 . Intraoperative blood loss was significantly greater in the conventional warming ( 618 mL ; interquartile range , 480–864 mL ) than the aggressive warming group ( 488 mL ; interquartile range , 368–721 mL;P = 0.002 ) , whereas postoperative blood loss did not differ in the two groups . Total blood loss during surgery and over the first two postoperative days was also significantly greater in the conventional warming group ( 1678 mL ; interquartile range , 1366–1965 mL ) than in the aggressively warmed group ( 1,531 mL ; interquartile range , 1055–1746 mL , P = 0.031 ) . A total of 40 conventionally warmed patients required 86 units of allogeneic red blood cells , whereas 29 aggressively warmed patients required 62 units ( P = 0.051 and 0.061 , respectively ) . We conclude that aggressive intraoperative warming reduces blood loss during hip arthroplasty . Implication s Aggressive warming better maintained core temperature ( 36.5 ° vs 36.1 ° C ) and slightly decreased intraoperative blood pressure . Aggressive warming also decreased blood loss by approximately 200 mL. Aggressive warming may thus , be beneficial in patients undergoing hip arthroplasty BACKGROUND The aim of this prospect i ve r and omized trial was to evaluate the efficacy of 3 intraoperative warming systems ( Warm-Touch , Thermamed SmartCare OP system , and Allon 2001 ) on maintenance of normothermia and to investigate their effects on perioperative bleeding and transfusion requirements in patients undergoing off-pump coronary artery bypass grafting . METHODS With institutional approval/patient informed consent , 90 patients presenting for elective multiple off-pump coronary artery bypass grafting were r and omly assigned to 1 of the 3 warming systems . Active warming was started after the induction of anesthesia . Perioperative transfusion was based on international guidelines . Body core temperature was recorded every 30 minutes during operation . Perioperative blood loss , autotransfusion , and allogenic transfusions were recorded . Analysis of variance was performed with post hoc Scheffé tests and chi 2 tests . RESULTS Normothermia could be sufficiently maintained during operation by the Allon 2001 only . Final body core temperature was 34.7 degrees C + /- 0.9 degrees C ( Warm-Touch ) , 35.6 degrees C + /- 0.8 degrees C ( Thermamed SmartCare OP ) , and 36.5 degrees C + /- 0.4 degrees C ( Allon 2001 ; P < .001 , Warm-Touch vs Thermamed SmartCare OP , Warm-Touch vs Allon 2001 , and Thermamed SmartCare OP vs Allon 2001 ) . Perioperative blood loss was 2683 + /- 1049 mL ( Warm-Touch ) , 2300 + /- 788 mL ( Thermamed SmartCare OP ) , and 1497 + /- 497 mL ( Allon 2001 ; P = .195 , Warm-Touch vs Thermamed SmartCare OP ; P < .001 , Warm-Touch vs Allon 2001 ; P = .001 , Thermamed SmartCare OP vs Allon 2001 ) . Transfusion requirements were 1097 + /- 874 mL ( Warm-Touch ) , 986 + /- 744 mL ( Thermamed SmartCare OP ) , and 431 + /- 387 mL ( Allon 2001 ; P = .838 , Warm-Touch vs Thermamed SmartCare OP ; P = .003 , Warm-Touch vs Allon 2001 ; P = .013 , Thermamed SmartCare OP vs Allon 2001 ) . Free of allogenic transfusion were 15 ( 51.7 % ; Warm-Touch ) , 18 ( 60 % ; Thermamed SmartCare OP ) , and 24 ( 82.8 % ; Allon 2001 ) patients ( P = .037 ) . CONCLUSIONS The goal of normothermia during off-pump coronary artery bypass grafting was best achieved by the Allon system . With this concept , overall blood loss and transfusion requirements were reduced , hence indicating improved quality of perioperative care Background Core hypothermia after induction of epidural anesthesia results from both an internal core‐to‐peripheral redistribution of body heat and a net loss of heat to the environment . However , the relative contributions of each mechanism remain unknown . The authors thus evaluated regional body heat content and the extent to which core hypothermia after induction of anesthesia result ed from altered heat balance and internal heat redistribution BACKGROUND Hypothermia in the perioperative period is associated with adverse effects , particularly bleeding . Before termination of cardiopulmonary bypass , rewarming times and perfusion temperatures are often increased to avoid post-cardiopulmonary bypass hypothermia and the presumed complications . This practice may , however , also have adverse effects , particularly cerebral hyperthermia . We present safety outcomes from a trial in which patients undergoing coronary artery surgery were r and omly assigned to normothermia or hypothermia for the entire surgical procedure . METHODS Consenting patients over the age of 60 years presenting for a first , elective coronary artery surgery with cardiopulmonary bypass were r and omly assigned to having their nasopharyngeal temperature maintained at either 37 degrees C ( group N ; 73 patients ) or 34 degrees C ( group H ; 71 patients ) throughout the intraoperative period , with no rewarming before arrival in the intensive care unit . All received tranexamic acid . RESULTS There was no clinical ly important difference in intraoperative blood product or inotrope use . Temperatures on arrival in the intensive care unit were 36.7 degrees C + /- 0.38 degrees C and 34.3 degrees C + /- 0.38 degrees C in groups N and H , respectively . Blood loss during the first 12 postoperative hours was 596 + /- 356 mL in group N and 666 + /- 405 mL in group H ( mean difference + /- 95 % confidence interval , 70 + /- 126 mL ; P = .28 ) . There was no significant difference in blood product utilization , intubation time , time in the hospital , myocardial infa rct ion , or mortality . The mean time in the intensive care unit was 8.4 hours less in the hypothermic group ( P = .02 ) . CONCLUSIONS Our data support the safety of perioperative mild hypothermia in patients undergoing elective nonreoperative coronary artery surgery with cardiopulmonary bypass . These findings suggest that complete rewarming after hypothermic cardiopulmonary bypass is not necessary in all cases STUDY OBJECTIVE To test the hypothesis that warming intravenous ( i.v . ) fluids in conjunction with convective warming results in less intraoperative hypothermia ( core temperature < 36.0 degrees C ) than that seen with convective warming alone . DESIGN Prospect i ve , r and omized study . SETTING University affiliated tertiary care teaching hospital . PATIENTS 61 ASA physical status , I , II , and III adults undergoing major surgery and general anesthesia with isoflurane . INTERVENTIONS All patients received convective warming . Group 1 patients received warmed fluids ( setpoint 42 degrees C ) . Group 2 patients received room temperature fluids ( approximately 21 degrees C ) . MEASUREMENTS AND MAIN RESULTS Lowest and final intraoperative distal esophageal temperatures were higher ( p < 0.05 ) in Group 1 ( mean + /- SEM : 35.8 + /- 0.1 degrees C and 36.6 + /- 0.1 degrees C ) versus Group 2 ( 35.4 + /- 0.1 degrees C and 36.1 + /- 0.1 degrees C , respectively ) . Compared with Group 1 , more Group 2 patients were hypothermic at the end of anesthesia ( 10 of 26 patients , or 38.5 % vs. 4 of 30 patients , or 13 % ; p < 0.05 ) . After 30 minutes in the recovery room , there were no differences in temperature between groups ( 36.7 + /- 0.1 degrees C and 36.5 + /- 0.1 degrees C in Groups 1 and 2 , respectively ) . Intraoperative cessation of convective warming because of core temperature greater than 37 degrees C was required in 33 % of Group 1 patients ( vs. 11.5 % in Group 2 ; p = 0.052 ) . CONCLUSIONS The combination of convective and fluid warming was associated with a decreased likelihood of patients leaving the operating room hypothermic . However , average final temperatures were greater than 36 degrees C in both groups , and intergroup differences were small . Care must be taken to avoid overheating the patient when both warming modalities are employed together Background : The effects of mild hypothermia on blood loss are little known BACKGROUND To compare passive thermal insulation by reflective blankets with forced-air active warming on the efficacy of normothermia maintenance and time for discharging from the recovery room after combined spinal/epidural anesthesia for total hip arthroplasty . METHODS DESIGN Prospect i ve , r and omized study . SETTING Inpatient anesthesia at three University Departments of orthopedic surgery . PATIENTS 50 ASA physical status I-III patients , who were scheduled for elective total hip arthroplasty . INTERVENTIONS Patients received combined spinal/epidural anesthesia ( CSE ) with intrathecal injection of 15 mg of 0.5 % hyperbaric bupivacaine . All procedures started 8 - 10 a.m. , and operating room temperature was maintained between 21 - 23 degrees C , with relative humidity ranging between 40 - 45 % . As warming therapy patients received either passive thermal insulation of the trunk , the two upper limbs and the unoperated lower limb with reflective blankets ( group passive , n = 25 ) , or forced-air active warming of the two upper limbs ( group active , n = 25 ) . Core temperature was measured before CSE placement ( baseline ) , and then every 30 min until recovery of normothermia . RESULTS Demographic data , duration of surgery , intraoperative blood losses , and crystalloid infusion were similar in the two groups . Arterial blood pressure decreased in both groups compared with baseline values , while no differences in heart rate were observed during the study . Core temperatures in passive group patients decreased more markedly than in actively warmed patients , with a 1 degree C difference between the two groups at the end of surgery ( p < 0.0005 ) . At recovery room entry seven patients in group active ( 24 % ) and 16 patients in group passive ( 64 % ) showed a core temperature < 36 degrees C ( p < 0.01 ) . Achievement of both discharging criteria and normothermia required 32 + /- 18 min in active group and 74 + /- 52 min in passive group ( p < 0.0005 ) . CONCLUSIONS Forced-air cutaneous warming allows the anesthesiologist to maintain normothermia during combined spinal/epidural anesthesia for total hip replacement even if the convective blanket is placed on a relatively small skin surface with reflex vasoconstriction . Maintaining core normothermia decreased the duration of postanesthesia recovery and may , therefore , reduce costs of care We have investigated the influence of active warming before and during operation on blood loss , transfusion requirements , duration of stay in the post-anaesthesia care unit ( PACU ) and perioperative costs in 40 patients undergoing major abdominal surgery . Patients were allocated r and omly to one of two groups : in the study group ( n = 20 ) , patients were actively warmed using forced air for 30 min before induction of general anaesthesia and during anaesthesia . Passive protection against heat loss consisted of circulating water mattresses , blankets and fluid warming devices , and was used both in the active warming group and in the control group ( n = 20 ) . At the end of surgery the change in core temperature was significantly less in the group of actively warmed patients ( 0.5 ( SD 0.8 ) degree C vs 1.5 ( 0.8 ) degree C ; P < or = 0.01 ) . Blood loss and transfusion requirements were less in the actively warmed patients , who had a shorter duration of stay in the PACU ( 94 ( SD 42 ) min vs 217 ( 169 ) min ; P < or = 0.01 ) and a 24 % reduction in total anaesthetic costs BACKGROUND Wound infection after clean surgery is an expensive and often underestimated cause of patient morbidity , and the benefits of using prophylactic antibiotics have not been proven . Warming patients during colorectal surgery has been shown to reduce infection rates . We aim ed to assess whether warming patients before short duration , clean surgery would have the same effect . METHODS 421 patients having clean ( breast , varicose vein , or hernia ) surgery were r and omly assigned to either a non-warmed ( st and ard ) group or one of two warmed groups ( local and systemic ) . We applied warming for at least 30 min before surgery . Patients were followed up and masked outcome assessment s made at 2 and 6 weeks . FINDINGS Analysis was done on an intention-to-treat basis . We identified 19 wound infections in 139 non-warmed patients ( 14 % ) but only 13 in 277 who received warming ( 5 % ; p=0.001 ) . Wound scores were also significantly lower ( p=0.007 ) in warmed patients . There was no significant difference in the development of haematomas or seromas after surgery but the non-warmed group were prescribed significantly more postoperative antibiotics ( p=0.002 ) . INTERPRETATION Warming patients before clean surgery seems to aid the prevention of postoperative wound infection . If applied according to the manufacturers guidelines these therapies have no known side-effects and might , with the support of further studies , provide an alternative to prophylactic antibiotics in this type of surgery STUDY OBJECTIVE To compare the effectiveness of three commonly used intraoperative warming devices . DESIGN A r and omized , prospect i ve clinical trial . SETTING The surgical suite of a university medical center . PATIENTS Twenty adult patients undergoing kidney transplantation for end-stage renal disease . INTERVENTIONS Patients were assigned to one of four warming therapy groups : circulating-water blanket ( 40 degrees C ) , heated humidifier ( 40 degrees C ) , forced-air warmer ( 43 degrees C , blanket covering legs ) , or control ( no extra warming ) . Intravenous fluids were warmed ( 37 degrees C ) , and fresh gas flow was 5 L/min for all groups . No passive heat and moisture exchangers were used . MEASUREMENTS AND MAIN RESULTS The central temperature ( tympanic membrane thermocouple ) decreased approximately 1 degree C during the first hour of anesthesia in all groups . After three hours of anesthesia , the decrease in the tympanic membrane temperature from baseline ( preinduction ) was least in the forced-air warmer group ( -0.5 degrees C + /- 0.4 degrees C ) , intermediate in the circulating-water blanket group ( -1.2 degrees C + /- 0.4 degrees C ) , and greatest in the heated humidifier and control groups ( -2.0 degrees C + /- 0.5 degrees C and -2.0 degrees C + /- 0.7 degrees C , respectively ) . Total cutaneous heat loss measured with distributed thermal flux transducers was approximately 35W ( watts = joules/sec ) less in the forced-air warmer group than in the others . Heat gain across the back from the circulating-water blanket was approximately 7W versus a loss of approximately 3W in patients lying on a st and ard foam mattress . CONCLUSION The forced-air warmer applied to only a limited skin surface area transferred more heat and was clinical ly more effective ( at maintaining central body temperature ) than were the other devices . The characteristic early decrease in central temperature observed in all groups regardless of warming therapy is consistent with the theory of anesthetic-induced heat redistribution within the body Background Desflurane decreases the vasoconstriction and shivering thresholds disproportionately at high anesthetic concentrations . This result contrasts with the authors ' previous report that isoflurane decreases the vasoconstriction threshold linearly . It is surprising that the basic shape of the concentration‐response curve should differ with these two otherwise similar anesthetics . Therefore , the hypothesis that isoflurane produces a nonlinear reduction in the vasoconstriction threshold was tested . Because the effect of isoflurane on shivering remains unknown , the extent to which isoflurane reduces the shivering threshold also was determined . Methods Eight men volunteered to be studied on four r and omly ordered days : ( 1 ) a target end‐tidal isoflurane concentration of 0.55 % , ( 2 ) a target concentration of 0.7 % , ( 3 ) control ( no anesthesia ) and a target end‐tidal concentration of 0.85 % , and ( 4 ) a target end‐tidal concentration of 1.0 % . Volunteers were surface‐cooled until peripheral vasoconstriction and shivering were observed . We arithmetically compensated for changes in skin temperature using the established linear cutaneous contributions to control for each response . From the calculated thresholds ( core temperatures triggering responses at a design ated skin temperature of 34 degrees C ) , the concentration‐response relation was determined . Results Isoflurane administration produced a dose‐dependent reduction in the vasoconstriction and shivering thresholds , decreasing each [ nearly equal ] 4.6 degrees C at an end‐tidal concentration of 1 % . Residual analysis indicated that the vasoconstriction and shivering thresholds were decreased in a nonlinear fashion during isoflurane administration . The vasoconstriction‐to‐shivering range was 1.5+/‐ 0.8 degree C without isoflurane , and did not change significantly during isoflurane administration . Conclusions The vasoconstriction‐to‐shivering range remained unchanged by isoflurane administration . In this regard , the effects of isoflurane are similar to those of desflurane , propofol , and alfentanil . The current data differ from the authors ' previous report , in that the dose‐dependence for vasoconstriction was nonlinear , with isoflurane reducing the threshold disproportionately at higher anesthetic concentrations . Differing dose‐dependence in the two studies may result either because the current study 's volunteers were not exposed to surgical stimulation and were given less isoflurane , or because of design limitations in the previous protocol Background and objective Hypothermia may alter the disposition of opioids . Because opioids are commonly used as analgesics in the postoperative period , it is of clinical interest to clarify whether perioperatively developed hypothermia affects postoperative opioid requirements . Methods Fifty-nine patients undergoing subtotal hysterectomy were prospect ively r and omized and either treated intraoperatively with forced air warming , or served as controls covered with conventional blankets without active warming . Both groups received postoperative patient-controlled analgesia with the opioid ketobemidone . Total analgesic requirements , dem and s , analgesic requirements over 6-h intervals and pain scores were measured for 48 h. Core temperature at the tympanic membrane and ambient room temperature were measured during the perioperative period . Results There were no postoperative differences in analgesic requirements or pain intensity between normothermic and hypothermic patients . Patients treated with warm air had an up to 1 ° C higher core temperature from 0.5 h after anaesthesia induction until almost 2 h postoperatively . The actively warmed patients also had a lower intraoperative blood loss than the hypothermic patients ( 186 ± 27 mL vs. 308 ± 47 mL;P < 0.05 ) . Conclusion In a clinical setting , opioid requirements do not seem to be affected by mild postoperative hypothermia after lower abdominal surgery STUDY OBJECTIVE To evaluate the efficacy of a forced-air warmer during spinal surgery for correction of scoliosis in children . DESIGN Prospect i ve r and omized study ( group allocation based on the availability of the warming device ) . SETTING Children 's teaching hospital . PATIENTS 51 ASA physical status I and II children ( mean age , 15 years ; mean weight , 45 kg ) scheduled for posterior spinal fusion with general anesthesia . INTERVENTIONS Study group ( warmed ; n = 26)--legs covered with the forced-air warmer ( Bair Hugger , Augustine Medical , Inc. , Eden Prairie , MN ) after installation of the patient in prone position -- versus control group ( n = 25)--400W heat lamp placed over the head during surgery as is usually done in our institution . MEASUREMENTS AND MAIN RESULTS Rectal temperature was taken every 15 minutes during surgery and during the first 2 hours in the recovery room . Time required for the wake-up test , time to extubation , and blood loss also were noted . Temperature profiles were very different in the 2 groups . In the control group , rectal temperature decreased during the first 180 minutes to a minimum of 34.8 degrees C + /- 0.6 degrees C , followed by a slow rewarming phase . In the warmed group , the lowest temperature ( 35.6 degrees C + /- 0.5 degrees C ) was recorded 45 minutes after placement of the forced-air warmer , followed by an effective warming phase . At the end of surgery , temperature was significantly higher in the warmed group than in the control group ( 36.5 degrees C + /- 0.8 degrees C vs. 35.4 degrees C + /- 0.9 degrees C ) . However , time required for the wake-up test , time to extubation , and blood loss did not differ between groups . CONCLUSION The forced-air warmer ( Bair Hugger ) is effective during spinal surgery , although only about 20 % of body surface area can be covered Background : Intraoperative hypothermia is common and persists for several hours after surgery . Hypothermia may prolong immediate recovery by augmenting anesthetic potency , delaying drug metabolism , producing hemodynamic instability , or depressing cognitive function . Accordingly , the authors tested the hypothesis that intraoperative hypothermia prolongs postoperative recovery . Methods : Patients undergoing elective major abdominal surgery ( n = 150 ) were anesthetized with isoflurane , nitrous oxide , and fentanyl . They were r and omly assigned to routine thermal management ( hypothermia ) or extra warming ( normothermia ) . Postoperative surgical pain was treated with patient‐controlled analgesia . Fitness for discharge from the post‐anesthesia care unit was evaluated at 20‐min intervals by investigators blinded to group assignment and postoperative core temperatures . Scoring was based on a modification of a previously published system that included activity , ventilation , consciousness , and hemodynamic responses . Patients were considered fit for discharge when they sustained a score of 80 % ( 13 points ) for at least two consecutive measurement periods . Results : Morphometric characteristics and anesthetic management were similar in each group . Final intraoperative core temperatures differed by [ nearly = ] 2 [ degree sign ] Celsius : 34.8 + /‐ 0.6 versus 36.7 + /‐ 0.6 [ degree sign ] Celsius ( mean + /‐ SD , P < 0.001 ) . Postoperative pain scores and postoperative use of patient‐controlled opioid were similar . Hypothermic patients required [ nearly = ] 40 min longer ( 94 + /‐ 65 vs. 53 + /‐ 36 min ) to reach fitness for discharge , even when return to normothermia was not a criterion ( P < 0.001 ) . Duration of recovery in the two groups differed by [ nearly = ] 90 min when a core temperature > 36 [ degree sign ] Celsius was also required ( P < 0.001 ) . Conclusion : Maintaining core normothermia decreases the duration of postanesthetic recovery and may , therefore , reduce costs of care |
655 | 29,877,837 | High-frequency alternating currents using frequencies of > 4–5 kHz effectively block nerve conduction .
There is no consensus about the block mechanism , although it has been showed that the frequency is a key factor to produce K+ channels activation or Na+ channels inactivation .
The nerve block produced by currents quickly reverts without causing further damage to the nerve . | Numerous neurological dysfunctions are accompanied by an undesirable increase of nerve activity , such as neuropathic pain or spasticity .
There have been several studies over the last years on peripheral nerve block using high-frequency alternating currents , which could become a therapeutic alternative for such nerve hyperactivity .
The main aim of this systematic review was to determine the optimal parameters of the electrical currents for producing peripheral nerve conduction block , the underlying neurophysiological mechanisms , and their possible adverse effects . | Background / Objectives . Vagal block therapy ( vBloc ) is effective for moderate to severe obesity at one year . Subjects/ Methods . The ReCharge trial is a double-blind , r and omized controlled clinical trial of 239 participants with body mass index ( BMI ) of 40 to 45 kg/m or 35 to 40 kg/m with one or more obesity-related conditions . Interventions were implantation of either vBloc or Sham devices and weight management counseling . Mixed models assessed percent excess weight loss ( % EWL ) and total weight loss ( % TWL ) in intent-to-treat analyses . At 18 months , 142 ( 88 % ) vBloc and 64 ( 83 % ) Sham patients remained enrolled in the study . Results . 18-month weight loss was 23 % EWL ( 8.8 % TWL ) for vBloc and 10 % EWL ( 3.8 % TWL ) for Sham ( P < 0.0001 ) . vBloc patients largely maintained 12-month weight loss of 26 % EWL ( 9.7 % TWL ) . Sham regained over 40 % of the 17 % EWL ( 6.4 % TWL ) by 18 months . Most weight regain preceded unblinding . Common adverse events of vBloc through 18 months were heartburn/dyspepsia and abdominal pain ; 98 % of events were reported as mild or moderate and 79 % had resolved . Conclusions . Weight loss with vBloc was sustained through 18 months , while Sham regained weight between 12 and 18 months . vBloc is effective with a low rate of serious complications BACKGROUND A laparoscopically implantable electrical device that intermittently blocks both vagi near the esophagogastric junction led to significant excess weight loss ( EWL ) in an initial clinical trial in obese patients . The study objective was to optimize therapy algorithms and determine the EWL achieved with a second-generation device at university hospitals in Australia , Norway , and Switzerl and . METHODS Data acquired during the initial clinical trial were analyzed and subsequently used to select alternative electrical algorithms . In the second trial , vagal blocking using one selected therapy algorithm was initiated 2 weeks after implanting the second-generation device . The patients were followed up for 6 months to assess the EWL and safety , including adverse events . RESULTS In the initial clinical trial , vagal blocking algorithm duration s of 90 - 150 s were associated with greater EWL compared with either shorter or longer algorithm duration s ( P<.01 ) . The second trial enrolled 27 patients ( mean body mass index 39.3+/-.8 kg/m2 ) to evaluate a 120-s blocking algorithm . At 6 months , greater EWL was achieved ( 22.7%+/-3.1 % , n=24 ) compared with the initial study and first-generation device ( 14.2%+/-2.2 % , n=29 , P=.03 ) . In both trials , an association was found between the number of 90 - 150-s algorithms delivered daily and greater EWL ( P=.03 ) . No deaths , unanticipated device-related adverse events , or medically serious adverse events were associated with the device . CONCLUSION This second-generation vagal blocking device , using a therapy algorithm of 120-s duration , result ed in a clinical ly acceptable safety profile and significantly greater EWL compared with the first-generation device delivering a wider range of therapy algorithm duration BACKGROUND A new medical device uses high-frequency electrical algorithms to create intermittent vagal blocking ( VBLOC therapy ) . The aim is to assess the effects of vagal blocking on excess weight loss ( EWL ) , safety , dietary intake , and vagal function . METHODS An open-label , 3-center study was conducted in obese subjects ( body mass index [ BMI ] 35 - 50 kg/m(2 ) ) . Electrodes were implanted laparoscopically on both vagi near the esophagogastric junction to provide electrical block . Patients were followed for 6 months for body weight , safety , electrocardiogram , dietary intake , satiation , satiety , and plasma pancreatic polypeptide ( PP ) response to sham feeding . To specifically assess device effects alone , no diet or exercise programs were instituted . RESULTS Thirty-one patients ( mean BMI , 41.2 + /- 1.4 kg/m(2 ) ) received the device . Mean EWL at 4 and 12 weeks and 6 months after implant was 7.5 % , 11.6 % , and 14.2 % , respectively ( all P < .001 ) ; 25 % of patients lost > 25 % EWL at 6 months ( maximum , 36.8 % ) . There were no deaths or device-related serious adverse events ( AEs ) . Calorie intake decreased by > 30 % at 4 and 12 weeks and 6 months ( all P < or= .01 ) , with earlier satiation ( P < .001 ) and reduced hunger ( P = .005 ) . After 12 weeks , plasma PP responses were suppressed ( 20 + /- 7 vs 42 + /- 19 pg/mL ) . Average percent EWL in patients with PP response < 25 pg/mL was double that with PP response > 25 pg/mL ( P = .02 ) . Three patients had serious AEs that required brief hospitalization , 1 each for lower respiratory tract , subcutaneous implant site seroma , and Clostridium difficile diarrhea . CONCLUSIONS Intermittent , intra-abdominal vagal blocking is associated with significant EWL and a desirable safety profile AIMS Uncoordinated contraction of the external urethral sphincter is prevalent in individuals with spinal cord injury and can prevent bladder voiding . The aim of this study was to demonstrate that complete and reversible sinusoidal high frequency alternating current ( HFAC ) conduction block of the pudendal nerves ( PN ) can eliminate external urethral sphincter activation and produce low residual bladder voiding . METHODS In four cats , tripolar nerve cuff electrodes were implanted bilaterally on both pudendal nerves and on both extradural S2 roots . Bladder and urethral pressures , bladder volumes and flow were recorded . Bilateral HFAC was applied to determine voltage and frequency parameters result ing in bilateral PN conduction block . Sacral root stimulation provided bladder activation . R and omized sets of voiding trials were conducted with and without HFAC PN block . Additional voiding trials were conducted following bilateral PN neurotomy to eliminate somatic sphincter resistance and provide an estimate of voiding with complete block . RESULTS Effective bilateral PN block and voiding was obtained in three of four animals . Application of bilateral PN HFAC stimulation improved voiding from 2 + /- 4 % to 77 + /- 18 % of the initial bladder volume and significantly ( P < 0.001 ) reduced maximum bladder pressure during voiding . Voiding in trials with PN block was not significantly different from voiding following PN neurotomy ( 82 + /- 19 % , P = 0.51 ) . CONCLUSIONS These results demonstrate that bilateral HFAC block of the PN can produce effective voiding . Neural prostheses using this approach may provide an alternative method for producing micturition for people with spinal cord injury OBJECTIVE To investigate the effect of unmodulated 5-kHz alternating current on mechanical pain threshold ( MPT ) , heat pain threshold ( HPT ) , tactile threshold ( TT ) , and peripheral nerve conduction ( PNC ) compared with transcutaneous electrical nerve stimulation ( TENS ) and sham stimulation . SETTING National referral center . DESIGN R and omized , double-blind , placebo-controlled crossover trial . PARTICIPANTS Healthy volunteers ( N=38 ) . No dropouts or adverse events were reported . INTERVENTION TENS , unmodulated 5-kHz currents , and sham stimulation were applied on the radial nerve for 20 minutes with a 24-hour washout period between them and concealed intervention allocation . MAIN OUTCOME MEASURES Four measures were taken : before , during , and 2 after the interventions . Algometry was used to assess MPT , a Peltier thermode for HPT using the method of limits , Von Frey filaments for TT , and radial nerve compound action potential . RESULTS No differences were observed on MPT , HPT , and PNC when 5-kHz current and TENS were compared . However , TT increased 56.2mN ( 95 % confidence interval [ CI ] , 28.8 - 83.6 ) in the TENS group compared with the 5-kHz current group during intervention . Compared with sham stimulation during intervention , MPT increased 4.7N ( 95 % CI , 0.3 - 9.2 ) using 5-kHz current and 10.4N ( 95 % CI , 3.5 - 17.3 ) with TENS . TT increased 17.2mN ( 95 % CI , 4.7 - 29.7 ) with 5-kHz current and 73.4mN ( 95 % CI , 47.5 - 99.2 ) with TENS . However , HPT increased 1.0 ° C ( 95 % CI , 0.2 - 2.0 ) only with TENS . For the PNC , no differences were found among the 3 groups . CONCLUSIONS Unmodulated 5-kHz current produced an increase in somatosensory thresholds that was greater than placebo but not when compared with TENS ; however , participants perceived 5-kHz currents to be more comfortable and showed more habituation to them Background Intermittent , reversible intraabdominal vagal blockade ( VBLOC ® Therapy ) demonstrated clinical ly important weight loss in feasibility trials . EMPOWER , a r and omized , double-blind , prospect i ve , controlled trial was conducted in USA and Australia . Methods Five hundred three subjects were enrolled at 15 centers . After informed consent , 294 subjects were implanted with the vagal blocking system and r and omized to the treated ( n = 192 ) or control ( n = 102 ) group . Main outcome measures were percent excess weight loss ( percent EWL ) at 12 months and serious adverse events . Subjects controlled duration of therapy using an external power source ; therapy involved a programmed algorithm of electrical energy delivered to the subdiaphragmatic vagal nerves to inhibit afferent/efferent vagal transmission . Devices in both groups performed regular , low-energy safety checks . Data are mean ± SEM . Results Study subjects consisted of 90 % females , body mass index of 41 ± 1 kg/m2 , and age of 46 ± 1 years . Device-related complications occurred in 3 % of subjects . There was no mortality . 12-month percent EWL was 17 ± 2 % for the treated and 16 ± 2 % for the control group . Weight loss was related linearly to hours of device use ; treated and controls with ≥12 h/day use achieved 30 ± 4 and 22 ± 8 % EWL , respectively . Conclusions VBLOC ® therapy to treat morbid obesity was safe , but weight loss was not greater in treated compared to controls ; clinical ly important weight loss , however , was related to hours of device use . Post- study analysis suggested that the system electrical safety checks ( low charge delivered via the system for electrical impedance , safety , and diagnostic checks ) may have contributed to weight loss in the control group |
656 | 30,425,742 | Other studies showed that fasting plasma glucose and HbA1c levels were increased by atorvastatin .
The majority of these articles showed that patients who used atorvastatin had a higher dose-dependent risk of developing NOD .
Conclusion This systematic review suggests that there is an association between atorvastatin treatment and NOD .
Moreover , it showed that atorvastatin in high dose causes worsening of the glycemic control in patients with DM | Background Current evidence indicates that statins increase the risk of new onset diabetes mellitus ( NOD ) and also deteriorate the glycemic control in patients with known diabetes mellitus ( DM ) after high-dose statin therapy .
Aims The aim of this review was to explore the effect of atorvastatin in causing NOD or deteriorating glycemic control in patients with DM . | Background : In addition to lipid lowering , further pleotropic effects of statins have been postulated . We aim ed to study if the various pleotropic effects are due indirectly to the modulation of adipocytokines . Material s and methods : We studied the effect of atorvastatin on insulin sensitivity and the plasma adiponectin and leptin concentrations . Our r and omized open labeled study had 29 hyperlipidemic Type 2 diabetic patients ( 14 females , 15 males , mean age 60.0±2.2 yr ) . They were r and omized into three 12-week atorvastatin intervention types . Each day patients were given either 10 mg ( no.=10 ) , 20 mg ( no.=10 ) or 40 mg ( no.=9 ) . Evaluations were performed before and after intervention . Results : All baseline characteristics were statistically identical in the 3 groups . Drop in total cholesterol , LDL-cholesterol , and triglyceride levels were measured at the end . With 10 mg the drop was 30 % , 37 % , and 30 % . The 20 mg group was 43 % , 54 % , and 34 % . The 40 mg group was 42 % , 51 % , and 27 % . Groups had no significant change of body mass index , HDL-cholesterol , and glycated hemoglobin levels . Also , levels of insulin , adiponectin , leptin , homeostasis model assessment index ( HOMA ) and Quantitative Insulin Sensitivity Check Index ( QUICKI ) stayed the same . Pooled parameters of all 29 patients showed no difference in levels of insulin , adiponectin , leptin , HOMA , and QUICKI before and after treatment . Conclusions : Atorvstatin does not affect insulin sensitivity and the adiponectin or leptin levels in hyperlipidemic Type 2 diabetes INTRODUCTION Diabetes is a prothrombotic state involving a more thrombogenic fibrin network . In the present study we investigated the effects of lipid-lowering therapy with atorvastatin on fibrin network structure and platelet-derived microparticles in patients with type 1 diabetes and dyslipidemia . MATERIAL S AND METHODS Twenty patients were treated with atorvastatin ( 80 mg daily ) or placebo during 2 months in a r and omized , double-blind , cross-over study . Fibrin network permeability , expression of glycoprotein IIIa , P-selectin and tissue factor on platelet-derived microparticles , plasma endogenous thrombin potential , plasminogen activator inhibitor-1 and tissue plasminogen activator antigen levels were assessed . Additionally , levels of plasma fibrinogen , high-sensitivity C-reactive protein and glycated haemoglobin were measured . RESULTS During treatment with atorvastatin , fibrin network permeability increased ( p=0.01 ) , while endogenous thrombin potential and expression of glycoprotein IIIa , P-selectin and tissue factor decreased ( p<0.01 ) . In vitro experiments indicated that platelet-derived microparticles influence the fibrin network formation as fibrin network permeability decreased significantly when platelet-derived microparticles were added to normal plasma . Baseline levels of plasminogen activator inhibitor-1 and tissue plasminogen activator antigen as well as plasma fibrinogen and high-sensitivity C-reactive protein were within reference values and not significantly changed during atorvastatin treatment , while glycated haemoglobin increased 0.3 % ( p<0.001 ) . CONCLUSIONS Novel treatment effects were found in patients with type 1 diabetes and dyslipidemia during atorvastatin therapy , i.e. a more porous fibrin network , to which reduced expression of glycoprotein IIIa , P-selectin and tissue factor on platelet-derived microparticles may contribute . The observed impairment of glycemic control during long-term statin treatment deserves attention Summary Background The lowering of cholesterol concentrations in individuals at high risk of cardiovascular disease improves outcome . No study , however , has assessed benefits of cholesterol lowering in the primary prevention of coronary heart disease ( CHD ) in hypertensive patients who are not conventionally deemed dyslipidaemic . Methods Of 19 342 hypertensive patients ( aged 40–79 years with at least three other cardiovascular risk factors ) r and omised to one of two antihypertensive regimens in the Anglo-Sc and inavian Cardiac Outcomes Trial , 10 305 with nonfasting total cholesterol concentrations 6.5 mmol/L or less were r and omly assigned additional atorvastatin 10 mg or placebo . These patients formed the lipid-lowering arm of the study . We planned follow-up for an average of 5 years , the primary endpoint being non-fatal myocardial infa rct ion and fatal CHD . Data were analysed by intention to treat . Findings Treatment was stopped after a median follow-up of 3.3 years . By that time , 100 primary events had occurred in the atorvastatin group compared with 154 events in the placebo group ( hazard ratio 0.64 [ 95 % CI 0.50–0.83 ] , p = 0.0005 ) . This benefit emerged in the first year of follow-up . There was no significant heterogeneity among prespecified subgroups . Fatal and non-fatal stroke ( 89 atorvastatin vs 121 placebo , 0.73 [ 0.56–0.96 ] , p = 0.024 ) , total cardiovascular events ( 389 vs 486 , 0.79 [ 0.69–0.90 ] , p = 0.0005 ) , and total coronary events ( 178 vs 247 , 0.71 [ 0.59–0.86 ] , p = 0.0005 ) were also significantly lowered . There were 185 deaths in the atorvastatin group and 212 in the placebo group ( 0.87 [ 0.71–1.06 ] , p = 0.16 ) . Atorvastatin lowered total serum cholesterol by about 1.3 mmol/L compared with placebo at 12 months , and by 1.1 mmol/L after 3 years of follow-up . Interpretation The reductions in major cardiovascular events with atorvastatin are large , given the short follow-up time . These findings may have implication s for future lipid-lowering guidelines OBJECTIVES We investigated whether atorvastatin might decrease insulin sensitivity and increase ambient glycemia in hypercholesterolemic patients . BACKGROUND Clinical trials suggest that some statin treatments might increase the incidence of diabetes despite reductions in low-density lipoprotein ( LDL ) cholesterol and improvement in endothelial dysfunction . METHODS A r and omized , single-blind , placebo-controlled parallel study was conducted in 44 patients taking placebo and in 42 , 44 , 43 , and 40 patients given daily atorvastatin 10 , 20 , 40 , and 80 mg , respectively , during a 2-month treatment period . RESULTS Atorvastatin 10 , 20 , 40 , and 80 mg significantly reduced LDL cholesterol ( 39 % , 47 % , 52 % , and 56 % , respectively ) and apolipoprotein B levels ( 33 % , 37 % , 42 % , and 46 % , respectively ) after 2 months of therapy when compared with either baseline ( all p < 0.001 by paired t test ) or placebo ( p < 0.001 by analysis of variance [ ANOVA ] ) . Atorvastatin 10 , 20 , 40 , and 80 mg significantly increased fasting plasma insulin ( mean changes : 25 % , 42 % , 31 % , and 45 % , respectively ) and glycated hemoglobin levels ( 2 % , 5 % , 5 % , and 5 % , respectively ) when compared with either baseline ( all p < 0.05 by paired t test ) or placebo ( p = 0.009 for insulin and p = 0.008 for glycated hemoglobin by ANOVA ) . Atorvastatin 10 , 20 , 40 , and 80 mg decreased insulin sensitivity ( 1 % , 3 % , 3 % , and 4 % , respectively ) when compared with either baseline ( p = 0.312 , p = 0.008 , p < 0.001 , and p = 0.008 , respectively , by paired t test ) or placebo ( p = 0.033 by ANOVA ) . CONCLUSIONS Despite beneficial reductions in LDL cholesterol and apolipoprotein B , atorvastatin treatment result ed in significant increases in fasting insulin and glycated hemoglobin levels consistent with insulin resistance and increased ambient glycemia in hypercholesterolemic patients . ( Effects of Atorvastatin on Adiponectin Levels and Insulin Sensitivity In Hypercholesterolemic Patients ; NCT00745836 ) BACKGROUND Despite established effects of atorvastatin on level of serum lipid profile in patients with different underlying clinical conditions , the effects of this drug on other serum biomarkers remain uncertain . We examined the effects of atorvastatin therapy on lipid profile , glycemic control , and liver enzymes in patients with ischemic cerebrovascular accident without any history or clinical evidence s of diabetes , heart failure , renal failure , or hepatic disease . METHODS In a r and omized double-blinded controlled trial , 140 hospitalized patients with an ischemic cerebrovascular accident were included and r and omly assigned to receive either atorvastatin 40 mg ( n = 70 ) or atorvastatin 20 mg daily ( n = 70 ) for 3 months . The levels of biomarkers were measured at the time of administrating drugs as well as at the time of completing the treatment . RESULTS A significant reduction was revealed in serum triglyceride , total cholesterol , low-density lipoprotein , non-high-density lipoprotein ( HDL ) cholesterol , and also aspartate aminotransferase levels as well as a significant increase in serum HDL level following administration of atorvastatin in both case and control groups who received the atorvastatin 40 mg/day and 20 mg/day , respectively ( all P < 0.050 ) . Although a significant increase in fasting blood sugar and hemoglobin A1c was observed in the case group received atorvastatin 40 mg/day ( both P < 0.001 ) , but this elevation was not occurred in another group treated with lower dose of the drug ( both P > 0.050 ) . CONCLUSION Daily administration of 20 mg and 40 mg doses of atorvastatin for 3 months provides improvement in serum lipid profiles ; however , because of interfering effect of high-dose atorvastatin on glycemic control status , the use of the former dose may be preferred . This is very important in these patients because the positive effects of high-dose atorvastatin in stroke patients are not confirmed In this prospect i ve study , we examined the effect of atorvastatin treatment on baroreflex sensitivity ( BRS ) in subjects with type 2 diabetes . A total of 79 patients with type 2 diabetes with dyslipidaemia were recruited . A total of 46 subjects were enrolled to atorvastatin 10 mg daily and low-fat diet and 33 patients to low-fat diet only . BRS was assessed non-invasively using the sequence method at baseline , 3 , 6 and 12 months . Treatment with atorvastatin increased BRS after 12 months ( from 6.46 ± 2.79 ms/mmHg to 8.05 ± 4.28 ms/mmHg , p = 0.03 ) , while no effect was seen with low-fat diet . Further sub- analysis according to obesity status showed that BRS increased significantly only in the non-obese group ( p = 0.036 ) . A low dose of atorvastatin increased BRS in non-obese subjects with type 2 diabetes and dyslipidaemia after 1-year treatment . This finding emphasizes the beneficial effect of atorvastatin on cardiovascular system , beyond the lipid-lowering effects CONTEXT Statins have been shown to improve hyper and rogenism in women with polycystic ovary syndrome ( PCOS ) . However , their use has also been associated with impairment of glucose metabolism and an increased risk of type 2 diabetes mellitus . Because women with PCOS are prone to disturbances in glucose metabolism , statin therapy could also have negative effects . OBJECTIVE Our objective was to explore the effects of atorvastatin therapy on hormonal and metabolic parameters in women with PCOS . DESIGN AND SETTING We conducted a r and omized , double-blind , placebo-controlled 6-month follow-up study conducted at Oulu University Hospital , Finl and . PATIENTS Women with PCOS ( Rotterdam criteria ) were treated with atorvastatin ( 20 mg/d , n = 15 ) or placebo ( n = 13 ) for 6 months . INTERVENTIONS Fasting serum sample s were collected at baseline and at 3 and 6 months . Oral and iv glucose tolerance tests were performed at 0 and 6 months . MAIN OUTCOME MEASURES And rogen secretion and glucose metabolism were measured . RESULTS Fasting levels and area under the curve of insulin increased significantly and insulin sensitivity ( insulinogenic and Matsuda indexes ) decreased during 6 months of atorvastatin therapy . Serum levels of dehydroepi and rosterone sulfate decreased in the atorvastatin group , whereas no change was observed in serum testosterone levels . Levels of C-reactive protein , total and low-density lipoprotein-cholesterol , and triglycerides decreased significantly during statin therapy . CONCLUSIONS Atorvastatin therapy improves chronic inflammation and lipid profile , but it impairs insulin sensitivity in women with PCOS . Because women with PCOS have an increased risk of developing type 2 diabetes mellitus , the results suggest that statin therapy should be initiated on the basis of generally accepted criteria and individual risk assessment of cardiovascular disease , and not only because of PCOS Reduction of serum cholesterol levels with statin therapy decreases the risk of coronary heart disease . Inhibition of HMG-CoA reductase by statin results in decreased synthesis of cholesterol and other products downstream of mevalonate , which may produce adverse effects in statin therapy . We studied the reductions of serum ubiquinol-10 and ubiquinone-10 levels in hypercholesterolemic patients treated with atorvastatin . Fourteen patients were treated with 10 mg/day of atorvastatin , and serum lipid , ubiquinol-10 and ubiquinone-10 levels were measured before and after 8 weeks of treatment . Serum total cholesterol and LDL-cholesterol levels decreased significantly . All patients showed definite reductions of serum ubiquinol-10 and ubiquinone-10 levels , and mean levels of serum ubiquinol-10 and ubiquinone-10 levels decreased significantly from 0.81 + /- 0.21 to 0.46 + /- 0.10 microg/ml ( p < 0.0001 ) , and from 0.10 + /- 0.06 to 0.06 + /- 0.02 microg/ml ( p = 0.0008 ) , respectively . Percent reductions of ubiquinol-10 and those of total cholesterol showed a positive correlation ( r = 0.627 , p = 0.0165 ) . As atorvastatin reduces serum ubiquinol-10 as well as serum cholesterol levels in all patients , it is imperative that physicians are forewarned about the risks associated with ubiquinol-10 depletion Background Recent evidence suggests that the lipid-lowering agent atorvastatin is also a potent immunomodulator . The aim of this study was to investigate the possible effect of atorvastatin on the decline of residual beta cell function in recent-onset type 1 diabetes . Methods and Findings The r and omised placebo-controlled Diabetes and Atorvastatin ( DIATOR ) Trial included 89 patients with newly diagnosed type 1 diabetes and islet autoantibodies ( mean age 30 years , 40 % females ) , in 12 centres in Germany . Patients received placebo or 80 mg/d atorvastatin for 18 months . As primary outcome stimulated serum C-peptide levels were determined 90 min after a st and ardized liquid mixed meal . An intent-to-treat analysis was performed . Fasting and stimulated C-peptide levels were not significantly different between groups at 18 months . However , median fasting serum C-peptide levels dropped from baseline to 12 and 18 months in the placebo group ( from 0 . 34 to 0.23 and 0.20 nmol/l , p<0.001 ) versus a nonsignificant decline in the atorvastatin group ( from 0.34 to 0.27 and 0.30 nmol/l , ns ) . Median stimulated C-peptide concentrations declined between baseline and 12 months ( placebo from 0.89 to 0.71 nmol/l , atorvastatin from 0.88 to 0.73 nmol/l , p<0.01 each ) followed by a major loss by month 18 in the placebo group ( to 0.48 nmol/l , p = 0.047 ) but not in the atorvastatin group ( to 0.71 nmol/l , ns ) . Median levels of total cholesterol and C-reactive protein decreased in the atorvastatin group only ( p<0.001 and p = 0.04 ) . Metabolic control was similar between groups . Conclusions Atorvastatin treatment did not significantly preserve beta cell function although there may have been a slower decline of beta-cell function which merits further study . Trial Registration Clinical Trials.gov BACKGROUND It is not known whether drugs that block the renin-angiotensin system reduce the risk of diabetes and cardiovascular events in patients with impaired glucose tolerance . METHODS In this double-blind , r and omized clinical trial with a 2-by-2 factorial design , we assigned 9306 patients with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors to receive valsartan ( up to 160 mg daily ) or placebo ( and nateglinide or placebo ) in addition to lifestyle modification . We then followed the patients for a median of 5.0 years for the development of diabetes ( 6.5 years for vital status ) . We studied the effects of valsartan on the occurrence of three co primary outcomes : the development of diabetes ; an extended composite outcome of death from cardiovascular causes , nonfatal myocardial infa rct ion , nonfatal stroke , hospitalization for heart failure , arterial revascularization , or hospitalization for unstable angina ; and a core composite outcome that excluded unstable angina and revascularization . RESULTS The cumulative incidence of diabetes was 33.1 % in the valsartan group , as compared with 36.8 % in the placebo group ( hazard ratio in the valsartan group , 0.86 ; 95 % confidence interval [ CI ] , 0.80 to 0.92 ; P<0.001 ) . Valsartan , as compared with placebo , did not significantly reduce the incidence of either the extended cardiovascular outcome ( 14.5 % vs. 14.8 % ; hazard ratio , 0.96 ; 95 % CI , 0.86 to 1.07 ; P=0.43 ) or the core cardiovascular outcome ( 8.1 % vs. 8.1 % ; hazard ratio , 0.99 ; 95 % CI , 0.86 to 1.14 ; P=0.85 ) . CONCLUSIONS Among patients with impaired glucose tolerance and cardiovascular disease or risk factors , the use of valsartan for 5 years , along with lifestyle modification , led to a relative reduction of 14 % in the incidence of diabetes but did not reduce the rate of cardiovascular events . ( Clinical Trials.gov number , NCT00097786 . CONTEXT Evidence suggests that more intensive lowering of low-density lipoprotein cholesterol ( LDL-C ) than is commonly applied clinical ly will provide further benefit in stable coronary artery disease . OBJECTIVE To compare the effects of 2 strategies of lipid lowering on the risk of cardiovascular disease among patients with a previous myocardial infa rct ion ( MI ) . DESIGN , SETTING , AND PARTICIPANTS The IDEAL study , a prospect i ve , r and omized , open-label , blinded end-point evaluation trial conducted at 190 ambulatory cardiology care and specialist practice s in northern Europe between March 1999 and March 2005 with a median follow-up of 4.8 years , which enrolled 8888 patients aged 80 years or younger with a history of acute MI . INTERVENTIONS Patients were r and omly assigned to receive a high dose of atorvastatin ( 80 mg/d ; n = 4439 ) , or usual-dose simvastatin ( 20 mg/d ; n = 4449 ) . MAIN OUTCOME MEASURE Occurrence of a major coronary event , defined as coronary death , confirmed nonfatal acute MI , or cardiac arrest with resuscitation . RESULTS During treatment , mean LDL-C levels were 104 ( SE , 0.3 ) mg/dL in the simvastatin group and 81 ( SE , 0.3 ) mg/dL in the atorvastatin group . A major coronary event occurred in 463 simvastatin patients ( 10.4 % ) and in 411 atorvastatin patients ( 9.3 % ) ( hazard ratio [ HR ] , 0.89 ; 95 % CI , 0.78 - 1.01 ; P = .07 ) . Nonfatal acute MI occurred in 321 ( 7.2 % ) and 267 ( 6.0 % ) in the 2 groups ( HR , 0.83 ; 95 % CI , 0.71 - 0.98 ; P = .02 ) , but no differences were seen in the 2 other components of the primary end point . Major cardiovascular events occurred in 608 and 533 in the 2 groups , respectively ( HR , 0.87 ; 95 % CI , 0.77 - 0.98 ; P = .02 ) . Occurrence of any coronary event was reported in 1059 simvastatin and 898 atorvastatin patients ( HR , 0.84 ; 95 % CI , 0.76 - 0.91 ; P<.001 ) . Noncardiovascular death occurred in 156 ( 3.5 % ) and 143 ( 3.2 % ) in the 2 groups ( HR , 0.92 ; 95 % CI , 0.73 - 1.15 ; P = .47 ) . Death from any cause occurred in 374 ( 8.4 % ) in the simvastatin group and 366 ( 8.2 % ) in the atorvastatin group ( HR , 0.98 ; 95 % CI , 0.85 - 1.13 ; P = .81 ) . Patients in the atorvastatin group had higher rates of drug discontinuation due to nonserious adverse events ; transaminase elevation result ed in 43 ( 1.0 % ) vs 5 ( 0.1 % ) withdrawals ( P<.001 ) . Serious myopathy and rhabdomyolysis were rare in both groups . CONCLUSIONS In this study of patients with previous MI , intensive lowering of LDL-C did not result in a significant reduction in the primary outcome of major coronary events , but did reduce the risk of other composite secondary end points and nonfatal acute MI . There were no differences in cardiovascular or all-cause mortality . Patients with MI may benefit from intensive lowering of LDL-C without an increase in noncardiovascular mortality or other serious adverse reactions . Trial Registration Clinical Trials.gov Identifier : NCT00159835 The renin-angiotensin system ( RAS ) has an important role in the endocrine pancreas . Although angiotensin II has significant effects on cell proliferation and apoptosis , the contribution of the RAS to changes in islet structure and function associated with type 2 diabetes is yet to be defined . This study examined the specific effects of RAS blockade on islet structure and function in diabetes . Thirty-six male Zucker diabetic fatty ( ZDF ) rats , 10 weeks of age , were r and omized to receive the angiotensin-converting enzyme inhibitor perindopril ( 8 mg/l in drinking water ; n = 12 ) , irbesartan ( 15 mg/kg via gavage ; n = 12 ) , or no treatment ( n = 12 ) for 10 weeks . Results were compared with lean littermates ( ZL ) ( n = 12 ) studied concurrently . ZDF rats had increased intra-islet expression of components of the RAS correlating with increased intraislet fibrosis , apoptosis , and oxidative stress . Disordered islet architecture , seen in ZDF rats , was attenuated after treatment with perindopril or irbesartan . Islet fibrogenesis was also diminished , as measured by picrosirius staining and expression of collagens I and IV . Gene expression of transforming growth factor-beta1 was increased in the ZDF pancreas ( ZL , 1.0 + /- 0.1 ; ZDF , 2.0 + /- 0.3 ; P < 0.05 ) and reduced after blockade of the RAS ( ZDF + P , 1.3 + /- 0.2 ; ZDF + I , 1.5 + /- 0.1 ; vs. ZDF , both P < 0.05 ) . Improvements in structural parameters were also associated with functional improvements in first-phase insulin secretion . These findings provide a possible mechanism for the reduced incidence of new-onset diabetes that has been observed in clinical trials of RAS blockade BACKGROUND High dose atorvastatin is known to be associated with new onset diabetes mellitus ( NODM ) in patients with high risk for developing diabetes mellitus ( DM ) . However , low dose atorvastatin is more commonly used as compared with high dose atorvastatin . The aim of this study is to investigate the impact of low dose atorvastatin ( LDA , 10 mg or 20 mg ) on the development of NODM up to three years in Asian patients . METHODS From January 2004 to September 2009 , we investigated a total of 3566 patients who did not have DM . To adjust for potential confounders , a propensity score matching ( PSM ) analysis was performed using the logistic regression model . After PSM ( C-statistics : 0.851 ) , a total of 818 patients ( LDA group , n=409 patients and control group , n=409 patients ) were enrolled for analysis . RESULTS Before PSM , the cumulative incidence of NODM ( 5.8 % vs. 2.1 % , p<0.001 ) , myocardial infa rct ion ( 0.5 % vs. 0.1 % , p-value=0.007 ) , and major adverse cardio-cerebral event ( MACCE , 1.8 % vs. 0.7 % , p-value=0.012 ) at three-years were higher in the LAD group . However , after PSM , there was a trend toward higher incidence of NODM ( 5.9 % vs. 3.2 % , p=0.064 ) in the LDA group , but the incidence of MACCE ( 1.2 % vs. 1.5 % , p-value=1.000 ) was similar between the two groups . In multivariable analysis , the LDA administration was tended to be an independent predictor of NODM ( OR : 1.99 , 95 % CI : 1.00 - 3.98 , p-value 0.050 ) . CONCLUSIONS In this study , the use of LDA tended to be a risk factor for NODM in Asian patients and reduced clinical events similar to the control group . However , large-scale r and omized controlled trials will be needed to get the final conclusion BACKGROUND Previous trials have demonstrated that lowering low-density lipoprotein ( LDL ) cholesterol levels below currently recommended levels is beneficial in patients with acute coronary syndromes . We prospect ively assessed the efficacy and safety of lowering LDL cholesterol levels below 100 mg per deciliter ( 2.6 mmol per liter ) in patients with stable coronary heart disease ( CHD ) . METHODS A total of 10,001 patients with clinical ly evident CHD and LDL cholesterol levels of less than 130 mg per deciliter ( 3.4 mmol per liter ) were r and omly assigned to double-blind therapy and received either 10 mg or 80 mg of atorvastatin per day . Patients were followed for a median of 4.9 years . The primary end point was the occurrence of a first major cardiovascular event , defined as death from CHD , nonfatal non-procedure-related myocardial infa rct ion , resuscitation after cardiac arrest , or fatal or nonfatal stroke . RESULTS The mean LDL cholesterol levels were 77 mg per deciliter ( 2.0 mmol per liter ) during treatment with 80 mg of atorvastatin and 101 mg per deciliter ( 2.6 mmol per liter ) during treatment with 10 mg of atorvastatin . The incidence of persistent elevations in liver aminotransferase levels was 0.2 percent in the group given 10 mg of atorvastatin and 1.2 percent in the group given 80 mg of atorvastatin ( P<0.001 ) . A primary event occurred in 434 patients ( 8.7 percent ) receiving 80 mg of atorvastatin , as compared with 548 patients ( 10.9 percent ) receiving 10 mg of atorvastatin , representing an absolute reduction in the rate of major cardiovascular events of 2.2 percent and a 22 percent relative reduction in risk ( hazard ratio , 0.78 ; 95 percent confidence interval , 0.69 to 0.89 ; P<0.001 ) . There was no difference between the two treatment groups in overall mortality . CONCLUSIONS Intensive lipid-lowering therapy with 80 mg of atorvastatin per day in patients with stable CHD provides significant clinical benefit beyond that afforded by treatment with 10 mg of atorvastatin per day . This occurred with a greater incidence of elevated aminotransferase levels OBJECTIVE Angiotensin II has been shown to increase hepatic glucose production and decrease insulin sensitivity . Patients who utilize either an ACE inhibitor ( ACEI ) or angiotensin receptor blocker ( ARB ) may experience a decreased incidence of new-onset type 2 diabetes . RESEARCH DESIGN AND METHODS Three review ers conducted a systematic literature search of Medline , EMBASE , CINAHL , and the Cochrane Library ( 1966 to present ) to extract a consensus of trial data involving an ACEI or ARB with an end point of new-onset type 2 diabetes . Studies were included if they were r and omized controlled trials verses placebo/routine therapy . A r and om-effects model was utilized . Subgroup and sensitivity analyses were conducted . RESULTS Eleven trials were identified , including 66,608 patients . An ACEI or ARB prevented new-onset type 2 diabetes ( odds ratio 0.78 [ 95 % CI 0.73 - 0.83 ] ) . The influence of either an ACEI ( six trials ) or an ARB ( five trials ) alone on new-onset type 2 diabetes was similar ( 0.79 [ 0.71 - 0.89 ] and 0.76 [ 0.70 - 0.82 ] , respectively ) . Regardless of indication for use , hypertension ( seven trials ) , coronary artery disease ( two trials ) , or heart failure ( two trials ) , reductions in new-onset type 2 diabetes were maintained ( 0.79 [ 0.72 - 0.85 ] , 0.76 [ 0.60 - 0.95 ] , and 0.70 [ 0.50 - 0.96 ] , respectively ) . No statistical heterogeneity was observed for any evaluation ( P > 0.1 for all comparisons ) . ACEIs and ARBs did not reduce the odds of mortality , cardiovascular , or cerebrovascular events versus control therapy among all of these studies combined or the hypertension trials . ACEIs and ARBs did reduce the odds of these outcomes among the coronary artery disease studies versus control therapy . CONCLUSIONS ACEIs or ARBs may decrease patients ' odds of developing new-onset type 2 diabetes but does not reduce the odds of mortality , cardiovascular , or cerebrovascular outcomes over the study follow-up periods among patients with hypertension AIMS To examine whether high-dose statin therapy in Dutch European patients with Type 2 diabetes and dyslipidaemia influenced variables of glycaemic control . METHODS The CORALL study , which was a 24-week , open-label , r and omized , parallel-group , phase IIIb , multi-centre study , was design ed to compare the cholesterol-lowering effects of rosuvastatin compared with atorvastatin in patients with Type 2 diabetes . Fasting plasma glucose levels and HbA(1c ) levels were collected at baseline and at 6 and 18 weeks . RESULTS Treatment with the highest dose of statins , i.e. atorvastatin 80 mg and rosuvastatin 40 mg at 18 weeks from baseline , was associated with increase in HbA(1c ) levels ; baseline 57 ± 11 mmol/l ( 7.4 ± 1.0 % ) to 61 ± 14 mmol/mol ( 7.7 ± 1.3 % ) ( range 5.0 - 11.9 ) for atorvastatin ( P = 0.003 ) and from baseline 60 ± 11 mmol/mol ( 7.6 ± 1.0 % ) to 63 ± 13 mmol/mol ( 7.9 ± 1.2 % ) ( range 5.7 - 12.3 ) for rosuvastatin ( P < 0.001 ) . Mean fasting plasma glucose increased from baseline 8.7 ± 2.4 mmol/l to 9.5 ± 3.0 mmol/l upon treatment with atorvastatin 20 mg ( P = 0.002 ) and 9.0 ± 3.0 mmol/l after treatment with 80 mg ( not significant compared with baseline ) . The mean fasting plasma glucose did not change after treatment with rosuvastatin ( 9.1 ± 2.7 mmol/l at baseline , 8.9 ± 2.7 mmol/l with 10 mg , 9.4 ± 2.9 mmol/l with 40 mg ) . CONCLUSIONS Glycaemic control deteriorated in patients with diabetes following high-dose statin therapy . Future controlled studies are needed to verify these findings and , if confirmed , determine whether such changes represent a true decline in glycaemic control . Presently , it appears that , based on the overwhelming prospect i ve trial data available , the preventive effect of statin therapy supersedes that of the slight increase in HbA(1c ) AngII ( angiotensin II ) may contribute to cardiovascular risk in obesity via adverse effects on insulin sensitivity and endothelial function . In the present study , we examined the effects of ARB ( angiotensin receptor blocker ) therapy ( losartan , 100 mg/day ) on insulin sensitivity and endothelial function in 53 subjects with stage I hypertension , abdominal obesity and impaired fasting glucose . The study design was a r and omized double-blinded parallel design placebo-controlled multi-centre trial of 8 weeks duration . We used the hyperinsulinaemic-euglycaemic clamp technique to measure insulin sensitivity ( expressed as the ' M/I ' value ) and RH-PAT ( reactive hyperaemia-peripheral arterial tonometry ) to measure endothelial function . Additional measures included HOMA ( homoeostasis model assessment ) -B , an index of pancreatic β-cell function , and markers of inflammation [ e.g. CRP ( C-reactive protein ) ] and oxidative stress ( e.g. F2-isoprostanes ) . ARB therapy did not alter insulin sensitivity [ 5.2 ( 2.7 ) pre-treatment and 4.6 ( 1.6 ) post-treatment ] compared with placebo therapy [ 6.1 ( 2.9 ) pre-treatment and 5.3 ( 2.7 ) post-treatment ; P value not significant ] , but did improve the HOMA-B compared with placebo therapy ( P=0.05 ) . ARB therapy also did not change endothelial function [ RH-PAT , 2.15 ( 0.7 ) pre-treatment and 2.11 ( 0.7 ) post-treatment ] compared with placebo therapy [ RH-PAT , 1.81 ( 0.5 ) pre-treatment and 1.76 ( 0.7 ) post-treatment ; P value not significant ] . Markers of inflammation and oxidative stress were not significantly changed by ARB therapy . In conclusion , ARB therapy did not alter peripheral insulin sensitivity or endothelial function in this cohort of patients with essential hypertension , abdominal obesity and impaired fasting glucose , but did improve pancreatic β-cell function Studies have reported an increased risk of developing diabetes in subjects receiving statins versus placebo . Our purpose was to compare the effects of maximum doses of rosuvastatin and atorvastatin on the plasma levels of the insulin , glycated albumin , adiponectin , and C-reactive protein compared to baseline in hyperlipidemic patients . We studied 252 hyperlipidemic men and women who had been r and omized to receive atorvastatin 80 mg/day or rosuvastatin 40 mg/day during a 6-week period . Atorvastatin and rosuvastatin were both highly effective in lowering the low-density lipoprotein cholesterol and triglyceride levels , with rosuvastatin more effective than atorvastatin in increasing high-density lipoprotein cholesterol . Atorvastatin and rosuvastatin at the maximum dosage both significantly ( p < 0.05 ) increased the median insulin levels by 5.2 % and 8.7 % , respectively , from baseline . However , only atorvastatin increased the glycated albumin levels from baseline ( + 0.8 % for atorvastatin vs -0.7 % for rosuvastatin , p = 0.002 ) . Both atorvastatin and rosuvastatin caused significant ( p < 0.001 ) and similar median reductions in the C-reactive protein level of -40 % and -26 % compared to the baseline values . However , no statistically significant difference was found between the 2 groups in the adiponectin changes from baseline ( -1.5 % vs -4.9 % , p = 0.15 ) . In conclusion , our data have indicated that the maximum dosage of atorvastatin or rosuvastatin therapy significantly lower C-reactive protein levels but also moderately increase insulin levels BACKGROUND In view of evidence that statin therapy increases risk of diabetes , the balance of benefit and risk of these drugs in primary prevention has become controversial . We undertook an analysis of participants from the JUPITER trial to address the balance of vascular benefits and diabetes hazard of statin use . METHODS In the r and omised , double-blind JUPITER trial , 17,603 men and women without previous cardiovascular disease or diabetes were r and omly assigned to rosuvastatin 20 mg or placebo and followed up for up to 5 years for the primary endpoint ( myocardial infa rct ion , stroke , admission to hospital for unstable angina , arterial revascularisation , or cardiovascular death ) and the protocol -prespecified secondary endpoints of venous thromboembolism , all-cause mortality , and incident physician-reported diabetes . In this analysis , participants were stratified on the basis of having none or at least one of four major risk factors for developing diabetes : metabolic syndrome , impaired fasting glucose , body-mass index 30 kg/m(2 ) or higher , or glycated haemoglobin A(1c ) greater than 6 % . The trial is registered at Clinical Trials.gov , NCT00239681 . FINDINGS Trial participants with one or more major diabetes risk factor ( n=11,508 ) were at higher risk of developing diabetes than were those without a major risk factor ( n=6095 ) . In individuals with one or more risk factors , statin allocation was associated with a 39 % reduction in the primary endpoint ( hazard ratio [ HR ] 0·61 , 95 % CI 0·47 - 0·79 , p=0·0001 ) , a 36 % reduction in venous thromboembolism ( 0·64 , 0·39 - 1·06 , p=0·08 ) , a 17 % reduction in total mortality ( 0·83 , 0·64 - 1·07 , p=0·15 ) , and a 28 % increase in diabetes ( 1·28 , 1·07 - 1·54 , p=0·01 ) . Thus , for those with diabetes risk factors , a total of 134 vascular events or deaths were avoided for every 54 new cases of diabetes diagnosed . For trial participants with no major diabetes risk factors , statin allocation was associated with a 52 % reduction in the primary endpoint ( HR 0·48 , 95 % CI 0·33 - 0·68 , p=0·0001 ) , a 53 % reduction in venous thromboembolism ( 0·47 , 0·21 - 1·03 , p=0·05 ) , a 22 % reduction in total mortality ( 0·78 , 0·59 - 1·03 , p=0·08 ) , and no increase in diabetes ( 0·99 , 0·45 - 2·21 , p=0·99 ) . For such individuals , a total of 86 vascular events or deaths were avoided with no new cases of diabetes diagnosed . In analysis limited to the 486 participants who developed diabetes during follow-up ( 270 on rosuvastatin vs 216 on placebo ; HR 1·25 , 95 % CI 1·05 - 1·49 , p=0·01 ) , the point estimate of cardiovascular risk reduction associated with statin therapy ( HR 0·63 , 95 % CI 0·25 - 1·60 ) was consistent with that for the trial as a whole ( 0·56 , 0·46 - 0·69 ) . By comparison with placebo , statins accelerated the average time to diagnosis of diabetes by 5·4 weeks ( 84·3 [ SD 47·8 ] weeks on rosuvastatin vs 89·7 [ 50·4 ] weeks on placebo ) . INTERPRETATION In the JUPITER primary prevention trial , the cardiovascular and mortality benefits of statin therapy exceed the diabetes hazard , including in participants at high risk of developing diabetes . FUNDING AstraZeneca OBJECTIVES We sought to examine the incidence and clinical predictors of new-onset type 2 diabetes mellitus ( T2DM ) within 3 large r and omized trials with atorvastatin . BACKGROUND Statin therapy might modestly increase the risk of new-onset T2DM . METHODS We used a st and ard definition of diabetes and excluded patients with prevalent diabetes at baseline . We identified baseline predictors of new-onset T2DM and compared the event rates in patients with and without new-onset T2DM . RESULTS In the TNT ( Treating to New Targets ) trial , 351 of 3,798 patients r and omized to 80 mg of atorvastatin and 308 of 3,797 r and omized to 10 mg developed new-onset T2DM ( 9.24 % vs. 8.11 % , adjusted hazard ratio [ HR ] : 1.10 , 95 % confidence interval [ CI ] : 0.94 to 1.29 , p = 0.226 ) . In the IDEAL ( Incremental Decrease in End Points Through Aggressive Lipid Lowering ) trial , 239 of 3,737 patients r and omized to atorvastatin 80 mg/day and 208 of 3,724 patients r and omized to simvastatin 20 mg/day developed new-onset T2DM ( 6.40 % vs. 5.59 % , adjusted HR : 1.19 , 95 % CI : 0.98 to 1.43 , p = 0.072 ) . In the SPARCL ( Stroke Prevention by Aggressive Reduction in Cholesterol Levels ) trial , new-onset T2DM developed in 166 of 1,905 patients r and omized to atorvastatin 80 mg/day and in 115 of 1,898 patients in the placebo group ( 8.71 % vs. 6.06 % , adjusted HR : 1.37 , 95 % CI : 1.08 to 1.75 , p = 0.011 ) . In each of the 3 trials , baseline fasting blood glucose , body mass index , hypertension , and fasting triglycerides were independent predictors of new-onset T2DM . Across the 3 trials , major cardiovascular events occurred in 11.3 % of patients with and 10.8 % of patients without new-onset T2DM ( adjusted HR : 1.02 , 95 % CI : 0.77 to 1.35 , p = 0.69 ) . CONCLUSIONS High-dose atorvastatin treatment compared with placebo in the SPARCL trial is associated with a slightly increased risk of new-onset T2DM . Baseline fasting glucose level and features of the metabolic syndrome are predictive of new-onset T2DM across the 3 trials OBJECTIVE The receptor for advanced glycation end-products ( RAGE ) plays an important role in the pathogenesis of diabetic complications and atherosclerosis . Interfering with the activation of RAGE by using a soluble form of the receptor ( sRAGE ) ameliorates the vascular complications of diabetes in animal models . We have investigated whether statin can influence the expression of sRAGE and esRAGE ( a splice variant of sRAGE ) in vitro and in vivo . METHODS THP-1 cells were incubated with atorvastatin in vitro and sRAGE and esRAGE in the medium was measured by Western immunoblot . Serum levels of sRAGE and esRAGE were measured by ELISA in archived serum sample s from a previous r and omized double-blind placebo-controlled clinical trial that explored the cardiovascular effects of atorvastatin in hypercholesterolemic Chinese type 2 diabetic patients . RESULTS sRAGE and esRAGE were induced by atorvastatin in a time- and dose-dependent manner in THP-1 cells . In the diabetic patients , there was a significant increase in serum sRAGE ( p<0.05 ) and esRAGE ( p<0.01 ) in the atorvastatin group at 6-month , but no change in placebo group . Serum esRAGE was higher in atorvastatin group than placebo group [ median 240.5pg/ml ( interquartile range 186.5 - 377.3 ) vs 194.8pg/ml ( 124.1 - 347.9 ) respectively , p<0.01 ] at 6-month , whereas the differences in sRAGE did not reach statistical significance ( p=0.051 ) . There was a correlation between the increase of serum esRAGE and reduction of serum LDL ( r=-0.36 , p=0.001 ) . CONCLUSIONS Statins are known to have pleiotropic effects and we have shown that atorvastatin can increase circulating esRAGE levels in type 2 diabetic patients Aims : The present study investigated the effects of lipid-lowering therapy with atorvastatin on skin microvascular function in patients with type 1 diabetes and dyslipidaemia . Methods : Twenty patients received daily treatment with atorvastatin 80 mg or placebo during 2 months in a r and omised , double-blind , cross-over study . Forearm skin microcirculation was investigated with laser Doppler perfusion imaging during iontophoresis of acetylcholine and sodium nitroprusside to assess endothelium-dependent and endothelium-independent microvascular reactivity , respectively . Various biochemical markers of endothelial function were also investigated . Results : Endothelium-dependent microvascular reactivity decreased during atorvastatin ( p < 0.001 ) , showing a significant treatment effect compared with placebo ( p = 0.04 ) . Atorvastatin treatment was also associated with increased haemoglobin A1C levels from 7.45 % to 7.77 % ( p = 0.008 ) . Conclusions : The present study shows impaired endothelium-dependent skin microvascular function during high-dose atorvastatin treatment in patients with type 1 diabetes , thus implicating a risk for deterioration of microvascular function during such therapy in these patients |
657 | 31,315,231 | There was no evidence for changes in the CMT .
This systematic review is the first to demonstrate evidence that patients with CAI present decreased spinal reflex excitability in the soleus and fibularis longus .
However , there is no evidence of changes in supraspinal excitability when considering only the CMT .
The latter result needs to be interpreted with caution as all except one study demonstrate some changes at the supraspinal level with CAI | The objective of this systematic review with meta- analysis was to determine alterations in spinal and corticospinal excitability of ankle muscles in patients with chronic ankle instability ( CAI ) compared to uninjured controls . | STUDY DESIGN Prospect i ve cohort study . OBJECTIVE To assess the effect of 6 weeks of balance training on sensorimotor measures previously found to be deficient in participants with chronic ankle instability ( CAI ) . BACKGROUND CAI is the tendency toward repeated ankle sprains and recurring symptoms , occurring in 40 % to 70 % of individuals who have previously sustained a lateral ankle sprain . Recent studies have found deficits in sensorimotor measures in individuals with CAI . As balance training is a common component of ankle rehabilitation , underst and ing its effect on the sensorimotorsystem in individuals with CAI may enable us to optimize protocol s to better utilize this rehabilitation method . METHODS Twelve participants with CAI and 9 healthy volunteers participated . Independent variables were group ( CAI , control ) and time ( pretraining , posttraining ) . Participants with CAI who completed a 6-week balance training program and healthy controls who did not get any training were pretested and posttested at the beginning and at the end of 6 weeks . RESULTS The individuals in the CAI group who performed balance training demonstrated better performance than control participants on baseline adjusted posttraining measures of dynamic balance in the anterior medial ( P = .021 ) , medial ( P = .048 ) , and posterior medial directions ( P = .030 ) ; motoneuron pool excitability Hmax/Mmax ratio ( P = .044 ) and single-limb presynaptic inhibition ( P = .012 ) ; and joint position sense inversion variable error ( P = .017 ) . It may be of note that no systematic differences were detected for static balance or plantar flexion joint position sense tasks . CONCLUSIONS After 6 weeks of balance training , individuals with CAI demonstrated enhanced dynamic balance , inversion joint position sense , and changes in motoneuron pool excitability compared to healthy controls who did not train . LEVEL OF EVIDENCE Therapy , level 2b Objectives The purpose of the international multicenter prospect i ve single arm clinical trial was to evaluate restorative neurostimulation eliciting episodic contraction of the lumbar multifidus for treatment of chronic mechanical low back pain ( CMLBP ) in patients who have failed conventional therapy and are not c and i date s for surgery or spinal cord stimulation ( SCS ) . Material s and Methods Fifty‐three subjects were implanted with a neurostimulator ( ReActiv8 , Mainstay Medical Limited , Dublin , Irel and ) . Leads were positioned bilaterally with electrodes close to the medial branch of the L2 dorsal ramus nerve . The primary outcome measure was low back pain evaluated on a 10‐Point Numerical Rating Scale ( NRS ) . Responders were defined as subjects with an improvement of at least the Minimal Clinical ly Important Difference ( MCID ) of ≥2‐point in low back pain NRS without a clinical ly meaningful increase in LBP medications at 90 days . Secondary outcome measures included Oswestry Disability Index ( ODI ) and Quality of Life ( QoL ; EQ‐5D ) . Results For 53 subjects with an average duration of CLBP of 14 years and average NRS of 7 and for whom no other therapies had provided satisfactory pain relief , the responder rate was 58 % . The percentage of subjects at 90 days , six months , and one year with ≥MCID improvement in single day NRS was 63 % , 61 % , and 57 % , respectively . Percentage of subjects with ≥MCID improvement in ODI was 52 % , 57 % , and 60 % while those with ≥MCID improvement in EQ‐5D was 88 % , 82 % , and 81 % . There were no unanticipated adverse events ( AEs ) or serious AEs related to the device , procedure , or therapy . The initial surgical approach led to a risk of lead fracture , which was mitigated by a modification to the surgical approach . Conclusions Electrical stimulation to elicit episodic lumbar multifidus contraction is a new treatment option for CMLBP . Results demonstrate clinical ly important , statistically significant , and lasting improvement in pain , disability , and Abstract The purpose of this investigation was to examine the effects of the combination of chronic ankle instability ( CAI ) and altered visual focus on strategies for dynamic stability during a drop-jump task . Nineteen participants with self-reported CAI and 19 healthy participants performed a drop-jump task in looking-up and looking-down conditions . For the looking-up condition , participants looked up and read a r and om number that flashed on a computer monitor . For the looking-down condition , participants focused their vision on the force plate . Sagittal- and frontal-plane kinematics in the hip , knee and ankle were calculated at the time points of 100 ms pre-initial foot contact to ground and at IC . The result ant vector time to stabilisation was calculated with ground reaction force data . The CAI group demonstrated less hip flexion at the point of 100 ms pre-initial contact ( P < 0.01 ) , and less hip flexion ( P = 0.03 ) and knee flexion at initial contact ( P = 0.047 ) compared to controls . No differences in kinematics or dynamic stability were observed in either looking-up or looking-down conditions ( P > 0.05 ) . Altered visual focus did not influence movement patterns during the drop-jump task , but the presence of CAI did . The current data suggests that central ly mediated changes associated with CAI may lead to global alterations in the sensorimotor control CONTEXT Focal ankle-joint cooling ( FAJC ) has been shown to increase Hoffmann ( H ) reflex amplitudes of select leg muscles while subjects lie prone , but it is unknown whether the neurophysiological cooling effects persist in st and ing . OBJECTIVE To assess the effects of FAJC on H-reflexes of the soleus and fibularis longus during 3 body positions ( prone , bipedal , and unipedal stances ) in individuals with and without chronic ankle instability ( CAI ) . DESIGN Crossover . SETTING Laboratory . PARTICIPANTS 15 young adults with CAI ( 9 male , 6 female ) and 15 healthy controls . INTERVENTION All subjects received both FAJC and sham treatments on separate days in a r and omized order . FAJC was accomplished by applying a 1.5-L plastic bag filled with crushed ice to the ankle for 20 min . Sham treatment involved room-temperature c and y corn . MAIN OUTCOME MEASURES Maximum amplitudes of H-reflexes and motor ( M ) waves were recorded while subjects lay prone and then stood in quiet bipedal and unipedal stances before and immediately after each treatment . Primary outcome measures were H(max):M(max ) ratios for the soleus and fibularis longus . Three-factor ( group × treatment condition × time ) repeated- measures ANOVAs and Fisher LSD tests were performed for statistical analyses . RESULTS Significant interactions of treatment condition by time for prone H(max):M(max ) ratios were found in the soleus ( P = .001 ) and fibularis longus ( P = .003 ) . In both muscles , prone H(max):M(max ) ratios moderately increased after FAJC but not after sham treatment . The CAI and healthy groups responded similarly to FAJC . In contrast , there were no significant interactions or main effects in the bipedal and unipedal stances in either muscle ( P > .05 ) . CONCLUSIONS FAJC moderately increased H-reflex amplitudes of the soleus and fibularis longus while subjects were prone but not during bipedal or unipedal st and ing . These results were not different between groups with and without CAI 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 We do not know the impact an ankle sprain has on physical activity levels across the lifespan . With the negative consequences of physical inactivity well established , underst and ing the effect of an ankle sprain on this outcome is critical . The objective of this study was to measure physical activity across the lifespan after a single ankle sprain in an animal model . Thirty male mice ( CBA/J ) were r and omly placed into one of three groups : the transected calcaneofibular ligament ( CFL ) group , the transected anterior talofibular ligament (ATFL)/CFL group , and a SHAM group . Three days after surgery , all of the mice were individually housed in a cage containing a solid surface running wheel . Physical activity levels were recorded and averaged every week across the mouse 's lifespan . The SHAM mice ran significantly more distance each day compared to the remaining two running groups ( post hoc p = 0.011 ) . Daily duration was different between the three running groups ( p = 0.048 ) . The SHAM mice ran significantly more minutes each day compared to the remaining two running groups ( post hoc p=0.046 ) while the ATFL/CFL mice ran significantly less minutes each day ( post hoc p = 0.028 ) compared to both the SHAM and CFL only group . The SHAM mice ran at a faster daily speed versus the remaining two groups of mice ( post hoc p = 0.019 ) and the ATFL/CFL mice ran significantly slower each day compared to the SHAM and CFL group ( post hoc p = 0.005 ) . The results of this study indicate that a single ankle sprain significantly decreases physical activity across the lifespan in mice . This decrease in physical activity can potentially lead to the development of numerous chronic diseases . An ankle sprain thus has the potential to lead to significant long term health risks if not treated appropriately . Key pointsA single ankle significantly decreased physical activity levels in mice across the lifespan . Decreased physical activity could significantly negatively impact overall health if not modified . Initial treatment and rehabilitation of ankle sprains needs to be studied to determine ways to keep physical activity levels up after injury While GABA(B ) receptors are thought to have an important role in mediating long interval intracortical inhibition ( LICI ) in the human motor cortex , the effect of a selective GABA(B ) receptor agonist on this measure has not been directly tested . Nine healthy volunteers ingested either 50 mg baclofen ( BAC ) or placebo ( PBO ) in a r and omized , double blind crossover design , with the second session one week later . We used transcranial magnetic stimulation to assess motor threshold , motor evoked potential ( MEP ) amplitude , cortical silent period ( CSP ) duration , short interval intracortical inhibition ( SICI ) and LICI before and 90 min following drug intake . There was no specific effect of drug on motor threshold , MEP amplitude or CSP duration . BAC result ed in a significant increase in LICI ( P=0.002 ) and a significant decrease in SICI ( P=0.046 ) while PBO had no effect . Our findings demonstrate that the enhanced GABA(B ) receptor activation results in differential effects on these two measures of intracortical inhibition in the human motor cortex . The increase in LICI is likely to be a result of increased GABA(B ) receptor mediated inhibitory post-synaptic potentials , while the reduction in SICI may relate to the activation of pre-synaptic GABA(B ) receptors reducing GABA release OBJECTIVES We aim ed to present a unique prospect i ve neurological data set for participants who experienced an ACL injury . DESIGN Prospect i ve longitudinal case-control . METHODS High school female soccer athletes were evaluated using functional magnetic resonance imaging to capture resting-state brain connectivity prior to their competitive season . Two of these athletes later experienced an ACL injury ( ACLI ) . We matched these ACLI participants with eight teammates who did not go on to sustain an ACL injury ( uninjured controls , Con ) based on age , grade , sex , height , and weight to examine differences in preseason connectivity . Knee-motor regions of interest ( ROIs ) were created based on previously published data from which five specific areas were selected as seeds for analysis . Independent- sample s t-tests with a false discovery rate correction for multiple comparisons determined differences in connectivity between the ACLI and Con . RESULTS There was significantly greater connectivity between the left primary sensory cortex ( a brain region responsible for proprioception ) and the right posterior lobe of the cerebellum ( a brain region responsible for balance and coordination ) for the Con relative to ACLI , t (8)=4.53 , p=0.03 ( false discovery rate corrected ) . CONCLUSIONS These preliminary data indicate that those who do not later sustain an ACL injury exhibit a stronger functional connection between a cortical sensory-motor region and a cerebellar region responsible for balance and coordination . These findings may help to guide development of brain-driven biofeedback training that optimizes and promotes adaptive neuroplasticity to reduce motor coordination errors and injury risk CONTEXT Following a lateral ankle sprain , ∼40 % of individuals develop chronic ankle instability ( CAI ) , characterized by recurrent injury and sensations of giving way . Deafferentation due to mechanoreceptor damage postinjury is suggested to contribute to arthrogenic muscle inhibition ( AMI ) . Whole-body vibration ( WBV ) has the potential to address the neurophysiologic deficits accompanied by CAI and , therefore , possibly prevent reinjury . OBJECTIVE To determine if an acute bout of WBV can improve AMI and proprioception in individuals with CAI . DESIGN AND PARTICIPANTS The authors examined if an acute bout of WBV can improve AMI and proprioception in individuals with CAI with a repeated- measures design . A total of 10 young adults with CAI and 10 age-matched healthy controls underwent a control , sham , and WBV condition in r and omized order . SETTING Biomechanics laboratory . INTERVENTION WBV . MAIN OUTCOME MEASURES Motoneuron pool recruitment was assessed via Hoffmann reflex ( H-reflex ) in the soleus . Proprioception was evaluated using ankle joint position sense at 15 ° and 20 ° of inversion . Both were assessed prior to , immediately following , and 30 minutes after the intervention ( pretest , posttest , and 30mPost , respectively ) . RESULTS Soleus maximum H-reflex : M-response ( H : M ) ratios were 25 % lower in the CAI group compared with the control group ( P = .03 ) . Joint position sense mean constant error did not differ between groups ( P = .45 ) . Error at 15 ° in the CAI ( pretest 0.8 [ 1.6 ] , posttest 2.0 [ 2.8 ] , 30mPost 2.0 [ 1.9 ] ) and control group ( pretest 0.8 [ 2.0 ] , posttest 0.6 [ 2.9 ] , 30mPost 0.5 [ 2.1 ] ) did not improve post-WBV . Error at 20 ° did not change post-WBV in the CAI ( pretest 1.3 [ 1.7 ] , posttest 1.0 [ 2.4 ] , 30mPost 1.5 [ 2.2 ] ) or control group ( pretest -0.3 [ 3.0 ] , posttest 0.8 [ 2.1 ] , 30mPost 0.6 [ 1.8 ] ) . CONCLUSION AMI is present in the involved limb of individuals with CAI . The acute response following a single bout of WBV did not ameliorate the presence of AMI nor improve proprioception in those with CAI |
658 | 31,443,149 | The results of this review found that the strongest treatment effects to date are those associated with exercise .
Strengthening exercises of the neck and upper quadrant have a moderate effect on neck pain in the short-term .
Lower quality evidence and smaller effects were found for other exercise approaches .
Other treatments , including education/advice and psychological treatment , showed only very small to small effects , based on low to moderate quality evidence . | Neck pain , whether from a traumatic event such as a motor vehicle crash or of a non-traumatic nature , is a leading cause of worldwide disability .
This narrative review evaluated the evidence from systematic review s , recent r and omised controlled trials , clinical practice guidelines , and other relevant studies for the effects of rehabilitation approaches for chronic neck pain . | STUDY DESIGN Systematic review and best evidence synthesis . OBJECTIVES To describe the prevalence and incidence of neck pain and disability in workers ; to identify risk factors for neck pain in workers ; to propose an etiological diagram ; and to make recommendations for future research . SUMMARY OF BACKGROUND DATA Previous review s of the etiology of neck pain in workers relied on cross-sectional evidence . Recently published cohorts and r and omized trials warrant a re- analysis of this body of research . METHODS We systematic ally search ed Medline for literature published from 1980 - 2006 . Retrieved articles were review ed for relevance . Relevant articles were critically appraised . Articles judged to have adequate internal validity were included in our best evidence synthesis . RESULTS One hundred and nine papers on the burden and determinants of neck pain in workers were scientifically admissible . The annual prevalence of neck pain varied from 27.1 % in Norway to 47.8 % in Québec , Canada . Each year , between 11 % and 14.1 % of workers were limited in their activities because of neck pain . Risk factors associated with neck pain in workers include age , previous musculoskeletal pain , high quantitative job dem and s , low social support at work , job insecurity , low physical capacity , poor computer workstation design and work posture , sedentary work position , repetitive work and precision work . We found preliminary evidence that gender , occupation , headaches , emotional problems , smoking , poor job satisfaction , awkward work postures , poor physical work environment , and workers ' ethnicity may be associated with neck pain . There is evidence that interventions aim ed at modifying workstations and worker posture are not effective in reducing the incidence of neck pain in workers . CONCLUSION Neck disorders are a significant source of pain and activity limitations in workers . Most neck pain results from complex relationships between individual and workplace risk factors . No prevention strategies have been shown to reduce the incidence of neck pain in workers Background : Non-specific chronic low back pain disorders have been proven resistant to change , and there is still a lack of clear evidence for one specific treatment intervention being superior to another . Methods : This r and omized controlled trial aim ed to investigate the efficacy of a behavioural approach to management , classification-based cognitive functional therapy , compared with traditional manual therapy and exercise . Linear mixed models were used to estimate the group differences in treatment effects . Primary outcomes at 12-month follow-up were Oswestry Disability Index and pain intensity , measured with numeric rating scale . Inclusion criteria were as follows : age between 18 and 65 years , diagnosed with non-specific chronic low back pain for > 3 months , localized pain from T12 to gluteal folds , provoked with postures , movement and activities . Oswestry Disability Index had to be > 14 % and pain intensity last 14 days > 2/10 . A total of 121 patients were r and omized to either classification-based cognitive functional therapy group n = 62 ) or manual therapy and exercise group ( n > = 59 ) . Results : The classification-based cognitive functional therapy group displayed significantly superior outcomes to the manual therapy and exercise group , both statistically ( p < 0.001 ) and clinical ly . For Oswestry Disability Index , the classification-based cognitive functional therapy group improved by 13.7 points , and the manual therapy and exercise group by 5.5 points . For pain intensity , the classification-based cognitive functional therapy improved by 3.2 points , and the manual therapy and exercise group by 1.5 points . Conclusions : The classification-based cognitive functional therapy produced superior outcomes for non-specific chronic low back pain compared with traditional manual therapy and exercise Musculoskeletal conditions represent a considerable burden worldwide , and are predominantly managed in primary care . Evidence suggests that many musculoskeletal conditions share similar prognostic factors . Systematic ally assessing patient ’s prognosis and matching treatments based on prognostic subgroups ( stratified care ) has been shown to be both clinical ly effective and cost-effective . This study ( Keele Aches and Pains Study ) aims to refine and examine the validity of a brief question naire ( Keele STarT MSK tool ) design ed to enable risk stratification of primary care patients with the five most common musculoskeletal pain presentations . We also describe the subgroups of patients , and explore the acceptability and feasibility of using the tool and how the tool is best implemented in clinical practice . The study design is mixed methods : a prospect i ve , quantitative observational cohort study with a linked qualitative focus group and interview study . Patients who have consulted their GP or health care practitioner about a relevant musculoskeletal condition will be recruited from general practice . Participating patients will complete a baseline question naire ( shortly after consultation ) , plus question naires 2 and 6 months later . A sub sample of patients , along with participating GPs and health care practitioners , will be invited to take part in qualitative focus groups and interviews . The Keele STarT MSK tool will be refined based on face , discriminant , construct , and predictive validity at baseline and 2 months , and vali date d using data from 6-month follow-up . Patient and clinician perspectives about using the tool will be explored . This study will provide a vali date d prognostic tool ( Keele STarT MSK ) with established cutoff points to stratify patients with the five most common musculoskeletal presentations into low- , medium- , and high-risk subgroups . The qualitative analysis of patient and health care perspectives will inform practitioners on how to embed the tool into clinical practice using established general practice IT systems and clinician-support packages Abstract We assessed the effectiveness of a 6-month healthy lifestyle intervention , on pain intensity in patients with chronic low back pain who were overweight or obese . We conducted a pragmatic r and omised controlled trial , embedded within a cohort multiple r and omised controlled trial of patients on a waiting list for outpatient orthopaedic consultation at a tertiary hospital in NSW , Australia . Eligible patients with chronic low back pain ( > 3 months in duration ) and body mass index ≥27 kg/m2 and < 40 kg/m2 were r and omly allocated , using a central concealed r and om allocation process , to receive advice and education and referral to a 6-month telephone-based healthy lifestyle coaching service , or usual care . The primary outcome was pain intensity measured using an 11-point numerical rating scale , at baseline , 2 weeks , and monthly for 6 months . Data analysis was by intention-to-treat according to a prepublished analysis plan . Between May 13 , 2015 , and October 27 , 2015 , 160 patients were r and omly assigned in a 1:1 ratio to the intervention or usual care . We found no difference between groups for pain intensity over 6 months ( area under the curve , mean difference = 6.5 , 95 % confidence interval −8.0 to 21.0 ; P = 0.38 ) or any secondary outcome . In the intervention group , 41 % ( n = 32 ) of participants reported an adverse event compared with 56 % ( n = 45 ) in the control group . Our findings show that providing education and advice and telephone-based healthy lifestyle coaching did not benefit patients with low back pain who were overweight or obese , compared with usual care . The intervention did not influence the targeted healthy lifestyle behaviours proposed to improve pain in this patient group BACKGROUND AND PURPOSE Patients with hip osteoarthritis have impairments in muscle function ( muscle strength and power ) and hip range of motion ( ROM ) , and it is commonly believed that effective clinical management of osteoarthritis should address these impairments to reduce pain and disability . Therefore , the purpose of this study was to compare the short- and long-term effects of 4 months of physiotherapist-supervised strength training , physiotherapist-supervised Nordic Walking ( NW ) , or unsupervised home-based exercise ( HBE ) on muscle function and hip ROM in patients diagnosed with hip osteoarthritis . METHODS Secondary outcome analyses from an observer-blinded three-armed parallel- design r and omized controlled trial in 60 + -year-old patients with clinical hip osteoarthritis ( American College of Rheumatology criteria ) who were not on a waiting list for hip replacement . One hundred and fifty-two patients were r and omized to either 4 months of physiotherapist-supervised , moderate , progressive , strength training ( n = 50 ) , physiotherapist-supervised NW ( n = 50 ) , or unsupervised HBE ( n = 52 ) . Maximal isometric hip and thigh muscle strength and leg extensor power and active hip ROM were assessed at baseline 2 , 4 , and 12 months . RESULTS Intention-to-treat-analyses did not show any significant between-group differences for improvements in muscle strength and power or ROM at any time points . Short-term significant ( p < .05 ) increases in muscle strength were present in the physiotherapist-supervised exercise groups and in the long-term for muscle power in the NW-group . All exercise modes result ed in significant increases of ROM but long-term improvements were only shown for NW and HBE . DISCUSSION Four months of physiotherapist-supervised , progressive , moderate , and strength training was less effective than hypothesized for improving muscle strength and power in patients with hip osteoarthritis who are not awaiting hip replacement . Our results may indicate that in these patients , improvements in disability are not necessarily dependent on improvements in strength and power or ROM OBJECTIVE To evaluate the effect of training and pain education vs pain education alone , on neck pain , neck muscle activity and postural sway in patients with chronic neck pain . METHODS Twenty women with chronic neck pain were r and omized to receive pain education and specific training ( neck-shoulder exercises , balance and aerobic training ) ( INV ) , or pain education alone ( CTRL ) . Effect on neck pain , function and Global Perceived Effect ( GPE ) were measured . Surface electromyography ( EMG ) was recorded from neck flexor and extensor muscles during performance of the Cranio-Cervical Flexion Test ( CCFT ) and three postural control tests ( two-legged : eyes open and closed , one-legged : eyes open ) . Sway parameters were calculated . RESULTS Fifteen participants ( CTRL : eight ; INV : seven ) completed the study . Per protocol analyses showed a larger pain reduction ( p = 0.002 ) for the INV group with tendencies for increased GPE ( p = 0.06 ) , reduced sternocleidomastoid activity during the CCFT ( p = 0.09 ) , reduced sway length ( p = 0.09 ) , and increased neck extensor activity ( p = 0.02 ) during sway compared to the CTRL group . CONCLUSION Pain education and specific training reduce neck pain more than pain education alone in patients with chronic neck pain . These results provide encouragement for a larger clinical trial to corroborate these observations Background Disturbed sleep and pain often co-exist and the relationship between the two conditions is complex and likely reciprocal . This 5-year prospect i ve study examines whether disturbed sleep can predict the onset of multi-site pain , and whether non-disturbed sleep can predict the resolution of multi-site pain . Methods The cohort ( n = 1599 ) was stratified by the number of self-reported pain sites : no pain , pain from 1–2 sites and multi-site pain ( ≥3 pain sites ) . Sleep was categorized by self-reported sleep disturbance : sleep A ( best sleep ) , sleep B and sleep C ( worst sleep ) . In the no-pain and pain-from-1–2 sites strata , the association between sleep ( A , B and C ) and multi-site pain 5 years later was analysed . Further , the prognostic value of sleep for the resolution of multi-site pain at follow-up was calculated for the stratum with multi-site pain at baseline . In the analyses , gender , age , body mass index , smoking , physical activity and work-related exposures were treated as potential confounders . Results For individuals with no pain at baseline , a significantly higher odds ratio for multi-site pain 5 years later was seen for the tertile reporting worst sleep [ odds ratio ( OR ) 4.55 ; 95 % confidence interval ( CI ) 1.28–16.12 ] . Non-disturbed ( or less disturbed ) sleep had a significant effect when predicting the resolution of multi-site pain ( to no pain ) ( OR 3.96 ; 95 % CI 1.69–9.31 ) . Conclusion In conclusion , sleep could be relevant for predicting both the onset and the resolution of multi-site pain . It seems to be a significant factor to include in research on multi-site pain and when conducting or evaluating intervention programmes for pain & NA ; An association is demonstrated between genetic polymorphisms in the gene coding for a key regulatory molecule in the hypothalamic‐pituitary‐adrenal axis and persistent pain after trauma . & NA ; Individual vulnerability factors influencing the function of the hypothalamic‐pituitary‐adrenal axis may contribute to the risk of the development of persistent musculoskeletal pain after traumatic stress exposure . The objective of the study was to evaluate the association between polymorphisms in the gene encoding FK506 binding protein 51 , FKBP5 , a glucocorticoid receptor co‐chaperone , and musculoskeletal pain severity 6 weeks after 2 common trauma exposures . The study included data from 2 prospect i ve emergency department‐based cohorts : a discovery cohort ( n = 949 ) of European Americans experiencing motor vehicle collision and a replication cohort of adult European American women experiencing sexual assault ( n = 53 ) . DNA was collected from trauma survivors at the time of initial assessment . Overall pain and neck pain 6 weeks after trauma exposure were assessed using a 0–10 numeric rating scale . After adjustment for multiple comparisons , 6 FKBP5 polymorphisms showed significant association ( minimum P < 0.0001 ) with both overall and neck pain in the discovery cohort . The association of rs3800373 , rs9380526 , rs9394314 , rs2817032 , and rs2817040 with neck pain and /or overall pain 6 weeks after trauma was replicated in the sexual assault cohort , showing the same direction of the effect in each case . The results of this study indicate that genetic variants in FKBP5 influence the severity of musculoskeletal pain symptoms experienced during the weeks after motor vehicle collision and sexual assault . These results suggest that glucocorticoid pathways influence the development of persistent posttraumatic pain , and that such pathways may be a target of pharmacologic interventions aim ed at improving recovery after trauma Objectives : To investigate sensory changes present in patients with chronic whiplash-associated disorders and chronic idiopathic neck pain using a variety of quantitative sensory tests to better underst and the pain processing mechanisms underlying persistent symptoms . Methods : A case control study was used with 29 subjects with chronic whiplash-associated disorders , 20 subjects with chronic idiopathic neck pain , and 20 pain-free volunteers . Pressure pain thresholds were measured over the articular pillars of C2-C3 , C5-C6 , the median , radial , and ulnar nerve trunks in the arm and over a remote site , the muscle belly of tibialis anterior . Heat pain thresholds , cold pain thresholds , and von Frey hair sensibility were measured over the cervical spine , tibialis anterior , and deltoid insertion . Anxiety was measured with the Short-Form of the Spielberger State Anxiety Inventory . Results : Pressure pain thresholds were decreased over cervical spine sites in both subject groups when compared with controls ( P < 0.05 ) . In the chronic whiplash-associated disorders group , pressure pain thresholds were also decreased over the tibialis anterior , median , and radial nerve trunks ( P < 0.001 ) . Heat pain thresholds were decreased and cold pain thresholds increased at all sites ( P < 0.03 ) . No differencesin heat pain thresholds or cold pain thresholds were evident in the idiopathic neck pain group at any site compared with the control group ( P > 0.27 ) . No abnormalities in von Frey hair sensibility were evident in either neck pain group ( P > 0.28 ) . Discussion : Both chronic whiplash-associated disorders and idiopathic neck pain groups were characterized by mechanical hyperalgesia over the cervical spine . Whiplash subjects showed additional widespread hypersensitivity to mechanical pressure and thermal stimuli , which was independent of state anxiety and may represent changes in central pain processing mechanisms . This may have implication s for future treatment approaches Summary Background Back pain remains a challenge for primary care internationally . One model that has not been tested is stratification of the management according to the patient 's prognosis ( low , medium , or high risk ) . We compared the clinical effectiveness and cost-effectiveness of stratified primary care ( intervention ) with non-stratified current best practice ( control ) . Methods 1573 adults ( aged ≥18 years ) with back pain ( with or without radiculopathy ) consultations at ten general practice s in Engl and responded to invitations to attend an assessment clinic . Eligible participants were r and omly assigned by use of computer-generated stratified blocks with a 2:1 ratio to intervention or control group . Primary outcome was the effect of treatment on the Rol and Morris Disability Question naire ( RMDQ ) score at 12 months . In the economic evaluation , we focused on estimating incremental quality -adjusted life years ( QALYs ) and health-care costs related to back pain . Analysis was by intention to treat . This study is registered , number IS RCT N37113406 . Findings 851 patients were assigned to the intervention ( n=568 ) and control groups ( n=283 ) . Overall , adjusted mean changes in RMDQ scores were significantly higher in the intervention group than in the control group at 4 months ( 4·7 [ SD 5·9 ] vs 3·0 [ 5·9 ] , between-group difference 1·81 [ 95 % CI 1·06–2·57 ] ) and at 12 months ( 4·3 [ 6·4 ] vs 3·3 [ 6·2 ] , 1·06 [ 0·25–1·86 ] ) , equating to effect sizes of 0·32 ( 0·19–0·45 ) and 0·19 ( 0·04–0·33 ) , respectively . At 12 months , stratified care was associated with a mean increase in generic health benefit ( 0·039 additional QALYs ) and cost savings ( £ 240·01 vs £ 274·40 ) compared with the control group . Interpretation The results show that a stratified approach , by use of prognostic screening with matched pathways , will have important implication s for the future management of back pain in primary care . Funding Arthritis Research UK Abstract Patients with chronic whiplash associated disorders present with varied sensory , motor and psychological features . In this first instance it was question ed whether a multimodal program of physical therapies was an appropriate management to be broadly prescribed for these patients when it was known that some would have sensory features suggestive of a notable pain syndrome . A r and omised controlled trial was conducted with 71 participants with persistent neck pain following a motor vehicle crash to explore this question . Participants were r and omly allocated to receive either a multimodal physiotherapy program ( MPT ) or a self‐management program ( SMP ) ( advice and exercise ) . In the r and omisation process , participants were stratified according to the presence or not of widespread mechanical or cold hyperalgesia . The intervention period was 10 weeks and outcomes were assessed immediately following treatment . Even with the presence of sensory hypersensitivity in 72.5 % of subjects , both groups reported some relief of neck pain and disability ( Neck Disability Index ) and it was superior in the group receiving multimodal physiotherapy ( p = 0.04 ) . Post‐hoc observations however suggested that relief was marginal in the subgroup with both widespread mechanical and cold hyperalgesia . Further research is required to test the validity of this sub‐group observation and to test the effect of the intervention in the long term AIM To investigate the effect of combining pain education , specific exercises and grade d physical activity training ( exercise ) compared with pain education alone ( control ) on physical health-related quality of life ( HR-QoL ) in chronic neck pain patients . METHODS A multicentre r and omised controlled trial of 200 neck pain patients receiving pain education . The exercise group received additional exercises for neck/shoulder , balance and oculomotor function , plus grade d physical activity training . Patient-reported outcome measures ( Short Form-36 Physical and Mental component summary scores , EuroQol-5D , Beck Depression Inventory-II , Neck Disability Index , Pain Bothersomeness , Patient-Specific Functioning Scale , Tampa Scale of Kinesiophobia , Global Perceived Effect ) and clinical tests ( Aastr and Physical Fitness , cervical Range of Motion , Pressure Pain Threshold at infraspinatus , tibialis anterior and cervical spine , Cranio-cervical Flexion , Cervical Extension muscle function , and oculomotion ) were recorded at baseline and after 4 months . RESULTS The exercise group showed statistically significant improvement in physical HR-QoL , mental HR-QoL , depression , cervical pressure pain threshold , cervical extension movement , muscle function , and oculomotion . Per protocol analyses confirmed these results with additional significant improvements in the exercise group compared with controls . CONCLUSIONS This multimodal intervention may be an effective intervention for chronic neck pain patients . TRIAL REGISTRATION The trial was registered on www . Clinical Trials.govNCT01431261 and at the Regional Scientific Ethics Committee of Southern Denmark S-20100069 Importance : Each year , millions of persons worldwide seek compensation for transport accident and workplace injuries . Previous research suggests that these cl aim ants have worse long-term health outcomes than persons whose injuries fall outside compensation schemes . However , existing studies have substantial method ological weaknesses and have not identified which aspects of the cl aim ing experience may drive these effects . Objective : To determine aspects of cl aims processes that cl aim ants to transport accident and workers ’ compensation schemes find stressful and whether such stressful experiences are associated with poorer long-term recovery . Design , Setting , and Participants : Prospect i ve cohort study of a r and om sample of 1010 patients hospitalized in 3 Australian states for injuries from 2004 through 2006 . At 6-year follow-up , we interviewed 332 participants who had cl aim ed compensation from transport accident and workers ’ compensation schemes ( “ cl aim ants � ? ) to determine which aspects of the cl aim ing experience they found stressful . We used multivariable regression analysis to test for associations between compensation-related stress and health status at 6 years , adjusting for baseline determinants of long-term health status and predisposition to stressful experiences ( via propensity scores ) . Main Outcomes and Measures : Disability , quality of life , anxiety , and depression . Results : Among cl aim ants , 33.9 % reported high levels of stress associated with underst and ing what they needed to do for their cl aim ; 30.4 % , with cl aim delays ; 26.9 % , with the number of medical assessment s ; and 26.1 % , with the amount of compensation they received . Six years after their injury , cl aim ants who reported high levels of stress had significantly higher levels of disability ( 6.94 points , World Health Organization Disability Assessment Schedule sum score ) , anxiety and depression ( 1.89 points and 2.61 points , respectively , Hospital Anxiety and Depression Scale ) , and lower quality of life ( -0.73 points , World Health Organization Quality of Life instrument , overall item ) , compared with other cl aim ants . Adjusting for cl aim ants ’ vulnerability to stress attenuated the strength of these associations , but most remained strong and statistically significant . Conclusions and Relevance : Many cl aim ants experience high levels of stress from engaging with injury compensation schemes , and this experience is positively correlated with poor long-term recovery . Intervening early to boost resilience among those at risk of stressful cl aims experiences and re design ing compensation processes to reduce their stressfulness may improve recovery and save money BACKGROUND Little is known about the effectiveness of treatments for acute whiplash injury . We aim ed to estimate whether training of staff in emergency departments to provide active management consultations was more effective than usual consultations ( Step 1 ) and to estimate whether a physiotherapy package was more effective than one additional physiotherapy advice session in patients with persisting symptoms ( Step 2 ) . METHODS Step 1 was a pragmatic , cluster r and omised trial of 12 NHS Trust hospitals including 15 emergency departments who treated patients with acute whiplash associated disorder of grade s I-III . The hospitals were r and omised by clusters to either active management or usual care consultations . In Step 2 , we used a nested individually r and omised trial . Patients were r and omly assigned to receive either a package of up to six physiotherapy sessions or a single advice session . R and omisation in Step 2 was stratified by centre . Investigator-masked outcomes were obtained at 4 , 8 , and 12 months . Masking of clinicians and patients was not possible in all steps of the trial . The primary outcome was the Neck Disability Index ( NDI ) . Analysis was intention to treat , and included an economic evaluation . The study is registered IS RCT N33302125 . FINDINGS Recruitment ran from Dec 5 , 2005 to Nov 30 , 2007 . Follow-up was completed on Dec 19 , 2008 . In Step 1 , 12 NHS Trusts were r and omised , and 3851 of 6952 eligible patients agreed to participate ( 1598 patients were assigned to usual care and 2253 patients were assigned to active management ) . 2704 ( 70 % ) of 3851 patients provided data at 12 months . NDI score did not differ between active management and usual care consultations ( difference at 12 months 0·5 , 95 % CI -1·5 to 2·5 ) . In Step 2 , 599 patients were r and omly assigned to receive either advice ( 299 patients ) or a physiotherapy package ( 300 patients ) . 479 ( 80 % ) patients provided data at 12 months . The physiotherapy package at 4 months showed a modest benefit compared to advice ( NDI difference -3·7 , -6·1 to -1·3 ) , but not at 8 or 12 months . Active management consultations and the physiotherapy package were more expensive than usual care and single advice session . No treatment-related serious adverse events or deaths were noted . INTERPRETATION Provision of active management consultation did not show additional benefit . A package of physiotherapy gave a modest acceleration to early recovery of persisting symptoms but was not cost effective from a UK NHS perspective . Usual consultations in emergency departments and a single physiotherapy advice session for persistent symptoms are recommended . FUNDING NIHR Health Technology Assessment programme & NA ; This study aim ed to identify distinctive trajectories for pain/disability and posttraumatic stress disorder ( PTSD ) symptoms following whiplash injury and to examine the effect of injury compensation cl aim lodgement on the trajectories . In a prospect i ve study , 155 individuals with whiplash were assessed at < 1 month , 3 , 6 and 12 months post injury . Outcomes at each time point were Neck Disability Index ( NDI ) and the Posttraumatic Stress Diagnostic Scale ( PDS ) . Group‐based trajectory analytical techniques were used to identify outcome profiles . The analyses were then repeated after including third party compensation cl aim lodgment as a binary time‐changing covariate . Three distinct NDI trajectories were determined : ( 1 ) Mild : mild or negligible pain/disability for the entire 12 months ( 45 % ) , ( 2 ) Moderate : initial moderate pain/disability that decreased to mild levels by 3 months ( 39 % ) and ( 3 ) Chronic‐severe : severe pain/disability persisting at moderate/severe levels for 12 months ( 16 % ) . Three distinct PTSD trajectories were also identified : ( 1 ) Resilient : mild symptoms throughout ( 40 % ) , ( 2 ) Recovering : initial moderate symptoms declining to mild levels by 3 months ( 43 % ) and ( 3 ) Chronic moderate‐severe : persistent moderate/severe symptoms throughout 12 months ( 17 % ) . Cl aim su bmi ssion had a detrimental effect on all trajectories ( p < 0.001 ) except for the Chronic‐severe NDI trajectory ( p = 0.098 ) . Following whiplash injury , there are distinct pathways of recovery for pain/ disability and PTSD symptoms . Management of whiplash should consider the detrimental association of compensation cl aim with psychological recovery and recovery of those with mild to moderate pain/disability levels . However , cl aim lodgement has no significant association with a more severe pain and disability trajectory Study Design Secondary analysis of a prospect i ve cohort study with cross-sectional and longitudinal analyses . Background The clinical importance of a history of whiplash-associated disorder ( WAD ) in people with neck pain remains uncertain . Objective To compare people with WAD to people with nonspecific neck pain , in terms of their baseline characteristics and pain and disability outcomes over 1 year . Methods Consecutive patients with neck pain who presented to a secondary -care spine center answered a comprehensive self-report question naire and underwent a physical examination . Patients were classified into a group of either those with WAD or those with nonspecific neck pain . We compared the outcomes of baseline characteristics of the 2 groups , as well as pain intensity and activity limitation at follow-ups of 6 and 12 months . Results A total of 2578 participants were included in the study . Of these , 488 ( 19 % ) were classified as having WAD . At presentation , patients with WAD were statistically different from patients without WAD for almost all characteristics investigated . While most differences were small ( 1.1 points on an 11-point pain-rating scale and 11 percentage points on the Neck Disability Index ) , others , including the presence of dizziness and memory difficulties , were substantial . The between-group differences in pain and disability increased significantly ( P<.001 ) over 12 months . At 12-month follow-up , the patients with WAD had on average approximately 2 points more pain and 17 percentage points more disability than those with nonspecific neck pain . Conclusion People referred to secondary care with WAD typically had more self-reported pain and disability and experienced worse outcomes than those with nonspecific neck pain . Caution is required when interpreting the longitudinal outcomes due to lower-than-optimal follow-up rates . Level of Evidence Prognosis , level 2 . J Orthop Sports Phys Ther 2016;46(10):894 - 901 . Epub 3 Sep 2016 . doi:10.2519/jospt.2016.6588 OBJECTIVES To determine whether adding a physiotherapist-led cognitive-behavioural intervention to an exercise programme improved outcome in patients with chronic neck pain ( CNP ) . DESIGN Multicentre r and omised controlled trial . SETTING Four outpatient physiotherapy departments . PARTICIPANTS Fifty-seven patients with CNP . Follow-up data were provided by 39 participants [ 57 % of the progressive neck exercise programme ( PNEP ) group and 79 % of the interactive behavioural modification therapy ( IBMT ) group ] . INTERVENTIONS Twenty-eight subjects were r and omised to the PNEP group and 29 subjects were r and omised to the IBMT group . IBMT is underpinned by cognitive-behavioural principles , and aims to modify cognitive risk factors through interactive educational sessions , grade d exercise and progressive goal setting . MAIN OUTCOME MEASURES The main outcome measure was disability , measured by the Northwick Park Question naire ( NPQ ) . Secondary outcomes were the Numeric Pain Rating Scale ( NPRS ) , Pain Catastrophising Scale , Tampa Scale for Kinesiophobia ( TSK ) , Chronic Pain Self-efficacy Scale ( CPSS ) and the Pain Vigilance and Awareness Question naire . RESULTS No significant between-group differences in disability were observed ( mean NPQ change : PNEP=-7.2 , IBMT=-10.2 ) . However , larger increases in functional self-efficacy ( mean CPSS change : PNEP=1.0 , IBMT=3.2 ) and greater reductions in pain intensity ( mean NPRS change : PNEP=-1.0 , IBMT=-2.2 ; P<0.05 ) and pain-related fear ( mean TSK change : PNEP=0.2 , IBMT=-4.7 , P<0.05 ) were observed with IBMT . Additionally , a significantly greater proportion of participants made clinical ly meaningful reductions in pain ( 25 % vs 55 % , P<0.05 ) and disability ( 25 % vs 59 % , P<0.05 ) with IBMT . CONCLUSIONS The primary outcome did not support the use of cognitive-behavioural physiotherapy in all patients with CNP . However , superior outcomes were observed for several secondary measures , and IBMT may offer additional benefit in some patients . CLINICAL TRIAL REGISTRATION NUMBER IS RCT N27611394 Summary This r and omised trial showed that multiprofessional stratified management had no effect beyond usual care in reducing transition rates to chronicity in patients with acute whiplash . ABSTRACT Acute whiplash is a heterogeneous disorder that becomes persistent in 40 % to 60 % of cases . Estimates of recovery have not changed in recent decades . This r and omized , single‐blind , controlled trial tested whether multidisciplinary individualized treatments for patients with acute whiplash ( < 4 weeks postinjury ) could reduce the incidence of chronicity at 6 mo by 50 % compared to usual care . Participants ( n = 101 ) were recruited from accident and emergency centres and the community . It was hypothesized that better recovery rates were achievable if the heterogeneity was recognised and patients received individualised interventions . Patients r and omized to pragmatic intervention ( n = 49 ) could receive pharmaceutical management ( ranging from simple medications to opioid analgesia ) , multimodal physiotherapy and psychology for post‐traumatic stress according to their presentations . The treatment period was 10 wks with follow‐up at 11 weeks and 6 and 12‐months . The primary outcome was neck pain and disability ( Neck Disability Index ( NDI ) ) . Analysis revealed no significant differences in frequency of recovery ( NDI ≤8 % ) between pragmatic and usual care groups at 6 months ( OR 95 % , CI = 0.55 , 0.23–1.29 ) , P = 0.163 ) or 12 mo ( OR 95 % , CI = 0.65 , 0.28–1.47 , P = 0.297 ) . There was no improvement in current nonrecovery rates at 6 mo ( 63.6 % , pragmatic care ; 48.8 % , usual care ) , indicating no advantage of the early multiprofessional intervention . Baseline levels of pain and disability had a significant bearing on recovery both at 6 and 12 mo in both groups , suggesting that future research focus on finding early effective pain management , particularly for the subgroup of patients with initial high levels of pain and disability , towards improving recovery rates Objectives : In chronic pain patients , impaired conditioned pain modulation ( CPM ) and exercise-induced hypoalgesia ( EIH ) have been reported . No studies have compared CPM and EIH in chronic musculoskeletal pain patients with high pain sensitivity ( HPS ) and low pain sensitivity ( LPS ) . Material s and Methods : On 2 days , manual pressure pain thresholds ( PPTs ) were recorded at the legs , arm , and shoulder in 61 chronic pain patients and they performed the cold pressor test , 2 exercise conditions ( bicycling and isometric contraction ) , and a control condition in a r and omized and counterbalanced order . PPTs , pain tolerance , pain tolerance limit , and temporal summation of pain were assessed with cuff algometry before and after the tests . On the basis of a median split of the average PPTs for women and men , respectively , low ( LPS ; N=30 ) and high ( HPS ; N=31 ) pain-sensitivity groups were created . Results : At baseline , cuff PPT and pain tolerance were decreased and temporal summation of pain was increased in the HPS group ( P<0.02 ) . Cuff PPT increased and pain tolerance limit decreased after the cold pressor test and exercises in LPS ( P<0.001 ) . Temporal summation of pain was increased after bicycling in HPS ( P<0.005 ) . Pain tolerance increased after the cold pressor test and exercise in both groups ( P<0.001 ) . Discussion : CPM and EIH were partly impaired in chronic pain patients with high versus less pain sensitivity , suggesting that the CPM and EIH responses depend on the degree of pain sensitivity . This has clinical implication s as clinicians should evaluate pain sensitivity when considering treatment options utilizing the descending modulatory pain control STUDY DESIGN R and omized clinical trial . Background The recommended initial management strategy for patients with low back pain and signs of nerve root compression is conservative treatment , but there is little evidence to guide the most appropriate management strategy . Preliminary research suggests that a treatment protocol of mechanical traction and extension-oriented exercises may be effective , particularly in a specific subgroup of patients . OBJECTIVE To examine the effectiveness of mechanical traction in patients with lumbar nerve root compression and within a predefined subgroup . METHODS One hundred twenty patients with low back pain with nerve root compression were recruited from physical therapy clinics . Using predefined subgrouping criteria , patients were stratified at baseline and r and omized to receive an extension-oriented treatment approach with or without the addition of mechanical traction . During a 6-week period , patients received up to 12 treatment visits . Primary outcomes of pain and disability were collected at 6 weeks , 6 months , and 1 year by assessors blinded to group allocation . Outcomes were examined using linear mixed-model analyses examining change over time by treatment and the interaction between treatment and subgrouping status . RESULTS The mean ± SD age of participants was 41.1 ± 11.3 years , median duration of symptoms was 62 days , and 57 % were male . No significant differences in disability or pain outcomes were noted between treatment groups at any time point , nor was any interaction found between subgroup status and treatment . CONCLUSION Patients with lumbar nerve root compression presenting for physical therapy can expect significant changes in disability and pain over a 6-week treatment period . There is no evidence that mechanical lumbar traction in combination with an extension-oriented treatment is superior to extension-oriented exercises alone in the management of these patients or within a predefined subgroup of patients . The study protocol was registered with Clinical Trials.gov ( NCT00942227 ) . Level of Evidence Therapy , level 2b Effectiveness of exercise therapy in video display unit ( VDU ) workers with work-related chronic neck pain ( W-RCNP ) is unclear . The aim of the study was to assess the efficacy of group-based neck-shoulder resistance exercises on symptoms and muscular function in VDU workers with W-RCNP . Thirty-five employees with CNP were r and omly assigned to neck-shoulder resistance exercise ( NSRE ) group or to conventional stretching and postural exercise ( SPE ) group . Participants trained 45 min , twice a week for 7 weeks . Primary outcomes were pain intensity ( 0–10 numeric rating scale , NRS ) and pain-related disability ( Vernon Neck Disability Index , NDI ) . Secondary outcomes were cervical active range of motion ( AROM ) , endurance of neck flexors , strength of shoulder abductors , and health-related quality of life ( SF-36 ) . Post-treatment , pain and disability decreased 2.5 and 5 points in NSRE ( p = 0.001 ) and 5 and 8 points in SPE ( p = 0.002 ) , with no significant differences between groups . AROM improved significantly in both groups ; between-group differences were not significant . Neck flexors endurance and shoulder abductors strength improved by 59.6 and 34.2 % ( p = 0.001 ) in the NSRE group and by 27.6 % ( p = 0.009 ) and 2.3 % ( p = 0.002 ) in the SPE group ; between-group differences were significant ( p = 0.016 and p < 0.001 , respectively ) . SF-36 score remained unchanged . NSRE and SPE are feasible and equally effective in reducing pain and pain-related disability as group exercises in W-RCNP . NSRE may provide some advantage in improving strength and endurance in neck muscles . Further , larger studies should confirm these findings and assess whether a better muscle function confers long-term clinical advantages Chronic musculoskeletal pain constitutes a large socioeconomic challenge , and preventive measures with documented effects are warranted . The authors ' aim in this study was to prospect ively investigate the association between physical exercise , body mass index ( BMI ) , and risk of chronic pain in the low back and neck/shoulders . The study comprised data on approximately 30,000 women and men in the Nord-Trøndelag Health Study ( Norway ) who reported no pain or physical impairment at baseline in 1984 - 1986 . Occurrence of chronic musculoskeletal pain was assessed at follow-up in 1995 - 1997 . A generalized linear model was used to calculate adjusted risk ratios . For both females and males , hours of physical exercise per week were linearly and inversely associated with risk of chronic pain in the low back ( women : P-trend = 0.02 ; men : P-trend < 0.001 ) and neck/shoulders ( women : P-trend = 0.002 ; men : P-trend < 0.001 ) . Obese women and men had an approximately 20 % increased risk of chronic pain in both the low back and the neck/shoulders . Exercising for 1 or more hours per week compensated , to some extent , for the adverse effect of high BMI on risk of chronic pain . The authors conclude that physical inactivity and high BMI are associated with an increased risk of chronic pain in the low back and neck/shoulders in the general adult population ABSTRACT Purpose : To compare the effectiveness of pain neuroscience education ( PNE ) and neck/shoulder exercises with no intervention in adolescents with chronic idiopathic neck pain ( CINP ) . Methods : Forty-three adolescents with CINP were r and omly allocated to receive PNE and shoulder/neck exercises ( n = 21 ) or no intervention ( n = 22 ) . Data on pain intensity , neck flexor and extensor muscles endurance , scapular stabilizers endurance , pain catastrophizing , anxiety , and knowledge of pain neurophysiology were collected . Measurements were taken before and after the intervention . Results : All participants completed the study . Analysis using ANCOVA revealed a significant increase in the neck extensors endurance capacity ( adjusted mean ± SE change = + 47.5 ± 13.5 s versus + 14.2 ± 13.1 s ) and knowledge of pain neurophysiology ( adjusted mean ± SE change = + 9.8 ± 3.2 versus −0.6 ± 0.6 ) in the group receiving the intervention . A higher mean decrease in pain intensity , pain catastrophizing and anxiety and a higher mean increase in the scapular stabilizers endurance capacity were also found in the intervention group , but differences did not reach statistical significance . Conclusions : Results suggest a potential benefit of PNE and exercise for adolescents with CINP . Further studies with larger sample sizes are needed STUDY DESIGN Retrospective secondary analysis of data . OBJECTIVES To investigate the external validity of the whiplash clinical prediction rule ( CPR ) . BACKGROUND We recently derived a whiplash CPR to consoli date previously established prognostic factors for poor recovery from a whiplash injury and predicted 2 recovery pathways . Prognostic factors for full recovery were being less than 35 years of age and having an initial Neck Disability Index ( NDI ) score of 32 % or less . Prognostic factors for ongoing moderate/severe pain and disability were being 35 years of age or older , having an initial NDI score of 40 % or more , and the presence of hyperarousal symptoms . Validation is required to confirm the reproducibility and accuracy of this CPR . Clinician feedback on the usefulness of the CPR is also important to gauge acceptability . METHODS A secondary analysis of data from 101 individuals with acute whiplash-associated disorder who had previously participated in either a r and omized controlled clinical trial or prospect i ve cohort study was performed using accuracy statistics . Full recovery was defined as NDI score at 6 months of 10 % or less , and ongoing moderate/severe pain and disability were defined as an NDI score at 6 months of 30 % or greater . In addition , a small sample of physical therapists completed an anonymous survey on the clinical acceptability and usability of the tool . Results The positive predictive value of ongoing moderate/severe pain and disability was 90.9 % in the validation cohort , and the positive predictive value of full recovery was 80.0 % . Surveyed physical therapists reported that the whiplash CPR was simple , underst and able , would be easy to use , and was an acceptable prognostic tool . CONCLUSION External validation of the whiplash CPR confirmed the reproducibility and accuracy of this dual-pathway tool for individuals with acute whiplash-associated disorder . Further research is needed to assess prospect i ve validation , the impact of inclusion on practice , and to examine the efficacy of linking treatment strategies with predicted prognosis . LEVEL OF EVIDENCE Prognosis , level 1b INTRODUCTION Whiplash-associated disorders ( WAD ) are a huge worldwide health and economic burden . The propensity towards developing into chronic , disabling conditions drives the rise in health and economic costs associated with treatment , productivity loss and compulsory third party insurance cl aims . Current treatments fail to address the well-documented heterogeneity of WAD and often result in poor outcomes . A novel approach is to evaluate whether the care provided according to the estimated risk of poor prognosis improves health outcomes while remaining cost-effective . RESEARCH QUESTIONS ( 1 ) Does a guideline -based clinical pathway of care improve health outcomes after whiplash injury compared to usual care ? ( 2 ) Does risk of recovery have a differential effect on health outcomes for the clinical pathway of care ? ( 3 ) Is the clinical pathway of care intervention cost-effective ? ( 4 ) What are the variations in professional practice between usual care and the clinical pathway of care ? DESIGN Multi-centre , r and omised , controlled trial conducted over two Australian states : Queensl and and New South Wales . PARTICIPANTS AND SETTING 236 people with WAD ( grade I-III , within 6 weeks of injury ) and their primary healthcare providers . INTERVENTION A clinical pathway of care , with care matched to the predicted risk of poor recovery . Participants at low risk of ongoing pain and disability ( hence , predicted to fully recover ) will receive up to three sessions of guideline -based advice and exercise with their primary healthcare provider . Participants at medium/high risk of developing ongoing pain and disability will be referred to a specialist ( defined as a practitioner with expertise in whiplash ) who will conduct a more in-depth physical and psychological assessment . As a result , the specialist will liaise with the original primary healthcare provider and determine one of three further pathways of care . CONTROL Usual care provided by the primary healthcare provider that is based on clinical judgment . MEASUREMENTS Primary ( global rating of change and neck-related disability ) and secondary ( self-efficacy , pain intensity , general health and disability and psychological health ) outcomes will be collected using vali date d scales . Direct ( eg , professional care , transportation costs , time spent for care , co-payments ) and indirect ( eg , lost economic productivity ) costs will be obtained through an electronic cost diary . Health and cost outcomes will be assessed at baseline , 3 , 6 and 12 months after r and omisation . Professional practice outcomes will be evaluated through question naires completed by healthcare providers and their patients at 3 months . PROCEDURE Potential participants ( patients ) will be identified through emergency departments , primary health clinics and advertisements . Eligible participants will complete baseline assessment s and will be categorised into low or medium/high risk of poor recovery using a clinical prediction rule . After this assessment , participants will be r and omly allocated to either a control group ( n=118 ) or intervention group ( n=118 ) , stratified by risk subgroup and treatment site . The participants ' nominated primary healthcare providers will be informed of their involvement in the trial . Consent will be obtained from the primary healthcare providers to participate and to obtain information about professional practice . Participants in the intervention group will additionally have access to an interactive website that provides information about whiplash and recovery relative to their risk category . ANALYSIS Analysis will be conducted on an intention-to-treat basis . Outcomes will be analysed independently through cross-sectional analyses using generalised linear models methods , with an appropriate link function , to test for an intervention effect , adjusted for the baseline values . The risk category will be tested for its association with treatment effect by adding risk group to the regression equation . Cost-effectiveness will be calculated using utility weights and the result ing measure will be cost per quality -adjusted life year ( QALY ) saved . Professional practice outcomes will be analysed using descriptive statistics . DISCUSSION This research is significant as it will be the first study to address the heterogeneity of whiplash by implementing a clinical pathway of care that matches evidence -based interventions to projected risk of poor recovery . The results of this trial have the potential to change clinical practice for WAD , thereby maximising treatment effects , improving patient outcomes , reducing costs and maintaining the compulsory third party system Objective : To determine the effectiveness of neck and shoulder stretching exercises for relief neck pain among office workers . Design : R and omized controlled trial . Setting : An outpatient setting . Participants : A total of 96 subjects with moderate-to-severe neck pain ( visual analogue score ⩾5/10 ) for ⩾3 months . Interventions : All participants received an informative brochure indicating the proper position and ergonomics to be applied during daily work . The treatment group received the additional instruction to perform neck and around shoulder stretching exercises two times/day , five days/week during four weeks . Main outcomes : Pain , neck functions , and quality of life were evaluated at baseline and week 4 using pain visual analogue scale , Northwick Park Neck Pain Question naire , and Short Form-36 , respectively . Results : Both groups had comparable baseline data . All outcomes were improved significantly from baseline . When compared between groups , the magnitude of improvement was significantly greater in the treatment group than in the control group ( –1.4 ; 95 % CI : –2.2 , –0.7 for visual analogue scale ; –4.8 ; 95 % CI : –9.3 , –0.4 for Northwick Park Neck Pain Question naire ; and 14.0 ; 95 % CI : 7.1 , 20.9 for physical dimension of the Short Form-36 ) . Compared with the patients who performed exercises <3 times/week , those who exercised ⩾3 times/week yielded significantly greater improvement in neck function and physical dimension of quality of life scores ( p = 0.005 and p = 0.018 , respectively ) . Conclusion : A regular stretching exercise program performed for four weeks can decrease neck and shoulder pain and improve neck function and quality of life for office workers who have chronic moderate-to-severe neck or shoulder pain Background The STarT Back strategy for categorizing and treating patients with low back pain ( LBP ) improved patients ’ function while reducing costs in Engl and . Objective This trial evaluated the effect of implementing an adaptation of this approach in a US setting . Design The Matching Appropriate Treatments to Consumer Healthcare needs ( MATCH ) trial was a pragmatic cluster r and omized trial with a pre-intervention baseline period . Six primary care clinics were pair r and omized , three to training in the STarT Back strategy and three to serve as controls . Participants Adults receiving primary care for non-specific LBP were invited to provide data 2 weeks after their primary care visit and follow-up data 2 and 6 months ( primary endpoint ) later . Interventions The STarT Back risk-stratification strategy matches treatments for LBP to physical and psychosocial obstacles to recovery using patient-reported data ( the STarT Back Tool ) to categorize patients ’ risk of persistent disabling pain . Primary care clinicians in the intervention clinics attended six didactic sessions to improve their underst and ing LBP management and received in-person training in the use of the tool that had been incorporated into the electronic health record ( EHR ) . Physical therapists received 5 days of intensive training . Control clinics received no training . Main measures Primary outcomes were back-related physical function and pain severity . Intervention effects were estimated by comparing mean changes in patient outcomes after 2 and 6 months between intervention and control clinics . Differences in change scores by trial arm and time period were estimated using linear mixed effect models . Secondary outcomes included healthcare utilization . Key Results Although clinicians used the tool for about half of their patients , they did not change the treatments they recommended . The intervention had no significant effect on patient outcomes or healthcare use . Conclusions A re source -intensive intervention to support stratified care for LBP in a US healthcare setting had no effect on patient outcomes or healthcare use . Trial Registration National Clinical Trial Number NCT02286141 Objective There are few effective treatments for acute whiplash-associated disorders ( WAD ) . Early symptoms of postinjury stress predict poor recovery . This r and omised controlled trial ( StressModex ) investigated whether physiotherapist-led stress inoculation training integrated with exercise is more effective than exercise alone for people with acute WAD . Methods 108 participants ( < 4 weeks ) at risk of poor recovery ( moderate pain-related disability and hyperarousal symptoms ) were r and omly assigned by concealed allocation to either physiotherapist-led stress inoculation training and guideline -based exercise ( n=53 ) or guideline -based exercise alone ( n=55 ) . Both interventions comprised 10 sessions over 6 weeks . Participants were assessed at 6 weeks and at 6 and 12 months postr and omisation . Analysis was by intention to treat using linear mixed models . Results The combined stress inoculation training and exercise intervention was more effective than exercise alone for the primary outcome of pain-related disability at all follow-up points . At 6 weeks , the treatment effect on the 0–100 Neck Disability Index was ( mean difference ) −10 ( 95 % CI −15.5 to −4.48 ) , at 6 months was −7.8 ( 95 % CI −13.8 to −1.8 ) and at 12 months was −10.1 ( 95 % CI −16.3 to −4.0 ) . A significant benefit of the stress inoculation and exercise intervention over exercise alone was also found for some secondary outcomes . Conclusion A physiotherapist-led intervention of stress inoculation training and exercise result ed in clinical ly relevant improvements in disability compared with exercise alone — the most commonly recommended treatment for acute WAD . This contributes to the case for physiotherapists to deliver an early psychological intervention to patients with acute WAD who are otherwise at high risk of a poor outcome . Trial registration number ACTRN12614001036606 Objectives : To assess which psychological factors are important in the development of chronic whiplash symptoms . Methods : Search es were conducted across PubMed , CINAHL , Scopus , and PsychINFO up until March 2017 . Studies were included if they investigated psychological prognostic factors in association with recovery from a whiplash injury . Studies also had to be prospect i ve , cohort , follow-up or observational studies , have a 6 month follow-up and published in English . Quality assessment s were conducted by 2 independent review ers . Thirty-one articles were included investigating 34 psychological factors . Results : Poor expectations of recovery , posttraumatic stress symptoms and passive coping emerged as the most consistent prognostic factors of chronic neck pain and /or disability after a whiplash injury . Anxiety , travel anxiety , depression , personality , precollision distress , general psychological distress , and avoidance behavior were not associated with chronic whiplash problems Objective : To investigate the comparative effectiveness of current st and ard treatment , against an individually tailored behavioural programme delivered via the Internet or face-to-face for people with acute whiplash associated disorders . Design : A multicentre , r and omized , three-group design , with concealed allocation . Subjects and setting s : A total of 55 participants ( 37 female ) , age 18–65 , with acute Whiplash Associated Disorder ( Grade I – II ) , recruited at two emergency clinics in Sweden . Interventions : Before r and omization all participants received st and ard self-care instructions . The Internet and face-to-face groups followed a seven-week behavioural programme involving individual tailoring , via email ( Internet group ) , or in sessions at a physical therapy unit ( face-to-face group ) . The control group only received the self-care instructions . Main measures : Pain-related disability , pain intensity , self-efficacy in daily activities , catastrophizing and fear of movement/(re)injury . Assessment s were performed at baseline ( 2–4 weeks postinjury ) and at three , six and 12 months postintervention . Results : Both the Internet ( n = 16 ) and face-to-face ( n = 14 ) group showed a larger decrease in pain-related disability than the control group ( n = 16 ) ; −12 and −11 , respectively , compared with −5 in the control group at 12-months follow-up . Significant differences between the groups in overall treatment effect were shown in all outcomes except pain intensity . All groups improved significantly over time in all outcomes , except for fear of movement/(re)injury and catastrophizing in the control group . Conclusion : An individually tailored behavioural programme improved biopsychosocial factors in patients with whiplash associated disorders up to 12 months after treatment . Internet-delivered intervention was as effective as clinic-based face-to-face therapy sessions |
659 | 23,760,885 | There was no significant difference in quality of life , rescue medication , requirement for oral corticosteroids , visits to the GP , emergency department ( ED ) or hospitalisations for asthma .
There was no significant difference in the house dust mite count and the antigen levels in the new trial , in contrast to the previous trial .
Evidence on clinical benefits of dehumidification using mechanical ventilation with dehumidifiers remains scanty , and the addition of a new double blind trial to this review does not indicate significant benefit in most measure of control of asthma from such environmental interventions | BACKGROUND Humidity control measures in the home environment of patients with asthma have been recommended , since a warm humid environment favours the growth of house dust mites .
However , there is no consensus about the usefulness of these measures .
OBJECTIVES To study the effect of dehumidification of the home environment on asthma control . | 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 Background : It is not clear whether associations between respiratory symptoms and indoor mould are causal . A r and omised controlled trial was conducted to see whether asthma improves when indoor mould is removed . Methods : Houses of patients with asthma were r and omly allocated into two groups . In one group , indoor mould was removed , fungicide was applied and a fan was installed in the loft . In the control group , intervention was delayed for 12 months . Question naires were administered and peak expiratory flow rate was measured at baseline , 6 months and 12 months . Results : Eighty-one houses were allocated to the intervention group and 83 to the control group ; 95 participants in 68 intervention houses and 87 in 63 control houses supplied follow-up information . Peak expiratory flow rate variability declined in both groups , with no significant differences between them . At 6 months , significantly more of the intervention group showed a net improvement in wheeze affecting activities ( difference between groups 25 % , 95 % CI 3 % to 47 % ; p = 0.028 ) , perceived improvement of breathing ( 52 % , 95 % CI 30 % to 74 % ; p<0.0001 ) and perceived reduction in medication ( 59 % , 95 % CI 35 % to 81 % ; p<0.0001 ) . By 12 months the intervention group showed significantly greater reductions than the controls in preventer and reliever use , and more improvement in rhinitis ( 24 % , 95 % CI 9 % to 39 % ; p = 0.001 ) and rhinoconjunctivitis ( 20 % , 95 % CI 5 % to 36 % ; p = 0.009 ) . Conclusions : Although there was no objective evidence of benefit , symptoms of asthma and rhinitis improved and medication use declined following removal of indoor mould . It is unlikely that this was entirely a placebo effect Objective Home dampness and the presence of mold and allergens have been associated with asthma morbidity . We examined changes in asthma morbidity in children as a result of home remediation aim ed at moisture sources . Design In this prospect i ve , r and omized controlled trial , symptomatic , asthmatic children ( n = 62 ) , 2–17 years of age , living in a home with indoor mold , received an asthma intervention including an action plan , education , and individualized problem solving . The remediation group also received household repairs , including reduction of water infiltration , removal of water-damaged building material s , and heating/ventilation/air-conditioning alterations . The control group received only home cleaning information . We measured children ’s total and allergen-specific serum immuno-globulin E , peripheral blood eosinophil counts , and urinary cotinine . Environmental dust sample s were analyzed for dust mite , cockroach , rodent urinary protein , endotoxin , and fungi . The follow-up period was 1 year . Results Children in both groups showed improvement in asthma symptomatic days during the preremediation portion of the study . The remediation group had a significant decrease in symptom days ( p = 0.003 , as r and omized ; p = 0.004 , intent to treat ) after remodeling , whereas these parameters in the control group did not significantly change . In the postremediation period , the remediation group had a lower rate of exacerbations compared with control asthmatics ( as treated : 1 of 29 vs. 11 of 33 , respectively , p = 0 . 003 ; intent to treat : 28.1 % and 10.0 % , respectively , p = 0.11 ) . Conclusion Construction remediation aim ed at the root cause of moisture sources and combined with a medical/behavioral intervention significantly reduces symptom days and health care use for asthmatic children who live in homes with a documented mold problem Exposure to house‐dust mites ( Dermatophagoides spp . ) was investigated in 30 asthmatic patients before and after moving to homes with mechanical ventilation systems . Median house‐dust mite concentration was 110 mites per gram of mattress dust at the initial investigation and 20 mites per gram at the first follow‐up after a mean of 4.7 months in the new homes . This was lower ( P < 0.05 ) than counts in a control group of 23 asthmatic patients that had unchanged counts . At a second follow‐up , after 15.0 months , mite counts in the study group were further reduced ( P < 0.01 ) from initial values . Among 16 patients , with initial mite counts above the recommended threshold limit value ( TLV ) of 100 mites per gram of dust , the mite counts fell , in most cases , below this TLV . Air‐exchange rates increased ( P < 0.001 ) from a median value of 0.40 air changes per hour ( ach ) to 1.52 ach at the second follow‐up investigation . Furthermore , a reduction ( P < 0.01 ) was found in indoor absolute air humidity , with a median value of 5.6 g of water/kg . No such changes were found in the control group . The present study indicates that reduction of air humidity through an increased supply of fresh air may significantly diminish and , in some cases , even eliminate house‐dust mites in homes To evaluate the effect of a room high-efficiency particulate air ( HEPA ) cleaner on cat-induced asthma and rhinitis , 35 cat-allergic subjects who were living with one or more cats were studied in a double-blind , placebo controlled trial . After a 1 mo baseline period , subjects ' bedrooms were equipped with an active or placebo air cleaner for the following 3 mo . Evaluations included monthly measurement of cat-allergen levels , daily morning , afternoon , and nighttime nasal- and chest-symptom scores , twice-daily measurement of peak-flow rates , daily medication scores , monthly spirometry , and methacholine ( MCh ) challenge testing before and after the study . Airborne allergen levels were reduced in the active-filter group as compared with the placebo group ( p = 0.045 ) . However , no differences were detected in settled-dust allergen levels ( p = 0.485 ) , morning , afternoon , or nighttime nasal-symptom scores ( p = 0.769 , 0.534 , and 0.138 ) , chest-symptom scores ( p = 0.388 , 0.179 , and 0.215 ) , sleep disturbance ( p = 0.101 ) , morning or afternoon peak-flow rates ( p = 0 . 424 and 0.679 ) , or rescue medication use ( nasal , p = 0.164 , chest , p = 0.650 ) , respectively . Although the combination of a HEPA room air cleaner , mattress and pillow covers , and cat exclusion from the bedroom did reduce airborne cat-allergen levels , no effect on disease activity was detected for any parameter studied This study looked at the influence of inspired air water content on exercise-induced bronchospasm ( EIB ) . On separate days , 12 mild asthmatics ( 4 M , 8F ) , aged 18 - 39 yrs ( mean : 27 yrs ) , performed four six minute steady-state exercises on ergometer at 80 % of their maximum workload . Exercises were r and omized to the following inspired air conditions : dry air ( 0 % relative humidity ( RH ] during exercise followed by dry ( DD ) or humid air ( 100 % RH ) ( DH ) after exercise , humid air during exercise followed by dry ( HD ) or humid air ( HH ) . Room temperature was kept constant ( 22 + /- 1 degree C ) at all visits . Forced expiratory volume in one second ( FEV1 ) was measured before and every 5 min for 25 min after exercise . Ventilation ( VE ) was not significantly different whether the exercise was done under dry or humid air . There was a residual bronchodilatation at the end of exercises performed in humid air , while at this time FEV1 was already lower than baseline when exercise was done in dry air conditions . The maximal fall in FEV1(% ) following exercise was significantly greater after those performed in dry air : DD ( 29 + /- 5.6 % ) and DH ( 30 + /- 5.8 % ) than in humid air : HD ( 12 + /- 4.9 % ) and HH ( 20 + /- 4.9 % ) ( p less than 0.05 ) . The time-course of recovery from bronchoconstriction was significantly improved when inhaling dry air after exercise . However , the difference found in the maximal % fall in FEV1 after exercise when recovery was in dry compared to humid air did not achieve statistical significance . In conclusion , EIB is influenced by the changes in water content during and after exercise . Bronchoconstriction following exercise is minimal if exercise is done in humid air and recovery in dry air , and maximal if the exercise is performed in dry air and recovery in humid air We have examined the effect of reducing relative humidity ( RH ) , with inbuilt mechanical ventilation and heat‐exchange ( MVHE ) units , on house‐dust‐ mite ( HDM ) counts and allergen levels , in a pilot study of 10 Wellington dwellings . Recent international prevalence studies in adults and children have confirmed a high prevalence of asthma in New Zeal and , Sensitivity to HDM is common among the general population , and HDM is the major allergen associated with asthma . Recent studies of allergen levels have confirmed high concentrations of Der p 1 in the domestic environment . While humidity was significantly reduced in those dwellings fitted with ventilation units , no systematic effect on mites or Der p 1 was observed during the study period . When the reductions in humidity were examined in the context of the time spent below the critical equilibrium humidity ( CEH ) , the intervention led to RH values below the CEH for only 39 % of the total of 24‐h periods for which measurements were made . Reducing RH by means of MVHE in New Zeal and domestic dwellings does not lower humidity sufficiently , or long enough , to have any measurable effect on HDM population To evaluate the effect of preventive measures 46 patients , all allergic to house‐dust mites ( Dermatophagoides spp . ) , were r and omly allocated to a study and a control group . According to the patients ' subjective recordings of symptom score and use of medicine , compared with the control group , the study group had improved . There was , however , no improvement when comparing the objective recordings of morning and evening peak flow and use of medicine , and it is concluded that the preventive measures in this programme are not very effective for patients allergic to house‐dust mites . The reduction in indoor humidity in the study group was limited and , as a high indoor humidity is the cause of huge population s of house‐dust mites in homes , it is emphasized that future programmes of preventive measures should focus more on damp problems , particularly those related to bad housing construction BACKGROUND The relationship between exposure to house dust mite ( HDM ) allergens and prevalence of sensitization to these allergens in patients with asthma has been confirmed in many studies . Mite population growth is regulated by humidity . Reducing humidity and removing allergen by efficient vacuuming should control mite allergen and reduce symptoms . OBJECTIVE We sought to investigate the effect of mechanical ventilation and high-efficiency vacuuming on HDM numbers and Der p 1 concentrations in the homes of mite-sensitive asthmatic subjects and to evaluate the effect of any reductions on symptoms . METHODS The homes of 40 HDM-sensitive asthmatic subjects were r and omized to receive ( 1 ) mechanical ventilation and a high-efficiency vacuum cleaner ( HEVC ) ; ( 2 ) mechanical ventilation alone ; ( 3 ) an HEVC alone ; and ( 4 ) no intervention . Homes and patients were monitored for 12 months . Change in absolute humidity , mite numbers , Der p 1 concentrations , lung function , bronchial hyperresponsiveness , and symptom scores were analyzed . RESULTS Homes with mechanical ventilation achieved significantly lower humidity levels than those without ( P < .001 ) , with an associated reduction of mite numbers ( P < .05 ) and Der p 1 concentrations ( P < .001 ¿ in nanograms per gram , P = .006 ¿ in milligrams per square meter ) in bedroom carpets and some other mite sources in the ventilated areas of the homes . The addition of a vacuum cleaner enhanced this effect . There was a trend for an improvement in histamine PC(20 ) ( P = .085 ) in the patients whose homes were ventilated . CONCLUSION The use of a mechanical ventilation system in suitable homes result ed in some reduction in numbers of HDM and Der p 1 concentrations . The addition of an HEVC slightly enhanced the effect but not sufficiently to see an improvement in symptoms House dust mites ( HDM ) are sensitive to humidity . Few studies have adequately examined the potential of dehumidification in reducing HDM numbers . |
660 | 22,513,926 | The effect of HBOT varied with different fractionation schemes .
Any advantage is achieved at the cost of some adverse effects .
AUTHORS ' CONCLUSIONS There is some evidence that HBOT improves local tumour control and mortality for cancers of the head and neck , and local tumour recurrence in cancers of the head and neck , and uterine cervix .
These benefits may only occur with unusual fractionation schemes .
HBOT is associated with significant adverse effects including oxygen toxic seizures and severe tissue radiation injury . | BACKGROUND Cancer is a common disease and radiotherapy is one well-established treatment for some solid tumours .
Hyperbaric oxygenation therapy ( HBOT ) may improve the ability of radiotherapy to kill hypoxic cancer cells , so the administration of radiotherapy while breathing hyperbaric oxygen may result in a reduction in mortality and recurrence .
OBJECTIVES To assess the benefits and harms of radiotherapy while breathing HBO . | Since 1971 , 82 patients with advanced carcinoma of the cervix have been included in a r and omised clinical trial in association with the Working Party on Radiotherapy and Hyperbaric Oxygen of the Medical Research Council . External irradiation was given in 10 fractions by an unconventional schedule , either in air or HBO , and combined with three large fractions of intracavitary irradiation using the Cathetron . The results are acceptable overall , with 69 % local control , 15 % with tumour developing outside the treated volume and 40 % survival at five years , but no improvement has been shown with HBO . Symptoms suggestive of some degree of late damage to the small bowel were present in 13 % of patients , with a higher but not statistically significant , incidence in the HBO group . It is postulated that the schedule of radiotherapy used has allowed reoxygenation during treatment and that no further gain due to the use of HBO may be achieved . After a review of the results from other centres and taking into account the difficulties of treatment in HBO it is concluded that for advanced carcinoma of the cervix the addition of HBO to radiotherapy is not clinical ly worthwhile BACKGROUND AND PURPOSE A r and omised controlled trial of hyperbaric oxygen in the radiotherapy of Stage IIb and III carcinoma of cervix was performed between 1971 and 1980 . Apart from an abstract giving an interim report in 1977 , results have not been published . MATERIAL AND METHODS In a four arm study , 335 patients were r and omised to treatment in 10 or 28 fractions , in hyperbaric oxygen or in air . Data is available concerning 327 cases and this has been analysed . RESULTS There was no advantage in tumour control shown with the use of hyperbaric oxygen . There was evidence for an increase in late radiation morbidity when treatment was given in hyperbaric oxygen rather than in air and when , using 10 fractions , a total dose of 45 rather than 40 Gy was achieved . For late intestinal morbidity , the fractionation sensitivity ( alpha/beta ratio ) was calculated to be 4.3 Gy and the steepness of the dose response curve ( gamma50 ) to be 2.6 . CONCLUSIONS Hyperbaric oxygen gave no benefit in the treatment of patients with stage IIb and III carcinoma of the cervix treated with radiotherapy using two fractionation regimes . Important data regarding late radiation morbidity has been revealed The 15 r and omised controlled clinical trials of hyperbaric oxygen in radiotherapy yielded three with highly significant benefit and six with useful margins not reaching statistical significance . The increase in tumour control was partly negated by an increase in normal tissue effect . Now simple carbogen breathing in animal tumour models has shown high efficiency and there is the potential for its use in man as a simple means of hypoxic cell radiosensitization Abstract In controlled trials using the hyperbaric oxygen chamber in the radiotherapy of carcinoma of the bladder , no benefit was found in a series of 40 patients treated using 30 fractions and a total dose of 6,000 R and in a series of 27 patients treated using 15 fractions and a total dose of 4,725R . In an uncontrolled trial in advanced cases using six fractions and a maximum tissue dose of 3,600 R results seemed improved despite the selection of cases . A new trial comparing this six-fraction technique with multiple fractions in air is now being carried out . Similar trials are being performed in a number of radiotherapy centres and it is planned to pool results so as to obtain a significant result at an early time . In the work reported , doses have been quoted in R units ; the absorbed dose can be obtained by multiplying stated values by 0·97 A controlled clinical trial is in progress to assess the value of hyperbaric oxygen and radiotherapy in the management of head and neck cancer . An established dose-fractionation schedule in hyperbaric oxygen is being compared with a widely used conventional schedule in air . Survival and local recurrence-free rates are significantly higher in the oxygen group , and the effects on normal tissue are similar in both groups . These findings suggest a genuine therapeutic advantage . There was a distinct improvement in the results of treating advanced laryngeal carcinoma , where there was a high survival rate , without resort to laryngectomy This is an interim report of a clinical trial of radiotherapy of advanced oropharyngeal cancer under hyperbaric oxygenation . Fifty-one cases are available for evaluation , 26 in the oxygen group , 12 in the Control Group I , and 13 in the Control Group II.The results are analyzed as to : ( 1 ) clearance rates of the primary tumor , in which a 23 per cent higher clearance rate for the primary tumor in the oxygen group than in the air Control Group I is noted ; ( 2 ) survival rates , in which a 13 - 15 per cent increase of the 5 year survival is revealed in the oxygen group , compared to the air Control Group I ; and ( 3 ) complication rates and incidence of distant metastases which are not higher in the oxygen group than in the control groups . Although the difference of local tumor clearance and the survival rates between the oxygen and the control groups are not statistically significant due to the small sample size , the evidence of improvement in both local tumor clearance and in survival rates from our series and from tha Twenty-seven patients with carcinoma of the bladder were treated at the Glasgow Institute of Radiotherapeutics as part of a national hyperbaric oxygen trial . These patients were treated on a 4 MeV linear accelerator either in air or in 3 atm , absolute , of oxygen , by r and om selection . Of these patients , one-third were found to have high-dose effects to an extent which necessitated surgery . No association was found between the incidence of high-dose effects and treatment in air or hyperbaric oxygen . The treatment protocol used in all cases was to give an intended modal tumour dose of 6000 rad in 24 fractions in approximately 5 weeks . As all patients had received the same modal dose , there was no apparent reason why some had developed high-dose effects . However , on the basis of a Cumulative Radiation Effect ( CRE ) analysis of the treatment regimes given , a close correlation was found between the maximum CRE achieved and the occurrence of high-dose effects . Above a threshold level of 1910 reu in the maximum CRE achieved , there was a high incidence and rapid onset of high-dose effects . The reasons for the occurrence of the exceptionally high CRE values found in some patients are discussed . From a review of clinical results of bladder treatments , it is apparent that at a CRE level of 1910 reu , the tumour control rate is still increasing with CRE . It is proposed that by choosing the dose given on any treatment schedule to keep the maximum value of the CRE achieved just below 1910 reu , the greatest probability of cure would be obtained with minimum complication rate Abstract An interim report is given of a r and omized controlled trial of hyperbaric oxygen in the treatment of carcinoma of the cervix . A total of 82 patients with late Stage II , Stage III and early Stage IV disease were included between January 1966 and June 1971 . A minimum tumour dose of 5,500 R was given to the pelvis , either in oxygen or in air , in 27 treatments over 37 days and was followed by a radium application . An assessment of the results in 77 cases is presented . Seventy per cent of patients treated in oxygen were alive and free from disease at one year and this compared with 50 per cent of the patients treated in air . The difference was not statistically significant and became less until the results were the same at three years . In the early years after treatment the local failure rate in oxygen cases was less than in air , but was not statistically significant . There is a significant correlation between the clinical and histological assessment of regression at the end of treatment and subsequen In a r and omized controlled clinical trial of hyperbaric oxygen in the radiotherapy of advanced carcinoma of the uterine cervix a total of 320 cases were contributed by four radiotherapy centres in the United Kingdom . The use of hyperbaric oxygen result ed in improved local control and survival . The benefit was greatest in patients under the age of 55 who presented with stage III disease . There was a slight increase in radiation morbidity but it seemed that the benefit of hyperbaric oxygen outweighed this increase in morbidity and that there was a true improvement in the therapeutic ratio We report the results of a prospect i ve controlled trial of the effect of hyperbaric oxygen as an adjuvant in radiotherapy of head and neck cancer . Patients were allocated r and omly to treatment in oxygen or air . The radiotherapy in both groups was identical in planning , dose , and fractionation -- i.e . , 3500 rads in 10 fractions in 3 weeks . There was no difference in the survival rate between the two groups . However , significantly better local tumour control was seen in the hyperbaric-oxygen group , particularly in smaller lesions ; there was significantly greater need for salvage surgery in the air group . Radiation effects on normal tissue appeared somewhat greater in the oxygen series , especially on laryngeal cartilage One hundred and thirty patients with locally advanced squamous carcinoma of the head and neck were treated in a prospect i ve r and omized trial to compare conventional irradiation ( 63.00 Gy in 30 fractions ) with a combination sensitizer regimen of misonidazole and hyperbaric oxygen . The drug ( 2.0 gm/m2 ) was given with each of six fractions of 6.0 Gy in hyperbaric oxygen at 3 ATA . The results support a previous study and favor the combination at 1 year at better than the 10 % level . This regimen could be useful for bulky primary or nodal disease The clinical trials of the use of hyperbaric oxygen in radiotherapy conducted by the Medical Research Council 's working party have shown that local cure and survival can be improved in head and neck and cervical cancer . Evidence for benefit has been presented in carcinoma of bronchus , but none has so far been found in carcinoma of the bladder . Although hyperbaric oxygen has produced increased effect upon normal tissues as well as upon tumour , a real improvement in therapeutic ratio appears to be present . The future use of hyperbaric oxygen in radiotherapy will depend upon a comparison of effectiveness with other methods now being tested to improve radiotherapy . The trials have yielded much fundamental and clinical data of general relevance in the radiotherapy of malignant disease Abstract A prospect i ve clinical trial has been established design ed to evaluate the role of hyperbaric oxygen in the treatment of patients with Stages 2b and 3 carcinoma of the cervix . Three Cathetron fractions using a line source , plus ten fractions of high energy external irradiation either in air or hyperbaric oxygen are given to the whole of the defined tumour volume . Details concerning the method of treatment adopted are presented and discussion of the problems involved . So far , 45 patients have been included and the preliminary results lend encouragement to the continuation of the overall treatment method irrespective of any possible benefits of hyperbaric oxygen which may appear in the long term Follow-up data at five years are reported for 24 patients with squamous cell carcinoma of the head and neck , included in a r and omised prospect i ve MRC study of radiotherapy in hyperbaric oxygen ( 10 fractions ) or air ( 15 or 20 fractions ) . Although few , the data show a significant gain in local control ( P less than 0.001 ) and survival ( P less than 0.05 ) with the use of hyperbaric oxygen but no increased tissue reactions or morbidity In a r and omized controlled clinical trial of hyperbaric oxygen in the radiotherapy of carcinoma of the bladder a total of 241 cases were contributed by four radiotherapy centres in the United Kingdom . In this trial where in each centre identical radiotherapy was employed for both oxygen and air cases , no benefit was shown with the use of hyperbaric oxygen Abstract A r and omized study of squamous cell carcinoma of the head and neck , with the exception of T , vocal cord lesions , compared 23 patients who were treated in air with doses of 250 rad four times a week to 6250 rad , to 21 patients who were treated at three atmospheres of hyperbaric oxygen with 12 x 400-rad fractions in approximately 32 days . Distribution by anatomic site and age were comparable . Distribution by stage was in favor of the air group since five Stage I patients were found in the air group but none in the hyperbaric oxygen group . The sex distribution was uneven-15 males to eight females in the air group and eight males to 13 females in the oxygen group . All patients were followed for a minimum of two years ; most patients were followed more than five years , with indefinite followup . The 12 × 400-rad schedule in four and one-half weeks in the hyperbaric oxygen group proved to be well tolerated without any significant increase in complications . Radiation myelitis can be avoided by limiting the spinal cord dose to 7 × 400 rad It is now well established that most animal solid tumors contain oxygen-deficient hypoxic cells and that these cells will influence the response of those tumors to radiation . Identifying hypoxic cells in human tumors has proven more difficult , primarily because most of the direct procedures used in animals are not applicable to humans . However , substantial indirect evidence , which goes back to as early as 1909 , clearly indicates the presence of hypoxia in human tumors , although with a considerable heterogeneity among individual tumors . Experimental studies during the last 30 years have shown that this source of radiation resistance can be effectively eliminated by a variety of procedures that include high oxygen-content gas breathing , nitrometric radiation sensitizers , blood transfusions , hemoglobin-oxygen affinity modifiers , and nicotinamide . A number of these procedures have also been tested clinical ly such that by 1995 over 10,000 patients in 83 r and omized trials had undergone treatment design ed to modify tumor hypoxia before radiation therapy . Although a number of these trials showed no benefit , an overview analysis showed that modification of tumor hypoxia significantly improved the locoregional tumor control after radiotherapy with an odds ratio of 1.21 ( 95 % confidence interval 1.12 - 1.30 ) . The treatment benefit could mostly be related to an improved response in head and neck with odds ratio 1.31 ( 1.19 - 1.43 ) and to a lesser extent in bladder tumors ; no significant effect was observed in other tumor sites ( cervix , lung and esophagus ) . Similar to the local control benefit , the overall survival rate improved with an overall odds ratio of 1.13 ( 1.05 - 1.21 ) . The overall results thus showed that the biological issue related to hypoxia appears to be a sound rationale , which may impact the outcome of radiotherapy , especially with head and neck carcinoma . However , despite this wealth of positive data , " hypoxic modification " still has no impact on general clinical practice In order to more comprehensively evaluate the potential of the oxygen effect in patients with advanced neoplastic disease of the head and neck , cervix , bladder , rectum , esophagus and brain , a r and omized series was design ed to test the efficacy of hyperbaric oxygen as an adjunct to radiation therapy as compared to radiation therapy alone . One-half of the patients admitted to this study of the theoretic potentials of hyperbaric oxygen received 100 per cent oxygen under 3 atmospheres absolute pressure as an adjunct to regularly fractionated daily radiation therapy . The other half received daily radiation therapy alone . This study was terminated prematurely by accidental explosive decompression and destruction of the chamber on the 52nd patient admitted to the series . Twelve of the original 52 patients remain at risk , 27 to 36 months . These patients are equally divided between the 2 modalities . There were no significant differences in survival noted in any of the anatomic areas of advanced neoplasms in the r and o From September 1968 to March 1974 , a r and omized clinical trial was carried out , using conventional fractionation , i.e. , five treatments per week , in 233 patients with advanced cancers of the uterine cervix — Stages IIB , IIIA IIIB and IVA . The age limit was 70 years and all patients had medical clearance . Lymphangiography and , in some patients , an exploratory laparotomy with selective lymphadenectomy , were done prior to treatment to determine the extent of nodal disease . The staging has not been changed either by lymphangiogram or lymphadenectomy findings . A few patients with bulky Stage I and IIA lesions were entered into the trial because of extensive nodal disease demonstrated either by lymphangiogram and /or lymphadenectomy . First , the patients were grouped according to the clinical stage . The second stratification was according to the lymphangiogram and /or selective lymphadenectomy findings . The patients were then r and omized to air or hyperbaric oxygen within each group . The patients were pressurized in a Vickers chamber at 3 atmosphere absolute , using a 20‐minute soak time prior to the irradiation . The size of the external beam portal was determined by the status of the nodes . The difference in absolute NED ( no evidence of disease ) survival rates for both groups as a whole and by stages is not statistically significant . There is no difference in the incidence of failures in the irradiated area between the HPO and air patients . There is no increase in distant metastases in the HPO group . It does not seem that the HPO has had an effect on the major complications . However , there was an increase in the incidence of complications with extended fields . The addition of lymphadenectomy has increased the incidence of fatal complications , even with routine pelvic portals . The negative results of this trial with conventional fractionation should not lead to the conclusion that HPO could not be useful with schemes using few high dose fractions 104 patients with head and neck cancer were entered into a prospect i ve controlled trial of radiotherapy in hyperbaric oxygen ( HBO ) . The trial compared 10 fractions of radiotherapy in HBO with 30 fractions of radiotherapy in air . Survival and local control rates were significantly higher in the HBO group . No difference in normal tissue effects were detected . The greatest advantage of HBO was seen in the less advanced tumors Abstract A total of 65 patients with Stage IIB , IIIA , III3 or IVA carcinoma of the cervix were r and omized to receive conventional radiation therapy in air or hyperbaric oxygen therapy with radiation at optimal schedules . Seven patients could not be evaluated . Of the 19 patients treated in oxygen , 14 ( 73 % ) were living or had died without evidence of disease . Of the 29 patients treated with radiation alone 15 ( 52 % ) were alive or had died without evidence of tumor . Two of 29 patients treated in air and 5 of 19 patients treated in oxygen were dead of complications or intercurrent disease . No significant difference in survival could be demonstrated PURPOSE The purpose of this study was to present the results of a r and omized trial evaluating HBO-4 in combination with hypofractionated radiation therapy in patients with locally advanced squamous cell carcinoma of the head and neck ( SCCHN ) . METHODS AND MATERIAL S Between April 1974 and December 1975 , 48 patients with locally advanced unresected SCCHN , referred for primary radiation therapy , were r and omized to radiation delivered in air in two fractions of 12.65 Gy over 21 days to a total of 25.30 Gy ( air , n = 25 ) ; or radiation under HBO-4 in two fractions of 11.50 Gy over 21 days to at total of 23.00 Gy ( HBO-4 , n = 23 ) . The HBO-4 was administered under general anesthesia to minimize patient discomfort and potential problems with seizures associated with rapid compression to 4 atmospheres . Patients were monitored regularly by the radiation oncologists for toxicity , response , local control , and survival . The original hospital records , radiation records , and hyperbaric treatment logs were recently review ed , and all data were entered onto a computerized data base for the current analysis . The results of this trial have not previously been published . RESULTS The air and HBO-4 arms were evenly matched with respect to age , sex , performance status , hemoglobin level , primary site , and stage of disease . Acute toxicities were acceptable with no significant differences between the two treatment arms . A trend toward excess severe late complications were noted in the hyperbaric arm ( 12 vs 7 ) . There was a highly significant difference in complete clinical responses between the two arms , with 21/25 in complete dinical responses in the HBO-4 arm compared with 13/25 in complete clinical responses in the air arm , and a statistically insignificant trend toward improved 5-year local control in the HBO-4 arm ( 29 % vs 16 % ) . There were no significant differences between the two arms with respect to 5-year survival , distant metastasis , or second primary tumors . CONCLUSIONS Long-term outcome from this historical r and omized trial demonstrate substantial improvements in response rate with the use of HBO-4 . The hypofractionation scheme used in the trial result ed in relatively low local control and high complication rates in this group of patients with very advanced SCCHN . However , these results support the theory that radioresistant hypoxic cells limit the radiocurability of SCCHN . Further investigations addressing the hypoxic cell problem with hypoxic cytotoxins or hypoxic cell sensitizers in combination with radiation therapy using more conventional fractionation schemes are warranted A controlled trial of megavoltage radiotherapy in hyperbaric oxygen in the management of carcinoma of the bronchus and bladder has been in progress since January 1964 . A dose of 6000 R is given with a 60Cobalt unit using daily fractionation for eight weeks , either in air or hyperbaric oxygen at 3 atm pressure , on a basis of r and om selection . A preliminary review is given of the results in the first 89 patients in the trial , with a minimum follow‐up period of six months . The response in 51 additional patients , treated for other conditions by megavoltage radiotherapy in hyperbaric oxygen outside the trial , is discussed briefly . In all , 2363 treatments have been given in hyperbaric oxygen to these two groups of patients . The results , although not yet conclusive , are disappointing and the possibility of increasing the rate of growth of metastases by hyperbaric oxygenation is raised The value of misonidazole in advanced head and neck cancer was examined in 3 ways and the preliminary results are reported in a r and omized study with large fractions of irradiation , when misonidazole appeared to confer no advantage ; whereas in previously ( partially ) treated patients misonidazole was possibly useful . The combination of hyperbaric oxygen and misonidazole did not appear to be toxic Abstract The Radiation Therapy Oncology Group ( RTOG ) Study , in which 254 patients were analyzed , adjunctive carbogen breathing in irradiation of carcinomas of the oral cavity , oropharynx , nasopharynx , hypopharynx , and larynx failed to bring about a gain in survival at any of these sites . In only two of the five regional subgroups did results show any improvement with respect to patients in the Carbogen group as compared to those in the Air group , i.e. , the larynx and hypopharynx subgroups . Since both of these subgroups contained relatively small numbers of patients ( 42 larynx , 39 hypopharynx ) , it was not possible to declare these improvements as definitely due to carbogen breathing . In the case of the larynx subgroup , improvement might have been due to the slightly unequal distribution with respect to T-stage ; in either subgroup , the possibility that apparent improvement was due to nothing more than r and om variation could not be ruled out . In the subgroups with larger numbers of patients , i.e. , the oral cavity and oropharynx groups , there was no demonstrated improvement accompanying carbogen breathing |
661 | 22,991,774 | High quality evidence showed that Clarithromycin is a safe and effective alternative for the treatment of URIs in pediatric patients .
Is superior to other antibiotics in relation to bacterial eradication . | PURPOSE Upper respiratory infections ( URIs ) are one of the most common infectious diseases in children .
Macrolides had been considered one of the best options of treatment .
Instead of clarithromycin is one of the macrolides most used , meta- analysis about the safety and efficacy of this drug has not been published . | Objective : To describe NP and AOM otopathogens during the time frame 2007 to 2009 , 6 to 8 years after the introduction of 7-valent pneumococcal conjugate ( PCV7 ) in the United States and to compare nasopharyngeal ( NP ) colonization and acute otitis media ( AOM ) microbiology in children 6 to 36 months of age having first and second AOM episodes with children who are otitis prone . Methods : Prospect ively , the microbiology of NP colonization and AOM episodes was determined in 120 children with absent or infrequent AOM episodes . NP sample s were collected at 7 routine visits between 6 and 30 months of age and at the time of AOM . For first and subsequent AOM episodes , middle ear fluid ( MEF ) was obtained by tympanocentesis . Eighty otitis prone children were comparatively studied . All 200 children received age-appropriate doses of PCV7 . Results : We found PCV7 serotypes were virtually absent : ( 0.9 % isolated from both NP and MEF ) in both study groups . However , non-PCV7 serotypes replaced PCV serotypes such that the frequency of isolation of S. pneumoniae ( Spn ) was nearly equal to that of non-typeable Haemophilus influenzae ( NTHi ) . M. catarrhalis ( Mcat ) was less common and Staphylococcus aureus infrequent in the NP and MEF from the 2 groups . The proportion of Spn , NTHi and Mcat causing AOM was similar in children with first and second AOM episodes compared to otitis prone children . However , oxacillin-resistant Spn isolated from the NP and MEF was 19 % for the absent/infrequent and 58 % for the otitis prone groups , P < 0.0001 . Beta-lactamase producing NTHi occurred more frequently in the otitis prone group , P = 0.04 . Conclusions : Six to 8 years after widespread use of PCV7 , Spn strains expressing vaccine-type serotypes have virtually disappeared from the NP and MEF of vaccinated children . NP colonization and AOM has changed to non-PCV7 strains of Spn . NTHi continues to be a major AOM pathogen . The otopathogens in first and second AOM and in otitis prone children are very similar although Spn and NTHi are more often antibiotic resistant in the otitis prone A prospect i ve cohort study was conducted to analyze factors associated with antibiotic noncompliance and waste among patients suffering acute respiratory infection ( ARI ) and acute diarrhea ( AD ) . The study took place in four primary health care clinics in Mexico City , two belonging to the Ministry of Health ( MoH ) and two to the Mexican Social Security Institute ( IMSS ) . Two hundred twenty-two patients with ARI and 155 with AD were included . Data about study variables and the assessment of compliance were obtained through patient interviews and direct observation . Factors associated with noncompliance were assessed through a multiple logistic regression procedure . Noncompliance was 60 % for ARI and 55.5 % for AD in both health care systems . Prescription of an antibiotic was justified only in 13.5 % of cases . Associated factors were : increased duration of illness ( OR 2.95 ; 95 % CI , 1.17 - 7.41 ) ; complexity of the treatment : 3 or more doses per day ( OR 2.47 ; 95 % CI , 1.56 - 3.92 ) , and treatment for more than 7 days ( OR 1.94 ; 95 % CI , 1.16 - 3.26 ) ; younger age of patient ( OR 1.89 ; 95 % CI , 1.18 - 3.02 ) ; and an inadequate physician-patient relationship ( OR 1.87 ; 95 % CI , 1.16 - 3.02 ) . Antibiotic waste was higher in IMSS ( ARI 39.3 % , AD 32.6 % ) , than in the MoH ( ARI 21.2 % , AD 16.4 % ) . Educational strategies to modify physician prescribing practice s and strengthen physician-patient relationships might improve compliance and decrease drug waste The treatment of streptococcal pharyngitis with azithromycin ( 10 mg/kg orally once daily for 3 days ) or clarithromycin ( 7.5 mg/kg orally twice daily for 10 days ) was compared in a r and omized observer-blind study carried out in 174 children with documented Streptococcus pyogenes infection . The observed cure rate 10 days after the beginning of treatment was 61/63 ( 96.8 % ) in the clarithromycin group and 71/74 ( 95.9 % ) in the azithromycin group . At days 17 – 20 the bacteriological eradication rate was 95.2 % for clarithromycin and 94.6 % for azithromycin . When children who did not complete treatment were included in the analysis the eradication rate was higher for azithromycin ( 93.6 % compared with 82.9 % ; P < 0.05 ) ; the difference was due to better compliance with the azithromycin regimen The usefulness of clinical and laboratory findings for prediction of the presence of Group A streptococci on throat culture and of an increase in antistreptococcal antibodies was investigated in 693 adult patients . Several findings were shown to increase the likelihood of streptococcal isolation , alone and in combination : tonsillar exu date , tonsillar enlargement , tender anterior cervical adenopathy , myalgias , and a positive throat culture in the preceding year . Compared with a frequency of 9.7 % in all patients , the probabilities of a positive culture were quite different ( ranging from 2 to 53 % ) in subgroups of patients with different combinations of these clinical findings . The results of a leukocyte count and measurement of C-reactive protein added little additional predictive information . While clinical findings can never predict perfectly the results of a throat culture , they nevertheless can provide useful information — particularly in tending to “ rule out ” streptococcal infection — in adult patients with pharyngitis The safety and efficacy of clarithromycin was compared with those of amoxicillin-potassium calvulanate for the treatment of acute otitis media in children . In a multicenter , r and omized , investigator-blinded trial , 180 patients ( 6 months to 12 years of age ) with acute otitis media were allocated to receive either clarithromycin , 15 mg/kg in two divided doses ( n = 90 ) , or amoxicillin-clavulanate , 40 mg/kg in three divided doses ( n = 90 ) , for 10 days . Middle ear sample s were obtained by tympanocentesis from 175 of 180 patients . Pathogens were isolated from 137 sample s ( 76 % ) . Eighty-six patients in each treatment group were considered for efficacy analysis . Clinical cure or improvement was achieved within 4 days after treatment in 80 ( 93 % ) of 86 patients receiving clarithromycin and in 82 ( 95 % ) of 86 patients receiving amoxicillin-clavulanate . Recurrence of infection was observed between 5 and 35 days after treatment in 9 ( 11 % ) of 80 patients in the clarithromycin group and in 8 ( 10 % ) of 82 patients in the amoxicillin-clavulanate group . Middle ear effusion was found with similar frequency at the end of therapy and at follow-up visits in both treatment groups . Mild gastrointestinal signs and symptoms , the most common side effects , were noted in 20 % and 52 % of patients in the clarithromycin group and the amoxicillin-clavulanate group , respectively ( p < 0.001 ) . We conclude that clarithromycin is a safe and effective antimicrobial agent for the treatment of acute otitis media in children & NA ; The safety and efficacy of a new oral suspension formulation of clarithromycin were evaluated in this multicenter , Phase III , single blind , comparative trial in 379 children ages 6 months to 12 years with signs or symptoms of acute otitis media . Children were r and omized to receive a 10‐day course of clarithromycin oral suspension ( 7.5 mg/kg ; maximum , 500 mg ) or cefaclor oral suspension ( 20 mg/kg ; maximum , 500 mg ) twice daily . Specific clinical response criteria were developed based on pretreatment signs and symptoms and results of tympanometry . Of the 379 enrolled patients 281 ( 74 % ) were evaluable ( clarithromycin , 150 ; cefaclor , 131 ) . There were no demographic differences between the two groups . Fifty percent of the patients had 2 to 4 episodes of otitis media ( including the current episode ) in the past 12 months ; 63 % of the patients had an infection of moderate severity . Clarithromycin and cefaclor suspensions were similarly effective for the treatment of acute otitis media . Clinical success ( cure , cure with effusion or improvement ) was achieved in 86 % of clarithromycin‐treated patients and 90 % of cefaclor‐treated patients . The majority of bacterial isolates for which susceptibility results were available were fully or moderately susceptible to the study drugs ( 96 % clarithromycin , 92 % cefaclor ) . Both drugs were welltolerated ; adverse events considered probably study drug‐related were reported by 30 ( 15 % ) of clarithromycin recipients and 31 ( 17 % ) of cefaclor recipients . There were no significant differences between the groups in the numbers of patients reporting events that were thought to be related to study medication . A 10‐day regimen of clarithromycin suspension ( 7.5 mg/kg twice daily ) appears to be as safe and effective as a 10‐day regimen of cefaclor suspension ( 20 mg/kg twice daily ) for the treatment of acute otitis media in children Objective . To compare the safety and efficacy of a short course ( 5 days ) of ceftibuten vs. azithromycin for 3 days for treatment of group A beta-hemolytic streptococcal ( GABHS ) pharyngitis in children . Methods . A multicenter , open label , prospect i ve , r and omized trial in which patients ≥3 to ≤16 years of age with proven GABHS pharyngitis were r and omized to receive either once daily ceftibuten for 5 days or azithromycin for 3 days . Patients were evaluated for clinical outcomes and /or for adverse events at days 6 to 8 , 13 to 15 and 33 to 35 posttherapy . Microbiologic assessment s ( pharyngeal cultures ) were conducted at baseline and at each follow-up visit . Results . A total of 132 patients in the ceftibuten arm and 116 in the azithromycin arm were enrolled in the safety analysis , whereas 126 and 101 , respectively , were enrolled for ceftibuten and azithromycin efficacy evaluation . Clinical success ( cure or marked amelioration ) at days 6 to 8 was recorded in 98 and 94 % in the 2 groups , respectively . In the bacteriologic efficacy analysis at 6 to 8 days , the GABHS strain was eradicated in 76 % of the patients treated with ceftibuten and in 76 % of those receiving azithromycin . At 33 to 35 days , 84 % of the patients in the ceftibuten arm and 71 % in the azithromycin arm were GABHS-negative , and bacteriologic relapse was observed in 4 and 7 % of the ceftibuten and azithromycin cases , respectively . Both treatments were well-tolerated by all patients . Conclusions . Ceftibuten and azithromycin allow simple treatment schedules ( i.e. once daily administration , short duration of treatment ) . The somewhat higher eradication rate recorded after ceftibuten administration is consistent with the overall superior bactericidal activity of beta-lactams compared with macrolides vs. GABHS in vitro Background : Short course antimicrobial therapy is suggested for group A streptococcal tonsillopharyngitis . Methods : The bacteriologic and clinical efficacies of clarithromycin [ 30 or 15 mg/kg/day twice daily ( b.i.d . ) ] or amoxicillin/clavulanate ( 43.8/6.2 mg/kg/day b.i.d . ) for 5 days or penicillin V ( 30 mg/kg/day 3 times a day ) for 10 days were compared . In a r and omized , open label , parallel group , multicenter study , 626 children ( 2–16 years old ) with tonsillopharyngitis were enrolled ; 537 were evaluable for efficacy . Follow-up evaluations were performed at 4–8 and 21–28 days after therapy . Results : At enrollment , 26 % of the Streptococcus pyogenes isolates were clarithromycin-nonsusceptible . All regimens had an apparently similar clinical efficacy . The long term S. pyogenes eradication rates were 102 of 123 ( 83 % ) with amoxicillin/clavulanate and 88 of 114 ( 77 % ) with penicillin V. In the 30- and 15-mg/kg/day clarithromycin groups , eradication occurred in 71 of 86 ( 83 % ) and 59 of 80 ( 74 % ) of the clarithromycin-susceptible isolates ( P = 0.33 ) , and in 4 of 28 ( 14 % ) and 5 of 26 ( 19 % ) of the clarithromycin-resistant isolates , respectively ( clarithromycin-susceptible versus -resistant , P < 0.0001 ) . Both clarithromycin dosages were well-tolerated . Conclusions : In group A streptococcal tonsillopharyngitis , 5 days of clarithromycin or amoxicillin/clavulanate treatment had clinical efficacy comparable with that of 10 days of penicillin V treatment ; however , amoxicillin/clavulanate and penicillin V were bacteriologically more effective than clarithromycin because of its failure to eradicate the clarithromycin-resistant S. pyogenes isolates . The 5-day clarithromycin regimens are not recommended for treatment of streptococcal tonsillopharyngitis in areas where in vitro resistance of group A streptococci to clarithromycin is common The efficacy and safety of azithromycin and penicillin V in the treatment of acute streptococcal pharyngitis/tonsillitis in paediatric patients were compared in a double-blind , double-dummy prospect i ve study . A total of 489 children ( age range , 2–13 years ) were r and omized to receive treatment with penicillin V ( 125–250 mg 4 × daily for 10 days ) or azithromycin in an oral suspension ( 10 or 20 mg/kg 1 × daily for 3 days ) . Only patients with baseline cultures positive forStreptococcus pyogenes and complete clinical and microbiological assessment s at the end of therapy and follow-up one month later were included in the efficacy analysis . A satisfactory clinical response ( cure or improvement ) was recorded in 99 % of the 10 mg/kg azithromycin group , 100 % of the 20 mg/kg azithromycin group , and 97 % of the penicillin V group at the end of therapy ( day 12–14 ) . At the follow-up evaluation ( day 28–30 ) , relapse rates in patients cured or improved at the end of therapy were 6 % , 5 % , and 2 % , respectively . Bacteriological eradication rates at the end of therapy were 98 % in both azithromycin groups and 92 % in patients who received penicillin V ( p=0.011 ) ; pathogen recurrence was recorded at follow-up in 4 % of the 20 mg/kg azithromycin group and in 6 % of both the 10 mg/kg azithromycin and penicillin V groups . Treatment-related adverse events , the majority of mild to moderate severity , occurred in 13 % of patients in the 20 mg/kg azithromycin group , 9 % in the 10 mg/kg azithromycin group , and 5 % in the penicillin V group . Azithromycin in a dosage of 10 or 20 mg/kg/day once daily for three days was as safe and effective as penicillin V administered four times daily in the treatment of paediatric patients with acute pharyngitis/tonsillitis Objective . Although early otitis media ( OM ) onset predicts later recurrent and chronic OM , little research has been directed at illuminating the role of prenatal exposures in early OM . This prospect i ve study examined prenatal , innate , and early environmental exposures associated with acute otitis media ( AOM ) onset and recurrent OM ( ROM ) by age 6 months . Design and Methods . Prospect i ve study of 596 infants from a health maintenance organization followed from birth to 6 months . Mothers completed monthly forms on prenatal exposures ( diet , medications , and illnesses ) and infant risk factors ( eg , smoke exposure and child care ) during pregnancy and until infants were 6 months old . Urine sample s were collected when infants were 2 months of age and analyzed for cotinine and creatinine . Physicians and nurse practitioners examined infants at each clinic visit and completed st and ard ear examination forms . Results . Thirty-nine percent had an episode of AOM and 20 % had ROM by age 6 months . Using Cox 's regression models to control for confounding , respiratory tract infection ( relative risk [ RR ] 7.5 ) , day care ( RR 1.7 ) , > 1 sibling ( RR 1.4 ) , maternal , paternal , and sibling OM history ( RR 1.6 , 1.5 , and 1.7 , respectively ) were significantly related to early OM onset . ROM was related to respiratory tract infection ( RR 9.5 ) , day care ( RR 1.9 ) , conjunctivitis ( RR 2.0 ) , maternal OM history ( RR 1.9 ) , and birth in the fall ( RR 2.6 ) . Among prenatal exposures , only high prenatal dietary vitamin C intake was significantly inversely related to early AOM with univariate but not multivariate analysis . Conclusion . Prenatal factors were not linked to early AOM onset with multivariate analysis , but environmental and innate factors play an important role in early AOM onset . Strategies to reduce exposure to environmental variables could reduce rates of early AOM , which could potentially result in declining rates of ROM and chronic OME Twenty-three general practice s in the UK r and omised 229 paediatric patients ( aged 1 - 12 years , body weight > 8 kg ) with clinical evidence suggestive of streptococcal tonsillitis and /or pharyngitis in this physician-blind study . Patients received either clarithromycin suspension ( 7.5 mg/kg twice daily ) or amoxycillin syrup ( 125 mg/kg three times daily body weight < 25 kg , or 250 mg/kg three times daily body weight 25 kg ) for 7 days and were followed up 3 - 8 days post treatment and 21 - 28 days later . Clinical and microbiological assessment s were made at each visit . A total of 189 patients ( 98 on clarithromycin and 91 on amoxycillin ) were clinical ly evaluable . At the post-treatment visit , clinical success rates were high and comparable : 98 % on clarithromycin and 97 % on amoxycillin . Streptococcus pyogenes was eradicated in 88 % of clarithromycin patients and 86 % of amoxycillin patients . Both treatments were well tolerated . In conclusion , clarithromycin suspension was as safe and at least as effective as amoxycillin syrup for the treatment of pharyngitis and /or tonsillitis in children , and would be a suitable alternative therapy & NA ; In a r and omized investigator‐blinded study , 506 children ages 6 months to 12 years with positive rapid direct antigen tests for Group A beta‐hemolytic Streptococcus ( GABHS ) received treatment with either clarithromycin suspension , 7.5 mg/kg twice daily , or penicillin VK suspension , 13.3 mg/kg three times per day for 10 days . Signs and symptoms of pharyngitis or tonsillitis were evaluated and throat cultures were obtained before treatment , once during treatment and 4 to 6 days and 19 to 25 days posttreatment . All GABHS isolates were susceptible in vitro to clarithromycin . Successful clinical responses at the end of treatment were demonstrated in 169 of 176 ( 96 % ) evaluable clarithromycin‐treated patients and 179 of 191 ( 94 % ) evaluable penicillin‐treated patients . GABHS was successfully eradicated at end of treatment in 168 of 183 ( 92 % ) evaluable clarithromycintreated patients compared with 162 of 199 ( 81 % ) evaluable penicillin‐treated patients ( P = 0.004).There were no significant changes in hematologic or serum chemistry parameters in either group . Both drugs were well‐tolerated . The incidence and nature of adverse events were similar in the clarithromycin and penicillin groups , except for gastrointestinal complaints reported in 35 of 250 ( 14 % ) clarithromycin recipients compared with 12 of 256 ( 5 % ) penicillin recipients ( P ≤ 0.001 ) . The results indicate that twice daily clarithromycin was as safe and effective as three times daily penicillin VK in the treatment of children with streptococcal pharyngitis or tonsillitis . Clarithromycin was statistically superior to penicillin VK in the eradication of GABHS A multicenter , r and omized , controlled , investigator-blind study was performed to evaluate the safety and efficacy of oral cefdinir versus oral penicillin V for the treatment of pharyngitis due to group A beta-hemolytic streptococci ( GABHS ) . Patients 13 years of age and older were r and omized to receive either oral cefdinir ( 300 mg twice a day ) for 5 days followed by placebo for 5 days or oral penicillin V ( 250 mg four times a day ) for 10 days . Throat cultures were obtained , and signs and symptoms of pharyngitis were recorded at study admission and follow-up visits on study days 11 to 15 , 16 to 20 , and 25 to 31 . Patients kept a diary to record medication intake and their assessment of throat pain at admission and at each day of study treatment . Five hundred fifty-eight patients were enrolled , of whom 432 ( 77.4 % ) were clinical ly and microbiologically evaluable . The GABHS eradication rates 5 to 10 days after completion of therapy were 193 of 218 ( 88.5 % ) in the cefdinir group and 176 of 214 ( 82.2 % ) in the penicillin group ( P = 0.053 ) . Clinical cure rates were 89.0 and 84.6 % , respectively ( P = 0.80 ) . By the time of the long-term follow-up visit , 2 to 3 weeks after completion of treatment , 156 of 191 ( 81.7 % ) of the assessable cefdinir patients and 152 of 195 ( 77.9 % ) of the penicillin patients remained free of GABHS . Both treatments were well tolerated , with adverse reaction rates of 18.3 % in the cefdinir study arm and 15.0 % in the penicillin study arm ( P = 0.278 ) . Five-day treatment with cefdinir is safe and effective therapy for GABHS pharyngitis . Based on its twice-a-day dosage and shorter course of therapy , leading to potentially greater patient compliance , cefdinir may be considered for use in the treatment of pharyngitis caused by GABHS 160 children aged 1 to 12 years with clinical diagnosis of bacterial pharyngitis and /or tonsillitis were treated either with cefixime ready-to-use-suspension or penicillin V in an open , controlled and r and omized multicenter study . Before treatment a rapid antigen detection test was accomplished and throat swabs were taken . After r and omization , the children were either treated for 5 days with 8 mg cefixime/kg bodyweight ready-to-use suspension once daily or with 20,000 I.U. penicillin V/kg bodyweight t.i.d . also administered as suspension . The data of 151 children could be evaluated for clinical ly efficacy . In the cefixime-group 86.7 % of the children were cured and 9.3 % significantly improved . After initial improvement , in one child ( 1.3 % ) a relapse occurred and in the two remaining children ( 2.7 % ) therapy failed . 90.8 % of the patients treated with penicillin V were cured , 6.6 % improved and in one child each a relapse was registered resp . therapy failed . Complete microbiological data were available in 137 patients . In the cefixime-group in 82.6 % of the patients the pathogens were eradicated . The elimination rate in the penicillin-group was 88.2 % . At the follow-up 3 - 4 weeks after end of treatment 6 relapses were seen in the cefixime-group , and 8 in the patients treated with penicillin . Both regimes were safe . Mild to moderate adverse events at least possibly related to the study medication were seen in only 4 children treated with cefixime and in 5 treated with penicillin . A 5 day treatment of bacterial pharyngitis and tonsillitis with cefixime was as effective as a ten day treatment with penicillin OBJECTIVE To compare bacteriologic and clinical efficacy and safety of 10 vs 5 days of cefpodoxime proxetil vs 10 days of penicillin V potassium for the treatment of acute group A beta-hemolytic streptococcal tonsillopharyngitis in children . DESIGN Prospect i ve , r and omized , observer-blind , multicenter study . PATIENTS / INTERVENTIONS Four hundred eighty-four children ( age range , 2 to 17 years ) with signs and symptoms of acute tonsillopharyngitis were enrolled ; 377 had a positive throat culture for group A beta-hemolytic streptococci and were fully evaluable . One hundred twenty-one patients received cefpodoxime once a day for 10 days , 126 received cefpodoxime twice a day for 5 days , and 130 received penicillin V three times a day for 10 days . RESULTS Cefpodoxime for 10 days vs cefpodoxime for 5 days vs penicillin V for 10 days produced bacteriologic eradication at the end of therapy in 95 % , 90 % , and 78 % of the patients , respectively . The 10- and 5-day cefpodoxime treatment regimens were more efficacious than penicillin V ( P = .003 and P = .02 , respectively ) . The cumulative bacteriologic failure rate among assessable patients by the 32- to 38-day posttreatment visit was 20 ( 17 % ) of 121 patients who were treated with cefpodoxime for 10 days , 24 ( 19 % ) of 125 patients who were treated with cefpodoxime for 5 days , and 45 ( 35 % ) of 130 patients who were treated with penicillin V for 10 days ( P = .001 and P = .005 , respectively ) . Clinical cure or improvement was observed at the end of therapy in 96 % , 94 % , and 91 % of the patients , respectively ( P = not significant ) . Adverse events were infrequent and similar in all three treatment groups , with minor gastrointestinal side effects predominating . CONCLUSIONS Five days of treatment with cefpodoxime is as efficacious in bacteriologic eradication and clinical response ( cure plus improvement ) as 10 days of cefpodoxime therapy , and both cefpodoxime regimens produced superior bacteriologic efficacy compared with a 10-day regimen of penicillin V in the treatment of group A beta-hemolytic streptococcal tonsillopharyngitis in children & NA ; Clarithromycin is a new macrolide antibiotic that is active in vitro against a variety of organisms that are responsible for acute otitis media in children . The parent compound is metabolized to microbiologically active 14‐hydroxy clarithromycin , which is especially active against Haemophilus influenzae . The safety and efficacy of clarithromycin and amoxicillin suspensions were compared in the treatment of acute otitis media in children 1 to 12 years of age inclusive . This was a Phase III , single blind ( investigator‐blind ) , r and omized , multicenter clinical trial . Clarithromycin oral suspension was given in a dose of 7.5 mg/kg ( maximum , 500 mg ) twice daily , and amoxicillin suspension in a dose of 20 mg/kg ( maximum , 750 mg ) was given twice daily for 7 to 10 days in a 1:1 ratio . Clinical evaluations were performed pretreatment , within 48 hours posttreatment and 10 to 14 days posttreatment . Myringotomy was performed in every child to obtain a microbiologic sample pretreatment and at subsequent visits as clinical ly indicated . A total of 79 children were enrolled , 39 in the clarithromycin and 40 in the amoxicillin treatment group . Thirty‐two children were excluded from the efficacy analysis for various reasons . Clinical success ( cure and improvement ) rates at 0 to 4 days posttreatment were 93 % for clarithromycin and 90 % for amoxicillin ( P > 0.999 ) . Altogether 17 children ( 10 receiving clarithromycin , 7 receiving amoxicillin ) experienced some adverse event , with gastrointestinal disorders being the most common complaint . No clinical ly significant differences in laboratory tests were found between the groups . This study showed that clarithromycin , 7.5 mg/kg/dose twice daily for 7 to 10 days , was as safe and effective as amoxicillin , 20 mg/kg/dose twice daily for 7 to 10 days , in the treatment of acute otitis media with effusion in children We examined the effect of antibiotic therapy on the clinical course of group A beta-hemolytic streptococcal ( GABHS ) pharyngitis in 260 children . After a throat culture had been obtained , each child was evaluated for the presence of predetermined signs and symptoms , and was then r and omized in a double-blind manner to receive penicillin V , cefadroxil , or placebo . Of the 194 children with throat cultures positive for GABHS , 68 received penicillin V , 70 received cefadroxil , and 56 received placebo . Approximately 18 to 24 hours later , each patient returned for reevaluation . Significantly fewer children who had received either penicillin or cefadroxil had persistence of each of the three objective signs and each of the three subjective symptoms than did children who had received placebo . In addition , the evaluating physician , parents , and patients all believed that significantly fewer of the patients given antibiotic failed to demonstrate overall clinical improvement The efficacy and safety of orally administered clarithromycin and erythromycin in the treatment of community-acquired pneumonia were assessed in a multicenter , double-blind , r and omized study . Two hundred sixty-eight patients were r and omized to receive either clarithromycin , 250 mg twice a day , or erythromycin stearate , 500 mg 4 times a day , for 7 to 14 days . Efficacy was evaluable in 173 patients ( 92 for clarithromycin , 81 for erythromycin ) . No statistically significant difference in clinical success rate ( cure or improvement ) was observed between the two groups ( clarithromycin , 97 percent ; erythromycin , 96 percent ) . Both groups had identical radiologic response ( 97 percent with resolution or improvement ) . Similarly , no statistically significant difference in bacteriologic response toward the target pathogens was observed among evaluable patients ( clarithromycin , 23/26 ; erythromycin , 17/17 ; p value = 0.287 ) . Clinical response toward Mycoplasma and Chlamydia pneumonia was comparable between the two groups ( clarithromycin , 15/16 ; erythromycin , 10/11 ) . However , patients receiving erythromycin had a twofold higher incidence of adverse events , mostly related to the gastrointestinal system , and were five times more likely to withdraw from therapy because of drug-related adverse events . These results show that clarithromycin is as effective as erythromycin in the outpatient treatment of community-acquired pneumonia . Furthermore , the lower incidence of adverse events associated with clarithromycin indicates that it is more acceptable to patients and , therefore , can enhance compliance Clarithromycin , an advanced-generation macrolide antibiotic , has demonstrated excellent in vitro activity against group A beta-hemolytic streptococcus ( GABHS ) . Potent activity againstStreptococcus pyogenes and a favorable pharmacokinetic profile have made it a reasonable alternative for treatment of patients with streptococcal pharyngitis . The safety and efficacy of clarithromycin and penicillin V were compared in a r and omized , investigator-blind study . Children 6 months to 12 years of age received 5 days of clarithromycin suspension 7.5 mg/kg twice daily ( n = 268 ) or 10 days of penicillin V suspension 13.3 mg/kg three times daily ( n = 260 ) . Patients were evaluated for signs and symptoms of pharyngitis , and throat swabs for culture were obtained prior to therapy , at the end of therapy , and at follow-up . Clarithromycin and penicillin V produced comparable rates of clinical success ( cure + improvement ) at the posttreatment ( 97 % and 94 % ) and follow-up ( 81 % and 82 % ) evaluations . The GABHS eradication rate , however , was significantly higher with clarithromycin ( 94 % vs 78%,P < .001 ) . Both drugs were well tolerated ; gastrointestinal complaints were similar and mild . Resistance did not occur with the short course of clarithromycin or the st and ard regimen of penicillin V. Five days ’ treatment with clarithromycin was superior to 10 daysof penicillin in eradicatingS. pyogenes We tested in vitro 49 isolates of Chlamydia pneumoniae obtained from 35 children with community-acquired pneumonia against clarithromycin and erythromycin . The children were part of a treatment study comparing the two drugs . Clarithromycin was 2- to 10-fold more active than erythromycin , with a MIC for 90 % of strains tested and minimal chlamydiacidal concentration for 90 % of strains tested of 0.031 microgram/ml compared with 0.125 microgram/ml for erythromycin . Eight of these children , two of whom were treated with erythromycin and six of whom received clarithromycin , remained culture positive after treatment . We were able to test 21 isolates from these children . All were susceptible to both drugs , and the MICs did not change after therapy BACKGROUND Tonsillopharyngitis caused by group A beta-hemolytic streptococci ( GABHS ) is common in pediatric clinical practice . St and ard penicillin therapy may be associated with poor compliance , penicillin tolerance in GABHS and microbial copathogenicity . Alternative treatments are available ( e.g. oral cephalosporins ) , and data suggest that shorter courses of these agents may be effective . OBJECTIVE This open , r and omized , multicenter study compared a conventional 10-day course of the broad spectrum oral cephalosporin , cefuroxime axetil , with a shorter 5-day course . METHODS Cefuroxime axetil suspension , 10 mg/kg , was given twice daily to children ( ages 3 to 13 years ) screened for GABHS tonsillopharyngitis . Patients were assessed clinical ly and bacteriologically 4 to 7 days after completing the course and followed up at 21 to 28 days . Among 651 patients recruited 520 had throat cultures positive for GABHS and were r and omized to treatment . RESULTS In the 406 patients with microbiologically confirmed GABHS infection , eradication of the initial pathogen was recorded in 177 of 201 ( 88 % ) and 189 of 205 ( 92 % ) of patients in the 5- and 10-day groups , respectively , at posttreatment . At follow-up , 137 of 162 ( 85 % ) of patients in the 5-day group and 145 of 167 ( 87 % ) in the 10-day group maintained bacteriologic eradication . All posttreatment isolates of GABHS were susceptible to cefuroxime , and reinfection with a different serotype of GABHS was rare ( < or = 2 % ) in both groups . The rates of recurrence of the pretreatment serotype were 10 and 7 % in the 5- and 10-day groups , respectively . CONCLUSIONS Short course therapy with cefuroxime axetil suspension may offer an effective alternative treatment to conventional regimens , with potential for better compliance and reduced costs & NA ; Clarithromycin is a new macrolide antibiotic with a wide spectrum of activity that includes the pathogens commonly causing pediatric otitis media . This r and omized , investigator‐blinded , multicenter trial compared the safety and efficacy of clarithromycin and amoxicillin/clavulanate in the treatment of acute otitis media in patients ages 6 months to 12 years . A total of 338 patients with acute otitis media diagnosed by otoscopy were r and omized to receive clarithromycin 7.5 mg/kg twice daily , maximum 500 mg twice daily ( n = 161 ) , or amoxicillin/clavulanate 13.3 mg/kg three times daily , maximum 500 mg three times daily ( n = 177 ) , for 10 days . Treatment groups were comparable with respect to demographics , severity of infection and number of previous episodes . Efficacy was assessed by clinical examination performed within 48 hours of finishing study medication . A successful clinical response was seen in 90 % ( 121 of 135 ) of evaluable clarithromycin patients vs. 92 % ( 133 of 145 ) of evaluable amoxicillin/clavulanate patients ( P = 0.681 ) . Clinical failure or relapse ( Posttreatment Days 0 to 4 ) occurred in 10 % ( 14 of 135 ) of clarithromycin‐treated patients vs. 8 % ( 12 of 145 ) of amoxicillin/clavulanate‐treated patients . Gastrointestinal adverse events were the most commonly reported in both groups . Of these events diarrhea was the most frequent , occurring in 12 % ( 19 of 161 ) of clarithromycin and 32 % ( 57 of 177 ) of amoxicillin/clavulanate‐treated patients ( P < 0.001 ) . These results indicate that the efficacy of clarithromycin oral suspension was comparable with amoxicillin/clavulanate oral suspension in the treatment of acute otitis media in children . Clarithromycin was better tolerated than amoxicillin/clavulanate with a lower incidence of gastrointestinal side effects Summary This phase III , single-blind , r and omized , multicentre clinical trial compared the safety and efficacy of clarithromycin and amoxycillin in the treatment of otitis media in pediatric patients . Two hundred and fifty-nine patients aged 1–12 were prescribed suspensions of clarithromycin ( 132 patients ) or amoxycillin ( 127 patients ) . Both suspensions were prescribed at a dose of 125 mg for children weighing less that 25 kg or at 250 mg for children weighing more than 25 kg , but three doses of amoxycillin per day were given , while only two doses clarithromycin per day were required . Each drug was administered for approximately 5 days . Clinical evaluations were performed pre-treatment ( Study Day 1 ) , at the end of treatment ( Study Days 6–9 ) , and post-treatment ( Study Days 28–32 ) . At the end of treatment , 91 out of 114 evaluable patients ( 80 % ) had clinical cures with clarithromycin , while 71 out of 105 evaluable patients ( 68 % ) had clinical cures with amoxycillin ( p=0.057 ) . Clinical success rates were 96 % for both treatments ( 110/114 , clarithromycin ; 101/105 amoxycillin ) . Adverse events related to the study medications occured in four of 132 patients receiving clarithromycin ( 3 % ) and eight out of 127 subjects receiving amoxycillin ( 6 % ) . Three patients discontinued treatment due to adverse events , all three receiving amoxycillin . At the doses administered , clarithromycin given twice-daily was as safe and effective as amoxycillin given three-times-daily in the treatment of acute otitis media in pediatric patients .ZusammenfassungIm Rahmen einer r and omisierten , einfach blind geführten , multizentrischen klinischen Studie wurde die Wirksamkeit und Sicherheit von Clarithromycin i m Vergleich zu Amoxicillin in der Therapie der akuten Otitis media bei Kindern geprüft . 259 Patienten i m Alter von 1–12 Jahren erhielten Clarithromycin ( 132 Kinder ) oder Amoxicillin ( 127 Kinder ) als Saftzubereitung verordnet . Die Dosis betrug bei beiden Medikamenten bei Kindern unter 25 kg Körpergewicht 125 mg und bei Kindern über 25 kg 250 mg . Doch wurden bei Amoxicillin drei Tagesdosen gegeben , während bei Clarithromycin nur zwei Dosen nötig waren . Jedes der beiden Medikamente wurde etwa 5 Tage lang verabreicht . Klinische Untersuchungen wurden vor Therapie ( Studientag 1 ) , am Ende der Therapie ( Studientage 6–9 ) und i m Anschluß an die Beh and lung ( Studientage 28–32 ) vorgenommen . Nach Abschluß der Beh and lung mit Clarithromycin waren 91 von 114 auswertbaren Patienten ( 80 % ) klinisch geheilt , nach Amoxicillin 71/105 ( 68 % ) ( p=0,057 ) . Die Gesamtansprechrate betrug bei beiden Therapien 96 % ( 110/114 bei Clarithromycin ; 101/105 bei Amoxicillin ) . Vier der 132 mit Clarithromycin beh and elten Patienten ( 3 % ) und acht der mit Amoxicillin beh and elten Patienten ( 6 % ) entwickelten Nebenwirkungen , die mit dem Prüfmedikament in Zusammenhang gebracht wurde . Bei drei Patienten — alle in der Amoxicillingruppe — machten die Nebenwirkungen ein Absetzen der Therapie erforderlich . In der verabreichten Dosierung war Clarithromycin bei zweimal täglicher Gabe in der Beh and lung der akuten Otitis media bei pädiatrischen Patienten ebenso sicher und wirksam wie Amoxicillin bei dreimal täglicher Gabe Forty-four children with a clinical diagnosis of streptococcal pharyngitis had throat cultures performed at the initial evaluation and were assigned by r and omization to receive either oral penicillin or a placebo for 72 hours . The treating physician , who remained blind to the treatment regimen , recorded the child 's temperature and assessed the presence and severity of other signs and symptoms initially and at 24 , 48 , and 72 hours . The throat culture was positive for group A beta-hemolytic streptococci in 26 ( 59 % ) of the initial study group , and most of these children developed a fourfold or greater titer rise in antistreptococcal antibodies in their serum , confirming the diagnosis of streptococcal pharyngitis . Statistically significant clinical improvement was observed in the group of 11 children who were later shown to have been taking penicillin compared with the group of 15 who had taken the placebo . Significant differences in the presence and degree of fever and severity of symptoms persisted in the placebo-treated group for 48 hours . We conclude that early penicillin treatment of children with streptococcal pharyngitis significantly alters the acute clinical course of the disease Two multicenter , r and omized , single-masked , parallel-group studies compared loracarbef and clarithromycin with regard to efficacy , tolerability , and patient acceptance . Three hundred thirty-four children aged 6 months to 3 years with acute otitis media with effusion received loracarbef ( 15 mg/kg ) or clarithromycin ( 7.5 mg/kg ) orally twice daily for 10 days . Patients were assessed for the presence of the diagnostic signs and symptoms of otitis media with effusion by physical examination and pneumatic otoscopy at 48 hours pretreatment , 3 to 5 days after initiation of treatment , 0 to 3 days after the final dose ( posttreatment ) , and 14 to 21 days later ( termination ) . Symptoms were assigned numeric values . Symptomatic response was assessed at the posttherapy and termination visits . Tolerability was determined by assessing adverse events , and a patient acceptance survey was completed by each patient 's caregiver . The combined results of these 2 studies showed that the efficacy and tolerability of loracarbef were comparable to those of clarithromycin . Adverse events were reported by 46.4 % of loracarbef patients and 41.0 % of clarithromycin patients , with no statistically significant difference between groups . In the intent-to-treat analysis , 57.9 % of loracarbef patients were cured at the termination of the study , compared with 55.7 % of clarithromycin patients . Improvement was seen in 4.1 % of loracarbef patients and 2.7 % of clarithromycin patients . Results of the patient acceptance survey showed a clear preference for loracarbef over clarithromycin . Difficulties with administration of treatment were reported by 36.3 % of clarithromycin caregivers , compared with 7.8 % of loracarbef caregivers ( P < 0.001 ) . A desire to stop treatment was reported by 23.8 % of clarithromycin caregivers , compared with 7.8 % of loracarbef caregivers ( P < 0.001 ) . Taste and texture issues were most frequently cited as reasons for nonacceptance The focus of a multicenter trial conducted in Germany was to investigate whether a 5-day short course of cefixime 400 mg was equivalent to a 10-day st and ard therapy of cefixime 400 mg in the treatment of acute exacerbation of chronic bronchitis ( AECB ) . In the 167 patients who were evaluated , on day 11 following treatment with once-daily oral cefixime result ed in clinical success in 91 and 89 % of cases in the 5-day and 10-day treatment groups , respectively . At days 6 , 11 and 30 after treatment there was no statistically significant difference between the 2 dose groups ( p < 0.01 ) . Bacteriological equivalence was also demonstrated . Gastrointestinal adverse events showed a tendency to occur less frequently in the 5-day group , but the difference was not significant . The results indicate that a short course therapy is equivalent in efficacy to the st and ard 10-day therapy in patients with AECB , and may thus offer cost advantages |
662 | 28,266,115 | High evidence of mostly high magnitude was retrieved for behavioural interventions in early childhood caries ( ECC ) , weak evidence for a small effect in proximal caries and an unclear effect of specific informational/motivational programmes on prevention of periodontal diseases and no evidence of root caries .
CONCLUSION Early childhood caries can be successfully prevented by population -based preventive programmes via aim ing at the change in behaviour .
The effect of individual specific motivational/informational interventions has not yet been clearly demonstrated neither for the prevention of caries nor for periodontal diseases | AIM Aim was to systematic ally review behavioural aspects in the prevention and control of dental caries and periodontal diseases at individual and population level . | Objectives We tested a dental health program in remote Aboriginal communities of Australia 's Northern Territory , hypothesizing that it would reduce dental caries in preschool children . Methods In this 2-year , prospect i ve , cluster-r and omized , concurrent controlled , open trial of the dental health program compared to no such program , 30 communities were allocated at r and om to intervention and control groups . All residents aged 18–47 months were invited to participate . Twice per year for 2 years in the 15 intervention communities , fluoride varnish was applied to children 's teeth , water consumption and daily tooth cleaning with toothpaste were advocated , dental health was promoted in community setting s , and primary health care workers were trained in preventive dental care . Data from dental examinations at baseline and after 2 years were used to compute net dental caries increment per child ( d3mfs ) . A multi-level statistical model compared d3mfs between intervention and control groups with adjustment for the clustered r and omization design ; four other models used additional variables for adjustment . Results At baseline , 666 children were examined ; 543 of them ( 82 % ) were re-examined 2 years later . The adjusted d3mfs increment was significantly lower in the intervention group compared to the control group by an average of 3.0 surfaces per child ( 95 % CI = 1.2 , 4.9 ) , a prevented fraction of 31 % . Adjustment for additional variables yielded caries reductions ranging from 2.3 to 3.5 surfaces per child and prevented fractions of 24–36 % . Conclusions These results corroborate findings from other studies where fluoride varnish was efficacious in preventing dental caries in young children OBJECTIVE This paper reports the results of a community trial to measure the clinical impact of a linked series of interventions on Early Childhood Caries ( ECC ) and general caries levels among five-year-old children . It exemplifies the problems of undertaking population based interventions in deprived communities . RESEARCH DESIGN Two health districts ( Primary Care Groups ) were matched for dental disease levels and socio-demographic factors . One was r and omly allocated to be the active intervention PCG , the other the comparison PCG . Children in the active PCG received a series of interventions to support positive dental health behaviour from the age of 8 to 32 months . Clinical examinations were undertaken on a cohort of 5-year-old children in both active and comparison PCGs . SETTING In the active PCG , children who attended design ated clinics for their 8-month developmental checks and /or MMR inoculations at 12 to 15 months , were given gift bags , the first contained a trainer cup , the second fluoride toothpaste ( 1450 ppm F ) and toothbrush . Parents were also given written , pictorial and verbal advice on oral care . Further supplies of toothpaste and brushes were posted to the children 's homes at 20 , 26 and 32 months . When five years of age children in the two PCGs were examined in school . OUTCOME MEASURES Severity and prevalence of ECC and general caries . Levels of participation . RESULTS Among participants in the active PCG the prevalence of ECC , general caries and extraction experience and mean dmft ( 20 % : 54 % : 3 % : 2.2 ) were lower than in ' participants ' in the comparison area ( 32 % : 64 % : 12 % : 3.7 ) . All differences were statistically significant . When all children ( participants and non- participants ) in the two PCGs were compared , the differences were much reduced ( 30 % : 63 % : 6 % : 3.1 vs. 32 % : 64 % : 12 % : 3.6 ) . A higher proportion of children in the active PCG area ( 47 % ) were found not to have participated in the interventions , when compared to 21 % in the comparison area . Disease levels in the non- participants in the active PCG were particularly high . The impact of participation bias , changes in baseline balance , population mobility and alternative study design on outcomes are explored . CONCLUSION The impact of non-participation in a deprived , urban conurbation with high levels of population mobility are sufficient to dilute the impact of a health intervention such that few benefits are discernible at a population level OBJECTIVE To assess the impact of regularly supplying free fluoride toothpaste regularly to children , initially aged 12 months , and living in deprived areas of the north west of Engl and on the level of caries in the deciduous dentition at 5 - 6 years of age . A further aim was to compare the effectiveness of a programme using a toothpaste containing 440 ppmF ( Colgate 0 - 6 Gel ) with one containing 1,450 ppmF ( Colgate Great Regular Flavour ) in reducing caries . DESIGN R and omised controlled parallel group clinical trial . Clinical data were collected from test and control groups when the children were 5 - 6 years old . SETTING A programme of posting toothpaste with dental health messages to the homes of children initially aged 12 months . Clinical examinations took place in primary schools . PARTICIPANTS 7,422 children born in 3-month birth cohorts living in high caries areas in nine health districts in north west Engl and . Within each district children were r and omly assigned to test or control groups . INTERVENTIONS Toothpaste , containing either 440 ppmF or 1450 ppmF , and dental health literature posted at three monthly intervals to children in test groups until they were aged 5 - 6 years . MAIN OUTCOME MEASURES The dmft index , missing teeth and the prevalence of caries experience . RESULTS An analysis of 3,731 children who were examined and remained in the programme showed the mean dmft to be 2.15 for the group who had received 1,450 ppmF toothpaste and 2.49 for the 440 ppmF group . The mean dmft for the control group was 2.57 . This 16 % reduction between the 1,450 ppmF and control group was statistically significant ( P<0.05 ) . The difference between the 440 ppmF group and control was not significant . Further analyses to estimate the population effect of the programme also confirmed this relationship . CONCLUSION This study demonstrates that a programme distributing free toothpaste containing 1,450 ppmF provides a significant clinical benefit for high caries risk children living in deprived , non-fluori date d districts OBJECTIVE The medical centre at Almirante Nef Naval Hospital , Vina del Mar , Chile , operates a mother and child preventive dental program ( PDP ) which includes women from their fourth month of pregnancy and mothers with their offspring . The aim was to evaluate the effectiveness of this prenatal and postnatal prevention program after the first four years . METHODS The prevalence of early childhood caries of 180 1- to 3.5-year-old children enrolled in the PDP was compared with 180 non-participating children . The control group was r and omly selected from the rolls of the healthy child system of of the Valparaiso-San Antonio Health Service and was comparable by age , socio-economic status and level of fluoride in the drinking water ( 1.0 p.p.m . F ) with the PDP group . Clinical caries examinations were conducted by two calibrated examiners using the WHO visual criteria . RESULTS In the PDP group , 97 % of the children were caries free compared with the 77 % in the control group . The dft ( mean + /- SD ) of the PDP children was 0.11 + /- 0.78 versus 0.66 + /- 1.55 for the control children , a difference of 83.3 % . The differences between the groups in caries-free status and caries prevalence were both statistically significant ( P < 0.05 ) . CONCLUSIONS The preventive dental program was effective in inhibiting caries in pre-school children , even in a population already receiving the benefits of community water fluoridation Background Motivational Interviewing ( MI ) has been used across primary healthcare and been shown to be effective in reducing the prevalence of early childhood caries ( ECC ) in preschool children . This study aim ed to compare the effect of MI , in contrast to traditional dental health education ( DHE ) , on oral health knowledge , attitudes , beliefs and behaviours among parents and caregivers of preschool children in Trinidad . Method The design of this exploratory study included a cluster r and omised controlled trial and semi-structured focus groups . Six preschools ( 79 parents and caregivers ) in Eastern Trinidad were r and omly assigned to a test or control group ( 3 preschools in each group ) . Parents and caregivers in the test-group ( n = 25 ) received a talk on dental health using an MI approach and the control-group ( n = 54 ) received a talk using traditional DHE . Both groups received additional , written dental health information . The MI group also received two telephone call follow-ups as part of the MI protocol . Both groups were given question naires before the talks and four months later . Question items included oral health knowledge , beliefs , attitudes , brushing behaviour , oral health self-efficacy , oral health fatalism and a specific instrument to asses ‘ readiness for change ’ , the Readiness Assessment of Parents Concerning Infant Dental Decay ( RAPIDD ) . Participants in the test-group were also invited to take part in a focus group to share their views on the dental health talk . Results At four month follow-up , knowledge items on fluoride use , tooth brushing , dietary practice and dental attendance increased in both the test ( DHE + MI ) and control ( DHE ) groups ( ( p < 0.05 , Chi Square test ) . In the test-group there were increases in mean child tooth brushing frequency and reduction in oral health fatalism ( p < 0.05 t-test ) . Findings from a thematic analysis of the focus group suggested that the MI talk and telephone follow-up were well accepted and helpful in supporting parent and caregiver efforts to improve oral health practice s for their preschool children . Conclusion In this exploratory controlled study there was some evidence that using an MI approach when delivering oral health information had a positive effect on parent/ caregiver oral health knowledge , attitudes and behaviours compared to traditional DHE . There is need for further research involving the use of brief-counselling techniques in this Caribbean population Abstract Objective . ( 1 ) To evaluate the dental status of 5-year-old children in Clermont-Ferr and ( France ) in 2009 ; ( 2 ) To measure changes in children 's dental status between 2003 and 2009 ; and ( 3 ) To estimate the impact of an Oral Health Promotion ( OHP ) program implemented in nine schools since 2005 . Material s and methods . All 5-year-olds attending public schools in deprived areas ( n = 15 ) and six r and omly selected other schools in Clermont-Ferr and were invited to participate . Dental status was recorded using d3mft , as in 2003 . Parents responded to questions about their child 's oral hygiene and provided socio-demographic information . Results . Of children invited , 478 ( 77 % ) were examined . Mean dmft was 1.18 ( SD 2.61 ) ; 27.6 % had at least one tooth affected . Caries experience varied significantly with deprivation status , oral hygiene and household SES indicators . The only difference observed between 2003 and 2009 was an increase in the ‘ f ’ component ( p < 0.001 ) . Dental status had slightly deteriorated in areas characterized in 2003 by low caries levels ( p=0.07 ) . In deprived areas , mean dmft increased in schools without the OHP program ( p = 0.04 ) . Changes between 2003 and 2009 were studied at school level using Multiple Factorial Analysis ; it tended to improve in four schools , which had the OHP program . Household indicators of SES changed little . Oral hygiene levels varied differently from one school to another . Conclusions . Caries experience was high , with large inequalities between children . No major differences were observed between 2003 and 2009 . The OHP program has done little to reduce disparities in oral health , even if dental status improved in four schools PURPOSE The aim of this study was to assess the caries prevalence in the adult population of Pomerania , Germany in comparison to national and international data . MATERIAL S AND METHODS The study sample comprised 4,022 r and omly selected subjects who were examined from October 1997 to May 2001 within the " Study of Health in Pomerania " ( medical and dental , population -based cross-sectional study in Pomerania , Northeast Germany . Response rate : 69 % . Age range of subjects : 25 - 79 yrs ) . Carious defects , fillings and missing teeth were diagnosed and the DMFT/S scores were calculated according to WHO guidelines ( 1997 ) . These figures were compared to other German , Swedish and US data . RESULTS Women exhibited higher mean DMFT and DMFS values in all age groups than men . The mean DMFT/S scores were slightly higher than the values for the only two available nationally representative age groups in Germany . The prevalence of primary carious lesions or secondary caries was very low , result ing in minor treatment needs ( decayed surfaces : mean 0.95 + /- 3.3 ) and high care indices ( FS/DFS ) for all age groups ( 90 - 95 % ) . In contrast to this , the mean numbers of fillings in adults and especially of missing teeth in seniors were much higher in Pomerania for all age groups than in the Swedish and US adult population , where a caries decline was demonstrated . CONCLUSION In spite of a very low prevalence of primary carious lesions and secondary caries , the mean number DMFT/S and especially MT/S scores in the Pomeranian adult population are high in comparison with Swedish and US data , but differed only slightly from the limited available national data for Germany BACKGROUND Since the mid-1990s , there has been an increase in early childhood caries ( ECC ) in Australia and an increase in children living in one-parent families . OBJECTIVE To examine whether single parenthood ( mother only ) affects the effectiveness of an oral health promotion programme to prevent ECC in their child . METHODS First-time mothers were enrolled in a r and omized controlled trial of anticipatory guidance to prevent ECC . The intervention was applied during pregnancy and when the child was 6 and 12 months old . Mothers in the control group received no intervention . The presence of ECC was assessed at 20 months of age and compared between children from one- and two-parent families . RESULTS Of 649 women enrolled , 441 brought their child for dental assessment . Eighty-seven ( 19.7 % ) had a one-parent family . Children from one-parent families had a 2.3 times higher incidence of ECC than children from two-parent families . The intervention reduced the frequency of ECC from 8.1 % to 1.1 % in two-parent families ( relative risk : 0.14 ) and from 16.3 % to 4.5 % ( relative risk : 0.28 ) in one-parent families . One case of ECC was prevented for every nine single mothers receiving anticipatory guidance compared with one case per 15 partnered mothers . Despite a greater reduction in the absolute risk of ECC in children from one-parent families , the intervention reduced their ECC experience only 3.5-fold compared with sevenfold in children from two-parent families . CONCLUSION The intervention produced a greater reduction in the frequency of ECC in children from one-parent families than in those from two-parent families . This did not reduce their disadvantage , though , as they still had a four times higher risk than children from two-parent families . Mothers and children in one-parent families need substantially more attention and support than those in two-parent families to eliminate their disadvantage in suffering ECC The aim of this study was to assess the prevalence and distribution of root caries in the adult population of Pomerania , Germany . The study sample comprised 6,267 r and omly selected subjects who were scheduled for examination from 1997 to 2001 ( population -based cross-sectional study , response rate : 69 % , age range 20–79 years ) . 499 edentulous persons were excluded from the dental examination ( 12 % ) performed according to WHO guidelines ( 1997 ) . In the statistical analysis , frequency distributions , means and median values were calculated and subdivided for different age groups . The percentage of exposed and affected root surfaces increased with age ( root caries index 4.6–10.6 % ) . The mean number of carious/filled root surfaces ( RDFS ) rose from 0.4 per person ( 25–34 years ) to 2.3 ( 55–64 years ) and dropped for seniors due to the low number of retained teeth . Fillings comprised the largest proportion of the RDFS ( 69.5 % ) . Most caries/fillings were found on buccal surfaces , the highest rate in m and ibular premolars . With about half of over-45-year-olds having at least one carious/filled root surface and increasing number of retained teeth in seniors , root caries is a relevant and probably growing disease in Pomerania and East Germany The purpose of this investigation was to test the safety and clinical effect of a new material for the treatment of proximal caries . In 50 patients with two proximal initial lesions , one of the lesions was r and omly chosen and sealed with a thin polyurethane-dimethacrylate foil using bonding . The other lesion received oral home care and was left as the control . In clinical follow-ups after 6 and 12 months and X-ray evaluation after 2 and 3 years , the sealants showed good retention , marginal adaptation , and color . No relevant significant differences in plaque accumulation or gingival status were found between sealed and control teeth . On the radiographs , almost all sealed and control lesions appeared stable , indicating an arrest of the lesion . In conclusion , sealing initial proximal lesions showed no clinical problems and mostly arrest of caries on bitewing radiographs There is a lack of clinical studies comparing dentifrices with high fluoride ( F ) concentration . The aim was to evaluate a dentifrice containing 5,000 ppm F compared to a dentifrice containing 1,450 ppm F in caries-active adolescents . The design was a 2-year , single-blind r and omized controlled trial and 211 adolescents of 279 ( 76 % ) completed the trial . The subjects were divided into two groups and were given one of the assigned F dentifrices for daily unsupervised toothbrushing : ( 1 ) Duraphat 5,000 ppm F and ( 2 ) Pepsodent Superfluor 1,450 ppm F , both as NaF. The outcome variables were caries incidence and progression of proximal and occlusal caries . The subjects were asked to fill in a question naire to evaluate their compliance and they were divided into two subgroups : subgroup A , excellent compliance , and subgroup B , poor compliance . The latter group ( 28 % ) comprised the subjects who did not brush twice a day or did not use the dentifrice regularly . Adolescents using 5,000 ppm F toothpaste had significantly lower progression of caries compared to those using 1,450 ppm F toothpaste ( A : p < 0.01 , B : p < 0.001 ) , with a prevented fraction of 40 % . Subjects using 5,000 ppm F toothpaste had significantly lower caries incidence for compliance B compared to those using 1,450 ppm F toothpaste ( p < 0.05 ) ; the prevented fraction was 42 % . This may indicate that 5,000 ppm F toothpaste has a greater impact on individuals who do not use toothpaste regularly or do not brush twice a day . Thus , 5,000 ppm F toothpaste appears to be an important vehicle for caries prevention and treatment of adolescents with a high caries risk The objective of this study was to estimate the caries impact of providing training in infant feeding guidelines to workers at Brazilian public primary care clinics . In a cluster-r and omized controlled trial ( n = 20 clinics ) , health care workers either were trained in guidelines for infant nutrition , stressing healthful complementary feeding , or were assigned to a ‘ usual practice s ’ control , which allowed for maternal counseling at practitioner discretion . Training occurred once ; the amount of counseling provided to mothers was not assessed . Eligible pregnant women were enrolled to follow health outcomes in their children . Early childhood caries ( ECC ) was measured at age three years ( n = 458 children ) . The overall reductions in ECC ( relative risk , 0.92 ; 95%CI , 0.75 , 1.12 ) and severe ECC ( RR , 0.87 ; 95%CI , 0.64 , 1.19 ) were not statistically significant . There was a protective effect among mothers who remained exclusively at the same health center ( S-ECC RR , 0.68 ; 95%CI , 0.47 , 0.99 ) and among those naming the health center as their principal source of feeding advice ( S-ECC RR , 0.53 ; 95%CI , 0.29 , 0.97 ) . Health care worker training did not yield a statistically significant reduction in caries overall , although caries was reduced among children of mothers more connected to their health centers ( Clinical Trials.gov NCT00635453 ) OBJECTIVES Assess the effectiveness of home visits for advising mothers about breast feeding and weaning on early childhood caries ( ECC ) at the age of 12 months . METHODS A r and omized field trial was conducted in mothers who gave birth within the public health system in the Brazilian city of Sao Leopoldo ( intervention group = 200 ; controls = 300 ) . The intervention group received the advice 10 days after the child 's birth , monthly up to 6 months , at 8 , 10 and 12 months , based on the ' Ten Steps for Healthy Feeding ' , a Brazilian national health policy for primary care , based on WHO guidelines . Both groups had research assessment at 6 and 12 months , with dental caries investigated in this last assessment ; 122 children were lost in the 1-year follow-up ; 378 were assessed for caries : two predentulous children were excluded from the analysis . Mann-Whitney U was used to test if the average number of decayed surfaces ( DS ; white spots and cavities ) differed between the intervention and control groups , and logistic regression to estimate the effects of the intervention on the odds of ECC . Chi-square test was used to test for differences between the intervention and control groups in the distribution of feeding behaviours tackled by the dietary intervention . RESULTS 10.2 % of the children in the intervention group and 18.3 % of the controls had caries . The odds of caries was 48 % lower for the intervention group , adjusted for number of teeth ( OR = 0.52 , 95 % CI = 0.27 - 0.97 ) . Mean DS were lower for the intervention group ( 0.37 ) when compared with the control group ( 0.63 ) , ( Mann-Whitney U , P = 0.03 ) . The intervention group had significantly longer duration of exclusive breast feeding ( P = 0.000 ) , later introduction of sugar ( P = 0.005 ) , and smaller probability of ever having eaten biscuits ( P = 0.000 ) , honey ( P = 0.003 ) , soft drinks ( P = 0.02 ) , fromage-frais ( P = 0.001 ) , chocolate and sweets ( P = 0.001 ) . CONCLUSIONS ECC is a public health problem in that population . The home visits for dietary advice appear to help reducing dental caries in infants . Greater efforts are needed to tackle cariogenic dietary behaviours even further , as a relevant proportion of children of the intervention group were shown to present with dental caries . Further studies should examine the effect of the intervention in the longer term Objectives The aim of this prospect i ve birth cohort study was to evaluate the effect of the interdisciplinary oral health programme ( OHP ) for early childhood caries ( ECC ) in 5-year-old German children . Material and methods All parents of newborns ( n = 1162 ; born 2009/2010 ) were visited after birth by the communal newborn visiting service of Jena , Thuringia , and advised on general and dental health . In the first year of life , children were invited to attend a dental examination in the Jena University Hospital . Participating children were included in a caries-risk-related recall system with continuous oral care over 5 years . The caries-risk assessment tool of the AAPD was used to determine the likelihood of carious lesion development and to categorize the children at low , moderate or high risk for caries . High-risk children received fluoride varnish . Families ( n = 563 ) who gave their approval for final examination after 5 years were invited again and examined by a blinded clinician . Dental caries was scored using WHO diagnostic criteria exp and ed to d1-level without radiography . Children were allocated to prevention ( PG ) and control group ( CG ) and matched on the basis of age , sex , ethnicity and socio-economic status ( SES ) . Results Two hundred and eighty-nine children ( mean age 5.2 ± 0.7 years ; 46.7 % female ) were examined . Children in the PG ( n = 174 ) showed significantly lower caries prevalence and experience ( 10.9 % , 0.2 ± 0.7 d3–4mft ) than children in the CG ( 57.4 % , 2.9 ± 3.8 d3–4mft ) . Multivariate analysis found that low SES , early start of tooth brushing , supervision/regular second brush by parent , regular dental visits and duration of breast-/bottle-feeding > 1 year were significantly related to d3–4mft . Conclusions The OHP was an effective approach for preventing early childhood caries in preschool children . Clinical relevance A programme consisting of early maternal counselling , establishment of a dental home , and inclusion of the children in a caries-risk-related recall system with continuous dental care and fluoride varnish application can prevent ECC.Trial registration German Clinical Trials Register DRKS00003438 , OBJECTIVE To explore the effectiveness of comprehensive oral health care to reduce the caries incidence for children with severe early childhood caries ( s-ECC ) in an urban area in China . METHODS A total of 357 children aged 3 to 4 years old and diagnosed with s-ECC were recruited in this r and omised controlled , single-blinded clinical trial for 1 year . Children of two different kindergarten classes were enrolled in this study and r and omly divided into a test group ( 205 children ) and a control group ( 152 children ) . The test group received comprehensive oral health care , which included : oral health examination , oral health education , topical fluoride application and dental treatment , and the children in the control group only received the oral health examination . The evaluation of the oral health question naire for parents was also performed . An evaluation was carried out at the time of recruitment and 1 year later to explore the effectiveness of the comprehensive oral health care model . RESULTS The differences in decayed teeth ( dt ) , decayed tooth surfaces ( ds ) , filled teeth ( ft ) , filled tooth surfaces ( fs ) and the ratio of ft /(dt + ft ) between the two groups were statistically significant ( P < 0.001 ) at 1 year . The incidence of caries in the control group was higher than that of the test group ( P = 0.02 ) . The rate of awareness of oral health knowledge ( P = 0.01 ) and the practice of good diet habits ( P = 0.02 ) by parents in the test group were significantly higher than those in the control group . CONCLUSION The present study demonstrated that the comprehensive oral health care program reduces and prevents caries amongst children with s-ECC BACKGROUND The authors conducted a study to compare the effect of a motivational interviewing counseling treatment with that of traditional health education on parents of young children at high risk of developing dental caries . OVERVIEW The authors enrolled in the study parents of 240 infants aged 6 to 18 months and r and omly assigned them to either a motivational interviewing , or MI , group or a traditional health education ( control ) group . Parents in the control group received a pamphlet and watched a video . Parents in the MI group also received the pamphlet and watched the video ; in addition , they received a personalized MI counseling session and six follow-up telephone calls . RESULTS After one year , children in the MI group had .71 new carious lesions ( st and ard deviation , or SD , = 2.8 ) , while those in the control group had 1.91 ( SD = 4.8 ) new carious lesions ( t[238 ] = 2.37 , one-tailed , P < .01 ) . CONCLUSIONS MI is a promising approach that should receive further attention . CLINICAL IMPLICATION S MI may lead parents and others to better accept dental recommendations about preventing caries in their children BACKGROUND Home visits ( HV ) provide excellent opportunities for health promotion . AIM This longitudinal study compared the effects of HV and telephone contacts ( TC ) in preventing early childhood caries ( ECC ) and colonisation of mutans streptococci ( MS ) and lactobacilli ( LB ) from 0 to 24 months . DESIGN A total of 325 children were recruited from community health centres at mean age of 42 days , and r and omly assigned to receive either HV or TC . A total of 188 children completed three , 6 monthly HV , and another 58 had three , 6 monthly TC . An additional 40 age-matched children from childcare facilities served as reference controls ( RC ) . At 24 months , all groups were examined at a community dental clinic . RESULTS At 24 months , three HV children of 188 ( 1.5 % ) had caries , compared to four TC of 58 ( 6.8 % ) and nine RC of 40 ( 22.5 % ) ( P < 0.001 for HV versus RC ; P = 0.05 for HV versus TC and P = 0.03 for TC versus RC ) . There were also more children with MS in the TC ( 47 % ) and RC ( 35 % ) compared to HV ( 28 % ) group ( P = 0.01 and P = 0.02 ) . CONCLUSIONS Home visits and telephone contacts conducted 6 monthly from birth are effective in reducing ECC prevalence by 24 months The aim of the present investigation was to study the prevalence of approximal caries lesions and fillings in posterior teeth at 15 years of age in a prospect ively followed Swedish population ( n = 568 ) , with special reference to their caries experience at the age of 3 years . Only approximal surfaces were recorded , since all children in the Community of Jönköping have had fissure sealing performed on all caries-free permanent molars . At 15 years of age , the mean number of approximal tooth surfaces with initial caries lesions ( Dia ) , manifest caries lesions and fillings ( DmFa ) and total caries experience and fillings ( Di + mFa ) – recorded on bitewing radiographs – was 2.78 , 0.45 and 3.23 , respectively . One third of the adolescents had no approximal caries or fillings ; the Dia constituted 86 % of the Di + mFa . Children with manifest caries at 3 years of age had a higher risk of developing approximal caries in their permanent teeth than caries-free children at the same age ( 41 vs. 17 % ) . Furthermore , children who were caries-free at 3 years of age were more likely to remain caries-free at 15 years of age compared to children with manifest caries ( 37 vs. 17 % ) . All these differences were statistically significant ( p < 0.001 ) . Additionally , early childhood caries experience ( developed before 3 years of age ) had a greater predictive value than late childhood caries experience ( developed between 3 and 6 years of age ) concerning approximal caries at 15 years of age The aim of this epidemiological study performed in 2013 was to analyze various clinical and radiographic data on oral health and compare the results to those of four cross-sectional studies carried out 1973 - 2003 . In 1973 , 1983 , 1993 , 2003 , and 2013 r and om sample s of 1,000 ; 1,104 ; 1,078 ; 987 ; and 1,010 individuals , respectively , were studied . The individuals were evenly distributed in the age groups 3 , 5 , 10 , 15 , 20 , 30 , 40 , 50 , 60 , 70 , and 80o years . Eighty-year-olds were not included in 1973 . All subjects were inhabitants of the city of Jönköping , Sweden . The clinical and radiographic examination assessed edentulousness , removable dentures , implants , number of teeth , caries , restorations , oral hygiene , calculus , periodontal status , and endodontic treatment . The frequency of edentulous individuals aged 40 - 70 years was 16 , 12 , 8 , 1 , and 0.3 % in 1973 , 1983 , 1993 , 2003 , and 2013 , respectively . No complete denture weareryounger than 80-years old was found in 2013 . During the 40-year period , the mean number of teeth in the age groups 30 - 80 years increased . In 2013 , the 60-year-olds had nearly complete dentitions . Implants were found in all age groups from 30 years of age . The total number of individuals with implants was 36 in 2013 . This was higher than earlier surveys , 4 in 1993 , and 18 in 2003 . The percentage of children and adults without caries and restorations increased during the 40-year period . It was found that the percentage of caries-free 3- and 5-year-olds were 79 % and 69 % , respectively , of the individuals in 2013 . In the age groups 10 - 20 years , the percentage of caries-free individuals increased between 2003 and 2013 . In 2013 , 43 % of the 15-year-olds were completely free from caries and restorations compared to 20 % in 2003 . In all age groups 5 - 60 years , DFS was lower in 2013 compared to the earlier examinations . There was no major change in DFS between 2003 and 2013 in the age groups 70 and 80 years . The most obvious change was the decrease in number of FS over the 40-year period of time . Regarding crowned teeth the most clear changes between 1973 to 2013 were the decrease in percentage of crowned teeth in the age groups 40 and 50-year-olds . The percentage of endodontically treated teeth decreased between 1973 and 2013 in all age groups . In age groups 10 - 30-year-olds a major reduction from about 30 % to 15 % in mean plaque score was seen between 1973 - 2003 . Only a minor change in plaque score was seen during the last decade . For the age groups 40 years and older , a decrease in the percentage of surfaces with plaque was observed between 2003 - 2013 . The percentage of tooth sites with gingivitis was for 20 years and older about 40 % in 1973 . In 2013 , the percentage was about 15 % . The frequency of sites with gingivitis was generally lower in 2013 compared with the otheryears,1973 - 1993 . The percentage of individuals with probing pocket depths > 4 mm increased with age . Between 2003 - 2013 a clear reduction was seen in all age groups in frequency of individuals with probing pocket depth > 4 mm . Over the 40-year period an increase in the number of individuals with no marginal bone loss and a decrease in the number of subjects with moderate alveolar bone loss were seen . The continuous improvement in oral health and the reduced need of restorative treatment will seriously affect the provision of dental helath care and dental delivery system in the near future The 2014 Early Childhood Caries Conference encompassed evidence -based review s on the state of the science regarding early childhood carries ( ECC ) epidemiology , etiology , prevention , and disease management . The purpose of this paper was to discuss the work presented at the conference and identify opportunities in research , policy , and clinical management that may improve early childhood caries outcomes and lower costs of care . While great progress has been made since the 1997 ECC Conference , there remains a paucity of high- quality evidence from r and omized controlled trials on what are the most effective means to prevent and manage ECC . Analyses of studies indicate that some approaches , such as chlorhexidine , iodine , and remineralizing agents , have not shown consistent findings in preventing ECC . However , evidence exists to yield recommendations in some areas . There are useful risk assessment indicators to identify preschool children at risk for caries . Fluori date d toothpaste and fluoride varnish currently are the most effective chemotherapeutic strategies to prevent ECC . Motivational interviewing , a form of patient-centered counseling , is effective for motivating oral health behaviors and shows promise for reducing caries . Additionally , evidence is emerging that shows the value of chronic disease management approaches and integrating ECC oral health care within medical care setting s. Recommendations for future directions in ECC research and policy were also key outcomes of the conference The caries preventive outcome of a school-based program with salivary lactobacillus counts as sugarmotivating tool was evaluated in six cohorts of totally 936 adolescents in a comprehensive school in Sweden . Students from a neighboring district with similar socioeconomic structure but with no corresponding dental health-promoting activities were selected as reference . The program started in the beginning of the 7th grade ( 13 years ) and was terminated at the end of the 9th grade ( 16 years ) . Salivary lactobacilli were evaluated semi-annually with a dip-slide method and used for individual counseling . Dental caries was scored from the dental records and bitewing radiographs of each 4th participant at baseline and at 16 and 19 years of age . The number of salivary lactobacilli decreased significantly ( P < 0.05 ) in all cohorts but one during the program . There was no significant difference in the increment of caries ( DFS ) between the participants from the study and reference schools , either at the end of the program or at 19 years of age . The increment of proximal enamel caries was slightly lower in the study group compared with the reference group ( P < 0.05 ) at the final registration . Considering the time and efforts spent , the results did not seem to justify a school-based intervention with lactobacillus counts as a sugar-motivating tool in an adolescent low-caries population OBJECTIVES To investigate the effectiveness of h and s-on training in parental toothbrushing , with or without semi-annual applications of 5 % sodium fluoride varnish in preventing ECC . METHODS Study was conducted in Hong Kong where water is optimally fluori date d. Children aged 8 - 23 months were recruited and r and omly allocated to one of three groups : Gp 1 - control , one-off oral health education talk to parents ; Gp 2 - oral health education talk and parental toothbrushing training , reinforced every 6 months ; Gp 3 - semi-annual application of fluoride varnish onto child 's teeth in addition to the intervention provided to Gp 2 . Clinical examinations of the children and interviews were conducted at baseline and after 24 months to assess the children 's dental caries status and toothbrushing behaviour . RESULTS Out of the 450 child-parent dyads recruited at baseline , 415 ( 92 % ) remained after 24 months . At baseline , 2 % of the children had non-cavitated enamel caries lesions and the mean dmft score was 0.03 ± 0.24 . Most of the children did not have daily parental toothbrushing ( 65 - 73 % ) and self toothbrushing ( 86 - 90 % ) . At 24-month follow-up , including both non-cavitated and cavitated carious lesions , the incidences of ECC in Gp 1 to Gp 3 were 11.9 % , 11.8 % , and 17.5 % , respectively ( p>0.05 ) ; and the mean new dmft scores in Gp 1 to Gp 3 were 0.3 , 0.2 , and 0.3 , respectively ( p>0.05 ) . Proportions of parents who practice d parental toothbrushing twice daily were 62.7 % , 60.4 % , and 65.7 % in Gp 1 to Gp 3 , respectively ( p>0.05 ) . CONCLUSIONS In a water fluori date d area , h and s-on training in parental toothbrushing , with or without semi-annual application of 5 % sodium fluoride varnish may not have additional effect on preventing ECC in young children with low risk of dental caries compared to provision of oral health education to parents . CLINICAL SIGNIFICANCE In a water fluori date d area , provision of individual oral health education to parents may be sufficient for preventing ECC in young children below age 3 . Supplemental training in parental toothbrushing and semi-annual applications of fluoride varnish may not have additional caries prevention effect in young children with low risk of dental caries |
663 | 26,741,877 | Based on this large meta- analysis , RA for primary PCI in the setting of ACS is associated with reduction in cardiac and safety endpoints when compared with FA in both urgent and elective procedures . | OBJECTIVES Radial artery access ( RA ) for left heart catheterization and percutaneous coronary interventions ( PCIs ) has been demonstrated to be safe and effective .
Despite consistent data showing less bleeding complications compared with femoral artery access ( FA ) , it continues to be underused in the United States , particularly in patients with acute coronary syndrome ( ACS ) in whom aggressive anticoagulation and platelet inhibition regimens are needed .
This systematic review and meta- analysis aims to compare major cardiovascular outcomes and safety endpoints in patients with ACS managed with PCI using radial versus femoral access . | BACKGROUND Percutaneous treatment of patients with ST segment elevation myocardial infa rct ion ( STEMI ) has become the st and ard and default mode of management as recommended by the European Society of Cardiology guidelines for managing acute myocardial infa rct ion in patients presenting with STEMI . The choice of vascular access is made by the operator and has a potential impact on the safety and efficacy of the procedure and outcomes . AIM To underst and the influence of a radial approach on bleeding complications and angiographic success , we performed a prospect i ve , controlled r and omised trial . METHODS Patients were allocated to radial ( TR ) or femoral ( TF ) vascular access . The primary endpoints were major bleeding by the REPLACE-2 scale and minor bleeding by the EASY scale ( TR arm ) or the FEMORAL scale ( TF arm ) . Other outcomes included procedural data , in-hospital and long-term survival . RESULTS There were 103 patients analysed in total , 52 in the TR arm and 51 in the TF arm . The demographic and clinical baseline characteristics were well matched between the two study groups . The frequency of the primary endpoint was the same in both arms ( TR : 25.0 % vs. TF : 33.3 % , p = 0.238 ) . In per protocol analysis , there was a significant benefit of the TR approach among independent operators ( 17.4 % vs. 36.8 % , p = 0.038 ) . Major bleeding by the REPLACE-2 scale occurred in 4.2 % of patients ( TR : 5.8 % vs. TF : 3.9 % , p = 0.509 ) . There were no differences in terms of the rate of major cardiac adverse events , which happened in 10.7 % of the study population ( TR : 9.6 % vs. TF : 11.8 % , p = 0.48 ) . In the TF arm , there was a trend towards a higher risk of local bleedings ( TR : 22.4 % vs. TF : 37.7 % , p = 0.081 ) and a significantly higher frequency of local haematoma ( class III , EASY/FEMORAL ) ( TR : 0 % vs. TF : 9.8 % , p = 0.027 ) . CONCLUSIONS There were no significant differences between the TR and TF approaches in terms of clinical efficacy and patient safety . However , patients treated by independent operators might benefit from TR access . The overall complication risk of percutaneous coronary intervention treatment of STEMI patients remains low OBJECTIVES The purpose of this study was to assess whether transradial access for ST-segment elevation acute coronary syndrome undergoing early invasive treatment is associated with better outcome compared with conventional transfemoral access . BACKGROUND In patients with acute coronary syndrome , bleeding is a significant predictor of worse outcome . Access site complications represent a significant source of bleeding for those patients undergoing revascularization , especially when femoral access is used . METHODS The RIFLE-STEACS ( Radial Versus Femoral R and omized Investigation in ST-Elevation Acute Coronary Syndrome ) was a multicenter , r and omized , parallel-group study . Between January 2009 and July 2011 , 1,001 acute ST-segment elevation acute coronary syndrome patients undergoing primary /rescue percutaneous coronary intervention were r and omized to the radial ( 500 ) or femoral ( 501 ) approach at 4 high-volume centers . The primary endpoint was the 30-day rate of net adverse clinical events ( NACEs ) , defined as a composite of cardiac death , stroke , myocardial infa rct ion , target lesion revascularization , and bleeding ) . Individual components of NACEs and length of hospital stay were secondary endpoints . RESULTS The primary endpoint of 30-day NACEs occurred in 68 patients ( 13.6 % ) in the radial arm and 105 patients ( 21.0 % ) in the femoral arm ( p = 0.003 ) . In particular , compared with femoral , radial access was associated with significantly lower rates of cardiac mortality ( 5.2 % vs. 9.2 % , p = 0.020 ) , bleeding ( 7.8 % vs. 12.2 % , p = 0.026 ) , and shorter hospital stay ( 5 days first to third quartile range , 4 to 7 days ] vs. 6 [ range , 5 to 8 days ] ; p = 0.03 ) . CONCLUSIONS Radial access in patients with ST-segment elevation acute coronary syndrome is associated with significant clinical benefits , in terms of both lower morbidity and cardiac mortality . Thus , it should become the recommended approach in these patients , provided adequate operator and center expertise is present . ( Radial Versus Femoral Investigation in ST Elevation Acute Coronary Syndrome [ RIFLE-STEACS ] ; NCT01420614 ) Although transradial angioplasty has been shown to have no major entry site – related complications , its clinical applicability for balloon angioplasty and stenting in acute myocardial infa rct ion ( AMI ) is unclear . In order to assess the feasibility , safety , and clinical outcome of transradial access for coronary angioplasty ( PTCA ) and stenting during AMI , transradial angioplasty for AMI was registered on a prospect i ve data base at two European sites ( A and B ) with experience in the radial approach ( RA ) ; 6 Fr catheters with an inner lumen of at least 0.064″ and low‐profile rapid‐exchange balloons were used . Primary success rates and procedural complications of 6 Fr RA were determined and compared to 6 Fr femoral approach ( FA ) procedures . A total of 1,224 AMI patients entered the registry . Study site A enrolled 185 RA patients ( 13.6 % AMI ) and study site B 92 RA patients ( 63.4 % ) . Patient baseline demographics were similar in both study centers and showed no differences between RA and FA patients , except a more frequent use of abciximab in study site B compared to A. PTCA was successful in > 95 % of both RA and FA patients . Total procedural time did not differ between RA and FA patients . Severe access site – related bleeding complications , however , were observed in FA patients only : study site A used closure devices routinely and found 2 % severe bleedings ; study site B used no closure device for FA patients and observed 7 % severe bleedings . In selected patients and in experienced h and s , transradial PTCA in AMI has a high success rate , is clinical ly safe , and could become an attractive alternative access site for patients being at high or even low risk for bleeding complications . Cathet Cardiovasc Intervent 2002;55:206–211 . © 2002 Wiley‐Liss , Transradial coronary intervention ( TRI ) can be performed in elective patients with low incidence of access site complications . However , the feasibility of primary stent implantation by TRI is still not clear in patients with acute myocardial infa rct ion ( AMI ) . We prospect ively r and omized 149 patients out of 213 patients with AMI within 12 hr from onset into two groups : 77 patients treated by TRI ( TRI group ) and 72 patients by transfemoral coronary intervention ( TFI ; TFI group ) . We compared the incidences of major adverse cardiac events ( MACE ; repeat MI , target lesion revascularization , and cardiac death ) during the initial hospitalization and 9‐month follow‐up periods in both groups . There were one patient who crossed over to the opposite arm , and two patients with severe bleeding complications in the TFI group . Background characteristics of patients were similar between the two groups . The success rate of reperfusion and the incidence of in‐hospital MACE were similar in both groups ( 96.1 % and 5.2 % vs. 97.1 % and 8.3 % in TRI and TFI groups , respectively ) . In selected patients with AMI , primary stent implantation by TRI is feasible as compared to TFI . Cathet Cardiovasc Intervent 2003;59:26–33 . © 2003 Wiley‐Liss , CONTEXT It is unclear if blood transfusion in anemic patients with acute coronary syndromes is associated with improved survival . OBJECTIVE To determine the association between blood transfusion and mortality among patients with acute coronary syndromes who develop bleeding , anemia , or both during their hospital course . DESIGN , SETTING , AND PATIENTS We analyzed 24,112 enrollees in 3 large international trials of patients with acute coronary syndromes ( the GUSTO IIb , PURSUIT , and PARAGON B trials ) . Patients were grouped according to whether they received a blood transfusion during the hospitalization . The association between transfusion and outcome was assessed using Cox proportional hazards modeling that incorporated transfusion as a time-dependent covariate and the propensity to receive blood , and a l and mark analysis . MAIN OUTCOME MEASURE Thirty-day mortality . RESULTS Of the patients included , 2401 ( 10.0 % ) underwent at least 1 blood transfusion during their hospitalization . Patients who underwent transfusion were older and had more comorbid illness at presentation and also had a significantly higher unadjusted rate of 30-day death ( 8.00 % vs 3.08 % ; P<.001 ) , myocardial infa rct ion ( MI ) ( 25.16 % vs 8.16 % ; P<.001 ) , and death/MI ( 29.24 % vs 10.02 % ; P<.001 ) compared with patients who did not undergo transfusion . Using Cox proportional hazards modeling that incorporated transfusion as a time-dependent covariate , transfusion was associated with an increased hazard for 30-day death ( adjusted hazard ratio [ HR ] , 3.94 ; 95 % confidence interval [ CI ] , 3.26 - 4.75 ) and 30-day death/MI ( HR , 2.92 ; 95 % CI , 2.55 - 3.35 ) . In the l and mark analysis that included procedures and bleeding events , transfusion was associated with a trend toward increased mortality . The predicted probability of 30-day death was higher with transfusion at nadir hematocrit values above 25 % . CONCLUSIONS Blood transfusion in the setting of acute coronary syndromes is associated with higher mortality , and this relationship persists after adjustment for other predictive factors and timing of events . Given the limitations of post hoc analysis of clinical trials data , a r and omized trial of transfusion strategies is warranted to resolve the disparity in results between our study and other observational studies . We suggest caution regarding the routine use of blood transfusion to maintain arbitrary hematocrit levels in stable patients with ischemic heart disease BACKGROUND The transradial approach for percutaneous coronary intervention ( PCI ) seems to be superior to transfemoral . The safety and efficacy of transradial approach for PCI in acute myocardial infa rct ion is not well-established . METHODS Hundred patients with acute myocardial infa rct ion qualified to PCI were r and omly assigned to transradial ( group I ; n = 50 ) and transfemoral ( group II ; n = 50 ) approaches . RESULTS PCI was successful for almost all patients , except one from group II . There were no significant differences between groups in X-ray exposition , volume of contrast and total procedure duration . Small but significant elongation of door to stent time in group I was caused mostly by a longer time between beginning of procedure and arterial sheath introduction . Major bleeding complications occurred in three patients from group I and seven from group II . There were no significant differences observed between the two groups . Time to ambulation in group I was significantly shorter then in group II ( 22.6 + /- 10.3 h vs. 34.7 + /- 34.6 h ; p = 0.003 ) . CONCLUSIONS The transradial approach for PCI in acute myocardial infa rct ion has the same efficacy as transfemoral . There are no differences in total procedure duration , X-ray exposition or volume of contrast between the two approaches . A longer time from the patient 's admission to the individual stages of the PCI procedure in group I was mostly due to the longer times of the initial stages of the procedure . The use of transradial approach reduces the time to ambulation and allows rehabilitation to begin sooner . In both groups , bleeding complications occurred rarely BACKGROUND Transradial percutaneous coronary intervention ( PCI ) results in fewer vascular complications , earlier ambulation , and improved patient comfort . Limited data exist for radial access in acute myocardial infa rct ion , where reperfusion must occur quickly . METHODS In a multicenter pilot trial , 50 patients with myocardial infa rct ion requiring either primary or rescue PCI were r and omized to radial or femoral access . All operators had previously performed at least 100 transradial cases . Procedure times were prospect ively recorded . RESULTS Thrombolysis was used in 66 % of the cases and glycoprotein IIb/IIIa inhibitors in 94 % . Crossover from radial to femoral access was required in one case . Percutaneous coronary intervention was performed in 47 patients , with stenting in 45 . One procedural failure occurred with radial access because of inability to cross the occlusion . The time from local anesthesia to first balloon inflation was 32 ( 25th percentile 26 , 75th percentile 38 ) minutes for radial access and 26 ( 22 , 33 ) minutes for femoral access ( P = .04 ) . There were no significant differences in contrast use or fluoroscopy time . No patient experienced major bleeding or required transfusion . Doppler studies demonstrated 2 asymptomatic radial occlusions and 2 pseudoaneurysms ( 1 from each group ) . One patient in the femoral group died 2 days after PCI . At 30 days , there were no strokes or reinfa rct ions and no patient required bypass surgery or repeat PCI . CONCLUSIONS Primary and rescue PCI can be performed with high success rates using either radial or femoral access . Although radial access was associated with a longer time to first balloon inflation , the difference was small and likely not clinical ly significant . In patients without shock , major bleeding and vascular complications are infrequent with either access site despite the high use of thrombolysis and glycoprotein IIb/IIIa inhibitors OBJECTIVES The purpose of this study was to determine the predictors of major bleeding and the impact of major bleeding on outcomes , including mortality , in acute coronary syndromes ( ACS ) . BACKGROUND Whether major bleeding independently predicts mortality in patients with ACS undergoing an early invasive strategy is undefined . METHODS Patients ( n = 13,819 ) with moderate- and high-risk ACS were r and omized to heparin ( unfractionated or enoxaparin ) plus glycoprotein IIb/IIIa inhibition ( GPI ) , bivalirudin plus GPI , or bivalirudin monotherapy ( plus provisional GPI ) . Logistic regression was used to determine predictors of 30-day major bleeding and mortality . RESULTS Major bleeding rates in patients treated with heparin plus GPI were higher versus bivalirudin monotherapy ( 5.7 % vs. 3.0 % , p < 0.001 ) and similar versus bivalirudin plus GPI ( 5.7 % vs. 5.3 % , p = 0.38 ) . Independent predictors of major bleeding were advanced age , female gender , diabetes , hypertension , renal insufficiency , anemia , no prior percutaneous coronary intervention , cardiac biomarker elevation , ST-segment deviation > /=1 mm , and treatment with heparin plus GPI versus bivalirudin monotherapy . Patients with major bleeding had higher 30-day rates of mortality ( 7.3 % vs. 1.2 % , p < 0.0001 ) , composite ischemia ( 23.1 % vs. 6.8 % , p < 0.0001 ) , and stent thrombosis ( 3.4 % vs. 0.6 % , p < 0.0001 ) versus those without major bleeding . Major bleeding was an independent predictor of 30-day mortality ( odds ratio 7.55 , 95 % confidence interval 4.68 to 12.18 , p < 0.0001 ) . CONCLUSIONS Major bleeding is a powerful independent predictor of 30-day mortality in patients with ACS managed invasively . Several factors independently predict major bleeding , including treatment with heparin plus GPI compared with bivalirudin monotherapy . Knowledge of these findings might be useful to reduce bleeding risk and improve outcomes in ACS Compared to the femoral approach , the use of radial arterial access has been demonstrated to reduce the incidence of access site bleeding complications in staged procedures . The purpose of this study was to evaluate clinical outcomes comparing radial and femoral approaches in the treatment of acute myocardial infa rct ion with primary angioplasty and the GP IIb/IIIa inhibitor abciximab . Between 15 September 1999 and 15 September 2002 , we prospect ively enrolled 119 consecutive patients undergoing primary angioplasty with abciximab comparing radial ( n = 64 ) and femoral ( n = 55 ) access . In this nonr and omized study , freedom from major cardiac events at 1‐month follow‐up occurred in 62 ( 97 % ) and 52 ( 94.5 % ) patients in the radial and the femoral groups , respectively ( P = 0.19 ) . There were no major access site bleeding complications in the radial group , as opposed to three ( 5.5 % ) in the femoral group ( P = 0.03 ) , all requiring transfusions , with surgical repair necessary in two . Uncomplicated clinical course occurred in 62 ( 97 % ) of patients in the radial group and 49 ( 89 % ) in the femoral group ( P = 0.04 ) . Total hospital length of stay was significantly higher in the femoral group ( 5.9 ± 2.1 vs. 4.5 ± 1.2 days ; P = 0.05 ) . Cannulation time ( from patient arrival at the catheterization laboratory to the effective placement of arterial sheath ) and procedural time were not significantly different in the radial and the femoral group ( respectively 8.5 ± 5.2 vs. 9.0 ± 5.8 min , P = 0.81 , and 42 ± 28 vs. 44 ± 27 min , P = 0.74 ) . Nevertheless , time of radiation ( 23.1 ± 11 vs. 16.5 ± 10.9 min ; P = 0.01 ) and dose‐area product ( 28,616 ± 16,571 vs. 18,819 ± 10,739 R · cm2 ; P = 0.01 ) were significantly higher in the radial group . In patients with acute myocardial infa rct ion treated with primary angioplasty and abciximab , the transradial access is efficacious with fewer major access site complications than transfemoral access . Transradial approach produces a shorter length of stay , as compared to the transfemoral approach , although with longer times of radiation and higher dose‐area product . Catheter Cardiovasc Interv 2004;61:67–73 . © 2004 Wiley‐Liss , Objective : To compare bleeding complications and results of percutaneous coronary intervention ( PCI ) between patients treated by radial and femoral approaches for acute myocardial infa rct ion ( AMI , ) and using abciximab and 5 French guiding-catheters . Patients : 114 consecutive patients with AMI were prospect ively r and omised . Exclusion criteria were a history of coronary artery bypass graft , cardiogenic shock , atrioventricular block , and contraindication to abciximab or a negative Allen test . Local haemostasis was achieved by manual compression . Results : Baseline characteristics were similar between the two groups . Peripheral arterial complication rates and delays to patient ambulation were significantly lower in the radial group than in the femoral group , whereas in-hospital stay was similar between the two groups . A cross over was more often necessary in the radial group than in the femoral group . Coronary angiography duration and fluoroscopy time were significantly longer in the radial group than in the femoral group , whereas PCI duration was similar in both groups . Conclusions : The FARMI trial showed that the radial route lowered peripheral arterial complication rates and allowed earlier ambulation , despite no significant benefit on the duration of hospitalisation Objective : To examine the safety and efficacy of emergency transradial primary percutaneous coronary intervention for ST-elevation myocardial infa rct ion . Design : Single-centre observational study with prospect i ve data collection . Setting : A regional cardiac centre , United Kingdom . Patients : 1051 consecutive patients admitted with ST-elevation myocardial infa rct ion , without cardiogenic shock , between November 2004 and October 2008 . Interventions : Percutaneous coronary interventions by radial and femoral access Main outcome measures : The primary outcome measures were procedural success , major vascular complication and failed initial access strategy . Secondary outcomes were in-hospital mortality and major adverse cardiac and cerebrovascular events , needle-to-balloon times , contrast volume used , radiation dose absorbed and time to discharge . Multiple regression analysis was used to adjust for potential differences between the groups . Results : 571 patients underwent radial access and 480 femoral . A variable preference for radial access was observed among the lead operators ( between 21 % and 90 % ) . Procedural success was similar between the radial and femoral groups , but major vascular complications were more frequent at the site of femoral access ( 0 % radial versus 1.9 % femoral , p = 0.001 ) . Failure of the initial access strategy was more frequent in the radial group ( 7.7 % versus 0.6 % , p<0.001 ) . Adjustment for other procedural and clinical predictors did not alter these findings . Needle-to-balloon time , as a measure of procedural efficiency , was equal for radial and femoral groups . Conclusions : In the setting of acute ST-elevation myocardial infa rct ion without cardiogenic shock , transradial primary angioplasty is safe , with comparable outcomes to a femoral approach and a lower risk of vascular complications BACKGROUND Early percutaneous coronary intervention ( PCI ) following thrombolysis may be beneficial in patients with ST-segment elevation myocardial infa rct ion ( STEMI ) who were admitted at a non-PCI hospital . The aim of this study was to evaluate the safety and efficacy of the radial artery as a vascular route for early PCI following thrombolysis in patients with STEMI . METHODS All consecutive STEMI patients within 12 hours after thrombolysis were enrolled , and eligible patients were r and omly assigned to either transfemoral ( TFI group ) or transradial catheterization ( TRI group ) . Several time intervals were measured . The puncture success rate and ambulation time were assessed . The vascular access-site complications were also assessed after the PCI procedure , and the incidence of major adverse cardiac events ( MACE ) in hospital was observed . RESULTS A total of 119 cases were enrolled , with 60 in the TRI group and 59 in the TFI group . There were no significant differences in transfer time and total procedure time . The puncture time in the TRI group was not significantly different compared to the TFI group . The time between PCI and ambulation in the TRI group was shorter than in the TFI group . There was a trend toward lower in the incidence of bleeding complications and vascular complications in the TRI group . CONCLUSION TRI for STEMI patients following intravenous thrombolysis was as safe and feasible as TFI , with a trend toward lower incidence of bleeding complications and vascular complications BACKGROUND The aim of the present study was to test the hypothesis that the transradial arterial approach ( TRA ) is not inferior to the transfemoral arterial approach ( TFA ) for < or = Killip 3 acute myocardial infa rct ion ( AMI ) patients undergoing primary percutaneous coronary intervention ( PCI ) . METHODS AND RESULTS This study enrolled 506 AMI patients undergoing primary PCI using the TRA ( group 1 ) between March 2002 and May 2007 , and 810 AMI patients undergoing primary PCI using TFA ( group 2 ) between May 1993 and February 2002 . The results demonstrated that puncture to first balloon-inflation time was similar in both groups ; however , the procedure time was shorter in group 1 than in group 2 ( P<0.0001 ) . Additionally , the incidences of stenting , tirofiban therapy and final normal coronary blood flow of the infa rct -related artery were higher , whereas the frequency of intra-aortic balloon pump support was lower in group 1 than in group 2 ( all P<0.02 ) . Although the 30-day mortality rate did not differ between the 2 groups ( P=0.341 ) , the rate of combined major vascular and bleeding complications was higher in group 2 than in group 1 ( P<0.0001 ) . CONCLUSIONS Initial selection of TRA is not inferior to initial selection of TFA for AMI patients undergoing primary PCI . However , in the present study , the incidence of combined vascular and bleeding complications was lower with the TRA than with the TFA approach BACKGROUND Compared to the transfemoral approach ( TFA ) , the transradial approach ( TRA ) for primary percutaneous coronary intervention ( PCI ) is associated with less risk of access site complications , greater patient comfort and faster mobilisation . Using vascular closure devices during TFA can offer similar advantages . AIM To compare the results of TRA and TFA using a StarClose device for primary PCI in patients with ST-elevation myocardial infa rct ion ( STEMI ) . METHODS Patients were r and omised to PCI using TRA ( n = 49 ) or PCI using TFA and StarClose ( n = 59 ) . RESULTS Door-to-balloon inflation time was 67.4 ± 17.1 vs 57.5 ± 17.5 min ( p = 0.009 ) in the TRA and TFA groups respectively . Procedural success rate was 100 % and 98.3 % , respectively ( NS ) . There were no significant differences in the incidence of major adverse cardiac events ( MACE ) or bleeding complications between the groups : 2.1 % and 8.2 % in the TRA group vs 1.7 % and 10.2 % in the TFA group ( NS ) . Time to resume an upright position and time to full mobility was comparable in both groups . CONCLUSIONS The TRA for PCI in patients with STEMI is related to a significantly longer door to balloon time compared to the TFA . This had no influence on the incidence of MACE . The duration and efficacy of PCI were comparable in both groups . Using StarClose after PCI performed via the TFA result ed in an incidence of access site and bleeding complications comparable to that found when using TRA OBJECTIVE To compare the transradial approach and transfemoral approach for primary percutaneous coronary intervention ( PCI ) in Chinese patients with acute myocardium infa rct ion ( AMI ) . METHODS From August 2005 to September 2008 , we r and omly divided 200 AMI patients into transradial intervention ( TRI ) group and transfemoral intervention ( TFI ) group . The study took place in the Department of Cardiology , The Tenth People 's Hospital , Tongji University , Shanghai , China . During the procedure , the puncture success , procedure success , infa rct ion related artery ( IRA ) , coronary flow , percentage of 3 vessel disease , stent used , and tirofiban used were observed . The procedural time intervals were also recorded . After the procedure , the major adverse cardiac events ( MACEs ) and the vascular complications were studied . In this trial , the hospital stay was also recorded . RESULTS The baseline clinical characteristics of the patients were similar in both groups . There were no statistical differences in IRA , 3 vessel disease , initial and final thrombolysis in myocardial infa rct ion ( TIMI ) flow , rate of stent and tirofiban used , and procedure rate ( p>0.05 ) . No statistical differences were observed in the puncture time , cannulation time , reperfusion time , procedural time , and fluoroscopy time in both groups ( p>0.05 ) . There was no statistical difference in the incidence of MACEs between the 2 groups ( p>0.05 ) . Not only the vascular complications were lower in the TRI group ( p<0.01 ) , but also the total hospital stay was longer in the TFI group than in the TRI group ( p<0.001 ) . CONCLUSION Transradial intervention for Chinese patients with AMI yields comparable procedural success , and has fewer vascular access site complications compared with the TFI group OBJECTIVES This study sought to compare radial and femoral approaches in patients presenting with ST-segment elevation myocardial infa rct ion ( STEMI ) and undergoing primary percutaneous coronary intervention ( PCI ) by high-volume operators experienced in both access sites . BACKGROUND The exact clinical benefit of the radial compared to the femoral approach remains controversial . METHODS STEMI-RADIAL ( ST Elevation Myocardial Infa rct ion treated by RADIAL or femoral approach ) was a r and omized , multicenter trial . A total of 707 patients referred for STEMI < 12 h of symptom onset were r and omized in 4 high-volume radial centers . The primary endpoint was the cumulative incidence of major bleeding and vascular access site complications at 30 days . The rate of net adverse clinical events ( NACE ) was defined as a composite of death , myocardial infa rct ion , stroke , and major bleeding/vascular complications . Access site crossover , contrast volume , duration of intensive care stay , and death at 6 months were secondary endpoints . RESULTS The primary endpoint occurred in 1.4 % of the radial group ( n = 348 ) and 7.2 % of the femoral group ( n = 359 ; p = 0.0001 ) . The NACE rate was 4.6 % versus 11.0 % ( p = 0.0028 ) , respectively . Crossover from radial to femoral approach was 3.7 % . Intensive care stay ( 2.5 ± 1.7 days vs. 3.0 ± 2.9 days , p = 0.0038 ) as well as contrast utilization ( 170 ± 71 ml vs. 182 ± 60 ml , p = 0.01 ) were significantly reduced in the radial group . Mortality in the radial and femoral groups was 2.3 % versus 3.1 % ( p = 0.64 ) at 30 days and 2.3 % versus 3.6 % ( p = 0.31 ) at 6 months , respectively . CONCLUSIONS In patients with STEMI undergoing primary PCI by operators experienced in both access sites , the radial approach was associated with significantly lower incidence of major bleeding and access site complications and superior net clinical benefit . These findings support the use of the radial approach in primary PCI as first choice after proper training . ( Trial Comparing Radial and Femoral Approach in Primary Percutaneous Coronary Intervention [ PCI ] [ STEMI-RADIAL ] ; NCT01136187 ) BACKGROUND There is growing evidence that transradial ( TRI ) as compared to transfemoral ( TFI ) percutaneous coronary intervention ( PCI ) is associated with improved clinical outcome driven by less hemorrhagic complications , in particular in STEMI patients receiving aggressive antithrombotic treatment . Feasibility rate of TRI in STEMI patients has not yet been evaluated . METHODS / RESULTS Four-hundred seventy-five consecutive STEMI patients ( < 12h ) without cardiogenic shock were prospect ively screened for this all-comer single-centre registry between January 2008 and August 2010 . Nine patients were excluded for a priori in eligibility for TRI ( forearm shunt for dialysis , prior TRI failure ) . In the 466 patients enrolled , the operator 's opinion about ease of radial puncture was assessed in 4 categories , based on radial pulse quality . Operators were advised not to attempt TRI if ease of puncture was judged " probably difficult/impossible " . In case of puncture failure the operator switched immediately to TFI . The mean age of patients was 61 ± 14 ( range 27 - 94 ) years . Seventy-three percent were men , 17 % had diabetes . Nine percent had previous PCI . Glycoprotein inhibitors were used in 70 % , and thrombectomy was performed in 70 % of patients . PCI was performed using 6F and 5F guiding catheters . Procedural success rate was 98.2 % ( TIMI flow ≥ 2 ) . In 4.1 % ( n=19 ) of patients the operator judged ease of radial puncture " probably difficult/impossible " and no TRI attempt was performed ( primary TFI ) . In the 447 patients with TRI attempt , TRI failure requiring switch to TFI ( secondary TFI ) was necessary in 22 patients ( 4.7 % of total ) following radial puncture failure ( n=15 ) , dissection of the radial artery ( n=1 ) , prohibitive tortuosities or stenosis of the upper limb axis ( n=2 ) , or non-selective position or lack of stability of the guiding catheter ( n=2 ) . After the start of the angioplasty procedure , switch from TR to TF was not necessary in any patient . In total , the overall feasibility rate of TRI was 91.2 % . Independent predictors of final TFI were age ≥ 80 years ( adjusted OR : 2.37 ; 95 % CI:1.05 - 5.34 , p=0.037 ) , body weight<60 kg ( adjusted OR : 2.84 ; 95 % CI:1.22 - 6.59 , p=0.015 ) ; and previous PCI ( adjusted OR : 3.42 ; 95 % CI:1.40 - 8.37 , p=0.007 ) ; female gender was borderline significant ( adjusted OR:2.10 ; 95 % CI:0.97 - 4.54 , p=0.059 ) . CONCLUSION In STEMI patients without cardiogenic shock and without a priori indication for TFI , PCI can be performed via the radial artery in more than 90 % of cases with high procedural success rate . Operator 's judgement of eligibility for TRI based on radial pulse quality is predictive of successful TRI in 95 % of cases . TR failure is significantly more common in the elderly and in patients with low body weight BACKGROUND Small trials have suggested that radial access for percutaneous coronary intervention ( PCI ) reduces vascular complications and bleeding compared with femoral access . We aim ed to assess whether radial access was superior to femoral access in patients with acute coronary syndromes ( ACS ) who were undergoing coronary angiography with possible intervention . METHODS The RadIal Vs femorAL access for coronary intervention ( RIVAL ) trial was a r and omised , parallel group , multicentre trial . Patients with ACS were r and omly assigned ( 1:1 ) by a 24 h computerised central automated voice response system to radial or femoral artery access . The primary outcome was a composite of death , myocardial infa rct ion , stroke , or non-coronary artery bypass graft (non-CABG)-related major bleeding at 30 days . Key secondary outcomes were death , myocardial infa rct ion , or stroke ; and non-CABG-related major bleeding at 30 days . A masked central committee adjudicated the primary outcome , components of the primary outcome , and stent thrombosis . All other outcomes were as reported by the investigators . Patients and investigators were not masked to treatment allocation . Analyses were by intention to treat . This trial is registered with Clinical Trials.gov , NCT01014273 . FINDINGS Between June 6 , 2006 , and Nov 3 , 2010 , 7021 patients were enrolled from 158 hospitals in 32 countries . 3507 patients were r and omly assigned to radial access and 3514 to femoral access . The primary outcome occurred in 128 ( 3·7 % ) of 3507 patients in the radial access group compared with 139 ( 4·0 % ) of 3514 in the femoral access group ( hazard ratio [ HR ] 0·92 , 95 % CI 0·72 - 1·17 ; p=0·50 ) . Of the six prespecified subgroups , there was a significant interaction for the primary outcome with benefit for radial access in highest tertile volume radial centres ( HR 0·49 , 95 % CI 0·28 - 0·87 ; p=0·015 ) and in patients with ST-segment elevation myocardial infa rct ion ( 0·60 , 0·38 - 0·94 ; p=0·026 ) . The rate of death , myocardial infa rct ion , or stroke at 30 days was 112 ( 3·2 % ) of 3507 patients in the radial group compared with 114 ( 3·2 % ) of 3514 in the femoral group ( HR 0·98 , 95 % CI 0·76 - 1·28 ; p=0·90 ) . The rate of non-CABG-related major bleeding at 30 days was 24 ( 0·7 % ) of 3507 patients in the radial group compared with 33 ( 0·9 % ) of 3514 patients in the femoral group ( HR 0·73 , 95 % CI 0·43 - 1·23 ; p=0·23 ) . At 30 days , 42 of 3507 patients in the radial group had large haematoma compared with 106 of 3514 in the femoral group ( HR 0·40 , 95 % CI 0·28 - 0·57 ; p<0·0001 ) . Pseudoaneurysm needing closure occurred in seven of 3507 patients in the radial group compared with 23 of 3514 in the femoral group ( HR 0·30 , 95 % CI 0·13 - 0·71 ; p=0·006 ) . INTERPRETATION Radial and femoral approaches are both safe and effective for PCI . However , the lower rate of local vascular complications may be a reason to use the radial approach . FUNDING Sanofi-Aventis , Population Health Research Institute , and Canadian Network for Trials Internationally ( CANNeCTIN ) , an initiative of the Canadian Institutes of Health Research OBJECTIVES The purpose of the present study was to compare the radial approach with the femoral approach for coronary stenting in patients with acute coronary syndromes . BACKGROUND Aggressive anticoagulation in patients with acute coronary syndromes increases the risk of femoral vascular complications . The transradial approach has the potential to significantly reduce the incidence of access site bleeding complications in this group of patients . METHODS One hundred forty-two patients with acute coronary syndromes undergoing coronary stenting were prospect ively r and omized to have their procedure performed from either the radial or femoral access site and the results compared . RESULTS Nine of 74 patients r and omized to the radial group crossed over to the femoral group ( 6 negative Allen tests , 3 access failures ) . Patient demographics were the same in both groups . Primary success was identical : 96 % radial , 96 % femoral , ns . There were no procedural myocardial infa rct ions or deaths , and no patient was referred for emergency bypass surgery . There were no access site bleeding complications in the radial group as opposed to 3 ( 4 % ) in the femoral group , p < 0.01 . Postprocedure length of stay , days ( 1.4+/-0.2 radial vs. 2.3+/-0.4 femoral , p < 0.01 ) as well as total hospital length of stay ( 3.0+/-0.3 radial vs. 4.5+/-0.5 femoral , p < 0.01 ) were significantly reduced in the radial group . Total hospital charge was also significantly lower in the radial group ( $ 20,476+/-811 radial versus $ 23,389+/-1,180 femoral , p < 0.01 ) . CONCLUSION Coronary stenting from the radial approach is efficacious in patients with acute coronary syndromes . Access site bleeding complications are less , and early ambulation results in a shorter hospital length of stay . There was a 15 % reduction in total hospital charge in the radial group The radial approach during percutaneous coronary intervention ( PCI ) has been reported to reduce the incidence of bleeding complications . However , the radial approach still accounts for < 10 % of procedures worldwide and only 1 % in the United States . Our objective was to compare the effect of radial versus femoral vascular access on the time to reperfusion , incidence of bleeding complications , and overall clinical outcomes in the setting of primary PCI . We prospect ively collected data on all patients undergoing primary PCI at the Montreal Heart Institute from April 1 , 2007 to March 30 , 2008 . The time to revascularization and major bleeding were prespecified as a co- primary end point , and major adverse cardiac events , including death , myocardial infa rct ion , and target vessel revascularization within 12 months , were considered a secondary end point . A total of 489 patients were included in the present longitudinal cohort study , 234 in the femoral group and 254 in the radial group . In the propensity-adjusted model , the use of the femoral approach was a strong independent predictor of bleeding ( odds ratio 4.22 , 95 % confidence interval 3.17 to 10.60 ) . No significant difference between the radial and femoral groups was observed relative to the time to revascularization ( 21.4 + /- 11.8 minutes vs 22.8 + /- 10.3 minutes , respectively ; p = 0.68 ) . Moreover , the radial approach was associated with a decreased risk of major adverse cardiac events ( odds ratio 0.31 , 95 % confidence interval 0.10 to 0.94 ) . In conclusion , primary PCI using the radial approach was associated with a fourfold reduction in major bleeding , without compromising the time to revascularization . Moreover , the radial approach was associated with a significant reduction in major adverse cardiac events at 12 months Transradial ( TR ) access is increasingly being used in percutaneous coronary intervention ( PCI ) . However , its role in PCI for ST-segment elevation myocardial infa rct ion remains controversial because of concerns of procedural complexity adversely affecting the promptness of reperfusion . In this study , 150 consecutive patients who underwent PCI for acute ST-segment elevation myocardial infa rct ion over a period of 24 months were prospect ively evaluated ; 46 had TR access ( 31 % ) and 104 ( 69 % ) had transfemoral ( TF ) access . All patients received thienopyridines , aspirin , and heparin per routine management . There were no significant differences between the TR access and TF access groups with respect to age ( 62.2 ± 11.6 vs 64.7 ± 14.1 , p = 0.28 ) , gender ( 76.1 % vs 72.1 % men , p = 0.69 ) , or incidence of diabetes ( 23.9 % vs 26.9 % , p = 0.84 ) . The TR and TF access groups were comparable with respect to door-to-balloon time ( 79.2 ± 32.3 vs 86.8 ± 51.8 minutes , p = 0.67 ) and amount of contrast used ( 190.5 ± 101.5 vs 172.2 ± 81.7 ml , p = 0.24 ) . Total fluoroscopy time was longer in the TR access group compared to the TF access group ( 21.7 ± 12.7 vs 14.4 ± 10.4 minutes , p < 0.0001 ) . Postprocedural Thrombolysis In Myocardial Infa rct ion ( TIMI ) grade 3 flow was comparable for the 2 groups ( 87 % for the TF group and 96 % for the TR group , p = 0.15 ) . There were no vascular complications in the TR access group compared to the TF access group ( 0 % vs 5.8 % , p = 0.18 ) . In conclusion , this single-center observational study shows that TR access for PCI in STEMI is feasible and that it has fewer vascular complications and shorter length of hospital stay than the TF approach |
664 | 21,735,396 | Ibuprofen negatively affects renal function .
Prophylactic use of ibuprofen decreased the incidence of PDA , decreased the need for rescue treatment with cyclo-oxygenase inhibitors and decreased the need for surgical closure . | BACKGROUND Patent ductus arteriosus ( PDA ) complicates the clinical course of preterm infants and increases the risk of adverse outcomes .
Indomethacin has been the st and ard treatment to close a PDA but is associated with renal , gastrointestinal and cerebral side-effects .
Ibuprofen has less effect on blood flow velocity to important organs .
OBJECTIVES To determine the effectiveness and safety of prophylactic ibuprofen compared to placebo/no intervention in the prevention of PDA in preterm infants . | OBJECTIVE To test whether early postnatal ( 0 to 3 hours ) intravenous administration of ibuprofen will prevent patent ductus arteriosus ( PDA ) in preterm neonates . DESIGN Prospect i ve sequential controlled trial with three treatment arms . SETTING Level 3 perinatal-neonatal intensive care nursery . PATIENTS Thirty-four premature newborn infants born from February to August 1993 with a mean birth weight of 913 g ( range , 565 to 1460 g ) and gestational age of 26.9 weeks ( range , 22.4 to 31.0 ) . INTERVENTION Infants were consecutively assigned within 3 hours of age to treatment with either one dose of ibuprofen lysine ( 10 mg/kg intravenously ) followed by 5 mg/kg per dose intravenously at 24 and 48 hours of age ( n = 12 ) , one dose of ibuprofen lysine ( 10 mg/kg intravenously ; n = 11 ) , or saline ( n = 11 ) . OUTCOME VARIABLES Primary outcome variable was the presence of ductus arteriosus by echocardiography and clinical assessment s at 3 , 7 , and 21 days of life . Secondary outcome variables included presence of intraventricular hemorrhage , renal function , ventilatory and oxygen needs , hematologic changes , gastrointestinal function , time to full enteral feeding , duration of hospitalization , and age at discharge . RESULTS The three groups of patients were comparable in birth weight , gestational age , antenatal administration of betamethasone , and other perinatal characteristics . Ibuprofen treatment significantly reduced plasma levels of prostagl and ins , and the levels remained low for 72 hours in newborns who received three doses of the drug . The incidence of PDA and other variables did not differ between patients who received a single dose of ibuprofen and those given saline . However , compared with the saline-treated newborns , babies who received three doses of ibuprofen had no PDA ( 0/12 vs 7/11 for saline ; P < .02 ) , had lower daily mean airway pressures ( mean + /- SD , 5.2 + /- 1.1 cm H2O vs 8.3 + /- 2.8 cm H2O for saline ; P < .02 ) and better oxygenation index ( 2.6 + /- 0.6 vs 4.7 + /- 1.8 for saline ; P < .02 ) at the end of the first week of life , and required fewer days of ventilation ( 25 + /- 14 days vs 44 + /- 26 days for saline ; P < .03 ) . Babies given three doses of ibuprofen tended to tolerate full oral feedings earlier ( 35 + /- 19 days vs 56 + /- 34 days for saline ; P = .09 ) , had shorter duration of hospitalization ( 71.2 + /- 22.6 days vs 127.3 + /- 74.7 days for saline ; P < .05 ) , and were discharged to home at an earlier postconceptional age ( 37.8 + /- 2.0 weeks vs 44.8 + /- 9.8 weeks for saline ; P < .05 ) . ibuprofen treatment in this phase I trial was not associated with any apparent early neurological , intestinal , renal , hepatic , or hematologic complications . CONCLUSIONS Administration of three doses of ibuprofen within 3 hours after birth in preterm neonates reduced the incidence of PDA without causing notable early adverse drug reactions in this phase I trial . Early closure of the ductus arteriosus was also associated with better respiratory outcome and earlier discharge from the hospital BACKGROUND Indomethacin is the conventional treatment for hemodynamically important patent ductus arteriosus in preterm infants . However , its use is associated with various side effects . In a prospect i ve study , we compared ibuprofen and indomethacin with regard to efficacy and safety for the early treatment of patent ductus arteriosus in preterm infants . METHODS We studied 148 infants ( gestational age , 24 to 32 weeks ) who had the respiratory distress syndrome and an echocardiographically confirmed , hemodynamically important patent ductus arteriosus . The infants were r and omly assigned at five neonatal intensive care centers to receive three intravenous doses of either indomethacin ( 0.2 mg per kilogram of body weight , given at 12-hour intervals ) or ibuprofen ( a first dose of 10 mg per kilogram , followed at 24-hour intervals by two doses of 5 mq per kilogram each ) , starting on the third day of life . The rate of ductal closure , the need for additional treatment , side effects , complications , and the infants ' clinical course were recorded . RESULTS The rate of ductal closure was similar with the two treatments : ductal closure occurred in 49 of 74 infants given indomethacin ( 66 percent ) , and in 52 of 74 given ibuprofen ( 70 percent ) ( relative risk , 0.94 ; 95 percent confidence interval , 0.76 to 1.17 ; P=0.41 ) . The numbers of infants who needed a second pharmacologic treatment or surgical ductal ligation did not differ significantly between the two groups . Oliguria occurred in 5 infants treated with ibuprofen and in 14 treated with indomethacin ( P=0.03 ) . There were no significant differences with respect to other side effects or complications . CONCLUSIONS Ibuprofen therapy on the third day of life is as efficacious as indomethacin for the treatment of patent ductus arteriosus in preterm infants with the respiratory distress syndrome and is significantly less likely to induce oliguria BACKGROUND Patent ductus arteriosus is a common complication of prematurity that frequently requires surgical or medical treatment . The benefit of prophylactic treatment by indometacin , a cyclo-oxygenase inhibitor , remains uncertain compared with curative treatment . This benefit could be improved with ibuprofen , another cyclo-oxygenase inhibitor with fewer adverse effects than indometacin on renal , mesenteric , and cerebral perfusion . We aim ed to compare prophylactic and curative ibuprofen in the treatment of this abnormality in very premature infants . METHODS We did a r and omised controlled trial in infants younger than 28 weeks of gestation , who were r and omly assigned to receive either three doses of ibuprofen or placebo within 6 h of birth . After day 3 , symptomatic patent ductus arteriosus was treated first by open curative ibuprofen , then back-up indometacin , surgery , or both . The primary endpoint was need for surgical ligation . Analysis was per protocol . FINDINGS The study was stopped prematurely after 135 enrollments because of three cases of severe pulmonary hypertension in the prophylactic group . 65 infants received prophylactic ibuprofen , and 66 received placebo . Prophylaxis reduced the need for surgical ligation from six ( 9 % ) to zero ( p=0.03 ) , and decreased the rate of severe intraventricular haemorrhage from 15 ( 23 % ) to seven ( 11 % ) ( p=0.10 ) . However , survival was not improved ( 47 [ 71 % ] placebo vs 47 [ 72 % ] treatment , p=1.00 ) , because of high frequency of adverse respiratory , renal , and digestive events . INTERPRETATION In premature infants , prophylactic ibuprofen reduces the need for surgical ligation of patent ductus arteriosus , but does not reduce mortality or morbidity . Therefore , it should not be preferred to early curative ibuprofen A prospect i ve r and omized controlled trial was performed to compare the effects of ibuprofen with indomethacin on cerebral hemodynamics measured using near infrared spectroscopy in preterm infants during treatment for patent ductus arteriosus . Infants were r and omly assigned to three intravenous doses of either indomethacin ( 0.20–0.25 mg/kg , 12 hourly ) or ibuprofen ( 5–10 mg/kg , 24 hourly ) and also received a dose of saline . The primary end points of the study were the effects of the first dose on cerebral blood flow ( CBF ) and cerebral blood volume . Fifteen infants received indomethacin and 18 received ibuprofen . The group mean ( SD ) values for CBF ( mL·100 g−1·min−1 ) before and after the first dose of indomethacin were 13.6 ( 4.1 ) and 8.3 ( 3.1 ) , respectively , the change being significant ( p < 0.001 ) . In contrast , no significant changes in CBF were observed with the first dose of ibuprofen , the respective before and after values being 13.3 ( 3.2 ) and 14.9 ( 4.7 ) mL·100 g−1·min−1 . The median ( interquartile range ) value for change in cerebral blood volume ( mL/100 g ) after the first dose in the indomethacin group was −0.4 ( −0.3 to −0.6 ) and in the ibuprofen group was 0.0 ( 0.1 to −0.1 ) , the difference between the two groups being significant ( p < 0.001 ) . Cerebral oxygen delivery changed significantly after the first dose in the indomethacin group but not in the ibuprofen group . Significant reductions in CBF , cerebral blood volume , and cerebral oxygen delivery also occurred after the 24-h dose of indomethacin , but there were no significant changes after the 48-h dose of saline in the indomethacin group or after the 24- and 48-h doses of ibuprofen . The patent ductus arteriosus closure rates after indomethacin and ibuprofen were 93 and 78 % , respectively . We conclude that ibuprofen , unlike indomethacin , has no adverse effects on cerebral hemodynamics and appears to mediate patent ductus arteriosus closure We investigated the effects of clinical ly comparable doses of ibuprofen and indomethacin on renal , gastrointestinal and cerebral perfusion in newborn piglets , and hypothesized that ibuprofen would have less effect on regional circulation . Animals were r and omly assigned to receive ibuprofen ( 20 mg/kg , n = 8) , indomethacin ( 0.3 mg/kg , n = 7 ) or vehicle ( n = 6 ) . Fluorescent microspheres were injected prior to and at 20 , 40 , 60 , 90 and 120 min after drug administration . Regional blood flow was measured and vascular resistances were calculated . Cardiovascular and respiratory variables were not significantly affected by either study drug or vehicle . Ibuprofen increased renal cortical and medullary resistance by 44 and 52 % ( p < 0.05 ) . However , ibuprofen had no significant effects on gastrointestinal or cerebral resistance . Indomethacin raised renal cortical and medullary resistance by 66 and 71 % at 60 min postinjection , respectively ( p < 0.05 ) . Indomethacin increased duodenojejunal , ileal and colon resistance by 97 , 102 and 75 % at 60 min , respectively ( p < 0.05 ) . Indomethacin increased cerebral cortical and cerebellar resistance by 92 and 86 % at 90 min ( p < 0.05 ) . While indomethacin and , to a lesser extent , ibuprofen both increase renal vascular resistance , indomethacin vasoconstricts the gastrointestinal and cerebral circulations which are unaffected by ibuprofen Aim The aim of this study was to explore the effects of early oral ibuprofen administration on the incidence of hemodynamically significant patent ductus arteriosus ( hsPDA ) and define the association between serum ibuprofen levels and ductal closure . Method Preterm infants with a gestational age of < 28 weeks and /or birth weight of < 1,000 g were r and omized either to the intervention ( ibuprofen prophylaxis ) or control group . The intervention group received oral ibuprofen 10 mg/kg within 12–24 h after birth followed by 5 mg/kg at 24 and 48 h. Serum ibuprofen levels after the treatment were analyzed in the intervention group , and the incidence of hsPDA and complication rates were compared between two groups . Results Nineteen infants who received one course ( three doses ) of prophylactic ibuprofen in the intervention group and 17 infants in the control group who underwent an echocardiographic examination on the fourth day of life were analyzed . hsPDA was observed in five ( 26 % ) infants in the intervention group and ten ( 58 % ) infants in the control group ( p = 0.09 ) . In the intervention group two infants experienced gastrointestinal bleeding two infants had spontaneous intestinal perforation , and two infants developed acute kidney failure . Mean serum ibuprofen level was 28.7 ± 16.9 mg/L in the intervention group , and there was no correlation between ibuprofen level obtained on the fourth day and ductal closure . Conclusion Oral ibuprofen prophylaxis reduces the rates of hsPDA even it is not statistically significant . The ductal closure rate did not correlate with serum ibuprofen levels . Due to high prevalence of adverse events observed , our data do not support the use of oral ibuprofen for prophylaxis of hsPDA The effect of repeated doses of indomethacin on mean peak velocity ( MPV ) and time-averaged mean velocity in the middle cerebral artery was assessed in 10 ventilated neonates with a patent ductus arteriosus using colour/duplex Doppler technique prior to , and 10 , 30 , and 120 min after the first and the third dose . Velocities were significantly reduced up to 120 min after the first dose . The third dose result ed in a significant reduction in MPV at 10 and 30 min following treatment . This reduction was half of that observed after the first dose . Systemic blood pressure ( BP ) and heart rate did not change significantly after each separate dose . However , by the third dose , mean and diastolic BP were significantly increased from pretreatment levels . The attenuated response of cerebral blood flow ( CBF ) velocities to the third dose of indomethacin compared with the first dose is probably related to altered haemodynamics . Indomethacin should be used cautiously in infants with other conditions which are known to decrease CBF such as hypotension , hypocarbia and polycythaemia AIM To evaluate the efficiency and side effects of ibuprofen for the early treatment of patent ductus arteriosus ( PDA ) and compare it with indomethacin . METHODS Forty preterm infants with gestational ages of less than 33 weeks , with respiratory distress syndrome ( RDS ) and echocardiographically confirmed PDA , were r and omly assigned at days 2 to 3 of life to receive either intravenous indomethacin 3 × 0.2 mg/kg at 12 hour intervals or intravenous ibuprofen 1 × 10 mg/kg , followed by 5 mg/kg 24 and 48 hours later . RESULTS PDA closed in 15 of 20 patients from the indomethacin group ( 75 % ) and in 16 of 20 ( 80 % ) from the ibuprofen group . Seven patients ( three indomethacin , four ibuprofen ) required a second treatment with indomethacin and in five ( three in the indomethacin group and two in the ibuprofen group ) the duct was ultimately ligated . Ibuprofen patients had a better urinary output and showed no increase in serum creatinine concentrations compared with the indomethacin group . Ibuprofen was not associated with any other side effect . CONCLUSIONS Ibuprofen treatment seems to be as efficient as indomethacin in closing PDA on the third day of life in preterm infants with respiratory distress syndrome and seems to have fewer renal side effects OBJECTIVE To determine whether a course of low-dose indomethacin therapy , when initiated within 24 hours of birth , would decrease ductal shunting in premature infants who received prophylactic surfactant in the delivery room . DESIGN Ninety infants , with birth weights of 600 to 1250 gm , were entered into a prospect i ve , r and omized , controlled trial to receive either indomethacin , 0.1 mg/kg per dose , or placebo less than 24 hours and again every 24 hours for six doses . Echocardiography was performed on day 1 before treatment and on day 7 , 24 hours after treatment . A hemodynamically significant patent ductus arteriosus ( PDA ) was confirmed with an out-of- study echocardiogram , and the nonresponders were treated with st and ard indomethacin or ligation . RESULTS Forty-three infants received indomethacin ( birth weight , 915 + /- 209 gm ; gestational age , 26.4 + /- 1.6 weeks ; 25 boys ) , and 47 received placebo ( birth weight , 879 + /- 202 gm ; gestational age , 26.4 + /- 1.8 weeks ; 22 boys ) ( P = not significant ) . Of 90 infants , 77 ( 86 % ) had a PDA by echocardiogram on the first day of life before study treatment ; 84 % of these PDAs were moderate or large in size in the indomethacin-treated group compared with 93 % in the placebo group . Nine of forty indomethacin-treated infants ( 21 % ) were study -dose nonresponders compared with 22 ( 47 % ) of 47 placebo-treated infants ( p < 0.018 ) . There were no significant differences between both groups in any of the long-term outcome variables , including intraventricular hemorrhage , duration of oxygen therapy , endotracheal intubation , duration of stay in neonatal intensive care unit , time to regain birth weight or reach full caloric intake , incidence of bronchopulmonary dysplasia , and survival . No significant differences were noted in the incidence of oliguria , elevated plasma creatinine concentration , thrombocytopenia , pulmonary hemorrhage , or necrotizing enterocolitis . CONCLUSION The prophylactic use of low doses of indomethacin , when initiated in the first 24 hours of life in low birth weight infants who receive prophylactic surfactant in the delivery room , decreases the incidence of left-to-right shunting at the level of the ductus arteriosus BACKGROUND Ibuprofen is used for treatment and prevention of patent ductus arteriosus in low-birthweight infants . Its effects on regional circulations differ from those of indometacin . Because prophylactic indometacin reduces the frequency of severe intraventricular haemorrhage and patent ductus arteriosus , we aim ed to study the efficacy of early ibuprofen in reducing these outcomes in a double-blind , multicentre trial . METHODS Within 6 h after birth , 415 low-birthweight infants ( gestational age < 31 weeks ) were r and omly allocated ibuprofen-lysine ( 10 mg/kg then two doses of 5 mg/kg after 24 h and 48 h ) or placebo intravenously . The primary outcome was occurrence of severe intraventricular haemorrhage ; secondary outcomes were occurrence of patent ductus arteriosus and possible adverse effects of ibuprofen . Analysis was by intention to treat . FINDINGS 17 ( 8 % ) of 205 infants assigned ibuprofen and 18 ( 9 % ) of 210 assigned placebo developed severe intraventricular haemorrhage ( relative risk 0.97 [ 95 % CI 0.51 - 1.82 ] ) . In 172 ( 84 % ) infants of the ibuprofen group , the ductus was closed on day 3 compared with 126 ( 60 % ) of the placebo group ( relative risk 1.40 [ 1.23 - 1.59 ] ) . No important differences in other outcomes or side-effects were noted ; however , urine production was significantly lower on day 1 and concentration of creatinine in serum was significantly higher on day 3 after ibuprofen . INTERPRETATION Ibuprofen prophylaxis in preterm infants does not reduce the frequency of intraventricular haemorrhage , but does decrease occurrence of patent ductus arteriosus Abstract This study was aim ed at evaluating the efficacy of ibuprofen in the prophylaxis of patent ductus arteriosus ( PDA ) in very preterm neonates and at detecting eventual side-effects . A total of 46 preterm neonates with gestational age under 31 weeks were r and omly assigned at 2 h of life : 23 to the prophylaxis group and 23 to the control group . The prophylaxis group received intravenous treatment with ibuprofen lysine ( 10 mg/kg ) , followed by 5 mg/kg after 24 h and 48 h. No placebo was given to the control group . No PDA was demonstrated at 72 h of life in 20 of the 23 babies in the ibuprofen group ( 87 % ) nor in 7 of the 23 control neonates ( 30.4 % ) . All neonates with PDA received treatment with indomethacin . One neonate in the prophylaxis group and three in the control group underwent surgical ligation . Prophylaxis with ibuprofen was not associated with any significant side-effect except for food intolerance . Conclusion Ibuprofen prophylaxis seems to be efficient in closing patent ductus arteriosus and in reducing indomethacin treatment . No significant early side-effects were found due to ibuprofen OBJECTIVE The authors evaluated the risk of necrotizing enterocolitis ( NEC ) in very low birth weight infants receiving indomethacin ( INDO ) to close patent ductus arteriosus ( PDA ) . BACKGROUND DATA Controversy exists regarding the best method of managing very low birth weight infants with PDA and whether to employ medical management using INDO or surgical ligation of the ductus . METHODS Two hundred fifty-two premature infants with symptomatic PDA were given intravenously INDO 0.2 mg/kg every 12 hours x 3 in an attempt to close the ductus . Patients were evaluated for sex , birth weight , gestational age , ductus closure , occurrence of NEC , bowel perforation , and mortality . RESULTS There were 135 boys and 117 girls . The PDA closed or became asymptomatic in 224 cases ( 89 % ) , whereas 28 ( 11 % ) required surgical ligation . Ninety infants ( 35 % ) developed evidence of NEC after INDO therapy . Fifty-six were managed medically ; surgical intervention was required in 34 of 90 cases ( 37.8 % ) or 13 % of the entire PDA/INDO study group . Bowel perforation was noted in 27 cases ( 30 % ) . Factors associated with the onset of NEC included gestational age < 28 weeks , birth weight < 1 kg , and prolonged ventilator support . The overall mortality rate was 25.5 % , but was higher in infants with NEC versus those without . The highest mortality was noted in perforated NEC cases . The PDA/INDO patients were compared with a control group of 764 infants with similar sex distribution , birth weights , and gestational ages without PDA who did not receive INDO . Necrotizing enterocolitis occurred in 105 of 764 control patients ( 13.7 % ) , including 13 ( 12.3 % ) with perforation . The overall mortality rate of controls was 25 % , which was similar to the overall 25.5 % mortality rate in the PDA/INDO study group . CONCLUSION These data indicate that there is increased risk of NEC and bowel perforation in premature infants with PDA receiving INDO . Mortality was higher in the PDA/INDO group with NEC than those PDA/INDO infants without NEC Abstract . Indomethacin ( INDO ) and , more recently , ibuprofen ( IBU ) have been used to treat haemodynamically significant patent ductus arteriosus ( PDA ) in preterm infants . Both are cyclo-oxygenase blockers , but seem to have a different influence on regional circulation . In a prospect i ve , r and omised , controlled study , we compared INDO and IBU with regard to efficacy and safety for the early non-invasive treatment of PDA . Doppler echocardiography was used to study 232 preterm infants ( gestational age 23–34 weeks ) with respiratory distress syndrome of whom 175 had persistent , haemodynamically significant PDA at 48–72 h of life . They were r and omised to receive three intravenous doses of either INDO ( 0.2 mg/kg , at 12 h intervals ) or IBU ( a first 10 mg/kg dose followed by two doses of 5 mg/kg at 24 h intervals ) , recording rate of ductal closure , need for additional treatment , side-effects and clinical course . The efficacy of the pharmacological treatment was similar in the two groups ( 56/81 , 69 % INDO ; 69/94 , 73 % IBU ) . Patients treated with INDO showed a significant increase in serum creatinine ( 89±24 versus 82±20 mmol/l , P=0.03 ) and a near-significant tendency for a lower fractional excretion of sodium ( 3±3 versus 4±2 % , P=0.08 ) ; moreover , 12/81 ( 15 % ) INDO patients versus 1/94 ( 1 % ) IBU patients became oliguric ( < 1 ml/kg per h ) during treatment ( P=0.017 ) . Conclusion : our findings confirm that , by comparison with indomethacin , ibuprofen has fewer effects on renal function in terms of urine output and fluid retention , with much the same efficacy and safety in closing patent ductus arteriosus in preterm infants with respiratory distress syndrome . In particular , no increased incidence of intracranial haemorrhage was observed after ibuprofen treatment The aim of our study was to evaluate whether the prophylactic use of ibuprofen would reduce the incidence of significant patent ductus arteriosus ( PDA ) and to confirm the effectiveness of ibuprofen as rescue treatment in closing PDA . Eighty preterm infants with gestational age less than 34 wk with infant respiratory distress syndrome ( iRDS ) were r and omized to receive intravenous ibuprofen lysine ( 10 mg/kg , followed by 5 mg/kg after 24 and 48 h ) either within 24 h of life ( group A ) or after echocardiographic diagnosis of PDA ( group B ) . To evaluate the severity of RDS in each patient , we calculated the initial and highest values of Oxygenation Index ( O.I. = mean airway pressure × FiO2 × 100 / PaO2 ) and Ventilatory Index ( V.I. = O.I. × mechanical respiratory rate ) . Other studied variables were ventilatory support , renal function , biochemical and haematological profiles , frequency of bronchopulmonary dysplasia ( BPD ) , intraventricular haemorrhage ( IVH ) , necrotizing enterocolitis ( NEC ) and retinopathy of prematurity ( ROP ) . On the 3rd day of life , 8 % ( 3/40 ) of patients of group A and 53 % of patients ( 21/40 ) of group B ( p < 0.0001 ) developed a significant PDA . Between patients of group B who presented PDA at 3 d of life 90 % ( 19/21 ) had a closure of ductus arteriosus after ibuprofen treatment . Initial and highest values of O.I. and V.I. were similar in both groups A and B. No significant differences between the groups were observed in regard to respiratory support , renal function and frequency of BPD , IVH , NEC and ROP . Ibuprofen was not associated with adverse effects Background . Previous reports of variations in outcomes among neonatal intensive care units ( NICUs ) examined only specific sub population s of interest ( eg , very low birth weight [ VLBW ] infants < 1500 g of birth weight [ BW ] ) . Objectives . We report on current practice and outcomes variations in a population -based national study of Canadian NICUs from January 8 , 1996 to October 31 , 1997 . Method . Information on 20 488 admissions to 17 tertiary level NICUs across Canada was prospect ively collected by trained abstract ors using a st and ard manual of operations and definitions . Data were verified and analyzed in concert with a steering committee comprising experienced research ers and neonatologists . Patient information included demographic information , antenatal history , mode of delivery , problems at delivery , status of infant and problems at birth , illness severity ( Clinical Risk Index for Babies , Score for Neonatal Acute Physiology , Score for Neonatal Acute Physiology-Version II ) , therapeutic intensity ( Neonatal Therapeutic Intensity Scoring System [ NTISS ] ) , selected NICU practice s and procedures , use of technology and re sources , and selected patient outcomes . Patients were tracked until death or discharge home . Results . The mean number of annual admissions to an NICU was 657 , with 26 % outborn infants . Fifty-three percent were < 2500 g BW , 20 % were < 1500 g BW ( VLBW ) , and 65 % were preterm ( < 38 weeks ' gestational age [ GA ] ) . Only 2 % of mothers received no prenatal care . Antenatal steroids were given to 58 % , but there was wide variation in use ( 23%–76 % ) . Congenital anomalies were present in 14 % , and 4 % were small for GA ( less than the third percentile ) . Admission illness severity was lowest among infants 33 to 37 weeks of GA and correlated with risk of death . Ninety-six percent of patients survived until discharge , but fewer survived at lower GA . No infant < 22 weeks ' GA survived . Seven percent of infants had at least 1 episode of infection , but 75 % received antibiotics in the NICU . Forty-three percent received respiratory support , and 14 % received surfactant . Nitric oxide was given to 150 term infants and to 102 preterm infants . Selected outcomes of VLBW infants were : survival rate ( 87 % ) ; chronic lung disease ( 26 % ) ; ≥stage 3 retinopathy of prematurity ( ROP ; 11 % ) ; ≥ grade 3 intraventricular hemorrhage ( IVH ; 10 % ) ; nosocomial infection ( 22 % ) ; necrotizing enterocolitis ( NEC ; 7 % ) . Sixty-nine percent of VLBW infants survived without major morbidity ( ≥ grade 3 IVH , chronic lung disease , NEC , ≥ grade 3 ROP ) . The mean duration of NICU stay was 19 days . Forty-seven percent of infants were discharged from the hospital , and 43 % were retrotransferred to a community facility before discharge home . Significant variation in practice s and outcomes were observed in all aspects of NICU care . Conclusion . This study provides population -based information about NICU outcomes . Significant variation in NICU practice s and outcomes was observed despite Canada 's universal health insurance system . This national data base provides valuable information for planning research , allocating re sources , design ing health and public policy , and serving as a basis for longitudinal studies of NICU care in Canada The effect of prophylactic administration of ibuprofen on the cerebral circulation in preterm babies was measured with near infrared spectroscopy . No significant difference in the change in cerebral blood volume , change in cerebral blood flow , or tissue oxygenation index was found between administration of ibuprofen or placebo BACKGROUND The oral suspension form of ibuprofen has been shown to have the same efficacy and safety as indomethacin in the treatment of symptomatic PDA , however its role is still question able in the prophylaxis of symptomatic PDA . OBJECTIVES 1 . To assess the efficacy and safety of the drug in the prevention of symptomatic PDA in premature infants . 2 . To study its pharmacokinetics-pharmacodynamics relationship . MATERIAL AND METHOD A r and omized , single-blinded , controlled study was performed on premature neonates with a gestational age between 28 - 32 weeks , birthweight < or = 1500 grams at the neonatal unit , Queen Sirikit National Institute of Child Health from July 2003 to April 2004 . Three doses of ibuprofen suspension or placebo were given 24 hours apart . Clinical evaluation was performed daily until the 28th day of life . Echocardiogram was performed prior to the drug administration , on the 3rd and 7th day of life . RESULTS There were 22 and 20 cases in the ibuprofen and control group respectively . The epidemiologic data between the groups before enrollment showed no significant differences . Prevalence of symptomatic PDA was lower in the ibuprofen than in the control group without any significant side effects ( 0/22 vs 5/20 , p = 0.015 on day 3 and 0/22 vs 6/20 , p = 0.006 on day 7 ) . Comparing with the pharmacokinetic study in older children and adult , the present study revealed nearly the same Cmax but longer Tmax and T1/2 in premature neonates . CONCLUSION Oral ibuprofen suspension could reduce the prevalence of symptomatic PDA without any significant side effects OBJECTIVE To compare the effects on cerebral perfusion and oxygenation of intravenous ibuprofen and indomethacin as treatment for patent ductus arteriosus in preterm infants . STUDY DESIGN Sixteen infants receiving mechanical ventilation ( < 31 weeks gestation ) with patent ductus arteriosus received either 0.2 mg/kg indomethacin ( n = 8) or 10 mg/kg ibuprofen ( n = 8) infused over 1 minute . Near-infrared spectroscopy was used to measure changes in cerebral blood volume and in oxidized cytochrome oxidase concentration . Cerebral blood flow velocity in the pericallosal artery was measured using Doppler ultrasonography . RESULTS Indomethacin caused a significant reduction of CBV ( maximal changes in cerebral blood volume : -320 + /- 171 microL/100 gm ) and , in four of eight patients , a fall in oxidized cytochrome oxidase concentration ( maximal change in oxidized cytochrome oxidase concentration in the eight patients : -0.68 + /- 0.98 mumol/L , NS ) . Cerebral blood flow velocity fell significantly . Ibuprofen caused no significant reduction of cerebral blood volume , oxidized cytochrome oxidase concentration , or cerebral blood flow velocity , whereas a significant increase of cerebral blood volume ( + 207 + /- 200 microL/100 gm ) was observed after 60 minutes . Ductus closure was seen in six of eight infants after the first dose of indomethacin and in five of eight infants after the first dose of ibuprofen . The therapeutic cycle involved administration of a second and third dose , provided no side effects occurred . Treatment was effective in all infants . CONCLUSION Compared with indomethacin , treatment with ibuprofen does not significantly reduce cerebral perfusion and oxygen availability ; the observed increase in cerebral blood volume requires further investigation In the course of a double-blind trial of intravenous indomethacin therapy in premature infants with patent ductus arteriosus , renal function and urinary kallikrein were studied in 21 infants following one dose of either saline placebo or indomethacin . Ten infants were assigned to the control group and 11 were in the indomethacin group . Significantly lower urine output , fraction excretion of sodium , fraction excretion of chloride , and urinary kallikrein were noted by 45 % , 59 % , 63 % , and 51 % , respectively , in the indomethacin group as compared to the control group . There was a concomitant decrease in serum sodium concentration ( P less than .05 ) at 24 hours following indomethacin therapy . No significant difference in glomerular filtration rate was seen between the control group and the indomethacin-treated infants Near infrared spectroscopy was used to investigate the effects of intravenously administered indomethacin ( 0.1 - 0.2 mg/kg ) on cerebral haemodynamics and oxygen delivery in 13 very preterm infants treated for patent ductus arteriosus . 7 infants received indomethacin by rapid injection ( 30 s ) and 6 by slow infusion ( 20 - 30 min ) . In all the infants cerebral blood flow , oxygen delivery , blood volume , and the reactivity of blood volume to changes in arterial carbon dioxide tension fell sharply after indomethacin . There were no differences in the effects of rapid and slow infusion . These falls in cerebral oxygen delivery and the disruption of cerebrovascular control might compromise cellular oxygen availability , particularly in regions of the brain where the arterial supply is precarious . Care should be taken to ensure that oxygen delivery is optimum before the administration of indomethacin to preterm infants OBJECTIVE To evaluate the effect of intravenous ibuprofen and indomethacin for treatment of patent ductus arteriosus ( PDA ) on mesenteric and renal blood flow velocity in preterm infants . STUDY DESIGN Seventeen mechanically ventilated preterm infants ( <33 weeks ' gestation ) with PDA received either 0.2 mg/kg indomethacin ( n = 8) or 10 mg/kg ibuprofen ( n = 9 ) , infused over 15 minutes . Mesenteric and renal blood flow velocity were measured by using Doppler ultrasonography . RESULTS Indomethacin caused a significant reduction in mesenteric and renal blood flow velocity 30 minutes after drug administration ; mesenteric and renal blood flow velocity did not return to the pretreatment values by 120 minutes . Ibuprofen did not alter blood flow 30 minutes after treatment , and blood flow increased 120 minutes after treatment . Mesenteric and renal blood flow velocity changes were significantly different between the 2 treatment groups . CONCLUSIONS Compared with indomethacin , ibuprofen did not significantly reduce mesenteric and renal blood flow velocity BACKGROUND The prophylactic administration of indomethacin reduces the frequency of patent ductus arteriosus and severe intraventricular hemorrhage in very-low-birth-weight infants ( those with birth weights below 1500 g ) . Whether prophylaxis with indomethacin confers any long-term benefits that outweigh the risks of drug-induced reductions in renal , intestinal , and cerebral blood flow is not known . METHODS Soon after they were born , we r and omly assigned 1202 infants with birth weights of 500 to 999 g ( extremely low birth weight ) to receive either indomethacin ( 0.1 mg per kilogram of body weight ) or placebo intravenously once daily for three days . The primary outcome was a composite of death , cerebral palsy , cognitive delay , deafness , and blindness at a corrected age of 18 months . Secondary long-term outcomes were hydrocephalus necessitating the placement of a shunt , seizure disorder , and microcephaly within the same time frame . Secondary short-term outcomes were patent ductus arteriosus , pulmonary hemorrhage , chronic lung disease , ultrasonographic evidence of intracranial abnormalities , necrotizing enterocolitis , and retinopathy . RESULTS Of the 574 infants with data on the primary outcome who were assigned to prophylaxis with indomethacin , 271 ( 47 percent ) died or survived with impairments , as compared with 261 of the 569 infants ( 46 percent ) assigned to placebo ( odds ratio , 1.1 ; 95 percent confidence interval , 0.8 to 1.4 ; P=0.61 ) . Indomethacin reduced the incidence of patent ductus arteriosus ( 24 percent vs. 50 percent in the placebo group ; odds ratio , 0.3 ; P<0.001 ) and of severe periventricular and intraventricular hemorrhage ( 9 percent vs. 13 percent in the placebo group ; odds ratio , 0.6 ; P=0.02 ) . No other outcomes were altered by the prophylactic administration of indomethacin . CONCLUSIONS In extremely-low-birth-weight infants , prophylaxis with indomethacin does not improve the rate of survival without neurosensory impairment at 18 months , despite the fact that it reduces the frequency of patent ductus arteriosus and severe periventricular and intraventricular hemorrhage Among 3559 newborn infants with birth weight less than 1750 gm , 421 developing a hemodynamically significant patent ductus arteriosus were entered into a r and omized trial to evaluate the role of indomethacin in the management of PDA . Indomethacin given concurrently with usual medical therapy at the time of diagnosis result ed in ductal closure in 79 % , versus 35 % with placebo ( P less than 0.001 ) . Indomethacin as backup to usual medical treatment result ed in similar closure rates . To assess overall effects through hospital discharge , three management strategies were compared . Although mortality did not differ significantly , infants given indomethacin only if usual therapy failed ( strategy 2 ) had a lower incidence of bleeding than those to whom indomethacin was given with initial medical therapy ( strategy 1 ) and lower rates of pneumothorax and retrolental fibroplasia than those to whom no indomethacin was administered , with surgery the only backup to medical therapy ( strategy 3 ) . Thus the administration of indomethacin only when medical treatment fails appears to be the preferable approach for the management of symptomatic PDA in premature infants |
665 | 25,390,767 | Finally , the risk for low birthweight ( < 2500 g ) did not differ between groups ( RR 0.74 , 95 % CI 0.41 to 1.32 , 306 infants , low quality ) .There were few statistically significant differences between intervention and control groups for depression during pregnancy and the postnatal period .
AUTHORS ' CONCLUSIONS There is insufficient evidence to assess the effectiveness of interventions for domestic violence on pregnancy outcomes .
There is a need for high- quality , RCTs with adequate statistical power to determine whether intervention programs prevent or reduce domestic violence episodes during pregnancy , or have any effect on maternal and neonatal mortality and morbidity outcomes | BACKGROUND Domestic violence during pregnancy is a major public health concern .
This preventable risk factor threatens both the mother and baby .
Routine perinatal care visits offer opportunities for healthcare professionals to screen and refer abused women for effective interventions .
It is , however , not clear which interventions best serve mothers during pregnancy and postpartum to ensure their safety .
OBJECTIVES To examine the effectiveness and safety of interventions in preventing or reducing domestic violence against pregnant women . | OBJECTIVE This project aim ed to evaluate the impact of a home visiting programme that targeted families where the child , for environmental reasons , was at great risk of poor health and developmental outcomes . METHODOLOGY Women in the immediate postpartum period were recruited to a r and omized double-blind controlled trial on the basis of self-reported vulnerability factors and were r and omly assigned to receive either a structured programme of nurse home visiting , supported by a social worker and paediatrician ( n = 90 ) , or assigned to a comparison group receiving st and ard community child health services ( n = 91 ) . Parenting stress and maternal depression were measured at enrollment and at 6 weeks . Preventive health behaviour , service satisfaction and home environment outcomes were tested at 6 weeks , as were child health outcomes . RESULTS At six weeks , women receiving the home-based programme had significant reductions in postnatal depression screening scores as well as improvements in their experience of the parental role and improvement in the ability to maintain their own identity . Maternal-infant interactions were more likely to be positive , with significantly higher ( better ) scores in aspects of the home environment related to optimal development in children , particularly maternal-infant secure attachment . Intervention group mothers were significantly more satisfied with the community child health service . CONCLUSIONS This form of intervention for families is effective in promoting secure maternal-infant attachment , preventing maternal mood disorder and is welcomed by the families receiving it . These findings may predict long-term benefits for the healthy development of children otherwise at risk of a range of poor health and development outcomes 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 : OBJECTIVES : Intimate partner violence ( IPV ) during pregnancy affects 0.9 % to 17 % of women and affects maternal health significantly . The impact of IPV extends to the health of children , including an increased risk of complications during pregnancy and the neonatal period , mental health problems , and cognitive delays . Despite substantial sequelae , there is limited research substantiating best practice s for engaging and retaining high-risk families in perinatal home visiting ( HV ) programs , which have been shown to improve infant development and reduce maltreatment . METHODS : The Domestic Violence Enhanced Home Visitation Program ( DOVE ) is a multistate longitudinal study testing the effectiveness of a structured IPV intervention integrated into health department perinatal HV programs . The DOVE intervention , based on an empowerment model , combined 2 evidence -based interventions : a 10-minute brochure-based IPV intervention and nurse home visitation . RESULTS : Across all sites , 689 referrals were received from participating health departments . A total of 339 abused pregnant women were eligible for r and omization ; 42 women refused , and 239 women were r and omly assigned ( 124 DOVE ; 115 usual care ) , result ing in a 71 % recruitment rate . Retention rates from baseline included 93 % at delivery , 80 % at 3 months , 76 % at 6 months , and 72 % at 12 months . CONCLUSIONS : Challenges for HV programs include identifying and retaining abused pregnant women in their programs . DOVE strategies for engaging and retaining abused pregnant women should be integrated into HV programs ’ federal government m and ates for the appropriate identification and intervention of women and children exposed to IPV Background Intimate partner violence ( IPV ) can result in significant harm to women and families and is especially prevalent when women are pregnant or recent mothers . Maternal and child health nurses ( MCHN ) in Victoria , Australia are community-based nurse/midwives who see over 95 % of all mothers with newborns . MCHN are in an ideal position to identify and support women experiencing IPV , or refer them to specialist family violence services . Evidence for IPV screening in primary health care is inconclusive to date . The Victorian government recently required nurses to screen all mothers when babies are four weeks old , offering an opportunity to examine the effectiveness of MCHN IPV screening practice s. This protocol describes the development and design of MOVE , a study to examine IPV screening effectiveness and the sustainability of screening practice . Methods / design MOVE is a cluster r and omised trial of a good practice model of MCHN IPV screening involving eight maternal and child health nurse teams in Melbourne , Victoria . Normalisation Process Theory ( NPT ) was incorporated into the design , implementation and evaluation of the MOVE trial to enhance and evaluate sustainability . Using NPT , the development stage combined participatory action research with intervention nurse teams and a systematic review of nurse IPV studies to develop an intervention model incorporating consensus guidelines , clinical pathway and strategies for individual nurses , their teams and family violence services . Following twelve months ’ implementation , primary outcomes assessed include IPV inquiry , IPV disclosure by women and referral using data from MCHN routine data collection and a survey to all women giving birth in the previous eight months . IPV will be measured using the Composite Abuse Scale . Process and impact evaluation data ( online surveys and key stakeholders interviews ) will highlight NPT concepts to enhance sustainability of IPV identification and referral . Data will be collected again in two years . Discussion MOVE will be the first r and omised trial to determine IPV screening effectiveness in a community based nurse setting and the first to examine sustainability of an IPV screening intervention . It will further inform the debate about the effectiveness of IPV screening and describe IPV prevalence in a community based post-partum and early infant population .Trial registration BACKGROUND Intimate partner violence ( IPV ) during pregnancy poses a significant health risk to the mother and developing fetus . Practice guidelines recommend that prenatal providers screen for and counsel their patients about IPV , yet many physicians express reluctance or discomfort regarding such discussion s. The Health in Pregnancy ( HIP ) computer program was design ed to improve prenatal providers ' counseling about behavioral risks . METHODS English-speaking women 18 years or older , less than 26-weeks pregnant , and receiving prenatal care at one of the five participating clinics in the San Francisco area , were r and omized in parallel groups in a controlled trial ( June 2006-present ; data analyzed June 2007 ) . Participants reporting one or more risks were r and omized to intervention or control in stratified blocks . Providers received summary " cueing sheets " alerting them to their patient 's risk(s ) and suggesting counseling statements . RESULTS Thirteen percent ( 37/286 ) of the sample reported current IPV . Provider cueing result ed in 85 % of the IPV-intervention group reporting discussion s with their provider , compared to 23.5 % of the control group ( p<0.001 ) . CONCLUSIONS IPV discussion s were influenced strongly by cueing providers . Provider cueing is an effective and appropriate adjunct to routine risk counseling in prenatal care 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 estimate whether home visitation beginning after childbirth was associated with changes in average rates of mothers ' intimate partner violence ( IPV ) victimization and perpetration as well as rates of specific IPV types ( physical assault , verbal abuse , sexual assault , and injury ) during the 3 years of program implementation and during 3 years of long-term follow-up . DESIGN R and omized controlled trial . SETTING Oahu , Hawaii . PARTICIPANTS Six hundred forty-three families with an infant at high risk for child maltreatment born between November 1994 and December 1995 . Intervention Home visitors provided direct services and linked families to community re sources . Home visits were to initially occur weekly and to continue for at least 3 years . MAIN OUTCOME MEASURES Women 's self-reports of past-year IPV victimization and perpetration using the Conflict Tactics Scale . Blinded research staff conducted maternal interviews following the child 's birth and annually when children were aged 1 to 3 years and then 7 to 9 years . RESULTS During program implementation , intervention mothers as compared with control mothers reported lower rates of IPV victimization ( incidence rate ratio [ IRR ] , 0.86 ; 95 % confidence interval [ CI ] , 0.73 - 1.01 ) and significantly lower rates of perpetration ( IRR , 0.83 ; 95 % CI , 0.72 - 0.96 ) . Considering specific IPV types , intervention women reported significantly lower rates of physical assault victimization ( IRR , 0.85 ; 95 % CI , 0.71 - 1.00 ) and perpetration ( IRR , 0.82 ; 95 % CI , 0.70 - 0.96 ) . During long-term follow-up , rates of overall IPV victimization and perpetration decreased , with nonsignificant between-group differences . Verbal abuse victimization rates ( IRR , 1.14 , 95 % CI , 0.97 - 1.34 ) may have increased among intervention mothers . CONCLUSION Early-childhood home visitation may be a promising strategy for reducing IPV Background : A pregnant woman 's psychological health is a significant predictor of postpartum outcomes . The Antenatal Psychosocial Health Assessment ( ALPHA ) form incorporates 15 risk factors associated with poor postpartum outcomes of woman abuse , child abuse , postpartum depression and couple dysfunction . We sought to determine whether health care providers using the ALPHA form detected more antenatal psychosocial concerns among pregnant women than providers practising usual prenatal care . Methods : A r and omized controlled trial was conducted in 4 communities in Ontario . Family physicians , obstetricians and midwives who see at least 10 prenatal patients a year enrolled 5 eligible women each . Providers in the intervention group attended an educational workshop on using the ALPHA form and completed the form with enrolled women . The control group provided usual care . After the women delivered , both groups of providers identified concerns related to the 15 risk factors on the ALPHA form for each patient and rated the level of concern . The primary outcome was the number of psychosocial concerns identified . Results were controlled for clustering . Results : There were 21 ( 44 % ) providers r and omly assigned to the ALPHA group and 27 ( 56 % ) to the control group . A total of 227 patients participated : 98 ( 43 % ) in the ALPHA group and 129 ( 57 % ) in the control group . ALPHA group providers were more likely than control group providers to identify psychosocial concerns ( odds ratio [ OR ] 1.8 , 95 % confidence interval [ CI ] 1.1–3.0 ; p = 0.02 ) and to rate the level of concern as “ high ” ( OR 4.8 , 95 % CI 1.1–20.2 ; p = 0.03 ) . ALPHA group providers were also more likely to detect concerns related to family violence ( OR 4.8 , 95 % CI 1.9–12.3 ; p = 0.001 ) . Interpretation : Using the ALPHA form helped health care providers detect more psychosocial risk factors for poor postpartum outcomes , especially those related to family violence . It is a useful prenatal tool , identifying women who would benefit from additional support and interventions Background Intimate partner violence ( IPV ) is a serious social issue in Japan . In order to start effective interventions for abused women , the appropriate method of screening for IPV in healthcare setting s needs clarifying . The objective of this study was to compare the effectiveness of a face-to-face interview with a self-administered question naire . We used the Violence Against Women Screen ( VAWS ) , a Japanese screening instrument for intimate partner violence ( IPV ) , for identifying pregnant women who have experienced abuse . Methods We conducted a r and omised controlled trial to screen participants at three points in time in a prenatal clinic in Tokyo , Japan . There were 328 consenting women between 14 and 25 weeks of pregnancy who were consecutively selected and r and omly assigned to either the interview or self-administered question naire group . Both groups completed the same screening instrument three times during their pregnancy . The primary outcome was the total number of women identified by each screening method and the secondary outcome was the effect of the screening as measured by the women 's comfort level and their expressed need to consult with the nurse . Results For all three screenings , the identification rate in the interview group was significantly lower than that for the self-administered question naire group ( relative risk 0.66 , 95 % CI 0.46 to 0.97 ) , even after controlling for smoking ( adjusted odds ratio 0.59 , 95 % CI 0.35 to 0.98 ) . The two groups did not differ for secondary outcomes . Conclusions The self-administered question naire identified more IPV than the face-to-face interview when screening pregnant women in a Japanese prenatal clinic . Trial Registration STUDY OBJECTIVE We evaluate the efficacy of emergency department ( ED ) brief intimate partner violence screening intervention in reducing short-term revictimization . METHODS A r and omized controlled trial with blinded 3-month follow-up was conducted in an urban New Zeal and ED . Participants included 399 nonacute , English-speaking women aged 16 years and older , 199 r and omly assigned to the treatment group and 200 to the control group . Participants in both groups received usual emergency health care . Women assigned to the treatment group received a st and ardized 3-item intimate partner violence screen , statements about the unacceptability of violence , risk assessment , and referral by a health professional research assistant . The main outcome measure was self-reported intimate partner violence exposure . Secondary outcomes included self-care strategies ( use of safety behaviors and community re sources ) . RESULTS Forty-four of 344 ( 12.8 % ) women reported intimate partner violence during the 3-month follow-up period : 24 of 177 ( 13.6.% ) among women in the usual care group and 20 of 167 ( 12.0 % ) among women in the treatment group . The adjusted odds ratio , controlling for design effects and covariates , was 0.86 ( 95 % confidence interval 0.39 to 1.92 ) . CONCLUSION This brief intimate partner violence screening intervention did not significantly reduce short-term violence exposure . Continuing work is needed to maximize intervention effectiveness and monitor medium- and long-term outcomes Although violence against women is recognized as a major public health problem , few interventions have been developed to reduce abuse . In this study , 132 pregnant women received three counseling sessions that were design ed to reduce further abuse . A comparison group of 67 abused women were offered wallet-sized cards listing community re sources for abuse . Women in both groups were followed at 6 months and 12 months post-delivery . Using repeated measures MANCOVA with entry scores as a covariate , we found significantly less violence reported by women in the intervention group than by women in the comparison group Abstract Background Effective interventions to increase safety and wellbeing of mothers experiencing intimate partner violence ( IPV ) are scarce . As much attention is focussed on professional intervention , this study aim ed to determine the effectiveness of non-professional mentor support in reducing IPV and depression among pregnant and recent mothers experiencing , or at risk of IPV . Methods MOSAIC was a cluster r and omised trial in 106 primary care ( maternal and child health nurse and general practitioner ) clinics in Melbourne , Australia . 63/106 clinics referred 215 eligible culturally and linguistically diverse women between January 2006 and December 2007 . 167 in the intervention ( I ) arm , and 91 in the comparison ( C ) arm . 174 ( 80.9 % ) were recruited . 133 ( 76.4 % ) women ( 90 I and 43 C ) completed follow-up at 12 months . Intervention : 12 months of weekly home visiting from trained and supervised local mothers , ( English & Vietnamese speaking ) offering non-professional befriending , advocacy , parenting support and referrals . Main outcome measures : Primary outcomes ; IPV ( Composite Abuse Scale CAS ) and depression ( Edinburgh Postnatal Depression Scale EPDS ) ; secondary measures included wellbeing ( SF-36 ) , parenting stress ( PSI-SF ) and social support ( MOS-SF ) at baseline and follow-up . Analysis : Intention-to-treat using multivariable logistic regression and propensity scoring . Results There was evidence of a true difference in mean abuse scores at follow-up in the intervention compared with the comparison arm ( 15.9 vs 21.8 , AdjDiff -8.67 , CI -16.2 to -1.15 ) . There was weak evidence for other outcomes , but a trend was evident favouring the intervention : proportions of women with CAS scores ≥7 , 51/88 ( 58.4 % ) vs 27/42 ( 64.3 % ) AdjOR 0.47 , CI 0.21 to 1.05 ) ; depression ( EPDS score ≥13 ) ( 19/85 , 22 % ( I ) vs 14/43 , 33 % ( C ) ; AdjOR 0.42 , CI 0.17 to 1.06 ) ; physical wellbeing mean scores ( PCS-SF36 : AdjDiff 2.79 ; CI -0.40 to 5.99 ) ; mental wellbeing mean scores ( MCS-SF36 : AdjDiff 2.26 ; CI -1.48 to 6.00 ) . There was no observed effect on parenting stress . 82 % of women mentored would recommend mentors to friends in similar situations . Conclusion Non-professional mentor mother support appears promising for improving safety and enhancing physical and mental wellbeing among mothers experiencing intimate partner violence referred from primary care . Trial registration Background Intimate partner violence ( IPV ) is prevalent globally , experienced by a significant minority of women in the early childbearing years and is harmful to the mental and physical health of women and children . There are very few studies with rigorous design s which have tested the effectiveness of IPV interventions to improve the health and wellbeing of abused women . Evidence for the separate benefit to victims of social support , advocacy and non-professional mentoring suggested that a combined model may reduce the levels of violence , the associated mental health damage and may increase a woman 's health , safety and connection with her children . This paper describes the development , design and implementation of a trial of mentor mother support set in primary care , including baseline characteristics of participating women . Methods / Design MOSAIC ( MOtherS ' Advocates In the Community ) was a cluster r and omised trial embedded in general practice and maternal and child health ( MCH ) nursing services in disadvantaged suburbs of Melbourne , Australia . Women who were pregnant or with infants , identified as abused or symptomatic of abuse , were referred by IPV-trained GPs and MCH nurses from 24 general practice s and eight nurse teams from January 2006 to December 2007 . Women in the intervention arm received up to 12 months support from trained and supported non-professional mentor mothers . Vietnamese health professionals also referred Vietnamese women to bilingual mentors in a sub- study . Baseline and follow-up surveys at 12 months measured IPV ( CAS ) , depression ( EPDS ) , general health ( SF-36 ) , social support ( MOS-SF ) and attachment to children ( PSI-SF ) . Significant development and piloting occurred prior to trial commencement . Implementation interviews with MCH nurses , GPs and mentors assisted further refinement of the intervention . In-depth interviews with participants and mentors , and follow-up surveys of MCH nurses and GPs at trial conclusion will shed further light on MOSAIC 's impact . Discussion Despite significant challenges , MOSAIC will make an important contribution to the need for evidence of effective partner violence interventions , the role of non-professional mentors in partner violence support services and the need for more evaluation of effective health professional training and support in caring for abused women and children among their population s . Trial registration INTRODUCTION There is growing recognition in the ranks of the South African government that violence against women is a serious problem facing us all . Until now data on the epidemiology of violence against women in South Africa have been scanty . This report presents the findings of the first major community-based prevalence study . OBJECTIVES To describe the prevalence of physical , sexual , financial , and emotional abuse of women . METHODS A cross-sectional study conducted in the Eastern Cape ( EC ) , Mpumalanga ( MP ) and the Northern Province ( NP ) . The sample included one r and omly selected woman aged 18 - 49 years living in each of 2,232 households . The sample was drawn using stratified , multistage , r and om methods , and 1,306 question naires were completed , giving a 90.3 % response rate after adjusting for households without an eligible woman . RESULTS The prevalences of ever having been physically abused by a current or ex-partner were 26.8 % ( EC ) , 28.4 % ( MP ) and 19.1 % ( NP ) . The prevalences of abuse in the last year were 10.9 % ( EC ) , 11.9 % ( MP ) and 4.5 % ( NP ) . The prevalences of rape were 4.5 % ( EC ) , 7.2 % ( MP ) and 4.8 % ( NP ) . Considerable emotional and financial abuse was also reported , e.g. the prevalences of a partner having boasted about or brought home girlfriends in the previous year were 5.0 % ( EC ) , 10.4 % ( MP ) and 7.0 % ( NP ) : The prevalences of physical abuse during a pregnancy were 9.1 % ( EC ) , 6.7 % ( MP ) and 4.7 % ( NP ) . The proportions of abused women who were injured in the year before the survey were 34.5 % ( EC ) , 48.0 % ( MP ) and 60.0 % ( NP ) . CONCLUSIONS This study is the first large-scale , community-based prevalence study to be undertaken in South Africa OBJECTIVES We evaluated the efficacy of a primary care intervention targeting pregnant African American women and focusing on psychosocial and behavioral risk factors for poor reproductive outcomes ( cigarette smoking , secondh and smoke exposure , depression , and intimate partner violence ) . METHODS Pregnant African American women ( N = 1044 ) were r and omized to an intervention or usual care group . Clinic-based , individually tailored counseling sessions were adapted from evidence -based interventions . Follow-up data were obtained for 850 women . Multiple imputation methodology was used to estimate missing data . Outcome measures were number of risks at baseline , first follow-up , and second follow-up and within-person changes in risk from baseline to the second follow-up . RESULTS Number of risks did not differ between the intervention and usual care groups at baseline , the second trimester , or the third trimester . Women in the intervention group more frequently resolved some or all of their risks than did women in the usual care group ( odds ratio = 1.61 ; 95 % confidence interval = 1.08 , 2.39 ; P = .021 ) . CONCLUSIONS In comparison with usual care , a clinic-based behavioral intervention significantly reduced psychosocial and behavioral pregnancy risk factors among high-risk African American women receiving prenatal care Background Research ers have frequently encountered difficulties in the recruitment and retention of minorities result ing in their under-representation in clinical trials . This report describes the successful strategies of recruitment and retention of African Americans and Latinos in a r and omized clinical trial to reduce smoking , depression and intimate partner violence during pregnancy . Socio-demographic characteristics and risk profiles of retained vs. non-retained women and lost to follow-up vs. dropped-out women are presented . In addition , subgroups of pregnant women who are less ( more ) likely to be retained are identified . Methods Pregnant African American women and Latinas who were Washington , DC residents , aged 18 years or more , and of 28 weeks gestational age or less were recruited at six prenatal care clinics . Potentially eligible women were screened for socio-demographic eligibility and the presence of the selected behavioral and psychological risks using an Audio Computer-Assisted Self-Interview . Eligible women who consented to participate completed a baseline telephone evaluation after which they were enrolled in the study and r and omly assigned to either the intervention or the usual care group . Results Of the 1,398 eligible women , 1,191 ( 85 % ) agreed to participate in the study . Of the 1,191 women agreeing to participate , 1,070 completed the baseline evaluation and were enrolled in the study and r and omized , for a recruitment rate of 90 % . Of those enrolled , 1,044 were African American women . A total of 849 women completed the study , for a retention rate of 79 % . Five percent dropped out and 12 % were lost-to-follow up . Women retained in the study and those not retained were not statistically different with regard to socio-demographic characteristics and the targeted risks . Retention strategies included financial and other incentives , regular up date s of contact information which was tracked and monitored by a computerized data management system available to all project staff , and attention to cultural competence with implementation of study procedures by appropriately selected , trained , and supervised staff . Single , less educated , alcohol and drug users , non-working , and non-WIC women represent minority women with expected low retention rates . Conclusion We conclude that with targeted recruitment and retention strategies , minority women will participate at high rates in behavioral clinical trials . We also found that women who drop out are different from women who are lost to follow-up , and require different strategies to optimize their completion of the study Background Domestic violence - physical , psychological , or sexual abuse perpetrated against women by one or more family members – is highly prevalent in India . However , relatively little research has been conducted on interventions with the potential to mitigate domestic violence and its adverse health consequences , and few re sources exist to guide safety planning and monitoring in the context of intervention research . Dil Mil is a promising women ’s empowerment-based intervention developed in India that engages with young women ( daughters-in-law ) and their mothers-in-law to mitigate domestic violence and related adverse health outcomes . This paper describes the design of a r and omized controlled trial of Dil Mil in Bengaluru , India , with a focus on strategies used to minimize study -related risks and monitor safety . Methods / design A phase 2 r and omized controlled trial using a parallel comparison of the Dil Mil intervention versus st and ard care will be implemented in three public primary health centers in Bengaluru . Young pregnant women in the first or second trimester of pregnancy will be recruited from antenatal services at study health centers and through community outreach . If eligible and willing , their mother-in-law will also be recruited . Once enrolled , dyads will participate in a baseline interview and then r and omized either to the control arm and receive st and ard care or to the intervention arm and receive st and ard care plus the Dil Mil intervention . Additional evaluations will be conducted at 3 months and 6 months postpartum . Data will be analyzed to examine the feasibility and safety of the intervention and the effect of the intervention on intermediary outcomes ( the empowerment of daughters-in-law and mothers-in-law ) , incidence of domestic violence among daughters-in-law , and health outcomes including perceived quality of life , psychosocial status and maternal and infant health outcomes . Discussion This study offers approaches that may help guide safety planning and monitoring in other domestic violence intervention trials in similar setting s. Moreover , given the staggeringly high prevalence of domestic violence against young women in India ( and indeed globally ) and the dearth of data on effective interventions , this study is poised to make an important contribution to the evidence -base for domestic violence prevention . Trial registration Clinical Trials.gov Identifier : OBJECTIVE Eliciting known risk factors for postpartum depression ( PPD ) during pregnancy may enable primary health care providers to identify women at increased risk of becoming depressed . The purpose of this study was to examine how well the Antenatal Psychosocial Health Assessment ( ALPHA ) form identified antenatal risk factors for PPD , compared with routine care , in a sample of pregnant women . METHODS A r and omized controlled trial was conducted to assess the effectiveness of the ALPHA form in detecting antenatal risk factors associated with the adverse postpartum outcomes of postpartum depression , intimate partner violence , child abuse , and couple dysfunction . The participants were primary antenatal care providers -- family physicians , obstetricians , and midwives -- from four diverse communities in Ontario . These providers were matched and then r and omly allocated into the intervention group , who used the ALPHA form , or into the control group , who administered usual care . In total , 227 pregnant women were recruited : 98 in the ALPHA group and 129 in the control group . The data presented in this paper are from a secondary analysis focusing on PPD as the outcome . RESULTS Providers r and omized to the ALPHA group identified a statistically significantly higher proportion of women with antenatal psychosocial risk factors for PPD ( 36 % vs. 26 % ) and a significantly higher number of risk factors per woman compared with the control group ( mean 2.1 vs.1.8 ) ( z = -1.96 , P = 0.05 ) . Providers in the ALPHA group also identified significantly more women having a " previous history of depression " ( 16 % vs. 6 % ) ( chi2 = 5.243 , df = 1 , P = 0.03 ) and " [ having ] witnessed or experienced abuse as a child " ( 17 % vs. 3 % ) ( chi2 = 12.488 , df = 1 , P = 0.0005 ) , which are both established risk factors for PPD . CONCLUSION The ALPHA provides a systematic means of eliciting antenatal psychosocial risk factors for PPD for primary care providers , and it may be particularly useful for raising and discussing sensitive issues . The detection of depressive symptomatology during pregnancy remains problematic , however , and detection may be improved by administering a simple st and ardized measure of depressive symptomatology during routine antenatal care Abstract While biomedical risks contribute to poor pregnancy and neonatal outcomes in African American ( AA ) population s , behavioral and psychosocial risks ( BPSR ) may also play a part . Among low income AA women with psychosocial risks , this report addresses the impacts on pregnancy and neonatal outcomes of an integrated education and counseling intervention to reduce BPSR , as well as the contributions of other psychosocial and biomedical risks . Subjects were low income AA women ≥18 years living in the Washington , DC , metropolitan area and seeking prenatal care . Subjects ( n = 1,044 ) were screened for active smoking , environmental tobacco smoke exposure ( ETSE ) , depression , or intimate partner violence ( IPV ) and then r and omized to intervention ( IG ) or usual care ( UCG ) groups . Data were collected prenatally , at delivery , and postpartum by maternal report and medical record abstract ion . Multiple imputation methodology was used to estimate missing variables . Rates of pregnancy outcomes ( miscarriage , live birth , perinatal death ) , preterm labor , Caesarean section , sexually transmitted infection ( STI ) during pregnancy , preterm birth ( < 37 weeks ) , low birth weight ( < 2,500 g ) , very low birth weight ( < 1,500 g ) , small for gestational age , neonatal intensive care unit ( NICU ) admission , and > 2 days of hospitalization were compared between IG and UCG . Logistic regression models were created to predict outcomes based on biomedical risk factors and the four psychosocial risks ( smoking , ETSE , depression , and IPV ) targeted by the intervention . Rates of adverse pregnancy and neonatal outcomes were high and did not differ significantly between IG and UCG . In adjusted analysis , STI during the current pregnancy was associated with IPV ( OR = 1.41 , 95 % CI 1.04–1.91 ) . Outcomes such as preterm labor , caesarian section in pregnancy and preterm birth , low birth weight , small for gestational age , NICU admissions and > 2 day hospitalization of the infants were associated with biomedical risk factors including preexisting hypertension and diabetes , previous preterm birth ( PTB ) , and late initiation of prenatal care , but they were not significantly associated with active smoking , ETSE , depression , or IPV . Neither the intervention to reduce BPSR nor the psychosocial factors significantly contributed to the pregnancy and neonatal outcomes . This study confirms that biomedical factors significantly contribute to adverse outcomes in low income AA women . Biomedical factors outweighed psychosocial factors in contributing to adverse pregnancy and neonatal outcomes in this high-risk population . Early identification and management of hypertension , diabetes and previous PTB in low income AA women may reduce health disparities in birth outcomes . Level of evidence Objectives We tested the effect of nurse-delivered telephone individualized social support ( “ Baby BEEP ” ) and eight mailed prenatal smoking cessation booklets singly and in combination ( 2 × 2 factorial design ) on smoking cessation in low-income rural pregnant women ( N = 695 ; 75 % participation ) . Methods Participants r and omized to Baby BEEP groups ( n = 345 ) received weekly calls throughout pregnancy plus 24 - 7 beeper access . Saliva cotinine sample s were collected monthly from all groups by other nurses at home visits up to 6 weeks post-delivery . Primary outcomes were point prevalence abstinence ( cotinine < 30 ng/ml ) in late pregnancy and post-delivery . Results Only 47 women were lost to follow-up . Intent-to-treat analyses showed no difference across intervention groups ( 17–22 % , late pregnancy ; 11–13.5 % , postpartum ) , and no difference from the controls ( 17 % , late pregnancy ; 13 % , postpartum ) . Post hoc analyses of study completers suggested a four percentage-point advantage for the intervention groups over controls in producing early and mid-pregnancy continuous abstainers . Partner smoking had no effect on late pregnancy abstinence ( OR = 1.7 , 95 % CI = 0.95 , 3.2 ) , but post-delivery , the effect was pronounced ( OR = 3.2 , 95 % CI = 1.8 , 5.9 ) . Conclusions High abstinence rates in the controls indicate the power of biologic monitoring and home visits to assess stress , support , depression , and intimate partner violence ; these elements plus booklets were as effective as more intensive interventions . Targeting partners who smoke is needed The current study explored the views of women experiencing interpersonal violence ( IPV ) and their relationship with their mothers or other supportive adult , and determines how this relationship affected perinatal depressive symptoms . The sample consisted of 30 urban and rural pregnant women enrolled in a larger ongoing r and omized controlled trial . Data from quantitative instruments that measured depressive symptoms were examined in combination with qualitative interview data collected at baseline and six months post-natal . Women describing positive relationships with their mothers or another supportive adult reported statistically significant lower depressive symptoms scores ( p < .05 ) BACKGROUND To estimate the prevalence of threats and actual acts of physical and sexual abuse during pregnancy . METHODS Two hundred and seven pregnant Swedish women married to or cohabiting with Swedish men were r and omly selected from three antenatal clinics in the city of Göteborg , Sweden . A st and ardized question naire was used for personal interviews about the women 's experience of physical and sexual abuse by a husb and or a boyfriend at some point in the past , during the last year and during current pregnancy . RESULTS Twenty-seven point five percent of the women reported that they had been exposed to physical violence at some point in the past by their husb and /boyfriend . Twenty-four and a half percent of the women had experienced some form of threat , physical or sexual violence during the last year . At some time ( once or more ) during their current pregnancy , the proportions of women who had been exposed to the following categories of violence , were as follows : 14.5%-symbolic violence , 14.5%-threats of mild violence , 2.9%-threats of moderate violence , 2.9%-threats of serious violence , 11%-mild violence , 4.3%-minor violence , 2.4%-moderate violence , 4.3%-serious violence and 3.3%-sexual violence . CONCLUSIONS This study demonstrates that a considerable number of women had experienced threats , physical and sexual abuse during pregnancy . There is an obvious need for screening of experience of domestic violence among pregnant women to enhance the safety of women and their unborn babies Two hundred five consecutive cases of noncatastrophic trauma occurring during the second half of pregnancy were evaluated prospect ively . Pregnancy complications as a result of trauma occurred in 18 of 205 patients ( 8.8 % ) : premature labor ( n = 10 ) , placental separation ( n = 5 ) , fetal injury ( n = 1 ) , and fetal death ( n = 2 ) . Multiple regression analysis of the data base showed obstetric findings ( contractions , uterine tenderness , and bleeding ) on presentation to be highly associated with complications ( 17/88 ; 19.3 % ) . In their absence complications were rare ( 1/117 ; 0.9 % ) . Detectable fetomaternal hemorrhage was significantly more common in trauma patients ( 18/205 ) than in control subjects ( 2/110 ) ( p less than 0.01 ) , but its role in managing trauma patients was limited to detection of rare massive hemorrhage ( 1/205 ) and detection of rare hemorrhage exceeding that covered by the st and ard Rho ( D ) immune globulin dose ( 2/205 ) . Fetomaternal hemorrhage need not be quantitated in patients who lack obstetric findings on presentation . Despite rare reports of delayed abruptio placentae , it is doubtful that prolonged observation ( greater than 2 to 3 hours ) in the hospital is necessary in patients who lack obstetric findings on initial presentation OBJECTIVE : To evaluate the efficacy of an integrated multiple risk intervention , delivered mainly during pregnancy , in reducing such risks ( cigarette smoking , environmental tobacco smoke exposure , depression , and intimate partner violence ) postpartum . METHODS : Data from this r and omized controlled trial were collected prenatally and on average 10 weeks postpartum in six prenatal care sites in the District of Columbia . African Americans were screened , recruited , and r and omly assigned to the behavioral intervention or usual care . Clinic-based , individually tailored counseling was delivered to intervention women . The outcome measures were number of risks reported postpartum and reduction of these risks between baseline and postpartum . RESULTS : The intervention was effective in significantly reducing the number of risks reported in the postpartum period . In bivariate analyses , the intervention group was more successful in resolving all risks ( 47 % compared with 35 % , P=.007 , number needed to treat=9 , 95 % confidence interval [ CI ] 5–31 ) and in resolving some risks ( 63 % compared with 54 % , P=.009 , number needed to treat=11 , 95 % CI 7–43 ) as compared with the usual care group . In logistic regression analyses , women in the intervention group were more likely to resolve all risks ( odds ratio 1.86 , 95 % CI 1.25–2.75 , number needed to treat=7 , 95 % CI 4–19 ) and resolve at least one risk ( odds ratio 1.60 , 95 % CI 1.15–2.22 , number needed to treat=9 , 95 % CI 6–29 ) . CONCLUSION : An integrated multiple risk factor intervention addressing psychosocial and behavioral risks delivered mainly during pregnancy can have beneficial effects in risk reduction postpartum . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00381823 LEVEL OF EVIDENCE : Objective To evaluate the effectiveness of an empowerment intervention in reducing intimate partner violence ( IPV ) and improving health status This study assessed the initial feasibility , acceptability , and efficacy of an intervention aim ed at reducing depression and posttraumatic stress disorder ( PTSD ) in a sample of low-income pregnant women with recent intimate partner violence ( IPV ) . Fifty-four women were r and omly assigned to the intervention or control group . The intervention consisted of four sessions during pregnancy and one “ booster ” session within 2 weeks of delivery . Based on principles of Interpersonal Psychotherapy , the intervention was design ed to help participants improve their interpersonal relationships , including their social support networks , and master their role transition to motherhood . Assessment s were administered at four time points ( intake , 5–6 weeks post-intake , 2 weeks postpartum , 3 months postpartum ) to assess for depression , PTSD , and IPV . The intervention did not significantly reduce the likelihood of a major depressive episode , PTSD , or IPV during pregnancy or up to 3-month postpartum . However , we found moderate effects for the intervention in reducing symptoms of PTSD and depression during pregnancy and a large effect for PTSD symptoms from pregnancy up to 3 months postpartum . This study suggests some initial support for our intervention . Larger r and omized trials are needed to further examine the intervention both during and after pregnancy OBJECTIVE To determine whether individualized nursing case management can decrease stress among pregnant women at risk for or in abusive relationships . DESIGN A multisite r and omized controlled trial . SETTING Two prenatal clinics in the Pacific Northwest and rural Midwest . PARTICIPANTS 1,000 women who spoke English and were 13 to 23 weeks pregnant at time of recruitment . INTERVENTION All intervention group women ( N = 499 ) were offered an abuse video and had access to a nurse case manager 24/7 . Additionally , participants at risk for or in abusive relationships received individualized nursing care management throughout the pregnancy . RESULTS The most frequent nursing care management activities were providing support ( 38 % ) and assessing needs ( 32 % ) . The nursing care management group received an average of 22 contacts , most ( 80 % ) by telephone and had a significant reduction in stress scores as measured by the Prenatal Psychosocial Profile . Compared to the control group , the differences were in the predicted direction , but not statistically different . A major finding was the choice by abused women to focus on basic needs and their pregnancies rather than the abuse , although all received safety planning . CONCLUSIONS Pregnant women at risk for or in abusive relationships experience very stressful and complex lives . Nurses need to focus on the needs they identify , which may not be the abusive relationship OBJECTIVE To establish the singular and combined occurrence of physical abuse , smoking , and substance use ( i.e. , alcohol and illicit drugs ) during pregnancy and its effect on birth weight . DESIGN Prospect i ve cohort analysis . SETTING Urban public prenatal clinics . PARTICIPANTS 414 African American , 412 Hispanic , and 377 white pregnant women . MAIN OUTCOME MEASURE(S ) Occurrence of physical abuse was 16 % ; smoking , 29.5 % ; and alcohol/illicit drug use , 11.9 % . Significant relationships existed between physical abuse and smoking for African American and white women . For African American women , 33.7 % of women who were not abused smoked , versus 49.5 % of women who were abused ( chi 2 = 8.21 ; df = 1 ; p < 0.005 ) . Alcohol/illicit drug use was 20.8 % for nonabused women compared with 42.1 % for abused women ( chi 2 = 18.18 ; df = 1 ; p < 0.001 ) . For white women , 46.6 % of women who were not abused smoked , versus 59.6 % of those who were abused ( chi 2 = 5.22 ; df = 1 ; p < 0.005 ) . As a triad , physical abuse , smoking , and alcohol/ illicit drug use were significantly related to birth weight ( F[3 , 1040 ] = 30.19 , p < 0.001 ) . CONCLUSIONS Physical abuse during pregnancy is common , readily detected with a five- question screen , and associated with significantly higher use of tobacco , alcohol , and illicit drugs . Clinical protocol s that integrate assessment and intervention for physical abuse , smoking , and substance use are essential for preventing further abuse and improving smoking and substance cessation rates OBJECTIVES Domestic violence is a medical and social issue that often leads to negative consequences for society . This paper examines the association between the prevalence of domestic violence in relation to the different socio-economic classes in Central Trinidad . The paper also explores the major perceived causes of physical abuse in Central Trinidad . SUBJECTS AND METHODS Participants were selected using a two-stage stratified sampling method within the Couva district . Households , each contributing one participant , were stratified into different socioeconomic classes ( SES Class ) and each stratum size ( or its share in the sample ) was determined by the portion of its size in the sampling frame to the total sample ; then its members were r and omly selected . The sampling method attempted to balance and then minimize racial , age , cultural biases and confounding factors . The participant chosen had to be older than 16-years of age , female and a resident of the household . If more than one female was at home , the most senior was interviewed . RESULTS The study found a statistically significant relationship between verbal abuse ( p = 0.0017 ) , physical abuse ( p = 0.0012 ) and financial abuse ( p = 0.001 ) and socio-economic class . For all the socio-economic classes considered , the highest prevalence of domestic violence occurred amongst the working class and lower middle socio-economic classes . The most prominent reasons cited for the physical violence was drug and alcohol abuse ( 37 % ) and communication differences ( 16.3 % ) . These were the other two main perceived causes of the violence . The power of the study was 0.78 and the all strata prevalence of domestic violence was 41 % . CONCLUSIONS Domestic violence was reported within all socio-economic class groupings but it was most prevalent within the working class and lower middle socio-economic classes . The major perceived cause of domestic violence was alcohol/drug abuse A r and omized trial tested the psychosocial efficacy of a home visitation model for women at risk of out-of-home placement of their newborns . After an average of ten months of exposure , the experimental group reported significantly increased social support , greater access to services , and decreased psychological distress . Implication s of the findings for interventions with at-risk families are discussed OBJECTIVE To examine the relationship of police-reported intimate partner violence during pregnancy and adverse birth outcomes . METHODS We conducted a population -based , retrospective , cohort study in Seattle , Washington , using Seattle police data and Washington State birth certificate files from January 1995 through September 1999 . Exposed subjects were women with an intimate partner violence incident reported to police during pregnancy and who subsequently had a singleton live birth or fetal death registered in the state of Washington . Unexposed subjects were r and omly selected Seattle residents with a singleton live birth or fetal death in the same time period and who did not report an incident . The main outcome measures were low birth weight ( LBW less than 2500 g ) , very LBW ( VLBW less than 1500 g ) , preterm birth ( 20–36 weeks ' gestation ) , very preterm birth ( 20–31 weeks ) , and neonatal death ( before discharge ) . RESULTS Women reporting any partner violence during pregnancy were significantly more likely to have a LBW infant ( adjusted odds ratio [ aOR ] 1.70 ; 95 % confidence interval [ CI ] 1.20 , 2.40 ) , a VLBW infant ( aOR 2.54 ; 95 % CI 1.32 , 4.91 ) , a preterm birth ( aOR 1.61 ; 95 % CI 1.14 , 2.28 ) , a very preterm birth ( aOR 3.71 ; 95 % CI 1.80 , 7.63 ) , and a neonatal death ( aOR 3.49 ; 95 % CI 1.43 , 8.50 ) . CONCLUSION Police-reported partner violence during pregnancy is significantly associated with an increased risk of adverse birth outcomes . There is a critical need to identify pregnancy among women with reported incidents and to provide women health and social service information and referrals , particularly referrals to high-risk pregnancy programs OBJECTIVES This study evaluated whether incorporation of an abuse assessment protocol into the routine procedures of the prenatal clinics of a large urban public health department led to increased referral for and assessment , identification , and documentation of abuse . METHODS Evaluation was conducted at 3 matched prenatal clinics serving a total of 12,000 maternity patients per year . Two clinics used the abuse protocol and 1 did not . An audit was performed at the clinics on a r and omly selected sample of 540 maternity patient charts for the 15 months before the protocol was initiated and of 540 records for the 15 months after the protocol was introduced . Ninety-six percent of the patients represented in the sample were Latina . RESULTS At the clinics using the protocol , abuse assessment increased from 0 to 88 % . Detection of abuse increased from 0.8 % to 7 % . There were no changes at the comparison clinic . CONCLUSIONS Incorporation of an abuse assessment protocol into the routine procedures of public health department prenatal clinics increases the assessment , identification , and documentation of and referral for abuse among pregnant women . An abuse protocol should be a routine part of maternity care OBJECTIVE To devise a brief screening instrument to detect partner violence and to partially vali date this screen against established instruments . DESIGN Prospect i ve survey . SETTING Two urban , hospital-based emergency departments . PARTICIPANTS Of 491 women presenting during 48 r and omly selected 4-hour time blocks , 322 ( 76 % of eligible patients ) participated . Respondents had a median age of 36 years ; 19 % were black , 45 % white , and 30 % Hispanic , while 6 % were of other racial or ethnic groups ; 54 % were insured . INTERVENTIONS We developed a partner violence screen ( PVS ) , consisting of 3 questions about past physical violence and perceived personal safety . We administered the PVS and 2 st and ardized measures of partner violence , the Index of Spouse Abuse ( ISA ) and the Conflict Tactics Scale ( CTS ) . MAIN OUTCOME MEASURES Sensitivity , specificity , and predictive values of the PVS were compared with the ISA and the CTS as criterion st and ards . RESULTS The prevalence rate of partner violence using the PVS was 29.5 % ( 95 % confidence interval [ CI ] , 24.6%-34.8 % ) . For the ISA and CTS , the prevalence rates were 24.3 % ( 95 % CI , 19.2%-30.1 % ) and 27.4 % ( 95 % CI , 21.7%-33.6 % ) , respectively . Compared with the ISA , the sensitivity of the PVS in detecting partner abuse was 64.5 % ; the specificity was 80.3 % . When compared with the CTS , sensitivity of the PVS was 71.4 % ; the specificity was 84.4 % . Positive predictive values ranged from 51.3 % to 63.4 % , and negative predictive values ranged from 87.6 % to 88.7 % . Overall , 13.7 % of visits were the result of acute episodes of partner violence . CONCLUSION Three brief directed questions can detect a large number of women who have a history of partner violence Objective . To examine the effects of prenatal and infancy home visiting by paraprofessionals and by nurses from child age 2 through age 4 years . Methods . We conducted , in public and private care setting s in Denver , Colorado , a r and omized , controlled trial with 3 arms , ie , control , paraprofessional visits , and nurse visits . Home visits were provided from pregnancy through child age 2 years . We invited 1178 consecutive , low-income , pregnant women with no previous live births to participate , and we r and omized 735 ; 85 % were unmarried , 47 % Mexican American , 35 % white non-Mexican American , 15 % black , and 3 % American Indian/Asian . Outcomes consisted of maternal reports of subsequent pregnancies , participation in education and work , use of welfare , marriage , cohabitation , experience of domestic violence , mental health , substance use , and sense of mastery ; observations of mother-child interaction and the home environment ; tests of children 's language and executive functioning ; and mothers ' reports of children 's externalizing behavior problems . Results . Two years after the program ended , women who were visited by paraprofessionals , compared with control subjects , were less likely to be married ( 32.2 % vs 44.0 % ) and to live with the biological father of the child ( 32.7 % vs 43.1 % ) but worked more ( 15.13 months vs 13.38 months ) and reported a greater sense of mastery and better mental health ( st and ardized scores [ mean = 100 , SD = 10 ] of 101.25 vs 99.31 and 101.21 vs 99.16 , respectively ) . Paraprofessional-visited women had fewer subsequent miscarriages ( 6.6 % vs 12.3 % ) and low birth weight newborns ( 2.8 % vs 7.7 % ) . Mothers and children who were visited by paraprofessionals , compared with control subjects , displayed greater sensitivity and responsiveness toward one another ( st and ardized score [ mean = 100 , SD = 10 ] of 100.92 vs 98.66 ) and , in cases in which the mothers had low levels of psychologic re sources at registration , had home environments that were more supportive of children 's early learning ( score of 24.63 vs 23.35 ) . Nurse-visited women reported greater intervals between the births of their first and second children ( 24.51 months vs 20.39 months ) and less domestic violence ( 6.9 % vs 13.6 % ) and enrolled their children less frequently in preschool , Head Start , or licensed day care than did control subjects . Nurse-visited children whose mothers had low levels of psychologic re sources at registration , compared with control group counterparts , demonstrated home environments that were more supportive of children 's early learning ( score of 24.61 vs 23.35 ) , more advanced language ( score of 91.39 vs 86.73 ) , superior executive functioning ( score of 100.16 vs 95.48 ) , and better behavioral adaptation during testing ( score of 100.41 vs 96.66 ) . There were no statistically significant effects of either nurse or paraprofessional visits on the number of subsequent pregnancies , women 's educational achievement , use of substances , use of welfare , or children 's externalizing behavior problems . Conclusions . Paraprofessional-visited mothers began to experience benefits from the program 2 years after the program ended at child age 2 years , but their first-born children were not statistically distinguishable from their control group counterparts . Nurse-visited mothers and children continued to benefit from the program 2 years after it ended . The impact of the nurse-delivered program on children was concentrated on children born to mothers with low levels of psychologic re sources Background : Despite the recognition of intimate partner violence ( IPV ) against women as a global health issue associated with significant morbidity and mortality , evidence -based treatment strategies for primary care setting s are lacking . Objective : To assess the comparative safety behaviors , use of community re sources , and extent of violence following two levels of intervention . Methods : A r and omized , two-arm , clinical trial was completed in urban public primary care clinics with 360 abused women who assessed positive for physical or sexual abuse within the preceding 12 months . Two interventions were tested : a wallet-sized referral card and a 20-minute nurse case management protocol . Outcome measures were differences in the number of threats of abuse , assaults , danger risks for homicide , events of work harassment , safety behaviors adopted , and use of community re sources between intervention groups over a 24-month period . Results : Two years following treatment , both treatment groups of women reported significantly ( p < .001 ) fewer threats of abuse ( M = 14.5 ; 95 % CI 12.6 , 16.4 ) , assaults ( M = 15.5 , 95 % CI 13.5 , 17.4 ) , danger risks for homicide ( M = 2.6 ; 95 % CI 2.1 , 3.0 ) , and events of work harassment ( M = 2.7 ; 95 % CI 2.3 , 3.1 ) , but there were no significant differences between groups . Compared to baseline , both groups of women adopted significantly ( p < .001 ) more safety behaviors by 24 months ( M = 2.0 ; 95 % CI 1.6 , 2.3 ) ; however , community re source use declined significantly ( p < .001 ) for both groups ( M = −0.2 ; 95 % CI −0.4,−0.2 ) . There were no significant differences between groups . Discussion : Disclosure of abuse , such as what happens with abuse assessment , was associated with the same reduction in violence and increase in safety behaviors as a nurse case management intervention . Simple assessment for abuse and offering of referrals has the potential to interrupt and prevent recurrence of IPV and associated trauma BACKGROUND Teenage pregnancies are associated with negative socioeconomic effects . Our aim was to ascertain whether a postnatal home-visiting service for teenage mothers younger than age 18 years could reduce the frequency of adverse neonatal outcomes and improve knowledge of contraception , breastfeeding , and infant vaccination schedules in this parent group . METHODS We enrolled 139 adolescents , attending a teenage pregnancy clinic , in a r and omised controlled trial . After completing an antenatal question naire design ed to assess their knowledge of contraception , infant vaccination , and breastfeeding , we assigned participants to either receive five structured postnatal home visits by nurse-midwives ( n=65 ) or not ( n=71 ) . Assessment interviews were done 6 months postpartum . Our primary endpoint was unadjusted difference in knowledge between groups , and incidence of predefined adverse neonatal outcomes . Analysis was by intention to treat . FINDINGS Three women withdrew before r and omisation because of late fetal loss , 11 mothers withdrew because of adverse neonatal outcomes ( adverse neonatal outcome was a primary endpoint , but result ed in withdrawal from the study for knowledge outcomes ) , and one left voluntarily . Follow-up data were , therefore , available for 124 teenagers . Postnatal home visits were associated with a reduction in adverse neonatal outcomes ( intervention : 2 ; control : 9 ; relative risk 0.24 , 95 % CI 0.05 - 1.08 ) , and a significant increase in contraception knowledge ( mean difference 0.92 , 95 % CI 0.32 - 1.52 ) . However , there was no significant increase in knowledge with respect to breastfeeding or infant vaccination schedules associated with the home visits . INTERPRETATION Postnatal home-visiting services by nurse-midwives reduce adverse neonatal events and improve contraception outcomes , but do not affect breastfeeding or infant vaccination knowledge or compliance BACKGROUND This study examined the efficacy of a family-planning-clinic-based intervention to address intimate partner violence ( IPV ) and reproductive coercion . STUDY DESIGN Four free-st and ing urban family planning clinics in Northern California were r and omized to intervention ( trained family planning counselors ) or st and ard of care . English-speaking and Spanish-speaking females ages 16 - 29 years ( N = 906 ) completed audio computer-assisted surveys prior to a clinic visit and 12 - 24 weeks later ( 75 % retention rate ) . Analyses included assessment of intervention effects on recent IPV , awareness of IPV services and reproductive coercion . RESULTS Among women reporting past-3-months IPV at baseline , there was a 71 % reduction in the odds of pregnancy coercion among participants in intervention clinics compared to participants in the control clinics that provided st and ard of care . Women in the intervention arm were more likely to report ending a relationship because the relationship was unhealthy or because they felt unsafe regardless of IPV status ( adjusted odds ratio = 1.63 ; 95 % confidence interval=1.01 - 2.63 ) . CONCLUSIONS Results of this pilot study suggest that this intervention may reduce the risk for reproductive coercion from abusive male partners among family planning clients and support such women to leave unsafe relationships The mental health consequences of living with intimate partner violence ( IPV ) are substantial . Despite the growing awareness of the incidence of depression and PTSD in women experiencing IPV , few studies have examined prospect ively the experience of IPV during pregnancy and the impact of the abuse on women 's mental health . As a component of a larger clinical trial of an intervention for pregnant abused women , 27 women participated in a qualitative study of their responses to the abuse in the context of pregnancy and parenting . Results indicate that women 's changing perceptions of self was related to mental distress , mental health , or both mental distress and mental health |
666 | 22,984,955 | SUMMARY The AHRQ systematic review of r and omized clinical trials reveals that both insulin delivery modalities ( CSII and MDI ) demonstrate similar effectiveness on glycemic control and severe hypoglycemia in children and adolescents with T1DM and in adults with T2DM .
In children and adults with T1DM , the use of CSII was associated with improved quality of life compared with MDI , with low strength of evidence , while there was insufficient strength of evidence to make conclusions regarding the quality of life for adults with T2DM .
The study investigators suggest that the modality to deliver intensive insulin therapy can be individualized to patient preference in order to maximize quality of life .
On all measured outcomes , there was insufficient or low strength of evidence regarding pregnant women with pre-existing diabetes .
The systematic review demonstrates that rt-CGM is associated with greater lowering of A1c compared with SMBG ( high strength of evidence ) without affecting the risk of severe hypoglycemia ( low strength of evidence ) or quality of life ( low strength of evidence ) in nonpregnant individuals with T1DM , particularly when compliance with device use is high .
Additional findings suggest that the use of sensor-augmented insulin pumps ( rt-CGM + CSII ) is superior to the use of MDI/SMBG use in lowering A1c in nonpregnant individuals with T1DM ( moderate strength of evidence ) . | BACKGROUND Diabetes mellitus is defined as a group of metabolic diseases characterized by hyperglycemia , which when untreated can lead to long-term complications , including micro- and macrovascular complications .
Tight glycemic control with intensive insulin therapy has been suggested to reduce the risk of such complications in several diabetes population s ; however , such an approach can also be associated with risks and challenges .
There are currently several modalities available to deliver insulin and monitor glucose levels to achieve glycemic goals in diabetic patients .
OBJECTIVES To ( a ) educate health care professionals on the findings from AHRQ 's 2012 comparative effectiveness review on insulin delivery and glucose-monitoring modalities in patients with diabetes ; ( b ) apply review findings to make treatment decisions in clinical practice ; and ( c ) identify shortcomings in the current research and future directions relating to the comparative effectiveness of insulin delivery and glucose-monitoring modalities for patients with diabetes . | OBJECTIVE Insulin pump therapy ( continuous subcutaneous insulin infusion [ CSII ] ) and multiple daily injections ( MDIs ) with insulin glargine as basal insulin and mealtime insulin lispro have not been prospect ively compared in people naïve to either regimen in a multicenter study . We aim ed to help close that deficiency . RESEARCH DESIGN AND METHODS People with type 1 diabetes on NPH-based insulin therapy were r and omized to CSII or glargine-based MDI ( both otherwise using lispro ) and followed for 24 weeks in an equivalence design . Fifty people were correctly r and omized , and 43 completed the study . RESULTS Total insulin requirement ( mean ± SD ) at end point was 36.2 ± 11.5 units/day on CSII and 42.6 ± 15.5 units/day on MDI . Mean A1C fell similarly in the two groups ( CSII −0.7 ± 0.7 % ; MDI −0.6 ± 0.8 % ) with a baseline-adjusted difference of −0.1 % ( 95 % CI −0.5 to 0.3 ) . Similarly , fasting blood glucose and other prepr and ial , postpr and ial , and nighttime self-monitored plasma glucose levels did not differ between the regimens , nor did measures of plasma glucose variability . On CSII , 1,152 hypoglycemia events were recorded by 23 of 28 participants ( 82 % ) and 1,022 in the MDI group by 27 of 29 patients ( 93 % ) ( all hypoglycemia differences were nonsignificant ) . Treatment satisfaction score increased more with CSII ; however , the change in score was similar for the groups . Costs were ∼3.9 times higher for CSII . CONCLUSIONS In unselected people with type 1 diabetes naïve to CSII or insulin glargine , glycemic control is no better with the more expensive CSII therapy compared with glargine-based MDI therapy OBJECTIVE Multiple daily injection ( MDI ) therapy of bolus insulin aspart and basal insulin glargine was compared with continuous subcutaneous insulin infusion ( CSII ) with aspart in type 1 diabetic patients previously treated with CSII . RESEARCH DESIGN AND METHODS One hundred patients were enrolled in a r and omized , multicenter , open-label , crossover study . After a 1-week run-in period with aspart by CSII , 50 subjects were r and omly assigned to MDI therapy ( aspart immediately before each meal and glargine at bedtime ) and 50 subjects continued CSII . After 5 weeks of the first treatment , subjects crossed over to the alternate treatment for 5 weeks . During the last week of each treatment period , subjects wore a continuous glucose monitoring system for 48 - 72 h. RESULTS Mean serum fructosamine levels were significantly lower after CSII therapy than after MDI therapy ( 343 + /- 47 vs. 355 + /- 50 micromol/l , respectively ; P = 0.0001 ) . Continuous glucose monitoring profiles over a 24-h time period showed that glucose exposure was 24 and 40 % lower for CSII than MDI as measured by area under the curve ( AUC ) glucose > /=80 mg/dl ( 1,270 + /- 742 vs. 1,664 + /- 1,039 mg . h . dl(-1 ) ; P < 0.001 ) and AUC glucose > /=140 mg/dl ( 464 + /- 452 vs. 777 + /- 746 mg . h . dl(-1 ) , CSII vs. MDI , respectively ; P < 0.001 ) . Similar percentages of subjects reported hypoglycemic episodes ( CSII : 92 % , MDI : 94 % ) and nocturnal ( 12:00 a.m. to 8:00 a.m. ) hypoglycemic episodes ( CSII : 73 % , MDI : 72 % ) . Major hypoglycemia was infrequent ( CSII : two episodes , MDI : five episodes ) . CONCLUSIONS In a trial of short duration , CSII therapy with insulin aspart result ed in lower glycemic exposure without increased risk of hypoglycemia , as compared with MDI with insulin aspart and glargine OBJECTIVE Effects of pump treatment vs. four times daily injections were explored in children with diabetes with regard to quality of life and impact of disease as well as adverse effects and parameters of metabolic control . METHODS An open , parallel , r and omized controlled prospect i ve comparative study lasting 14 months was completed by 38 type 1 children with diabetes ( age 4 - 16 yr ) following a 3.5-months run-in phase . St and ardized quality -of-life Pediatric Quality of life Inventory ( PedsQL ) and impact of disease scores were obtained every 3.5 months as well as regular medical parameters . Parallel treatment group data and longitudinal within-patient data were analysed for each treatment modality . RESULTS Within-patient comparisons of the two treatment modalities showed significant improvement in PedsQL and impact scores after pump treatment . Treatment group comparisons did not show significant improvement . Pump treatment result ed in decreased symptomatic hypoglycaemia and lowered haemoglobin A1c by 0.22 % after run in . CONCLUSIONS Within-patient comparison suggests that metabolic control , frequency of severe hypoglycaemia ( a threefold decrease ) , quality of life and impact of disease scores are improved by pump treatment in comparison to regular treatment with four daily insulin injections AIMS The goal of the study was to determine whether continuous subcutaneous insulin infusion ( CSII ) differs from a multiple daily injection ( MDI ) regimen based on neutral protamine hagedorn ( NPH ) as basal insulin with respect to glycaemic control and quality of life in people with Type 1 diabetes . METHODS The 5-Nations trial was a r and omized , controlled , crossover trial conducted in 11 European centres . Two hundred and seventy-two patients were treated with CSII or MDI during a 2-month run-in period followed by a 6-month treatment period , respectively . The quality of glycaemic control was assessed by HbA(1c ) , blood glucose values , and the frequency of hypoglycaemic events . For the evaluation of the quality of life , three different self-report question naires have been assessed . RESULTS CSII treatment result ed in lower HbA(1c ) ( 7.45 vs. 7.67 % , P < 0.001 ) , mean blood glucose level ( 8.6 vs. 9.4 mmol/l , P < 0.001 ) and less fluctuation in blood glucose levels than MDI ( + /- 3.9 vs. + /- 4.3 mmol/l , P < 0.001 ) . There was a marked reduction in the frequency of hypoglycaemic events using CSII compared with MDI , with an incidence ratio of 1.12 [ 95 % confidence interval ( CI ) : 1.08 - 1.17 ] and 2.61 ( 95 % CI : 1.59 - 4.29 ) for mild and severe hypoglycaemia , respectively . The overall score of the diabetes quality of life question naire was higher for CSII ( P < 0.001 ) , and an improvement in pump users ' perception of mental health was detected when using the SF-12 question naire ( P < 0.05 ) . CONCLUSION CSII usage offers significant benefits over NPH-based MDI for individuals with Type 1 diabetes , with improvement in all significant metabolic parameters as well as in patients ' quality of life . Additional studies are needed to compare CSII with glargine- and detemir-based MDI No long-term data are available on the efficacy of glargine insulin in comparison with continuous sc insulin infusion ( CSII ) in children and adolescents affected by Type 1 diabetes ( T1D ) . Our aim was to compare the 2-yr efficacy of the 2 insulin approaches , in order to know how to best supply basal insulin in these patients . Thirty-six 9 to 18-yr-old consecutive children with at least 3 yr previous T1D diagnosis were enrolled . As part of routine clinical care , the patients consecutively changed their previous insulin scheme ( isophane insulin at bedtime and human regular insulin at meals ) and were r and omly selected in order to receive either multiple daily injections ( MDI ) treatment with once-daily glargine and human regular insulin at meals , or CSII with aspart or lispro insulin . Both groups showed a significant decrease in glycosylated hemoglobin ( HbA1c ) values during the 1st year of therapy , though only in the CSII treated children was the decrease also observed during the 2nd year . The overall insulin requirement significantly decreased only in the CSII group and exclusively during the 1st year , while no significant differences were observed concerning body mass index SD score , severe hypoglycémic episodes and basal insulin supplementation . The work illustrates the first long-term study comparing the efficacy of CSII to MDI using glargine as basal insulin in children . Only with CSII were better HbA1c values obtained for prolonged periods of time , so that CSII might be considered the gold st and ard of intensive insulin therapy also for long-term follow-ups OBJECTIVE To assess the impact of continuous glucose monitoring on hypoglycemia in people with type 1 diabetes . RESEARCH DESIGN AND METHODS In this r and omized , controlled , multicenter study , 120 children and adults on intensive therapy for type 1 diabetes and a screening level of glycated hemoglobin A1c ( HbA1c ) < 7.5 % were r and omly assigned to a control group performing conventional home monitoring with a blood glucose meter and wearing a masked continuous glucose monitor every second week for five days or to a group with real-time continuous glucose monitoring . The primary outcome was the time spent in hypoglycemia ( interstitial glucose concentration < 63 mg/dL ) over a period of 26 weeks . Analysis was by intention to treat for all r and omized patients . RESULTS The time per day spent in hypoglycemia was significantly shorter in the continuous monitoring group than in the control group ( mean ± SD 0.48 ± 0.57 and 0.97 ± 1.55 h/day , respectively ; ratio of means 0.49 ; 95 % CI 0.26–0.76 ; P = 0.03 ) . HbA1c at 26 weeks was lower in the continuous monitoring group than in the control group ( difference −0.27 % ; 95 % CI −0.47 to −0.07 ; P = 0.008 ) . Time spent in 70 to 180 mg/dL normoglycemia was significantly longer in the continuous glucose monitoring group compared with the control group ( mean hours per day , 17.6 vs. 16.0 , P = 0.009 ) . CONCLUSIONS Continuous glucose monitoring was associated with reduced time spent in hypoglycemia and a concomitant decrease in HbA1c in children and adults with type 1 diabetes Aims /hypothesisThe value of managing children with type 1 diabetes using a combination of insulin pump and continuous glucose monitoring starting from diagnosis for improving subsequent glycaemic control and preserving residual beta cell function was determined . Methods A total of 160 children ( aged 1–16 years , mean ± SD : 8.7 ± 4.4 years ; 47.5 % girls ) were r and omised to receive insulin pump treatment with continuous glucose monitoring or conventional self-monitoring blood glucose measurements . The primary outcome was the level of HbA1c after 12 months . Other analyses included fasting C-peptide , glycaemic variability , sensor usage , adverse events , children ’s health-related quality of life and parent ’s wellbeing . Results HbA1c was not significantly different between the two groups , but patients with regular sensor use had lower values ( mean 7.1 % , 95 % CI 6.8–7.4 % ) compared with the combined group with no or low sensor usage ( mean 7.6 % , 95 % CI 7.3–7.9 % ; p = 0.032 ) . At 12 months , glycaemic variability was lower in the sensor group ( mean amplitude of glycaemic excursions 80.2 ± 26.2 vs 92.0 ± 33.7 ; p = 0.037 ) . Higher C-peptide concentrations were seen in sensor-treated 12- to 16-year-old patients ( 0.25 ± 0.12 nmol/l ) compared with those treated with insulin pump alone ( 0.19 ± 0.07 nmol/l ; p = 0.033 ) . Severe hypoglycaemia was reported only in the group without sensors ( four episodes ) . Conclusion /interpretationSensor-augmented pump therapy starting from the diagnosis of type 1 diabetes can be associated with less decline in fasting C-peptide particularly in older children , although regular sensor use is a prerequisite for improved glycaemic control . Trial registration IS RCT N.org IS RCT N05450731 Funding Medtronic International Trading Sàrl , Tolochenaz , Switzerl OBJECTIVE To evaluate glycemic control , hypoglycemic events , and quality of life in patients treated with continuous subcutaneous insulin infusion ( CSII ) and multiple daily insulin injection ( MDI ) , with insulin lispro as the principal insulin . RESEARCH DESIGN AND METHODS This clinical trial enrolled 27 patients with type 1 diabetes . They were r and omly assigned to CSII ( n = 13 ) or MDI ( n = 14 ) treatment regimens . Glycemic control ( HbA(1c ) level ) was the primary outcome and was measured monthly for 9 months . Secondary outcomes were patient reports of hypoglycemic events ( recorded monthly for 9 months ) and quality of life assessed at 9 months using the Diabetes Quality of Life ( DQOL ) question naire . RESULTS A significant decrease in HbA(1c ) from baseline was shown for both groups . However , the overall treatment effect ( CSII - MDI ) for HbA(1c ) was + 0.08 % ( 95 % CI -0.23 to + 0.39 , P > 0.10 ) . This was significantly less than the a priori limit of + /-0.5 % ( P = 0.004 ) . The relative treatment effect ( [ CSII - MDI]/MDI ) for the overall number of hypoglycemic events was + 9 % ( 95 % CI -37 to + 87 , P > 0.10 ) . There were no statistically significant differences between treatment groups for any of the DQOL subscales . CONCLUSIONS No statistically significant differences in glycemic control , reported hypoglycemic events , or quality of life were found in this study . Furthermore , a clinical ly significant difference of more than + /-0.5 % HbA(1c ) between the two regimens can be confidently ruled out . We conclude that the choice of intensive insulin therapy should be a matter of patient preference , consistent with lifestyle OBJECTIVE The potential benefits of continuous glucose monitoring ( CGM ) in the management of adults and children with well-controlled type 1 diabetes have not been examined . RESEARCH DESIGN AND METHODS A total of 129 adults and children with intensively treated type 1 diabetes ( age range 8–69 years ) and A1C < 7.0 % were r and omly assigned to either continuous or st and ard glucose monitoring for 26 weeks . The main study outcomes were time with glucose level ≤70 mg/dl , A1C level , and severe hypoglycemic events . RESULTS At 26 weeks , biochemical hypoglycemia ( ≤70 mg/dl ) was less frequent in the CGM group than in the control group ( median 54 vs. 91 min/day ) , but the difference was not statistically significant ( P = 0.16 ) . Median time with a glucose level ≤60 mg/dl was 18 versus 35 min/day , respectively ( P = 0.05 ) . Time out of range ( ≤70 or > 180 mg/dl ) was significantly lower in the CGM group than in the control group ( 377 vs. 491 min/day , P = 0.003 ) . There was a significant treatment group difference favoring the CGM group in mean A1C at 26 weeks adjusted for baseline ( P < 0.001 ) . One or more severe hypoglycemic events occurred in 10 and 11 % of the two groups , respectively ( P = 1.0 ) . Four outcome measures combining A1C and hypoglycemia data favored the CGM group in comparison with the control group ( P < 0.001 , 0.007 , 0.005 , and 0.003 ) . CONCLUSIONS Most outcomes , including those combining A1C and hypoglycemia , favored the CGM group . The weight of evidence suggests that CGM is beneficial for individuals with type 1 diabetes who have already achieved excellent control with A1C < 7.0 % BACKGROUND Recently developed technologies for the treatment of type 1 diabetes mellitus include a variety of pumps and pumps with glucose sensors . METHODS In this 1-year , multicenter , r and omized , controlled trial , we compared the efficacy of sensor-augmented pump therapy ( pump therapy ) with that of a regimen of multiple daily insulin injections ( injection therapy ) in 485 patients ( 329 adults and 156 children ) with inadequately controlled type 1 diabetes . Patients received recombinant insulin analogues and were supervised by expert clinical teams . The primary end point was the change from the baseline glycated hemoglobin level . RESULTS At 1 year , the baseline mean glycated hemoglobin level ( 8.3 % in the two study groups ) had decreased to 7.5 % in the pump-therapy group , as compared with 8.1 % in the injection-therapy group ( P<0.001 ) . The proportion of patients who reached the glycated hemoglobin target ( < 7 % ) was greater in the pump-therapy group than in the injection-therapy group . The rate of severe hypoglycemia in the pump-therapy group ( 13.31 cases per 100 person-years ) did not differ significantly from that in the injection-therapy group ( 13.48 per 100 person-years , P=0.58 ) . There was no significant weight gain in either group . CONCLUSIONS In both adults and children with inadequately controlled type 1 diabetes , sensor-augmented pump therapy result ed in significant improvement in glycated hemoglobin levels , as compared with injection therapy . A significantly greater proportion of both adults and children in the pump-therapy group than in the injection-therapy group reached the target glycated hemoglobin level . ( Funded by Medtronic and others ; Clinical Trials.gov number , NCT00417989 . OBJECTIVE To compare the efficacy of 2 intensified insulin regimens , continuous subcutaneous insulin infusion ( CSII ) and multiple daily injections ( MDI ) , by using the short-acting insulin analog lispro in type 1 diabetic patients . RESEARCH DESIGN AND METHODS A total of 41 C-peptide-negative type 1 diabetic patients ( age 43.5+/-10.3 years ; 21 men and 20 women , BMI 24.0+/-2.4 kg/m2 , diabetes duration 20.0+/-11.3 years ) on intensified insulin therapy ( MDI with regular insulin or lispro , n = 9 , CSII with regular insulin , n = 32 ) were included in an open-label r and omized crossover study comparing two 4-month periods of intensified insulin therapy with lispro : one period by MDI and the other by CSII . Blood glucose ( BG ) was monitored before and after each of the 3 meals each day . RESULTS The basal insulin regimen had to be optimized in 75 % of the patients during the MDI period ( mean number of NPH injections per day = 2.65 ) . HbA1c values were lower when lispro was used in CSII than in MDI ( 7.89+/-0.77 vs. 8.24+/-0.77 % , P<0.001 ) . BG levels were lower with CSII ( 165+/-27 vs. 175+/-33 mg/dl , P<0.05 ) . The SD of all the BG values ( 73+/-15 vs. 82+/-18 mg/dl , P<0.01 ) was lower with CSII . The frequency of hypoglycemic events , defined as BG levels < 60 mg/dl , did not differ significantly between the 2 modalities ( CSII 3.9+/-4.2 per 14 days vs. MDI 4.3+/-3.9 per 14 days ) . Mean insulin doses were significantly lower with CSII than with MDI ( 38.5+/-9.8 vs. 47.3+/-14.9 U/day . respectively , P < 0.0001 ) . CONCLUSIONS When used with external pumps versus MDI , lispro provides better glycemic control and stability with much lower doses of insulin and does not increase the frequency of hypoglycemic episodes OBJECTIVE To assess in a r and omized crossover trial the efficacy of continuous subcutaneous insulin infusion in improving glycemic control and health-related quality of life in type 1 diabetic patients with long-st and ing poor glycemic control . RESEARCH DESIGN AND METHODS A total of 79 patients in 11 Dutch centers were r and omized to 16 weeks of continuous subcutaneous insulin infusion followed by 16 weeks intensive injection therapy or the reverse order . Glycemic control was assessed by HbA(1c ) , self-reported hypoglycemic events , and blood glucose memory meter read outs . Changes in quality of life were assessed by self-report question naires administered at baseline and 16 weeks . RESULTS As the drop-out rate after crossover was high ( 17 of 79 patients [ 22 % ] ) , we analyzed the trial as a parallel clinical trial , using data of the first half of the crossover phase only . At 16 weeks , mean HbA(1c ) was 0.84 % ( 95 % CI -1.31 to -0.36 ) lower in the continuous subcutaneous insulin infusion group compared with the insulin injection group ( P = 0.002 ) . Stability of blood glucose self-measurement values , expressed as SD of the nine-point blood glucose profiles , improved in the insulin pump group by 29.3 + /- 41.1 vs. 8.2 + /- 36.5 % in the injection group ( P = 0.039 ) . The number of mild hypoglycemic episodes per patient-week was 0.99 ( 95 % CI 0.11 - 1.87 ) higher in the insulin pump group ( P = 0.028 ) . Weight gain was similar in both groups . Scores on the Short-Form 36-Item subscales ' general health ' and ' mental health ' improved in the continuous subcutaneous insulin infusion group , compared with stable values in the injection group ( P = 0.048 and 0.050 , respectively ) . CONCLUSIONS Continuous subcutaneous insulin infusion improves glycemic control and some aspects of health-related quality of life in patients with a history of long-term poor glycemic control OBJECTIVE The efficacy of the insulin analogs now available for multiple daily injection ( MDI ) and continuous subcutaneous insulin infusion ( CSII ) therapy in type 1 diabetes has not yet been established in pediatric patients . Our principal aim in this short-term study was to compare the efficacy of CSII to MDI with glargine in lowering HbA(1c ) levels in children and adolescents with type 1 diabetes . RESEARCH DESIGN AND METHODS Thirty-two youth with type 1 diabetes ( age 8 - 21 years ) were r and omly assigned to receive either MDI treatment with once-daily glargine and premeal/snack insulin aspart or CSII with insulin aspart . Dose titration in both groups was based on home self-monitored blood glucose measurements and monthly HbA(1c ) . HbA(1c ) , total daily insulin dose ( TDD ) , self-monitored blood glucose readings , and adverse events were compared after 16 weeks of therapy . RESULTS While there was no significant change in the glargine group ( HbA(1c ) 8.2 % at baseline vs. 8.1 % at 16 weeks ) , youth r and omized to CSII had a sharp reduction in HbA(1c ) levels , from 8.1 to 7.2 % after 16 weeks of therapy ( P < 0.02 vs. baseline and < 0.05 vs. glargine group ) . TDD was unchanged in the glargine group , but significantly dropped with CSII ( 1.4 units/kg at baseline vs. 0.9 units/kg at 16 weeks , P < 0.01 ) . Both groups had similar basal doses and insulin-to-carbohydrate ratios . Fasting self-monitored blood glucose was similar in both groups , but lunch , dinner , and bedtime readings were significantly lower in the CSII group ( P < 0.01 ) . CONCLUSIONS Lower HbA(1c ) and premeal glucose levels were more achievable in this short-term study with CSII than with glargine-based MDI treatment . CSII is an efficacious treatment to improve metabolic control in youth with type 1 diabetes OBJECTIVE To compare the efficacy and safety of continuous subcutaneous insulin infusion ( CSII ) and multiple daily injection ( MDI ) in older adults with insulin-treated type 2 diabetes and to assess treatment satisfaction and quality of life . RESEARCH DESIGN AND METHODS Adults ( n = 107 ) > or = 60 years of age ( mean age 66 years ) with insulin-treated type 2 diabetes ( mean duration 16 years , BMI 32 kg/m(2 ) , and HbA(1C ) [ A1C ] 8.2 % ) were r and omized to CSII ( using insulin lispro ) or MDI ( using insulin lispro and insulin glargine ) in a two-center , 12-month , prospect i ve , r and omized , controlled clinical trial . Efficacy was assessed with A1C , safety by frequency of hypoglycemia , and treatment satisfaction and quality of life with the Diabetes Quality of Life Clinical Trial Question naire and the 36-item short-form health survey , version 2 . RESULTS Forty-eight CSII subjects ( 91 % ) and 50 MDI subjects ( 93 % ) completed the study . Mean A1C fell by 1.7 + /- 1.0 % in the CSII group to 6.6 % and by 1.6 + /- 1.2 % in the MDI group to 6.4 % . The difference in A1C between treatment groups was not statistically significant ( P = 0.20 ) . Eighty-one percent of CSII subjects and 90 % of MDI subjects experienced at least one episode of minor ( self-treated ) hypoglycemia ( P = 0.17 ) , and three CSII and six MDI subjects experienced severe hypoglycemia ( P = 0.49 ) . Rates of severe hypoglycemia were similarly low in the two groups ( CSII 0.08 and MDI 0.23 events per person-year , P = 0.61 ) . Weight gain did not differ between groups ( P = 0.70 ) . Treatment satisfaction improved significantly with both CSII and MDI ( P < 0.0001 ) , and the difference between groups was not statistically significant ( P = 0.58 ) . CONCLUSIONS In older subjects with insulin-treated type 2 diabetes , both CSII and MDI achieved excellent glycemic control with good safety and patient satisfaction 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 Background : Decisions regarding diabetes management traditionally have been driven by the results of fasting plasma glucose measurement or measurement of glycosylated hemoglobin ( A1C ) , yet glycemic control remains far from optimal in many individuals with diabetes . Mounting evidence implicates glycemic variability , manifested predominantly as postpr and ial glycemic spikes , as a key factor in the development of macrovascular complications . Recent studies suggest that newer therapies specifically targeting postpr and ial hyperglycemia can significantly reduce postpr and ial glucose levels and improve overall glycemic control . Methods : A Medline search was performed using the term ‘ postchallenge ’ or ‘ postpr and ial ’ , together with glucose or diabetes . After excluding review articles and case studies , we review ed primary articles , meta-analyses , and references therein and selected those that best addressed this topic . Selection bias may be considered a potential limitation of this approach . Findings : Although not conclusively demonstrated by prospect i ve studies , a wealth of evidence suggests that postpr and ial hyperglycemia should not be ignored as an important target for preventing complications of diabetes . Conclusions : Improved detection and management of postpr and ial hyperglycemia and glycemic variability is necessary to optimize glycemic control . Meal-based self-monitoring of blood glucose ( SMBG ) has been shown to improve glycemic control as part of a comprehensive management strategy by helping patients underst and the effects of food choices , physical activity , and medications on blood glucose concentrations . SMBG can also help healthcare professionals recognize postpr and ial hyperglycemia , guide therapeutic adjustments and receive more timely feedback regarding medication changes . The arrival of new therapies that specifically target postpr and ial hyperglycemia offer healthcare professionals the opportunity to optimally manage diabetes Abstract Aims /hypothesisThe objective of this study was to assess the impact of patient-led sensor-guided pump management on glycaemic control , and compare the effect with that of st and ard insulin pump therapy . Methods An open multicentre parallel r and omised controlled trial was conducted at five tertiary diabetes centres . Participants aged 13.0–40.0 years with well-controlled type 1 diabetes were r and omised 1:1 to either study group for 3 months . R and omisation was carried out using a central computer-generated schedule . Participants in the intervention group used sensor-guided pump management ; no instructive guidelines in interpreting real-time data were provided ( ‘ patient-led ’ use ) . Participants in the control group continued their original insulin pump regimen . Continuous glucose monitoring ( CGM ) and HbA1c level were used to assess outcomes . The primary outcome was the difference in the proportion of time in the target glycaemic range during the 3 month study period ( derived from CGM , target range 4–10 mmol/l ) . Secondary outcomes were difference in HbA1c , time in hypoglycaemic ( ≤3.9 mmol/l ) and hyperglycaemic ( ≥10.1 mmol/l ) ranges and glycaemic variability . Results Sixty-two participants were recruited and r and omised ; 5/31 and 2/31 withdrew from intervention and control groups , respectively , leaving 26/31 and 29/31 for the intention-to-treat analyses . When adjusted for baseline values , the mean end-of- study HbA1c was 0.43 % lower in the intervention group compared with the control group ( 95 % CI 0.19 to 0.75 % ; p = 0.009 ) . No difference was observed in CGM-derived time in target ( measured difference 1.72 ; 95 % CI −5.37 to 8.81 ) , hypoglycaemic ( 0.54 ; 95 % CI −3.48 to 4.55 ) or hyperglycaemic ( −2.18 ; 95 % CI −10.0 to 5.69 ) range or in glycaemic variability ( −0.29 ; 95 % CI −0.34 to 0.28 ) . Within the intervention group , HbA1c was 0.51 % lower in participants with sensor use ≥70 % compared with participants with sensor use < 70 % ( 95 % CI −0.98 to −0.04 , p = 0.04 ) . Five episodes of device malfunction occurred . Conclusions /interpretationIndividuals established on insulin pump therapy can employ sensor-guided pump management to improve glycaemic control . An apparent dose-dependent effect of sensor usage was noted ; however , frequent use of this technology ( ≥70 % ) was not universally acceptable . Trial registration : ACTRN12606000049572 Funding : Funding support and equipment were provided by Medtronic Australasia AIMS To investigate the efficacy of sensor-augmented pump therapy vs. multiple daily injection therapy in patients with suboptimally controlled Type 1 diabetes . METHODS In this investigator-initiated multi-centre trial ( the Eurythmics Trial ) in eight outpatient centres in Europe , we r and omized 83 patients with Type 1 diabetes ( 40 women ) currently treated with multiple daily injections , age 18 - 65 years and HbA(1c ) ≥ 8.2 % ( ≥ 66 mmol/mol ) to 26 weeks of treatment with either a sensor-augmented insulin pump ( n = 44 ) ( Paradigm ( ® ) REAL-Time ) or continued with multiple daily injections ( n = 39 ) . Change in HbA(1c ) between baseline and 26 weeks , sensor-derived endpoints and patient-reported outcomes were assessed . RESULTS The trial was completed by 43/44 ( 98 % ) patients in the sensor-augmented insulin pump group and 35/39 ( 90 % ) patients in the multiple daily injections group . Mean HbA(1c ) at baseline and at 26 weeks changed from 8.46 % ( SD 0.95 ) ( 69 mmol/mol ) to 7.23 % ( SD 0.65 ) ( 56 mmol/mol ) in the sensor-augmented insulin pump group and from 8.59 % ( SD 0.82 ) ( 70 mmol/mol ) to 8.46 % ( SD 1.04 ) ( 69 mmol/mol ) in the multiple daily injections group . Mean difference in change in HbA(1c ) after 26 weeks was -1.21 % ( 95 % confidence interval -1.52 to -0.90 , P < 0.001 ) in favour of the sensor-augmented insulin pump group . This was achieved without an increase in percentage of time spent in hypoglycaemia : between-group difference 0.0 % ( 95 % confidence interval -1.6 to 1.7 , P = 0.96 ) . There were four episodes of severe hypoglycaemia in the sensor-augmented insulin pump group and one episode in the multiple daily injections group ( P = 0.21 ) . Problem Areas in Diabetes and Diabetes Treatment Satisfaction Question naire scores improved in the sensor-augmented insulin pump group . CONCLUSIONS Sensor augmented pump therapy effectively lowers HbA(1c ) in patients with Type 1 diabetes suboptimally controlled with multiple daily injections Aims To compare the efficacy of insulin pump treatment with multiple daily injections in the treatment of poorly controlled obese Type 2 diabetic patients already receiving two or more daily injections of insulin plus metformin AIM To determine potential for amelioration of recurrent severe hypoglycaemia without worsening in overall control in individuals with long-st and ing Type 1 diabetes ( T1DM ) . METHODS Twenty-one people with T1DM characterized by altered hypoglycaemia awareness and debilitating severe hypoglycaemia were r and omized in a pilot 24-week prospect i ve study to optimized analogue therapy ( ANALOGUE ; lispro/glargine ) ; continuous subcutaneous insulin infusion therapy ( CSII ; lispro ) ; or re-education with relaxation of blood glucose targets on existing conventional insulin regimen ( EDUCATION ) . Glycaemic profiles and duration of biochemical hypoglycaemia were measured by continuous subcutaneous glucose monitoring and self-monitored blood glucose . RESULTS Further severe hypoglycaemia was prevented in five participants ( 71 % ) in each group ( P = 0.06 ) . Incidence of severe hypoglycaemia was : 0.6 ( ANALOGUE ) , 0.9 ( CSII ) , and 3.7 ( EDUCATION ) episodes per patient year . Restoration of hypoglycaemia awareness was confirmed by vali date d question naire in three ( 43 % ) ANALOGUE , four ( 57 % ) CSII and five ( 71 % ) EDUCATION patients . Glycated haemoglobin ( HbA1c ) was significantly improved in the ANALOGUE group between weeks 0 and 24 ( 8.6 + /- 1.1 vs. 7.6 + /- 0.8 % ; P = 0.04 for change ) . Non-significant improvement was seen in the CSII group ( 8.5 + /- 1.9 vs. 7.4 + /- 1.0 % ; P = 0.06 ) . No change in HbA1c was seen in the EDUCATION group ( 8.5 + /- 1.1 vs. 8.3 + /- 1.0 % ; P = 0.54 ) . There were no episodes of diabetic ketoacidosis or any other adverse events in any group . CONCLUSIONS In this pilot r and omized trial comparing optimized ANALOGUE , CSII or EDUCATION alone in unselected individuals with recurrent severe hypoglycaemia , we show potential for restoring hypoglycaemia awareness and preventing further severe hypoglycaemia with concomitant improvement in glycaemic control in ANALOGUE and CSII groups Objectives : This study assessed the safety and clinical effectiveness of the training protocol for initiating insulin pump therapy with real-time continuous glucose monitoring ( MiniMed Paradigm REAL-Time System ) in a stepwise approach on pump naive subjects with type 1 diabetes compared to a control group who remained on multiple daily injection ( MDI ) therapy . Methods : This was a 15-week treat-to-target pilot study of 16 adult subjects ( n = 50 % male , age 45.9 ± 16 years ) with type 1 diabetes ( duration of diabetes 21.9 ± 11 years ) on MDI therapy with hemoglobin A1c levels at or above 7.5 % at baseline . Subjects were r and omized to either the study arm ( using a combined insulin pump and real-time continuous glucose monitoring system ) or the control arm [ which continued on MDI therapy with self-monitored blood glucose ( SMBG ) only ] . All subjects dosed insulin according to results of SMBG by finger stick and uploaded data into the CareLink data management software . Results : Significant improvements in glycemic control were observed from baseline in both study groups— study arm : pre-A1c 9.45 ± 0.55 and post-A1c 7.4 ± 0.66 ( p = 0.00037 ) ; control arm : pre-A1c 8.58 ± 1.30 and post-A1c 7.5 ±1.01 ( p = 0.04 ) . Both arms had no incidence of severe hypoglycemia . Conclusion : In this pilot study , the Paradigm REAL-Time System was initiated safely and effectively in type 1 diabetes patients who were pump naïve using a stepwise educational protocol BACKGROUND Studies comparing continuous subcutaneous insulin infusion ( CSII ) and glargine in pediatric patients are scarce and cover only 1 year follow up . Although short-term results are favorable for CSII , there is no clear evidence whether this therapy leads to a sustained improvement of glycemic control . OBJECTIVE To evaluate long-term effects and safety of CSII versus multiple daily injections ( MDI ) of glargine over 2 years of treatment in children and adolescents . PATIENTS AND METHODS 32 patients ( aged 12.5 + /- 2.4 years ; 19 females ) with intensively treated type 1 diabetes mellitus were eligible . They were divided into two groups , virtually identical at study entry : eight on CSII and 24 on MDI of glargine . Variables at 0 , 6 , 12 , 18 and 24 months were compared between groups by two-sided Mann-Whitney and Fisher tests . RESULTS No significant differences were found between groups ( CSII vs MDI ) throughout the study period . At 24 months hemoglobin A1c was 7.70 + /- 0.64 % vs 7.54 + /- 0.74 % ( p = 0.8 ) ; body mass index SDS was 0.33 + /- 0.74 vs 0.40 + /- 1.01 ( p = 0.9 ) ; total daily insulin requirements were 0.95 + /- 0.10 vs 1.05 + /- 0.18 U/kg ( p = 0.4 ) , incidence of severe hypoglycemia was 0.00 + /- 0.00 vs 0.04 + /- 0.14 episodes/patient/year ( p = 0.8 ) ; and incidence of ketoacidosis was 0.20 + /- 0.27 vs 0.04 + /- 0.14 episodes/patient/year ( p = 0.2 ) . CONCLUSION CSII and MDI with glargine are equally effective and safe in pediatric patients at 2-year follow-up BACKGROUND A 16-week , two-site study evaluated outcomes for a new device ( the Paradigm 722 System , Medtronic MiniMed , Northridge , CA ) that combines a " smart " continuous subcutaneous insulin infusion ( CSII ) pump with real-time ( RT ) continuous glucose monitoring ( CGM ) and CareLinktrade mark data management software ( DMS ) . METHODS CSII-naive adults with type 1 diabetes in suboptimal control ( mean glycosylated hemoglobin [ A1C ] = 8.6 % ) were r and omized to the control arm , consisting of multiple daily injections ( MDI ) and self-monitoring of blood glucose ( SMBG ) , or the study arm ( CSII with RT-CGM as an adjunct to SMBG ) . Participants ( n = 28 ) completed the vali date d Insulin Delivery System Rating Question naire ( IDSRQ ) and the parallel Blood Glucose ( BG ) Monitoring System Rating Question naire ( BGMSRQ ) at study start and end . Participants in the study arm ( n = 14 ) also completed newly developed User Acceptance Question naires ( UAQs ) for CSII , RT-CGM , and DMS at study end . RESULTS A1C reduction from study start to end was significant ( P < 0.05 ) in both arms ( -1.7 % for study arm;-1.0 % for control arm ) ; there was no significant change in weight in either arm . The IDSRQ showed significantly ( P < 0.05 ) greater benefit for the study arm in convenience , acceptability of BG monitoring requirements , BG control efficacy , diabetes worries , and interpersonal hassles , as well as higher overall satisfaction/preference . The BGMSRQ showed significantly ( P < 0.05 ) greater benefit for the study arm in the BG monitoring system 's ability to help manage glycemic control and less interest in changing to another BG monitoring system . The Study Arm UAQs showed positive ratings of system features . CONCLUSIONS Several patient-reported outcomes were significantly more positive in the study arm than the control arm ; none was significantly more positive in the control arm . The features of the integrated RT-CGM/CSII system were frequently used and highly rated by participants , with high user satisfaction Intensive therapy for type 1 diabetes mellitus ( DM ) is usually provided by either multiple daily injections of insulin ( MDI ) or by insulin pump ( continuous subcutaneous insulin infusion CSII ) . We design ed an open , r and omized , crossover trial to compare CSII with MDI for glycemic control , dose requirements , weight change , incidence of adverse events , quality of life and satisfaction in adolescents OBJECTIVE Fetal hyperinsulinaemia secondary to maternal hyperglycaemia is considered to be the driving force behind excessive fetal growth . We hypothesised that insulin pump therapy ( continuous subcutaneous insulin infusion , CSII ) would improve maternal glycaemic control and normalise fetal growth parameters . To this end , this study compares maternal glycaemic control and fetal growth of women receiving insulin pump therapy with those receiving conventional insulin therapy . STUDY DESIGN Prospect i ve non-r and omised study of 42 women with pre-existing diabetes attending a joint obstetric diabetic clinic . Each woman was offered the choice of commencing insulin pump therapy or remaining on a conventional insulin regime . Estimated fetal weight and fetal growth velocity were calculated from routinely collected third trimester ultrasound biometry and expressed as st and ard deviation ( Z ) scores . RESULTS Eighteen women commenced insulin pump therapy . There was no difference in pre-conception glycosylated haemoglobin A1c concentrations ( HbA1c ) between pump and conventional therapy groups ( mean HbA1c 7.62 versus 8.01 ; p=0.49 ) or third trimester glycaemic control ( mean HbA1c 6.63 versus 6.44 ; p=0.51 ) . Women using pump therapy had similar mean growth velocity Z scores ( 1.5 versus 1.36 ; p=0.83 ) , similar mean estimated fetal weight Z scores prior to delivery ( 2.80 versus 2.16 ; p=0.16 ) and similar mean birthweight Z scores ( 2.09 versus 2.00 ; p=0.86 ) compared to women using conventional insulin therapy . CONCLUSION This small , non-r and omised study suggests that the use of insulin pump therapy offers no benefit in terms of normalising fetal growth velocity , fetal size , birthweight or improving maternal glycaemic control compared to conventional insulin therapy OBJECTIVE To compare the efficacy and feasibility of continuous subcutaneous insulin infusion ( CSII ) with multiple daily insulin injections ( MDI ) in children with type 1 diabetes . METHODS The study sample included 23 children ( 10 males ) aged 9.4 to 13.9 years with type 1 diabetes . An open r and omized crossover design was used to compare 3.5 months of CSII to 3.5 months of MDI therapy for the following variables : diabetic control , incidence of adverse events , daily insulin requirement , body mass index st and ard deviation scores , treatment satisfaction , and quality of life . RESULTS The changes in HbA(1c ) and fructoseamine values were similar in the 2 arms over time . At the end of the study , mean HbA(1c ) level measured 8.05 + /- 0.78 % . There were no differences between the treatment modes in frequency of symptomatic hypoglycemic or hyperglycemic events . There was 1 event of severe hypoglycemia during pump therapy and 3 during MDI , yielding a rate of 0.26 events per patient-year . There were no episodes of diabetic ketoacidosis . Body mass index st and ard deviation scores decreased during CSII and increased during MDI , as did mean insulin dose . Patients expressed a higher treatment satisfaction from CSII than MDI , although there was no difference in quality of life between the 2 modes . CONCLUSIONS Intensive insulin therapy by either insulin pump or MDI is safe in children and young adolescents with type 1 diabetes , with similar diabetes control and a very low rate of adverse events . We suggest that both modes be available to the diabetic team to better tailor therapy OBJECTIVE To compare medical , nutritional , and psychosocial outcomes of continuous subcutaneous insulin infusion ( CSII ) therapy and multiple daily insulin injections ( MDI ) in preschoolers with type 1 diabetes mellitus ( T1DM ) in a r and omized controlled trial . STUDY DESIGN Sixteen children ( mean age 4.4 + /- 0.7 yr , range 3.1 - 5.3 yr ) with T1DM were r and omly assigned to CSII or MDI . Hemoglobin A1c ( HbA1c ) was measured monthly for 6 months . Glucose variability was measured at baseline and at 6 months using continuous blood glucose sensing . Quality of life , adverse events , and nutrition information were assessed . RESULTS Parents of the CSII group reported a significant decrease in diabetes-related worry , while parents of the MDI group reported an increased frequency of stress associated with their child 's medical care . Mean HbA1c levels from baseline ( CSII 8.3 + /- 1.4 % , MDI 8.0 + /- 0.8 % ) to 6 months ( CSII 8.4 + /- 0.8 % , MDI 8.2 + /- 0.4 % ) remained stable , and group differences were not significant . There were no significant group differences in duration of hypo- or hyperglycemic events or frequency of adverse events . CONCLUSION ( S ) For young children with T1DM , CSII therapy is comparable to MDI therapy with regard to glucose control but is associated with higher treatment satisfaction and improved quality of life AIMS The superiority of continuous subcutaneous insulin infusion ( CSII ) over multiple daily injections ( MDI ) with glargine is uncertain . In this r and omized cross-over study , we compared CSII and MDI with glargine in patients with Type 1 diabetes well controlled with CSII . The primary end-point was glucose variability . METHODS Thirty-nine patients [ 38.1 + /- 9.3 years old ( mean + /- sd ) , diabetes duration 16.6 + /- 8.2 years , glycated haemoglobin ( HbA(1c ) ) 7.6 + /- 0.8 % ] , already on CSII for at least 6 months , were r and omly assigned to CSII with lispro or MDI with lispro and glargine . After 4 months they were switched to the alternative treatment . During the last month of each treatment blood glucose variability was analysed using glucose st and ard deviation , mean amplitude of glycaemic excursions ( MAGE ) , lability index and average daily risk range ( ADRR ) . As secondary end-points we analysed blood glucose profile , HbA(1c ) , number of episodes of hypo- and hyperglycaemia , lipid profile , free fatty acids ( FFA ) , growth hormone and treatment satisfaction . RESULTS During CSII , glucose variability was 5 - 12 % lower than during MDI with glargine . The difference was significant only before breakfast considering glucose st and ard deviation ( P = 0.011 ) , significant overall using MAGE ( P = 0.016 ) and lability index ( P = 0.005 ) and not significant using ADRR . Although HbA(1c ) was similar during both treatments , during CSII blood glucose levels were significantly lower , hyperglycaemic episodes were fewer , daily insulin dose was less , FFA were lower and treatment satisfaction was greater than during MDI with glargine . The frequency of hypoglycaemic episodes was similar during both treatments . CONCLUSIONS During CSII , glucose variability is lower , glycaemic control better and treatment satisfaction higher than during MDI with glargine This document presents consensus panel recommendations for the medical care of pregnant women with preexisting diabetes , including type 1 and type 2 diabetes . The intent is to help clinicians deal with the broad spectrum of problems that arise in management of diabetes before and during pregnancy , and to prepare diabetic women for treatment that may reduce complications in the years after pregnancy . A thorough discussion of the evidence supporting the recommendations is presented in the book , Management of Preexisting Diabetes and Pregnancy , authored by the consensus panel and published by the American Diabetes Association ( ADA ) in 2008 ( 1 ) . A consensus statement on obstetrical and postpartum management will appear separately . The recommendations are diagnostic and therapeutic actions that are known or believed to favorably affect maternal and perinatal outcomes in pregnancies complicated by diabetes . The grading system adapted by the ADA was used to clarify and codify the evidence that forms the basis for the recommendations ( 2 ) . Unfortunately there is a paucity of r and omized controlled trials ( RCTs ) of the different aspects of management of diabetes and pregnancy . Therefore our recommendations are often based on trials conducted in nonpregnant diabetic women or nondiabetic pregnant women , as well as on peer- review ed experience before and during pregnancy in women with preexisting diabetes ( 3–4 ) . We also review ed and adapted existing diabetes and pregnancy guidelines ( 5–10 ) and guidelines on diabetes complications and comorbidities ( 2,3,11–14 ) . # # # A. Organization of preconception and pregnancy care # # # # BACKGROUND The objective of the study was to evaluate the clinical effectiveness and safety of a device that combines an insulin pump with real-time continuous glucose monitoring ( CGM ) , compared to using an insulin pump with st and ard blood glucose monitoring systems . METHODS This 6-month , r and omized , multicenter , treat-to-target study enrolled 146 subjects treated with continuous subcutaneous insulin infusion between the ages of 12 and 72 years with type 1 diabetes and initial A1C levels of > or=7.5 % . Subjects were r and omized to pump therapy with real-time CGM ( sensor group [ SG ] ) or to pump therapy and self-monitoring of blood glucose only ( control group [ CG ] ) . Clinical effectiveness and safety were evaluated . RESULTS A1C levels decreased ( P<0.001 ) from baseline ( 8.44+/-0.70 % ) in both groups ( SG , -0.71+/-0.71 % ; CG , -0.56+/-0.072 % ) ; however , between-group differences did not achieve significance . SG subjects showed no change in mean hypoglycemia area under the curve ( AUC ) , whereas CG subjects showed an increase ( P=0.001 ) in hypoglycemia AUC during the blinded periods of the study . The between-group difference in hypoglycemia AUC was significant ( P<0.0002 ) . Greater than 60 % sensor utilization was associated with A1C reduction ( P=0.0456 ) . Fourteen severe hypoglycemic events occurred ( 11 in the SG group and three in the CG group , P=0.04 ) . CONCLUSIONS A1C reduction was no different between the two groups . Subjects in the CG group had increased hypoglycemia AUC and number of events during blinded CGM use ; however , there was no increase in hypoglycemia AUC or number of events in the SG group . Subjects with greater sensor utilization showed a greater improvement in A1C levels OBJECTIVE To evaluate the impact of continuous glucose monitoring ( CGM ) on quality of life ( QOL ) among individuals with type 1 diabetes . RESEARCH DESIGN AND METHODS In a multicenter trial , 451 children and adults with type 1 diabetes were r and omly assigned to CGM treatment or the control group . Generic and diabetes-specific QOL question naires were completed at baseline and 26 weeks by all participants and parents of participants < 18 years old , and the CGM satisfaction scale was completed by the CGM group ( participants and parents ) at 26 weeks . RESULTS After 26 weeks , QOL scores remained largely unchanged for both the treatment and the control group , although there was a slight difference favoring the adult CGM group on several subscales ( P < 0.05 ) . There was substantial satisfaction with CGM technology after 26 weeks among participants and parents . CONCLUSIONS Baseline QOL was high , and the measures showed little change with CGM use , although a high level of CGM satisfaction was reported |
667 | 28,396,101 | Conclusions This meta‐ analysis strongly suggests that minoxidil , finasteride , and low‐level laser light therapy are effective for promoting hair growth in men with and rogenetic alopecia and that minoxidil is effective in women with and rogenetic alopecia . | Background And rogenetic alopecia , or male pattern hair loss , is a hair loss disorder mediated by dihydrotestosterone , the potent form of testosterone .
Currently , minoxidil and finasteride are Food and Drug Administration ( FDA ) –approved , and HairMax LaserComb , which is FDA ‐cleared , are the only treatments recognized by the FDA as treatments of and rogenetic alopecia .
Objective This systematic review and meta‐ analysis assesses the efficacy of nonsurgical treatments of and rogenetic alopecia in comparison to placebo for improving hair density , thickness , growth ( defined by an increased anagen : telogen ratio ) , or subjective global assessment s done by patients and investigators . | One-hundred twenty-six healthy men with early male pattern baldness completed a 12-month double-blind , controlled trial of 2 % and 3 % topical minoxidil . Subjects were initially r and omly assigned to use placebo or 2 % or 3 % topical minoxidil . After 4 months of study , the placebo group was crossed over to 3 % topical minoxidil . Both objective measurement of hair growth by counting of vellus , terminal , and total hairs in a vertex target balding area and subjective assessment by subject and investigator were done . Treatment of subjects with topical minoxidil for 4 months result ed in a statistically significant increase in terminal hair growth in comparison with placebo therapy . In addition , subjects initially treated with placebo , when crossed over to topical minoxidil , showed a significant increase in the number of terminal hairs . No subject had a net hair loss in the target area during the study . These results indicate that topical minoxidil can increase terminal hair growth in early male pattern baldness A double-blind 12-month trial was conducted to evaluate the safety and efficacy of topical minoxidil in patients with and rogenetic alopecia . During the first 4 months of the study , patients applied a topical solution containing either 2 % minoxidil , 3 % minoxidil , or placebo to their scalps twice daily . At the end of the fourth month , patients taking placebo were crossed over to treatment with 3 % minoxidil solution . Of 60 patients enrolled in the study , 43 were evaluable at month 12 . Hairs were counted in a 1-inch target area and classified as vellus , indeterminate , and terminal ; the latter two classifications were combined as nonvellus hairs for further statistical analysis . All three groups had significant increases in total , nonvellus , and terminal hair counts between baseline and month 4 and between month 4 and month 12 . At month 4 the average total hair counts increased from a baseline mean of 158.2 to 270.2 in the 2 % minoxidil group , from 156.6 to 287.0 in the 3 % minoxidil group , and from 162.6 to 246.9 in the placebo group . At month 12 the means were 415.6 , 448.5 , and 471.1 in the 2 % minoxidil , 3 % minoxidil , and placebo-3 % minoxidil crossover subjects , respectively . The increases from month 4 to month 12 were highly significant for each group ( p = 0.0001 ) . Average increases in nonvellus hair counts between months 4 and 12 were 216 , 181 , and 264 in the 2 % minoxidil , 3 % minoxidil , and placebo-to-3 % minoxidil crossover groups , respectively , all highly significant differences from zero ( p = 0.0001 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Fifty-eight men with Hamilton scale type III vertex or type IV male pattern baldness were studied to determine the dose-response activity of low concentrations of topical minoxidil in promoting hair growth . The patients were treated with topical minoxidil at doses of 0.01 % , 0.1 % , 1 % , or 2 % or placebo in a r and omized double-blind design for 6 months . At the end of 6 months , patients using 0.1 % , 1 % , and 2 % topical minoxidil solutions showed a significantly greater difference in the mean increase of nonvellus hair growth in comparison with those using 0.01 % minoxidil or placebo . There was a clear dose-response correlation for the increase of nonvellus hairs in the 0.1 % , 1 % , and 2 % minoxidil treatment groups . There was a statistically significant difference in patient 's self-evaluation of overall hair growth and degree of decreased hair shedding in the 1 % and 2 % minoxidil groups when compared with the other study groups . From this study we conclude that significant increases in nonvellus hair counts occur with 0.1 % and greater doses of minoxidil . However , only in patients treated with the 1 % and 2 % solutions of minoxidil was there clinical ly perceptible hair growth BACKGROUND Finasteride , a specific inhibitor of type II 5alpha-reductase , decreases serum and scalp dihydrotestosterone and has been shown to be effective in men with vertex male pattern hair loss . OBJECTIVE This study evaluated the efficacy of finasteride 1 mg/day in men with frontal ( anterior/mid ) scalp hair thinning . METHODS This was a 1-year , double-blind , placebo-controlled study followed by a 1-year open extension . Efficacy was assessed by hair counts ( 1 cm2 circular area ) , patient and investigator assessment s , and global photographic review . RESULTS There was a significant increase in hair count in the frontal scalp of finasteride-treated patients ( P < .001 ) , as well as significant improvements in patient , investigator , and global photographic assessment s. Efficacy was maintained or improved throughout the second year of the study . Finasteride was generally well tolerated . CONCLUSION In men with hair loss in the anterior/mid area of the scalp , finasteride 1 mg/day slowed hair loss and increased hair growth BACKGROUND To pical minoxidil solution 2 % stimulates new hair growth and helps stop the loss of hair in men with and rogenetic alopecia and women with female pattern hair loss . Results can be variable , and historic experience suggests that higher concentrations of topical minoxidil may enhance efficacy . OBJECTIVE The purpose of this 48-week , double-blind , placebo-controlled , r and omized , multicenter trial was to compare the efficacy and safety of 5 % topical minoxidil with 2 % topical minoxidil and placebo in the treatment of female pattern hair loss . METHODS A total of 381 women ( 18 - 49 years old ) with female pattern hair loss applied 5 % topical minoxidil solution ( n = 153 ) , 2 % topical minoxidil solution ( n = 154 ) , or placebo ( vehicle for 5 % solution ; n = 74 ) twice daily . Primary efficacy variables were change in nonvellus hair count at week 48 , and patient and investigator assessment s of change in hair growth/scalp coverage at week 48 . RESULTS After 48 weeks of therapy , 5 % topical minoxidil was superior to placebo for each of the 3 primary efficacy measures . The 2 % topical minoxidil group demonstrated superiority over placebo for hair count and investigator assessment of hair growth/scalp coverage at week 48 ; differences in patient assessment of hair growth at week 48 were not significantly different from placebo . The 5 % topical minoxidil group demonstrated statistical superiority over the 2 % topical minoxidil group in the patient assessment of treatment benefit at week 48 . Both 5 % and 2 % topical minoxidil helped improve psychosocial perceptions of hair loss in women with female pattern hair loss . An increased occurrence of pruritus , local irritation , and hypertrichosis was observed with 5 % topical minoxidil versus 2 % topical minoxidil and placebo . CONCLUSION In this 48-week study of 381 women with female pattern hair loss , 5 % topical minoxidil was superior to placebo on each of the 3 primary efficacy end points : promoting hair growth as measured by change in nonvellus hair count and patient/investigator assessment s of hair growth and scalp coverage . Application of 2 % topical minoxidil was superior to placebo for assessment s of nonvellus hair counts and investigator assessment of hair growth/scalp coverage at week 48 ; differences in patient assessment of hair growth at week 48 were not significantly different from placebo . At week 48 , the 5 % topical minoxidil group demonstrated statistical superiority over the 2 % topical minoxidil group in the patient assessment of treatment benefit . Both concentrations of topical minoxidil were well tolerated by the women in this trial without evidence of systemic adverse effects . With the introduction of numerous herbal remedies for hair loss , of which most have not been tested in r and omized , double-blind , placebo-controlled trials , it is important to describe well-controlled trials that demonstrate the efficacy and safety of topical drugs BACKGROUND Male pattern hair loss ( MPHL ) is a potentially reversible condition in which dihydrotestosterone is an important etiologic factor . OBJECTIVE Our aim was to evaluate the efficacy of the type 1 and 2 5alpha-reductase inhibitor dutasteride in men with MPHL . METHODS Four hundred sixteen men , 21 to 45 years old , were r and omized to receive dutasteride 0.05 , 0.1 , 0.5 or 2.5 mg , finasteride 5 mg , or placebo daily for 24 weeks . RESULTS Dutasteride increased target area hair count versus placebo in a dose-dependent fashion and dutasteride 2.5 mg was superior to finasteride at 12 and 24 weeks . Expert panel photographic review and investigator assessment of hair growth confirmed these results . Scalp and serum dihydrotestosterone levels decreased , and testosterone levels increased , in a dose-dependent fashion with dutasteride . LIMITATIONS The study was limited to 24 weeks . CONCLUSION Dutasteride increases scalp hair growth in men with MPHL . Type 1 and type 2 5alpha-reductase may be important in the pathogenesis and treatment of MPHL BACKGROUND Women generally regard their hair loss as socially unacceptable and go to great measures to conceal their problem . In some cases , the negative self-image brought about by hair loss may be the basis of psychiatric illness . The purpose of this study was to evaluate a 2 % topical minoxidil solution ( Rogaine/Regaine , The Upjohn Co , Kalamazoo , Mich ) for the treatment of female and rogenetic alopecia . A 32-week , double-blind , placebo-controlled trial was conducted in 11 US centers . Three hundred eight women with and rogenetic alopecia were enrolled . Two hundred fifty-six of these women completed the trial . A refined photographic technique was used to objective ly determine the number of nonvellus hairs regrown . RESULTS After 32 weeks of treatment , the number of nonvellus hairs in a 1-cm2 evaluation site was increased by an average of 23 hairs in the 2 % minoxidil group and by an average of 11 hairs in the placebo group . The 95 % confidence interval for the difference in mean hair count change between the treatment groups was 5.9 to 17.5 hairs . The investigators determined that 13 % in the minoxidil-treated group had moderate growth and 50 % had minimal growth . This compared with 6 % and 33 % , respectively , in the placebo-treated group . Similarly , 60 % of the patients in the 2 % minoxidil group reported that they had new hair growth ( 20 % moderate , 40 % minimal ) compared with 40 % ( 7 % moderate , 33 % minimal ) of the patients in the placebo group . No evaluations of dense hair growth were reported for either treatment group . No clinical ly significant changes in vital signs were observed and no serious or unexpected medical events were reported . CONCLUSIONS Topical minoxidil was significantly more effective than placebo in the treatment of female and rogenetic alopecia BACKGROUND Topical minoxidil solution 2 % stimulates new hair growth and helps stop the loss of hair in individuals with and rogenetic alopecia ( AGA ) . Results can be variable , and historical experience suggests that higher concentrations of topical minoxidil may enhance efficacy . OBJECTIVE The purpose of this 48-week , double-blind , placebo-controlled , r and omized , multicenter trial was to compare 5 % topical minoxidil with 2 % topical minoxidil and placebo in the treatment of men with AGA . METHODS A total of 393 men ( 18 - 49 years old ) with AGA applied 5 % topical minoxidil solution ( n = 157 ) , 2 % topical minoxidil solution ( n = 158 ) , or placebo ( vehicle for 5 % solution ; n = 78 ) twice daily . Efficacy was evaluated by scalp target area hair counts and patient and investigator assessment s of change in scalp coverage and benefit of treatment . RESULTS After 48 weeks of therapy , 5 % topical minoxidil was significantly superior to 2 % topical minoxidil and placebo in terms of change from baseline in nonvellus hair count , patient rating of scalp coverage and treatment benefit , and investigator rating of scalp coverage . Hair count data indicate that response to treatment occurred earlier with 5 % compared with 2 % topical minoxidil . Additionally , data from a patient question naire on quality of life , global benefit , hair growth , and hair styling demonstrated that 5 % topical minoxidil helped improve patients ' psychosocial perceptions of hair loss . An increased occurrence of pruritus and local irritation was observed with 5 % topical minoxidil compared with 2 % topical minoxidil . CONCLUSION In men with AGA , 5 % topical minoxidil was clearly superior to 2 % topical minoxidil and placebo in increasing hair regrowth , and the magnitude of its effect was marked ( 45 % more hair regrowth than 2 % topical minoxidil at week 48 ) . Men who used 5 % topical minoxidil also had an earlier response to treatment than those who used 2 % topical minoxidil . Psychosocial perceptions of hair loss in men with AGA were also improved . Topical minoxidil ( 5 % and 2 % ) was well tolerated by the men in this trial without evidence of systemic effects BACKGROUND Dutasteride ( Avodart ) is a dual inhibitor of both type I and type II 5 alpha reductases , and thus inhibits conversion of testosterone to dihydrotestosterone , a key mediator of male pattern hair loss . OBJECTIVES The aim of this r and omized double-blind phase III study was to compare the efficacy , safety , and tolerability of dutasteride ( 0.5 mg ) and placebo for 6 months of treatment in male patients with male pattern hair loss . METHODS A total of 153 men , 18 to 49 years old , were r and omized to receive 0.5 mg of dutasteride or placebo daily for 6 months . Efficacy was evaluated by the change of hair counts , subject assessment , and photographic assessment by investigators and panels . RESULTS Mean change of hair counts from baseline to 6 months after treatment start was an increase of 12.2/cm(2 ) in dutasteride group and 4.7/cm(2 ) in placebo group and this difference was statistically significant ( P = .0319 ) . Dutasteride showed significantly higher efficacy than placebo group by subject self- assessment and by investigator and panel photographic assessment . There was no major difference in adverse events between two groups . LIMITATIONS The study was limited to 6 months . CONCLUSIONS This study clearly showed that 0.5 mg of dutasteride improved hair growth and was relatively well tolerated for the treatment of male pattern hair loss Twenty-eight women with mild to moderate and rogenetic alopecia were r and omly assigned to apply either 2 percent topical minoxidil or placebo ( vehicle ) to their involved scalp areas twice daily . At the end of thirty-two weeks , there was a statistically significant increase of nonvellus target area hairs in the minoxidil-treated versus the vehicle-treated group ( p = 0.006 ) . Investigator assessment of moderate regrowth showed better results in subjects who used 2 percent topical minoxidil solution than those who used vehicle ( p = 0.007 ) , although subjects discerned no difference between treatment groups . Two percent topical minoxidil appears to be effective in the treatment of female and rogenetic alopecia The safety and efficacy of minoxidil 2 % for the treatment of female and rogenetic alopecia was assessed in a 32-week double-blind placebo-controlled trial . Thirty-three women aged 22 to 44 years with hair loss classified as Ludwig 's grade I or II were enrolled , and 28 completed the trial . Before the administration of treatment , mean nonvellus hair counts were taken within a 1-cm2 target area of the scalp . For the 15 patients in the minoxidil group , the mean count was 169 hairs compared with 161 hairs for the 13 patients in the placebo group . At the completion of the trial , the patients treated with minoxidil 2 % had a mean nonvellus hair count of 195 hairs versus a mean hair count of 177 for patients in the placebo group ; 60 % ( 9 ) of the patients in the minoxidil group showed minimal to moderate hair growth compared with 46 % ( 6 ) of the patients in the placebo group . No serious side effects were encountered during this study , nor any significant changes in safety parameters . There were no dropouts due to medical events related to minoxidil 2 % BACKGROUND AND OBJECTIVES Low level laser therapy ( LLLT ) has been used to promote hair growth . A double-blind r and omized controlled trial was undertaken to define the safety and physiologic effects of LLLT on males with and rogenic alopecia . METHODS Forty-four males ( 18 - 48 yo , Fitzpatrick I-IV , Hamilton-Norwood IIa-V ) were recruited . A transition zone scalp site was selected ; hairs were trimmed to 3 mm height ; the area was tattooed and photographed . The active group received a " TOPHAT655 " unit containing 21 , 5 mW lasers ( 655 ± 5 nm ) , and 30 LEDS ( 655 ± 20 nm ) , in a bicycle-helmet like apparatus . The placebo group unit appeared identical , containing inc and escent red lights . Patients treated at home every other day × 16 weeks ( 60 treatments , 67.3 J/cm(2 ) irradiance/25 minute treatment ) , with follow up and photography at 16 weeks . A masked 2.85 cm(2 ) photographic area was evaluated by another blinded investigator . The primary endpoint was the percent increase in hair counts from baseline . RESULTS Forty-one patients completed the study ( 22 active , 19 placebo ) . No adverse events or side effects were reported . Baseline hair counts were 162.7 ± 95.9 ( N = 22 ) in placebo and 142.0 ± 73.0 ( N = 22 ) and active groups respectively ( P = 0.426 ) . Post Treatment hair counts were 162.4 ± 62.5 ( N = 19 ) and 228.7 ± 102.8 ( N = 22 ) , respectively ( P = 0.0161 ) . A 39 % percent hair increase was demonstrated ( 28.4 ± 46.2 placebo , N = 19 ; 67.2 ± 33.4 , active , N = 22 ) ( P = 0.001 ) Deleting one placebo group subject with a very high baseline count and a very large decrease , result ed in baseline hair counts of 151.1 ± 81.0 ( N = 21 ) and 142.0 ± 73.0 ( N = 22 ) , respectively ( P = 0.680 ) . Post treatment hair counts were 158.2 ± 61.5 ( N = 18 ) and 228.7 ± 102.8 ( N = 22 ) ( P = 0.011 ) , result ing in a 35 % percent increase in hair growth ( 32.3 ± 44.2 , placebo , N = 18 ; 67.2 ± 33.4 , active , N = 22 ) ( P = 0.003 ) . CONCLUSIONS LLLT of the scalp at 655 nm significantly improved hair counts in males with and rogenetic alopecia Context : Male and rogenetic alopecia ( AGA ) is a common condition . There is limited information on its prevalence and patterns . Aims : ( 1 ) . To find the prevalence and most common pattern ( 2 ) . To correlate the age and pattern of alopecia . Setting s and Design : Population -based study . Material s and Methods : This is a population -based study from the public . The selection was r and om . The method involved was asking the age and , if found to between 30 and 50 years , the scalp was examined for alopecia and the pattern was determined using the Hamilton Norwood classification . Results : Of 1,005 subjects , the youngest was 30 years old and the oldest 49 years old , with a mean age of 37.05 ± st and ard deviation 4.79 . 39.2 % of the subjects were in the age group of 30 - 35 , 34.4 % in the 36 - 40 year age group , 26.0 % in the 41 - 45 years age group and 0.4 % in the 46 - 50 years age group . Five hundred and eighty-three subjects ( 58 % ) had AGA , the most common type being grade II ( 27.27 % ) followed by grade I ( 22.12 % ) and grade III ( 21.78 % ) . 47.5 % ( P = 0.003 ) had pattern alopecia in the 30 - 35 years age group , 58.7 % in the 36 - 40 years age group ( P = 0.8 ) and 73.2 % in the 41 - 45 years age group ( P ≤ 0.001 ) . In the 30 - 35 years age group , grade I was 51.18 % , grade II was 42.77 % and grade VI was 18.52 % . In the 41 - 45 years age group , grade I was 13.38 % , grade III was 33.85 % and grade VI was 66.67 % . Conclusions : Fifty-eight percent of the male population aged 30 - 50 years had AGA . Its grade increased with increase in age . 12.9 % of the male population had grade s IV to VI , and would benefit from hair transplantation while 44.1 % had grade s I to III and are potential c and i date s for medical Background And rogenetic alopecia ( AGA ) is a common disorder affecting men and women . Finasteride and minoxidil are well‐known , effective treatment methods , but patients who exhibit a poor response to these methods have no additional adequate treatment modalities . Objective To evaluate the efficacy and safety of a low‐level light therapy ( LLLT ) device for the treatment of AGA . Methods This study was design ed as a 24‐week , r and omized , double‐blind , sham device – controlled trial . Forty subjects with AGA were enrolled and scheduled to receive treatment with a helmet‐type , home‐use LLLT device emitting wavelengths of 630 , 650 , and 660 nm or a sham device for 18 minutes daily . Investigator and subject performed phototrichogram assessment ( hair density and thickness ) and global assessment of hair regrowth for evaluation . Results After 24 weeks of treatment , the LLLT group showed significantly greater hair density than the sham device group . Mean hair diameter improved statistically significantly more in the LLLT group than in the sham device group . Investigator global assessment showed a significant difference between the two groups , but that of the subject did not . No serious adverse reactions were detected . Conclusion LLLT could be an effective treatment for AGA Background The growth of scalp hair is a cyclical process of successive phases of growth ( anagen ) and rest ( telogen ) . In previous clinical trials in men with and rogenetic alopecia , treatment with finasteride increased scalp hair counts in a defined area ( i.e. increased hair density ) . Objectives The current study used a phototrichogram methodology to assess the effect of finasteride on the phases of the hair growth cycle . Patients / Methods Two hundred and twelve men , age 18–40 years , with and rogenetic alopecia were r and omized to receive finasteride 1 mg daily or placebo for 48 weeks . At baseline and at 24 and 48 weeks , macrophotographs were taken to measure total and anagen hair count in a 1‐cm2 target area of the scalp . Results At baseline , mean total and anagen hair counts in the finasteride group were 200 and 124 hairs , respectively ( % anagen = 62 % ) and the anagen to telogen ratio was 1·74 ( geometric mean ) . In the placebo group , the respective values were 196 and 119 hairs ( % anagen = 60 % ) and 1·57 . At week 48 , the finasteride group had a net improvement ( mean ± SE ) compared with placebo in total and anagen hair counts of 17·3 ± 2·5 hairs ( 8·3 % ± 1·4 % ) and 27·0 ± 2·9 hairs ( 26 % ± 3·1 % ) , respectively ( P < 0·001 ) . Furthermore , treatment with finasteride result ed in a net improvement in the anagen to telogen ratio of 47 % ( P < 0·001 ) . In this study , treatment with finasteride 1 mg day−1 for 48 weeks increased both total and anagen hair counts , and improved the anagen to telogen ratio . Conclusions These data provide direct evidence that finasteride 1 mg daily promotes the conversion of hairs into the anagen phase . These data support that finasteride treatment results in favourable effects on hair quality that contribute to the visible improvements in hair growth observed in treated patients Abstract Background and objective : The use of low levels of visible or near infrared light for reducing pain , inflammation and oedema , promoting healing of wounds , deeper tissue and nerves , and preventing tissue damage has been known for almost 40 years since the invention of lasers . The HairMax LaserComb ® is a h and -held Class 3R lower level laser therapy device that contains a single laser module that emulates 9 beams at a wavelength of 655 nm ( ±5 % ) . The device uses a technique of parting the user ’s hair by combs that are attached to the device . This improves delivery of distributed laser light to the scalp . The combs are design ed so that each of the teeth on the combs aligns with a laser beam . By aligning the teeth with the laser beams , the hair can be parted and the laser energy delivered to the scalp of the user without obstruction by the individual hairs on the scalp . The primary aim of the study was to assess the safety and effectiveness of the HairMax LaserComb ® laser phototherapy device in the promotion of hair growth and in the cessation of hair loss in males diagnosed with and rogenetic alopecia ( AGA ) . Methods : This double-blind , sham device-controlled , multicentre , 26-week trial r and omized male patients with Norwood-Hamilton classes IIa-V AGA to treatment with the HairMax LaserComb ® or the sham device ( 2 : 1 ) . The sham device used in the study was identical to the active device except that the laser light was replaced by a non-active inc and escent light source . Results : Of the 110 patients who completed the study , subjects in the HairMax LaserComb ® treatment group exhibited a significantly greater increase in mean terminal hair density than subjects in the sham device group ( p < 0.0001 ) . Consistent with this evidence for primary effectiveness , significant improvements in overall hair regrowth were demonstrated in terms of patients ’ subjective assessment ( p < 0.015 ) at 26 weeks over baseline . The HairMax LaserComb ® was well tolerated with no serious adverse events reported and no statistical difference in adverse effects between the study groups . Conclusions : The results of this study suggest that the HairMax LaserComb ® is an effective , well tolerated and safe laser phototherapy device for the treatment of AGA in males OBJECTIVES This study compared the efficacy of finasteride with placebo in the treatment of male pattern hair loss ( and rogenetic alopecia ) in nine pairs of male identical twins . METHODS In this r and omized , double-blind , placebo-controlled , single-center study , one twin from each identical twin pair received finasteride 1 mg/day for one year while the other received placebo . Hair growth was evaluated from st and ardized clinical photographs , hair counts and patient self- assessment question naires . Serum dihydrotestosterone and testosterone levels were analyzed and adverse events recorded . RESULTS Finasteride significantly improved hair growth at one year compared to placebo ( p < 0.05 ) based on analysis of photographs of the vertex and superior-frontal scalp . These results were consistent with the hair count change measured in the finasteride group , which was superior ( p < 0.05 ) to the change measured in the placebo group . Patient self- assessment demonstrated that treatment with finasteride , in comparison to placebo , led to improvements in scalp hair growth and patients ' satisfaction with appearance of hair . No drug-related adverse events were reported during the study . CONCLUSION Through the use of identical twins , this study provides further evidence that finasteride significantly reduces hair loss progression and restores hair growth in men with male pattern hair loss Relatively little is known about the progression of and rogenetic alopecia ( AGA ; male pattern hair loss ) in untreated men . We evaluated the long-term ( 5-year ) progression of AGA in men treated with placebo in a controlled clinical trial setting . We analyzed pooled data over 5 years from two replicate studies with finasteride 1 mg/day in men with predominantly vertex-pattern AGA . Each study consisted of an initial 1-year , r and omized , double-blind , placebo-controlled base study and four consecutive , 1-year , double-blind , placebo-controlled extension studies . Change over time in scalp hair growth was evaluated by four predefined endpoints : scalp hair counts ; assessment of st and ardized clinical photographs by an expert panel ; investigator clinical assessment ; and patient self- assessment . All four predefined endpoints demonstrated progressive scalp hair loss in men receiving placebo over the 5-year study period , with a loss of 239 hairs from baseline ( 26.3 % decline in hair density ) measured in the target area at 5 years ( p < 0.001 vs. baseline ) . Similarly , visible progression of scalp hair loss was demonstrated by global photographic assessment , with 75 % of placebo patients rated as worsened from baseline at 5 years . We found that scalp hair loss continued in a progressive manner over a 5-year period in placebo-treated men with AGA BACKGROUND And rogenetic alopecia is the most common cause of hair loss in men and women . And rogenetic alopecia in women begins as a diffuse and progressive thinning of the frontoparietal area of the scalp . In women , hair loss at any age is socially unacceptable and may be the basis of psychiatric illness . METHODS A 32-week , double-blind , placebo-controlled trial was conducted in 10 European centers to assess the efficacy and safety of 2 % topical minoxidil solution for the treatment of and rogenetic alopecia in women . Two hundred ninety-four of the 346 women enrolled ( 85 % ) completed the 32-week trial . Photographic and computer imaging techniques were used at each visit to determine objective ly the number of nonvellus hairs present in a 1-cm2 area selected as the target evaluation site . RESULTS In the 2 % minoxidil group , the mean increase in nonvellus hair count was 33 hairs , which was significantly greater than that of 19 hairs in the placebo group ( P = 0.0001 ) . The investigators observed that 44 % of the patients in the 2 % minoxidil group achieved new hair growth compared with 29 % in the placebo group . When asked to evaluate their own hair growth , 55 % of the women in the 2 % minoxidil group compared to 41 % of the women in the placebo group believed that they had achieved new hair growth . No clinical ly significant changes in vital signs were observed during the study and no serious or unexpected medical events were reported . CONCLUSION Topical minoxidil solution was significantly more effective than placebo in the treatment of and rogenetic alopecia in women Background Recent studies of antid and ruff shampoos or tonics containing antifungal or antibacterial agents produced effects suggestive of a potential hair growth benefit |
668 | 30,334,937 | Conclusions : This is the first systematic review to identify and critically appraise patient-reported outcome measures for soft-tissue facial reconstruction using internationally accepted criteria .
Through the use of psychometrically well-vali date d question naires , it is hoped that patients ’ concerns can be truly appreciated , the level of care improved , and the quality of reconstructive options offered advanced | Background : A patient ’s health-related quality of life can be significantly impacted by facial scarring and disfigurement .
Facial soft-tissue reconstruction should aim to improve this , with outcomes measured from the patient ’s perspective using patient-reported outcome measures .
This systematic review identifies patient-reported outcome measures for soft-tissue facial reconstruction and appraises their method ologic and psychometric properties using up-to- date methods . | Correctable weaknesses in the design , conduct , and analysis of biomedical and public health research studies can produce misleading results and waste valuable re sources . Small effects can be difficult to distinguish from bias introduced by study design and analyses . An absence of detailed written protocol s and poor documentation of research is common . Information obtained might not be useful or important , and statistical precision or power is often too low or used in a misleading way . Insufficient consideration might be given to both previous and continuing studies . Arbitrary choice of analyses and an overemphasis on r and om extremes might affect the reported findings . Several problems relate to the research workforce , including failure to involve experienced statisticians and method ologists , failure to train clinical research ers and laboratory scientists in research methods and design , and the involvement of stakeholders with conflicts of interest . Inadequate emphasis is placed on recording of research decisions and on reproducibility of research . Finally , reward systems incentivise quantity more than quality , and novelty more than reliability . We propose potential solutions for these problems , including improvements in protocol s and documentation , consideration of evidence from studies in progress , st and ardisation of research efforts , optimisation and training of an experienced and non-conflicted scientific workforce , and reconsideration of scientific reward systems Background The COSMIN checklist is a tool for evaluating the method ological quality of studies on measurement properties of health-related patient-reported outcomes . The aim of this study is to determine the inter-rater agreement and reliability of each item score of the COSMIN checklist ( n = 114 ) . Methods 75 articles evaluating measurement properties were r and omly selected from the bibliographic data base compiled by the Patient-Reported Outcome Measurement Group , Oxford , UK . Raters were asked to assess the method ological quality of three articles , using the COSMIN checklist . In a one-way design , percentage agreement and intraclass kappa coefficients or quadratic-weighted kappa coefficients were calculated for each item . Results 88 raters participated . Of the 75 selected articles , 26 articles were rated by four to six participants , and 49 by two or three participants . Overall , percentage agreement was appropriate ( 68 % was above 80 % agreement ) , and the kappa coefficients for the COSMIN items were low ( 61 % was below 0.40 , 6 % was above 0.75 ) . Reasons for low inter-rater agreement were need for subjective judgement , and accustom to different st and ards , terminology and definitions . Conclusions Results indicated that raters often choose the same response option , but that it is difficult on item level to distinguish between articles . When using the COSMIN checklist in a systematic review , we recommend getting some training and experience , completing it by two independent raters , and reaching consensus on one final rating . Instructions for using the checklist are improved OBJECTIVE The Derriford Appearance Scale ( DAS ) 59 was specifically design ed to measure psychosocial adjustment in patients with appearance problems . Previous studies using the DAS59 have proven it to be a reliable method of assessing the appearance-related quality of life after plastic surgery procedures . The aim of this study was to develop a valid and reliable Italian version of the DAS59 . PATIENTS AND METHODS The first Italian translation of this question naire was conducted according to the DAS59 protocol that was design ed by the original authors of the question naire . Eight hundred patients participated in this study and filled out three question naires ( DAS59 , General Health Question naire (GHQ)12 and Beck 's Depression Inventory (BDI)-II ) . There were 400 adult patients with a history of previous plastic surgeries and 400 adult patients without any personal history of previous plastic surgery procedures . A total of 50 patients were selected r and omly for test-retest analysis . RESULTS The overall internal consistency was excellent ( α = 0.95 ) and equal to that of the original article that first described the scale . There was a good correlation between all the items . Domains demonstrated good internal consistency ( Cronbach 's alpha ) and correlation within themselves . The construct validity of the Italian DAS59 was assessed under convergent validity that confirmed the correlation with scales related to other psychological conditions . GHQ12 showed relevant correlation with DAS59 , while BDI-II did not . CONCLUSIONS A valid and reliable Italian DAS59 version was developed that can be used for research and clinical assessment of patients with appearance problems and concerns , especially before and after plastic surgery procedures Objectives For the measurement of patient-reported outcomes , such as ( health-related ) quality of life , often many measurement instruments exist that intend to measure the same construct . To facilitate instrument selection , our aim was to develop a highly sensitive search filter for finding studies on measurement properties of measurement instruments in PubMed and a more precise search filter that needs less abstract s to be screened , but at a higher risk of missing relevant studies . Methods A r and om sample of 10,000 PubMed records ( 01 - 01 - 1990 to 31 - 12 - 2006 ) was used as a gold st and ard . Studies on measurement properties were identified using an exclusion filter and h and search ing . Search terms were selected from the relevant records in the gold st and ard as well as from 100 systematic review s of measurement properties and combined based on sensitivity and precision . The performance of the filters was tested in the gold st and ard as well as in two validation sets , by calculating sensitivity , precision , specificity , and number needed to read . Results We identified 116 studies on measurement properties in the gold st and ard . The sensitive search filter was able to retrieve 113 of these 116 studies ( sensitivity 97.4 % , precision 4.4 % ) . The precise search filter had a sensitivity of 93.1 % and a precision of 9.4 % . Both filters performed very well in the validation sets . Conclusion The use of these search filters will contribute to evidence -based selection of measurement instruments in all medical fields OBJECTIVE To assess the reliability , validity and sensitivity to change of the Derriford Scale , a quality of life instrument design ed to assess the distress and dysfunction experienced by people who are self-conscious about their physical appearance . SUBJECTS AND DESIGN Postal question naire survey of 656 cosmetic surgery patients recruited from new referral letters and plastic surgery waiting list reports . A total of 443 subjects completed and returned the question naire . Of these respondents , 203 were sent a second question naire to assess reproducibility , of whom 155 subjects responded . MAIN OUTCOME MEASURES Reliability was assessed in terms of internal consistency and reproducibility . Face , content and construct validity were also investigated . RESULTS The analyses led to mixed results . There was some evidence of internal consistency , but a number of items had low endorsement levels and there may be scope for reducing the overall size of the instrument . When assessed for reproducibility , the level of agreement between scores of individuals completing the question naire on two occasions was high , but an important systematic shift in responses was also detected . Correlations between the other health status measures and the Derriford Scale provided some evidence of construct validity . CONCLUSION In its present form the Derriford Scale has good descriptive value , but there are some measurement problems identified in this report that need to be addressed before the scale is taken up into general use IMPORTANCE The impact of facial defects on quality of life as perceived by society and the value society places on facial reconstruction are important outcomes measures . OBJECTIVE To measure the health state utility and dollar value of surgically reconstructing facial defects as perceived by society . DESIGN , SETTING , AND PARTICIPANTS A r and omized observational study conducted in an academic tertiary referral center using a socioeconomically diverse group of 200 casual observers . MAIN OUTCOMES AND MEASURES Observers viewed images of faces with defects of varying sizes and locations before and after surgical reconstruction . Observers imagined if the defect in each image were on their own face and rated ( 1 ) their health state utility with the defect and ( 2 ) how much they would be willing to pay to have the defect surgically repaired to normal ( perfect repair ) . Established health state utility and contingent valuation metrics were used . RESULTS Data from 200 observers were analyzed . Facial defects significantly decreased perceived health state utility with the greatest penalty attributed to large and central ly located defects . Surgical reconstruction of the facial defects increased health state utility to near-normal ranges for all groups except large central defects . Participants were willing to pay an average of $ 1170 ( 95 % CI , $ 767-$1572 ) to repair a de novo small peripheral defect ; they were willing to pay $ 4274 more than the average ( 95 % CI , $ 3296-$5251 ) to repair a large defect and $ 2372 more ( 95 % CI , $ 1379-$3366 ) to repair a central defect . Using these valuation and health utility data , we calculated willingness to pay per quality -adjusted life-year ( WTP/QALY ) , a value-related metric . Mean WTP/QALY ratios ranged from $ 639/QALY for repairing small peripheral defects to $ 2838/QALY for repairing large central defects , well below all cost-effectiveness thresholds . CONCLUSIONS AND RELEVANCE Casual observers perceived that facial defects significantly decrease quality of life , an effect improved by reconstructive surgery . Measuring WTP and calculating WTP/QALY provides novel data to assess the social importance and value of facial reconstructive surgery . To our knowledge , these are the first data demonstrating that surgical reconstruction of facial defects is a high-value intervention as perceived by society . These findings have implication s for a broad range of stakeholders , including patients , surgeons , health policy makers , and payers . LEVEL OF EVIDENCE NA Background : The FACE-Q is a new patient-reported outcome instrument to evaluate a range of outcomes for patients undergoing any type of facial cosmetic operation , minimally invasive cosmetic procedure , or facial injectable . This article describes the development and validation of FACE-Q scales relevant to face-lift patients . Methods : The FACE-Q was developed by following international guidelines for patient-reported outcome instrument development . For outcomes following a face lift , the authors developed five appearance appraisal scales ( i.e. , Satisfaction with Cheeks , Satisfaction with Lower Face and Jawline , Appraisal of Nasolabial Folds , Appraisal of Area Under the Chin , and Appraisal of the Neck ) and an adverse effects checklist . A field test of these scales was performed in a sample of 225 face-lift patients , and were evaluated using both modern and traditional psychometric methods . Results : The five FACE-Q appearance appraisal scales were found to be clinical ly meaningful , reliable , valid , and responsive to clinical change . These findings were supported by Rasch measurement theory analysis ( e.g. , overall chi-square values of p ≥ 0.18 ; Person Separation Index ≥ 0.88 ) . Responsiveness analyses showed that patient scores for facial appearance improved significantly after treatment ( p < 0.001 ) ; changes in scores were associated with moderate effect sizes ( range effect size , 0.40 to 0.79 ; range st and ardized response mean , 0.37 to 0.69 ) . Traditional psychometric statistics provided further support ( e.g. , Cronbach ’s alpha values ≥0.94 ) Conclusions : The FACE-Q appearance appraisal scales are scientifically sound and clinical ly meaningful and can be used with the adverse effects checklist to measure patient-reported outcomes following a face lift . CLINICAL QUESTION /LEVEL OF EVIDENCE : Diagnostic , III OBJECTIVE To establish the clinical responsiveness of the Skin Cancer Index ( SCI ) , a new disease-specific quality of life ( QOL ) instrument , and to assess demographic and clinical factors which impact QOL in patients with nonmelanoma skin cancer ( NMSC ) . STUDY DESIGN Prospect i ve study of 183 patients with NMSC of the face and neck referred to a tertiary care Mohs surgery clinic . METHODS The SCI is a 15 item , vali date d , disease-specific QOL instrument with 3 distinct subscales , Emotion , Social , and Appearance . Higher scores reflect better QOL . The SCI and the Dermatology Life Quality Index ( DLQI ) , a general dermatology instrument , was administered at initial consultation and 4 months after surgical treatment . Multivariate analysis was conducted to assess demographic and clinical factors predictive of QOL for both instruments . RESULTS The SCI total score and all three subscale scores increased with treatment , demonstrating strong evidence of responsiveness over time ( P < .001 ) in contrast with the DLQI ( P = .46 ) . Predictors of poorer QOL for the SCI included female sex and cancers located on the lip . Patients who demonstrated greatest improvement in QOL with treatment included those who were younger ( < 50 yr ) and had lower reported household income . Also , first time NMSC patients and those patients who underwent less extensive reconstructions demonstrated greater improvements in QOL . CONCLUSION The SCI is a sensitive and responsive QOL instrument for patients with NMSC . Distinct demographic and clinical variables that impact QOL have been demonstrated using this multidimensional , disease-specific instrument OBJECTIVE To test 4 previously published outcomes instruments ( the Facelift Outcomes Evaluation , the Rhinoplasty Outcomes Evaluation , the Blepharoplasty Outcomes Evaluation , and the Skin Rejuvenation Outcomes Evaluation ) in terms of their reliability and validity in assessing patient-related outcomes of surgical intervention . DESIGN A prospect i ve pilot study of 78 patients in 3 similar private cosmetic surgery centers undergoing a total of 100 face-lift , rhinoplasty , blepharoplasty , and skin rejuvenation procedures . Patients were evaluated at 2 preoperative and 1 postoperative time points and the instruments were analyzed with regard to their test-retest reliability , internal consistency , and responsiveness to change . RESULTS All 4 outcomes instruments had excellent reliability , consistency , and validity scores . Test-retest reliability was 0.74 to 0.83 ( Pearson correlation coefficients ) , internal consistency scores were.83 to.88 ( Cronbach alpha ) , and responsiveness to change was statistically significant for each instrument tested ( P < or = .001 ) . In addition , patients experienced significant quality of life improvement , with overall satisfaction increasing on average from 37 % to more than 84 % after these procedures . CONCLUSIONS These 4 instruments are reliable and valid and can be used to accurately assess patient-related satisfaction in studies of face-lift , rhinoplasty , blepharoplasty , and skin resurfacing outcomes . These brief question naires provide the cosmetic surgeon with quantitative tools to evaluate otherwise subjective and purely qualitative outcomes and are recommended for use in future prospect i ve studies There is a growing recognition that insufficient attention has been paid to the selection of the outcomes to measure in clinical trials and clinical audit . Outcomes need to be relevant to patients , clinicians , purchasers and policy-makers if the findings of research are to influence practice and future research . In addition , st and ardization of outcomes is needed to combine data from different studies to allow evidence synthesis and to compare data sets . Inconsistent choice of outcome measures means that many meta-analyses are unable to include data from all the relevant studies . For example , the five most accessed Cochrane review s in 2009 , together with the top cited review in that year , all described inconsistencies in the outcomes reported in eligible trials . A call for the st and ardization of outcomes is a regular conclusion of systematic review s. Furthermore , outcome reporting bias , defined as the bias arising from selecting outcomes for publication based on the results , affects many r and omized trials and ‘ is an under-recognized problem that affects the conclusions in a substantial proportion of Cochrane review s ’ . That bias is likely to affect systematic review s more widely as well as affecting individual studies when considered on their own . Similar problems occur with clinical audit , highlighting the importance of establishing national audits that use and report the same outcomes for all participants . All these issues could be addressed with the development and application of agreed st and ardized sets of outcomes that have been termed ‘ core outcome sets ’ . These should be measured and reported , as a minimum , in all relevant clinical trials and national clinical audits for a specific condition . Adopting a core outcome set does not imply that a particular study , review or audit should be restricted to only those outcomes . Rather , the expectation is that , as a minimum , core outcomes will always be collected and reported to allow the results of trials to be compared , contrasted and combined as appropriate . The adoption of core outcomes would have implication s across all areas of research in health and health care , reduce heterogeneity between trials , and lead to research that is more likely to have measured relevant outcomes . Importantly , they would enhance the value of evidence synthesis by reducing the risk of outcome reporting bias and ensuring that all trials contribute usable information . In addition , they will increase the efficiency and value of research . An important rationale for core outcome sets is that outcomes currently reported for trials do not consistently reflect endpoints that are meaningful for patients . Examples exist where trials failed to include all outcomes important to patients and where involvement of patients has identified an outcome that might not have been considered by practitioners on their own . Despite increasing recognition of the importance of incorporating patients ’ opinions , their involvement has been limited . Recent regulatory guidance in the USA requires documented evidence of patient input during the development of instruments to measure patient reported outcomes ( PROs ) . However , measurement of PROs in clinical trials is hampered by the multiplicity and heterogeneity of tools currently available . Many generic , disease and domain-specific instruments have been developed and vali date d , each containing multiple scales and items . As a result , synthesis of PRO data from trials is difficult and review s aim ing to summarize treatment effect according to PROs may fail . There is synergy between the development of core outcome sets for trials and work to select up to seven outcomes that are important to patients for inclusion in Summary of Findings tables in systematic review s. Developed by the GRADE group ( http://www . grade workinggroup.org ) , Cochrane review s have featured such tables since 2008 , and they play a key role in presenting research in guidelines , such as those produced by the World Health Organization ( WHO ) . The development of core outcome sets needs to be accelerated and undertaken in ways that maximize efficiency . The COMET ( Core Outcome Measures in Effectiveness Trials , http://www.comet-initiative.org ) Initiative in the UK brings together research ers interested in the development and application of core outcome sets . These include key participants in a collaboration of research ers in rheumatology who have done the most notable work to date in this area . The COMET Initiative was launched in January 2010 , with a second meeting in July 2011 . Attendees included trialists , systematic review ers , patients , clinicians , journal editors , research funders , policy-makers , people responsible for trials registries and regulators . Data on individual studies , both published and ongoing , are being included in a free , publically available internet-based re source . This will be up date d periodically , to minimize the risk of duplication . Seventy-eight published or ongoing studies have already been entered into the repository . In addition , published review s of outcomes used in clinical trials or studies examining patients ’ views , will be entered |
669 | 30,930,769 | Conclusion : Medication adherence in the oldest old hypertensive patients seems to be higher than in younger persons .
Adherence in older persons was associated with age , socioeconomic status , and therapy-related factors | Background : The aim of this systematic review and meta- analysis was to estimate medication adherence in hypertensive patients aged ≥60 years and to explore potential determinants of adherence with antihypertensive treatment in this age group . | Abstract Background Adherence to prescribed medication is an imperative issue which can be directly linked with the management of chronic diseases like hypertension ; failure to adhere can affect the effectiveness of medication as well as the efficiency of the health care system . There is scarcity of information regarding the level of drug adherence for antihypertensive medications and its determinants in Ethiopia , particularly in the study area . Therefore , the aim of this study was to assess adherence level and its determinants for antihypertensive medications among adult hypertensive patients attending the chronic illness clinics of the referral hospitals in northwest Ethiopia . Methods Institution based cross sectional study was conducted from March to April , 2016 . The systematic r and om sampling technique was used to select 409 study participants from three referral hospitals . The question naire was prepared using the World Health Organization ( WHO ) conceptual model and by review ing international literature . The data were collected using an interviewer administered question naire . The data were entered in to Epi - Info version 7 and then transferred to the statistical package for social science ( SPSS ) version 20 for data cleaning and analysis .Bivariate analysis was first done to see the association between each independent variables and dependent variable . Variables with a P-value of less than 0.2 in the bivariate analysis were entered in to the multivariate logistic regression model for final analysis . Multivariate analysis was done using Backward logistic regression method . P-value less than 0.05 was considered to determine the statistical significance of the association and odds ratio with a 95 % confidence interval was used to determine the presence , strength , and direction of association between covariates ( explanatory variables ) and the outcome variable . The Morisky medication adherence scale was used to assess the adherence status using > = 6 as adherent or < 6 as non adherent score . Results Four hundred and nine ( 409 ) study participants were interviewed with a response rate of 100 % . The mean age of the respondents was 54.5 years with ( St and ard Deviation ( SD ) ± 13.58 ) . The overall rate of good adherence was 67.2 % ( 95 % CI = 62.8 , 71.6 ) . Participants who had a favourable attitude towards antihypertensive medications ( Adjusted odds ratio ( AOR ) = 9.88 , 95 % confidence interval ( CI ) : 5.34 , 18.27 ) , having good patient- provider relationship ( AOR = 4.25 , 95 % CI : 2.32 , 7.86 ) , having one ( AOR = 4.36 , 95 % CI : 1.34 , 14.12 ) or no ( AOR = 3.38 , 95 % CI:1.01,11.31 ) co-morbidities , a long duration of treatment ( AOR = 1.89 , 95%CI : 1.07 , 3.35 ) , and a low medical cost ( AOR = 2.06 , 95 % CI : 1.13 , 3.76 ) had associations with good drug adherence for antihypertensive medication/s . Conclusions The prevalence of good drug adherence for anti-hypertensive medications in this study was high . Prevention of co- morbidities , making medical services accessible , and maintaining good client-provider interaction are of paramount importance for good drug adherence Background : Adherence to hypertension management in patients with hypertension is known to influence their blood pressure control . It is important to measure patients ’ adherence behaviours to assist with design ing appropriate interventions to improve blood pressure control . Aims : The purpose s of this study were to use confirmatory factor analysis to revali date the Therapeutic Adherence Scale for Hypertensive Patients ( TASHP ) , and to calculate the cut-off score for classifying adherence behaviours into two groups : satisfactory and low adherence behaviours . Methods : Systematic r and om sampling was used to recruit patients with hypertension in China . Demographic characteristics , the TASHP and blood pressure were collected . The psychometric tests of the TASHP included : construct validity , criteria -related validity , internal reliability , and split-half reliability . The area under the receiver operating characteristics curve and Youden index were used to identify the cut-off score of the TASHP for blood pressure control . Results : This study involved 366 patients . Confirmatory factor analysis supported the four-component structure of the TASHP proposed in the original scale development study . The TASHP has a satisfactory internal reliability ( Cronbach ’s α > 0.7 ) and a satisfactory split-half reliability ( Spearman – Brown coefficients > 0.7 ) . The patients with overall scores of the TASHP ⩾ 109 points were considered to have satisfactory adherence behaviours . Conclusion : The TASHP is a vali date d and reliable instrument to measure the adherence to hypertension management in Chinese patients with hypertension . The cut-off score of 109 points can be considered as an effective measure to classify the level of adherence into satisfactory and low adherence behaviours Background The Morisky Medication Adherence scale ( MMAS-8 ) is a widely used self-reported measure of adherence to antihypertensive medications that has not been vali date d in hypertensive patients in sub-Saharan Africa . Methods We carried out a cross-sectional study to examine psychometric properties of a translated MMAS-8 ( MMAS-U ) in a tertiary care hypertension clinic in Ug and a. We administered the MMAS-U to consecutively selected hypertensive adults and used principal factor analysis and Cronbach ’s alpha to determine its validity and internal consistency respectively . Then we r and omly selected one-sixth of participants for a 2-week test-retest telephone interview . Lastly , we used ordinal logistic regression modeling to explore factors associated with levels of medication adherence . Results Of the 329 participants , 228 ( 69 % ) were females , median age of 55 years [ Interquartile range ( IQR ) ( 46–66 ) ] , and median duration of hypertension of 4 years [ IQR ( 2–8 ) ] . The adherence levels were low ( MMAS-U score ≤ 5 ) in 85 % , moderate ( MMAS-U score 6–7 ) in 12 % and high ( MMAS-U score ≥8 ) in 3 % . The factor analysis of construct validity was good ( overall Kaiser ’s measure of sampling adequacy for residuals of 0.72 ) and identified unidimensionality of MMAS-U. The internal consistency of MMAS-U was moderate ( Cronbach α = 0.65 ) , and test-retest reliability was low ( weighted kappa = 0.36 ; 95 % CI -0.01 , 0.73 ) . Age of 40 years or greater was associated with low medication adherence ( p = 0.02 ) whereas a family member buying medication for participants ( p = 0.02 ) and purchasing medication from a private clinic ( p = 0.02 ) were associated with high adherence . Conclusion The Ug and an version of the MMAS-8 ( MMAS-U ) is a valid and reliable measure of adherence to antihypertensive medication among Ug and an out patients receiving care at a public tertiary facility . Though the limited supply of medication affected adherence , this easy to use tool can be adapted to assess medication adherence among adults with hypertension in Ug and Background Medication adherence is an important predictor of optimal blood pressure control ; hence , it significantly reduces the risk of cardiovascular disease ( CVD ) and associated deaths . However , studies on medication adherence and its associated factors are scarce . Thus , this study aim ed to assess adherence to antihypertensive medications and identify associated factors at Debre Tabor General Hospital , northwest Ethiopia . Methods A hospital-based cross-sectional study was conducted . Simple r and om sampling technique was used to select 346 participants . A structured question naire adapted from the World Health Organization ( WHO ) STEPwise approach was used to collect data . Medication adherence was measured by the four-item Morisky – Green – Levine Scale , with a score ≥3 defined as “ good adherence ” . Data were entered using Epi Info version 7 and exported to SPSS version 20 for analysis . Descriptive and summary statistics were used . Bivariate and multivariable analyses were also carried out . Results A total of 337 hypertensive patients participated in the study . Three-quarters ( 75.1 % ) of the participants were found to be adherent to their medication therapy . The multivariable logistic regression analysis showed that urban residence ( adjusted odd ratio [AOR]=2.10 , 95 % confidence interval [ CI ] : 1.15 , 3.85 ) , taking less than two drugs per day ( AOR=3.04 , 95 % CI : 1.53 , 6.06 ) , and having knowledge about hypertension ( HTN ) and its treatment ( AOR=8.86 , 95 % CI : 4.67 , 16.82 ) were positively and significantly associated with medication adherence , while age > 60 years ( AOR=0.33 , 95 % CI : 0.11 , 0.98 ) was negatively and significantly associated with good medication adherence . Conclusion A significant proportion of hypertensive patients poorly adhere to antihypertensive medications . Age , residence , pill burden , and knowledge about HTN and its treatment are important predictors of medication adherence . Attention should be given to increase the knowledge of patients about their disease and its treatment , and due emphasis should also be given to older and rural patients Confirmation of medication adherence is a challenge in clinical practice and essential for the accurate diagnosis of resistant hypertension . Although it is well established that drug adherence is critical for controlling blood pressure , there are still difficulties applying a simple , inexpensive , and reliable assessment of adherence in the clinical setting . We aim ed to test a simple method to assess adherence in resistant hypertensive ( RH ) patients . A pilot study with normotensives or mild/moderate hypertensive subjects was performed to provide a fluorescence cutoff point for adherence . After that , 21 patients referred to the Resistant Hypertension Clinic had triamterene prescribed and were monitored for a 30-day period . We conducted two unannounced r and omly selected home visits for urine collection to test drug intake that day . Office , home and 24-hour ambulatory blood pressure , biochemical data , and the 8-item Morisky Medication Adherence Scale ( MMAS-8 ) were systematic ally acquired . According to adherence indicated by urine fluorescence , subjects were divided into adherent and nonadherent groups . We found 57 % of nonadherence . No differences were found between groups regarding baseline characteristics or prescribed medications ; Kappa 's test showed concordance between adherence through MMAS-8 items and fluorescence ( kappa = 0.61 ; 95 % confidence interval : 0.28 - 0.94 ; P = .005 ) . Nonadherent patients had higher office ( 81 ± 11 vs. 73 ± 6 mm Hg , P = .03 ) , 24-hour ambulatory blood pressure monitoring ( 75 ± 9 vs. 66 ± 7 mm Hg , P = .01 ) , and home blood pressure measurement ( 77 ± 9 vs. 67 ± 8 mm Hg , P = .01 ) diastolic blood pressure than their counterparts . Nonadherence to antihypertensive therapy is high in patients with RH , even when assessed in clinics specialized in this condition . Fluorometry to detect a drug in the urine of RH patients is safe , easy , and reliable method to assess adherence |
670 | 30,786,308 | This result , in the clinical practice , does not compromise the fetal well-being , since all babies were born at term .
To date , the evidence analyzed has a moderate-to-high risk of bias and does not allow the conclusion that insulin analogs are more effective when compared with human insulin to treat diabetic pregnant women | Diabetes during pregnancy has been linked to unfavorable maternal-fetal outcomes .
Human insulins are the first drug of choice because of the proven safety in their use .
However , there are still questions about the use of insulin analogs during pregnancy .
The objective of the present study was to determine the effectiveness of insulin analogs compared with human insulin in the treatment of pregnant women with diabetes through a systematic review with meta- analysis . | OBJECTIVE This r and omized , controlled noninferiority trial aim ed to compare the efficacy and safety of insulin detemir ( IDet ) versus neutral protamine Hagedorn ( NPH ) ( both with pr and ial insulin aspart ) in pregnant women with type 1 diabetes . RESEARCH DESIGN AND METHODS Patients were r and omized and exposed to IDet or NPH up to 12 months before pregnancy or at 8–12 weeks gestation . The primary analysis aim ed to demonstrate noninferiority of IDet to NPH with respect to A1C at 36 gestational weeks ( GWs ) ( margin of 0.4 % ) . The data were analyzed using linear regression , taking several baseline factors and covariates into account . RESULTS A total of 310 type 1 diabetic women were r and omized and exposed to IDet ( n = 152 ) or NPH ( n = 158 ) up to 12 months before pregnancy ( 48 % ) or during pregnancy at 8–12 weeks ( 52 % ) . The estimated A1C at 36 GWs was 6.27 % for IDet and 6.33 % for NPH in the full analysis set ( FAS ) . IDet was declared noninferior to NPH ( FAS , –0.06 % [ 95 % CI –0.21 to 0.08 ] ; per protocol , –0.15 % [ –0.34 to 0.04 ] ) . Fasting plasma glucose ( FPG ) was significantly lower with IDet versus NPH at both 24 GWs ( 96.8 vs. 113.8 mg/dL , P = 0.012 ) and 36 GWs ( 85.7 vs. 97.4 mg/dL , P = 0.017 ) . Major and minor hypoglycemia rates during pregnancy were similar between groups . CONCLUSIONS Treatment with IDet result ed in lower FPG and noninferior A1C in late pregnancy compared with NPH insulin . Rates of hypoglycemia were comparable OBJECTIVE To evaluate the progression of retinopathy during pregnancy and postpartum in ( insulin-dependent ) women with type 1 diabetes treated with insulin lispro or with regular human insulin . RESEARCH DESIGN AND METHODS A prospect i ve open study of 69 pregnant women with diabetes was performed . A total of 36 of the women were treated with insulin lispro ( lispro group ) and 33 were treated with conventional short-acting human insulin ( regular insulin group ) . The retinopathy level was estimated by color fundus photography every trimester and postpartum . Glycemic control during pregnancy , hypoglycemia ( blood glucose level <3 mmol/l ) in 24-h glucose profile , blood pressure , and proteinuria were registered . RESULTS HbA(1c ) values were similar at baseline in the first trimester but thereafter were lower in the lispro group than in the regular insulin group throughout pregnancy ( P = 0.022 , repeated- measures ANOVA ) . The number of hypoglycemic episodes did not differ between the treatment groups . In multivariable logistic regression analysis with retinopathy severity ( Diabetes Control and Complications Trial level ) in the third trimester as the dependent variable , only nulliparity qualified as a predictor in the model [ Exp(B ) = 4.0 , 95 % CI 1.1 - 13.7 , P = 0.030 ] . Factors such as duration of diabetes , type of insulin used , mean HbA(1c ) level throughout pregnancy , blood pressure ( systolic or diastolic ) , preeclampsia in the current pregnancy , smoking , or prepregnancy planning did not explain the retinopathy progression . CONCLUSIONS Insulin lispro improves glycemic control during diabetic pregnancy compared with regular insulin with no adverse impact on progression of diabetic retinopathy Background Women with hyperglycaemia detected during pregnancy are at greater risk for adverse pregnancy outcomes . Data on hyperglycaemia in pregnancy in sub-Saharan Africa is scanty and varied depending on the population s studied and the method ologies used to define hyperglycaemia in pregnancy . With the recent 2013 World Health Organisation ( WHO ) diagnostic criteria and classification , there is yet no sufficient data on the prevalence of hyperglycaemia in sub-Saharan Africa . The objective was to determine the prevalence of Hyperglycaemia first detected during pregnancy and subsequent obstetric outcomes among patients attending antenatal care ( ANC ) at St. Francis Hospital Nsambya . Methods A prospect i ve cohort study . All women with no history of diabetes mellitus attending at or after 24 weeks gestation were eligible to participate in the study . Participants underwent a st and ard 75 g oral glucose tolerance test ( OGTT ) after an informed written consent . The primary outcome was diagnosis of hyperglycaemia . Enrolled participants were followed up to delivery to assess obstetric outcomes ( secondary outcomes were birth weight , neonatal admission , maternal genital trauma , delivery mode , neonatal and maternal status at discharge ) . Results 251 women were screened between December 2013 and February 2014 . The prevalence of hyperglycaemia first detected in pregnancy was 31.9 % . We found 23.8 % of women with hyperglycaemia had no known risk factor . Macrosomia was the only obstetric outcome that was significantly associated with hyperglycaemia . Conclusion The prevalence of hyperglycaemia first detected in pregnancy was high in the studied population . Clinicians , therefore , should become more vigilant to screen for the condition . Selective screening may miss 23.8 % of pregnant women with hyperglycaemia . However the cost/benefit implication s of screening strategy and the recent 2013 WHO diagnostic criteria need to be studied in our setting OBJECTIVE —To assess the safety and efficacy of insulin aspart ( IAsp ) versus regular human insulin ( HI ) in basal-bolus therapy with NPH insulin in pregnant women with type 1 diabetes . RESEARCH DESIGN AND METHODS —Subjects ( n = 322 ) who were pregnant or planning pregnancy were r and omized to IAsp or HI as meal-time insulin in an open-label , parallel-group , multicenter study . Subjects had A1C ≤8 % at confirmation of pregnancy . Insulin doses were titrated toward predefined glucose targets and A1C < 6.5 % . Outcomes assessed included risk of major maternal hypoglycemia , A1C , plasma glucose profiles , and maternal safety outcomes . RESULTS —Major hypoglycemia occurred at a rate of 1.4 vs. 2.1 episodes/year exposure with IAsp and HI , respectively ( relative risk 0.720 [ 95 % CI 0.36–1.46 ] ) . Risk of major/major nocturnal hypoglycemia was 52 % ( RR 0.48 [ 0.20–1.143 ] ; P = NS ) lower with IAsp compared with HI . A1C was comparable with human insulin in second ( IAsp-HI −0.04 [ −0.18 to 0.11 ] ) and third ( −0.08 [ −0.23 to 0.06 ] ) trimesters . A total of 80 % of subjects achieved an A1C ≤6.5 % . At the end of first and third trimesters , average postpr and ial plasma glucose increments were significantly lower with IAsp than HI ( P = 0.003 and P = 0.044 , respectively ) , as were mean plasma glucose levels 90 min after breakfast ( P = 0.044 and P = 0.001 , respectively ) . Maternal safety profiles and pregnancy outcomes were similar between treatments . CONCLUSIONS —IAsp is at least as safe and effective as HI when used in basal-bolus therapy with NPH insulin in pregnant women with type 1 diabetes and may potentially offer some benefits in terms of postpr and ial glucose control and preventing severe hypoglycemia Objective . To describe perinatal outcomes of women with pregestational diabetes treated with short-acting , regular insulin and the short-acting insulin analogue , lispro . Study design . This was a prospect i ve observational study of women with pregestational diabetes maintained on short-acting insulin regimens over a 3-year period . Clinical characteristics , aspects of diabetic therapy , and perinatal/neonatal outcomes were collected . Results . Of 107 women , 49 were maintained on regular insulin and 58 utilized the insulin analogue , lispro . Frequency of type 1 diabetes , maternal age , overweight/obese pregravid body mass index ( ≥25 kg/m2 ) , preexisting hypertension , and presence of vascular disease were similar between groups . Women treated with lispro had a longer duration of diabetes ( 11.4 vs. 8.3 years , p = 0.04 ) . Glycemic control was improved in women managed with lispro compared to regular insulin ( HgbA1c 5.9 vs. 6.7 , p = 0.009 ) . Total insulin requirements were lower in the lispro group in the first ( 0.58 vs. 0.79 units/kg , p = 0.02 ) , second ( 0.75 vs. 1.10 units/kg , p = 0.002 ) , and third ( 0.98 vs. 1.25 units/kg , p = 0.03 ) trimesters of pregnancy . Mean infant birth weight was greater in the lispro group , whereas the rate of large for gestational age infants and ponderal indices were similar between groups . Malformation rate , gestational age at delivery , neonatal intensive care unit admission , neonatal length of stay , rates of respiratory distress syndrome , and hypoglycemia were similar . Conclusions . Women treated with lispro demonstrated improved glycemic control and lower total insulin requirements during pregnancy compared to those receiving regular insulin . Perinatal outcomes were similar between women treated with both types of insulin Objective To investigate maternal , perinatal , and neonatal outcomes of pregnancies in women with type 1 diabetes in the Netherl and s. Design Nationwide prospect i ve cohort study . Setting All 118 hospitals in the Netherl and s. Participants 323 women with type 1 diabetes who became pregnant between 1 April 1999 and 1 April 2000 . Main outcome measures Maternal , perinatal , and neonatal outcomes of pregnancy . Results 84 % ( n = 271 ) of the pregnancies were planned . Glycaemic control early in pregnancy was good in most women ( HbA1c 7.0 % in 75 % ( n = 212 ) of the population ) , and folic acid supplementation was adequate in 70 % ( n = 226 ) . 314 pregnancies that went beyond 24 weeks ' gestation result ed in 324 infants . The rates of pre-eclampsia ( 40 ; 12.7 % ) , preterm delivery ( 101 ; 32.2 % ) , caesarean section ( 139 ; 44.3 % ) , maternal mortality ( 2 ; 0.6 % ) , congenital malformations ( 29 ; 8.8 % ) , perinatal mortality ( 9 ; 2.8 % ) , and macrosomia ( 146 ; 45.1 % ) were considerably higher than in the general population . Neonatal morbidity ( one or more complications ) was extremely high ( 260 ; 80.2 % ) . The incidence of major congenital malformations was significantly lower in planned pregnancies than in unplanned pregnancies ( 4.2 % ( n = 11 ) v 12.2 % ( n = 6 ) ; relative risk 0.34 , 95 % confidence interval 0.13 to 0.88 ) . Conclusion Despite a high frequency of planned pregnancies , result ing in overall good glycaemic control ( early ) in pregnancy and a high rate of adequate use of folic acid , maternal and perinatal complications were still increased in women with type 1 diabetes . Neonatal morbidity , especially hypoglycaemia , was also extremely high . Near optimal maternal glycaemic control ( HbA1c 7.0 % ) apparently is not good enough BACKGROUND Improved blood-glucose control decreases the progression of diabetic microvascular disease , but the effect on macrovascular complications is unknown . There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation . We compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a r and omised controlled trial . METHODS 3867 newly diagnosed patients with type 2 diabetes , median age 54 years ( IQR 48 - 60 years ) , who after 3 months ' diet treatment had a mean of two fasting plasma glucose ( FPG ) concentrations of 6.1 - 15.0 mmol/L were r and omly assigned intensive policy with a sulphonylurea ( chlorpropamide , glibenclamide , or glipizide ) or with insulin , or conventional policy with diet . The aim in the intensive group was FPG less than 6 mmol/L. In the conventional group , the aim was the best achievable FPG with diet alone ; drugs were added only if there were hyperglycaemic symptoms or FPG greater than 15 mmol/L. Three aggregate endpoints were used to assess differences between conventional and intensive treatment : any diabetes-related endpoint ( sudden death , death from hyperglycaemia or hypoglycaemia , fatal or non-fatal myocardial infa rct ion , angina , heart failure , stroke , renal failure , amputation [ of at least one digit ] , vitreous haemorrhage , retinopathy requiring photocoagulation , blindness in one eye , or cataract extraction ) ; diabetes-related death ( death from myocardial infa rct ion , stroke , peripheral vascular disease , renal disease , hyperglycaemia or hypoglycaemia , and sudden death ) ; all-cause mortality . Single clinical endpoints and surrogate sub clinical endpoints were also assessed . All analyses were by intention to treat and frequency of hypoglycaemia was also analysed by actual therapy . FINDINGS Over 10 years , haemoglobin A1c ( HbA1c ) was 7.0 % ( 6.2 - 8.2 ) in the intensive group compared with 7.9 % ( 6.9 - 8.8 ) in the conventional group -- an 11 % reduction . There was no difference in HbA1c among agents in the intensive group . Compared with the conventional group , the risk in the intensive group was 12 % lower ( 95 % CI 1 - 21 , p=0.029 ) for any diabetes-related endpoint ; 10 % lower ( -11 to 27 , p=0.34 ) for any diabetes-related death ; and 6 % lower ( -10 to 20 , p=0.44 ) for all-cause mortality . Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25 % risk reduction ( 7 - 40 , p=0.0099 ) in microvascular endpoints , including the need for retinal photocoagulation . There was no difference for any of the three aggregate endpoints between the three intensive agents ( chlorpropamide , glibenclamide , or insulin ) . Patients in the intensive group had more hypoglycaemic episodes than those in the conventional group on both types of analysis ( both p<0.0001 ) . The rates of major hypoglycaemic episodes per year were 0.7 % with conventional treatment , 1.0 % with chlorpropamide , 1.4 % with glibenclamide , and 1.8 % with insulin . Weight gain was significantly higher in the intensive group ( mean 2.9 kg ) than in the conventional group ( p<0.001 ) , and patients assigned insulin had a greater gain in weight ( 4.0 kg ) than those assigned chlorpropamide ( 2.6 kg ) or glibenclamide ( 1.7 kg ) . INTERPRETATION Intensive blood-glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications , but not macrovascular disease , in patients with type 2 diabetes . ( ABSTRACT TRUNCATED Aim The efficacy and safety of insulin aspart ( IAsp ) , a rapid-acting human insulin analogue , were compared with regular human insulin ( HI ) as the bolus component of basal-bolus therapy for subjects with gestational diabetes mellitus ( GDM ) . Methods In a r and omized , parallel-group , open-labelled trial , 27 women with GDM ( age 30.7 ± 6.3 years , HbA1c < 7 % ) were r and omized to receive IAsp ( 5 min before meal ) or HI ( 30 min before meal ) . The trial period extended from diagnosis of GDM ( 18–28 weeks ) to 6 weeks postpartum . Results Both treatment groups maintained good overall glycaemic control during the study ( beginning and end of study HbA1c≤ 6 % ) . During the meal test , mean glucose at week 6 ( IAsp 4.2 ± 0.57 mmol/l , HI 4.8 ± 0.86 mmol/l ) was slightly lower than at week 0 ( IAsp 4.9 ± 0.59 mmol/l , HI 5.1 ± 0.36 mmol/l ) . However , change from baseline values for average glucose ( IAsp –1.09 ± 0.54 mmol/l , HI –0.54 ± 0.74 mmol/l ; P = 0.003 ) and C-peptide ( IAsp –0.50 ± 0.67 nmol/l , HI –0.30 ± 0.70 nmol/l ; P = 0.027 ) were significantly lower after IAsp treatment than HI treatment . No major hypoglycaemic events were reported during the study . Cross-reacting insulin antibody binding increased slightly from baseline in both treatments groups ( end of study : IAsp 2.1 ± 5.4 % , HI 6.4 ± 13.9 % ) , whereas antibodies specific to IAsp or HI remained relatively low ( < 1 % binding ) . Conclusion IAsp was more effective than HI in decreasing postpr and ial glucose concentrations . Duration of IAsp injection 5 min before a meal rather than 30 min prior to meals offers a more convenient therapy for subjects with GDM . Overall safety and effectiveness of IAsp were comparable to HI in pregnant women with GDM . Diabet . Med . 24 , 1129–1135 ( 2007 Abstract Objective : This r and omized controlled trial aim ed to compare the efficacy and safety of insulin detemir ( IDet ) with neutral protamine Hagedorn ( NPH ) , both with insulin aspart , in pregnant women with type 1 diabetes . The perinatal and obstetric pregnancy outcomes are presented . Methods : Subjects were r and omized to IDet ( n = 152 ) or NPH ( n = 158 ) ≤12 months before pregnancy or at 8–12 gestational weeks . Results : For IDet and NPH , there were 128 and 136 live births , 11 and 9 early fetal losses , and two and one perinatal deaths , respectively . Gestational age at delivery was greater for children from the IDet arm than the NPH arm ( treatment difference : 0.49 weeks [ 95 % CI 0.11;0.88 ] , p = 0.012 , linear regression ) . Sixteen children had a malformation ( IDet : n = 8/142 , 5.6 % ; NPH : n = 8/145 , 5.5 % ) . The incidence of adverse events was similar between treatments . Conclusion : IDet is as well tolerated as NPH as regards perinatal outcomes in pregnant women with type 1 diabetes and no safety issues were identified OBJECTIVE The objective of the study was a comparison of insulin aspart ( IAsp ) with human insulin ( HI ) in basal-bolus therapy with neutral protamine Hagedorn for fetal and perinatal outcomes of type 1 diabetes in pregnancy . STUDY DESIGN This was a r and omized , parallel , open-label , controlled , multicenter , multinational study . Subjects were pregnant ( gestational age ; < 10 weeks ) or planning pregnancy at enrollment . Three hundred twenty-two women with type 1 diabetes received IAsp ( n = 157 ) or HI ( n = 165 ) . RESULTS For IAsp and HI , respectively , there were 137 and 131 live births and 14 and 21 fetal losses . Perinatal mortality was 14 and 22 per 1000 births ; number of congenital malformations were 6 and 9 ; mean ( SEM ) birthweight corrected for gestational age was 3438 g ( 71.5 ) and 3555 g ( 72.9 ; P = .091 ) . Mean gestational age was 37.6 vs 37.4 weeks . Preterm delivery occurred in 20.3 % ( IAsp ) and 30.6 % ( HI ) of pregnancies ( P = .053 ) . CONCLUSION The fetal outcome using IAsp was comparable with HI with a tendency toward fewer fetal losses and preterm deliveries Maternal insulin-dependent diabetes has long been associated with congenital malformations . As other causes of mortality and morbidity have been eliminated or reduced , malformations have become increasingly prominent . Although there is not universal agreement , the great majority of investigators find a two- to threefold increase in malformations in infants of insulin-dependent diabetic mothers . This increase is not seen in infants of gestational diabetics . It probably is not present in women whose diabetes can be controlled by diet or oral hypoglycemic agents . The risk does not appear to be primarily genetic since diabetic fathers do not have an increased number of malformed offspring . Most studies show a generalized increase in malformations involving multiple organ systems . Multiple malformations seem to be more common in diabetic than nondiabetic infants . Caudal regression has the strongest association with diabetes , occurring roughly 200 times more frequently in infants of diabetic mothers than in other infants . The teratogenic mechanism in diabetes is not known . Hyperglycemia may be important but human studies focusing on the period of organogenesis are lacking . Hypoglycemia has also been suggested based mainly on animal experiments . Insulin appears unlikely . Numerous other factors including vascular disease , hypoxia , ketone and amino acid abnormalities , glycosylation of proteins , or hormone imbalances could be teratogenic . None has been studied in sufficient detail to make a judgment . A large-scale prospect i ve study is required to determine early fetal loss rates , correlate metabolic status during organogenesis with outcome , and assess the effect of diabetic control on malformation rates OBJECTIVE To compare the efficacy and safety of prepr and ial administration of rapid-acting lispro analogue with regular short-acting insulin to pregnant women with type 1 diabetes . STUDY DESIGN Open r and omised multicentre study . Women were treated with multiple insulin injections aim ing at normoglycaemia . Blood glucose was determined six times daily , HbA(1c ) every 4 weeks . Diurnal profiles of blood glucose were analysed at gestational week 14 and during the study period at weeks 21 , 28 and 34 . PARTICIPANTS 33 pregnant women with type 1 DM were r and omised to treatment with lispro insulin ( n=16 ) or regular insulin ( n=17 ) . RESULTS Blood glucose was significantly lower ( P<0.01 ) after breakfast in the lispro group , while there were no significant group differences in glycemic control during the rest of the day . Severe hypoglycaemia occurred in two patients in the regular group but biochemical hypoglycaemia ( blood glucose < 3.0 mmol/l ) was more frequent in the lispro than in the regular group ( 5.5 vs. 3.9 % , respectively ) . HbA(1c ) values at inclusion were 6.5 and 6.6 % in the lispro and regular group respectively . HbA(1c ) values declined during the study period and were similar in both groups . There was no perinatal mortality . Complications during pregnancy , route of delivery and foetal outcome did not differ between the groups . Retinopathy progressed in both groups , one patient in the regular group developed proliferative retinopathy . CONCLUSION The results suggest that it is possible to achieve at least as adequate glycemic control with lispro as with regular insulin therapy in type 1 diabetic pregnancies BACKGROUND Pregnancy outcome in diabetic women is strictly related to glycemic control during pregnancy . The aim of our study was to compare pregnancy outcome between patients subjected to intensive insulin therapy using regular human insulin and those treated with insulin lispro ( Humalog ) . MATERIAL / METHODS Group A ( n=25 ) was treated with Humalog , and the control group B ( n=46 ) with regular human insulin . Mean age , duration of diabetes , presence of chronic diabetic complications ( according to the White classification ) parity , and BMI did not differ between groups . RESULTS The mean HbA1c concentrations in groups A and B were respectively : 7.8+/-1.4 % vs. 7.5+/-1.5 % in the first trimester , 6.4+/-0.8 % vs. 6.5+/-1.6 % in the second , and 6.7+/-0.7 % vs. 6.3+/-1.2 % in the third ( no significant differences ) . The duration of pregnancy was 36.4+/-3.9 weeks in group A and 37.1+/-1.9 weeks in group B , while the mean neonatal birth weight was 3467+/-790 and 3367+/-666 g , respectively . Neither the frequency of preterm labor and cesarean section nor the frequency of fetal macrosomia and hypoglycemia differed between groups . There was only one malformed infant in the human insulin-treated group , and no statistical difference in the rate of spontaneous abortion between groups . Also , there were no differences in the frequencies of occurrence of hypertension ( essential and pregnancy induced ) and urinary tract infections . CONCLUSIONS The course of pregnancy and perinatal outcome is comparable in intensively treated diabetic women regardless of the short-acting insulin used . Humalog appears to be a safe alternative to human insulin in the treatment of diabetes during pregnancy This prospect i ve nationwide study conducted during 1982 - 1985 examined the rates of hypertensive disorders , perinatal mortality and morbidity in 491 insulin-dependent diabetic pregnancies ( White 's classes : B , 164 ; C , 129 ; D , 172 ; F , 26 ) and in the total population of 279,000 . The rates of pregnancy-induced hypertension ( PIH ) or pre-eclampsia ( 20.6 % ) , premature delivery ( 24.6 % ) , and cesarean section ( 45.2 % ) in the diabetic group were more than four times higher than normal . PIH or preeclampsia occurred significantly ( p < 0.01 ) more frequently in patients with diabetic microangiopathy . Mean birthweight was similar in the two population s but gestational age was significantly ( p < 0.001 ) shorter ( 38 weeks ) in the diabetic group . The rate of large for gestational age infants ( 20 % ) in the diabetic group was considerably above normal ( 3.5 % ) . Although perinatal mortality rate in the diabetic group was only 3.1 % , it was 4.4 times higher than normal ; five of ten fetal deaths were associated with poor glycemic control and thus may not really be unexplained . Neonatal morbidity was significantly more frequent in the diabetic group ; still , the incidence of idiopathic respiratory distress syndrome was only 1.6 % compared with 0.6 % in the general population . Discriminant analysis revealed that gestational age at birth and elevated maternal HbA1c values in early pregnancy independently of each other had a significant impact on the occurrence of neonatal morbidity BACKGROUND Insulin glargine is a once-daily basal insulin analog with prolonged duration of action and absence of an evident peak . Glargine is associated with reduced frequency of hypoglycemic episodes ( mostly nocturnal ) as well as effective glycemic control . Maintenance of good metabolic control before conception and throughout pregnancy is essential to lower the risk of fetal malformations . Glargine might be a valuable alternative in the management of pregnancies complicated by diabetes mellitus . However , because its clinical utility has not been established , the use of glargine is not currently recommended during pregnancy . OBJECTIVE The aim of this study was to retrospectively evaluate ( years 2004 - 2007 ) the effectiveness and safety of insulin glargine compared with neutral protamine Hagedorn ( NPH ) in women affected by type 1 diabetes mellitus ( T1DM ) during pregnancy . METHODS The study comprised pregnant women affected by T1DM who were followed up in the Diabetes and Pregnancy Outpatient Clinic at the University of Palermo , Palermo , Italy , within 8 + /- 3.4 weeks subsequent to a positive pregnancy test . All patients with T1DM were treated with conventional basal-bolus insulin therapy ( aspart or lispro analogs at the 3 main meals plus glargine or NPH at bedtime ) . Healthy pregnant women were used as controls for fetal and neonatal parameters . Patients were consecutively enrolled . In all women , metabolic status was determined daily by mean glycemic values ( 2-hour postpr and ial blood glucose ) and glycosylated hemoglobin ( HbA1c ) values ( at 3-month intervals ) . Fetal measurements ( < 50th and > 90th centiles of the head circumference , abdomen circumference , and femoral length ) were evaluated by ultrasound at second and third trimesters . Weight and femoral length were assessed at birth , and neonates were classified according to the fetal growth curve for the Italian population ( < 10th centile = small for gestational age ; and > 90th centile = large for gestational age ( LGA ) . RESULTS A total of 73 pregnant women ( 30 with T1DM and 43 healthy [ control ] ) were included in the study . Of the 30 diabetic pregnant women included in the study , 15 ( mean [ SD ] age , 27.4 [ 5.2 ] years ; mean pregravidic weight , 59.7 [ 11.7 ] kg ) maintained their preconception therapy with glargine , and 15 ( mean age , 30.1 [ 2.4 ] years ; mean pregravidic weight , 60.7 [ 8.7 ] kg ) with NPH . No significant difference was observed between the glargine-treated group and the NPH-treated group with regard to pregravidic hypertension , third-trimester preeclampsia , maternal complications and /or their progression during pregnancy ( diabetic retinopathy , micro- or macroalbuminuria ) and episodes of mild hypoglycemia , severe hypoglycemia , and ketosis . There were no significant between group differences in insulin requirements ( IU/kg of body weight ) and glycemic profile , with the exception of better fasting and 2 hours after breakfast glycemic values in the glargine group during the first ( P = 0.008 and P < 0.001 , respectively ) and the second ( P = 0.015 and P = 0.016 ) trimesters , confirmed by the lower HbA1c levels in the first trimester ( P = 0.037 ) . The frequency of femoral length < 50th centile at both second and third trimesters was 4/15 ( 26.7 % ) in the glargine-treated group ( P = 0.033 and P = 0.013 , respectively , vs control ) , 3/15 ( 20.0 % ) and 1/15 ( 6.7 % ) , respectively , in the NPH-treated group ( both , P = NS vs control ) , and 2/43 ( 4.7 % ) and 1/43 ( 2.3 % ) , respectively , in the control group . The prevalence of LGA was 7/15 ( 46.7 % ) in the glargine group ( P < 0.001 vs control ) , 4/15 ( 27.6 % ) in the NPH group ( P = 0.033 vs control ) , and 2/43 ( 4.7 % ) in the control group . CONCLUSIONS Although our retrospective study involved only a small number of participants , no significant difference was found in glycemic control between glargine and NPH treatments . Use of glargine was associated with a significantly higher frequency of femoral length < 50th centile . Further larger prospect i ve studies are necessary to assess the safety profile of glargine in T1DM during pregnancy OBJECTIVE We sought to determine if insulin detemir ( IDet ) is noninferior to insulin neutral protamine Hagedorn ( NPH ) for the treatment of gestational diabetes mellitus ( GDM ) and type 2 diabetes mellitus ( T2DM ) in pregnancy . STUDY DESIGN We conducted a r and omized , controlled noninferiority trial of women with GDM and T2DM who entered our Diabetes in Pregnancy Program from March 2013 through October 2014 . Exclusion criteria were type 1 diabetes , age < 18 years , and insulin allergy . Women who failed to achieve good glycemic control ( GC ) ( mean blood glucose [ BG ] < 100 mg/dL ) on diet and /or hypoglycemic agents were r and omized to receive either IDet or NPH , with short-acting insulin aspart added as needed . Patients were instructed to test BG 4 times a day ( fasting and 2-hour postpr and ial ) . Targets of GC were fasting BG < 90 mg/dL and postpr and ial BG < 120 mg/dL , and insulin was adjusted as needed to achieve the targets . The primary outcome was overall mean BG during insulin treatment ; secondary outcomes included overall mean postpr and ial and fasting BG , median number of weeks to achieve GC , percent of patients with overall GC , maternal weight gain , perinatal/neonatal outcomes , and number of hypoglycemic events . Power analysis ( 90 % power ) determined that 88 patients would need to be r and omized , assuming a maximal acceptable difference in overall mean BG of 7 mg/dL ( SD ± 10 mg/dL ) . A per protocol analysis was performed . RESULTS In all , 105 women were r and omized . Eighteen women were excluded leaving 87 participants for analysis ( 45 NPH , 42 IDet ) . Maternal characteristics were similar in both groups . The difference in the mean BG of the groups was 2.1 mg/dL with a 1-sided upper 95 % confidence limit of 5.5 mg/dL ( less than the maximal acceptable difference of 7 mg/dL ; P = .2937 ) . There was no significant difference in the primary outcome when an intent-to-treat analysis was performed or when the T2DM patients were excluded . The time to achieve GC was similar in both groups . There were no differences in perinatal outcomes and maternal weight gain among the groups . There were more hypoglycemic events per patient in the NPH group . CONCLUSION IDet is noninferior to insulin NPH for the treatment of GDM and T2DM in pregnancy OBJECTIVE A recent r and omized trial compared pr and ial insulin aspart ( IAsp ) with human insulin in type 1 diabetic pregnancy . The aim of this exploratory analysis was to investigate the incidence of severe hypoglycemia during pregnancy and compare women enrolled preconception with women enrolled during early pregnancy . RESEARCH DESIGN AND METHODS IAsp administered immediately before each meal was compared with human insulin administered 30 min before each meal in 99 subjects ( 44 to IAsp and 55 to human insulin ) r and omly assigned preconception and in 223 subjects ( 113 for IAsp and 110 for human insulin ) r and omly assigned in early pregnancy ( < 10 weeks ) . NPH insulin was the basal insulin . Severe hypoglycemia ( requiring third-party assistance ) was recorded prospect ively preconception ( where possible ) , during pregnancy , and postpartum . Relative risk ( RR ) of severe hypoglycemia was evaluated with a gamma frailty model . RESULTS Of the patients , 23 % experienced severe hypoglycemia during pregnancy with the peak incidence in early pregnancy . In the first half of pregnancy , the RR of severe hypoglycemia in women r and omly assigned in early pregnancy/preconception was 1.70 ( 95 % CI 0.91–3.18 , P = 0.097 ) ; the RR in the second half of pregnancy was 1.35 ( 0.38–4.77 , P = 0.640 ) . In women r and omly assigned preconception , severe hypoglycemia rates occurring before and during the first and second halves of pregnancy and postpartum for IAsp versus human insulin were 0.9 versus 2.4 , 0.9 versus 2.4 , 0.3 versus 1.2 , and 0.2 versus 2.2 episodes per patient per year , respectively ( NS ) . CONCLUSIONS These data suggest that initiation of insulin analog treatment preconception rather than during early pregnancy may result in a lower risk of severe hypoglycemia in women with type 1 diabetes A r and omized , open-label , parallel study was conducted to assess the efficacy and safety of premixed insulin aspart 30 ( biphasic insulin aspart [ BIAsp ] 30 ) in managing gestational diabetes mellitus ( GDM ) . A total of 323 women with GDM registered at a single center in India were r and omly assigned to receive 6 U of either BIAsp 30 ( Group A ) or premixed human insulin ( biphasic human insulin [ BHI ] 30 ; Group B ) in a 1:1 ratio . Subjects performed home glucose monitoring and visited their care provider twice a month . The primary outcome was the degree of neonatal macrosomia ( neonatal birth weight > 90th percentile ) . Groups A and B were demographically comparable at study entry . Before labor onset , Groups A and B achieved similar degrees of fasting plasma glucose and postpr and ial plasma glucose control ( 92.97 ± 14.44 vs. 95.43 ± 18.96 and 127.59 ± 28.99 vs. 126.98 ± 29.89 , respectively ; both p = NS ) . Neonatal macrosomia frequency was 6.3 % in Group A and 6.9 % in Group B ; however , this difference was not statistically significant . By last visit , the required insulin dose was significantly lower for Group A than Group B ( 19.83 ± 15.75 IU vs. 26.34 ± 23.15 IU , respectively ; p = 0.006 ) . BIAsp 30 was noninferior to BHI 30 , producing comparable fetal outcomes when administered during pregnancy . Based on final doses , BIAsp 30 may offer greater treat-to-target potential for pregnant women |
671 | 20,166,093 | There is insufficient evidence that carnitine for the treatment of MS-related fatigue offers a therapeutic advantage over placebo or active comparators | BACKGROUND Fatigue is reported to occur in up to 92 % of patients with multiple sclerosis ( MS ) and has been described as the most debilitating of all MS symptoms by 28 % to 40 % of MS patients .
OBJECTIVES To assess whether carnitine ( enteral or intravenous ) supplementation can improve the quality of life and reduce the symptoms of fatigue in patients with MS-related fatigue and to identify any adverse effects of carnitine when used for this purpose . | Objective : To assess the efficacy and safety of modafinil for the treatment of fatigue in multiple sclerosis ( MS ) . Methods : Patients aged 18–65 years with a diagnosis of MS , a stable disability level ≤6 on the Kurtzke extended disability status scale ( EDSS ) , and a mean score > 4 on the fatigue severity scale ( FSS ) were eligible for the 9 week , single blind , phase 2 , two centre study . Exclusion criteria included a diagnosis of narcolepsy , sleep apnoea , or clinical ly significant major systemic disease and recent use of medications affecting fatigue . All patients , who remained blinded for the treatment regimen , received placebo during weeks 1–2 , 200 mg/day modafinil during weeks 3–4 , 400 mg/day modafinil during weeks 5–6 , and placebo during weeks 7–9 . Safety was evaluated by unblinded investigators . Efficacy was evaluated by self rating scales , using the FSS , the modified fatigue impact scale ( MFIS ) , a visual analogue scale for fatigue ( VAS-F ) , and the Epworth sleepiness scale ( ESS ) . Adverse events were recorded . Results : Seventy two patients ( MS type : 74 % relapsing-remitting ; 7 % primary progressive ; 19 % secondary progressive ) received treatment . After treatment with 200 mg/day modafinil for 2 weeks , a significant improvement in fatigue versus placebo run in was demonstrated . Mean scores after treatment with 200 mg/day modafinil were : FSS , 4.7 versus 5.5 for placebo ( p<0.001 ) ; MFIS , 37.7 versus 44.7 ( p<0.001 ) ; and VAS-F , 5.4 versus 4.5 ( p=0.003 ) . Fatigue scores for 400 mg/day modafinil were not significantly improved versus placebo run in . Mean ESS scores were significantly improved ( p<0.001 ) with 200 mg/day modafinil ( 7.2 ) and 400 mg/day ( 7.0 ) versus the score at baseline ( 9.5 ) . Serious adverse events were not found at either dose . The most common adverse events were headache , nausea , and aesthenia . Sixty five patients ( 90 % ) completed the study . Conclusions : These data suggest that 200 mg/day modafinil significantly improves fatigue and is well tolerated in patients with MS BACKGROUND Centenarians are characterized by weakness , decreasing mental health , impaired mobility , and poor endurance . L-Carnitine is an important contributor to cellular energy metabolism . OBJECTIVE This study evaluated the efficacy of L-carnitine on physical and mental fatigue and on cognitive functions of centenarians . DESIGN This was a placebo-controlled , r and omized , double-blind , 2-phase study . Sixty-six centenarians with onset of fatigue after even slight physical activity were recruited to the study . The 2 groups received either 2 g levocarnitine once daily ( n = 32 ) or placebo ( n = 34 ) . Efficacy measures included changes in total fat mass , total muscle mass , serum triacylglycerol , total cholesterol , HDL cholesterol , LDL cholesterol , Mini-Mental State Examination ( MMSE ) , Activities of Daily Living , and a 6-min walking corridor test . RESULTS At the end of the study period , the levocarnitine-treated centenarians , compared with the placebo group , showed significant improvements in the following markers : total fat mass ( -1.80 compared with 0.6 kg ; P < 0.01 ) , total muscle mass ( 3.80 compared with 0.8 kg ; P < 0.01 ) , plasma concentrations of total carnitine ( 12.60 compared with -1.70 mumol ; P < 0.05 ) , plasma long-chain acylcarnitine ( 1.50 compared with -0.1 micromol ; P < 0.001 ) , and plasma short-chain acylcarnitine ( 6.0 compared with -1.50 micromol ; P < 0.001 ) . Significant differences were also found in physical fatigue ( -4.10 compared with -1.10 ; P < 0.01 ) , mental fatigue ( -2.70 compared with 0.30 ; P < 0.001 ) , fatigue severity ( -23.60 compared with 1.90 ; P < 0.001 ) , and MMSE ( 4.1 compared with 0.6 ; P < 0.001 ) . CONCLUSIONS Our study indicates that oral administration of levocarnitine produces a reduction of total fat mass , increases total muscular mass , and facilitates an increased capacity for physical and cognitive activity by reducing fatigue and improving cognitive functions Nutritional factors and comedications are among the postulated causes of fatigue , a highly prevalent symptom in the multiple sclerosis ( MS ) population , with serious impact on patients ’ quality of life . Deficiency of carnitine may play a role by reducing energy production through fatty acid oxidation and numerous MS therapies can induce fatigue syndrome . The aim of this prospect i ve open-labelled study was to collect and study serum carnitine levels in MS patients with and without disease-modifying treatment-induced fatigue syndrome . We investigated whether restoration of the carnitine pool might improve treatment-induced fatigue in MS patients . In our study , there was no statistical difference in fatigue frequency between treated and untreated patients ( P=0.5 ) . Matched to age , gender and treatments , carnitine levels were lower for MS treated patients compared to untreated MS patients ( P<0.05 ) or controls ( P<0.001 ) . Consecutive patients with low plasma carnitine levels who experienced fatigue were substituted . Treatment consisted of oral levocarnitine , 3 - 6 g daily . All patients achieved normal plasma carnitine levels . For 63 % of patients treated with immunosuppressive or immunomodulatory therapies , oral levocarnitine adjunction decreased fatigue intensity , especially in patients treated with cyclophosphamide and interferon beta We carried out a double blind control study of fatigue in 32 patients with multiple sclerosis , comparing amantadine hydrochloride 100 mg twice a day and placebo . On amantadine 31 % had marked improvement ; 15.6 % moderate improvement ; 15.6 % mild improvement ; and 36.5 % unchanged . On placebo , none noted marked improvement ; one cl aim ed moderate improvement on either amantadine or placebo . 18.7 % reported mild improvement on placebo ; and most of them had similar or more response to amantadine . No patient selected placebo over amantadine at the end of the trial . Overall improvement was seen in 62.5 % of patients on amantadine and 21.8 % on placebo . Additional experience up to two years suggests continued benefit but common and important side-effects Aim Levocarnitine is an important contributor to cellular energy metabolism . This study aims to evaluate the effects of levocarnitine supplementation on body composition , lipid profile and fatigue in elderly subjects with rapid muscle fatigue . Method This was a placebo-controlled , r and omised , double-blind , two-phase study . Eighty-four elderly subjects with onset of fatigue following slight physical activity were recruited to the study . Prior to r and omisation all patients entered a 2-week normalisation phase where they were given an ‘ ad libitum ’ diet , according to the National Cholesterol Education Program ( Step 2 ) . Subjects were asked to record their daily food intake every 2 days . Before the 30-day treatment phase , subjects were r and omly assigned to two groups ( matched for male/female ratio , age and body mass index ) . One group received levocarnitine 2 g twice daily ( n = 42 ) and the other placebo ( n = 42 ) . Efficacy measures included changes in total fat mass , total muscle mass , serum triglyceride , total cholesterol , high-density lipoprotein-cholesterol ( HDL-C ) , low-density lipoprotein-cholesterol ( LDL-C ) , apolipoprotein (apo)A1 , and apoB levels . The Wessely and Powell scale was used to evaluate physical and mental fatigue . Subjects were assessed at the beginning and end of the study period . Results At the end of the study , compared with placebo , the levocarnitine-treated patients showed significant improvements in the following parameters : total fat mass ( −3.1 vs −0.5 kg ) , total muscle mass ( + 2.1 vs + 0.2 kg ) , total cholesterol ( −1.2 vs + 0.1 mmol/L ) , LDL-C ( −1.1 vs −0.2 mmol/L ) , HDL-C ( + 0.2 vs + 0.01 mmol/ L ) , triglycerides ( −0.3 vs 0.0 mmol/L ) , apoA1 ( −0.2 vs 0.0 g/L ) , and apoB ( −0.3 vs −0.1 g/L ) . Wessely and Powell scores decreased significantly by 40 % ( physical fatigue ) and 45 % ( mental fatigue ) in subjects taking levocarnitine , compared with 11 % and 8 % , respectively , in the placebo group ( p < 0.001 vs placebo for both parameters ) . No adverse events were reported in any treatment group . Conclusion Administration of levocarnitine to healthy elderly subjects result ed in a reduction of total fat mass , an increase of total muscle mass , and appeared to exert a favourable effect on fatigue and serum lipids Background Modafinil is a unique wake-promoting agent that is chemically distinct from traditional stimulants . Results of a placebo-controlled study showed it to improve fatigue in multiple sclerosis ( MS ) at a dose of 200 mg daily , but not at a dose of 400 mg daily . Objective To establish the efficacy , safety and appropriate dose of modafinil in the treatment of fatigue and sleepiness in patients with multiple sclerosis . Method A total of 50 patients diagnosed with MS ( mean age 40.4 ± 10.3 years , 30 females/20 males ; MS type : 36 relapsing remitting , 1 primary progressive , 13 secondary progressive ; mean disability level 3.8 ± 1.5 on the Kurtzke EDSS ) and complaining of chronic fatigue were enrolled in a prospect i ve 3-month , two-center , open-label study . Efficacy was evaluated with the Fatigue Severity Scale ( FSS , score range 0 - 42 ) , the Epworth Sleepiness Scale ( ESS , score range 0 - 24 ) and by subjective patient appraisal of change of fatigue , quality of life and overall satisfaction with treatment . Adverse effects ( AEs ) were recorded throughout the study . Treatment was started with a single daily dose of 100 mg in all patients . In non-responders the dose was increased by 100 mg increments up to a maximum daily dose of 400 mg . Results Three patients discontinued modafinil because of AEs ( nervousness , dizziness ) . Two patients ( 4 % ) were treated with 50 mg , 25 ( 50 % ) with 100 mg , 21 ( 42 % ) with 200 mg and 2 ( 4 % ) with 300 mg daily . No patient required 400 mg daily . Mean FSS scores were 30.3 ± 8.5 at baseline and 25.4 ± 3.7 at 3 months ( p < 0.0001 ) . Mean ESS scores were 9.7 ± 3.9 at baseline and 4.9 ± 2.9 at 3 months ( p < 0.0001 ) . Self- appraisal of change of fatigue showed clear improvement in 41 patients ( 87.2 % ) , some improvement in 4 ( 8.5 % ) and no change in 2 ( 4.3 % ) . Overall clinical condition was clearly improved in 43 patients ( 91.5 % ) , somewhat improved in 1 patient ( 2.1 % ) , and unchanged in 3 patients ( 6.4 % ) . No patient reported worsening of overall clinical condition . Conclusions Treatment with modafinil significantly improves fatigue and sleepiness and is well tolerated by patients with MS . Unlike the higher dose regimen required in narcolepsy , a low-dose regimen of modafinil is effective in MS Multiple sclerosis ( MS ) patients of an inpatient rehabilitation program have been r and omly assigned to an exercise training ( MS-ET ) or nontraining group ( MS-NI ) . Before and after 4 weeks of aerobic exercise training , a grade d maximal exercise test with measurement of gas exchange and a lung function test was administered to all 26 patients fulfilling the inclusion criteria . Activity level , fatigue and health perception were measured by means of question naires . Twenty-six healthy persons served as control group and were matched in respect of age , gender and activity level . Training intervention consisted of 5 × 30 min sessions per week of bicycle exercise with individualised intensity . Compared with baseline , the MS training group demonstrated a significant rightward placement of the aerobic threshold ( AT ) ( VO2 + 13 % ; work rate [WR])+11 % ) , an improvement of health perception ( vitality+46 % ; social interaction+36 % ) , an increase of activity level ( + 17 % ) and a tendency to less fatigue . No changes were observed for the MS-NI group and the control groups . Maximal aerobic capacity and lung function were not changed by either training or nontraining in all four groups . Overall compliance to the training program was quite low ( 65 % ) , whereas incidence of symptom exacerbation by physical activity has been lower than expected ( 6 % ) Fatigue occurs in a majority of patients with MS and is generally independent of measurable neurologic disability . Few options for treatment are available . We conducted a double-blind , placebo-controlled , crossover trial for each of two 4-week treatment periods . Forty-six eligible patients entered and five dropped out due to concurrent exacerbations . Nineteen patients ( 46.3 % ) experienced excellent or good relief of fatigue with pemoline , and eight patients ( 19.5 % ) with placebo ( p = 0.06 , Fisher 's exact test ) . One-fourth of patients did not tolerate the drug well , and 7 % had to discontinue pemoline during the study due to side effects . The most common side effects were anorexia , irritability , and insomnia . Pemoline may be an effective short-term treatment for fatigue associated with MS , but its adverse effects are not well tolerated by many patients Quality of Life ( QOL ) is impaired in multiple sclerosis ( MS ) in part due to physical disability . MS-associated fatigue ( MSF ) and depression ( MSD ) are common and treatable features of MS , which could also impact on QOL , independent of physical disability . We prospect ively studied 60 consecutive patients with MS . QOL was assessed using Multiple Sclerosis Quality of Life (MSQOL)-54 . Group differences in QOL scores were assessed after adjusting for Exp and ed Disability Status Scale ( EDSS ) , Fatigue Severity Scale ( FSS ) and Hamilton Depression Inventory scores . MS patients were grouped into relapsing-remitting ( RR ) or secondary -progressive ( SP ) , MSF ( FSS > or = 5 ) or MS-nonfatigue ( MSNF ) ( FSS < or = 4 ) , and MSD or MS-nondepression ( MSND ) . After accounting for disability and depression , fatigue was associated with impaired QOL with respect to health perception ( p=0.03 ) and limitations due to physical dysfunction ( p=0.008 ) . After accounting for disability and fatigue , depression was associated with lower QOL with respect to health perception ( p=0.02 ) , sexual dysfunction ( p=0.03 ) , health distress ( p=0.03 ) , mental health ( p=0.006 ) , overall QOL ( p=0.006 ) , emotional dysfunction ( p=0.04 ) , and limitations due to emotional dysfunction ( p=0.03 ) . This study demonstrates that fatigue and depression are independently associated with impaired QOL in MS , after accounting for physical disability , suggesting that their recognition and treatment can potentially improve QOL |
672 | 27,412,353 | A few studies reported that relative to no-exercise interventions , aerobic exercise could significantly decrease the atrophy of the medial temporal lobe , slow the anterior cingulate cortex ( ACC ) volume loss , increase functional connectivity within the hippocampus and improve signal activation in the cingulate gyrus and ACC .
The current review suggests that aerobic exercise may have positive effects on the right hippocampus and potentially beneficial effects on the overall and other parts of the hippocampus , the cingulate cortex and the medial temporal areas of the DMN .
Moreover , aerobic exercise may increase functional connectivity or activation in the hippocampus , cingulate cortex and parahippocampal gyrus regions of the DMN . | Physical activity may play a role in both the prevention and slowing of brain volume loss and may be beneficial in terms of improving the functional connectivity of brain regions .
But much less is known about the potential benefit of aerobic exercise for the structure and function of the default mode network ( DMN ) brain regions .
This systematic review examines the effects of aerobic exercise on the structure and function of DMN brain regions in human adulthood . | Background Mild cognitive impairment ( MCI ) is a well-recognised risk factor for dementia and represents a vital opportunity for intervening . Exercise is a promising strategy for combating cognitive decline by improving brain structure and function . Specifically , aerobic training ( AT ) improved spatial memory and hippocampal volume in healthy community-dwelling older adults . In older women with probable MCI , we previously demonstrated that resistance training ( RT ) and AT improved memory . In this secondary analysis , we investigated : ( 1 ) the effect of RT and AT on hippocampal volume and ( 2 ) the association between change in hippocampal volume and change in memory . Methods 86 women aged 70–80 years with probable MCI were r and omly assigned to a 6-month , twice-weekly programme of : ( 1 ) AT , ( 2 ) RT or ( 3 ) balance and tone training ( BAT ; ie , control ) . At baseline and trial completion , participants performed a 3 T MRI scan to determine hippocampal volume . Verbal memory and learning were assessed by Rey 's Auditory Verbal Learning Test . Results Compared with the BAT group , AT significantly improved left , right and total hippocampal volumes ( p≤0.03 ) . After accounting for baseline cognitive function and experimental group , increased left hippocampal volume was independently associated with reduced verbal memory and learning performance as indexed by loss after interference ( r=0.42 , p=0.03 ) . Conclusions Aerobic training significantly increased hippocampal volume in older women with probable MCI . More research is needed to ascertain the relevance of exercise-induced changes in hippocampal volume on memory performance in older adults with MCI . Trail registration number NCT00958867 Background To examine the effect of multicomponent exercise program on memory function in older adults with mild cognitive impairment ( MCI ) , and identify biomarkers associated with improvement of cognitive functions . Methodology /Principal Findings Subjects were 100 older adults ( mean age , 75 years ) with MCI . The subjects were classified to an amnestic MCI group ( n = 50 ) with neuroimaging measures , and other MCI group ( n = 50 ) before the r and omization . Subjects in each group were r and omized to either a multicomponent exercise or an education control group using a ratio of 1∶1 . The exercise group exercised for 90 min/d , 2 d/wk , 40 times for 6 months . The exercise program was conducted under multitask conditions to stimulate attention and memory . The control group attended two education classes . A repeated- measures ANOVA revealed that no group × time interactions on the cognitive tests and brain atrophy in MCI patients . A sub- analysis of amnestic MCI patients for group × time interactions revealed that the exercise group exhibited significantly better Mini-Mental State Examination ( p = .04 ) and logical memory scores ( p = .04 ) , and reducing whole brain cortical atrophy ( p<.05 ) compared to the control group . Low total cholesterol levels before the intervention were associated with an improvement of logical memory scores ( p<.05 ) , and a higher level of brain-derived neurotrophic factor was significantly related to improved ADAS-cog scores ( p<.05 ) . Conclusions / Significance The results suggested that an exercise intervention is beneficial for improving logical memory and maintaining general cognitive function and reducing whole brain cortical atrophy in older adults with amnestic MCI . Low total cholesterol and higher brain-derived neurotrophic factor may predict improvement of cognitive functions in older adults with MCI . Further studies are required to determine the positive effects of exercise on cognitive function in older adults with MCI . Trial Registration UMIN-CTR UMIN000003662 ctr.cgi?function = brows&action = brows&type = summary & recptno = R000004436 & language = BACKGROUND The present study examined whether aerobic fitness training of older humans can increase brain volume in regions associated with age-related decline in both brain structure and cognition . METHODS Fifty-nine healthy but sedentary community-dwelling volunteers , aged 60 - 79 years , participated in the 6-month r and omized clinical trial . Half of the older adults served in the aerobic training group , the other half of the older adults participated in the toning and stretching control group . Twenty young adults served as controls for the magnetic resonance imaging ( MRI ) , and did not participate in the exercise intervention . High spatial resolution estimates of gray and white matter volume , derived from 3D spoiled gradient recalled acquisition MRI images , were collected before and after the 6-month fitness intervention . Estimates of maximal oxygen uptake ( VO2 ) were also obtained . RESULTS Significant increases in brain volume , in both gray and white matter regions , were found as a function of fitness training for the older adults who participated in the aerobic fitness training but not for the older adults who participated in the stretching and toning ( nonaerobic ) control group . As predicted , no significant changes in either gray or white matter volume were detected for our younger participants . CONCLUSIONS These results suggest that cardiovascular fitness is associated with the sparing of brain tissue in aging humans . Furthermore , these results suggest a strong biological basis for the role of aerobic fitness in maintaining and enhancing central nervous system health and cognitive functioning in older adults The hippocampus shrinks in late adulthood , leading to impaired memory and increased risk for dementia . Hippocampal and medial temporal lobe volumes are larger in higher-fit adults , and physical activity training increases hippocampal perfusion , but the extent to which aerobic exercise training can modify hippocampal volume in late adulthood remains unknown . Here we show , in a r and omized controlled trial with 120 older adults , that aerobic exercise training increases the size of the anterior hippocampus , leading to improvements in spatial memory . Exercise training increased hippocampal volume by 2 % , effectively reversing age-related loss in volume by 1 to 2 y. We also demonstrate that increased hippocampal volume is associated with greater serum levels of BDNF , a mediator of neurogenesis in the dentate gyrus . Hippocampal volume declined in the control group , but higher preintervention fitness partially attenuated the decline , suggesting that fitness protects against volume loss . Cau date nucleus and thalamus volumes were unaffected by the intervention . These theoretically important findings indicate that aerobic exercise training is effective at reversing hippocampal volume loss in late adulthood , which is accompanied by improved memory function The objective of this study was to examine exercise effects on global brain volume , hippocampal volume , and cortical thickness in schizophrenia patients and healthy controls . Irrespective of diagnosis and intervention , associations between brain changes and cardiorespiratory fitness improvement were examined . Sixty-three schizophrenia patients and fifty-five healthy controls participated in this r and omised controlled trial . Global brain volumes , hippocampal volume , and cortical thickness were estimated from 3-Tesla MRI scans . Cardiorespiratory fitness was assessed with a cardiopulmonary ergometer test . Subjects were assigned exercise therapy or occupational therapy ( patients ) and exercise therapy or life-as-usual ( healthy controls ) for six months 2h weekly . Exercise therapy effects were analysed for subjects who were compliant at least 50 % of sessions offered . Significantly smaller baseline cerebral ( grey ) matter , and larger third ventricle volumes , and thinner cortex in most areas of the brain were found in patients versus controls . Exercise therapy did not affect global brain and hippocampal volume or cortical thickness in patients and controls . Cardiorespiratory fitness improvement was related to increased cerebral matter volume and lateral and third ventricle volume decrease in patients and to thickening in the left hemisphere in large areas of the frontal , temporal and cingulate cortex irrespective of diagnosis . One to 2h of exercise therapy did not elicit significant brain volume changes in patients or controls . However , cardiorespiratory fitness improvement attenuated brain volume changes in schizophrenia patients and increased thickness in large areas of the left cortex in both schizophrenia patients and healthy controls Cardiovascular fitness is thought to offset declines in cognitive performance , but little is known about the cortical mechanisms that underlie these changes in humans . Research using animal models shows that aerobic training increases cortical capillary supplies , the number of synaptic connections , and the development of new neurons . The end result is a brain that is more efficient , plastic , and adaptive , which translates into better performance in aging animals . Here , in two separate experiments , we demonstrate for the first time to our knowledge , in humans that increases in cardiovascular fitness results in increased functioning of key aspects of the attentional network of the brain during a cognitively challenging task . Specifically , highly fit ( Study 1 ) or aerobically trained ( Study 2 ) persons show greater task-related activity in regions of the prefrontal and parietal cortices that are involved in spatial selection and inhibitory functioning , when compared with low-fit ( Study 1 ) or nonaerobic control ( Study 2 ) participants . Additionally , in both studies there exist groupwise differences in activation of the anterior cingulate cortex , which is thought to monitor for conflict in the attentional system , and signal the need for adaptation in the attentional network . These data suggest that increased cardiovascular fitness can affect improvements in the plasticity of the aging human brain , and may serve to reduce both biological and cognitive senescence in humans Cardiovascular activity has been shown to be positively associated with gray and white matter volume of , amongst others , frontal and temporal brain regions in older adults . This is particularly true for the hippocampus , a brain structure that plays an important role in learning and memory , and whose decline has been related to the development of Alzheimer ’s disease . In the current study , we were interested in whether not only cardiovascular activity but also other types of physical activity , i.e. , coordination training , were also positively associated with the volume of the hippocampus in older adults . For this purpose we first collected cross-sectional data on “ metabolic fitness ” ( cardiovascular fitness and muscular strength ) and “ motor fitness ” ( e.g. , balance , movement speed , fine coordination ) . Second , we performed a 12-month r and omized controlled trial . Results revealed that motor fitness but not metabolic fitness was associated with hippocampal volume . After the 12-month intervention period , both , cardiovascular and coordination training led to increases in hippocampal volume . Our findings suggest that a high motor fitness level as well as different types of physical activity were beneficial to diminish age-related hippocampal volume shrinkage or even increase hippocampal volume We present a general method for automatic meta-analyses in neuroscience and apply it on text data from published functional imaging studies to extract main functions associated with a brain area-the posterior cingulate cortex ( PCC ) . Abstract s from PubMed are downloaded , words extracted and converted to a bag-of-words matrix representation . The combined data are analyzed with hierarchical non-negative matrix factorization . We find that the prominent themes in the PCC corpus are episodic memory retrieval and pain . We further characterize the distribution in PCC of the Talairach coordinates available in some of the articles . This shows a tendency to functional segregation between memory and pain components where memory activations are predominantly in the caudal part and pain in the rostral part of PCC Exercise is considered an important component of a healthy lifestyle but there remains controversy on effects of exercise on non-exercise physical activity ( PA ) . The present study examined the prospect i ve association of aerobic and resistance exercise with total daily energy expenditure and PA in previously sedentary , young men . Nine men ( 27.0 ± 3.3 years ) completed two 16-week exercise programs ( 3 exercise sessions per week ) of aerobic and resistance exercise separated by a minimum of 6 weeks in r and om order . Energy expenditure and PA were measured with the SenseWear Mini Armb and prior to each intervention as well as during week 1 , week 8 and week 16 of the aerobic and resistance exercise program . Body composition was measured via dual x-ray absorptiometry . Body composition did not change in response to either exercise intervention . Total daily energy expenditure on exercise days increased by 443 ± 126 kcal/d and 239 ± 152 kcal/d for aerobic and resistance exercise , respectively ( p < 0.01 ) . Non-exercise moderate-to-vigorous PA , however , decreased on aerobic exercise days ( −148 ± 161 kcal/d ; p = 0.03 ) . There was no change in total daily energy expenditure and PA on non-exercise days with aerobic exercise while resistance exercise was associated with an increase in moderate-to-vigorous PA during non-exercise days ( 216 ± 178 kcal/d , p = 0.01 ) . Results of the present study suggest a compensatory reduction in PA in response to aerobic exercise . Resistance exercise , on the other h and , appears to facilitate non-exercise PA , particularly on non-exercise days , which may lead to more sustainable adaptations in response to an exercise program BACKGROUND The hippocampal volume is reduced in patients with major depression . Exercise leads to an increased hippocampal volume in schizophrenia and in healthy old adults . The effect of exercise on hippocampal volume is potentially mediated by brain derived neurotrophic factor ( BDNF ) , vascular endothelial growth factor ( VEGF ) , and insulin like growth factor 1 ( IGF-1 ) . The aim of this trial was to assess the effect of an aerobic exercise intervention on hippocampal volume and serum BDNF , VEGF , and IGF-1 in patients with major depression . METHODS Patients were r and omized to an aerobic exercise intervention ( n=41 ) or a control condition ( n=38 ) . Both interventions consisted of three supervised sessions per week during a three months period . RESULTS Post-intervention the increase in maximal oxygen uptake was 3.90 ml/kg/min ( SD 5.1 ) in the aerobic exercise group and 0.95 ml/kg/min ( SD 6.2 ) in the control group ( p=0.03 ) . The hippocampal volume , BDNF , VEGF , or IGF-1 did not differ between the two groups . Post-hoc we found a positive association between change in hippocampal volume and verbal memory ( Rho=0.27 ; p=0.05 ) and change in hippocampal volume and depressive symptoms ( Rho=0.30 ; p=0.03 ) . LIMITATIONS Participation was low in both groups corresponding to an average participation of one session per week . CONCLUSION Despite a significant increase in maximal oxygen uptake , a pragmatic exercise intervention did not increase hippocampal volume or resting levels of neurotrophines in out- patients with mild to moderate major depression . Trial identifier : Clinical Trials.gov ( NCT00695552 ) Multiple sclerosis leads to prominent hippocampal atrophy , which is linked to memory deficits . Indeed , 50 % of multiple sclerosis patients suffer memory impairment , with negative consequences for quality of life . There are currently no effective memory treatments for multiple sclerosis either pharmacological or behavioral . Aerobic exercise improves memory and promotes hippocampal neurogenesis in nonhuman animals . Here , we investigate the benefits of aerobic exercise in memory-impaired multiple sclerosis patients . Pilot data were collected from two ambulatory , memory-impaired multiple sclerosis participants r and omized to non-aerobic ( stretching ) and aerobic ( stationary cycling ) conditions . The following baseline/follow-up measurements were taken : high-resolution MRI ( neuroanatomical volumes ) , fMRI ( functional connectivity ) , and memory assessment . Intervention was 30-minute sessions 3 times per week for 3 months . Aerobic exercise result ed in 16.5 % increase in hippocampal volume and 53.7 % increase in memory , as well as increased hippocampal resting-state functional connectivity . Improvements were specific , with no comparable changes in overall cerebral gray matter ( + 2.4 % ) , non-hippocampal deep gray matter structures ( thalamus , cau date : −4.0 % ) , or in non-memory cognitive functioning ( executive functions , processing speed , working memory : changes ranged from −11 % to + 4 % ) . Non-aerobic exercise result ed in relatively no change in hippocampal volume ( 2.8 % ) or memory ( 0.0 % ) , and no changes in hippocampal functional connectivity . This is the first evidence for aerobic exercise to increase hippocampal volume and connectivity and improve memory in multiple sclerosis . Aerobic exercise represents a cost-effective , widely available , natural , and self-administered treatment with no adverse side effects that may be the first effective memory treatment for multiple sclerosis patients OBJECTIVE An important problem in systems neuroscience is the relation between complex structural and functional brain networks . Here we use simulations of a simple dynamic process based upon the susceptible-infected-susceptible ( SIS ) model of infection dynamics on an empirical structural brain network to investigate the extent to which the functional interactions between any two brain areas depend upon ( i ) the presence of a direct structural connection ; and ( ii ) the degree product of the two areas in the structural network . METHODS For the structural brain network , we used a 78 × 78 matrix representing known anatomical connections between brain regions at the level of the AAL atlas ( Gong et al. , 2009 ) . On this structural network we simulated brain dynamics using a model derived from the study of epidemic processes on networks . Analogous to the SIS model , each vertex/brain region could be in one of two states ( inactive/active ) with two parameters β and δ determining the transition probabilities . First , the phase transition between the fully inactive and partially active state was investigated as a function of β and δ . Second , the statistical interdependencies between time series of node states were determined ( close to and far away from the critical state ) with two measures : ( i ) functional connectivity based upon the correlation coefficient of integrated activation time series ; and ( ii ) effective connectivity based upon conditional co-activation at different time intervals . RESULTS We find a phase transition between an inactive and a partially active state for a critical ratio τ = β/δ of the transition rates in agreement with the theory of SIS models . Slightly above the critical threshold , node activity increases with degree , also in line with epidemic theory . The functional , but not the effective connectivity matrix closely resembled the underlying structural matrix . Both functional connectivity and , to a lesser extent , effective connectivity were higher for connected as compared to disconnected ( i.e. : not directly connected ) nodes . Effective connectivity scaled with the degree product . For functional connectivity , a weaker scaling relation was only observed for disconnected node pairs . For r and om networks with the same degree distribution as the original structural network , similar patterns were seen , but the scaling exponent was significantly decreased especially for effective connectivity . CONCLUSIONS Even with a very simple dynamical model it can be shown that functional relations between nodes of a realistic anatomical network display clear patterns if the system is studied near the critical transition . The detailed nature of these patterns depends on the properties of the functional or effective connectivity measure that is used . While the strength of functional interactions between any two nodes clearly depends upon the presence or absence of a direct connection , this study has shown that the degree product of the nodes also plays a large role in explaining interaction strength , especially for disconnected nodes and in combination with an effective connectivity measure . The influence of degree product on node interaction strength probably reflects the presence of large numbers of indirect connections CONTEXT Hippocampal volume is lower than expected in patients with schizophrenia ; however , whether this represents a fixed deficit is uncertain . Exercise is a stimulus to hippocampal plasticity . OBJECTIVE To determine whether hippocampal volume would increase with exercise in humans and whether this effect would be related to improved aerobic fitness . DESIGN R and omized controlled study . SETTING Patients attending a day hospital program or an outpatient clinic . PATIENTS OR OTHER PARTICIPANTS Male patients with chronic schizophrenia and matched healthy subjects . INTERVENTIONS Aerobic exercise training ( cycling ) and playing table football ( control group ) for a period of 3 months . MAIN OUTCOME MEASURES Magnetic resonance imaging of the hippocampus . Secondary outcome measures were magnetic resonance spectroscopy , neuropsychological ( Rey Auditory Verbal Learning Test , Corsi block-tapping test ) , and clinical ( Positive and Negative Syndrome Scale ) features . RESULTS Following exercise training , relative hippocampal volume increased significantly in patients ( 12 % ) and healthy subjects ( 16 % ) , with no change in the nonexercise group of patients ( -1 % ) . Changes in hippocampal volume in the exercise group were correlated with improvements in aerobic fitness measured by change in maximum oxygen consumption ( r = 0.71 ; P = .003 ) . In the schizophrenia exercise group ( but not the controls ) , change in hippocampal volume was associated with a 35 % increase in the N-acetylaspartate to creatine ratio in the hippocampus . Finally , improvement in test scores for short-term memory in the combined exercise and nonexercise schizophrenia group was correlated with change in hippocampal volume ( r = 0.51 ; P < .05 ) . CONCLUSION These results indicate that in both healthy subjects and patients with schizophrenia hippocampal volume is plastic in response to aerobic exercise |
673 | 28,585,290 | Nevertheless , the overall interpretation of the literature supports the vulnerable brain concept , that is , that biomarker evidence of , for example , Alzheimer 's disease pathology and /or neuroinflammation , is associated with delirium | OBJECTIVE In recent years , there has been a blossoming of studies examining cerebrospinal fluid ( CSF ) as a method of study ing the pathophysiology of delirium .
We systematic ally review ed the literature for CSF studies in delirium and provide here a summary of the implication s for our underst and ing of delirium pathophysiology .
We also summarise the methods used for CSF analysis and discuss challenges and implication s for future studies . | Recent studies suggest that delirium is associated with risk of dementia and also acceleration of decline in existing dementia . However , previous studies may have been confounded by incomplete ascertainment of cognitive status at baseline . Herein , we used a true population sample to determine if delirium is a risk factor for incident dementia and cognitive decline . We also examined the effect of delirium at the pathological level by determining associations between dementia and neuropathological markers of dementia in patients with and without a history of delirium . The Vantaa 85 + study examined 553 individuals ( 92 % of those eligible ) aged ≥85 years at baseline , 3 , 5 , 8 and 10 years . Brain autopsy was performed in 52 % . Fixed and r and om-effects regression models were used to assess associations between ( i ) delirium and incident dementia and ( ii ) decline in Mini-Mental State Examination scores in the whole group . The relationship between dementia and common neuropathological markers ( Alzheimer-type , infa rcts and Lewy-body ) was modelled , stratified by history of delirium . Delirium increased the risk of incident dementia ( odds ratio 8.7 , 95 % confidence interval 2.1–35 ) . Delirium was also associated with worsening dementia severity ( odds ratio 3.1 , 95 % confidence interval 1.5–6.3 ) as well as deterioration in global function score ( odds ratio 2.8 , 95 % confidence interval 1.4–5.5 ) . In the whole study population , delirium was associated with loss of 1.0 more Mini-Mental State Examination points per year ( 95 % confidence interval 0.11–1.89 ) than those with no history of delirium . In individuals with dementia and no history of delirium ( n = 232 ) , all pathologies were significantly associated with dementia . However , in individuals with delirium and dementia ( n = 58 ) , no relationship between dementia and these markers was found . For example , higher Braak stage was associated with dementia when no history of delirium ( odds ratio 2.0 , 95 % confidence interval 1.1–3.5 , P = 0.02 ) , but in those with a history of delirium , there was no significant relationship ( odds ratio 1.2 , 95 % confidence interval 0.2–6.7 , P = 0.85 ) . This trend for odds ratios to be closer to unity in the delirium and dementia group was observed for neuritic amyloid , apolipoprotein ε status , presence of infa rcts , α-synucleinopathy and neuronal loss in substantia nigra . These findings are the first to demonstrate in a true population study that delirium is a strong risk factor for incident dementia and cognitive decline in the oldest-old . However , in this study , the relationship did not appear to be mediated by classical neuropathologies associated with dementia Background The inflammatory cell product neopterin is elevated in serum before and during delirium . This suggests a role for disordered cell-mediated immunity or oxidative stress . Cerebrospinal fluid ( CSF ) neopterin levels reflect brain neopterin levels more closely than serum levels . Here we hypothesized that CSF neopterin levels would be higher in delirium . Methods In this prospect i ve cohort study , 139 elderly patients with acute hip fracture were recruited in Oslo and Edinburgh . Delirium was diagnosed with the confusion assessment method performed daily pre-operatively and on the first 5 days post-operatively . Paired CSF and blood sample s were collected at the onset of spinal anaesthesia . Neopterin levels were measured using high-performance liquid chromatography . Results Sixty-four ( 46 % ) of 139 hip fracture patients developed delirium perioperatively . CSF neopterin levels were higher in delirium compared to controls ( median 29.6 vs 24.7 nmol/mL , p = 0.003 ) , with highest levels in patients who developed delirium post-operatively . Serum neopterin levels were also higher in delirium ( median 37.0 vs 27.1 nmol/mL , p = 0.003 ) . CSF neopterin remained significantly associated with delirium after controlling for relevant risk factors . Higher neopterin levels were associated with poorer outcomes ( death or new institutionalization ) 1 year after surgery ( p = 0.02 for CSF and p = 0.03 for serum ) . Conclusions This study is the first to examine neopterin in CSF from patients with delirium . Our findings suggest potential roles for activation of cell-mediated immune responses or oxidative stress in the delirium process . High levels of serum or CSF neopterin in hip fracture patients may also be useful in predicting poor outcomes Background To examine whether delirium in hip fracture patients was associated with changes in the levels of amino acids and /or monoamine metabolites in cerebrospinal fluid ( CSF ) and serum . Methods In this prospect i ve cohort study , 77 patients admitted with an acute hip fracture to Oslo University Hospital , Norway , were studied . The concentrations of amino acids in CSF and serum were determined by high performance liquid chromatography . The patients were assessed daily for delirium by the Confusion Assessment Method ( pre-operatively and post-operative day 1–5 ( all ) or until discharge ( delirious patients ) ) . Pre-fracture dementia status was decided by an expert panel . Serum was collected pre-operatively and CSF immediately before spinal anesthesia . Results Fifty-three ( 71 % ) hip fracture patients developed delirium . In hip fracture patients without dementia ( n = 39 ) , those with delirium had significantly higher CSF levels of tryptophan ( 40 % higher ) , tyrosine ( 60 % higher ) , phenylalanine ( 59 % higher ) and the monoamine metabolite 5-hydroxyindoleacetate ( 23 % higher ) compared to those without delirium . The same amino acids were also higher in CSF in delirious patients with dementia ( n = 38 ) . The correlations between serum and CSF amino acid levels were poor . Conclusion Higher CSF levels of monoamine precursors in hip fracture patients with delirium suggest a higher monoaminergic activity in the central nervous system during delirium in this patient group BACKGROUND Delirium is a risk factor for dementia in cognitively intact patients . Whether an episode of delirium accelerates cognitive decline in patients with known dementia , is less explored . METHODS This is a prospect i ve follow-up study of 287 hip fracture patients with pre-fracture cognitive impairment . During the hospitalization , the patients were screened daily for delirium using the Confusion Assessment Method . Pre-fracture cognitive impairment was defined as a score of 3.44 or higher on the pre-fracture Informant Question naire on Cognitive Decline in the Elderly Short Form ( IQCODE-SF ) . At follow-up after 4 - 6 months , the caregivers rated cognitive changes emerging after the fracture using the IQCODE-SF , and the patients were tested with the Mini Mental State Examination ( MMSE ) . A sub-group of the patients had a pre-fracture MMSE score which was used to calculate the yearly decline on the MMSE in patients with and without delirium . RESULTS 201 of the 287 patients developed delirium in the acute phase . In linear regression analysis , delirium was a significant and independent predictor of a more prominent cognitive decline at follow-up measured by the IQCODE-SF question naire ( p=0.002 ) . Among patients having a pre-fracture MMSE score , the patients developing delirium had a median ( IQR ) yearly decline of 2.4 points ( 1.1 - 3.9 ) , compared to 1.0 points ( 0 - 1.9 ) in the group without delirium ( p=0.001 , Mann-Whitney test ) . CONCLUSIONS Hip fracture patients with pre-fracture dementia run a higher risk of developing delirium . Delirium superimposed on dementia is a significant predictor of an accelerated further cognitive decline Importance Delirium is associated with accelerated cognitive decline . The pathologic substrates of this association are not yet known , that is , whether they are the same as those associated with dementia , are independent , or are interrelated . Objective To examine whether the accelerated cognitive decline observed after delirium is independent of the pathologic processes of classic dementia . Design , Setting , and Participants Harmonized data from 987 individual brain donors from 3 observational cohort studies with population -based sampling ( Vantaa 85 + , Cambridge City Over-75s Cohort , Cognitive Function and Ageing Study ) performed from January 1 , 1985 , through December 31 , 2011 , with a median follow-up of 5.2 years until death , were used in this study . Neuropathologic assessment s were performed with investigators masked to clinical data . Data analysis was performed from January 1 , 2012 , through December 31 , 2013 . Clinical characteristics of brain donors were not different from the rest of the cohort . Outcome ascertainment was complete given that the participants were brain donors . Exposures Delirium ( never vs ever ) and pathologic burden of neurofibrillary tangles , amyloid plaques , vascular lesions , and Lewy bodies . Effects modeled using r and om-effects linear regression and interactions between delirium and pathologic burden were assessed . Outcomes Change in Mini-Mental State Examination ( MMSE ) scores during the 6 years before death . Results There were 987 participants ( 290 from Vantaa 85 + , 241 from the Cambridge City Over-75s Cohort , and 456 from the Cognitive Function and Ageing Study ) with neuropathologic data ; mean ( SD ) age at death was 90 ( 6.4 ) years , including 682 women ( 69 % ) . The mean MMSE score 6 years before death was 24.7 points . The 279 individuals with delirium ( 75 % women ) had worse initial scores ( −2.8 points ; 95 % CI , −4.5 to −1.0 ; P < .001 ) . Cognitive decline attributable to delirium was −0.37 MMSE points per year ( 95 % CI , −0.60 to −0.13 ; P < .001 ) . Decline attributable to the pathologic processes of dementia was −0.39 MMSE points per year ( 95 % CI , −0.57 to −0.22 ; P < .001 ) . However , the combination of delirium and the pathologic processes of dementia result ed in the greatest decline , in which the interaction contributed an additional −0.16 MMSE points per year ( 95 % CI , −0.29 to −0.03 ; P = .01 ) . The multiplicative nature of these variables result ed in individuals with delirium and the pathologic processes of dementia declining 0.72 MMSE points per year faster than age- , sex- , and educational level – matched controls . Conclusions and Relevance Delirium in the presence of the pathologic processes of dementia is associated with accelerated cognitive decline beyond that expected for delirium or the pathologic process itself . These findings suggest that additional unmeasured pathologic processes specifically relate to delirium . Age-related cognitive decline has many contributors , and these findings at the population level support a role for delirium acting independently and multiplicatively to the pathologic processes of classic dementia OBJECTIVES To examine whether anticholinergic activity ( AA ) in cerebrospinal fluid ( CSF ) and serum is associated with risk of delirium in individuals with hip fracture . DESIGN Prospect i ve cohort study . SETTING Two university hospitals in Oslo , Norway , and Edinburgh , UK . PARTICIPANTS Individuals admitted with acute hip fracture ( N = 151 ) . MEASUREMENTS Participants were assessed daily for delirium using the Confusion Assessment Method ( preoperatively and postoperative days 1 - 5 ( all ) or until discharge ( participants with delirium ) ) . Prefracture cognitive function was assessed using the Informant Question naire on Cognitive Decline in the Elderly ( IQCODE ) . Serum was collected preoperatively and CSF at the onset of spinal anesthesia . AA in serum ( SAA ) and CSF sample s was determined according to a muscarinic radio receptor bioassay . The association between AA measures and delirium was evaluated using logistic multivariate analyses . RESULTS Fifty-two ( 54 % ) of the participants in Oslo and 20 ( 39 % ) in Edinburgh developed delirium . There was no statistically significant difference in AA between participants with and without delirium in Oslo ( serum : 7.02 vs 6.08 pmol/mL , P = .54 ; CSF : 0.39 vs 0.48 pmol/mL , P = .26 ) or in Edinburgh ( serum : 1.35 vs 1.62 pmol/mL , P = .76 ; CSF : 0.36 vs 0.31 pmol/mL , P = .93 ) . Nor was there any difference in SAA ( Oslo , P = .74 ; Edinburgh , P = .51 ) or CSF AA ( Oslo , P = .21 ; Edinburgh , P = .93 ) when participants were subdivided into prevalent , incident , subsyndromal , and never delirium . Stratifying participants according to prefracture cognitive status ( IQCODE ) gave the same results . CONCLUSION This is the first study of AA in CSF of individuals with and without delirium . The study does not support the hypothesis that central ( CSF ) or peripheral ( serum ) AA is an important mechanism of delirium in individuals with hip fracture OBJECTIVES To examine whether delirium in individuals with hip fracture is associated with high C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , and soluble IL-6 receptor ( sIL-6R ) levels in the cerebrospinal fluid ( CSF ) . DESIGN Prospect i ve cohort study . SETTING Two university hospitals in Oslo , Norway , and Edinburgh , United Kingdom . PARTICIPANTS Individuals admitted with acute hip fracture ( N = 151 ) . MEASUREMENTS Participants were assessed for delirium pre- and postoperatively using the Confusion Assessment Method . Prefracture cognitive impairment was detected using the Informant Question naire on Cognitive Decline in the Elderly ( IQCODE ) . Serum was collected preoperatively and CSF just before the onset of spinal anesthesia . Cytokine levels in serum and CSF sample s were determined using an enzyme-linked immunosorbent assay . Student t-tests or Mann-Whitney U-tests were used for between-group comparisons . Spearman rho was used for correlations . RESULTS Sixty participants had prior cognitive impairment ( IQCODE score ≥3.44 ) . Delirium was diagnosed in 46 participants ( 77 % ) with prior cognitive impairment and 25 ( 29 % ) without . In participants without prior cognitive impairment , CSF CRP levels were higher in participants with delirium ( median 0.05 μg/mL , interquartile range ( IQR ) 0.02 - 0.12 μg/mL ) than in those without delirium ( median 0.01 μg/mL , IQR 0.00 - 0.06 μg/mL ) ( P = .01 ) ; there were no differences in participants with prior cognitive impairment . In secondary analyses , in participants with prior cognitive impairment , the concentration of CSF sIL-6R was higher in those participants who developed delirium than in the other subgroups , but this difference was not statistically significant . Serum levels of CRP , IL-6 , and sIL-6R were not different according to delirium in participants with or without prefracture cognitive impairment . CONCLUSION High CSF levels of CRP and sIL-6R may be associated with delirium . Different pathophysiological mechanisms may operate in different subgroups , notably in relation to the presence of prior cognitive impairment OBJECTIVES To examine the association between cerebrospinal fluid ( CSF ) β-amyloid ( Aβ1 - 42 ) , tau , and hyperphosphorylated tau ( Ptau ) and risk of delirium in older adults with hip fracture . DESIGN Prospect i ve cohort study . SETTING University-affiliated general hospital in Alkmaar , the Netherl and s. PARTICIPANTS Seventy-six participants aged 75 and older admitted for surgical repair of acute hip fracture . MEASUREMENTS Presurgical baseline screening and assessment included the Informant Question naire on Cognitive Decline-short form ( IQCODE-N ) , Mini-Mental State Examination , st and ardized Snellen test for visual impairment , Geriatric Depression Scale , Barthel Index ( BI ) , and Lawton Instrumental Activity of Daily Living ( IADL ) scale . The number of medical comorbidities and medications at home , American Society of Anesthesiologists score , and Acute Physiology and Chronic Health Evaluation II score were determined according to chart review . Delirium was diagnosed using the Confusion Assessment Method . CSF was collected at the onset of spinal anesthesia . RESULTS Postoperative delirium occurred in 30 ( 39.5 % ) participants . Participants with delirium were older , showed more signs of cognitive decline , were more dependent at home in activity of daily living and IADL functioning , and used more medications before admission . Preoperative CSF Aβ1 - 42 , tau , and Ptau levels were not significantly different in participants who did and did not develop delirium during subsequent hospitalization . In contrast , prefracture cognitive decline ( IQCODE-N ) was significantly related to delirium ( odds ratio=9.43 , 95 % confidence interval=2.45 - 36.31 ) . CONCLUSION Cognitive impairment predisposes to delirium , but in this study , postoperative delirium was not associated with baseline CSF Aβ1 - 42 , tau , and Ptau levels . These findings suggest that CSF markers for plaque and tangle formation are not strongly associated with delirium risk in older adults with hip fracture OBJECTIVES To develop and vali date a new risk-of-bias tool for nonr and omized studies ( NRSs ) . STUDY DESIGN AND SETTING We developed the Risk of Bias Assessment Tool for Nonr and omized Studies ( RoBANS ) . A validation process with 39 NRSs examined the reliability ( interrater agreement ) , validity ( the degree of correlation between the overall assessment s of RoBANS and Method ological Index for Nonr and omized Studies [ MINORS ] , obtained by plotting the overall risk of bias relative to effect size and funding source ) , face validity with eight experts , and completion time for the RoBANS approach . RESULTS RoBANS contains six domains : the selection of participants , confounding variables , the measurement of exposure , the blinding of the outcome assessment s , incomplete outcome data , and selective outcome reporting . The interrater agreement of the RoBANS tool except the measurement of exposure and selective outcome reporting domains ranged from fair to substantial . There was a moderate correlation between the overall risks of bias determined using RoBANS and MINORS . The observed differences in effect sizes and funding sources among the assessed studies were not correlated with the overall risk of bias in these studies . The mean time required to complete RoBANS was approximately 10 min . The external experts who were interviewed evaluated RoBANS as a " fair " assessment tool . CONCLUSIONS RoBANS shows moderate reliability , promising feasibility , and validity . The further refinement of this tool and larger validation studies are required Background / Aims : Delirium is a common and serious complication in hospitalised patients and its pathophysiology is incompletely understood . We aim ed to examine whether blood-cerebrospinal fluid barrier dysfunction , as measured by Q-albumin ( the ratio of cerebrospinal fluid albumin to serum albumin ) , was associated with delirium . Methods : In this prospect i ve cohort study of hip fracture patients from Oslo University Hospital , Norway , serum was collected preoperatively and cerebrospinal fluid just before the onset of spinal anaesthesia . Albumin levels in serum and cerebrospinal fluid were analysed consecutively , and Q-albumin was calculated using the formula [ cerebrospinal fluid albumin ( mg/dl ) × 1,000]/[serum albumin ( mg/dl ) ] . Q-albumin > 10.2 was used as the cut-off for blood-cerebrospinal fluid barrier dysfunction . Patients were assessed daily for delirium using the Confusion Assessment Method . Results : Out of 120 patients , 69 had delirium , 22 had subsyndromal delirium , and 29 were free from delirium . The majority of patients , i.e. 106 ( 88 % ) , had intact blood-cerebrospinal fluid barrier integrity , but all 14 patients with blood-cerebrospinal barrier dysfunction had delirium ( n = 11 ) or subsyndromal delirium ( n = 3 ) . Conclusions : The results suggest that blood-cerebrospinal fluid barrier dysfunction may be relevant for delirium pathophysiology when it occurs . However , the low prevalence ( 16 % of delirium patients ) indicates that this is not a prerequisite for the development of delirium |
674 | 29,492,826 | Published trials continue to support the use of bisphosphonates and short courses of oral steroids in the setting of CRPS .
Similarly , trials also suggest an exp and ing role for peripheral sympathetic blockade ( i.e. , lumbar/thoracic sympathetic , stellate ganglion , and brachial plexus blocks ) .
Les essais suggèrent également un plus gr and rôle pour le bloc sympathique périphérique ( c’est-à-dire , blocs sympathiques lombaires/thoraciques , bloc du ganglion cervico-thoracique et du plexus brachial ) . | Purpose Although multiple treatments have been advocated for complex regional pain syndrome ( CRPS ) , the levels of supportive evidence are variable and sometimes limited .
The purpose of this up date d review is to provide a critical analysis of the evidence pertaining to the treatment of CRPS derived from recent r and omized-controlled trials ( RCTs ) . | The microcirculation appears to be impaired in cold chronic complex regional pain syndrome ( CRPS ) . This double-blind , placebo-controlled , r and omized trial investigated the effect of the nitric oxide ( NO ) donor isosorbide dinitrate ( ISDN ) on the peripheral blood flow in patients with chronic CRPS . Twenty-four patients received 1 % ISDN in Vaseline or a placebo ointment applied to the dorsum of the affected h and four times daily for 10 weeks . The patients participated in a physical therapy program to improve activity . The primary outcome measure was blood distribution in the affected extremity , which was determined by measuring the skin temperature using videothermography . We also measured NO and endothelin-1 concentrations in blister fluid , pain using the visual analog scale , and activity limitations using an upper limb activity monitor and the Disabilities of Arm Shoulder and H and Question naire . ISDN failed to produce a significant improvement in temperature asymmetry in chronic cold CRPS patients , and it did not result in the expected reduction in pain and increase in activity compared with placebo either . There may be other central or peripheral factors contributing to the disturbed vasodynamics in cold chronic CRPS that are not influenced by NO substitution . This study does not show an improvement of the regional blood distribution by ISDN in the involved extremity of patients with cold-type CRPS Abstract Animal and human studies indicate that electrical stimulation of dorsal root ganglion ( DRG ) neurons may modulate neuropathic pain signals . ACCURATE , a pivotal , prospect i ve , multicenter , r and omized comparative effectiveness trial , was conducted in 152 subjects diagnosed with complex regional pain syndrome or causalgia in the lower extremities . Subjects received neurostimulation of the DRG or dorsal column ( spinal cord stimulation , SCS ) . The primary end point was a composite of safety and efficacy at 3 months , and subjects were assessed through 12 months for long-term outcomes and adverse events . The predefined primary composite end point of treatment success was met for subjects with a permanent implant who reported 50 % or greater decrease in visual analog scale score from preimplant baseline and who did not report any stimulation-related neurological deficits . No subjects reported stimulation-related neurological deficits . The percentage of subjects receiving ≥50 % pain relief and treatment success was greater in the DRG arm ( 81.2 % ) than in the SCS arm ( 55.7 % , P < 0.001 ) at 3 months . Device-related and serious adverse events were not different between the 2 groups . Dorsal root ganglion stimulation also demonstrated greater improvements in quality of life and psychological disposition . Finally , subjects using DRG stimulation reported less postural variation in paresthesia ( P < 0.001 ) and reduced extraneous stimulation in nonpainful areas ( P = 0.014 ) , indicating DRG stimulation provided more targeted therapy to painful parts of the lower extremities . As the largest prospect i ve , r and omized comparative effectiveness trial to date , the results show that DRG stimulation provided a higher rate of treatment success with less postural variation in paresthesia intensity compared to SCS OBJECTIVES Complex regional pain syndrome ( CRPS ) , formerly known as reflex sympathetic dystrophy ( RSD ) , is a painful , disabling disorder for which treatment is difficult . The aim of this study was to determine the efficacy of pamidronate in a double-blind r and omized placebo-controlled trial . METHODS Patients referred to our regional multidisciplinary pain management center who fulfilled the International Association for the Study of Pain criteria for CRPS Type I were enrolled in the study over a 2-year period . Patients were administered , intravenously , either pamidronate , 60 mg as a single dose , or normal saline . Patients ' pain scores , global assessment of disease severity scores , and functional assessment ( SF-36 ) scores were documented at baseline and at 1 and 3 months . RESULTS Twenty-seven patients ( 18 female , 9 male ; average age 45 years ) were recruited , of whom 14 received pamidronate and 13 received placebo . Overall improvements in pain score , patient 's global assessment of disease severity score , and physical function ( SF-36 ) score were noted in the pamidronate group at 3 months , and improvements in role physical ( SF-36 ) score were noted at 1 and 3 months . There was variability in pamidronate response among individuals . CONCLUSIONS Pamidronate may be a useful treatment option in the management of patients with CRPS Type I. Although treatment response was variable , the majority of patients improved . Early administration in t and em with other treatment measures is recommended Chronic reflex sympathetic dystrophy is a painful , disabling disorder for which no treatment with proven effect is available . We performed a r and omized trial in a 2 to 1 ratio of patients , in which 36 patients were treated with spinal cord stimulation and physical therapy ( SCS+PT ) , and 18 patients received solely PT . Twenty‐four SCS+PT patients were given a permanent spinal cord stimulation system after successful test stimulation ; the remaining 12 patients received no permanent system . We assessed pain intensity , global perceived effect , functional status , and health‐related quality of life . Patients were examined before r and omization , before implantation , and also at 1 , 3 , 6 , 12 , and 24 months thereafter . At 2 years , three patients were excluded from the analysis . The intention‐to‐treat analysis showed improvements in the SCS+PT group concerning pain intensity ( −2.1 vs 0.0 cm ; p < 0.001 ) and global perceived effect ( 43 % vs 6 % “ much improved ” ; p = 0.001 ) . There was no clinical ly important improvement of functional status . Health‐related quality of life improved only in the group receiving spinal cord stimulation . After careful selection and successful test stimulation , spinal cord stimulation results in a long‐term pain reduction and health‐related quality of life improvement in chronic reflex sympathetic dystrophy & NA ; Complex regional pain syndrome type 1 ( CRPS1 ) involves cortical abnormalities similar to those observed in phantom pain and after stroke . In those groups , treatment is aim ed at activation of cortical networks that subserve the affected limb , for example mirror therapy . However , mirror therapy is not effective for chronic CRPS1 , possibly because movement of the limb evokes intolerable pain . It was hypothesised that preceding mirror therapy with activation of cortical networks without limb movement would reduce pain and swelling in patients with chronic CRPS1 . Thirteen chronic CRPS1 patients were r and omly allocated to a motor imagery program ( MIP ) or to ongoing management . The MIP consisted of two weeks each of a h and laterality recognition task , imagined h and movements and mirror therapy . After 12 weeks , the control group was crossed‐over to MIP . There was a main effect of treatment group ( F(1,11)=57 , P<0.01 ) and an effect size of ∼25 points on the Neuropathic pain scale . The number needed to treat for a 50 % reduction in NPS score was ∼2 . The effect of treatment was replicated in the crossed‐over control subjects . The results uphold the hypothesis that a MIP initially not involving limb movement is effective for CRPS1 and support the involvement of cortical abnormalities in the development of this disorder . Although the mechanisms of effect of the MIP are not clear , possible explanations are sequential activation of cortical pre‐motor and motor networks , or sustained and focussed attention on the affected limb , or both OBJECTIVES To explore the feasibility of intravenous magnesium administration as a potential c and i date intervention for a large size trial in Complex Regional Pain Syndrome Type 1 ( CRPS 1 ) . DESIGN R and omized clinical trial . SETTING Outpatient pain clinic . PATIENTS Ten CRPS 1 patients . INTERVENTIONS Eight patients received 70 mg/kg magnesium sulphate infusions in 4 hours for 5 days . For blinding purpose s , 2 patients received equal amount NaCl 0.9 % solutions ( data not analyzed or presented ) . Interventions were accompanied by st and ardized physical therapy . OUTCOME MEASURES Pain was assessed using an 11-point Box scale ( three times daily for a week ) and the McGill Pain Question naire . Skin sensitivity was measured with the Semmes Weinstein Monofilaments , ( other ) impairments with the Impairment Level Sumscore . In addition , functional limitations ( Radboud Skills Question naire , question naire rising and sitting down ) and quality of life ( Short Form-36 [ SF-36 ] , EuroQol ) were evaluated . Assessment s were performed at baseline , 1 , 3 , 6 , and 12 weeks after intervention . RESULTS Mild systemic side effects were experienced and the infusions were locally well tolerated . Pain was significantly reduced at all follow up compared with baseline ( T1 : P = 0.01 , T3 : P = 0.04 , T6 : P = 0.02 , T12 : P = 0.02 ) . McGill sensory subscale improved significantly at T1 ( number of words chosen : P = 0.03 and pain rating index : P = 0.03 ) . Impairment level ( P = 0.03 ) and quality of life ( EuroQol P = 0.04 , SF-36 physical P = 0.01 ) were significantly improved at T12 . No improvement was found for skin sensitivity and functional limitations . CONCLUSION Intravenous magnesium significantly improved pain , impairment and quality of life and was well tolerated . The results of this pilot study are encouraging and suggest that magnesium IV as a treatment in CRPS 1 should be further explored in a large size formal trial design & NA ; In complex regional pain syndrome ( CRPS1 ) initiated by wrist fracture , a motor imagery program ( MIP ) , consisting of h and laterality recognition followed by imagined movements and then mirror movements , reduces pain and disability , but the mechanism of effect is unclear . Possibilities include sustained attention to the affected limb , in which case the order of MIP components would not alter the effect , and sequential activation of cortical motor networks , in which case it would . Twenty subjects with chronic CRPS1 initiated by wrist fracture and who satisfied stringent inclusion criteria , were r and omly allocated to one of three groups : h and laterality recognition , imagined movements , mirror movements ( RecImMir , MIP ) ; imagined movements , recognition , imagined movements ( ImRecIm ) ; recognition , mirror movements , recognition ( RecMirRec ) . At 6 and 18 weeks , reduced pain and disability were greater for the RecImMir group than for the other groups ( P<0.05 ) . H and laterality recognition imparted a consistent reduction in pain and disability across groups , however , this effect was limited in magnitude . Imagined movements imparted a further reduction in pain and disability , but only if they followed h and laterality recognition . Mirror movements also imparted a reduction in pain and disability , but only when they followed imagined movements . The effect of the MIP seems to be dependent on the order of components , which suggests that it is not due to sustained attention to the affected limb , but is consistent with sequential activation of cortical motor networks Background . Complex regional pain syndrome type 1 ( CRPSt1 ) of the upper limb is a painful and debilitating condition , frequent after stroke , and interferes with the rehabilitative process and outcome . However , treatments used for CRPSt1 of the upper limb are limited . Objective . This r and omized controlled study was conducted to compare the effectiveness on pain and upper limb function of mirror therapy on CRPSt1 of upper limb in patients with acute stroke . Methods . Of 208 patients with first episode of unilateral stroke admitted to the authors ’ rehabilitation center , 48 patients with CRPSt1 of the affected upper limb were enrolled in a r and omized controlled study , with a 6-month follow-up , and assigned to either a mirror therapy group or placebo control group . The primary end points were a reduction in the visual analogue scale score of pain at rest , on movement , and brush-induced tactile allodynia . The secondary end points were improvement in motor function as assessed by the Wolf Motor Function Test and Motor Activity Log . Results . The mean scores of both the primary and secondary end points significantly improved in the mirror group ( P < .001 ) . No statistically significant improvement was observed in any of the control group values ( P > .001 ) . Moreover , statistically significant differences after treatment ( P < .001 ) and at the 6-month follow-up were found between the 2 groups . Conclusions . The results indicate that mirror therapy effectively reduces pain and enhances upper limb motor function in stroke patients with upper limb CRPSt1 Objective To compare the effectiveness of pain exposure physical therapy ( PEPT ) with conventional treatment in patients with complex regional pain syndrome type 1 ( CRPS-1 ) in a r and omised controlled trial with a blinded assessor . Setting The study was conducted at a level 1 trauma centre in the Netherl and s. Participants 56 adult patients with CRPS-1 participated . Three patients were lost to follow-up . Interventions Patients received either PEPT in a maximum of five treatment sessions , or conventional treatment following the Dutch multidisciplinary guideline . Measurements Outcomes were assessed at baseline and at 3 , 6 and 9 months after r and omisation . The primary outcome measure was the Impairment level Sum Score — Restricted Version ( ISS-RV ) , consisting of visual analogue scale for pain ( VAS-pain ) , McGill Pain Question naire , active range of motion ( AROM ) and skin temperature . Secondary outcome measures included Pain Disability Index ( PDI ) ; muscle strength ; Short Form 36 ( SF-36 ) ; disability of arm , shoulder and h and ; Lower Limb Tasks Question naire ( LLTQ ) ; 10 m walk test ; timed up- and -go test ( TUG ) and EuroQol-5D . Results The intention-to-treat analysis showed a clinical ly relevant decrease in ISS-RV ( 6.7 points for PEPT and 6.2 points for conventional treatment ) , but the between-group difference was not significant ( 0.96 , 95 % CI −1.56 to 3.48 ) . Participants allocated to PEPT experienced a greater improvement in AROM ( between-group difference 0.51 , 95 % CI 0.07 to 0.94 ; p=0.02 ) . The per protocol analysis showed larger and significant between-group effects on ISS-RV , VAS-pain , AROM , PDI , SF-36 , LLTQ and TUG . Conclusions We can not conclude that PEPT is superior to conventional treatment for patients with CRPS-1 . Further high- quality research on the effects of PEPT is warranted given the potential effects as indicated by the per protocol analysis . Trial registration numbers NCT00817128 and NTR 2090 OBJECTIVE Complex regional pain syndrome type I ( CRPS-I ) is a severely disabling pain syndrome for which no definite treatment has been established . The aim of this multi-centre , r and omized , double-blind placebo-controlled trial was to test the efficacy of the amino-bisphosphonate neridronate in patients with CRP-I. METHODS Eighty-two patients with CRP-I at either h and or foot were r and omly assigned to i.v . infusion of 100 mg neridronate given four times over 10 days or placebo . After 50 days the former placebo patients were given open label the same regimen of neridronate . RESULTS Within the first 20 days , visual analogue scale ( VAS ) score decreased significantly more in the neridronate group . In the following 20 days , VAS remained unchanged in the placebo group and further decreased in the active group by 46.5 mm ( 95 % CI -52.5 , -40.5 ) vs 22.6 mm ( 95 % CI -28.8 , -16.3 ) for placebo group ( P < 0.0001 ) . Significant improvements vs placebo were observed also for a number of other indices of pain and quality of life . During the open-extension phase in the formerly placebo group the results of treatment were superimposable on those seen during the blind phase in the active group . A year later none of the patients was referring symptoms linked to CRPS-I. CONCLUSION In patients with acute CRPS-I , four i.v . infusions of neridronate 100 mg are associated with clinical ly relevant and persistent benefits . These results provide conclusive evidence that the use of bisphosphonates , at appropriate doses , is the treatment of choice for CRPS-I. TRIAL REGISTRATION EU Clinical Trials Register , https://www . clinical trialsregister.eu/ , 2007 - 003372 - 18 Objective To compare the efficacy of ultrasonography guided stellate ganglion block ( US-SGB ) with that of blind SGB in management of the stroke patients with complex regional pain syndrome ( CRPS ) type 1 . Method Forty-two patients with post-stroke CRPS were r and omly assigned to either US-guided SGB ( 22 patients ) or blind SGB group ( 20 patients ) . The mean age of US-guided SGB and blind SGB groups was 61.3±5.6 years and 59.1±4.5 years . We performed two blockades at 7-day intervals on the affected side of patients with CRPS . Pain intensity , using a visual analog score ( VAS ) , score of CRPS clinical severity , and the amounts of affected h and swelling with a h and volumeter were assessed before , 2 weeks and 4 weeks after treatment . Results In both groups , VAS and the amount of h and swelling were significantly decreased after 2 weeks and after 4 weeks . Between two groups , VAS difference of US-guided SGB group and that of blind SGB group were 2.61±1.09 , 1.88±0.62 at 2 weeks and 3.67±1.03 , 3.13±0.62 at 4 weeks , respectively . US-guided SGB group showed more significant improvement in mean change of VAS compared to the blind SGB group ( p-value<0.05 ) . Conclusion Both US-guided SGB and blind SGB techniques were effective in relieving pain in subacute stroke patients with CRPS . US-guided SGB was better in pain relief but has no advantages in reduction of h and swelling in this study Background and Objectives Intravenous regional blocks ( IVRBs ) with ketorolac and lidocaine have been reported to be useful in the treatment of complex regional pain syndrome ( CRPS ) . This is the first controlled prospect i ve study of IVRB with lidocaine and ketorolac for treatment of pain and edema in CRPS of the lower extremity in adults . Methods A prospect i ve , r and omized , double-blinded , crossover design was used . The primary outcome was overall pain numeric rating scale ( NRS ) at 1 week postinjection ; secondary outcomes included pain with motion , allodynia , joint pain score , edema , range of ankle motion , skin temperature , and short-term pain relief . Ten of 12 adult patients diagnosed with unilateral lower extremity CRPS ( type I ) completed the study . Four IVRBs were performed 1 week apart in a r and om sequence with 50 mL lidocaine 0.5 % and 0 , 30 , 60 , and 120 mg ketorolac . Results Only 1 outcome achieved significant improvement ; there was 1 day of significant pain reduction in the ketorolac groups ( median NRS 6 to 4 , P=0.002 ) . Overall pain NRS ( 10-point scale , mean±SE ) at 1 week was 6.2±0.53 , 6.5±0.89 , 6.0±0.88 , 5.9±0.82 , and 5.8±0.9 at baseline , 0 , 30 , 60 , and 120 mg , respectively ( P=0.8 ) . Pain with movement was 7.15±0.69 , 5.7±1.07 , 6.1±0.86 , 5.0±0.97 , and 5.6±0.86 , ( P=0.059 ) . Edema was not significantly reduced ( 2 % reduction , P=0.6 ) . Conclusions IVRB with ketorolac and lidocaine produced only short-term pain reduction in patients with CRPS involving the lower extremity after 4 serial injections in our study group . Prospect i ve study is warranted , particularly in the pediatric population BACKGROUND AND METHODS Patients with reflex sympathetic dystrophy ( also known as the complex regional pain syndrome ) may have dystonia , which is often unresponsive to treatment . Some forms of dystonia respond to the intrathecal administration of baclofen , a specific gamma-aminobutyric acid-receptor ( type B ) agonist that inhibits sensory input to the neurons of the spinal cord . We evaluated this treatment in seven women who had reflex sympathetic dystrophy with multifocal or generalized tonic dystonia . First , we performed a double-blind , r and omized , controlled crossover trial of bolus intrathecal injections of 25 , 50 , and 75 microg of baclofen and placebo . Changes in the severity of dystonia were assessed by the woman and by an investigator after each injection . In the second phase of the study , six of the women received a subcutaneous pump for continuous intrathecal administration of baclofen and were followed for 0.5 to 3 years . RESULTS In six women , bolus injections of 50 and 75 microg of baclofen result ed in complete or partial resolution of focal dystonia of the h and s but little improvement in dystonia of the legs . During continuous therapy , three women regained normal h and function , and two of these three women regained the ability to walk ( one only indoors ) . In one woman who received continuous therapy , the pain and violent jerks disappeared and the dystonic posturing of the arm decreased . In two women the spasms or restlessness of the legs decreased , without any change in the dystonia . CONCLUSIONS In some patients , the dystonia associated with reflex sympathetic dystrophy responds markedly to intrathecal baclofen UNLABELLED To assess the effects of intravenous administration of the free radical scavenger mannitol 10 % on complaints associated with complex regional pain syndrome Type I ( CRPS I ) , a r and omized , placebo-controlled , double-blinded trial was performed . Forty-one CRPS I patients according to the Bruehl et al diagnostic criteria , were included in 2 outpatient pain clinics of 2 university medical centers and r and omly assigned to receive either 10 % mannitol iv in 1 L 0.9 % NaCL in 4 hours for 5 consecutive days or equal volumes of 0.9 % NaCL ( placebo ) . Patients in both groups received physical therapy according to protocol and rescue pain medication if required . Complaints on impairment and disability level and quality of life were assessed up to 9 weeks after baseline , with primary measurement points at 2 , 6 , and 9 weeks . Monitoring of pain using the visual analogue scale took place continuously during the course of the trial . Except for a significant improvement on a subscale of the Jebsen-Taylor h and function test , no significant differences were found between mannitol and placebo treatment . Changes in both groups in the course of the trial were small and clinical ly irrelevant on all measurement indices . We conclude that intravenous administration of 10 % mannitol is not more effective than placebo in reducing complaints for CRPS I patients and provides no addition to already-established interventions for CRPS I. Whether 10 % mannitol can provide beneficial effects for subgroups of CRPS I patients with a pathophysiological profile more closely fitting the presumed mode of action for this intervention remains to be established . PERSPECTIVE This article addresses the efficacy of the intravenous administration of the free radical scavenger mannitol for treatment of CRPS type 1 . This intervention is not more effective than placebo in reducing complaints for CRPS I patients and provides no addition to already-established interventions for CRPS Background This double-blind , r and omized , controlled trial investigated the effect of the phosphodiesterase-5 inhibitor tadalafil on the microcirculation in patients with cold Complex Regional Pain Syndrome ( CRPS ) in one lower extremity . Methods Twenty-four patients received 20 mg tadalafil or placebo daily for 12 weeks . The patients also participated in a physical therapy program . The primary outcome measure was temperature difference between the CRPS side and the contralateral side , determined by measuring the skin temperature with videothermography . Secondary outcomes were : pain measured on a Visual Analogue Scale , muscle force measured with a MicroFet 2 dynamometer , and level of activity measured with an Activity Monitor ( AM ) and walking tests . Results At the end of the study period , the temperature asymmetry was not significantly reduced in the tadalafil group compared with the placebo group , but there was a significant and clinical ly relevant reduction of pain in the tadalafil group . Muscle force improved in both treatment groups and the AM revealed small , non-significant improvements in time spent st and ing , walking , and the number of short walking periods . Conclusion Tadalafil may be a promising new treatment for patients that have chronic cold CRPS due to endothelial dysfunction , and deserves further investigation . Trial Registration The registration number in the Dutch Trial Register is IS RCT N60226869 & NA ; Seventeen chronic upper limb complex regional pain syndrome type I patients treated with thoracic sympathetic block were better than 19 treated with active‐control regarding pain , quality of life and mood at 1 , 2 , and 12 months . & NA ; Pain relief in complex regional pain syndrome ( CRPS ) remains a major challenge , in part due to the lack of evidence ‐based treatment trials specific for this condition . We performed a long‐term r and omized , double‐blinded active‐control study to evaluate the efficacy of thoracic sympathetic block ( TSB ) for upper limb type I CRPS . The study objective was to evaluate the analgesic effect of TSB in CRPS . Patients with CRPS type I were treated with st and ardized pharmacological and physical therapy and were r and omized to either TSB or control procedure as an add‐on treatment . Clinical data , pain intensity , and interference ( Brief Pain Inventory ) , pain dimensions ( McGill Pain Question naire [ MPQ ] ) , neuropathic characteristics ( Neuropathic Pain Symptom Inventory [ NPSI ] ) , mood , upper limb function ( Disabilities of Arm , Shoulder and H and ) , and quality of life were assessed before , and at 1 month and 12 months after the procedure . Thirty‐six patients ( 19 female , 44.7 ± 11.1 years of age ) underwent the procedure ( 17 in the TSB group ) . Average pain intensity at 1 month was not significantly different after TSB ( 3.5 ± 3.2 ) compared to control procedure ( 4.8 ± 2.7 ; P = 0.249 ) . At 12 months , however , the average pain item was significantly lower in the TSB group ( 3.47 ± 3.5 ) compared to the control group ( 5.86 ± 2.9 ; P = 0.046 ) . Scores from the MPQ , evoked‐pain symptoms subscores ( NPSI ) , and depression scores ( Hospital Anxiety and Depression Scale ) were significantly lower in the TSB group compared to the control group at 1 and at 12 months . Other measurements were not influenced by the treatment . Quality of life was only slightly improved by TSB . No major adverse events occurred . Larger , multicentric trials should be performed to confirm these original findings & NA ; To compare the effects of two free radical scavengers , dimethylsulfoxide 50 % ( DMSO ) and N‐acetylcysteine ( NAC ) , for treatment of complex regional pain syndrome I ( CRPS I ) , a r and omized , double‐dummy controlled , double‐blind trial was conducted . Two outpatient clinics of two university hospitals in The Netherl and s participated in the study and 146 patients , were included over a period of 24 months . Patients were r and omized into two treatment groups , one was instructed to apply DMSO 50 % five times daily to the affected extremity , the second was treated with NAC 600 mg effervescent tablets three times daily , both combined with placebo . Interventions were accompanied by pain medication , occupational therapy for upper extremity CRPS I and physical therapy for lower extremity CRPS I in specific circumstances . Treatment was given for 17 weeks , with a possibility to continue or switch medication after this period , up to 1 year following the onset of treatment . An impairment level sum score was the primary outcome measure . Upper and lower extremity skills and functions , and general health status were also evaluated . Overall , no significant differences were found between NAC and DMSO after 17 and 52 weeks on impairment level and general health status . Significant differences were found for subscores of lower extremity function , in favor of DMSO‐treatment . Subgroup analysis showed more favorable results for DMSO for warm CRPS I and significantly better performance of NAC for patients with a cold CRPS I. Results tended to be negatively influenced if the duration of the complaint was longer . Treatment with DMSO and NAC are generally equally effective in treatment of CRPS I. Strong indications exist for differences in effects for subgroups of patients with warm or cold CRPS I : for warm CRPS I , DMSO‐treatment appears more favorable , while for cold CRPS I , NAC‐treatment appears to be more effective Shoulder‐h and syndrome developed in 36 ( 27 % ) of 132 hemiplegic patients in a prospect i ve study . Subluxation , paresis of the shoulder girdle , moderate spasticity , and deficits in confrontation visual field testing were the major risk factors . In a placebo‐controlled , nonblinded trial , 31 of the 36 patients became almost symptom free within 10 days ' treatment with low doses of oral corticosteroids . Shoulder joint capsules taken at autopsy of 7 patients showed signs of previous trauma of the affected shoulder . In the second part of this study on another 86 patients , early awareness of potential injuries to shoulder joint structures reduced the frequency of shoulder‐h and syndrome from 27 to 8 % . These clinical findings suggest that shoulder‐h and syndrome in hemiplegia is initiated by peripheral lesions . A self‐perpetuating vicious cycle may be established , followed by the clinical picture of a “ reflex sympathetic dystrophy . ” In the majortity of stroke patients , this clinical phenomenon seems to be preventable by avoiding shoulder trauma BACKGROUND We aim ed to determine the sympatholytic and clinical effects of low dose high frequency ultrasound ( US ) applied on stellate ganglion in Complex Regional Pain Syndrome ( CRPS ) type I patients . MATERIAL AND METHOD Fourty-five patients with CRPS type I were r and omly allocated into three groups . Pharmacological treatment , transcutaneous electrical nerve stimulation ( TENS ) , contrast bath and exercise were applied to all groups for 20 sessions . In addition to this treatment protocol , low dose high frequency US was applied on stellate ganglion as 0.5 watts/cm(2 ) in group I ; 3 watts/cm(2 ) in group II and as placebo in group III . Forty age and sex matched healthy controls were served as controls . Sympathetic skin response ( SSR ) was used for determining the sympatholytic effects of US . Pain was assessed with visual analog scale ( VAS ) , limitation of total finger flexion was assessed with finger pulp-distal crease distance , muscle strength was assessed with measuring the grip strength , upper extremity disability was assessed with Disability of the Arm , Shoulder and H and ( DASH ) scale before and after the treatment . RESULTS All groups evalueted in terms of VAS score , finger pulp-distal crease distance , grip strength and DASH score after the treatment . The improvements in those parameters were not statistically significant between the groups ( P > 0.05 ) . SSR latency was significantly shorter in CRPS patients than controls ( P < 0.05 ) . Pre- and post-treatment SSR amplitude and latency values were not different within patient groups ( P > 0.05 ) . The differences in pre- and post-treatment SSR amplitude and latency values were not statistically different between patient groups ( P > 0.05 ) . CONCLUSION Low dose high frequency US applied on stellate ganglion did not make a sympathetic blockade and was not of further benefit for pain , range of motion , grip strength and upper extremity disability in CRPS type I patients ABSTRACT Complex Regional Pain Syndrome Type 1 ( CRPS‐1 ) responds poorly to st and ard pain treatment . We evaluated if the N‐methyl‐d‐aspartate receptor antagonist S(+)‐ketamine improves pain in CRPS‐1 patients . Sixty CRPS‐1 patients ( 48 females ) with severe pain participated in a double‐blind r and omized placebo‐controlled parallel‐group trial . Patients were given a 4.2‐day intravenous infusion of low‐dose ketamine ( n = 30 ) or placebo ( n = 30 ) using an individualized stepwise tailoring of dosage based on effect ( pain relief ) and side effects ( nausea/vomiting/psychomimetic effects ) . The primary outcome of the study was the pain score ( numerical rating score : 0–10 ) during the 12‐week study period . The median ( range ) disease duration of the patients was 7.4 ( 0.1–31.9 ) years . At the end of infusion , the ketamine dose was 22.2 ± 2.0 mg/h/70 kg . Pain scores over the 12‐week study period in patients receiving ketamine were significantly lower than those in patients receiving placebo ( P < 0.001 ) . The lowest pain score was at the end of week 1 : ketamine 2.68 ± 0.51 , placebo 5.45 ± 0.48 . In week 12 , significance in pain relief between groups was lost ( P = 0.07 ) . Treatment did not cause functional improvement . Patients receiving ketamine more often experienced mild to moderate psychomimetic side effects during drug infusion ( 76 % versus 18 % , P < 0.001 ) . In conclusion , in a population of mostly chronic CRPS‐1 patients with severe pain at baseline , a multiple day ketamine infusion result ed in significant pain relief without functional improvement . Treatment with ketamine was safe with psychomimetic side effects that were acceptable to most patients OBJECTIVE To assess the effects of intravenous administration of magnesium on complex regional pain syndrome type 1 ( CRPS-1 ) , a r and omized double-blind placebo-controlled trial was performed . METHODS Fifty-six patients with CRPS-1 ( International Association for the Study of Pain Orl and o criteria ) received MgSO(4 ) 70 mg/kg or placebo ( NaCl 0.9 % ) in 4 hours over 5 consecutive days . Pain ( BOX-11 and McGill ) , the level of impairment ( Impairment level Sum Score [ ISS ] ) , functional limitations ( Radboud Skills Question naire , Walking Skills Question naire/ question naire rising and sitting down ) , participation ( Impact on Participation and Autonomy [ IPA ] ) , and quality of life ( Short Form-36 , EuroQol , IPA ) were evaluated at baseline and at 1 , 3 , 6 , and 12 weeks . RESULTS No significant differences were found between MgSO(4 ) and placebo on the BOX-11 and ISS at different time points during the trial on intention-to-treat and per- protocol analysis . A significant improvement on the BOX-11 was found after the first week of the trial in both groups ( mean 0.7 ; st and ard deviation 1.1 ) . For the MgSO(4 ) group , a clinical ly relevant and statistically significant improvement on the ISS at 1 week ( median 5 , interquartile range [ IQR ] -1 to 8) and a significant improvement on the McGill up to 6 weeks ( median 2 words , IQR 0 - 4.5 ) were found compared with baseline , which were not found in the placebo group . Significant improvement in perceived job participation was found for the MgSO(4 ) group at 12 weeks ( median improvement 1.44 - 1.17 ; P = 0.01 ) . ISS improved significantly more in patients with a low Hospital Anxiety and Depression Scale ( HADS ) score ( ≤10 ) in the MgSO(4 ) group ( mean 4.4 vs mean -3.1 ; P = 0.02 ) . CONCLUSION Administration of the physiological competitive N-methyl-D-aspartate receptor antagonist magnesium in chronic CRPS provides insufficient benefit over placebo . Future research should focus on patients with acute CRPS and early signs and symptoms of central sensitization BACKGROUND There is no study on the long-term use of prednisolone in post-stroke complex regional pain syndrome-1 ( CRPS1 ) . OBJECTIVE To evaluate the efficacy and safety of long-term low dose prednisolone in post-stroke CRPS-I. STUDY DESIGN Open-labeled r and omized controlled trial . SETTING Tertiary care teaching institute . METHODS Seventy-seven out of 396 ( 19.4 % ) patients with stroke had CRPS-1 and 58 met the inclusion criteria . Their clinical details and CRPS , Visual Analogue Scale ( VAS ) , modified Rankin Scale ( mRS ) , and Barthel Index ( BI ) scores were noted . The patients were prescribed 40 mg prednisolone for 2 weeks followed by tapering in the next 2 weeks . Patients who responded were r and omly assigned prednisolone 10 mg daily ( group I ) or no prednisolone ( group II ) . They were followed up for the first and second month of r and omization and their CRPS , VAS , mRS , and BI scores were noted . The primary outcome was improvement in CRPS score and secondary outcomes were VAS , mRS , BI scores , and severe adverse events ( SAE ) . RESULTS Fifty-six of fifty-eight ( 96.5 % ) patients responded to the initial high dose prednisolone and 26 each were assigned group I and group II treatment . Group I patients had further improvement in CRPS score . Fifty percent of patients in group II had deterioration at one month and needed reinstitution of prednisolone ; following which 77 % of them improved in the next month . The improvement in CRPS score paralleled the VAS score but not mRS and BI scores in the first and second months in group I compared to group II . There was no SAE necessitating withdrawal of prednisolone . LIMITATION The design of the study is not double blind . CONCLUSION In post-stroke CRPS-I , continuation of low dose prednisolone for 2 months is safe and effective . Key words : Shoulder h and syndrome , CRPS , corticosteroid , prednisolone , stroke , Visual Analogue Scale OBJECTIVE To evaluate the therapeutic effects of acupuncture and massage for shoulder-h and syndrome in hemiplegia patients . METHODS One hundred and twenty hemiplegia patients with stage I shoulder-h and syndrome were r and omly divided into a group treated with st and ardized electric acupuncture and massage , and a group treated with rehabilitation therapy for 6 weeks . The primary indices evaluated were pain on passive movement of the shoulder using the numeric pain rating scale ( NPRS ) , and the number of patients with shoulder-h and syndrome at Steinbrocker stage II or III after treatment . The secondary indices were Fugl-Meyer evaluation of functional movement of the upper limb and h and using the modified rankin scale ( MRS ) . RESULTS At post-treatment evaluation and a 12-week follow-up visit , NPRS score , number of patients with stage II or III shoulder-h and syndrome , and MRS score were all improved in the acupuncture-massage group compared with the rehabilitation group ( P<0.05 ) . On Fugl-Meyer evaluation , functional movement of the upper limb was also improved in the acupuncture-massage group compared with the rehabilitation group ( P<0.05 ) . CONCLUSION St and ardized acupuncture-massage therapy may have curative effects on shoulder-h and syndrome in hemiplegia patients OBJECTIVE To evaluate the effects of the antiresorptive agent alendronate at a daily oral dose of 40 mg in patients with posttraumatic complex regional pain syndrome type I ( CRPS I ) of the lower extremity . METHODS Forty patients were enrolled in this 8-week r and omized , double-blind , placebo-controlled study of alendronate therapy for CRPS I , a condition associated with regional osteoclastic overactivity . An optional 8-week open extension of alendronate therapy ( weeks 12 - 20 ) was available after a 4-week period without therapy . Clinical assessment s included joint mobility , edema of the lower extremity , tolerance to pressure in the lower extremity , and levels of spontaneous pain . Urinary levels of type I collagen N-telopeptide ( NTX ) were assessed by enzyme-linked immunosorbent assay . Patients were examined at weeks 4 , 8 , 12 , 16 , 20 , and 24 . Statistical analysis included two-way factorial analysis of variance . RESULTS In contrast to placebo-treated patients ( n = 20 ) , all of the alendronate-treated patients ( n = 19 ) exhibited a marked and sustained improvement in levels of spontaneous pain , pressure tolerance , and joint mobility , as well as a significant reduction in urinary levels of NTX at weeks 4 and 8 . The improvement was maintained at week 12 . Twelve patients from each treatment group volunteered for the 8-week open trial , and all of them had a positive response to alendronate . CONCLUSION Our findings support the use of oral alendronate in posttraumatic CRPS I. By reducing local acceleration of bone remodeling , alendronate might relieve pain by effects on nociceptive primary afferents in bone , pain-associated changes in the spinal cord , and possibly also through a central mechanism Background Complex Regional Pain Syndrome ( CRPS ) is a disabling disease that is sometimes difficult to treat . Although spinal cord stimulation ( SCS ) can reduce pain in most patients with CRPS , some do not achieve the desired reduction in pain . Moreover , the pain reduction can diminish over time even after an initially successful period of SCS . Pain reduction can be regained by increasing the SCS frequency , but this has not been investigated in a prospect i ve trial . This study compares pain reduction using five SCS frequencies ( st and ard 40 Hz , 500 Hz , 1200 Hz , burst and placebo stimulation ) in patients with CRPS to determine which of the modalities is most effective . Design All patients with a confirmed CRPS diagnosis that have unsuccessfully tried all other therapies and are eligible for SCS , can enroll in this trial ( primary implantation group ) . CRPS patients that already receive SCS therapy , or those previously treated with SCS but with loss of therapeutic effect over time , can also participate ( re-implantation group ) . Once all inclusion criteria are met and written informed consent obtained , patients will undergo a baseline assessment ( T0 ) . A 2-week trial with SCS is performed and , if successful , a rechargeable internal pulse generator ( IPG ) is implanted . For the following 3 months the patient will have st and ard 40 Hz stimulation therapy before a follow-up assessment ( T1 ) is performed . Those who have completed the T1 assessment will enroll in a 10-week crossover period in which the five SCS frequencies are tested in five periods , each frequency lasting for 2 weeks . At the end of the crossover period , the patient will choose which frequency is to be used for stimulation for an additional 3 months , until the T2 assessment . Discussion Currently no trials are available that systematic ally investigate the importance of variation in frequency during SCS in patients with CRPS . Data from this trial will provide better insight as to whether SCS with a higher frequency , or with burst stimulation , results in more effective pain relief . Trial registration Current Controlled Trials IS RCT BACKGROUND Complex regional pain syndrome ( CRPS ) following stroke aggravates morbidity . CRPS is categorized as CRPSI when no clear nerve injury is defined , and CRPSII when associated with clear nerve injury . AIM To compare the effect of prednisolone with that of piroxicam in patients with CRPSI following stroke . DESIGN R and omized controlled trial . METHODS Patients with CRPSI fulfilling the inclusion criteria ( n = 60 ) underwent a detailed neurological examination , cranial CT scan , radiograph of chest and shoulder joint , blood counts and serum chemistry . Severity of stroke was assessed by the Canadian Neurological Scale ( CNS ) , CRPS by scoring sensory , autonomic and motor symptoms , and activity of daily living by Barthel index ( BI ) score . Patients were r and omly assigned prednisolone 40 mg or piroxicam 20 mg daily , and outcome was assessed at 1 month on the basis of CRPS and BI score . RESULTS Mean patient age was 56 years and 20 were female . Baseline clinical and radiological parameters were comparable between the two groups . In the prednisolone group , 83.3 % patients showed significant improvement , compared to 16.7 % in the piroxicam group . The mean change in CRPS score in prednisolone group was 6.47 ( 95%CI 4.37 - 7.36 ) , whereas in piroxicam group it was only 0.47 . The mean change in BI score was 7.9 ( 95%CI 0.82 - 5.98 ) in the prednisolone group , and 4.5 in the piroxicam group . DISCUSSION In this patient group , prednisolone result ed in significant improvement in the symptoms and signs of CRPSI following stroke , compared to piroxicam . Both drugs produced an improvement in the BI score BACKGROUND Chronic reflex sympathetic dystrophy ( also called the complex regional pain syndrome ) is a painful , disabling disorder for which there is no proven treatment . In observational studies , spinal cord stimulation has reduced the pain associated with the disorder . METHODS We performed a r and omized trial involving patients who had had reflex sympathetic dystrophy for at least six months . Thirty-six patients were assigned to receive treatment with spinal cord stimulation plus physical therapy , and 18 were assigned to receive physical therapy alone . The spinal cord stimulator was implanted only if a test stimulation was successful . We assessed the intensity of pain ( on a visual-analogue scale from 0 cm [ no pain ] to 10 cm [ very severe pain ] ) , the global perceived effect ( on a scale from 1 [ worst ever ] to 7 [ best ever ] ) , functional status , and the health-related quality of life . RESULTS The test stimulation of the spinal cord was successful in 24 patients ; the other 12 patients did not receive implanted stimulators . In an intention-to-treat analysis , the group assigned to receive spinal cord stimulation plus physical therapy had a mean reduction of 2.4 cm in the intensity of pain at six months , as compared with an increase of 0.2 cm in the group assigned to receive physical therapy alone ( P<0.001 for the comparison between the two groups ) . In addition , the proportion of patients with a score of 6 ( " much improved " ) for the global perceived effect was much higher in the spinal cord stimulation group than in the control group ( 39 percent vs. 6 percent , P=0.01 ) . There was no clinical ly important improvement in functional status . The health-related quality of life improved only in the 24 patients who actually underwent implantation of a spinal cord stimulator . Six of the 24 patients had complications that required additional procedures , including removal of the device in 1 patient . CONCLUSIONS In carefully selected patients with chronic reflex sympathetic dystrophy , electrical stimulation of the spinal cord can reduce pain and improve the health-related quality of life ABSTRACT Since glycinergic neurotransmission plays an important inhibitory role in the processing of sensory and motor information , intrathecal glycine ( ITG ) administration may be a potential therapy for both pain and movement disorders in patients with complex regional pain syndrome ( CRPS ) . Aims of the current study , which is the first report on ITG in humans , were to evaluate its safety and efficacy . ITG treatment during 4 weeks was studied in CRPS patients with dystonia in the period before they received intrathecal baclofen treatment . Twenty patients were assessed and after exclusion of one patient , the remaining 19 patients were r and omized in a double‐blind placebo‐controlled crossover study . Safety was assessed by clinical evaluation , blood examinations and electrocardiograms . Efficacy measures involved pain ( numeric rating scale , McGill pain question naire ) , movement disorders ( Burke – Fahn – Marsden dystonia rating scale , unified myoclonus rating scale , tremor research group rating scale ) , activity ( Radboud skills question naire , walking ability question naire ) , and a clinical global impression ( CGI ) and patient 's global impression score ( PGI ) . Treatment‐emergent adverse events were generally mild to moderate and not different from placebo treatment . During ITG treatment growth hormone levels were slightly increased . Although there was a trend to worsening on the CGI and PGI during ITG treatment , there were no significant differences between ITG and placebo treatment in any of the outcomes . ITG given over 4 weeks was ineffective for pain or dystonia in CRPS . Although no serious adverse events occurred , further studies are required to rule out potential neurotoxicity of ITG This study aim ed to apply virtual body swapping through mental rehearsal for patients with complex regional pain syndrome ( CRPS ) and to investigate whether it is applicable to them . Ten patients who met the diagnostic criterion for CRPS type 1 were r and omly assigned to either the treatment or control group . All participants were asked to watch the virtual body swapping training video clip with a head mounted display . The treatment group was additionally asked to assume a posture similar to the body on the screen and rehearse the movements mentally , as if the body presented on the screen was their body . No difference between the groups was found for pain intensity , however , the treatment group showed significantly more improvement in body perception disturbance ( BPD ) after the treatment than the control group . Even if the presented study is a preliminary one , the above results suggest that virtual body swapping through mental rehearsal is applicable for patients with CRPS and may be useful for improving BPD . The limitations of the study and the future investigations needed to provide clearer clinical suggestions are presented and discussed & NA ; A combination therapy of morphine with an NMDA‐receptor antagonist might be more effective than morphine without a NMDA‐receptor antagonist for the relief of neuropathic pain in patients with complex regional pain syndrome ( CRPS ) . In order to test the efficacy of this combination therapy we performed a double‐blind r and omized placebo‐controlled study on patients suffering from CRPS of the upper extremity . We used functional magnetic resonance imaging during movement of the affected and unaffected upper h and before and after a treatment regimen of 49 days that contrasted morphine and an NMDA‐receptor antagonist with morphine and placebo . We postulated superior pain relief for the combination therapy and concomitant changes in brain areas associated with nociceptive processing . Only the combination therapy reduced pain at rest and during movement , and disability . After treatment , activation in the contralateral primary somatosensory ( cS1 ) and anterior cingulate cortex was significantly reduced when the affected h and was moved . Pain relief during therapy was related to decreased activation in cS1 and secondary somatosensory cortex ( S2 ) . Our data suggest that the combination of morphine with an NMDA‐receptor antagonist significantly affects the cerebral processing of nociceptive information in CRPS . The correlation of pain relief and decrease in cortical activity in cS1 and S2 is in accordance with the expected impact of the NMDA‐receptor antagonist on cerebral pain processing with emphasis on sensory‐discriminative aspects of pain UNLABELLED The treatment of dystonia related to complex regional pain syndrome ( CRPS ) remains unsatisfactory , raising the need of alternative targets for intervention . In dystonia , pathologic muscle changes may occur , which contributes to stiffness . Because magnesium sulphate may act as a muscle relaxant through its actions on the neuromuscular junction and muscle , we performed an explanatory study of the muscle relaxant effect and safety of intramuscular magnesium sulphate ( IMMG ) in CRPS patients with dystonia . In a double-blind r and omized placebo-controlled crossover study , 30 patients were assigned to 3-week treatments of IMMG and placebo . Treatments were separated by a 1-week washout period . The daily dose of IMMG was 1,000 mg in week 1 , 1,500 mg in week 2 , and 2,000 mg in week 3 . The primary outcome measure was the difference in change in Burke-Fahn-Marsden scores after 3 weeks of treatment between both interventions . Secondary outcomes involved severity of dystonia , myoclonus , tremor , and pain , and functional activity . Data of 22 patients available for the explanatory analysis revealed no significant differences between IMMG and placebo treatment in any of the outcomes . In conclusion , we found no indication of efficacy of IMMG in a daily dose of 2,000 mg as a muscle relaxant in CRPS-related dystonia . PERSPECTIVE In this double-blind placebo-controlled crossover study there was no evidence found of a muscle relaxant effect of intramuscular magnesium sulphate in dystonia related to CRPS . Consequently , there is insufficient support for new studies evaluating the efficacy of other routes of MG administration in CRPS-related dystonia OBJECTIVE The reflex sympathetic dystrophy syndrome ( RSDS ) is a painful limb disorder , for which a consistently effective treatment has not yet been identified . The disease is associated with increased bone resorption and patchy osteoporosis , which might benefit from treatment with bisphosphonates , powerful inhibitors of bone resorption . METHODS Twenty patients with RSDS of foot and h and , were r and omly assigned to blind administration of either alendronate intravenously ( Istituto Gentili , Pisa , Italy ) 7.5 mg dissolved in 250 ml saline solution or placebo saline infusions daily for three days . Two weeks later all patients had an identical treatment course with open labelled alendronate ( 7.5 mg/day for three days ) , independent from the results of the first blind treatment . RESULTS In the patients treated with blind alendronate the diminution in spontaneous pain , tenderness , and swelling ( circumference of the affected limb ) and the improvement in motion were significantly different from baseline ( p<0.001 ) , from those observed within the first two weeks in the control group ( p<0.01 ) , and from week 2 to week 4 ( p<0.01 ) . In the patients given blind placebo infusions no relevant symptomatic changes were observed after the first two weeks of follow up , but they responded to the open alendronate therapy given afterwards . In 12 patients with RSDS of the h and the ultradistal bone mineral content ( BMC ) of the affected arm was considerably lower than that of the controlateral arm ( mean ( SD ) ) ( 426(82 ) mg/cm versus 688(49 ) ) . Six weeks after the beginning of the trial BMC rose by 77(12 ) mg/cm ( p<0.001 ) in the affected arm , but it did not change in the controlateral . CONCLUSIONS These results indicate that bisphosphonates should be considered for the treatment of RSDS , producing consistent and rapid remission of the disease Acute Reflex Sympathetic Dystrophy ( acute RSD ) was defined using a reproducible classification . Elevated temperature of the affected extremity ( “ calor ” ) , measured by the dorsal side of the observer 's h and and mentioned by the patient , pain ( “ dolor ” ) measured by the Visual Analogue Scale ( VAS ) , redness ( “ rubor ” ) , edema ( “ tumor ” ) and limited active range of motion ( “ functio laesa ” ) , all contributed to the classification system . Patients scoring 4 or 5 positive symptoms were considered to have acute RSD BACKGROUND : Complex regional pain syndrome type 1 can be difficult to treat . The purpose of this study was to compare the safety and efficacy of two therapeutic options : percutaneous radiofrequency thermal lumbar sympathectomy and lumbar sympathetic neurolysis . METHODS : We r and omized 20 patients to receive percutaneous radiofrequency lumbar sympathectomy or lumbar sympathetic neurolysis with phenol 7 % in lower limb complex regional pain syndrome type 1 . The study end points were pain relief and side effects . RESULTS : Within each group , there were statistically significant reductions from baseline in various pain scores after the procedure . However , there was no statistically significant difference in mean pain scores between the groups . CONCLUSIONS : Based on this pilot study , radiofrequency lumbar sympathectomy may be comparable to phenol lumbar sympathectomy . A larger trial is required to confirm these findings There are no adequate comparative studies on physical therapy ( PT ) versus occupational therapy ( OT ) in patients with complex regional pain syndrome I ( CRPS I ) . Therefore , we conducted a prospect i ve r and omised clinical trial to assess their effectiveness . The outcomes regarding reducing pain and normalising active range of motion ( AROM ) are discussed . Included in the study were 135 patients who had been suffering from CRPS I of one upper extremity for less than one year . They were r and omly assigned to one of three groups : PT , OT , or control ( social work , CT ) . Measurements were taken at base-line ( t0 ) , after 6 weeks , and after 3 , 6 and 12 months ( t1 to t4 ) . Pain was measured on four visual analogue scales ( VAS ) and the McGill Pain Question naire , Dutch Language Version ( MPQ-DLV ) . The AROM was recorded relative to the contralateral side . Explorative statistical evaluations were performed ( Wilcoxon ; alpha=0.05 ) . PT and to a lesser extent OT , result ed in more rapid improvement in the VAS scores than CT , especially for the VAS during or after effort ( P<0.05 at t1 to t3 ) . PT was superior to CT and OT according to the MPQ-DLV particularly at t4 . Improvement on the MPQ-DLV over the year was significantly greater for PT than for OT and CT ( P<0.05 ) . PT - and to a lesser degree OT- led to better results than CT for the AROM of the wrist , fingers and thumb at t1 to t3 ( most-times P<0.05 for PT ) , but the improvements over the year were not significantly different . Our results indicated that PT , and to a lesser extent OT , were helpful for reducing pain and improving active mobility in patients with CRPS I of less than one year duration , localised in one upper extremity The aim of the study was to assess the efficacy of salmon calcitonin , which was suggested as effective in the treatment of complex regional pain syndrome type 1 ( CRPS 1 ) . Patients who had suffered trauma to their upper extremities and developed CRPS 1 were included into this r and omised , controlled single-blind study . The diagnosis was made according to the clinical examination and scintigraphy . The evaluation parameters were : pain [ visual analogue scale ( VAS ) ] , the angle of dorsiflexion ( DF ) and palmar flexion ( PF ) of the wrist , distance between the fingertip and distal palmar crease ( FT-DPC ) , allodynia , hyperalgesia and trophic changes . One group received paracetamol 1500 m/day and the other group salmon calcitonin 200 IU/day for 2 months . All of the patients participated in a physical therapy and exercise programme . A total of 35 patients were divided into two groups , who were found to be similar for age , body mass index , period of trauma , period of rest in a plaster splint or b and age , the duration of symptoms , VAS , DF and PF angle , FT-DPC , presence of allodynia , hyperalgesia and trophic changes ( p>0.05 ) . The control examination showed similar results for allodynia , hyperalgesia and trophic changes , whereas remarkable improvement was observed in the rest of the parameters within groups . On the other h and , between the two groups there was no significant difference in any of the parameters ( p>0.05 ) This r and omised , single-blind study showed that all of the patients with acute CRPS 1 in their upper extremities after trauma , who were treated with either paracetamol or calcitonin along with physical therapy , recovered in all parameters significantly , but without any difference between groups . We can conclude that calcitonin does not make any favourable contribution in the treatment of patients with acute CRPS 1 ; physical therapy combined with only a simple analgesic is an efficient means of therapy UNLABELLED Complex regional pain syndrome ( CRPS ) is a potentially debilitating chronic pain syndrome with a poorly understood but likely neuroimmune/multifactorial pathophysiology associated with axonal injury . Based on the potential contribution of proinflammatory cytokines to CRPS pathogenesis and prior research with thalidomide , we investigated lenalidomide , a thalidomide derivative , for CRPS treatment . We conducted a phase II , r and omized , double-blind , placebo-controlled study to evaluate the efficacy of oral lenalidomide 10 mg once daily in consenting patients with unilateral or bilateral CRPS type 1 . The study comprised 12 weeks of treatment followed by a long-term extension . The primary efficacy outcome was reduced pain in the index limb , defined as ≥30 % improvement from baseline using an 11-point numeric rating scale . One hundred eighty-four subjects enrolled . The primary endpoint was not met because equal proportions of treated ( 16.1 % ) and control ( 16.1 % ) subjects achieved the outcome ; however , lenalidomide was well tolerated , with no evidence of neuropathy or major adverse effects . This study is the largest controlled , blinded clinical trial in subjects with chronic CRPS using the Budapest research criteria . It demonstrates the feasibility of conducting high- quality clinical trials in CRPS type 1 and provides considerations for design ing future trials . PERSPECTIVE This article reports an adequately powered , controlled clinical trial in subjects with CRPS . Treatment and placebo were equally effective , but the study demonstrated that lenalidomide treatment is feasible in this population . The study provides examples to consider in design ing future CRPS trials Activated immune cells in the spinal cord may play an important role in the development and maintenance of neuropathic pain , such as occurs in response to peripheral inflammation or tissue injury . Immune activation may therefore serve as a therapeutic target for immune modulating drugs like corticosteroids . This double-blind r and omized placebo-controlled parallel-group trial aim ed to investigate the efficacy and safety of a single intrathecal administration of 60 mg methylprednisolone ( ITM ) in chronic patients with complex regional pain syndrome ( CRPS ) . The primary outcome measure was change in pain ( pain intensity numeric rating scale ; range 0 - 10 ) after 6 weeks . With 21 subjects per group the study had a 90 % power to detect a clinical ly relevant difference ( > or = 2 points ) . After 21 patients ( 10 on ITM ) were included , the trial was stopped prematurely after the interim analysis had shown that ITM had no effect on pain ( difference in mean pain intensity numeric rating scale at 6 weeks 0.3 , 95 % confidence interval -0.7 to 1.3 ) or any other outcome measure . We did not find any difference in treatment-emergent adverse events between the ITM and placebo group . We conclude that a single bolus administration of ITM is not efficacious in chronic CRPS patients , which may indicate that spinal immune activation does not play an important role in this phase of the syndrome OBJECTIVE To investigate the efficacy and tolerability of Botulinum toxin A ( BoNT-A ) in allodynia of patients with complex regional pain syndrome . DESIGN A total of 14 patients were studied . Eight patients were participants of a r and omized , prospect i ve , double-blind , placebo-controlled protocol . Six patients were studied prospect ively in an open-label protocol . Patients were rated at baseline and at 3 weeks and 2 months after BoNT-A administration . Ratings included brief pain inventory , McGill pain question naire , clinical pain impact question naire , quantitative skin sensory test , sleep satisfaction scale , and patient global satisfaction scale . BoNT-A was injected intradermally and subcutaneously , five units/site into the allodynic area ( total dose 40 - 200 units ) . RESULTS None of the patients with allodynia showed a significant response after treatment . The treatment was painful and poorly tolerated . CONCLUSION Intrademal and subcutaneous administration of BoNT-A into the allodynic skin of the patients with complex regional pain syndrome ( CRPS ) failed to improve pain and was poorly tolerated Background Intraspinally administered α2-adrenerglc agonists may relieve pain in sympathetically maintained pain ( SMP ) syndromes , such as reflex sympathetic dystrophy ( RSD ) , by spinal , peripheral , and central nervous system actions . This study examined analgesic efficacy and side effects of epidurally administered clonidine in patients with severe , refractory RSD . Methods Twenty-six patients with severe chronic pain consistent with RSD were studied in a r and omized , blinded , placebo-controlled design . Cervical or lumbar epidural catheters were inserted for patients with upper or lower extremity RSD , respectively , and patients received , in r and om order on three consecutive days , epidural injection of clonidine , 300 or 700 μg , or placebo . Pain ( by visual analog score ( VAS ) and McGill Pain Question naire ) , sedation , blood pressure , and heart rate were monitored at specified Intervals for 6 h after injection . Patients who responded to clonidine , but not placebo , then entered a trial of open-label , continuous epidural infusion of clonidine ( 10–50 μg/h ) . Results Clonidine , but not placebo , caused pain relief , sedation , and decreased blood pressure and heart rate after bolus epidural injection . The smaller clonidine dose ( 300 μg ) , produced pain relief and decreases in blood pressure and heart rate similar to those of the 700 μg dose , but with less sedation . Epidural clonidine was infused for a mean of 43 days in 19 patients at a mean rate of 32 μg/h for sustained analgesia . Conclusions Transdermal clonidine has been demonstrated to produce analgesia in the area surrounding its application site in patients with SMP . The current study indicates that extensive analgesia may be obtained by epidural administration . Sedation and hypotension may limit bolus epidural clonidine administration for RSD . The role for chronic epidural Infusion of clonidine has not yet been established The objective of this study is to investigate the efficacy of manual lymphatic drainage ( MLD ) therapy in edema secondary to the reflex sympathetic dystrophy ( RSD ) . A total of 34 patients were allocated r and omly into two groups . All of the patients undertook nonstreoidal anti-inflammatory drug , physical therapy and therapeutic exercise program for 3 weeks . Patients in study group undertook MLD therapy additionally . Then the patients continued 2-month maintenance period with recommended home programs . Volumetric measurements pain scores and functional measurements were assessed at baseline , after treatment and 2 months after the treatment . After treatment , improvement in edema was statistically significant in the study group but not in the control group . At follow-up , with respect to baseline , improvements were not significant in both of the groups . Between the groups , difference of the percentage improvements in edema was statistically significant with superiority of MLD group after treatment , but not significant at follow-up . In this pilot study , MLD therapy was found to be beneficial in the management of edema result ed from RSD . Although the long-term results showed tendency towards improvement , the difference was not significant Summary Reflex sympathetic dystrophy syndrome is a difficult condition to treat . Many modalities have been proposed , all of them being clinical ly effective but whose efficacy is often difficult to assess , and has not been properly compared . A regimen of physical therapy ( pressure therapy , antalgic electrotherapy and exercise therapy ) with or without calcitonin was investigated in 24 patients r and omly assigned to 2 groups , one given physical therapy alone ( Group I ) and the other physical therapy plus salmon calcitonin 100 MRC units daily for 3 weeks ( Group II ) . Efficacy assessment was based on clinical ( pain , oedema and movement in the affected parts ) , biochemical ( blood and urinary phosphorus and calcium levels , plasma 25-OH-D , plasma parathyroid hormone ( PTH ) , creatinin , alkaline phosphatases and urinary hydroxyproline ) and scintigraphic parameters , as well as on the patient 's ability to resume working . There was significant improvement in pain in the Group II patients after one week of treatment . As a result the authors advocate the use of calcitonin in addition to physical therapy in reflex sympathetic dystrophy syndrome — and even of calcitonin alone where physical therapy is not possible OBJECTIVE To investigate the effectiveness and cost of physical therapy ( PT ) or occupational therapy ( OT ) in patients with reflex sympathetic dystrophy ( RSD ) . DESIGN Prospect i ve r and omized controlled trial , with 1 year follow-up . SETTING Two university hospitals . PATIENTS One hundred thirty-five patients who had been suffering from RSD of one upper extremity for less than 1 year . INTERVENTIONS Patients were assigned to PT , OT , or a control group ( social work ) . MAIN OUTCOME MEASURES Improvement in impairment level sumscore ( ISS ) over 1 year ( Student 's t test ) . A difference of 5 ISS points between the groups was defined as being clinical ly relevant . Furthermore , severity of disability and h and icap was measured and tested exploratively ( Wilcoxon ; alpha = .05 ) , and cost-effectiveness of the groups was calculated . RESULTS PT and , to a lesser extent , OT result ed in a significant and also more rapid improvement in the ISS as compared with controls ( 6 and 4 ISS points , respectively ) . On a disability level , a positive trend was found in favor of OT . On a h and icap level , no differences were found between the groups . PT had an advantage over OT regarding the cost-effectiveness ratio . CONCLUSION In different ways PT and OT each contribute to the recovery from RSD of the upper extremity Background : The efficacy of Grade d Motor Imagery ( GMI ) for the management of Complex Regional Pain Syndrome ( CRPS ) is supported by evidence , but its treatment effect remains generally modest . Transcranial Direct Current Stimulation ( tDCS ) has been advocated as an adjunct intervention to enhance the effect of motor imagery approaches in pain population s. Objective : The purpose of this study was to investigate the effectiveness of GMI+active tDCS compared with the GMI+sham tDCS in the treatment of CRPS type I. Methods : A total of 22 patients ( n=11/group ) were r and omly assigned to the experimental ( GMI+tDCS ) or placebo ( GMI+sham tDCS ) group . GMI treatments lasted 6 weeks ; anodal tDCS was applied over the motor cortex for 5 consecutive days during the first 2 weeks and once a week thereafter . Changes in pain perception , quality of life , kinesiophobia , pain catastrophizing , anxiety and mood were monitored after 6 weeks of treatment ( T1 ) and 1-month posttreatment ( T2 ) . Results : GMI+tDCS induced no statistically significant reduction in pain compared with GMI+sham tDCS . Although we observed significant group differences in kinesiophobia ( P=0.012 ) , pain catastrophizing ( P=0.049 ) , and anxiety ( P=0.046 ) at T1 , these improvements were not maintained at T2 and did not reached a clinical ly significant difference . Discussion : We found no added value of tDCS combined with GMI treatments for reducing pain in patients with chronic CRPS . However , given that GMI+sham tDCS induced no significant change , further studies comparing GMI+tDCS and tDCS alone are needed to further document tDCS ’s effect in CRPS OBJECTIVE To evaluate the efficacy of intravenous ( i.v . ) clodronate in patients with reflex sympathetic dystrophy syndrome ( RSDS ) and to assess the urinary excretion of type I collagen crosslinked N-telopeptide ( NTx ) before and after the treatment . METHODS Thirty-two patients with RSDS were r and omized to receive either i.v . clodronate 300 mg daily for 10 consecutive days or placebo . Forty days later , the placebo treated patients received the clodronate treatment . Outcome measures included as a primary endpoint the visual analog scale of pain ( VAS , range 0 - 100 ) ; secondary endpoints were a clinical global assessment ( CGA , range 0 - 3 ) and an efficacy verbal score ( EVS , range 0 - 3 ) . Clinical and biochemical assessment s were performed before the treatment , 40 ( T40 ) , 90 ( T90 ) , and 180 ( T180 ) days later . RESULTS At T40 the 15 patients r and omized to clodronate treatment showed significant decreases of VAS and CGA ( p = 0.002 , p = 0.001 , respectively ) . Compared with the placebo group ( 17 patients ) , significant differences were found in all clinical variables ( VAS : p = 0.001 ; CGA : p = 0.001 ; EVS : p<0.0001 ) . A further clinical improvement was observed throughout the study . Pooling the results of all 32 patients after clodronate treatment , at T180 the overall percentage decrease of VAS was 93.2+/-15.6 % , with 30 patients significantly improved or asymptomatic . Significant inverse correlations between baseline NTx values and decreases of VAS were found at T90 ( p = 0.03 ) and T180 ( p = 0.01 ) . No adverse events related to treatment occurred . CONCLUSION A 10 day i.v . clodronate course is better than placebo and effective in the treatment of RSDS . NTx seems to be a predictive factor for clodronate efficacy BACKGROUND AND OBJECTIVES Patients with complex regional pain syndrome ( CRPS ) confined to the knee are often therapy resistant . Neurostimulation is an accepted treatment for CRPS . Although results with dorsal column ( DC ) stimulation in patients with CRPS confined to the knee are often disappointing , the availability of dorsal root ganglion ( DRG ) stimulation may provide new opportunities for this complaint . Therefore , this study explores patients ' preference for DC stimulation vs. DRG stimulation in treating chronic pain due to CRPS confined to the knee . METHODS A prospect i ve , observational crossover cohort study was conducted comparing 2 methods of neurostimulation , in r and omized order , in patients with CRPS confined to the knee . After receiving DC and DRG stimulation during a trial period of 16 days , patients were asked which of the 2 methods they preferred . Patients with a successful trial period with one or both stimulation methods received a fully implantable system . RESULTS Twelve patients were included . After finishing the trial period , 10 patients ( 83.3 % ) preferred DRG stimulation and 2 ( 16.7 % ) preferred DC stimulation ( P = 0.04 ) . CONCLUSION To our knowledge , this is the first study to compare these 2 neurostimulation methods in patients with CRPS confined to the knee . Results show that the probability of the preference for either neurostimulation treatment significantly deviates from chance in favor of DRG stimulation Complex regional pain syndromes ( CRPS ; type 1 , reflex sympathetic dystrophy , and type 2 , causalgia ) involve persistent pain , allodynia , and vasomotor signs . We conducted a prospect i ve , r and omized , single-blind trial of physical therapy ( PT ) and cognitive-behavioral treatment for children and adolescents with CRPS . Children 8 to 17 years of age ( n = 28 ) were r and omly assigned to either group A ( PT once per week for 6 weeks ) or group B ( PT 3 times per week for 6 weeks ) . Both groups received 6 sessions of cognitive-behavioral treatment . Assessment s of pain and function were repeated at two follow-up time periods . Outcomes were compared at the three time points through the use of parametric or nonparametric analysis of variance and post hoc tests . All five measures of pain and function improved significantly in both groups after treatment , with sustained benefit evident in the majority of patients at long-term follow-up . Recurrent episodes were reported in 50 % of patients , and 10 patients eventually received sympathetic blockade . Most children with CRPS showed reduced pain and improved function with a noninvasive rehabilitative treatment approach . Long-term functional outcomes were also very good Calcitonin is widely used in the treatment of algodystrophy but a major disadvantage is the need for its parenteral administration . For this reason , we evaluated the effect of 400 iu of nasal calcitonin in the treatment of post-traumatic algodystrophy in a prospect i ve r and omized double-blind study . We found no demonstrable effect on the clinical or skeletal progression of the disorder using sensitive methods of measuring the response to treatment . There was , however , a small but significant hypocalcaemic response in the treatment group despite no change in the other indices of bone turnover . Possible reasons for this lack of clinical and skeletal effect are discussed & NA ; The efficacy of intranasal salmon calcitonin was examined in a double‐blind r and omized study in reflex sympathetic dystrophy . Sixty‐six patients were r and omly divided in two groups receiving physiotherapy . In addition group I also received 3 × 100 U/day of salmon calcitonin by intranasal spray whereas group II received 3 sprays of placebo . The pain and the range of motion were improved by calcitonin administration . Similarly the patients ' ability to work was also improved . The results confirmed that salmon calcitonin has an effect but that this effect was not equally observed on all parameters analyzed . It was most marked on pain ( at rest and on movement ) and on the ability to work BACKGROUND Complex regional pain syndrome ( CRPS ) is characterized by signs and symptoms of peripheral inflammation , which leads to peripheral neural sensitization associated most frequently ( in about 70 % ) with blunt pressure hyperalgesia . Therefore , we hypothesized that treatment of CRPS patients with a selective COX-2-inhibitor would alleviate the abnormally low pressure pain threshold ( PPT ) and reduce pain intensity and edema . METHODS Twenty patients with CRPS type I ( n = 16 ) and II of the upper limb and abnormally low PPT were double-blind r and omised into 2 groups of 10 patients each to receive a 2-day intravenous treatment of either 80 mg parecoxib per day ( group I ) or placebo ( NaCl 0.9 % , group II ) . St and ardized quantitative sensory testing ( QST ) using the DFNS protocol was performed before and after treatment . Pain intensity ( NRS 0 - 10 ) ; circumferences of the fingers II , IV , and V ( mm ) ; PPT ( kPa , thenar/hypothenar ) ; and adverse events were recorded daily . STATISTICS Wilcoxon-test , Mann-Whitney-U-test , Friedman-test , Fisher-test , significance level : P < 0.05 . STUDY DESIGN Proof of concept trial performed in r and omized , placebo-controlled , double blind style . SETTING Pain Management Center in Germany . RESULTS There were no group differences in PTT or other QST parameters . After treatment , PPT decreased insignificantly in group I ( median [ range ] ; before : 224.0 [ 121.0 - 52937 ] kPa , afterwards : 186.4 [ 101.4 - 526.5 ] kPa ) and increased insignificantly in group II ( before : 207.6 [ 170.0 - 320.5 ] kPa ; afterwards : 235.4 [ 163.5 - 349.9 ] kPa ) . Pain scores and finger circumferences remained unchanged in both groups . LIMITATIONS Due to difficulty in recruitment the trial was closed after inclusion of 20 patients . CONCLUSION In the present proof-of-concept trial , short-term treatment with the selective COX-2-inhibitor parecoxib influenced neither PPT nor edema or pain . COX-2 might be less important than previously assumed . However , the results are limited due to the small number of patients , short-term treatment , and focus on the PPT , which could have led to false negative results of the present study and covered the expected therapeutic effect OBJECTIVE To investigate the effect of transcutaneous electrical nerve stimulation ( TENS ) on clinical recovery in the management of patients with complex regional pain syndrome Type I ( CRPS Type I ) . MATERIAL AND METHOD The study included 30 patients with stage 1 and 2 CRPS Type I in the upper extremities . The patients were r and omly assigned into 2 groups , group 1 ( n= 15 ) received conventional TENS therapy for 20 minutes , and group 2 ( n= 15 ) received sham TENS therapy . The st and ard physical therapy program , which included contrast bath for 20 minutes ; whirlpool bath for 15 minutes ; assisted active and passive range of motion , and static stretching exercises up to the pain threshold , was also conducted in both groups . Therapy was scheduled for 15 sessions . A visual analogue scale ( VAS ) was used to assess spontaneous pain . The Leeds Assessment of Neuropathic Signs and Symptoms ( LANSS ) scale and the Douleur Neuropathique en 4 Questions ( DN-4 ) were used to assess neuropathic pain . In addition , range of motion ( ROM ) was measured using a goniometer and volumetric measurements were taken to assess edema . Functional capacity was assessed using a h and dynamometer and the Duruöz H and Index ( DHI ) . All measurements were performed at baseline and after therapy . RESULTS Significant improvements were achieved in spontaneous and neuropathic pain scores , edema , ROM , and functional capacity in both groups ( p < 0.05 ) . However , improvement was found to be significantly greater in group 1 regarding pain intensity , neuropathic pain assessed using LANNS , edema , and in the 2nd-3rd finger ROM measurements ( p < 0.05 ) . No significant difference was detected between groups regarding improvements in 4th-5th finger and wrist ROM measurements , grip strength , and DN4 and DHI scores ( p > 0.05 ) . CONCLUSION The addition of TENS to the physical therapy program was seen to make a significant contribution to clinical recovery in CRPS Type 1 Abstract Background and purpose : Complex regional pain syndrome type I ( CPRS I ) , is a complex of symptoms characterized by diffuse pain usually with associated swelling , vasomotor instability , and severe functional impairment of the affected extremity in stroke patients . Pain is a prominent feature and is often refractory to variety of treatment . Methods : To investigate the clinical , functional , and psychosocial effects of upper extremity aerobic exercise ( UEAE ) and compare the effect of aerobic exercise with that of conventional physiotherapy in patients with CPRS type I following stroke as a r and omized controlled assesor blinded 4 week- study . A total of 52 in patients with stroke [ mean age : 65.95 ± 8.7 ( min . = 53 , max . = 80 ) years , and the mean age of the control group was 67.50 ± 11.2 years ] , all within 6 months post-stroke and diagnosed with CPRS I. The UEAE program consisted of an arm crank ergometer ( 10 W/min ) , in addition to a conventional physiotherapy ( whirlpool , TENS , retrograd massage ) . Primary outcome measures were CPRS clinical determinants ( pain , hyperalgesia , allodynia , and autonomic abnormalities ) secondary outcome measures were functional independence measure ( FIM ) , Nottingham Health Profile ( NHP ) , and Beck Depression Scale scores that were performed at 0 month ( baseline ) and 4 weeks ( post-treatment ) . Results : In UEAE group , patients reported significant pain relief ( 89.9 % ) and significant decline in CRPS signs and symptoms . The mean change in pain at shoulder , pain at the h and as well as and NHP and BDS scores between groups were statistically significant ( P < 0.05 ) . Conclusions : UEAE made an excellent improvement in the symptoms and signs of CRPS I. Combined treatment of conventional physiotherapy and aerobic exercises may be an excellent synthesis for this syndrome in these patients Reflex sympathetic dystrophy ( RSD ) is a disorder that can potentially result in permanent impairment . Because there are no adequate comparative studies regarding the additional value of physical therapy ( PT ) or occupational therapy ( OT ) for reducing the severity of permanent impairment in RSD , we prospect ively investigated their effectiveness . At two university hospitals , we r and omly assigned 135 patients with RSD of one upper limb , existing for < 1 yr , to PT , OT , or control therapy ( CT ) . One year after inclusion , impairment percentages were calculated according to the general method of the American Medical Association 's Guides to the Evaluation of Permanent Impairment . For statistical evaluation , the Wilcoxon 's signed-rank test ( two-sided ; alpha = 0.05 ) was used . The mean whole body impairments were as follows : PT , 21.6 % and 19.1 % ; OT , 22.8 % and 22.1 % ; CT , 22.0 % and 22.1 % ( intention-to-treat and per protocol analysis , respectively ) . There were no significant differences between the groups . We conclude that impairment percentages in RSD patients treated with PT or OT did not differ significantly from those treated with CT at 12 months after inclusion Patients with reflex sympathetic dystrophy , who received transient pain relief from stellate ganglion blocks or lumbar sympathetic blocks and had abnormal isolated cold stress tests , were enrolled in a study to determine the efficacy of intravenous regional bretylium . Each patient received two control treatments ( 0.5 % lidocaine ) and two treatments with 0.5 % lidocaine and bretylium 1.5 mg/kg in a r and omized , double-blind fashion . A st and ard intravenous regional technique was used with a 300-mm Hg tourniquet pressure for 20 min . Patients kept a daily record of pain relief ( 0 = no relief , 100 % = complete relief ) . A decrease in pain of more than 30 % was considered clinical ly significant . Therefore , once the patient 's pain relief was less than 30 % , the next intravenous regional treatment was performed . Bretylium and lidocaine provided more than 30 % pain relief for a mean of 20.0 ( + /- 17.5 ) days , whereas lidocaine alone provided relief for only 2.7 ( + /- 3.7 ) days ( Mann-Whitney U-test , P less than 0.001 ) . A mean temperature increase in the treated limb of + 2.64 + /- 3.41 degrees C above the baseline temperature was noted after bretylium administration , whereas after control treatments the change was -0.086 + /- 1.30 degrees C ( Mann-Whitney U-test , P less than 0.02 ) . We conclude that the combination of bretylium and lidocaine is significantly more effective than lidocaine alone when an intravenous block is used to treat reflex sympathetic dystrophy OBJECTIVES This study aims to compare the effectiveness of a bisphosphonate ( pamidronate ) and a steroid ( prednisolone ) in complex regional pain syndrome ( CRPS ) type I during four weeks of follow-up in hemiplegic stroke patients . METHODS Twenty-one hemiplegic stroke patients with CRPS type I were enrolled in the study . Patients were r and omly assigned to receive either intravenous pamidronate ( n = 11 ; total cumulative dose of 180 mg ) or oral prednisolone ( n = 10 ) . Subjective pain and h and oedema ( circumference of the middle finger , CMF , and the wrist , CW ) were measured at baseline and at one , two and four weeks after the end of treatment . RESULTS Both groups showed significant improvement in subjective pain VAS scores at 1-week follow-up and this effect was maintained until 4-week follow-up . Time-by-group interactions were not significant at 4-week follow-up . The reduction of the CMF observed at 1-week follow-up in both groups was maintained until 4-week follow-up in the steroid group , but until 2-week follow-up in the pamidronate group . A significant change in CW was observed at 4-week follow-up in the pamidronate group . There were no significant adverse effects in either treatment group during the follow-up period . CONCLUSIONS Intravenous pamidronate therapy was safe , well tolerated and appeared as effective as a steroid for pain control for post-stroke CRPS . However , this result should be interpreted with caution , since it included a relatively small number of patients . Further larger controlled studies followed over a longer period are needed to vali date these findings and to determine clinical treatment st and ards We report the results of two prospect i ve studies of early treatment and psychological aspects in a series of 26 patients with sympathetic reflex dystrophy of the h and in which treatment was started within 3 months after diagnosis . Ismelin blocks is an often used therapy in sympathetic reflex dystrophy but a probable better therapy in the first stage of the dystrophy was also investigated . Thirteen patients were treated with Regional Intravenous Ismelin blocks and 13 other patients were treated with a hydroxyl radical scavenger , dimethylsulfoxide ( DMSO ) . After 9 weeks there was a better result in the group treated with DMSO . This report also describes psychological research in a group of 24 dystrophy patients compared with a control group of 42 patients who underwent elective h and -surgery . Women dystrophy patients were more depressed and emotionally unstable . Eighty percent of all dystrophy patients had a recent life-event while only 20 % of the control group members reported such an event . These two features seem to be independent . Early diagnosis in combination with early stress management training and a multidisciplinary treatment tends to be a very good solution BACKGROUND Conventional tonic spinal cord stimulation ( SCS ) is an effective treatment for patients with therapy-resistant complex regional pain syndrome ( CRPS ) . Although the therapeutic effect of SCS can diminish over time due to tolerance , pain control can be regained by changing the pulse width and the amplitude and /or by increasing the stimulation frequency . This multicentre , double-blind , r and omized and placebo-controlled crossover trial was conducted to investigate whether more effective pain reduction is achieved with different frequencies ( trial registration , current controlled trials , IS RCT N 36655259 ) . METHODS The investigated setting s are as follows : st and ard 40 , 500 , 1200 Hz , burst and placebo stimulation . All five were programmed in r and om order during the 10-week crossover period ( 2 weeks/ setting ) . The primary outcome parameters were scores on the visual analogue scale ( VAS ) , McGill Pain Question naire ( MPQ ) and the Global Perceived Effect ( GPE ) ; at the end of the crossover period , patients decided which SCS setting they preferred . A linear mixed models analysis was performed in 29 patients who completed the crossover trial . RESULTS Significant pain reduction and GPE satisfaction was achieved with four SCS setting s compared with placebo stimulation , and these four setting s did not differ significantly from each other . St and ard stimulation was preferred by 48 % of the patients , while 52 % preferred non-st and ard stimulation . Other than pain reduction , factors such as user-friendliness , comfort and recharging time may have influenced the patient 's final decision for the preferred stimulation setting . CONCLUSIONS Apparently , for various reasons , patients have a preference for different SCS setting . Therefore , future neuromodulation should aim to implement customized individual patient care by incorporating all stimulation options in one device . SIGNIFICANCE This study demonstrates that st and ard frequency SCS is an effective therapy for patients with CRPS . However , it also demonstrates that patients can often gain better pain reduction with non-st and ard frequencies of SCS . Furthermore , it shows that the preferred stimulation setting is not solely driven by the amount of pain reduction , but is also influenced by which stimulation setting feels most comfortable and provides the best user-friendliness . Therefore , we strive to maximize the therapeutic effects of SCS in as many patients as possible . This can be achieved with customized individual patient care by incorporating the various frequencies and waveforms into one single device Twenty-three patients with reflex dystrophy syndrome were r and omly allocated to medication with oral prednisone , 10 mg thrice daily , or placebo , previous reports having indicated effect of systemic corticosteroids . The medication was continued until clinical remission , maximally 12 weeks . The diagnosis was based on fulfillment of at least four of seven criteria which included clinical , radiological and circulatory changes . All 13 patients in the prednisone-treated group showed more than 75 % clinical improvement within the twelve-week period . Of the ten patients who received placebo , only two reported improvement . Prednisone appears to be superior to other treatment in reflex dystrophy syndrome , although the mode of action is not known OBJECTIVE Pain-relieving effects of lidocaine/bupivicaine local anesthetic ( LA ) and saline ( S ) block of sympathetic ganglia ( stellate block , 4 patients ; lumbar sympathetic block , 3 patients ) were compared in 7 complex regional pain syndrome ( CRPS ) patients on a double-blind crossover basis to evaluate the diagnostic and therapeutic value of local anesthetic sympathetic blocks . DESIGN Patients rated their pain on a visual analog scale before and after blocks and were tested for mechanical allodynia one-half hour after blocks . Thereafter , they rated their pain intensity in diaries four times a day for 7 days . Each patient received two blocks , S and LA , and served as his own control . RESULTS Both S and LA injections of sympathetic ganglia produced large reductions in pain intensity in 6 of 7 patients 30 minutes after block . These large reductions were accompanied by the reversal of mechanical allodynia in both S and LA . The mean difference between initial peak reduction in pain intensity produced by saline ( 68.7 % ) and active local anesthetic ( 74.4 % ) did not approach statistical significance . In striking contrast , the mean duration of pain relief was reliably longer in the case of LA ( 3 days , 18 hours ) as compared with S ( 19.9 hours ) , a difference that occurred in all 7 patients . In a larger sample of 41 CRPS patients , signs of sympathetic efferent blockade , including Homer ' s syndrome or skin surface temperature change , were not predictive of initial peak magnitude of pain relief from sympathetic blockade but were predictive of duration of pain reduction . CONCLUSION The combination of these results provides evidence that duration of pain relief is affected by injection of local anesthetics into sympathetic ganglia . These results indicate that both magnitude and duration of pain reduction should be closely monitored to provide optimal efficacy in procedures that use local anesthetics to treat CRPS UNLABELLED Interventional pain management techniques play an important role in the multidisciplinary approach to management of complex regional pain syndrome ( CRPS ) . In this preliminary study we compared the efficacy of continuous stellate ganglion ( CSG ) block with that of continuous infraclavicular brachial plexus ( CIBP ) block in management of CRPS type I of upper extremity . METHODS Thirty-three patients with CRPS type I of upper extremity were r and omly assigned to either CSG or CIBP group . Patients were treated for 1 week with continuous infusion of 0.125 % bupivacaine at 2 and 5mL/h , respectively . Catheter was removed at 1 week and patients were followed up for 4 weeks . The outcome was evaluated in terms of neuropathic pain scale score ( NPSS ) , edema scores ( Grade s 0 - 2 ) , and range of motion ( ROM ) of all upper extremity joints ( Grade s 0 - 2 ) . RESULTS CIBP group showed statistically significant improvement in NPSS compared with CSG group during the first 12 hours after the procedures ( P value < 0.05 ) . After 12 hours , the NPSS was comparable between the groups . At 4 weeks , both groups showed clinical ly significant improvement in edema score and ROM of all upper extremity joints when compared with the baseline . CONCLUSION This preliminary study suggests that CIBP block and CSG block may be feasible and effective interventional techniques for the management of CRPS type I of upper extremities . Hence , we recommend a larger well-r and omized , well-controlled , clinical trial to confirm our findings and determine if any significant difference exists between the groups in terms of long-term pain relief and functional restoration |
675 | 29,746,627 | Conclusions A high DGI and DGL are associated with a higher risk of osteoporosis-related fractures in an elderly Mediterranean population at high cardiovascular disease risk . | Background High glucose and insulin concentrations seem to have a negative impact on bone health .
However , the relation between the dietary glycemic index ( DGI ) and the dietary glycemic load ( DGL ) , which has proved to be effective at modulating blood glucose concentrations after carbohydrate consumption , has yet to be explored in relation to bone health .
Objective The aim of the study was to examine the associations between the DGI or DGL and the risk of osteoporotic-related fractures in an elderly Mediterranean population . | OBJECTIVE Individuals with type 2 diabetes have increased fracture risk despite higher bone mineral density ( BMD ) . Our aim was to examine the influence of glucose control on skeletal complications . RESEARCH DESIGN AND METHODS Data of 4,135 participants of the Rotterdam Study , a prospect i ve population -based cohort , were available ( mean follow-up 12.2 years ) . At baseline , 420 participants with type 2 diabetes were classified by glucose control ( according to HbA1c calculated from fructosamine ) , result ing in three comparison groups : adequately controlled diabetes ( ACD ; n = 203 ; HbA1c < 7.5 % ) , inadequately controlled diabetes ( ICD ; n = 217 ; HbA1c ≥7.5 % ) , and no diabetes ( n = 3,715 ) . Models adjusted for sex , age , height , and weight ( and femoral neck BMD ) were used to test for differences in bone parameters and fracture risk ( hazard ratio [ HR ] [ 95 % CI ] ) . RESULTS The ICD group had 1.1–5.6 % higher BMD , 4.6–5.6 % thicker cortices , and −1.2 to −1.8 % narrower femoral necks than ACD and ND , respectively . Participants with ICD had 47–62 % higher fracture risk than individuals without diabetes ( HR 1.47 [ 1.12–1.92 ] ) and ACD ( 1.62 [ 1.09–2.40 ] ) , whereas those with ACD had a risk similar to those without diabetes ( 0.91 [ 0.67–1.23 ] ) . CONCLUSIONS Poor glycemic control in type 2 diabetes is associated with fracture risk , high BMD , and thicker femoral cortices in narrower bones . We postulate that fragility in apparently “ strong ” bones in ICD can result from microcrack accumulation and /or cortical porosity , reflecting impaired bone repair The determine the effect of different foods on the blood glucose , 62 commonly eaten foods and sugars were fed individually to groups of 5 to 10 healthy fasting volunteers . Blood glucose levels were measured over 2 h , and expressed as a percentage of the area under the glucose response curve when the same amount of carbohydrate was taken as glucose . The largest rises were seen with vegetables ( 70 + /- 5 % ) , followed by breakfast cereals ( 65 + /- 5 % ) , cereals and biscuits ( 60 + /- 3 % ) , fruit ( 50 + /- 5 % ) , dairy products ( 35 + /- 1 % ) , and dried legumes ( 31 + /- 3 % ) . A significant negative relationship was seen between fat ( p less than 0.01 ) and protein ( p less than 0.001 ) and postpr and ial glucose rise but not with fiber or sugar content The aim of the present study was to assess reproducibility and relative validity of a self-administered FFQ used in the PREDIMED Study , a clinical trial for primary prevention of CVD by Mediterranean diet in a population at high cardiovascular risk . The FFQ was administered twice ( FFQ1 and FFQ2 ) to explore reproducibility at 1 year . Four 3 d dietary records ( DR ) were used as reference to explore validity ; participants therefore recorded their food intake over 12 d in the course of 1 year . The degree of misclassification in the FFQ was also evaluated by a contingency table of quintiles comparing the information from the FFQ2 and the DR . A total of 158 men and women ( aged 55 - 80 years ) were asked not to modify their dietary habits during the study period . Reproducibility for food groups , energy and nutrient intake , explored by the Pearson correlation coefficient ( r ) ranged 0.50 - 0.82 , and the intraclass correlation coefficient ( ICC ) ranged from 0.63 to 0.90 . The FFQ2 tended to report higher energy and nutrient intake than the DR . The validity indices of the FFQ in relation to the DR for food groups and energy and nutrient intake ranged ( r ) from 0.24 to 0.72 , while the range of the ICC was between 0.40 and 0.84 . With regard to food groups , 68 - 83 % of individuals were in the same or adjacent quintile in both methods , a figure which decreased to 55 - 75 % for energy and nutrient intake . We concluded that FFQ measurements had good reproducibility and a relative validity similar to those of FFQ used in other prospect i ve studies Hip fractures are the most devastating consequence of osteoporosis and impact 1 in 6 white women leading to a two- to threefold increased mortality risk in the first year . Despite evidence of inflammatory markers in the pathogenesis of osteoporosis , few studies have examined their effect on hip fracture . To determine if high levels of inflammation increase hip fracture risk and to explore mediation pathways , a case-cohort design nested in a cohort of 4709 white women from the Study of Osteoporotic Fractures was used . A r and om sample of 1171 women was selected as the subcohort ( mean age 80.1 ± 4.2 years ) plus the first 300 women with incident hip fracture . Inflammatory markers interleukin-6 ( IL-6 ) and soluble receptors ( SR ) for IL-6 ( IL-6 SR ) and tumor necrosis factor ( TNF SR1 and TNF SR2 ) were measured , and participants were followed for a median ( interquartile range ) of 6.3 ( 3.7 , 6.9 ) years . In multivariable models , the hazard ratio ( HR ) of hip fracture for women in the highest inflammatory marker level ( quartile 4 ) was 1.64 ( 95 % confidence interval [ CI ] , 1.09 - 2.48 , p trend = 0.03 ) for IL-6 and 2.05 ( 95 % CI , 1.35 - 3.12 , p trend < 0.01 ) for TNF SR1 when compared with women in the lowest level ( quartile 1 ) . Among women with 2 and 3 - 4 inflammatory markers in the highest quartile , the HR of hip fracture was 1.51 ( 95 % CI , 1.07 - 2.14 ) and 1.42 ( 95 % CI , 0.87 - 2.31 ) compared with women with zero to one marker(s ) in the highest quartile ( p trend = 0.03 ) . After individually adjusting for seven potential mediators , cystatin-C ( a biomarker of renal function ) and bone mineral density ( BMD ) attenuated HRs among women with the highest inflammatory burden by 64 % and 50 % , respectively , suggesting a potential mediating role . Older white women with high inflammatory burden are at increased risk of hip fracture in part due to poor renal function and low BMD CONTEXT AND OBJECTIVE Because it has been suggested that osteocalcin ( OC ) , an osteoblast-derived hormone , is a new link between bone and glucose metabolism , we tested whether serum carboxylated osteocalcin ( cOC ) and undercarboxylated osteocalcin ( ucOC ) levels are independently associated with the development of type 2 diabetes in subjects at high cardiovascular risk . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve , nested case-control study was conducted using data from the Prevención con Dieta Mediterránea ( PREDIMED ) study . We included 153 case subjects with newly diagnosed diabetes and 306 individually matched control subjects free of diabetes identified during a mean 5-year follow-up . Conditional logistic regression models were used to estimate matched odds ratios for incident diabetes according to categories of both forms of OC measured by ELISAs . RESULTS Baseline serum concentrations of both forms of OC were significantly lower in case subjects than in control subjects . In subjects with incident cases of diabetes , concentrations of cOC , but not of ucOC , were inversely and significantly associated with homeostasis model assessment of insulin resistance levels ( β = -0.335 ) and with fasting glucose concentrations ( β = -0.044 ) in control subjects , independent of other relevant confounders . In the conditional logistic model that took into account the matching factors , the odds ratios for diabetes incidence in the lowest vs the highest tertile of cOC and ucOC were 2.03 ( 95 % confidence interval , 1.32 - 3.13 ) and 1.88 ( 1.23 - 2.85 ) , respectively . Further adjustment for family history of diabetes , lifestyle , and other confounding factors did not appreciably change the magnitude of these associations . CONCLUSION In a population at high cardiovascular risk , low concentrations of serum cOC and ucOC were strongly associated with an increased risk of incident diabetes OBJECTIVE To examine prospect ively the relationship between glycemic diets , low fiber intake , and risk of non-insulin-dependent diabetes mellitus . DESIGN Cohort study . SETTING In 1986 , a total of 65173 US women 40 to 65 years of age and free from diagnosed cardiovascular disease , cancer , and diabetes completed a detailed dietary question naire from which we calculated usual intake of total and specific sources of dietary fiber , dietary glycemic index , and glycemic load . MAIN OUTCOME MEASURE Non-insulin-dependent diabetes mellitus . RESULTS During 6 years of follow-up , 915 incident cases of diabetes were documented . The dietary glycemic index was positively associated with risk of diabetes after adjustment for age , body mass index , smoking , physical activity , family history of diabetes , alcohol and cereal fiber intake , and total energy intake . Comparing the highest with the lowest quintile , the relative risk ( RR ) of diabetes was 1.37 ( 95 % confidence interval [ CI ] , 1.09 - 1.71 , P trend=.005 ) . The glycemic load ( an indicator of a global dietary insulin dem and ) was also positively associated with diabetes ( RR= 1.47 ; 95 % CI , 1.16 - 1.86 , P trend=.003 ) . Cereal fiber intake was inversely associated with risk of diabetes when comparing the extreme quintiles ( RR=0.72 , 95 % CI , 0.58 - 0.90 , P trend=.001 ) . The combination of a high glycemic load and a low cereal fiber intake further increased the risk of diabetes ( RR=2.50 , 95 % CI , 1.14 - 5.51 ) when compared with a low glycemic load and high cereal fiber intake . CONCLUSIONS Our results support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of diabetes in women . Further , they suggest that grains should be consumed in a minimally refined form to reduce the incidence of diabetes BACKGROUND Osteocalcin has been related to insulin secretion in experimental models . Few prospect i ve studies have evaluated the association between circulating osteocalcin concentrations and insulin secretion and sensitivity in humans . OBJECTIVE The objective was to examine cross-sectional and longitudinal associations between circulating forms of osteocalcin and insulin secretion and sensitivity in elderly men at high cardiovascular risk . DESIGN We examined cross-sectional and longitudinal associations between serum measurements of total osteocalcin and undercarboxylated osteocalcin ( ucOC ) with fasting glucose , fasting insulin , HOMA-IR , and HOMA β cell function ( HOMA-BCF ) in 79 elderly men . We also examined the association between 2-y changes in osteocalcin and changes in fasting glucose , insulin , HOMA-IR , and HOMA-BCF . RESULTS In an adjusted multivariable linear regression analysis , increases in serum osteocalcin were significantly associated with an increase in HOMA-BCF ( β coefficient : 2.87 ; 95 % CI : 0.23 , 5.52 ; P = 0.033 ) , and changes in ucOC were linked to a decrease in HOMA-IR ( β coefficient : -0.31 ; 95 % CI : -0.60 , 0.03 ; P = 0.032 ) . Moreover , in subjects not taking oral antidiabetic drugs , baseline osteocalcin concentrations were positively associated with higher fasting insulin concentrations and HOMA-BCF even after adjustment for BMI , physical activity , intervention group , presence of type 2 diabetes mellitus , and baseline values of each dependent variable . CONCLUSIONS Changes in serum osteocalcin and ucOC are associated with an improvement in insulin secretion and sensitivity , which suggests a possible role of bone in the development of type 2 diabetes . This trial is registered at clinical trials.gov as IS RCT N35739639 The proinflammatory cytokines interleukin-1 beta ( IL-1 beta ) and IL-6 may play a central role in the acceleration of postmenopausal bone loss , but observational studies have led to contradictory results . Estrogen-dependent changes in the production of IL-1 receptor antagonist ( IL-1ra ) and the soluble IL-6 receptor ( sIL-6R ) potentially modify cytokine bioactivity . We therefore assessed the impact of menopause and hormone replacement therapy ( HRT ) on cytokines and activity modifiers in serum within a 5-year longitudinal study . One hundred sixty perimenopausal women ( age 50.1 + /- 2.8 years ) were r and omized to HRT or no treatment . Serum IL-6 increased with age ( r = 0.16 ; p < 0.05 ) , but cytokines did not correlate with baseline bone mineral density ( BMD ) . HRT led to small increases in IL-1ra ( p < 0.001 ) and IL-6 ( p < 0.05 ) , with a decrease in sIL-6R ( p < 0.01 ) and no change in IL-1 beta . No changes were observed in the control group . IL-1ra was inversely correlated with bone loss at the ultradistal forearm ( r = 0.29 ; p < 0.05 ) and to a lesser degree at the spine ( r = 0.20 ; p = 0.09 ) . In addition , there was a weak positive correlation between sIL-6R and bone loss at the ultradistal forearm ( r = 0.26 ; p < 0.05 ) . High IL-6 levels were associated with slower bone loss ( spine r = 0.31 , p < 0.01 ) and controlling for age did not diminish this association . The percent change in sIL-6R during HRT was correlated with the bone loss at the femoral neck ( r = -0.29 ; p < 0.01 ) and weakly with bone loss in the spine ( r = -0.16 ; p = 0.17 ) . In conclusion , serum IL-1ra and sIL-6R are influenced by HRT and are associated with the rate of bone loss in perimenopausal women |
676 | 21,458,274 | No significant differences between computer-navigated and conventional groups were found in terms of knee stability and functional assessment during short-term follow-up . | Inaccurate tunnel placement is an important cause of failure in conventional anterior cruciate ligament ( ACL ) reconstruction .
Controversy currently exists over the usefulness of computer-assisted navigation systems in addressing this problem . | Conflict between clinical importance and statistical significance is an important problem in medical research . Although clinical importance is best described by asking for the effect size or how much , statistical significance can only suggest whether there is any difference . One way to combine statistical significance and effect sizes is to report confidence intervals . We therefore assessed the reporting of confidence intervals in the orthopaedic literature and factors influencing this frequency . In parallel , we tested the predictive value of statistical significance for effect size . In a r and om sample of predetermined size , we found one in five orthopaedic articles reported confidence intervals . Participation of an individual trained in research methods increased the odds of doing so fivefold . The use of confidence intervals was independent of impact factor , year of publication , and significance of outcomes . The probability of statistically significant results to predict at least a 10 % between-group difference was only 69 % ( 95 % confidence interval , 55%–83 % ) , suggesting that a high proportion of statistically significant results do not reflect large treatment effects . Confidence intervals could help avoid such erroneous interpretation by showing the effect size explicitly Delayed rather than early reconstruction of the anterior cruciate ligament is the current recommended treatment for injury to this ligament since it is thought to give a better functional outcome . We r and omised 105 consecutive patients with injury associated with chondral lesions no more severe than grade s 1 and 2 and /or meniscal tears which only required trimming , to early ( < two weeks ) or delayed ( > four to six weeks ) reconstruction of the anterior cruciate ligament using a quadrupled hamstring graft . All operations were performed by a single surgeon and a st and ard rehabilitation regime was followed in both groups . The outcomes were assessed using the Lysholm score , the Tegner score and measurement of the range of movement . Stability was assessed by clinical tests and measurements taken with the KT-1000 arthrometer , with all testing performed by a blinded uninvolved experienced observer . A total of six patients were lost to follow-up , with 48 patients assigned to the delayed group and 51 to the early group . None was a competitive athlete . The mean interval between injury and the surgery was seven days ( 2 to 14 ) in the early group and 32 days ( 29 to 42 ) in the delayed group . The mean follow-up was 32 months ( 26 to 36 ) . The results did not show a statistically significant difference for the Lysholm score ( p = 0.86 ) , Tegner activity score ( p = 0.913 ) or the range of movement ( p = 1 ) . Similarly , no distinction could be made for stability testing by clinical examination ( p = 0.56 ) and measurements with the KT-1000 arthrometer ( p = 0.93 ) . Reconstruction of the anterior cruciate ligament gave a similar clinical and functional outcome whether performed early ( < two weeks ) or late at four to six weeks after injury Introduction Correct placement of both tibial and femoral tunnels is one of the main factors for a favorable clinical outcome after anterior cruciate ligament ( ACL ) reconstruction . We used an original system of computer assisted surgery ( CAS ) . The system , based on fluoroscopic guidance combined with special graphical software of image analyzing , showed to the surgeon , before drilling , the recommended placement of tibial and femoral tunnel centers . We compared the first anatomical and clinical results of this procedure to the usual one single incision technique . Material s and methods We conducted a prospect i ve study on 73 patients ; 37 patients were operated on with CAS and 36 without CAS , by the same senior surgeon . The mean age was 27 years for both groups . Every patient was review ed at an average of 2.2 years ( range 1–4.5 ) by an independent observer , using IKDC scoring system , KT-1000 , and passive stress radiographs . Results Time between ACL rupture and reconstruction averaged 30 months for both groups . CAS needed 9.3 min extra surgery time . Clinical evaluation was grade d from A to C as per the IKDC scoring system : 67.6 % A , 29.7 % B , 2.7 % C with CAS ; and 60 % A , 37.1 % B , 2.9 % C without CAS . IKDC subjective knee evaluation score averaged 89.7 with CAS and 89.5 without CAS . Pre operative KT-1000 maxi manual differential laxity averaged 7 . At revision time , all the patients after CAS had a differential laxity less than 2 and 97.7 % without CAS . Stress X-rays differential laxity averaged 2.4 mm with CAS and 3 mm without CAS . The area of dispersion of the tunnels ’ center was smaller on the femoral side using the CAS method . There was no statistically significant difference between both groups using IKDC score , KT-1000 and passive stress radiographs . Conclusions The CAS method provided a more accurate and reproducible tunnels placement without clinical significant effect OBJECTIVES : To compare the accuracy of tunnel placement and graft isometry for anterior cruciate ligament reconstruction performed using a computer-assisted navigation system ( Orthopilot ) and using traditional instruments . METHODS : The anterior cruciate ligament was removed intact from 36 pairs of human cadaver knees . From each pair , one knee was r and omized to Group 1 ( conventional ) and the other to Group 2 ( Orthopilot ) . An inelastic suture was then passed through the central points of the tibial and femoral tunnels . Neither of the tunnels was drilled . All knees were then dissected , and six parameters were obtained : distances from the tibial tunnel center to the 1 ) posterior cruciate ligament , 2 ) anterior horn of the lateral meniscus and 3 ) medial tibial spine ; 4 ) distance from the femoral tunnel center to the posterior femoral cortex ; 5 ) femoral tunnel coronal angle ; and 6 ) variation of the distance from the femoral to the tibial tunnel with the knee extended and at 90 degrees of flexion . RESULTS : The variation of the distance from the femoral to the tibial tunnel during flexion and extension was smaller in the Orthopilot group ( better isometry ) compared to the conventional group . There were no statistical differences in any other parameters between the groups , and all tunnels were considered to be in satisfactory positions . DISCUSSION : The results obtained for anterior cruciate ligament reconstruction depend on precise isometric point positioning , and a navigation system is a precision tool that can assist surgeons in tunnel positioning . CONCLUSION : No differences in tunnel position were observed between the groups . Nonetheless , better isometry was achieved in the Orthopilot group than with conventional instruments Evidence -based medicine integrates clinical expertise , patients ' values and preferences , and the best available evidence from the medical literature . Evidence -based orthopedics is a model to assist surgeons to improve the process of asking questions , obtaining relevant information efficiently , and making informed decisions with patients . With an increasing appreciation for higher levels of evidence , orthopedic surgeons should move away from lower forms of evidence . The adoption of r and omized trials and high- quality prospect i ve studies to guide patient care requires 2 prerequisites : ( 1 ) greater appreciation for the conduct of r and omized trials in orthopedics and ( 2 ) improved education and training in evidence -based method ologies in surgery To correlate clinical results after anterior cruciate liga ment reconstruction with tunnel placement measured radiographically , we prospect ively studied 128 patients who had arthroscopically assisted bone-patellar ten don-bone reconstructions . Patients with bilateral ante rior cruciate ligament reconstructions , other significant knee ligament injuries , or those undergoing chondro plasty or meniscal repairs were excluded , leaving 42 patients . The relationship between radiographic tunnel position and clinical results was determined using the Lysholm score , KT-1000 arthrometer testing , the Teg ner activity level , and the pivot shift and Lachman tests . Clinical results correlated positively with posterior fem oral tunnel placement on lateral radiographs and neg atively with excessive anterior tibial tunnel placement . Specifically , when femoral tunnels were placed at least 60 % posterior along Blumensaat 's line and tibial tun nels were at least 20 % posterior along the tibial pla teau , 69 % of patients had good or excellent Lysholm scores and 79 % had KT-1000 arthrometer maximum manual side-to-side differences of 3 mm or less . When the above criteria were not met , 50 % of patients had good or excellent Lysholm scores and 22 % had KT- 1000 arthrometer maximum manual side-to-side differ ences of 3 mm or less . This close correlation indicates that satisfactory radiographic tunnel position influences outcome after anterior cruciate ligament reconstruc tion PURPOSE The purpose of this study was to evaluate the benefits of computer navigation on tunnel placement during anterior cruciate ligament reconstruction . METHODS A prospect i ve , r and omized , controlled study comparing computer navigation with manual operation was performed between December 2003 and April 2004 . We assigned 20 patients to the computer navigation group and 20 patients to the manual navigation group . Surgery was performed by use of a patellar tendon autograft with press-fit fixation . A lateral radiograph of the knee at maximum extension was used to determine the exact position of the tibial tunnel at 4 days postoperatively . Outcomes were evaluated with International Knee Documentation Committee 2000 , Tegner , and Lysholm scoring . There was an additional magnetic resonance imaging ( MRI ) evaluation of tunnel placement and graft quality at the most recent follow-up , approximately 24 months after surgery . RESULTS The postoperative radiographs and 2-year postoperative MRI scans showed no differences between groups for tibial or femoral tunnel placement . In both groups the mean tibial tunnel placement was 46 % of the maximal diameter of the tibia . There were no significant differences between groups for objective and subjective outcomes scoring . Although some qualitative differences existed between groups with respect to MRI graft appearance at 2 years , this had no correlation with overall results . CONCLUSIONS No significant differences were found between computer-assisted and manually navigated anterior cruciate ligament reconstruction with regard to tunnel placement and clinical results at a mean of 2 years postoperatively . LEVEL OF EVIDENCE Level I , r and omized , single-blinded , controlled trial Background Poor outcome in anterior cruciate ligament reconstruction is often related to tunnel position . Hypothesis Improving accuracy of the tunnel position will lead to improved outcome . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods Sixty patients were r and omized to either st and ard instrumentation or computer-assisted guides to position the tibial and femoral tunnels . The results were evaluated on clinical outcome based on International Knee Documentation Committee form ( laxity ) and radiologic assessment : radiologic Lachman ( Telos at 150 and 200 N ) and analysis of the tunnel positions . Results International Knee Documentation Committee laxity was level A in 22 knees in the conventional group ( mean , 1.5 mm at 200 N ) compared with 26 navigated knees ( mean laxity , 1.3 mm ; P= .49 ) . Laxity was less than 2 mm in 96.7 % of the navigated group and 83 % of the conventional group ( P= .292 ) . The variability of laxity in the navigated group was significantly less than in the conventional group , with the st and ard deviation of the navigated group being smaller than that in the conventional group ( P= .0003 at 150 N and .0005 at 200 N Telos ) . A significant difference ( P= .03 ) was found between the groups in the ATB value ( distance between the projection of the Blumensaat line on the tibial plateau and the anterior edge of the tibial tunnel ) , characterizing the sagittal position of the tibial tunnel ( negative ATB values imply graft impingement in extension ) . In the conventional group , mean ATB was –0.2 ( –5 to + 4 ) , whereas it was 0.4 ( 0 to 3 ) in the navigated patients . There were no negative ATB values in the navigated group . Conclusion This study confirms that the accuracy and consistency of tibial tunnel position can be improved by the use of computer-assisted navigation and that the clinical result in terms of laxity is more reliable Background Next to graft fixation , correct positioning of the tibial and femoral tunnel is a deciding factor for the clinical result of anterior cruciate ligament reconstruction surgery . Computer-assisted navigation has been proposed as a method to improve tunnel positioning . Purpose To examine the differences in tibial tunnel placement between cruciate ligament operations using manual and computer-assisted navigation . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods Between December 2003 and April 2004 , 53 athletes underwent anterior cruciate ligament reconstruction surgery with arthroscopic press-fit technique . The first group ( group N ; 24 athletes ) were operated on with the aid of a navigation system ( OrthoPilot , Aesculap AG & Co. KG , Braun ) , and the second group ( group M ; 29 athletes ) were “ manually ” operated on . A lateral radiograph of the knee at maximum extension was used to determine the exact position of the tibial tunnel four days postoperatively . In the measurements , the anterior and posterior boundaries of the tibial tunnel , as well as the center of the tibial tunnel in relation to the maximum tibia anteroposterior diameter were evaluated ( indicated in percent ) . An analysis of the tibial tunnel position proportional to the slope of the intercondylar roof was done to determine intercondylar impingement ( method according to Howell ) . The centers of the tibial tunnels were compared with the “ optimal ” position noted in previous studies . The st and ard deviation was determined for both groups to determine the variance of placement . Results The anterior tibial tunnel border was 19.4 mm in group M ( 29.7 % ) and 21.2 mm in group N ( 32.2 % ) ( P=.18 ) . The center of the tibial tunnel was located at 24.6 mm in group M ( 35.6 % ) and at 26.6 mm in group N ( 40.3 % ) ( P=.19 ) . In group M , the posterior tibial tunnel position was located at 30.2 mm ( 46.2 % ) , and in group N at 32.2 mm ( 49.1 % ) ( P=.21 ) . When comparing the centers of the tibial tunnels with the optimal 44 % found in previous studies , the value for group M ( 37.6 % ) varied significantly , while group N ( 40.5 % ) did not . However , there was no significant difference in the range variance for either group ; the st and ard deviation was 6.9 % ( 4.3 mm ) for group M and 5.9 % ( 3.5 mm ) for group N. One athlete showed moderate impingement in group N , and two athletes in group M. Conclusion Assisted navigation offers good support for correct placement of the tibial tunnel , although experienced surgeons can achieve essentially the same positioning as surgeons using computer-assisted navigation . Whether it is advisable to implement this procedure in daily surgical routine should be decided based on clinical results In a prospect i ve blinded non-r and omised cohort study , 32 patients were assessed following anterior cruciate ligament reconstruction using autograft middle-third bone-patellar tendon-bone , over a period of 10 months . Two experienced surgeons performed the procedures , one using an arthroscopically assisted technique ( 16 patients ) and the other by mini-arthrotomy ( 16 patients ) . A comparison was made between the positions of the tunnels as perceived by the surgeon intra-operatively with the actual position as shown on the post-operative X-ray . An independent blinded observer made the latter assessment . Actual vs. expected tunnel placement was analysed using the coefficient of correlation . The anteroposterior femoral tunnel position indicated perfect correlation ( R(2)=1.00 , P=0 ) , and on the lateral view showed good correlation ( R(2)=0.55 , P=0.005 ) . However , the tibial tunnel position anteroposteriorly showed poor correlation ( R(2)=0.14 , P=0.22 ) , and on the lateral view no correlation ( R(2)=0.07 , P=0.36 ) . The ideal tibial tunnel position is controversial , and in this study , two tibial tunnels were just anterior to the acceptable position and one was posterior . Altogether these three , and one other , were in very different positions to that expected by the surgeon . Surgeons may consider that before drilling the tibial tunnel , intra-operative confirmation of the guide-wire position would be helpful AIM AND METHOD The anterior cruciate ligament ( ACL ) is of great importance for the knee joint function . In the case of a complete ligament injury there is hardly any chance for complete recovery . The clear advantages of an operative reconstruction by replacing the ACL has been shown in many trails . The accurate placement of the graft 's insertions has a significant effect on the mid- and probably long-term outcome of this procedure . Review ing the literature , there are poor long-term results of ACL replacement in 5 to 52 % of all cases , depending on the score system . One of the main reasons for unacceptable results is graft misplacement . This led to the construction of a CAS system for ACL replacement . The system assists this surgical procedure by navigating the exact position of the drilling holes . The Potential deformation quantity of the transplant can be controlled by this system in real time . RESULTS 40 computer-assisted ACL replacements have been performed under active use of the CAS system . The short-term results are encouraging , no special complications have been seen so far . Prospect i ve long-term follow-up studies are ongoing . CONCLUSION ACL reconstruction by manual devices has many sources of error . The CAS system is able to give the surgeon reasonable views that are unachieveable by conventional surgery . He is therefore able to control a source of error and to optimise the results . The feasibility of this device in clinical routine use has been proven Evidence -based medicine is using the best available evidence in order to make accurate and knowledgeable treatment decisions . It is not the automatic gainsay of " low quality " evidence and acceptance of r and omized controlled trials ( RCT ' s ) . To be able to make a sound recommendation for a therapy based on the best available evidence , it is necessary to follow steps in acquiring literature , appraising it for study design and quality , and to assess its results , as well as look at the net benefits and net harms . The purpose of this r and omized , prospect i ve study was to compare accuracy in tunnel placement as performed with a traditional arthroscopic anterior cruciate ligament ( ACL ) reconstruction technique and with KneeNavTM ACL , a computer-assisted surgical navigation technique . Two surgeons experienced in ACL reconstruction , but inexperienced in computer-assisted surgical navigation technique , each r and omly used traditional arthroscopic guides or KneeNavTM ACL to drill a tunnel in twenty identical foam knees . Placement of the result ing tibial and femoral tunnels was measured with a computer-assisted digitizing method and compared to traditional biplanar radiographs . Statistical analysis with Student 's t-test was used to compare the distance from the ideal tunnel placement to the femoral and tibial tunnels . Accuracy of tunnel placement with KneeNavTM ACL was significantly better than that obtained with the traditional arthroscopic technique . Distances from the ideal tunnel placement to the femoral and tibial tunnels were 4.2 + /- 1.8 mm ( mean + /- SD ) and 4.9 + /- 2.3 mm , respectively , for the traditional arthroscopic technique , and 2.7 + /- 1.9 mm ( femur ) and 3.4 + /- 2.3 mm ( tibia ) for KneeNavTM ACL . These differences were statistically different . Tunnel placement for ACL reconstruction with KneeNavTM ACL , an image-based , computer-assisted surgical navigation device with a simple and intuitive interface , was more accurate than with the traditional arthroscopic technique |
677 | 19,221,352 | There were insufficient data to determine whether insulin analogues are better than conventional insulins in reducing long-term diabetes-related complications or death .
INTERPRETATION Rapid- and long-acting insulin analogues offer little benefit relative to conventional insulins in terms of glycemic control or reduced hypoglycemia . | BACKGROUND Although insulin analogues are commonly prescribed for the management of diabetes mellitus , there is uncertainty regarding their optimal use .
We conducted meta-analyses to compare the outcomes of insulin analogues with conventional insulins in the treatment of type 1 , type 2 and gestational diabetes . | OBJECTIVE The goal of this study was to compare the efficacy and safety profiles of biphasic insulin aspart 30 ( 30 % soluble insulin aspart and 70 % protaminated insulin aspart [ BIAsp 30 ] ) and biphasic insulin lispro 25 ( 25 % soluble insulin lispro and 75 % neutral protamine lispro [ Mix25 ] ) used in a BID injection regimen in patients with type 2 diabetes mellitus ( DM ) . Also assessed was patients ' preference for pen device -- the NovoMix 30 FlexPen /NovoLog Mix 70/30 FlexPen ( FlexPen ) versus the Humalog Mix25 Pen/Humalog Mix75/25 Pen ( Humalog Pen ) . METHODS Patients with type 2 DM receiving current insulin treatment were r and omized to a multinational , multicenter , open-label , 2-period , crossover comparison of BIAsp 30 and Mix25 . Efficacy ( by analyses of variance ) and safety profiles were assessed after 12 weeks of treatment . Patients ' preference for pen device was assessed by question naires . RESULTS A total of 137 patients were r and omized to treatment ; 4 were withdrawn during the 2-week run-in treatment with biphasic human insulin 30 . The mean ( SD ) characteristics of the remaining 133 patients ( 79 men , 54 women ) were as follows : age , 62.3 ( 9.2 ) years ; body mass index , 28.1 ( 3.9 ) kg/m(2 ) ; and glycosylated hemoglobin ( HbA(1c ) ) , 8.5 % ( 1.1 ) . Glycemic control was assessed by the measurement of HbA(1c ) after 12 weeks of treatment . Treatment with BIAsp 30 was noninferior to treatment with Mix25 ( upper limit of 90 % CI for estimated difference [ BIAsp 30 - Mix25 ] was < 0.4 % ) . Self-monitored blood glucose levels were comparable ( P = NS ) . Adverse-event profiles were similar between treatments , as was the incidence of hypoglycemic episodes ( 0.69 episode/mo with BIAsp 30 and 0.62 episode/mo with Mix25 , P = 0.292 ) . For all device features assessed , the FlexPen consistently received higher scores ( all P < 0.005 ) . A total of 9.0 % of patients experienced problems with the FlexPen , compared with 32.4 % with the Humalog Pen ( P < 0.001 ) . Furthermore , 74.6 % preferred to continue using the FlexPen , whereas 14.3 % preferred the Humalog Pen ( P < 0.001 ) . CONCLUSIONS In this study , glycemic control with BIAsp 30 and Mix25 was found to be comparable in these patients with type 2 DM . Safety profiles were similar for both regimens . Patients preferred and experienced fewer problems with the FlexPen than the Humalog Pen OBJECTIVE Insulin detemir is a soluble long-acting basal insulin analog design ed to overcome the limitations of conventional basal insulin formulations . Accordingly , insulin detemir has been compared with NPH insulin with respect to glycemic control ( HbA1c , prebreakfast glucose levels and variability , and hypoglycemia ) and timing of administration . RESEARCH DESIGN AND METHODS People with type 1 diabetes ( n = 408 ) were r and omized in an open-label , parallel-group trial of 16-week treatment duration using either insulin detemir or NPH insulin . Insulin detemir was administered twice daily using two different regimens , either before breakfast and at bedtime ( IDet(morn+bed ) ) or at a 12-h interval ( IDet(12h ) ) . NPH insulin was administered before breakfast and at bedtime . Mealtime insulin was given as the rapid-acting insulin analog insulin aspart . RESULTS With both insulin detemir groups , clinic fasting plasma glucose was lower than with NPH insulin ( IDet(12h ) vs. NPH , -1.5 mmol/l [ 95 % CI -2.51 to -0.48 ] , P = 0.004 ; IDet(morn+bed ) vs. NPH , -2.3 mmol/l ( -3.32 to -1.29 ) , P < 0.001 ) , as was self-measured prebreakfast plasma glucose ( P = 0.006 and P = 0.004 , respectively ) . The risk of minor hypoglycemia was lower in both insulin detemir groups ( 25 % , P = 0.046 ; 32 % , P = 0.002 ; respectively ) compared with NPH insulin in the last 12 weeks of treatment , this being mainly attributable to a 53 % reduction in nocturnal hypoglycemia in the IDet(morn+bed ) group ( P < 0.001 ) . Although HbA1c for each insulin detemir group was not different from the NPH group , HbA1c for the pooled insulin detemir groups was significantly lower than for the NPH group ( mean difference -0.18 % [ -0.34 to -0.02 ] , P = 0.027 ) . Within-person between-day variation in self-measured prebreakfast plasma glucose was lower for both detemir groups ( both P < 0.001 ) . The NPH group gained weight during the study , but there was no change in weight in either of the insulin detemir groups ( IDet(12h ) vs. NPH , -0.8 kg [ -1.44 to -0.24 ] , P = 0.006 ; IDet(morn+bed ) vs. NPH , -0.6 kg [ -1.23 to -0.03 ] , P = 0.040 ) . CONCLUSIONS Overall glycemic control with insulin detemir was improved compared with NPH insulin . The data provide a basis for tailoring the timing of administration of insulin detemir to the individual person 's needs BACKGROUND AND AIM While lispro insulin has been reported to lower postpr and ial blood glucose concentrations , less consistent effects have been shown for glycosylated hemoglobin ( HbA1c ) levels . Aim of this study was to determine whether pre-meal association of NPH , an intermediate-acting insulin , with lispro improves overall glycemic control in type 1 diabetic patients . METHODS AND RESULTS Eighty-five type 1 diabetic patients were studied in a multicenter r and omized comparative ( human regular vs lispro insulin ) crossover ( 3-month ) study in which NPH insulin was given as a dinner or bedtime injection and at breakfast and lunch if necessary . The number of injections was kept constant : 42 % and 58 % of patients injected insulin 3 and 4 times per day , respectively . Fasting and prepr and ial blood glucose levels were similar , while postpr and ial levels improved after lispro compared to human regular insulin ( breakfast : 8.28 + /- 2.39 vs 9.28 + /- 2.72 mmol/l ; lunch : 8.33 + /- 2.67 vs 9.06 + /- 2.67 mmol/l , dinner : 8.06 + /- 2.72 vs 9.28 + /- 2.44 mmol/l , ANOVA : p = 0.003 ) . HbA1c also improved after lispro : 8.1 + /- 0.9 vs 8.3 + /- 0.8 % , p < 0.05 . The rate of hypoglycemia was similar . Patients showed better acceptance of lispro treatment ( p < 0.001 ) . CONCLUSIONS Lispro improves overall blood glucose control in type 1 diabetic patients without increasing the incidence of hypoglycemia . This can be achieved by an optimal combination of lispro insulin with NPH whenever the time intervals between meals are too long OBJECTIVE This study investigated the effect of insulin glargine ( LANTUS ) versus NPH insulin on metabolic control and safety in Asian patients with Type 2 diabetes , inadequately controlled on oral hypoglycemic agents ( OHAs ) . STUDY DESIGN AND METHODS In this open-label , r and omized , parallel , multinational , 24-week , non-inferiority study , 443 patients received either once-daily insulin glargine ( n=220 ) or NPH insulin ( n=223 ) at bedtime , plus glimepiride ( Amaryl ) . RESULTS Baseline characteristics were similar between the two groups . HbA(1c ) levels decreased in the insulin glargine and NPH groups over the study period in the per- protocol ( PP ; -1.10 % versus 0.92 % ) and full- analysis ( FA ; -0.99 % versus -0.77 % ) population s. In the PP population , the difference between adjusted means ( predefined equivalence region > -0.4 % ) was 0.19 % ( 90 % confidence interval [ CI ] : 0.02 , 0.36 ) , demonstrating non-inferiority between the two treatments . In a superiority analysis ( FA population ) , the difference between adjusted mean changes in the two groups was 0.22 % ( 95 % CI : 0.02 , 0.42 ) , demonstrating the superiority of insulin glargine ( p=0.0319 ) . Moreover , the number of hypoglycemic episodes was significantly lower with insulin glargine versus NPH insulin ( p<0.004 ) , particularly severe ( p<0.03 ) and nocturnal ( p<0.001 ) . Daily insulin dose increased from 9.6+/-1.5 to 32.1+/-17.6 U in the insulin glargine group and from 9.8+/-1.9 to 32.8+/-18.9 U in the NPH insulin group . CONCLUSION These results confirm earlier reports that insulin glargine provides superior glycemic control with less hypoglycemia and demonstrates that these benefits are consistent between different ethnicities Aims /hypothesisThe aim of the trial was to compare the efficacy and tolerability of two types of basal-bolus therapy , using either the soluble long-acting basal insulin analogue , insulin detemir , in combination with the rapid-acting analogue , insulin aspart , or NPH insulin in combination with mealtime regular human insulin . Methods In this 18-week , 1:1 r and omised , open-labelled , parallel trial , 595 patients with Type 1 diabetes mellitus received insulin detemir or NPH insulin in the morning and at bedtime in combination with mealtime insulin aspart or regular human insulin respectively . Results Glycaemic control with insulin detemir/insulin aspart was improved in comparison with NPH insulin/regular human insulin ( HbA1c : 7.88 % vs 8.11 % ; mean difference : −0.22 % point [ 95 % CI : −0.34 to −0.10 ] ; p<0.001 ) . Self-measured 8-point plasma glucose profiles differed between the groups ( p<0.001 ) , with lower postpr and ial plasma glucose levels in the insulin detemir/insulin aspart group . Within-person day-to-day variation in plasma glucose was lower with insulin detemir/insulin aspart than with NPH insulin/regular human insulin ( SD : 2.88 vs 3.12 mmol/l ; p<0.001 ) . Risk of overall and nocturnal hypoglycaemia ( 23.00–06.00 hours ) was , respectively , 21 % ( p=0.036 ) and 55 % ( p<0.001 ) lower in the insulin detemir/insulin aspart group than in the NPH insulin/regular human insulin group . Body weight ( adjusted for baseline and change in HbA1c ) was 1 kg lower with insulin detemir/insulin aspart than with NPH insulin/regular human insulin ( p<0.001 ) . Conclusions /interpretationBasal-bolus therapy using insulin detemir/insulin aspart offers a better balance of control and tolerability than with NPH insulin/regular human insulin . The low variability and more physiological action profiles generated with these insulin analogues result ed in improved glycaemic control with lower risk of hypoglycaemia and no concomitant body weight increase OBJECTIVE —To assess the safety and efficacy of insulin aspart ( IAsp ) versus regular human insulin ( HI ) in basal-bolus therapy with NPH insulin in pregnant women with type 1 diabetes . RESEARCH DESIGN AND METHODS —Subjects ( n = 322 ) who were pregnant or planning pregnancy were r and omized to IAsp or HI as meal-time insulin in an open-label , parallel-group , multicenter study . Subjects had A1C ≤8 % at confirmation of pregnancy . Insulin doses were titrated toward predefined glucose targets and A1C < 6.5 % . Outcomes assessed included risk of major maternal hypoglycemia , A1C , plasma glucose profiles , and maternal safety outcomes . RESULTS —Major hypoglycemia occurred at a rate of 1.4 vs. 2.1 episodes/year exposure with IAsp and HI , respectively ( relative risk 0.720 [ 95 % CI 0.36–1.46 ] ) . Risk of major/major nocturnal hypoglycemia was 52 % ( RR 0.48 [ 0.20–1.143 ] ; P = NS ) lower with IAsp compared with HI . A1C was comparable with human insulin in second ( IAsp-HI −0.04 [ −0.18 to 0.11 ] ) and third ( −0.08 [ −0.23 to 0.06 ] ) trimesters . A total of 80 % of subjects achieved an A1C ≤6.5 % . At the end of first and third trimesters , average postpr and ial plasma glucose increments were significantly lower with IAsp than HI ( P = 0.003 and P = 0.044 , respectively ) , as were mean plasma glucose levels 90 min after breakfast ( P = 0.044 and P = 0.001 , respectively ) . Maternal safety profiles and pregnancy outcomes were similar between treatments . CONCLUSIONS —IAsp is at least as safe and effective as HI when used in basal-bolus therapy with NPH insulin in pregnant women with type 1 diabetes and may potentially offer some benefits in terms of postpr and ial glucose control and preventing severe hypoglycemia Insulin lispro is an insulin analogue that has the advantages of being fast-acting , convenient , and less likely to lead to hypoglycaemic episodes . Previous studies have proven its value in treating both Type 1 and Type 2 diabetes both alone and in combination with different treatment regimens.1,2 However , diabetes is heterogeneous and differs in etiology and clinical characteristics in different ethnic groups . Even with the same insulin treatment , different diets will produce different glycaemic profiles . Diet patterns differ between different ethnic groups . Traditional oriental foods are characterized by a higher proportion of carbohydrates and a lower proportion of fat compared to Caucasian diets . To date , there has been no study on the use of insulin lispro in Chinese diabetic patients . Whether the Chinese dietary pattern will affect the efficacy of insulin lispro treatment remains unknown . Therefore , we conducted this trial to assess the efficacy of insulin lispro treatment in Chinese patients The short-acting insulin analogue lispro ( [ LYS(B28 ) , PRO(B29 ) ] is absorbed from the subcutis more rapidly than soluble insulin ( S ) . To compare the clinical effectiveness of lispro vs S , 11 Type 1 patients using continuous subcutaneous insulin infusion ( CSII ) therapy ( 6 F , 5 M , age 30 + /- 2.5 years , diabetes duration 14 + /- 1.0 years , BMI 24.0 + /- 0.8 kg m(-2 ) , HbA1c 6.5 + /- 0.2 % ) were studied in an open , r and omized , crossover study for 6 months ( 3 months lispro and 3 months S or vice versa ) . During lispro treatment mean fasting and 2 h postpr and ial blood glucose were lower compared to the S phase ( fasting 6.5 + /- 0.4 vs 7.5 + /- 0.4 mmol l(-1 ) ( NS ) , postpr and ial 6.8 + /- 0.3 vs 8.3 + /- 0.3 mmol l(-1 ) , p = 0.03 ) . In patients treated first with lispro HbA1c levels improved from 6.3 + /- 0.2 % to 5.7 + /- 0.3 % ; On reversion to S HbA1c increased to 6.2 + /- 0.2 % . In the group treated first with S , HbA1c fell ( 6.7 + /- 0.4 % vs 6.5 + /- 0.3 % ) and then improved further to 6.3 + /- 0.3 % with lispro . None of these changes were significant . There was no significant difference with respect to hypoglycaemic or other adverse events . It can be concluded that lispro in CSII therapy is safe and may improve postpr and ial glucose excursions BACKGROUND Although insulin lispro ( insulin LP ) has been shown to improve postpr and ial blood glucose ( BG ) control and reduce hypoglycemic episodes in adult patients with type I diabetes , there appear to have been few clinical studies focusing on its use in adolescents . OBJECTIVE This study compared the effects of insulin LP with those of regular human insulin ( insulin R ) on postpr and ial BG control and hypoglycemia in adolescents with type diabetes . METHODS In this crossover , open-label study , adolescents between the ages of 9 and 18 years who had reached Tanner stage II puberty were r and omized to receive either insulin LP immediately before meals or insulin R 30 to 45 minutes before meals , in addition to daily intermediate-acting insulin . After 4 months , patients were switched to the alternate treatment sequence . Eight-point BG profiles , hypoglycemia rate , and glycosylated hemoglobin ( HbA1c ) were measured at baseline and end point . RESULTS Four hundred eighty-one adolescents participated in the study at 53 investigative sites in 15 countries ; 463 were r and omized to treatment ( 228 insulin LP , 235 insulin R ) , and 457 completed the study . Insulin LP given before breakfast result ed in significantly lower mean ( + /-SD ) 2-hour postpr and ial BG levels compared with insulin R ( 9.7 + /- 4.0 mmol/L vs 10.6 + /- 4.3 mmol/L , respectively ; P < 0.001 ) . Insulin LP given before dinner result ed in significantly lower 2-hour postpr and ial BG levels compared with insulin R ( 8.6 + /- 3.5 mmol/L vs 9.3 + /- 3.7 mmol/L ; P = 0.003 ) . No differences were seen between treatments in 2-hour postpr and ial BG levels after the midday meal . Mean baseline HbA1c values were similar between sequence groups , and no between-group difference in HbA1c was observed at end point ( insulin LP , 8.69 % + /- 1.52 % ; insulin R , 8.70 % + /- 1.65 % ) . Treatment with insulin LP result ed in a significantly lower incidence of hypoglycemic episodes per patient per 30 days compared with insulin R ( 4.02 + /- 4.5 vs 4.37 + /- 4.5 , respectively ; P = 0.023 ) and significantly fewer hypoglycemic episodes between midnight and 6 AM ( 1.0 + /- 1.9 vs 1.7 + /- 2.6 ; P < 0.001 ) . CONCLUSIONS In adolescents with type 1 diabetes , insulin LP significantly improved postpr and ial glycemic control and reduced episodes of nocturnal hypoglycemia compared with insulin R. Insulin LP was well tolerated and effective as part of an intensified insulin regimen in this study population AIM To compare glycaemic control and symptomatic hypoglycaemia rates with glargine versus neutral protamine Hagedorn ( NPH ) in poorly controlled type 1 diabetes patients . METHODS Patients ( n = 125 ) received prepr and ial insulin lispro and either glargine ( n = 62 ) or NPH ( n = 63 ) at bedtime for 30 weeks in a multicentre , r and omized , single-blind ( a blinded investigator made titration decisions ) study . Basal insulin dosage was titrated to achieve fasting blood glucose ( FBG ) values < 5.5 mmol/L. RESULTS Baseline characteristics were similar for the two groups ( mean diabetes duration 17.5 + /- 10.1 years ) except mean glycated haemoglobin ( HbA(1c ) ) , which was lower in the glargine versus NPH group ( 9.2 + /- 1.1 % vs 9.7 + /- 1.3 % ; P < 0.02 ) . At end-point , mean HbA(1c ) was 8.3 versus 9.1 % for the glargine versus NPH groups . Adjusted least-squares mean ( LSM ) change from baseline was -1.04 versus -0.51 % , a significant treatment benefit of 0.53 % for HbA(1c ) in favour of glargine ( P < 0.01 ) . Mean baseline FBG were similar for the glargine and NPH groups ( 11.2 vs 11.4 mmol/L ) . The means for end-point FBG were 7.9 versus 9.0 mmol/L. Adjusted LSM change from baseline was -3.46 versus -2.34 mmol/L , with a significant difference of 1.12 mmol/L in favour of glargine ( P < 0.05 ) . There were similar total numbers of daytime mild , moderate or severe hypoglycaemia episodes in the two treatment arms . However , significantly fewer moderate or severe nocturnal hypoglycaemic episodes were observed in the glargine group ( P = 0.04 and P = 0.02 ) . CONCLUSION Glargine is superior to NPH for improving HbA(1c ) and FBG levels during intensive insulin therapy in patients with type 1 diabetes , and is associated with less severe nocturnal hypoglycaemia OBJECTIVE To determine the safety and efficacy of the long-acting analog insulin glargine compared with NPH insulin in patients with type 2 diabetes who were previously treated with insulin alone . RESEARCH DESIGN AND METHODS A total of 518 subjects with type 2 diabetes who were receiving NPH insulin with or without regular insulin for postpr and ial control were r and omized to receive insulin glargine ( HOE 901 ) once daily ( n = 259 ) or NPH insulin once or twice daily in = 259 ) for 28 weeks in an open-label , multicenter trial . Doses were adjusted to obtain target fasting glucose < 6.7 mmol/l . At study end point , the median total daily insulin dose in both treatment groups was 0.75 IU/kg . RESULTS The treatment groups showed similar improvements in HbA1c from baseline to end point on intent-to-treat analysis . The mean change ( means + /- SD ) in HbA1c from baseline to end point was similar in the insulin glargine group ( -0.41 + /- 0.1 % ) and the NPH group ( -0.59 + /- 0.1 % ) after patients began with an average baseline HbA1c of approximately 8.5 % . The treatments were associated with similar reductions in fasting glucose levels . Overall , mild symptomatic hypoglycemia was similar in insulin glargine subjects ( 61.4 % ) and NPH insulin subjects ( 66.% ) However , nocturnal hypoglycemia in the insulin glargine group was reduced by 25 % during the treatment period after the dose-titration phase(26.5 vs. 35.5 % , P = 0.0136 ) . Subjects in the insulin glargine group experienced less weight gain than those in the NPH group ( 0.4 vs. 1.4 kg , P < 0.0007 ) . CONCLUSIONS In patients with type 2 diabetes , once-daily bedtime insulin glargine is as effective as once- or twice-daily NPH in improving and maintaining glycemic control . In addition , insulin glargine deonstrates a lower risk of nocturnal hypoglycemia and less weight gain compared with NPH insulin Lispro ( LP ) and regular human ( HR ) insulins were compared in Type 1 diabetic ( T1DM ) patients on either a Mediterranean diet or normal diet . Twelve T1DM patients were recruited and r and omized into two groups of 6 , groups A and B. They were treated in different sequences ( in 3-month intervals for 1 year ) . Group A : LP insulin and normal diet , LP insulin and Mediterranean diet , regular insulin and Mediterranean diet , regular insulin and normal diet . Group B : regular insulin and normal diet , regular insulin and Mediterranean diet , LP insulin and Mediterranean diet , LP insulin and normal diet . Each patient was treated with rapid acting insulin , either LP insulin or HR insulin , before each main meal and a dose of slow acting insulin at bedtime . Every 15 days the glycemic control , the incidence and frequency of hypoglycemic episodes , and any adverse events were evaluated . Every 3 months , hematology and a chemistry panel , pre- and post-pr and ial glycemic and insulinemic profiles were evaluated in all patients . HbA1c levels significantly decreased in LP patients on normal diet , post-pr and ial glycemic levels were significantly lower in LP than in HR patients from 30 min onwards , 15-min post-pr and ial insulin levels higher in LP- than in HR-treated patients , and hypoglycemic episodes were significantly less in LP- than in HR-treated patients . LP insulin , irrespective of the type of diet , results in more effective glycemic control , significantly reduces hypoglycemic episodes as opposed to traditional insulin therapy and seems to be more effective with a normal diet than with a Mediterranean diet Aims /hypothesisIn type 2 diabetic patients we compared 9 months of combination therapy with insulin glargine and metformin with 9 months of NPH insulin combined with metformin . The primary focus was changes in HbA1c ; secondary focus was diurnal glucose profiles and symptomatic hypoglycaemia . Methods In this investigator-initiated open , parallel-group clinical trial involving seven centres , 110 insulin-naive type 2 diabetic patients with poor glycaemic control ( HbA1c ≥8.0 % ) on oral hypoglycaemic agents ( 90 % using sulfonylurea plus metformin ) were r and omised to receive bedtime insulin glargine with metformin ( G+MET ) or bedtime NPH with metformin ( NPH+MET ) for 36 weeks . The patients were taught how to self-adjust their insulin dose and use a modem to send the results of home glucose monitoring to treatment centres . The goal was to achieve a fasting plasma glucose ( FPG ) of 4.0 to 5.5 mmol/l in both groups . Results During the last 12 weeks , FPGs averaged 5.75±0.02 and 5.96±0.03 mmol/l ( p<0.001 ) and insulin doses were 68±5 and 70±6 IU/day ( 0.69±0.05 and 0.66±0.04 IU kg–1 day–1 , NS ) in the G+MET and NPH+MET groups , respectively . At 36 weeks , mean HbA1c was 7.14±0.12 and 7.16±0.14 % , respectively ( NS ) . Symptomatic , but not confirmed symptomatic , hypoglycaemia was significantly lower during the first 12 weeks in the G+MET group ( 4.1±0.8 episodes/patient-year ) than in the NPH+MET group ( 9.0±2.3 episodes/patient-year , p<0.05 ) , but not significantly different thereafter . Glucose levels before dinner were higher in the NPH+MET group ( 10.1±0.3 mmol/l ) than in the G+MET group ( 8.6±0.3 mmol/l , p=0.002 ) throughout the 36-week study . With regard to baseline characteristics such as initial glycaemia or C-peptide , there was no difference between patients who achieved good glycaemic control ( HbA1c < 7.0 % ) and those who did not . Differences were seen in the following : between study centres , weight gain during the run-in period and insulin therapy , and FPG during the last 12 weeks ( 5.7±0.2 vs 6.7±0.3 mmol/l for patients reaching vs those not reaching target , p<0.01 ) . Conclusions /interpretationGood glycaemic control can be achieved with both G+MET and NPH+MET . Use of G+MET reduces symptomatic hypoglycaemia during the first 12 weeks and dinnertime hyperglycaemia compared with NPH+MET OBJECTIVE To determine the safety and efficacy of the long-acting insulin analog , insulin glargine , as a component of basal bolus therapy in patients with type 1 diabetes . RESEARCH DESIGN AND METHODS Patients with type 1 diabetes receiving basal-bolus insulin treatment with NPH human insulin and insulin lispro were r and omized to receive insulin glargine ( HOE 901 ) , a long-acting basal insulin analog , once a day ( n = 310 ) or NPH human insulin ( n = 309 ) as basal treatment with continued bolus insulin lispro for 16 weeks in an open-label study NPH insulin patients maintained their prior schedule of administration once or twice a day , whereas insulin glargine patients received basal insulin once a day at bedtime . RESULTS Compared with all NPH insulin patients , insulin glargine patients had significant decreases in fasting blood glucose measured at home ( means + /- SEM , -42.0 + /- 4.7 vs. -12.4 + /- 4.7 mg/dl [ -2.33 + /- 0.26 vs. -0.69 + /- 0.26 mmol/l ] ; P = 0.0001 ) . These differences were evident early and persisted throughout the study More patients in the insulin glargine group ( 29.6 % ) than in the NPH group ( 16.8 % ) reached a target fasting blood glucose of 119 mg/dl ( < 6.6 mmol/l ) . However , there were no differences between the groups with respect to change in GHb . Insulin glargine treatment was also associated with a significant decrease in the variability of fasting blood glucose values ( P = 0.0124 ) . No differences in the occurrence of symptomatic hypoglycemia , including nocturnal hypoglycemia , were observed . Overall , adverse events were similar in the two treatment groups with the exception of injection site pain , which was more common in the insulin glargine group ( 6.1 % ) than in the NPH group ( 0.3 % ) . Weight gain was 0.12 kg in insulin glargine patients and 0.54 kg in NPH insulin patients ( P = 0.034 ) . CONCLUSIONS Basal insulin therapy with insulin glargine once a day appears to be as safe and at least as effective as using NPH insulin once or twice a day in maintaining glycemic control in patients with type 1 diabetes receiving basal-bolus insulin treatment with insulin lispro AIMS To compare blood glucose control using insulin glargine + insulin lispro with that on NPH insulin + unmodified human insulin in adults with Type 1 diabetes managed with a multiple injection regimen . METHODS In this 32-week , five-centre , two-way cross-over study , people with Type 1 diabetes ( n = 56 , baseline HbA1c 8.0 + /- 0.8 % ) were r and omized to evening insulin glargine + mealtime insulin lispro or to NPH insulin ( once- or twice-daily ) + mealtime unmodified human insulin . Each 16-week period concluded with a 24-h inpatient plasma glucose profile . RESULTS HbA1c was lower with glargine + lispro than with NPH + human insulin [ 7.5 vs. 8.0 % , difference -0.5 ( 95 % CI -0.7 , -0.3 ) % , P < 0.001 ] . This was confirmed by an 8 % lower 24-h plasma glucose area under the curve ( AUC ) ( 187 vs. 203 mmol l(-1 ) h(-1 ) , P = 0.037 ) , a 24 % reduction in plasma glucose AUC > 7.0 mmol/l1 ( 47 vs. 62 mmol l(-1 ) h(-1 ) , P = 0.017 ) and a 15 % lower post-pr and ial plasma glucose AUC ( 75 vs. 88 mmol l(-1 ) h(-1 ) , P = 0.002 ) . There was no reduction in night-time plasma glucose AUC or increase in plasma glucose area < 3.5 mmol/l . Monthly rate of nocturnal hypoglycaemia was reduced by 44 % with glargine + lispro ( 0.66 vs. 1.18 episodes/month , P < 0.001 ) . CONCLUSIONS Compared with NPH insulin + unmodified human insulin , the combination of insulin glargine with a rapid-acting insulin analogue as multiple-injection therapy for Type 1 diabetes improves overall glycaemic control as assessed by HbA1c and 24-h plasma glucose monitoring to a clinical ly significant degree , together with a reduction in nocturnal hypoglycaemia To compare insulin glargine with NPH human insulin for basal insulin supply in adults with type 1 diabetes The aim of the study was to compare lispro ( LP ) and Insuman(R ) ( I ) insulin in continuous subcutaneous insulin infusion ( CSII ) therapy with respect to blood glucose control as expressed by the st and ard deviation of blood glucose ( SD(BG ) ) and HbA(1c ) and to monitor the well-being ( WBQ ) and treatment satisfaction ( DTSQ ) parameters during such treatment . Forty-one IDDM patients who had used CSII for at least 6 months participated in an open-label , r and omized , cross-over , multicenter study for 4 months ( 2 months LP and 2 months I or vice versa ) . Boluses with LP were given 5 min before each meal and with I 30 min before each meal . During LP administration compared with I , the SD(BG ) of all blood glucose values ( 3.6 mmol/l vs. 3.9 mmol/l , p=0.012 ) , as well as the SD(BG ) of the postpr and ial , blood glucose values ( 3.6 mmol/l vs. 4.0 mmol/l , p=0.006 ) , were significantly reduced . The HbA(1c ) was significantly lower during LP administration ( 7.4 % vs. 7.6 % , p=0.047 ) . The incidence of hypoglycemic events per 30 days ( capillary blood glucose<3.0 mmol/l and /or symptoms ) did not significantly differ between LP and I ( 9.7 vs. 8.0 per month , p=0.23 ) . The total amount of daily insulin was slightly but significantly lower with LP , compared to I ( 38.0 IU vs. 40.3 IU , p=0.004 ) . There was no treatment effects of LP compared to I concerning WBQ and DTSQ . It is concluded that in CSII therapy LP is superior to I with respect to the stability of blood glucose control , a lower HbA(1c ) , a less insulin requirement without increasing the frequency of hypoglycemia The absorption of regular human insulin from subcutaneous injection sites is delayed due to the self-association of insulin to multimeric forms . The insulin analogue insulin lispro has a weak self-association and a fast absorption rate . We examined the safety and efficacy of insulin lispro in the premeal treatment of patients with diabetes mellitus . A 12-month study was performed in 336 patients with insulin-dependent diabetes mellitus ( IDDM ) and 295 patients with non-insulin-dependent diabetes mellitus ( NIDDM ) . The patients were r and omized to inject either regular human insulin 30 to 45 minutes before eating , or insulin lispro immediately before each meal , in addition to basal insulin . The postpr and ial rise in serum glucose was lower in patients receiving insulin lispro than in those receiving regular human insulin therapy . At end point the increment was significantly lower at 1 hour ( 35 % ) and at 2 hours ( 64 % ) after the meal in IDDM patients ; in NIDDM patients , the increment was nonsignificantly lower at 1 hour ( 19 % ) and significantly lower at 2 hours ( 48 % ) . IDDM patients receiving insulin lispro achieved significantly lower glycated hemoglobin ( HbA1c ) levels in patients receiving regular human insulin ( 8.1 % vs 8.3 % ) . In NIDDM patients , HbA1c levels decreased equally in both treatment groups . Due to its fast absorption rate , insulin lispro improves postpr and ial control in diabetes . Insulin lispro can be considered one step toward optimal insulin therapy and improved patient convenience The purpose of the study was to find out differences between treatments of diabetes type 2 after secondary oral antidiabetic drug failure . Three different methods of treatment were compared : lispro insulin in combination with metformin , glimepiride and metformin combination or two daily doses of biphasic insulin 30/70 together with bed-time NPH insulin . The study included 87 patients with diabetes mellitus type 2 r and omly distributed into 3 different treatment groups . Fasting and postpr and ial glucose were analyzed by enzymatic colorimetric method and HbA1c was measured by ion exchange chromatography . HbA1c significantly decreased in all three study groups . The decrease was mostly expressed among patients treated with lispro and metformin . When focused on postpr and ial glucose control , antihyperglycemic metformin and insulin lispro therapy has greater impact on the overall metabolic control ( decrease in level of HbA1c ) in comparison with the above mentioned more traditional approaches AIMS To compare quality of life ( QoL ) and treatment satisfaction in patients with Type 1 diabetes receiving the rapid-acting insulin analogue , insulin aspart ( IAsp ) , with that in patients receiving soluble human insulin ( HI ) . METHODS In this 6-month , multinational , r and omized , open-label trial , 424 patients from German-speaking countries were subjected to psychometric assessment before and after r and omization ( ratio 2 : 1 ) to basal-bolus treatment with either IAsp ( n = 283 ) or HI ( n = 141 ) . Patients on HI were advised to keep an injection-meal interval of 30 min , whereas patients on IAsp were advised to inject immediately before meals . Treatment satisfaction and diabetes-related QoL were assessed using vali date d instruments to measure the domains of patients ' individual treatment goals , physical complaints , worries about the future , social relations , leisure time flexibility , daily hassles , diet restrictions , burdens and fear of hypoglycaemia , blood glucose fluctuations , self-efficacy , and fear of insulin analogues . RESULTS After 6 months , IAsp was associated with significantly greater improvement in treatment satisfaction than HI in two different scales ( P < 0.01 ) , and in QoL with respect to diet restrictions ( P < 0.01 ) . Improved satisfaction was mainly due to increased dietary and leisure time flexibility ( P < 0.0001 ) . Twenty-three percent of the IAsp group vs. 14 % of the HI group achieved small but important improvements of total QoL ( between-group difference , P < 0.06 ) . The number needed to treat ( NNT ) with IAsp for an important increase in QoL was calculated to be 10 . Regression analyses of potential predictors of improvement in QoL highlighted patients intensely striving for physical strength ( P < 0.01 ; NNT = 7 ) and patients feeling less protected against hypoglycaemia ( P < 0.005 ; NNT = 8) as being the most likely to benefit from IAsp . CONCLUSIONS Under these study conditions , IAsp improved treatment satisfaction and quality of life regarding diet restrictions when compared with human insulin . The ' numbers needed to treat ' for important quality of life benefits indicate that the effect of IAsp in this regard is not trivial OBJECTIVE Insulin detemir is a soluble basal insulin analog with a unique mechanism of protracted action design ed to reduce the variability associated with conventional basal insulins . This trial compared the glycemic control , risk of hypoglycemia , and effect on body weight of insulin detemir and NPH insulin in patients with type 1 diabetes treated with rapid-acting insulin aspart at meals . RESEARCH DESIGN AND METHODS This study was a 6-month multinational open parallel-group comparison conducted at 46 centers in five countries and included 448 patients with type 1 diabetes r and omized 2:1 to insulin detemir or NPH insulin , respectively . RESULTS After 6 months , comparable HbA(1c ) levels were found between the two treatment groups . Fasting plasma glucose tended to be lower in patients treated with insulin detemir , but this difference was not statistically significant ( -0.76 mmol/l , P = 0.097 ) . Within-subject variation in self-measured fasting blood glucose was lower with insulin detemir than with NPH insulin ( SD 3.37 vs. 3.78 mmol/l , P < 0.001 ) . Risk of hypoglycemia was 22 % lower with insulin detemir than with NPH insulin ( P < 0.05 ) and 34 % lower for nocturnal ( 2300 - 0600 ) hypoglycemia ( P < 0.005 ) . Nightly plasma glucose profiles were smoother and more stable with insulin detemir ( P = 0.05 ) . Body weight was significantly lower with insulin detemir at the end of the trial ( P < 0.001 ) . CONCLUSIONS Treatment with insulin detemir result ed in more predictable glycemic control , with smoother plasma glucose profiles than NPH insulin and a significant reduction in the risk of hypoglycemia . The reduction in body weight with insulin detemir is a potential additional advantage . Regimens optimized for insulin detemir may be able to improve glycemic control beyond that possible with NPH insulin BACKGROUND Glargine is a long-acting insulin analogue potentially more suitable than NPH insulin in intensive treatment of Type 1 diabetes mellitus ( T1 DM ) , but no study has proven superiority . The aim of this study was to test superiority of glargine on long-term blood glucose ( BG ) as well as on responses to hypoglycaemia vs. NPH . METHODS One hundred and twenty-one patients with T1 DM on intensive therapy on four times/day NPH and lispro insulin at each meal , were r and omized to either continuation of NPH four times/day ( n = 60 ) , or once daily glargine at dinner-time ( n = 61 ) for 1 year . Lispro insulin at meal-time was continued in both groups . In 11 patients from each group , responses to stepped hyperinsulinaemic-hypoglycaemia were measured before and after 1 year 's treatment . RESULTS Mean daily BG was lower with glargine [ 7.6 + /- 0.11 mmol/l ( 137 + /- 2 mg/dl ) ] vs. NPH [ 8.1 + /- 0.22 mmol/l ( 146 + /- 4 mg/dl ) ] ( P < 0.05 ) . HbA(1c ) at 4 months did not change with NPH , but decreased with glargine ( from 7.1 + /- 0.1 to 6.7 + /- 0.1 % ) , and remained lower than NPH at 12 months ( 6.6 + /- 0.1 % , P < 0.05 vs. NPH ) . Frequency of mild hypoglycaemia [ self-assisted episodes , blood glucose < or = 4.0 mmol/l ( 72 mg/dl ) ] was lower with glargine vs. NPH ( 7.2 + /- 0.5 and 13.2 + /- 0.6 episodes/patient-month , P < 0.05 ) . After 1 year , NPH treatment result ed in no change of responses to hypoglycaemia , whereas with glargine plasma glucose , thresholds and maximal responses of plasma adrenaline and symptoms to hypoglycaemia improved ( P < 0.05 ) . CONCLUSIONS The simpler glargine regimen decreases the percentage of HbA(1c ) and frequency of hypoglycaemia and improves responses to hypoglycaemia more than NPH . Thus , glargine appears more suitable than NPH as basal insulin for intensive treatment of T1 DM OBJECTIVE Available basal insulin formulations do not provide a constant and reliable 24-h insulin supply . We compared the efficacy and safety of glargine ( a long-acting insulin analog ) and NPH insulins in insulin-naive type 2 diabetic patients treated with oral antidiabetic agents . RESEARCH DESIGN AND METHODS There were 426 type 2 diabetic patients ( age 59 + /- 9 years , BMI 28.9 + /- 4.3 kg/m2 , mean + /- SD ) with poor glycemic control on oral antidiabetic agents r and omized to treatment for 1 year with bedtime insulin glargine or bedtime NPH insulin . Oral agents were continued unchanged . The fasting blood glucose ( FBG ) target was 6.7 mmol/l ( 120 mg/dl ) . RESULTS Average glycemic control improved similarly with both insulins ( HbA(1c ) , [ reference range < 6.5 % ] 8.3 + /- 0.1 vs. 8.2 + /- 0.1 % at 1 year , glargine vs. NPH , mean + /- SEM , P < 0.001 vs. baseline for both ) . However , there was less nocturnal hypoglycemia ( 9.9 vs. 24.0 % of all patients , glargine vs. NPH , P < 0.001 ) and lower post-dinner glucose concentrations ( 9.9 + /- 0.2 vs. 10.7 + /- 0.3 mmol/l , P < 0.02 ) with insulin glargine than with NPH . Insulin doses and weight gain were comparable . In patients reaching target FBG , HbA(1c ) averaged 7.7 and 7.6 % in the glargine and NPH groups at 1 year . CONCLUSIONS Use of insulin glargine compared with NPH is associated with less nocturnal hypoglycemia and lower post-dinner glucose levels . These data are consistent with peakless and longer duration of action of insulin glargine compared with NPH . Achievement of acceptable average glucose control requires titration of the insulin dose to an FBG target < or = 6.7 mmol/l . These data support use of insulin glargine instead of NPH in insulin combination regimens in type 2 diabetes OBJECTIVE To compare the abilities and associated hypoglycemia risks of insulin glargine and human NPH insulin added to oral therapy of type 2 diabetes to achieve 7 % HbA(1c ) . RESEARCH DESIGN AND METHODS In a r and omized , open-label , parallel , 24-week multicenter trial , 756 overweight men and women with inadequate glycemic control ( HbA(1c ) > 7.5 % ) on one or two oral agents continued pre study oral agents and received bedtime glargine or NPH once daily , titrated using a simple algorithm seeking a target fasting plasma glucose ( FPG ) < or=100 mg/dl ( 5.5 mmol/l ) . Outcome measures were FPG , HbA(1c ) , hypoglycemia , and percentage of patients reaching HbA(1c ) < or=7 % without documented nocturnal hypoglycemia . RESULTS Mean FPG at end point was similar with glargine and NPH ( 117 vs. 120 mg/dl [ 6.5 vs. 6.7 mmol/l ] ) , as was HbA(1c ) ( 6.96 vs. 6.97 % ) . A majority of patients ( approximately 60 % ) attained HbA(1c ) < or=7 % with each insulin type . However , nearly 25 % more patients attained this without documented nocturnal hypoglycemia ( < or=72 mg/dl [ 4.0 mmol/l ] ) with glargine ( 33.2 vs. 26.7 % , P < 0.05 ) . Moreover , rates of other categories of symptomatic hypoglycemia were 21 - 48 % lower with glargine . CONCLUSIONS Systematic ally titrating bedtime basal insulin added to oral therapy can safely achieve 7 % HbA(1c ) in a majority of overweight patients with type 2 diabetes with HbA(1c ) between 7.5 and 10.0 % on oral agents alone . In doing this , glargine causes significantly less nocturnal hypoglycemia than NPH , thus reducing a leading barrier to initiating insulin . This simple regimen may facilitate earlier and effective insulin use in routine medical practice , improving achievement of recommended st and ards of diabetes care BACKGROUND This trial compared the long-term safety and efficacy of the basal insulin preparations , insulin detemir and NPH insulin , in basal-bolus therapy for patients with type 1 diabetes . METHODS This multinational open , parallel-group trial r and omized patients to receive insulin detemir or NPH insulin twice daily in addition to mealtime human soluble insulin . Doses were titrated towards predefined glycemic targets . After an initial 6-month treatment period , patients were invited to participate in a 6-month extension period . A total of 289 from 421 elected to continue in the trial , of which 252 completed . RESULTS Glycemic control as assessed by hemoglobin A1c ( insulin detemir , 7.88 % ; NPH insulin , 7.78 % ; difference not significant ) and fasting plasma glucose ( insulin detemir , 10.1 mmol/L ; NPH insulin , 9.84 mmol/L ; difference not significant ) was similar in both treatment groups at end point , with hemoglobin A1c little changed from baseline and fasting plasma glucose slightly decreased . There was some evidence for a risk reduction for hypoglycemia in association with insulin detemir , although this was not statistically significant ( relative risk overall hypoglycemia , 0.71 , P = 0.139 ; relative risk nocturnal hypoglycemia , 0.71 , P = 0.067 ) , and hypoglycemic events were fewer in each of the 12 months . There was a significant treatment difference with regard to weight outcome ; NPH insulin was associated with weight gain ( 1.4 kg ) , but there was no mean weight gain ( -0.3 kg ) in the insulin detemir cohort ( baseline-adjusted between-group difference at 12 months , 1.66 kg , P = 0.002 ) . There were no obvious between-group differences in other safety parameters . CONCLUSIONS Glycemic control is maintained with insulin detemir during long-term treatment . At equivalent glycemic control to NPH insulin , insulin detemir is associated with a lack of weight gain and a trend towards a reduced risk of nocturnal hypoglycemia when used in basal-bolus therapy with mealtime soluble human insulin Aim : It has been found that non‐fasting plasma glucose is a better marker of diabetic control than fasting plasma glucose in type 2 diabetes . The main aim of treatment of type 2 diabetic patients is to control plasma glucose and HbA1c levels . In this study , we aim ed to assess the effects of three different insulin regimens ( group I : lispro insulin + NPH insulin , group II : lispro insulin + metformin and group III : regular insulin + NPH insulin ) on overall glycaemic control and metabolic parameters in type 2 diabetic patients with secondary oral anti‐diabetic drug failure Background : Insulin analogues may be associated with fewer episodes of hypoglycemia than conventional insulins . However , they are costly alternatives . We compared the cost-effectiveness of insulin analogues and conventional insulins used to treat type 1 and type 2 diabetes mellitus in adults . Methods : We conducted a cost-effectiveness evaluation of insulin analogues versus conventional insulins using the Center for Outcomes Research Diabetes Model . We compared rapid-acting analogues ( insulin aspart and insulin lispro ) with regular human insulin , and long-acting analogues ( insulin glargine and insulin detemir ) with neutral protamine Hagedorn insulin . We derived clinical information for the comparisons from meta-analyses of r and omized controlled trials . We obtained cost and utility estimates from published sources . We performed sensitivity analyses to test the robustness of our results . Results : For type 1 diabetes , insulin aspart was more effective and less costly than regular human insulin . Insulin lispro was associated with an incremental cost of Can$28 996 per quality -adjusted life-year . The incremental cost per quality -adjusted life-year was Can$87 932 for insulin glargine and Can$387 729 for insulin detemir , compared with neutral protamine Hagedorn insulin . For type 2 diabetes , insulin aspart was associated with an incremental cost of Can$22 488 per quality -adjusted life-year compared with regular human insulin . For insulin lispro , the incremental cost was Can$130 865 . Compared with neutral protamine Hagedorn insulin , insulin detemir was less effective and more costly . Insulin glargine was associated with an incremental cost of Can$642 994 per quality -adjusted life-year . The model was sensitive to changes in the effect size of hemoglobin A1c and to decrements applied to utility scores when fear of hypoglycemia was included as a factor . Interpretation : The cost-effectiveness of insulin analogues depends on the type of insulin analogue and whether the patient receiving the treatment has type 1 or type 2 diabetes . With the exception of rapid-acting insulin analogues in type 1 diabetes , routine use of insulin analogues , especially long-acting analogues in type 2 diabetes , is unlikely to represent an efficient use of finite health care re sources OBJECTIVE Multiple daily insulin injection programs are commonly accompanied by considerable glycemic variation and hypoglycemia . We conducted a r and omized crossover design clinical trial to compare glargine with ultralente insulin as a basal insulin in type 1 diabetes . RESEARCH DESIGN AND METHODS To determine whether the use of glargine insulin as a basal insulin would result in a comparable HbA1c and less glycemic variation and hypoglycemia than ultralente insulin , 22 individuals ( aged 44 + /- 14 years [ + /-SD ] , 55 % men ) with type 1 diabetes who were experienced with multiple daily insulin injections and had an HbA1c of < 7.8 % were r and omized in a crossover design to receive either glargine or ultralente as the basal insulin for 4 months . Aspart insulin was used as the pr and ial insulin . Physicians providing insulin dose adjustment advice were masked to the type of basal insulin . RESULTS Treatment with glargine result ed in lower mean HbA1c ( 6.82 + /- 0.13 vs. 7.02 + /- 0.13 , difference : 0.2 + /- 0.08 , P = 0.026 ) , less nocturnal variability ( plasma glucose 49.06 + /- 4.74 vs. 62.36 + /- 5.21 mg/dl , P = 0.04 ) , and less hypoglycemia ( 24.5 + /- 2.99 vs. 31.3 + /- 4.04 events , P = 0.05 ) , primarily due to less daytime hypoglycemia ( P = 0.002 ) . On the other h and , serious hypoglycemia and average glucose concentration measured with continuous subcutaneous glucose monitoring did not differ . CONCLUSIONS We conclude that while use of either ultralente or glargine as a basal insulin can result in excellent glycemic control , treatment with glargine is associated with slightly but significantly lower HbA1c and less nocturnal glycemic variability and hypoglycemia OBJECTIVE To compare blood glucose control and incidence of nocturnal hypoglycemia in adolescents with type 1 diabetes on multiple injection regimens managed with either an insulin analog combination or NPH insulin plus regular human insulin . RESEARCH DESIGN AND METHODS In a r and omized cross-over study , 28 adolescents with type 1 diabetes on multiple injection therapy received either insulin glargine prebedtime plus lispro prepr and ially ( LIS/GLAR ) or NPH insulin prebedtime plus regular human insulin prepr and ially ( R/NPH ) . During each 16-week treatment arm , subjects completed home blood glucose profiles , and at the end of each treatment arm , they were admitted for an overnight metabolic profile . A total of 25 subjects completed the study . RESULTS Compared with R/NPH therapy , LIS/GLAR was associated with lower mean blood glucose levels ( LIS/GLAR versus R/NPH ) : fasting ( 8.0 vs. 9.2 mmol/l , P < 0.0001 ) , 2 h postbreakfast ( 8.1 vs. 10.7 mmol/l , P < 0.0005 ) , prelunch ( 8.9 vs. 10.1 mmol/l , P < 0.01 ) , and 2 h postlunch ( 8.0 vs. 9.5 mmol/l , P < 0.002 ) . However , there was no difference in mean blood glucose levels before or after the evening meal . Incidence of nocturnal hypoglycemia on overnight profiles was 43 % lower on LIS/GLAR compared with R/NPH therapy ; however , there was no difference in rates of self-reported symptomatic hypoglycemia . Total insulin dose required to achieve target blood glucose control was lower on LIS/GLAR ( 1.16 IU/kg ) compared with R/NPH therapy ( 1.26 IU/kg , P < 0.005 ) , but there was no significant difference in HbA(1c ) levels ( LIS/GLAR versus R/NPH : 8.7 vs. 9.1 % , P = 0.13 ) . CONCLUSIONS Combination therapy with insulin glargine plus lispro reduced the incidence of nocturnal hypoglycemia and was at least as effective as R/NPH insulin therapy in maintaining glycemic control in adolescents on multiple injection regimens OBJECTIVE Insulin glargine ( 21A-Gly-30Ba-L-Arg-30Bb-L-Arg-human insulin ) is a biosynthetic insulin analog with a prolonged duration of action compared with NPH human insulin . This study compared insulin glargine with NPH human insulin in subjects with type 1 diabetes who had been previously treated with multiple daily injections of NPH insulin and regular insulin . RESEARCH DESIGN AND METHODS This study was a multicenter r and omized parallel-group study in which subjects were r and omized to receive premeal regular insulin and either insulin glargine ( at bedtime ) or NPH insulin ( at bedtime for patients on once-daily therapy and at bedtime and in the morning for patients on twice-daily therapy ) for up to 28 weeks . Dose titration of both basal insulins was based on capillary fasting whole blood glucose ( FBG ) levels ; the goal was a premeal blood glucose concentration of 4.4 - 6.7 mmol/l . RESULTS A total of 534 well-controlled type 1 diabetic subjects ( mean GHb 7.7 % , mean fasting plasma glucose [ FPG ] 11.8 mmo/l ) were treated . A small decrease in GHb levels was noted with both insulin glargine ( -0.16 % ) and NPH insulin ( -0.21 % ; P > 0.05 ) . Significant reductions in median FPG levels from baseline ( -1.67 vs. -0.33 mmol/l with NPH insulin , P = 0.0145 ) and a trend for a reduction in capillary FBG levels were achieved with insulin glargine . After the 1-month titration phase , significantly fewer subjects receiving insulin glargine experienced symptomatic hypoglycemia ( 39.9 vs. 49.2 % , P = 0.0219 ) or nocturnal hypoglycemia ( 18.2 vs. 27.1 % , P = 0.0116 ) with a blood glucose level < 2.0 mmol/l compared with subjects receiving NPH insulin . CONCLUSIONS Lower FPG levels with fewer episodes of hypoglycemia were achieved with insulin glargine compared with once- or twice-daily NPH insulin as part of a basal-bolus regimen in patients with type 1 diabetes OBJECTIVE Because there are limited data on the comparison of insulin aspart and mixed insulin in type 2 diabetes , this trial was performed to compare the efficacy and safety of prepr and ial insulin aspart with human soluble insulin ( HI ) and human premix ( 70 % NPH/30 % regular ) insulin ( MIX ) . RESEARCH DESIGN AND METHODS A total of 231 type 2 diabetic patients were r and omized to insulin aspart ( n = 75 ) , HI ( n = 80 ) , or MIX ( n = 76 ) for 3 months . Insulin aspart and HI were administered with or without bedtime NPH insulin . A total of 204 patients completed the trial according to protocol . HbA1c , 7-point blood glucose , insulin dosage , and hypoglycemic episodes were recorded . The primary end point was " change of HbA1c " from baseline to last visit . Analysis for equivalence was performed by t tests with three subtests . RESULTS HbA1c decreased 0.91 + /- 1.00 for insulin aspart , 0.73 + /- 0.87 for HI , and 0.65 + /- 1.10 for MIX with the following confidence intervals : insulin aspart HI ( -0.21 to 0.57 , P = 0.025 ) , insulin aspart MIX ( -0.17 to 0.69 , P = 0.092 ) , and HI-MIX ( -0.33 to 0.48 , P = 0.006 ) . Postpr and ial blood glucose decreased in the insulin aspart group : 0.44 mmol/l to > 1.67 mmol/l compared with HI and 1.1 mmol/l to > 1.67 mmol/l compared with MIX . Prepr and ial insulin doses were similar in the insulin aspart and HI groups ( 10 - 14.5 U ) . Hypoglycemic events per month were 0.56 HI , 0.40 insulin aspart , and 0.19 MIX . CONCLUSIONS Statistically , insulin aspart was not equivalent to another treatment in terms of HbA1c reduction . Insulin aspart treatment result ed in improved HbA1c and postpr and ial blood glucose . The application of insulin aspart was safe and well tolerated OBJECTIVE The purpose of this study was to compare the efficacy , safety and pump compatibility of insulin aspart ( a rapid-acting insulin analog ) and buffered regular human insulin in patients with type 1 diabetes undergoing continuous subcutaneous insulin infusion ( CSII ) therapy . RESEARCH DESIGN AND METHODS This was a single-center r and omized open-label study Patients received CSII therapy with insulin aspart ( n = 19 ) or buffered regular human insulin ( n = 10 ) for 7 weeks . Bolus doses of insulin aspart were administered immediately before meals and buffered regular human insulin 30 min before meals . RESULTS Insulin aspart and buffered regular human insulin were both effective in controlling average daily blood glucose levels ( 8.2 + /- 1.9 and 8.5 + /- 2.1 mmol/l , respectively ) ( mean + /- SD ) and maintaining serum fructosamine ( 343 + /- 25.7 and 336 + /- 27.4 micromol/l ) and HbA1c ( 6.9 + /- 0.6 and 7.1 + /- 0.6 % ) levels . Possible obstructions and set leakages were infrequently reported in both groups . Similar numbers of patients experienced hypoglycemia ( blood glucose < 2.5 mmol/l ) : 14 ( 74 % ) insulin aspart patients versus 6 ( 60 % ) buffered regular human insulin patients . Patients receiving insulin aspart had fewer hypoglycemic events per patient ( 2.9 ) than those patients receiving buffered regular human insulin ( 6.2 ) . There were no differences between the two insulins in the occurrence of hyperglycemic events ( blood glucose > 19 mmol/l ) or in the number and type of adverse events . CONCLUSIONS Insulin aspart and buffered regular human insulin were effective and well tolerated and provided similar pump compatibility when used in CSII therapy OBJECTIVE To compare the safety and efficacy of insulin aspart ( IAsp ) , buffered regular insulin ( BR ) , and insulin lispro administered by continuous subcutaneous insulin infusion ( CSII ) in patients with type 1 diabetes . RESEARCH DESIGN AND METHODS After completing a 4-week run-in period with BR , 146 adult patients with type 1 diabetes ( with pretrial CSII experience ) were r and omly assigned ( 2:2:1 ) to CSII treatment with IAsp , BR , or lispro for 16 weeks in a multicenter , open-label , r and omized , parallel-group study . Bolus insulin doses were administered 30 min before meals ( BR ) or immediately before meals ( IAsp or lispro ) . RESULTS Treatment groups had similar baseline HbA(1c ) ( 7.3 % + /- 0.7 for IAsp , 7.5 % + /- 0.8 for BR , and 7.3 % + /- 0.7 for lispro ) . After 16 weeks of treatment , HbA1c values were relatively unchanged from baseline , and the mean changes in baseline HbA1c values were not significantly different between the three groups ( 0.00 + /- 0.51 , 0.15 + /- 0.63 , and 0.18 + /- 0.84 for the IAsp , BR , and lispro groups , respectively ) . The rates of hypoglycemic episodes ( blood glucose < 50 mg/dl ) per patient per month were similar ( 3.7 , 4.8 , and 4.4 for the IAsp , BR , and lispro groups , respectively ) . Clogs/blockages in pumps or infusion sets were infrequent ; most subjects ( 76 , 83 , and 75 % in the IAsp , BR , and lispro groups , respectively ) had < or = 1 clog or blockage per 4 weeks during the trial . CONCLUSIONS Insulin aspart in CSII was as efficacious and well tolerated as BR and lispro and is a suitable insulin for continuous subcutaneous insulin infusion using external pumps OBJECTIVE To quantitate the contribution of postpr and ial blood glucose , which improves with the short-acting insulin analog lispro [ Lys(B28),Pro(B29 ) ] in type 1 diabetes , to the overall 24-h blood glucose concentration and the long-term HbA1c concentration under conditions of different postabsorptive blood glucose . RESEARCH DESIGN AND METHODS A total of 24 type 1 diabetic patients on long-term intensive therapy with premeal human regular insulin ( Hum-R ) and bedtime NPH were r and omly assigned to a continuation of Hum-R ( group 1 , n = 8) , lispro ( group 2 , n = 8) , or lispro + NPH ( in variable proportions ) administered at mealtime ( group 3 , n = 8) for 3 months , NPH administered at bedtime was continued in all three groups . Data from home blood glucose monitoring were collected , and a 24-h plasma glucose and insulin profile was obtained during a 2-day hospital visit to calculate areas under the postpr and ial glucose curve ( 3.5 h after breakfast , 3.5 h after lunch , and 3.0 h after dinner for a total of 10.0 h ) and the postabsorptive blood glucose curve ( the remaining 14.0 h out of 24.0 h ) ( AUC ) . Eight nondiabetic subjects were also studied . RESULTS The substitution of Hum-R with lispro ( group 2 ) result ed in lower postpr and ial blood glucose , but greater postabsorptive blood glucose ( P < 0.05 vs. group 1 ) . The postpr and ial blood glucose AUC was lower ( 161 + /- 19 vs. 167 + /- 20 mg.100 ml-1.h-1 ) , but the postabsorptive blood glucose AUC was greater ( 155 + /- 22 vs. 142 + /- 19 mg.100 ml-1.h-1 ) ( P < 0.05 ) . Therefore , the 24-h blood glucose AUC was no different ( NS ) . Consequently , HbA1c was no different ( NS ) . This occurred because in group 2 , mealtime lispro result ed in normal pr and ial plasma insulin , but also result ed in lower interpr and ial concentration ( P < 0.05 vs. group 1 ) . When NPH was added to lispro ( 30 % at breakfast , 40 % at lunch , 10 % at dinner ) in group 3 , postabsorptive plasma insulin was similar to group 1 ( NS ) , in group 3 , the postpr and ial blood glucose AUC ( 153 + /- 17 mg.100 ml-1.h-1 ) was lower and the postabsorptive blood glucose AUC was no different , as compared with group 1 ( NS ) . Therefore , the 24-h blood glucose AUC was lower ( 147 + /- 17 vs. 155 + /- 21 and 158 + /- 20 mg.100 ml-1.h-1 ) , and HbA1c was lower ( 6.41 + /- 0.12 vs. 6.84 + /- 0.2 and 6.96 + /- 0.2 % ( groups 3 , 1 , and 2 respectively , P < 0.05 ) . Frequency of hypoglycemia was greater in group 2 ( P < 0.05 ) , but not in group 3 ( NS ) vs. group 1 The present prospect i ve one-year r and omized study was conducted to compare soluble human insulin , with a new rapid-acting human insulin analogue , lispro , with respect to postpr and ial glucose excursions , frequency of hypoglycaemic episodes , glucose control , and long-term safety in 39 subjects ( 20 females , 19 males ) with Type 1 diabetes . The duration of diabetes , gender distribution , and age were similar in the two groups . The total number of hypoglycaemic episodes was significantly less ( p < 0.04 , Wilcoxon rank sum test ) in subjects receiving insulin lispro compared with regular human insulin over the 12-month period . The 2-h postpr and ial glucose excursion at 1 year was also significantly less ( p < 0.05 , ANOVA ) in the group treated with insulin lispro . The reductions in the total number of hypoglycaemic episodes and in the postpr and ial glucose excursion with use of insulin lispro may be beneficial for the long-term management of subjects with Type 1 diabetes . However , the greatest benefit identified by the subjects receiving insulin lispro was the greater convenience of the rapid-acting analogue OBJECTIVE To compare the effects of insulin lispro ( LP ) and human regular insulin ( HR ) when given twice daily with NPH insulin on glycemic control ( HbA1c ) , daily blood glucose profiles and rates of hypoglycemia in patients with type 2 diabetes mellitus after failure to respond to sulfonylurea drugs . RESEARCH DESIGN AND METHODS A 5.5-month r and omized , open-label , parallel study of 148 patients receiving either LP ( n = 70 ) or HR ( n = 78 ) . Eight-point blood glucose profiles and HbA1c measurements were collected at baseline , 1.5 , 3.5 and 5.5 months . RESULTS Two-hour post-breakfast and 2-hour post-supper blood glucose levels ( means [ and st and ard errors ] ) were significantly lower for LP than for HR at the end point ( 9.5 [ 0.4 ] mmol/L v. 10.9 [ 0.4 ] mmol/L and 8.4 [ 0.4 ] mmol/L v. 9.7 [ 0.4 ] mmol/L , respectively , p = 0.02 in both cases ) . HbA1c improved from 10.5 % ( 0.2 % ) ( LP ) and 10.3 % ( 0.2 % ) ( HR ) to 8.0 % ( 0.1 % ) . Hypoglycemia rates were similar during the day ; however , there was an overnight trend to reduced rates with LP ( 0.08 [ 0.03 ] episodes/30 d v. 0.16 [ 0.04 ] episodes/30 d , p = 0.057 ) . Quality -of life assessment showed significant improvement ( p < 0.05 ) in the diabetes-related worry scale for LP subjects whereas HR subjects slightly worsened . CONCLUSIONS With traditional twice-daily insulin administration algorithms , LP improves 2-hour postpr and ial glucose levels , quality of life and overnight hypoglycemia rates while delivering an equivalent level of glycemic control ( HbA1c ) compared with HR to insulin-naïve patients with type 2 diabetes who require insulin OBJECTIVE To assess the potential of insulin lispro to limit the frequency of severe hypoglycaemia without compromising glycaemic control in a cohort of patients with type 1 diabetes who are at a high risk of severe hypoglycemia . Research design and methods An open-label , r and omised , 12-month comparative crossover study of insulin lispro and regular human insulin was performed in 33 patients with type 1 diabetes with impaired hypoglycaemia awareness . The efficacy of each treatment was evaluated by glycaemic control ( HbA(1c ) ) , eight-point home blood glucose profiles , and the frequency and severity of hypoglycaemic episodes and quality of life . RESULTS Eighteen ( 55 % ) patients experienced one or more episodes of severe hypoglycaemia in the 48 weeks of study . There was a trend to a lower incidence of severe hypoglycaemia during treatment with insulin lispro in comparison with regular human insulin ( 55 vs 84 episodes , p=0.087 ) . This result ed principally from a 47 % lower incidence of nocturnal severe hypoglycaemia with insulin lispro ( 25 vs 47 episodes , p=0.11 ) . The lower frequency of severe hypoglycaemia associated with insulin lispro was not explained by differences in glycated haemoglobin between insulin treatments ( HbA(1c ) 9.1 % insulin lispro vs 9.3 % regular human insulin ) . CONCLUSIONS In individuals with type 1 diabetes , who have impaired awareness of hypoglycaemia , treatment with insulin lispro may be associated with a lower incidence of severe hypoglycaemia manifested predominantly through less frequent nocturnal episodes . Insulin lispro may have a beneficial role in the management of patients with diabetes at risk of severe hypoglycaemia , although a larger study is required to confirm these findings BACKGROUND Type 2 diabetes ( T2DM ) patients often fail to achieve adequate glycemic control with oral antidiabetic drugs ( OADs ) . Insulin has been shown to improve glycemic control in these patients but with increased risk of hypoglycemia . This study compared the efficacy and safety of insulin glargine and NPH insulin , both in combination with a once-daily fixed dose of glimepiride , in terms of glycemic control and incidence of hypoglycemia . METHODS In this open-label , 24-week r and omized trial in ten Latin American countries , T2DM patients poorly controlled on OADs ( HbA1c > or = 7.5 and < or = 10.5 % ) received glimepiride plus insulin glargine ( n = 231 ) or NPH insulin ( n = 250 ) using a forced titration algorithm . The primary endpoint was the equivalence of 24-week mean changes in HbA1c . RESULTS Insulin glargine and NPH insulin achieved similar HbA1c reductions ( adjusted mean difference -0.047 ; 90 % CI -0.232 , 0.138 ; per- protocol analysis ) . Confirmed nocturnal hypoglycemia was significantly lower with insulin glargine vs. NPH insulin ( 16.9 vs. 30.0 % ; p < 0.01 ; safety analysis ) . Patients receiving insulin glargine were significantly more likely to achieve HbA1c levels < 7.0 % without hypoglycemia ( 27 vs. 17 % ; p = 0.014 ; per- protocol analysis ) . There was a more pronounced treatment satisfaction improvement with insulin glargine vs. NPH insulin ( p < 0.02 ; full analysis ) . The proportion of patients who lost time from work or normal activities due to diabetes was lower with insulin glargine vs. NPH ( 1.8 vs. 3.3 % ; full analysis ) . CONCLUSIONS In patients with T2DM , inadequately controlled on OADs , once-daily insulin glargine plus glimepiride is effective in improving metabolic control with a reduced incidence of nocturnal hypoglycemia compared with NPH insulin OBJECTIVE To compare glycemic control obtained with the new rapid-acting insulin analog insulin aspart with that obtained with unmodified human insulin using algorithm-driven dosage adjustment . RESEARCH DESIGN AND METHODS This was a multicenter r and omized double-blind crossover study of 90 male subjects with type 1 diabetes . Insulin aspart or soluble human insulin was administered before meals , and NPH insulin was administered at bedtime as basal therapy . Each 4-week study period ended with a 24-h inpatient serum insulin and plasma glucose profile . RESULTS The 24-h plasma glucose control obtained with insulin aspart , as assessed by excursions of blood glucose outside a predefined normal range ( 4.0 - 7.0 mmo/l ) , was superior ( 22 % reduction in excursion , P < 0.01 ) . Fructosamine levels remained unchanged with insulin aspart , with daytime glycemic control superior but nighttime glycemic control inferior . Eight-point home blood glucose profiles confirmed that insulin aspart significantly improved postpr and ial blood glucose control after lunch and dinner ( P < 0.05 ) without deterioration of prepr and ial blood glucose control . Hypoglycemic episodes requiring third-party intervention were significantly fewer with insulin aspart than with human insulin ( 20 vs. 44 events , P < 0.002 ) . Insulin aspart was well tolerated . CONCLUSIONS In comparison with human insulin , insulin aspart can improve postpr and ial glycemic control as assessed by a reduction in hyper- and hypoglycemic excursions in people with type 1 diabetes . For its full potential to be realized , it will need to provide better control of nighttime hyperglycemia OBJECTIVE To compare the efficacy of the short-acting insulin analog lispro ( LP ) with that of regular insulin in IDDM patients treated with an external pump . RESEARCH DESIGN AND METHODS Thirty-nine IDDM patients ( age , 39.4 ± 1.5 years ; sex ratio , 22M/17W ; BMI , 24.4 ± 0.4 kg/m2 ; diabetes duration , 22.5 ± 1.6 years ) who were treated by external pump for 5.1 ± 0.5 years were involved in an open-label , r and omized , crossover multicenter study comparing two periods of 3 months of continuous subcutaneous insulin infusion with LP or with Actrapid HM , U-100 ( ACT ) . Boluses were given 0–5 min ( LP ) or 20–30 min ( ACT ) before meals . Blood glucose ( BG ) was monitored before and after the three meals every day . RESULTS The decrease in HbA1c was more pronounced with LP than with ACT ( −0.62 ± 0.13 vs. −0.09 ± 0.15 % , P = 0.01 ) . BG levels were lower with LP ( 7.93 ± 0.15 vs. 8.61 ± 0.18 mmol/l , P < 0.0001 ) , particularly postpr and ial BG levels ( 8.26 ± 0.19 vs. 9.90 ± 0.20 mmol/l , P < 0.0001 ) . St and ard deviations of all the BG values ( 3.44 ± 0.10 vs. 3.80 ± 0.10 mmol/l , P = 0.0001 ) and of postpr and ial BG values ( 3.58 ± 0.10 vs. 3.84 ± 0.10 mmol/l . P < 0.02 ) were lower with LP . The rate of hypoglycemic events defined by BG < 3.0 mmol/l did not significantly differ between LP and ACT ( 7.03 ± 0.94 vs. 7.94 ± 0.88 per month , respectively ) , but the rate of occurrences of very low BG , defined as BG < 2.0 mmol/l , were significantly reduced with LP ( 0.05 ± 0.05 vs. 0.47 ± 0.19 per month , P < 0.05 ) . At the end of the study , all but two ( 95 % ) of the patients chose LP for the extension phase . CONCLUSIONS When used in external pumps , LP provides better glycemic control and stability than regular insulin and does not increase the frequency of hypoglycemic episodes This study compared glycemic control achieved with insulin lispro or buffered regular human insulin in patients with Type 1 diabetes treated with continuous subcutaneous insulin infusion ( CSII ) using an external insulin pump . In this 24-week multicenter , r and omized , two-way crossover , open-label trial , 58 patients on CSII with adequate glycemic control received either insulin lispro or buffered regular human insulin for 12 weeks , followed by the alternate treatment for another 12 weeks . Efficacy and safety measures included hemoglobin A(1c ) ( HbA(1c ) ) at baseline and endpoint , home blood glucose monitoring , hypoglycemia , and frequency of pump catheter occlusion . Patients consumed a st and ard test meal on three occasions , with determinations of fasting , 1- and 2-h postpr and ial glucose values . Insulin lispro use was associated with a significantly lower HbA(1c ) than was buffered regular human insulin ( 7.41+/-0.97 vs. 7.65+/-0.85 mmol/l ; P=.004 ) . Fasting serum glucose values before the test meal were similar between the two therapies . The 1-h ( 11.16+/-4.29 vs. 13.20+/-4.68 mmol/l ; P=.012 ) and 2-h ( 9.64+/-4.10 vs. 12.53+/-4.64 mmol/l ; P=.001 ) postpr and ial glucose concentrations were significantly lower during treatment with insulin lispro . No differences between treatments were observed in basal or bolus insulin doses , weight gain , or the incidence and rate of hypoglycemia , hyperglycemia , or pump occlusions . When used in external pumps , insulin lispro provides better glycemic control than buffered regular human insulin with a similar adverse event profile OBJECTIVE Insulin glargine ( HOE 901 , 21(A)-Gly-30(B)a-L-Arg-30(B)b-L-Arg human insulin ) is a novel recombinant analog of human insulin with a shift in the isoelectric point producing a retarded absorption rate and an increased duration of action that closely mimics normal basal insulin secretion . It recently received approval from the Food and Drug Administration . The aim of this study was to evaluate 2 formulations of insulin glargine for safety and efficacy in the treatment of patients with type 1 diabetes . RESEARCH DESIGN AND METHODS In a 4-week trial , 256 patients with type 1 diabetes received either NPH insulin or insulin glargine containing 30 microg/ml zinc ( insulin glargine[30 ] ) or 80 microg/ml zinc ( insulin glargine[80 ] ) . Insulin glargine was given subcutaneously once daily at bedtime . NPH insulin was given either once daily ( at bedtime ) or twice daily ( before breakfast and at bedtime ) , according to the patient 's pre study regimen . The initial doses of insulin glargine and NPH were based on the previous NPH total daily dose . RESULTS At study end point , insulin glargine-pooled groups had significantly lower fasting plasma glucose ( FPG ) levels than the NPH insulin group , with adjusted mean FPG levels reduced by 2.2 mmol/l ( P = 0.0001 ) . Insulin glargine was superior to NPH insulin in reducing FPG levels in patients who had previously received NPH insulin twice daily but not in patients who had previously received NPH once daily . FPG levels were more stable in patients using insulin glargine than in patients using NPH insulin . A subset of patients ( n = 71 ) underwent hourly overnight plasma glucose measurements . Insulin glargine patients exhibited lower FPG levels after 5:00 A.M. ; the difference was significant by 8:00 A.M. The adjusted mean FPG for insulin glargine[30 ] was 7.8 mmol/l ; for insulin glargine[80 ] , 7.3 mmol/l ; and for NPH , 10.7 mmol/l . Both formulations of insulin glargine were well tolerated , similar to NPH insulin . CONCLUSIONS Basal insulin glargine administered once daily for 4 weeks as part of a basal-bolus multiple daily insulin regimen was safe and more effective in lowering fasting plasma glucose levels than NPH in patients with type 1 diabetes Aims This trial investigated the efficacy and safety of two different administration‐time regimens with insulin detemir ( IDet ) to that of a conventional basal insulin regimen with NPH insulin ( NPH ) Insulin aspart ( IAsp ) , is a rapid-acting analogue of human insulin ( HI ) , for use in the meal related treatment of diabetes mellitus . The degree of glycaemic control achieved by IAsp in comparison with HI after algorithm-driven dose optimisation was tested over 3 months . The prospect i ve , multicentre , r and omised , open-label study with parallel groups was performed in 48 centres in 11 countries and included 423 basal-bolus treated patients with Type 1 diabetes . Main outcome measures were blood glucose control assessed by HbA1c , nine-point self-monitored blood glucose profiles , insulin dose , quality of life , hypoglycaemia and adverse events . An algorithm-driven increase occurred in the dose and number of daily injections of basal insulin , particularly in the IAsp group . After 12 weeks of treatment , HbA1c was significantly lower in IAsp compared to HI treated subjects by 0.17 ( 95 % CI 0.30 - 0.04 ) ( P<0.05 ) . Comparison of the blood glucose profiles showed lower blood glucose levels with IAsp after breakfast ( mean 8.4 vs 10.1 mmol/l ; P<0.0001 ) and dinner ( 8.2 vs 9.3 mmol/l ; P<0.01 ) . There were no differences between treatments in the incidence of hypoglycaemic episodes or in the adverse event profiles . The WHO Diabetes Treatment Satisfaction Question naire score for perceived hyperglycaemia was lower with Iasp ( P=0.005 ) , and patients found the insulin aspart treatment more flexible ( P=0.022 ) . The current study underlines the need for optimising the basal insulin regimen in order to take full advantage of the pharmacodynamics of IAsp Objective : To compare the safety , efficacy and management of insulin lispro ( LP ) with regular human insulin ( RH ) in young diabetic children treated with continuous subcutaneous insulin infusion ( CSII ) . Study Design : 27 very young diabetic children ( age 4.6 ± 2.2 years ) treated with CSII participated in an open-label , r and omized cross-over multicenter study comparing 2 periods of 16 weeks of CSII with LP or RH . Results : Mean daily basal rate was significantly higher during the LP period ( p = 0.04 ) . No differences were seen in changes in HbA1c levels , number of hypoglycemic events , cutaneous infections and catheter occlusions . There was no significant difference between the two treatments for prepr and ial and postpr and ial glucose values , although pr and ial glucose excursions tended to be lower with LP ( significant at dinner , p = 0.01 ) . Mean blood glucose levels were significantly higher at 0.00 and 3.00 a.m. during LP therapy ( p < 0.05 ) . No episode of ketoacidosis occurred during LP treatment . More parents indicated that LP made their own and the child ’s daily life easier ( p = 0.02 ) and preferred LP ( p = 0.01 ) . Conclusions : LP in CSII therapy in children is safe , as effective as RH , improved postpr and ial excursions , met the needs of young children in their daily life well , and gained their parents ’ satisfaction and preference . However , a shorter duration of LP result ed in hyperglycemia during the first part of the night , which must be compensated for by increasing nocturnal basal rates during this time OBJECTIVE To compare the efficacy and safety of prepr and ial administration of rapid-acting lispro analogue with regular short-acting insulin to pregnant women with type 1 diabetes . STUDY DESIGN Open r and omised multicentre study . Women were treated with multiple insulin injections aim ing at normoglycaemia . Blood glucose was determined six times daily , HbA(1c ) every 4 weeks . Diurnal profiles of blood glucose were analysed at gestational week 14 and during the study period at weeks 21 , 28 and 34 . PARTICIPANTS 33 pregnant women with type 1 DM were r and omised to treatment with lispro insulin ( n=16 ) or regular insulin ( n=17 ) . RESULTS Blood glucose was significantly lower ( P<0.01 ) after breakfast in the lispro group , while there were no significant group differences in glycemic control during the rest of the day . Severe hypoglycaemia occurred in two patients in the regular group but biochemical hypoglycaemia ( blood glucose < 3.0 mmol/l ) was more frequent in the lispro than in the regular group ( 5.5 vs. 3.9 % , respectively ) . HbA(1c ) values at inclusion were 6.5 and 6.6 % in the lispro and regular group respectively . HbA(1c ) values declined during the study period and were similar in both groups . There was no perinatal mortality . Complications during pregnancy , route of delivery and foetal outcome did not differ between the groups . Retinopathy progressed in both groups , one patient in the regular group developed proliferative retinopathy . CONCLUSION The results suggest that it is possible to achieve at least as adequate glycemic control with lispro as with regular insulin therapy in type 1 diabetic pregnancies Insulin lispro is absorbed more rapidly and has a shorter duration of action than regular human insulin . It improves glycaemic control but large-scale studies are required to identify regimens that optimise efficacy and safety with local dietary habits . This study involved 1184 Italian patients with Type 1 diabetes , r and omised to insulin lispro ( n=586 ) or regular human insulin ( n=598 ) as pre-meal bolus for 3 months . Optimisation of basal NPH insulin was carried out in both groups . The number of administrations of NPH insulin was increased when using insulin lispro but , because basal and bolus insulins were mixed before meals , the total number of injections per day was unchanged . Compliance to administration time was significantly ( p<0.001 ) greater with insulin lispro than with regular human insulin . Post-pr and ial blood glucose levels were lower with insulin lispro after breakfast ( p<0.001 ) , lunch ( p<0.005 ) and dinner ( p<0.001 ) . The HbA1c level was decreased from baseline by both insulins , but the percent increase in patients with acceptable ( < 8 % ) HbA1c was greater with insulin lispro . While frequency of hypoglycaemia was decreased from baseline by both insulins , the proportion of episodes classified as severe was significantly increased from baseline with regular human insulin , but not with insulin lispro . Thus , compared with regular human insulin , improved glycaemic control was achieved with insulin lispro without an increase in severe hypoglyeaemia AIMS To assess satisfaction with treatment and psychological well-being associated with insulin glargine and Neutral Protamine Hagedorn ( NPH ) . Insulin glargine , a new long-acting insulin analogue , provides constant , peakless insulin release following once-daily administration and is associated with fewer hypoglycaemic episodes , despite metabolic control equivalent to that achieved with NPH human basal insulin . METHODS The Diabetes Treatment Satisfaction Question naire ( DTSQ ) and Well-being Question naire ( W-BQ ) were completed at baseline and at weeks 8 , 20 or 28 by 517 patients with Type 1 diabetes participating in a r and omized , controlled European trial comparing insulin glargine and NPH . Analysis of covariance was performed on change from baseline scores ( main effects : treatment and pooled site ; covariate : baseline scores ) . RESULTS Treatment satisfaction improved with insulin glargine at all time points , including endpoint , but deteriorated slightly with NPH . These differences were significant throughout the study ( change from baseline to endpoint : + 1.27 vs. -0.56 ; P = 0.0001 ) . Outcomes were better with insulin glargine for the DTSQ items , Perceived Frequency of Hyperglycaemia and Hypoglycaemia , with statistically significant differences at week 28 and endpoint for hyperglycaemia ( P = 0.0373 and 0.0379 ) and at week 20 for hypoglycaemia ( P = 0.0024 ) . There was no difference in psychological well-being between the treatment groups , with mean scores increasing in both . CONCLUSIONS Study participants had treatment-independent improvements in General Well-being . Advantages for insulin glargine were seen in significantly improved Treatment Satisfaction throughout the study , together with lower Perceived Frequency of Hyperglycaemia than for patients on NPH , without a significant increase in Perceived Frequency of Hypoglycaemia A common treatment regimen for patients with either insulin-dependent diabetes mellitus ( IDDM ) or non-insulin-dependent diabetes mellitus ( NIDDM ) is a combination of rapid-acting insulin and intermediate-acting insulin administered twice each day . It is usually recommended that regular human insulin be injected 30 to 45 minutes before a meal . In practice , patients often inject regular human insulin closer to mealtime , causing a higher post-pr and ial serum glucose level and an increased potential for hypoglycemia in the postabsorptive period . Insulin lispro , a rapid-acting insulin analogue , is best injected just before a meal because of its more rapid absorption and shorter duration of action . In 707 r and omized patients , 379 with IDDM and 328 with NIDDM , we studied the effect of twice-daily insulin lispro or regular human insulin in combination with NPH human insulin ( isophane insulin ) on premeal , 2-hour postpr and ial , and bedtime glycemic control . Assessment s were based on the results of a seven-point blood glucose profile , the insulin dose ( by formulation and time of administration ) , the incidence and frequency of hypoglycemic episodes , and the glycated hemoglobin value . Treatment with insulin lispro result ed in lower postpr and ial glucose levels and smaller increases in glucose level after the morning and evening meals compared with treatment with regular human insulin . Overall glycemic control , frequency of hypoglycemic events , and total insulin dose were not different between the two groups . Insulin lispro in combination with NPH human insulin in a twice-per-day regimen allows injection closer to mealtime and improves post-pr and ial glycemic control without increasing the risk of hypoglycemia This trial compared the efficacy and safety of basal-bolus therapy using either the soluble basal insulin analogue insulin detemir ( IDet ) in combination with meal-time rapid-acting analogue insulin aspart ( IAsp ) , or NPH insulin ( NPH ) in combination with meal-time regular human insulin ( HSI ) . This was a 22-week , multinational , open-labelled , symmetrically r and omised , parallel group trial including 395 people with type 2 diabetes ( IDet + IAsp : 195 , NPH + HSI : 200 ) . At 22 weeks , HbA1c was comparable between treatments ( IDet + IAsp : 7.46 % , NPH + HSI : 7.52 % , P = 0.515 ) with decreases from baseline of 0.65 % and 0.58 % , respectively . Treatment with IDet + IAsp was associated with a significantly lower within-person variation in self-measured fasting plasma glucose ( FPG ) ( SD:1.20 versus 1.54 mmol/L , p < 0.001 ) , as well as a lower body weight gain ( 0.51 versus 1.13 kg , p = 0.038 ) than with NPH + HSI . The risk of nocturnal hypoglycaemia was 38 % lower with IDet + IAsp than with NPH + HSI , but statistical significance was not attained ( P = 0.14 ) . The overall safety profile was similar between the two treatments . Basal-bolus treatment with IDet + IAsp is an effective and well tolerated insulin regimen in people with type 2 diabetes , result ing in glycaemic control comparable to that of NPH + HSI , but with the advantages of less weight gain and a lower day-to-day within-person variation in FPG AIMS A European , r and omized , 29-centre , open-label study compared the safety and efficacy of two formulations of insulin glargine and neutral protamine Hagedorn ( NPH ) human insulin , in combination with oral agents , in patients with Type 2 diabetes mellitus ( DM ) . METHODS Two-hundred- and -four patients with Type 2 DM , in whom oral treatment alone was inadequate , were r and omized to insulin glargine with 30 micro g/ml zinc [ insulin glargine ( 30 ) ] , or insulin glargine with 80 micro g/ml zinc [ insulin glargine ( 80 ) ] or NPH insulin subcutaneously once daily . Insulin was titrated to aim for fasting blood glucose ( FBG ) values between 4 and 7 mmol/l . All participants received oral therapy during the 3-week titration phase and 1-week maintenance phase of the trial . RESULTS No differences between treatment groups were observed in adjusted mean fasting plasma glucose ; significant decreases of 3.4 mmol/l , 3.5 mmol/l and 3.1 mmol/l were observed within the insulin glargine ( 30 ) , insulin glargine ( 80 ) and NPH insulin groups , respectively ( P<0.0001 in each case ) . No differences between groups , but significant changes within groups , were observed in self-monitored FBG , mean FBG , blood glucose profile , stability of FBG , nocturnal blood glucose , fasting serum C-peptide , non-esterified fatty acids , haemoglobin A1c , fructosamine and fasting serum insulin . A significantly greater proportion of NPH insulin patients experienced symptomatic nocturnal hypoglycaemia ( 19.1 NPH group vs. 7.3 % glargine groups ; P=0.0123 ) . Both insulins were well tolerated ; one patient in each group experienced an injection site reaction . CONCLUSIONS Insulin glargine is as safe and effective as NPH insulin given once daily and in this study caused fewer episodes of nocturnal hypoglycaemia To establish whether lispro may be a suitable short-acting insulin preparation for meals in intensive treatment of Type 1 diabetes mellitus ( DM ) in patients already in chronic good glycaemic control with conventional insulins , 69 patients on intensive therapy ( 4 daily s.c . insulin injections , soluble at each meal , NPH at bedtime , HbA1c < 7.5 % ) were studied with an open , cross-over design for two periods of 3 months each ( lispro or soluble ) . The % HbA1c and frequency of hypoglycaemia were assessed under four different conditions ( Groups I-IV ) . Lispro was always injected at mealtime , soluble 10 - 40 min prior to meals ( with the exception of Group IV ) . Bedtime NPH was continued with both treatments . When lispro replaced soluble with no increase in number of daily NPH injections ( Group I , n = 15 ) , HbA1c was no different ( p = NS ) , but frequency of hypoglycaemia was greater ( p < 0.05 ) . When NPH was given 3 - 4 times daily , lispro ( Group II , n = 18 ) , but not soluble ( Group III , n = 12 ) decreased HbA1c by 0.35 + /- 0.25 % with no increase in hypoglycaemia . When soluble was injected at mealtimes , HbA1c increased by 0.18 + /- 0.15 % and hypoglycaemia was more frequent than when soluble was injected 10 - 40 min prior to meals ( Group IV , n = 24 ) ( p < 0.05 ) . It is concluded that in intensive management of Type 1 DM , lispro is superior to soluble in terms of reduction of % HbA1c and frequency of hypoglycaemia , especially for those patients who do not use a time interval between insulin injection and meal . However , these goals can not be achieved without optimization of basal insulin OBJECTIVE To present the findings in a r and omized , parallel-group study , comparing once-daily insulin glargine with twice-daily NPH insulin in patients with type 1 diabetes previously treated with multiple daily injections of basal and regular insulin . METHODS Of 394 patients with type 1 diabetes treated for up to 28 weeks , 195 received insulin glargine and 199 received NPH insulin , in addition to prepr and ial regular insulin . Glycemic control and hypoglycemic episodes were assessed . RESULTS A greater mean decrease in fasting blood glucose ( FBG ) was achieved at endpoint with insulin glargine than with NPH insulin ( -21 mg/dL versus -10 mg/dL [ -1.17 mmol/L versus -0.56 mmol/L ] ; P = 0.015 ) , and a greater percentage of patients treated with insulin glargine reached the target FBG ( 32.6 % versus 21.3 % ; P = 0.015 ) . Similar percentages of patients in both treatment groups achieved glycosylated hemoglobin values of 7.0 % or less at endpoint ( insulin glargine , 35.8 % ; NPH insulin , 35.4 % ) . After the 1-month titration phase , the percentage of patients who reported at least one symptomatic hypoglycemic event confirmed by a blood glucose value of less than 50 mg/dL ( 2.8 mmol/L ) was significantly lower with insulin glargine than with NPH insulin ( 73.3 % versus 81.7 % ; P = 0.021 ) . Furthermore , the percentage of patients who reported at least one symptomatic hypoglycemic event confirmed by a blood glucose value of less than 36 mg/dL ( 2.0 mmol/L ) was significantly lower with insulin glargine than with NPH insulin ( 36.6 % versus 46.2 % ; P = 0.033 ) . CONCLUSION Once-daily insulin glargine was at least as effective as twice-daily NPH insulin in improving fasting glycemic control and result ed in fewer reported symptomatic hypoglycemic events OBJECTIVE HOE 901 ( Hoechst Marion Roussel , Frankfurt , Germany ) is a biosynthetic insulin with a prolonged action . The aim of this study was to compare the effect of the long-acting insulin analog HOE 901 with NPH insulin regarding glycemic control in patients with type 1 diabetes . RESEARCH DESIGN AND METHODS A total of 333 type 1 diabetic patients were enrolled in this multinational parallel group trial . Subjects were r and omized either to two different formulations of HOE 901 ( the formulations differed only in zinc content ) or to NPH insulin . The study was only partially blinded because patients can distinguish HOE 901 ( a clear solution ) from NPH ( a cloudy suspension ) . In addition to premeal injections of regular insulin , patients received HOE 901 at bedtime or NPH once daily at bedtime or twice daily in the morning and at bedtime . RESULTS Fasting plasma glucose levels were significantly lower with HOE 901 ( -1.88 mmol/l . P = 0.0005 ) as were fasting self-monitored blood glucose levels ( -0.80 mmol/l , P = 0.0020 ) . HbA1c levels also showed a significant reduction with HOE 901 ( -0.14 % ) versus NPH ( P = 0.030 ) . The overall frequency of hypoglycemia did not differ , but the frequency of nocturnal hypoglycemia was significantly ( P = 0.0037 ) lower with HOE 901 ( 36 vs. 55 % ) . However , this effect on nocturnal hypoglycemia was significant only versus NPH once daily not NPH twice daily . The pattern of adverse events and injection site reactions with HOE 901 was similar to that with NPH . CONCLUSIONS This study indicates that HOE 901 achieves better control of fasting glucose and HbA1c levels over 4 weeks , and HOE 901 has a possible safety benefit in terms of nocturnal hypoglycemia OBJECTIVE To compare long-term glycemic control and safety of using insulin aspart ( IAsp ) with that of regular human insulin ( HI ) . RESEARCH DESIGN AND METHODS This was a multicenter r and omized open-label 6-month study ( 882 subjects ) with a 6-month extension period ( 714 subjects ) that enrolled subjects with type 1 diabetes . Subjects administered IAsp immediately before meals or regular HI 30 min before meals ; basal NPH insulin was taken as a single bedtime dose in the majority of subjects . Glycemic control was assessed with HbA1c values and 8-point blood glucose profiles at 3-month intervals . RESULTS Mean postpr and ial blood glucose levels ( mg/dl + /- SEM ) were significantly lower for subjects in the IAsp group compared with subjects in the HI group after breakfast ( 156 + /- 3.4 vs. 185 + /- 4.7 ) , lunch ( 137 + /- 3.1 vs. 162 + /- 4.1 ) , and dinner ( 153 + /- 3.1 vs. 168 + /- 4.1 ) , when assessed after 6 months of treatment . Mean HbA1c values ( % + /- SEM ) were slightly , but significantly , lower for the IAsp group ( 7.78 % + /- 0.03 ) than for the regular HI group ( 7.93 % + /- 0.05 , P = 0.005 ) at 6 months . Similar postpr and ial blood glucose and HbA1c values were observed at 12 months . Adverse events and overall hypoglycemic episodes were similar for both treatment groups . CONCLUSIONS Postpr and ial glycemic control was significantly better with IAsp compared with HI after 6 and 12 months of treatment . The improvement was not obtained at an increased risk of hypoglycemia . HbA1c was slightly , but significantly , lower for IAsp compared with HI at 6 and 12 months To evaluate the superiority of insulin glargine as basal insulin replacement by continuous glucose monitoring system ( CGMS ) . Twenty-four patients with type 2 diabetes mellitus ( T2DM ) whose blood glucose was not well controlled with sulphanylureas were enrolled . At first , they were treated with extended-release glipizide ( glucotrol XL ) 5mg/d before breakfast for 2 weeks , then r and omized to combination treatment with glargine ( 16 patients ) or NPH ( 8 patients ) and treated for 12 weeks . CGMS were carried in the second week after treatment with glucotrol XL , and in the 12th week after combination treatment . The data of CGMS showed : ( 1 ) When FPG were well controlled in both groups ( glargine group versus NPH group : 6.0+/-1.0 mmol/L versus 5.8+/-1.3 mmol/L ) , the blood glucose level at 3:00 a.m. ( 5.1+/-0.9 mmol/L versus 4.2+/-0.8 mmol/L ) were higher ( P<0.05 ) , TPG < or = 3.0 mmol/L at night were lower ( 2.56+/-1.79 versus 5.88+/-1.96 ) , and the rate of nocturnal hypoglycemia ( 1/16 versus 4/8 ) were less ( P=0.028 ) in glargine group than those in NPH group . ( 2 ) CGMS showed that the daily blood glucose profile excursion were more smoother in glargine group than those in NPH group . In conclusion , it was confirmed with CGMS that compared with traditionally basal insulin replacement with NPH , the combination treatment with glargine injection at bedtime may be predominant for stabilizing the daily blood glucose profile excursion and decreasing the nocturnal hypoglycemia events incidence . So glargine may be a more ideal basal insulin replacement than NPH OBJECTIVE The purpose of this trial was to compare the effects of QD basal insulin replacement using insulin detemir versus neutral protamine Hagedorn ( NPH ) insulin in basal-bolus therapy in combination with regular human insulin ( HI ) in patients with type 1 diabetes mellitus ( DM ) . METHODS This was a 6-month , prospect i ve , r and omized , open-label , controlled , parallel-group trial conducted at 92 sites in Europe and Australia . The trial population included men and women with type 1 DM for at least 1 year aged > or = 18 years with glycosylated hemoglobin ( HbA(1c ) ) < = = 12 % already taking QD basal-bolus treatment with an intermediate- or long-acting insulin and a fast-acting human insulin or insulin analogue as bolus insulin . Patients were r and omly assigned ( 2:1 ) to 6 months of treatment with insulin detemir or NPH at bedtime in combination with HI with main meals . Main outcome measures were blood glucose control as assessed by HbA(1c ) , fasting plasma glucose ( FPG ) , 9-point self-monitored blood glucose ( SMBG ) profiles , 24-hour continuous blood glucose profiles , hypoglycemia , weight gain , and adverse events . RESULTS Of the 749 patients r and omized to treatment , 747 were exposed to trial products and included in the intent-to-treat analysis set . Seven hundred patients completed the trial : 465 ( 94.7 % ) in the insulin detemir group and 235 ( 91.8 % ) in the NPH group . After 6 months , FPG was lower with insulin detemir than with NPH ( -1.16 mmol/L difference ; P = 0.001 ) , whereas HbA(1c ) did not differ significantly between treatments ( -0.12 % [ 95 % CI , -0.25 to 0.02 ] ; P = NS ) . Day-to-day variability in self-measured fasting blood glucose was lower with insulin detemir ( SD , 2.82 vs 3.60 mmol/L ; P < 0.001 ) . The overall shape of the 9-point SMBG profiles differed significantly between treatments ( P = 0.006 ) , with lower glucose levels before breakfast with insulin detemir than with NPH ( P < 0.001 ) . There was a 26 % reduction in the relative risk of nocturnal hypoglycemia with insulin detemir compared with NPH ( P = 0.003 ) . Gain in body weight was significantly lower after 6 months with insulin detemir than with NPH ( -0.54 kg difference ; P = 0.024 ) . The frequency and type of adverse events were similar between treatment groups . CONCLUSIONS In this study , QD administration of insulin detemir at bedtime result ed in lower fasting blood glucose levels with less day-to-day variability and less fluctuation from ean blood glucose levels over 24 hours than NPH insulin , combined with an overall reduction in the risk of nocturnal hypoglycemia . These findings suggest that evening administration of insulin detemir may provide an opportunity to further improve fasting blood glucose targets OBJECTIVE To measure the effectiveness of insulin lispro , a fast-acting insulin analog , in reducing hypoglycemic episodes when used in a basal bolus regimen by patients with type 1 diabetes using intensive insulin therapy . RESEARCH DESIGN AND METHODS In 11 diabetes outpatient clinics in the U.K. , 165 subjects with type 1 diabetes were enrolled in a r and omized crossover open-label study with a 2-month run-in period and then treated with a basal bolus regimen . Patients used human NPH insulin at night with either premeal insulin lispro for 4 months followed by human regular insulin for another 4 months or human regular insulin for 4 months followed by insulin lispro for another 4 months . The main outcome measures were the number of hypoglycemic episodes during both treatments and HbA1c level . RESULTS A total of 135 patients were r and omized , with 68 receiving insulin lispro and 67 receiving human regular insulin for the first 4 months . The data for the first 4 months of treatment only were compared as two independent groups because of a period effect and a treatment-period interaction . Glycemic control was equally tight during treatment with human regular insulin ( HbA1c , 6.2 + /- 0.8 % ) and insulin lispro ( 6.0 + /- 0.9 % ) . A total of 1,156 hypoglycemic episodes occurred during treatment with human regular insulin compared with 775 hypoglycemic episodes that occurred during treatment with insulin lispro ( P = 0.04 ) . This difference was chiefly because of a reduced number of nocturnal episodes ( 181 vs. 52 , P = 0.001 ) in the insulin lispro group . CONCLUSIONS The use of a fast-acting insulin analog , insulin lispro , as part of a basal bolus regimen reduces nocturnal hypoglycemia in patients with type 1 diabetes who maintain tight glycemic control during intensive insulin therapy Summary Objective : To compare the plasma glucose ( PG ) response with a fixed mixture of 25 % insulin lispro and 75 % NPL ( Mix25 ) , prior to a meal and 3 h before exercise , to human insulin 30/70 ( 30/70 ) in patients with type 2 diabetes . Research design and methods : Thirty-seven patients were treated in a r and omized , open-label , 8-week , two-period crossover study . Mix25 was injected 5 min before breakfast and dinner throughout the study , as was 30/70 on inpatient test days and on outpatient dose titration days . Following the 4-week outpatient phase , patients were hospitalized , and exercised at a heart rate of 120 beats/min on a cycle ergometer two times for 30 min , separated by 30 min rest , starting 3 h after a 339 kcal breakfast . Results : The 2-h postpr and ial PG was significantly lower with Mix25 ( ( mean ± SEM ) 10.5 ± 0.4 mmol/lvs 11.6 ± 0.4 mmol/l ; p = 0.016 ) . Maximum decrease in PG from onset of exercise to end of exercise was significantly less with Mix25 ( -3.6 ± 0.29 mmol/l vs -4.7 ± 0.31 mmol/l ; p = 0.001 ) . The maximum decrease in PG over 6 h , after exercise onset , was significantly less with Mix25 ( -4.3 ± 0.4 mmol/l vs -5.9 ± 0.4 mmol/l ; p < 0.001 ) . The frequency of hypoglycemia ( blood glucose ( BG ) < 3 mmol/l or symptoms ) during the inpatient test was not different between treatments . During the outpatient phase , the frequency of patient-recorded hypoglycemia was significantly lower with Mix25 ( 0.7 ± 0.2 episodes/30d vs 1.2 ± 0.3 episodes/30 d ; p = 0.042 ) . Conclusions : Mix25 result ed in better postpr and ial PG control without an increase in exercise-induced hypoglycemia . The smaller decrease in PG during the postpr and ial phase after exercise may suggest a lower risk of exercise-induced hypoglycemia with Mix25 than with human insulin 30/70 , especially for patients in tight glycemic control OBJECTIVE IGF‐I levels in patients with type 1 diabetes without endogenous insulin production are low . Our aim was to examine whether the plasma insulin profile obtained by treatment with the insulin analogue lispro has a different effect on plasma concentrations of IGF‐I and IGFBP‐1 than that seen during treatment with conventional human insulin ( regular insulin ) OBJECTIVE The aim of this study was to compare the clinical efficacy and safety of insulin lispro with regular insulin in 5- to 10-yr-old prepubertal children on twice daily insulin . RESEARCH DESIGN AND METHODS Thirty-five children ( 16 M , 19 F ) completed an open-label r and omised crossover study , with each child receiving insulin lispro for 3 months and regular insulin for 3 months in addition to their intermediate-acting insulin . Families were instructed to give regular insulin 30 min before meals and insulin lispro immediately before meals . Glycaemic control was monitored by eight-point blood glucose profiles and six weekly hemoglobin A1cs ( HbA1cs ) and the frequency and severity of hypoglycaemia was documented . RESULTS The endpoint HbA1c after 3 months on insulin lispro ( 8.33 % , SD+/-0.89 ) was not significantly different to that on regular insulin ( 8.14 % , SD+/-0.77 ) . No significant differences were found in blood glucose levels before or after meals , 2-h postpr and ial glucose excursions or in blood glucose levels before bed between the treatments . However , blood glucose levels at 3 am were significantly lower on regular insulin than on insulin lispro ( mean difference -2.35 mmol/L ( 95%CI : -3.98 , -0.72 , p=0.01 ) . There was no significant difference in the frequency of hypoglycaemic episodes between the groups . CONCLUSIONS The main advantage of insulin lispro in children on twice daily insulin was found to be its greater convenience , this being achieved without a deterioration in glycaemic control . The higher 3 am blood glucose levels in those on insulin lispro could translate to reduced nocturnal hypoglycaemia in some individuals AIMS To compare the effects of the rapid-acting insulin analogue insulin aspart and soluble human insulin on hypoglycaemia and glycaemic control in patients with Type 1 diabetes when injected immediately before meals as part of intensive insulin therapy . METHODS In this multinational , double-blind , r and omised , crossover trial , 155 patients with Type 1 diabetes ( HbA(1c ) < 8.0 % ) were symmetrically r and omised to two 16-week treatment periods on either type of insulin , both injected 0 - 5 min before meals . NPH insulin was given as basal insulin once or twice daily as needed , and insulin dosages were regularly adjusted using pre-defined algorithms to maintain tight glycaemic control . Treatment periods were separated by a 4-week washout . RESULTS The rate of major nocturnal ( 24.00 - 06.00 h ) hypoglycaemic episodes was 72 % lower with insulin aspart than with human insulin ( 0.067 vs. 0.225 events/month ; P = 0.001 ) . Total rate of major hypoglycaemia did not differ significantly between treatments ( insulin aspart/human insulin relative risk 0.72 ; 95 % CI 0.47 - 1.09 , P = 0.12 ) . The rate of minor events was significantly reduced by 7 % with insulin aspart ( P = 0.048 ) . Reductions in rate of hypoglycaemia were achieved with maintained overall glycaemic control : Mean HbA(1c ) remained constant , slightly below 7.7 % on both treatments . CONCLUSIONS The use of insulin aspart in an intensive insulin regimen in patients with tightly controlled Type 1 diabetes led to clinical ly significant reductions in major nocturnal hypoglycaemia with no deterioration in glycaemic control . Major nocturnal hypoglycaemia appears to be a strong clinical indication for the use of rapid-acting insulin analogues during intensive insulin therapy OBJECTIVE To establish differences in blood glucose between different regimens of optimized basal insulin substitution in type 1 diabetic patients given lispro insulin at meals , i.e. , NPH injected four times a day versus glargine insulin once daily at dinner or at bedtime . RESEARCH DESIGN AND METHODS A total of 51 patients with type 1 diabetes on intensive therapy ( NPH four times/day and lispro insulin at each meal ) were r and omized to three different regimens of basal insulin substitution while continuing lispro insulin at meals : continuation of NPH four times/day ( n = 17 ) , once daily glargine at dinnertime ( n = 17 ) , and once daily glargine at bedtime ( n = 17 ) for 3 months . Blood glucose targets were fasting , prepr and ial , and bedtime concentrations at 6.4 - 7.2 mmol/l and 2 h after meals at 8.0 - 9.2 mmol/l . The primary end point was HbA(1c ) . RESULTS Mean daily blood glucose was lower with dinnertime glargine ( 7.5 + /- 0.2 mmol/l ) or bedtime glargine ( 7.4 + /- 0.2 mmol/l ) versus NPH ( 8.3 + /- 0.2 mmol/l ) ( P < 0.05 ) . A greater percentage of blood glucose values were at the target value with glargine at dinner and bedtime versus those with NPH ( P < 0.05 ) . HbA(1c ) at 3 months did not change with NPH but decreased with glargine at dinnertime ( from 6.8 + /- 0.2 to 6.4 + /- 0.1 % ) and glargine at bedtime ( from 7.0 + /- 0.2 to 6.6 + /- 0.1 % ) ( P < 0.04 vs. NPH ) . Total daily insulin doses were similar with the three treatments , but with glargine there was an increase in basal and a decrease in mealtime insulin requirements ( P < 0.05 ) . Frequency of mild hypoglycemia ( self-assisted episodes , blood glucose < or = 4.0 mmol/l ) was lower with glargine ( dinnertime 8.1 + /- 0.8 mmol/l , bedtime 7.7 + /- 0.9 mmol/l ) than with NPH ( 12.2 + /- 1.3 mmol/l ) ( episodes/patient-month , P < 0.04 ) . In-hospital profiles confirmed outpatient blood glucose data and indicated more steady plasma insulin concentrations at night and before meals with glargine versus NPH ( P < 0.05 ) . There were no differences between glargine given at dinnertime and at bedtime . CONCLUSIONS Regimens of basal insulin with either NPH four times/day or glargine once/day in type 1 diabetic patients both result in good glycemic control . However , the simpler glargine regimen decreases the HbA(1c ) level and frequency of hypoglycemia versus NPH . In contrast to NPH , which should be given at bedtime , insulin glargine can be administered at dinnertime without deteriorating blood glucose control Insulin aspart has been shown , in medium-term studies , to achieve reductions in HbA(1c ) without increasing the risk of major hypoglycaemia compared with pre-meal human insulin . The aim of the present 3-year study was to evaluate the long-term safety and efficacy of insulin aspart in people with type 1 diabetes . This was a 30-month extension of a multinational , multicentre , open-label , parallel-group study of 753 people with type 1 diabetes , originally r and omly allocated to treatment with insulin aspart or unmodified human insulin before meals , with NPH insulin as basal insulin . Main outcomes measures were hypoglycaemia ( major or minor ) , adverse events and HbA(1c ) . As insulin aspart became commercially available in some countries before the end of the trial , analyses of HbA(1c ) used 30-month data to maintain statistical power . The relative risk estimate of major hypoglycaemia was similar between treatment groups ( relative risk [ RR ] 1.00 [ 95 % CI 0.72 , 1.39 ] ) . The risk of having a minor hypoglycaemic episode was higher with insulin aspart than with human soluble insulin ( RR 1.24 [ 1.09 , 1.39 ] p=0.024 ) . Insulin aspart was significantly superior to human insulin with respect to overall glycaemic control , with a baseline-adjusted HbA(1c ) difference of -0.16 ( -0.32 , -0.01)% ( p=0.035 ) . Insulin aspart was well tolerated and effective during long-term treatment . The HbA(1c ) advantage was maintained with insulin aspart without any adverse impact on the rate of major hypoglycaemia OBJECTIVE To compare health-related quality of life ( HRQOL ) in patients with diabetes receiving insulin lispro with patients receiving regular human insulin ( Humulin R ) . RESEARCH DESIGN AND METHODS We performed two r and omized comparative studies over a 6-month period ( 3 months per treatment ) . Primary analyses used crossover baseline to 3-month changes in HRQOL scores . Ninety-three principal investigators in Canada , France , Germany , and the U.S. participated in these studies . One HRQOL crossover study included 468 patients with type I diabetes ; the other HRQOL crossover study included 474 patients with type II diabetes . In both studies , patients were taking insulin at least 2 months before enrollment . Primary outcomes included two generic HRQOL domains , energy/fatigue and health distress , and two diabetes-specific domains , treatment satisfaction and treatment flexibility . Thirty secondary outcomes included both generic and diabetes-specific measures . Secondary outcome domains were controlled for multiplicity in the analyses . RESULTS Primary analyses showed that treatment satisfaction scores ( P < 0.001 ) and treatment flexibility scores ( P = 0.001 ) were higher for insulin lispro in type I diabetic patients . No other significant treatment differences were detected using the data from these 6-month crossover studies . CONCLUSIONS Treatment satisfaction and treatment flexibility were significantly improved in patients with type I diabetes using insulin lispro . Other HRQOL findings were comparable for insulin lispro and regular human insulin . Insulin lispro appears to have a measurable impact on lifestyle benefits in patients with type I diabetes , as demonstrated by increased treatment satisfaction and treatment flexibility AIMS To compare the efficacy of insulin aspart , a rapid-acting insulin analogue , with that of unmodified human insulin on long-term blood glucose control in Type 1 diabetes mellitus . METHODS Prospect i ve , multi-centre , r and omized , open-labelled , parallel-group trial lasting 6 months in 88 centres in eight European countries and including 1,070 adult subjects with Type 1 diabetes . Study patients were r and omized 2:1 to insulin aspart or unmodified human insulin before main meals , with NPH-insulin as basal insulin . Main outcome measures were blood glucose control as assessed by HbA1c , eight-point self-monitored blood glucose profiles , insulin dose , quality of life , hypoglycaemia , and adverse events . RESULTS After 6 months , insulin aspart was superior to human insulin with respect to HbA1c with a baseline-adjusted difference in HbA1c of 0.12 ( 95 % confidence interval 0.03 - 0.22 ) % Hb , P < 0.02 . Eight-point blood glucose profiles showed lower post-pr and ial glucose levels ( mean baseline-adjusted -0.6 to -1.2 mmol/l , P < 0.01 ) after all main meals , but higher pre-pr and ial glucose levels before breakfast and dinner ( 0.7 - 0.8 mmol/l , P < 0.01 ) with insulin aspart . Satisfaction with treatment was significantly better in patients treated with insulin aspart ( WHO Diabetes Treatment Satisfaction Question naire ( DTSQ ) baseline-adjusted difference 2.3 ( 1.2 - 3.3 ) points , P < 0.001 ) . The relative risk of experiencing a major hypoglycaemic episode with insulin aspart compared to human insulin was 0.83 ( 0.59 - 1.18 , NS ) . Major night hypoglycaemic events requiring parenteral treatment were less with insulin aspart ( 1.3 vs. 3.4 % of patients , P < 0.05 ) , as were late post-pr and ial ( 4 - 6 h ) events ( 1.8 vs. 5.0 % of patients , P < 0.005 ) . CONCLUSIONS These results show small but useful advantage for the rapid-acting insulin analogue insulin aspart as a tool to improve long-term blood glucose control , hypoglycaemia , and quality of life , in people with Type 1 diabetes mellitus Aim : The aim of this study was to compare the efficacy and safety of a basal‐bolus insulin regimen comprising either insulin detemir or neural protamine hagedorn ( NPH ) insulin in combination with mealtime insulin aspart in patients with type 2 diabetes AIMS The aim of the trial was to compare the efficacy and safety of the new , long-acting basal insulin , insulin glargine ( LANTUS(R ) ) , with NPH human insulin , each administered in a combination regimen with oral antidiabetic drugs in patients with Type 2 diabetes . METHODS In a multicentre , open , r and omised study , 570 patients with Type 2 diabetes , aged 34 - 80 years , were treated for 52 weeks with insulin glargine or NPH insulin given once daily at bedtime . Previous oral antidiabetic therapy was continued throughout the study . RESULTS There was a clinical ly relevant decrease in glycosylated haemoglobin ( GHb ) values from baseline to endpoint with both drugs ( insulin glargine : - 0.46 % ; NPH insulin : - 0.38 % ; p = 0.415 ) ; also , this difference was statistically significant in the subgroup of overweight patients with BMI > 28 kg/m 2 ( insulin glargine : - 0.42 % , NPH insulin : - 0.11 % ; p = 0.0237 ) . Over the entire treatment period , NPH insulin-treated patients ( 41 % ) and insulin glargine-treated patients ( 35 % ) experienced a similar level of symptomatic hypoglycaemia . A statistically significant difference was observed in the number of patients treated with NPH insulin who reported at least one episode of nocturnal hypoglycaemia compared with those treated with insulin glargine in the overall population and in the overweight subgroup ( overall : 24 % vs. 12 % , p = 0.002 ; overweight : 22.2 % vs. 9.5 % , p = 0.0006 ) , using the Cochran-Mantel-Haenszel test . These differences were most pronounced in insulin-naïve and overweight ( BMI > 28 kg/m 2 ) sub-groups . The incidence of adverse events was similar for the two treatments . CONCLUSIONS This study demonstrated that insulin glargine is as effective as NPH insulin in achieving glycaemic control in patients with Type 2 diabetes , and is associated with fewer episodes of symptomatic hypoglycaemia , particularly nocturnal episodes OBJECTIVE Several studies have suggested that use of the short-acting insulin analog , insulin lispro , in multiple injection therapy may reduce the risk of hypoglycemia in comparison with regular insulin . This effect might be more pronounced in well-controlled patients , since intensive treatment of IDDM increases the rate of severe hypoglycemic events . This study evaluated the effects of insulin lispro on glycemic control and hypoglycemia rates in well-controlled IDDM patients . RESEARCH DESIGN AND METHODS This was an open , r and omized , 6-month crossover study of 199 IDDM patients . Glycemic control was evaluated by HbA1c , home blood glucose measurements , and rate and timing of hypoglycemic events . At the end of the study , patients completed an evaluation form regarding therapy-related quality of life . RESULTS HbA1c remained constant at ∼ 7.3 % throughout the study . Meal-related glucose excursions were significantly lower with insulin lispro compared with regular insulin ( mean −0.8 ± 1.7 vs. 1.1 ± 1.6 mmol/l , P < 0.001 ) , as was the within-day variability ( M value 27.7 ± 19.7 vs. 30.2 ± 23.1 , P = 0.007 ) . The incidence of severe hypoglycemic events ( 58 vs. 36 , P = 0.037 ) including coma ( 16 vs. 3 , P = 0.004 ) was significantly lower with insulin lispro than with regular insulin . Patients felt that insulin lispro increased flexibility and freedom of lifestyle . CONCLUSIONS In well-controlled IDDM patients , insulin lispro is associated with a lower risk of severe hypoglycemia and coma The objective of this 6-month , open-label , r and omized , two-period crossover study was to compare glycemic control when patients were treated with ( 1 ) 2 manufactured premixed insulin formulations containing insulin lispro and a novel insulin lispro-protamine formulation , neutral protamine lispro ( NPL ) , and ( 2 ) 2 manufactured premixed human insulin formulations , human insulin 50/50 and human insulin 30/70 . One hundred individuals , 37 with type 1 diabetes mellitus ( 12 females , 25 males ; mean age , 39.4 years ; mean body mass index [ BMI ] , 24.8 ; mean duration of diabetes , 12.9 years ) and 63 with type 2 diabetes mellitus ( 33 females , 30 males ; mean age , 59.0 years ; mean BMI , 28.4 ; mean duration of diabetes , 12.6 years ) , were treated with insulin lispro mixtures . Insulin lispro Mix50 ( 50 % insulin lispro/50 % NPL ) and human insulin 50/50 ( 50 % regular insulin/50 % neutral protamine Hagedorn [ NPH ] insulin ) were administered before breakfast ; insulin lispro Mix25 ( 25 % insulin lispro/75 % NPL ) and human insulin 30/70 ( 30 % regular insulin/70 % NPH ) were administered before dinner . Blood glucose ( BG ) , hypoglycemic episodes ( hypoglycemic signs or symptoms or BG < 3.0 mmol/L ) , insulin dose and timing of dose before meals , and hemoglobin A1c were measured . Mean doses of insulin lispro and human insulin mixtures were similar overall and for both diabetes subgroups . However , compared with human insulin mixtures , twice-daily administration of insulin lispro mixtures result ed in improved postpr and ial glycemic control , similar overall glycemic control , and less nocturnal hypoglycemia , as well as offering the convenience of dosing closer to meals OBJECTIVE This study compared the glucose-lowering effect of insulin lispro , given before or after meals , with regular human insulin given before meals in prepubertal children with diabetes . RESEARCH DESIGN AND METHODS A 3-way crossover , open-label study involving 61 prepubertal children ( ages 2.9 - 11.4 years ) with type 1 diabetes . The children were r and omly assigned to receive regular human insulin 30 to 45 minutes before meals , insulin lispro within 15 minutes before or immediately after meals , combined with basal insulin . Each treatment lasted 3 months . Hemoglobin A(1c ) levels and home glucose monitoring profiles were measured at the end of each treatment period . RESULTS Treatment with insulin lispro before breakfast result ed in lower 2-hour postpr and ial glucose values than regular human insulin ( 11.7 + /- 4.4 mmol/L vs 15.0 + /- 5.4 mmol/L ) . Similarly , insulin lispro given before dinner result ed in lower blood glucose values 2 hours postpr and ially ( 8.8 + /- 5.0 mmol/L vs 10.8 + /- 5.4 mmol/L ) than regular human insulin . When insulin lispro was administered after meals , the 2-hour glucose levels were between those seen with either insulin lispro or regular human insulin given before meals . The number and types of adverse events , the rates of hypoglycemia , and the HbA(1c ) levels did not differ among the 3 therapies . CONCLUSIONS In prepubertal children , insulin lispro given before meals is safe and significantly lowers postpr and ial glucose levels after breakfast and dinner compared with regular human insulin , and insulin lispro given after the meal provides similar benefits as regular human insulin before the meal OBJECTIVE To compare the effects of Humalog Mix25 ( Humalog Mix75/25 in the USA ) ( Mix25 ) and human insulin 30/70 ( 30/70 ) on the 24-hour inpatient plasma glucose ( PG ) profile in patients with type 2 diabetes mellitus ( T2DM ) . DESIGN A r and omised , open-label , 8-week crossover study . Study insulins were injected twice daily , 5 minutes before breakfast and dinner . SETTING Four-week outpatient ( dose-adjustment ) treatment phase , and 3-day inpatient ( test ) phase . PATIENTS Twenty-five insulin-treated patients with T2DM ( ages 40 - 66 years ) , mean ( + /- st and ard error of the mean ) ( SEM ) HbA1c 7.7 % + /- 0.23 % , and body mass index ( BMI ) 29.3 + /- 0.83 kg/m2 . OUTCOME MEASURES 24-hour PG profiles , PG excursions after meals , PG area under the curve ( AUC ) , and 30-day hypoglycaemia rate . RESULTS The 2-hour PG excursions following breakfast ( 5.5 + /- 0.34 v. 7.2 + /- 0.34 mmol/l , p = 0.002 ) and dinner ( 2.4 + /- 0.27 v. 3.4 + /- 0.27 mmol/l , p = 0.018 ) were smaller with Mix25 than with 30/70 . PG AUC between breakfast and lunch was smaller with Mix25 than with 30/70 ( 77.6 + /- 3.8 v. 89.5 + /- 4.3 mmol/h/ml , p = 0.001 ) . PG AUC between lunch and dinner , dinner and bedtime , and bedtime and breakfast did not differ between treatments . Pre-meal and nocturnal PG were comparable . The postpr and ial insulin requirement for lunch meals was supplied equally by the two insulin treatments . The thirty-day hypoglycaemia rate was low ( Mix25 0.049 + /- 0.018 v. 30/70 0.100 + /- 0.018 episodes/patient/30 days , p = 0.586 ) for both treatments . CONCLUSION In patients with T2DM , Mix25 improved the 24-hour PG profile with lower postpr and ial PG excursions than with human insulin 30/70 Context Insulin glargine is a long-acting insulin preparation that has recently become available . Its optimal role in the treatment of type 2 diabetes is being defined . Contribution In this r and omized , controlled trial of patients who were taking the sulfonylurea glimepiride , those receiving morning glargine had greater improvement in hemoglobin A1c levels and less frequent nocturnal hypoglycemia than did patients receiving either bedtime neutral protamine Hagedorn ( NPH ) or bedtime glargine . Implication s Morning glargine may be a better option for optimizing glycemic control in patients with type 2 diabetes who are also taking sulfonylureas than is either bedtime glargine or bedtime NPH . The Editors Type 2 diabetes is an increasing health problem in all western societies ( 1 ) ; the development of macrovascular complications in patients with type 2 diabetes is a major determinant of morbidity and mortality rates ( 1 , 2 ) . It has also been demonstrated that achieving good glycemic control substantially contributes to the prevention of microvascular complications in patients with type 2 diabetes ( 3 ) . In addition , epidemiologic association analysis of the data suggests that macrovascular complications can also be prevented ( 4 ) . However , current therapeutic approaches have not attained the defined targets of good metabolic control in most patients with type 2 diabetes ( 5 ) . During the natural course of type 2 diabetes , -cell function is progressively lost ( 6 ) , which limits the period when lifestyle modification , diet , and oral antidiabetic drug therapy are sufficient to meet targets of glycemic control . Thus , the therapeutic regimens for patients with type 2 diabetes have to be continually adapted to allow patients to consistently achieve and maintain good glycemic control . Patients with type 2 diabetes benefit from the addition of insulin to their therapeutic regimen ( 7 - 9 ) . However , some patients express reservations regarding the administration and side effects of insulin therapy ( 10 ) ; therefore , effective and convenient regimens must be developed . Combination therapy with oral antidiabetic drugs and bedtime neutral protamine Hagedorn ( NPH ) insulin has proven to be as effective as other , more complex insulin regimens and is associated with less weight gain ( 11 , 12 ) . Combination therapy with insulin and oral antidiabetic drugs is a regimen that can be managed at outpatient visits and that can be conveniently adapted to the patient 's needs by adjusting the insulin dose on the basis of self-measured fasting blood glucose levels (13)a therapeutic target predictive of overall glycemic control ( 13 ) . There are , however , limitations to achieving optimal results in daily practice with a combination of oral antidiabetic drugs and NPH insulin . Neutral protamine Hagedorn insulin exhibits a peak in its timeaction profile 4 to 6 hours after injection ; thus , bedtime NPH insulin is associated with a risk for nocturnal hypoglycemia ( 14 ) . This risk may limit the feasibility of titrating the NPH insulin dose to reach adequately low fasting blood glucose target values . Furthermore , the activity profile of NPH insulin is too short to provide optimal 24-hour insulin supplementation . Insulin glargine ( Lantus , Aventis , Bridgewater , New Jersey ) is a recently introduced human insulin analogue that exhibits a 24-hour action profile with no pronounced peak ( 15 - 17 ) . One study of patients with type 2 diabetes who were treated with basal and bolus insulin ( 18 ) and one study of patients with type 2 diabetes who were receiving oral antidiabetic drugs ( 14 ) have suggested that the addition of insulin glargine , injected at bedtime , decreases the risk for nocturnal hypoglycemia compared with NPH insulin . Thus , insulin glargine is an improved basal component for combination regimens with oral antidiabetic drugs in the treatment of type 2 diabetes . It remains unclear whether insulin glargine provides both better metabolic control and decreases the risk for hypoglycemia than compared with NPH insulin when used with sulfonylureas , such as glimepiride . The best timing for insulin glargine administration is also unclear . We investigated the efficacy and safety of a combination therapy of sulfonylurea ( 3 mg of glimepiride ) with either morning insulin glargine , bedtime insulin glargine , or bedtime NPH insulin in patients with type 2 diabetes whose diabetes was poorly controlled with oral antidiabetic drugs alone . Methods Study Design Our study was a 28-week , open-label , r and omized , controlled , multinational , multicenter , parallel-group clinical trial . Patients with type 2 diabetes who did not achieve good metabolic control while receiving oral antidiabetic drugs had their oral agents replaced by 3 mg of glimepiride for 4 weeks and were then r and omly assigned to receive additional treatment for 24 weeks with insulin glargine in the morning or at bedtime or NPH insulin at bedtime . Our primary objective was to investigate the effect of the different treatment regimens on glycemic control ( hemoglobin A1c [ HbA1c ] ) and on the percentage of patients who experienced hypoglycemia . Secondary objectives were to compare the three different interventions in terms of response rates , blood glucose levels , insulin dose , and body weight , as well as adjustment of insulin dose by the investigator . A total of 111 centers in 13 European countries participated in this study . The institutional ethics committee of each participating center approved the trial , and written informed consent was obtained from all participants before enrollment in the study . Patients We recruited patients from January 2000 to October 2000 ; treatment took place between February 2000 and June 2001 . Criteria for study inclusion were as follows : 1 ) type 2 diabetes , 2 ) age younger than 75 years , 3 ) body mass index less than 35 kg/m2 , and 4 ) previous oral therapy with any sulfonylurea as monotherapy or in combination with metformin or acarbose . Furthermore , the fasting blood glucose level had to be 6.7 mmol/L or greater [ 120 mg/dL ] , and the HbA1c level had to be between 7.5 % and 10.5 % . Main exclusion criteria were as follows : 1 ) pregnancy or breast-feeding , 2 ) pretreatment with insulin or any investigational drugs within the previous 3 months , or 3 ) presence of any clinical ly relevant somatic or mental diseases . Screening Phase The study consisted of a 4-week screening phase and a 24-week treatment phase . Before the start of the study , patients gave informed consent , medical histories were recorded , physical examinations were performed , and inclusion as well as exclusion criteria were satisfied . Blood sample s were taken for determination of HbA1c levels , complete hematologic and clinical chemistry analyses , and lipid status . Patients were trained to use the OptiPen Pro ( Aventis , Bridgewater , New Jersey ) insulin injection device and the One Touch II ( LifeScan , Milpitas , California ) blood glucose meter . Patients discontinued use of their previous oral antidiabetic drug treatment and received 3 mg of glimepiride in the morning . Patients provided a complete 8-point , 24-hour blood glucose profile on the 2 consecutive days of the screening phase . R and omization A sequence of screening patient numbers was assigned to each study center . All patients who had entered the screening phase received a patient number . With a r and omization schedule generated by the sponsor , eligible patients were linked sequentially to treatment codes allocated at r and om . This schedule was stratified by center on a 1:1:1 basis . Intervention During the treatment phase , patients visited the investigation sites 1 , 2 , 3 , 4 , 6 , 8 , 12 , 16 , 20 , and 24 weeks after r and omization . At these visits , patients had to provide daily self-measured fasting blood glucose values , and episodes of hypoglycemia were recorded in a st and ardized diary . The investigators checked these values , and the insulin dose was adjusted according to a predefined titration regimen . Furthermore , vital signs ( including blood pressure and body weight ) were recorded at every visit . At baseline , 12 weeks , and 24 weeks after r and omization , blood was drawn for measurement of complete hematologic and clinical chemistry analyses . At baseline and 8 , 12 , and 24 weeks , blood was drawn for measurement of HbA1c levels , and patients had to provide an 8-point daily blood glucose profile on 2 consecutive days . When combination therapy was initiated , insulin glargine or NPH insulin was injected subcutaneously once daily . The insulin glargine and NPH insulin formulation consisted of a cartridge containing 3 mL of either insulin preparation . Neutral protamine Hagedorn insulin had to be mixed thoroughly by rotating the injection device . The insulin dose for the first day of the treatment phase was calculated according to the formula of Holman and Turner ( 19 ) by subtracting 2.8 mmol/L ( 50 mg/dL ) from the actual fasting blood glucose value and dividing the result by 0.56 mmol/L ( 10 mg/dL ) . During the treatment phase , the insulin dose was titrated every visit by using a predefined regimen : If the fasting blood glucose level was greater than 5.6 , 6.7 , 7.8 , or 8.9 mmol/L ( > 100 , 120 , 140 , 160 mg/dL ) for at least 1 of 2 consecutive days before the visit with no hypoglycemia , the insulin dose was increased by 2 , 4 , 6 , or 8 units , respectively . Doses of glimepiride remained unchanged throughout the study . Analytical Methods Hemoglobin A1c levels were measured by high-performance liquid chromatography ( Bio-Rad Diamat , Munich , Germany ) in the central laboratory ( INTERLAB , Munich , Germany ) ; the reference range was 4.4 % to 6.1 % . Hematologic and clinical chemistry analyses were measured in local laboratories according to st and ard laboratory procedures . Statistical Analysis The primary efficacy assessment was the change in HbA1c level from baseline to end point and the frequency of patients who experienced hypoglycemic episodes during the study . Secondary efficacy measurements were HbA1c level ( 7.5 % ) , fasting blood OBJECTIVE Insulin lispro is an analog of human insulin with a faster onset and a shorter duration of action than regular human insulin . Efficacy and tolerability of insulin lispro in continuous subcutaneous insulin infusion ( CSII ) treatment were assessed in an open r and omized crossover trial comparing insulin lispro and regular human insulin , both applied with insulin pumps . RESEARCH DESIGN AND METHODS A total of 113 type 1 patients ( 60 male , 53 female , age [ mean + /- SD ] 37 + /- 12 years , duration of diabetes 19 + /- 9 years ) participated in this open , r and omized crossover study . Both insulins were applied for 4 months each with the appropriate intervals between the pr and ial insulin bolus and the meal ( human insulin : 30 min ; lispro : 0 min ) . Observation parameters were HbA1c , daily and postpr and ial blood glucose profiles , adverse events , rate of hypoglycemic and hyperglycemic events , number of catheter obstructions , and treatment satisfaction as assessed with an international vali date d question naire . RESULTS The patients were well controlled with a mean HBA1c of 7.24 + /- 1.0 % at baseline . HbA1c decreased in both treatment periods , but it was better during insulin lispro treatment ( insulin lispro : 6.8 + /- 0.9 % , regular human insulin : 6.9 + /- 1.0 % , Friedman 's rank-sum test : P < 0.02 ) . In addition , the 1-h and 2-h postpr and ial rises in blood glucose were significantly lower ( P < 0.001 for each meal ) with insulin lispro , result ing in smoother daily glucose profiles as compared with regular human insulin . No significant differences were reported for the rate of hypoglycemia ( mean + /- SD [ median ] : insulin lispro 12.4 + /- 13.9 [ 8 ] , regular human insulin 11.0 + /- 11.2 [ 8 ] ) , for the rate of catheter obstructions ( 42 events in each treatment arm ) , and for the number and type of adverse events . No severe case of ketoacidosis was seen during insulin lispro treatment , whereas one case was reported during therapy with regular human insulin . Treatment satisfaction was better when patients were treated with insulin lispro . CONCLUSIONS Insulin lispro is a suitable and very convenient pump insulin that may result in an improvement of long-term glucose control during CSII treatment . Its safety profile does not differ from that of regular human insulin OBJECTIVE Insulin detemir ( NN304 ) is a soluble basal insulin analog developed to cover basal insulin requirements . This trial aim ed to compare the blood glucose-lowering effect of insulin detemir with that of NPH insulin ( NPH ) and to evaluate the two treatments with regard to intrasubject variation of fasting blood glucose , incidence of hypoglycemia , dose requirements , and safety . RESEARCH DESIGN AND METHODS This multicenter open r and omized crossover trial in 59 type 1 diabetic subjects comprised a 2-week run-in period on a basal-bolus regimen with NPH insulin once daily , followed by two 6-week periods of optimized basal-bolus therapy with either once-daily insulin detemir or NPH insulin . RESULTS The area under the curve , in the time interval 23:00 - 8:00 , derived from 24-h serum glucose profiles , was not statistically significantly different for the two treatment periods ( insulin detemir : NPH ratio 89.2:83.5 , P = 0.59 ) . The intrasubject variation in fasting blood glucose during the last 4 days of treatment was lower for insulin detemir compared with NPH ( P < 0.001 ) . Mean dose requirements of insulin detemir were 2.35 times higher ( 95 % CI 2.22 - 2.48 ) compared with NPH . During the last week of treatment , fewer subjects experienced hypoglycemic episodes on insulin detemir ( 60 % ) compared with NPH treatment ( 77 % ) ( P = 0.049 ) . CONCLUSIONS Insulin detemir was as effective as NPH in maintaining glycemic control when administered at a higher molar dose . The results indicate that insulin detemir may provide more predictable fasting blood glucose with lower intrasubject variation and reduced risk of hypoglycemia compared with NPH The abnormal glucose tolerance of Type 2 diabetes is characterized by post-pr and ial hyperglycaemia . We aim ed to examine whether the restoration of a more physiological insulin profile using rapid-acting insulin analogues might , through effects on glucose toxicity , improve endogenous insulin secretion rate ( ISR ) and secondly improve markers of vascular risk . Eighteen people with insulin-treated Type 2 diabetes were recruited into a single centre , cross-over , open-labeled study . The order of pre-meal unmodified human insulin or insulin aspart was r and omized : treatment periods lasted at least 8 - 12 weeks after which ISR was assessed by stepped low-dose glucose infusion and fasting markers of vascular risk measured . Glucose control was good ( HbA(1c ) 6.94+/-0.12 (+/-S.E.)% versus 7.07+/-0.13 % , NS ) with insulin aspart and human insulin . Mean post-pr and ial self-monitored blood glucose concentration was also good particularly with insulin aspart ( 7.5+/-0.41 mmol/l versus 8.19+/-0.34 mmol/l ) but the difference did not reach statistical significance . Over 160 min ISR did not differ between insulin aspart and human insulin and there was also no change in various markers of vascular risk . In conclusion a meal-time+basal insulin regimen gave close to normal post-pr and ial blood glucose control with both the insulin aspart and human insulin regimens , such that no difference in ISR or markers of vascular risk could be demonstrated OBJECTIVE Humalog Mix25 is a manufactured premixed insulin formulation containing insulin lispro and a novel insulin lispro-protamine formulation ( NPL ) in a ratio of 25:75 % . The objective of this study was to compare Humalog Mix25 to human insulin 30/70 ( 30 % regular insulin/70 % NPH ) with respect to glycemic control . RESEARCH DESIGN AND METHODS Humalog Mix25 was compared with human insulin 30/70 in 89 individuals with type 2 diabetes during a 6-month r and omized open-label two-period crossover study . Each insulin was administered twice daily , before the morning and evening meals . Information regarding self-monitored blood glucose ( BG ) , hypoglycemic episodes ( hypoglycemic signs or symptoms or BG < or = 3.0 mmol/l ) , insulin dose , and HbA1c was collected . RESULTS Treatment with Humalog Mix25 result ed in better postpr and ial glycemic control after the morning and evening meals compared with treatment with human insulin 30/70 . Overall glycemic control and the incidence of hypoglycemia were comparable between the treatments . CONCLUSIONS In comparison to treatment with human insulin 30/70 , twice daily administration of Humalog Mix25 result ed in improved postpr and ial glycemic control , similar overall glycemic control , and the convenience of dosing immediately before meals Aim : The aim of this study was to compare the long‐term safety and efficacy of twice‐daily insulin detemir or NPH insulin as the basal component of basal‐bolus therapy in people with type 1 diabetes BACKGROUND Many patients with poorly controlled type 2 diabetes mellitus ( DM ) receive , as initial insulin treatment , the addition of a basal formulation to an existing regimen of oral antidiabetic drug ( OAD ) therapy . Used this way , the insulin analogue detemir has been associated with improved glycemic control of a magnitude similar to neutral protamine Hagedorn ( NPH ) , with lower rates of hypoglycemia and weight gain . Initial studies investigated detemir administered BID , but pharmacologic data suggest that detemir might be effective with QD administration . OBJECTIVES The aims of this study were to compare the effectiveness and tolerability of detemir versus NPH administered QD together with > or = 1 OAD in poorly controlled type 2 DM , and to compare different administration times of detemir . METHODS This 20-week , multicenter , r and omized , open-label , 3-arm , parallel-group trial was conducted at 91 centers across Europe and the United States . Men and women were eligible for participation if they were aged > or = 18 years , had a body mass index ( BMI ) < or = 40 kg/m(2 ) , had a diagnosis of type 2 DM of at least 12 months ' duration , and were insulin naive . Eligible patients also had a glycosylated hemoglobin ( HbA(1c ) ) concentration value not outside the range of 7.5 % to 11.0 % following at least 3 months ' treatment with > or = 10 AD . Patients were r and omly assigned to receive an evening SC injection of detemir , a prebreakfast injection of detemir , or an evening injection of NPH insulin ( 1:1:1 ) , administered at initial doses of 10 IU ( U ) . RESULTS A total of 504 patients were enrolled 5 men , 219 women ; mean [ SD ] age , 59 [ 11 ] years ; mean [ SD ] BMI , 30 [ 5 ] kg/m2 ; insulin detemir before breakfast , 168 ; insulin detemir evening , 170 ; NPH insulin evening , 166 ) . The intent-to-treat population comprised 498 patients . Morning and evening detemir were associated with reductions in HbA(1c ) similar to those with evening NPH ( raw mean decreases , -1.58 % , -1.48 % , and -1.74 % , respectively ) . Nine-point profile and fasting and predinner plasma glucose data found morning detemir to be associated with a different diurnal glycemic profile compared with the evening regimens . Compared with evening NPH , 24-hour and nocturnal hypoglycemia were reduced by 53 % ( P = 0.019 ) and 65 % ( P = 0.031 ) , respectively , with evening detemir . Incidences of hypoglycemia did not differ significantly between groups that received morning and evening detemir , but nocturnal hypoglycemia was reduced further , by 87 % , with morning detemir compared with evening NPH ( P < 0.001 ) . Weight gain was 1.2 , 0.7 , and 1.6 kg with morning detemir , evening detemir , and NPH , respectively ( P = 0.005 for evening detemir vs NPH ) . No between-treatment differences were seen in other tolerability end points . CONCLUSIONS The results of this study in patients whose type 2 DM was poorly controlled with > or = 1 OAD suggest that insulin detemir QD in the morning or evening can be used to improve glycemic control . Compared with NPH , insulin detemir may offer some tolerability advantages in this role Aims The long duration of action of soluble insulin given in the evening could contribute to the high prevalence of nocturnal hypoglycaemia seen in young children with Type 1 diabetes mellitus ( T1DM ) . We examined whether replacing soluble insulin with insulin lispro reduced this risk in children on a three times daily insulin regimen Transitioning safely to insulin therapy when oral antidiabetic agents fail to provide adequate glycemic control is a critical aspect of care for the patient with type 2 diabetes mellitus ( T2DM ) . We evaluated the clinical effectiveness of starting patients on a relatively simple regimen of once-daily injections of either biphasic insulin aspart 70/30 ( 10 min before dinner ) , NPH insulin ( at 10 p.m. ) , or biphasic human insulin 70/30 ( 30 min before dinner ) in combination with metformin . Enrolled patients had T2DM and inadequate glycemic control ( AlC>/=7.5 % ) on a previous regimen of metformin as monotherapy or in combination with a sulphonylurea . One hundred and forty ( 140 ) patients received metformin monotherapy for 4 weeks followed by 12 weeks of combination treatment with metformin and once-daily insulin injections . AlC levels decreased from baseline by 1.1 - 1.3 % for patients in each of the three treatment groups . Overall , FPG values decreased from baseline by 31 % ( biphasic insulin aspart ) , 37 % ( NPH insulin ) , and 28 % ( biphasic human insulin ) . Subjects whose final FPG level was < 126 mg/dl experienced the largest decreases in AlC values ( -2.3 % , -1.9 % , -1.8 % , respectively ) . All three treatment regimens were well tolerated . The results indicate that patients with T2DM can safely and effectively begin insulin therapy using once-daily injections of biphasic insulin aspart 70/30 , biphasic human insulin 70/30 , or NPH insulin in combination with metformin Aims To study whether post‐pr and ial insulin lispro ( PL ) could be used as a part of insulin therapy instead of premeal human regular insulin ( HR ) in prepubertal children with Type 1 diabetes mellitus ( Type 1 DM ) AIMS This study compared the effect of insulin detemir on glycaemic control ( HbA(1c ) , fasting plasma glucose and variability thereof ) with that of Neutral Protamine Hagedorn human isophane ( NPH ) insulin , both combined with insulin aspart , in children with Type 1 diabetes mellitus , and compared the safety of these treatments . METHODS In this 26-week , open-label , r and omized ( 2 : 1 ) , parallel-group study , 347 ( 140 prepubertal and 207 pubertal ) children with Type 1 diabetes , aged 6 - 17 years , received insulin detemir ( n = 232 ) or NPH insulin ( n = 115 ) once or twice daily , according to the pre study regimen , plus premeal insulin aspart . RESULTS The mean HbA(1c ) decreased by approximately 0.8 % with both treatments . After 26 weeks , the mean difference in HbA(1c ) was 0.1 % ( 95 % confidence interval -0.1 , 0.3 ) ( insulin detemir 8.0 % , NPH insulin 7.9 % ) . Within-subject variation in self-measured fasting plasma glucose was significantly lower with insulin detemir than with NPH insulin ( SD 3.3 vs. 4.3 , P < 0.001 ) , as was mean fasting plasma glucose ( 8.4 vs. 9.6 mmol/l , P = 0.022 ) . The risk of nocturnal hypoglycaemia ( 22.00 - 07.00 h ) was 26 % lower with insulin detemir ( P = 0.041 ) and the risk of 24-h hypoglycaemia was similar with the two treatments ( P = 0.351 ) . The mean body mass index ( BMI ) Z-score was lower with insulin detemir ( P < 0.001 ) . CONCLUSIONS Basal-bolus treatment with insulin detemir or NPH insulin and premeal insulin aspart in children and adolescents with Type 1 diabetes mellitus improved HbA(1c ) to a similar degree . The lower and more predictable fasting plasma glucose , lower risk of nocturnal hypoglycaemia and lower BMI observed with insulin detemir are clinical ly significant advantages compared with NPH insulin Insulin lispro is a human insulin analog that dissociates more rapidly than human regular insulin after subcutaneous injection , result ing in higher insulin levels at an earlier point in time and a shorter duration of action . The aim of the study was to evaluate if this pharmacokinetic difference would translate into better postpr and ial and overall control in 30 IDDM patients ( age , 35.1 ± 1.5 years ; male-female ratio , 17:13 ; BMI , 24.8 ± 0.5 kg/m2 ; HbA1c , 8.03 ± 0.13 % at baseline ) treated with continuous subcutaneous insulin infusion ( CSII ; Disetronic H-TRON V100 ) in a double-blind crossover clinical study . Patients were r and omized to insulin lispro or human regular insulin for 3 months before crossing over to the other insulin for another 3 months . All meal boluses were given immediately before breakfast , lunch , and supper . An eight-point blood glucose profile was measured once weekly , and HbA1c levels were measured monthly . At the end of the 3-month treatment period , HbA1c levels were significantly lower with insulin lispro , compared with human regular insulin : 7.66 ± 0.13 vs. 8.00 ± 0.16 % ( P = 0.0041 ) . While prepr and ial , bedtime , and 2:00 A.M. values for blood glucose were not significantly different , 1-h postpr and ial blood glucose was significantly improved after breakfast , lunch , and dinner with insulin lispro , compared with human regular insulin : 8.35 vs. 9.79 mmol/l ( P = 0.006 ) , 7.58 vs. 8.74 mmol/l ( P = 0.049 ) , and 7.85 vs. 9.01 mmol/l ( P = 0.03 ) . The incidence of hypoglycemia per 30 days ( blood glucose levels , < 3.0 mmol/l ) was 8.4 ± 1.3 before r and omization , decreasing to 6.0 ± 0.9 for insulin lispro and to 7.6 ± 1.3 for regular insulin during the last month of the study . Two patients in each group reported insulin precipitation . We conclude that insulin lispro improves glycemic control in CSII without increasing the risk of hypoglycemia |
678 | 27,552,521 | Sensitivity analysis suggested that inclusion of studies with high risk of bias did not affect the general direction of findings nor the size of the treatment effect for main outcomes . | BACKGROUND Kangaroo mother care ( KMC ) , originally defined as skin-to-skin contact between a mother and her newborn , frequent and exclusive or nearly exclusive breastfeeding , and early discharge from hospital , has been proposed as an alternative to conventional neonatal care for low birthweight ( LBW ) infants .
OBJECTIVES To determine whether evidence is available to support the use of KMC in LBW infants as an alternative to conventional neonatal care before or after the initial period of stabilization with conventional care , and to assess beneficial and adverse effects . | Kangaroo care ( KC ) has been the intervention for preterm infants in numerous published studies . However , most well design ed studies to date have used a one-group repeated measure design . This methodology is not as definitive as an experimental design . Because of the absence of a comparable control group , change between pretest and posttest may be due to any other environmental variables or normal variation of subjects ( Kirk , 1995 ) . This r and omized controlled trial ( RCT ) was done to test the hypotheses that KC infants would have higher mean tympanic temperatures , less weight loss , more optimal behavioral states , and lower acuity ( length of stay ) . Thirty-four eligible mother-infant dyads were r and omly assigned to the KC or the control group by computerized minimization on the day following birth . Stratification variables included infant gender , birth weight , delivery method , and parity . KC infants compared to control infants had higher mean tympanic temperature ( 37.3 degrees C vs. 37.0 degrees C ) , more quiet sleep ( 62 % vs. 22 % ) , and less crying ( 2 % vs. 6 % ) all at p=.000 . No significant difference was found for weight loss and acuity ( length of stay ) . These findings can be used for evidence -based nursing practice in Taiwan . With the knowledge attained from this RCT , nurses can educate and motivate mothers to keep their stable preterm infants warm by skin-to- skin contact inside their clothing , thereby encouraging self-regulatory feeding Purpose : To compare kangaroo mother care ( KMC ) and conventional cuddling care ( CCC ) in premature and smallfor-gestational-age infants . Design and Sample : Thirty mother-infant dyads in two Australian neonatal nurseries were r and omly assigned to the KMC group or the CCC group . Both groups of mothers cuddled their babies for a minimum of two hours a day , five days a week while in the study , with the KMC group having skin-to-skin contact while the CCC group had contact through normal clothing . Main Outcome Variable : The main outcome variables were infant weight gain , temperature maintenance during KMC and CCC , and length of hospital stay . Results : The results showed no difference between groups on the Parental Stress Scale ( NICU ) or the Parental Expectations Survey . Infants in both groups experienced equivalent maintenance of or rise in temperature while out of the incubators , equal weight gain , equal length of stay in the hospital , and equal duration of breastfeeding BACKGROUND Extremely preterm birth , even in the absence of significant neurological impairment , is associated with altered pain responses and impaired memory and behaviour . Preterm birth increases the risk of maternal depression and may impede the development of the mother-infant relationship , factors that in turn are also associated with impaired infant outcome . Mother-infant skin-to-skin contact has been recommended as a simple means of ameliorating these effects . METHODS We conducted a pragmatic , prospect i ve , controlled , intention-to-treat trial in two neonatal intensive care units . Infants born below 32 weeks gestation were recruited within the first week after birth and assigned to a control group receiving st and ard care , or an intervention group in which mothers were encouraged to provide a session of skin-to-skin contact once daily for 4 weeks . We assessed infant behaviour at time of discharge from hospital , responses to immunisation at 4 and 12 months of age , and memory , behaviour and development at 1 year corrected ( postmenstrual ) age . Indices of maternal depression , stress , anxiety , lactation performance and infant interaction were assessed at time of infant discharge , 4 months and 1 year . RESULTS No significant difference was identified in any infant or maternal measure at any time point . CONCLUSIONS Mother-infant skin-to-skin contact after extremely preterm birth results in neither benefit nor adverse consequences . Although there is no reason to dissuade mothers who wish to provide STS contact , we are unable to recommend re source allocation for the implementation of STS programmes for extremely preterm infants in a neonatal intensive care unit setting Background . Based on the general bonding hypothesis , it is suggested that kangaroo mother care ( KMC ) creates a climate in the family whereby parents become prone to sensitive caregiving . The general hypothesis is that skin-to-skin contact in the KMC group will build up a positive perception in the mothers and a state of readiness to detect and respond to infant 's cues . Method . The r and omized controlled trial was conducted on a set of 488 infants weighing < 2001 g , with 246 in the KMC group and 242 in the traditional care ( TC ) group . The design allows precise observation of the timing and duration of mother – infant contact , and takes into account the infant 's health status at birth and the socioeconomic status of the parents . Bonding Assessment . Two series of outcomes are assessed as manifestations of a mother 's attachment behavior . The first is the mother 's feelings and perceptions of her premature birth experience , including her sense of competence , feelings of worry and stress , and perception of social support . The second outcome is derived from observations of the mother and child 's responsivity to each other during breastfeeding at 41 weeks of gestational age . Interventions . KMC has three components . The first is the kangaroo position . Once the premature infant has adapted to extrauterine life and is able to breastfeed , he is positioned on the mother 's chest , in a upright position , with direct skin-to-skin contact . The second component is kangaroo nutrition . Although breastfeeding is the prime source of nutrition , infants also may receive preterm formula whenever necessary and vitamin supplements . The third component is the clinical control ; infants are monitored on a regular basis , daily until they are gaining at least 20 g per day . Afterward , weekly clinic visits are scheduled until term , which constitutes the ambulatory minimal neonatal care . In the TC group , infants are kept in incubators until they are able to self-regulate their temperature and are thriving ( ie , have an appropriate weight gain ) . Infants are discharged according to current hospital practice , usually not before their weight is ∼1700 g. Afterward , as with the KMC group , weekly clinic visits are scheduled until term . Results . We observed a change in the mothers ' perception of her child , attributable to the skin-to-skin contact in the kangaroo-carrying position . This effect is related to a subjective “ bonding effect ” that may be understood readily by the empowering nature of the KMC intervention . Moreover , in stressful situations when the infant has to remain in the hospital longer , mothers practicing KMC feel more competent than do mothers in the TC group . This is what we call a resilience effect . In these stressful situations we also found a negative effect on the feelings of received support of mothers practicing KMC . We interpret this as an isolation effect . To thwart this deleterious effect , we would suggest adding social support as an integral component of KMC . The observations of the mothers ' sensitive behavior did not show a definite bonding effect , but rather a resilience effect . This is attributable to the KMC intervention ; mothers practicing KMC were more responsive to an at-risk infant whose development has been threatened by a longer hospital stay . Otherwise , we observed that the mothers ( in both the KMC group and the TC group ) had behavioral patterns that were adapted to the child 's at-risk health status and to the precarious condition of some premature infants requiring intensive care . We conclude that the infant 's health status may be a more prominent factor in explaining a mother 's more sensitive behavior , which overshadows the kangaroo-carrying effect . Conclusion . These results suggest that KMC should be promoted actively and that mothers should be encouraged to use it as soon as possible during the intensive care period up to the 40 weeks of gestational age . Thus , KMC should be viewed as a means of humanizing the process of giving birth in a context of prematurity . This finding confirms the conclusions of the 1996 Trieste workshop suggesting that KMC should be promoted both in hospitals and after early discharge OBJECTIVE To evaluate the effects of maternal-infant skin-to-skin contact ( SSC ) vs st and ard contact ( SC ) on low-birth-weight infants ' physiological profile , maternal milk production , and duration of breast-feeding . DESIGN Prospect i ve , r and omized , interventional study with cohort followed up for 6 months after discharge from the hospital . SETTING Special care nursery with follow-up telephone calls after discharge from the hospital . PATIENTS Fifty infants , with birth weights less than 1500 g and whose mothers planned to breast-feed , r and omized to 2 groups : SSC ( experimental ) and SC ( control ) . INTERVENTION In the SSC group , infants were clothed in diaper and held upright between mothers ' breasts ; both mother and infant were covered with a blanket . In the SC group , infants were clothed , wrapped in blankets , and held cradled in mother 's arms . MAIN OUTCOME MEASURES Infant physiological data , ie , oxygen saturation , heart rate , respiratory rate , and axillary temperature ; maternal milk production ; and duration of breast-feeding . RESULTS Oxygen saturation was higher during SSC than during SC ( P < .001 ) ; 11 % of the oxygen saturation recordings during SSC vs 24 % during SC indicated the values less than 90 % ( P < .001 ) . A more stable milk production was noted in the SSC group . No differences were noted in infant temperature , heart rate , or respiratory rate . Ninety percent of mothers in the SSC group vs 61 % in the SC group continued breast-feeding for the duration of the infants ' hospitalization ( P < .05 ) , and 50 % in the SSC group vs 11 % in the SC continued breast-feeding through 1 month after discharge ( P < .01 ) . CONCLUSIONS During SSC with their mothers , low-birth-weight infants maintain a higher oxygen saturation and are less likely to have desaturation to less than 90 % oxygen than are infants exposed to SC . Mothers in the SSC group are more likely to continue breast-feeding until 1 month after discharge OBJECTIVE To test the effects of kangaroo care ( KC ) on breastfeeding outcomes in preterm infants compared with two control groups and to explore whether maternal-infant characteristics and the mother 's choice to use KC were related to breastfeeding measures . DESIGN Secondary analysis of a multisite , stratified , r and omized three-arm trial . The treatment groups used KC , auditory-tactile-visual-vestibular ( ATVV ) intervention , or received preterm infant care information . SETTING Neonatal intensive care units from 4 hospitals in the United States from 2006 to 2011 . PARTICIPANTS Racially diverse mothers ( N = 231 ) and their preterm infants born weighing less than 1,750 g. METHODS Mothers and their infants were enrolled once the infants were no longer critically ill , weighed at least 1,000 g , and could be safely held outside the incubator by parents . Participants were instructed by study nurses ; those allocated to the KC or ATVV groups were asked to engage in these interactions with their infants for a minimum of 3 times a week in the hospital and at home until their infants reached age 2 months adjusted for prematurity . RESULTS Feeding at the breast during hospitalization , the duration of postdischarge breastfeeding , and breastfeeding exclusivity after hospital discharge did not differ statistically among the treatment groups . Regardless of group assignment , married , older , and more educated women were more likely to feed at the breast during hospitalization . Mothers who practice d KC , regardless of r and omly allocated group , were more likely to provide their milk than those who did not practice KC . Breastfeeding duration was greatest among more educated women . CONCLUSION As implemented in this study , assignment to the KC group did not appear to influence the measured breastfeeding outcomes OBJECTIVE To investigate the feasibility and safety of skin-to-skin care after birth for moderately preterm infants . DESIGN Prospect i ve cohort study . SETTING The study was conducted at the maternity wards and NICUs of three study sites in Norway . PARTICIPANTS Ninety preterm infants born vaginally with gestational ages of 32 weeks/0 days to 34 weeks/6 days . METHODS Comparison of groups of preterm infants who received skin-to-skin care or conventional treatment in incubators after birth . RESULTS Median gestational age and birth weight were similar in the two groups : 33 weeks/5 days versus 34 weeks/3 days ( p = .464 ) and 2,100 versus 2,010 g ( p = .519 ) . There were no differences in the first body temperature ( p = .841 ) and blood glucose level ( p = .539 ) between the groups . CONCLUSION Early skin-to-skin contact in the delivery room for moderately preterm infants may be feasible and safe Purpose : To determine the effects of kangaroo care ( KC ) ( skin-to-skin contact ) on breastfeeding status in mother – preterm infant dyads from postpartum through 18 months . Design : R and omized , controlled trial . The control group received st and ard nursery care ; in the intervention group , unlimited KC was encouraged . Sample : A sub sample of 66 mothers and their preterm infants ( 32–36 completed weeks gestation , 1,300–3,000 g , 5 minute Apgar ≥6 ) who intended to breastfeed . Main Outcome Variables : Breastfeeding status at hospital discharge and at 1.5 , 3 , 6 , 12 , and 18 months as measured by the Index of Breastfeeding Status . Results : KC dyads , compared to control dyads , breastfed significantly longer ( 5.08 months vs 2.05 months ) , p = .003 . KC dyads also breastfed more exclusively at each measurement , p = .047 . More KC dyads than control dyads breastfed at full exclusivity ( 100 percent breast milk , index of breastfeeding status levels 1 or 2 ) at discharge and at 1.5 , 3 , and 6 months . Mean KC contact per day was 4.47 hours BACKGROUND . Sleep is important to brain organization , but few strategies to promote sleep among premature infants have been tested . Behaviorally based measures of sleep have shown increased quiet sleep ( QS ) and decreased active sleep ( AS ) during skin-to-skin contact ( SSC ) with the mother , but these results have not been confirmed with objective electroencephalographic/polysomnographic measures of sleep organization . Important differences exist between behavioral and electroencephalographic/polysomnographic definitions of sleep state . METHODS . Data for the first 28 relatively healthy , preterm subjects of an ongoing r and omized trial of one 2- to 3-hour session of SSC or incubator care between feedings are reported here . Infants were positioned prone , inclined , and nested in an incubator during the 2- to 3-hour pretest period , were fed , and then went into the test period of SSC or incubator care . Infants were left largely undisturbed throughout testing . A mixed-model regression analysis compared the test-pretest differences in outcome measures within and between groups . RESULTS . Results showed that arousals were significantly lower in the SSC group , compared with the control group , for the entire study period and for test-pretest matched segments of QS and AS . Rapid eye movement was significantly lower for the SSC group for the study period and AS segments . Indeterminate sleep was significantly lower for the SSC group when confounding environmental variables were included in the regression analysis . When 4 subjects who experienced excessive ambient light levels during SSC were removed from analysis , QS increased during SSC . CONCLUSIONS . The patterns demonstrated by the SSC group are analogous to more-mature sleep organization . SSC may be used as an intervention to improve sleep organization in this population of preterm infants OBJECTIVE To evaluate the results of the kangaroo mother method in Brazil . METHODS A prospect i ve cohort study comparing 16 units that have or do not have the second phase of the kangaroo mother method : eight were national centers of excellence for the kangaroo mother method ( study group ) and eight were part of the Brazilian Neonatal Research Network ( control group ) . A total of 985 newborn infants with birth weights of 500 to 1,749 g were enrolled . Multivariate analyses employed multiple linear regression and Poisson regression with robust adjustment . RESULTS The adjusted analysis ( controlled for birth weight , gestational age , Score for Neonatal Acute Physiology Perinatal Extension II , Neonatal Therapeutic Intervention Scoring System , and maternal age and educational level ) demonstrated that mean length of hospital stay ( p = 0.14 ) and intercurrent clinical conditions in the intermediate or kangaroo unit were equal for both groups . Weight ( p = 0.012 ) , length ( p = 0.039 ) and head circumference ( p = 0.006 ) at 36 weeks ' corrected gestational age were all lower at the kangaroo units . The kangaroo units exhibited superior performance in relation to exclusive breastfeeding at discharge ( 69.2 vs. 23.8 % , p = 0.022 ) . CONCLUSIONS The evidence suggests that the humanization strategy adopted by the Brazilian Ministry of Health is a safe alternative to conventional treatment and a good strategy for promoting breastfeeding A r and omized controlled trial was conducted over a 1-year period ( November 2001-November 2002 ) in Addis Ababa to study the effectiveness of early Kangaroo mother care before stabilization of low birthweight infants as compared with the conventional method of care . There were 259 babies weighing less than 2000 g during the study period and a total of 123 ( 47.5 per cent ) low birthweight infants were included in to the study . Sixty-two infants were enrolled as Kangaroo Mother Care ( KMC ) and the remaining 61 were Conventional Method of Care ( CMC ) cases . The demographic and socioeconomic characteristics for both groups were comparable . The mean age at the time of enrollment was 10 and 9.8 h for KMC and CMC , respectively ( p>0.05 with 95 per cent confidence interval ) . The mean birthweight was 1514.8 g ( range 1000 - 1900 g ) for KMC and 1471.8 g ( range 930 - 1900 g ) for CMC ( p>0.05 with 95 per cent CI ) and the mean gestational age was 32.42 and 31.59 weeks for KMC and CMC cases , respectively . Fifty-eight per cent of KMC and 52 per cent of CMC cases were on i.v . fluid . Twenty-one of 62 ( 34 per cent ) of KMC and 23/61 ( 37 per cent ) of CMC babies were on oxygen through nasopharyngeal catheter . The mean age at exit from the study was 4.6 days for KMC and 5.4 days for CMC . Ninety-one per cent and 88 per cent of babies in KMC and CMC were discharged from the study in the first 7 days of life , respectively . The study showed that 14/62 ( 22.5 per cent ) of KMC vs. 24/63 ( 38 per cent ) CMC babies died during the study ( p<0.05 and CI of 95 per cent . ) The majority of deaths occurred during the first 12 h of life . Survival for the preterm low birthweight infants was remarkably better for the early kangaroo mother care group than the babies in the conventional method of care in the first 12 h and there after . More than 95 per cent of mothers reported that they were happy to care for their low birthweight babies using the early Kangaroo mother method . It was recommended to study the feasibility and effectiveness of Kangaroo mother care at the community level OBJECTIVE To evaluate the effect of kangaroo-mother care ( KMC ) in preterm ( PT ) neurobehavior between 36 and 41 weeks post-conceptual age ( PCA ) . METHOD A prospect i ve cohort of 61 preterm infants with gestational age ( GA ) of 28 - 32 w evaluated by the Neonatal Intensive Care Unit Network Neurobehavioral Scale ( NNNS ) , with 36 - 41 w PCA . Infants with clinical instability were excluded . They were analyzed in 2 groups : - Kangaroo ( KAN ) : KMC for 7 or more days ; Conventional ( CON ) : did not receive KMC . Scores of the 13 NNNS variables were compared between groups and the effect of KMC in the scores of the variables of NNNS were evaluated by multiple linear regression , controlling for confounders . RESULTS The KAN groups ( n=24 ) and CON ( n=37 ) were similar regarding main demographic and clinical maternal and neonatal characteristics . Mean GA was 30.3 w ; and birth weight was 1170 g for both groups . PT of KAN group were admitted in KMC with PCA of 35.8 w ( 38.5 days of life ) and remained with this care for 14.3 days . The NNNS was applied 13 days after the start of KMC . PT su bmi tted to KMC showed higher quality of movements ( KAN : 4.98 ± 0.53 vs CON : 4.53 ± 0.47 ; p=0.001 ) and lower scores on Signs of stress and abstinence ( KAN : 0.03 ± 0.03 vs CON : 0.05 ± 0.03 ; p=0.001 ) . Controlling for confounders , the KMC was associated with higher scores on the variables Attention , Quality of movements , and lower scores on Asymmetry and Signs of stress and abstinence . CONCLUSION PT su bmi tted to the KMC , compared to those non-su bmi tted , have better neurobehavior performance between 36 and 41 weeks of post-conceptual age Background Decolonization with topical antibiotics is necessary to control outbreaks of multidrug-resistant bacterial infection in the Neonatal Intensive Care Unit ( NICU ) , but can trigger bacterial resistance . The objective of this study was to determine whether skin-to-skin contact of newborns colonized with Methicillin-Oxacillin Resistant Staphylococcus aureus or Methicillin-Oxacillin-Resistant Coagulase-Negative Staphylococcus aureus ( MRSA/MRSE ) with their mothers could be an effective alternative to promote bacterial decolonization of newborns ’ nostrils . Methods We performed a r and omized clinical trial with 102 newborns admitted to the NICU in three hospitals in São Luís , Brazil . Inclusion criteria were birth weight of 1300 to 1800 g , more than 4 days of hospitalization , newborns with positive nostril cultures for MRSA and /or multidrug-resistant coagulase-negative Staphylococcus and mothers not colonized by these bacteria . We used a r and om number algorithm for r and omization . Allocation was performed using sealed opaque envelopes . Skin-to-skin contact was given twice a day for 60 minutes for seven consecutive days . The control group received routine care without skin-to-skin contact . There was no masking of newborn ’s mothers or research ers but the individuals who carried out bacterial cultures and assessed results were kept blind to group allocation . The primary outcome was colonization status of newborns ’ nostrils after 7 days of intervention . The directional hypothesis was that more newborns who receive skin-to-skin holding 2 hours/day for 7 days than newborns who receive normal care will be decolonized . Results Decolonization of MRSA/MRSE was greater in the intervention group ( Risk Ratio = 2.27 ; 95 % CI 1.27 - 4.07 , p-value = 0.003 ) . Number Needed to Treat ( NNT ) was 4.0 ( 95 % CI 2.2 – 9.4 ) . After adjustment for the possible confounding effects of small for gestational age birth , antibiotic use , need for resuscitation , sex and cesarean delivery , skin-to-skin contact remained strongly associated with decolonization of newborns ’ nostrils from MRSA/MRSE bacteria ( p = 0.007 ) . There was no need to interrupt the trial for safety reasons . ConclusionS kin-to-skin contact might be an effective and safe method for promoting decolonization of newborns ’ nostrils colonized by MRSA/MRSE.Trial Registration The study was registered with Clinical Trials.gov ( NCT01498133 , November 21 , 2011 ) BACKGROUND In rural India , most births take place in the home , where high-risk care practice s are common . We developed an intervention of behaviour change management , with a focus on prevention of hypothermia , aim ed at modifying practice s and reducing neonatal mortality . METHODS We did a cluster-r and omised controlled efficacy trial in Shivgarh , a rural area in Uttar Pradesh . 39 village administrative units ( population 104,123 ) were allocated to one of three groups : a control group , which received the usual services of governmental and non-governmental organisations in the area ; an intervention group , which received a preventive package of interventions for essential newborn care ( birth preparedness , clean delivery and cord care , thermal care [ including skin-to-skin care ] , breastfeeding promotion , and danger sign recognition ) ; or another intervention group , which received the package of essential newborn care plus use of a liquid crystal hypothermia indicator ( ThermoSpot ) . In the intervention clusters , community health workers delivered the packages via collective meetings and two antenatal and two postnatal household visitations . Outcome measures included changes in newborn-care practice s and neonatal mortality rate compared with the control group . Analysis was by intention to treat . This study is registered as International St and ard R and omised Control Trial , number NCT00198653 . FINDINGS Improvements in birth preparedness , hygienic delivery , thermal care ( including skin-to-skin care ) , umbilical cord care , skin care , and breastfeeding were seen in intervention arms . There was little change in care-seeking . Compared with controls , neonatal mortality rate was reduced by 54 % in the essential newborn-care intervention ( rate ratio 0.46 [ 95 % CI 0.35 - 0.60 ] , p<0.0001 ) and by 52 % in the essential newborn care plus ThermoSpot arm ( 0.48 [ 95 % CI 0.35 - 0.66 ] , p<0.0001 ) . INTERPRETATION A socioculturally context ualised , community-based intervention , targeted at high-risk newborn-care practice s , can lead to substantial behavioural modification and reduction in neonatal mortality . This approach can be applied to behaviour change along the continuum of care , harmonise vertical interventions , and build community capacity for sustained development . FUNDING USAID and Save the Children-US through a grant from the Bill & Melinda Gates Foundation The purpose of this r and omized controlled trial was to investigate the influences of music during kangaroo care ( KC ) on maternal anxiety and preterm infants ' responses . There are no experimental studies that explore the influences of combination of music and KC on psychophysiological responses in mother-infant dyads . Purposive sampling was used to recruit 30 hospitalized preterm infants body weight 1500 gm and over , gestational age 37 weeks and lower from two NICUs . Mother-infant dyads were r and omly assigned to the treatment and the control group using permuted block r and omization stratified on gender . There were 15 mother-infant dyads in each group . Subjects in the treatment dyads listened to their choice of a lullaby music during KC for 60 min/section/day for three consecutive days . Control dyads received routine incubator care . Using a repeated measures design with a pretest and three posttests , the responses of treatment dyads including maternal anxiety and infants ' physiologic responses ( heart rate , respiratory rate , and O2 saturation ) as well as behavioural state were measured . The results revealed that there were no significant differences between the two groups on infants ' physiologic responses and the values were all in the normal range . However , infants in the treatment group had more occurrence of quiet sleep states and less crying ( p<0.05 - 0.01 ) . Music during KC also result ed in significantly lower maternal anxiety in the treatment group ( p<0.01 ) . Maternal state anxiety improved daily , indicating a cumulative dose effect . The findings provide evidence for the use of music during KC as an empirically-based intervention for bahavioural state stability and maternal anxiety in mother-infant dyads OBJECTIVE . We adapted kangaroo mother care for immediate postnatal community-based application in rural Bangladesh , where the incidence of home delivery , low birth weight , and neonatal and infant mortality is high and neonatal intensive care is unavailable . This trial tested whether community-based kangaroo mother care reduces the overall neonatal mortality rate by 27.5 % , infant mortality rate by 25 % , and low birth weight neonatal mortality rate by 30 % . METHODS . Half of 42 unions in 2 Bangladesh divisions with the highest infant mortality rates were r and omly assigned to community-based kangaroo mother care , and half were not . One village per union was r and omly selected proportionate to union population size . A baseline survey of 39888 eligible consenting women collected sociodemographic information . Community-based workers were taught to teach community-based kangaroo mother care to all expectant and postpartum women in the intervention villages . A total of 4165 live births were identified and enrolled . Newborns were followed for 30 to 45 days and infants were followed quarterly through their first birthday to record infant care , feeding , growth , health , and vital status . RESULTS . Forty percent overall and ∼65 % of newborns who died were not weighed at birth , and missing birth weight was differential by study group . There was no difference in overall neonatal mortality rate or infant mortality rate . Except for care seeking , community-based kangaroo mother care behaviors were more common in the intervention than control group , but implementation was weak compared with the pilot study . CONCLUSIONS . The extensive missing birth weight and its potential bias render the evidence insufficient to justify implementing community-based kangaroo mother care . Additional experimental research ensuring baseline comparability of mortality , adequate kangaroo mother care implementation , and birth weight assessment is necessary to clarify the effect of community-based kangaroo mother care on survival Aim : Conventional care of prematurely born infants involves extended maternal‐infant separation and incubator care . Recent research has shown that separation causes adverse effects . Maternal‐infant skin‐to‐skin contact ( SSC ) provides an alternative habitat to the incubator , with proven benefits for stable prematures ; this has not been established for unstable or newborn low‐birthweight infants . SSC from birth was therefore compared to incubator care for infants between 1200 and 2199 g at birth . Methods : This was a prospect i ve , unblinded , r and omized controlled clinical trial ; potential subjects were identified before delivery and r and omized by computerized minimization technique at 5 min if eligible . St and ardized care and observations were maintained for 6 h. Stability was measured in terms of a set of pre‐determined physiological parameters , and a composite cardio‐respiratory stabilization score ( SCRIP ) . Results : 34 infants were analysed in comparable groups : 3/18 SSC compared to 12/13 incubator babies exceeded the pre‐determined parameters ( p < 0.001 ) . Stabilization scores were 77.11 for SSC versus 74.23 for incubator ( maximum 78 ) , mean difference 2.88 ( 95 % CI : 0.3–5.46 , p = 0.031 ) . All 18 SSC subjects were stable in the sixth hour , compared to 6/13 incubator infants . Eight out of 13 incubator subjects experienced hypothermia Although studies have examined the effects of interventions focused on preterm infants , few studies have examined the effects on maternal distress ( anxiety , depressive symptoms , post-traumatic stress symptoms , parenting stress ) or parenting . This study examined the effects of the auditory-tactile-visual-vestibular ( ATVV ) intervention and kangaroo care ( KC ) on maternal distress and the mother-infant relationship compared to an attention control group . 240 mothers from four hospitals were r and omly assigned to the three groups . Maternal characteristics in the three groups were similar : 64.1 % of ATVV mothers , 64.2 % of KC mothers , and 76.5 % of control mothers were African American ; maternal age averaged 26.3 years for ATVV mothers , 28.1 for KC mothers , and 26.6 for control mothers ; and years of education averaged 13.6 for ATVV and KC mothers , and 13.1 for control mothers . Mothers only differed on parity : 68.4 % of ATVV and 54.7 % of KC mothers were first-time mothers as compared to 43.6 % of control mothers . Their infants had a similar mean gestational ages ( 27.0 weeks for ATVV , 27.2 for KC , and 27.4 for control ) and mean birthweights ( 993 g for ATVV , 1022 for KC , and 1023 for control ) . Mothers completed question naires during hospitalization , and at 2 , 6 and 12 months corrected age on demographic characteristics , depressive symptoms , state anxiety , post-traumatic stress symptoms , parenting stress , worry about child health , and child vulnerability ( only at 12 months ) . At 2 and 6 months , 45-min videotapes of mother-infant interactions were made , and the HOME Inventory was scored . Behaviors coded from the videotapes and a HOME subscale were combined into five interactive dimensions : maternal positive involvement and developmental stimulation and child social behaviors , developmental maturity , and irritability . Intervention effects were examined using general linear mixed models controlling for parity and recruitment site . The groups did not differ on any maternal distress variable . Kangaroo care mothers showed a more rapid decline in worry than the other mothers . The only interactive dimensions that differed between the groups were child social behaviors and developmental maturity , which were both higher for kangaroo care infants . Change over time in several individual infant behaviors was affected by the interventions . When mothers reported on the interventions they performed , regardless of group assignment , massage ( any form including ATVV ) was associated with a more rapid decline in depressive symptoms and higher HOME scores . Performing either intervention was associated with lower parenting stress . These findings suggest that as short-term interventions , KC and ATVV have important effects on mothers and their preterm infants , especially in the first half of the first year AIM To evaluate the effects of almost continuous skin-to-skin contact ( SSC ) on salivary cortisol , parental stress , parental depression , and breastfeeding . STUDY DESIGN This is a r and omised study engaging families of late preterm infants ( 32 - 35 weeks gestation ) . Salivary cortisol reactivity was measured in infants during a nappy change at one month corrected age , and in infants and mothers during still-face at four month corrected age . Both parents completed the Swedish Parenthood Stress Question naire ( SPSQ ) at one month and the Edinburgh Postnatal Depression Scale ( EPDS ) at one and four months . Ainsworth 's sensitivity scale was used to control for parental sensitivity . SUBJECTS Thirty-seven families from two different neonatal care units in Sweden , r and omised to either almost continuous SSC or st and ard care ( SC ) . RESULTS Infants r and omised to SSC had a lower salivary cortisol reactivity at one month ( p=0.01 ) . There was a correlation between the mothers ' and the preterm infants ' salivary cortisol levels at four months in the SSC group ( ρ=0.65 , p=0.005 ) , but not in the SC group ( ρ=0.14 , p=0.63 ) . Fathers in SSC scored lower on the SPSQ sub-scale spouse relationship problems compared to fathers in SC ( p<0.05 ) . CONCLUSIONS Almost continuous SSC decreases infants ' cortisol reactivity in response to h and ling , improves the concordance between mothers ' and infants ' salivary cortisol levels , and decreases fathers ' experiences of spouse relationship problems A r and omized controlled trial was carried out for 1 y in three tertiary and teaching hospitals , in Addis Ababa ( Ethiopia ) , Yogyakarta ( Indonesia ) and Merida ( Mexico ) , to study the effectiveness , feasibility , acceptability and cost of kangaroo mother care ( KMC ) when compared to conventional methods of care ( CMC ) . About 29 % of 649 low birthweight infants ( LBWI ; 1000‐1999 g ) died before eligibility . Of the survivors , 38 % were excluded for various reasons , 149 were r and omly assigned to KMC ( almost exclusive skin‐to‐skin care after stabilization ) , and 136 to CMC ( warm room or incubator care ) . There were three deaths in each group and no difference in the incidence of severe disease . Hypothermia was significantly less common in KMC infants in Merida ( 13.5 vs 31.5 episodes/100 infants/d ) and overall ( 10.8 vs 14.6 ) . Exclusive breastfeeding at discharge was more common in KMC infants in Merida ( 80 % vs 16 % ) and overall ( 88 % vs 70 % ) . KMC infants had a higher mean daily weight gain ( 21.3 g vs 17.7 g ) and were discharged earlier ( 13.4 vs 16.3 d after enrolment ) . KMC was considered feasible and presented advantages over CMC in terms of maintenance of equipment . Mothers expressed a clear preference for KMC and health workers found it safe and convenient . KMC was cheaper than CMC in terms of salaries ( US$ 11 788 vs US$ 29 888 ) and other running costs ( US$ 7501 vs US$ 9876 ) . This study confirms that hospital KMC for stabilized LBWI 1000‐1999 g is at least as effective and safe as CMC , and shows that it is feasible in different setting s , acceptable to mothers of different cultures , and less expensive . Where exclusive breastfeeding is uncommon among LBWI , KMC may bring about an increase in its prevalence and duration , with consequent benefits for health and growth . For hospitals in low‐income countries KMC may represent an appropriate use of scarce re sources OBJECTIVE To examine the costs of implementing kangaroo mother care ( KMC ) in a referral hospital in Nicaragua , including training , implementation , and ongoing operating costs , and to estimate the economic impact on the Nicaraguan health system if KMC were implemented in other maternity hospitals in the country . METHODS After receiving clinical training in KMC , the implementation team trained their colleagues , wrote guidelines for clinicians and education material for parents , and ensured adherence to the new guidelines . The intervention began September 2010 The study compared data on infant weight , medication use , formula consumption , incubator use , and hospitalization for six months before and after implementation . Cost data were collected from accounting records of the implementers and health ministry formularies . RESULTS A total of 46 r and omly selected infants before implementation were compared to 52 after implementation . Controlling for confounders , neonates after implementation had lower lengths of hospitalization by 4.64 days ( P = 0.017 ) and 71 % were exclusively breastfed ( P < 0.001 ) . The intervention cost US$ 23 113 but the money saved with shorter hospitalization , elimination of incubator use , and lower antibiotic and infant formula costs made up for this expense in 1 - 2 months . Extending KMC to 12 other facilities in Nicaragua is projected to save approximately US$ 166 000 ( based on the referral hospital incubator use estimate ) or US$ 233 000 after one year ( based on the more conservative incubator use estimate ) . CONCLUSIONS Treating premature and low-birth-weight infants in Nicaragua with KMC implemented as a quality improvement program saves money within a short period even without considering the beneficial health effects of KMC . Implementation in more facilities is strongly recommended BACKGROUND Skin-to-skin contact reduces pain response in preterm infants subjected to minor painful procedures , such as heel lance . Diaper change is a procedure performed several times daily in hospitalized preterm infants . Routine care giving tasks such as diaper change may be stressful for the infant . AIMS The purpose of this study was to investigate whether diaper change induces stress and if skin-to-skin contact could reduce such stress , measured by changes in skin conductance . STUDY DESIGN This was a r and omized crossover pilot study in 19 preterm infants with gestational age between 28 and 34 weeks . The diaper change procedure was done twice in each infant , once during skin-to-skin contact , and once in incubator or bed with the mother present . OUTCOME MEASURES During diaper change heart rate ( HR ) , peripheral oxygen saturation ( SpO2 ) , and changes in skin conductance ( SC ) peaks per sec , using the Skin Conductance Algesimeter ( SCA ) , were registered . RESULTS The mean SC peaks/sec increased/decreased significantly under/after change of diapers which thereby underpins that this is a stressful procedure for the preterm infant . Skin-to-skin contact ( SSC ) entails significantly lower stress levels ( p<0.05 ) compared to diaper changed in an incubator/bed measured by the SCA . CONCLUSIONS Diaper change is a stressful procedure for preterm infants and may be ameliorated by skin-to-skin contact Purpose : To examine the effect of skin-to-skin care ( SSC ) on stress perception between mothers who provided SSC to their late-preterm born infants and mothers who provided blanket holding . Design and Methods : This was a longitudinal 2-group r and omized controlled trial of 40 infant – mother dyads recruited from a level 3 neonatal intensive care unit in the upper Midwest . Outcome Measure : Maternal stress was measured using the Parental Stressor : Neonatal Intensive Care Unit ( PSS : NICU ) scale pre- and post-SSC intervention . Demographic and other mother and infant covariates were extracted from medical records . Physiologic stability was measured by the Stability of the Cardiorespiratory System in Preterm Infants ( SCRIP ) score . Study personnel used daily logs to track frequency and duration of SSC and holding sessions . Results : The intervention and the control groups had similar pre- ( mean ± st and ard deviation , 2.34 ± 0.86 for SSC and 2.94 ± 0.87 for holding ) and post-intervention ( mean ± st and ard deviation , 2.55 ± 0.95 for SSC and 2.78 ± 0.90 for holding ) overall stress scores . Hours of SSC holding positively correlated with the change in stress scores for the entire scale ( r = 0.58 ; P = .001 ) , and for infant appearance ( r = 0.58 ; P = .001 ) and parent role alteration ( r = 0.48 ; P = .02 ) subscales . This relationship remained significant after controlling for the infant 's length of stay and SCRIP score . Implication s for Practice : Mothers who provide SSC may experience more stress related to a more facilitated progression in the mother and infant relationship . Implication s for Research : The relationship between increased stress and the number of hours of SSC holding warrants further investigation OBJECTIVE To compare the effect of Kangaroo mother care ( KMC ) and conventional methods of care ( CMC ) on growth in LBW babies ( > 2000 g ) . STUDY DESIGN R and omized controlled trial . SETTING Level III NICU of a teaching institution in western India . SUBJECTS 206 neonates with birth weight < 2000 g. INTERVENTION The subjects were r and omized into two groups : the intervention group ( KMC-103 ) received Kangaroo mother care . The control group ( CMC : 103 ) received conventional care . OUTCOME MEASURES Growth , as measured by average daily weight gain and by other anthropometrical parameters at 40 weeks postmenstrual age in preterm babies and at 2500 g in term SGA infants was assessed . RESULTS The KMC babies had better average weight gain per day ( KMC : 23.99 g vs CMC : 15.58 g , P < 0.0001 ) . The weekly increments in head circumference ( KMC : 0.75 cm vs CMC : 0.49 cm , P = 0.02 ) and length ( KMC : 0.99 cm vs CMC : 0.7 cm , P = 0.008 ) were higher in the KMC group . A significantly higher number of babies in the CMC group suffered from hypothermia , hypoglycemia , and sepsis . There was no effect on time to discharge . More KMC babies were exclusively breastfed at the end of the study ( 98 % vs 76 % ) . KMC was acceptable to most mothers and families at home . CONCLUSION Kangaroo mother care improves growth and reduces morbidities in low birth weight infants . It is simple , acceptable to mothers and can be continued at home OBJECTIVE To describe the type and percent time of contact 0 - 48 hours postbirth for mother-preterm newborn ( infant ) dyads given kangaroo care ( skin-to-skin ) or st and ard care ( controls ) . DESIGN R and omized controlled trial with assignment by computerized minimization to kangaroo care ( n = 48 ) or control ( n = 43 ) . SETTING Postpartum units and neonatal intensive-care units ( NICU ) . PARTICIPANTS Preterm infants 32 to less than 37 weeks gestation and their mothers . INTERVENTION Kangaroo ( skin-to-skin , SS ) care ( KC ) . MAIN OUTCOME MEASURES Type and percent time of mother-infant contact ( SS versus holding wrapped in blankets ) . RESULTS Analyses were based on four groups : assignment for infants in each group to postpartum or NICU . For KC dyads , SS postpartum was 22.0 % ; SS NICU was 7.5 % . KC wrapped holding postpartum was 11.6 % ; NICU was 1.8 % . For control dyads , wrapped holding postpartum was 13.9 % ; NICU was 6.1 % . CONCLUSION Amount of SS was much less than expected . Reasons include unavailability of infants or mothers and hospital staff interrupting contact . However , KC postpartum dyads were held wrapped almost as often as control postpartum dyads . Total contact time for KC dyads ( SS plus wrapped ) was more than double that of controls . These data suggest that hospital and social supports for families are needed to facilitate early initiation of SS , prolonged periods of mother-infant SS contact , and reduction of maternal stress Because re sources for care of low-birthweight ( LBW ) infants in developing countries are scarce , the Kangaroo mother method ( KMM ) was developed . The infant is kept upright in skin-to-skin contact with the mother 's breast . Previous studies reported several benefits with the KMM but interpretation of their findings is limited by small size and design weaknesses . We have done a longitudinal , r and omised , controlled trial at the Isidro Ayora Maternity Hospital in Quito , Ecuador . Infants with LBW ( < 2000 g ) who satisfied out-of-risk criteria of tolerance of food and weight stabilisation were r and omly assigned to KMM and control ( st and ard incubator care ) groups ( n = 128 and 147 , respectively ) . During 6 months of follow-up the KMM group had a significantly lower rate than the control group of serious illness ( lower-respiratory-tract disorders , apnoea , aspiration , pneumonia , septicaemia , general infections ; 7 [ 5 % ] vs 27 [ 18 % ] , p < 0.002 ) , although differences between the groups in less severe morbidity were not significant . There was no significant difference in growth or in the proportion of women breastfeeding , perhaps because the proportion breastfeeding was high in both groups owing to strong promotion . Mortality was the same in both groups ; most deaths occurred during the stabilisation period before r and omisation . KMM mothers made more unscheduled clinic visits than control mothers but their infants had fewer re-admissions and so the cost of care was lower with the KMM . Since the eligibility criteria excluded nearly 50 % of LBW infants from the study , the KMM is not universally applicable to these infants . The benefits might be greater in population s where breastfeeding is not so common Increased morbidity and mortality has been associated with neonates admitted with body temperatures below 36 degrees C. We employed an experimental design in a r and omized control trial to compare the effectiveness of using early kangaroo care ( KC ) for extrauterine temperature adaptation against that of using radiant warmers . Trial subjects included 78 consecutive cesarean newborn infants with hypothermia problems . The KC group received skin-to-skin contact with their mothers in the post-operative room , while infants in the control group received routine care under radiant warmers . The mean temperature of the KC group was slightly higher than that of the control group ( 36.29 degrees C vs. 36.22 degrees C , p = .044 ) . After four hours , 97.43 % of KC group infants had reached normal body temperatures , compared with 82.05 % in the radiant warmer group . Results demonstrate the positive effects of KC for extrauterine temperature adaptation in hypothermia infants . In the course of evidence -based practice , KC could be incorporated into the st and ard care regimen in order to improve hypothermia care Objective : This study was conducted ( i ) to study through a r and omized control trial the effect of Kangaroo Mother Care ( KMC ) on breast feeding rates , weight gain and length of hospitalization of very low birth neonates and ( ii ) to assess the acceptability of Kangaroo Mother Care by nurses and mothers . Methods : Babies whose birth weight was less than 1500 Grams were included in the study once they were stable . The effect of Kangaroo Mother Care on breast feeding rates , weight gain and length of hospitalization of very low birth weight neonates was studied through a r and omized control trial in 28 neonates . The Kangaroo group ( n=14 ) was subjected to Kangaroo Mother Care of at least 4 hours per day in not more than 3 sittings . The babies received Kangaroo Care after shifting out from NICU and at home . The control group ( n=14 ) received only st and ard care ( incubator or open care system ) . Attitude of mothers and nurses towards KMC was assessed on Day 3 ± 1 and on day 7 ± 1 after starting Kangaroo Care in a question naire using Likert ’s scale . Results : The results of the clinical trial reveal that the neonates in the KMC group demonstrated better weight gain after the first week of life ( 15.9 ± 4.5 gm/day vs. 10.6 ± 4.5 gm/day in the KMC group and control group respectively p<0.05 ) and earlier hospital discharge ( 27.2 ± 7 vs. 34.6 ± 7 days in KMC and control group respectively , p<0.05 ) . The number of mothers exclusively breastfeeding their babies at 6 week follow-up was double in the KMC group than in the control group ( 12/14 vs. 6/14 ) ( p < 0.05 ) . Conclusion : KMC managed babies had better weight gain , earlier hospital discharge and , more impressively , higher exclusive breast-feeding rates . KMC is an excellent adjunct to the routine preterm care in a nursery Objective : To investigate the impact of early skin-to-skin contact ( SSC ) provided for first 24 h on incidence of hypothermia in stable newborns weighing 1800 g or more during first 48 h of life . Study Design : Stable newborns ( term and late preterm : Mean gestational age 37.7 ( 1.35 ) weeks , range 34–40 weeks ) having birth weight 1800 g or more ( Mean weight 2605.6 ( 419.8 ) grams ) were enrolled after approval from Institutional Human Research Ethics Committee ( CTRI/2013/06/003790 ) and r and omized into early SSC ( intervention group ) and conventional care ( control group ) . Initial care in the delivery room for few minutes immediately after birth in both the groups was given under radiant warmer . In the intervention group , newborns were provided SSC by their mother started between 30 min and 1 h after birth for first 24 h with minimal interruption and were provided conventional care other than SSC for next 24 h of life . In the control group , newborns were kept with their mother and received conventional care other than SSC for first 48 h. Temperature and heart rate of newborns were recorded at 30 min , 1 , 2 , 3 , 4 , 5 , 6 , 12 , 24 and at 48 h of life in both the groups . Independent Sample s t-Test and relative risk were used to analyze the data . Result : Both groups had 50 neonates each with similar baseline characteristics . Heart rates were in normal range in both the groups . The intervention group provided an average ( s.d . ) of 16.98 ( 0.28 ) h of SSC over the first 24 h period . The mean temperature was significantly high in the SSC group at all time intervals starting from 1 to 48 h ( P<0.05 for all ) . In the SSC group only two newborns ( 4 % ) had mild hypothermia ( cold stress ) , and , of these two newborns , one had two episodes of hypothermia . All these three episodes of hypothermia occurred within first 3 h of life . In the control group 16 newborns ( 32 % ) developed hypothermia ( temperature<36.5 ° C ) during first 48 h of life . Of them , 11 newborns had single episode , 4 newborns had two episodes and one newborn had three episodes of hypothermia . Of these 22 hypothermic episodes , 20 occurred in the first 6 h of life and 2 episodes occurred at 48 h of life . Moderate hypothermia was seen in two newborns , whereas rest had mild hypothermia . The relative risk of developing hypothermia in the control group as compared with the SSC group was 8.00 ( 95 % CI 1.94–32.99 ) . There was no seasonal variation in incidence of hypothermia in both the groups . Conclusion : Newborns in the SSC group achieved rapid thermal control as compared with the control group . Early SSC for 24 h after birth decreases incidence of hypothermia for initial 48 h of life . Early SSC needs to be aggressively promoted in term and late-preterm newborns to reduce incidence of hypothermia OBJECTIVE To examine whether a supportive nursing intervention that promoted kangaroo holding of healthy preterm infants by their mothers during the early weeks of the infant 's life facilitated coregulation between mother and infant at 6 months of age . DESIGN R and omized controlled trial . PARTICIPANTS Sixty-five mother/infant dyads with mean gestational age at birth of 33 weeks . Fifty percent of infants were male , and 50 % were non-White . INTERVENTIONS An 8-week home intervention encouraged daily 1-hour , uninterrupted holding with either blanket ( baby wrapped in blanket and held in mother 's arms ) or the kangaroo ( baby in skin-to-skin contact on mother 's chest ) method . In both conditions , weekly home visits by an experienced RN included encouragement to hold the infant , emotional support , and information about infant behavior and development . A control group received brief social visits , had no holding constraints , and participated in all assessment s. MAIN OUTCOME MEASURES When infants were 6 months of age , the Still-Face Paradigm was used to assess mother/infant interaction . Outcome measures were coregulation of the dyad 's responses during the play episodes of the Still-Face Paradigm and vitality in infant efforts to reengage the mother during the neutral face portion of the Still-Face Procedure . RESULTS Significant differences among groups were found in mother/infant coregulation . Post hoc analysis showed that dyads who were supported in kangaroo holding displayed more coregulation behavior during play than dyads in the blanket-holding group . No differences were found between groups in infant vitality during the neutral face portion of the Still-Face Procedure . CONCLUSION Dyads supported in practicing kangaroo holding in the early weeks of life may develop more coregulated interactional strategies than other dyads Separation between mothers and very low birthweight infants is often prolonged with subsequent psychological distress , behaviour problems , and lactation failure . Babies as small as 700 g , who no longer require oxygen , can be safely and enjoyably held naked , except for a nappy , between the mother 's breasts for up to four hours a day . We have carried out a r and omised trial among babies less than 1500 g. Seventy one infants were r and omised . In 35 , the mother was helped to hold her baby in skin to skin contact and encouraged to do so whenever she visited the baby . In 36 , the mother was encouraged to h and le her baby but without skin to skin contact . Mothers using skin to skin contact lactated for four weeks longer on average than the control group . At 6 months of age the infants who had skin to skin contact cried significantly less than the control group . Skin to skin contact can safely and enjoyably be offered to very low birthweight infants especially in developing countries where the mother 's lactation is vital Objective : Assessment of clinimetric properties and diagnostic quality of a stress measurement scale ( COMFORT scale ) . Design : Sample of an open population . Setting : Neonatology department ( Neonatal Intensive Care Unit ) , Academic Medical Centre/Emma Children ’s Hospital , Amsterdam , the Netherl and s. Method : One clinical expert and 9 observers observed ventilated premature born babies simultaneously . Criterion validity was assessed by correlating the COMFORT scale with the clinical judgment regarding the amount of stress . Interobserver reliability was assessed on the clinical judgment as well as on the COMFORT scale . Diagnostic qualities were evaluated with a ROC curve . Results : On 19 ventilated prematurely born babies ( mean gestational age 30 weeks , mean birth weight 1385 gm ) , one clinical expert and 9 observers made 30 paired observations . The criterion validity of the COMFORT scale was good ( Pearson ’s r of 0.84 ) . The interobserver reliability of the clinical judgment was very good ( weighted Kappa 0.84 ) . The interobserver reliability of each item varied from good to almost perfect ( weighted Kappa of 0.64 for muscle tone to 1.00 on heart rate ) . The reliability of the total COMFORT scale score was satisfying ( intraclass correlation coefficient of 0.94 ) . The diagnostic quality of the COMFORT scale was excellent , at a cut-off point of 20 the sensitivity was 100 percent , the specificity was 77 percent , and the area under the curve ( AUC ) of 0.95 . Conclusion : In this first evaluation , the COMFORT scale appears to be a valid and reliable measurement tool to assess the stress of ventilated prematurely born babies OBJECTIVE To examine mothers ' satisfaction with administering interventions for their preterm infants and with the helpfulness of the study nurse by comparing massage with auditory , tactile , visual , and vestibular stimulation ( ATVV intervention ) , kangaroo care , and education about equipment needed at home and to explore whether mother and infant characteristics affected maternal satisfaction ratings . DESIGN Three-group experimental design . SETTING Four neonatal intensive care units ( NICUs ) ( two in North Carolina , two in Illinois ) . PARTICIPANTS Two hundred and eight ( 208 ) preterm infants and their mothers . METHODS When the infant was no longer critically ill , mother/infant dyads were r and omly assigned to ATVV , kangaroo care , or the education group all taught by study nurses . At discharge and 2 months corrected age , mothers completed question naires . RESULTS All groups were satisfied with the intervention and with nurse helpfulness , and the degree of satisfaction did not differ among them . Intervention satisfaction , but not nurse helpfulness , was related to recruitment site . Older , married , and minority mothers were less satisfied with the intervention but only at 2 months . Higher anxiety was related to lower intervention satisfaction at discharge and lower ratings of nurse helpfulness at discharge and 2 months . More depressive symptoms were related to lower nurse helpfulness ratings at 2 months . CONCLUSIONS Mothers were satisfied with interventions for their infants regardless of the intervention performed . Maternal satisfaction with the intervention was related to recruitment site , maternal demographic characteristics , and maternal psychological distress , especially at 2 months . Thus , nursing interventions that provide mothers with a role to play in the infant 's care during hospitalization are particularly likely to be appreciated by mothers Objective Studies reporting the developmental outcomes for very preterm ( VPT ) children often focus on development at age 2 years . The aim of this study was to assess the stability of the rates of diagnosis of developmental disability from age 2 to 8 years in a regional cohort of VPT and extremely low – birth weight ( ELBW ) children and compare these with term controls . Methods VPT ( 22–27 completed weeks of gestation ) and ELBW ( birth weight 500–999 g ) children and matched term controls born in Victoria , Australia , in 1997 were enrolled at birth in a regional prospect i ve longitudinal study . Outcomes were assessed at ages 2 and 8 years . Results Of the 283 VPT/ELBW live births , 71 % survived to age 8 years and 94 % were assessed . Of the 199 controls , 100 % survived to age 8 years and 86.9 % were assessed . At age 2 years , the rates of nil , mild , moderate and severe disabilities in the VPT/ELBW children were respectively 51.9 % , 20.9 % , 13.4 % and 13.9 % ; and at age 8 years , 43.9 % , 36.9 % , 10.7 % and 8.6 % . The Cohen κ statistic revealed poor agreement between disability status at ages 2 and 8 years for VPT/ELBW children ( 0.20 , p<0.001 ) but a higher level of agreement ( 0.37 , p<0.001 ) for the control children . This was primarily driven by differences in classification of cognitive disability between ages 2 and 8 years . Conclusions Developmental outcomes at age 2 years are only a moderate predictor of long-term outcome and are not a reliable end point for follow-up studies of VPT and ELBW children Objective : The purpose of this study was to determine the feasibility and acceptability of kangaroo care in a tertiary care hospital in India . Methods : A r and omized controlled trial was performed over one year period in which 89 neonates were r and omized into two groups kangaroo mother care ( KMC ) and conventional method of care ( CMC ) . Results : Forty-four babies were r and omized into KMC group and 45 to CMC . There was significant reduction in KMCvs CMC group of hypothermia ( 10/44vs 21/45 , p-value<0.01 ) . There were no statistically significant differences in the incidence of hyperthernia , sepsis , apnea , onset of breastfeeding and hospital stay in two groups . 79 % of mothers felt comfortable during the KMC and 73 % felt they would be able to give KMC at home . KMC is feasible , as mothers are already admitted in hospitals and are involved in the care of newborn . Conclusion : KMC is a simple and feasible intervention ; acceptable to most mothers admitted in hospitals . There may be benefits in terms of reducing the incidence of hypothermia with no adverse effects of KMC demonstrated in the study . The present study has important implication s in the care of LBW infants in the developing countries , where expensive facilities for conventional care may not be available at all place OBJECTIVE To assess the effectiveness and safety of Kangaroo Mother Care ( KMC ) for infants of low birth weight . METHODS An open , r and omized , controlled trial of a Colombian social security referral hospital was conducted . A total of 1084 consecutive infants who were born at < /=2000 g were followed , and 746 newborns were r and omized when eligible for minimal care , with 382 to KMC and 364 to " traditional " care . Information on vital status was available for 693 infants ( 93 % ) at 12 months of corrected age . KMC consisted of skin-to-skin contact on the mother 's chest 24 hours/day , nearly exclusive breastfeeding , and early discharge , with close ambulatory monitoring . Control infants remained in incubators until the usual discharge criteria were met . Both groups were followed at term and at 3 , 6 , 9 , and 12 months of corrected age . The main outcomes measured were morbidity , mortality , growth , development , breastfeeding , hospital stay , and sequelae . RESULTS Baseline variables were evenly distributed , except for weight at recruitment ( KMC : 1678 g ; control participants : 1713 g ) . The risk for death was lower among infants who were given KMC , although the difference was not significant ( KMC : 11 [ 3.1 % ] of 339 ; control participants : 19 [ 5.5 % ] of 324 ; relative risk : 0.57 ; 95 % confidence interval : 0.17 - 1.18 ) . The growth index of head circumference was statistically significantly greater in the group given KMC , but the developmental indices of the 2 groups were similar . Infants who weighed < /=1500 g at birth and were given KMC spent less time in the hospital than those who were given st and ard care . The number of infections was similar in the 2 groups , but the severity was less among infants who received KMC . More of these infants were breastfed until 3 months of corrected age . CONCLUSION These results support earlier findings of the beneficial effects of KMC on mortality and growth . Use of this technique would humanize the practice of neonatology , promote breastfeeding , and shorten the neonatal hospital stay without compromising survival , growth , or development Kangaroo mother care ( KMC ) is a nonconventional low‐cost method of newborn care . Our aim was to assess the effect of sustained KMC on the growth and development of low birthweight Indian babies up to the age of 12 months Purpose : The purpose of this r and omized , controlled trial was to determine if nurse-supported kangaroo holding of healthy preterm infants in the first 8 weeks of the infant 's life facilitates early behavioral organization and development . Methods : We r and omized 87 infants born between 32 and 35 weeks gestation and their mothers to one of three holding groups : kangaroo ( skin-to-skin between mother 's breasts ) , blanket ( held in mother 's arms ) , or control ( no holding restrictions ) . Nurse-supported groups ( kangaroo and blanket ) received 8 weekly visits from a registered nurse who encouraged holding and provided education about infant development . The control group received brief social visits . Mothers recorded time held in a daily diary . The Assessment of Preterm Infant Behavior was administered when infants were 40 to 44 weeks postconceptional age . Results : Total holding time averaged 4 to 5 hr/day and did not differ among groups . Mothers held kangaroo style an average of 59 min/day in the kangaroo group , and 5 and 9 min/day in the blanket and control groups , respectively ( p < .001 ) . Infants in the kangaroo and blanket groups had more optimal scores than the control group in Robust Crying ( p = .015 ) indicating that they could arouse to vigorous crying and calm . Scores , except for Attention and State Regulation , were at least as high as those of full-term infants . Clinical Implication s : When kangaroo holding is compared to blanket holding , both methods may provide equal early behavioral organization and developmental benefit to the infant Many preterm infants cared for in incubators do not experience Kangaroo Care ( KC ) , skin-to-skin contact with their mothers , due to fear of body heat loss when being held outside the incubator . A r and omized clinical trial of 16 KC and 13 control infants using a pretest-test-posttest design of three consecutive interfeeding intervals of 2.5 to 3.0 h duration each was conducted over 1 day . Infant abdominal and toe temperatures were measured in and out of the incubator ; maternal breast temperature was measured during KC . Repeated measures ANOVA showed no change in abdominal temperature across all periods and between groups . Toe temperatures were significantly higher during KC than incubator periods , and maternal breast temperature met each infant ’s neutral thermal zone requirements within 5 min of onset of KC . Preterm infants similar to those studied here will maintain body warmth with up to 3 h of KC BACKGROUND Preterm birth often negatively influences mother-infant interaction . Skin-to-skin contact postbirth has positive effects on maternal feelings toward their preterm infants and on infant development and family interaction . However , little is known about the long-term effects of skin-to-skin contact on mother-late preterm infant interaction when skin-to-skin contact was experienced early postbirth and intermittently throughout the next five days . OBJECTIVE The purpose of this report was to examine the effect of skin-to-skin contact on mother-late preterm infant interaction through 18 months . DESIGN R and omized controlled trial with follow-up . SETTING Two hospitals in the United States of America . PARTICIPANTS 100 mothers and their late preterm infants , 32 to < 37 weeks ' gestation , were recruited . Mother-preterm infant interactions were assessed in 69 , 70 , and 76 dyads at 6 , 12 , and 18 months . METHODS Mothers and their preterm infants were videotaped during a feeding session at 6 and 12 months , and a teaching session at 6 , 12 , and 18 months . Their interactions were then scored using the Nursing Child Assessment Satellite Feeding Scale and Teaching Scale . RESULTS Skin-to-skin contact and control dyads had comparable feeding scores at 6 and 12 months . Skin-to-skin contact infants had lower infant teaching scores at six months , a difference that disappeared thereafter . CONCLUSIONS These inconclusive results call for additional studies with larger doses of skin-to-skin contact , larger sample sizes , and other outcome measures of mother-late preterm infant interactions . Such measures include the Parent-Child Early Relational Assessment and behavioral coding during play OBJECTIVE To compare the kangaroo and traditional methods of removing an infant from an incubator in terms of four physiologic parameters , mother 's satisfaction , and mother 's preference . DESIGN Time-series design ( quasi-experimental ) , with infant-mother dyads subjected to both methods . SETTING Intermediate neonatal care unit in a tertiary hospital in Canada . PARTICIPANTS A convenience sample of 71 infant-mother dyads . INTERVENTION AND MEASURES : The intervention was use of the kangaroo or traditional method of maintaining body temperature of preterm infants . The dependent variables were physiologic parameters ( skin temperature , heart rate , respiratory rate , and oxygen saturation ) measured five times with each method . Mother 's satisfaction was measured at the end of each testing period and mother 's preference at the end of the experiment . RESULTS The kangaroo method produced less variation in oxygen saturation and longer duration of testing , and it was preferred by most of the mothers . CONCLUSIONS The kangaroo method is safe for the preterm infant and allows for early contact between parents and infants The National Institute of Child Health and Human Development conducts and supports research on all stages of human development from preconception to adulthood in order to better underst and the health of children , youths , adults , families , and communities . Health and human development information is made easily available on the site with a simple A to Z list , along with clinical trials and health education campaign information . Links to clinical trials , news releases , publications , and related web sites are also available , as well as information on research being conducted at present and supported by the National Institute of Child Health and Human Development The aim of this study was to determine whether the implementation of Kangaroo Mother Care ( KMC ) to low birth weight infants would improve physical growth , breastfeeding and its acceptability . A r and omized controlled trial was performed over 16 months in which 110 neonates were r and omized into a KMC group and a control group using a r and om number table . The KMC group was subjected to KMC for at least 6 h per day . The babies also received KMC after moving from the neonatal intensive care unit and at home . The control group received st and ard care ( incubator or open care system ) . Weight , length and occipitofrontal circumference ( OFC ) were measured weekly for three months . The acceptability of KMC by mothers and nursing staff was assessed on day 7 after the start of KMC using a question naire incorporating the Likert scale . Breastfeeding rates were calculated based on history at end of three months . The mean gestational age was 35.48 ± 1.20 weeks in the KMC group and 35.04 ± 1.09 weeks in the control group ( P > 0.05 ) . KMC was initiated at a mean age of 1.72 ± 0.45 days and the duration of KMC was 9.74 ± 1.48 h/day . The mean birth weight was 1.69 ± 0.11 kg in the KMC group compared to 1.69 ± 0.12 kg in the control group ( P > 0.05 ) . The mean weight gain in gm/day in the KMC group was 21.92 ± 1.44 compared to 18.61 ± 1.28 in the control group ( P < 0.05 ) . The mean length gain in cm/week was 1.03 ± 0.5 in the KMC group compared to 0.74 ± 0.05 in the control group ( P < 0.05 ) . The mean OFC gain in cm/week was 0.59 ± 0.04 in the KMC group compared to 0.47 ± 0.03 in the control group ( P < 0.05 ) . The exclusive breast-feeding rate at end of three months was 88 % in the KMC group compared to 72 % in the control group ( P < 0.05 ) . KMC improved physical growth , breastfeeding rates and was well accepted by both mothers and nursing staff AIM To compare weight gain and head growth in very-low-birthweight ( VLBW , < 1501 g ) infants with or without exposure to short duration of skin-to-skin contact ( STSC ) during their stay in a neonatal intensive care unit . METHODS Stable VLBW infants were r and omised into either STSC or control group . Parents of the STSC group were encouraged to provide STSC for at least 1 h daily . RESULTS One hundred and forty-six infants were r and omised , but only 126 were enrolled ( STSC group : n = 64 ; CONTROLS n = 62 ) . Infants in the STSC group had better mean weekly increase in head circumference ( 1.0 cm ( SD = 0.3 ) vs. 0.7 cm ( SD = 0.3 ) ; P < 0.0001 ) and higher breastfeeding rate at discharge ( 29.7 % vs. 14.5 % ; P = 0.04 ) . Although the mean duration of maternal education was longer in STSC ( 13.0 vs. 12.1 years ; P = 0.04 ) than in controls , linear regression analysis showed that the significant predictors associated with weekly head growth were exposure to STSC ( unst and ardised coefficient : 0.2 ; 95 % confidence intervals ( CI ) : 0.1 , 0.3 ; P < 0.0001 ) and head circumference of infants at the time of enrollment ( unst and ardised coefficient : -0.05 ; 95 % CI : -08 , -0.03 ; P < 0.0001 ) ; the number of years of maternal education was not a significant predictor . Logistic regression analysis showed that the only significant predictors of successful breastfeeding at discharge were receiving expressed breast milk at enrollment ( adjusted OR : 4.1 ; 95 % CI : 1.4 , 11.7 ; P = 0.009 ) and receiving expressed breast milk during intervention period ( adjusted OR : 8.3 ; 95 % CI : 2.8 , 24.4 ; P < 0.0001 ) ; exposure to STSC and maternal education were not significant predictors . CONCLUSION Exposure to short duration of STSC may promote head growth in VLBW infants Background : The mothers of premature infants are at risk of psychological stress because of separation from their infants . One of the methods influencing the maternal mental health in the postpartum period is kangaroo mother care ( KMC ) . This study was conducted to evaluate the effect of KMC of low birth weight infants on their maternal mental health . Material s and Methods : The study was conducted in the Department of Pediatrics of Isfahan University of Medical Sciences , Isfahan , Iran . Premature infants were r and omly allocated into two groups . The control group received st and ard caring in the incubator . In the experimental group , caring with three sessions of 60 min KMC daily for 1 week was practice d. Mental health scores of the mothers were evaluated by using the 28-item General Health Question naire . Statistical analysis was performed by the analysis of covariance using SPSS . Results : The scores of 50 infant-mother pairs were analyzed totally ( 25 in KMC group and 25 in st and ard care group ) . Results of covariance analysis showed the positive effects of KMC on the rate of maternal mental health scores . There were statistically significant differences between the mean scores of the experimental group and control subjects in the posttest period ( P < 0.001 ) . Conclusion : KMC for low birth weight infants is a safe way to improve maternal mental health . Therefore , it is suggested as a useful method that can be recommended for improving the mental health of mothers OBJECTIVES To assess the effectiveness and safety of the Kangaroo mother intervention ( KMI ) . DESIGN Observational , analytic , prospect i ve ( two cohorts ) study . SETTING Two large tertiary care obstetric hospitals , one offering " traditional " care and the other KMI . PATIENTS Newborn infants with birth weights < or = 2000 g , who survive the neonatal period and are eligible for an in-patient minimal care unit ( MCU ) ( having overcome major adaptation problems to extra uterine life ) . INTERVENTIONS " Kangaroo infants " ( KI ) were discharged as soon as they were eligible for MCU , regardless of weight or gestational age . Infants were kept 24 hours a day in an upright position , in skin-to-skin contact and firmly attached to the mother 's chest until the KMI was not tolerated anymore . Control babies ( from the other facility ) were kept in incubators at the MCU until they satisfied usual discharge criteria for the control hospital . Both groups were followed periodically up to the age of 1 year . RESULTS Three hundred thirty-two eligible infants were recruited , 162 at the Kangaroo hospital and 170 at the control hospital . KI came from a much lower socio-economic class and were more ill before eligibility . Relative risk of death was higher for KI ( RR 1.9 ) , although this figure was reversed after adjusting for weight at birth and gestational age ( RR 0.5 ) . KI grew less in the first 3 months and had a higher proportion of developmental delay at 1 year , and a multivariate analysis failed to control for the large baseline differences in socioeconomic levels and babies ' health status between the two cohorts . CONCLUSIONS In spite of major baseline differences between studied cohorts , the survival of LBW infants in Bogotá is similar between the KMI and the " traditional care " . Questions remain about quality of life , especially regarding weight gain and neurodevelopment , that may be answered by a R and omized Controlled Trial Objective To determine whether Kangaroo mother care ( KMC ) facilitates mother baby attachment in low birth weight infants . Methods Over 16 month period 110 neonates were r and omized into kangaroo mother care group and control group using a r and om number table . The kangaroo group was subjected to Kangaroo mother care for at least 6 hours per day . The babies also received kangaroo care after shifting out from NICU and at home . The control group received st and ard care ( incubator or open care system ) . After 3 months followup , structured maternal interview was conducted to assess attachment between mothers and their babies . Results Mean birth weight was 1.69 ± 0.11 Kg in KMC group compared to 1.690 ± 0.12 Kg in control group ( p>0.05 ) . Mean gestational age was 35.48 ± 1.20 week in KMC group and 35.04±1.09 week in the control group ( p>0.05 ) . KMC was initiated at a mean age of 1.72±0.45 days . The duration of KMC in first month was 10.21±1.50 hour , in the 2nd month was 10.03±1.57 hour and in the 3rd month was 8.97±1.37 hours . The duration of hospital stay was significantly shorter in the KMC group ( 3.56±0.57 days ) compared to control group ( 6.80±1.30 days ) . The total attachment score ( 24.46±1.64 ) in the KMC group was significantly higher than that obtained in control group ( 18.22±1.79 , p<0.001 ) . In KMC group , mother was more often the main caretaker of the baby . Mothers were significantly more involved in care taking activities like bathing , diapering , sleeping with their babies and spent more time beyond usual care taking . They went out without their babies less often and only for unavoidable reasons . They derived greater pleasure from their babies . Conclusion KMC facilitates mother baby attachment in low birth weight infants This pilot study was conducted to compare the effectiveness of the kangaroo care method with current , mainly incubator-based care in managing well preterm infants in a tertiary level hospital in a developing country . Altogether , 74 infants ( 37 per group ) were consecutively allocated to receive either kangaroo care or incubator care . After adjusting for age and weight on admission to the study , we found that infants in the kangaroo care group gained twice as much weight per day ( 20.8 vs 10.2 g , p = 0.0001 ) , had a shorter stay in hospital ( 16.6 vs 20.7 days , p = 0.0457 ) and had a better survival rate ( 0 % vs 9 % deaths ) . Also , they were ill less frequently , but after adjusting for age and weight this difference was not significant . This pilot study suggests that the kangaroo care method has major advantages over incubator care of preterm infants in our hospital . Hospitals which can not use incubators optimally may find kangaroo care to be a better method of improving perinatal and neonatal morbidity and mortality BACKGROUND / AIMS Kangaroo care ( KC ) has possible benefits for promoting physiological stability and positive developmental outcomes in preterm infants . The purpose of this study was to compare bradycardia and oxygen desaturation events in preterm infants in st and ard incubator care versus KC . METHODS Thirty-eight infants 27 to 30 weeks gestational age were r and omly assigned to 2 hours of KC daily between days of life 5 to 10 or to st and ard incubator care . Infants were monitored for bradycardia ( heart rate < 80 ) or oxygen desaturation ( < 80 % ) . Analysis of hourly events was based on three sets of data : st and ard care group 24 hours daily , KC group during incubator time 22 hours daily , and KC group during holding time 2 hours daily . RESULTS The KC group had fewer bradycardia events per hour while being held compared to time spent in an incubator ( p = 0.048 ) . The KC group also had significantly fewer oxygen desaturation events while being held than while in the incubator ( p = 0.017 ) and significantly fewer desaturation events than infants in st and ard care ( p = 0.02 ) . CONCLUSION KC reduces bradycardia and oxygen desaturation events in preterm infants , providing physiological stability and possible benefits for neurodevelopmental outcomes & NA ; We performed this r and omized trial to determine whether infants receiving skin‐to‐skin care ( SSC ) grew more rapidly and had a shorter duration of hospital stay compared with infants held by their parents in a traditional way . Infants who met eligibility criteria ( ≤32 wk of gestation , ≤1500 g , minimal ventilatory support , and hemodynamically stable ) were r and omized to traditional holding ( TH ) or SSC groups . Parents in both groups were allowed to hold infants for a total of 8 hours per day ( periods of up to 4 hr , twice/d ) . During the study , infants in the TH group were held 4.8 ± 3.5 times per week and 76 ± 39 minutes per day , and infants in the SSC group were held 4.0 ± 2.8 times per week and 79 ± 40 minutes per day . No significant differences were observed in weight accretion or linear growth . However , exposure to SSC was associated with greater head growth , even after controlling for head circumference at birth ( p = .03 ) . SSC may increase the likelihood of successful breastfeeding . J Dev Behav Pediatr 24:163‐168 , 2003 . Index terms : skin‐to‐skin care , growth Purpose : To determine the safety and effects on healthy preterm infants of three continuous hours of kangaroo care ( KC ) compared to st and ard NICU care by measuring cardiorespiratory and thermal responses . Design : R and omized controlled trial — pretest-test-posttest control group design . Sample : Twenty-four healthy preterm infants ( 33–35 weeks gestation at birth ) nearing discharge . Eleven of the infants received KC ; 13 received st and ard NICU care . Main Outcome Variables : Heart rate , respiratory rate , oxygen saturation , and abdominal skin temperature were manually recorded every minute . Apnea , bradycardia , periodic breathing , and regular breathing were captured continuously on a pneumocardiogram printout . Three consecutive interfeeding intervals ( three hours each ) on one day constituted the pretest , test , and posttest periods . Results : Mean cardiorespiratory and temperature outcomes remained within clinical ly acceptable ranges during KC . Apnea , bradycardia , and periodic breathing were absent during KC . Regular breathing increased for infants receiving KC compared to infants receiving st and ard NICU care This study compared two methods of holding preterm infants : 1 ) the kangaroo , or skin-to-skin method ( K ) and 2 ) the traditional method , or normal h and ling ( T ) . Skin temperature , heart rate , respiratory rate and oxygen saturation were monitored during both the kangaroo and the traditional h and ling methods . After testing with the two methods , the mothers indicated their satisfaction and preference . Sixty-one pairs of mothers and babies were tested once with the K method and once with the T method . The first method tested was determined at r and om : 50 % began with K and 50 % with T. Skin temperature , heart rate and respiratory rate were similar with both K and T methods . Whereas oxygen saturation was significantly lower ( 92.8 % vs 90.5 % , p < 0.0001 ) under the T method , time of testing was longer ( 29.5 min vs 25.3 min , p = 0.02 ) for the K method than for T method . In summary , the findings suggested that mothers preferred the K method because the cold stress factor was avoided , oxygenation was better maintained , and mothers felt closer to their infants |
679 | 28,722,671 | PSK treatment significantly increased 1 - 5 year OS and result ed in positive trends in 6 - 7 year OS ; significant increases were also found in 1 - 7 year DFS , while no increase in side effects was observed .
Significant efficacy outcomes obvious in colorectal and gastric cancer groups , as well as PSK combined with chemotherapy groups ( iv , po , iv+po ) .
Network meta- analysis revealed that PSK combined with chemotherapy was superior , with significantly increased 3-year and 5-year OS .
The study is registered with PROSPERO ( CRD42017065193 ) Conclusions : The adjuvant immunochemotherapy agent PSK is effective and safe for patients with GIC .
PSK combined with chemotherapy appears to be the preferred application of PSK | OBJECTIVE To assess the comparative efficacy and safety of polysaccharide K ( PSK ) , with or without chemotherapy , for patients with gastrointestinal cancer ( GIC ) through a systematic review and network meta- analysis . | The prognostic value of immunosuppressive acidic protein ( IAP ) , which is known to suppress various immune responses in cancer patients , was studied in a prospect i ve r and omized trial of advanced gastric cancer patients , design ed to evaluate the effect of PSK , a kind of biological response modifier with protein-bound polysaccharides . Preoperative serum IAP levels were determined in 228 patients who received radical gastric resection and tests conducted in one laboratory by the single radial immunodiffusion ( SRID ) method . All patients were followed up for 24 months or more . There was an overall significant difference in disease-free survival time in favour of the PSK-treated group compared with the control group . Preoperative IAP values were strongly associated with disease-free survival time . The statistical analysis to define an appropriate cut-off level for IAP was performed using Cox 's proportional hazards model . The most significant difference was observed at the threshold value of 580 μg/ml , the hazard ratio being 2.13 with a 95 % confidence interval [ 1.17 , 3.88 ] ( P=0.013 ) . Patients in the PSK-treated group with a preoperative IAP of lower than 580 μg/ml showed improved disease-free survival ( P=0.029 ) , however , no significant difference was seen between the two groups when the preoperative IAP exceeded the threshold level . From these results , 580 μg/ml is postulated to be the most appropriate threshold value for predicting the prognosis of advanced gastric cancer patients , and it is suggested that PSK would be most effective in patients whose preoperative IAP level is lower than the threshold level Protein-bound polysaccharide K ( PSK ) increased the 5-year disease-free survival rate and reduced the risk of recurrence in a r and omised , controlled study for stage II and III colorectal cancer . In order to eluci date the disease-free survival benefits with PSK and what immunological markers could indicate a PSK responder , serial changes in immunological parameters were monitored in the study . PSK decreased the mean serum immunosuppressive acidic protein ( IAP ) level , and increased the mean population of natural killer ( NK ) cells compared with the controls . The 5-year disease-free and overall survival rate for patients with serum IAP values < or=500 microg ml(-1 ) , which represents the normal value , were 75.5 % ( 95 % CI : 66.8 - 84.2 % ; p=0.016 ) and 85.1 % ( 95 % CI : 77.9 - 92.3 % ; p=0.032 ) , respectively , in the PSK group compared with 57.5 % ( 95 % CI : 43.3 - 71.6 % ) and 70.2 % ( 95 % CI : 57.1 - 83.3 % ) in the control group . In patients with NK cell population > or=8 % at 3 months after surgery , PSK conferred a significantly better ( p=0.038 ) 5-year disease-free survival ( 86.7 % ; 95 % CI : 74.5 - 98.8 % ) compared to the control group ( 60.0 % ; 95 % CI : 29.6 - 90.4 % ) . In the proportional hazards model , the presence of regional metastases ( relative risk , 3.595 ; 95 % CI : 1.518 to 8.518 ; p=0.004 ) and omission of PSK treatment ( relative risk , 3.099 ; 95 % CI : 1.202 to 7.990 ; p=0.019 ) were significant indicators of recurrence . PSK acts as an immunomodulatory activity and biochemical modulator in stage II or III colorectal cancer . Pre-operative serum IAP values < or=500 microg ml(-1 ) and an NK cell population > or=8 % at 3 months after surgery are possible PSK response predictors Intravenous fluorouracil and leucovorin is the st and ard adjuvant treatment for stage III colon cancer . However , oral adjuvant chemotherapy is attractive because it has low toxicity and greater convenience . We investigated the benefits of oral protein-bound polysaccharide K ( PSK ) with tegafur/uracil ( UFT ) as an adjuvant in stage II and III colorectal cancer . Patients were assigned to groups that received either 3 g PSK plus 300 mg UFT , or 300 mg UFT alone orally each day for a 2-year period following intravenous mitomycin C. Of 207 registered patients , 205 with stage II ( n=123 ) or III ( n=82 ) were analysed . The 5-year disease-free survival was 73.0 % ( 95 % CI 65.6–80.4 % ) with PSK ( n=137 ) and 58.8 % ( 95 % CI 47.1–70.5 % ) in the controls ( n=68 ) ( P=0.016 ) . Polysaccharide K reduced the recurrence by 43.6 % ( 95 % CI 4.5–66.7 % ) and mortality by 40.2 % ( 95 % CI −12.5 to 68.3 % ) . The 5-year survival was 81.8 % ( 95 % CI 75.3–88.2 % ) in the PSK group and 72.1 % ( 95 % CI 61.4–82.7 % ) in the control group ( P=0.056 ) . In stage III patients , disease-free and overall survivals in patients receiving PSK were increased significantly : 60.0 % ( 95 % CI 47.1–72.9 % ) and 74.6 % ( 95 % CI 63.0–86.1 % ) in the PSK group as compared with 32.1 % ( 95 % CI 14.8–49.4 % ) and 46.4 % ( 95 % CI 28.0–64.9 % ) in the controls ( P=0.002 and 0.003 , respectively ) . Polysaccharide K prevented recurrence , particularly lung metastases ( P=0.02 ; odds ratio 0.27 ; 95 % CI 0.09–0.77 ) . In the models , the presence of regional metastases ( relative risk , 2.973 ; 95 % CI 1.712–5.165 ; P<0.001 ) , omission of PSK ( relative risk , 2.106 ; 95 % CI 1.221–3.633 ; P=0.007 ) , and higher primary tumour ( relative risk , 4.398 ; 95 % CI 1.017–19.014 ; P=0.047 ) were each significant indicators of recurrence . Adverse effects were mild and compliance was good . Oral PSK with UFT reduced recurrence in stage II and III colorectal cancer , and increased survival in stage III Background Protein-bound polysaccharide ( PSK ) is derived from the CM-101 strain of the fungus Coriolus versicolor and has shown anticancer activity in vitro and in in vivo experimental models and human cancers . Several r and omized clinical trials have demonstrated that PSK has great potential in adjuvant cancer therapy , with positive results in the adjuvant treatment of gastric , esophageal , colorectal , breast and lung cancers . These studies have suggested the efficacy of PSK as an immunomodulator of biological responses . The precise molecular mechanisms responsible for its biological activity have yet to be fully eluci date d. Methods The in vitro cytotoxic anti-tumour activity of PSK has been evaluated in various tumour cell lines derived from leukaemias , melanomas , fibrosarcomas and cervix , lung , pancreas and gastric cancers . Tumour cell proliferation in vitro was measured by BrdU incorporation and viable cell count . Effect of PSK on human peripheral blood lymphocyte ( PBL ) proliferation in vitro was also analyzed . Studies of cell cycle and apoptosis were performed in PSK-treated cells . Results PSK showed in vitro inhibition of tumour cell proliferation as measured by BrdU incorporation and viable cell count . The inhibition ranged from 22 to 84 % . Inhibition mechanisms were identified as cell cycle arrest , with cell accumulation in G0/G1 phase and increase in apoptosis and caspase-3 expression . These results indicate that PSK has a direct cytotoxic activity in vitro , inhibiting tumour cell proliferation . In contrast , PSK shows a synergistic effect with IL-2 that increases PBL proliferation . Conclusion These results indicate that PSK has cytotoxic activity in vitro on tumour cell lines . This new cytotoxic activity of PSK on tumour cells is independent of its previously described immunomodulatory activity on NK cells Background : Despite the small but significant survival benefit of adjuvant chemotherapy in locally advanced gastric cancer ( LAGC ) , the optimal regimen remains to be determined . We conducted a r and omized trial comparing oral ( PO ) chemoimmunotherapy ( CITX ) with intravenous ( IV ) CITX in LAGC patients ( stages IB-IIIB ) with curative resection ( ≥ D2 dissection ) . Methods : The patients were r and omized to the IV ( 5-fluorouracil 500 mg/m2 weekly for 24 weeks , mitomycin-C 8 mg/m2 every 6 weeks × 4 ) or the PO ( uracil-ftorafur ( UFT ) 400 - 600 mg/day for 12 months ) group . Patients in both groups received PO polysaccharide-K ( 3 g/day for 4 months ) . The planned number of patients was 368 for proving the non-inferiority of PO CITX compared to IV CITX for overall survival . Results : The trial was closed prematurely after enrolling 82 patients ( 44 in the IV group , 38 in the PO group ) . With a median follow-up of 82 months , there were no significant differences in the 5-year disease-free survival ( 73 % vs. 55 % , p = 0.358 ) and overall survival ( 77 % vs. 66 % , p = 0.159 ) between the 2 groups . The IV group demonstrated a higher incidence of grade 2 or 3 neutropenia , thrombocytopenia , and vomiting . Conclusions : PO CITX with UFT appeared to be at least non-inferior to 5-fluorouracil and mitomycin-C CITX , with lower toxicity in the adjuvant treatment for LAGC Summary To examine the clinical efficacy and the mechanism of action of polysaccharide K ( PSK ) , a proteinbound polysaccharide extracted from a Basidiomycetes fungus , a r and omized double-blind trial was performed by administering PSK to 56 patients and a placebo to another group of 55 patients after surgical operations on their colorectal cancers . The rate of patients in remission ( or disease-free ) was significantly higher in the PSK group than in the placebo group ; the difference between both groups was statistically significant atP < 0.05 by the logrank test . The survival rate of patients was also significantly ( P < 0.05 ) higher in the PSK group than in the control group . The most significant laboratory finding was that polymorphonuclear leukocytes from PSK-treated patients showed remarkable enhancement in their activities , such as r and om and /or chemotactic locomotion , and phagocytic activity , when compared with those in the control group . In conclusion , PSK was useful as a maintenance therapy for patients after their curative surgical operations for colorectal cancer . The beneficial effects were probably due to the activation of leukocyte functions as one of the many biological-response-modifying ( activities induced by PSK ) Abstract PURPOSE : Intravenous fluorouracil and leucovorin for six to eight months is currently a st and ard adjuvant treatment for Stage III colon cancer ; however , this regimen is complex , inconvenient , and has a high intolerability . Adjuvant chemotherapies are cl aim ed for objective response rates with an acceptable safety profile and complexity . We investigated the benefits of oral protein-bound polysaccharide K added to oral tegafur/uracil on curatively resected Stage II or III colorectal cancer . METHODS : We prospect ively r and omized 207 patients to treatments of either oral 3.0 g protein-bound polysaccharide K plus 300 mg tegafur/uracil or 300 mg tegafur/uracil alone for two years following 12 mg/m2 and 8 mg/m2 mitomycin treatment on postoperative Days 1 and 2 , respectively . The primary end points were disease-free and overall survival , and recurrence rates . RESULTS : Three ( 1.4 percent ) patients were declared ineligible , and three patients did not start treatment . In total , 201 patients were analyzed . The three-year , disease-free survival rate was 80.6 percent ( st and ard error = 3.4 percent ) in the protein-bound polysaccharide K group ( P = 0.02 ) compared with 68.7 percent ( SE = 5.7 percent ) in the control group after a median follow-up of 3.7 years . The estimated relative risk of recurrence in the control group was 1.87 ( 95 percent confidence interval , 1.10–3.20 ) at three years . The three-year , overall survival rate was 87.3 percent ( st and ard error = 2.9 percent ) in the protein-bound polysaccharide K group and 80.6 percent ( st and ard error = 4.8 percent ) in the control group ( P = 0.24 ) . The three-year , overall survival rate in 80 pathological TNM Stage III patients was 83.0 percent ( st and ard error = 5.2 percent ) in the protein-bound polysaccharide K group and 59.3 percent ( st and ard error = 9.5 percent ) in the control group ( P = 0.02 ) . Protein-bound polysaccharide K prevented distant metastases ( P = 0.05 ) , particularly lung metastases ( P = 0.01 ) . The incidence of adverse effects was minimal , and compliance was good . CONCLUSION : Adjuvant therapy using a combination of oral protein-bound polysaccharide K and tegafur/uracil is highly effective in preventing the recurrence of colorectal cancer in Stage II or III patients , and increases overall survival in pathological TNM Stage III . These results will be a sufficient proof to conduct a larger study to compare tegafur/uracil/protein-bound polysaccharide K with 5-fluorouracil/ leucovorin We examined the effectiveness of postoperative adjuvant chemotherapy with mitomycin C ( MMC ) , 1-(2-tetrahydrofuryl)-5-fluorouracil ( tegafur ) , plus PSK , an immunomodulator , for patients with advanced gastric cancer who underwent histological curative resection . The effect of chemotherapy on prognostic serosal ( ps ) invasion [ ps(- ) or ps(+ ) ] and lymph node metastasis [ n(- ) or N(+ ) ] was examined . One hundred eighteen patients were in the no-chemotherapy group and 137 were on the drugs . The median follow-up time for the 86 survivors at the time of analysis was 13.8 years . With regard to prognostic factors , there were no differences between the two groups . Generalized Wilcoxon test of the two survival patterns revealed a P value of .0351 , and the survival rate for 15 years was 45.7 % for patients in the no-chemotherapy group and 56.9 % for those of the chemotherapy group . In particular , adjuvant chemotherapy was effective for patients with ps(-)n(+ ) ( P less than .05 ) and ps(+)n(- ) ( P less than .05 ) , but not for those with ps(-)n(- ) and ps(+)n(+ ) . Our findings show that the concomitant prescription of MMC , tegafur , and PSK improves the 15-year survival rate for patients with advanced gastric cancer , following curative resection . As the survival rate is low for the patients with ps(+)n(+ ) , an even more aggressive postoperative chemotherapy is recommended The aim of this report is to evaluate retrospectively the data from a prospect i ve r and omized study of 158 esophageal cancer patients who actually completed therapy with protein-bound polysaccharide P ( PSK ) and the 5-year survivals with and without raised alpha 1-antichymotrypsin and sialic acid levels to determine the value of these parameters in predicting effectiveness of immunotherapy . There was a significant difference in survival between the patients with and without PSK therapy . The survival of the radiochemotherapy plus PSK group treated for > 3 months was significantly better than that of the radiochemotherapy group . Among the patients with abnormal levels of alpha 1-antichymotrypsin and sialic acid , those who received PSK may have a significantly better survival than those without PSK . These results indicate that the preoperative serum levels of alpha 1-antichymotrypsin and sialic acid may possibly predict the effectiveness of immunotherapy using PSK PURPOSE Immunochemotherapy using PSK used as postoperative adjuvant chemotherapy for colorectal cancer in Japan , is a treatment that depends on the immunocompetence of the host . Therefore , we analyzed the data of Hokuriku district conducted by the CIP study group to compare the long-term survival for preoperative CEA level and PPD reaction . PATIENTS AND METHODS Between February 1991 and March 1993 , 87 patients with primary colon cancer and macroscopic lymph node metastasis ( macroscopic Dukes ' C ) underwent macroscopic curative resection . The patients were r and omly allocated to receive 5-FU/PSK therapy or 5-FU alone . The 7-year disease-free survival ( DFS ) , 7-year overall survival ( OS ) and 7-year cancer death survival ( CDS ) were compared using the preoperative CEA levels and PPD values . RESULTS In cases with preoperative CEA level > or = 3.0 ng/mL , the 7-year DFS , 7-year OS and 7-year CDS were significantly better in the PSK group ( 85.7 , 90.5 , 90.5 % ) than in the control group ( 52.4 , 52.4 , 57 1 % ; p=0.019 , 0.007 , 0.014 , ) . In cases with preoperative PPD level < 19.0 mm , the 7-year DFS , 7-year OS and 7-year CDS were significantly better in the PSK group ( 85.7 , 85.7 , 89.3 % ) than in the control group ( 56.7 , 60.0 , 63.3 % ; p=0.018 , 0.036 , 0.028 ) . Recurrence was significantly less in the PSK group . The DFS tended to be superior in the PSK group ( 87.4 % ) compared to the control group ( 69.9 % ) for hematogenous metastasis . CONCLUSION The present study demonstrated that preoperative CEA and PPD , that can be measured easily in the clinical setting , may be effective indicators of postoperative adjuvant immunochemotherapy using PSK In order to evaluate the efficacy of combined immunochemotherapy with mitomycin-C , tegafur , PSK and /or OK-432 as an adjunct for curatively resected gastric cancer , a prospect i ve r and omized controlled study using the envelope method was performed , in which 266 institutions from around Japan participated . The 3 year survival rates for all cases , and for ps(+)·n(+ ) cases , were insignificantly higher in the immunochemotherapy groups receiving PSK and /or OK-432 than in the control group . However , because 28.2 per cent of the cases were excluded from the final statistical analyses , the results of this study may have question able statistical credibility . Changes in the stimulation index ( SI ) suggest that the administration of PSK may result in an inhibition of the immunosuppressive activity of cancer patients . The high SI group showed a significantly higher 4 year survival rate than the low SI group A multicenter comparative trial of mitomycin C and futraful ( MMC+FT ) , with or without protein-bound polysaccharide ( PSK ) , was carried out by the Study Group for Surgical Adjuvant Chemotherapy for Gastric Cancer from 1978 to 1981 . In 751 patients who underwent macroscopically curative resection preoperative granulocyte and lymphocyte count ratios ( G/L ) were measured . These patients were stratified with a preoperative cut-off of G/L:2.0 , and those with or without PSK were compared in terms of survival rates . In the overall ( non-stratified ) series , the 5-year survival rate of the PSK group was 67.9 % , while that of the non-PSK group was 61.8 % ( p=0.053 ) . In the group with a preoperative G/L ratio of > /=2.0 , the 5-year survival rate of the PSK group ( n=182 ) was 68.7 % , while that of the non-PSK group ( n=182 ) was 55.4 % ( p=0.007 ) . In the cases with a preoperative G/L ratio of < 2.0 , there was no significant difference in the survival rates : 67.1 % in the PSK group ( n=195 ) and 67.8 % in the non-PSK group ( n=192 ) . It was found that PSK extended survival in the group of patients with a preoperative G/L ratio of > /=2.0 , perhaps through restoration of immunocompetence The present study was design ed to assess the effects of the protein-bound polysaccharide PSK on the immunological status of patients with gastrointestinal cancer . Twenty-nine gastric and 18 colorectal cancer patients were r and omly assigned to either the control or PSK group . Patients in the PSK group were given 3.0 g of PSK orally before surgery , either daily or every other day . Patients in the control group received no PSK . The data of peripheral blood lymphocytes ( PBL ) were compared before and after administration of PSK , and those of the regional node lymphocytes ( RNL ) were compared between the control and the PSK group . The results indicate that the effects of PSK were significantly influenced by the duration of administration , but not by the frequency of administration . In the patients belonging to the short term PSK group ( administration < 14 days ) , the response of the PBL to PSK and Con A become significantly stronger compared to before the administration of PSK , whereas the cytotoxicity against K562 and KATO-3 , and the proportion of CD16 + cells increased significantly in those patients belonging to the long term PSK group ( ≧14 days ) . In addition , the proportion of CD9 + 11b + suppressor T cells decreased in the RNL of the short term PSK group , whereas the proportion of CD4 + Leu8 - helper T cells in the RNL increased in the long term PSK group . These results suggest that the oral administration of PSK leads to the suppression of suppressor cells in the RNL . Thus , increased numbers of cytotoxic effector cells appear to be activated in the PBL while helper T cells predominate in the RNL This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence Background A recent report showed that oral adjuvant immunochemotherapy with protein-bound polysaccharide K ( PSK ) and tegafur/uracil ( UFT ) for stage II and III colorectal cancer improves overall survival compared with UFT alone . PSK has been supposed to improve survival through immunological mechanisms such as induction of cytokines , regulation of Th1/Th2 balance , and inhibition of immunosuppressive molecules . Methods We investigated the mechanisms by which PSK influences immunological parameters such as Th1 cells ( IFN-γ-positive CD4 + T cells ) , Th2 cells ( IL-4-positive CD4 + T cells ) , Th1/Th2 ratio , NKT cells ( CD56 + T cells and CD57 + T cells ) , NK cells , and CD25+CD4 + T cells in stage III gastric cancer patients . Patients were r and omly assigned to receive either 3 g PSK plus 300 mg UFT ( PSK group ) or 300 mg UFT alone ( control ) orally each day for at least 1 year following their operation . Results Twenty-one registered patients with stage III gastric cancer were analyzed . The 3-year overall survival was 62.2 % in the PSK group ( n = 10 ) and 12.5 % in the control group ( n = 11 ) ( P = 0.038 ) . Before operation , there were no significant differences in the proportions of Th1 cells , Th2 cells , Th1/Th2 ratio , CD56 + T cells , CD57 + T cells , NK cells , and CD4+CD25 + T cells between PSK and control groups . However , after operation , CD57 + T cells decreased significantly in the PSK group compared to the control ( P = 0.0486 ) . When all patients were analyzed , patients with increased proportion ( > 18 % ) of CD57 + T cells showed worse survival than those with lower ( ≤18 % ) CD57 + T cells ( 3-year survival , 25.0 and 45.7 % , respectively ; P = 0.046 ) , consistent with our previous report that high CD57 + is an indicator of poor prognosis in patients with advanced gastric cancer . However , in the group treated with PSK + UFT , 3-year survival of CD57-high patients was as great as that of CD57-low patients ( 66.7 and 51.4 % , respectively ; P = 0.67 ) . Conclusion The present findings suggest that PSK improves overall survival of stage III gastric cancer patients partly by inhibiting CD57 + T cells , a proven poor prognostic factor in advanced gastric cancer In Japan the st and ard adjuvant treatment after resection of gastric cancer is intravenous mitomycin plus oral fluorouracil . We have assessed the efficacy of protein-bound polysaccharide ( PSK ) in addition to st and ard chemotherapy in patients who had undergone curative gastrectomy at 46 institutions in central Japan . 262 patients were r and omly assigned st and ard treatment alone or with PSK . The minimum follow-up time was 5 years ( range 5 - 7 years ) . PSK improved both the 5-year disease-free rate ( 70.7 vs 59.4 % in st and ard treatment group , p = 0.047 ) and 5-year survival ( 73.0 vs 60.0 % , p = 0.044 ) . The two regimens had only slight toxic effects , consisting of nausea , leucopenia , and liver function impairment , and there were no significant differences between the groups . The treatments were clinical ly well tolerated and compliance was good . Addition of PSK to adjuvant chemotherapy with mitomycin and fluorouracil is beneficial as treatment after curative gastrectomy BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . Minoru Sugita , and the Cooperative Study Group for Esophageal Cancer in Japan We investigated the effect of multimodal therapy in 187 patients with esophageal cancer . All patients were followed up over a period of 5 years . Among the 187 patients , 174 ( 93.1 % ) eligible patients with biopsy-proved esophageal squamous cell carcinoma underwent esophagectomy and were r and omly assigned to receive radiotherapy ( RT ) with or without protein-bound polysaccharide ( PSK ) , or RT plus chemotherapy ( CT ) with or without PSK . The 5-year survival rates of patients with RT , RT + PSK , RT + CT and RT + CT + PSK were 40.0 % , 42.3 % , 29.1 % and 37.2 % , respectively . There was a tendency for longer survival on PSK , but statistical significance was not reached ( RT + CT group versus RT + CT + PSK group : log-rank and generalized Wilcoxon tests , P = .1930 , P = .1034 ) . However , Cox multivariate regression analysis indicated that postoperative therapy with or without PSK was the most significant prognostic factor for patients receiving RT + CT and for the eligible patients . These results indicate that PSK may have a beneficial effect on esophageal carcinoma when given in combination with CT + RT In order to evaluate the combination of immunochemotherapy with mitomycin C ( MMC ) , futraful ( FT ) and PSK , as an adjuvant to surgery for curatively resected gastric cancer , a r and omized controlled study by the sealed envelope method was performed with the participation of 97 hospitals in the Kyushu and Chugoku districts of Japan . The MMC+FT+ PSK group showed a significant increase in 5 year survival from the other groups ( p<0.05 ) . Moreover the survival rate was significantly higher in the MMC+FT+PSK group than in the MMC+FT group ( p<0.01 ) . According to the analysis on stratification , the MMC+FT+PSK group showed the best survival rate in cases with positive lymph node metastases , positive serosal invasion and positive lymph node metastases plus serosal invasion , and in cases of undifferentiated carcinoma by histological type and in those with a preoperative positive PPD reaction ( p<0.01 or p<0.05 ) . Thus , the combination of MMC , FT and PSK was indicated to be useful as an adjuvant immunochemotherapy for those patients with gastric cancer su bmi tted to curative resection A total of 103 patients with advanced gastric carcinoma were r and omized after curative surgery to receive an alternate administration of carbazilquinone ( CQ and PSK ( Krestin ) or carbazilquinone alone . Each course of therapies started 1 week after the surgical operation and therapy schedules consisted of 9 courses . In each course of 6 weeks , CQ ( 2 mg/m2/week ) was administered on day 0 , 8 , and 15 . In combined immunochemotherapy group , PSK was given orally in 3-divided doses of 2 g/m2/day from the day of the third CQ administration for consecutive 4 weeks . Estimated survival rate and cumulative survival curve were compared utilizing the data up to 7 years after the operation . There was no overall significant difference in survival rates between the CQ plus PSK group and the CQ alone group , but a group of patients whose disease was classified as S1 + S2(N1–2 ) survived significantly longer when treated with the combination of CQ and PSK . Neither in more advanced cases ( > S3 or > N3 ) nor in cancers of early stages , the addition of PSK provided an additive effect . The favorable result obtained in one subgroup treated with PSK , suggests that the use of this agent in treating gastric cancers should be carefully evaluated in terms of serosal infiltration and nodal metastasis Background and Methods : It has been shown that T-cell dysfunction , including apoptosis of peripheral blood T cells , commonly occurs in patients receiving chemotherapy . In order to evaluate whether concomitant administration of the oral biological response modifier protein-bound polysaccharide K ( PSK ) could induce anti-apoptotic effects in patients treated with the anti-cancer drug , S-1 , peripheral blood T cells were analyzed for induction of apoptosis , caspase-3 activities and expression of proapoptotic protein Bax and anti-apoptotic protein Bcl-2 in patients with curatively resected stage III gastric cancer , who were r and omly assigned to postoperative adjuvant therapy with S-1 alone ( n = 10 ) or S-1 combined with PSK ( n = 10 ) . Results : T-cell apoptosis 5 weeks after adjuvant therapy was significantly higher in the S-1 group ( 24.1 ± 5.0 % ) than in the S-1 + PSK group ( 19.1 ± 3.9 % ) . S-1 induced T-cell apoptosis and concomitantly elevated caspase-3 activities and Bax expression in peripheral blood T cells . In addition , PSK partially prevented the T-cell apoptosis induced by S-1 . Conclusion : PSK could partially prevent the T-cell apoptosis induced by S-1 |
680 | 18,755,610 | RESULTS Prevention methods remain the key to avoiding this complication .
Prophylactic placement of topical antibiotics can be considered , whereas systemic antibiotics should be reserved for patients who are immunocompromised .
This paper provided a comprehensive review of the etiology , pathophysiology , and current treatment of dry socket in dental practice | OBJECTIVES This paper provides a comprehensive review of the etiology , pathophysiology and current treatment of dry socket . | Treatment of osteitis after surgical removal of the third molar of the m and ible is still a clinical problem . A total of 140 patients undergoing operations for removal of an impacted third molar of the m and ible , were included in a double-blind study . Placebo or antibiotics - azidocillin , erythromycin , clindamycin and doxycycline - were given to the patients preoperatively and for the following 7 days . The concentrations in serum , alveolar serum and m and ibular bone were measured and the postoperative courses - pain , trismus , swelling and wound-healing - were recorded . No correlation was obtained between the antibiotic concentration and the postoperative complaints , except in the azidocillin group on day 2 , in which fewer complaints were noticed in patients with high concentrations of the drug at the time of operations . The 80 patients in the antibiotic groups responded significantly better with respect to wound-healing than the 60 patients in the placebo groups . Only 15 operations lasted more than 15 min and the three of them which subsequently result ed in alveolitis were in the placebo groups . Antibiotics significantly reduced pain on day 7 postoperatively . In general , no statistically significant differences in trismus and swelling could be demonstrated between the patient groups . However , there was a significant difference between the placebo and doxycycline groups with respect to swelling ( day 2 postoperative , P < 0.01 ; day 5 postoperative , P < 0.05 ) . Thus systemically administered antibiotics offered only slight advantages in routine operations of impacted third m and ibular molars , but could decrease the rate of infections after traumatic operations OBJECTIVES The purpose s of this study were to evaluate the use of 0.12 % chlorhexidine gluconate as a prophylactic therapy for the prevention of alveolar osteitis and to further examine subject-based risk factors associated with alveolar osteitis . STUDY DESIGN The trial was a r and omized , double-blind , placebo-controlled , parallel-group study conducted among 279 subjects , each of whom required oral surgery for the removal of a minimum of one impacted m and ibular third molar . Subjects were instructed to rinse twice daily with 15 ml of chlorhexidine or placebo mouthrinse for 30 seconds for 1 week before and 1 week after the surgical extraction s. This regimen included a supervised presurgical rinse . Alveolar osteitis diagnosis was based on the subjective finding of increasing postoperative pain at the surgical site that was not relieved with mild analgesics , supported by clinical evidence of one or more of the following : loss of blood clot , necrosis of blood clot , and exposed alveolar bone . RESULTS In comparison with use of the placebo mouthrinse , prophylactic use of the chlorhexidine mouthrinse result ed in statistically significant ( p < 0.05 ) reductions in the incidence of alveolar osteitis . With chlorhexidine therapy , the subject- and extraction -based incidences of alveolar osteitis in the evaluable subset ( 271 subjects ) were reduced , relative to placebo , by 38 % and 44 % , respectively . The corresponding odds ratios that describe the increased odds of experiencing alveolar osteitis in the placebo group were 1.87 and 2.05 for subject- and extraction -based analyses , respectively . In comparison with nonuse of oral contraceptives , the use of oral contraceptives in female subjects was related to a statistically significant increase in the incidence of alveolar osteitis ( odds ratio = 1.92 , p = 0.035 ) . Relative to male subjects , the observed incidence of alveolar osteitis for female subjects not using oral contraceptives was not statistically significant ( odds ratio = 1.18 , p = 0.64 ) . Smoking did not increase the incidence of alveolar osteitis relative to not smoking ( odds ratio = 1.20 , p = 0.33 ) . CONCLUSIONS These data confirm that the prophylactic use of 0.12 % chlorhexidine gluconate mouthrinse results in a significant reduction in the incidence of alveolar osteitis after the extraction of impacted m and ibular third molars . In addition , oral contraceptive use in females was confirmed to be a risk factor for the development of alveolar osteitis A double-blind study evaluated the ability of 0.12 % chlorhexidine rinse to decrease the incidence of localized alveolar osteitis after the removal of m and ibular third molar teeth . One hundred sixty extraction sites in 80 patients were evaluated . A statistically significant decrease in the incidence of dry socket was seen in patients using the chlorhexidine rinse with no significant adverse reactions . Thus a 0.12 % chlorhexidine rinse is shown to be an effective means of decreasing alveolar osteitis that may follow removal of third molar teeth OBJECTIVE The purpose of this study was to evaluate whether immediate placement of medicated dry socket packing would decrease the incidence of alveolar osteitis ( dry socket ) with lower third molar extraction s. STUDY DESIGN In 100 patients , 200 lower third molars were extracted . One half of the sockets were packed to the crest of the alveolar ridge with a one-quarter-inch radiograph-detectable filament gauze that contained 9 % eugenol , 36 % balsam of Peru , and 55 % petroleum jelly . The medicated packing was removed 1 week after surgery . None of the patients were taking antibiotics . Patients were instructed to increase their oral hygiene before and after surgery and were to use 0.12 % chlorhexidine gluconate 2 days before and 3 days after surgery . RESULTS ; Two hundred bilateral lower third molars of varying difficulty were extracted . The overall alveolar osteitis rate was 34 ( 17 % ) . The immediately packed lower third molar sites had an alveolar osteitis rate of 8 ( 8 % ) . The sockets that were not packed with medicated packing the day of surgery had an alveolar osteitis rate of 26 ( 26 % ) . The difference was statistically significant ( P = .001 ) . CONCLUSION The results of this study suggest that placement of medicated dry socket packing immediately after lower third molar extraction decreases the alveolar osteitis rate PURPOSE This study evaluated the efficacy of topical viscous 2 % lidocaine jelly for the alleviation of pain experienced during the instrumentation of m and ibular third molar extraction sites diagnosed with alveolar osteitis and for pain relief during the postinstrumentation period . PATIENTS AND METHODS Thirty adult patients with a diagnosis of alveolar osteitis in a m and ibular third molar extraction site were included in this prospect i ve , double-blind study . Each patient had their sutures removed , the socket irrigated , and 2 % lidocaine jelly placed on the tip and side of the tongue to blind the patient against the test substances . The subjects were then r and omly distributed into two groups . Group 1 had a nonactive jelly base placed into the socket 2 minutes prior to the placement of a st and ard obtundant dressing . Group 2 had viscous 2 % lidocaine jelly placed into the socket in the same manner . Patients subjectively quantified their pain intensity pretreatment , during instrumentation , immediately postmanipulation , at 5-minute intervals to 30 minutes , and at 45 and 60 minutes . They also subjectively quantified their pain relief at each of the time intervals following instrumentation . RESULTS There was no statistical difference between the pretreatment pain experienced by both groups . The use of 2 % lidocaine jelly had a measurable ( P = .056 ) , but not statistically significant , effect on pain due to instrumentation . At every time interval thereafter , the use of 2 % lidocaine jelly elicited a statistically significant ( P < .05 ) decrease in pain perception , and a statistically significant increase in pain relief when compared with the inactive jelly . CONCLUSION Topical viscous 2 % lidocaine jelly is a useful adjunct during the treatment of alveolar osteitis , especially in the early ( < or = 60 minutes ) postinstrumentation period The incidence of alveolar osteitis can be reduced significantly by lavage of the oral cavity and the area around the lower third molar with an antiseptic mouthwash before extraction . Evaluation of m and ibular third molar extraction s provides indications of preventive measures to avoid the occurrence of alveolar osteitis . A group of r and omly selected patients was given an oral lavage with a phenolated antiseptic mouthwash before extraction . The use of an oral lavage before extraction result ed in fewer instances of alveolar osteitis than in extraction s that were not preceded by lavage Prophylactic metronidazole was found to be an effective means of preventing ' dry socket ' after routine dental extraction s. The oral anaerobic bacterial may be implicated therefore in the development of the disorder . It has been confirmed in this study that ' dry socket ' occurs following three per cent of routine dental extraction s and almost exclusively in the m and ible . The causes of the condition are probably numerous and may even vary from patient to patient , but the control of infection by anerobic organisms may be important in its prevention or early resolution . The prophylactic administration of metronidazole ( Flagyl ) has been shown to be a simple and effective method of prevention which would suggest the implication of anaerobic organisms in ' dry socket ' . The drug appears to be free from side effects when a dosage of 200 mgs eight hourly for three days is given Abstract Gelfoam saturated with sterile lincomycin solution was effective in the reduction of dry socket in subjects who had undergone extraction of impacted m and ibular third molars . The occurrence of dry socket was reduced to 1.1 per cent in the patients who received topical lincomycin in Gelfoam , as compared to 7.8 per cent when the Gelfoam contained saline solution instead of lincomycin |
681 | 24,398,141 | IL-6 is the most corroborated predictive biomarker based on its consistent predictive value in two different trials . | BACKGROUND Vascular endothelial growth factor (VEGF)-targeted therapy is the currently st and ard treatment for advanced and metastatic renal cell carcinoma ( RCC ) .
Multiple c and i date predictive and prognostic biomarkers have been evaluated .
We performed a systematic review and grade d the available evidence on the biomarkers for VEGF-targeted therapy in RCC . | The development of tumor biomarkers ready for clinical use is complex . We propose a refined system for biomarker study design , conduct , analysis , and evaluation that incorporates a hierarchal level of evidence scale for tumor marker studies , including those using archived specimens . Although fully prospect i ve r and omized clinical trials to evaluate the medical utility of a prognostic or predictive biomarker are the gold st and ard , such trials are costly , so we discuss more efficient indirect " prospect ive-retrospective " design s using archived specimens . In particular , we propose new guidelines that stipulate that 1 ) adequate amounts of archived tissue must be available from enough patients from a prospect i ve trial ( which for predictive factors should generally be a r and omized design ) for analyses to have adequate statistical power and for the patients included in the evaluation to be clearly representative of the patients in the trial ; 2 ) the test should be analytically and preanalytically vali date d for use with archived tissue ; 3 ) the plan for biomarker evaluation should be completely specified in writing before the performance of biomarker assays on archived tissue and should be focused on evaluation of a single completely defined classifier ; and 4 ) the results from archived specimens should be vali date d using specimens from one or more similar , but separate , studies Purpose : Plasma proteins [ vascular endothelial growth factor ( VEGF ) , soluble VEGF receptor 2 ( sVEGFR-2 ) , carbonic anhydrase IX ( CAIX ) , tissue inhibitor of metalloproteinase 1 ( TIMP-1 ) , and Ras p21 ] and one tumor gene ( VHL ) were analyzed to identify prognostic biomarkers or indicators of response to sorafenib in a subset of patients enrolled in the Treatment Approaches in Renal Cancer Global Evaluation Trial . Experimental Design : Nine hundred three patients with advanced renal cell carcinoma ( RCC ) were r and omized to 400 mg sorafenib twice a day or placebo . Sample s collected at baseline and after 3 and 12 weeks were subjected to enzyme-linked immunosorbent assays . VHL exons were sequenced from tumor biopsies . Results : Baseline biomarker data were available for VEGF ( n = 712 ) , sVEGFR-2 ( n = 713 ) , CAIX ( n = 128 ) , TIMP-1 ( n = 123 ) , Ras p21 ( n = 125 ) , and VHL mutational status ( n = 134 ) . Higher Eastern Cooperative Oncology Group performance status ( ECOG PS ) score correlated with elevated baseline VEGF ( P < 0.0001 ) and a higher incidence of VHL mutations ( P = 0.008 ) , whereas higher Memorial Sloan-Kettering Cancer Center ( MSKCC ) score correlated with elevated VEGF ( P < 0.0001 ) , CAIX ( P = 0.027 ) , and TIMP-1 ( P = 0.0001 ) . Univariable analyses of baseline levels in the placebo cohort identified VEGF ( P = 0.0024 ) , CAIX ( P = 0.034 ) , TIMP-1 ( P = 0.001 ) , and Ras p21 ( P = 0.016 ) as prognostic biomarkers for survival . TIMP-1 remained prognostic for survival in a multivariable analysis model ( P = 0.002 ) that also included ECOG PS , MSKCC score , and the other biomarkers assayed . In the placebo cohort , TIMP-1 ( P < 0.001 ) and Ras p21 ( P = 0.048 ) levels increased at 12 weeks . In the sorafenib cohort , VEGF levels increased at 3 and 12 weeks of treatment ( both weeks P < 0.0001 ) , whereas sVEGFR-2 ( both weeks P < 0.0001 ) and TIMP-1 levels ( P = 0.002 , week 3 ; P = 0.006 , week 12 ) decreased . Conclusions : VEGF , CAIX , TIMP-1 , and Ras p21 levels were prognostic for survival in RCC patients . Of these , TIMP-1 has emerged as being independently prognostic . Clin Cancer Res ; 16(19 ) ; 4853–63 . © 2010 AACR BACKGROUND Previous studies suggest that expression of hypoxia markers may be associated with response to antiangiogenic drugs . Thus , we aim ed to identify predictors of sunitinib outcome in clear-cell renal cell carcinoma ( ccRCC ) . PATIENTS AND METHODS The expression of eight key proteins related to hypoxia ( CAIX , HIF1A , HIF2A , VEGFA , VEGFR1 , VEGFR2 , VEGFR3 and PDGFRB ) and P-glycoprotein were assessed by immunohistochemistry in 67 primary ccRCC sample s from prospect ively recruited patients treated with first-line sunitinib . The proteins expression , VHL inactivation and EGLN3 mRNA content were compared with the patients ' response to sunitinib . RESULTS High expression of HIF2A and PDGFRB was associated with better sunitinib RECIST objective response ( P = 0.024 and P = 0.026 ; respectively ) and increased VEGFR3 expression was associated with longer progression-free survival ( P = 0.012 ) . VEGFR3 overexpression showed a negative correlation with VEGFR3 polymorphism rs307826 ( P = 0.002 ) , a sunitinib resistance predictor . With respect to overall survival ( OS ) , high VEGFA was associated with short ( P = 0.009 ) and HIF2A with long ( P = 0.048 ) survival times . High EGLN3 mRNA content was associated with shorter OS ( P = 0.023 ) . CONCLUSIONS We found an association between several proteins involved in hypoxia and sunitinib efficacy . In addition , low VEGFR3 expression was associated with worse outcome and with VEGFR3 rs307826 variant allele , reinforcing VEGFR3 as a marker of sunitinib resistance BACKGROUND Metastatic renal cell carcinoma ( mRCC ) patients treated with anti-vascular endothelial growth factor ( VEGF ) therapies demonstrate promising outcomes but not all patients benefit . Factors that predict response remain to be eluci date d. PATIENTS AND METHODS Nephrectomy material from 37 patients with mRCC receiving bevacizumab + /- erlotinib was used for protein and gene expression assessment . Protein lysates were subjected to reverse-phase protein array profiling . RNA extracts were used to carry out gene expression microarray-based profiling . Normalized protein and gene expression data were correlated with overall survival ( OS ) and progression-free survival ( PFS ) using univariate Cox hazard model and linear regression . Immunoblotting was carried out to vali date the results . RESULTS High protein levels of AMP-activated protein kinase and low levels of cyclin B1 ( CCNB1 ) were associated with longer OS and PFS . Further validation revealed reduced expression and activation of phosphoinositide 3-kinase ( PI3 K ) pathway components and cell cycle factors in patients with prolonged survival after therapy . Gene expression analysis revealed up-regulation of PI3K- and cell cycle-related pathways in patients with shorter PFS . CONCLUSIONS The OS and PFS of bevacizumab + /- erlotinib-treated patients with renal cell carcinoma were associated with changes in expression of protein and gene expression markers related to PI3 K pathway and cell cycle signaling BACKGROUND We conducted a phase 3 , r and omized , double-blind , placebo-controlled trial of sorafenib , a multikinase inhibitor of tumor-cell proliferation and angiogenesis , in patients with advanced clear-cell renal-cell carcinoma . METHODS From November 2003 to March 2005 , we r and omly assigned 903 patients with renal-cell carcinoma that was resistant to st and ard therapy to receive either continuous treatment with oral sorafenib ( at a dose of 400 mg twice daily ) or placebo ; 451 patients received sorafenib and 452 received placebo . The primary end point was overall survival . A single planned analysis of progression-free survival in January 2005 showed a statistically significant benefit of sorafenib over placebo . Consequently , crossover was permitted from placebo to sorafenib , beginning in May 2005 . RESULTS At the January 2005 cutoff , the median progression-free survival was 5.5 months in the sorafenib group and 2.8 months in the placebo group ( hazard ratio for disease progression in the sorafenib group , 0.44 ; 95 % confidence interval [ CI ] , 0.35 to 0.55 ; P<0.01 ) . The first interim analysis of overall survival in May 2005 showed that sorafenib reduced the risk of death , as compared with placebo ( hazard ratio , 0.72 ; 95 % CI , 0.54 to 0.94 ; P=0.02 ) , although this benefit was not statistically significant according to the O'Brien-Fleming threshold . Partial responses were reported as the best response in 10 % of patients receiving sorafenib and in 2 % of those receiving placebo ( P<0.001 ) . Diarrhea , rash , fatigue , and h and -foot skin reactions were the most common adverse events associated with sorafenib . Hypertension and cardiac ischemia were rare serious adverse events that were more common in patients receiving sorafenib than in those receiving placebo . CONCLUSIONS As compared with placebo , treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal-cell carcinoma in whom previous therapy has failed ; however , treatment is associated with increased toxic effects . ( Clinical Trials.gov number , NCT00073307 [ Clinical Trials.gov ] . ) BACKGROUND No biomarkers that could guide patient selection for treatment with the anti-VEGF monoclonal antibody bevacizumab have been identified . We assessed whether genetic variants in the VEGF pathway could act as biomarkers for bevacizumab treatment outcome . METHODS We investigated DNA from white patients from two phase 3 r and omised studies . In AViTA , patients with metastatic pancreatic adenocarcinoma were r and omly assigned to receive gemcitabine and erlotinib plus either bevacizumab or placebo . In AVOREN , patients with metastatic renal-cell carcinoma were r and omly assigned to receive interferon alfa-2a plus either bevacizumab or placebo . We assessed the correlation of 138 SNPs in the VEGF pathway with progression-free survival and overall survival in a sub population of patients from AViTA . Significant findings were confirmed in a sub population of patients from AVOREN and functionally studied at the molecular level . FINDINGS We investigated DNA of 154 patients from AViTA , of whom 77 received bevacizumab , and 110 patients from AVOREN , of whom 59 received bevacizumab . Only rs9582036 , a SNP in VEGF receptor 1 ( VEGFR1 or FLT1 ) , was significantly associated with overall survival in the bevacizumab group of AViTA after correction for multiplicity ( per-allele hazard ratio [ HR ] 2·1 , 95 % CI 1·45 - 3·06 , p=0·00014 ) . This SNP was also associated with progression-free survival ( per-allele HR 1·89 , 1·31 - 2·71 , p=0·00081 ) in bevacizumab-treated patients from AViTA . AC and CC carriers of this SNP exhibited HRs for overall survival of 2·0 ( 1·19 - 3·36 ; p=0·0091 ) and 4·72 ( 2·08 - 10·68 ; p=0·0002 ) relative to AA carriers . No effects were seen in placebo-treated patients and a significant genotype by treatment interaction ( p=0·041 ) was recorded , indicating that the VEGFR1 locus containing this SNP serves as a predictive marker for bevacizumab treatment outcome in AViTA . Fine-mapping experiments of this locus identified rs7993418 , a synonymous SNP affecting tyrosine 1213 in the VEGFR1 tyrosine-kinase domain , as the functional variant underlying the association . This SNP causes a shift in codon usage , leading to increased VEGFR1 expression and downstream VEGFR1 signalling . This VEGFR1 locus correlated significantly with progression-free survival ( HR 1·81 , 1·08 - 3·05 ; p=0·033 ) but not overall survival ( HR 0·91 , 0·45 - 1·82 , p=0·78 ) in the bevacizumab group in AVOREN . INTERPRETATION A locus in VEGFR1 correlates with increased VEGFR1 expression and poor outcome of bevacizumab treatment . Prospect i ve assessment is underway to vali date the predictive value of this novel biomarker . FUNDING F Hoffmann-La Roche Anti-angiogenic therapy benefits many patients with advanced renal cell carcinoma ( RCC ) , but there is still a need for predictive markers that help in selecting the best therapy for individual patients . MicroRNAs ( miRNAs ) regulate cancer cell behavior and may be attractive biomarkers for prognosis and prediction of response . Forty-four patients with RCC were recruited into this observational prospect i ve study conducted in nine Spanish institutions . Peripheral blood sample s were taken before initiation of therapy and 14 days later in patients receiving first-line therapy with sunitinib for advanced RCC . miRNA expression in peripheral blood was assessed using microarrays and L2 boosting was applied to filtered miRNA expression data . Several models predicting poor and prolonged response to sunitinib were constructed and evaluated by binary logistic regression . Blood sample s from 38 patients and 287 miRNAs were evaluated . Twenty-eight miRNAs of the 287 were related to poor response and 23 of the 287 were related to prolonged response to sunitinib treatment . Predictive models identified population s with differences in the established end points . In the poor response group , median time to progression was 3.5 months and the overall survival was 8.5 , whereas in the prolonged response group these values were 24 and 29.5 months , respectively . Ontology analyses pointed out to cancer-related pathways , such angiogenesis and apoptosis . miRNA expression signatures , measured in peripheral blood , may stratify patients with advanced RCC according to their response to first-line therapy with sunitinib , improving diagnostic accuracy . After proper validation , these signatures could be used to tailor therapy in this setting BACKGROUND Sunitinib is a tyrosine kinase inhibitor with proven efficacy in renal-cell carcinoma , but some patients do not respond or need dose reductions due to toxicity . Because there are no vali date d molecular predictors of response or toxicity to sunitinib , we aim ed to identify genetic markers predictive of outcome and toxic effects . METHODS In our observational , prospect i ve study we enrolled previously untreated adults ( ≥ 18 years ) with clear-cell renal-cell carcinoma at 15 institutions in the Spanish Oncology Genitourinary Group in Spain . Patients received sunitinib according to local practice guidelines . We assessed RECIST response , progression-free survival ( PFS ) , overall survival , and toxicity of sunitinib with 16 key polymorphisms in nine genes : VEGFR2 ( rs2305948 and rs1870377 ) , VEGFR3 ( rs307826 , rs448012 , and rs307821 ) , PDGFR-α ( rs35597368 ) , VEGF-A ( rs2010963 , rs699947 , and rs1570360 ) , IL8 ( rs1126647 ) , CYP3A4 ( rs2740574 ) , CYP3A5 ( rs776746 ) , ABCB1 ( rs1045642 , rs1128503 , and rs2032582 ) , and ABCB2 ( rs2231142 ) . We assessed associations with efficacy and toxicity by use of univariable and multivariable analyses ( with clinical factors associated with outcomes as covariates ) . We adjusted for multiplicity using the Bonferroni method ; p values of less than 0·0031 before adjustment were deemed to still be significant after adjustment . FINDINGS We enrolled 101 patients between Oct 10 , 2007 , and Dec 13 , 2010 . 95 of these patients were included in toxicity analyses and 89 in the efficacy analyses . Two VEGFR3 missense polymorphisms were associated with reduced PFS with sunitinib on multivariable analysis : rs307826 ( hazard ratio [ HR ] per allele 3·57 , 1·75 - 7·30 ; p(unadjusted)=0·00049 , p(adjusted)=0·0079 ) and rs307821 ( 3·31 , 1·64 - 6·68 ; p(unadjusted)=0·00085 , p(adjusted)=0·014 ) . The CYP3A5 * 1 ( rs776746 ) high metabolising allele was associated in a multivariable analysis with an increased risk of dose reductions due to toxicity ( HR per allele 3·75 , 1·67 - 8·41 ; p(unadjusted)=0·0014 , p(adjusted)=0·022 ) . No other SNPs were associated with sunitinib response or toxicity . INTERPRETATION Polymorphisms in VEGFR3 and CYP3A5 * 1 might be able to define a subset of patients with renal-cell carcinoma with decreased sunitinib response and tolerability . If confirmed , these results should promote interventional studies testing alternative therapeutic approaches for patients with such variants . FUNDING Pfizer Despite years of research and hundreds of reports on tumor markers in oncology , the number of markers that have emerged as clinical ly useful is pitifully small . Often initially reported studies of a marker show great promise , but subsequent studies on the same or related markers yield inconsistent conclusions or st and in direct contradiction to the promising results . It is imperative that we attempt to underst and the reasons why multiple studies of the same marker lead to differing conclusions . A variety of method ological problems have been cited to explain these discrepancies . Unfortunately , many tumor marker studies have not been reported in a rigorous fashion , and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of study results . The development of guidelines for the reporting of tumor marker studies was a major recommendation of the National Cancer Institute – European Organisation for Research and Treatment of Cancer ( NCI – EORTC ) First International Meeting on Cancer Diagnostics in 2000 . As for the successful CONSORT initiative for r and omized trials and for the STARD statement for diagnostic studies , we suggest guidelines to provide relevant information about the study design , preplanned hypotheses , patient and specimen characteristics , assay methods , and statistical analysis methods . In addition , the guidelines provide helpful suggestions on how to present data and important elements to include in discussion s. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and underst and the context in which the conclusions apply The objective of this study was to independently evaluate the objective response rate of sorafenib and sorafenib plus low‐dose interferon‐alfa 2b ( IFN ) as frontline therapy in patients with metastatic renal cell carcinoma ( mRCC ) |
682 | 30,112,181 | The trials indicate that recreational soccer may result in improvement in cardiovascular function , body composition and functional ability , although no significant changes were observed in postural balance . | Background Strategies to prevent or attenuate the age-related decline in physical and physiological function and reduce chronic disease risk factors are of clinical importance .
Objective To examine the health benefits of recreational soccer in middle-aged and older adults . | CONTEXT R and omized controlled trials have been developed essentially in the context of pharmacological treatments ( ie , oral drugs ; intra-articular injection ; and topical , intramuscular , and intravenous treatments ) , but assessment of the effectiveness of nonpharmacological treatments ( ie , surgery , arthroscopy , joint lavage , rehabilitation , acupuncture , and education ) presents specific issues . OBJECTIVES To compare the quality of articles of nonpharmacological and pharmacological treatments of hip and knee osteoarthritis and to identify specific method ological issues related to assessment of nonpharmacological treatments . DESIGN AND SETTING We search ed MEDLINE and the Cochrane Central Register of Controlled Trials for articles of r and omized controlled trials published between January 1 , 1992 , and February 28 , 2002 , in 28 general medical and specialty journals with high impact factors and assessing nonpharmacological and pharmacological treatments in patients with hip or knee osteoarthritis . MAIN OUTCOME MEASURES The quality of the methods reported in the selected articles was assessed by 2 independent review ers using the Jadad scale , the Delphi list , and guidelines found in the Users ' Guides to the Medical Literature . Investigators also used a checklist of items developed by the authors to analyze study characteristics . RESULTS A total of 110 articles were included in the analysis ; 50 ( 45.5 % ) assessed nonpharmacological treatments and 60 ( 54.5 % ) assessed pharmacological treatments . Reports of nonpharmacological treatments had a lower global quality score than did reports of pharmacological treatments as measured by the Jadad scale ( mean [ SD ] score , 1.4 [ 1.3 ] vs 3.0 [ 1.3 ] ) and the Delphi list ( mean [ SD ] score , 5.2 [ 1.5 ] vs 7.5 [ 1.1 ] ) . Lack of reporting adequate r and om sequence generation and intention-to-treat analyses were found in both nonpharmacological and pharmacological articles . Nonpharmacological treatments were less often compared with a placebo than were pharmacological treatments ( 28.0 % of articles vs 71.7 % ) . Compared with pharmacological articles , nonpharmacological articles less often described blinding of patients ( 26.0 % vs 96.7 % ) , care providers ( 6.0 % vs 81.7 % ) , and outcome assessors ( 68.0 % vs 98.3 % ) . Care providers ' skill levels could influence treatment effect in 84.0 % of nonpharmacological articles vs 23.3 % of pharmacological articles . CONCLUSIONS In this analysis of reports of hip and knee osteoarthritis therapy , nonpharmacological articles scored lower than pharmacological articles in terms of quality . Assessment s of nonpharmacological treatments must take into consideration additional method ological issues The present study investigated whether football has favorable effects in the treatment of mild-to-moderate arterial hypertension in untrained middle-aged men . Twenty-five untrained males aged 31 - 54 year with mild-to-moderate hypertension were r and omized to a football training group ( FTG , two 1-h sessions per week ) and a control group receiving physician-guided traditional recommendations on cardiovascular risk factor modification ( doctoral advice group , DAG ) . After 3 months , systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) were lowered ( P<0.05 ) by 12 + /- 3 and 7 + /- 1 mmHg in FTG , respectively , whereas no significant changes were observed for DAG , with the 3 months values being lower ( P<0.05 ) in FTG than DAG ( SBP : 138 + /- 2 vs 148 + /- 2 mmHg ; DBP : 84 + /- 2 vs 92 + /- 2 mmHg ) . The resting heart rate was lowered ( P<0.05 ) by 12 + /- 2 b.p.m . in FTG after 3 months ( 67 + /- 3 vs 79 + /- 3 b.p.m . ) , whereas no change was observed for DAG . After 3 months , FTG had higher ( P<0.05 ) VO(2max ) ( 8 + /- 2 % ; 35.0 + /- 1.6 vs 32.5 + /- 1.3 mL/min/kg ) and lower ( P<0.05 ) fat mass ( 1.7 + /- 0.6 kg ) , whereas no change was observed for DAG . In conclusion , football training is an attractive non-pharmacological supplement to the treatment of mild-to-moderate arterial hypertension in untrained middle-aged men The effects of 16 weeks of football or strength training on performance and functional ability were investigated in 26 ( 68.2 ± 3.2 years ) untrained men r and omized into a football ( FG ; n = 9 ) , a strength training ( ST ; n = 9 ) , or a control group ( CO ; n = 8) . FG and ST trained 1.6 ± 0.1 and 1.5 ± 0.1 times per week , respectively , with higher ( P < 0.05 ) average heart rate ( HR ) ( ∼140 vs 100 bpm ) and time > 90%HRmax ( 17 vs 0 % ) in FG than ST , and lower ( P < 0.05 ) peak blood lactate in FG than ST ( 7.2 ± 0.9 vs 10.5 ± 0.6 mmol/L ) . After the intervention period ( IP ) , VO₂ max ( 15 % ; P < 0.001 ) , cycle time to exhaustion ( 7 % ; P < 0.05 ) , and Yo-Yo Intermittent Endurance Level 1 performance ( 43 % ; P < 0.01 ) were improved in FG , but unchanged in ST and CO . HR during walking was 12 % and 10 % lower ( P < 0.05 ) in FG and ST , respectively , after IP . After IP , HR and blood lactate during jogging were 7 % ( P < 0.05 ) and 30 % lower ( P < 0.001 ) in FG , but unchanged in ST and CO . Sit-to-st and performance was improved ( P < 0.01 ) by 29 % in FG and 26 % in ST , but not in CO . In conclusion , football and strength training for old men improves functional ability and physiological response to submaximal exercise , while football additionally elevates maximal aerobic fitness and exhaustive exercise performance The study tested the hypothesis that long-term soccer training has positive impact on cardiovascular profile , body composition , bone health , and physical capacity in inactive , pre-menopausal women with mild hypertension . The study applied a r and omized controlled design in which physically inactive middle-aged women were separated into a soccer training group ( n=19 ; SOC ) and a control group ( n=12 ; CON ) . SOC performed 128±29 ( ±SD ) one-h small-sided soccer training sessions over one year . Blood pressure , body composition , blood lipid profile , and fitness level were determined pre- and post-intervention . Over one year , mean arterial pressure decreased more in SOC than in CON ( -5±7 vs + 4±5 mmHg ; P<.05 ) . Total-body fat mass decreased more ( P<.05 ) in SOC than in CON ( -2.5±2.5 vs + 0.6±3.2 kg ; P<.05 ) , while the change scores for lean body mass were not significantly different in SOC ( 2.6±2.7 kg ) compared to CON ( 1.1±1.9 kg , P=.09 ) . Over one year , change scores in whole-body bone mineral density ( 0.004±0.032 vs -0.019±0.026 g·cm2 ) as well as bone mineral content ( 30±70 vs -39±113 g ) were positive in SOC compared to CON ( P<.05 ) . Post-intervention plasma triglycerides decreased more ( -0.1±0.7 vs + 0.2±0.2 mmol·L-1 ) and HDL cholesterol increased more ( 0.2±0.7 vs -0.2±0.2 mmol·L-1 ) in SOC than in CON ( P<.05 ) . Yo-Yo intermittent endurance level 1 ( 122±105 vs 2±21 % ) and 20-m sprint performance ( 6±6 vs -1±2 % ) increased more ( P<.05 ) in SOC than in CON . In conclusion , long-term soccer training result ed in broad-spectrum improvements in the health profile of untrained , pre-menopausal women with mild hypertension , including cardiovascular , metabolic , and musculo-skeletal benefits Summary And rogen deprivation therapy ( ADT ) for prostate cancer ( PCa ) impairs musculoskeletal health . We evaluated the efficacy of 32-week football training on bone mineral density ( BMD ) and physical functioning in men undergoing ADT for PCa . Football training improved the femoral shaft and total hip BMD and physical functioning parameters compared to control . Introduction ADT is a mainstay in PCa management . Side effects include decreased bone and muscle strength and increased fracture rates . The purpose of the present study was to evaluate the effects of 32 weeks of football training on BMD , bone turnover markers ( BTMs ) , body composition , and physical functioning in men with PCa undergoing ADT . Methods Men receiving ADT > 6 months ( n = 57 ) were r and omly allocated to a football training group ( FTG ) ( n = 29 ) practising 2–3 times per week for 45–60 min or to a st and ard care control group ( CON ) ( n = 28 ) for 32 weeks . Outcomes were total hip , femoral shaft , femoral neck and lumbar spine ( L2-L4 ) BMD and systemic BTMs ( procollagen type 1 amino-terminal propeptide , osteocalcin , C-terminal telopeptide of type 1 collagen ) . Additionally , physical functioning ( postural balance , jump height , repeated chair rise , stair climbing ) was evaluated . Results Thirty-two-week follow-up measures were obtained for FTG ( n = 21 ) and for CON ( n = 20 ) , respectively . Analysis of mean changes from baseline to 32 weeks showed significant differences between FTG and CON in right ( 0.015 g/cm2 ) and left ( 0.017 g/cm2 ) total hip and in right ( 0.018 g/cm2 ) and left ( 0.024 g/cm2 ) femoral shaft BMD , jump height ( 1.7 cm ) and stair climbing ( −0.21 s ) all in favour of FTG ( p < 0.05 ) . No other significant between-group differences were observed . Conclusions Compared to st and ard care , 32 weeks of football training improved BMD at clinical ly important femoral sites and parameters of physical functioning in men undergoing ADT for PCa The study examined the effects of 1 year of football or strength training on cardiovascular function in 65- to 75-year-old men . Twenty-six untrained men ( age : 68.2 ± 3.2 years ) were r and omized to football training ( FTG ; n = 9 ) , strength training ( STG ; n = 9 ) , or control ( CG ; n = 8) . In FTG , left ventricular ( LV ) internal diastolic diameter , end-diastolic volume , and mass index were 8 % , 21 % , and 18 % higher ( P < 0.01 ) , respectively , after 12 months , with no changes in STG and CG . After 12 months , LV ejection fraction was increased ( P < 0.05 ) by 8 % and 5 % in FTG and STG , respectively , and systolic longitudinal two-dimensional strain by 8 % and 6 % , whereas right ventricular systolic function improved ( P < 0.05 ) by 22 % in FTG , but not in STG and CG . In FTG , LV diastolic mitral inflow ( E/A ) ratio and peak early diastolic velocity ( E ' ) improved ( P < 0.05 ) by 25 % and 12 % , respectively , after 12 months , with no changes in STG and CG . In FTG , maximum oxygen uptake was 16 % and 18 % higher ( P < 0.001 ) after 4 and 12 months , respectively , and resting heart rate was 6 and 8 beats per minute lower ( P < 0.001 ) , respectively , with no changes in STG and CG . In conclusion , football training elicited superior cardiovascular effects compared with strength training in elderly untrained men Abstract We investigated the musculoskeletal health profile of elite female football players ( ET ) in comparison to untrained ( UT ) young women subjected to 16 weeks of football training ( 2 × 1 h per week ) . DXA scans , blood sampling , sprint testing and Flamingo postural balance testing were carried out for 27 Danish national team players and 28 untrained women , with eight women being tested after training . At baseline total BMD and BMC were 13 % ( 1.305 ± 0.050 versus 1.159 ± 0.056 g · cm−2 ) and 23 % ( 3047 ± 235 versus 2477 ± 526 g ) higher ( P < 0.001 ) and leg BMD and BMC were 24 and 28 % higher ( P < 0.01 ) in ET than in UT . Resting plasma osteocalcin was 45 % higher in ET than in UT ( 28.8 ± 10.9 versus 19.9 ± 9.9 µg · L−1 , P < 0.05 ) . Total lean body mass was 14 % higher ( 50.4 ± 3.3 versus 44.3 ± 4.0 kg ) in ET compared with UT , with no difference in total body mass . The number of Flamingo test falls was 56–63 % less ( P < 0.01 ) and 30 m sprinting speed was 31 % faster ( P < 0.001 ) in ET than UT . After 16 weeks of football training for UT , lean body mass increased by 1.4 ± 0.5 kg and the number of left leg falls decreased by 29 % ( P < 0.05 ) . No significant changes occurred in BMD or BMC , but plasma osteocalcin increased ( P < 0.05 ) by 37 % . In summary , elite women footballers have an impressive musculoskeletal health profile compared with untrained controls , but short-term football training seems to reduce the risk of falls and increase bone formation Abstract The aim of this study was to evaluate the physiological effects of soccer and Zumba among female hospital employees during a 40-week intervention period . Hospital employees ( n = 118 ) were cluster-r and omised to either a soccer group ( n = 41 ) , a Zumba group ( n = 38 ) or a control group ( n = 39 ) . Both training groups were encouraged to perform 1-h training sessions twice a week outside working hours throughout the 40 weeks . Maximal oxygen uptake ( VO2 max ) , blood pressure and body composition were measured and blood sample s collected before and after the intervention period . Using intention-to-treat analyses , the Zumba group improved VO2 max compared to the control group ( 2.2 mL · kg−1 · min−1 , 95 % CI , 0.9 , 3.5 , P = 0.001 ) , with no significant increase in the soccer group ( 1.1 mL · kg−1 · min−1 , 95 % CI , −0.2 , 2.4 , P = 0.08 ) . Both intervention groups reduced total body fat mass and fat percentage compared to the control group ( P < 0.01 ) . In the soccer group , but not the Zumba group , a significant difference in lower limb bone mineral density and bone mineral content was observed in comparison to the control group ( P < 0.01 ) . Furthermore , the soccer group , but not the Zumba group , had increased plasma osteocalcin ( 6.6 µg · L−1 , 95 % CI , 2.2 , 11.0 , P < 0.01 ) and decreased plasma leptin ( −6.6 µg · L−1 , 95 % CI , −12.5 , −0.7 , P < 0.05 ) compared to the control group . The present study suggests that workplace-initiated soccer and Zumba training comprising 1–2 sessions per week outside working hours may promote physiological health among female hospital employees Abstract The health benefits of playing football and the importance of exercise and social contact for healthy ageing are well established , but few older adults in the UK take enough exercise . Football is popular , flexible in format and draws players into engrossing , effortful and social exercise , but the physical dem and s of play at full speed may make it unsustainable for some older adults . Restricted to walking pace , will play still be engaging ? Will health benefits be retained ? Will physical dem and s remain manageable ? This pilot study aims to investigate : ( 1 ) the experience of older adults playing walking football every week , is it sustainable and rewarding , ( 2 ) the intensity and locomotor pattern of walking football , ( 3 ) the scale and nature of walking football health benefits and ( 4 ) possible cognitive benefits of playing walking football through measures of processing speed , selective and divided attention and updating and inhibition components of executive function . ‘ Walking football ’ and ‘ waiting list ’ groups were compared before and after 12 weeks of one-hour per week football . Walking football was found to be engaging , sustainable for older adults and moderately intensive ; however , selective health and cognitive benefits were not found from this brief intervention . Highlights Walking football is a lower impact but authentic form of football that enables older players to extend their active participation . Walking football is enjoyable and moderately dem and ing and may be a sustainable form of exercise for older adults . Health and cognitive benefits to playing walking football were not found The effects of 52 weeks of soccer or resistance training were investigated in untrained elderly men . The subjects aged 68.1±2.1 yrs were r and omised into a soccer ( SG ; n = 9 ) , a resistance ( RG ; n = 9 ) and a control group ( CG ; n = 8) . The subjects in SG and RG , respectively , trained 1.7±0.3 and 1.8±0.3 times weekly on average during the intervention period . Muscle function and body composition were determined before and after 16 and 52 weeks of the intervention period . In SG , BMI was reduced by 1.5 % and 3.0 % ( p<0.05 ) after 16 and 52 weeks , respectively , unchanged in RG and 2 % higher ( p<0.05 ) in CG after 52 weeks of the intervention period . In SG , the response to a glucose tolerance test was 16 % lower ( p<0.05 ) after 16 wks , but not after 52 wks , compared to before the intervention period , and unchanged in RG and CG . In SG , superoxide dismutase-2 expression was 59 % higher ( p<0.05 ) after 52 wks compared to before the intervention period , and unchanged in RG and CG . In RG , upper body lean mass was 3 and 2 % higher ( p<0.05 ) after 16 and 52 wks , respectively , compared to before the intervention period , and unchanged in SG and CG . In RG , Akt-2 expression increased by 28 % ( p<0.01 ) and follistatin expression decreased by 38 % ( p<0.05 ) during the 52-wk intervention period , and was unchanged in SG and CG . Thus , long-term soccer training reduces BMI and improves anti-oxidative capacity , while long-term resistance training impacts muscle protein enzyme expression and increases lean body mass in elderly men . Trial Registration Clinical Trials.gov : Purpose The present study examined the effects of 15 weeks of soccer training and two different swimming training protocol s on bone turnover in sedentary middle-aged women . Methods Eighty-three premenopausal mildly hypertensive women [ age : 45 ± 6 ( ±SD ) years , height : 165 ± 6 cm , weight : 80.0 ± 14.1 kg , body fat : 42.6 ± 5.7 % , systolic blood pressure/diastolic blood pressure : 138 ± 6/85 ± 3 mmHg ] were r and omized into soccer training ( SOC , n = 21 ) , high-intensity intermittent swimming ( HS , n = 21 ) , moderate-intensity swimming ( MS , n = 21 ) intervention groups , and a control group ( C , n = 20 ) . The training groups completed three sessions per week for 15 weeks . DXA scans were performed and resting blood sample s were drawn pre- and post-intervention . Results In SOC , plasma osteocalcin , procollagen type I N propeptide and C-terminal telopeptide increased ( P < 0.05 ) by 37 ± 15 , 52 ± 23 and 42 ± 18 % , respectively , with no changes in MS , HS and C. The intervention-induced increase in SOC was larger ( P < 0.05 ) than in MS , HS and C. In SOC , leg BMC increased ( P < 0.05 ) by 3.1 ± 4.5 % , with a larger increase in SOC than in C. Femoral shaft and trochanter bone mineral density ( BMD ) increased ( P < 0.05 ) by 1.7 ± 1.9 and 2.4 ± 2.9 % , respectively , in SOC , with a greater ( P < 0.05 ) change in SOC than in MS and C , whereas total body and total leg BMD did not change in any of the groups . Conclusion In conclusion , 15 weeks of soccer training with sedentary middle-aged women caused marked increases in bone turnover markers , with concomitant increases in leg bone mass . No changes in bone formation and resorption markers were seen after prolonged submaximal or high-intensity intermittent swimming training . Thus , soccer training appears to provide a powerful osteogenic stimulus in middle-aged women Purpose A decline in physical capacity takes place with increasing age that negatively affects overall physical function including work ability and the ability to perform typical activities of daily living ( ADL ) . The overall aim of the present study was to determine the neuromuscular adaptations to long-term ( 1 year ) football and strength training in older untrained adults , and to assess the concurrent effect on functional ADL capacity . Methods Twenty-seven healthy elderly males ( 68.2 ± 3.2 years ) were r and omly assigned to 12 months of either recreational football training ( FT : n = 10 ) , strength training ( ST : n = 9 ) or served as inactive controls ( CON : n = 8) . Recreational football training consisted of small-sided training sessions whereas strength training consisted of high intensity exercises targeting the lower extremity and upper body . Maximal thigh muscle strength and rate of force development ( RFD ) were assessed with isokinetic dynamometry , while postural balance and vertical jumping performance were evaluated using force plate analysis . Furthermore , functional ability was evaluated by stair-ascent and chair-rising testing . Results A total of nine , nine and seven participants from FT , ST and CON , respectively , were included in the analysis . Both exercise regimens led to substantial gains in functional ability , evidence d by 24 and 18 % reduced stair-ascent time , and 32 and 21 % increased chair-rising performance in FT and ST , respectively ( all P < 0.05 ) . Long-term strength training led to increased concentric ( 14 % ; P < 0.01 ) and isometric ( 23 % ; P < 0.001 ) quadriceps and isometric hamstring strength ( 44 % ; P < 0.0001 ) , whereas football training mainly result ed in enhanced hamstring strength ( 18 % , P < 0.05 ) and RFD ( 89 % , P < 0.0001 ) . Conclusions Long-term ( 1 year ) strength training led to increased quadriceps and hamstring strength , whereas the adaptations to football training mainly included enhanced strength and rapid force capacity of the hamstring muscles . Gains in functional ability were observed in response to both training regimens , evidence d by reduced stair-ascent time and increased chair-rising performance . Long-term football exercise and strength training both appear to be effective interventional strategies to improve factors of importance for ADL by counteracting the age-related decline in lower limb strength and functional capacity among old male adults . This could potentially be a way to improve work ability of senior workers Recreational soccer ( RS ) is becoming a popular alternative to the classical continuous exercise mode used for the improvement of cardiovascular and metabolic fitness in untrained people . The objective of this paper was to conduct a detailed systematic review of the literature , identifying the physiological responses to RS and the training effects of RS on aerobic fitness and health in untrained healthy individuals and clinical patients . PubMed , Google Scholar and ScienceDirect data bases were search ed using terms related to recreational soccer . Inclusion criteria were r and omized controlled trials ( RCT ) that assessed acute physiological responses to RS or the training effects of RS on physical fitness and health in sedentary , untrained subjects of any age or health status . All studies were assessed for method ological quality using the PEDro scale . Thirty-five articles met the inclusion criteria ; seven examined the acute response to RS , and 28 assessed training effects . Clear evidence was found that RS had positive effects on many health-related indices and variables , including VO2max ( gains of 7 - 16 % ) , blood pressure ( reductions of 6 - 13 mmHg ) , body composition ( decreased fat mass and improved indices of bone health ) , and metabolic and cardiac function . These positive effects were observed in both healthy individuals and clinical patients , irrespective of age or sex . Although this review provides clear evidence of the positive effects of RS on health , most studies had limitations of methodology ( an average PEDro score < 6 ) . Furthermore , many of the training studies were from a small number of research groups . Future studies should be extended to other countries and institutions to ensure generality of the results . Regular RS training leads to significant cardiovascular and muscular adaptations and gains of health both in sedentary individuals and clinical patients at all ages , suggesting that RS is a potentially highly motivational method to enhance population health Purpose To investigate the activity profile of football training and its short-term effects on bone mass , bone turnover markers ( BTMs ) and postural balance in men with prostate cancer ( PCa ) undergoing and rogen deprivation therapy ( ADT ) . Methods This was a r and omised 12-week study in which men with PCa undergoing ADT were assigned to a football intervention group [ FTG , n = 29 , 67 ± 7 ( ±SD ) years ] training 2‒3 times per week for 45‒60 min or to a control group ( n = 28 , 66 ± 5 years ) . The activity profile was measured using a 5-Hz GPS . The outcomes were total body and leg bone mineral content ( BMC ) and density , BTMs and postural balance . Results In the last part of the 12 weeks , FTG performed 194 ± 41 accelerations and 296 ± 65 decelerations at > 0.6 m/s/s and covered a distance of 905 ± 297 m at speeds > 6 km/h and 2646 ± 705 m per training session . Analysis of baseline-to-12-week change scores showed between-group differences in favour of FTG in total body BMC [ 26.4 g , 95 % confidence interval ( CI ) : 5.8–46.9 g , p = 0.013 ] , leg BMC ( 13.8 g , 95 % CI : 7.0‒20.5 g , p < 0.001 ) and markers of bone formation : P1NP ( 36.6 µg/L , 95 % CI : 10.4‒62.8 µg/L , p = 0.008 ) and osteocalcin ( 8.6 µg/L , 95 % CI : 3.3‒13.8 µg/L , p < 0.01 ) . The number of decelerations correlated to the increase in leg BMC ( r = 0.65 , p = 0.012 ) . No between-group differences were observed for the remaining outcomes . Conclusion Football training involves numerous runs , accelerations and decelerations , which may be linked to marked increases in bone formation markers and preserved bone mass in middle-aged and elderly men with PCa undergoing ADT.Trial registration Clinical Trials.gov : NCT01711892 We investigated the effects of 3 and 6 months of regular football training on cardiac structure and function in hypertensive men . Thirty-one untrained males with mild-to-moderate hypertension were r and omized 2:1 to a football training group ( n = 20 ) and a control group receiving traditional recommendations on healthy lifestyle ( n = 11 ) . Cardiac measures were evaluated by echocardiography . The football group exhibited significant ( P < 0.05 ) changes in cardiac dimensions and function after just 3 months : Left ventricular ( LV ) end-diastolic volume increased from 104 ± 25 to 117 ± 29 mL. LV diastolic function improved measured as E/A ratio ( 1.15 ± 0.32 to 1.54 ± 0.38 ) , early diastolic velocity , E ' ( 11.0 ± 2.5 to 11.9 ± 2.6 cm/s ) , and isovolumetric relaxation time ( 74 ± 13 to 62 ± 13 ms ) . LV systolic function improved measured as longitudinal displacement ( 10.7 ± 2.1 to 12.1 ± 2.3 mm ) . Right ventricular function improved with respect to tricuspid annular plane systolic excursion ( 21.8 ± 3.2 to 24.5 ± 3.7 mm ) . Arterial blood pressure decreased in both groups , but significantly more in the football training group . No significant changes were observed in the control group . In conclusion , short-term football training improves LV diastolic function in untrained men with mild-to-moderate arterial hypertension . Furthermore , it may improve longitudinal systolic function of both ventricles . The results suggest that football training has favorable effects on cardiac function in hypertensive men To examine the effects of regular participation in recreational soccer on health profile , 36 healthy untrained Danish men aged 20–43 years were r and omised into a soccer group ( SO ; n = 13 ) , a running group ( RU ; n = 12 ) and a control group ( CO ; n = 11 ) . Training was performed for 1 h two or three times per week for 12 weeks ; at an average heart rate of 82 % ( SEM 2 % ) and 82 % ( 1 % ) of HRmax for SO and RU , respectively . During the 12 week period , maximal oxygen uptake increased ( p<0.05 ) by 13 % ( 3 % ) and 8 % ( 3 % ) in SO and RU , respectively . In SO , systolic and diastolic blood pressure were reduced ( p<0.05 ) from 130 ( 2 ) to 122 ( 2 ) mm Hg and from 77 ( 2 ) to 72 ( 2 ) mm Hg , respectively , after 12 weeks , with similar decreases observed for RU . After the 12 weeks of training , fat mass was 3.0 % ( 2.7 ( 0.6 ) kg ) and 1.8 % ( 1.8 ( 0.4 ) kg ) lower ( p<0.05 ) for SO and RU , respectively . Only SO had an increase in lean body mass ( 1.7 ( 0.4 ) kg , p<0.05 ) , an increase in lower extremity bone mass ( 41 ( 8) g , p<0.05 ) , a decrease in LDL-cholesterol ( 2.7 ( 0.2 ) to 2.3 ( 0.2 ) mmol/l ; p<0.05 ) and an increase ( p<0.05 ) in fat oxidation during running at 9.5 km/h . The number of capillaries per muscle fibre was 23 % ( 4 % ) and 16 % ( 7 % ) higher ( p<0.05 ) in SO and RU , respectively , after 12 weeks . No changes in any of the measured variables were observed for CO . In conclusion , participation in regular recreational soccer training , organised as small-sided drills , has significant beneficial effects on health profile and physical capacity for untrained men , and in some aspects it is superior to frequent moderate-intensity running And rogen deprivation therapy ( ADT ) remains a cornerstone in the management of patients with prostate cancer ( PCa ) despite adverse effects on body composition and functional parameters . We compared the effects of football training with st and ard care in PCa patients managed with ADT ( > 6 months ) . Fifty-seven men aged 67 ( range : 43 - 74 ) were r and omly assigned to a football group ( FG , n = 29 ) or a usual care control group ( CON , n = 28 ) . The primary outcome was change in lean body mass ( LBM ) assessed by dual-energy X-ray absorptiometry scanning . Secondary outcomes included changes in knee-extensor muscle strength ( one repetition maximum ) , fat percentage , and maximal oxygen uptake ( VO2max ) . Mean heart rate during training was 137.7 ( st and ard deviation 13.7 ) bpm or 84.6 (3.9)% HRmax . In FG , LBM increased by 0.5 kg [ 95 % confidence interval ( CI ) 0.1 - 0.9 ; P = 0.02 ] with no change in CON ( mean group difference 0.7 kg ; 95 % CI 0.1 - 1.2 ; P = 0.02 ) . Also , muscle strength increased in FG ( 8.9 kg ; 95 % CI 6.0 - 11.8 ; P < 0.001 ) with no change in CON ( mean group difference 6.7 kg ; 95 % CI 2.8 - 10.7 ; P < 0.001 ) . In FG , VO2max increased ( 1.0 mL/kg/min ; 95 % CI 0.2 - 1.9 ; P = 0.02 ) and fat percentage tended to decrease ( 0.7 % ; 95%CI 1.3 - 0.0 ; P = 0.06 ) , but these changes were not significantly different from CON . In conclusion , football training over 12 weeks improved LBM and muscle strength compared with usual care in men with prostate cancer receiving ADT 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 Metformin often promotes weight loss in patients with obesity with non-insulin-dependent diabetes mellitus ( NIDDM ) . The mechanism may be attributed to decreased food intake . This study has tested the effect of metformin on satiety and its efficacy in inducing weight loss . Twelve diet-treated NIDDM women with obesity were r and omly given two dose levels ( 850 mg or 1700 mg ) of metformin or placebo at 0800 for three consecutive days followed by a meal test on the third day on three occasions using a 3x3 Latin square design . The number of s and wich canapes eaten in three consecutive 10-minute periods beginning at 1400 hours was used to quantitate food intake , and the level of subjective hunger was rated just before the s and wich meal with a linear analogue hunger rating scale at 1400 after a 6-hour fast . The prior administration of metformin produced a reduction in calorie intake after each of the two doses of metformin treatment . The 1700-mg metformin dose had the most marked appetite suppressant action . Similarly , hunger ratings were significantly lowered after metformin , and the effect was most pronounced after the administration of 1700 mg of metformin . To assess the efficacy of metformin in reducing bodyweight , 48 diet-treated NIDDM women with obesity who had failed to lose weight by diet therapy were first placed on a 1200-kcal ADA ( American Diabetes Association ) diet before being r and omized to receive either metformin ( 850 mg ) or placebo twice daily in a double-blind fashion for 24 weeks . A 4-week single-blind placebo lead-in period preceded and a 6-week single-blind placebo period followed the 24-week double-blind treatment period . Subjects treated with metformin continued to lose weight throughout 24 weeks of treatment ; their mean maximum weight loss was 8 kg greater than that of the placebo group , with corresponding lower HbA1C and fasting blood glucose levels at the end of the active treatment period . These results indicate that metformin decreases calorie intake in a dose-dependent manner and leads to a reduction in bodyweight in NIDDM patients with obesity INTRODUCTION The present study investigated the fitness and health effects of medium-term soccer training for untrained hypertensive middle-age men . METHODS Thirty-three untrained males ( 31 - 54 yr ) with mild-to-moderate hypertension were r and omized 2:1 to a soccer training group ( STG , two 1-h sessions per week , n = 22 , 68 % on medication ) and a doctor advice group receiving traditional physician-guided recommendations on cardiovascular risk factor modification ( DAG , n = 11 , 73 % on medication ) . Two-way repeated- measures ANOVA time-group statistics was applied . RESULTS During soccer training , average HR was 155 ± 9 bpm or 85 % ± 7 % HRmax . In STG , systolic and diastolic blood pressures decreased ( P < 0.01 ) over 6 months from 151 ± 10 to 139 ± 10 mm Hg and from 92 ± 7 to 84 ± 6 mm Hg , respectively , with smaller ( P < 0.05 ) decreases in DAG ( from 153 ± 8 to 145 ± 8 mm Hg and from 96 ± 6 to 93 ± 6 mm Hg , respectively ) . In STG , V˙O2max increased ( P < 0.01 ) from 32.6 ± 4.9 to 35.4 ± 6.6 mL·min-1·kg-1 and relative V˙O2 during cycling at 100 W was lowered ( P < 0.05 ) from 55 % ± 7 % to 50 % ± 8 % V˙O2max over 6 months , with no changes in DAG . In STG , resting HR was lowered by 8 ± 11 bpm ( P < 0.05 ) , and the augmentation index ( a measure of arterial stiffness ) was lowered ( P < 0.05 ) by 7.3 ± 14.0 over 6 months , with no change in DAG . CONCLUSIONS Six months of soccer training improved aerobic fitness , reduced blood pressure , and result ed in an array of other favorable effects on cardiovascular risk profile for untrained middle-age hypertensive men . Soccer training , therefore , may be a better nonpharmacological treatment for hypertensive men than traditional physician-guided advice Background Moderate calorie-restricted diets and exercise training prevent loss of lean mass and cardiovascular risk . Because adherence to routine exercise recommendation is generally poor , we utilized recreational soccer training as a novel therapeutic exercise intervention in type 2 diabetes ( T2D ) patients . Objective We compared the effects of acute and chronic soccer training plus calorie-restricted diet on protein catabolism and cardiovascular risk markers in T2D . Design , setting and subjectsFifty-one T2D patients ( 61.1±6.4 years , 29 females : 22 males ) were r and omly allocated to the soccer+diet-group ( SDG ) or to the dietgroup ( DG ) . The 40-min soccer sessions were held 3 times per week for 12 weeks . Results Nineteen participants attended 100 % of scheduled soccer sessions , and none suffered any injuries . The SDG group showed higher levels of growth hormone ( GH ) , free fatty acids and ammonia compared with DG . After 12 weeks , insulin-like growth factor binding protein (IGFPB)-3 and glucose levels were lower in SDG , whereas insulin-like growth factor (IGF)-1/ IGFBP-3 ratio increased in both groups . After the last training session , an increase in IGF-1/IGFBP-3 and attenuation in ammonia levels were suggestive of lower muscle protein catabolism . Conclusions Recreational soccer training was popular and safe , and was associated with decreased plasma glucose and IGFBP-3 levels , decreased ammoniagenesis , and increased lipolytic activity and IGF-1/IGFBP-3 ratio , all indicative of attenuated catabolism We examined the physical dem and s of small-sided soccer games in untrained middle-age males and muscle adaptations and performance effects over 12 weeks of recreational soccer training in comparison with continuous running . Thirty-eight healthy subjects ( 20–43 years ) were r and omized into a soccer ( SO ) , running ( RU ) and control ( CO ) group . Two – three weekly 1-h training sessions were performed . Muscle lactate ( 30.1 ± 4.1 vs. 15.6 ± 3.3 mmol/kg d.w . ) , blood lactate , blood glucose and time above 90 % HRmax ( 20 ± 4 % vs. 1 ± 1 % ) were higher ( p < 0.05 ) during training in SO than in RU . After 12 weeks of training , quadriceps muscle mass and mean muscle fibre area were 9 and 15 % larger ( p < 0.05 ) in SO , but unaltered in RU , and in SO , the fraction of FTx fibres was lowered ( 10.7 ± 1.8 vs. 17.9 ± 3.2 % ) . In SO , citrate synthase activity was 10 and 14 % higher ( p < 0.05 ) after 4 and 12 weeks , but unaltered in RU . After 4 weeks VO2max and Yo-Yo IE2 performance were elevated ( p < 0.05 ) to a similar extent in SO ( 7 and 37 % ) and RU ( 6 and 36 % ) but increased further ( p < 0.05 ) from 4 to 12 weeks in SO ( 6 and 23 % ) . In SO , 30-m sprint performance was improved ( p < 0.05 ) by 0.11 ± 0.02 s. Blood lactate during running at 11 km/h was lowered ( p < 0.05 ) from 0 to 4 and 4 to 12 weeks ( 2.6 ± 0.3 vs. 3.8 ± 0.6 vs. 6.1 ± 0.9 mM ) and from 0 to 12 weeks in RU . No changes occurred for CO . In conclusion , recreational soccer organized as small-sided games stimulates both aerobic and anaerobic energy turnover and is an effective type of training leading to significant cardiovascular and muscular adaptations as well as performance enhancements throughout a 12-week training period PURPOSE To characterize changes in lean body mass ( LBM ) in men with prostate cancer receiving and rogen-deprivation therapy ( ADT ) . PATIENTS AND METHODS We prospect ively evaluated LBM in a prespecified sub study of a r and omized controlled trial of denosumab to prevent fractures in men receiving ADT for nonmetastatic prostate cancer . LBM was measured by total-body dual-energy x-ray absorptiometry at study baseline and at 12 , 24 , and 36 months . The analyses included 252 patients ( 132 , denosumab ; 120 , placebo ) with a baseline and at least one on- study LBM assessment . Patients were stratified by age ( < 70 v ≥ 70 years ) and by ADT duration ( ≤ 6 v > 6 months ) . RESULTS Median ADT duration was 20.4 months at study baseline . Mean LBM decreased significantly from baseline , by 1.0 % at month 12 ( 95 % CI , 0.4 % to 1.5 % ; P < .001 ; n = 248 ) , by 2.1 % at month 24 ( 95 % CI , 1.5 % to 2.7 % ; P < .001 ; n = 205 ) , and by 2.4 % at month 36 ( 95 % CI , 1.6 % to 3.2 % ; P < .001 ; n = 168 ) . Men age ≥ 70 years ( n = 127 ) had significantly greater changes in LBM at all measured time points than younger men . At 36 months , LBM decreased by 2.8 % in men age ≥ 70 years and by 0.9 % in younger men ( P = .035 ) . Men with ≤ 6 months of ADT at study entry ( n = 36 ) had a greater rate of decrease in LBM compared with men who had received more than 6 months of ADT at study entry ( 3.7 % v 2.0 % ; P = .0645 ) . CONCLUSION In men receiving ADT , LBM decreased significantly after 12 , 24 , and 36 months This study examined the effect of recreational football and resistance training on bone mineral density ( BMD ) and bone turnover markers ( BTMs ) in elderly men . Twenty-six healthy sedentary men ( age 68.2 ± 3.2 years ) were r and omized into three groups : football ( F ; n = 9 ) and resistance training ( R ; n = 9 ) , completing 45 - 60 min training two to three times weekly , and inactive controls ( C ; n = 8) . Before , after 4 months , and after 12 months , BMD in proximal femur ( PF ) and whole body ( WB ) were determined together with plasma osteocalcin ( OC ) , procollagen type-1 amino-terminal propeptide ( P1NP ) , and carboxy-terminal type-1 collagen crosslinks ( CTX-1 ) . In F , BMD in PF increased up to 1.8 % ( P < 0.05 ) from 0 to 4 months and up to 5.4 % ( P < 0.001 ) from 0 to 12 months ; WB-BMD remained unchanged . After 4 and 12 months of football , OC was 45 % and 46 % higher ( P < 0.001 ) , and P1NP was 41 % and 40 % higher ( P < 0.001 ) than at baseline , respectively . After 12 months , CTX-1 showed a main effect of 43 % ( P < 0.05 ) . In R and C , BMD and BTM remained unchanged . In conclusion , 4 months of recreational football for elderly men had an osteogenic effect , which was further developed after 12 months , whereas resistance training had no effect . The anabolic response may be due to increased bone turnover , especially improved bone formation The aim of this study was to examine the effect of intense intermittent exercise performed as soccer training or interval running in comparison with continuous endurance running exercise on postural balance in young healthy untrained males . Young sedentary men were r and omized to soccer training ( SOC , n = 10 ) , continuous running ( RUN ; n = 9 ) , high-intensity interval running ( INT ; n = 7 ) or no training ( CON ; n = 9 ) . Postural balance was evaluated pre and post 12 weeks of training using a 30-s single-leg stance test on a force plate ( AMTI ) to yield center of pressure ( CoP ) sway path and 1-min beam st and ing ( Flamingo test ) . CoP sway length decreased by 18.2 % ( p < 0.01 ) , 14.6 % ( p < 0.05 ) and 12.8 % ( p < 0.05 ) in SOC , INT and RUN , respectively . CoP sway area decreased in SOC ( −30.2 % ; p < 0.01 ) and INT ( −23.4 % ; p < 0.01 ) but remained unaffected in RUN . Acceleration parameters ( Mean CoP acc , SD accX , SD accY ) decreased in SOC only ( 17–19 % , p < 0.05 ) . All training groups demonstrated fewer falls ( 37–41 % , p < 0.01 ) in the Flamingo test . No changes were observed in CON . Relationships ( r > 0.40 ) were observed between pre-training values in CoP sway area versus muscle fiber area , explosive muscle strength and countermovement jump velocity . Postural control was improved in response to 12 weeks of soccer training and high-intensity interval running , respectively , while less-marked changes were observed following continuous running . Notably , the reduced variability in CoP acceleration after soccer training indicates that this training regimen may produce superior improvements in postural sensory-motor function 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 The present intervention was design ed to investigate whether a 14-week period of regular recreational association football ( F ) or endurance running ( R ) has an effect on the risk of falls and bone fractures due to gains in muscle function and volumetric bone mineral density ( vBMD ) . Fifty healthy untrained Danish premenopausal women were r and omized into two training groups ( F and R ) that trained 1.8+/-0.3 ( + /-SD ) and 1.9+/-0.3 h/week , respectively , and these groups were compared with an inactive control group ( C ) . Jumping and dynamic muscle strength were tested and tibial vBMD was measured using peripheral quantitative computed tomography . Total vBMD in left and right tibia increased by 2.6+/-2.3 % and 2.1+/-1.8 % ( P<0.005 ) , respectively , in F and by 0.7+/-1.3 % ( P=0.05 ) and 1.1+/-1.5 % ( P<0.01 ) , respectively , in R without any significant changes in C. Similar results were found for trabecular vBMD . In F , peak jump power increased by 3+/-6 % ( P<0.05 ) , and hamstring strength during fast ( 240 degrees /s ) and slow ( 30 degrees /s ) contractions increased by 11+/-25 % and 9+/-21 % , respectively , ( P<0.05 ) without any significant changes in R or C. In conclusion , 14 weeks of regular recreational football improved peak jump power , maximal hamstring strength and vBMD in the distal tibia , suggesting a decreased fracture risk due to stronger bones and a reduced risk of falling The effects of regular football training on glycemic control , body composition , and peak oxygen uptake ( VO₂ peak ) were investigated in men with type 2 diabetes mellitus ( T2DM ) . Twenty-one middle-aged men ( 49.8 ± 1.7 years ± SEM ) with T2DM were divided into a football training group ( FG ; n = 12 ) and an inactive control group ( CG ; n = 9 ) during a 24-week intervention period ( IP ) . During a 1-h football training session , the distance covered was 4.7 ± 0.2 km , mean heart rate ( HR ) was 83 ± 2 % of HRmax , and blood lactate levels increased ( P < 0.001 ) from 2.1 ± 0.3 to 8.2 ± 1.3 mmol/L. In FG , VO₂ peak was 11 % higher ( P < 0.01 ) , and total fat mass and and roid fat mass were 1.7 kg and 12.8 % lower ( P < 0.001 ) , respectively , after IP . After IP , the reduction in plasma glucose was greater ( P = 0.02 ) in FG than the increase in CG , and in FG , GLUT-4 tended to be higher ( P = 0.072 ) after IP . For glycosylated hemoglobin ( HbA1 ) , an overall time effect ( P < 0.01 ) was detected after 24 weeks . After IP , the number of capillaries around type I fibers was 7 % higher ( P < 0.05 ) in FG and 5 % lower ( P < 0.05 ) in CG . Thus , in men with T2DM , regular football training improves VO₂ peak , reduces fat mass , and may positively influence glycemic control The aims of this study were : 1 ) To determine the effects of a 12-week recreational soccer training programme and continuous endurance running on body composition of young adult men and 2 ) to determine which of these two programmes was more effective concerning body composition . Sixty-four participants completed the r and omized controlled trial and were r and omly assigned to one of three groups : a soccer training group ( SOC ; n=20 ) , a running group ( RUN ; n=21 ) or a control group performing no physical training ( CON ; n=23 ) . Training programmes for SOC and RUN lasted 12-week with 3 training sessions per week . Soccer sessions consisted of 60 min ordinary five-a-side , six-a-side or seven-a-side matches on a 30 - 45 m wide and 45 - 60 m long plastic grass pitch . Running sessions consisted of 60 min of continuous moderate intensity running at the same average heart rate as in SOC ( ~80 % HRmax ) . All participants , regardless of group assignment , were tested for each of the following dependent variables : body weight , body height , body mass index , percent body fat , body fat mass , fat-free mass and total body water . In the SOC and RUN groups there was a significant decrease ( p < 0.05 ) in body composition parameters from pre- to post-training values for all measures with the exception of fat-free mass and total body water . Body mass index , percent body fat and body fat mass did not differ between groups at baseline , but by week 12 were significantly lower ( p < 0.05 ) in the SOC and RUN groups compared to CON . To conclude , recreational soccer training provides at least the same changes in body composition parameters as continuous running in young adult men when the training intensity is well matched This r and omized controlled study investigated the effectiveness of soccer and Zumba on fitness and health indicators in female participants recruited from a workplace . One hundred seven hospital employees were cluster-r and omized to either a soccer group ( SG ) , Zumba group ( ZG ) , or control group ( CG ) . Intervention effects for the two training groups were compared with CG . The training was conducted outside working hours as 2 - 3 1-h sessions per week for 12 weeks . Peak oxygen uptake ( VO2peak ) , fat percentage , fat mass , bone mineral content , and plasma osteocalcin were measured before and after the intervention period . Based on intention-to-treat-analyses , SG significantly improved the VO2peak relative to body mass ( 5 % ; P = 0.02 ) and decreased heart rate during 100-W cycle exercise ( -7 bpm ; P = 0.01 ) , total body fat percentage ( -1.1 % ; P = 0.002 ) , and total body fat mass ( -1.0 kg ; P = 0.001 ) compared with CG . ZG significantly improved the VO2peak relative to body mass ( 5 % ; P = 0.03 ) and decreased total fat mass ( -0.6 kg ; P < 0.05 ) compared with CG . Plasma osteocalcin increased in SG ( 21 % ; P < 0.001 ) and ZG ( 10 % ; P = 0.01 ) compared with CG . The present study indicates that workplace initiated short-term soccer training as well as Zumba outside working hours may result in fitness and modest health benefits among female hospital employees We evaluated the effects of recreational football training combined with calorie-restricted diet ( football + diet ) vs calorie-restricted diet alone ( diet ) on aerobic fitness , lipid profile , and insulin resistance indicators in type 2 diabetes ( T2D ) patients . Forty-four T2D patients aged 48 - 68 years ( 27 females , 17 males ) were r and omly allocated to the football + diet group ( FDG ; n = 22 ) or to the diet group ( DG ; n = 22 ) , of whom 19 FDG and 15 DG subjects completed the study . The football training was performed for 3 × 40 min/week for 12 weeks . Dual-energy X-ray absorptiometry scanning , treadmill testing , and fasting blood samplings were performed pre and post-intervention . After 12 weeks , maximal oxygen uptake ( VO₂max ) was elevated ( P < 0.05 ) by 10 ± 4 % in FDG but not in DG ( -3 ± 4 % , P < 0.05 ) . After 12 weeks , reductions in blood triglycerides ( 0.4 ± 0.1 mmol/L ) , total cholesterol ( 0.6 ± 0.2 mmol/L ) , low-density lipoprotein , and very low-density lipoprotein levels were observed only in FDG . Fat mass decreased ( P < 0.05 ) by 3.4 ± 0.4 kg in FDG and 3.7 ± 0.4 kg in DG . The lower ( P < 0.05 ) glucagon and homeostatic model assessment of insulin resistance indicated an improvement in insulin sensitivity in FDG . In conclusion , football combined with restricted diet was effective in enhancing VO₂max , reducing total cholesterol and triglycerides , and increasing insulin sensitivity , potentially providing better tools for the prevention of T2D complications than diet alone The present study examined the effects of short-term recreational football training on blood pressure ( BP ) , fat mass , and fitness in sedentary , 35 - 50-year-old premenopausal women with mild hypertension . Forty-one untrained , hypertensive women were r and omized into a football training group ( n = 21 ; FTG ) and a control group ( n = 20 ; CON ) . FTG performed 45 ± 1 1-h small-sided football training sessions during the 15-week intervention period . BP , body composition ( dual-energy x-ray absorptiometry ) , blood lipid profile , and fitness level were determined pre- and post-intervention . After 15 weeks , systolic and diastolic BP , respectively , were lowered more ( P < 0.05 ) in FTG ( -12 ± 3 and -6 ± 2 mmHg ) than in CON ( -1 ± 1 and 1 ± 2 mmHg ) . Total body fat mass decreased more ( P < 0.05 ) in FTG than in CON during the 15-week intervention period ( -2.3 ± 0.5 kg vs 0.4 ± 0.3 kg ) . After 15 weeks , both total cholesterol ( -0.4 ± 0.1 mmol/L vs 0.1 ± 0.2 mmol/L ) and triglyceride ( -0.2 ± 0.1 mmol/L vs 0.3 ± 0.2 mmol/L ) were lowered more ( P < 0.05 ) in FTG than in CON . Yo-Yo intermittent endurance level 1 test performance increased more ( P < 0.05 ) in FTG than in CON ( 111 ± 18 % vs 1 ± 3 % ) during the 15-week intervention period . In conclusion , short-term football training result ed in a marked reduction in BP and induced multiple improvements in fitness and cardiovascular health profile of untrained , premenopausal women with mild hypertension |
683 | 19,821,337 | AUTHORS ' CONCLUSIONS An anthracycline infusion duration of six hours or longer reduces the risk of clinical heart failure and it seems to reduce the risk of sub clinical cardiac damage .
No significant difference in the occurrence of clinical heart failure was identified in patients treated with a doxorubicin peak dose of less than 60 mg/m(2 ) or 60 mg/m(2 ) or more .
For the other identified peak doses only one RCT was available , so no definitive conclusions can be made about the occurrence of cardiotoxicity . | BACKGROUND The use of anthracycline chemotherapy is limited by the occurrence of cardiotoxicity .
To prevent this cardiotoxicity , different anthracycline dosage schedules have been studied .
OBJECTIVES To determine the occurrence of cardiotoxicity with the use of different anthracycline dosage schedules ( i.e. peak doses and infusion duration s ) in cancer patients . | BACKGROUND A r and omized phase III trial in high-risk breast cancer patients was conducted , to further explore the impact of dose-density in the adjuvant treatment for breast cancer . The safety analysis is presented . PATIENTS AND METHODS From October 2000 until June 2005 , 1121 node-positive patients were r and omized to sequential dose-dense epirubicin 110 mg/m(2 ) and paclitaxel ( Taxol , Bristol Myers-Squibb , Princeton , New Jersey , USA ) 250 mg/m(2 ) ( group A ) , or concurrent epirubicin 83 mg/m(2 ) and paclitaxel 187 mg/m(2 ) ( group B ) , both followed by three cycles of ' intensified ' combination chemotherapy with cyclophosphamide , methotrexate and fluorouracil ( CMF ) . Granulocyte colony-stimulating factor was given prophylactically with the dose-dense treatments . RESULTS Median dose intensity of epirubicin and paclitaxel was double in group A , as design ed , with significantly less cycles administered at full dose ( P < 0.001 ) . Median cumulative dose of all drugs and total treatment duration , however , were identical between groups . Severe taxane-related toxic effects were more frequent in group A , while severe thrombocytopenia was low and present only in group A. There were no differences in the rates of other hematological toxic effects , including febrile neutropenia . The rates of secondary malignancies were low . CONCLUSION Both regimens as used in the present study are well tolerated and safe . The rates of severe taxane-related toxic effects and thrombocytopenia , although low overall , are significantly increased with the dose-dense sequential regimen PURPOSE This study was design ed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a st and ard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival . PATIENTS AND METHODS After surgical treatment , 3,121 women with operable breast cancer and involved lymph nodes were r and omly assigned to receive a combination of cyclophosphamide ( C ) , 600 mg/m(2 ) , with one of three doses of doxorubicin ( A ) , 60 , 75 , or 90 mg/m(2 ) , for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 mg/m(2 ) . Tamoxifen was given to 94 % of patients with hormone receptor-positive tumors . RESULTS There was no evidence of a doxorubicin dose effect . At 5 years , disease-free survival was 69 % , 66 % , and 67 % for patients r and omly assigned to 60 , 75 , and 90 mg/m(2 ) , respectively . The hazard reductions from adding paclitaxel to CA were 17 % for recurrence ( adjusted Wald chi(2 ) P = .0023 ; unadjusted Wilcoxon P = .0011 ) and 18 % for death ( adjusted P = .0064 ; unadjusted P = .0098 ) . At 5 years , the disease-free survival ( + /- SE ) was 65 % ( + /- 1 ) and 70 % ( + /- 1 ) , and overall survival was 77 % ( + /- 1 ) and 80 % ( + /- 1 ) after CA alone or CA plus paclitaxel , respectively . The effects of adding paclitaxel were not significantly different in subsets defined by the protocol , but in an unplanned subset analysis , the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 ( 95 % confidence interval , 0.59 to 0.86 ) for those with estrogen receptor-negative tumors and only 0.91 ( 95 % confidence interval , 0.78 to 1.07 ) for patients with estrogen receptor-positive tumors , almost all of whom received adjuvant tamoxifen . The additional toxicity from adding four cycles of paclitaxel was generally modest . CONCLUSION The addition of four cycles of paclitaxel after the completion of a st and ard course of CA improves the disease-free and overall survival of patients with early breast cancer PURPOSE We conducted an open-label , r and omized trial to determine whether ICRF-187 would reduce doxorubicin-induced cardiotoxicity in pediatric sarcoma patients . METHODS Thirty-eight patients were r and omized to receive doxorubicin-containing chemotherapy ( given as an intravenous bolus ) with or without ICRF-187 . Resting left ventricular ejection fraction ( LVEF ) was monitored serially with multigated radionuclide angiography ( MUGA ) scan . The two groups were compared for incidence and degree of cardiotoxicity , response rates to four cycles of chemotherapy , event-free and overall survival , and incidence and severity of noncardiac toxicities . RESULTS Eighteen ICRF-187-treated and 15 control patients were assessable for cardiac toxicity . ICRF-187-treated patients were less likely to develop sub clinical cardiotoxicity ( 22 % v 67 % , P < .01 ) , had a smaller decline in LVEF per 100 mg/m2 of doxorubicin ( 1.0 v 2.7 percentage points , P = .02 ) , and received a higher median cumulative dose of doxorubicin ( 410 v 310 mg/m2 , P < .05 ) than did control patients . Objective response rates were identical in the two groups , with no significant differences seen in event-free or overall survival . ICRF-187-treated patients had a significantly higher incidence of transient grade 1 serum transaminase elevations and a trend toward increased hematologic toxicity . CONCLUSION ICRF-187 reduces the risk of developing short-term sub clinical cardiotoxicity in pediatric sarcoma patients who receive up to 410 mg/m2 of doxorubicin . Response rates to chemotherapy , event-free and overall survival , and noncardiac toxicities appear to be unaffected by the use of ICRF-187 . Additional clinical trials with larger numbers of patients are needed to determine if the short-term cardioprotection afforded by ICRF-187 will reduce the incidence of late cardiac complications in long-term survivors of childhood cancer A phase II study utilizing VP-16 and adriamycin in a r and omized fashion tested the concept of synchronization of the drugs in treatment of metastatic breast cancer . Although there was a trend in median survival following the synchronized schedule , there was no significant difference in survival or progression-free intervals . The concept of synchronization was not established The Dana-Farber Cancer Institute ( DFCI ) acute lymphoblastic leukemia ( ALL ) Consortium Protocol 91 - 01 was design ed to improve the outcome of children with newly diagnosed ALL while minimizing toxicity . Compared with prior protocol s , post-remission therapy was intensified by substituting dexamethasone for prednisone and prolonging the asparaginase intensification from 20 to 30 weeks . Between 1991 and 1995 , 377 patients ( age , 0 - 18 years ) were enrolled ; 137 patients were considered st and ard risk ( SR ) , and 240 patients were high risk ( HR ) . Following a 5.0-year median follow-up , the estimated 5-year event-free survival ( EFS ) + /- SE for all patients was 83 % + /- 2 % , which is superior to prior DFCI ALL Consortium protocol s conducted between 1981 and 1991 ( P = .03 ) . There was no significant difference in 5-year EFS based upon risk group ( 87 % + /- 3 % for SR and 81 % + /- 3 % for HR , P = .24 ) . Age at diagnosis was a statistically significant prognostic factor ( P = .03 ) , with inferior outcomes observed in infants and children 9 years or older . Patients who tolerated 25 or fewer weeks of asparaginase had a significantly worse outcome than those who received at least 26 weeks of asparaginase ( P < .01 , both univariate and multivariate ) . Older children ( at least 9 years of age ) were significantly more likely to have tolerated 25 or fewer weeks of asparaginase ( P < .01 ) . Treatment on Protocol 91 - 01 significantly improved the outcome of children with ALL , perhaps due to the prolonged asparaginase intensification and /or the use of dexamethasone . The inferior outcome of older children may be due , in part , to increased intolerance of intensive therapy A prospect i ve r and omized trial was conducted to compare the cardiotoxic and therapeutic effects of doxorubicin ( 60 mg/m2 every 3 to 4 weeks ) administered by bolus or 72‐hour continuous infusion as adjuvant chemotherapy in 82 eligible patients after resection of high‐ grade soft tissue sarcoma of the extremity or superficial trunk . Cardiac toxicity , defined as a 10 % or greater decrease in left ventricular ejection fraction as assessed by radionuclide cineangiography , was evaluated in 69 patients . Cardiotoxicity was seen in 61 % of patients in the bolus treatment arm with the median doxorubicin dose of 420 mg/m2 . Among patients who received continuous infusion , 42 % had cardiotoxicity with a median dose of 540 mg/m2 . The rate of cardiotoxicity as a function of the cumulative dose of doxorubicin was significantly higher in the bolus treatment arm ( P = 0.0017 ) . Two patients in each group had clinical congestive heart failure , with one cardiac death occurring in each . There was a trend toward a lower rate of metastasis ( P = 0.19 ) and a significantly lower rate of death of disease ( P = 0.036 ) for patients treated with the bolus dose . Cox model analysis identified three unfavorable characteristics for the rate of developing a distant metastasis : blood transfusion within 24 hours of operation ( P < 0.00001 ) , tumor deep to the fascia and 5 cm or more in size ( P = 0.0043 ) , and a histologic subtype other than liposarcoma ( P = 0.0002 ) . The unfavorable effect of continuous infusion was not selected in the model ( P = 0.16 ) . Adjuvant chemotherapy for patients with soft tissue sarcoma is investigational . Furthermore , the impact of perioperative blood transfusion merits further study Forty-eight patients with advanced breast carcinoma who had not received prior chemotherapy ( minimum follow up 21 months ) were r and omised to receive either adriamycin 70 mg m-2 i.v . 3-weekly for 8 cycles ( Regimen A ) or adriamycin 35 mg m-2 i.v . 3-weekly for 16 courses ( Regimen B ) . Objective responses were seen in 14/24 ( 58 % ) patients with regimen A ( 4 complete ) and 6/24 ( 25 % ) with regimen B ( 1 complete ) ( P less than 0.02 ) . The median duration of response was 14 months with regimen A and 6.5 months with regimen B. The median duration of survival was 20 months and 8 months respectively ( P less than 0.01 ) . The toxicity was similar with each regimen . There was no evidence of deterioration in left ventricular ejection fraction nor congestive heart failure in any patient . It is concluded that when given at 3-weekly intervals adriamycin is a more effective treatment for advanced breast cancer at higher rather than lower dosage The activity and toxicity of single-agent st and ard-dose doxorubicin were compared with that of two schedules of high-dose epirubicin . A total of 334 chemonaive patients with histologically confirmed advanced soft-tissue sarcomas received ( A ) doxorubicin 75 mg m(-2 ) on day 1 ( 112 patients ) , ( B ) epirubicin 150 mg m(-2 ) on day 1 ( 111 patients ) or ( C ) epirubicin 50 mg m(-2 ) day(-1 ) on days 1 , 2 and 3 ( 111 patients ) ; all given as bolus injection at 3-week intervals . A median of four treatment cycles was given . Median age was 52 years ( 19 - 70 years ) and performance score 1 ( 0 - 2 ) . Of 314 evaluable patients , 45 ( 14 % ) had an objective tumour response ( eight complete response , 35 partial response ) . There were no differences among the three groups . Median time to progression for groups A , B and C was 16 , 14 and 12 weeks , and median survival 45 , 47 and 45 weeks respectively . Neither progression-free ( P = 0.93 ) nor overall survival ( P = 0.89 ) differed among the three groups . After the first cycle of therapy , two patients died of infection and one owing to cardiovascular disease , all on epirubicin . Both dose schedules of epirubicin were more myelotoxic than doxorubicin . Cardiotoxicity ( > or = grade 3 ) occurred in 1 % , 0 % and 2 % respectively . Regardless of the schedule , high-dose epirubicin is not a preferred alternative to st and ard-dose doxorubicin in the treatment of patients with advanced soft-tissue sarcomas PURPOSE Several multicomponent regimens have been reported to be useful in advanced and rogen-independent prostate cancer . We used a r and omized phase II design to evaluate and compare two such regimens . Patients were accrued primarily in the community setting . PATIENTS AND METHODS Patients with progressive , and rogen-independent prostate cancer were r and omly assigned to one of two treatments : either ketoconazole/doxorubicin alternating with vinblastine/estramustine ( KA/VE ) or paclitaxel , estramustine , and oral etoposide ( TEE ) . Patients were prospect ively stratified on the basis of disease volume . The primary end points were response and overall survival time . RESULTS A total of 75 patients were registered ; 71 are included in the analysis . By the criterion of an 80 % prostate-specific antigen reduction maintained for at least 8 weeks , 11 ( 30 % ) of 37 patients in the TEE arm responded , whereas 11 ( 32 % ) of 34 assigned to KA/VE responded . Median survival was 16.9 months ( 95 % confidence interval [ CI ] , 10.5 to 21.2 months ) in the TEE arm and 23.4 months ( 95 % CI , 12.9 to 30.6 months ) for patients treated with KA/VE . Many patients ( 24 % ) failed to complete at least 6 weeks of therapy , including five ( 8 % ) treatment-related early deaths . CONCLUSION Each of these regimens produced clinical ly significant responses , and the observed median survival ( 18.9 months for all 71 patients ) compares favorably with previously published results , especially in the community setting . Nonetheless , it is apparent that these first-generation regimens must be applied judiciously , and thus we view efforts at better patient selection and the development of more tolerable therapies as higher priorities than carrying either of these regimens to phase III evaluation in the cooperative group setting Fifty-six patients were r and omly assigned to receive either one-day cisplatin , doxorubicin , and cyclophosphamide ( PAC ) chemotherapy ( PAC-I ) or five-day PAC ( PAC-V ) for advanced epithelial ovarian carcinoma . Follow-up has been 120 + months or to death . Ninety-one percent had either suboptimal stage III or stage IV disease and 55 % had grade 2 or 3 lesions . Two patients died of toxicity and were free of disease at autopsy . A third patient died of congestive heart failure with no disease at 103 months . Additionally , eight patients had a negative second-look laparotomy , and three ( 37.5 % ) are alive with no evidence of disease ( NED ) 133 to 144 months after diagnosis . Five patients ( 62.5 % ) died of disease 2 to 123 months after negative second-look . Patients with optimal stage III disease had a longer median progression-free interval ( PFI ) and survival ( 33.3 and 44.5 months , respectively ) than those with suboptimal or stage IV disease ( 16.4 and 22.5 months , respectively ) , and the difference in median PFI is significant ( P less than .02 ) . Patients with ascites at diagnosis had a shorter median PFI and survival ( 14.7 and 18 months ) than those without ascites ( 30.0 and 33.0 months ) . Both differences were significant ( PFI , P less than .04 ; survival , P = .005 ) . PAC produces response rates that are superior to those obtained historically with single-agent alkylating therapy . Late recurrences after negative second-look laparotomy suggest that 5-year survival data may be inadequate in ovarian carcinoma PURPOSE The aim of this study was to explore the effect of dose-dense sequential chemotherapy with or without paclitaxel primarily on disease-free survival ( DFS ) and secondarily on overall survival ( OS ) in patients with high-risk operable breast cancer . PATIENTS AND METHODS From June 1997 until November 2000 , 604 patients with T1 - 3N1M0 or T3N0M0 tumors were r and omized to three cycles of epirubicin 110 mg/m2 followed by three cycles of paclitaxel 250 mg/m2 followed by three cycles of ' intensified ' CMF ( cyclophosphamide 840 mg/m2 , methotrexate 47 mg/m2 and fluorouracil 840 mg/m2 ) ( group A ) , or to four cycles of epirubicin followed by four cycles of CMF , as in group A ( group B ) . All cycles were given every 2 weeks with granulocyte colony-stimulating factor support . RESULTS A total of 595 patients were eligible . Median follow-up was 61.7 months for group A and 62 months for group B. The 3-year DFS was 80 % in group A and 77 % in group B. Survival rates were 93 % and 90 % , respectively . The effect of treatment on the hazard of death was different according to hormonal receptor status . More specifically , in patients with negative receptor status the hazard of death was significantly higher for group B ( hazard ratio 2.42 ) . Both regimens were well tolerated and severe acute side-effects were infrequent . No cases of severe cardiotoxicity or acute leukemia were recorded . CONCLUSIONS The present study failed to demonstrate a significant difference in DFS or OS between the two treatment groups . However , our study has shown clearly that high-dose paclitaxel can be safely incorporated to dose-dense sequential chemotherapy Thirty adult patients with non-Hodgkin 's lymphoma were studied to evaluate prospect ively the significance of early decline in left ventricular ejection fraction after low cumulative doxorubicin dose ( 200 mg m−2 ) in predicting the later impairment of left ventricular function . Cardiac function was monitored with radionuclide ventriculography at baseline and after cumulative doxorubicin doses of 200 , 400 and 500 mg m−2 . Cardiotoxicity was defined as a decrease in left ventricular ejection fraction of more than 10 % units to a final left ventricular ejection fraction ⩽50 % . Twenty-eight patients received doxorubicin ⩾400 mg m−2 and were evaluable for cardiotoxicity . Clinical heart failure developed in two patients ( 7 % ) after a cumulative doxorubicin dose of 500 mg m−2 . Left ventricular ejection fraction decreased more than 10 % absolute ejection fraction units to a final left ventricular ejection fraction ⩽50 % in 10 patients ( 36 % ) . Left ventricular ejection fraction decreased from 56±1.5 % to 53.6±1.5 % ( P=0.016 ) in patients with no cardiotoxicity , and from 60.8±2.4 % to 41.8±2.0 % ( P<0.001 ) in patients with cardiotoxicity . For patients who developed cardiotoxicity , the fall in left ventricular ejection fraction after a cumulative doxorubicin dose of only 200 mg m−2 was highly significant ( left ventricular ejection fraction 49.7±1.8 % , P=0.001 vs baseline ) . In receiver operator characteristic analysis , the area under the curve for the decrease in left ventricular ejection fraction at a cumulative doxorubicin dose of 200 mg m−2 for predicting cardiotoxicity in all patients was 0.858 . The decrease in left ventricular ejection fraction of more than 4 % units after a cumulative doxorubicin dose of 200 mg m−2 had a 90 % sensitivity and 72 % specificity for predicting later cardiotoxicity . Our results show that the significant impairment of left ventricular function during doxorubicin therapy can be predicted early , already at low cumulative doxorubicin doses . This finding may be of value in identifying patients at high or low risk for the development of anthracycline cardiotoxicity BACKGROUND Both total dose and dose intensity of adjuvant chemotherapy are postulated to be important variables in the outcome for patients with operable breast cancer . The Cancer and Leukemia Group B study 8541 examined the effects of adjuvant treatment using conventional-range dose and dose intensity in female patients with stage II ( axillary lymph node-positive ) breast cancer . METHODS Within 6 weeks of surgery ( radical mastectomy , modified radical mastectomy , or lumpectomy ) , 1550 patients with unilateral breast cancer were r and omly assigned to one of three treatment arms : high- , moderate- , or low-dose intensity . The patients received cyclophosphamide , doxorubicin , and 5-fluorouracil on day 1 of each chemotherapy cycle , with 5-fluorouracil administration repeated on day 8 . The high-dose arm had twice the dose intensity and twice the drug dose as the low-dose arm . The moderate-dose arm had two thirds the dose intensity as the high-dose arm but the same total drug dose . Disease-free survival and overall survival were primary end points of the study . RESULTS At a median follow-up of 9 years , disease-free survival and overall survival for patients on the moderate- and high-dose arms are superior to the corresponding survival measures for patients on the low-dose arm ( two-sided P<.0001 and two-sided P = .004 , respectively ) , with no difference in disease-free or overall survival between the moderate- and the high-dose arms . At 5 years , overall survival ( average + /- st and ard error ) is 79 % + /- 2 % for patients on the high-dose arm , 77 % + /- 2 % for the patients on the moderate-dose arm , and 72 % + /- 2 % for patients on the low-dose arm ; disease-free survival is 66 % + /- 2 % , 61 % + /- 2 % , and 56 % + /- 2 % , respectively . CONCLUSION Within the conventional dose range for this chemotherapy regimen , a higher dose is associated with better disease-free survival and overall survival One hundred patients with non-small cell lung cancer were entered into a r and omized evaluation of two schedules of doxorubicin combined with ftorafur , cyclophosphamide , and cisplatin ( FACP ) . Doxorubicin was given either weekly at 20 mg/m2 , or every three weeks ( st and ard ) at 60 mg/m2 . Fifty-two patients were r and omized to the FACP/weekly doxorubicin arm and 48 patients to the FACP/st and ard doxorubicin arm . The FACP/weekly doxorubicin regimen was associated with higher complete and partial remission rates ( 31 % versus 19 % ) , longer response duration ( median , 33 versus 21 weeks ) , and longer survival duration for responders ( median , 58 versus 50 weeks ) . These differences were not significant . Less neutropenia ( p = 0.01 ) and less infectious morbidity ( p = 0.05 ) were observed in the FACP/weekly doxorubicin arm . Twenty-eight patients underwent 35 endomyocardial biopsies to assess doxorubicin-induced cardiotoxicity . Sixteen biopsies were performed in 12 patients receiving cumulative doxorubicin doses ranging from 250 to 1,190 mg/m2 within the FACP/weekly doxorubicin arm . Nineteen biopsies were performed in 16 patients receiving cumulative doxorubicin doses ranging from 250 to 540 mg/m2 within the FACP/st and ard doxorubicin regimen . The FACP/weekly doxorubicin regimen was associated with significantly lower cardiotoxicity scores ( p = 0.01 ) . This study indicates that weekly administered doxorubicin is as effective and less cardiotoxic than the st and ard schedule PURPOSE Acute doxorubicin-induced cardiotoxicity can be prevented in adults by continuous infusion of the drug , but mechanisms of cardiotoxicity are different in children . We compared cardiac outcomes in children receiving bolus or continuous infusion of doxorubicin . PATIENTS AND METHODS In a r and omized study , children with high-risk acute lymphoblastic leukemia received doxorubicin 360 mg/m(2 ) in 30-mg/m(2 ) doses every 3 weeks either by bolus ( within 1 hour , n = 57 ) or by continuous infusion ( over 48 hours , n = 64 ) . Echocardiograms obtained before doxorubicin and at longest follow-up times were central ly remeasured , and z scores of cardiac measurements were calculated based on a healthy population . RESULTS The groups were similar in age , sex distribution , doxorubicin dose , and duration of follow-up . Before treatment , measures of left ventricular ( LV ) structure and function did not reveal dilated cardiomyopathy and were not statistically different between bolus and continuous-infusion groups . The follow-up echocardiograms demonstrated no significant difference between the two groups for any cardiac characteristic , but both groups showed significant abnormalities of LV structure and function compared with normal and with baseline . For example , the mean LV fractional shortening fell by approximately two SD in both groups between the two echocardiograms . LV contractility was depressed in both groups ( for bolus patients , median z score = -0.70 SD , P = .006 ; for continuous-infusion patients , median z score = -0.765 , P = .005 ) . Dilated cardiomyopathy and inadequate LV hypertrophy were noted in both groups . Clinical cardiac manifestations and event-free survival did not differ . CONCLUSION Continuous doxorubicin infusion over 48 hours for childhood leukemia did not offer a cardioprotective advantage over bolus infusion . Both regimens were associated with progressive sub clinical cardiotoxicity . Other cardioprotective strategies should be explored In order to evaluate the possible cardiosparing effect of a prolonged infusion of doxorubicin as compared with the st and ard mode of administration 62 consecutive patients with metastatic carcinoma of the breast or carcinoma of the ovary Stage III or IV were prospect ively r and omized to receive doxorubicin either as a rapid infusion over 15 to 20 minutes at 8 AM or as a continuous infusion over 6 hours , 8 AM to 2 PM . The remaining protocol was identical for the two groups . The cardiotoxic effect of doxorubicin was evaluated by history and physical examination and by the decline in resting ventricular ejection fraction ( LVEF ) as determined by gated pool radionuclide angiography with technetium 99 m ( 99mTc ) and by the decline in the height of the QRS complexes in the st and ard leads of the echocardiogram ( ECG ) . Initially there were 31 patients in each group . The cumulative dose of doxorubicin , was 410 mg/m2 ± 42 SD in the st and ard infusion group and 428 mg/m2 ± 48 SD in the 6‐hour infusion group . The mean decline in LVEF after a cumulative doxorubicin dose of 300 mg/m2 was 17 % in the first group and only 4.1 % in the second . After 400 mg/m2 the mean fall in LVEF was 21 % in the first group and 6 % in the second . The mean decline in QRS voltage after 300 mg/m2 was 29 % and 1.5 % , respectively . Four patients , all in the st and ard infusion group , developed congestive heart failure . These data suggest that slow infusion of doxorubicin is associated with reduced cardiotoxicity A prospect i ve r and omized study was done to determine the effect of different doxorubicin ( Adriamycin [ ADR ] , Adria Laboratories , Columbus , OH ) administration ( schedules every week versus every 3 weeks ) on the productivity of a cyclophosphamide , ADR , cisplatin ( CAP ) chemotherapy regimen for patients with non‐small cell lung cancer ( NSCLC ) . Electrocardiograms , multigated cardiac scans , echocardiograms , and endomyocardial biopsies were done serially for cardiac monitoring . Of 102 patients , 47 had inoperable limited disease ( LD ) , 47 had extensive disease ( ED ) , and eight had no evidence of disease . In the last group chemotherapy was given adjuvantly . Fifty‐one patients were entered into each treatment arm . The groups were formed according to extent of disease and were comparable in terms of patient characteristics . In these groups , the overall response rates using both schedules in LD patients were similar : in patients without chest irradiation previously , there was a response of 35 % with ADR weekly , and 31 % with ADR triweekly ; in LD patients with chest irradiation previously , the response was 20 % with ADR weekly , and 25 % with ADR triweekly ; and in ED patients , 16 % with ADR weekly , and 11 % with ADR triweekly . There was no significant difference in survival between the two treatment groups . However , results for all responders suggested a longer duration of response with weekly than with triweekly ADR ( complete plus partial response : 35.8 versus 11A weeks , P = 0.06 ; minor response : 34 versus 11.5 weeks , P = 0.003 , respectively ) . Results also suggested that weekly ADR was less cardiotoxic than triweekly ADR : 29 % of patients in the former group had no changes or only minor changes in endomyocardial biopsy results , whereas all patients in the latter group had at least grade 0.5 changes at a similar dosage . The median doses of weekly ADR were higher at the same endomyocardial biopsy‐defined toxicity levels . No correlation was found between toxic effects defined by endomyocardial biopsy results and those defined by noninvasive monitoring techniques , although the number of patients assessed was small . Weekly ADR produced less granulocytopenia and a lower incidence of fever ( 6 % versus 16 % , P < 0.001 ) than did triweekly ADR . Alopecia , nausea , vomiting , and diarrhea were significantly less for weekly ADR than triweekly Adr ( P < 0.0005 , < 0.0005 , and < 0.005 , respectively ) . These data suggest that weekly ADR can achieve the same therapeutic results as the st and ard triweekly regimen with less cardiotoxicity , myelotoxicity , alopecia , diarrhea , nausea , and vomiting in patients with NSCLC BACKGROUND Daunorubicin ( DNR ) is one of the most important drugs in treatment of acute lymphoblastic leukemia ( ALL ) . Prolonged infusions of anthracyclines are less cardiotoxic but it has not been investigated whether the in vivo leukemic cell kill is equivalent to short-term infusions . PROCEDURE In the cooperative treatment study COALL-92 for childhood ALL 178 patients were r and omized to receive in a therapeutic window a single dose of 36 mg/m ( 2 ) DNR either as a 1-h ( 85 patients ) or 24-h infusion ( 93 patients ) . Daily measurements of white blood cell count ( WBC ) and peripheral blood smears for seven days could be evaluated central ly in 101 patients ( 1-h : 43 patients , 24-h : 58 patients ) . RESULTS The proportional decline of blasts at day 7 after DNR infusion showed no statistically significant difference between the two treatment arms . At day 3 the median percentage of blasts was less than 10 % , at day 7 less than 2 % for either the 1-h or 24-h infusion . Twelve patients ( 1-h : 5 patients , 24-h : 7 patients ) had an absolute number of more than 1000 blasts per mul peripheral blood ( PB ) at day 7 after DNR infusion ( DNR poor responders ) . Kaplan-Meier analysis showed an equal probability of EFS for the short- and long-term infusion group ( 24-h : 83%+/-5 ; 1-h : 81+/-6 ) after a median observation time of 12.3 years . CONCLUSIONS We conclude that in children with ALL a 24-h infusion of DNR has the same in vivo cytotoxicity for leukemic cells as a 1-h infusion . This offers the possibility to use prolonged infusions with hopefully less cardiotoxicity without loss of efficacy Background : To determine the incidence of early and late arrhythmogenic effects of doxorubicin-containing chemotherapy regimens . Patients and Methods : A prospect i ve study including 29 patients who were treated with doxorubicin-containing regimens . Cardiac evaluation was based on 24-hour electrocardiographic monitorization ( Holter ) , which was performed during the first cycle of doxorubicin-containing regimens , as well as after the last cycle of chemotherapy . Results : The mean age of the patients was 45.8 ± 15.1 ( range 18–69 ) . Holter records obtained during the first cycle of treatment revealed varying arrhythmias in 19 patients ( 65.5 % ) and in 18 ( 62.1 % ) patients after completion of therapy . One patient presented with syncope and both Mobitz Type 2 atrioventricular block and complete atrioventricular block were demonstrated . The patient subsequently underwent permanent pacemaker implantation . Conclusions : Doxorubicin may result in arrhythmias both in early and late periods of treatment . These arrhythmias are rarely life threatening Background . Improved survival of children with acute lymphoblastic leukemia ( ALL ) has made it more difficult to develop new protocol s to further improve results . The authors report the pilot experience with the Memorial Sloan‐Kettering‐New York‐II ( MSK‐NY‐II ) protocol , based on the New York regimen with changes made in an attempt to improve efficacy while reducing toxicity The results of a clinical trial involving 599 patients with inoperable squamous cell , large cell anaplastic , and adenocarcinoma of the lung are summarized . Patients were r and omized to initial therapy with Cytoxan ( CTX ) ( cyclophosphamide ) , or to one of two schedules of Adriamycin ( doxorubicin ) 50 , or 75 mg/m2 IV every three weeks , or to a combined regimen of ADR and CTX . Upon disease progression , CTX patients were r and omized to one of the two ADR schedules , while ADR patients were r and omly assigned to CTX alone , or in combination with Cisdiamminedichloroplatinum ( Cis‐Platinum ) 15 mg/m2 IV every three weeks . No statistically significant response or survival differences were observed between the two dose schedules of Adriamycin for any of the cell types studied . The two dose levels did , however , differ with respect to toxicity . There were some response and survival differences among the various cell types in the comparison of low‐dose Adriamycin and Cytoxan : ( 1 ) patients with adenocarcinoma treated with low‐dose Adriamycin tended to survive longer ( P = 0.04 ) than those treated with Cytoxan ; and ( 2 ) patients with large cell carcinoma receiving Cytoxan experienced a greater tumor response rate than those receiving low dose Adriamycin ( P = 0.03 ) . Because of the difficulties involved in distinguishing these two cell types on pathologic examination , the evidence of apparent treatment differences should not be regarded as definitive . During the period when Adriamycin plus Cytoxan was open to patient entry 61 evaluable patients received that regimen , 21 received low‐dose Adriamycin and 22 received Cytoxan . Because relatively few patients received the latter two regimens , comparisons of these treatments with Adriamycin plus Cytoxan lack statistical power . However , there is no suggestion in the available data that Adriamycin plus Cytoxan increased survival either in the overall population or in the subset of patients with squamous histology . Initial performance status , metastatic disease symptoms , primary disease symptoms , and weight loss were significantly correlated to survival time , and are recommended as stratification factors in future studies PURPOSE To assess the incidence of long-term toxicity after postmastectomy radiation and doxorubicin-based adjuvant chemotherapy . METHODS Records of 470 patients treated with mastectomy , doxorubicin-based chemotherapy , and postmastectomy radiation in five institutional prospect i ve trials were retrospectively review ed . Actuarial toxicity rates were compared with those of 1031 patients treated with mastectomy and doxorubicin-based chemotherapy who did not receive postmastectomy radiation . For those treated with radiation , the chest wall received a median dose of 55 Gy with Co-60 ( 42 % ) or electrons ( 51 % ) . Adjuvant chemotherapy consisted of a doxorubicin-based regimen , often followed by 2 years of cyclophosphamide , methotrexate , and fluorouracil . RESULTS Median follow-up was 10 years . The overall 10-year actuarial rates of RTOG toxicity Grade > 1 and > or=3 after radiation were 4 % and 2 % , respectively . The overall 10- and 15-year actuarial rates of second non-breast cancer malignancy were 3.8 % and 7 % , respectively . There was no statistical difference between the rates of non-breast cancer second malignancy in the radiated and unirradiated cohorts ( 3.4 % vs. 4.7 % 10-year actuarial rates ) . Increasing age and treatment with > 10 cycles of chemotherapy were associated with higher rates of second malignancy ( p = 0.025 , p = 0.016 ) . The 10-year actuarial rate of death from myocardial infa rct ion ( MI ) was 2.4 % ( eight events ) and 0.5 % ( five events ) in the radiated and unirradiated groups , respectively ( p = 0.058 ) . Of the 8 irradiated patients who died of MI , 2 patients had left-sided breast cancer . CONCLUSIONS We found very low rates of serious sequelae after postmastectomy radiation , including death from myocardial infa rct ion and non-breast cancer second malignancy . The rate of second non-breast cancer malignancy was increased among patients treated with > 10 cycles of cyclophosphamide-containing chemotherapy PURPOSE To evaluate the efficacy and toxicity of combination and sequential dose-dense chemotherapy with doxorubicin and docetaxel ( Taxotere ; Rhône-Poulenc Rorer , Collegeville , PA ) as primary chemotherapy of breast cancer . PATIENTS AND METHODS Patients with newly diagnosed stage II or noninflammatory stage III breast cancer were r and omly assigned to receive the same total doses of doxorubicin and docetaxel over a 12-week period before definitive surgery . Patients in arm A received sequential therapy with doxorubicin 75 mg/m(2 ) every 2 weeks for three cycles followed by docetaxel 100 mg/m(2 ) every 2 weeks for three cycles . Patients in arm B received combination therapy with doxorubicin 56 mg/m(2 ) plus docetaxel 75 mg/m(2 ) every 3 weeks for four cycles . Granulocyte colony-stimulating factor was administered on days 2 to 12 of each cycle in both groups . RESULTS Forty patients were entered onto the trial . Pretreatment tumor size averaged 5.7 cm with clinical ly positive axillary lymph nodes in 23 patients ( 57 % ) . As expected , myelosuppression was severe in both groups ; however , > /= 80 % of planned dose-intensity was delivered . H and -foot syndrome was more common after sequential therapy . Clinical responses were similar in both groups , with an overall response rate of 87 % , including 20 % clinical complete remissions . Pathologic complete remission or residual in situ disease only was confirmed in five patients ( 12.8 % ) . Patients who received sequential therapy had fewer positive lymph nodes ( mean , 2.17 v 4.81 ; P < .037 ) at definitive surgery . CONCLUSION Primary chemotherapy with doxorubicin and docetaxel is well tolerated and highly active . A sequential treatment schedule increases toxicity but may result in more substantial lymph node clearance than combination therapy Doxorubicin ( Adriamycin ) was administered by continuous infusion to reduce peak plasma levels and thus lessen cardiac toxicity . Cardiotoxicity was monitored by noninvasive methods , and endomyocardial biopsy specimens were studied by electronmicroscopy . Cardiotoxicity was compared in 21 patients receiving doxorubicin intravenously over 48 or 96 hours and in 30 control patients treated by st and ard intravenous injection . Both groups were studied prospect ively and were well matched by risk factors for doxorubicin cardiotoxicity . The median cumulative dose for those receiving continuous infusion was 600 mg/m2 body surface area ( range , 360 to 1500 mg/m2 ) compared with 465 mg/m2 ( range 290 to 680 mg/m2 ) in the control group ( p = 0.002 ) . Fourteen of the 30 patients in the control group showed severe morphologic changes in the biopsy specimens , precluding further doxorubicin administration , as compared with two of 21 patients receiving the drug by continuous infusion ( p less than 0.02 ) . The mean pathologic score for the infusion group , 0.9 , was lower than the mean for the control group , 1.6 ( p = 0.004 ) . Antitumor activity was not compromised . Decreasing peak plasma levels of doxorubicin by continuous infusion reduces cardiotoxicity Two hundred eleven patients with advanced breast cancer were r and omized to receive either epirubicin ( E ) 50 mg/m2 and prednisolone ( LEP ) or E 100 mg/m2 and prednisolone ( HEP ) . The intended treatment consisted of 16 courses of LEP or eight courses of HEP given at 3-weekly intervals . Reasons for stopping treatment early included progressive disease , stable disease without symptomatic improvement , or severe toxicity deemed intolerable by either the patient or physician . Toxicity was recorded at 3-weekly and response at 9-weekly intervals using the World Health Organization ( WHO ) criteria of response and toxicity . Two hundred nine patients were eligible for analysis , 98 % of whom have been followed for more than a year . One hundred four patients received LEP and 105 HEP . Significantly worse myelosuppression , alopecia , nausea and vomiting , and mucositis were seen in the high-dose arm ( P less than or equal to .001 ) . More patients in the LEP arm stopped treatment before the fourth course than in the HEP arm , and the commonest reason for stopping was progressive disease . A similar median number of courses was given in each arm . There was a significantly higher response in the HEP arm ( HEP - complete response [ CR ] + partial response [ PR ] = 41 % , LEP - CR + PR = 23 % ) . Despite this , no statistically significant differences was seen in overall survival or progression-free interval . The median survival for HEP and LEP was 44 and 46 weeks , respectively We report the first r and omized study assessing the efficacy and safety of daunorubicin ( DNR ) continuous infusion ( CI ) compared to the more conventional 30-min infusion ( i.v . ) in newly diagnosed adult acute lymphoblastic leukemia ( ALL ) . Seventy-seven patients were initially r and omized to receive either a 24-h CI DNR ( 60 mg/m2 days 2–4 ) ( 40 patients ) or bolus DNR at the same dosage ( 37 patients ) with vincristine ( 2 mg i.v . days 1 , 8 , 15 ) and oral prednisone ( 60 mg/m2 days 1–15 ) , without hematopoietic growth factor support , as an induction regimen . The distribution of adverse prognostic factors was comparable in the two-induction arm . Acute toxicity was more important in the CI arm . Gram negative infection ( 9 vs 1 gram negative septicemia , P = 0.01 ) and infection-related deaths ( 6 vs 1 deaths , P = NS ) occurred more frequently in the CI arm during the induction treatment than in the i.v . arm , leading to the study interruption . Neutropenia but not thrombopenia duration was significantly longer in the CI arm than in the i.v . arm ( 18 days vs 14 days , P > 0.05 and 16 days vs 12 days , P > 0.05 , respectively ) . Despite a similar CR rate according to the method of DNR administration ( 68 % in the CI DNR arm vs 76 % in the i.v . arm after the first course ) , there was a trend toward higher freedom from relapse ( FFR ) after DNR CI ( 48 % vs 28 % in the i.v . arm at 5 years , P = NS ) , suggesting that despite this high toxicity , DNR CI may improve the CR quality and decrease further the residual disease PURPOSE A potential application of hematopoietic growth factors is to obtain an increased dose-intensity . This can be achieved by either higher doses of chemotherapy with st and ard intervals , or by st and ard doses with shorter intervals . The potential of these approaches has not been investigated systematic ally . PATIENTS AND METHODS In a r and omized , multicenter study , 49 advanced breast cancer patients were treated with granulocyte colony-stimulating factor ( G-CSF ) and either increasing doses of epirubicin and cyclophosphamide with fixed intervals ( arm one ) or progressively shorter intervals with fixed doses of epirubicin and cyclophosphamide ( arm two ) . A cohort of at least six patients was studied at each interval/dose . A more intensified interval/dose was given if less than 50 % of patients encountered a dose-intensity limiting criterium ( DILC ) in the first three courses . RESULTS In arm one , epirubicin 140 mg/m2 and cyclophosphamide 800 mg/m2 every 21 days was too toxic . Subsequently , epirubicin 120 mg/m2 and cyclophosphamide 700 mg/m2 was tested with two of 10 patients encountering a DILC . All initial DILCs consisted of febrile neutropenia . In arm two , epirubicin 75 mg/m2 and cyclophosphamide 500 mg/m2 could be administered safely with 14- and 12-day intervals . In the 10-day interval , eight of 12 patients completed the first three cycles without a DILC . In the 8-day interval , seven of eight patients encountered a DILC . Incomplete neutrophil recovery , and to a lesser extent stomatitis , were dose-limiting . CONCLUSION In combination with G-CSF , epirubicin 120 mg/m2 and cyclophosphamide 700 mg/m2 every 21 days was feasible ( projected dose-intensity , 40 mg/m2/wk and 233 mg/m2/wk , respectively ) . Epirubicin 75 mg/m2 and cyclophosphamide 500 mg/m2 could be administered safely every 10 days , allowing a projected dose-intensity of 52.5 mg/m2/wk and 350 mg/m2/wk , respectively PURPOSE We conducted a phase III r and omized study of two adjuvant treatment schedules of doxorubicin ( A ) and cyclophosphamide ( C ) in early-stage breast cancer to determine if administration of sequential single agents ( A -- > C ) results in superior disease-free survival ( DFS ) and overall survival ( OS ) versus the same total dose given in combination ( AC ) . PATIENTS AND METHODS High-risk node-negative or low-risk node-positive breast cancer patients received AC given : ( arm I ) concurrently ( AC ) doxorubicin 54 mg/m2 and cyclophosphamide 1.2 g/m2 intravenously ( IV ) every 3 weeks for six cycles ; or ( arm II ) in sequence ( A C ) doxorubicin 40.5 mg/m2 IV days 1 and 2 every 3 weeks for four cycles followed by cyclophosphamide 2.4 gm/m2 IV every 2 weeks for three cycles . Total dose and duration were identical , but the intensity of each drug was increased on A C. Both arms included granulocyte colony-stimulating factor support and prophylactic antibiotics . All but premenopausal women with receptor negative tumors received tamoxifen after chemotherapy . RESULTS Between 1994 and 1997 , 3,176 patients were r and omly assigned . Arms were well balanced ; 48 % of eligible patients were node-negative and 48 % were estrogen receptor-positive . No significant differences in OS or DFS were observed ; 5-year estimates of OS ( 95 % CI ) were 88 % ( 87 % to 90 % ) on AC and 89 % ( 87 % to 91 % ) on A -- > C. Grade 4 hematologic toxicity was greater on A -- > C , but nonhematological grade 4 was similar . CONCLUSION The overall result does not support superiority of dose-intense sequenced single agents . The greater toxicity of higher doses of single agents does not support their sequential use The severity of late cardiotoxicity after anthracycline treatment for childhood cancer relates mainly to the cumulative anthracycline dose received , but all dose ranges cause some cardiac dysfunction . Anthracycline administration by infusion in order to lower peak drug concentration has been used in an attempt to reduce cardiotoxicity . Cardiac performance was assessed by echocardiography in children who were relapse‐free survivors of treatment for acute lymphoblastic leukaemia ( ALL ) . They received the same cumulative anthracycline dose ( daunorubicin 180 mg/m2 ) either by bolus injection ( UKALL X protocol , n = 40 ) or by infusion ( UKALL XI protocol , n = 71 ) with a follow‐up duration of 5·3 ± 2·0 and 5·4 ± 1·0 years respectively . On analysis , both the bolus administration and infusion groups showed similar mild impairment of cardiac performance , characterized by increased left ventricular end systolic stress and impaired left ventricular function . In conclusion , sub clinical abnormality of left ventricular performance was confirmed in both groups despite the relatively modest cumulative anthracycline dose received . We were unable to demonstrate an advantage of anthracycline administration by 6‐h infusion with respect to late cardiotoxicity at this dose BACKGROUND Adjuvant chemotherapy is widely used for breast cancer and is known to extend survival . Some clinicians seek a greater survival benefit by increasing the intensity of the dose , whereas others lower it to diminish toxicity . METHODS The Cancer and Leukemia Group B ( CALGB ) conducted a r and omized trial of different levels of doses and dose intensity ( dose per unit of time ) of adjuvant chemotherapy in 1572 women with node-positive , stage II breast cancer who were assigned to three treatment groups . One group received 400 mg of cyclophosphamide per square meter of body-surface area and 40 mg of doxorubicin per square meter once every 28 days and 400 mg of fluorouracil per square meter twice every 28 days , for six cycles . Another group received 50 percent higher doses of the three drugs ( 600 mg , 60 mg , and 600 mg , respectively ) but for only four cycles , so that the total dose was identical in these two groups but the dose intensity was higher in the first . The third group of women received half the total dose used in the other two groups and at half the dose intensity used in the second group . RESULTS After a median of 3.4 years of follow-up , the women treated with a high or moderate dose intensity had significantly longer disease-free survival ( P < 0.001 ) and overall survival ( P = 0.004 ) than those treated with a low dose intensity , in three-way log-rank comparisons . However , the difference in survival between the two groups treated with a moderate or high dose intensity was not significant . These results are consistent with either a dose-response effect or a threshold level of the dose or dose intensity . CONCLUSIONS The doses of chemotherapy used to treat breast cancer , especially early breast cancer , should not be reduced if the maximal benefit is to be achieved Echocardiography is a sensitive method for detecting wall motion abnormalities , as well as for monitoring cardiotoxicity during treatment with anthracyclines . Using echocardiography , this study investigated possible acute cardiotoxicty associated with primary treatment of Hodgkin 's disease according to German Hodgkin 's Lymphoma Study Group ( GHSG ) clinical trial protocol s for adults . A group of 88 patients ( 48 men ) was registered in the prospect i ve , r and omized clinical trial involving the treatment of Hodgkin 's disease using third and fourth generation GHSG protocol s. These patients were monitored by echocardiography . The average age was 34 years ( range , 18 - 65 ; median , 32 ) . The average anthracycline dose was 174 mg/m2 ( median 200 mg/m2 ) , and the average mediastinum irradiation dose was 21 Gy ( median 30 Gy ) . Left ventricle end-systolic diameter ( ESD ) and left ventricle end-diastolic diameter ( EDD ) , as well as fractional shortening ( FS ) and ejection fraction ( EF ) ( M-mode calculation ) were evaluated , as was the presence of pericardial effusion and wall motion abnormalities . The examinations were conducted before and at the end of therapy ( up to 2 months ) . Results show that all evaluated parameters changed from one follow-up examination to the other , but these changes did not reach statistical significance . ESD increased from 30 + /- 4 to 31 + /- 4 mm . EDD increased from 49 + /- 4 to 49 + /- 5 mm . Ejection fraction changed from 69 + /- 7 to 66 + /- 7 % and fractional shortening was unchanged ( from 38 + /- 7 to 38 + /- 7 % ) . In seven patients ( 8 % ) , we observed new wall motion abnormalities characterized by hypokinesis without decrease of left ventricular function . Significant changes in the amount of pericardial effusion were not observed . In four patients ( 5 % ) , there was progression of Hodgkin 's disease . In conclusion , treatment according to third and fourth generation clinical trial protocol s of the GHSG leads only to minimal wall motion changes , without concomitant reduction of left ventricular function , thus not meeting the criteria , acute cardiotoxicity Disseminated soft-tissue sarcomas are a group of uncommon malignancies generally treated in a uniform manner . This study question ed the impact of schedule on response rate and toxicity in patients with metastatic soft-tissue sarcoma treated with the two-drug combination doxorubicin and dacarbazine . Patients were r and omly assigned to receive either bolus therapy with doxorubicin at a dose of 60 mg/m2 and dacarbazine at a dose of 750 mg/m2 intravenously on day 1 ( 118 patients ) or infusional therapy with doxorubicin at 60 mg/m2 and dacarbazine at 750 mg/m2 delivered by continuous intravenous infusion for 96 hours on days 1 - 4 ( 122 patients ) . Chemotherapy was to be repeated every 3 weeks . A unique feature of this cooperative group protocol was a provision for surgical resection of residual disease in patients with a partial response or with stable disease following chemotherapy . Similar overall response rates ( 17 % in both treatment arms ) and complete response rates ( 5 % in both treatment arms ) were observed . For patients receiving bolus therapy , the median response duration was 19.6 months for those in complete remission and 6.6 months for those in partial remission . For patients receiving infusional therapy , the median response duration was 12.6 months for those in complete remission and 9.3 months for those in partial remission . Examination of dose intensity received when combining treatment arms revealed a weak doxorubicin dose-response relationship . There was no difference in median survival times between the two treatment arms ( bolus therapy , 10.6 months ; infusional therapy , 10.5 months ; logrank P = .97 ) . Analysis of toxic effects favored infusional therapy . Significant reductions in cardiac toxicity ( all events , P = .04 ; clinical events , P = .01 ) and nausea and emesis ( P = .04 ) were seen in infusional therapy . Of 47 patients eligible for cytoreductive surgery following chemotherapy , 12 received surgery , and of those 12 , eight were rendered disease free . The use of a 96-hour continuous intravenous infusion of doxorubicin-dacarbazine was comparable therapeutically with bolus dosing of these two agents and was better tolerated by the patients Doxorubicin is a highly effective and widely used cytotoxic agent with application that is limited by cardiotoxicity related to the cumulative dose of the drug . A large‐scale study that retrospectively evaluated the cardiotoxicity of doxorubicin reported that an estimated 7 % of patients developed doxorubicin‐related congestive heart failure ( CHF ) after a cumulative dose of 550 mg/m2 . To assess whether this estimate is reflective of the incidence in the broader clinical oncology setting , the authors evaluated data from three prospect i ve studies to determine both the incidence of doxorubicin‐related CHF and the accumulated dose of doxorubicin at which CHF occurs BACKGROUND Anthracyclines are effective antineoplastic drugs in acute myelogenous leukemia ( AML ) . However , their use is limited by cardiomyopathy , which occurs in children already at cumulative doses of 300 mg/m(2 ) ( given as daunorubicin equivalent ) . PROCEDURE To evaluate anthracycline-associated cardiomyopathy in pediatric AML- patients , the incidence of early and late ( > 1 year after intensive AML chemotherapy ) clinical and sub clinical cardiotoxicity was analyzed out of a total of 1,207 patients < 18 years treated between 1993 and 2003 in trials AML-BFM93/98 : 1,010 protocol patients with de novo AML , 121 with Down syndrome (DS)-AML , and 76 with secondary AML . The cumulative dose of anthracyclines was generally risk-adapted : 300 - 450 mg/m(2 ) using 1 - 4-hr infusions of anthracyclines with the assumed lowest cardiotoxic potential . Eight hundred eighty-five patients ( 73 % ) were eligible for the analysis of early and 547 ( 45 % ) of late cardiotoxicity ( 1,399 follow-up data ) . RESULTS Thirty-eight patients ( 4.3 % ) , including 3 DS-AML and 1 secondary AML , suffered from early cardiomyopathy . After 5 years , four patients showed temporarily or persistently a reduced shortening fraction , which led to death in one DS-AML patient . Including these 4 patients , late cardiomyopathy was seen in 16 patients ( cumulative incidence after 11 years : 5 % + /- 1 % ) . Nine patients ( 2.5 + /- 1 % ) showed clinical symptoms , five of them had persistent abnormal shortening fraction . Late sub clinical cardiomyopathy occurred temporarily in seven patients . Late clinical cardiomyopathy mainly affected patients with a second anthracycline therapy ( secondary malignancy ) and those with early cardiotoxicity . CONCLUSION In spite of a highly intensive and effective treatment , the frequency of anthracycline-associated cardiomyopathy was low in the AML-BFM studies Liposomal encapsulation of doxorubicin has been shown to reduce nonspecific delivery of this agent to normal tissue and to increase specific delivery to malignant cells . On the basis of doxorubicin 's demonstrated clinical efficacy against hormone‐refractory prostate carcinoma ( HRPCA ) , the authors conducted a prospect i ve , r and omized Phase II clinical trial to evaluate the feasibility , toxicity , and therapeutic efficacy associated with the pegylated form of this agent The effect of enhancing the dose intensity ( DI ) of the key drugs in multidrug combination chemotherapy for malignant lymphoma is uncertain . We investigated the survival benefit of dose-intensified multidrug combination chemotherapy for intermediate- or high- grade non-Hodgkin ’s lymphoma ( NHL ) . Patients without any prior chemotherapy were r and omly assigned either to dose-intensified multidrug combination chemotherapy , LSG9 ( VEPA-B/FEPP-AB/M-FEPA , treated 3 times every 10 weeks for 28 weeks total ) , or to control-arm combination chemotherapy , mLSG4 ( VEPA-B/FEPP-B/M-FEPA , treated 4 times every 14 weeks for 54 weeks total ) . The planned DI of doxorubicin and cyclophosphamide were 1.96 and 1.47 times higher , respectively , in LSG9 than in mLSG4 . Overall survival , complete response ( CR ) rate , and toxicities were evaluated . The 447 patients ( 230 for LSG9 and 217 for mLSG4 ) were enrolled between February 1991 and March 1995.The 5-year overall survival rates were 56.8 % for LSG9 patients and 55.1 % for mLSG4 patients ( log-rank P = .42).The rates for CR plus uncertain CR were 70.0 % for LSG9 and 64.5 % for mLSG4 . The toxicities of both regimens were similar and tolerable . The median actual DI of doxorubicin and cyclophosphamide were 1.56 and 1.17 times higher , respectively , in LSG9 than in mLSG4 . Compared with the control regimen mLSG4 , the dose-intensified regimen LSG9 did not show significant survival benefit . An increase in the DI of doxorubicin in multidrug combination chemotherapy did not improve the survival of patients with intermediate- or high- grade NHL Pre clinical studies show that docetaxel ( Taxotere ) and cyclophosphamide ( Cytoxan , Neosar ) are synergistic against MA 13/C mammary adenocarcinoma . Both agents are highly active as monotherapy in a number of tumors , including metastatic breast cancer . Therefore , we performed a phase I dose-finding study to determine the maximum tolerated dose of this combination regimen in patients with advanced solid tumors . A total of 45 patients were enrolled and received cyclophosphamide followed by docetaxel , both administered as 1-hour intravenous infusions once every 3 weeks . The dose levels of cyclophosphamide/docetaxel were 600/60 mg/m2 ( group 0 ) , 600/75 mg/m2 ( group I ) , 700/75 mg/m2 ( group 2 ) , 800/75 mg/m2 ( group 3 ) , 800/85 mg/m2 ( group 4 ) , 800/75 mg/m2 ( group 5 ) , and 800/85 mg/m2 ( group 6 ) . Patients with dose-limiting neutropenia in groups 5 and 6 received 300 micrograms of granulocyte colony-stimulating factor ( G-CSF ) ( filgrastim [ Neupogen ] ) support on days 2 through 9 during subsequent cycles of chemotherapy . All patients received premedication with 8 mg of dexamethasone twice daily for 5 days , beginning 1 day prior to chemotherapy . The dose-limiting toxicity was neutropenia fever . The recommended dose for phase II studies of cyclophosphamide/docetaxel is 700/75 mg/m2 in previously treated patients and 800/75 mg/m2 in previously untreated patients . G-CSF support did not allow for further dose escalation . Preliminary results from this phase I trial indicate that the combination of docetaxel and cyclophosphamide produced an objective response rate of 69 % in 32 patients with metastatic breast cancer ( including 3 patients who achieved complete responses ) Doxil , a doxorubicin formulation of polyethylene glycol-coated liposomes , has anti-tumor activity against Kaposi 's sarcoma and other solid tumors with mild myelosuppression , minimal hair loss and a low risk of cardiotoxicity . Non-liposomal doxorubicin has modest activity in hormone-refractory prostate cancer ( HRPC ) with considerable toxicity . A pilot study of Doxil was conducted in 15 patients with HRPC . Doxil was administered i.v . using two regimes of equal dose intensity , either 45 mg/m2 every 3 weeks or 60 mg/m2 every 4 weeks . Plasma levels of doxorubicin were analyzed in 10 patients . The most common side effect was stomatitis with a higher incidence at the 60 mg/m2 dose level . In contrast , h and -foot syndrome was more frequent and severe in patients treated with the 3 week schedule of 45 mg/m2 . Three patients responded to treatment ( based on objective response in one patient and reduction of PSA level greater than 50 % in the other two ) and two patients had stable disease , all of them receiving 60 mg/m2 . Pharmacokinetic analysis shows a proportional increase of plasma drug levels with dose and the characteristic long circulation time of Doxil with half-lives in the range of 3 days , somewhat longer than previously reported . In conclusion , Doxil at 60 mg/m2 every 4 weeks appears to be active against HRPC , but severe mucocutaneous toxicities prevented further investigation of this regime |
684 | 26,001,854 | The evidence suggests that transition interventions /strategies do lead to improvements in confidence and competence , job satisfaction , critical thinking and reductions in stress and anxiety for the newly qualified nurse .
CONCLUSIONS This systematic review demonstrates the beneficial effects of transitional support strategies for newly qualified nurses from the perspective of the new nurse and their employer .
The overall impact of support strategies appears positive , irrespective of the type of support provided .
This may suggest that it is the organisations ' focus on new graduate nurses that is important , rather than simply leaving them to acclimatise to their new role themselves . | BACKGROUND The transition from student to newly qualified nurse can be stressful for many newly qualified nurses who feel inadequately prepared .
A variety of support strategies to improve the transition process have been reported across the international literature but the effectiveness of such strategies is unknown .
OBJECTIVES / AIM To determine the effectiveness of the main strategies used to support newly qualified nurses during the transition into the clinical workplace and , where identified , evaluate the impact of these on individual and organisational outcomes . | Title Turnover intention in new graduate nurses : a multivariate analysis Aim This paper is a report of a study to determine the relationship of new nurse turnover intent with individual characteristics , work environment variables and organizational factors and to compare new nurse turnover with actual turnover in the 18 months of employment following completion of a residency . Background Because of their influence on patient safety and health outcomes nurse turnover and turnover intent have received considerable attention worldwide . When nurse staffing is inadequate , especially during nursing shortages , unfavourable clinical outcomes have been documented . Method Prospect i ve data collection took place from 1999 to 2006 with 889 new paediatric nurses who completed the same residency . Scores on study instruments were related to likelihood of turnover intent using logistic regression analysis models . Relationships between turnover intent and actual turnover were compared using Kaplan – Meier survivorship . Results The final model demonstrated that older respondents were more likely to have turnover intent if they did not get their ward choice . Also higher scores on work environment and organizational characteristics contributed to likelihood that the new nurse would not be in the turnover intent group . These factors distinguish a new nurse with turnover intent from one without 79 % of the time . Increased seeking of social support was related to turnover intent and older new graduates were more likely to be in the turnover intent group if they did not get their ward choice . Conclusion When new graduate nurses are satisfied with their jobs and pay and feel committed to the organization , the odds against turnover intent decrease . What is already known about this topic There is concern in many countries about nurse turnover and the result ing effects on patient safety and quality of care . Decreasing ability to recruit experienced nurses has increased the emphasis on recruitment of new graduate nurses , particularly in the United States of America . Historically , new graduate nurses have a high turnover rate within the first year of employment . What this paper adds When new graduate nurses are satisfied with their jobs and pay and feel committed to the organization , the odds of turnover intent decrease . Increased seeking social support to cope with the transition from student to competent Registered Nurse is related to turnover intent . Older graduates ( > 30 ) are 4·5 times more likely to have turnover intent if they do not get their ward of choice Purpose : Although simulation technology in nursing education is becoming increasingly commonplace , a review of the literature reveals a paucity of rigorous , high-level research comparing the effectiveness of simulation with other traditional education methods in the acquisition of clinical knowledge and skills . This research aim ed to investigate the impact of three learning interventions on graduate nurse health assessment knowledge and skills . It was hypothesized that the patient assessment skills of graduate nurses who completed a simulation learning activity would be superior to those who completed traditional education activities . Methods : Graduate nurses ( n = 74 ) were r and omly allocated to three groups ( 1 : self-directed learning package [ SDLP ] only ; 2 : SDLP plus two scenario-based PowerPoint workshops ; and 3 : SDLP plus two simulation education sessions using a manikin with low-fidelity capabilities . Following the education activities , graduates completed an individual test involving a systematic patient assessment upon a manikin . They were scored using a checklist of relevant responses . Results : Analysis of variance results suggest that the mean test score for nurses in the simulation group ( mean = 135.52 , SD = 26.63 ) was significantly higher ( P < 0.001 ) than those in the learning package group ( mean = 107.42 , SD = 29.82 ) and the PowerPoint group ( mean = 102.77 , SD = 31.68 ) . Conclusions : Simulation appears to be an effective educational tool for teaching patient assessment knowledge and skills to graduate nurses . Incorporation of such technology into graduate nurse education may decrease the time required to become clinical ly proficient , result ing in more confident and work-ready practitioners Rapid turnover of novice nurses eventually results in a shortage of veteran nurses . This study aim ed to clarify the factors affecting rapid turnover of novice nurses in a prospect i ve manner . We carried out an investigation in 20 university hospitals whose directors of nursing service departments accepted our request to cooperate with our research program . These hospitals were selected from all of the 102 university hospitals listed in The Hospital Catalog of Japan . The subjects were 1,203 novice hospital nurses who gave their informed consent for participation in our study . The question naires , which dealt with burnout , assertiveness , stressful life events , reality shock , ward assignment preference , transfer preference , job satisfaction ( workplace , salary , workload , and overtime ) , social support and coping mechanisms were completed by 923 novice nurses in June 2003 . Then , their turnover was investigated in December 2003 . Thirty-seven novice nurses ( 4.0 % ) quit during this period . Multiple logistic regression analysis showed that the factors affecting rapid turnover were 1 ) graduation from vocational nursing schools , 2 ) dissatisfaction with assignment to a ward contrary to their desire , and 3 ) no peers for support . Assignment of novice nurses to wards they choose as far as possible , avoidance of assigning novice nurses to wards alone , and establishment of a support system for nurses who graduate from vocational nursing schools seem to be important for preventing rapid turnover of novice nurses Specialised support for student nurses making the transition to graduate nurse can be crucial to successful and smooth adjustment , and can create a path to positive and stable career experiences . This paper describes an enhanced model of final year nursing student placements which was trialled in 2006 at the Queensl and University of Technology . The model involved collaboration with two major urban health services and re sources were developed to support effective transition experiences . Ninety-two students , including 29 trial participants and 63 non-trial participants were assessed on preparedness for professional practice , before and after the trial semester . Results indicated an increase in preparedness across the entire sample , but students participating in the trial did not differ significantly in overall preparedness change from those who did not participate . Higher baseline preparedness in the trial group highlighted the possibility that proactive students who choose enrichment experiences tend to be likelier to gain benefit from such options than those who do not . Qualitative findings from focus groups conducted with 12 transition group students highlighted that one of the main beneficial aspects of the experience for students was the sense of belonging to a team that understood their learning needs and could work constructively with them Abstract The transition from student to an accountable health professional is a difficult time for the novice nurse and can result in significant anxiety , stress and poor socialisation into the nursing profession . A strategy applied at a major tertiary teaching hospital to address transitional issues for novice nurses is that of group debriefing sessions . This qualitative study used focus groups to explore the effectiveness of these debriefing sessions for new graduate nurses and trainee enrolled nurses . The results demonstrated that the sessions provided nurses with a supportive environment , access to peer support and a sense of belonging . This provided an opportunity to develop confidence in their nursing competence and improvement in interpersonal communication skills . Debriefing sessions are an effective psychosocial support mechanism that can ameliorate the ‘ reality shock ’ experienced by nurses in their first year of practice . Group debriefing is an important component in the transitional support process and should be used to complement other strategies to enhance the psychosocial experiences of novice nurses Objective In an effort to better underst and turnover rates in hospitals and the effect of new nurses on them , this study sought to describe the characteristics and attitudes toward work of newly licensed RNs , a population important to both the nursing profession and the health care system . Methods A survey was mailed to a r and om sample of new RNs in 35 states and the District of Columbia . A total of 3,266 returned surveys met the inclusion criteria , for a response rate of 56 % . RNs who qualified had completed the licensing examination and obtained a first license between August 1 , 2004 , and July 31 , 2005 . Data pertaining to four areas were collected : respondent characteristics , work- setting characteristics , respondents ' attitudes toward work , and job opportunities . Respondents who were not working were asked to specify why . Results Of the eligible newly licensed RNs , 58.1 % had an associate 's degree , 37.6 % had a bachelor 's degree , and 4.3 % had a diploma or a master 's or higher degree as their first professional degree . They were generally pleased with their work groups but felt they had only moderate support from supervisors . About 13 % had changed principal jobs after one year , and 37 % reported that they felt ready to change jobs . More than half of the respondents ( 51 % ) worked voluntary overtime , and almost 13 % worked m and atory overtime . Also , 25 % reported at least one on-the-job needlestick in a year ; 39 % , at least one strain or sprain ; 21 % , a cut or laceration ; and 46 % , a bruise or contusion ; 62 % reported experiencing verbal abuse . A quarter of them found it “ difficult or impossible ” to do their jobs at least once per week because of inadequate supplies . Conclusions This study provides descriptive evidence that a majority of newly licensed RNs are reasonably satisfied and have no plans to change jobs , but the group is not homogeneous . The negative attitudes expressed in response to some survey questions suggest that newly licensed RNs may not remain in the acute care setting s where they start out . Investing in better orientation and management may be the key to retaining them in hospitals . The authors will be following these RNs for two years and will develop predictive models of turnover rates ProblemNew nurse graduates experience a stressful role transition into healthcare organizations , with 30 % leaving their first job within 1 year and 57 % leaving by 2 years of employment . Aim This study tests whether an internship program , Social and Professional Reality Integration for Nurse Graduates ( SPRING ) , improves new nurse graduate retention , sense of belonging , organizational commitment , and anticipated turnover . Design Quasi-experimental , posttest only , control group design . Method New nurse graduates hired by an academic institution that completed SPRING were compared with baseline nurse graduates who did not complete SPRING , using the Organizational Commitment Question naire , Modified Hagerty-Patusky Sense of Belonging Instrument , and Anticipated Turnover Scale . Retention was also examined . Results Anticipated Turnover was higher for baseline nurses than for 6-month SPRING nurses . Six-month SPRING nurses have lower antecedent sense of belonging than baseline or 12-month SPRING nurses . One-year retention is higher for SPRING new graduates than for non-SPRING new graduates . Conclusion Internship programs for nurse graduates must support the socialization of nurses and their transition into the professional role as well as teach the skills and knowledge needed for competence . This study supports the value of a comprehensive program for new nurse graduates in improving nurse retention and decreasing new nurse graduate intent to leave the organization at 6 months This is the third and final part of a series of articles that report the findings of a study that investigated the effects of a summer externship program on the transition into a professional role among nurses who participated in a summer nurse externship program at an acute care pediatric hospital . Specifically , this article reports the retention and recruitment benefits of a summer nurse externship program for the institution from 1998 through 2003 . A total of 153 externs out of the 193 ( 79.0 % ) assumed a registered nurse position at the institution , and 77 % remained in that role for 12 months . Overall , the nurse extern program for this institution appeared to be an effective recruitment and retention strategy that is on par with the institution and national data for retention and turnover data BACKGROUND Research regarding the relationship between preceptorship and development of critical thinking in new graduate nurses is sparse . No studies could be found that examined the relationship of preceptor education to critical thinking scores of new graduate nurses . METHODS A quasi-experimental , mixed- methods design measured critical thinking ability of new graduate nurses . Focus group interviews were conducted with preceptors who attended an author-developed educational program . RESULTS Preceptors ' participation in the educational session contributed to the evaluation subscale of critical thinking skills of the experimental group on the California Critical Thinking Skills Test ( F = 4.709 , p = .039 ) . Preceptors had positive qualitative responses . CONCLUSIONS Critical thinking skills of new graduate nurses can be improved and learning relationships developed through preceptor education . Further study is suggested |
685 | 28,819,377 | Pomalidomide was generally well tolerated by patients reported in the studies . | In this work , we aim to further analyze the effect of pomalidomide for relapsed and /or refractory multiple myeloma ( RRMM ) . | Pomalidomide and low-dose dexamethasone ( PomDex ) is st and ard treatment of lenalidomide refractory myeloma patients who have received > 2 prior therapies . We aim ed to assess the safety and efficacy of the addition of oral weekly cyclophosphamide to st and ard PomDex . We first performed a dose escalation phase 1 study to determine the recommended phase 2 dose of cyclophosphamide in combination with PomDex ( arm A ) . A r and omized , multicenter phase 2 study followed , enrolling patients with lenalidomide refractory myeloma . Patients were r and omized ( 1:1 ) to receive pomalidomide 4 mg on days 1 to 21 of a 28-day cycle in combination with weekly dexamethasone ( arm B ) or pomalidomide , dexamethasone , and cyclophosphamide ( PomCyDex ) 400 mg orally on days 1 , 8 , and 15 ( arm C ) . The primary end point was overall response rate ( ORR ) . Eighty patients were enrolled ( 10 in phase 1 and 70 r and omized in phase 2 : 36 to arm B and 34 to arm C ) . The ORR was 38.9 % ( 95 % confidence interval [ CI ] , 23 - 54.8 % ) and 64.7 % ( 95 % CI , 48.6 - 80.8 % ) for arms B and C , respectively ( P = .035 ) . As of June 2015 , 62 of the 70 r and omized patients had progressed . The median progression-free survival ( PFS ) was 4.4 ( 95 % CI , 2.3 - 5.7 ) and 9.5 months ( 95 % CI , 4.6 - 14 ) for arms B and C , respectively ( P = .106 ) . Toxicity was predominantly hematologic in nature but was not statistically higher in arm C. The combination of PomCyDex results in a superior ORR and PFS compared with PomDex in patients with lenalidomide refractory multiple myeloma . The trial was registered at www . clinical trials.gov as # NCT01432600 Bortezomib frequently produces severe treatment-related peripheral neuropathy ( PN ) in Waldenström 's macroglobulinemia ( WM ) . Carfilzomib is a neuropathy-sparing proteasome inhibitor . We examined carfilzomib , rituximab , and dexamethasone ( CaRD ) in symptomatic WM patients naïve to bortezomib and rituximab . Protocol therapy consisted of intravenous carfilzomib , 20 mg/m2 ( cycle 1 ) and 36 mg/m(2 ) ( cycles 2 - 6 ) , with intravenous dexamethasone , 20 mg , on days 1 , 2 , 8 , and 9 , and rituximab , 375 mg/m(2 ) , on days 2 and 9 every 21 days . Maintenance therapy followed 8 weeks later with intravenous carfilzomib , 36 mg/m(2 ) , and intravenous dexamethasone , 20 mg , on days 1 and 2 , and rituximab , 375 mg/m(2 ) , on day 2 every 8 weeks for 8 cycles . Overall response rate was 87.1 % ( 1 complete response , 10 very good partial responses , 10 partial responses , and 6 minimal responses ) and was not impacted by MYD88(L265P ) or CXCR4(WHIM ) mutation status . With a median follow-up of 15.4 months , 20 patients remain progression free . Grade ≥2 toxicities included asymptomatic hyperlipasemia ( 41.9 % ) , reversible neutropenia ( 12.9 % ) , and cardiomyopathy in 1 patient ( 3.2 % ) with multiple risk factors , and PN in 1 patient ( 3.2 % ) which was grade 2 . Declines in serum IgA and IgG were common . CaRD offers a neuropathy-sparing approach for proteasome inhibitor-based therapy in WM . This trial is registered at www . clinical trials.gov as # NCT01470196 BACKGROUND Few effective treatments exist for patients with refractory or relapsed and refractory multiple myeloma not responding to treatment with bortezomib and lenalidomide . Pomalidomide alone has shown limited efficacy in patients with relapsed multiple myeloma , but synergistic effects have been noted when combined with dexamethasone . We compared the efficacy and safety of pomalidomide plus low-dose dexamethasone with high-dose dexamethasone alone in these patients . METHODS This multicentre , open-label , r and omised phase 3 trial was undertaken in Australia , Canada , Europe , Russia , and the USA . Patients were eligible if they had been diagnosed with refractory or relapsed and refractory multiple myeloma , and had failed at least two previous treatments of bortezomib and lenalidomide . They were assigned in a 2:1 ratio with a vali date d interactive voice and internet response system to either 28 day cycles of pomalidomide ( 4 mg/day on days 1 - 21 , orally ) plus low-dose dexamethasone ( 40 mg/day on days 1 , 8 , 15 , and 22 , orally ) or high-dose dexamethasone ( 40 mg/day on days 1 - 4 , 9 - 12 , and 17 - 20 , orally ) until disease progression or unacceptable toxicity . Stratification factors were age ( ≤75 years vs > 75 years ) , disease population ( refractory vs relapsed and refractory vs bortezomib intolerant ) , and number of previous treatments ( two vs more than two ) . The primary endpoint was progression-free survival ( PFS ) . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT01311687 , and with EudraCT , number 2010 - 019820 - 30 . FINDINGS The accrual for the study has been completed and the analyses are presented . 302 patients were r and omly assigned to receive pomalidomide plus low-dose dexamethasone and 153 high-dose dexamethasone . After a median follow-up of 10·0 months ( IQR 7·2 - 13·2 ) , median PFS with pomalidomide plus low-dose dexamethasone was 4·0 months ( 95 % CI 3·6 - 4·7 ) versus 1·9 months ( 1·9 - 2·2 ) with high-dose dexamethasone ( hazard ratio 0·48 [ 95 % CI 0·39 - 0·60 ] ; p<0·0001 ) . The most common grade 3 - 4 haematological adverse events in the pomalidomide plus low-dose dexamethasone and high-dose dexamethasone groups were neutropenia ( 143 [ 48 % ] of 300 vs 24 [ 16 % ] of 150 , respectively ) , anaemia ( 99 [ 33 % ] vs 55 [ 37 % ] , respectively ) , and thrombocytopenia ( 67 [ 22 % ] vs 39 [ 26 % ] , respectively ) . Grade 3 - 4 non-haematological adverse events in the pomalidomide plus low-dose dexamethasone and high-dose dexamethasone groups included pneumonia ( 38 [ 13 % ] vs 12 [ 8 % ] , respectively ) , bone pain ( 21 [ 7 % ] vs seven [ 5 % ] , respectively ) , and fatigue ( 16 [ 5 % ] vs nine [ 6 % ] , respectively ) . There were 11 ( 4 % ) treatment-related adverse events leading to death in the pomalidomide plus low-dose dexamethasone group and seven ( 5 % ) in the high-dose dexamethasone group . INTERPRETATION Pomalidomide plus low-dose dexamethasone , an oral regimen , could be considered a new treatment option in patients with refractory or relapsed and refractory multiple myeloma . FUNDING Celgene Corporation The combination of pomalidomide and low-dose dexamethasone ( Pom-Dex ) can be safely administered to patients with end-stage relapsed/refractory multiple myeloma ( RRMM ) . However , we observed a shorter median progression-free survival ( PFS ) and overall survival ( OS ) in these patients when characterized with adverse cytogenetics ( deletion 17p and translocation [ 4;14 ] ) in the Intergroupe Francophone Myélome ( IFM ) 2009 - 02 trial . We then sought to determine whether MM with adverse cytogenetics would benefit more from Pom-Dex if exposed earlier in the multicenter IFM 2010 - 02 trial . The intention-to-treat population included 50 patients , with a median age of 63 years ( 38 % were ≥65 years ) . Interestingly , there was a striking difference in time to progression ( TTP ) , duration of response , and overall response rate ( ORR ) according to the presence of del(17p ) compared with t(4;14 ) ( TTP , 7.3 vs 2.8 months ; duration of response , 8.3 vs 2.4 months ; and ORR , 32 % vs 15 % ) . OS was prolonged after Pom-Dex , particularly in t(4;14 ) , given the short TTP , suggesting that patients were rescued at relapse with further lines of therapy . Pom-Dex , a doublet immunomodulatory drug-based regimen , is active and well tolerated in adverse cytogenetic patients with early RRMM , particularly in those with del(17p ) , who are characterized by a high and rapid development of a refractoriness state and known for their poor prognosis . Future studies will determine the underlying mechanisms of Pom-Dex activity in del(17p ) . This trial is registered at www . clinical trials.gov as # NCT01745640 This multicenter , open-label , r and omized phase 2 study assessed the efficacy and safety of pomalidomide ( POM ) with/without low-dose dexamethasone ( LoDEX ) in patients with relapsed/refractory multiple myeloma ( RRMM ) . Patients who had received ≥2 prior therapies ( including lenalidomide [ LEN ] and bortezomib [ BORT ] ) and had progressed within 60 days of their last therapy were r and omized to POM ( 4 mg/day on days 1 - 21 of each 28-day cycle ) with/without LoDEX ( 40 mg/week ) . The primary end point was progression-free survival ( PFS ) . In total , 221 patients ( median 5 prior therapies , range 1 - 13 ) received POM+LoDEX ( n = 113 ) or POM ( n = 108 ) . With a median follow-up of 14.2 months , median PFS was 4.2 and 2.7 months ( hazard ratio = 0.68 , P = .003 ) , overall response rates ( ORRs ) were 33 % and 18 % ( P = .013 ) , median response duration was 8.3 and 10.7 months , and median overall survival ( OS ) was 16.5 and 13.6 months , respectively . Refractoriness to LEN , or resistance to both LEN and BORT , did not affect outcomes with POM+LoDEX ( median PFS 3.8 months for both ; ORRs 30 % and 31 % ; and median OS 16 and 13.4 months ) . Grade 3 - 4 neutropenia occurred in 41 % ( POM+LoDEX ) and 48 % ( POM ) ; no grade 3 - 4 peripheral neuropathy was reported . POM+LoDEX was effective and generally well tolerated and provides an important new treatment option for RRMM patients who have received multiple prior therapies . This trial was registered at www . clinical trials.gov as # NCT00833833 The combination of pomalidomide and dexamethasone can be safely administered to patients with multiple myeloma ( MM ) and has significant efficacy , although the optimal regimen remains to be determined . Patients with MM whose disease progressed after multiple lines of therapy have limited treatment options . We design ed a multicenter , phase 2 r and omized study assessing two different dose regimens of pomalidomide and dexamethasone in advanced MM . Treatment response was assessed central ly . Pomalidomide ( 4 mg ) was given orally on days 1 to 21 ( arm 21/28 ) or continuously ( arm 28/28 ) over a 28-day cycle , plus dexamethasone given weekly . Eighty-four patients ( 43 , arm 21/28 and 41 , arm 28/28 ) were r and omized . The median number of prior lines was 5 . Overall response rate was 35 % ( arm 21/28 ) and 34 % ( arm 28/28 ) , independent of the number of prior lines and level of refractoriness . Median duration of response , time to disease progression , and progression-free survival was 7.3 , 5.4 , and 4.6 months , respectively , which was similar across cohorts . At 23 months follow-up , median overall survival was 14.9 months , with 44 % of the patients alive at 18 months . Toxicity consisted primarily of myelosuppression , which was manageable . The efficacy and safety data presented here , along with data from other phase 2 trials , suggest that pomalidomide 4 mg per day on days 1 to 21 of 28 with dexamethasone should be investigated in future trials . This trial is registered at Clinical Trials.gov ( No. NCT01053949 ) This multicenter phase 2 study of the European Myeloma Network investigated the combination of carfilzomib , thalidomide , and dexamethasone ( KTd ) as induction/consolidation therapy for transplant-eligible patients with previously untreated multiple myeloma ( N = 91 ) . During KTd induction therapy , patients received 4 cycles of carfilzomib 20/27 mg/m(2 ) ( n = 50 ) , 20/36 mg/m(2 ) ( n = 20 ) , 20/45 mg/m(2 ) ( n = 21 ) , or 20/56 mg/m(2 ) ( n = 20 ) on days 1 , 2 , 8 , 9 , 15 , and 16 of a 28-day cycle ; thalidomide 200 mg on days 1 to 28 ; and dexamethasone 20 mg on days 1 , 2 , 8 , 9 , 15 , and 16 . After autologous stem cell transplantation , patients proceeded to KTd consolidation therapy , where the target doses of carfilzomib were 27 mg/m(2 ) , 36 mg/m(2 ) , 45 mg/m(2 ) , or 56 mg/m(2 ) , respectively , and thalidomide 50 mg . Common grade 3/4 adverse events included respiratory ( 15 % ) , gastrointestinal ( 12 % ) , and skin disorders ( 10 % ) ; polyneuropathy was infrequent ( 1 % ) . Complete response rates after induction and consolidation treatment were 25 % and 63 % , respectively ; rates of very good partial response or better after induction and consolidation were 68 % and 89 % , respectively . At a median follow-up of 23 months , the 36-month progression-free survival rate was 72 % . The KTd induction and consolidation regimens were active , safe , and well tolerated . This study was registered at http://www.trialregister.nl as # NTR2422 This multicenter , open-label phase 2 trial determined the safety and efficacy of carfilzomib , a novel and irreversible proteasome inhibitor , in combination with cyclophosphamide and dexamethasone ( CCyd ) in patients with newly diagnosed multiple myeloma ( NDMM ) ≥65 years of age or who were ineligible for autologous stem cell transplantation . Patients ( N = 58 ) received CCyd for up to 9 28-day cycles , followed by maintenance with carfilzomib until progression or intolerance . After a median of 9 CCyd induction cycles ( range 1 - 9 ) , 95 % of patients achieved at least a partial response , 71 % achieved at least a very good partial response , 49 % achieved at least a near complete response , and 20 % achieved stringent complete response . After a median follow-up of 18 months , the 2-year progression-free survival and overall survival rates were 76 % and 87 % , respectively . The most frequent grade 3 to 5 toxicities were neutropenia ( 20 % ) , anemia ( 11 % ) , and cardiopulmonary adverse events ( 7 % ) . Peripheral neuropathy was limited to grade s 1 and 2 ( 9 % ) . Fourteen percent of patients discontinued treatment because of adverse events , and 21 % of patients required carfilzomib dose reductions . In summary , results showed high complete response rates and a good safety profile . This trial was registered at clinical trials.gov as # NCT01346787 We performed a phase 1/2 trial to determine the maximum tolerated dose ( MTD ) of pomalidomide and to explore its efficacy when combined with cyclophosphamide-prednisone in relapsed/refractory myeloma patients . Pomalidomide was given at 1 to 2.5 mg/d , cyclophosphamide at 50 mg every other day , prednisone at 50 mg every other day , for 6 28-day cycles , followed by pomalidomide-prednisone maintenance therapy . Thromboprophylaxis was recommended . Sixty-nine patients were enrolled , 55 received the MTD ( 2.5 mg/d ) and were evaluated . Best responses included complete response in 3 patients ( 5 % ) , very good partial response in 10 ( 18 % ) , partial response in 15 ( 27 % ) , minimal response in 11 ( 20 % ) , stable disease in 15 ( 27 % ) , and progressive disease in 1 ( 3 % ) , for an overall response rate of 51 % . The median time-to-response was 1.83 months . After a median follow-up of 14.8 months , median progression-free survival was 10.4 months and 1-year overall survival was 69 % . At the MTD , grade 3 to 4 toxicities included anemia ( 9 % ) , thrombocytopenia ( 11 % ) , neutropenia ( 42 % ) , neurologic events ( 7 % ) , dermatologic events ( 7 % ) , and thromboembolism ( 2 % ) . Grade 3 to 5 infections occurred in 5 patients ( 9 % ) . Five patients ( 9 % ) discontinued treatment for toxicity . New grade 3 to 4 adverse events were low during maintenance . Pomalidomide-cyclophosphamide-prednisone is safe and effective in relapsed/refractory myeloma patients . This trial was registered at www . clinical trials.gov as # NCT01166113 PURPOSE Thalidomide and lenalidomide are immunomodulatory drugs ( IMiDs ) that produce high remission rates in the treatment of multiple myeloma . Pomalidomide is a new IMiD with high in vitro potency . We report , to our knowledge , the first phase II trial of pomalidomide administered in combination with low-dose dexamethasone for the treatment of relapsed or refractory multiple myeloma . PATIENTS AND METHODS Pomalidomide was administered orally at a dose of 2 mg daily on days 1 through 28 of a 28-day cycle . Dexamethasone 40 mg daily was administered orally on days 1 , 8 , 15 , and 22 of each cycle . Responses were recorded using the criteria of the International Myeloma Working Group . RESULTS Sixty patients were enrolled . Thirty-eight patients ( 63 % ) achieved confirmed response including complete response in three patients ( 5 % ) , very good partial response in 17 patients ( 28 % ) , and partial response in 18 patients ( 30 % ) . Responses were seen in 40 % of lenalidomide-refractory patients , 37 % of thalidomide-refractory patients , and 60 % of bortezomib-refractory patients . Responses were seen in 74 % of patients with high-risk cytogenetic or molecular markers . Toxicity consisted primarily of myelosuppression . Grade 3 or 4 hematologic toxicity consisted of anemia ( 5 % ) , thrombocytopenia ( 3 % ) , and neutropenia ( 32 % ) . One patient ( 1.6 % ) had a thromboembolic event . The median progression-free survival time was 11.6 months and was not significantly different in patients with high-risk disease compared with patients with st and ard-risk disease . CONCLUSION The combination of pomalidomide and low-dose dexamethasone is extremely active in the treatment of relapsed multiple myeloma , including high response rates in patients refractory to other novel agents Sixty‐four transplant‐eligible patients with newly diagnosed multiple myeloma ( NDMM ) received carfilzomib ( days 1 , 2 , 8 , 9 , 15 , 16 ) , 300 mg/m2 cyclophosphamide ( days 1 , 8 , 15 ) , 100 mg thalidomide ( days 1–28 ) and 40 mg dexamethasone ( days 1 , 8 , 15 , 22 ) in 28‐day cycles ( CYKLONE regimen ) . Carfilzomib was dose‐escalated to 15/20 , 20/27 , 20/36 and 20/45 mg/m2 to determine the maximum tolerated dose ( MTD ) , which was 20/36 mg/m2 . Regardless of attribution , common Grade 3 or higher adverse events were lymphopenia ( 38 % ) , neutropenia ( 23 % ) and anaemia ( 20 % ) . All peripheral neuropathy ( 31 % ) was Grade 1 and considered most likely to be thalidomide‐related . Common cardiac or pulmonary events of any grade in ≥5 % of patients included dyspnoea ( 20 % ) and cough ( 6 % ) . Overall ( N = 64 ) , 91 % of patients achieved a best response of partial response or better across all cycles of treatment , including five patients with complete responses . At the MTD ( n = 29 ) , 59 % of patients achieved a very good partial response or better after four cycles ( primary end point ) . Stem cell collection was successful in all patients in whom it was attempted ( n = 42 ) . Progression‐free survival and overall survival at 24 months was 76 % and 96 % , respectively ( median follow‐up of 17·5 months ) . CYKLONE appears highly efficacious in NDMM patients , with manageable toxicities Pomalidomide at doses of 2 or 4 mg/d has demonstrated excellent activity in patients with multiple myeloma ( MM ) . We opened 2 sequential phase 2 trials using the pomalidomide with weekly dexamethasone ( Pom/dex ) regimen at differing doses to study the efficacy of this regimen in patients who have failed both lenalidomide and bortezomib . Pomalidomide was given orally 2 or 4 mg daily with dexamethasone 40 mg weekly . Thirty-five patients were enrolled in each cohort . Confirmed responses in the 2-mg cohort consisted of very good partial response ( VGPR ) in 5 ( 14 % ) , partial response ( PR ) in 4 ( 11 % ) , minor response ( MR ) in 8 ( 23 % ) for an overall response rate of 49 % . In the 4-mg cohort , confirmed responses consisted of complete response ( CR ) in 1 ( 3 % ) , VGPR in 3 ( 9 % ) , PR in 6 ( 17 % ) , MR in 5 ( 14 % ) for an overall response rate of 43 % . Overall survival at 6 months is 78 % and 67 % in the 2- and 4-mg cohort , respectively . Myelosuppression was the most common toxicity . This nonr and omized data suggests no advantage for 4 mg over the 2 mg daily . Pomalidomide overcomes resistance in myeloma refractory to both lenalidomide and bortezomib . This trial is registered at http:// Clinical Trials.gov , number NCT00558896 Pomalidomide is a distinct oral IMiD ® immunomodulatory agent with direct antimyeloma , stromal-support inhibitory , and immunomodulatory effects . The pivotal , multicenter , open-label , r and omized phase 3 trial MM-003 compared pomalidomide + low-dose dexamethasone vs high-dose dexamethasone in 455 patients with refractory or relapsed and refractory multiple myeloma after failure of bortezomib and lenalidomide treatment . Initial results demonstrated significantly longer progression-free survival and overall survival with an acceptable tolerability profile for pomalidomide + low-dose dexamethasone vs high-dose dexamethasone . This secondary analysis describes patient outcomes by treatment history and depth of response . Pomalidomide + low-dose dexamethasone significantly prolonged progression-free survival and favored overall survival vs high-dose dexamethasone for all subgroups analyzed , regardless of prior treatments or refractory status . Both univariate and multivariate analyses showed that no variable relating to either the number ( ≤ or > 3 ) or type of prior treatment was a significant predictor of progression-free survival or overall survival . No cross-resistance with prior lenalidomide or thalidomide treatment was observed . Patients achieving a minimal response or better to pomalidomide + low-dose dexamethasone treatment experienced a survival benefit , which was even higher in those achieving at least a partial response ( 17.2 and 19.9 months , respectively , as compared with 7.5 months for patients with less than minimal response ) . These data suggest that pomalidomide + low-dose dexamethasone should be considered a st and ard of care in patients with refractory or relapsed and refractory multiple myeloma regardless of prior treatment . Clinical Trials.gov : NCT01311687 ; EudraCT : 2010 - 019820 - 30 |
686 | 17,054,198 | In view of the low quality methodology of almost all the studies , this review does not provide sufficient evidence to support any specific surgical or conservative intervention for chronic ankle instability .
However , after surgical reconstruction , early functional rehabilitation was shown to be superior to six weeks immobilisation regarding time to return to work and sports | BACKGROUND Chronic lateral ankle instability occurs in 10 % to 20 % of people after an acute ankle sprain .
The initial form of treatment is conservative but if this fails and ligament laxity is present , surgical intervention is considered .
OBJECTIVES To compare different treatments , both conservative and surgical , for chronic lateral ankle instability . | 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 ( enrolment , 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 Functional outcome , stability at radiographic investigation and ankle joint torque after anatomical reconstruction of the lateral ankle ligaments were evaluated in patients with early postoperative mobilization versus those with cast immobilization . Thirty patients with chronic lateral ligament instability of the ankle underwent anatomical reconstruction of the ligaments . Postoperatively the patients were r and omly allocated to two groups : Group A ( n=15 ) were immobilized in a below-knee plaster for 6 weeks and Group B ( n=15 ) underwent early controlled range of motion training using an Air-Cast ankle brace . The functional results were evaluated using a scoring scale and objective results using st and ardized stress radiographs . Also eccentric and concentric muscle torque at 60 degrees/s was measured in plantar flexion and dorsiflexion , respectively . The functional results were satisfactory in 12/15 ankles in Group A and 14/15 in Group B ( n.s . ) . All the patients with satisfactory results regained normal range of motion . Patients with unsatisfactory results had either residual pain or recurrent instability . In Group B , the strength measurements revealed significantly higher peak torque values after three months in plantar flexion at 60 degrees/s . Six months postoperatively , the torque values did not differ significantly between the groups . Also , there was no group difference in the laxity of the ankle joint , including both anterior talar translation test and talar tilt test , at the two-year follow-up . One patient had a superficial wound infection . We conclude that after the reconstruction of chronic lateral ligament instability of the ankle the functional and stability results were equally good with early postoperative mobilization and 6-week immobilization . However , using early mobilization plantar flexion strength was regained earlier than with cast immobilization , without any risk of short- or medium-term complications , such as increased ankle laxity . We recommend early mobilization after anatomical reconstruction of the lateral ankle ligaments To study the efficacy of an injury prevention program in a r and omized trial , 12 teams ( 180 players ) in a male senior soccer division were followed up for 6 months . The 12 teams were allocated at r and om to two groups of six teams , one being given a prophylactic program and the other serving as control . The program was based on previous studies of injury mechanisms . It comprised ( 1 ) correction of training , ( 2 ) provision of optimum equipment ; ( 3 ) prophylactic ankle taping ; ( 4 ) controlled rehabilitation ; ( 5 ) exclusion of players with grave knee instability ; ( 6 ) information about the impor tance of disciplined play and the increased risk of injury at training camps ; and ( 7 ) correction and supervision by doctor(s ) and physiotherapist(s ) . The injuries in the test teams were 75 % fewer than in the controls . The most common types of soccer injuries , sprains and strains to ankles and knees , were all significantly reduced . It is concluded that the pro posed prophylactic program , including close supervi sion and correction by doctors and physiotherapists , significantly reduces soccer injuries STUDY DESIGN Within-group repeated measures . OBJECTIVES To determine the effect of a semi-rigid prophylactic ankle stabilizer ( PAS ) on performance of subjects with post-acute , unilateral ankle sprains who have mechanically stable ankles , but are functionally impaired . BACKGROUND Most studies on PAS performance to date are limited to subjects with noninjured , nonimpaired ankles . No research has been reported to determine the effect PASs have on performance in subjects who have a mechanically stable , nonacute ankle sprain with functional impairment . METHODS AND MEASURES Twenty-five subjects ( 8 men and 17 women ; average height = 168.91 + /- 33.02 cm , average weight = 61.10 + /- 29.5 kg , and average age = 16.2 + /- 6 years ) met the qualification criteria of the study . Subjects had unilateral grade I or II lateral ankle sprains of 3 to 4 weeks duration and were cleared medically to return to activities of daily living . Each subject 's injured ankle was mechanically stable as determined by physical exam but was functionally impaired as determined by instability during the modified Rhomberg test . Separate 2 x 2 ANOVAs with repeated measures on brace condition ( Aircast SportStirrup and nonbraced control ) and test session ( test session 1 and test session 2 ) were completed to assess the effect of ankle stabilization on 2 dependent variables ( 36.58-m shuttle-run and vertical-jump ) . RESULTS Shuttle-run time was significantly faster for the braced condition ( mean = 9.43 + /- .72 seconds ) than for the nonbraced control ( mean = 9.57 + /- .75 seconds ) , regardless of test session . Shuttle-run time was significantly faster for test session 2 ( mean = 9.43 + /- .79 seconds ) than for test session 1 ( mean = 9.57 + /- .68 seconds ) , regardless of brace condition . No significant main or interaction effects occurred for vertical-jump . CONCLUSIONS Use of a semi-rigid PAS significantly increased shuttle-run but not vertical-jump performance . This effect was immediate and did not require PAS acclimation A bi-directional bicycle pedal that combines proprioceptive training and evertor strengthening has been developed for the treatment of residual instability after ankle sprains . A prospect i ve r and omized study was carried out on 19 subjects with recurrent ankle sprains and positive stress X-ray films . The subjects were r and omized to use either a bi-directional test pedal or a traditional uni-directional bicycle pedal and then completed a 6-week high-intensity training program on a cycle ergometer . Assessment of training intensity level was based on maximum oxygen uptake values , heart rate and lactate concentration in blood at various submaximal workloads . After completion of the training program , the subjects who had used the test pedal increased peak eversion torque at 180 degrees degrees s-1 by 14.2 % ( P = 0.020 ) , reduced figure-of-eight running time by 0.24 s ( P = 0.003 ) , improved single leg stance speed from 72.5 % to the maximum speed of 80 % ( P = 0.005 ) , and improved Karlsson functional score by 5.1 points ( P = 0.005 ) . In the control group , single leg stance improved from 56.1 to 67.8 % ( P = 0.018 ) , but otherwise no significant effects were found . This study indicates that short-term high-intensity training with a bi-directional pedal improves ankle performance and may be an option in the treatment of recurrent ankle sprains Early range of motion training after ligament reconstruction of the ankle ligaments for chronic ankle joint instability was evaluated . Forty patients were operated on with anatomic reconstruction of the lateral ankle ligaments , i.e. shortening , imbrication and reinsertion . The patients were r and omized postoperatively between two groups : ( 1 ) immobilization for 6 weeks in a plaster cast and ( 2 ) early range of motion training , in a Walker-Boot . Both groups underwent an identical rehabilitation program . with peroneal strengthening and co-ordination training after 6 weeks . The functional results were evaluated using a scoring scale and the mechanical stability with st and ardized stress radiographs . The minimum follow-up was 2 years . The functional results were satisfactory in 16 ( 80 % ) of the patients in group I , and 19 ( 95 % ) in group II . The mean values of anterior talar translation and talar tilt were not significantly different between the groups preoperatively nor at follow-up . The mean time period for sick leave was significantly shorter for group II , 6.5±1.6 weeks compared with 8.5±1.8 weeks for group I. The mean time period for return to sports activity was significantly shorter for group II , 9.5±2.2 weeks , compared with 12.5±2.6 weeks for group I. Early range of motion training is recommended after ligament reconstruction of the ankle , as it will enable earlier return to sports activities , shorter sick leave and preserved mechanical stability Objectives : To examine the effect of six weeks of strength and proprioception training on eversion to inversion isokinetic strength ratios ( E/I ratios ) in subjects with unilateral functional ankle instability . Methods : Thirty eight subjects were r and omly assigned to one of four treatment groups : strength training ( S ) ; proprioception training ( P ) ; strength + proprioception training ( B ) ; control ( C ) . Isokinetic strength was tested before and after training using a Kin Com 125 automatic positioning isokinetic dynamometer . Subtalar joint eversion and inversion motions were tested both concentrically and eccentrically through a range of motion involving 40 ° . All peak torque and average torque values were normalised for body mass . E/I ratios were calculated from average torque and peak torque measures by taking the concentric eversion value and combining it with the eccentric inversion value . Data were analysed using a mixed model analysis of variance with repeated measures on the test factor . Average torque and peak torque E/I ratios at 30 and 120 ° /s were analysed separately . Results : There were no significant differences in average torque and peak torque E/I ratios of the functionally unstable ankle for any of the groups after training compared with before . Conclusions : Six weeks of strength and proprioception training ( either alone or combined ) had no effect on isokinetic measures of strength in subjects with self reported unilateral functional instability . Further studies examining this agonist ( concentric ) to antagonist ( eccentric ) muscle group strength ratio are needed A study was undertaken to evaluate the effect of a semi rigid ankle orthosis ( Sport-Stirrup ) on the incidence of ankle sprains in soccer players during 1 playing season . Senior soccer players were divided into 2 groups : play ers with previous ankle sprains ( N = 258 ) and players without such history ( N = 246 ) . The players in these groups were each r and omly allocated to either a semi rigid orthosis or a control group at the start of the playing season . All subsequent injuries during the season and the total number of playing hours were documented . There was a significant reduction in the incidence of ankle sprains ( injuries/1 000 playing hours ) by ankles in the orthosis group with previous sprains ( 0.14 ) com pared with the nonbraced group with previous sprains ( 0.86 ) . The incidence of ankle sprains was significantly higher in the nonbraced group with previous sprains ( 0.86 ) compared with the nonbraced group without pre vious sprains ( 0.46 ) . Thus , in this study , a semirigid or thosis significantly reduced the incidence of recurrent ankle sprains in soccer players with previous history of ankle sprains Exercises to improve joint proprioception and coordination of the functionally unstable ankle are advocated throughout the literature , yet there is little evidence that these exercise have any effect on proprioception and balance . The purpose of this study was to determine the effects of a 6-week coordination and balance training program on proprioception of subjects with functional ankle instability . Forty-five subjects ( age = 22.53 + /- 3.95 years , height = 172.04 + /- 10.0 cm , weight = 71.72 + /- 15.7 kg ) were r and omly placed into a control ( Group 1 ) , sham ( Group 2 ) , or experimental ( Group 3 ) group . The experimental group trained 3 days per week , 10 minutes each day , performing various balance and proprioception exercises . Postural sway and active and passive joint position sense were assessed . Analysis of variance for postural sway modified equilibrium score for anterior and posterior sway , as well as medial and lateral sway revealed significant four-way interactions . Tukey post hoc analyses revealed that Group 3 performed significantly better ( p < .05 ) than Group 1 and Group 2 on the posttests . There were no significant differences for joint position sense or postural sway index . Results suggest that balance and coordination training can improve some measures of postural sway . It is still unclear if joint position sense can be improved in the functionally unstable ankle The present study investigated the effects of two different surgical procedures for the treatment of chronic ankle instability . Ten patients treated with an anatomic reconstruction using a periosteal flap were compared with a second group that received an Evans tenodesis . All patients were evaluated before and after surgery with clinical and radiographic examinations as well as dynamic pedobarography . Patient satisfaction and radiographic and functional results were comparable in both groups and revealed a good restoration of joint stability and gait symmetry . Our results indicate that both methods of ankle ligament reconstruction achieve a comparable clinical and functional outcome within 1 year after surgery OBJECTIVE To examine the effects of ankle-strengthening exercises on joint position sense and strength development in subjects with functionally unstable ankles . DESIGN AND SETTING Subjects were r and omly assigned to a training or control group . The training group participated in a 6-week strength-training protocol using rubber tubing 3 times a week throughout the training period . The control group did not participate in the strength-training protocol . SUBJECTS Twenty healthy college students ( 10 females , 10 males , age = 20.6 + /- 2.23 years ; ht = 176.40 + /- 7.14 cm ; wt = 74.18 + /- 10.17 kg ) with a history of functional ankle instability volunteered to participate in this study . MEASUREMENTS We pretested and posttested dorsiflexor and evertor isometric strength with a h and held dynamometer and collected joint position sense ( JPS ) data at 20 degrees for inversion and plantar flexion and at 10 degrees for eversion and dorsiflexion . RESULTS Statistical tests for strength and JPS revealed significant group-by-time interactions for dorsiflexion strength , eversion strength , inversion JPS , and plantar flexion JPS . Simple main-effects testing revealed improvements in training group strength and JPS at posttesting . There were no significant effects for eversion JPS , but the group main effect for dorsiflexion JPS was significant , with the experimental group having better scores than the control group . CONCLUSIONS Ankle-strengthening exercises improved strength , inversion JPS , dorsiflexion JPS , and plantar flexion JPS in subjects with functionally unstable ankles Twenty-two university students with unilateral functional instability of the ankle participated in this study . They were r and omly assigned to one of two experimental groups . Subjects in both groups were trained to st and on the affected limb on an ankle disk . In group 1 , two pieces of 1-cm wide nonelastic adhesive tape were applied to the skin around the lateral malleolus from the distal third of the lower leg to the sole of the foot before the training sessions . Subjects in group 2 participated in the training sessions without the application of the adhesive tape . Training was performed for 10 minutes a day , five times per week , for a period of 10 weeks . Subjects were tested for postural sway while st and ing on the affected limb before , during , and after the training period . In group 1 , postural sway values decreased significantly after 4 weeks compared with the pretraining performance , and they were within the normal range after not more than 6 weeks of training . In group 2 , the values did not improve significantly compared with the pretraining performance until after 6 weeks of training , and they were not within the normal range until after 8 weeks of training . The findings suggest that the 2-week earlier correction of postural sway in group 1 was due to an increased afferent input from skin receptors that were stimulated by the traction of the adhesive tape OBJECTIVE The purpose of this study was to determine the efficacy of adjusting the ankle in the treatment of subacute and chronic grade I and grade II ankle inversion sprains . DESIGN A single-blind , comparative , controlled pilot study . SETTING Technikon Natal Chiropractic Day Clinic . PARTICIPANTS Thirty patients with subacute and chronic grade I and grade II ankle inversion sprains . Patients were recruited from the public ; they responded to advertisements placed in newspapers and on notice boards around the campus and local sports clubs . INTERVENTION Each of the 15 patients in the treatment group received the ankle mortise separation adjustment . Each of the 15 patients in the placebo group received 5 minutes of detuned ultrasound treatment . Each participant received a maximum of 8 treatment sessions spread over a period of 4 weeks . MAIN OUTCOME MEASURE Patients were evaluated at the first treatment , at the final treatment , and at a 1-month follow-up consultation . Subjective scores were obtained by means of the short-form McGill Pain Question naire and the Numerical Pain Rating Scale 101 . Objective measurements were obtained from goniometer readings measuring ankle dorsiflexion range of motion and algometer readings measuring pain threshold over the ankle lateral ligaments . A functional evaluation of ankle function was also used . RESULTS Although both groups showed improvement , statistically significant differences in favor of the adjustment group were noted with respect to reduction in pain , increased ankle range of motion , and ankle function . CONCLUSIONS This study appears to indicate that the mortise separation adjustment may be superior to detuned ultrasound therapy in the management of subacute and chronic grade I and grade II inversion ankle sprains Physiotherapists frequently use manipulative therapy techniques to treat dysfunction and pain result ing from ankle sprain . This study investigated whether a Mulligan 's mobilization with movement ( MWM ) technique improves talocrural dorsiflexion , a major impairment following ankle sprain , and relieves pain in subacute population s. Fourteen subjects with subacute grade II lateral ankle sprains served as their own control in a repeated measures , double-blind r and omized controlled trial that measured the initial effects of the MWM treatment on weight bearing dorsiflexion and pressure and thermal pain threshold . The subacute ankle sprain group studied displayed deficits in dorsiflexion and local pressure pain threshold in the symptomatic ankle . Significant improvements in dorsiflexion occurred initially post-MWM ( F(2,26 ) = 7.82 , P = 0.002 ) , but no significant changes in pressure or thermal pain threshold were observed after the treatment condition . Results indicate that the MWM treatment for ankle dorsiflexion has a mechanical rather than hypoalgesic effect in subacute ankle sprains . The mechanism by which this occurs requires investigation if we are to better underst and the role of manipulative therapy in ankle sprain management Eighty-six patients with acute ( < 24 h ) grade II or III lateral ligament ruptures were r and omized into two different non-surgical treatment groups . The main difference in treatment protocol s between the two groups was during the first week after injury . Group I ( n = 46 ) was to receive functional treatment using specially design ed compression pads , elevation of the injured foot ( 24 h ) , repeated elastic wrapping ( compression b and age followed by ankle tape ) , early full weight-bearing and proprioceptive range-of-motion training . Group II ( n = 40 ) was to receive conventional treatment with an elastic b and age , partial weight bearing and crutches until the pain subsided . One week after the injury , patients from both groups were given identical rehabilitation instructions . No early surgery was performed . The mean follow-up period was 18 months . The functional results were satisfactory in 91 % of the patients in group I and in 87 % of the patients in group II ( NS ) . Five patients had been operated on due to recurrent instability , two in group I and three in group II ( NS ) . The mean sick leave was significantly shorter in group I ; 5.6 + /- 4.2 days compared with 10.2 + /- 6.8 days in group II . Return to sports activities was also significantly earlier in group I , 9.6 + /- 4.8 days compared with 19.2 + /- 9.5 days in group II . In this study , non-surgical treatment of acute grade II and III ligament injuries of the ankle produced satisfactory results in the majority of patients . Early functional treatment result ed in shorter sick leave and facilitated an earlier return to sports , but it did not influence the final results This r and omized clinical study was design ed to pro spectively determine the efficacy of a semirigid ankle stabilizer in reducing the frequency and severity of acute ankle injuries in basketball . Athletic shoe , playing surface , athlete-exposure , ankle injury history , and brace assignment were either statistically or experimen tally controlled . Participants in the study were 1601 United States Military Academy cadets with no prepar ticipation , clinical , functional , or radiographic evidence of ankle instability . Subjects experienced a total of 13,430 athlete-exposures in the 1990 and 1991 intra mural basketball seasons . Ankle injury was defined as acute trauma to the ankle ligaments that result ed in an athlete 's inability to participate in basketball 1 day after the injury . Use of ankle stabilizers significantly reduced the frequency of ankle injuries . Reduction in ankle in juries , however , depended on the nature of injury ( fewer contact injuries occurred among those who wore braces ) . Injury severity was not statistically reduced , and wearing the ankle stabilizer did not affect the fre quency of knee injuries . Attitude toward ankle stabilizer use improved as use of the stabilizer increased Background : A search of the literature shows that the effect of surgery on ankle proprioception has been hardly investigated . Objective : To examine the effect of anatomical reconstruction of the anterolateral capsuloligamentous complex on ankle joint position sense . Methods : A prospect i ve study using the “ slope box ” test . Ten consecutive patients were included in the study , and 10 healthy athletes represented the control group . Results : Similar test-retest reliability rates ( overall reliability 0.92 ; p = 0.0013 ) were obtained to those of the original design ers of the method . There were no significant differences with respect to side dominance ( p = 0.9216 ) . Investigation of the characteristics of mean absolute estimate errors showed that the controls tested became error prone in the range of slope altitudes 7.5–25 ° in every direction , compared with the range 0–5 ° ( range of p values 0.00003–0.00072 ) . The results of the intervention group showed that , for the two main directions of interest ( anterior and lateral ) , preoperative differences in mean absolute estimate errors between injured ( anterior 3.91 ( 2.81 ) ° ; lateral 4.06 ( 2.85 ) ° ) and healthy ( anterior 2.94 ( 2.21 ) ° , lateral 3.19 ( 2.64 ) ° ) sides ( anterior , p = 0.0124 ; lateral , p = 0.0250 ) had disappeared ( postoperative differences : anterior , p = 0.6906 ; lateral , p = 0.4491 ) . The afflicted ankle had improved significantly after surgery in both important directions ( anterior , p<0.0001 ; lateral , p = 0.0023 ) . Conclusions : The study shows that differences in joint position sense between healthy and injured ankles disappeared as the result of surgery . Preoperative data show that proprioceptive malfunction is a cause of functional instability . If treatment is by means of surgery , the retensioning of the original anterolateral structures is inevitable , even if other grafting or surgical techniques are used We prospect ively and r and omly compared the out comes of the Chrisman-Snook and modified-Broström procedures for chronic lateral ankle instability in 40 patients . Both operations provided good or excellent stability in more than 80 % of the patients . However , the modified-Broström procedure result ed in higher Sefton scores than the Chrisman-Snook procedure . In addi tion , a statistically significant greater proportion of complications occurred in patients treated with the Chrisman-Snook procedure Functional ankle instability , orthoses , and passive resistive torque tolerated have not been research ed . The purpose of the study was to evaluate the passive resistance torque exerted by a flexible and semirigid orthosis for individuals with chronic instability . Twenty-two subjects were evaluated on the passive ankle resistance unit during unbraced , flexible , and semirigid brace conditions . Data from the final three trials for each condition were analyzed using a multiple analysis of variance with repeated measures for resistive torque and inversion range of motion . The semirigid and flexible braces tolerated significantly greater torque forces and less inversion range than the unbraced condition ( P < 0.000 ) . External orthotic support , in particular that of a semirigid orthosis , may be beneficial toward reducing injury or be an effective prophylactic for the healthy population In a prospect i ve study , 82 patients with 89 chronic lateral unstable ankles were r and omly allocated to either static ( Group S ) or dynamic ( Group D ) reconstruction . For static reconstruction a procedure involving the distal part of the peroneus brevis tendon was used . The bore holes in the lateral malleolus were placed at the insertions of the original ligaments . For dynamic reconstruction the anterior one-half of the peroneus brevis tendon was used . On muscular contraction the split tendon will slide through a bore canal in the lateral malleolus . Theoretically , both procedures can stabilize the ankle and subtalar joint . Fifty-six patients were assigned to static reconstruction and , because of thin tendons , only 26 were assigned to dynamic reconstruction . Thirty-three cases had increased subtalar mobility . All patients had st and ardized clinical and roentgenographic examinations preoperatively and at nine and 25 months postoperatively . At the 25-month follow-up examinations the clinical results were best in Group S. The number of reinjuries was highest in Group D , and two patients had given up sports . The inversion movement was most restricted in Group S but without functional importance . A significant reduction of talar tilting and anterorotational talar displacement was seen in both groups but was most pronounced in Group S. Also , postural balance improved in both groups . Complications in Group S were venous thrombosis in two patients , dysesthesia in the cicatrix in two , hyposensibility of the lateral foot edge in one , and calcification at one bore hole in one patient . Complications in Group D were hyposensibility and dysesthesia in the cicatrix in one patient . The static procedure is recommended for reconstruction of chronically unstable ankles , especially if associated with increased subtalar mobility OBJECTIVE The aim of the present investigation was to test the stability of 10 different ankle braces under passive and rapidly induced loading conditions in a population suffering from chronic ankle instability in order to provide objective information to choose or recommend an appropriate model for specific needs . In addition , the relationship between passive and rapidly induced testing of the stabilizing effect against inversion was evaluated to identify if passive support characteristics of braces are reflected under rapidly induced conditions . DESIGN An experimental in vivo study with a repeated- measures design was used . BACKGROUND Ankle braces are commonly used for treatment , rehabilitation , and prevention of ankle injuries . A variety of products exists but there is few information available to assist clinicians , physiotherapists and coaches as well as consumers in choosing a brace on a basis of objective information . Furthermore , there is a lack of studies that provide data for both passively and rapidly induced movement of the ankle joint when using different ankle braces . METHODS Twenty-four subjects with chronic ankle instability participated in the project . Passive ankle range of motion measurements were performed in a custom-built fixture and simulated inversion sprains were elicited on a tilting platform . RESULTS The tested braces restrict range of motion significantly compared to the no-brace condition for both the passively and rapidly induced inversion and marked differences between braces were revealed . A close relationship between passive and rapidly induced test results for inversion was found . CONCLUSIONS Passive as well as rapidly induced stability tests provide a basis of objective information to describe the characteristics of different ankle braces . Combined results of passive and rapidly induced inversion as well as correlation between results demonstrate that passive support characteristics of braces are reflected under rapidly induced conditions but the amount of restriction is reduced . Therefore , caution should be taken when recommending braces for applications under dynamic circumstances only on the basis of passive support characteristics . RELEVANCE A basis of information regarding the stability characteristics of different ankle braces under passive and rapidly induced conditions will help the clinician and consumer in choosing the most appropriate brace model for specific use . The results also provide more insights into factors that influence stability characteristics of ankle braces Two anatomic reconstructions for correction of chronic lateral ankle joint instability were compared . In a pro spective , r and omized study , 60 patients were allocated to one of two treatment groups : reconstruction of the ligaments as described by Karlsson et al. ( Group I ) or with the modification of the Broström procedure as described by Gould et al. ( Group II ) . The functional results were evaluated with a scoring scale , and the mechanical stability with st and ardized stress radio graphs . The minimum follow-up period was 2 years . The functional results were satisfactory in 27 of 30 ( 90 % ) patients in Group I and 25 of 30 ( 83 % ) in Group II . There was no significant difference between the groups regarding mechanical stability . The mean an terior talar translation in Group I was 7.1 mm ( range , 4 to 10 ) at followup , compared with 6.7 mm ( range , 3 to 9 ) in Group II . The corresponding values for talar tilt were 4.9 ° ( range , 0 ° to 8 ° ) in Group I and 4.4 ° ( range , 0 ° to 8 ° ) in Group II . The duration of operation time was significantly longer in Group II and surgical complica tions were more frequent , probably due to the more extensive surgical exposure . This study showed that the majority of patients with chronic ankle instability can be successfully treated with anatomic reconstruc tion of the lateral ankle ligaments . Mechanical stability was restored with both methods The authors analyze the r and omized use of three ankle arthrodesis techniques . Indications for this procedure , which are pain , instability , deformity and articular degeneration , are common to the three groups . In group I the Gatellier-Adams technique was used by transfibular approach . In group II the Kenneth-Johnson technique was adopted , using Cal and ruccio external fixator . The same surgical procedure was adopted in group III , using crossed canulated screws as fixation device . The specific advantages and disadvantages of each method are discussed . The criteria for evaluation of the results are the final roentgenographic position of the foot and the achievement of union . The critical analysis conclude that the major indications for group I technique are cases of " in situ " arthrodesis , for group II infected cases and for group III cases with severe malalignment OBJECTIVE To test whether a rigid or a flexible ankle orthosis affects postural sway in single-limb stance as quantified by stabilometry . DESIGN Crossover trial . SETTING University laboratory . PARTICIPANTS Twenty-two athletes with functional ankle instability ( consecutive sample of patients with recurrent ankle sprains but without mechanical instability ) and 22 healthy athletes ( control group of volunteers matched to age , height , weight , physical activity ) . INTERVENTIONS Stabilometry in single-limb stance on a force platform . Participants were tested on each leg with and without a rigid or a flexible ankle orthosis . The order of test conditions was r and omized . MAIN OUTCOME MEASURES Sway velocities , sway pattern , and sway area as calculated from center of pressure movements . The two groups were compared by Mann-Whitney test , and the different orthoses within each group were compared by Wilcoxon test , paired sample s ( type I error 5 % , Bonferroni adjustment ) . RESULTS In athletes with functional ankle instability , both a rigid and a flexible ankle orthosis significantly reduced mediolateral sway velocity . A flexible ankle orthosis also changed sway pattern significantly , by reducing the percentage of linear movements of less than 5 degrees per .01 sec. CONCLUSIONS In athletes with functional ankle instability , ankle orthoses reduce mediolateral sway velocity , possibly because of improved mediolateral proprioception |
687 | 28,362,876 | Our systematic review suggests supervised ET has an inconsistent effect on exercise capacity and QoL when compared to control groups undergoing usual care .
These results suggest that supervised ET is safe and can improve patient outcomes in LVAD patients when compared to the usual care | Implantation of left ventricular assist devices ( LVAD ) has increased because of improved safety profile and limited availability of heart transplantation .
Although supervised exercise training ( ET ) programs are known to improve exercise capacity and quality of life ( QoL ) in heart failure ( HF ) patients , similar data is inconclusive in LVAD patients .
Thus , we performed a systematic review on studies that incorporated supervised ET and measured peak oxygen uptake in LVAD patients . | Background : Capacity to exercise may not be fully restored in patients with heart failure even in the long term after ventricular assist device ( VAD ) implantation . The benefits of exercise training in patients with VAD are unknown . Design and methods : Fifteen patients , aged 38.3 ± 15.9 years , bridged to heart transplantation with left ventricular assist device or biventricular assist device were r and omized at a ratio of 2 : 1 to a training group ( TG , n = 10 ) or a control group ( n = 5 ) , 6.3 ± 4 months after implantation . Both the groups were advised to walk 30–45 min/day . TG also underwent moderate-intensity aerobic exercise using a bike or treadmill for 45 min , three to five times a week , combined with high-intensity inspiratory muscle training using a computer- design ed software to respiratory exhaustion , two to three times a week for 10 weeks . The patients were tested using cardiopulmonary exercise testing , 6-min walk test , spirometry and electronic pressure manometer for inspiratory muscle strength ( Pimax ) and endurance ( sustained Pimax ) measurement . Quality of life was assessed with the Minnesota Living with Heart Failure question naire . Results : TG improved peak oxygen consumption ( 19.3 ± 4.5 vs. 16.8 ± 3.7 ml/kg per min , P = 0.008 ) and VO2 at ventilatory threshold ( 15.1 ± 4.2 vs. 12 ± 5.6 ml/kg per min , P = 0.01 ) , whereas the ventilation/carbon dioxide slope decreased ( 35.9 ± 5.6 vs. 40 ± 6.5 , P = 0.009 ) . The 6-min walk test distance increased ( 527 ± 76 vs. 462 ± 88 m , P = 0.005 ) and quality of life was improved ( 38.2 ± 11.6 vs. 48.9 ± 12.8 , P = 0.005 ) , as well as Pimax ( 131.8 ± 33 vs. 95.5 ± 28cmH2O , P = 0.005 ) , sustained Pimax ( 484 ± 195 vs. 340 ± 193cmH2O/s/10 3 , P = 0.005 ) , and inspiratoty lung capacity ( 2.4 ± 0.9 vs. 1.7 ± 0.7 L , P = 0.008 ) were improved . No significant changes were noted in the control group . Conclusion : Our findings indicate that exercise training may improve the functional status of VAD recipients even at a later period after implantation and thus , may have additional importance in cases of destination therapy PURPOSE Patients with chronic heart failure ( CHF ) report difficulty performing activities of daily living . To our knowledge , however , no study has directly measured performance in activities of daily living in these patients to systematic ally assess their level of physical disability . Moreover , the contribution of skeletal muscle weakness to physical disability in CHF remains unclear . Thus , we measured performance in activities of daily living in CHF patients and controls , its relationship to aerobic capacity and muscle strength , and the effect of resistance exercise training to improve muscle strength and physical disability . METHODS Patients and controls were assessed for performance in activities of daily living , self-reported physical function , peak aerobic capacity , body composition , and muscle strength before and after an 18-wk resistance training program . To remove the confounding effects of several disease-related factors ( muscle disuse , hospitalization , acute illness ) , we recruited controls with similar activity levels as CHF patients and tested patients > 6 months after any disease exacerbation/hospitalization . RESULTS Performance in activities of daily living was 30 % lower ( P < 0.05 ) in CHF patients versus controls and was related to both reduced aerobic capacity ( P < 0.001 ) and muscle strength ( P < 0.01 ) . Moreover , resistance training improved ( P < 0.05 to P < 0.001 ) physical function and muscle strength in patients and controls similarly , without altering aerobic capacity . CONCLUSIONS CHF patients are characterized by marked physical disability compared with age- and physical activity-matched controls , which is related to reduced aerobic capacity and muscle strength . CHF patients respond to resistance training with normal strength/functional adaptations . Our results support muscle weakness as a determinant of physical disability in CHF and show that interventions that increase muscle strength ( resistance training ) reduce physical disability CONTEXT Guidelines recommend that exercise training be considered for medically stable out patients with heart failure . Previous studies have not had adequate statistical power to measure the effects of exercise training on clinical outcomes . OBJECTIVE To test the efficacy and safety of exercise training among patients with heart failure . DESIGN , SETTING , AND PATIENTS Multicenter , r and omized controlled trial of 2331 medically stable out patients with heart failure and reduced ejection fraction . Participants in Heart Failure : A Controlled Trial Investigating Outcomes of Exercise Training ( HF-ACTION ) were r and omized from April 2003 through February 2007 at 82 centers within the United States , Canada , and France ; median follow-up was 30 months . INTERVENTIONS Usual care plus aerobic exercise training , consisting of 36 supervised sessions followed by home-based training , or usual care alone . MAIN OUTCOME MEASURES Composite primary end point of all-cause mortality or hospitalization and prespecified secondary end points of all-cause mortality , cardiovascular mortality or cardiovascular hospitalization , and cardiovascular mortality or heart failure hospitalization . RESULTS The median age was 59 years , 28 % were women , and 37 % had New York Heart Association class III or IV symptoms . Heart failure etiology was ischemic in 51 % , and median left ventricular ejection fraction was 25 % . Exercise adherence decreased from a median of 95 minutes per week during months 4 through 6 of follow-up to 74 minutes per week during months 10 through 12 . A total of 759 patients ( 65 % ) in the exercise training group died or were hospitalized compared with 796 patients ( 68 % ) in the usual care group ( hazard ratio [ HR ] , 0.93 [ 95 % confidence interval { CI } , 0.84 - 1.02 ] ; P = .13 ) . There were nonsignificant reductions in the exercise training group for mortality ( 189 patients [ 16 % ] in the exercise training group vs 198 patients [ 17 % ] in the usual care group ; HR , 0.96 [ 95 % CI , 0.79 - 1.17 ] ; P = .70 ) , cardiovascular mortality or cardiovascular hospitalization ( 632 [ 55 % ] in the exercise training group vs 677 [ 58 % ] in the usual care group ; HR , 0.92 [ 95 % CI , 0.83 - 1.03 ] ; P = .14 ) , and cardiovascular mortality or heart failure hospitalization ( 344 [ 30 % ] in the exercise training group vs 393 [ 34 % ] in the usual care group ; HR , 0.87 [ 95 % CI , 0.75 - 1.00 ] ; P = .06 ) . In prespecified supplementary analyses adjusting for highly prognostic baseline characteristics , the HRs were 0.89 ( 95 % CI , 0.81 - 0.99 ; P = .03 ) for all-cause mortality or hospitalization , 0.91 ( 95 % CI , 0.82 - 1.01 ; P = .09 ) for cardiovascular mortality or cardiovascular hospitalization , and 0.85 ( 95 % CI , 0.74 - 0.99 ; P = .03 ) for cardiovascular mortality or heart failure hospitalization . Other adverse events were similar between the groups . CONCLUSIONS In the protocol -specified primary analysis , exercise training result ed in nonsignificant reductions in the primary end point of all-cause mortality or hospitalization and in key secondary clinical end points . After adjustment for highly prognostic predictors of the primary end point , exercise training was associated with modest significant reductions for both all-cause mortality or hospitalization and cardiovascular mortality or heart failure hospitalization . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00047437 OBJECTIVE Newer generation left ventricular assist devices ( LVADs ) are established for long-term support . The aim of this multi-modal intervention was to improve the body weight , exercise tolerance and psychosocial status in out patients on long-term LVAD support . METHODS Seventy patients participated in this non-r and omized intervention study [ intervention group ( IGr ) n = 34 ; control group ( CGr ) n = 36 ] over 18 months ( T1-T4 ) ; the baseline sample characteristics showed no differences between groups . Dietary counselling and weight management intervention was performed by a dietician based on a specific algorithm . Physical reconditioning followed a home ergometry protocol and was supplemented by psychosocial counselling . The outcomes were measured based on the body mass index ( BMI ) , cardiopulmonary exercise testing and self-report [ hospital anxiety and depression scale ( HADS ) , SF-36 ] . RESULTS The intervention showed a strong positive effect on nutrition and weight management [ 95 % confidence interval ( CI ) : -0.71 - 0.69 ; effect size ( ES ) : 0.907 ; P = 0.02 ) ] , result ing in the normal BMI ( kg/m(2 ) ) values in the IGr ( T1 : 24.0 ± 0.6 ; T4 : 24.5 ± 1.1 ; P = 0.35 ) compared with a significant BMI increase in the CGr ( T1 : 23.8 ± 0.6 ; T4 : 29.7 ± 0.8 ; P = 0.05 ) . Significant differences appeared regarding exercise tolerance ( VO(2)max/% predicted ) in favour of IGr patients ( IGr : 69 ± 2.9 ; CGr 62 ± 3.7 ; P = 0.04 ) . This increase was reflected by patients ' self-reporting based on the SF-36 physical component score ( IGr : P = 0.04 ; CGr : P = 0.54 ) . SF-36 psychosocial component scores showed no changes for both groups . However , CGr showed a tendency for increased anxiety scores relative to their counterparts ( IGr : 4.95 ± 0.4 ; CGr : 6.6 ± 0.9 ; P = 0.03 ) . CONCLUSIONS IGr patients showed a strong benefit from a multi-modal intervention , including dietary counselling , controlled exercise and psychosocial support . Dietary counselling holds potential to prevent obesity in this patient population Twenty-five patients ( aged 62 + /- 2 years ) with stable , moderate to severe ischemic congestive heart failure ( CHF ) ( New York Heart Association class II/III : 15/10 ; ejection fraction 21.6 + /- 2 % ; and peak oxygen uptake 13.6 + /- 0.7 ml/kg/min ) were studied to evaluate the ability of different methods to characterize autonomic tone in chronic CHF . Sympathovagal balance was assessed by : ( 1 ) heart rate variability in the time domain , assessed by the SD of RR intervals ; ( 2 ) heart rate variability in the frequency domain , assessed by low- ( 0.03 to 0.14 Hz ) and high- ( 0.18 to 0.40 Hz ) frequency components of heart rate variability by autoregressive power spectral analysis ; ( 3 ) 24-hour , daytime and nighttime heart rate ; ( 4 ) submaximal heart rate during upright bicycle exercise , with respiratory gas analysis to obtain peak oxygen uptake ; and ( 5 ) radiolabeled norepinephrine spillover . These methods did not correlate , with the exception of day and nighttime heart rate ( r = 0.74 ; p < 0.001 ) and the expected inverse correlation between low and high frequency ( r = -0.92 ; p < 0.001 ) . No method correlated significantly with peak oxygen uptake , exercise tolerance or ejection fraction . After 8 weeks of physical training at home , all methods showed improvement in autonomic balance : increases in SD of RR intervals ( + 21 % ; p < 0.02 ) and high frequency ( + 41 % ; p < 0.007 ) , and decreases in low frequency ( -19 % ; p < 0.002 ) , low-/high-frequency ratio ( -48 % ; p < 0.03 ) , norepinephrine spillover ( -28.9 % ; p < 0.03 ) , 24-hour heart rate ( -2.7 % ; p < 0.005 ) and submaximal heart rate ( -10.8 % ; p < 0.01 ) . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Patients with advanced heart failure have improved survival rates and quality of life when treated with implanted pulsatile-flow left ventricular assist devices as compared with medical therapy . New continuous-flow devices are smaller and may be more durable than the pulsatile-flow devices . METHODS In this r and omized trial , we enrolled patients with advanced heart failure who were ineligible for transplantation , in a 2:1 ratio , to undergo implantation of a continuous-flow device ( 134 patients ) or the currently approved pulsatile-flow device ( 66 patients ) . The primary composite end point was , at 2 years , survival free from disabling stroke and reoperation to repair or replace the device . Secondary end points included survival , frequency of adverse events , the quality of life , and functional capacity . RESULTS Preoperative characteristics were similar in the two treatment groups , with a median age of 64 years ( range , 26 to 81 ) , a mean left ventricular ejection fraction of 17 % , and nearly 80 % of patients receiving intravenous inotropic agents . The primary composite end point was achieved in more patients with continuous-flow devices than with pulsatile-flow devices ( 62 of 134 [ 46 % ] vs. 7 of 66 [ 11 % ] ; P<0.001 ; hazard ratio , 0.38 ; 95 % confidence interval , 0.27 to 0.54 ; P<0.001 ) , and patients with continuous-flow devices had superior actuarial survival rates at 2 years ( 58 % vs. 24 % , P=0.008 ) . Adverse events and device replacements were less frequent in patients with the continuous-flow device . The quality of life and functional capacity improved significantly in both groups . CONCLUSIONS Treatment with a continuous-flow left ventricular assist device in patients with advanced heart failure significantly improved the probability of survival free from stroke and device failure at 2 years as compared with a pulsatile device . Both devices significantly improved the quality of life and functional capacity . ( Clinical Trials.gov number , NCT00121485 . OBJECTIVES This study examined the effects of a cardiac rehabilitation ( CR ) program on functional capacity and health status ( HS ) in patients with newly implanted left ventricular assist devices ( LVADs ) . BACKGROUND Reduced functional capacity and HS are independent predictors of mortality in patients with heart failure . CR improves both , and is related to improved outcomes in patients with heart failure ; however , there is a paucity of data that describe the effects of CR in patients with LVADs . METHODS Enrolled subjects ( n = 26 ; 7 women ; age 55 ± 13 years ; ejection fraction 21 ± 8 % ) completed a symptom-limited cardiopulmonary exercise test , the Kansas City Cardiomyopathy Question naire ( KCCQ ) , a 6-min walk test ( 6MW ) , and single-leg isokinetic strength test before 2:1 r and omization to CR versus usual care . Subjects in the CR group underwent 18 visits of aerobic exercise at 60 % to 80 % of heart rate reserve . Within-group changes from baseline to follow-up were analyzed with a paired t-test , whereas an independent t-test was used to determine differences in the change between groups . RESULTS Within-group improvements were observed in the CR group for peak oxygen uptake ( 10 % ) , treadmill time ( 3.1 min ) , KCCQ score ( 14.4 points ) , 6MW distance ( 52.3 m ) , and leg strength ( 17 % ) . Significant differences among groups were observed for KCCQ , leg strength , and total treadmill time . CONCLUSIONS Indicators of functional capacity and HS are improved in patients with continuous-flow LVADs who attend CR . Future trials should examine the mechanisms responsible for these improvements , and if such improvements translate into improved clinical outcomes . ( Cardiac Rehabilitation in Patients With Continuous Flow Left Ventricular Assist Devices : Rehab VAD Trial [ RehabVAD ] ; NCT01584895 ) Background Many secondary abnormalities in chronic heart failure ( CHF ) may reflect physical deconditioning . There has been no prospect i ve , controlled study of the effects of physical training on hemodynamics and autonomic function in CHIF . Methods and Results In a controlled crossover trial of 8 weeks of exercise training , 17 men with stable moderate to severe CHF ( age , 61.8±1.5 years ; left ventricular ejection fraction , 19.6±2.3 % ) , increased exercise tolerance ( 13.9±1.0 to 16.5±1.0 minutes , p<0.001 ) , and peak oxygen uptake ( 13.2±0.9 to 15.6±1.0 mI/kg/min , p<0.01 ) significantly compared with controls . Training increased cardiac output at submaximal ( 5.9 - 6.7 1/min , p<0.05 ) and peak exercise ( 6.3 - 7.1 /min , p<0.05 ) , with a significant reduction in systemic vascular resistance . Training reduced minute ventilation and the slope relating minute ventilation to carbon dioxide production ( −10.5 % , p<0.05 ) . Sympathovagal balance was altered by physical training when assessed by three methods : 1 ) RR variability ( + 19.2 % , p<0.05 ) ; 2 ) autoregressive power spectral analysis of the resting ECG divided into low-frequency ( −21.2 % , p<0.01 ) and high-frequency ( + 51.3 % , p<0.05 ) components ; and 3 ) whole-body radiolabeled norepinephrine spillover ( −16 % , p<0.05 ) . These measurements all showed a significant shift away from sympathetic toward enhanced vagal activity after training . Conclusions Carefully selected patients with moderate to severe CHF can achieve significant , worthwhile improvements with exercise training . Physical deconditioning may be partly responsible for some of the associated abnormalities and exercise limitation of CHF , including abnormalities in autonomic balance 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 BACKGROUND A paucity of studies has examined the effect of exercise training after left ventricular assist device ( LVAD ) implantation . Previous research has demonstrated that insertion of the LVAD alone improves exercise capacity and quality of life ( QOL ) . This study investigated whether supervised exercise training results in a further improvement . METHODS This prospect i ve , r and omized controlled trial with concealed allocation , assessor blinding , and intention-to-treat analysis investigated the effect of exercise training on exercise capacity and QOL in 14 patients who underwent LVAD insertion as a bridge to heart transplantation . Exercise training consisted of 8 weeks of gym-based aerobic and strengthening exercises 3 times a week , with a progressive mobilization program , compared with the control group that completed mobilization alone . Exercise capacity was measured before and after the intervention using maximal cardiopulmonary exercise testing and 6-minute walk distance ( 6MWD ) . QOL was measured using the Short Form 36-item assessment . RESULTS No adverse events were reported . There was a trend toward greater improvement in peak oxygen consumption ( Vo(2 ) ) , 6MWD , and QOL in the exercise group ( n = 7 ) compared with the control group ( n = 7 ) ; however , no significant between-group difference was detected for improvements in peak Vo(2 ) [ mean difference ( exercise -- control ) ] of 2.96 ml/kg/min ( 95 % confidence interval , -1.04 to 6.97 ) , 6MWD at 54 meters ( -51 to 159 meters ) , and QOL scores over time ( p > 0.05 ) . CONCLUSION Exercise training is feasible and safe in patients with a LVAD . Trends toward greater improvement in exercise capacity and QOL after exercise training warrant further investigation in a larger trial INTRODUCTION : Patient health status ( PHS ) and peak oxygen uptake ( O2 ) are important predictors of clinical outcomes in individuals with heart failure . Preliminary studies of individuals with left ventricular assist devices ( LVADs ) show improvements in both PHS and peak O2 . However , the relationship between peak O2 and PHS in this population is not well described . Likewise , data regarding muscular strength are also lacking in this population . We sought to describe the association between peak O2 , muscular strength , and PHS in patients with continuous-flow LVADs . METHODS : Subjects ( n = 26 ; 7 women ) completed a symptom-limited grade d exercise test within an average of 82 days ( range , 33 - 167 days ) of LVAD implant . In addition , subjects underwent a 6-Minute Walk Test and an isokinetic knee extension strength test and completed the Kansas City Cardiomyopathy Question naire ( KCCQ ) . Spearman correlation coefficients were performed , adjusting for body weight and gender , to examine relationships between variables . RESULTS : Muscular strength , as measured by peak torque , and peak O2 were both moderately associated with the KCCQ ( r = 0.58 , P = .006 ; r = 0.51 , P = .019 ) . A sub analysis revealed that muscular strength and peak O2 were related to different domains within the KCCQ . CONCLUSIONS : Leg muscle strength and peak O2 appear to be important factors related to PHS in patients with continuous-flow LVADs . This is likely partially a result of deconditioning due to recent hospitalization , as well as persistent heart failure – related peripheral maladaptations in skeletal muscle . Incorporating both a cardiovascular as well as strength training program before and after LVAD implant surgery may be beneficial |
688 | 26,830,837 | However , the results were not statistically significant between different kinds of mechanical chest compression devices and manual resuscitation in survival to admission , discharge and CPC scores for OHCA patients and survival to discharge for in-hospital CA patients .
Conclusions The ability to achieve ROSC with mechanical devise was inferior to manual chest compression during resuscitation .
The use of mechanical chest compression can not be recommended as a replacement for manual CPR , but rather a supplemental treatment in an overall strategy for treating CA patients | Background The aim of this paper was to conduct a systematic review of the published literature s comparing the use of mechanical chest compression device and manual chest compression during cardiac arrest ( CA ) with respect to short-term survival outcomes and neurological function . | Background —Interruptions to chest compression – generated blood flow during cardiopulmonary resuscitation ( CPR ) are detrimental . Data show that such interruptions for mouth-to-mouth ventilation require a period of “ rebuilding ” of coronary perfusion pressure to obtain the level achieved before the interruption . Whether such hemodynamic compromise from pausing to ventilate is enough to affect outcome is unknown . Methods and Results —Thirty swine ( weight 35±2 kg ) underwent 3 minutes of untreated ventricular fibrillation before 12 minutes of basic life support CPR . Animals were r and omized to receive either st and ard airway ( A ) , breathing ( B ) , and compression ( C ) CPR with expired-gas ventilation in a 15:2 compression-to-ventilation ratio or continuous chest compression CPR . Those r and omized to the st and ard 15:2 group had no chest compressions for a period of 16 seconds each time the 2 ventilations were delivered . Defibrillation was attempted at 15 minutes of cardiac arrest . All resuscitated animals were supported in an intensive care environment for 1 hour , then in a maintenance facility for 24 hours . The primary end point of neurologically normal 24-hour survival was significantly better in the experimental group receiving continuous chest compression CPR ( 12 of 15 versus 2 of 15;P < 0.0001 ) . Conclusions —Mouth-to-mouth ventilation performed by single layperson rescuers produces substantial interruptions in chest compression – supported circulation . Continuous chest compression CPR produces greater neurologically normal 24-hour survival than st and ard ABC CPR when performed in a clinical ly realistic fashion . Any technique that minimizes lengthy interruptions of chest compressions during the first 10 to 15 minutes of basic life support should be given serious consideration in future efforts to improve outcome results from cardiac arrest CONTEXT The survival benefit of well-performed cardiopulmonary resuscitation ( CPR ) is well-documented , but little objective data exist regarding actual CPR quality during cardiac arrest . Recent studies have challenged the notion that CPR is uniformly performed according to established international guidelines . OBJECTIVES To measure multiple parameters of in-hospital CPR quality and to determine compliance with published American Heart Association and international guidelines . DESIGN AND SETTING A prospect i ve observational study of 67 patients who experienced in-hospital cardiac arrest at the University of Chicago Hospitals , Chicago , Ill , between December 11 , 2002 , and April 5 , 2004 . Using a monitor/defibrillator with novel additional sensing capabilities , the parameters of CPR quality including chest compression rate , compression depth , ventilation rate , and the fraction of arrest time without chest compressions ( no-flow fraction ) were recorded . MAIN OUTCOME MEASURE Adherence to American Heart Association and international CPR guidelines . RESULTS Analysis of the first 5 minutes of each resuscitation by 30-second segments revealed that chest compression rates were less than 90/min in 28.1 % of segments . Compression depth was too shallow ( defined as < 38 mm ) for 37.4 % of compressions . Ventilation rates were high , with 60.9 % of segments containing a rate of more than 20/min . Additionally , the mean ( SD ) no-flow fraction was 0.24 ( 0.18 ) . A 10-second pause each minute of arrest would yield a no-flow fraction of 0.17 . A total of 27 patients ( 40.3 % ) achieved return of spontaneous circulation and 7 ( 10.4 % ) were discharged from the hospital . CONCLUSIONS In this study of in-hospital cardiac arrest , the quality of multiple parameters of CPR was inconsistent and often did not meet published guideline recommendations , even when performed by well-trained hospital staff . The importance of high- quality CPR suggests the need for rescuer feedback and monitoring of CPR quality during resuscitation efforts IMPORTANCE A strategy using mechanical chest compressions might improve the poor outcome in out-of-hospital cardiac arrest , but such a strategy has not been tested in large clinical trials . OBJECTIVE To determine whether administering mechanical chest compressions with defibrillation during ongoing compressions ( mechanical CPR ) , compared with manual cardiopulmonary resuscitation ( manual CPR ) , according to guidelines , would improve 4-hour survival . DESIGN , SETTING , AND PARTICIPANTS Multicenter r and omized clinical trial of 2589 patients with out-of-hospital cardiac arrest conducted between January 2008 and February 2013 in 4 Swedish , 1 British , and 1 Dutch ambulance services and their referring hospitals . Duration of follow-up was 6 months . INTERVENTIONS Patients were r and omized to receive either mechanical chest compressions ( LUCAS Chest Compression System , Physio-Control/Jolife AB ) combined with defibrillation during ongoing compressions ( n = 1300 ) or to manual CPR according to guidelines ( n = 1289 ) . MAIN OUTCOMES AND MEASURES Four-hour survival , with secondary end points of survival up to 6 months with good neurological outcome using the Cerebral Performance Category ( CPC ) score . A CPC score of 1 or 2 was classified as a good outcome . RESULTS Four-hour survival was achieved in 307 patients ( 23.6 % ) with mechanical CPR and 305 ( 23.7 % ) with manual CPR ( risk difference , -0.05 % ; 95 % CI , -3.3 % to 3.2 % ; P > .99 ) . Survival with a CPC score of 1 or 2 occurred in 98 ( 7.5 % ) vs 82 ( 6.4 % ) ( risk difference , 1.18 % ; 95 % CI , -0.78 % to 3.1 % ) at intensive care unit discharge , in 108 ( 8.3 % ) vs 100 ( 7.8 % ) ( risk difference , 0.55 % ; 95 % CI , -1.5 % to 2.6 % ) at hospital discharge , in 105 ( 8.1 % ) vs 94 ( 7.3 % ) ( risk difference , 0.78 % ; 95 % CI , -1.3 % to 2.8 % ) at 1 month , and in 110 ( 8.5 % ) vs 98 ( 7.6 % ) ( risk difference , 0.86 % ; 95 % CI , -1.2 % to 3.0 % ) at 6 months with mechanical CPR and manual CPR , respectively . Among patients surviving at 6 months , 99 % in the mechanical CPR group and 94 % in the manual CPR group had CPC scores of 1 or 2 . CONCLUSIONS AND RELEVANCE Among adults with out-of-hospital cardiac arrest , there was no significant difference in 4-hour survival between patients treated with the mechanical CPR algorithm or those treated with guideline -adherent manual CPR . The vast majority of survivors in both groups had good neurological outcomes by 6 months . In clinical practice , mechanical CPR using the presented algorithm did not result in improved effectiveness compared with manual CPR . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00609778 AIM Recently three large post product placement studies , comparing mechanical chest compression ( cc ) devices to those who received manual cc , found equivalent outcome results for both groups . Thus the question arises whether those results could be replicated using the devices on a daily routine . METHODS We prospect ively enrolled 948 patients over a 12 months period . Chi-Square test and Mann-Whitney-U test were used to assess differences between " manual " and " mechanical " cc subgroups . Uni- and multivariate Cox regression hazard analysis were used to assess the influence of cc type on survival . RESULTS A mechanical cc device was used in 30.1 % ( n=283 ) cases . Patients who received mechanical cc had a significantly worse neurological outcome - measured in cerebral performance category ( CPC ) - than the manual cc group ( 56.8 % vs. 78.6 % , p=0.009 ) . Patients receiving mechanical cc were significantly younger , more were male and were more likely to have byst and er CPR and an initially shock-able ECG rhythm . There was no difference in the quality of CPR that might explain the worse outcome in mechanical cc patients . CONCLUSION Even with high quality CPR in both , manual and mechanical cc groups , outcome in patients who received mechanical cc was significantly worse . The anticipated benefits of a higher compression ratio and a steadier compression depth of a mechanical cc device remain uncertain . In this study selection for mechanical cc was not st and ardized , and was non-r and om . This merits further investigation . Further research on how mechanical cc is chosen and used should be considered . CLINICAL TRIAL REGISTRATION https://ekmeduniwien.at/core/catalog/2013/ ( EK-Nr:1221/2013 ) Background —Recent data highlight a vital link between well-performed cardiopulmonary resuscitation ( CPR ) and survival after cardiac arrest ; however , the quality of CPR as actually performed by trained healthcare providers is largely unknown . We sought to measure in-hospital chest compression rates and to determine compliance with published international guidelines . Methods and Results —We developed and vali date d a h and held recording device to measure chest compression rate as a surrogate for CPR quality . A prospect i ve observational study of adult cardiac arrests was performed at 3 hospitals from April 2002 to October 2003 . Resuscitations were witnessed by trained observers using a customized personal digital assistant programmed to store the exact time of each chest compression , allowing offline calculation of compression rates at serial time points . In 97 arrests , data from 813 minutes during which chest compressions were delivered were analyzed in 30-second time segments . In 36.9 % of the total number of segments , compression rates were < 80 compressions per minute ( cpm ) , and 21.7 % had rates < 70 cpm . Higher chest compression rates were significantly correlated with initial return of spontaneous circulation ( mean chest compression rates for initial survivors and nonsurvivors , 90±17 and 79±18 cpm , respectively ; P=0.0033 ) . Conclusions —In-hospital chest compression rates were below published resuscitation recommendations , and suboptimal compression rates in our study correlated with poor return of spontaneous circulation . CPR quality is likely a critical determinant of survival after cardiac arrest , suggesting the need for routine measurement , monitoring , and feedback systems during actual resuscitation CONTEXT Defibrillation as soon as possible is st and ard treatment for patients with ventricular fibrillation . A nonr and omized study indicates that after a few minutes of ventricular fibrillation , delaying defibrillation to give cardiopulmonary resuscitation ( CPR ) first might improve the outcome . OBJECTIVE To determine the effects of CPR before defibrillation on outcome in patients with ventricular fibrillation and with response times either up to or longer than 5 minutes . DESIGN , SETTING , AND PATIENTS R and omized trial of 200 patients with out-of-hospital ventricular fibrillation in Oslo , Norway , between June 1998 and May 2001 . Patients received either st and ard care with immediate defibrillation ( n = 96 ) or CPR first with 3 minutes of basic CPR by ambulance personnel prior to defibrillation ( n = 104 ) . If initial defibrillation was unsuccessful , the st and ard group received 1 minute of CPR before additional defibrillation attempts compared with 3 minutes in the CPR first group . MAIN OUTCOME MEASURE Primary end point was survival to hospital discharge . Secondary end points were hospital admission with return of spontaneous circulation ( ROSC ) , 1-year survival , and neurological outcome . A prespecified analysis examined subgroups with response times either up to or longer than 5 minutes . RESULTS In the st and ard group , 14 ( 15 % ) of 96 patients survived to hospital discharge vs 23 ( 22 % ) of 104 in the CPR first group ( P = .17 ) . There were no differences in ROSC rates between the st and ard group ( 56 % [ 58/104 ] ) and the CPR first group ( 46 % [ 44/96 ] ; P = .16 ) ; or in 1-year survival ( 20 % [ 21/104 ] and 15 % [ 14/96 ] , respectively ; P = .30 ) . In subgroup analysis for patients with ambulance response times of either up to 5 minutes or shorter , there were no differences in any outcome variables between the CPR first group ( n = 40 ) and the st and ard group ( n = 41 ) . For patients with response intervals of longer than 5 minutes , more patients achieved ROSC in the CPR first group ( 58 % [ 37/64 ] ) compared with the st and ard group ( 38 % [ 21/55 ] ; odds ratio [ OR ] , 2.22 ; 95 % confidence interval [ CI ] , 1.06 - 4.63 ; P = .04 ) ; survival to hospital discharge ( 22 % [ 14/64 ] vs 4 % [ 2/55 ] ; OR , 7.42 ; 95 % CI , 1.61 - 34.3 ; P = .006 ) ; and 1-year survival ( 20 % [ 13/64 ] vs 4 % [ 2/55 ] ; OR , 6.76 ; 95 % CI , 1.42 - 31.4 ; P = .01 ) . Thirty-three ( 89 % ) of 37 patients who survived to hospital discharge had no or minor reductions in neurological status with no difference between the groups . CONCLUSIONS Compared with st and ard care for ventricular fibrillation , CPR first prior to defibrillation offered no advantage in improving outcomes for this entire study population or for patients with ambulance response times shorter than 5 minutes . However , the patients with ventricular fibrillation and ambulance response intervals longer than 5 minutes had better outcomes with CPR first before defibrillation was attempted . These results require confirmation in additional r and omized trials CONTEXT High- quality cardiopulmonary resuscitation ( CPR ) may improve both cardiac and brain resuscitation following cardiac arrest . Compared with manual chest compression , an automated load-distributing b and ( LDB ) chest compression device produces greater blood flow to vital organs and may improve resuscitation outcomes . OBJECTIVE To compare resuscitation outcomes following out-of-hospital cardiac arrest when an automated LDB-CPR device was added to st and ard emergency medical services ( EMS ) care with manual CPR . DESIGN , SETTING , AND PATIENTS Multicenter , r and omized trial of patients experiencing out-of-hospital cardiac arrest in the United States and Canada . The a priori primary population was patients with cardiac arrest that was presumed to be of cardiac origin and that had occurred prior to the arrival of EMS personnel . Initial study enrollment varied by site , ranging from late July to mid November 2004 ; all sites halted study enrollment on March 31 , 2005 . INTERVENTION St and ard EMS care for cardiac arrest with an LDB-CPR device ( n = 554 ) or manual CPR ( n = 517 ) . MAIN OUTCOME MEASURES The primary end point was survival to 4 hours after the 911 call . Secondary end points were survival to hospital discharge and neurological status among survivors . RESULTS Following the first planned interim monitoring conducted by an independent data and safety monitoring board , study enrollment was terminated . No difference existed in the primary end point of survival to 4 hours between the manual CPR group and the LDB-CPR group overall ( N = 1071 ; 29.5 % vs 28.5 % ; P = .74 ) or among the primary study population ( n = 767 ; 24.7 % vs 26.4 % , respectively ; P = .62 ) . However , among the primary population , survival to hospital discharge was 9.9 % in the manual CPR group and 5.8 % in the LDB-CPR group ( P = .06 , adjusted for covariates and clustering ) . A cerebral performance category of 1 or 2 at hospital discharge was recorded in 7.5 % of patients in the manual CPR group and in 3.1 % of the LDB-CPR group ( P = .006 ) . CONCLUSIONS Use of an automated LDB-CPR device as implemented in this study was associated with worse neurological outcomes and a trend toward worse survival than manual CPR . Device design or implementation strategies require further evaluation . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00120965 INTRODUCTION Most manikin and clinical studies have found decreased quality of CPR during transport to hospital . We wanted to study quality of CPR before and during transport for out-of-hospital cardiac arrest patients and also whether quality of CPR before initiation of transport was different from the quality in patients only receiving CPR on scene . MATERIAL S AND METHODS Quality of CPR was prospect ively registered with a modified defibrillator for consecutive cases of out-of-hospital cardiac arrest in three ambulance services during 2002 - 2005 . Ventilations were registered via changes in transthoracic impedance and chest compressions were measured with an extra chest compression pad placed on the patients ' sternum . Paired t-tests were used to analyse quality of CPR before vs. during transport with ongoing CPR . Unpaired t-tests were used to compare CPR quality prior to transport to CPR quality in patients with CPR terminated on site . RESULTS Quality of CPR did not deteriorate during transport , but as previously reported overall quality of CPR was subst and ard . Quality of CPR performed on site was significantly better when transport was not initiated with ongoing CPR compared to episodes with initiation of transport during CPR : fraction of time without chest compressions was 0.45 and 0.53 ( p<0.001 ) , compression depth 37 mm and 34 mm ( p=0.04 ) , and number of chest compressions per minute 61 and 56 ( p=0.01 ) , respectively . CONCLUSION CPR quality was sub-st and ard both before and during transport . Early decision to transport might have negatively affected CPR quality from the early stages of resuscitation BACKGROUND Mechanical chest compression devices have the potential to help maintain high- quality cardiopulmonary resuscitation ( CPR ) , but despite their increasing use , little evidence exists for their effectiveness . We aim ed to study whether the introduction of LUCAS-2 mechanical CPR into front-line emergency response vehicles would improve survival from out-of-hospital cardiac arrest . METHODS The pre-hospital r and omised assessment of a mechanical compression device in cardiac arrest ( PARAMEDIC ) trial was a pragmatic , cluster-r and omised open-label trial including adults with non-traumatic , out-of-hospital cardiac arrest from four UK Ambulance Services ( West Midl and s , North East Engl and , Wales , South Central ) . 91 urban and semi-urban ambulance stations were selected for participation . Clusters were ambulance service vehicles , which were r and omly assigned ( 1:2 ) to LUCAS-2 or manual CPR . Patients received LUCAS-2 mechanical chest compression or manual chest compressions according to the first trial vehicle to arrive on scene . The primary outcome was survival at 30 days following cardiac arrest and was analysed by intention to treat . Ambulance dispatch staff and those collecting the primary outcome were masked to treatment allocation . Masking of the ambulance staff who delivered the interventions and reported initial response to treatment was not possible . The study is registered with Current Controlled Trials , number IS RCT N08233942 . FINDINGS We enrolled 4471 eligible patients ( 1652 assigned to the LUCAS-2 group , 2819 assigned to the control group ) between April 15 , 2010 and June 10 , 2013 . 985 ( 60 % ) patients in the LUCAS-2 group received mechanical chest compression , and 11 ( < 1 % ) patients in the control group received LUCAS-2 . In the intention-to-treat analysis , 30 day survival was similar in the LUCAS-2 group ( 104 [ 6 % ] of 1652 patients ) and in the manual CPR group ( 193 [ 7 % ] of 2819 patients ; adjusted odds ratio [ OR ] 0·86 , 95 % CI 0·64 - 1·15 ) . No serious adverse events were noted . Seven clinical adverse events were reported in the LUCAS-2 group ( three patients with chest bruising , two with chest lacerations , and two with blood in mouth ) . 15 device incidents occurred during operational use . No adverse or serious adverse events were reported in the manual group . INTERPRETATION We noted no evidence of improvement in 30 day survival with LUCAS-2 compared with manual compressions . On the basis of ours and other recent r and omised trials , widespread adoption of mechanical CPR devices for routine use does not improve survival . FUNDING National Institute for Health Research HTA - 07/37/69 Background The ' Hawthorne Effect ' may be an important factor affecting the generalisability of clinical research to routine practice , but has been little studied . Hawthorne Effects have been reported in previous clinical trials in dementia but to our knowledge , no attempt has been made to quantify them . Our aim was to compare minimal follow-up to intensive follow-up in participants in a placebo controlled trial of Ginkgo biloba for treating mild-moderate dementia . Methods Participants in a dementia trial were r and omised to intensive follow-up ( with comprehensive assessment visits at baseline and two , four and six months post r and omisation ) or minimal follow-up ( with an abbreviated assessment at baseline and a full assessment at six months ) . Our primary outcomes were cognitive functioning ( ADAS-Cog ) and participant and carer-rated quality of life ( QOL-AD ) . Results We recruited 176 participants , mainly through general practice s. The main analysis was based on Intention to treat ( ITT ) , with available data . In the ANCOVA model with baseline score as a co-variate , follow-up group had a significant effect on outcome at six months on the ADAS-Cog score ( n = 140 ; mean difference = -2.018 ; 95%CI -3.914 , -0.121 ; p = 0.037 favouring the intensive follow-up group ) , and on participant-rated quality of life score ( n = 142 ; mean difference = -1.382 ; 95%CI -2.642 , -0.122 ; p = 0.032 favouring minimal follow-up group ) . There was no significant difference on carer quality of life . Conclusion We found that more intensive follow-up of individuals in a placebo-controlled clinical trial of Ginkgo biloba for treating mild-moderate dementia result ed in a better outcome than minimal follow-up , as measured by their cognitive functioning . Trial registration Current controlled trials : IS RCT Introduction It has been unclear if mechanical cardiopulmonary resuscitation ( CPR ) is a viable alternative to manual CPR . We aim ed to compare resuscitation outcomes before and after switching from manual CPR to load-distributing b and ( LDB ) CPR in a multi-center emergency department ( ED ) trial . Methods We conducted a phased , prospect i ve cohort evaluation with intention-to-treat analysis of adults with non-traumatic cardiac arrest . At these two urban EDs , systems were changed from manual CPR to LDB-CPR . Primary outcome was survival to hospital discharge , with secondary outcome measures of return of spontaneous circulation , survival to hospital admission and neurological outcome at discharge . Results A total of 1,011 patients were included in the study , with 459 in the manual CPR phase ( January 01 , 2004 , to August 24 , 2007 ) and 552 patients in the LDB-CPR phase ( August 16 , 2007 , to December 31 , 2009 ) . In the LDB phase , the LDB device was applied in 454 patients ( 82.3 % ) . Patients in the manual CPR and LDB-CPR phases were comparable for mean age , gender and ethnicity . The mean duration from collapse to arrival at ED ( min ) for manual CPR and LDB-CPR phases was 34:03 ( SD16:59 ) and 33:18 ( SD14:57 ) respectively . The rate of survival to hospital discharge tended to be higher in the LDB-CPR phase ( LDB 3.3 % vs Manual 1.3 % ; adjusted OR , 1.42 ; 95 % CI , 0.47 , 4.29 ) . There were more survivors in LDB group with cerebral performance category 1 ( good ) ( Manual 1 vs LDB 12 , P = 0.01 ) . Overall performance category 1 ( good ) was Manual 1 vs LDB 10 , P = 0.06 . Conclusions A resuscitation strategy using LDB-CPR in an ED environment was associated with improved neurologically intact survival on discharge in adults with prolonged , non-traumatic cardiac arrest AIM The LUCAS ™ device has been shown to improve organ perfusion during cardiac arrest in experimental studies . In this pilot study the aim was to compare short-term survival between cardiopulmonary resuscitation ( CPR ) performed with mechanical chest compressions using the LUCAS ™ device and CPR performed with manual chest compressions . The intention was to use the results for power calculation in a larger r and omised multicentre trial . METHODS In a prospect i ve pilot study , from February 1 , 2005 , to April 1 , 2007 , 149 patients with out-of hospital cardiac arrest in two Swedish cities were r and omised to mechanical chest compressions or st and ard CPR with manual chest compressions . RESULTS After exclusion , the LUCAS and the manual groups contained 75 and 73 patients , respectively . In the LUCAS and manual groups , spontaneous circulation with a palpable pulse returned in 30 and 23 patients ( p = 0.30 ) , spontaneous circulation with blood pressure above 80/50 mm Hg remained for at least 5 min in 23 and 19 patients ( p = 0.59 ) , the number of patients hospitalised alive > 4h were 18 and 15 ( p = 0.69 ) , and the number discharged , alive 6 and 7 ( p = 0.78 ) , respectively . CONCLUSIONS In this pilot study of out-of-hospital cardiac arrest patients we found no difference in early survival between CPR performed with mechanical chest compression with the LUCAS ™ device and CPR with manual chest compressions . Data have been used for power calculation in a forthcoming multicentre trial Objective . The San Francisco Fire Department deployed an automated , load-distributing-b and chest compression device ( AutoPulse , Revivant Corporation ) to evaluate its function in a large urban emergency medical services ( EMS ) service . A retrospective chart review was undertaken to determine whether the AutoPulse had altered short-term patient outcome , specifically , return of spontaneous circulation ( ROSC ) . Methods . AutoPulse cardiopulmonary resuscitation ( A-CPR ) was used by paramedic captains responding to adult cardiac arrests with an average ±SD response time of 15 ± 5 minutes . The primary endpoint was patient arrival to an emergency department with measurable spontaneous pulses . The manual CPR comparison group was case-matched for age , gender , initial presenting electrocardiogram rhythm , and the number of doses of Advanced Cardiac Life Support medications as a proxy for treatment time . Matching was performed by an investigator blinded to outcome and treatment group . Results . Sixty-nine AutoPulse uses were matched to 93 manual-CPR-only cases . A-CPR showed improvement in the primary outcome when compared with manual CPR with any presenting rhythm ( A-CPR 39 % , manual 29 % , p = 0.003 ) . When patients were classified by first presenting rhythm , shockable rhythms showed no difference in outcome ( A-CPR 44 % , manual 50 % , p = 0.340 ) . Outcome was improved with A-CPR in initial presenting asystole and approached significance with pulseless electrical activity (PEA)(asystole : A-CPR 37 % , manual 22 % , p = 0.008 ; PEA : A-CPR 38 % , manual 23 % , p = 0.079 ) . Conclusion . The AutoPulse may improve the overall likelihood of sustained ROSC and may particularly benefit patients with nonshockable rhythms . A prospect i ve r and omized trial comparing the AutoPulse with manual CPR in the setting of out-of-hospital sudden cardiac arrest is under way STUDY OBJECTIVE To characterize fatigue-induced deterioration in the adequacy of closed-chest compressions performed over a period of 5 minutes and to determine whether CPR providers can recognize the effects of fatigue on compression adequacy . DESIGN Prospect i ve evaluation of study subjects performing closed-chest compressions on an electronic mannequin that assesses compression placement and depth . SETTING Major resuscitation room in rural university hospital emergency department . PARTICIPANTS Eleven experienced nursing assistants who regularly provide CPR in the ED . RESULTS Each study participant performed 5 minutes of closed-chest compressions . Compression adequacy ( for placement and depth ) was assessed with the mannequin and reported on an attached monitor out of view of the study subjects . Subjects were asked to verbally indicate the point during their 5-minute compression period at which they felt too fatigued to provide effective compressions ( arbitrarily defined as a minimum of 90 % of all compressions being judged correct by the mannequin ) . We used one-way repeated- measures ANOVA and regression analysis to determine whether compression adequacy diminished over time . ANOVA was also used to determine whether the total compressions performed per minute diminished over time . The percentage of correct chest compressions decreased significantly after 1 minute of compressions ( P = .0001 ) . We found 92.9 % of compressions performed during minute 1 to be correct . The percentages for minutes 2 through 5 were as follows : 67.1 % , 39.2 % , 31.2 % , and 18.0 % . Regression analysis revealed a decrement in compression adequacy of 18.6 % per minute after the first minute of compressions . The number of total compressions attempted per minute did not decrease ( P = .98 ) . Study subjects did not accurately identify the point during their 5-minute sessions at which their fatigue caused compressions to become impaired . Whereas mean compression adequacy declined below 90 % after only 1 minute , the time of indicated fatigue was 253 + /- 40 seconds ( mean + /- SD ) . CONCLUSION Although compression rate was maintained over time , chest compression quality declined significantly over the study period . Because CPR providers could not recognize their inability to provide proper compressions , cardiac arrest team leaders should carefully monitor compression adequacy during CPR to assure maximally effective care for patients receiving CPR To compare the effectiveness of manual and mechanical chest compression during cardiopulmonary resuscitation , 50 patients who suffered cardiac arrest were r and omly allocated to receive manual or mechanical chest compression . R and omization was performed after failure of initial resuscitative measures but within ten minutes after the onset of cardiac arrest ( mean , 6.4 + /- 1.2 min ) . Ten patients from each group survived longer than one hour following resuscitation . Three from the mechanical group and two from the manual group were eventually able to leave the hospital . Thus mechanical compression appears comparable with manual compression when manual compression is performed under ideal conditions . Mechanical chest compression may be employed when trained personnel are not readily available or where manual compression is technically difficult to perform OBJECTIVE This study was performed to determine the potential efficacy of an automated device with a load-distributing b and ( AutoPulse , Revivant Corporation ) , in improving neurologically intact survival after cardiac arrest . DESIGN R and omized , controlled trial . SETTING University animal laboratory . SUBJECTS Forty-four swine ( 18 - 23 kg ) . INTERVENTIONS Eight minutes after induction of untreated ventricular fibrillation , pigs were r and omized to AutoPulse-CPR ( A-CPR , n = 22 ) , conventional cardiopulmonary resuscitation ( CPR ) with 20 % anterior-posterior chest displacement ( C-CPR20 , n = 10 ) or 30 % chest displacement ( C-CPR30 , n = 12 ) , followed by resuscitation protocol with ventilation , defibrillation and intravenous epinephrine ( adrenaline ) . MEASUREMENTS AND MAIN RESULTS Aortic and right atrium blood pressure was measured with micromanometers . Regional blood flows were measured with microspheres . Coronary perfusion pressure during A-CPR was significantly higher as compared to C-CPR without epinephrine ( A-CPR versus C-CPR20 versus C-CPR30 ; 16 + /- 1 mmHg versus 7 + /- 2 mmHg versus 11 + /- 2 mmHg , p < 0.05 ) . A-CPR improved both myocardial flow without epinephrine ( A-CPR versus C-CPR20 versus C-CPR30 ; 23 % versus 0 % versus 4 % ; percent of baseline , p < 0.05 ) and cerebral blood flow ( 40 % versus 4 % versus 19 % , percent of baseline , p < 0.05 ) . Sixteen of 22 animals receiving A-CPR regained spontaneous circulation and survived ; 14/22 had normal cerebral performance ( CPC 1 ) . Four of 12 animals receiving C-CPR30 regained spontaneous circulation and survived , but only one animal had normal neurological function ( 14/22 versus 1/12 , p < 0.0001 ) . No animal receiving C-CPR20 achieved spontaneous circulation . At necropsy , 67 % of C-CPR30 had rib fracture and 33 % showed lung injury , while A-CPR and C-CPR20 result ed in no detectable injuries . CONCLUSIONS Improved hemodynamics with AutoPulse performed CPR results in improved neurologically intact survival without subsequent thoracic or pulmonary injuries in this porcine model of prolonged cardiac arrest CONTEXT Transport of patients during resuscitation is a critical procedure . In both , ambulances and helicopters the quality of resuscitation is potentially hampered due to the movement of the vehicle and confined space . To date , however , no direct comparison of the quality of resuscitation at the scene , during a helicopter flight and in a moving ambulance has been made . OBJECTIVE Direct comparison of the quality of resuscitation at the scene , during a helicopter flight and in a moving ambulance . DESIGN The study was performed in July 2005 as a r and omised cross-over trial comparing different environments for resuscitation . SETTING Medical University of Vienna . PARTICIPANTS Eleven European Resuscitation Council ( ERC ) approved health care professionals . INTERVENTIONS Interventions during resuscitation : ( a ) in a moving ambulance , ( b ) in a flying helicopter , were compared to those staying at the ( c ) scene ( control ) . Each participant performed resuscitation in all three environments . MAIN OUTCOME MEASURES Quality of chest compression during resuscitation . RESULTS Compared to resuscitation at the scene , efficiency of chest compressions during a helicopter flight was 86 % and 95 % in the moving ambulance 95 % . There were no differences in secondary outcomes ( time without chest compression , total number of incorrect h and position relative to total compressions , and total number of incorrect pressure release relative to total compressions ) . CONCLUSIONS Resuscitation during transport is feasible and relatively efficient . There is some difference between the environments , but there is no relevant difference between helicopters and ambulances regarding the effectiveness of CPR BACKGROUND The quality of cardiopulmonary resuscitation ( CPR ) during ambulance transportation is suboptimal , and therefore measures that can improve the quality are desirable . PURPOSE To evaluate whether the use of a stabilization device can improve the quality of CPR during ambulance transportation . METHODS This r and omized controlled crossover trial enrolled 22 experienced ambulance officers . Each participant performed CPR in an ambulance under three conditions with 72 h apart , each condition for 10 min : non-moving ( NM ) , moving without device ( MND ) , and moving with device ( MD ) . The sequences of conditions were r and omized . The primary outcomes were effective chest compressions recorded by the Laerdal Resusci-Anne Skill-reporter manikin . The secondary outcomes included the severity of back pain scored using the Brief Pain Inventory short-form , the physiology parameter before and after CPR , and the changes in postural stability which was represented by the sway index ( SI ) of lower back measured using a goniometer . RESULTS The overall effective compressions in 10 min were 87.0±17 % for NM , 59.0±19 % for MND , and 69.0±23 % for MD ( p<0.001 ) . Compared to MND , MD had a lower no-flow fraction while driving on curved sections ( 0.04 vs. 0.29 , p<0.001 ) . Whereas the pain severity and social interference scores were similar under all conditions , MND had a higher SI than MD and NM . CONCLUSIONS The use of a stabilization device can improve the quality of CPR and posture stability during ambulance transportation , although the effects on the severity of back pain were not significant A prospect i ve , r and omized effectiveness trial was undertaken to compare mechanical versus manual chest compressions as measured by end-tidal CO2 ( ETCO2 ) in out-of-hospital cardiac arrest patients receiving advanced cardiac life support ( ACLS ) resuscitation from a municipal third-service , emergency medical services ( EMS ) agency . The EMS agency responds to approximately 6,700 emergencies annually , 79 of which were cardiac arrests in 1994 , the study year . Following endotracheal intubation , all cardiac arrest patients were placed on 100 % oxygen via the ventilator circuit of the mechanical cardiopulmonary resuscitation ( CPR ) device . Patients were r and omized to receive mechanical CPR ( TCPR ) or human/manual CPR ( HCPR ) based on an odd/even day basis , with TCPR being performed on odd days . ETCO2 readings were obtained 5 minutes after the initiation of either TCPR or HCPR and again at the initiation of patient transport to the hospital . All patients received st and ard ACLS pharmacotherapy during the monitoring interval with the exception of sodium bicarbonate . CPR was continued until the patient was delivered to the hospital emergency department . Age , call response interval , initial electrocardiogram ( ECG ) rhythm , scene time , ETCO2 measurements , and arrest outcome were identified for all patients . Twenty patients were entered into the study , with 10 in each treatment group . Three patients in the TCPR group were excluded . Measurements in the HCPR group revealed a decreasing ETCO2 during the resuscitation in 8 of 10 patients ( 80 % ) and an increasing ETCO2 in the remaining 2 patients . No decrease in ETCO2 was noted in the TCPR group , with 4 of 7 patients ( 57 % ) actually showing an increased reading and 3 of 7 patients ( 43 % ) showing a constant ETCO2 reading . The differences in the ETCO2 measurements between TCPR and HCPR groups were statistically significant . Both groups were similar with regards to call response intervals , patient ages , scene times , and initial ECG rhythms . One patient in the TCPR group was admitted to the hospital but later died , leaving no survivors in the study . TCPR appears to be superior to st and ard HCPR as measured by ETCO2 in maintaining cardiac output during ACLS resuscitation of out-of-hospital cardiac arrest patients OBJECTIVE To determine whether shorter compression duration s combined with fixed increased compression velocity during mechanical high-impulse CPR ( HI-CPR ) improve resuscitation hemodynamics , compared with mechanical st and ard CPR ( SCPR ) . METHODS A porcine model of ventricular fibrillation was used , with each animal serving as its own control . Twelve anesthetized swine ( 20 - 25 kg each ) were instrumented for hemodynamic monitoring . Ventricular fibrillation was induced and followed , after 3 minutes , by mechanical SCPR ( 50 % duty cycle ) for 10 minutes . Mechanical HI-CPR was then applied , with compression duration s varied r and omly at 2-minute intervals for 20 % ( COM20 ) , 30 % ( COM30 ) , and 40 % ( COM40 ) of the CPR cycle . A 2-minute mechanical SCPR control phase completed the experiment . RESULTS Hemodynamic measurements were significantly better for COM20 and COM30 vs SCPR , including , respectively : mean arterial pressure ( MAP ) , 45 + /- 8 and 43 + /- 7 vs 36 + /- 7 torr ; coronary perfusion pressure ( CPP ) , 21 + /- 6 and 21 + /- 8 vs 16 + /- 6 torr ; and end-tidal CO2 ( ETCO2 ) , 7 + /- 2 and 6.6 + /- 2 vs 5 + /- 1.4 torr . MAP , CPP , and ETCO2 during COM40 were not significantly different from those during SCPR , and there was no difference between COM20 and COM30 for any hemodynamic parameter . Aortic flow velocity was significantly better in COM20 , COM30 , and COM40 vs SCPR : 2.3 + /- 0.7 , 2.1 + /- 0.9 , and 1.95 + /- 0.9 vs 1.3 + /- 0.5 cm/sec , respectively . CONCLUSION In a swine model of mechanical HI-CPR , shorter compression duration s combined with fixed increased compression velocity significantly improve resuscitation hemodynamics , compared with those afforded by mechanical SCPR AIM To evaluate the outcome among patients suffering from out-of-hospital cardiac arrest ( OHCA ) after the introduction of mechanical chest compression ( MCC ) compared with st and ard cardiopulmonary resuscitation ( SCPR ) in two emergency medical service ( EMS ) systems . METHODS The inclusion criterion was witnessed OHCA . The exclusion criteria were age < 18 years , the following judged etiologies behind OHCA : trauma , pregnancy , hypothermia , intoxication , hanging and drowning or return of spontaneous circulation ( ROSC ) prior to the arrival of the advanced life support ( ALS ) unit . Two MCC devices were allocated during six-month periods between four ALS units for a period of two years ( cluster r and omisation ) . RESULTS In all , 328 patients fulfilled the criteria for participation and 159 were allocated to the MCC tier ( the device was used in 66 % of cases ) and 169 to the SCPR tier . In the MCC tier , 51 % had ROSC ( primary end-point ) versus 51 % in the SCPR tier . The corresponding values for hospital admission alive ( secondary end-point ) were 38 % and 37 % ( NS ) . In the subset of patients in whom the device was used , the percentage who had ROSC was 49 % versus 50 % in a control group matched for age , initial rhythm , aetiology , byst and er-/crew-witnessed status and delay to CPR . The percentage of patients discharged alive from hospital after OHCA was 8 % versus 10 % ( NS ) for all patients and 2 % versus 4 % , respectively ( NS ) for the patients in the subset ( where the device was used and the matched control population ) . CONCLUSION In this pilot study , the results did not support the hypothesis that the introduction of mechanical chest compression in OHCA improves outcome . However , there is room for further improvement in the use of the device . The hypothesis that this will improve outcome needs to be tested in further prospect i ve trials BACKGROUND More than 300,000 people die each year of cardiac arrest . Studies have shown that raising vascular pressures during cardiopulmonary resuscitation ( CPR ) can improve survival and that vascular pressures can be raised by increasing intrathoracic pressure . METHODS To produce periodic increases in intrathoracic pressure , we developed a pneumatically cycled circumferential thoracic vest system and compared the results of the use of this system in CPR ( vest CPR ) with those of manual CPR . In phase 1 of the study , aortic and right-atrial pressures were measured during both vest CPR ( 60 inflations per minute ) and manual CPR in 15 patients in whom a mean ( + /- SD ) of 42 + /- 16 minutes of initial manual CPR had been unsuccessful . Vest CPR was also carried out on 14 other patients in whom pressure measurements were not made . In phase 2 of the study , short-term survival was assessed in 34 additional patients r and omly assigned to undergo vest CPR ( 17 patients ) or continued manual CPR ( 17 patients ) after initial manual CPR ( duration , 11 + /- 4 minutes ) had been unsuccessful . RESULTS In phase 1 of the study , vest CPR increased the peak aortic pressure from 78 + /- 26 mm Hg to 138 + /- 28 mm Hg ( P < 0.001 ) and the coronary perfusion pressure from 15 + /- 8 mm Hg to 23 + /- 11 mm Hg ( P < 0.003 ) . Despite prolonged unsuccessful manual CPR , spontaneous circulation returned with vest CPR in 4 of the 29 patients . In phase 2 of the study , spontaneous circulation returned in 8 of the 17 patients who underwent vest CPR as compared with only 3 of the 17 patients who received continued manual CPR ( P = 0.14 ) . More patients in the vest-CPR group than in the manual-CPR group were alive 6 hours after attempted resuscitation ( 6 of 17 vs. 1 of 17 ) and 24 hours after attempted resuscitation ( 3 of 17 vs. 1 of 17 ) , but none survived to leave the hospital . CONCLUSIONS In this preliminary study , vest CPR , despite its late application , successfully increased aortic pressure and coronary perfusion pressure , and there was an insignificant trend toward a greater likelihood of the return of spontaneous circulation with vest CPR than with continued manual CPR . The effect of vest CPR on survival , however , is currently unknown and will require further study |
689 | 19,364,995 | RESULTS Strong evidence supports valid associations ( 4 criteria satisfied ) of protective factors , including intake of vegetables , nuts , and " Mediterranean " and high- quality dietary patterns with CHD , and associations of harmful factors , including intake of trans-fatty acids and foods with a high glycemic index or load .
Among studies of higher method ologic quality , there was also strong evidence for monounsaturated fatty acids and " prudent " and " western " dietary patterns .
Insufficient evidence ( < or = 2 criteria ) of association is present for intake of supplementary vitamin E and ascorbic acid ( vitamin C ) ; saturated and polyunsaturated fatty acids ; total fat ; alpha-linolenic acid ; meat ; eggs ; and milk .
Among the dietary exposures with strong evidence of causation from cohort studies , only a Mediterranean dietary pattern is related to CHD in r and omized trials .
The evidence supports a valid association of a limited number of dietary factors and dietary patterns with CHD . | BACKGROUND Although a wealth of literature links dietary factors and coronary heart disease ( CHD ) , the strength of the evidence supporting valid associations has not been evaluated systematic ally in a single investigation . | BACKGROUND The effects of a carbohydrate-restricted diet on weight loss and risk factors for atherosclerosis have been incompletely assessed . METHODS We r and omly assigned 132 severely obese subjects ( including 77 blacks and 23 women ) with a mean body-mass index of 43 and a high prevalence of diabetes ( 39 percent ) or the metabolic syndrome ( 43 percent ) to a carbohydrate-restricted ( low-carbohydrate ) diet or a calorie- and fat-restricted ( low-fat ) diet . RESULTS Seventy-nine subjects completed the six-month study . An analysis including all subjects , with the last observation carried forward for those who dropped out , showed that subjects on the low-carbohydrate diet lost more weight than those on the low-fat diet ( mean [ + /-SD ] , -5.8+/-8.6 kg vs. -1.9+/-4.2 kg ; P=0.002 ) and had greater decreases in triglyceride levels ( mean , -20+/-43 percent vs. -4+/-31 percent ; P=0.001 ) , irrespective of the use or nonuse of hypoglycemic or lipid-lowering medications . Insulin sensitivity , measured only in subjects without diabetes , also improved more among subjects on the low-carbohydrate diet ( 6+/-9 percent vs. -3+/-8 percent , P=0.01 ) . The amount of weight lost ( P<0.001 ) and assignment to the low-carbohydrate diet ( P=0.01 ) were independent predictors of improvement in triglyceride levels and insulin sensitivity . CONCLUSIONS Severely obese subjects with a high prevalence of diabetes or the metabolic syndrome lost more weight during six months on a carbohydrate-restricted diet than on a calorie- and fat-restricted diet , with a relative improvement in insulin sensitivity and triglyceride levels , even after adjustment for the amount of weight lost . This finding should be interpreted with caution , given the small magnitude of overall and between-group differences in weight loss in these markedly obese subjects and the short duration of the study . Future studies evaluating long-term cardiovascular outcomes are needed before a carbohydrate-restricted diet can be endorsed BACKGROUND Adherence to a Mediterranean diet may improve longevity , but relevant data are limited . METHODS We conducted a population -based , prospect i ve investigation involving 22,043 adults in Greece who completed an extensive , vali date d , food-frequency question naire at base line . Adherence to the traditional Mediterranean diet was assessed by a 10-point Mediterranean-diet scale that incorporated the salient characteristics of this diet ( range of scores , 0 to 9 , with higher scores indicating greater adherence ) . We used proportional-hazards regression to assess the relation between adherence to the Mediterranean diet and total mortality , as well as mortality due to coronary heart disease and mortality due to cancer , with adjustment for age , sex , body-mass index , physical-activity level , and other potential confounders . RESULTS During a median of 44 months of follow-up , there were 275 deaths . A higher degree of adherence to the Mediterranean diet was associated with a reduction in total mortality ( adjusted hazard ratio for death associated with a two-point increment in the Mediterranean-diet score , 0.75 [ 95 percent confidence interval , 0.64 to 0.87 ] ) . An inverse association with greater adherence to this diet was evident for both death due to coronary heart disease ( adjusted hazard ratio , 0.67 [ 95 percent confidence interval , 0.47 to 0.94 ] ) and death due to cancer ( adjusted hazard ratio , 0.76 [ 95 percent confidence interval , 0.59 to 0.98 ] ) . Associations between individual food groups contributing to the Mediterranean-diet score and total mortality were generally not significant . CONCLUSIONS Greater adherence to the traditional Mediterranean diet is associated with a significant reduction in total mortality BACKGROUND There is conflicting evidence on the benefits of foods rich in vitamin E ( alpha-tocopherol ) , n-3 polyunsaturated fatty acids ( PUFA ) , and their pharmacological substitutes . We investigated the effects of these substances as supplements in patients who had myocardial infa rct ion . METHODS From October , 1993 , to September , 1995 , 11,324 patients surviving recent ( < or = 3 months ) myocardial infa rct ion were r and omly assigned supplements of n-3 PUFA ( 1 g daily , n=2836 ) , vitamin E ( 300 mg daily , n=2830 ) , both ( n=2830 ) , or none ( control , n=2828 ) for 3.5 years . The primary combined efficacy endpoint was death , non-fatal myocardial infa rct ion , and stroke . Intention-to-treat analyses were done according to a factorial design ( two-way ) and by treatment group ( four-way ) . FINDINGS Treatment with n-3 PUFA , but not vitamin E , significantly lowered the risk of the primary endpoint ( relative-risk decrease 10 % [ 95 % CI 1 - 18 ] by two-way analysis , 15 % [ 2 - 26 ] by four-way analysis ) . Benefit was attributable to a decrease in the risk of death ( 14 % [ 3 - 24 ] two-way , 20 % [ 6 - 33 ] four-way ) and cardiovascular death ( 17 % [ 3 - 29 ] two-way , 30 % [ 13 - 44 ] four-way ) . The effect of the combined treatment was similar to that for n-3 PUFA for the primary endpoint ( 14 % [ 1 - 26 ] ) and for fatal events ( 20 % [ 5 - 33 ] ) . INTERPRETATION Dietary supplementation with n-3 PUFA led to a clinical ly important and statistically significant benefit . Vitamin E had no benefit . Its effects on fatal cardiovascular events require further exploration The effects of variations in dietary carbohydrate and fat on various aspects of carbohydrate and lipoprotein metabolism were evaluated in 10 healthy , postmenopausal women . The two diets were isoenergetic , assigned in r and om fashion , and consisted ( as a % of total energy ) of 15 % protein , 60 % carbohydrate , and 25 % fat ( 60%-carbohydrate diet ) or 15 % protein , 40 % carbohydrate , and 45 % fat ( 40%-carbohydrate diet ) . Fasting plasma triacylglycerol , very-low-density-lipoprotein ( VLDL ) triacylglycerol , and VLDL-cholesterol concentrations were higher ( P < 0.05 - 0.001 ) after the 60%-carbohydrate diet , whereas high-density-lipoprotein ( HDL ) cholesterol was lower ( P < 0.05 ) . Plasma insulin and triacylglycerol concentrations were also higher ( P < 0.001 ) from 0800 to 0000 with the 60%-carbohydrate diet than with the 40%-carbohydrate diet . In addition , when vitamin A was given with the noon meal , the ensuing concentrations of retinyl palmitate were also higher after ingestion of the 60%-carbohydrate diet . Resistance to insulin-mediated glucose disposal , quantified at baseline by determining the steady state plasma glucose ( SSPG ) concentration at the end of a 180-min infusion of somatostatin , insulin , and glucose , correlated with the incremental increases in postpr and ial concentrations of plasma glucose ( r = 0.68 , P = 0.06 ) , insulin ( r = 0.82 , P < 0.02 ) , triacylglycerol ( r = 0.77 , P < 0.05 ) , and retinyl palmitate ( r = 0.68 , P = 0.06 ) and with the Sf > 400 triacylglycerol ( r = 0.77 , P < 0.05 ) , Sf 20 - 400 triacylglycerol ( r = 0.72 , P < 0.05 ) , and Sf > 400 retinyl palmitate ( r = 0.75 , P < 0.01 ) lipoprotein fractions . Because all of these changes would increase risk of ischemic heart disease in postmenopausal women , it seems reasonable to question the wisdom of recommending that postmenopausal women consume low-fat , high-carbohydrate diets BACKGROUND Metabolic studies suggest that saturated fatty acids differ in their effects on blood lipids . OBJECTIVE The objective was to examine the associations between intakes of individual saturated fatty acids and their food sources in relation to the risk of coronary heart disease ( CHD ) . DESIGN This was a prospect i ve cohort study of 80082 women in the Nurses ' Health Study aged 34 - 59 y. Subjects had no known cardiovascular disease , cancer , hypercholesterolemia , or diabetes , and completed vali date d food-frequency question naires in 1980 . RESULTS During 14 y of follow-up , we documented 939 incident cases of major CHD events . In multivariate analyses in which age , smoking , and other covariates were controlled for , intakes of short- to medium-chain saturated fatty acids ( 4:0 - 10:0 ) were not significantly associated with the risk of CHD . In contrast , intakes of longer-chain saturated fatty acids ( 12:0 - 18:0 ) were each separately associated with a small increase in risk . The multivariate RR for a 1 % energy increase from stearic acid was 1.19 ( 95 % CI : 1.02 , 1.37 ) . The ratio of polyunsaturated to saturated fat was strongly and inversely associated with CHD risk ( multivariate RR for a comparison of the highest with the lowest deciles : 0.58 ; 95 % CI : 0.41 , 0.83 ; P for trend < 0.0001 ) . Conversely , higher ratios of red meat to poultry and fish consumption and of high-fat to low-fat dairy consumption were associated with significantly greater risk . CONCLUSION A distinction between stearic acid and other saturated fats does not appear to be important in dietary advice to reduce CHD risk , in part because of the high correlation between stearic acid and other saturated fatty acids in typical diets BACKGROUND Data on the relation between alpha-linolenic acid intake and coronary artery disease ( CAD ) are limited . Other dietary components appear to modify the reported relation between alpha-linolenic acid intake and CAD . OBJECTIVE We examined whether dietary alpha-linolenic acid intake was inversely associated with risk of CAD . DESIGN We prospect ively studied 667 men aged 64 - 84 y from the Zutphen Elderly Study who were free of CAD at baseline . Dietary intake was assessed by using a cross-check dietary history method . RESULTS During the 10-y follow-up , we documented 98 cases of CAD . After adjustment for age , st and ard coronary risk factors , and intake of trans fatty acids and other nutrients , alpha-linolenic acid intake was not significantly associated with CAD risk . The relative risk of CAD for the highest compared with the lowest tertile of alpha-linolenic acid intake was 1.68 ( 95 % CI : 0.86 , 3.29 ) . alpha-Linolenic acid intake from sources containing trans fatty acids was also nonsignificantly , yet positively , associated with CAD risk . alpha-Linolenic acid intake from foods that did not contain trans fatty acids was not associated with CAD risk , the relative risk of CAD for the highest compared with the lowest tertile was 1.15 ( 95 % CI : 0.63 , 2.11 ) . CONCLUSION We did not observe a beneficial effect of dietary alpha-linolenic acid intake on the risk of 10-y CAD incidence . Investigating this hypothesis was complicated by the association between intakes of alpha-linolenic acid and trans fatty acids . Given the results of current prospect i ve studies , a protective cardiac effect of alpha-linolenic acid is question able BACKGROUND Previous studies on diet and coronary heart disease ( CHD ) focused primarily on individual nutrients or foods . OBJECTIVE We examined whether overall dietary patterns derived from a food-frequency question naire ( FFQ ) predict risk of CHD in men . DESIGN This was a prospect i ve cohort study of 44875 men aged 40 - 75 y without diagnosed cardiovascular disease or cancer at baseline in 1986 . RESULTS During 8 y of follow-up , we documented 1089 cases of CHD ( nonfatal myocardial infa rct ion and fatal CHD ) . Using factor analysis , we identified 2 major dietary patterns using dietary data collected through a 131-item FFQ . The first factor , which we labeled the " prudent pattern , " was characterized by higher intake of vegetables , fruit , legumes , whole grains , fish , and poultry , whereas the second factor , the " Western pattern , " was characterized by higher intake of red meat , processed meat , refined grains , sweets and dessert , French fries , and high-fat dairy products . After adjustment for age and CHD risk factors , the relative risks from the lowest to highest quintiles of the prudent pattern score were 1.0 , 0 . 87 , 0.79 , 0.75 , and 0.70 ( 95 % CI : 0.56 , 0.86 ; P : for trend = 0.0009 ) . In contrast , the relative risks across increasing quintiles of the Western pattern score were 1.0 , 1.21 , 1.36 , 1.40 , and 1.64 ( 95 % CI : 1.24 , 2.17 ; P : for trend < 0.0001 ) . These associations persisted in subgroup analyses according to cigarette smoking , body mass index , and parental history of myocardial infa rct ion . CONCLUSIONS These data suggest that major dietary patterns derived from the FFQ predict risk of CHD , independent of other lifestyle variables BACKGROUND In observational studies , individuals with high intakes of fruits and vegetables containing beta-carotene experience lower risks of developing cancer . However , the few r and omized trials of beta-carotene supplementation show no overall benefits ; some even suggest harm . This trial was design ed to test the effects of beta-carotene supplementation in women . METHODS The Women 's Health Study is a r and omized , double-blind , placebo-controlled trial originally testing aspirin , vitamin E , and beta-carotene in the prevention of cancer and cardiovascular disease among 39 876 women aged 45 years or older . The beta-carotene component was terminated early after a median treatment duration of 2.1 years ( range = 0.00 - 2 . 72 years ) . Statistical tests were two-sided . RESULTS Among women r and omly assigned to receive beta-carotene ( 50 mg on alternate days ; n = 19 939 ) or placebo ( n = 19 937 ) , there were no statistically significant differences in incidence of cancer , cardiovascular disease , or total mortality after a median of 4.1 years ( 2.1 years ' treatment plus another 2.0 years ' follow-up ) . There were 378 cancers in the beta-carotene group and 369 cancers in the placebo group ( relative risk [ RR ] = 1.03 ; 95 % confidence interval [ CI ] = 0.89 - 1 . 18 ) . There were no statistically significant differences for any site-specific cancer or during years 1 and 2 combined and years 3 and up combined . For cardiovascular disease , there were no statistically significant differences for myocardial infa rct ion ( 42 in the beta-carotene group versus 50 in the placebo group ) , stroke ( 61 versus 43 ) , deaths from cardiovascular causes ( 14 versus 12 ) , or the combined end point of these three events ( 116 versus 102 ; among women with more than one event , only the first was counted ) . Deaths from any cause were similar in the two groups ( 59 versus 55 ) . Among smokers at baseline ( 13 % of all women ) , there were no statistically significant differences in overall incidence of cancer ( RR = 1.11 ; 95 % CI = 0.78 - 1.58 ) or cardiovascular disease ( RR = 1.01 ; 95 % CI = 0 . 62 - 1.63 ) . CONCLUSION Among apparently healthy women , there was no benefit or harm from beta-carotene supplementation for a limited period on the incidence of cancer and of cardiovascular disease BACKGROUND Epidemiologic evidence indicates that diets high in carotenoid-rich fruits and vegetables , as well as high serum levels of vitamin E ( alpha-tocopherol ) and beta carotene , are associated with a reduced risk of lung cancer . METHODS We performed a r and omized , double-blind , placebo-controlled primary -prevention trial to determine whether daily supplementation with alpha-tocopherol , beta carotene , or both would reduce the incidence of lung cancer and other cancers . A total of 29,133 male smokers 50 to 69 years of age from southwestern Finl and were r and omly assigned to one of four regimens : alpha-tocopherol ( 50 mg per day ) alone , beta carotene ( 20 mg per day ) alone , both alpha-tocopherol and beta carotene , or placebo . Follow-up continued for five to eight years . RESULTS Among the 876 new cases of lung cancer diagnosed during the trial , no reduction in incidence was observed among the men who received alpha-tocopherol ( change in incidence as compared with those who did not , -2 percent ; 95 percent confidence interval , -14 to 12 percent ) . Unexpectedly , we observed a higher incidence of lung cancer among the men who received beta carotene than among those who did not ( change in incidence , 18 percent ; 95 percent confidence interval , 3 to 36 percent ) . We found no evidence of an interaction between alpha-tocopherol and beta carotene with respect to the incidence of lung cancer . Fewer cases of prostate cancer were diagnosed among those who received alpha-tocopherol than among those who did not . Beta carotene had little or no effect on the incidence of cancer other than lung cancer . Alpha-tocopherol had no apparent effect on total mortality , although more deaths from hemorrhagic stroke were observed among the men who received this supplement than among those who did not . Total mortality was 8 percent higher ( 95 percent confidence interval , 1 to 16 percent ) among the participants who received beta carotene than among those who did not , primarily because there were more deaths from lung cancer and ischemic heart disease . CONCLUSIONS We found no reduction in the incidence of lung cancer among male smokers after five to eight years of dietary supplementation with alpha-tocopherol or beta carotene . In fact , this trial raises the possibility that these supplements may actually have harmful as well as beneficial effects CONTEXT Reduction in egg consumption has been widely recommended to lower blood cholesterol levels and prevent coronary heart disease ( CHD ) . Epidemiologic studies on egg consumption and risk of CHD are sparse . OBJECTIVE To examine the association between egg consumption and risk of CHD and stroke in men and women . DESIGN AND SETTING Two prospect i ve cohort studies , the Health Professionals Follow-up Study ( 1986 - 1994 ) and the Nurses ' Health Study ( 1980 - 1994 ) . PARTICIPANTS A total of 37851 men aged 40 to 75 years at study outset and 80082 women aged 34 to 59 years at study outset , free of cardiovascular disease , diabetes , hypercholesterolemia , or cancer . MAIN OUTCOME MEASURES Incident nonfatal myocardial infa rct ion , fatal CHD , and stroke corresponding to daily egg consumption as determined by a food-frequency question naire . RESULTS We documented 866 incident cases of CHD and 258 incident cases of stroke in men during 8 years of follow-up and 939 incident cases of CHD and 563 incident cases of stroke in women during 14 years of follow-up . After adjustment for age , smoking , and other potential CHD risk factors , we found no evidence of an overall significant association between egg consumption and risk of CHD or stroke in either men or women . The relative risks ( RRs ) of CHD across categories of intake were less than 1 per week ( 1.0 ) , 1 per week ( 1.06 ) , 2 to 4 per week ( 1.12 ) , 5 to 6 per week ( 0.90 ) , and > or = 1 per day ( 1.08 ) ( P for trend = .75 ) for men ; and less than 1 per week ( 1.0 ) , 1 per week ( 0.82 ) , 2 to 4 per week ( 0.99 ) , 5 to 6 per week ( 0.95 ) , and > or = 1 per day ( 0.82 ) ( P for trend = .95 ) for women . In subgroup analyses , higher egg consumption appeared to be associated with increased risk of CHD only among diabetic subjects ( RR of CHD comparing more than 1 egg per day with less than 1 egg per week among diabetic men , 2.02 [ 95 % confidence interval , 1.05 - 3.87 ; P for trend = .04 ] , and among diabetic women , 1.49 [ 0.88 - 2.52 ; P for trend = .008 ] ) . CONCLUSIONS These findings suggest that consumption of up to 1 egg per day is unlikely to have substantial overall impact on the risk of CHD or stroke among healthy men and women . The apparent increased risk of CHD associated with higher egg consumption among diabetic participants warrants further research Background —Epidemiological studies have demonstrated an inverse relationship between vitamin E intake and cardiovascular disease ( CVD ) risk . In contrast , r and omized controlled trials have reported conflicting results as to whether vitamin E supplementation reduces atherosclerosis progression and CVD events . Methods and Results —The study population consisted of men and women ≥40 years old with an LDL cholesterol level ≥3.37 mmol/L ( 130 mg/dL ) and no clinical signs or symptoms of CVD . Eligible participants were r and omized to DL-&agr;-tocopherol 400 IU per day or placebo and followed every 3 months for an average of 3 years . The primary trial end point was the rate of change in the common carotid artery far-wall intima-media thickness ( IMT ) assessed by computer image-processed B-mode ultrasonograms . A mixed effects model using all determinations of IMT was used to test the hypothesis of treatment differences in IMT change rates . Compared with placebo , & agr;-tocopherol supplementation significantly raised plasma vitamin E levels ( P < 0.0001 ) , reduced circulating oxidized LDL ( P = 0.03 ) , and reduced LDL oxidative susceptibility ( P < 0.01 ) . However , vitamin E supplementation did not reduce the progression of IMT over a 3-year period compared with subjects r and omized to placebo . Conclusions —The results are consistent with previous r and omized controlled trials and extend the null results of vitamin E supplementation to the progression of IMT in healthy men and women at low risk for CVD CONTEXT Most studies of diet and health care have focused on the role of single nutrients , foods , or food groups in disease prevention or promotion . Few studies have addressed the health effects of dietary patterns , which include complex mixtures of foods containing multiple nutrients and nonnutrients . OBJECTIVE To examine the association of mortality with a multifactorial diet quality index . DESIGN AND SETTING Data from phase 2 ( 1987 - 1989 ) of a prospect i ve cohort study of breast cancer screening , the Breast Cancer Detection Demonstration Project , with a median follow-up of 5.6 years . PARTICIPANTS A total of 42,254 women ( mean age , 61.1 years ) who completed the food frequency question naire portion of the survey . MAIN OUTCOME MEASURE All-cause mortality by quartile of Recommended Food Score ( RFS ; the sum of the number of foods recommended by current dietary guidelines [ fruits , vegetables , whole grains , low-fat dairy , and lean meats and poultry ] that were reported on the question naire to be consumed at least once a week , for a maximum score of 23 ) . RESULTS There were 2065 deaths due to all causes in the cohort . The RFS was inversely associated with all-cause mortality . Compared with those in the lowest quartile , subjects in the upper quartiles of the RFS had relative risks for all-cause mortality of 0.82 ( 95 % confidence interval [ CI ] , 0.73 - 0.92 ) for quartile 2 , 0.71 ( 95 % CI , 0.62 - 0.81 ) for quartile 3 , and 0.69 ( 95 % CI , 0.61 - 0.78 ) for quartile 4 adjusted for education , ethnicity , age , body mass index , smoking status , alcohol use , level of physical activity , menopausal hormone use , and history of disease ( chi2 for trend = 35.64 , P<.001 for trend ) . CONCLUSIONS These data suggest that a dietary pattern characterized by consumption of foods recommended in current dietary guidelines is associated with decreased risk of mortality in women STUDY OBJECTIVE To study the association between reported milk consumption and cardiovascular and all cause mortality . DESIGN A prospect i ve study of 5765 men aged 35–64 at the time of examination . SETTING Workplaces in the west of Scotl and between 1970 and 1973 . PARTICIPANTS Men who completed a health and lifestyle question naire , which asked about daily milk consumption , and who attended for a medical examination . MAIN RESULTS 150 ( 2.6 % ) men reported drinking more than one and a third pints a day , Some 2977 ( 51.6 % ) reported drinking between a third and one and a third pints a day and 2638 ( 45.8 % ) reported drinking less than a third of a pint a day . There were a total of 2350 deaths over the 25 year follow up period , of which 892 deaths were attributed to coronary heart disease . The relative risk , adjusted for socioeconomic position , health behaviours and health status for deaths from all causes for men who drank one third to one and a third pints a day versus those who drank less than a third of a pint was 0.90 ( 95 % CI 0.83 , 0.97 ) . The adjusted relative risk for deaths attributed to coronary heart disease for men who drank one third to one and a third pints a day versus those who drank less than one third of a pint was 0.92 ( 95 % CI 0.81 , 1.06 ) . CONCLUSIONS No evidence was found that men who consumed milk each day , at a time when most milk consumed was full fat milk , were at increased risk of death from all causes or death from coronary heart disease BACKGROUND Observational studies suggest that people who consume more fruits and vegetables containing beta carotene have somewhat lower risks of cancer and cardiovascular disease , and earlier basic research suggested plausible mechanisms . Because large r and omized trials of long duration were necessary to test this hypothesis directly , we conducted a trial of beta carotene supplementation . METHODS In a r and omized , double-blind , placebo-controlled trial of beta carotene ( 50 mg on alternate days ) , we enrolled 22,071 male physicians , 40 to 84 years of age , in the United States ; 11 percent were current smokers and 39 percent were former smokers at the beginning of the study in 1982 . By December 31 , 1995 , the scheduled end of the study , fewer than 1 percent had been lost to follow-up , and compliance was 78 percent in the group that received beta carotene . RESULTS Among 11,036 physicians r and omly assigned to receive beta carotene and 11,035 assigned to receive placebo , there were virtually no early or late differences in the overall incidence of malignant neoplasms or cardiovascular disease , or in overall mortality . In the beta carotene group , 1273 men had any malignant neoplasm ( except nonmelanoma skin cancer ) , as compared with 1293 in the placebo group ( relative risk , 0.98 ; 95 percent confidence interval , 0.91 to 1.06 ) . There were also no significant differences in the number of cases of lung cancer ( 82 in the beta carotene group vs. 88 in the placebo group ) ; the number of deaths from cancer ( 386 vs. 380 ) , deaths from any cause ( 979 vs. 968 ) , or deaths from cardiovascular disease ( 338 vs. 313 ) ; the number of men with myocardial infa rct ion ( 468 vs. 489 ) ; the number with stroke ( 367 vs. 382 ) ; or the number with any one of the previous three end points ( 967 vs. 972 ) . Among current and former smokers , there were also no significant early or late differences in any of these end points . CONCLUSIONS In this trial among healthy men , 12 years of supplementation with beta carotene produced neither benefit nor harm in terms of the incidence of malignant neoplasms , cardiovascular disease , or death from all causes BACKGROUND Evidence on the relation between trans fatty acid intake and coronary heart disease is limited . We investigated this relation in a Dutch population with a fairly high trans fatty acid intake , including trans fatty acids from partly hydrogenated fish oils . METHODS We prospect ively studied 667 men of the Zutphen Elderly Study aged 64 - 84 years and free of coronary heart disease at baseline . We used dietary surveys to establish the participants ' food consumption patterns . Information on risk factors and diet was obtained in 1985 , 1990 , and 1995 . After 10 years of follow-up from 1985 - 95 , there were 98 cases of fatal or non-fatal coronary heart disease . FINDINGS Between 1985 and 1995 , average trans fatty acid intake decreased from 4.3 % to 1.9 % of energy . After adjustment for age , body mass index , smoking , and dietary covariates , trans fatty acid intake at baseline was positively associated with the 10-year risk of coronary heart disease . The relative risk for a difference of 2 % of energy in trans fatty acid intake at baseline was 1.28 ( 95 % CI 1.01 - 1.61 ) . INTERPRETATION A high intake of trans fatty acids ( all types of isomers ) contributes to the risk of coronary heart disease . The substantial decrease in trans fatty acid intake , mainly due to industrial lowering of trans contents in Dutch edible fats , could therefore have had a large public-health impact BACKGROUND Epidemiological data suggest that the intake of antioxidants such as alpha-tocopherol ( vitamin E ) and beta-carotene has an inverse correlation with the incidence of coronary heart disease . The results from clinical trials of antioxidant supplementation in people with known coronary heart disease are inconclusive . METHODS We studied the frequency of major coronary events in 1862 men enrolled in the alpha-tocopherol beta-carotene Cancer Prevention Study ( smokers aged between 50 and 69 years ) who had a previous myocardial infa rct ion . In this r and omised , double-blind . placebo-controlled study , men had received dietary supplements of alpha-tocopherol ( 50 mg/day ) , beta-carotene ( 20 mg/day ) , both , or placebo . The median follow-up was 5.3 years . The endpoint of this sub study was the first major coronary event after r and omisation . Analyses were by intention to treat . FINDINGS 424 major coronary events ( non-fatal myocardial infa rct ion and fatal coronary heart disease ) occurred during follow-up . There were no significant differences in the number of major coronary events between any supplementation group and the placebo group ( alpha-tocopherol 94/466 ; beta-carotene 113/461 ; alpha-tocopherol and beta-carotene 123/497 ; placebo 94/438 [ log-rank test , p = 0.25 ] ) . There were significantly more deaths from fatal coronary heart disease in the beta-carotene ( 74/461 , multivariate-adjusted relative risk 1.75 [ 95 % CI 1.16 - 2.64 ] , p = 0.007 ) and combined alpha-tocopherol and beta-carotene groups ( 67/497 , relative risk 1.58 [ 1.05 - 2.40 ] , p = 0.03 ) than in the placebo group ( 39/438 ) , but there was no significant increase in the alpha-tocopherol supplementation group ( 54/466 , relative risk 1.33 [ 0.86 - 2.05 ] , p = 0.20 ) . INTERPRETATION The proportion of major coronary events in men with a previous myocardial infa rct ion who smoke was not decreased with either alpha-tocopherol or beta-carotene supplements . In fact , the risk of fatal coronary heart disease increased in the groups that received either beta-carotene or the combination of alpha-tocopherol and beta-carotene ; there was a non-significant trend of increased deaths in the alpha-tocopherol group . We do not recommend the use of alpha-tocopherol or beta-carotene supplements in this group of patients BACKGROUND Observational and experimental studies suggest that the amount of vitamin E ingested in food and in supplements is associated with a lower risk of coronary heart disease and atherosclerosis . METHODS We enrolled a total of 2545 women and 6996 men 55 years of age or older who were at high risk for cardiovascular events because they had cardiovascular disease or diabetes in addition to one other risk factor . These patients were r and omly assigned according to a two-by-two factorial design to receive either 400 IU of vitamin E daily from natural sources or matching placebo and either an angiotensin-converting-enzyme inhibitor ( ramipril ) or matching placebo for a mean of 4.5 years ( the results of the comparison of ramipril and placebo are reported in a companion article ) . The primary outcome was a composite of myocardial infa rct ion , stroke , and death from cardiovascular causes . The secondary outcomes included unstable angina , congestive heart failure , revascularization or amputation , death from any cause , complications of diabetes , and cancer . RESULTS A total of 772 of the 4761 patients assigned to vitamin E ( 16.2 percent ) and 739 of the 4780 assigned to placebo ( 15.5 percent ) had a primary outcome event ( relative risk , 1.05 ; 95 percent confidence interval , 0.95 to 1.16 ; P=0.33 ) . There were no significant differences in the numbers of deaths from cardiovascular causes ( 342 of those assigned to vitamin E vs. 328 of those assigned to placebo ; relative risk , 1.05 ; 95 percent confidence interval , 0.90 to 1.22 ) , myocardial infa rct ion ( 532 vs. 524 ; relative risk , 1.02 ; 95 percent confidence interval , 0.90 to 1.15 ) , or stroke ( 209 vs. 180 ; relative risk , 1.17 ; 95 percent confidence interval , 0.95 to 1.42 ) . There were also no significant differences in the incidence of secondary cardiovascular outcomes or in death from any cause . There were no significant adverse effects of vitamin E. CONCLUSIONS In patients at high risk for cardiovascular events , treatment with vitamin E for a mean of 4.5 years had no apparent effect on cardiovascular outcomes OBJECTIVES Experimental and observational studies suggest that vitamin E may reduce the risk of cardiovascular ( CV ) events and of microvascular complications in people with diabetes . However , data from r and omized clinical trials are limited . Therefore , we evaluated the effects of vitamin E supplementation on major CV outcomes and on the development of nephropathy in people with diabetes . RESEARCH DESIGN AND METHODS The Heart Outcomes Prevention Evaluation ( HOPE ) trial is a r and omized clinical trial with a 2 x 2 factorial design , which evaluated the effects of vitamin E and of ramipril in patients at high risk for CV events . Patients were eligible for the study if they were 55 years or older and if they had CV disease or diabetes with at least one additional coronary risk factor . The study was design ed to recruit a large number of people with diabetes , and the analyses of the effects of vitamin E in this group were preplanned . Patients were r and omly allocated to daily treatment with 400 IU vitamin E and with 10 mg ramipril or their respective placebos and were followed for an average of 4.5 years . The primary study outcome was the composite of myocardial infa rct ion , stroke , or CV death . Secondary outcomes included total mortality , hospitalizations for heart failure , hospitalizations for unstable angina , revascularizations , and overt nephropathy . RESULTS There were 3,654 people with diabetes . Vitamin E had a neutral effect on the primary study outcome ( relative risk = 1.03 , 95 % CI 0.88 - 1.21 ; P = 0.70 ) , on each component of the composite primary outcome , and on all predefined secondary outcomes . CONCLUSIONS The daily administration of 400 IU vitamin E for an average of 4.5 years to middle-aged and elderly people with diabetes and CV disease and /or additional coronary risk factor(s ) has no effect on CV outcomes or nephropathy CONTEXT Experimental and epidemiological data suggest that vitamin E supplementation may prevent cancer and cardiovascular events . Clinical trials have generally failed to confirm benefits , possibly due to their relatively short duration . OBJECTIVE To evaluate whether long-term supplementation with vitamin E decreases the risk of cancer , cancer death , and major cardiovascular events . DESIGN , SETTING , AND PATIENTS A r and omized , double-blind , placebo-controlled international trial ( the initial Heart Outcomes Prevention Evaluation [ HOPE ] trial conducted between December 21 , 1993 , and April 15 , 1999 ) of patients at least 55 years old with vascular disease or diabetes mellitus was extended ( HOPE-The Ongoing Outcomes [ HOPE-TOO ] ) between April 16 , 1999 , and May 26 , 2003 . Of the initial 267 HOPE centers that had enrolled 9541 patients , 174 centers participated in the HOPE-TOO trial . Of 7030 patients enrolled at these centers , 916 were deceased at the beginning of the extension , 1382 refused participation , 3994 continued to take the study intervention , and 738 agreed to passive follow-up . Median duration of follow-up was 7.0 years . INTERVENTION Daily dose of natural source vitamin E ( 400 IU ) or matching placebo . MAIN OUTCOME MEASURES Primary outcomes included cancer incidence , cancer deaths , and major cardiovascular events ( myocardial infa rct ion , stroke , and cardiovascular death ) . Secondary outcomes included heart failure , unstable angina , and revascularizations . RESULTS Among all HOPE patients , there were no significant differences in the primary analysis : for cancer incidence , there were 552 patients ( 11.6 % ) in the vitamin E group vs 586 ( 12.3 % ) in the placebo group ( relative risk [ RR ] , 0.94 ; 95 % confidence interval [ CI ] , 0.84 - 1.06 ; P = .30 ) ; for cancer deaths , 156 ( 3.3 % ) vs 178 ( 3.7 % ) , respectively ( RR , 0.88 ; 95 % CI , 0.71 - 1.09 ; P = .24 ) ; and for major cardiovascular events , 1022 ( 21.5 % ) vs 985 ( 20.6 % ) , respectively ( RR , 1.04 ; 95 % CI , 0.96 - 1.14 ; P = .34 ) . Patients in the vitamin E group had a higher risk of heart failure ( RR , 1.13 ; 95 % CI , 1.01 - 1.26 ; P = .03 ) and hospitalization for heart failure ( RR , 1.21 ; 95 % CI , 1.00 - 1.47 ; P = .045 ) . Similarly , among patients enrolled at the centers participating in the HOPE-TOO trial , there were no differences in cancer incidence , cancer deaths , and major cardiovascular events , but higher rates of heart failure and hospitalizations for heart failure . CONCLUSION In patients with vascular disease or diabetes mellitus , long-term vitamin E supplementation does not prevent cancer or major cardiovascular events and may increase the risk for heart failure BACKGROUND Although substantial information on individual nutrients or foods and risk of coronary heart disease ( CHD ) is available , little is known about the role of overall eating pattern . METHODS Using dietary information from a food frequency question naire in 1984 from the Nurses ' Health Study , we conducted factor analysis and identified 2 major dietary patterns-"prudent " and " Western"- and calculated factor scores of each pattern for individuals in the cohort . We used logistic regression to examine prospect ively the associations between dietary patterns and CHD risk among 69 017 women aged 38 to 63 years in 1984 without history of major chronic diseases . RESULTS The prudent pattern was characterized by higher intakes of fruits , vegetables , legumes , fish , poultry , and whole grains , while the Western pattern was characterized by higher intakes of red and processed meats , sweets and desserts , french fries , and refined grains . Between 1984 and 1996 , we documented 821 CHD cases . After adjusting for coronary risk factors , the prudent diet score was associated with a relative risk ( RR ) of 0.76 ( 95 % confidence interval ( CI ) , 0.60 - 0.98 ; P for trend test,.03 ) comparing the highest with lowest quintile . Extreme quintile comparison yielded an RR of 1.46 ( 95 % CI , 1.07 - 1.99 ; P for trend test,.02 ) for the Western pattern . Those who were jointly in the highest prudent diet quintile and lowest Western diet quintile had an RR of 0.64 ( 95 % CI , 0.44 - 0.92 ) compared with those with the opposite pattern profile . CONCLUSION A diet high in fruits , vegetables , whole grains , legumes , poultry , and fish and low in refined grains , potatoes , and red and processed meats may lower risk of CHD BACKGROUND Oxidized low-density lipoprotein is involved in the pathogenesis of atherosclerosis . In epidemiological studies antioxidants have been inversely related with coronary heart disease . Findings from controlled trials are inconclusive . METHODS We studied the primary preventive effect of vitamin E ( alpha tocopherol ) and beta carotene supplementation on major coronary events in the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study , a controlled trial undertaken primarily to examine the effects of these agents on cancer . A total of 27 271 Finnish male smokers aged 50 to 69 years with no history of myocardial infa rct ion were r and omly assigned to receive vitamin E ( 50 mg ) , beta carotene ( 20 mg ) , both agents , or placebo daily for 5 to 8 years ( median , 6.1 years ) . The end point was the first major coronary event , either nonfatal myocardial infa rct ion ( surviving at least 28 days ; n = 1204 ) or fatal coronary heart disease ( n = 907 ) . RESULTS The incidence of primary major coronary events decreased 4 % ( 95 % confidence interval , -12 % to 4 % ) among recipients of vitamin E and increased 1 % ( 95 % confidence interval , -7 % to 10 % ) among recipients of beta carotene compared with the respective nonrecipients . Neither agent affected the incidence of nonfatal myocardial infa rct ion . Supplementation with vitamin E decreased the incidence of fatal coronary heart disease by 8 % ( 95 % confidence interval , -19 % to 5 % ) , but beta carotene had no effect on this end point . CONCLUSIONS Supplementation with a small dose of vitamin E has only marginal effect on the incidence of fatal coronary heart disease in male smokers with no history of myocardial infa rct ion , but no influence on nonfatal myocardial infa rct ion . Supplementation with beta carotene has no primary preventive effect on major coronary events BACKGROUND Fatty acids that contain a trans double bond are consumed in large amounts as hydrogenated oils , but their effects on serum lipoprotein levels are unknown . METHODS We placed 34 women ( mean age , 26 years ) and 25 men ( mean age , 25 years ) on three mixed natural diets of identical nutrient composition , except that 10 percent of the daily energy intake was provided as oleic acid ( which contains one cis double bond ) , trans isomers of oleic acid , or saturated fatty acids . The three diets were consumed for three weeks each , in r and om order . RESULTS On the oleic acid diet , the mean ( + /- SD ) serum values for the entire group for total , low-density lipoprotein ( LDL ) , and high-density lipoprotein ( HDL ) cholesterol were 4.46 + /- 0.66 . 2.67 + /- 0.54 , and 1.42 + /- 0.32 mmol per liter ( 172 + /- 26 , 103 + /- 21 , and 55 + /- 12 mg per deciliter ) , respectively . On the trans-fatty-acid diet , the subjects ' mean HDL cholesterol level was 0.17 mmol per liter ( 7 mg per deciliter ) lower than the mean value on the diet high in oleic acid ( P less than 0.0001 ; 95 percent confidence interval , 0.13 to 0.20 mmol per liter ) . The HDL cholesterol level on the saturated-fat diet was the same as on the oleic acid diet . The LDL cholesterol level was 0.37 mmol per liter ( 14 mg per deciliter ) higher on the trans-fatty-acid diet than on the oleic acid diet ( P less than 0.0001 ; 95 percent confidence interval , 0.28 to 0.45 mmol per liter ) and 0.47 mmol per liter ( 18 mg per deciliter ) higher on the saturated-fat diet ( P less than 0.001 ; 95 percent confidence interval , 0.39 to 0.55 mmol per liter ) than on the oleic acid diet . The effects on lipoprotein levels did not differ between women and men . CONCLUSIONS The effect of trans fatty acids on the serum lipoprotein profile is at least as unfavorable as that of the cholesterol-raising saturated fatty acids , because they not only raise LDL cholesterol levels but also lower HDL cholesterol levels In a prospect i ve , r and omised single-blinded secondary prevention trial we compared the effect of a Mediterranean alpha-linolenic acid-rich diet to the usual post-infa rct prudent diet . After a first myocardial infa rct ion , patients were r and omly assigned to the experimental ( n = 302 ) or control group ( n = 303 ) . Patients were seen again 8 weeks after r and omisation , and each year for 5 years . The experimental group consumed significantly less lipids , saturated fat , cholesterol , and linoleic acid but more oleic and alpha-linolenic acids confirmed by measurements in plasma . Serum lipids , blood pressure , and body mass index remained similar in the 2 groups . In the experimental group , plasma levels of albumin , vitamin E , and vitamin C were increased , and granulocyte count decreased . After a mean follow up of 27 months , there were 16 cardiac deaths in the control and 3 in the experimental group ; 17 non-fatal myocardial infa rct ion in the control and 5 in the experimental groups : a risk ratio for these two main endpoints combined of 0.27 ( 95 % CI 0.12 - 0.59 , p = 0.001 ) after adjustment for prognostic variables . Overall mortality was 20 in the control , 8 in the experimental group , an adjusted risk ratio of 0.30 ( 95 % CI 0.11 - 0.82 , p = 0.02 ) . An alpha-linolenic acid-rich Mediterranean diet seems to be more efficient than presently used diets in the secondary prevention of coronary events and death |
690 | 27,820,087 | The results of this review support the prone position in preterm infants for improvement of arterial oxygen saturation , improved lung and chest wall synchrony of respiratory improvements , decreased incidence of apnea in infants with a clinical history of apnea , promoted sleep , and decreased gastroesophageal reflux .
However , the prone position increased postural abnormalities , orthopaedic abnormalities of the feet , and delayed developmental musculature .
The combined use of a postural support roll and a postural nappy while very preterm infants are nursed , improved hip and shoulder posture up to term postmenstrual age .
The change in body position from horizontal to head-up tilt in very immature and unstable infants may affect the cerebral homodynamic .
The management of position per se may not be sufficient for assisting preterm neonates to cope with the painful procedure .
Furthermore , preterm infants are susceptible to oxygen desaturation in car seats and carrying slings .
Prone positioning was shown to have many advantages for prematurely born infants .
But the longer , deep sleep period and fewer awakenings associated with a prone position would support higher vulnerability for preterm infants to sudden infant death syndrome ( SIDS ) . | EXECUTIVE SUMMARY Positioning of preterm infants is a basic task of neonatal nursing care .
A variety of outcomes are affected by different body positioning of preterm infants .
This review evaluates the clinical evidence of the effects of positioning of preterm infants with regard to physiological outcomes and sleep states .
OBJECTIVES To conduct a systematic review to determine the best available evidence related to the positioning of preterm infants .
The specific review questions addressed were : the physiological outcomes affected by different positioning , and the best position for promoting sleep . | Fourteen intubated infants recovering from neonatal respiratory disease had arterial blood gases and lung mechanics measured in the supine position and in two variants of the prone position . Prone positioning result ed in significant increases in mean ( + /- SEM ) arterial oxygen tension ( Pa(o2 70.4 + /- 2.5 to 81.1 + /- 4.4 mm Hg ) , dynamic lung compliance ( 1.7 + /- 0.24 to 2.55 + /- 0.37 ml/cm H2O ) , and tidal volume ( 8.6 + /- 1.0 to 10.5 + /- 1.2 ml ) when all prone values were compared to supine values . Prone positioning with the abdomen protruding freely , when compared to all supine values , was associated with significantly increased dynamic lung compliance and tidal volume . Values for prone-abdomen free were not significantly different from values for prone-abdomen restricted . This suggests that there are clinical benefits from prone positioning in neonates recovering from respiratory disease Our objective was to determine the effect of posture on respiratory function and drive in prematurely born infants immediately prior to discharge . Twenty infants ( 6 oxygen-dependent ) , median gestational age 29 weeks ( range , 25 - 32 ) , were studied at a median postconceptional age ( PCA ) of 36 weeks ( range , 33 - 39 ) . On 2 successive days , infants were studied both supine and prone ; each posture was maintained for 3 hr . The order on each day in which postures were studied was r and omized between infants . At the end of each 3-hr period , tidal volume ( Vt ) , inspiratory ( Ti ) and expiratory ( Te ) time , respiratory rate , and minute ventilation were measured . In addition , respiratory drive was assessed by measuring the pressure generated in the first 100 msec of an imposed airway occlusion ( P(0.1 ) ) , and respiratory muscle strength was assessed by recording the maximum inspiratory pressure ( Pimax ) generated against an occlusion which was maintained for at least five breaths . Overall , tidal volume was higher ( P < 0.05 ) , but respiratory rate ( P < 0.05 ) , P(0.1 ) ( P < 0.05 ) , and Pimax ( P < 0.05 ) were lower in the prone compared to the supine position . There were no significant differences in Ti or Te between the two postures . In oxygen-dependent infants only , minute volume was higher in the prone position ( P < 0.05 ) . In conclusion , posture-related differences in respiratory function are present in prematurely born infants studied prior to neonatal unit discharge Studies of the effect of body position during and after bolus feeding upon gastric emptying or gastric residual have not had consistent results . We tested the hypotheses that right lateral decubitus leads to less gastric residual than left lateral decubitus and that the prone position leads to less gastric residual than the supine position . A prospect i ve r and omized clinical trial with triple crossover of healthy growing , appropriate for gestational age preterm infants . Each infant was successively studied while fed in the four different positions . Gastric residuals were measured at 1 and 3 hours after initiation of feeding and returned . Thirty-one patients were studied . At 1 hour , right lateral decubitus led to less significant residuals than the left lateral decubitus and the prone position led to less residual than the left lateral decubitus . The amount of gastric residuals 1 hour after a meal appears to be in the following decreasing order : left , supine , prone , right UNLABELLED BACKGROUND . The preterm infant is subject to the force of gravity : when its body lies pressed against the mattress on which it is placed . AIMS The purpose of this study was to investigate short-term effects of varied post-natal lying positions in order to prevent neuromuscular and postural abnormalities . METHODS 60 low risk preterm infants of 31 - 36 weeks gestational age were enrolled for this r and omised clinical trial . Initially each child underwent neurological and psychomotor assessment s which included tonus and reflex protocol s as well as behavioral , sensory motor and postural examinations . The lying positions of the treated group were varied ( back , prone , and side ) using a specially design ed moldable mattress that maintained the functional position of the infant 's body . The control group was placed on their stomachs , ( the st and ard lying position used in 1994 ) with a st and ard orthopaedic bolster support under their hips . All infants underwent a second round of examinations upon discharge to assess any changes in neurological and psychomotor outcomes . RESULTS The sensory-motor skills examinations showed significant abnormalities in the control group : ( 1 ) dominance of the extensor muscles due to muscle shortening , ( 2 ) hyper abduction and flexion of the arms , and ( 3 ) global neuromuscular rigidity . Psychomotor and neurological exams of the control and treatment groups showed delayed developmental muscular acquisitions for infants in the control group . CONCLUSION Regular changes in posture , while retaining correct functional positions , allowed maintenance of normal neuromuscular and osteo-articular function and permitted the development of spontaneous and functional motor activity in low-risk perterm infants OBJECTIVE : The purpose of this study was to determine the effects of prone and supine positioning on the cardiorespiratory stability of preterm infants with apnea and bradycardia . METHODS : A total of 22 preterm infants with symptomatic apnea and bradycardia ( gestational age of 26.9 ± 1.8 weeks and birth weight of 865 ± 235 gm ) were monitored for 24 hours ( in four sequential 6-hour blocks ) for apnea , bradycardia , and oxygen desaturation in alternating positions ( prone or supine ) following r and omization . Postconceptional age at the time of study was 31.9 ± 3.0 weeks . Respiratory rate , heart rate , and transcutaneous oxygen saturation were continuously monitored . All episodes of apnea ( ≥10 seconds ) , bradycardia ( < 100 beats per minute ) , and oxygen desaturation ( < 90 % ) were recorded on an event monitor . Episodes of apnea , bradycardia , and oxygen desaturation were defined as clinical ly significant if the following criteria were met : apnea , ≥15 seconds ; bradycardia , < 90 beats per minute ; and oxygen desaturation , < 80 % . All other recorded episodes were considered mild . The episodes were analyzed for statistical significance using the paired t-test . RESULTS : No significant differences ( p > 0.05 ) in the incidence of clinical ly significant apnea , bradycardia , or desaturation between supine and prone positions were seen in these preterm infants . CONCLUSION : Our results suggest that the cardiorespiratory stability of preterm infants is not significantly compromised by supine positioning Objective The purpose of this study was to examine the influence of prone and supine position in preterm infants during acute pain of blood collection . Setting Level III Neonatal Intensive Care Unit ( NICU ) . Study Design Thirty-eight preterm infants ( birthweight 1339 [ 590–2525 ] g , GA 29 [ 25– 32 ] wks ) were in 2 groups depending on their position in the isolette prior to and during heel lance at 32 weeks post-conceptional age . The study design was a comparison between groups ( Prone , Supine ) during 2 events ( Baseline , Heel lance ) . Outcome MeasurePain measures were multidimensional , including behavioral ( sleep – wake state and facial activity ) and physiological ( heart rate ) responses measured continuously prior to ( Baseline ) and during blood collection ( Lance ) . Results Both groups of infants displayed statistically significant shifts in sleep – wake state to greater arousal , and increased facial activity and heart rate , from Baseline to Lance . Prone position was associated with significantly more deep sleep during Baseline , compared with Supine position , but there were no differences in sleep-wake state during Lance . Minor increased facial activity was shown in some time segments of Baseline for infants in Supine compared with Prone , but did not differ overall between positions . Prone and Supine position did not affect heart rate significantly during Baseline or Lance events . Conclusions Prone position promotes deep sleep in preterm neonates at 32 weeks post-conceptional age when they are undisturbed . However , placement in prone position is not a sufficient environmental comfort intervention for painful invasive procedures such as heel lance for blood sampling in the NICU . Neonates require other environmental supports to promote coping with this stressful event Background . As a result of the American Academy of Pediatrics ' recommendation that healthy infants be placed on their side or back for sleep , the percentage of infants sleeping prone has decreased dramatically . With the increase in supine sleeping , pediatricians have question ed if there are differences in the rate of acquisition of early motor milestones between prone and supine sleeping infants . Methods . To examine this question , we performed a prospect i ve , practice -based study of healthy term infants . Infants were recruited before the age of 2 months . Parents were asked to record infant sleep position and awake time spent prone until 6 months of age . A developmental log was used to track milestones from birth until the infant was walking . Age of acquisition of eight motor milestones was determined , and the mean ages of milestone attainment of prone and supine sleepers were compared . Results . Three hundred fifty-one infants completed the study . Prone sleepers acquired motor milestones at an earlier age than supine sleepers . There was a significant difference in the age of attainment of rolling prone to supine , tripod sitting , creeping , crawling , and pulling to st and . There was no significant difference in age when infants walked . Conclusions . The pattern of early motor development is affected by sleep position . Prone sleepers attain several motor milestones earlier than supine sleepers . However , all infants achieved all milestones within the accepted normal age range . Pediatricians can use this information to reassure parents . This difference in milestone attainment is not a reason to ab and on the American Academy of Pediatrics ' sleep position recommendations OBJECTIVE We investigated whether nursing in the head elevated tilt position ( HETP ) , compared with the horizontal position , has any effect on the incidence of bradycardic and hypoxemic episodes in preterm infants . METHODS Twelve spontaneously breathing preterm infants with idiopathic recurrent apnea were studied in a r and omized controlled crossover trial . Nine infants were treated with aminophylline . Each spent a total of 24 hours in the horizontal prone position and a total of 24 hours in HETP ( prone , 15 degrees ) . The position was changed in r and om order every 6 hours . Thoracic impedance , heart rate , and arterial oxygen saturation were recorded continuously . The frequency of isolated hypoxemia ( arterial saturation < 80 % ) , of isolated bradycardia ( heart rate < 90 beats per minute ) , and of mixed events was analyzed and compared without knowledge of the allocated position . RESULTS In total , there were significantly fewer bradycardic and /or hypoxemic episodes ( 28.2 % ) in HETP compared with the horizontal position ( mean difference , 13.35 episodes/24 hours ; 95 % confidence interval [ CI ] : 5.9- 20.8 ) . The decrease was largest for isolated hypoxemic episodes ( 48.5 % ; mean difference , 11.74 episodes/24 hours ; 95 % CI : 6.1 - 17.4 ) . Isolated bradycardic episodes ( mean difference , 2.27 episodes/24 hours ; 95 % CI : -0.78 - 5.31 ) and mixed events were not decreased significantly in HETP . CONCLUSIONS Nursing in a moderately tilted position ( 15 degrees ) reduces hypoxemic events in preterm infants . This intervention is easy to apply , quickly reversible , and can be combined with drugs such as aminophylline OBJECTIVE . Prematurely born compared with term born infants are at increased risk of sudden infant death syndrome , particularly if slept prone . The purpose of this work was to test the hypothesis that preterm infants with or without bronchopulmonary dysplasia being prepared for neonatal unit discharge would sleep longer and have less arousals and more central apneas in the prone position . METHODS . This was a prospect i ve observational study in a tertiary NICU . Twenty-four infants ( 14 with bronchopulmonary dysplasia ) with a median gestational age of 27 weeks were studied at a median postconceptional age of 37 weeks . Video polysomnographic recordings of 2-channel electroencephalogram , 2-channel electro-oculogram , nasal airflow , chest and abdominal wall movements , limb movements , electrocardiogram , and oxygen saturation were made in the supine and prone positions , each position maintained for 3 hours . The duration of sleep , sleep efficiency ( total sleep time/total recording time ) , and number and type of apneas , arousals , and awakenings were recorded . RESULTS . Overall , in the prone position , infants slept longer , had greater sleep efficiency ( 89.5 % vs 72.5 % ) , and had more central apneas ( median : 5.6 vs 2.2 ) , but fewer obstructive apneas ( 0.5 vs 0.9 ) . The infants had more awakenings ( 9.7 vs 3.5 ) and arousals per hour ( 13.6 vs 9.0 ) when supine . There were similar findings in the bronchopulmonary dysplasia infants . CONCLUSIONS . Very prematurely born infants studied before neonatal unit discharge sleep more efficiently with fewer arousals and more central apneas in the prone position , emphasizing the importance of recommending supine sleeping after neonatal unit discharge for prematurely born infants OBJECTIVE To determine whether infants with chronic lung disease ( CLD ) , ready for neonatal unit discharge , maintain cardiorespiratory stability while sleeping supine . METHODS Subjects were 15 infants born < 32 weeks gestational age ( GA ) and ready for discharge from the regional tertiary neonatal intensive care unit . Polysomnography recordings of sleep state , heart rate , arterial oxygen saturation , respiratory effort and nasal/oral airflow were taken prone and supine for up to 3 h post feed with the first position r and omly allocated . The main outcome measures were oxygen saturation and apnoea hypopnoea index ( AHI ) . RESULTS Seven infants ( median GA 27 weeks , birthweight 945 g ) had CLD and eight infants ( median GA 29 weeks , birthweight 1160 g ) did not . CLD infants were more mature at study than non-CLD infants ( median 39 vs 36 weeks , P = 0.019 ) . Neither oxygen saturation nor AHI were position dependent and no group differences were noted with respect to CLD status . There was a significant interaction of GA and sleep position with less-mature infants spending less time in quiet sleep ( QS ) in supine position ( P = 0.006 ) . These less-mature infants also had a higher AHI ( P = 0.033 ) . As expected , the AHI and arousal index ( AI ) were higher in active sleep ( P < or = 0.001 , P = 0.013 , respectively ) and mean oxygen saturation was lower ( P = 0.001 ) . CONCLUSIONS The supine position appears appropriate for very preterm infants with CLD going home from the neonatal unit . Respiratory instability on neonatal discharge is more likely to be associated with immaturity than CLD BACKGROUND AND PURPOSE Body position can play an important role in an infant 's recovery from respiratory disease , but few studies have accounted for sleep state which is known to have a direct influence on the control of respiratory muscles as well as on metabolic and circulatory changes . The purpose of this study was to examine the influence of body position on respiratory function in pre-term infants whilst accounting for sleep state . METHOD Thoraco-abdominal motion was assessed using respiratory inductance plethysmography ( RIP ) to provide measures of relative rib cage ( RC ) and abdominal ( AB ) movement in ten non-ventilated pre-term infants . Continuous measurements of oxygen saturation ( SaO2 ) , pulse and heart rate ( HR ) , were made and sleep state was recorded using behavioural criteria and electro-oculogram ( EOG ) measurements . RESULTS The results showed a significant increase in HR in supine , but no significant difference in SaO2 as a function of position , compared to the prone position where a significant reduction was found in thoraco-abdominal asynchrony for both groups and a reduction in variability in both HR and SaO2 . Intra-subject variability of thoraco-abdominal motion as a function of position demonstrated no significant difference on return to supine or on return to prone , illustrating good repeatability of measures . CONCLUSIONS Prone positioning of pre-term infants recovering from respiratory disease may improve respiratory function . As measured , the improvement in respiratory synchrony in prone position brings pre-term infants ' breathing pattern into line with that expected in term infants The objective of the present study was to evaluate sleeping position-dependent effects on cerebral hemodynamics during apnea in preterm infants . To this end , polygraphic studies were performed on 15 stable preterm infants lying prone and lying supine . Changes in cerebral blood volume ( DeltaCBV ) and in cerebral hemoglobin oxygenation ( (Delta)cHbD ) in association with apnea were measured by near infrared spectroscopy . For comparison , apnea in the prone position was matched for duration to apnea in the supine position . A total number of 98 pairs of apnea were compared . The mean duration of apnea was 8.2+/-3 s. In both positions there was a predominance of decrease in CBV and cHbD in association with apnea . The mean decrease of cHbD ( -1.57+/-1.82 micromol/l ) and of CBV ( -0.120+/-0.137 ml/100 g brain ) in the supine position was significantly pronounced compared to prone position ( DeltacHbD : -1.18+/-1.77 micromol/l , DeltaCBV : -0.080+/-0.095 ml/100 g brain ) . The degree of DeltaCBV and DeltaHbD did not correlate with postconceptional or postnatal age ( r2<0.01 ) . In both positions there was a similar small decrease of SaO2 in association with apnea . In the supine position heart rate decreased slightly during apnea , whereas in the prone position no change in heart rate could be observed . The present study revealed a position-dependent different impact of apnea on cerebral hemodynamics . With regard to cerebral blood volume and oxygenation in association with apnea no negative effects of prone sleeping position could be observed in preterm infants OBJECTIVES To test prospect ively the hypothesis that an infant car seat modification to allow the infant 's head to rest in a neutral position on the trunk would prevent narrowing of the upper airway and thus reduce oxygen desaturation in preterm infants who are restrained in car seats . METHODS Seventeen preterm infants who were approved for discharge were evaluated in a car seat for newborns , with and without a foam insert that provided a slot for the back of the infants ' head . Respiration timed inspiratory radiographs for assessment of upper airway dimensions were taken during quiet sleep in each position . Infants were monitored in each position for 30 minutes with continuous polygraphic recording of respiratory , cardiac , and nasal airflow activity and pulse oximetry . RESULTS Placement of the insert in the car seat was associated with a larger upper airway space ( mean + /- st and ard deviation , 5.2 + /- 1.3 vs 3.6 + /- 1.4 mm ) . This radiologic improvement was associated with a significant reduction in the frequency of episodes of oxygen desaturation to < 85 % ( 1.5 + /- 2.1 vs 3.5 + /- 3.5 episodes/infant ) , of bradycardia < 90 bpm ( 0.1 + /- 0.3 vs 1 + /- 1.7 ) , and of arousal ( median [ 25th , 75th ] , 2.5 [ 1.3 , 4.0 ] vs 5.0 [ 4.0 , 7.0 ] ) . CONCLUSIONS The cause of oxygen desaturation in preterm infants who are restrained in car seats is multifactorial . The present data strongly support the hypothesis that flexion of the head on the body is a significant contributor to these episodes and that the mechanism is posterocephalic displacement of the m and ible , leading to narrowing of the upper airway . Critically , this pilot study demonstrates that the frequency of episodes of desaturation in a st and ard newborn car seat can be substantially reduced by placement of a simple foam insert that allows the infant to maintain the head in a neutral position on the trunk during sleep OBJECTIVE To determine the effect of a postural support nappy and /or a postural support roll on neuromotor function in very preterm infants when nursed prone to term equivalent age . METHODS A r and omized observer blind controlled trial of 123 very preterm infants was conducted in the neonatal intensive care unit of the sole tertiary referral centre in Western Australia . Infants were stratified by gestational age ( < 29 weeks or 29 - 30 weeks ) , then r and omized into one of three intervention groups : postural support nappy , postural support nappy and postural support roll , or disposable nappy and postural support roll . Interventions started when infants were stable and ceased when routine side-lying commenced . Measurements of shoulder and hip posture were performed pre-intervention , 5 weeks post-intervention and term postmenstrual age . RESULTS Infants nursed with a postural support roll and a postural support nappy demonstrated improved hip posture to term equivalent age compared with infants nursed with either a postural support roll only , or a postural support nappy only . Infants nursed with a postural support roll either with or without a postural support nappy demonstrated improved shoulder posture to term equivalent age . CONCLUSIONS Combined use of a postural support roll and a postural support nappy while very preterm infants are nursed prone improves hip posture up to term postmenstrual age . Use of a postural support roll improves shoulder posture up to term equivalent age Premature infants with respiratory distress oxygenate better and have improved breathing synchrony when they are nursed in the prone position . We investigated whether work of breathing ( WOB ) is decreased in the prone position in healthy premature infants nearing discharge from the neonatal intensive care unit . Nineteen convalescing premature infants in room air were studied in both supine and prone position . Positioning order was r and omized . Mean birth weight was 1358 + /- 332 ( SD ) g , gestational age 29.7 + /- 2.1 weeks , weight at study 1757 + /- 248 g , and age at study 33.6 + /- 1.4 days . Calibrated respiratory inductance plethysmography ( RIP ) was used to measure tidal volume ; an esophageal catheter estimated pleural pressure . Inspiratory , elastic , and resistive WOB were calculated and were unaffected by prone versus supine positioning ( P = 0.46 , 0.36 , and 0.87 , respectively ) . Similarly , respiratory rate , tidal volume , minute ventilation , and lung compliance did not differ between positions . These data suggest that sleep position recommendations for healthy premature infants discharged home without oxygen should be no different than for term infants Purpose This study was design ed to determine whether supine positioning of infants born preterm in a hammock instead of the prone position affects their neuromuscular maturity , growth , and autonomic stability . Methods Twenty healthy infants who were born premature with very low birth weight ( VLBW ) ( < 1500 g ) were r and omized into two groups . Subjects were pair-matched for weight ( difference less than 100 g ) , gestational age ( difference less than eight days ) , and postnatal age ( difference less than eight days ) . Ten infants were placed supine in a hammock for three hours daily for ten consecutive days , and ten infants were maintained nested in the prone position . Neuromuscular maturity ( based on three neurological parameters adopted from the Ballard examination ) , heart rate , respiratory rate , and weight gain ( g/cal ) were compared between the groups . Results Compared with nested prone positioning , supine positioning in a hammock was associated with a higher neuromuscular maturity score ( p < 0.003 ) and a more relaxed condition , as expressed by lower heart rate and respiratory rate ( p < 0.05 and p < 0.01 , respectively ) . Conclusions Maintaining infants who were born preterm with VLBW in the supine position in a hammock may positively affect their autonomic stability and neuromuscular maturity Objective The aim of our study was to determine the effect of the irregular spontaneous breathing pattern and posture on the spatial distribution of ventilation in neonates free from respiratory disease by the non-invasive imaging method of electrical impedance tomography ( EIT ) . Scanning of spontaneously breathing neonates is the prerequisite for later routine application of EIT in babies with lung pathology undergoing ventilator therapy . Design Prospect i ve study . Setting Neonatal intensive care unit at a university hospital . Patients Twelve pre-term and term neonates ( mean age : 23 days ; mean body weight : 2,465 g ; mean gestational age : 34 weeks ; mean birth weight : 2,040 g ) . Interventions Change in body position in the sequence : supine , right lateral , prone , supine . Measurements and results EIT measurements were performed using the Göttingen GoeMF I system . EIT scans of regional lung ventilation showing the distribution of respired air in the chest cross-section were generated during phases of rapid tidal breathing and deep breaths . During tidal breathing , 54.5±8.3 % , 55.2±10.5 % , 59.9±8.4 % and 54.2±8.5 % of inspired air ( mean values ± SD ) were directed into the right lung in the supine , right lateral , prone and repeated supine postures respectively . During deep inspirations , the right lung ventilation accounted for 52.6±7.9 % , 68.5±8.5 % , 55.4±8.2 % and 50.5±6.6 % of total ventilation respectively . Conclusion The study identified the significant effect of breathing pattern and posture on the spatial distribution of lung ventilation in spontaneously breathing neonates . The results demonstrate that changes in regional ventilation can easily be determined by EIT and bode well for the future use of this method in paediatric intensive care OBJECTIVE To determine whether the use of a postural support nappy ( PSN ) would reduce the features of ' flattened posture ' in the lower extremities of infants < 31 weeks gestation who are nursed prone . METHODOLOGY R and omized , observer blind , controlled trial conducted at King Edward Memorial Hospital for Women , Perth , Western Australia . Infants were r and omly assigned and stratified by gestational age to be nursed in a conventional nappy ( n = 29 ) or a PSN ( n = 31 ) when in the prone position . The features of ' flattened posture ' were measured as angles and assessed by blinded observers prior to commencement of the intervention , 4 weeks post intervention , then bi-weekly until discharge . RESULTS A significant reduction in the features of ' flattened posture ' occurred in the PSN group after 4 - 6 weeks of intervention and stabilized by 8 weeks until discharge . No changes were detected in the control group . No significant difference was observed between infants < 29 weeks gestation compared to infants of 29 - 30 weeks gestation in either treatment group . CONCLUSIONS Use of the PSN in infants < 31 weeks gestation who are nursed in the prone position significantly reduces the features of ' flattened posture ' in the lower extremities . This is of benefit in the short term , and follow up of these infants into childhood will demonstrate whether the long-term effects of ' flattened posture ' can be prevented AIM To examine the effect of body position on clinical ly significant gastro-oesophageal reflux ( GOR ) in preterm infants . METHODS Eighteen preterm infants with clinical ly significant GOR were studied prospect ively using 24 hour lower oesophageal pH monitoring . Infants were nursed in three positions ( prone , left , and right lateral ) for 8 hours in each position , with the order r and omly assigned . Data were analysed using analysis of covariance . RESULTS The median ( range ) reflux index ( RI ) for the group was 13.8 % ( 5.8–40.4 ) . There was no significant difference in the mean time spent in each position . RI ( mean % ( SEM ) ) was significantly less in prone ( 6.3 ( 1.7 ) ) and left lateral positions ( 11.0 ( 2.2 ) ) , when compared with the right lateral position ( 29.4 ( 3.2 ) ) ; p<0.001 . The mean ( SEM ) longest episodes ( mins ) of GOR were reduced by prone and left positions ( 8.6 ( 2.2 ) and 10.0 ( 2.4 ) , respectively ) compared with the right position ( 26.0 ( 3.9 ) ) ; p<0.001 . The mean ( SE ) number of episodes was reduced by prone ( 15.4 ( 2.8 ) ) and left ( 24.6 ( 3.5 ) ) positions when compared with right ( 41.6 ( 4.6 ) ) ( p<0.001 ) . CONCLUSIONS Prone and left lateral positions significantly reduce the severity of GOR , by reducing the number of episodes and the duration of the longest episodes . Such positioning offers a useful adjunct to the treatment in hospital of preterm infants with gastro-oesophageal reflux Objective : To evaluate the effects of prone and supine sleeping positions on electrocortical activity during active ( AS ) and quiet ( QS ) sleep in low birthweight infants . Design : R and omised/crossover study . Setting : Infant Physiology Laboratory at Children ’s Hospital of New York . Patients : Sixty three healthy , growing , low birthweight ( birth weight 795–1600 g ) infants , 26–37 weeks gestational age . Interventions : Six hour continuous two channel electrocortical recordings , together with minute by minute behavioural state assignment , were performed . The infants were r and omly assigned to prone or supine position during the first three hours , and positions were reversed during the second three hours . Outcome measures and results : Fast Fourier transforms of electroencephalograms ( EEGs ) were performed each minute and the total EEG power ( TP ) , spectral edge frequency ( SEF ) , absolute ( AP ) and relative ( RP ) powers in five frequency b and s ( 0.01–1.0 Hz , 1–4 Hz , 4–8 Hz , 8–12 Hz , 12–24 Hz ) were computed . Mean values for TP , SEF , AP , and RP in the five frequency b and s in the prone and supine positions during AS and QS were then compared . In the prone sleeping position , during AS , infants showed significantly lower TP , decreased AP in frequency b and s 0.01–1.0 Hz , 4–8 Hz , 8–12 Hz , 12–24 Hz , increased RP in 1–4 Hz , and a decrease in SEF . Similar trends were observed during QS , although they did not reach statistical significance . Conclusions : The prone sleeping position promotes a shift in EEG activity towards slower frequencies . These changes in electrocortical activity may be related to mechanisms associated with decreased arousal in the prone position and , in turn , increased risk of sudden infant death syndrome OBJECTIVE Prone sleeping position has a strong link to sudden infant death syndrome ( SIDS ) , and the " Back to Sleep " campaign has played an important role in reducing SIDS . We tested the hypothesis that the mechanism of the sleep position effect is based on changes in sleep , arousal , heart rate variability ( HRV ) , and the QT interval of the electrocardiogram . STUDY DESIGN We studied 16 premature infants longitudinally , at 1 and 3 months ' corrected age . Videosomnography recordings were made during the infants ' normal daytime naps . Each infant was recorded in both supine and prone positions . The recordings were analyzed in 30-second epochs , which were classified as awake , active sleep ( AS ) , quiet sleep ( QS ) , or indeterminate sleep . Electrocardiogram data were sample d with an accuracy of 1 millisecond . Time domain analysis of HRV was measured by st and ard deviation of all R-R intervals and by the square root of the mean of the sum of the squares of the differences between adjacent R-R intervals . Frequency domain analysis was done for low frequency ( 0.04 - 0.14 Hz ) and high frequency ( 0.15 - 0.5 Hz ) HRV . We measured QT , JT , and R-R intervals during AS and QS for each position . RESULTS We found no significant differences between supine and prone position , either in total sleep time or in percentage of QS . Percentage of AS was significantly lower in the supine position , but only at 1 month corrected age . The incidence of short , spontaneous , sleep transitions was significantly higher in supine , also only at 1 month corrected age . Time domain analysis of HRV showed a significantly lower variability in prone , but only during QS . Frequency domain analysis of HRV showed no differences between the 2 sleeping positions . Both QT and JT intervals were significantly longer in prone during QS , but only at 1 month corrected age . CONCLUSIONS Despite the commonly held belief , prone position did not substantially increase total sleep at these ages . On the other h and , prone sleeping decreased the number of sleep transitions at 1 month corrected age , increased QT and JT intervals , and reduced HRV , thereby potentially increasing the vulnerability for SIDS . This study supports " Back to Sleep " as the position of choice not only for term but also for preterm infants after discharge home |
691 | 20,146,579 | Ixabepilone plus capecitabine has prolonged the median time to progression , increased overall survival and significantly increased response rates compared with capecitabine alone .
Adverse events observed with the combination arm were generally manageable and well tolerated with neutropenia and febrile neutropenia , and peripheral neuropathy , myalgia , diarrhea , stomatitis and h and -foot syndrome were easily controlled .
Ixabepilone plus capecitabine demonstrated clinical activity with an acceptable safety profile , which seems to be a valid option for patients with anthracycline-pretreated/resistant and taxane-resistant metastatic breast cancer | AIM We conducted a systematic review to estimate efficacy and safety of ixabepilone plus capecitabine compared with capecitabine alone for patients of anthracycline- and /or taxane-resistant metastatic breast cancer . | PURPOSE To evaluate the efficacy and safety of ixabepilone in patients with metastatic breast cancer ( MBC ) resistant to anthracycline , taxane , and capecitabine , in this multicenter , phase II study . PATIENTS AND METHODS Patients with measurable disease who had tumor progression while receiving prior anthracycline , taxane , and capecitabine were enrolled . Ixabepilone 40 mg/m(2 ) monotherapy was administered as a 3-hour intravenous infusion on day 1 of a 21-day cycle . The primary end point was objective response rate ( ORR ) , assessed by an independent radiology facility ( IRF ) . RESULTS A total of 126 patients were treated and 113 were assessable for response . Patients were heavily pretreated : 88 % had received at least two lines of prior chemotherapy in the metastatic setting . IRF-assessed ORR was 11.5 % ( 95 % CI , 6.3 % to 18.9 % ) for response-assessable patients . Investigator-assessed ORR for all treated patients was 18.3 % ( 95 % CI , 11.9 % to 26.1 % ) . Fifty percent of patients achieved stable disease ( SD ) ; 14.3 % achieved SD > or= 6 months . Median duration of response and progression-free survival were 5.7 and 3.1 months , respectively . Median overall survival was 8.6 months . Patients received a median of 4.0 treatment cycles ( range , one to 16 cycles ) , and 25 % of patients received > or= eight cycles . Grade 3/4 treatment-related events included peripheral sensory neuropathy ( 14 % ) , fatigue/asthenia ( 13 % ) , myalgia ( 8 % ) , and stomatitis/mucositis ( 6 % ) . Resolution of grade 3/4 peripheral sensory neuropathy occurred after a median period of 5.4 weeks . CONCLUSION Ixabepilone demonstrated clear activity and a manageable safety profile in patients with MBC resistant to anthracycline , taxane , and capecitabine . Responses were durable and notable in patients who had not previously responded to multiple prior therapies |
692 | 10,832,181 | CONCLUSIONS Positive short-term changes in health-protective awareness , knowledge and self-reported behaviour appear to be associated with relatively intensive interventions that use multiple methods and setting s , and /or are delivered over multiple sessions | PURPOSE To evaluate and summarize evidence on the effectiveness of interventions available to public health staff regarding the protection of the public from environmental risks . | OBJECTIVE We evaluated the impact of an intervention promoting sun protection behavior among children 2 to 11 years of age through schools and day care centers , primary care practice s , and recreation areas . METHODS Ten towns in New Hampshire were paired , then assigned r and omly to intervention or control status . The multicomponent SunSafe intervention was provided to children and caregivers through primary care practice s , day care centers , schools , and beach recreation areas . Training support and material s were provided by the SunSafe project , but project staff had no direct contact with children or parents in providing the intervention . All intervention components promoted the same message : avoid the sun between 11 AM and 3 PM , cover up using hats and protective clothing , use sun block with a sun protection factor > /=15 , and encourage sun protection among family and friends . The impact of the intervention was determined by observing children 's sun protection behavior at the beach during baseline compared with 1 year later . The primary outcomes of interest were changes in the proportion of children per town using at least some sun protection and changes in the proportion of children fully protected . Children were clustered by town , with the town thus being the unit of analysis . The primary care practice component included one practice meeting for clinicians and staff at which project staff presented background on skin cancer and how to promote its prevention ; a sun protection office system manual based on our previous work , which provided specific direction on how to share responsibility among office staff and clinicians in carrying out routines that promote sun protection ; and educational posters , pamphlets , and self-adhesive reminder notes design ed to enhance sun protection counseling . SunSafe removable tattoos and stickers were offered to children at well-child and illness visits during the summer months . Schools each received three project staff visits : a brief visit with the principal to describe the intervention and to answer questions ; an in-service program to educate teachers about skin cancer and to introduce curricular material s ; and help with one parent outreach program . Larger day care centers each received one project staff visit . An additional six smaller day care centers received curricular material s through the mail but no visits . Two similar sets of curricular material s were used , one for grade schools and the other for preschools and day care centers . Both emphasized the importance of sun protection rather than the danger of skin cancer . Material s emphasized dynamic activities modeled after the " Slip , Slop , Slap " and " SunSmart " programs and included new material developed to suit regional needs . Both manuals offered structured plans but also provided a variety of activities from which teachers could choose . Teachers agreed to devote a minimum of two class periods to these material s. For recreation areas , lifeguards in each of the intervention communities attended an in-service meeting , during which background about skin cancer prevention was presented by project staff . The project also provided displays about the ultraviolet ( UV ) light index and about sun protection to be posted at each beach . Subsequently , project staff called beach staff in each community each morning with the predicted UV index for the day to post on the display . Educational pamphlets about the UV index and free sun-block sample s were available to beachgoers through the lifeguards . One brief follow-up visit by project staff was made to each beach area to provide reinforcement . RESULTS We observed 1930 children . Use of some sunscreen on at least one body area increased in all 5 intervention towns compared with paired control towns . In intervention towns , this mean proportion increased from 0.56 of those observed at baseline to 0.76 of those observed postintervention , with a minimal increase among control town children . ( ABSTRACT Childhood and adolescence are critical periods in the etiology of subsequent melanoma and nonmelanocytic skin cancers . The aims of the study were ( a ) to develop a valid measure of solar protection in 9 to 11-year-old school students , ( b ) to evaluate the differential effectiveness of two interventions aim ed at changing solar protection in this age group , and ( c ) to identify the predictors of use of a high level of solar protection . A Solar Protection Behavior Diary was developed and vali date d during a pilot , after which 11 schools were r and omly allocated to one of three groups : intensive intervention ( 247 students ) , st and ard intervention ( 180 students ) , or control ( 185 students ) , with students in years 5 and 6 participating in the study . Students completed the vali date d diary ( for 5 days ) and a knowledge and attitudes question naire at pretest and at two posttest periods ( 4 weeks and 8 months after pretest ) . Results indicated that students in the intensive intervention group were significantly more likely to have used a high level of protection at both posttest periods compared to the control and st and ard intervention groups . There was no difference in the protection level of the control and st and ard intervention groups at either posttest , indicating that this minimal intervention was not effective in changing the solar protection behavior of the students . Students with a high level of solar protection at pretest were also significantly more likely to have a high level of protection at both posttest periods , and those with a greater number of opportunities to protect were less likely to protect at the second posttest The effects of supplementary computer instruction in house dust mite-avoidance measures on adherence to implementing measures , on home dust mite-allergen levels , and on symptomatology were investigated in 52 adult patients with mite-associated asthma . Twenty-six patients received conventional instruction ( counseling and written instruction ) and the other 26 patients received conventional plus 22 minutes of interactive computer-assisted instruction . Instructions were aim ed at mite-avoidance measures . Pre- and postinstruction dust sample s were collected , and adherence was monitored . All patients kept symptom diaries twice a day . Patients ' progress was followed for 12 weeks , and all patients completed the study . Adherence , number of observed and self-reported mite-avoidance measures implemented after visit , was higher for the computer group ( p = 0.023 ) . The computer-instructed group achieved significantly lower levels of mite allergen in bedroom carpets ( p = 0.004 ) with mean levels of mite allergen declining from 6.5 + /- 7.6 to 2.2 + /- 4.3 micrograms/gm of dust ( two-site monoclonal antibody assays ) , whereas levels for the conventional-instructed group did not change . Moreover , by study weeks 9 and 10 , the computer-instructed group was significantly less symptomatic ( p = 0.033 ) . Mean symptom scores for this group decreased from 12.4 to 7.7 , compared with 16.4 to 14.3 . Conventional instruction supplemented with computer instruction is suggested in mite education College and high-school students were administered a question naire to assess their knowledge about skin cancer , and afterward an educational program was design ed to correct the identified deficiencies . Results showed that the students were relatively uninformed about how to recognize and prevent skin cancer — high-school students more so than college students — but that their knowledge of the disease ( e.g. , risk factors , preventive measures , and identification of “ warning signs ” for early detection ) increased significantly after training . Some forgetting was noted at a 2-week follow-up but knowledge levels were still significantly higher than baseline . If these findings are representative of the general population , more preventive education will be needed in this area . This is especially true because the potentially deadly melanoma appears to be increasing at an alarming rate Excessive exposure to the sun 's ultraviolet radiation ( UVR ) contributes to the etiology of melanoma and nonmelanoma skin cancers . Many behaviors that increase lifetime risk of skin cancer -- sun exposure , sunburn , and lack of sun protection -- occur early in childhood . A 1-day school-based skin cancer prevention effort -- Sun Smart Day -- was implemented and evaluated in three elementary schools to improve fourth- grade rs ' knowledge , attitudes , and behaviors related to skin cancer prevention . A classroom-based skin cancer prevention lesson was compared to an interactive sun safety fair was vehicles for promoting comprehensive photoprotection . Sun Smart Day interventions had their greatest impact on fourth- grade rs ' awareness and knowledge of skin cancer and children 's increased knowledge persisted through the summer break . While both the classroom curriculum and the health fair boosted awareness and knowledge of sun safety among fourth grade rs , the classroom curriculum demonstrated a slight immediate advantage over the health fair on these outcomes . Also the curriculum was less difficult to implement , but the health fair was more engaging . A Sun Smart Day program may be an important first step in increasing public awareness and underst and ing of skin cancer and its prevention Children with asthma who are exposed to environmental tobacco smoke are at increased risk for adverse health consequences . An experimental design was used to evaluate a minimal-contact intervention aim ed at modifying parents ' smoking behavior in their homes . All subjects received counseling on the health effects of passive smoking and advice to quit smoking inside the home . Treatment subjects were also mailed the results of a urine cotinine test on their child and a self-help manual . More treatment ( 35 % ) than control ( 17 % ) subjects reported smoking outside their homes at posttest ( and their children 's cotinine levels were lower ) , but this difference was not statistically significant STUDY OBJECTIVE To examine the long-term maintenance of a previously reported behavioral counseling intervention to reduce asthmatic children 's exposure to environmental tobacco smoke ( ETS ) . PARTICIPANTS Families of asthmatic children ( 6 to 17 years ) , including at least one parent who smoked in the home , recruited from four pediatric allergy clinics . DESIGN Participants were r and omized to one of three groups : behavioral counseling to reduce ETS exposure , self-monitoring control , and usual medical care control . Counseling concluded at month 6 , and the original trial ended at month 12 . Two follow-up interviews occurred at months 20 and 30 . MEASUREMENTS AND RESULTS The originally reported analysis of baseline to 12 months was reanalyzed with a more robust restricted maximum likelihood procedure . The 2-year follow-up period was analyzed similarly . Significantly greater change occurred in the counseling group than the control groups and was sustained throughout the 2 years of follow-up . Further exploratory analyses suggested that printed counseling material s given to all participants at month 12 ( conclusion of the original study ) were associated with decreased exposure in the control groups . CONCLUSION Such long-term maintenance of behavior change is highly unusual in the general behavioral science literature , let alone for addictive behaviors . We conclude that ETS exposure can be reduced and that a clinician-delivered treatment may provide substantial benefit BACKGROUND Project SUNWISE evaluated the effectiveness of a multicomponent intervention in reducing children 's ultraviolet radiation ( UVR ) exposure . METHODS Across four YMCAs , 48 aquatics classes ( N = 169 children , mean age = 7 ) were r and omly assigned to either the intervention or the control condition . The 6-week intervention included a UVR reduction curriculum presented at poolside by aquatics instructors and home-based activities for children and their parents . Outcome measures were ( a ) tanness-associated skin color dimensions assessed with a colorimeter , ( b ) specific daily solar protection behaviors of children as reported by parents , and ( c ) general solar protection behaviors . RESULTS Controlling for intraclass clustering in all analyses , at posttest , no statistically significant between-group differences were found in tanness , daily solar protection scores , or general sunscreen use . The intervention group showed significantly greater general hat use relative to controls . CONCLUSIONS The intervention failed to impact most of the outcome measures . Supplementing the behavior-focused intervention package with environmental supports may be warranted OBJECTIVES This feasibility study examined whether a sun safety curriculum design ed for and administered to preschoolers affects their cognition ( knowledge , comprehension , application ) regarding sun safety . METHODS Twelve classes of 4- to 5-year-olds were recruited from local preschools and r and omly assigned to an intervention group or a control group . The intervention group received an investigator-developed sun safety curriculum ; the control group did not . Children in both groups were tested at the beginning of the study about their cognition related to sun safety . They then received posttests 2 and 7 weeks following the pretest . RESULTS The curriculum had a significant effect on the knowledge ( P = .01 ) and comprehension ( P = .006 ) components of cognition . The application component of cognition was not significantly changed by the curriculum . CONCLUSIONS A structured curriculum was found to be an efficacious means of enhancing knowledge and comprehension of sun safety in preschool children . At the preoperational developmental stage , however , children may not be able to apply such knowledge and comprehension |
693 | 19,672,167 | Gender was not found to be a consistent predictor as traditionally believed .
Early identification of the predictors in patients at risk of postoperative pain will allow more effective intervention and better management . | Pain is a subjective and multidimensional experience that is often inadequately managed in clinical practice .
Effective control of postoperative pain is important after anesthesia and surgery .
A systematic review was conducted to identify the independent predictive factors for postoperative pain and analgesic consumption . | Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items Background : Sex-related differences in the perception of pain and susceptibility to opioids remain a matter of debate . Intravenous morphine titration used to obtain pain relief in the immediate postoperative period is a unique clinical model for assessing the effect of sex on reported pain . Because of the wide variation in dose requirements for pain management , the authors conducted a prospect i ve study in a large population and also assessed the effect of aging . Methods : Intravenous morphine titration was administered as a bolus of 2 ( body weight ≪ 60 kg ) or 3 mg ( body weight > 60 kg ) during the immediate postoperative period . The interval between each bolus was 5 min . The visual analog pain scale ( VAS ) threshold required to administer morphine was 30 , and pain relief was defined as a VAS score of 30 or less . Data are expressed as mean ± SD . Results : Data from 4,317 patients were analyzed ; 54 % of the patients were male , and 46 % were female . The mean morphine dose required to obtain pain relief was 11.9 ± 6.8 mg or 0.173 ± 0.103 mg/kg . Women had a higher initial VAS score ( 74 ± 19 vs. 71 ± 19 ; P < 0.001 ) and required a greater dose of morphine ( 0.183 ± 0.111 vs. 0.165 ± 0.095 mg/kg ; P < 0.001 ) . In contrast , no significant difference was noted in elderly ( aged > 75 yr ) patients ( 0.163 ± 0.083 vs. 0.157 ± 0.085 mg/kg ) . Conclusion : Women experienced more severe postoperative pain and required a greater dose ( + 11 % ) of morphine than men in the immediate postoperative period . This sex-related difference disappeared in elderly patients BACKGROUND : IV morphine titration ( IMT ) is widely used in the postanesthesia care unit to achieve pain relief . Numerous factors contribute to variability in postoperative pain or morphine consumption . We analyzed prospect ively the pre- and intraoperative predictive factors of severe postoperative pain defined as a dose of IMT > 0.15 mg/kg or a failure of IMT . METHODS : We assessed the role of preoperative information about pain , medical treatments , and intraoperative events and their role on postoperative pain . After IMT , patients were divided into two groups : severe pain ( SP ) and nonsevere pain . Data are expressed as mean ± sd . RESULTS : Three hundred forty-two patients were included in the study : 200 ( 58 % ) in the nonsevere pain group and 142 ( 42 % ) in the SP group . Using a univariate analysis , there was no significant difference between groups related to medical or surgical history except for more frequent preoperative treatments in the SP group ( P < 0.05 ) . Duration of the surgical procedure and anesthesia were longer in the SP group ( P < 0.001 ) . The dose of sufentanil and visual analog scale scores before and at the end of IMT were higher in the SP group ( P < 0.001 ) . Using a multivariate analysis , a high dose of intraoperative opioid ( sufentanil dose > 0.6 μg/kg ) ( Odds ratio = 2.68 , P < 0.001 ) , a general anesthetic procedure ( Odd ratio = 3.96 , P = 0.03 ) , and the use of preoperative analgesic drugs ( Odds ratio = 1.91 , P < 0.01 ) were independent factors associated with severe postoperative pain . CONCLUSION : A higher intraoperative dose of sufentanil , general anesthesia , and preoperative treatment with analgesics were significantly associated with severe postoperative pain We have evaluated the level of state and trait anxiety , neuroticism , extroversion and coping style as predictors of the effectiveness of patient-controlled analgesia ( PCA ) in 110 patients undergoing total abdominal hysterectomy . After operation patients were allocated to receive pain control with either PCA or i.m . injections ( IMI ) . Pain was assessed using the short form McGill pain question naire at 6 , 18 and 24 h after operation , and by recording the amount of analgesic consumed in the first 24 h after surgery . Both state anxiety and coping style were significant predictors of postoperative pain , irrespective of the method of analgesia used . Patients using PCA experienced significantly better pain control than those receiving IMI . However , it was those with high levels of state anxiety who experienced the greatest reduction in pain with PCA . In addition to achieving better pain control , patients who received PCA used significantly less analgesia and were discharged earlier than patients who received IMI Postoperative pain is a common reason for the delayed discharge and unanticipated hospital admission of out patients .In this study , we examined the pattern of pain in ambulatory surgical patients and determined those factors that predict postoperative pain . Ten thous and eight consecutive ambulatory surgical patients were prospect ively studied . Preoperative patient characteristics , intraoperative variables , and pain in the postanesthesia care unit ( PACU ) and the ambulatory surgical unit ( ASU ) and 24 h postoperatively were documented . The incidence of severe pain was 5.3 % in the PACU , 1.7 % in the ASU , and 5.3 % 24 h postoperatively . In the PACU , younger male adults ( 36 + /- 13 vs 47 + /- 22 yr ) , ASA physical status I patients , and patients with a higher body mass index ( 26 + /- 5 vs 25 + /- 5 kg ) had a higher incidence of severe pain . In the group with severe pain , the duration of anesthesia , the duration of stay in the PACU and the ASU , and the time to discharge was longer than in the group without severe pain . In the PACU , orthopedic patients had the highest incidence of pain ( 16.1 % ) , followed by urologic ( 13.4 % ) , general surgery ( 11.5 % ) , and plastic surgery ( 10.0 % ) patients . In patients who had general anesthesia , the intraoperative dose of fentanyl was significantly smaller in the group with severe pain than in the group without severe pain when body mass index and duration of anesthesia were taken into consideration . Body mass index , duration of anesthesia , and certain types of surgery were significant predictors of severe pain in the PACU . This knowledge will allow us to identify those patients at risk of severe postoperative pain and manage them prophylactically . Implication s : The pattern of pain was examined in 10,008 consecutive ambulatory surgical patients . The incidence of severe pain was 5.3 % in the postanesthesia care unit , 1.7 % in the ambulatory surgical unit , and 5.3 % 24 h postoperatively . Body mass , duration of anesthesia , and certain types of surgery were significant predictors of pain in the postanesthesia care unit . These data will allow us to better predict those patients who need intense prophylactic analgesic therapy . ( Anesth Analg 1997;85:808 - 16 The immunomodulatory effects of acute laboratory stressors were examined by comparing active and passive stressors in a between-subjecls design . Healthy male volunteers ( N = 67 ) were recruited and r and omly assigned to an active . passive , or no stressor condition . Subjects were exposed to either the Stroop and mental arithmetic tasks ( active ) , two surgery films ( passive ) , or two nature films ( no stress ) . Cardiovascular reactivity , plasma catecholamines and Cortisol . and self-reported distress were measured pretask and posttask . Lymphocyte proliferation to concanavalin A ( Con A ) , pokeweed mitogen ( PWM ) , and phytohemagglutinin was assessed at baseline , after the first task , after the second task , and 30 min later . Lymphocyte proliferation to Con A and PWM was significantly reduced in response to the stressors . Different response patterns emerged , depending on the type of stressor and the mitogen used . Changes in lymphocyte proliferation were significantly associated with cardiovascular reactivity during the tasks . Results are discussed in terms of potency of the stressors and mechanisms underlying passive versus active laboratory tasks . Implication s for future research are addressed Forty-one DSM-III-R hypochondriacs and seventy-five r and omly chosen patients were obtained from a medical outpatient clinic , and completed a psychiatric diagnostic interview and a ten-item self-report question naire , the Somatosensory Amplification Scale ( SSAS ) ; The SSAS asks the respondent how much s/he is bothered by various uncomfortable visceral and somatic sensations , most of which are not the pathological symptoms of serious diseases . SSAS scores were normally distributed , and had acceptable test-retest reliability and internal consistency . They were not related to sociodemographic characteristics , or to aggregate medical morbidity . Amplification was significantly higher in the DSM-III-R hypochondriacs than in the comparison sample , and was significantly correlated with the degree of hypochondriacal symptomatology within each sample . In the comparison sample , it was also significantly associated with depressive and anxiety disorders , but not with antisocial personality or substance abuse . The association between the amplification scale and DSM-III-R hypochondriasis remained highly significant after controlling for these concurrent psychiatric disorders OBJECTIVE Long-term pain is a common sequela of thoracotomy , occurring in approximately 50 % of patients 2 years after thoracic surgery . Despite this alarming statistic , little is known about the factors responsible for the transition of acute to chronic pain . The aim of the present study is to identify predictors of long-term post-thoracotomy pain . DESIGN Follow-up was for 1.5 years for patients who had participated in a prospect i ve , r and omized , controlled trial of preemptive , multimodal analgesia . SETTING Subjects were recruited from a tertiary care center . PATIENTS Thirty patients who had undergone lateral thoracotomy were followed up by telephone , administered a structured interview , and classified according to long-term pain status . MAIN OUTCOME MEASURES Present pain status was measured by a verbal rating scale ( VAS ) . Measures obtained within the first 48 h after surgery were compared between patients with and without pain 1.5 years later . These include VAS pain scores at rest and after movement , McGill Pain Question naire data , patient-controlled morphine consumption ( mg ) , and pain thresholds to pressure applied to a rib contralateral to the thoracotomy incision . RESULTS Fifty-two percent of patients reported long-term pain . Early postoperative pain was the only factor that significantly predicted long-term pain . Pain intensity 24 h after surgery , at rest , and after movement was significantly greater among patients who developed long-term pain compared with pain-free patients . A significant predictive relationship was also found at 24 and 48 h using the McGill Pain Question naire . Cumulative morphine was comparable for the two groups . Pain thresholds to pressure applied to a rib contralateral to the incision did not differ significantly between the groups . CONCLUSION Aggressive management of early postoperative pain may reduce the likelihood of long-term post-thoracotomy pain Sex differences in pain perception and in response to opioids have been described , but the findings are inconsistent . We sought to determine the effect of sex on pain perception , morphine consumption , and morphine analgesia after surgery . We design ed a prospect i ve cohort study and included 423 women and 277 men who emerged from general anesthesia after surgical procedures and who reported pain intensity of ≥5 on the 0–10 numeric rating scale ( NRS ) . We administered 2.5 mg of morphine IV every 10 min until the pain intensity was ≤4 of 10 . Every 10 min , patients rated their pain on the NRS and indicated the degree of pain relief on a 5-point Likert scale . After adjustment for type of operation and age , we found that women had more intense pain and had larger morphine consumption than men . The difference in NRS pain intensity was 0.4 U ( 95 % confidence interval , 0.1–0.6 U ) . Women required 0.03 mg/kg more morphine than men ( 95 % confidence interval , 0.02–0.04 mg/kg ) . We conclude that women have more intense pain and require 30 % more morphine to achieve a similar degree of analgesia compared with men . Clinicians should anticipate the differences in opioid requirement to avoid undertreatment of pain in women It is common clinical experience that anxiety about pain can exacerbate the pain sensation . Using event-related functional magnetic resonance imaging ( FMRI ) , we compared activation responses to noxious thermal stimulation while perceived pain intensity was manipulated by changes in either physical intensity or induced anxiety . One visual signal , which reliably predicted noxious stimulation of moderate intensity , came to evoke low anxiety about the impending pain . Another visual signal was followed by the same , moderate-intensity stimulation on most of the trials , but occasionally by discriminably stronger noxious stimuli , and came to evoke higher anxiety . We found that the entorhinal cortex of the hippocampal formation responded differentially to identical noxious stimuli , dependent on whether the perceived pain intensity was enhanced by pain-relevant anxiety . During this emotional pain modulation , entorhinal responses predicted activity in closely connected , affective ( perigenual cingulate ) , and intensity coding ( mid-insula ) areas . Our finding suggests that accurate preparatory information during medical and dental procedures alleviates pain by disengaging the hippocampus . It supports the proposal that during anxiety , the hippocampal formation amplifies aversive events to prime behavioral responses that are adaptive to the worst possible outcome Although patients with chronic pain are often psychologically distressed , it has been difficult to determine whether this distress is an antecedent of chronic pain or whether it is caused by the experience of living with chronic pain . The aim of this investigation was to develop a method that would allow individuals who are at risk for the development of chronic pain to be studied before their pain has become chronic . Patients with acute herpes zoster were assessed with demographic , medical , pain , and psychosocial measures . Pain was assessed in follow-up interviews at 6 weeks and 3 , 5 , 8 , and 12 months after these initial assessment s. There were no significant differences between patients who developed short-term herpes zoster pain and patients who did not develop short-term pain for any of the measures at the initial assessment , except for one measure of pain intensity . Patients who developed chronic herpes zoster pain , however , had significantly greater pain intensity , higher state and trait anxiety , greater depression , lower life satisfaction , and greater disease conviction at the initial assessment than patients who did not develop chronic pain . In discriminant analyses , disease conviction , pain intensity , and state anxiety each made a unique contribution to discriminating patients who did and who did not develop chronic pain . This study demonstrates the feasibility of investigating psychosocial antecedents of the development of chronic pain by prospect ively examining the longitudinal course of herpes zoster OBJECTIVE The purpose of the study was to investigate anxiety and other factors that may predict pain magnitude following termination of pregnancy ( TOP ) during the first trimester . DESIGN Prospect i ve , nonr and omized study . SETTING Department of Obstetrics and Gynecology , Rambam Medical Center in Haifa , Israel . PATIENTS Forty consecutive women undergoing TOP . OUTCOME MEASURES Women undergoing a TOP were asked to fill out the State-Trait Anxiety Inventory . Pain magnitude was measured by using a visual analog scale ( VAS ) at 15 , 30 , and 60 minutes following the procedure . Correlations between state anxiety , trait anxiety , age , parity , number of TOP , gestational age , and pain magnitude were measured . RESULTS State anxiety was able to predict pain magnitude on VAS 15 minutes after TOP ( P = 0.023 ) , and trait anxiety was able to predict pain magnitude on VAS 30 minutes after TOP ( P = 0.013 ) . Other variables failed to show significant results . CONCLUSIONS Preoperative assessment of anxiety levels may lead to appropriate treatment in order to alleviate discomfort and ensure pain control outcome Objectives : This study was a prospect i ve investigation of the extent to which psychologic variables could be predictive of postoperative pain . Study aims were : 1 ) to evaluate whether an assessment of pre-operative distress factors could predict the intensity of postoperative pain ; and 2 ) to characterize the unique pattern in which anxiety and pain catastrophizing scores relate to postoperative pain . Methods : The Pain Catastrophizing Scale and the State-Trait Anxiety Inventory were administered to 38 patients scheduled for elective abdominal surgery . The question naires were completed on the day of admission , a day before the operation . On day 1 and day 2 following the operation , perception of pain intensity at the surgical wound was assessed by visual analog scale . Results : The Pain Catastrophizing Scale and State-Trait Anxiety Inventory scores were significantly correlated with the postoperative pain scores . A linear regression analysis showed that Pain Catastrophizing Scale predicted the level of postoperative pain intensity even after controlling for state anxiety and that trait anxiety was not a significant predictor . In addition , analysis of the unique pattern of each predictor related to postoperative pain intensity indicated a linear curve for the Pain Catastrophizing Scale and curvilinear curve for the state anxiety . Discussion : The results are discussed in light of appraisal and coping theories . It is suggested that a simple assessment of preoperative catastrophizing tendency and anxiety scores may assist medical teams in postoperative pain management Perioperative myocardial ischaemia is a predictor of postoperative cardiac morbidity ( PCM ) . Epidural anaesthesia and adequate perioperative analgesia have been shown to improve myocardial oxygen dynamics due to interruption of pain and sympathetic pathways . The aim of the present study was to compare the incidence of ischaemia after either general anaesthesia followed by parenteral analgesia with morphine or combined epidural/general anaesthesia followed by analgesia with epidural morphine . In a prospect i ve observer-blinded analysis of the occurrence of ischaemia , 55 patients ( epidural = 29/ parenteral = 26 ) scheduled for elective surgery with defined risks for ischaemic cardiac disease were entered and followed for 24 hr after surgery with two-lead continuous Hotter monitoring . Groups were similar with respect to age , weight , modified Goldman ( Detsky ) risk classification and the use of cardiac medications . Fewer patients receiving the epidural anaesthesia/ analgesia had ischaemic episodes ( 17.2 vs 50.0 % , P = 0.01 ) , and tachyarrhythmias ( 20.7 vs 50.0 % , P < 0.05 ) . Epidural patients had a four-fold reduction of the relative risk for either event ( P < 0.001 ) . All ischaemic events were asymptomatic and unrecognized ( silent ) . All major morbid events ( n = 5 ) ( MI , congestive heart failure and death ) occurred in patients who had perioperative episodes of ischaemia . There were three distinct peaks in onset of ischaemia , at 1–4 hr , 9–12 hr and 22–24 hr postoperatively . One third of postoperative ischaemic events occurred within the first four hours after operation and lasted from 1 to 31 min . Forty-two percent of ischaemic episodes were associated with a heart rate > 100 bpm , or an increase of 20 % over the baseline heart rate . We conclude that epidural anaesthesia/analgesia reduces but does not eliminate the risk of myocardial ischaemia and tachyarrhythmia . We were unable to determine any associated reduction in the risk of PCM.RésuméL’ischémie myocardique périopératoire a une bonne valeur pronostique sur la morbidité cardiaque postopératoire ( MCP ) . II a été démontré que l’anesthésie et l’analgésie post-opératoire épidurales favorisaient l’oxygénation myocardique par interruption des voies de conductions algiques et sympathiques . L’objectif de la présente étude est de comparer l’incidence de l’ischémie après l’anesthésie générale suivie d’analgésie parentérale à la morphine à l’association anesthésie générale-épidurale suivie d’analgésie à la morphine épidurale . Sont inclus dans cette étude prospect i ve , à l’insu de l’observateur , 55 patients ( 29 dans le group épidural , 26 dans le groupe parentéral ) programmés pour une chirurgie réglée et présentant des risques définis de maladie cardiaque ischémique . Les patients sont monitorés continuellement pendant 24 heures après la chirurgie avec un Hotter à deux dérivations . Il n’y a pas de différence entre les deux groupes pour l’âge , le poids , l’échelle de risque de Goldman ( Detsky ) et la médication cardiaque . Moins de patients du groupe anesthésie générale-épidurale souffrent d’épisodes ischémiques ( 17,2 vs 50 % , P = 0,01 ) , et de tachyarythmies ( 20,7 vs 50 % , P < 0,05 ) . Les patients du groupe épidural courent un risque quatre fois moins élevé de souffrir de l’une ou de l’autre complication ( P < 0,001 ) . Tous les épisodes ischémiques ont été asymptomatiques et sont passés inaperçus . Toutes les complications ( n = 5 ) ( infa rct us du myocarde , défaillance cardiaque et décès ) sont survenus chez des patients qui avaient présenté de l’ischémie périopératoire . On a identifié trois pointes d’incidence ischémiques postopératoires : à 1–4 hres , 9–12 hres et 22–24 hres . Un tiers des épisodes ischemiques est survenu en-deçà de quatre heures après l’opération et a duré de 1 à 31 min . Quarante-deux pourcent de ces épisodes étaient associés à une fréquence de plus de cent b · min−1 ou à une augmentation de 20 % du niveau de base . Nous concluons que l’anesthésie / analgésie épidurale diminue mais n’élimine pas le risque d’ischémie cardiaque et de tachyarythmies . Nous n’avons pas démontré une réduction associée de la MCP Summary : An open prospect i ve observational study was performed , aim ing to measure symptom severity following operative gynaecological laparoscopy and explore any associated factors . Women having concomitant procedures were excluded . Each woman had st and ardized analgesia , completed a symptom diary for 7 days postoperation , and had a st and ardized form completed by the surgeon detailing the operation . Back pain , nausea and vaginal pain were found to not be of clinical significance . Cutting major vessels , ligaments , vagina or ovary had major impacts on postoperative symptoms . In the presence of a st and ardized analgesic regimen , symptoms did not resolve for at least 5 days Background Postcesarean section pain is a common cause of acute pain in obstetrics , yet pain relief and patient satisfaction are still inadequate in many cases . The present study was conducted to determine whether preoperative assessment of experimental pain perception by quantitative sensory tests could predict the level of postcesarean section pain . Methods Fifty-eight women who were scheduled for elective cesarean section were enrolled in the study . Heat pain threshold and magnitude estimation of suprathreshold pain stimuli at 44 ° –48 ° C were assessed for both algosity ( the sensory dimension of pain intensity ) and unpleasantness 1 or 2 days before surgery . The day after the operation , the women reported the level of pain at the surgical wound on a visual analog scale at rest and during activity . Regression analysis was performed to evaluate the usefulness of preoperative scores in predicting postcesarean section pain . Results Postoperative visual analog scale scores at rest and during activity significantly correlated with preoperative suprathreshold pain scores at 44 ° –48 ° C ( r = 0.31–0.58 for algosity and r = 0.33–0.74 for unpleasantness ) . The stimulus of 48 ° C was found to be the best predictor of postoperative pain for both conditions ( r = 0.434–0.527;P < 0.01 ) . In contrast to suprathreshold pain stimuli , pain threshold was not correlated with postoperative pain . Conclusions The results show that a simple and quick preoperative test is useful in identifying those women who will experience greater pain after a cesarean section . This test may be suggested for caregivers to tailor the postoperative treatment to specific patient needs and to improve postoperative outcome and patient satisfaction & NA ; A prospect i ve observational study of cohorts of patients undergoing hip replacement ( 30 ) , knee replacement ( 31 ) , and spinal nerve root decompressive surgery ( 30 ) were interviewed pre‐operatively to identify factors which might correlate with and potentially predict severe post‐operative pain and dissatisfaction with analgesic management . The hip patients comprised 33 % females and averaged 64 years , while the knee patients were 45 % female and older ( mean 71 years ) and the spinal patients were 43 % female and averaged 50 years . The three groups were similar with respect to all other pre‐operative variables . Pain intensity was assessed mainly by self‐report using the Present Pain Intensity ( PPI ) and Visual Analogue Scales ( VAS ) of the McGill Pain Question naire . The PPI was preferred by patients and nurses and , as there were no analytical advantages for the VAS , the PPI data are presented . The average post‐operative pain during routine management mainly with patient controlled intravenous opiate , was mild to moderate and declined over days 1–5 , declined further at discharge but rose slightly 1 month after discharge . The hip replacement patients experienced significantly ( P<0.01 ) less pain overall than the patients in the other two groups . Nurses ’ assessment s of pain severity from observed behaviour were low and agreed poorly with the patients ’ self reports . Assessed on Likert Scales ( 0–6 ) , the patients generally indicated good or excellent pain control , better than expected pain experience , and high levels of satisfaction with analgesic management . Significant ( P≤0.01 ) multivariate correlates of severe post‐operative pain assessed by logistic regression analysis of 11 variables were female gender , high pre‐operative pain severity , and younger age . Significant ( P≤0.01 ) multivariate correlates of both worse than expected pain experience and low satisfaction were female gender , high pre‐operative pain severity , high anxiety about risks and problems , low expected pain severity , age ( younger ) and high willingness to report pain . These variables may reasonably be tested in further studies as potential predictors of adverse post‐operative pain experience Purpose To test the hypothesis that the type of surgical procedure influences the incidence of postoperative symptoms . Also the effect of demographic and clinical risk variables : age , sex , ASA status , duration of anaesthesia on the postoperative symptoms were evaluated for each type of surgery . Methods Demographic , medical , anaesthetic and surgical data on 1,017 patients were prospect ively collected by a research assistant who telephoned each patient 24 hr after discharge to administer a question naire to determine postoperative symptoms . Postoperative symptoms included incisional pain , nausea/vomiting , drowsiness , dizziness , headache and fever . In addition , 270 patients were asked the % ( 0–100 ) of their return to daily living function at 24 hr . Results Incisionat pain ( 26.9 % ) , headache ( 11.6 % ) , and drowsiness ( 11.5 % ) were the most frequently reported symptoms . Dizziness was reported by 9.7 % and nausea/vomiting by 7.1 % . Approximately 50 % of patients undergoing laparoscopy , orthopaedic and general surgery reported 24-hr postoperative incisionat pain . The incidence of 24-hr postoperative nausea/vomiting was highest after general 17.4 % , orthopaedic , 11.2 % , and laparoscopic surgery , 9.4 % . Drowsiness was highest after laparoscopy 36.1 % , followed by general surgery , 21.4 % . Dizziness was most frequent after laparoscopy , 24.1 % , followed by general surgery , 16.1 % . After laparoscopy , postoperative drowsiness or dizziness was related to anaesthesia duration . After general surgery , postoperative dizziness or drowsiness were related to age ; the younger the patient , the more likely the symptoms . Conclusions Postoperative pain , nausea/vomiting , drowsiness , dizziness , and headache were the more frequent postoperative symptoms 24 hr after ambulatory surgery and they were influenced by the type of surgical procedure . In addition , the type of surgery and the 24-hr postoperative symptoms determined the degree of return to daily living function . RésuméObjectifVérifier l’hypothèse selon laquelle le type d’intervention influence la symptomatologie postopératoire . De plus , l’influence sur les symptômes postopératoires des facteurs de risque démographiques et cliniques comme l’âge , le sexe , la classe ASA , la durée de l’anesthésie a été évaluée en tenant compte du type de chirurgie . MéthodesUn assistant de recherche a recueilli propectivement les données démographiques , médicales , anesthésiques et chirurgicales de 1 017 opérés qui ont été contactés par téléphone 24 h après leur congé de l’hôpital pour connaître leurs symptômes postopératoires . Ces symptômes comprenaient la douleur au site de l’incision , les nausées et vomissements , la somnolence , les étourdissements , la céphalée et la fièvre . En outre , on a dem and é à 270 patients d’estimer en pourcentage ( 0–100 % ) la reprise de leurs activités quotidiennes usuelles après 24 h . RésultatsLa douleur de l’incision ( 26,90 % ) , la céphalée ( 11,6 % ) et la somnolence ( 11.5 % ) représentaient les symptômes les plus fréquents . Les patients se sont aussi plaints d’étourdissements ( 9,7 % ) et de nausées et vomissements ( 7,1 % ) . Environ 50 % des patients soumis à une laparoscopie , à des interventions orthopédiques et chirurgicales générales ont rapporté une douleur au site de l’incision à la 24 ’ heure . À la suite d’une chirurgie générale , l’incidence après 24 h de nausées et vomissements était plus élevée ( 17,4 % ) qu’après une chirurgie orthopédique ( 11,2 % ) ou laparoscopique ( 9,4 % ) . L’incidence de la somnolence était la plus élevée après une laparoscopie ( 26,1 % ) ; suivait la chirurgie générale ( 21,4 % ) . Les étourdissements étaient les plus fréquents après la laparoscopie ( 24,1 % ) ; suivait la chirurgie générale ( 16,1 % ) . Après une laparoscopie , la somnolence et les étourdissements étaient proportionnels à la durée de l’anesthésie . Après une chirurgie générale , la somnolence et tes étourdissements postopératoires dépendaient de l’âge , la susceptibilité étant plus gr and e chez le patient jeune . Conclusion La douleur postopératoire , les nausées , les vomissements , la somnolence , les étourdissements et la céphalée constituaient les symptômes postopératoires les plus fréquents 24 h après une chirurgie ambulatoire . Ces symptômes étaient influencés par le type d’intervention . En outre , le type d’intervention et les symptômes déterminaient 24 h après l’intervention le degré de retour à la vie quotidienne fonctionnelle 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 Background : The present study examined the relationship between psychological variables , including anxiety , depression , and patient‐controlled analgesia ( PCA ) use in patients who underwent radical mastectomy UNLABELLED This prospect i ve study assessed the relation between pain catastrophizing , response to experimental pain stimuli , and pain perceived by women after elective cesarean sections . Forty-seven women who were scheduled for elective cesarean section were enrolled in the study . Magnitude estimation to suprathreshold phasic and tonic heat pain stimuli was assessed 1 or 2 days before surgery . Women completed the Pain Catastrophizing Scale after the heat stimuli and again on the first postoperative day . During the first and second postoperative days , perception of pain intensity was assessed by visual analog scale at each analgesia request . A multiple regression analysis revealed that pain on the first postoperative day was predicted by patient response to preoperative tonic heat stimuli ( r(2 ) = .167 , P = .008 ) . Pain on the second postoperative day was predicted by preoperative pain catastrophizing ( r(2 ) = .139 , P = .021 ) . No significant association was observed between preoperative response to heat stimuli or pain catastrophizing and the patient 's analgesic consumption in the obstetrical ward . It is concluded that pain catastrophizing and response to experimental tonic heat pain correlate with post-cesarean section pain . PERSPECTIVE This article presents psychological and psychophysical measures that may be of help in the prediction of post-cesarean section pain . It may therefore contribute to the treatment of the sequelae of the most common major surgical procedure performed in women in their reproductive years OBJECTIVES The aim of the present study was to predict postoperative pain and morphine consumption based on preoperative psychosocial factors . METHODS One hundred and twenty-two women completed measures of distress and coping 1 week before major abdominal gynecological surgery by laparotomy . Forty-eight hours after surgery , measures of pain and negative affect ( NA ) were completed , and morphine consumption was recorded from a patient-controlled analgesia pump . Four weeks after surgery , measures of pain and NA were completed . RESULTS Multivariate analyses revealed that preoperative self-distraction coping ( P=.039 ) positively predicted postoperative pain levels in the hospital , after accounting for the effects of age , concurrent NA , and morphine consumption . Emotional support ( P=.031 ) and religious-based coping ( P=.036 ) positively predicted morphine consumption in the hospital , after accounting for the effects of age , concurrent NA , and pain levels . Preoperative distress ( P<.04 to .008 ) and behavioral disengagement ( P=.034 ) , emotional support ( P=.049 ) , and religious-based coping ( P=.001 ) positively predicted pain levels 4 weeks after surgery , after accounting for the effects of age and concurrent NA . CONCLUSION The results suggest that preoperative psychosocial factors are associated with postoperative pain and morphine consumption The aim of this study was to investigate the respective influence of genetic and nongenetic factors on morphine dose requirements and adverse effects after colorectal surgery Of the various types of pain problems , post-operative pain should be the least complex to manage because its source is usually distinct and its course is self-limiting ( Keeri-Szanto , 1979 ) . Nonetheless , there is widespread evidence that the management of pain in surgical patients is regularly and systematic ally inadequate ( Angell , 1982 ; Cartwright , 1985 ; Marks & Sachar , 1973 ; Smith & Utting , 1976 ) . Concern about this apparent failure in pain management has produced a substantial body of literature that addresses factors influencing the degree of pain reported , the analgesia required and the amount of analgesia administered post-operatively . A variety of demographic , clinical and treatment variables have been shown to be associated with the administration of post-operative analgesia . However , there are discrepancies in the results of the studies , and there is no indication as to the importance of these diverse variables in explaining the use of analgesics post-operatively . The purpose of this prospect i ve study was to weigh simultaneously the importance of selected patient characteristics , intra-operative procedures and the post-operative analgesic management regimen as factors that may combine to explain the frequency of administered analgesic doses . More specifically , the purpose of the study was to quantify the contribution of these selected variables to the use of analgesics in adult surgical patients in the first 48 hours post operation Abstract Although more severe acute postoperative pain increases the risk of chronic pain following breast cancer surgery , few studies have examined the characteristics of patients who develop greater acute pain . To identify risk factors for acute pain and its persistence one month following breast cancer surgery , a sample of 114 women scheduled for breast cancer surgery was assessed preoperatively for demographic , clinical , and emotional functioning variables that were hypothesized to be associated with acute pain severity . Clinical ly meaningful postoperative pain was assessed at follow‐up interviews 2 , 10 , and 30 days after surgery . In univariate analyses , the risk of clinical ly meaningful acute pain was increased among women who were younger , unmarried , had more invasive surgeries , and had greater preoperative emotional distress . In multiple logistic regression analyses , greater preoperative anxiety was the only variable that made an independent contribution to predicting clinical ly meaningful acute pain at 2 days after surgery whereas younger age , being unmarried , and preoperative anxiety each made an independent contribution to predicting clinical ly meaningful acute pain that persisted from 2 to 30 days after surgery . These results increase underst and ing of neurobiologic mechanisms and psychosocial processes that contribute to the development of acute pain following breast cancer surgery and have implication s for the development of interventions to prevent it & NA ; In our recent retrospective study on breast cancer patients , the intensity of the past postoperative pain was a primary factor in predisposing the development of chronic post‐treatment pain . The present prospect i ve study was design ed to find out if the remembered intensity of postoperative pain ( RIPP ) after breast surgery was influenced by the development of chronic pain and if the RIPP had any correlation with the development of depression or anxiety . The patient 's estimation of the severity of the RIPP was determined three times in the year after surgery . The state anxiety and depression and the presence of pain in the ipsilateral arm were assessed before the operation , and 1 , 6 and 12 mos after surgery . Ninety‐three consecutive female patients with breast cancer who were enrolled for surgical treatment were recruited to the study during 1993–1994 . The patients were treated with modified radical mastectomy with axillary clearance ( n = 53 ) or breast resection with axillary clearance ( n = 40 ) . The patients ' records were checked for the consumption of analgesics within the first 48 h after surgery . The patients were analysed in three groups according to the presence or absence of preoperative or chronic post‐treatment pain . There was a significant correlation between the RIPP and the consumption of both opioids and NSAIDs on the ward . The women who had chronic pain remembered having had more severe postoperative pain compared with those women who had no chronic pain . The RIPP increased with time in the chronic pain patients whereas it decreased in the patients who had no chronic pain . In all patients the preoperatively measured state anxiety and depression scores were higher than in healthy Finnish women . One year after surgery anxiety and depression had returned to normal levels except in the patients who had chronic pain . Their depression remained at a higher level during the first year after surgery . The results suggest that the amount of postoperative pain may play a role in the development of chronic pain . However , the development of chronic pain is connected to a tendency to overestimate previous pain and to higher levels of depression & NA ; Small‐scale studies have suggested a large inter‐individual variation in early postoperative pain after laparoscopic cholecystectomy , emphasizing the need for improved analgesic treatment and valid predictors . We investigated prospect ively the association between a preoperative nociceptive stimulus by ice water ( cold pressor test ) , neuroticism , dyspepsia , patient history of biliary symptoms , intraoperative factors , and demographic information in 150 consecutive patients undergoing uncomplicated laparoscopic cholecystectomy for their influence on early postoperative pain . During the first postoperative week patients registered overall pain , incisional , visceral , and shoulder pain on a visual analogue scale and verbal rating scale , and daily analgesic requirements were noted . Throughout the first postoperative week overall pain showed a pronounced inter‐individual variability . Incisional pain dominated in incidence and intensity compared with visceral pain , which in turn dominated over shoulder pain . In a multivariate analysis model , preoperative neuroticism , sensitivity to cold pressor‐induced pain , and age were identified as independent risk factors for early postoperative pain . Our results suggest that future analgesic studies after laparoscopic cholecystectomy should focus on reduction of incisional pain Objectives Patient-controlled epidural analgesia ( PCEA ) has been widely used in postoperative pain management . Many factors may correlate with PCEA requirements but no previous study has ever investigated this subject . Therefore , we conducted this study to explore the relationship among patients ' characteristics and total PCEA consumption during the 3-day postoperative course . Methods This prospect i ve study was conducted with surgical patients receiving postoperative PCEA and completing the 3-day course . The PCEA regimen was prepared as 0.0625 % bupivacaine with fentanyl ( l μg/mL ) . Patients ' characteristics including demographic data and surgical procedures were collected . The total doses were recorded after the course terminated . Stepwise regression analyses were conducted to select significant variables , which could determine total PCEA dem and . Subgroup analyses were also performed to investigate whether differences exist among distinct surgical sites . Results There were 1753 patients ( 1094 men and 659 women ) included in the analysis . Weight , age , height , body mass index , sex distribution , and total PCEA consumption were significantly different among various surgical sites ( all P<0.001 ) . Operational sites , procedures involving malignant disease , weight , and age are the most significant factors in sequence to determine total PCEA requirements . Height and sex have no impact on PCEA dem and . The multiple correlation coefficient of our model is 0.688 and the predictive formula of the 3-day postoperative PCEA requirement was 240.1+(130.5 × site)+(66.6 × malignancy)+(1.7 × weight)−(0.4 × age ) . Conclusions Our study demonstrated the association between patients ' characteristics and total PCEA requirements from a large-scaled clinical data . Surgical procedures have more influence on PCEA consumption than demographic variables . Background infusion rate of PCEA could be determined from our predictive model Purpose To investigate prospect ively the influence of patient characteristics upon , and the association of postoperative measurements with , the requirements for postoperative morphine and the assessment of resting pain and pain upon movement in Chinese patients . Methods From January 1998 to December 1999 , patients receiving patient-controllediv morphine subsequent to general anesthesia and surgery at our institute ( Kaohsiung Veterans General Hospital ) , were enrolled in the study . Demographic data ( such as gender , age , weight , height and education level ) and postoperative measurements , including pain scores at rest or during movement , sedation scores and morphine consumption , were recorded . Results In total 2,298 patients were recruited . Females consumed significantly less morphine via patient-controlled analgesia ( PCA ) in the first three postoperative days than was the case for males ( P < 0.05 ) . Gender was the strongest predictor for postoperative morphine requirements . Postoperative pain upon movement was another effective predictor for morphine requirement ( P < 0.05 ) . Age , body height , body weight , education and operation sites were not associated with morphine consumption . Conclusion Gender and postoperative pain upon movement are the major factors influencing morphine requirement for patientcontrollediv morphine analgesia during the first three postoperative days in Chinese patients .RésuméObjectifExaminer prospect ivement si les caractéristiques du patient , et l’association des mesures postopératoires des douleurs , influencent les besoins de morphine postopératoire et l’évaluation de la douleur au repos et lors de mouvement chez des malades chinois . MéthodeDe janvier 1998 à décembre 1999 , les patients qui ont reçu de la morphine iv auto-contrôlée , à la suite d’une opération sous anesthésie générale au Kaohsiung Veterans General Hospital , ont participé à l’étude . Les données démographiques ( sexe , âge , poids , taille et niveau d’instruction ) et les mesures postopératoires , incluant les scores de douleur au repos et pendant le mouvement , les scores de sédation et la consommation de morphine , ont été enregistrées . RésultatsNous avons recruté 2 298 patients . Pendant les trois premiers jours postopératoires , les femmes ont utilisé significativement moins de morphine que les hommes ( P < 0,05 ) au moyen de l’analgésie auto-contrôlée ( AAC ) . La variable prédictive la plus significative de la consommation de morphine postopératoire a été le sexe du patient . La douleur postopératoire pendant le mouvement a été un autre prédicteur efficace ( P < 0,05 ) . L’âge , la taille , le poids , l’instruction et le type d’opération n’ont pas été significatifs pour la consommation de morphine . Conclusion Le sexe et la douleur postopératoire pendant le mouvement sont les principaux facteurs d’influence des besoins de morphine pour l’analgésie iv auto-contrôlée pendant les trois premiers jours postopératoires chez des sujets chinois OBJECTIVE To investigate the use of a measure of selective processing bias associated with anxiety as a predictor of post-operative pain independently of self-report measures of anxiety . METHODS Forty-seven women admitted for minor gynaecological surgical procedures completed a selective processing task ( modified Stroop ) and the State-Trait Anxiety Inventory immediately prior to surgery . Following surgery they completed the McGill Short-Form Pain Question naire . Intraoperative analgesia consumption was also recorded . RESULTS Participants demonstrated significantly slower colour-naming times for physical threat cues than control cues . This was not due to an emotionality effect , as colour-naming times for neutral and positive cues were not significantly different . This bias was congruent with the participants ' current concerns , as colour-naming times were significantly slower for physical threat words than for social threat words . This index of selective processing bias significantly predicted post-operative pain independently of self-reported state and trait anxiety . CONCLUSIONS The advantages of measures of psychological constructs that are not reliant on self-reporting are discussed Abstract Animal studies suggest that fear inhibits pain whereas anxiety enhances it ; however it is unclear whether these effects generalize to humans . The present study examined the effects of experimentally induced fear and anxiety on radiant heat pain thresholds . Sixty male and female human subjects were r and omly assigned to 1 of 3 emotion induction conditions : ( 1 ) fear , induced by exposure to three brief shocks ; ( 2 ) anxiety , elicited by the threat of shock ; ( 3 ) neutral , with no intervention . Pain thresholds were tested before and after emotion induction . Results suggest that findings from animal studies extend to humans : fear result ed in decreased pain reactivity , while anxiety led to increased reactivity . Pain rating data indicated that participants used consistent subjective criteria to indicate pain thresholds . Both subjective and physiological indicators ( skin conductance level , heart rate ) confirmed that the treatment conditions produced the targeted emotional states . These results support the view that emotional states modulate human pain reactivity |
694 | 18,333,931 | Telepsychiatry and the internet seem to be the most promising strategies to diffuse knowledge with lower costs . | BACKGROUND Child and adolescent mental health problems are prevalent and require adequate interventions .
Despite several evidence -based interventions for these problems described in the literature , few studies addressed strategies to diffuse efficacious interventions for child mental disorders especially in developing countries .
RESULTS Substantial evidence -based information is available to guide preventive , psychosocial and psychopharmacological interventions . | The Fast Track prevention trial was used to test hypotheses from the Early-Starter Model of the development of chronic conduct problems . We r and omly assigned 891 high-risk first- grade boys and girls ( 51 % African American ) to receive the long-term Fast Track prevention or not . After 4 years , outcomes were assessed through teacher ratings , parent ratings , peer nominations , and child self-report . Positive effects of assignment to intervention were evident in teacher and parent ratings of conduct problems , peer social preference scores , and association with deviant peers . Assessment s of proximal goals of intervention ( e.g. , hostile attributional bias , problem-solving skill , harsh parental discipline , aggressive and prosocial behavior at home and school ) collected after grade 3 were found to partially mediate these effects . The findings are interpreted as consistent with developmental theory OBJECTIVE To evaluate the effect of the middle and junior high school Drug Abuse Resistance Education ( D.A.R.E. ) and D.A.R.E. Plus programs on drug use and violence . DESIGN R and omized controlled trial of 24 schools , with 3 conditions : D.A.R.E. only , D.A.R.E. Plus , and delayed program control . SETTING Schools and neighborhoods , primarily in Minneapolis-St Paul . PARTICIPANTS All seventh- grade students in 24 schools in the academic year 1999 - 2000 ( N = 6237 at baseline , 67.3 % were white , and there was 84.0 % retention at final follow-up ) . INTERVENTIONS The middle and junior high school D.A.R.E. curriculum in the 16 schools that received D.A.R.E. only and D.A.R.E. Plus . In the 8 schoolts that received D.A.R.E. Plus , additional components included a peer-led parental involvement classroom program called " On the VERGE , " youth-led extracurricular activities , community adult action teams , and postcard mailings to parents . The interventions were implemented during 2 school years , when the cohort was in the seventh and eighth grade s. MAIN OUTCOME MEASURES Self-reported tobacco , alcohol , and marijuana use ; multidrug use ; violence ; and victimization , assessed at the beginning and end of seventh grade and at the end of eighth grade . Growth curve analytic methods were used to assess changes over time by condition . RESULTS There were no significant differences between D.A.R.E. only and the controls ; significant differences among boys between D.A.R.E. Plus and controls for tobacco , alcohol , and multidrug use and victimization ; significant differences among boys between D.A.R.E. Plus and D.A.R.E. only in tobacco use and violence ; and no significant behavioral differences among girls . CONCLUSION D.A.R.E. Plus significantly enhanced the effectiveness of the D.A.R.E. curriculum among boys and was more effective than the delayed program controls , underscoring the potential for multiyear , multicomponent prevention programs and demonstrating sex differences in response to intervention programs CONTEXT Most studies of the long-term effects of early childhood educational interventions are of demonstration programs rather than large-scale public programs . Previous studies of one of the oldest federally funded preschool programs have reported positive effects on school performance , but effects on educational attainment and crime are unknown . OBJECTIVE To determine the long-term effectiveness of a federal center-based preschool and school-based intervention program for urban low-income children . DESIGN , SETTING , AND PARTICIPANTS Fifteen-year follow-up of a nonr and omized , matched-group cohort of 1539 low-income , mostly black children born in 1980 and enrolled in alternative early childhood programs in 25 sites in Chicago , Ill. INTERVENTIONS The Chicago Child-Parent Center ( CPC ) Program ( n = 989 children ) provides comprehensive education , family , and health services and includes half-day preschool at ages 3 to 4 years , half- or full-day kindergarten , and school-age services in linked elementary schools at ages 6 to 9 years . The comparison group ( n = 550 ) consisted of children who participated in alternative early childhood programs ( full-day kindergarten ) : 374 in the preschool comparison group from 5 r and omly selected schools plus 2 others that provided full-day kindergarten and additional instructional re sources and 176 who attended full-day kindergartens in 6 CPCs without preschool participation . MAIN OUTCOME MEASURES Rates of high school completion and school dropout by age 20 years , juvenile arrests for violent and nonviolent offenses , and grade retention and special education placement by age 18 years . RESULTS Relative to the preschool comparison group and adjusted for several covariates , children who participated in the preschool intervention for 1 or 2 years had a higher rate of high school completion ( 49.7 % vs 38.5 % ; P = .01 ) ; more years of completed education ( 10.6 vs 10.2 ; P = .03 ) ; and lower rates of juvenile arrest ( 16.9 % vs 25.1 % ; P = .003 ) , violent arrests ( 9.0 % vs 15.3 % ; P = .002 ) , and school dropout ( 46.7 % vs 55.0 % ; P = .047 ) . Both preschool and school-age participation were significantly associated with lower rates of grade retention and special education services . The effects of preschool participation on educational attainment were greater for boys than girls , especially in reducing school dropout rates ( P = .03 ) . Relative to less extensive participation , children with extended program participation from preschool through second or third grade also experienced lower rates of grade retention ( 21.9 % vs 32.3 % ; P = .001 ) and special education ( 13.5 % vs 20.7 % ; P = .004 ) . CONCLUSIONS Participation in an established early childhood intervention for low-income children was associated with better educational and social outcomes up to age 20 years . These findings are among the strongest evidence that established programs administered through public schools can promote children 's long-term success Annual screenings of preschool children at kindergarten registration identified 158 children having high levels of aggressive , hyperactive , impulsive , and inattentive behavior . These " disruptive " children were r and omly assigned to four treatment conditions lasting the kindergarten school year : no treatment , parent training only , full-day treatment classroom only , and the combination of parent training with the classroom treatment . Results showed that parent training produced no significant treatment effects , probably owing largely to poor attendance . The classroom treatment produced improvement in multiple domains : parent ratings of adaptive behavior , teacher ratings of attention , aggression , self-control , and social skills , as well as direct observations of externalizing behavior in the classroom . Neither treatment improved academic achievement skills or parent ratings of home behavior problems , nor were effects evident on any lab measures of attention , impulse control , or mother-child interactions . It is concluded that when parent training is offered at school registration to parents of disruptive children identified through a brief school registration screening , it may not be a useful approach to treating the home and community behavioral problems of such children . The kindergarten classroom intervention was far more effective in reducing the perceived behavioral problems and impaired social skills of these children . Even so , most treatment effects were specific to the school environment and did not affect achievement skills . These findings must be viewed as tentative until follow-up evaluations can be done to determine the long-term outcomes of these interventions BACKGROUND Previous studies have demonstrated the short-term efficacy of pharmacotherapy and behavior therapy for attention-deficit/hyperactivity disorder ( ADHD ) , but no longer-term ( i.e. , > 4 months ) investigations have compared these 2 treatments or their combination . METHODS A group of 579 children with ADHD Combined Type , aged 7 to 9.9 years , were assigned to 14 months of medication management ( titration followed by monthly visits ) ; intensive behavioral treatment ( parent , school , and child components , with therapist involvement gradually reduced over time ) ; the two combined ; or st and ard community care ( treatments by community providers ) . Outcomes were assessed in multiple domains before and during treatment and at treatment end point ( with the combined treatment and medication management groups continuing medication at all assessment points ) . Data were analyzed through intent-to-treat r and om-effects regression procedures . RESULTS All 4 groups showed sizable reductions in symptoms over time , with significant differences among them in degrees of change . For most ADHD symptoms , children in the combined treatment and medication management groups showed significantly greater improvement than those given intensive behavioral treatment and community care . Combined and medication management treatments did not differ significantly on any direct comparisons , but in several instances ( oppositional/aggressive symptoms , internalizing symptoms , teacher-rated social skills , parent-child relations , and reading achievement ) combined treatment proved superior to intensive behavioral treatment and /or community care while medication management did not . Study medication strategies were superior to community care treatments , despite the fact that two thirds of community-treated subjects received medication during the study period . CONCLUSIONS For ADHD symptoms , our carefully crafted medication management was superior to behavioral treatment and to routine community care that included medication . Our combined treatment did not yield significantly greater benefits than medication management for core ADHD symptoms , but may have provided modest advantages for non-ADHD symptom and positive functioning outcomes 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 OBJECTIVE As psychoeducational eating disorder prevention programs have not been shown to reduce bulimic pathology , we developed and evaluated a dissonance-based intervention for high-risk population s. METHOD Young women ( N = 87 ) with body image concerns were r and omized to this intervention , which involves verbal , written , and behavioral exercises requiring them to critique the thin-ideal , or to a healthy weight management control group . Participants completed a baseline , termination , and 4-week follow-up survey . RESULTS Participants in the dissonance intervention reported decreased thin-ideal internalization , body dissatisfaction , dieting , negative affect , and bulimic symptoms at termination and at 4-week follow-up . Unexpectedly , participants in the healthy weight management control group also reported some benefits . DISCUSSION Taken in conjunction with past findings , these preliminary results suggest that the dissonance intervention , and to a lesser extent the healthy weight management intervention , may reduce bulimic pathology and risk factors for eating disturbances OBJECTIVES We examined the effectiveness of the Signs of Suicide ( SOS ) prevention program in reducing suicidal behavior . METHODS Twenty-one hundred students in 5 high schools in Columbus , Ga , and Hartford , Conn , were r and omly assigned to intervention and control groups . Self-administered question naires were completed by students in both groups approximately 3 months after program implementation . RESULTS Significantly lower rates of suicide attempts and greater knowledge and more adaptive attitudes about depression and suicide were observed among students in the intervention group . The modest changes in knowledge and attitudes partially explained the beneficial effects of the program . CONCLUSIONS SOS is the first school-based suicide prevention program to demonstrate significant reductions in self-reported suicide attempts Project Northl and was a r and omized trial to reduce alcohol use among adolescents in 24 school districts in northeastern Minnesota . Phase 1 ( 1991 - 1994 ) , when the targeted cohort was in grade s 6 - 8 , included school curricula , parent involvement , peer leadership and community task forces . The Interim Phase ( 1994 - 1996 ) involved minimal intervention . Phase 2 ( 1996 - 1998 ) , when the cohort was in grade s 11 and 12 , included a classroom curriculum , parent education , print media , youth development and community organizing . Outcomes of these interventions were assessed by annual student surveys from 1991 to 1998 , alcohol purchase attempts by young-looking buyers in 1991 , 1994 and 1998 , and parent telephone surveys in 1996 and 1998 . Growth curve analysis was used to examine the student survey data over time . Project Northl and was most successful when the students were young adolescents . The lack of intervention in the Interim Phase when the students were in grade s 9 and 10 had a significant and negative impact on alcohol use . The intervention used with the high school students as those in grade s 11 and 12 made a positive impact on their tendency to use alcohol use , binge drinking and ability to obtain alcohol . There was no impact in Phase 2 on other student-level behavioral and psychosocial factors . Developmentally appropriate , multi-component , community-wide programs throughout adolescence appear to be needed to reduce alcohol use Thirty-seven families who had a child between the ages of 8 and 15 ( mean age = 12.0 years ) and had at least one parent , who had experienced a recent episode of affective disorder were assigned r and omly to one of two psychoeducational interventions . The interventions ( clinician-facilitated or lecture-group discussion ) were design ed to prevent childhood depression and related problems through decreasing the impact of related risk factors and encouraging resiliency-promoting behaviors and attitudes . They were similar in content but differed in the level of the children 's involvement and the degree to which the families ' individual life experiences were linked to the educational material . Assessment s included st and ard diagnostic and social functioning instruments and interviews design ed specifically for this project to assess behavior and attitude change . Each parent and child was individually assessed by separate assessors who were blind to information about the other family members . Parent participants in both groups reported being satisfied with the intervention . Clinician group participants reported a significantly larger number of overall changes , as well as higher levels of change regarding communications about the illness with their children and increased underst and ing by the children of their illness . Significantly more children in the clinician group also reported they gained a better underst and ing of parental affective illness as a result of their participation in the project This paper describes the development and preliminary efficacy of a program design ed to prevent depressive symptoms in at-risk 10 - 13 year-olds , and relates the findings to the current underst and ing of childhood depression . The treatment targets depressive symptoms and related difficulties such as conduct problems , low academic achievement , low social competence , and poor peer relations , by proactively teaching cognitive techniques . Children were identified as ' at-risk ' based on depressive symptoms and their reports of parental conflict . Sixty-nine children participated in treatment groups and were compared to 73 children in control groups . Depressive symptoms were significantly reduced and classroom behavior was significantly improved in the treatment group as compared to controls at post-test . Six-month follow-up showed continued reduction in depressive symptoms , as well as significantly fewer externalizing conduct problems , as compared to controls . The reduction in symptoms was most pronounced in the children who were most at risk The Queensl and Early Intervention and Prevention of Anxiety Project evaluated the effectiveness of a cognitive-behavioral and family-based group intervention for preventing the onset and development of anxiety problems in children . A total of 1,786 7- to 14-year-olds were screened for anxiety problems using teacher nominations and children 's self-report . After recruitment and diagnostic interviews , 128 children were selected and assigned to a 10-week school-based child- and parent-focused psychosocial intervention or to a monitoring group . Both groups showed improvements immediately postintervention . At 6 months follow-up , the improvement maintained in the intervention group only , reducing the rate of existing anxiety disorder and preventing the onset of new anxiety disorders . Overall , the results showed that anxiety problems and disorders identified using child and teacher reports can be successfully targeted through an early intervention school-based program Evaluated an experimental preventive intervention developed for children who perceived their parents as problem drinkers . The 8-session program was design ed to improve children 's coping , self-esteem , and social competence , and modify alcohol expectancies which were specified as mediators of the effects of parental alcohol abuse on child mental health . Participants were 271 self-selected 4th- , 5th- , and 6th- grade students in 13 schools . The children were r and omly assigned to treatment or delayed treatment conditions and the program was given to three successive cohorts of students . A meta- analysis across three different cohorts indicated significant program effects to improve knowledge of the program content and the use of support- and emotion-focused coping behaviors for the full sample . A slightly stronger range of effects was found for a high-risk sub sample CONTEXT No r and omized controlled studies have been conducted to date on the effectiveness of psychological interventions for children with symptoms of posttraumatic stress disorder ( PTSD ) that has result ed from personally witnessing or being personally exposed to violence . OBJECTIVE To evaluate the effectiveness of a collaboratively design ed school-based intervention for reducing children 's symptoms of PTSD and depression that has result ed from exposure to violence . DESIGN A r and omized controlled trial conducted during the 2001 - 2002 academic year . SETTING AND PARTICIPANTS Sixth- grade students at 2 large middle schools in Los Angeles who reported exposure to violence and had clinical levels of symptoms of PTSD . INTERVENTION Students were r and omly assigned to a 10-session st and ardized cognitive-behavioral therapy ( the Cognitive-Behavioral Intervention for Trauma in Schools ) early intervention group ( n = 61 ) or to a wait-list delayed intervention comparison group ( n = 65 ) conducted by trained school mental health clinicians . MAIN OUTCOME MEASURES Students were assessed before the intervention and 3 months after the intervention on measures assessing child-reported symptoms of PTSD ( Child PTSD Symptom Scale ; range , 0 - 51 points ) and depression ( Child Depression Inventory ; range , 0 - 52 points ) , parent-reported psychosocial dysfunction ( Pediatric Symptom Checklist ; range , 0 - 70 points ) , and teacher-reported classroom problems using the Teacher-Child Rating Scale ( acting out , shyness/anxiousness , and learning problems ; range of subscales , 6 - 30 points ) . RESULTS Compared with the wait-list delayed intervention group ( no intervention ) , after 3 months of intervention students who were r and omly assigned to the early intervention group had significantly lower scores on symptoms of PTSD ( 8.9 vs 15.5 , adjusted mean difference , - 7.0 ; 95 % confidence interval [ CI ] , - 10.8 to - 3.2 ) , depression ( 9.4 vs 12.7 , adjusted mean difference , - 3.4 ; 95 % CI , - 6.5 to - 0.4 ) , and psychosocial dysfunction ( 12.5 vs 16.5 , adjusted mean difference , - 6.4 ; 95 % CI , -10.4 to -2.3 ) . Adjusted mean differences between the 2 groups at 3 months did not show significant differences for teacher-reported classroom problems in acting out ( -1.0 ; 95 % CI , -2.5 to 0.5 ) , shyness/anxiousness ( 0.1 ; 95 % CI , -1.5 to 1.7 ) , and learning ( -1.1 , 95 % CI , -2.9 to 0.8 ) . At 6 months , after both groups had received the intervention , the differences between the 2 groups were not significantly different for symptoms of PTSD and depression ; showed similar ratings for psychosocial function ; and teachers did not report significant differences in classroom behaviors . CONCLUSION A st and ardized 10-session cognitive-behavioral group intervention can significantly decrease symptoms of PTSD and depression in students who are exposed to violence and can be effectively delivered on school campuses by trained school-based mental health clinicians OBJECTIVE To evaluate a community-based intervention aim ed at the primary prevention of disordered eating among preadolescent girls . DESIGN Girl Scout troop members were r and omized into control and intervention groups . Program feasibility and effect at postintervention and 3-month follow-up were evaluated . SUBJECTS/ SETTING 226 girls ( mean age = 10.6 years , st and ard deviation = 0.7 ) from 24 Girl Scout troops . INTERVENTION Six 90-minute sessions focusing on media literacy and advocacy skills . MAIN OUTCOME MEASURES Evaluation focused on program satisfaction and short-term effect on dieting behaviors , body image attitudes , and media knowledge , attitudes , and habits . STATISTICAL ANALYSES Performed t tests , chi 2 tests , and analyses of covariance including troop as a r and om source of variation . RESULTS At baseline , 29 % of the girls were trying to lose weight . The program had a notable positive influence on media-related attitudes and behaviors including internalization of sociocultural ideals , self-efficacy to impact weight-related social norms , and print media habits . A modest program effect on body-related knowledge and attitudes was apparent at post-intervention ( i.e. , on body size acceptance , puberty knowledge , and perceived weight status ) but not at follow-up . Significant changes were not noted for dieting behaviors , but they were in the hypothesized direction . Satisfaction with the program was high among girls , parents , and leaders . APPLICATIONS/ CONCLUSIONS It is feasible to use community youth setting s , such as the Girl Scouts , to implement interventions to prevent disordered eating behaviors . The program led to positive trends in outcome variables ; however , longer and more intensive interventions are needed for lasting changes in body image and dieting behaviors OBJECTIVE Depressive disorders in adolescents are a widespread problem with extensive psychosocial consequences . The authors design ed a school-based program to prevent the increase in depressive symptoms . The authors expect the program to reduce dysfunctional automatic thoughts and improve social skills and thus prevent the increase in depressive symptoms . METHOD The design includes a training group and a nontreatment control group with pre- and post-measurement and 3- and 6-month follow-up . The authors followed up 324 eighth grade rs in both groups . School classes were r and omly assigned to one of the two groups . The prevention program , LISA-T , is based on cognitive-behavioral therapy concepts and targets of cognitive and social aspects . It comprises 10 meetings of 1.5 hours in a regular school setting . RESULTS Increases in depressive symptoms in nondepressed adolescents in the training group were prevented over a 6-month period . Furthermore , adolescents with subsyndromal depression in the training group reported fewer symptoms , whereas depressive symptoms within the control group did not change . However , the groups did not differ with regard to social skills , frequency of negative automatic thoughts , and depressive symptoms before the prevention program . CONCLUSIONS LISA-T is an effective school-based prevention program for eighth grade rs with minimal to mild depressive symptoms , but further research is needed Five hundred and eleven fourth , fifth , and sixth grade students and their parents from six schools in northwest Arkansas participated in this study . Students were blocked on school and grade level , then assigned r and omly by class to either the intervention Keep A Clear Mind ( KACM ) program or a waiting list control . KACM students received four weekly correspondence lessons design ed to be completed at home with a parent . KACM students reported significantly less perceived peer use of alcohol , tobacco , and marijuana , as well as significantly less peer pressure susceptibility to experiment with cigarettes . Mothers in the KACM program reported significantly more recent and frequent communication with their children about refusing drugs , and significantly greater discussion s with their children regarding how to resist peer pressure to use alcohol , tobacco , and marijuana . Intervention program fathers reported significantly more communication with their children concerning how to resist peer pressure to drink alcohol and use tobacco , and significantly greater motivation to help their children avoid drug use . No significant differences were found between groups on student intentions to use drugs . These data suggest a print medium that emphasizes parent-child activities holds promise for accessing families and enhancing drug prevention communication OBJECTIVE Treatment outcome in sexually abused preschool children was evaluated 6 and 12 months after treatment . METHOD Forty-three sexually abused preschool children and their parents were evaluated 6 and 12 months after completion of either Cognitive-Behavioral Therapy for Sexually Abused Preschoolers ( CBT-SAP ) or nondirective supportive therapy ( NST ) . Parents completed the Child Behavior Checklist , Child Sexual Behavior inventory , and Weekly Behavior Report to measure a variety of symptoms in their children . RESULTS Repeated- measures analyses indicated that there were significant group by time interactions on several outcome measures from the beginning of the study to the end of the 12-month follow-up period , with the CBT-SAP group exhibiting significantly more improvement over time than the NST group . Clinical findings also indicated the superior effectiveness of CBT-SAP over NST in reducing sexually inappropriate behavior . CONCLUSIONS Findings support the superior efficacy of CBT-SAP over NST in maintaining symptom reduction in the year after treatment completion . The importance of using cognitive-behavioral interventions for sexually inappropriate behaviors and including nonoffending parents in the treatment of sexually abused preschool children is discussed Two drug abuse prevention curricula were tested to determine their efficacy in preventing the onset of tobacco , alcohol , and marijuana use among adolescents . The first program focused on prevention through social pressure resistance training . The second featured affective education approaches to prevention . Curricula were tested on seventh grade students . Subjects were pretested just prior to the program and were post-tested at 12 and 24 months . Post-test analyses indicated that the social program delivered to seventh grade subjects was effective in delaying the onset of tobacco , alcohol , and marijuana use . No preventive effect of the affective education program was observed . By the final post-test , classrooms that had received the affective program had significantly more drug use than controls PURPOSE To describe the Gatehouse Project which addresses the social context of high school with an aim of changing students ' sense of school connection and in turn , health risk behavior and well-being . METHODS Distinguishing features of the project were its conceptual framework , implementation process , and evaluation design . The conceptual framework derived from attachment theory and focused on three aspects of the school social context : security , communication , and participation . Implementation was st and ardized around a survey of the school social environment , creation of a school-based action team , and the implementation of strategies matched to a school 's profile of need . In addition , an early high school curriculum addressed the skills relevant to social functioning and emotional adjustment . The evaluation design was based on a cluster r and omized trial involving 26 schools . It used follow-up of an individual cohort and repeat cross-sectional surveys to capture outcomes at an individual student and whole-school level . RESULTS AND CONCLUSIONS The Gatehouse Project drew on both health and education research to develop and coordinate a broad-based school health promotion intervention . It represents a promising new direction for school-based preventive work Conducted the 1st r and omized clinical trial evaluating the efficacy of the FRIENDS program , a family-based group cognitive-behavioral treatment ( FGCBT ) for anxious children . Children ( n = 71 ) ranging from 6 to 10 years of age who fulfilled diagnostic criteria for separation anxiety ( SAD ) , generalized anxiety disorder ( GAD ) , or social phobia ( SOP ) were r and omly allocated to FRIENDS or to a 10-week wait-list control group . The effectiveness of the intervention was evaluated at posttreatment and 12-month follow-up . Results indicated that 69 % of children who completed FGCBT were diagnosis-free , compared to 6 % of children completing the wait-list condition . At 12-month follow-up , 68 % of children were diagnosis-free . Beneficial treatment effects were also evident on the self-report measures completed by the children and their mothers . Parents and children reported high treatment satisfaction . Results suggest that FRIENDS is an effective treatment for clinical ly anxious children . Limitations of this study and directions for future research are discussed PROBLEM Few empirically tested , school-based , suicide-prevention programs exist . The purpose of this study was to evaluate the postintervention efficacy of Counselors-CARE ( C-CAST ) and Coping and Support Training ( CAST ) vs. " usual care " controls for reducing suicide risk . METHODS A r and omized prevention trial ; 341 potential dropouts , 14 to 19 years old , from seven high schools ( 52 % female , 56 % minorities ) participated . Trend analyses using data from three time points assessed over time changes . FINDINGS Significant decreases occurred for all youth in suicide-risk behaviors , depression , and drug involvement . Intervention-specific effects occurred for decreases in depression . CONCLUSIONS School-based prevention approaches are feasible and show promise for reducing suicidal behaviors and related depression AIMS To examine the effects of the ' Healthy School and Drugs ' project , a Dutch school-based drug prevention project that was developed in the late 1980s and disseminated during the 1990s . This programme is currently being used by 64 - 73 % of Dutch secondary schools and it is estimated that at least 350000 high school students receive this intervention each year . DESIGN , SETTING AND PARTICIPANTS A quasi-experimental study in which students of nine experimental ( N = 1156 ) schools were compared with students of three control schools ( N = 774 ) . The groups were compared before the intervention , 1 year later , 2 years later and 3 years later . MEASUREMENTS Self-report measures of tobacco , alcohol and marijuana use , attitudes towards substance use , knowledge about substances and self-efficacy . FINDINGS Some effects on the use of tobacco , alcohol and cannabis were found . Two years after the intervention , significant effects could still be shown on alcohol use . Effects of the intervention were also found on knowledge , but there was no clear evidence for any effects on attitude towards substance use and on self-efficacy . CONCLUSIONS This study shows the Healthy School and Drugs project as implemented in Holl and may have some effect on drug use in the children exposed to it OBJECTIVE This study examines the effect of an interactive , school-based , self-esteem education program on the body image and eating attitudes and behaviors of young male and female adolescents following the program and after 12 months . METHOD All 470 eligible students ( 63 % female ) aged 11 - 14 years volunteered to participate . The intervention group students participated in the program , whereas the control group students received their scheduled personal development and health class . RESULTS The program significantly improved the body satisfaction of the intervention students and significantly changed aspects of their self-esteem ; social acceptance , physical appearance , and athletic ability became less important for the intervention students and more important for control students . Female intervention students rated their physical appearance as perceived by others significantly higher than control students and allowed their body weight to increase appropriately by preventing the age increase in weight-losing behaviors of the control students . One year after the intervention , body image and attitude changes were still present . These findings also held for the 116 students ( 63 % females ) with low self-esteem and higher anxiety , who were considered at risk for the development of eating disorders . These students also had significantly lower drive for thinness and greater body satisfaction following the intervention and the decreased importance of physical appearance to their self-esteem was present at 12 months . Control at-risk students significantly decreased their body weight , whereas the weight of the intervention at-risk students significantly increased . The intervention program was effective , safe , having no effect on measures of students ' anxiety or depression , and was rated highly by students . DISCUSSION This is the first controlled educational intervention to successfully improve body image and to produce long-term changes in the attitudes and self-image of young adolescents . This new approach to prevent the development of eating disorders by improving self-esteem may be effective , particularly if reinforced by teachers and family This study examined the effects of brief nurse consultations in preventing alcohol use among inner-city youth . Participants included 138 sixth-eighth grade students attending an inner-city public school in Jacksonville , Florida . Subjects were r and omly assigned by computer to either the intervention ( STARS program ) or a control group . Baseline and three-month post-tests were conducted at the target school site . A significant difference was found on heavy alcohol use with intervention subjects showing a reduction and control subjects an increase in heavy drinking ( t = -2.33 , 120df , p = .02 ) . No differences were found between groups on other alcohol use measures . This study 's findings indicate that a series of brief nurse consultations appear to reduce heavy alcohol consumption among urban school youth A peer-managed self-control program to teach responsible drinking was tested with 30 American Indian teenagers at high risk for problem drinking . Students were r and omly assigned to three groups incorporating combinations of self-monitoring , peer-assisted self-control training , and alcohol education . Significant decreases were observed in quantity and frequency of drinking and in peak blood alcohol levels . These improvements were maintained at follow-ups of 4 , 9 , and 12 months posttreatment . Self-report data were corroborated by breath tests and official records . No group differences were found , indicating that minimal and full program interventions had comparable effects OBJECTIVE This study evaluates the effectiveness and feasibility of a primary prevention program for risk factors for eating disorders in adolescent girls . METHOD Nearly 500 seventh- grade girls participated in " Full of Ourselves : Advancing Girl Power , Health , and Leadership , " and were assessed at baseline , immediately after program completion , and 6 months later on several self-report measures of knowledge , body image , and eating and weight-related behaviors . RESULTS Significant differences were found between participants and controls on measures of knowledge and weight-related body esteem , which were maintained at 6-month follow-up . Eating related behaviors , including skipping meals and dieting , appeared unaffected by program participation . DISCUSSION The program was feasible , safe , and result ed in positive and maintained changes in knowledge and weight satisfaction for adolescent girls Two versions of a school-based alcohol prevention programme for 7th grade students were evaluated against a non-treated comparison condition . Both programme versions were based on a social-cognitive theory approach to alcohol prevention , and differed in the level of role-specifications for participating teachers and peer leaders . Twelve schools with 955 students in Bergen , Norway , participated in the study . Four schools were r and omly assigned to each of the three conditions , and the programme was implemented during 10 class periods over 2 months in Spring , 1992 . Pre- and post-test surveys were conducted , assessing alcohol use , as well as cognitive variables related to alcohol use in a specific context ( intentions , attitudes , norms and self-efficacy expectations ) . Results showed that the highly role-specified ( HRS ) version had a higher degree of student involvement than the less role-specified ( LRS ) version , indicating that the HRS programme was more successful in engaging students in alcohol prevention activities . A significant difference in programme effectiveness was found , as measured by an overall programme effect across all dependent variables . This effect was explained by significantly more positive outcomes in the HRS version compared to both the LRS and the non-treated conditions , while the LRS version did not differ significantly from the non-treated condition |
695 | 31,266,920 | CONCLUSION Reminiscence therapy is an effective non-pharmacological therapy to improve depressive symptoms in older adults with dementia . | PURPOSE The purpose of this study was to evaluate the effects of reminiscence therapy on depressive symptoms in older adults with dementia using a systematic review and meta- analysis . | This r and omized controlled trial investigated the effect of live music on quality of life and depression in 47 older people with dementia using the Dementia Quality of Life and Geriatric Depression Scale . The control/reading group reported higher mid-point feelings of belonging than the music group ( F(1 , 45 ) = 6.672 , p < .05 ) . Sub-analyses of ≥ 50 per cent music session attendance found improvements in self-esteem over time ( F(2 , 46 ) = 4.471 , p < .05 ) . Participants with scores that were suggestive of increased depressive symptoms had fewer depressive symptoms over time ( F(2 , 22 ) = 8.129 , p < .01 ) . Findings suggest music and reading activities can improve self-esteem , belonging and depression in some older people with dementia This study aim ed to investigate the long-term effects of group music therapy on agitation manifested by nursing home residents with Alzheimer 's disease . A non-r and omised experimental design was employed with one group receiving weekly music therapy ( n = 26 ) and another group receiving st and ard nursing home care ( n = 19 ) . Agitation levels were measured five times over one year using the Cohen-Mansfield Agitation Inventory ( Cohen-Mansfield , J. ( 1989 ) . Agitation in the elderly . In N. Billig & P. V. Rabins ( Eds . ) , Issues in geriatric psychiatry ( pp . 101–113 ) . Basel , Switzerl and : Karger ) . Although music therapy participants showed short-term reductions in agitation , there were no significant differences between the groups in the range , frequency , and severity of agitated behaviours manifested over time . Multiple measures of treatment efficacy are necessary to better underst and the long-term effects music therapy programs have on this population Objective : Reminiscence therapy is a psychological intervention which is specifically design ed to address issues of particular relevance to older adults , such as depression . The latest approach to the research on therapeutic utility of reminiscence is gaining popularity among research ers and practitioners , and has yielded promising results . Specifying different types of reminiscence is a crucial component of the approach . The aim of this study was to examine the therapeutic effectiveness of integrative and instrumental types of reminiscence for the treatment of depression in institutionalized older adults dwelling in a nursing home . Method : The study employed a three-group pre – post-test design with r and om allocation to instrumental or integrative reminiscence or an active social discussion control condition . Twenty-nine institutionalized older adults ( 12 men and 17 women ) with depressive symptoms varying from mild to severe constituted the sample . The interventions were implemented in a short-form group format . Findings : Analysis of changes from pre-test to post-test revealed that integrative reminiscence therapy led to statistically significant reduction in symptoms of depression in contrast with the control group . Although instrumental reminiscence therapy also reduced depressive symptoms , this improvement was not statistically significant compared to the control group . Conclusion : This study provides additional support for the effectiveness of integrative reminiscence therapy as an intervention for depressed older adults living in residential care setting s. This study also provides support for the hypothesis that certain types of reminiscence produce their own specific effects Objectives : To evaluate the effect of different pathways for developing a life story book ( LSB ) for people with dementia . Method : Preliminary r and omised control trial ; 23 people with dementia in care homes ( mean age 86 ) r and omly assigned to receive either 12 individual life review sessions and co-creating a LSB or a personal LSB created by their relatives as a ‘ gift ’ Results : No difference in quality of life ( quality of life – Alzheimer 's disease ( QOL – AD ) ) was observed between the two groups , six weeks after having received the LSB ( F(1,20 ) = 0.08 , p = 0.77 ) . At this point , QOL – AD had improved for both groups , but there was a significant between-group difference at an intermediate assessment immediately after the life review sessions had been completed , before the LSBs were received ( F(1 , 20 ) = 5.11 , p = 0.035 ) , in favour of life review . A similar pattern was observed on autobiographical memory ( extended autobiographical memory interview ) , with the life review group improving significantly more than the gift group during the life review sessions , but no difference was observed once all participants had had their LSB for six weeks . After the LSBs were produced – by either pathway – quality of relationship as rated by relatives improved significantly ( F(2 , 39 ) = 19.37 , p < 0.001 ) and staff knowledge regarding the resident and attitudes to dementia improved . Conclusion : The creation of LSBs – either through a life review process or by relatives without involving the person with dementia – has benefits for people with dementia , relatives and staff in care homes . However , undertaking a life review requires training and supervision OBJECTIVE To examine effects of individual thematically-based reminiscence sessions based on the SolCos model for older adults with dementia because of Alzheimer disease ( AD ) as a pilot study . BACKGROUND Reminiscence activities are popular within nursing homes and generally considered to be enjoyable and helpful , however , there is a paucity of robust data demonstrating therapeutic impact . Criticisms of existing reminiscence studies include the failure to explicate the reminiscence protocol and to st and ardize delivery and choice of outcome measures . METHODS In this study , 82 older adults with probable AD were recruited from psychiatric day care , inpatient , and long term care facilities . Of the study group , 41 participants were r and omly selected for individual reminiscence sessions during 4 weeks performed by 1 facilitator . A control group of 41 older adults were r and omly involved and had no planned reminiscence treatment of any kind in the study period . All study participants were tested pre- and postintervention period with vali date d assessment scales to evaluate cognition and behavior . Analyses were based on delta scores , the differences between assessment scales pre- and postintervention scores , compared between the intervention and the control group . RESULTS A structured reminiscence protocol was developed with user involvement , and intervention group participants received 6 - 8 reminiscence sessions ( average 7.4 ) . The primary outcomes of Mini- Mental State Examination ( MMSE ) and Geriatric Depression Scale ( GDS-30 ) delta scores of the intervention group were significantly better than those of the control group . Participants of the intervention group with both mild and moderate AD had significantly better GDS-30 delta scores compared with the control group . Significantly better MMSE delta scores were found only in the intervention sub-group with moderate AD . Logistic regression analyses with all study participants showed an impact of reminiscence sessions on depressive symptoms measured with GDS-30 . CONCLUSIONS The pilot study results showed positive effects associated with individual thematically-based reminiscence on well-being such as depressive symptoms and cognition of participants . This is an encouraging finding after a relatively short period . Further study is necessary to confirm these results , determine sustainability and optimal delivery methods WHAT IS KNOWN ON THE SUBJECT ? : To stimulate reminiscence of older adults with dementia performed individually or through group sessions is a well-known practice in nursing homes result ing in effects on behaviour and well-being as an alternative for medication . Robust scientific proof of the effectiveness of individual reminiscence therapy performed in nursing homes is sparse . WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE ? : We have provided individual st and ardized reminiscence therapy to residents with dementia . The therapy was developed and tested in a previous study and performed in this study by trained nursing home volunteers . In comparison with a control group who received usual care , residents who received the reminiscence therapy showed significant less depressive symptoms . Moreover , residents were , in general , attentive , open and collaborative during the sessions and volunteers experienced the sessions as useful and pleasant . WHAT ARE THE IMPLICATION S FOR PRACTICE ? : Individual reminiscence therapy can be learned and used by nursing home volunteers to improve care in nursing homes . ABSTRACT Aim To investigate the effect of a st and ardized individualized intervention based on the SolCos transformational reminiscence model on depressive symptoms ( primary outcome ) , cognition and behaviour ( secondary outcomes ) for older people with mild to moderate dementia , performed by trained nursing home volunteers as facilitators . Background Because of limited pharmacological treatment options for older adults with dementia relevant physical , sensory , psychological or social interventions offer alternative opportunities . Method R and omized controlled trial ( IS RCT N74355073 ) was set up in two nursing homes with 29 and 31 residents in the intervention and the control groups respectively . Eighteen nursing home volunteers were trained to perform the reminiscence therapy . Various assessment scales were measured pre- and post-sessions . Results Linear regression analysis showed an impact on depressive symptoms . However , no impact was identified on cognition and behaviour . Facilitators experienced the sessions as useful and pleasant , and study participants were , in general , attentive , open and collaborative . Discussion Study results showed that organizing st and ardized individual reminiscence therapy with nursing home volunteers was feasible and study participants ' attention and participation were overall good . Further study initiatives to explore the potential of individual reminiscence therapy within a person-centred framework are recommended in order to improve care in nursing homes BACKGROUND Elderly people with cognitive impairments are often associated with depressed mood and are heavy consumers in both medical services and need in caregivers . Reminiscence is believed to be effective in improving the cognition and mood of demented people . OBJECTIVES This study tested the hypothesis that structured group reminiscence therapy can prevent the progression of cognitive impairment and enhance affective function in the cognitively impaired elderly . METHODS A r and omized controlled trial ( RCT ) based on a two group pre- and post-test design was used . The experimental subjects underwent eight group sessions , one session per week . The measurements were performed using Mini-Mental State Examination ( MMSE ) , Geriatric Depression Scale short form ( GDS-SF ) , and Cornell Scale for Depression in Dementia ( CSDD ) . RESULTS The sample consisted of 102 subjects , with 51 in the experimental group and 51 in the control group . Results demonstrated that the intervention significantly affected cognitive function and affective function as measured by MMSE and CSDD ( p = 0.015 and 0.026 ) , indicating that the cognitive function of the experimental subjects increased and their depressive symptoms diminished following intervention . CONCLUSION Participation in reminiscence activities can be a positive and valuable experience for demented older persons . Consequently , the development of a structured care program for elderly persons with cognitive impairment and the need for long-term care is essential . Thus , health providers in long-term care facilities should be trained in reminiscence group therapy , and to be able to deliver such a program to the targeted group BACKGROUND There is increasing recognition of the potential use of reminiscence in maintaining or improving the quality of life of people with dementia . Despite being used widely in dementia care , evidence on the effectiveness of reminiscence remains uncertain . AIMS This study aims to evaluate the effectiveness of a structured education-based reminiscence programme-the Dementia Education Programme Incorporating Reminiscence for Staff-for people with dementia residing in long-stay care setting s in Irel and . METHODS Dementia Education Programme Incorporating Reminiscence for Staff is a two-group , single-blind , cluster r and omised trial conducted in long-stay residential care setting s in Irel and . The primary outcome was the self-rated quality of life of residents as measured by the Quality of Life-Alzheimer 's Disease instrument . RESULTS Using an intention-to-treat analysis , we found that the estimated effect of the intervention on the quality of life of residents was a non-significant 3.54 ( p = 0.1 ; 95 % confidence interval -0.83 , 7.90 ) , expressed as the difference in mean improvement between the intervention and control groups . However , the per- protocol analysis yielded a significant effect for the intervention on the quality of life of residents of 5.22 ( p = 0.04 ; 95 % confidence interval 0.11 , 10.34 ) . CONCLUSIONS Reminiscence may , in certain circumstances , be an effective care option for people with dementia in long-stay setting s with potential to impact positively on the quality of life of residents The purpose of this study was , conducted with experimental design , to investigate the effect of reminiscence therapy on cognition , depression , activities of daily living of institutionalized mild and moderate Alzheimer patients . The study was conducted with a total of 62 patients ( 31 intervention group and 31 control group ) in four home care in Ankara , Turkey . Study was done between the July 1 , 2013 and December 20 , 2014 . Reminiscence therapy sessions were held with groups consists of 4 - 5 patients , once a week with 30 - 35 minute duration for 12 weeks . St and ardized Mini Mental Test was used in sample selection . Patients were listed through their mini mental test scores , and r and omized as odd numbers to control group and even numbers to intervention group . Data were collected with forms developed by research er ‘ Data Sheet ’ and ‘ Activities of Daily Living Follow-up Form ’ as well as scales ‘ St and ardized Mini Mental Test ’ and ‘ Geriatric Depression Scale ’ . Chi-square , Mann Whitney-U test , variance analyses in repeated measures and Bonferroni tests were used for analysis . The increase in mean St and ardized Mini Mental Test score and the decrease in mean Geriatric Depression Scale score of the individuals in the intervention group compared to the control group at the end of the reminiscence therapy was statistically significant ( P < 0.05 ) . At the end of reminiscence therapy sessions , increase in cognition and decrease in depression were found statistically significant in intervention group Objective : The purpose of this study was to conduct a r and omized controlled trial of a nursing home intervention to reduce depressive symptoms in residents with dementia . Method : The multicomponent intervention included group activity sessions , which used question -asking-reading ( QAR ) , reminiscence , and cognitive-behavioral therapy techniques , as well as environmental supports and individualized behavioral activity programs . Fifty-one residents from five nursing homes participated in the study . Results : A significant difference in depressive symptoms was found , with residents in the QAR-Depression condition showing improvement compared with those in the treatment as usual condition . Residents in the treatment group also exhibited significantly higher levels of expressive verbalizations , engagement with material s , and laughter . Few differences in resident behavior occurring outside of the group activities were noted . Discussion : Findings suggest that structured group activities can positively impact a resident ’s psychological well-being . In addition , the QAR structure may be suitable for older adults with cognitive impairment by distributing group tasks and providing external cognitive supports Background : Depression among institutionalized elders is a common problem associated with physical and functional limitations , and effective interventions are needed . Objective : The objective of this study was to determine the effect of group reminiscence on physical function , behavioral competence , and depression among clinical ly depressed , institutionalized elders . Methods : A two-group , r and om-assignment quasi-experimental study was conducted in four long-term care facilities in southern Taiwan . The experimental group ( n = 21 ) received six to eight group reminiscence sessions over 2 months compared with a routine care control group ( n = 24 ) . Outcome measurements included the Behavioral Rating Scale , Barthel 's Index , and the Geriatric Depression Scale-short form . Results : Reminiscence sessions result ed in a significant 2-point decrease in theGeriatric Depression Scale-short form ( p = .002 ) and improved behavioral competence ( p = .001 ) . No change was identified in functional ability . Conclusions : Group reminiscence is a therapeutic intervention for depressed , institutionalized elders that can be managed by trained nursing staff . It is a cost-effective approach to improve psychosocial well-being for institutionalized older people . Additional research is needed on a larger sample across different diseases and cultural groups OBJECTIVE To investigate the feasibility and effectiveness of Sonas , a group intervention involving multisensory stimulation , reminiscence , and light physical activity . METHODS A total of 39 participants with moderate to severe dementia were r and omized to receive either 14 sessions of Sonas or treatment as usual . Measures such as quality of life ( QoL ) , communication , depression , anxiety , and behavioral disturbance were administered at baseline and follow-up . RESULTS No statistically significant results were found . However , participant attendance to sessions was good ( mean = 12.4 sessions of 14 offered ) . CONCLUSIONS Sonas sessions did not lead to improvements in QoL and behavioral and psychological symptoms of dementia |
696 | 18,254,088 | Increased intraocular pressure and cataract formation were side effects requiring monitoring and management .
RCTs included in this review suggest that steroids placed inside the eye by either intravitreal injection or surgical implantation may improve visual outcomes in eyes with persistent or refractory DME .
Since the studies in our report focused on chronic or refractory DME , the question arises whether intravitreal steroids therapy could be of value in other stages of DME , especially the earlier stages either as st and alone therapy or in combination with other therapies , such as laser photocoagulation | BACKGROUND Macular edema is secondary to leakage from diseased retinal capillaries and is an important cause of poor central visual acuity in patients with diabetic retinopathy .
OBJECTIVES This review evaluated the effectiveness and safety of intraocular steroids in treating diabetic macular edema ( DME ) . | OBJECTIVE To evaluate prospect ively the efficacy and safety of 1 intravitreal injection of 4 mg of triamcinolone acetonide for refractory diffuse diabetic macular edema . DESIGN Interventional case series . PARTICIPANTS Fifteen patients with bilateral diabetic macular edema unresponsive to laser photocoagulation . In all patients , one eye received the injection , and the other served as a control . INTERVENTION Intravitreal injection of 4 mg of triamcinolone acetonide under subconjunctival anesthesia . MAIN OUTCOME MEASURES The main outcome measure was central macular thickness ( CMT ) at 1 , 3 , and 6 months , measured by optical coherence tomography . Secondary outcomes were Early Treatment Diabetic Retinopathy Study ( ETDRS ) scores , intraocular pressure , and cataract progression . RESULTS In this preliminary report , we give the results for 12 patients who had a follow-up of at least 3 months . Seven of them were followed up for 6 months . Before injection , CMT was 509.6+/-143.5 microm ( mean + /- st and ard deviation [ SD ] ) in injected eyes , versus 474.4+/-82.6 microm in control eyes . Four weeks after injection , it was 207.3+/-44.2 microm in injected eyes and 506.7+/-122.4 microm in control eyes ( P<0.001 , bilateral Wilcoxon test for paired sample s ) , and after 12 weeks , 207+/-96.7 microm and 469.3+/-117.6 microm , respectively ( P = 0.005 ) . The difference between the CMTs of injected and control eyes was no longer significant at 24 weeks because of the recurrence of macular edema in 5 of 12 injected eyes . Before triamcinolone injection , the ETDRS score was 47.8+/-13 ( mean + /- SD ; range , 28 - 66 ) in injected eyes , versus 51.9+/-14.6 ( range , 31 - 71 ) in control eyes . Twelve weeks thereafter , the corresponding values were 52.7+/-10.8 ( range , 34 - 70 ) and 50.8+/-14.3 ( range , 29 - 69 ) , respectively , and at 24 weeks , 54.7+/-7.6 ( range , 47 - 68 ) and 50.6+/-18.4 ( range , 28 - 71 ) . At no time was the difference between the ETDRS scores for injected and control eyes significant . In 6 of the 12 injected eyes , intraocular pressure exceeded 25 mmHg , and was controlled by topical medication . CONCLUSION Intravitreal injection of triamcinolone effectively reduces macular thickening due to diffuse diabetic macular edema , at least in the short term . Further studies are required to demonstrate that it provides visual benefit PURPOSE To compare the effectiveness of posterior sub-Tenon 's infusion ( STi ) and intravitreal injection ( IVI ) of triamcinolone acetonide ( TA ) for treatment of refractory diffuse diabetic macular edema . METHODS Thirty-six phakic diabetic patients with refractory diffuse diabetic macular edema were prospect ively enrolled . Patients r and omly received either 40 mg STi or 4 mg IVI of TA . Comprehensive ophthalmic evaluation was performed at baseline and 1 , 2 , 4 , 8 + /- 1 , 12 + /- 2 and 24 + /- 2 weeks after treatment . Macular morphologic changes detected by optical coherence tomography and visual acuity , intraocular pressure , and lens status were evaluated . RESULTS Twenty-eight patients ( 28 eyes ) completed the 24-week study . Central macular thickness was significantly reduced in the IVI group when compared with the STi group at 2 , 4 , 8 , 12 , and 24 weeks after treatment ( P < 0.01 ) . Mean visual acuities ( in logarithm of the minimum angle of resolution [ logMAR ] ) at week-4 , -8 , and -12 follow-up examinations were significantly higher in the IVI group ( 0.74 , 0.75 , and 0.82 , respectively ) when compared with the STi group ( 0.88 , 0.88 , and 0.90 , respectively ; P < 0.01 ) . A significant change from baseline in mean intraocular pressure ( mm Hg ) was seen at weeks 4 ( + /-3.21 ) and 8 ( + /-3.35 ) in STi the group ( P < 0.01 ) , and at week 8 ( + /-2.78 ) in the IVI group ( P < 0.05 ) . No patient had cataract progression during the study . CONCLUSIONS Although the number of patients and length of follow-up in this preliminary study were limited , the changes in central macular thickness and visual acuity observed after treatment suggest that IVI TA may be more effective than STi for the management of refractory diffuse diabetic macular edema . Further studies are needed to confirm these preliminary findings OBJECTIVE The epidemiological risk factors for the different forms of diabetic macular edema ( focal or diffuse ) are not differentiated in the literature . In the present study , the objective was to determine which risk factors influence the appearance of focal or diffuse macular edema . RESEARCH , DESIGN , AND METHODS : A 4-year prospect i ve study in a population of Type II diabetic patients ( NIDDM ) in three groups , the first with 29 patients with diffuse diabetic macular edema ( Group A ) , the second with 32 patients with focal macular edema ( Group B ) , and the third with 32 patients with diabetic retinopathy but without diabetic macular edema ( Group C ) ; the three groups were selected on the basis of sex , age , and duration of diabetes with similar patterns . We studied the following risk factors : treatment of diabetes mellitus by insulin , presence of diastolic blood hypertension , presence of microalbuminuria or diabetic nephropathy , levels of HbA1c , type of diabetic retinopathy , presence of previous panretinal photocoagulation , and levels of triglycerides and fractions of cholesterol . RESULTS In discriminant analysis and in order of importance , the epidemiological risk factors for Group A were the following : presence of panretinal laser , diastolic blood hypertension , diabetic nephropathy , and insulin treatment ; for group B , the risk factors were the following : insulin treatment , presence of diastolic blood hypertension , and high levels of glycated haemoglobin ( HbA1c ) ; and for group , C the risk factors were the following : diastolic blood hypertension , insulin treatment of diabetes , and high levels of HbA1c . CONCLUSIONS In the present study , the group of patients with focal macular edema were epidemiologically similar to the group of patients with diabetic retinopathy without macular edema , the group of patients with diffuse macular edema were epidemiologically different OBJECTIVE To evaluate the clinical outcome of an intravitreal injection of triamcinolone acetonide as treatment of diffuse diabetic macular edema . PARTICIPANTS This prospect i ve , interventional , clinical case series study included 20 patients ( 26 eyes ) who received an intravitreal injection of 25 mg of triamcinolone acetonide for treatment of diffuse diabetic macular edema . Mean + /- SD follow-up time was 6.64 + /- 6.10 months . The study group was compared with a control group of 16 patients who underwent macular grid laser coagulation . MAIN OUTCOME MEASURES Visual acuity and intraocular pressure . RESULTS In the study group , visual acuity improved significantly ( P<.001 ) , from 0.12 + /- 0.08 at baseline to a maximum of 0.19 + /- 0.14 during follow-up . Seventeen ( 81 % ) of 21 eyes with a follow-up period of more than 1 month had improved visual acuity . In the control group , visual acuity did not change significantly . In the study group , intraocular pressure increased significantly ( P<.001 ) , from 16.9 + /- 2.5 mm Hg to a mean maximal value of 21.3 + /- 4.7 mm Hg , and decreased significantly ( P = .03 ) to 17.7 + /- 4.7 mm Hg at the study 's end . CONCLUSION Intravitreal injection of 25 mg of triamcinolone acetonide may be beneficial for improving visual acuity in patients with clinical ly significant diffuse diabetic macular edema Aim : To evaluate the effect of different doses of intravitreal triamcinolone acetonide on diffuse diabetic macular oedema . Methods : The prospect i ve , r and omised , double masked , clinical interventional study included 27 eyes ( 27 patients ) with diffuse diabetic macular oedema . They were r and omly divided into three study groups receiving an intravitreal injection of filtered triamcinolone acetonide of about 2 mg ( n = 8 eyes ) , 5 mg ( n = 10 ) , or 13 mg ( n = 9 ) , respectively . Dosage measurement was performed before filtration . Mean follow up was 6.6 ( SD 2.4 ) months ( 3–12 months ) . Main outcome measures were visual acuity and intraocular pressure . Results : Maximal increase in visual acuity was significantly ( p = 0.046 ; 95 % CI : 0.032 to 2.99 ; r = 0.38 ) correlated with the dosage of intravitreal triamcinolone acetonide . Additionally , the duration of the effect of intravitreal triamcinolone acetonide increased significantly with the dosage of intravitreal triamcinolone acetonide ( r = 0.45 ; p = 0.014 ) . Increase in intraocular pressure during follow up was statistically not significantly associated with the dosage used ( p = 0.77 ) . Conclusions : In patients with diffuse diabetic macular oedema receiving intravitreal triamcinolone acetonide , treatment response may last longer and be more pronounced with a dosage of 13 mg than in lower doses of 5 mg or 2 mg . Triamcinolone acetonide induced increase in intraocular pressure may not be markedly associated with the dosage used PURPOSE To report on visual outcome of patients receiving intravitreal triamcinolone acetonide for treatment of diffuse diabetic macular edema . DESIGN Prospect i ve , comparative clinical interventional study . METHODS SETTING Institutional . patient population : The study included 25 consecutive patients ( 50 eyes ) with bilateral diabetic macular edema . Intervention procedure : Unilateral intravitreal injection of about 20 mg triamcinolone acetonide into the eye ( study group ) more severely affected by diabetic maculopathy . The contralateral eyes served as control group . Mean follow-up was 7.1 + /- 4.1 months . MAIN OUTCOME MEASURE Visual acuity , intraocular pressure . RESULTS In the study group , visual acuity increased significantly ( P < or = .001 ) by 3.0 + /- 2.6 Snellen lines to a peak at two to six months after the injection , and decreased significantly ( P = .001 ) towards the end of follow up . At the end of follow-up , visual acuity was higher , not significantly ( P = .18 ) higher , than at baseline . An increase in visual acuity was found in 23 eyes ( 92 % ) . In the control group , differences between visual acuity at baseline and at any of the re-examinations during follow-up were not significant ( P > .10 ) . In an intra-individual inter-eye comparison , gain in visual acuity was significantly ( P < .05 ) higher in the injected eyes , for the measurements obtained up to four months after injection . CONCLUSIONS Intravitreal triamcinolone acetonide may temporarily increase visual acuity in eyes with diabetic macular edema PURPOSE The aim of this study was to examine the visual outcome of patients receiving an intravitreal injection of triamcinolone acetonide ( TA ) as treatment of diffuse diabetic macular edema ( DDME ) . METHODS This prospect i ve , placebo-controlled , r and omized , clinical interventional study included 40 eyes ( 38 patients ) with DDME , with 28 ( 70 % ) eyes r and omized to treatment and 12 ( 30 % ) eyes r and omized to receive a placebo injection . Thirty-six ( 36 ) ( 90 % ) eyes completed the 3-month study visit , and 32 ( 80 % ) eyes completed the 6-month study visit . The treatment group received an intravitreal injection of approximately 20 mg of TA . RESULTS Visual acuity increased significantly ( P < 0.001 ) in the study group by 3.4 + /- 2.5 Snellen lines . In the control group , visual acuity did not change significantly ( P = 0.07 ) during follow-up . Difference in change of best visual acuity was significant ( P < 0.001 ) between both groups . At 3 months after baseline , 11 ( 11/26 ; 42 % ) eyes and 10 ( 10/26 ; 39 % ) eyes , respectively , improved by at least 2 and 3 lines , respectively , in the study group , versus 2 ( 2/10 ; 20 % ) eyes and 1 ( 1/10 ; 10 % ) eye in the control group . At 6 months after baseline , 11 ( 11/23 ; 48 % ) eyes and 9 ( 9/23 ; 39 % ) eyes , respectively , improved by at least 2 and 3 lines , respectively , in the study group , versus 0 ( 0 % ) eyes and 0 ( 0 % ) eyes in the control group . The difference was significant for the 2-line improvement ( P = 0.01 ) and 3-line improvement ( P = 0.03 ) . CONCLUSIONS Using a dosage of approximately 20 mg of intravitreal TA , visual acuity temporarily increases for 6 months after injection PURPOSE To evaluate the outcome of cystoid macular edema ( CME ) treated with intravitreal injections of triamcinolone acetonide ( TA ) , macular laser grid photocoagulation ( MLG ) , or both ( TA+MLG ) . DESIGN Prospect i ve , r and omized , interventional , parallel , three-arm clinical trial . METHODS SETTING Institutional clinical study . PATIENTS Fifty-six patients ( 63 eyes ) affected by diabetic or retinal vein occlusion CME . PROCEDURES Twenty-two eyes received intravitreal injections of 4 mg TA ; 21 eyes underwent MLG ; and 20 eyes received intravitreal injection of 4 mg TA , and after 3 months , MLG . MAIN OUTCOME MEASURES Best-corrected visual acuity ( VA ) , central macular thickness ( CMT ) ( by optical coherence tomography ) , and postoperative complications . RESULTS Mean follow-up was 9 + /- 2 months ( range 6 to 12 months ) . Baseline VA ( logarithm of minimal angle of resolution [ logMAR ] ) and CMT were , respectively , 0.82 + /- 0.19 and 556 + /- 139 microm microns for the TA group , 0.84 + /- 0.15 and 601 + /- 102 microm microns for the MLG group , and 0.83 + /- 0.22 and 573 + /- 106 microm microns for the TA+MLG group ( no statistically significant difference among the groups ) . After the treatment , at 45 days , 3 , 6 , and 9 months in the TA group , VA had improved ( P = .004 ) by 0.26 , 0.25 , 0.22 , and 0.23 logMAR and CMT had decreased by 37 % , 33 % , 29 % , and 31 % ( P = < .001 ) . In the MLG group , VA was unchanged although CMT had decreased by 5 % , 13 % , 14 % , and 16 % ( P = .021 ) . In the TA+MLG group , VA had improved ( P = .003 ) by 0.26 , 0.24 , 0.19 , and 0.20 logMAR , and CMT had decreased by 36 % , 34 % , 28 % , and 29 % ( P = < .001 ) . The groups receiving triamcinolone had better VA and lower CMT values at all time points ( P < .05 ) . A reinjection was performed in eight eyes ; intraocular pressure increased in nine eyes ( treated with medical therapy ) , and cataract progressed in one eye . No injection-related complications occurred . CONCLUSIONS TA intravitreal injection improves VA and reduces CMT more than MLG , which in triamcinolone-treated eyes does not offer further advantages . Intravitreal TA injection could be used as primary treatment in patients with CME OBJECTIVE To report 2-year safety and efficacy outcomes from a trial of intravitreal triamcinolone acetonide ( TA ) injections ( 4 mg ) in eyes with diabetic macular edema and impaired vision that persisted or recurred after laser treatment . DESIGN Prospect i ve , double-masked , placebo-controlled , r and omized clinical trial . PARTICIPANTS AND CONTROLS Sixty-nine eyes of 43 patients were entered into the study , with 34 eyes r and omized to receive active treatment and 35 placebo . Two-year data were available for 60 of 69 ( 87 % ) eyes of 35 of 41 ( 85 % ) patients ; 9 eyes of 6 patients were lost to follow-up , of which 6 received a placebo and 3 received intravitreal TA . INTERVENTION Triamcinolone acetonide ( 0.1 ml ) was injected through the pars plana using a 27-gauge needle . Eyes r and omized to placebo received a subconjunctival injection of saline . MAIN OUTCOME MEASURES Improvement of best-corrected logarithm of the minimum angle of resolution visual acuity ( VA ) by > or = 5 letters after 2 years and incidence of moderate or severe adverse events . RESULTS Improvement of > or = 5 letters ' best-corrected VA was found in 19 of 34 ( 56 % ) eyes treated with intravitreal TA , compared with 9 of 35 ( 26 % ) eyes treated with the placebo ( z(generalized estimating equation ) = 2.73 , P = 0.006 ) . The mean improvement in VA was 5.7 letters ( 95 % confidence interval , 1.4 - 9.9 ) more in the intravitreal TA-treated eyes than in those treated with the placebo . An increase of intraocular pressure ( IOP ) of > or = 5 mmHg was observed in 23 of 34 ( 68 % ) treated versus 3 of 30 ( 10 % ) untreated eyes ( P<0.0001 ) . Glaucoma medication was required in 15 of 34 ( 44 % ) treated versus 1 of 30 ( 3 % ) untreated eyes ( P = 0.0002 ) . Cataract surgery was performed in 15 of 28 ( 54 % ) treated versus 0 of 21 ( 0 % ) untreated eyes ( P<0.0001 ) . Two eyes in the intravitreal TA-treated group required trabeculectomy . There was one case of infectious endophthalmitis in the treatment group . CONCLUSION Intravitreal TA improves vision and reduces macular thickness in eyes with refractory diabetic macular edema . This beneficial effect persists for up to 2 years with repeated treatment . Progression of cataract and elevation of IOP commonly occur but appear manageable . Spontaneous improvement over years can still occur in eyes that are apparently severely affected by diabetic macular edema PURPOSE To compare the safety and efficacy of intravitreal versus posterior Sub-Tenon 's capsule injection of triamcinolone acetonide for diffuse diabetic macular edema . DESIGN Prospect i ve , double-masked , r and omized controlled trial . PARTICIPANTS Twelve patients ( 24 eyes ) with bilateral diffuse diabetic macular edema . INTERVENTION One eye of each patient was r and omly assigned to receive a single 4-mg triamcinolone acetonide intravitreal injection and the fellow eye to receive a 40-mg triamcinolone acetonide posterior Sub-Tenon 's capsule injection . MAIN OUTCOME MEASURES Changes in visual acuity and central macular thickness obtained using optical coherence tomography were measured during a 6-month follow-up . Potential treatment complications were monitored , including increases in intraocular pressure ( IOP ) and cataract progression . RESULTS Both intravitreal and Sub-Tenon 's capsule injections of triamcinolone acetonide result ed in significant but transient improvements in central macular thickness . The mean ( + /-st and ard deviation [ SD ] ) central macular thickness in eyes with intravitreal injection was significantly thinner than in the Sub-Tenon 's capsule-injected eyes at 1 month ( 226.8+/-41.7 microm and 431.5+/-165.8 microm , respectively ; P = 0.002 ) and 3 months ( 242.3 + /- 93.9 microm and 364.7+/-78.2 microm , respectively ; P = 0.005 ) after triamcinolone acetonide injection . The mean visual acuity ( logarithm of the minimum angle of resolution ) in the intravitreally injected eyes was significantly better than in the Sub-Tenon 's capsule-injected eyes at 3 months post injection ( 0.832+/-0.293 and 1.107+/-0.339 , respectively ; P = 0.004 ) . Intraocular pressure did not show any significant difference between the 2 forms of triamcinolone acetonide delivery at any follow-up visit , and no eyes had IOPs > 25 mmHg . CONCLUSIONS The findings from our study neither advocate nor support the use of corticosteroids for the treatment of diabetic macular edema , but do imply that both intravitreal and Sub-Tenon 's capsule injections of triamcinolone acetonide may be equally tolerated , with short-term performance clearly favoring the intravitreal ( 4 mg ) more than the SBT capsule ( 40 mg ) route for the anatomic and functional aspects of improvement tested in this investigation PURPOSE To evaluate prospect ively the efficacy and safety of one intravitreal injection of 4 mg triamcinolone acetonide for refractory diffuse diabetic macular edema . METHODS Seventeen patients with bilateral diabetic macular edema unresponsive to laser photocoagulation . In all patients , one eye was injected , and the other served as a control . The intervention consisted in intravitreal injection of 4 mg triamcinolone acetonide . The main outcome measure was central macular thickness ( CMT ) at 4 , 12 and 24 weeks , measured by Optical Coherence Tomography . Secondary outcomes were Early Treatment Diabetic Rentinopathy Study ( ETDRS ) scores , intraocular pressure and cataract PROGRESSION . RESULTS Before injection , mean + /- SD CMT was 566.4 + /- 182.4 mum in injected eyes . Four , 12 , and 24 weeks after injection , it was 228.4 + /- 47.5 mum , 210.9 + /- 87.2 mum and 358.5 + /- 160.5 mum respectively . CMT was significantly lower in injected eyes vs. control eyes except 24 weeks after injection because of a recurrence of macular edema in 9/17 injected eyes . Mean + /- SD gain in ETDRS score was significantly better in injected eyes vs. control eyes 4 , 12 and 24 weeks after TA injection . In 9 of the 17 injected eyes , intraocular pressure exceeded 24 mmHg and was controlled by topical medication . CONCLUSION In the short-term , intravitreal injection of triamcinolone effectively reduces macular thickening due to diffuse diabetic macular edema and improves visual acuity in most cases . The long-term effect of this treatment and predictive factors of visual recovery remain to be eluci date OBJECTIVE The research ers sought to assess whether the widely used 1994 Cochrane Highly Sensitive Search Strategy ( HSSS ) for r and omized controlled trials ( RCTs ) in MEDLINE could be improved in terms of sensitivity , precision , or parsimony . METHODS A gold st and ard of 1,347 RCT records and a comparison group of 2,400 non-trials were r and omly selected from MEDLINE . Terms occurring in at least 1 % of RCT records were identified . Fifty percent of the RCT and comparison group records were r and omly selected , and the ability of the terms to discriminate RCTs from non-trial records was determined using logistic regression . The best performing combinations of terms were tested on the remaining records and in MEDLINE . RESULTS The best discriminating term was " Clinical Trial " ( Publication Type ) . In years where the Cochrane assessment of MEDLINE records had taken place , the strategies identified few additional unindexed records of trials . In years where Cochrane assessment has yet to take place , " R and omized Controlled Trial " ( Publication Type ) proved highly sensitive and precise . Adding six more search terms identified further , unindexed trials at reasonable levels of precision and with sensitivity almost equal to the Cochrane HSSS . CONCLUSIONS Most reports of RCTs in MEDLINE can now be identified easily using " R and omized Controlled Trial " ( Publication Type ) . More sensitive search es can be achieved by a brief strategy , the Centre for Review s and Dissemination/Cochrane Highly Sensitive Search Strategy ( 2005 revision ) The aim of the present prospect i ve controlled trial was to evaluate the adjuvant role of posterior subtenon triamcinolone in the treatment of diffuse diabetic macular edema ( DDME ) . Thirty one ( 31 ) eyes with DDME were divided into an interventional group subjected to grid laser photocoagulation and 0.5 mL of 40 mg/mL posterior subtenon triamcinolone , and a noninterventional group subjected to grid laser photocoagulation only . Best-corrected visual acuity , contrast sensitivity , and intraocular pressures were assessed at presentation , and at 6 , 12 , and 24 weeks after intervention . The interventional group showed a statistically significant ( p < 0.05 ) change in both mean best corrected visual acuity , from 20/160 to 20/100 ( two-line increase on Early Treatment Diabetic Retinopathy Study ( ETDRS ) ) ( p = 0.024 ) , and mean contrast sensitivity , from 0.9 to 1.09 ( p = 0.01 ) , at the end of 24 weeks . A significant rise in intraocular pressure was not described in any of the patients in either group . Posterior subtenon triamcinolone injection is a useful and safe adjunct to the conventional management of diabetic macular edema Data from the Diabetic Retinopathy Study ( DRS ) show that photocoagulad inhibited the progression of retinopathy . These beneficial effects were noted to some degree in all those stages of diabetic retinopathy which were included in the Study . Some deleterious effects of treatment were also found , including losses of visual acuity and constriction of peripheral visual field . The risk of these harmful effects was considered acceptable in eyes with retinopathy in the moderate or severe retinopathy in the moderate or severe proliferative stage when the risk of severe visual loss without treatment was great . In early proliferative or severe nonproliferative retinopathy , when the risk of severe visual loss without treatment was less , the risks of harmful treatment effects assumed greater importance . In these earlier stages , DRS findings have not led to a clear choice between prompt treatment and deferral of treatment unless and until progression to a more severe stage occurs OBJECTIVE To evaluate a dexamethasone intravitreous drug delivery system ( DDS ) in patients with persistent ( > or = 90 days despite treatment ) macular edema . METHODS This 6-month study r and omized 315 patients with persistent macular edema with best-corrected visual acuity ( BCVA ) of 20/40 to 20/200 in the study eye to observation or a single treatment with dexamethasone DDS , 350 or 700 microg . MAIN OUTCOME MEASURES Proportion of patients achieving a BCVA improvement of 10 or more letters or 15 or more letters , safety measures , change in fluorescein angiographic leakage , and central retinal thickness . RESULTS At day 90 ( primary end point ) , an improvement in BCVA of 10 letters or more was achieved by a greater proportion of patients treated with dexamethasone DDS , 700 microg ( 35 % ) or 350 microg ( 24 % ) , than observed patients ( 13 % ; P<.001 vs 700-microg group ; P = .04 vs 350-microg group ) ; an improvement in BCVA of 15 letters or more was achieved in 18 % of patients treated with dexamethasone DDS , 700 microg , vs 6 % of observed patients ( P = .006 ) . Results were similar in patients with diabetic retinopathy , vein occlusion , or uveitis or Irvine-Gass syndrome . During 3 months of observation , 11 % of treated patients and 2 % of observed patients had intraocular pressure increases of 10 mm Hg or higher . CONCLUSION In persistent macular edema , a single dexamethasone DDS treatment produced statistically significant BCVA improvements 90 days after treatment and was well tolerated for 180 days . Application to Clinical Practice Dexamethasone DDS , 700 microg , may have potential as a treatment for persistent macular edema Diabetic macular edema can be classified into a focal variety , characterized by focal leakage from microaneurysms , often with accumulation of extravascular lipoprotein in a circinate pattern around the focal leakage , and a diffuse variety , with diffuse leakage from retinal vessels often accompanied by cystoid macular changes . Laser photocoagulation is directed at microaneurysms for focal leakage and is applied in a grid pattern for diffuse leakage . Several prospect i ve r and omized clinical trials have shown that laser-treated eyes fare better than untreated eyes : there is a higher rate of modest visual improvement and a lower rate of visual deterioration in eyes treated with laser photocoagulation . In patients with diabetic macular edema , especially the diffuse variety , systemic factors also may play a pathogenic role . Fluid retention and hypertension due to cardiovascular and renal disease exacerbate retinal capillary leakage . Correction of systemic abnormalities ( reduced blood pressure , diuresis ) may reduce macular edema and should be included as part of the total management of patients with diabetic macular edema OBJECTIVE To determine whether an intravitreal injection of triamcinolone acetonide for persistent diabetic macular edema after adequate laser treatment improves visual acuity . DESIGN Prospect i ve , double-masked , placebo-controlled , r and omized clinical trial . PARTICIPANTS AND CONTROLS Sixty-nine eyes of 43 patients were entered into the study , with 34 eyes r and omized to receive active treatment and 35 r and omized to receive a placebo injection . Sixty-five of 69 eyes ( 94 % ) completed the 3-month study visit . INTERVENTION Using a 27-gauge needle , 0.1 ml of triamcinolone acetonide was injected through the pars plana . The procedure was performed in a minor procedures area in the outpatient clinic under sterile conditions and using topical and subconjunctival anesthesia . Eyes r and omized to placebo received a subconjunctival saline injection using the identical procedure for preparation . MAIN OUTCOME MEASURES The main outcome measures were improvement of best-corrected logarithm of the minimum angle of resolution visual acuity by 5 or more letters and incidence of moderate or severe adverse events . RESULTS Eighteen of 33 eyes ( 55 % ) treated with triamcinolone gained 5 or more letters of best-corrected visual acuity compared with 5 of 32 eyes ( 16 % ) treated with placebo ( P = 0.002 ) . Macular edema was reduced by 1 or more grade s as determined by masked semiquantitative contact lens examination in 25 of 33 treated eyes ( 75 % ) versus 5 of 32 untreated eyes ( 16 % ; P<0.0001 ) . Optical coherence tomography showed a mean reduction of central retinal thickness of 152 mum in the 21 treated eyes that were examined compared with a reduction of 36 mum in 20 placebo-treated eyes . Infectious endophthalmitis developed in 1 triamcinolone-treated eye that was treated adequately without loss of visual acuity . CONCLUSIONS In the short term , intravitreal triamcinolone is an effective and relatively safe treatment for eyes with diabetic macular edema that have failed laser treatment . Although it will be essential to study longer-term outcomes , the use of intravitreal triamcinolone may be considered in 1 eye of patients who continue to lose vision from diabetic macular edema despite conventional management |
697 | 24,249,483 | AUTHORS ' CONCLUSIONS We found no evidence to make an informed decision about PROMs for follow-up after gynaecological cancer . | BACKGROUND Cancer is a leading cause of death worldwide .
Gynaecologic cancer treatment is known to have the potential for a major impact on quality of life ( QoL ) .
Patient-reported outcome measures ( PROMs ) is an umbrella term that covers a range of potential types of measurement but is used specifically to refer to self reports by the patient of their health and well-being .
Use of QoL and cancer-specific question naires as alternatives to follow-up may have immense psychological benefit to the patient and cost benefit to the healthcare system .
OBJECTIVES To evaluate the effectiveness of PROMs as an alternative to routine follow-up of women after treatment for gynaecological cancers to identify recurrences , affect overall survival and assess psychological benefit . | The objective of our study was to compare prospect ively the QoL in long‐term ovarian cancer survivors with short‐term survivors and to explore discriminating variables between short‐term and long‐term survival . Thirty‐three patients were included , 22 died within 5 years post diagnosis and 11 survived beyond 10 years . QoL data were collected pre‐treatment ( baseline ) , 1‐year post diagnoses and for long‐term survivors 10 years post‐treatment using the EORTC QLQ‐C30 . At baseline , there was no difference in terms of FIGO stage , residual tumor and adjuvant chemotherapy . Significantly , more short‐term survivors ( 96 % ) had intra operative ascites as compared to long‐term survivors ( 55 % ) ( p=0.01 ) . Before treatment , short‐term survivors had clinical ly significantly lower QoL scores on the physical functioning ( mean 75.45 ) and role functioning scale ( mean 68.94 ) compared to long‐term survivors ( mean 68.94 and 84.85 , respectively ) . They also reported higher levels of symptoms . One year post‐diagnosis , QoL scores were comparable in most domains . Long‐term survivors had a significantly better global QoL but more insomnia . Emotional functioning and global QoL/health status improved significantly from baseline to 1‐year post‐diagnosis and remained relatively stable at the 10‐year follow‐up . The presence of intra operative ascites and a supporting social network were identified as significant variables that discriminated between short‐term and long‐term survival . Compared to a reference sample , long‐term survivors showed similar QoL scores but more dyspnoea . Although ovarian cancer patients do not belong to the most prevalent survivor population s , we found that long‐term survivors have QoL scores similar to females without a history of cancer Background Surgeons , along with the Centers for Disease Control and Prevention , emphasize the importance of managing symptoms and improving the quality of life of cancer survivors . A 2008 meta- analysis of mindfulness-based stress reduction ( MBSR ) concluded that this technique might improve patients ’ adjustment to their disease . However , r and omized controlled trials using st and ardized measures for evaluating MBSR are limited . The primary objective of this study was to evaluate , using valid and reliable measures , the effects of a unique , interactive , 8-week cancer recovery and wellness program on symptoms and quality of life of female cancer survivors . Methods Sixty-eight female cancer patients were r and omized into either an intervention or waitlisted control group . Patients were evaluated using the Symptoms Checklist ( SCL-90-R ) , the European Organization for Research and Treatment of Cancer Quality of Life Question naire ( EORTC QLQ-30 ) , and the Symptoms of Stress Inventory ( SOSI ) . Results Of the participants , 70.6 % were breast cancer survivors . Mean age was 57.5 years ( treatment group ) and 56.4 years ( control group ) . Between-group demographic differences were not significant ( P > 0.6 ) . The treatment group improved significantly on the EORTC QLQ-30 ( P = 0.005 ) , on six of the eight SOSI subscales ( P ≤ 0.049 ) , and on both SCL-90-R subscales ( P ≤ 0.023 ) , while the control group did not improve on any of these measures ( P > 0.2 ) . Conclusion The MBSR-based cancer recovery and wellness intervention improved the symptoms and quality of life of this largely breast cancer survivor population across a variety of cancer symptoms and quality -of-life measures OBJECTIVE The aims of this study were to compare the quality of life ( QOL ) of women with different cancer sites ; to identify predictors of QOL ; and to examine the agreement between patient self-reported QOL and QOL ratings provided by clinicians and significant others . METHODS A prospect i ve study was conducted including 248 patients with gynecologic and breast cancer . QOL data were collected at six time points before , during , and after treatment , using the EORTC QLQ-C30 and the Spitzer QL index ( QL-I ) . RESULTS Baseline assessment s showed comparable QOL scores among patients with different gynecologic malignancies and breast cancer . During active treatment breast cancer patients had significantly higher mean scores in physical functioning compared to women with gynecologic cancers and higher scores in role functioning compared to patients with cervical cancer . After completion of treatment there were no statistically significant differences in QOL among the groups . For all women , global QOL and emotional functioning were mostly affected during and after treatment . Regression analysis showed that patients ' global QOL was significantly predicted by severity of surgery ( t = 3.903 , P < 0.01 ) and pretreatment performance status ( t = 3.116 , P = < 0.01 ) . Comorbidity , family support , number of treatments , age , and stage of disease were not predictive . The comparison of patient self-rated QOL and observer-rated QOL showed that the QL-I mean scores of health providers and relatives were generally in close agreement with those of patients . Intraclass correlations were moderate to high during active treatment and excellent after completion of treatment . CONCLUSION In female cancer patients , global QOL and emotional functioning are mostly affected during the course of disease , independent of their diagnosis . Significant others and health professionals are able to provide useful information on QOL of patients recovering from cancer The objective of this study was to determine current practice with regards to follow-up after gynecological malignancy . A question naire survey of all lead clinicians in gynecological cancer centers in Engl and was done . The most common duration of routine follow-up was 5 years for all of the main gynecological cancers ( ovarian , endometrial , vulval , and cervical ) . The most common follow-up patterns were three monthly for 2 years then six monthly for 3 years after ovarian cancer ; three monthly for the first year , four monthly for the second year , six monthly for the third year then annually for 1 year after endometrial cancer ; three monthly for the first year , four monthly for the second year , six monthly for the third and fourth years , then annually for 1 year after vulval cancer ; three monthly for the first year , four monthly for the second year , six monthly for the third and fourth years , then annually for 1 year after cervical cancer . The test for CA125 was routinely performed by 67 % of cancer networks to detect recurrence after ovarian cancer . Routine follow-up after gynecological cancer continues to be st and ard practice , despite limited evidence to support its use . Prospect i ve research is needed to determine best practice The aim of this study was to derive population -based norms for women completing the EORTC QLQ-C30 version 1 which is design ed for use with patients who have cancer . The study was conducted using two different question naires : one design ed for use in female patients with breast cancer , the other for those with gynaecological cancers , but both including the EORTC QLQ-C30 . The women were drawn from the Danish Central Population Register without knowledge of their health status and divided at r and om between the two question naires . All procedures for collecting data were identical . The response rate for those receiving the gynaecological cancer ( GS ) question naire was 49 % and it was 71 % for the breast cancer ( BS ) question naire . Detailed comparison between the two sample s revealed several EORTC QLQ-C30 items showing a clear difference in distribution of scores between them . Because of this and the possible bias due to the relative low age-related response rate in GS , only the results from the BS are used for constructing norms . The norms cover all 30 single items on the EORTC QLQ-C30 and the nine derived scales , for women in four 10-year age groups commencing at 30 years and for those aged 70 - 75 . Clear trends in , for example , declining ability to undertake strenuous activity are illustrated and quantified . Levels of certain symptoms , such as pain , are surprisingly high although it is recognized that the population sample d will contain a proportion of women with active disease including cancer . We recommend the use of these norms both as an aid to the clinical assessment of an individual patient , and to assist in the interpretation of clinical trial and longitudinal quality of life data . As a secondary result , we note that a population -based sample will have a lower response rate to a question naire with more questions , especially if many of these extra questions are on sexual issues This study defines the psychometric properties of the European Organisation for Research and Treatment of Cancer ( EORTC ) quality of life ( QOL ) question naire design ed to measure the QOL of patients with ovarian cancer . The ovarian cancer module ( EORTC QLQ-OV28 ) was developed to supplement the EORTC QLQ-C30 . The core question naire and the QLQ-OV28 were prospect ively administered to 368 ovarian cancer patients after they had been treated with radical or debulking surgery followed by chemotherapy . The QLQ-OV28 module assesses abdominal/gastrointestinal symptoms , peripheral neuropathy , other chemotherapy side-effects , hormonal/menopausal symptoms , body image , attitude to disease/treatment and sexual functioning . Question naires were well accepted by patients , baseline compliance rates were 86 % , 72 % provided a second assessment , less than 3 % of the items had missing data . Multi-trait scaling analyses confirmed the hypothesised scales . All hypothesised scales exhibited good psychometric properties . These results support the clinical and psychometric validity of the EORTC QLQ-OV28 module as a supplement to the EORTC QLQ-C30 |
698 | 24,816,503 | All included studies on exercise therapy , and most of the studies on interventions combined with patient education , reported a positive effect on pain , disability , and /or sick leave . | OBJECTIVES To review and assess the peer- review ed literature on the effectiveness of physical therapy interventions in treating lumbopelvic pain during pregnancy .
BACKGROUND Current guidelines on interventions for lumbopelvic pain during pregnancy differ in their recommendations for assessment and intervention .
Recent publications may allow revising current recommendations for the treatment of this complex problem . | Background This pilot r and omized controlled trial evaluated the feasibility of conducting a full scale study and compared the efficacy of exercise , spinal manipulation , and a mind-body therapy called Neuro Emotional Technique for the treatment of pregnancy-related low back pain , a common morbidity of pregnancy . Methods Healthy pregnant women with low back pain of insidious onset were eligible to enroll in the study at any point in their pregnancy . Once enrolled , they remained in the study until they had their babies . Women were r and omly allocated into one of three treatment groups using opaque envelopes . The treatment schedule paralleled the prenatal care schedule and women received individualized intervention . Our null hypothesis was that spinal manipulation and Neuro Emotional Technique would perform no better than exercise in enhancing function and decreasing pain . Our primary outcome measure was the Rol and Morris Disability Question naire and our secondary outcome measure was the Numeric Pain Rating Scale . Intention to treat analysis was conducted . For the primary analysis , regression was conducted to compare groups on the outcome measure scores . In a secondary responder analysis , difference in proportions of participants in attaining 30 % and 50 % improvement were calculated . Feasibility factors for conducting a future larger trial were also evaluated such as recruitment , compliance to study protocol s , cost , and adverse events . Results Fifty-seven participants were r and omized into the exercise ( n = 22 ) , spinal manipulation ( n = 15 ) , and Neuro Emotional Technique ( n = 20 ) treatment arms . At least 50 % of participants in each treatment group experienced clinical ly meaningful improvement in symptoms for the Rol and Morris Disability Question naire . At least 50 % of the exercise and spinal manipulation participants also experienced clinical ly meaningful improvement for the Numeric Pain Rating Scale . There were no clinical ly meaningful or statistically significant differences between groups in any analysis . Conclusions This pilot study demonstrated feasibility for recruitment , compliance , safety , and affordability for conducting a larger study in the future . Spinal manipulation and exercise generally performed slightly better than did Neuro Emotional Technique for improving function and decreasing pain , but the study was not powered to detect the between-group differences as statistically significant . Trial registration Clinical Trials.gov ( Identifier : NCT00937365 ) OBJECTIVE Pregnancy-related lumbopelvic pain is a major problem for the majority of pregnant women . Complementary medicine has been used to alleviate pain , and yoga is one of the most commonly chosen alternative methods . The objective of this study was to assess the effectiveness of Hatha yoga in the reduction of lumbopelvic pain in pregnancy . METHODS A r and omized controlled trial with 60 pregnant women ( age range , 14 - 40 years ) who reported lumbopelvic pain at 12 to 32 weeks of gestation was conducted from June 2009 to June 2011 . Pregnant women who had twin pregnancies , had medical restrictions for exercise , used analgesics , and participated in physical therapy were excluded from the study . Pregnant women were divided into two groups : the yoga group , practicing exercises guided by this method , and the postural orientation group , performing st and ardized posture orientation according to instructions provided in a pamphlet . Treatment in each group lasted 10 weeks . A visual analog scale ( VAS ) was used to measure pain intensity . Lumbar pain and posterior pelvic pain provocation tests were used to confirm the presence of pain . Statistical analysis included the Mann-Whitney test , the McNemar test , a paired Wilcoxon test , and analysis of covariance . RESULTS The median pain score was lower in the yoga group ( p<.0058 ) than the postural orientation group . Lumbar pain provocation tests showed a decreased response in relation to posterior pelvic pain provocation tests and a gradual reduction in pain intensity during 10 yoga sessions ( p<.024 ) . CONCLUSIONS The yoga method was more effective at reducing lumbopelvic pain intensity compared with postural orientation OBJECTIVE To investigate the effect of an exercise program , including specific stabilizing exercises , on pain intensity and functional ability in women with pregnancy-related low back pain . METHODS Fifty women between 16 and 24 weeks of pregnancy were recruited at Tygerberg and Paarl Hospitals , Western Cape , South Africa . Twenty-six women were r and omized to a 10-week exercise program and 24 were r and omized as controls . RESULTS Overall , the most frequent type of back pain experienced was lumbar pain ( 36 [ 72.0 % ] ) . Pain intensity ( P=0.76 ) and functional ability ( P=0.29 ) were comparable between the groups on study entry . In the study group , there was a significant improvement in pain intensity ( P<0.01 ) and an improvement in functional ability ( P=0.06 ) at the end of the study . In the control group , there were no significant changes in pain intensity ( P=0.89 ) or functional ability ( P=0.70 ) at the end of the study . CONCLUSION A specific exercise program decreased back pain intensity and increased functional ability during pregnancy in South African women with lumbar and pelvic girdle pain Eighty-four depressed pregnant women were recruited during the second trimester of pregnancy and r and omly assigned to a massage therapy group , a progressive muscle relaxation group or a control group that received st and ard prenatal care alone . These groups were compared to each other and to a non-depressed group at the end of pregnancy . The massage therapy group participants received two 20 min therapy sessions by their significant others each week for 16 weeks of pregnancy , starting during the second trimester . The relaxation group provided themselves with progressive muscle relaxation sessions on the same time schedule . Immediately after the massage therapy sessions on the first and last days of the 16-week period the women reported lower levels of anxiety and depressed mood and less leg and back pain . By the end of the study the massage group had higher dopamine and serotonin levels and lower levels of cortisol and norepinephrine . These changes may have contributed to the reduced fetal activity and the better neonatal outcome for the massage group ( i.e. lesser incidence of prematurity and low birthweight ) , as well as their better performance on the Brazelton Neonatal Behavior Assessment . The data suggest that depressed pregnant women and their offspring can benefit from massage therapy Objective . To study lumbopelvic pain in women r and omized to a regular exercise program during pregnancy in comparison to women receiving st and ard antenatal care . Design . A two‐armed , two‐center , r and omized controlled trial . Setting . St Olavs Hospital , Trondheim University Hospital and Stavanger University Hospital . Population . A total of 855 pregnant women were r and omized to intervention or control groups . Methods . The intervention was a 12 week exercise program , including aerobic and strengthening exercises , conducted between 20 and 36 weeks of pregnancy . One weekly group session was led by physiotherapists , and home exercises were encouraged twice a week . The control group received st and ard antenatal care . Main outcome measures . Self‐reports of lumbopelvic pain and sick leave due to lumbopelvic pain . The data were analysed according to the “ intention‐to‐treat ” principle . Results . There were no significant differences between groups of women reporting lumbopelvic pain at 36 weeks ( 74 vs. 75 % , p=0.76 ) . The proportion of women on sick leave due to lumbopelvic pain was lower in the intervention group ( 22 % vs 31 % , p=0.01 ) . Conclusions . Exercise during pregnancy does not influence the prevalence of lumbopelvic pain , but women offered a regular exercise course seem to h and le the disorder better Background Absence of knowledge of pregnancy-related pelvic girdle pain ( PPGP ) has prompted the start of a large cohort study in the Netherl and s. The objective of this study was to investigate the prevalence and incidence of PPGP , to identify risk factors involved in the onset and to determine the prognosis of pregnancy-related pelvic girdle pain . Methods / design 7,526 pregnant women of the southeast of the Netherl and s participated in a prospect i ve cohort study . During a 2-year period , they were recruited by midwives and gynecologists at 14 weeks of pregnancy . Participants completed a question naire at baseline , at 30 weeks of pregnancy , at 2 weeks after delivery , at 6 months after delivery and at 1 year after delivery . The study uses extensive question naires with questions ranging from physical complaints , limitations in activities , restriction in participation , work situation , demographics , lifestyle , pregnancy-related factors and psychosocial factors . Discussion This large-scale prospect i ve cohort study will provide reliable insights in incidence , prevalence and factors related to etiology and prognosis of pregnancy-related pelvic girdle pain OBJECTIVE Women commonly experience low back pain during pregnancy . We examined whether a multimodal approach of musculoskeletal and obstetric management ( MOM ) was superior to st and ard obstetric care to reduce pain , impairment , and disability in the antepartum period . STUDY DESIGN A prospect i ve , r and omized trial of 169 women was conducted . Baseline evaluation occurred at 24 - 28 weeks ' gestation , with follow-up at 33 weeks ' gestation . Primary outcomes were the Numerical Rating Scale ( NRS ) for pain and the Quebec Disability Question naire ( QDQ ) . Both groups received routine obstetric care . Chiropractic specialists provided manual therapy , stabilization exercises , and patient education to MOM participants . RESULTS The MOM group demonstrated significant mean reductions in Numerical Rating Scale scores ( 5.8 ± 2.2 vs 2.9 ± 2.5 ; P < .001 ) and Quebec Disability Question naire scores ( 4.9 ± 2.2 vs 3.9 ± 2.4 ; P < .001 ) from baseline to follow-up evaluation . The group that received st and ard obstetric care demonstrated no significant improvements . CONCLUSION A multimodal approach to low back and pelvic pain in mid pregnancy benefits patients more than st and ard obstetric care OBJECTIVE To study osteopathic manipulative treatment of back pain and related symptoms during the third trimester of pregnancy . STUDY DESIGN A r and omized , placebo-controlled trial was conducted to compare usual obstetric care and osteopathic manipulative treatment , usual obstetric care and sham ultrasound treatment , and usual obstetric care only . Outcomes included average pain levels and the Rol and -Morris Disability Question naire to assess back-specific functioning . RESULTS Intention-to-treat analyses included 144 subjects . The Rol and -Morris Disability Question naire scores worsened during pregnancy ; however , back-specific functioning deteriorated significantly less in the usual obstetric care and osteopathic manipulative treatment group ( effect size , 0.72 ; 95 % confidence interval , 0.31 - 1.14 ; P = .001 vs usual obstetric care only ; and effect size , 0.35 ; 95 % confidence interval , -0.06 to 0.76 ; P = .09 vs usual obstetric care and sham ultrasound treatment ) . During pregnancy , back pain decreased in the usual obstetric care and osteopathic manipulative treatment group , remained unchanged in the usual obstetric care and sham ultrasound treatment group , and increased in the usual obstetric care only group , although no between-group difference achieved statistical significance . CONCLUSION Osteopathic manipulative treatment slows or halts the deterioration of back-specific functioning during the third trimester of pregnancy OBJECTIVE To investigate if water-gymnastics during pregnancy may reduce the intensity of back/low back pain and the number of days on sick-leave . METHODS A prospect i ve , r and omized study . One hundred and twenty-nine women were r and omized to participate in water-gymnastics once a week during the second half of pregnancy and 129 were r and omized to a control group . The women in both groups filled in question naires in gestational weeks 18 , 34 and within the first postpartum week . Every day from week 18 to labor they assessed the intensity of back/low back pain . RESULTS Back pain intensity increased during pregnancy . No excess risk for the pregnancy associated with water-gymnastics was observed . The women participating in water-gymnastics recorded a lower intensity of back/low back pain . The total number of days on sick-leave because of back/low back pain was 982 in the water-gymnastics group ( 124 women ) compared with 1484 in the control group ( 120 women ) . After weeks 32 33 , seven women in the water-gymnastics group compared with 17 in the control group were on sickleave because of back/ low back pain ( p=0.031 ) . CONCLUSIONS Intensity of back/low back pain increased with advancing pregnancy . There was no excess risk for urinary or vaginal infections associated with water-gymnastics . Water-gymnastics during the second half of pregnancy significantly reduced the intensity of back/ low back pain . Water-gymnastics decreased the number of women on sick-leave because of back/low back pain . Water-gymnastics during pregnancy can be recommended as a method to relieve back pain and may reduce the need for sick-leave Lower back pain and lordosis are among the most common complications during pregnancy ; their frequency in pregnant women is 4 times that in non-pregnant women [ 1 ] . The present study evaluated the effect of exercise on back pain during pregnancy . Inclusion criteria were maternal age of 20–30 years ; nulliparity ; gestational age of 16 weeks ( according to reliable last menstrual period and ultrasound confirmation in the first trimester ) ; and no regular exercise before entering the study . Exclusion criteria were any kind of systemic disorder or drug use ; any previous trauma , surgery , or damage to the spine or lower limbs ; any complications of pregnancy such as preterm labor , abortion , or pelvic pain ; and absence from the study exercise program on at least 3 occasions . All eligible women completed the Rol and –Morris question naire [ 2 ] , and lordosis was measured using a flexible ruler and the formula Θ=4 × [a rct an(2H/L ) ] ( Fig. 1 ) ; these measurements were repeated after 1 and 2 months . The participants were r and omly assigned to either the study group or the control group . In the study group ( n=15 ) , there was an initial 1-hour training session in which 7 main exercises — together with preparation and relaxation movements — were taught to the participants , who then performed 30 minutes of exercise 3 times per week Table 1 Prevalence of PAI-1 4G/5 G polymorphisms in the different groups of women studied Abstract Objectives To compare the efficacy of st and ard treatment , st and ard treatment plus acupuncture , and st and ard treatment plus stabilising exercises for pelvic girdle pain during pregnancy . Design R and omised single blind controlled trial . Setting s East Hospital , Gothenburg , and 27 maternity care centres in Sweden . Participants 386 pregnant women with pelvic girdle pain . Interventions Treatment for six weeks with st and ard treatment ( n = 130 ) , st and ard treatment plus acupuncture ( n = 125 ) , or st and ard treatment plus stabilising exercises ( n = 131 ) . Main outcome measures Primary outcome measure was pain ( visual analogue scale ) ; secondary outcome measure was assessment of severity of pelvic girdle pain by an independent examiner before and after treatment . Results After treatment the stabilising exercise group had less pain than the st and ard group in the morning ( median difference = 9 , 95 % confidence interval 1.7 to 12.8 ; P = 0.0312 ) and in the evening ( 13 , 2.7 to 17.5 ; P = 0.0245 ) . The acupuncture group , in turn , had less pain in the evening than the stabilising exercise group ( −14 , −18.1 to −3.3 ; P = 0.0130 ) . Furthermore , the acupuncture group had less pain than the st and ard treatment group in the morning ( 12 , 5.9 to 17.3 ; P < 0.001 ) and in the evening ( 27 , 13.3 to 29.5 ; P < 0.001 ) . Attenuation of pelvic girdle pain as assessed by the independent examiner was greatest in the acupuncture group . Conclusion Acupuncture and stabilising exercises constitute efficient complements to st and ard treatment for the management of pelvic girdle pain during pregnancy . Acupuncture was superior to stabilising exercises in this study Background . The study was design ed to evaluate the analgesic effect and possible adverse effects of acupuncture for pelvic and low‐back pain during the last trimester of pregnancy A single center , prospect i ve , r and omized , single blinded , controlled study comparing the effects and safety of " sitting pelvic tilt exercise " in relieving back pain during the third trimester in primigravida was carried out . The sample s were composed of 67 primigravidas who attended the prenatal clinic at King Chulalongkorn Memorial Hospital . All subjects were selected by the r and om sampling technique and allocated into two groups for the experimental group and the control group ; for 32 and 35 pregnants , respectively . The experimental group received the pelvic tilt exercise program for 8 weeks during the third trimester . Pain intensity was measured by visual analogue scale ( VAS ) at day 0 and day 56 in both groups . The result of the study revealed 1 ) The mean VAS of back pain in the experimental group was significantly lower at day 56 than at day 0 and lower than the control group at day 56 ( p < 0.05 ) by unpaired t-test 2 ) There was no incidence of preterm labor , low birth weight or neonatal complication in the experimental group . In conclusion , the " sitting pelvic tilt exercise " during the third trimester in primigravidas could decrease back pain intensity without incidence of preterm labor , low birth weight or neonatal complication Background Many women have low back pain ( LBP ) or pelvic girdle pain ( PGP ) during pregnancy , but there is limited evidence of effective primary and secondary preventive strategies . Objective The purpose of this study was to investigate whether a group-based exercise program can reduce the prevalence and severity of LBP and PGP in pregnant women . Design An observer-blinded r and omized controlled trial with equal assignments to a training group and a control group was conducted . Setting The study was conducted in primary care maternity units in 2 suburban municipalities in the southeastern part of Norway . Patients The participants were 257 pregnant women who were healthy and between 18 and 40 years of age before gestation week 20 . Intervention The training group received supervised exercises in groups once a week , and the control group received st and ard care . Measurements The main outcome measures were self-reported LBP and self-reported PGP . Secondary outcome measures were pain intensity in the morning and evening , disability , and 8-Item Short-Form Health Survey ( SF-8 ) Physical Component Summary ( PCS ) and Mental Component Summary ( MCS ) scores . Follow-up measurements were performed at gestation weeks 24 , 28 , 32 , and 36 . Results Overall , there was no effect of the program on the prevalence of PGP ( odds ratio=1.03 , 95 % confidence interval [CI]=0.66 to 1.59 ) or LBP ( odds ratio=0.77 , 95 % CI=0.50 to 1.19 ) . For the secondary outcomes , the estimated mean differences between the groups were −0.4 ( 95 % CI=−0.8 to 0.1 ) for pain intensity in the morning , −0.4 ( 95 % CI=−1.0 to 0.2 ) for pain intensity in the evening , −1.0 ( 95 % CI=−2.2 to 0.0 ) for disability , 1.8 ( 95 % CI=0.0 to 3.7 ) for the SF-8 PCS , and −0.6 ( 95 % CI=−2.2 to 1.4 ) for the SF-8 MCS . Limitations Due to low statistical power , the estimates for the primary outcomes are imprecise . Conclusions Supervised group exercise did not reduce the prevalence of LBP or PGP in pregnancy BACKGROUND AND PURPOSE Symphysis pubis pain is a significant problem for some pregnant women . The purpose of this study was to investigate the effects of exercise , advice , and pelvic support belts on the management of symphysis pubis dysfunction during pregnancy . SUBJECTS Ninety pregnant women with symphysis pubis dysfunction were r and omly assigned to 3 treatment groups . METHODS A r and omized masked prospect i ve experimental clinical trial was conducted . Specific muscle strengthening exercises and advice concerning appropriate methods for performing activities of daily living were given to the 3 groups , and 2 of the groups were given either a rigid pelvic support belt or a nonrigid pelvic support belt . The dependent variables , which were measured before and after the intervention , were a Rol and -Morris Question naire score , a Patient-Specific Functional Scale score , and a pain score ( 101-point numerical rating score ) . RESULTS After the intervention , there was a significant reduction in the Rol and -Morris Question naire score , the Patient-Specific Functional Scale score , and the average and worst pain scores in all groups . With the exception of average pain , there were no significant differences between groups for the other measures . DISCUSSION AND CONCLUSION The findings indicate that the use of either a rigid or a nonrigid pelvic support belt did not add to the effects provided by exercise and advice OBJECTIVE The primary aim of this study was to examine whether 1 week of continuous auricular acupuncture could reduce low back and posterior pelvic pain associated with pregnancy . STUDY DESIGN A r and omized controlled trial was conducted on pregnant women who have lower back and posterior pelvic pain . These women were r and omly assigned into an acupuncture group , a sham acupuncture group , or a waiting list control group . All participants were monitored for 2 weeks . RESULTS Baseline and day 7 showed significant group differences in pain ( F = 15 ; P < .0001 ) and in the disability rating index score ( F = 7 ; P < .0001 ) . The participants in the acupuncture group reported a significant reduction of pain and improvement of functional status as compared with those in the sham acupuncture and control groups . CONCLUSION One week of continuous auricular acupuncture decreases the pain and disability experienced by women with pregnancy-related low back and posterior pelvic pain OBJECTIVE Pelvic girdle pain is a common complaint of pregnant women . There are limited data on comparison between the effectiveness of stabilizing exercises and lumbopelvic belt on the treatment of these patients . The objective of this study was to compare the effect of lumbopelvic belt plus information , home based pelvic girdle stabilizing exercises plus information and information alone on pain intensity , functional status and quality of life of pregnant women with pelvic girdle pain . METHODS In this r and omized clinical trial pregnant women with pelvic girdle pain ( n=105 ) were r and omly allocated to three groups ; Control group ( n=35 ) that received general information , exercise group ( n=31 ) that in addition to general information were asked to perform specific pelvic stabilizing exercises at home and belt group ( n=31 ) that received non-rigid lumbopelvic belt and the information . The primary outcome variables were pain intensity and functional status of the participants which were measured using visual analogue scale and Oswestry Disability Index ( ODI ) respectively . Quality of life of participants was measured using WHOQOL-BREF question naire . All measurements were performed at baseline , 3 and 6 weeks after the study conduction . RESULTS The pain intensity of patients in belt group in comparison to other groups was decreased significantly at both 3 and 6 weeks follow-ups . The mean score of ODI of patients in belt group was also improved more than exercise and control groups significantly . CONCLUSIONS On base of our results , it can be found that in short term lumbopelvic belt and information in treatment of pregnant women with pelvic girdle pain is superior to exercise plus information or information alone Background . Prevention of lumbopelvic pain in pregnancy has been sparsely studied . One aim of this study was to assess if a 12‐week training program during pregnancy can prevent and /or treat lumbopelvic pain . A r and omized controlled trial was conducted at Trondheim University Hospital and three outpatient physiotherapy clinics . Three hundred and one healthy nulliparous women were included at 20 weeks of pregnancy and r and omly allocated to a training group ( 148 ) or a control group ( 153 ) . Methods . The outcome measures were self‐reported symptoms of lumbopelvic pain ( once per week or more ) , sick leave , and functional status . Pain drawing was used to document the painful area of the body . The intervention included daily pelvic floor muscle training at home , and weekly group training over 12 weeks including aerobic exercises , pelvic floor muscle and additional exercises , and information related to pregnancy . Results . At 36 weeks of gestation women in the training group were significantly less likely to report lumbopelvic pain : 65/148 ( 44 % ) versus 86/153 ( 56 % ) ( p = 0.03 ) . Three months after delivery the difference was 39/148 ( 26 % ) in the training group versus 56/153 ( 37 % ) in the control group ( p = 0.06 ) . There was no difference in sick leave during pregnancy , but women in the training group had significantly ( p = 0.01 ) higher scores on functional status . Conclusions . A 12‐week specially design ed training program during pregnancy was effective in preventing lumbopelvic pain in pregnancy Study Design . Pragmatic , cross-sectional study . Objective . To assess the interrater reliability of 3 tools used by the Cervical Overview Group ( COG ) for the assessment of the internal validity of r and omized controlled trials ( RCTs ): Jadad , van Tulder , and risk of bias ( RoB ) . Summary of Background Data . For clinicians to implement evidence -based practice , they need to critically appraise health care literature . Checklists , scales , and domain-based criteria exist to evaluate the internal validity of RCTs for rehabilitation studies , but there is a lack of research reporting the reliability of existing assessment tools . Methods . Four members of the COG with multiprofessional and method ological background independently evaluated the internal validity of 54 RCTs using prepiloted Jadad and van Tulder reporting forms , and 18 RCTs using RoB , from June 2003 to May 2009 . The & kgr ; statistic was calculated for each combination of raters and assessment tools . St and ard agreement categorizations were used . Results . For Jadad , 4 of 7 items demonstrated mean & kgr ; statistic ranges from moderate to substantial agreement ( mean values , 0.42–0.78 ) , as did 8 of 11 items on the van Tulder tool ( mean values , 0.44–0.77 ) . The RoB demonstrated moderate to substantial ( mean values , 0.56–0.76 ) agreement on 3 of 12 items . Consistent substantial agreement was found across all assessment tools for the domain “ allocation concealment ” : Jadad 0.69 ( mean range , 0.60–0.77 ) ; van Tulder 0.77 ( mean range , 0.73–0.81 ) ; RoB 0.76 ( mean range , 0.65–0.88 ) ; and moderate to substantial across 2 tools for the domain “ sequence generation ” : van Tulder 0.53 ( mean range , 0.37–0.66 ) and RoB 0.66 ( mean range , 0.45–0.88 ) . Other domains demonstrated slight or fair agreement . Conclusion . Consistent interrater agreement was found across the 3 assessment tools for allocation concealment and for 2 tools for sequence generation . However , users should acknowledge that moderate variation exists within other items requiring more judgment . When evaluating rehabilitation RCTs , clinicians should consider limitations of rating certain items within the selected assessment tool Study Design This study analyzed an education and training program concerning back and pelvic problems among pregnant women . Objective The program was aim ed at reducing tack and pelvic posterior pain during pregnancy . Summary of Background Data Low back and posterior pelvic pain accounts for the majority of sick leave among pregnant women . No previous study has suggested any type of solution to this problem . Methods Four hundred and seven consecutive pregnant women were included in the study and r and omly assigned into three groups . Group A served as controls while different degrees of interventions were made in groups B and C. Results Serious back or posterior pelvic pain developed in 47 % of all women . Pain-related problems were reduced in groups B and C ( P < 0.05 ) , and sick-leave frequency was reduced in group C ( P < 0.01 ) . For some of the women in this group pain intensity was also reduced 8 weeks post partum ( P < 0.005 ) . Weekly physical exercise before pregnancy reduced the risk for back pain problems in pregnancy ( P < 0.05 ) . A non-elastic sacro-illac belt offered some pain relief to 82 % of the women with posterior pelvic pain . Conclusions An individually design ed program reduced sick leave during pregnancy . Working with groups was less effective . Differentiation between low back and posterior pelvic pain was essential . Good physical fitness reduced the risk of back pain in a subsequent pregnency . Reduction of posterior pelvic pain by a non-elastic pelvic support was experienced by 82 % of the women with posterior pelvic pain OBJECTIVE To investigate the effect of exercise during pregnancy on the intensity of low back pain and kinematics of spine . METHOD A prospect i ve r and omized study was design ed . 107 women participated in an exercise program three times a week during second half of pregnancy for 12 weeks and 105 as control group . All filled a question naire between 17 - 22 weeks of gestation and 12 weeks later for assessment of their back pain intensity . Lordosis and flexibility of spine were measured by Flexible ruler and Side bending test , respectively , at the same times . Weight gain during pregnancy , Pregnancy length and neonatal weight were recorded . RESULT Low back pain intensity was increased in the control group . The exercise group showed significant reduction in the intensity of low back pain after exercise ( p<0.0001 ) . Flexibility of spine decreased more in the exercise group ( p<0.0001 ) . Weight gain during pregnancy , pregnancy length and neonatal weight were not different between the two groups . CONCLUSION Exercise during second half of the pregnancy significantly reduced the intensity of low back pain , had no detectable effect on lordosis and had significant effect on flexibility of spine BACKGROUND Although many pregnant women experience back pain , it has not considered an important health problem . No study has investigated the effects of a back-pain-reducing program ( BPRP ) during pregnancy for Korean women . OBJECTIVE The purpose of this study was to evaluate the effect of a program design ed to reduce back pain in pregnant women . METHODS A non-equivalent control-group pretest-posttest design was used . Pregnant women who attended an antenatal clinic and experienced back pain during their pregnancy were included in an intervention group ( n=29 ) , and their intensity of back pain , functional limitation and anxiety were compared with women in a control group from another antenatal clinic ( n=27 ) . The data were collected at three time points : prior to intervention , and 6 and 12 weeks after intervention . RESULTS At 12 weeks after intervention , the intensity of back pain experienced by the intervention group was significantly lower than that of the control group . However , there were no statistically significant differences between the groups with respect to functional limitations and anxiety . CONCLUSIONS The findings show that the pain-reducing program developed for this study was effective in reducing the intensity of back pain experienced by pregnant women . Promoting good posture and regular exercise can be recommended as a method to relieve back pain in pregnancy women . Further studies are needed to confirm the effect of the BPRP during pregnancy OBJECTIVE To compare the effect of a l and -based , physical exercise program versus water aerobics on low back or pelvic pain and sick leave during pregnancy . DESIGN R and omized controlled clinical trial . SETTING Three antenatal care centers . PARTICIPANTS 390 healthy pregnant women . INTERVENTIONS A l and -based physical exercise program or water aerobic once a week during pregnancy . MAIN OUTCOME MEASURES Sick leave , pregnancy-related low back pain or pregnancy-related pelvic girdle pain , or both . RESULTS Water aerobics diminished pregnancy-related low back pain ( p=.04 ) and sick leave due to pregnancy-related low back pain ( p=.03 ) more than a l and -based physical exercise program . CONCLUSIONS Water aerobics can be recommended for the treatment of low back pain during pregnancy . The benefits of a l and -based physical exercise program are question able and further evaluation is needed Study Design . A r and omized assessor-blinded clinical trial was conducted . Objective . To compare 3 different physical therapy treatments with respect to pain and activity in women with pelvic girdle pain during pregnancy and 3 , 6 , and 12 months postpartum . Summary of Background Data . In spite of the high prevalence of back pain during pregnancy , documented treatment programs are limited . Methods . Based on a clinical examination , 118 women with pelvic girdle pain diagnosed during pregnancy were r and omized into 3 different treatment groups : Information Group , use of a nonelastic sacroiliac belt and oral/written information about pelvic girdle pain ( n = 40 ) ; Home Exercise Group , same as in the Information Group , with the addition of a home exercise program ( n = 41 ) ; and the In Clinic Exercise Group , same as in the Information Group , plus participation in a training program ( n = 37 ) . Pain intensity was rated on a visual analogue scale ( 0–100 mm ) and marked on a pain drawing concerning localization . The activity ability was scored using the Disability Rating Index , covering 12 daily activity items . Outcome measures were obtained at inclusion , on average in gestation week 38 , and 3 , 6 , and 12 months postpartum . Results . There was no significant difference among the 3 groups during pregnancy or at the follow-ups postpartum regarding pain and activity . In all groups , pain decreased and the activity ability increased between gestation week 38 and at 12 months postpartum . Conclusions . Women with pelvic girdle pain seemed to improve with time in all 3 treatment groups . Neitherhome nor in clinic exercises had any additional value above giving a nonelastic sacroiliac belt and information Prenatally depressed women ( N=47 ) were r and omly assigned to a group that received massage twice weekly from their partners from 20 weeks gestation until the end of pregnancy or a control group . Self-reported leg pain , back pain , depression , anxiety and anger decreased more for the massaged pregnant women than for the control group women . In addition , the partners who massaged the pregnant women versus the control group partners reported less depressed mood , anxiety and anger across the course of the massage therapy period . Finally , scores on a relationship question naire improved more for both the women and the partners in the massage group . These data suggest that not only mood states but also relationships improve mutually when depressed pregnant women are massaged by their partners Background . The efficacy of acupuncture on low‐back and /or pelvic pain in late pregnancy is review ed in few reports . Our aim was to evaluate the effects of two different acupuncture stimulation modes on pelvic pain intensity and some emotional symptoms due to the pain condition . Methods . In a prospect i ve r and omized controlled single‐blind study , pregnant women with pelvic pain , median gestational age 26 weeks ( range 18–35 ) , were given 10 acupuncture treatments . Needles were inserted subcutaneously over acupuncture points without further stimulation ( superficial , n=22 ) , or intramuscular and stimulated repeatedly until a perceived sensation of numbness , de qi , ( deep , n=25 ) . Self‐reported pain intensity at rest and during daily activities was assessed on a visual analog scale . The variables pain , emotional reactions , and loss of energy were assessed according to the Nottingham Health Profile question naire . Changes in assessed variables were analyzed with a nonparametric statistical method allowing for analysis of systematic group changes separated from additional individual changes . Results . After acupuncture stimulation , significant systematic group changes towards lower levels of pain intensity at rest and in daily activities as well as in rated emotional reaction and loss of energy were seen . The results also showed additional individual changes in most variables . In this study , no differences between the effects induced by the superficial and deep acupuncture stimulation modes were observed . Conclusion . Acupuncture stimulation that is individually design ed may be a valuable treatment to ameliorate suffering in the condition of pelvic pain in late pregnancy Twenty-six pregnant women were assigned to a massage therapy or a relaxation therapy group for 5 weeks . The therapies consisted of 20-min sessions twice a week . Both groups reported feeling less anxious after the first session and less leg pain after the first and last session . Only the massage therapy group , however , reported reduced anxiety , improved mood , better sleep and less back pain by the last day of the study . In addition , urinary stress hormone levels ( norepinephrine ) decreased for the massage therapy group and the women had fewer complications during labor and their infants had fewer postnatal complications ( e.g. , less prematurity ) |
699 | 28,543,332 | In conclusion , antibiotic use in healthy patients for the prophylaxis of surgical infection associated with dental implant placement does not appear to improve clinical outcomes . | This systematic review aim ed to determine whether there is consensus for antibiotic prescription in healthy patients undergoing implant placement . | BACKGROUND The purpose of this statement is to up date the recommendations by the American Heart Association ( AHA ) for the prevention of infective endocarditis that were last published in 1997 . METHODS AND RESULTS A writing group was appointed by the AHA for their expertise in prevention and treatment of infective endocarditis , with liaison members representing the American Dental Association , the Infectious Diseases Society of America , and the American Academy of Pediatrics . The writing group review ed input from national and international experts on infective endocarditis . The recommendations in this document reflect analyses of relevant literature regarding procedure-related bacteremia and infective endocarditis , in vitro susceptibility data of the most common microorganisms that cause infective endocarditis , results of prophylactic studies in animal models of experimental endocarditis , and retrospective and prospect i ve studies of prevention of infective endocarditis . MEDLINE data base search es from 1950 to 2006 were done for English- language papers using the following search terms : endocarditis , infective endocarditis , prophylaxis , prevention , antibiotic , antimicrobial , pathogens , organisms , dental , gastrointestinal , genitourinary , streptococcus , enterococcus , staphylococcus , respiratory , dental surgery , pathogenesis , vaccine , immunization , and bacteremia . The reference lists of the identified papers were also search ed . We also search ed the AHA online library . The American College of Cardiology/AHA classification of recommendations and levels of evidence for practice guidelines were used . The paper was subsequently review ed by outside experts not affiliated with the writing group and by the AHA Science Advisory and Coordinating Committee . CONCLUSIONS The major changes in the up date d recommendations include the following : ( 1 ) The Committee concluded that only an extremely small number of cases of infective endocarditis might be prevented by antibiotic prophylaxis for dental procedures even if such prophylactic therapy were 100 % effective . ( 2 ) Infective endocarditis prophylaxis for dental procedures is reasonable only for patients with underlying cardiac conditions associated with the highest risk of adverse outcome from infective endocarditis . ( 3 ) For patients with these underlying cardiac conditions , prophylaxis is reasonable for all dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa . ( 4 ) Prophylaxis is not recommended based solely on an increased lifetime risk of acquisition of infective endocarditis . ( 5 ) Administration of antibiotics solely to prevent endocarditis is not recommended for patients who undergo a genitourinary or gastrointestinal tract procedure . These changes are intended to define more clearly when infective endocarditis prophylaxis is or is not recommended and to provide more uniform and consistent global recommendations Introduction : The study aim ed at evaluating the effect of chlorhexidine ( CHX ) in preventing plaque biofilm ( PB ) formation on healing abutments ( HAs ) in patients rehabilitated with osseointegrated implants . Material s and Methods : Fifty HAs were placed in 34 voluntary patients 1 week after implant surgery ( test group ) . After 7 days , a new set of 50 HAs was placed in the same implant sites and removed 1 week after ( control group ) . During the 2 testing periods , patients were instructed to apply : CHX mouth rinsing twice daily and no brushing ( test ) ; no CHX mouth rinsing and no brushing ( control ) . Scanning electron microscopy and image analysis were blindly used to objective ly quantify PB amount on removed HAs . Results : Median values and interquartile ranges of the percent ratio of titanium surface covered from PB were 0.9 ( 0.1–4.1 ) and 1.2 ( 0.1–11.6 ) for test and control groups , respectively ( P = 0.0275 ) . Conclusions : CHX mouth rinsing significantly limited plaque formation on HAs , being a valid contribution to mechanical brushing in early phases of plaque control on dental implants There are many reasons for dental implant failure , the development of bacteremia is concern for dentists . This is due to the possibility of unfavorable result such as implant loss or the need for re-treatment . In general , antibiotic prophylaxis is recommended for high risk patients such as individuals with an immunodeficiency , infectious endocarditis , or previous prosthetic instrumentation . However regarding clinical ly healthy , low and moderate risk individuals the use of antibiotics in implant dentistry is controversial . Another major concern regarding the over prescription of antibiotics is the selection of antibiotic resistant bacteria . A better underst and ing of the efficacy of prophylactic treatments regarding dental implantation is crucial . Thus a literature review and comparison of survival rates of dental implants with regimens of no , pre or post prophylaxis was performed using systematic literature review using reliable electronic data bases . Retrospective or prospect i ve controlled studies were examined for the influence of preoperative and /or postoperative or no antibiosis on dental implant success rate . Of the 11406 implants used in this literature review , cases with no antibiotics had a 92 % success rate , cases with pre-op antibiotic alone had a 96 % success rate , cases with post-op antibiotic alone had a 97 % success rate and cases with both pre and post-op antibiotic had a success rate of 96 % . Thus , the results from this literature review show a > 90 % success rate when antibiotics are used compared to when they are not used . Thus , no benefit is seen from the use of antibiotic prophylaxis in low and moderate risk dental implant patients . Keywords Dental implants ; Pre-operative prophylactics ; Post-operative prophylactics ; Success The purpose of this study was to compare the efficacy of two antibiotic regimens in reducing early dental implant failure . A preoperative single-dose regimen and a 3-day antibiotic course were compared . Eighty subjects needing dental implant placement were r and omly allocated to one of the two antibiotic prophylaxis regimen groups . In the first group , dental implants were placed after the administration of a single preoperative dose of antibiotic ( 1 g of amoxicillin ) ; no postoperative antibiotics were given . In the second group , dental implants were inserted in patients who received the same preoperative dose of antibiotic as the first group , but the antibiotic was then continued postoperatively for 3 days . Patients returned for postoperative evaluation at 3 days , 7 days , and 12 weeks . The surgical sites were assessed for pain , swelling , wound dehiscence , and pus formation . No statistically significant difference was observed between the two groups , probably because of the limited number of patients . Although minor complications were seen in a few patients , all implants were successfully osseointegrated . Until a study with a larger population rules definitively on the role of antibiotics in implant surgery , a single dose of antibiotic before implant placement may be sufficient OBJECTIVES This r and omized clinical trial compares the usefulness of pre- and post-operative antibiotics while strict asepsis was followed during periodontal surgery . MATERIAL AND METHODS Two groups of 40 consecutive patients each with fully or partially edentulous jaws were enrolled . Antibiotics group ( GrAB(+ ) ) : 23 men , mean age 60 , 128 implants , received oral amoxicillin 1 g , 1 h pre-operatively and 2 g for 2 days post-operatively . Non-antibiotics group ( GrAB(- ) ) : 20 men , mean age 57 , 119 implants , received no antibiotics . Bacterial sample s were taken from the peri-oral skin before and at the end of surgery . In 12 patients in each group , sample s were also taken from the nares . A VAS question naire evaluated symptoms of infection/inflammation by both the patient and the periodontologist at suture removal . RESULTS There were no significant differences between both groups , neither for the clinical parameters nor for the microbiota . Staphylococcus aureus was detected in the nares of one patient only . The patients ' subjective perception of post-operative discomfort was significantly smaller in the group receiving antibiotics . Three patients lost one or two implants . CONCLUSIONS Antibiotics do not provide significant advantages concerning post-operative infections in case of proper asepsis . It also does not reduce peri-oral microbial contamination . It does on the other h and reduce post-operative discomfort PURPOSE To evaluate the efficacy of prophylactic antibiotics for dental implant placement . MATERIAL S AND METHODS Twelve Italian private practice s agreed to participate in this trial , each centre providing 30 patients . One hour prior to implant placement , patients were r and omised , for consumption orally of 2 g amoxicillin or identical placebo tablets . Patients needing bone augmentation procedures were not included . Outcome measures were prosthesis and implant failures , adverse events and post-operative biological complications . Patients were seen 1 week , 2 weeks and 4 months post-operatively . RESULTS One centre did not deliver any data and 14 patients had to be excluded from the trial for various reasons . One hundred and fifty-eight patients were evaluated in each group and none dropped out at 4 months . Two prostheses and two implants failed in the antibiotics group , compared with four prostheses and nine implants in the placebo group . There were no statistically significant differences for prosthesis failures , implant losses , complications and side effects . CONCLUSIONS No statistically significant differences were observed . However , four times more patients in the placebo group experienced implant failures than in the antibiotic group , and this requires further investigation PURPOSE To evaluate the difference between a single preoperative dose versus an additional two-day postoperative course of oral amoxicillin in patients undergoing conventional dental implant placement . MATERIAL S AND METHODS Two dentists in two different private practice s conducted this study . One hour prior to surgery , patients had to take a single prophylactic antibiotic dose , consisting of 2 g of amoxicillin orally ; after implant placement , patients were r and omly allocated to two different groups : protocol A ( no other antibiotic administration ) and protocol B , ( 1 g of amoxicillin in the evening of the day of surgery and 1 g twice a day for the 2 days after ) . Outcome measures were prosthetic and implant failures , adverse events and early postoperative complications . Patients were followed up to 6 months after functional loading . RESULTS Three hundred and sixty patients were r and omised and treated ( 192 patients in one centre and 168 in the other ) . Five hundred and sixty-seven implants were placed . Protocol A was applied to 180 patients ( 278 implants ) and protocol B also to 180 patients ( 289 implants ) . Data for 17 patients , 14 from protocol A and three from protocol B , were not available . No statistically significant differences were found for the reported outcomes . Two patients of protocol B experienced a prosthetic failure , losing four implants , while no prosthetic failures were reported for protocol A ( P=0.4836 ; difference in proportions=-0.0110 ; 95 % CI : -0.0412 to 0.0119 ) . Five patients ( 3.0 % ) of protocol A lost five implants versus 5 patients ( 2.8 % ) who lost eight implants in protocol B ( P=1.0000 ; difference in proportions=0.0020 ; 95 % CI : -0.0384 to 0.0438 ) . Three adverse events were observed in the total population , all occurring in protocol B ( 1.69 % ) , with no statistically significant differences between the two groups ( P=0.1199 ; difference in proportions=-0.0170 ; 95 % CI : -0.0487 to 0.0059 ) . However , one patient experienced a severe allergic reaction requiring therapy discontinuation and hospital admission . Early postoperative complications occurred in six patients of protocol A and in four patients of protocol B , with no statistically significant differences ( P=0.5170 ; difference in proportions=0.0130 ; 95 % CI : -0.0254 to 0.0568 ) . CONCLUSIONS No statistically significant differences were observed between 2 g of preoperative amoxicillin and an additional 2-day postoperative course , although adverse events were reported only in the additional 2-day postoperative group . Based on these findings , it might be sufficient to routinely administer preoperatively 2 g of amoxicillin to patients undergoing routine dental implant placement procedures rather than administering additional postoperative doses AIM The aim of this prospect i ve cohort study was to evaluate an anti-infective surgical protocol for the treatment of peri-implantitis . MATERIAL S AND METHODS Thirty-six implants in 24 partially dentate patients with moderate to advanced peri-implantitis were treated using an anti-infective surgical protocol incorporating open flap debridement and implant surface decontamination , with adjunctive systemic amoxicillin and metronidazole . Treatment outcomes were assessed at 3 , 6 and 12 months . Patient-based statistical analyses using multiple regression analyses were performed . RESULTS There was 100 % survival of treated implants at 12 months . At 3 months , there were statistically significant ( P < 0.01 ) reductions in mean probing depths ( PD ) , Bleeding on Probing ( BoP ) and suppuration . The greater the mean PD at baseline , the greater the PD reduction at 3 months . At 3 months , there was also a significant mean facial mucosal recession of 1 mm ( P < 0.001 ) . All these changes were maintained at 6 and 12 months . At 12 months , all treated implants had a mean PD < 5 mm , while 47 % of the implants had complete resolution of inflammation ( BoP negative ) . At 12 months , 92 % of implants had stable crestal bone levels or bone gain . There were no significant effects of smoking on any of the treatment outcomes . CONCLUSIONS For the treatment of peri-implantitis , an anti-infective protocol incorporating surgical access , implant surface decontamination and systemic antimicrobials followed by a strict postoperative protocol was effective at 3 months with the results maintained for up to 12 months after treatment OBJECTIVES A prospect i ve double-blind r and omised controlled trial was conducted to test the effect of prophylactic antibiotics on post-operative morbidity and osseointegration of dental implants . MATERIAL S AND METHODS Fifty-five subjects scheduled for implant surgery were enrolled . The patients were r and omly assigned to the antibiotic ( test group ) and placebo ( control group ) . Twenty-seven patients ( test group ) received 3 g amoxicillin one hour pre-operatively , and 28 patients ( control group ) received placebo capsules 1 h pre-operatively . No post-operative antibiotics were prescribed . Pain diaries and interference with daily activities diaries were kept by the patients for 1 week post-operatively . Signs of post-operative morbidity ( swelling , bruising , suppuration and wound dehiscence ) were recorded by the principal investigators at day 2 and day 7 following the operation . Osseointegration was assessed at 2nd stage surgery or 3 - 4 months post-operatively . RESULTS The results of this study suggest that the use of prophylactic pre-operative antibiotics may result in higher dental implant survival rates ( 100 % vs. 82 % ) . Five implant failures , one in each of five patients , were reported in the placebo group and none in the antibiotic group ( P = 0.0515 ) . No significant differences were found for most of the signs of post-operative morbidity 2 and 7 days post-operatively . Only bruising at 2 days following the operation appeared to be higher in the placebo group ( P = 0.0511 ) . Post-operative pain ( P = 0.01 ) and interference with daily activities ( P = 0.01 ) appeared to be significantly lower for the antibiotic group after 7 days . Those patients with implant failure reported higher pain ( based on the VAS scores ) after 2 days ( P = 0.003 ) and after 7 days ( P = 0.0005 ) , higher pain ( based on the amount of analgesics used ) after 7 days ( P = 0.001 ) and higher interference with daily activities ( based on the VAS scores ) after 2 days ( P = 0.005 ) . CONCLUSIONS The use of for dental implant surgery may be justified , as it appears to improve implant survival in the short term and also results in less post-operative pain and interference with daily activities . From the results of this study , it appears that prophylactic antibiotics may also be beneficial both in terms of implant survival , especially when the surgical procedure is prolonged due to its difficulty , high number of implants placed or operator 's inexperience PURPOSE The purpose of this prospect i ve study was to compare the efficacy of prophylactic antibiotic regimens commonly used in dental implant surgery . Preoperative single-dose and long-term prophylactic antibiotic regimens were compared . MATERIAL S AND METHODS This was a 2-center prospect i ve study in which 215 patients underwent ambulatory endosseous implant placement . In the first group , 445 dental implants were placed in 125 patients after the administration of a single preoperative dose of prophylactic antibiotic with no postoperative antibiotics . In the second group , 302 dental implants were placed in 90 patients who received a preoperative dose of antibiotics and were instructed to take antibiotics postoperatively for 7 days . In both groups , 0.12 % chlorhexidine pre- and postoperative mouth rinses were used . Patients returned for postoperative evaluation at 1 week , 2 weeks , and just prior to surgical uncovering . The surgical sites were assessed for pain , swelling , erythema , and purulence . RESULTS In the first group , 3 patients developed wound dehiscence at 5 implant sites and 1 developed a minor inflammatory response . None of the patients in this group received further antibiotics . In the second group , 3 patients developed wound dehiscence , 2 developed an inflammatory response , and 1 was diagnosed with infection , for which another course of antibiotics was required . There was no statistical difference between the 2 groups according to the Fisher 2 x 4 exact test ( P = .56 ) . DISCUSSION Indiscriminate use of antibiotics is unacceptable in clinical practice today . Surgeons must adhere to basic principles to gain the most benefit from the use of prophylactic antibiotics . CONCLUSION Long-term prophylactic antibiotic use in implant surgery was of no advantage or benefit over a single-dose preoperative antibiotic regimen in this patient population The benefits of prophylactic antibiotics are well recognized in dentistry . However , their routine use in the placement of endosseous dental implants remains controversial . As part of the comprehensive Dental Implant Clinical Research Group ( DICRG ) clinical implant study , the preoperative or postoperative use of antibiotics , the type used , and the duration of coverage were left to the discretion of the surgeon . These data for 2,973 implants were recorded and correlated with failure of osseointegration during healing ( Stage 1 ) , at surgical uncovering ( Stage 2 ) , before loading the prosthesis ( Stage 3 ) , and from prosthesis loading to 36 months ( Stage 4 ) . The results showed a significantly higher survival rate at each stage of treatment in patients who had received preoperative antibiotics PURPOSE To evaluate the efficacy of prophylactic antibiotics for dental implant placement . MATERIAL S AND METHODS Thirteen dentists working in private practice s agreed to participate in this trial , each centre providing 50 patients . One hour prior to implant placement , patients were r and omised to take orally 2 g amoxicillin or identical placebo tablets . Patients needing bone augmentation at implant placement were not included . Outcome measures were prosthesis and implant failures , adverse events and post-operative complications . Patients were seen 1 week , 2 weeks and 4 months post-operatively . RESULTS Two centres did not deliver any data , two centres did not manage to include the agreed quota of patients and three patients had to be excluded . Two-hundred and fifty-two patients were evaluated in the antibiotic group and 254 in the placebo group , and none dropped out at 4 months . Four prostheses and seven implants ( in five patients ) failed in the antibiotics group versus 10 prostheses and 13 implants ( in 12 patients ) in the placebo group . Eleven complications were reported in the antibiotic group versus 13 ( in 12 patients ) in the placebo group . No side effects were reported . There were no statistically significant differences for prosthesis failures , implant losses and complications . Patients receiving immediate post-extractive implants had an increased failure risk compared with patients receiving delayed implants ( 9 % versus 2 % ) . CONCLUSIONS No statistically significant differences were observed , although trends clearly favoured the antibiotic group . Immediate post-extractive implants were more likely to fail In past decades , warnings about overprescription and misuse of antibiotics- which are now considered to be responsible for antimicrobial resistance , allergies , ineffectiveness , and suprainfections-have been made to both medical and dental clinicians . To help assess the antibiotic prescribing habits of dentists , a survey was created and emailed through the Survey Monkey tool to 102 r and omly selected board-certified periodontists . Each was asked to answer multiple-choice questions regarding their use of an antibiotic protocol in 10 specific periodontal or implant-related clinical circumstances . This group of practitioners and the 10 clinical circumstances were chosen to limit the wide variety of clinical conditions treated by dentists and to narrow the scope of variables when antibiotics are considered . All 102 participants returned the question naire , and 96 % to 100 % of respondents reported that they had treated 8 of the 10 circumstances , with 89.9 % and 80.8 % having treated the other two conditions listed in the survey ; this allowed subsequent question ing of the respondents on their antibiotic prescribing protocol s. Although the validity of antibiotics for dental procedures may be question ed based on present information , as many as 50 % or more of the dentists answering the survey prescribed antibiotics . The prescription , initiation , and duration of antibiotics varied considerably in many of the 10 specific circumstances , including treatment of acute and chronic periodontitis , sinus or ridge augmentation , and immediate or delayed implant placement . Based on the results of the survey , it was obvious that definitive guidelines and protocol s are needed as well as exp and ed postgraduate training regarding antibiotic use According to the American College of Surgeons , complex oral surgical procedures , including the transoral placement of endosseous implants , are of the type that may require prophylactic antibiotics . However , the routine use of prophylactic antibiotics in the field of dental implantology continues to be controversial , and their utilization varies widely . No data from a r and omized prospect i ve clinical study of the prophylactic use of antibiotics in implant surgery have been previously published . As part of the comprehensive Dental Implant Clinical Research Group clinical implant study , the preoperative or postoperative use of antibiotics , the type used , and the duration of coverage was left to the discretion of the surgeon . These data were recorded and correlated with failure of osseointegration during healing ( stage I ) and at stage II surgery ( uncovering ) . The results showed that significantly fewer failures occurred when preoperative antibiotics were used OBJECTIVES To determine the effect of various systemic antibiotic prophylaxis regimes on patient-reported outcomes and postsurgical complications in patients undergoing conventional implant installation . MATERIAL AND METHODS Three hundred and twenty-nine healthy adults in need of conventional implant installation were r and omly assigned to one of four groups : ( i ) preoperatively 2 g of amoxycillin 1 h before surgery ( positive control , PC ) , ( ii ) postoperatively 2 g of amoxycillin immediately following surgery ( test 1 , T1 ) , ( iii ) preoperatively 2 g of amoxycillin 1 h before and 500 mg thrice daily on days 2 and 3 after surgery ( test 2 , T2 ) , ( iv ) preoperatively 2 g of placebo 1 h before surgery ( negative control , NC ) . Subjects were examined clinical ly by blinded examiners over 8 weeks after implant installation . In addition , Visual Analogue Scales ( VAS ) for pain , swelling , bruising and bleeding were obtained over 14 days . ANOVA was performed for the VAS . Chi-square tests were applied for postsurgical complications . RESULTS All VAS scores were low for all groups and decreased over time ( P < 0.001 ) . There were no significant differences for the VAS scores between the various groups at any time point ( P > 0.05 ) . There was only a significant difference in flap closure at week 4 , where NC had 5 % of the subjects not achieving complete wound closure compared to 0 % for the three other groups ( P = 0.01 ) , with no other significant differences for any postsurgical complications ( P > 0.05 ) . CONCLUSION For st and ard single implant placement , prophylactic systemic antibiotics either before or after , or before and after the surgical procedure do not improve patient-reported outcomes or prevalence of postsurgical complications The aim of this study was to attempt to determine the minimum effective regimen of amoxicillin antibiotic prophylaxis for dental implant surgery . One hundred patients were r and omly allocated to 4 different antibiotic prophylactic treatment groups . At second-stage surgery , only 2 implants failed in the nonantibiotic group . No statistically significant differences were found in the 4 groups , probably because of the limited number of the sample s. Until a study with a larger population may definitely rule on the role of antibiotics in oral implant surgery , in may be prudent for the practitioner to adopt the single preoperative antibiotic dose as the minimal effective regimen PURPOSE This r and omised double-blind placebo-controlled trial was carried out to investigate the effect of a one-week post-operative course of 600 mg of ibuprofen taken four times a day on marginal bone level around dental implants . MATERIAL S AND METHODS A total of 61 patients were allocated to the ibuprofen ( 31 patients ) or placebo group ( 30 patients ) . Overall , 132 implants were inserted , 67 implants in the ibuprofen group and 65 implants in the placebo group . Preparation of the implant sites was carried out with an intermittent drilling sequence adapted to the fixture diameter and the local bone quality according to the Astra Tech implant installation guide . The primary outcome measure was the change in marginal bone level around dental implants from the baseline ( 2 weeks post-placement ) to the 3- and 6-month radiographic examinations . The paralleling technique and a film holder coupled to a beam aim ing device were used to take the periapical radiographs . Measurement of changes in bone level was made using a viewing box and x8 magnifier . RESULTS Two patients from the ibuprofen group were unable to complete the prescribed course of ibuprofen owing to a minor self-reported stomach upset . A patient from the control group did not attend any of the scheduled appointments following implant placement . A total of three patients dropped out . All implants survived in either group during the 6-month observation period . The mean marginal bone level changes from the baseline were ( -0.33 mm ) at the 3-month and ( -0.29 mm ) at the 6-month follow-up for the ibuprofen group while the corresponding values for the placebo group were ( -0.12 mm ) and ( -0.30 mm ) . There were no statistically significant differences between groups for mean marginal bone level changes at 3 months ( P = 0.27 ) or 6 months ( P = 0.97 ) . CONCLUSIONS Administration of a short course of systemic ibuprofen for post-operative pain management subsequent to implant placement may not have a significant effect on the marginal bone around dental implants in the early healing period PURPOSE To compare the efficacy and safety of 2 g amoxicillin orally with identical placebo tablets 1 hour before implant placement when placing single implants in bone types II and III . MATERIAL AND METHODS 12 private dental clinics in Spain agreed to participate in this trial . A total of 105 patients were recruited . Patients were r and omised for consumption orally of 2 g amoxicillin or identical placebo tablets . Only patients needing single implants were included . Outcome measures were post-operative infections , adverse events and implant failures . Characteristics of the saprophytic flora were also studied in all patients . Patients were seen 3 days , 10 days , 1 month and 3 months postoperatively . RESULTS A total of 105 patients ( n = 52 in the amoxicillin group and n = 53 in the placebo group ) were evaluated and none were excluded from the study at 3 months . Six post-operative infections occurred and two implants were lost in each group . There were no statistically significant differences for postoperative infection , adverse events , implant failures and the characteristics of saprophytic flora between groups . The use of amoxicillin did not either alter or modify the characteristics of the saprophytic flora nor provoke remarkable side effects . CONCLUSIONS Antibiotic prophylaxis may not be needed when placing single implants in patients with bone types II and III PURPOSE The American College of Surgeons guidelines suggest that complex oral surgery may benefit from prophylactic antibiotic coverage . The use of preoperative antibiotics , postoperative antibiotics , or both during implant placement is a widely accepted practice in the United States , whereas dentists in other countries rarely use antibiotics . PURPOSE The purpose of this study was to determine if antibiotic coverage at the time of implant placement improves the survival of the Ankylos implant . METHODS As part of a comprehensive , multicentered , multidisciplinary , prospect i ve , independent , international clinical study , design ed and coordinated in the United States by the Ankylos Implant Clinical Research Group ( AICRG ) , the use of preoperative ( several regimens ) and postoperative antibiotics ( yes/no ) were carefully documented to assess their influence on improving survival . A total of 1500 Ankylos implants were placed and followed for a period of 3 to 5 years . The decision to use antibiotics and the regimen to be employed was made by the treating surgeon . Failure was defined as removal of the implant for any reason . All data were entered into a computerized data base for analysis . RESULTS The use of preoperative antibiotics produced no significant improvement ( P = .21 , Fisher 's exact test ) in survival compared with those placed without antibiotic coverage . There was no significant difference between the regimens defined as AHA-1990 , AHA-1997 , and Peterson 's recommendations . CONCLUSIONS The results of this study suggest that there was little or no advantage to providing antibiotic coverage when placing this implant . These findings also suggest that the use of antibiotics for implant placement may not be as beneficial as once believed . If vali date d by other studies , the elimination of this practice for routine implant placement would represent a small but significant step forward in the reduction of unnecessary antibiotic use |
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